CORD-19:2008f024274c53b0de1276f4047a6a641813fd98 / 0-1703 6 Projects
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ABSTRACTS: CONCURRENT SESSIONS
Abstract
INTRODUCTION: The effect of anti IgE has been described as a function of complexing free IgE to reduce mast cell implantation and consequent reduction of mast cell degranulation upon exposure to antigen. Theoretically, as total free IgE drops below 10 ng/ml, improvement occurs as free and cell bound IgE equilibrate and allergic reactions subside. Initial observations ( Togias A et al. J Allergy Clin Immunol. 1998 ;101:S171)suggested that prick skin tests consistently reached their low point at 98 days with significant reduction in size. Laynadier (Leynadier F, Doudou O, Gaouar H, Le Gros V, Bourdeix I, Guyomarch-Cocco L, Trunet P : Effect of omalizumab in health care workers with occupational latex allergy.J Allergy Clin Immunol 2004;113:360-1) noted some reduction in skin testing in sixty percent of patients treated over a six month period with monoclonal antiIgE. But clinicians since approval of the drug in 2002 have noted that even in the presence of good clinical response to asthma, skin test reactivity is still obvious, and in many cases unchanged. METHODS: Following the suggestions for standard clinical follow up by Lanier and Marshall ( Annals May 2003) , routine skin prick skin testing was completed after informed consent on 24 patients at onset of anti-IgE therapy, and repeated at 6-7 months. In all instances were skin tests done and photographed in a standard manner. In a few cases, skin tests were repeated on patients receiving anti IgE for as long as five years. RESULTS: Photographic evidence will be presented. In 22 of 24 patients on current therapy, prick skin testing remained at an almost identical photographic level to the baseline analysis, but there was a correlation between the patients with the lowest serum IgE and the likelihood of apparent reduction. There was no correlation to reduction of skin testing and clinical response to anti IgE since all 24 patients had experience significant quality of life improvements. CONCLUSION: Anti IgE has variable effects on reducing prick skin testing, with a greater likely hood associated with low or extremely low initial total IgE levels. Skin testing is more sensitive for detection of allergen-specific IgE than is immunoassay for allergen-specific IgE. For some assay methods, the qualitative cutoff of 0.35 kU/L is inappropriately high. This study was conducted in order to determine whether a particular assay system can be used to measure lower levels of allergen-specific IgE. The Pharmacia UniCAP System was studied. All reagents were purchased from the manufacturer, and the study was approved by a local human assurance committee. To determine background of the calibration curve, the fluorescent unit (FU) response of 6 replicates of assay diluent measured with an anti-IgE solid phase was determined. The background responses of 7 arbitrarily selected allergen solid phases (oak, timothy and short ragweed pollen; cat; peanut; yellow jacket venom; penicillin G) were also measured. Lower detection limits (LLD) were calculated using the mean background measurement + 3 standard deviations (SD). To examine linearity of a low-range calibration curve, 1:2 dilutions to extinction were made, starting with the 3.5 kU/L calibrator. The mean background of the anti-IgE solid phase was 15.4 FU, SD 2.7 and coefficient of variation (CV) of 18%; the LLD was 24. This LLD corresponded to a level of approximately 0.01 kU/L of IgE. The LLD of the allergen solid phases ranged from 17.2 FU (yellow jacket venom) to 71.6 FU (short ragweed); this corresponded to about 0.08 kU/L IgE. The low level dilution curve exhibited parallelism with a curve constructed using a zero (diluent) calibrator as a 7th point in the assay's reference curve. A low level method is capable of measuring specific IgE levels lower than the manufacturer's 0.35 kU/L cutoff. This would seem to be particularly important in research applications, and in the analysis of certain highrisk allergens. The clinical significance of very low levels of specific IgE in the serum warrants study. Allergists/immunologists are often consulted on patients with rashes or recurrent infections. The differential diagnosis can comprise a variety of disorders, some of which are rare syndromes that require early diagnosis and specific management. A 3 mo old WM developed persistent rash and worsening eczema. Later, he had recurrent severe skin infections, skin abscesses, recurrent sinusitis, and chronic otitis media that required multiple placement of tympanostomy tubes, yet had a persistent tympanic membrane perforation. Recurrent wheezing was noted from 3-7 yr of age. He had several episodes of pneumonia since 3 yr of age affecting different lobes. He failed to shed the primary teeth and had history of periodontitis and oral thrush. He developed scoliosis and multiple fractures of the upper extremities and ribs. At 12 yr he had staphylococcal bacteremia and osteomyelitis of the acetabulum. In spite of antibiotics prophylaxis, he continued to have recurrent skin infections and lymphadenitis. Laboratory evaluation revealed eosinophilia (up to 3138/mm3), normal levels of IgG, IgA, IgM & IgG subclasses, except for decreased IgG2 (51 mg/dl). He had protective levels of anti S. pneumoniae and H. influenzae, but low anti-tetanus and anti-diphtheria titers. At 4 yr, total IgE level was 42, 500 IU/ml which supported the diagnosis of hyper IgE (HIE) syndrome; it decreased to 197 IU/ml by 12 yr. RAST was positive to HD mite, cat, dog, egg, milk, and pollens. Flow cytomerty, NBT and phagocytic index were normal; CH50 was low (66 mg/dl). DEXA scan showed osteopenia. Chest X-ray showed bilateral infiltrate, atelectasis and scoliosis of the thoracic spine. During his hospitalization at 13 yr, his skin was fair, lichenified with widespread maculopapular erythematous rash. The palms and fingers showed open cracks and pustules, but no weeping lesions. In addition to coarse facial features, his face was eczematous. Conclusion: HIE syndrome is an autosomal dominant disorder that mimics atopic dermatitis but has severe course, multiple infections, and several complications. Although a markedly elevated total IgE level Introduction: Mannose-binding lectin (MBL) is a serum protein in the lectin complement pathway. It is important in innate immunity, and is thought to be particularly relevant in young children during the development of adaptive immunity. Deficiency in MBL has been reported in population-based studies as a risk factor in children for infection and hospitalization. Additionally, age-dependent variability of MBL has been previously noted. This study evaluates the prevalence of MBL deficiency in children with established recurrent infection who were referred for evaluation of immunodeficiency. Method: We prospectively evaluated MBL status of children referred for recurrent infection. Serum was collected from October 2002 to September 2003. Children with known primary or secondary immunodeficiencies were excluded. MBL analysis was performed by standardized ELISA using MBL oligomer assays. We performed chart and laboratory review for comorbid diagnoses, quantitative immunoglobulin levels and subclasses, and complement function with CH50 and AH50. Results: Two-hundred thirty five children were evaluated. Mean age was 4.5 years (range 0.08-17 years). Mean MBL was 1780 ng/ml (range 17-4806 ng/ml). Thirty-one of 235 children (13.1%) were MBL deficient, levels <200, and among this group the mean MBL level was 61.3 ng/ml (range 17-163 ng/ml). Mean age in this group was 3.6 years (range 0.3-16 years). Of the children with MBL deficiency, 13 (5.1%) children had levels <50. The M:F ratio of children with abnormal MBL levels was 1.08. Linear regression analysis showed no correlation of MBL level with age. Comorbid diagnoses were variable, including asthma, allergy, and atopic dermatitis. None of the children had symptoms compatible with connective tissue disease. No child with an abnormal MBL level was found to have significant deficiency of IgG, IgA, or IgM. Several children had low IgG4, which were within normal physiologic range. No other concomitant complement pathway disorders were detected. Conclusions: Our study did not reveal any correlation between MBL level and age. In children with recurrent infections, MBL deficiency was approximately twice the estimated rate of the general population. Contrary to previous studies, no other significant immunologic disorders were identified. Therefore, MBL deficiency alone is a risk factor for infection in children.
T.B. Fausnight * , Hershey, PA.
INTRODUCTION: The incidence of perioperative anaphylaxis is estimated to be between 1 in 10, 000 and 1 in 20, 000 procedures. Approximately 60% of cases of perioperative anaphylaxis are attributed to neuromuscular agents. Very little information is reported in the literature regarding pediatric perioperative anaphylaxis. I describe a pediatric patient with suspected perioperative anaphylaxis to rocuronium. METHODS: A 10 year-old girl with a history of sacral agenesis and neurogenic bladder was scheduled to have bladder augmentation surgery. The patient was taken to a latex-free operating room. During induction of general anesthesia, she was found to be difficult to ventilate. She also became hypotensive. Examination of the patient revealed urticaria on her right arm. She was given epinephrine, diphenhydramine, and dexamethasone. The procedure was aborted. The reaction was believed to be from either rocuronium or propofol. RESULTS: Because of the high incidence of anaphylaxis to neuromuscular agents, allergy skin testing was performed for rocuronium, vecuronium, and succinylcholine. The patient had negative percutaneous skin tests (1:10) for rocuronium, vecuronium, and succinylcholine. She had a negative intradermal skin test to rocuronium at the 1:1000 dilution. She had a positive intradermal skin test to rocuronium at the 1:100 dilution. She had negative intradermal skin tests to both vecuronium and succinylcholine at the 1:1000, 1:100, and 1:10 dilutions. She underwent surgery 2 weeks after skin testing. She received a test dose of vecuronium and had no reaction. She received 3 doses of vecuronium and multiple doses of morphine without any adverse reactions. Propofol was avoided. The surgery was completed without difficulty CONCLUSIONS: This case illustrates the usefulness of skin testing for neuromuscular agents in a pediatric patient. Introduction: Extrapulmonary pneumocystis jiroveci infection is rare in non-HIV infected individuals and, to our knowledge, it has not been reported before in a patient with Good's Syndrome. We report a case of extrapulmonary pneumocystis in a patient with Good's Syndrome. Case report: A 44-year-old African American male patient with a history of Good's Syndrome presented with left flank pain of 3 months duration. The pain was constant and associated with night sweats, fever, and chills. Furthermore, the patient also reported a 20-pound weight loss. On exam, patient was found to have multiple hypopigmented areas over his abdomen and left lower extremity, bitemporal wasting, sunken eyeballs, and oral thrush. The patient was also found to have left costovertebral angle tenderness with a palpable solid fixed mass along the left mid axillary line overlying the splenic area. ComputedTomography (CT) scan of the chest and abdomen showed a 2.2 x 2.9 cm soft tissue mass at the left lateral aspect of the T11 vertebral body and 7.0 x 5.2 cm soft tissue parasplenic mass. The parasplenic mass involved the inferior anterior aspect of the left 11th and 12th ribs (See Figure) . The Giemsastained biopsy of the parasplenic mass revealed pneumocystis jiroveci and was confirmed using immunohistochemical stain with monoclonal antipnumocystis antibodies. The patient's symptoms of night sweats and loss of appetite improved within 48 hours following initiation of Trimethoprim-Sulfamethoxazole therapy. A CT of the chest and abdomen, repeated six months post treatment, confirmed the resolution of both the paravertebral and the parasplenic masses. Conclusion: To our knowledge, this is the first case of extrapulmonary pneumocystis presenting in a patient with Good's Syndrome. Although it is rare, extrapulmonary pneumocystis should be considered in the differential diagnosis of patients with Good's Syndrome and chest or abdominal mass. Introduction: T cells are regulated by cellular interactions with the environment during development. They play a critical role in the regulation and development of autoimmune diseases. We report inflammatory myositis in a 10-year-old Caucasian female with primary T cell-deficiency since infancy. Methods: At nine months of age, our patient developed lymphoid interstitial pneumonitis. Immunologic evaluation revealed isolated T-cell deficiency. During the first 3 years of life, she had failure to thrive, recurrent sinusitis, oral candidiasis, fungal skin infections, and Pseudomonas pneumonia. At 5 years, autoimmune conditions, characterized by a purpuric rash over the nose; face and exposure area of elbows; knees and fingers; Raynaud's phenomenon; and nasal septum perforation, developed. Inflammatory markers were persistently elevated and autoantibodies detected. By age 9, she developed proximal muscle weakness with distal joint contractures. Dry gangrene of the fingers from a thrombotic incident occurred. Results: Serial immunologic evaluation revealed low CD4 9-36%, # 153-335 (normal 36-61%, # 900-2860 cell/mm3), low CD8 5-23%, #142-237 (normal 16-34%, # 630-1910 cell/mm3) , decreased lymphocyte transformation to antigens but appropriate to mitogens. IgG 1320-2560 (normal 667-1179 mg/dL); IgA 470-780 (normal 79-169 mg/dL), and IgM 215-340, (normal 40-90 mg/dL) with appropriate antibody responses to vaccine antigens. Bone marrow and thymus biopsies were normal. Further evaluation was not consistent with known primary or secondary immunodeficiencies. Several skin biopsies revealed nonspecific dermatitis without vasculitis. MRI of lower extremities showed abnormal signals involving bilateral muscles of thighs and calves. Muscle biopsy revealed inflammatory myositis with plasma cell predominance, inconsistent with dermatomyositis or polymyositis. Aldolase 8-10 IU/L (< 5), CRP 8-16 mg/dL (< 0.5), ESR 50-70 (< 20), RF 1:1280 (< 1:40) and type II collagen Ab 26-35 EI/mL (< 20) . ANA, ANCA and ACE were within normal range. Antibodies for myositis and myositis related-antibodies were negative. Diagnosis of nonspecific plasma-cell inflammatory myositis was made. A trial of monthly IVIG 2 gm/kg resulted in clinical improvement. Conclusion: This novel plasma cell myositis occurring in a child with primary T cell deficiency underscores the role T cells play in the development of autoimmune diseases.
Introduction The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 6-hour, 12-step desensitization protocol and to characterize the immune mechanism of carboplatin HR. Methods We analyzed ten consecutive patients over a two year period with documented HR to carboplatin who required continued treatment with a platinum agent. The patients were treated with carboplatin using a 6-hour, 12-step desensitization protocol. Skin tests were performed on five patients. Results Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n=3) and third (n=1) desensitizations but tolerated the re-administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. Conclusions The 6-hour, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE-mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen-specific mast cell desensitization. Hypothesis: There is an association between food allergies and acid reflux in atopic adults Study Design: A retrospective chart review of 60 patients was conducted. 30 people who tested positive and 30 people who tested negative for food allergy were included. The prevalence of gastroesophageal reflux disease (GERD) in the total group and each of the study arms was compared to population prevalence. Methods: Results of 70 allergen specific IgE tests (Pharmacia Immunocap, NJ) run for food allergies were reviewed to help locate charts of 60 atopic subjects, 30 with positive, and 30 with negative food allergy results. We reviewed charts for history of heartburn and acid regurgitation or the diagnosis of GERD, laryngopharyngeal reflux (LPR) or Peptic ulcer disease (PUD). Population prevalence (19.8%; CI 17.7-21.9) of acid reflux was estimated from a historical comparison that studied adults in a similar geographical location. Results: In the food allergy positive group, 26.7% of the subjects (95% CI 11.8-41.6) had either a history of heartburn and/or a diagnosis of GERD, LPR or PUD. In the food allergy negative group, 40% (95% CI 25.1-54) had acid related disorders. In the total study group of atopic subjects, the prevalence of heartburn, GERD, LPR or PUD was 33.34% ). On Chi square analysis, the prevalence of acid reflux disorders was significantly higher in the total study group when compared with population prevalence (p=0.013). The prevalence of acid reflux disorders between the food allergy study group and in the population shows no significant difference (p=0.41). The prevalence of acid reflux disorders was significantly higher in the food allergy negative group when compared with the prevalence in the population (p=0.003). There was no significant difference in the prevalence of acid reflux disorders between the two study groups with and without food allergy (p = 0.27). Conclusions: The prevalence of acid reflux disorders was higher in people with food allergy when compared to the population, but missed statistical significance. Patients without food allergy had a significantly higher prevalence of acid reflux disorders compared to the population. Atopic individuals have a statistically significant higher prevalence of acid reflux disorders, but there is no statistically significant difference between atopics with and without food allergy.
Abstract Background: Analysis of dispensing patterns of injectable epinephrine offers a method to study the characteristics of school children with allergic or anaphylactic reactions. Objective: To analyze the demographics of children prescribed injectable epinephrine in Massachusetts school districts with diverse racial and ethnic enrollment patterns. Methods: School nurses in 44 schools (grades PK-12) enrolling 21, 870 students recorded the characteristics of students prescribed injectable epinephrine including the number and racial mix of students in each school, student age, grade level, race, sex, and allergic disorder requiring epinephrine. Surveyed school districts were two predominately white (98%) suburban districts enrolling 5855 students and one urban area with a minority population of 60% enrolling 16, 020 students. The use of epinephrine for peanut allergy was analyzed in detail. Results: A total of 181 of 21, 875 (0.83%) students in three school systems were dispensed injectable epinephrine. Males outnumbered females (110 to 71). Whites outnumbered non-whites 153 to 28. Two thirds (n=116) of children dispensed epinephrine had peanut allergy. The second most common allergy was stinging insect allergy (n=34). The rate of dispensed epinephrine for peanut allergy was lowest in the urban school district (0.30%) versus the two suburban districts, 1.1% and 1.26% respectively. Whites with peanut allergy outnumbered nonwhites 99 to 19. Males outnumbered females 69 to 49. The lowest rate of prescribed injectable epinephrine for peanut allergy in all three school districts was found in 9612 non-white school children-0.17%. Eighty-nine of 118 (75%) school children with peanut allergy were enrolled in grades PK through 5. There were twice as many white versus non-white (32 to 16) school children in the urban system with prescribed injectable epinephrine for peanut allergy. Only eight (.11%) of 7209 Hispanic and Asian students in the were dispensed injectable epinephrine for peanut allergy. Conclusions: This is the first study to suggest that there may be a racial disparity in the prevalence of childhood peanut allergy. One possible explanation for this disparity is that varied feeding practices in minority infants and children may induce a state of tolerance and lead to a lower incidence of peanut allergy.
F.I. Hsu * , H.J. Burstein, M.C. Castells, Boston, MA. INTRODUCTION: Trastuzumab is a humanized IgG1 kappa monoclonal antibody specific for human epidermal growth factor receptor 2 protein, HER2, used in the treatment of Her2/neu positive breast cancer. We present the first report of desensitization to trastuzumab in a patient with an IgE-mediated reaction to trastuzumab and documented IgG-anti-IgG1 human antibodies. METH-ODS: A 37 year old woman with metastatic invasive ductal breast cancer (ER/PR positive, Her-2 strongly positive), unresponsive to conventional therapy, presented with an anaphylactic reaction to trastuzumab and was evaluated for rapid desensitization by skin testing and serum specific IgG antibodies. The patient had previously received trastuzumab. RESULTS: The anaphylactic reaction to trastuzumab consisted of diffuse erythema, urticaria, respiratory distress and laryngeal edema. Premedication with steroids, H1 and H2 blockade, and slow infusion did not prevent a subsequent reaction. Skin prick testing with trastuzumab (21mg/ml) was positive with 2 negative controls, confirming an IgE-mediated mechanism. IgG anti-human IgG1 antibodies (HAHA) to trastuzumab were confirmed by ELISA. The patient was desensitized to trastuzumab 2 mg/kg with an intravenous protocol that started at 0.5 mcg/h, and increased in rate every 15 minutes until a final rate of 30 mg/h, for a total infusion time of 6 to 8 hours. Premedication included diphenhydramine, prednisone, famotidine, and montelukast. Desensitization was confirmed by negative skin prick and intradermal tests (2 mg/ml and 21 mg/ml), with positive histamine control. The patient tolerated a total of 10 weekly doses of trastuzumab 2 mg/kg. Intradermal skin testing prior to her 5th and 10th courses showed reactivity, indicating resensitization. Serum levels of tratuzumab were undetectable at 1 week after desensitization. CONCLUSION: Allergic reactions to trastuzumab are rare but can include anaphylaxis. In patients with documented HAHA and/or IgE-mediated reactions to trastuzumab and clinical symptoms of type I/mast cell mediator-related symptoms, desensitization can allow continued administration of this treatment by providing tolerance. The clinical effectiveness of desensitizations in patients with IgE and HAHA antibodies remains to be defined. In contrast to reports in the medical literature, details of the medical aspects were limited. There were 2 attacks on infants bringing the total to 3 reported infant attacks to date. Two of the 3 infants suffered long term morbidity and 1 died. Like those reported in the medical literature, the majority of adults were in long term care facilities, although 2 were in hospitals. Overall, 6 of the 20 individuals stung died within one week of stings. No significant medical consequences of stings were reported in 6 of 10 of the newspaper reports as opposed to 2 of 10 reports in the medical literature. CONCLUSION: Our data suggest that increasing numbers of fire ant attacks are occurring in medical facilities, where chronically ill, frequently immobile patients come in contact with foraging ants. Unattended infants in private homes in fire ant endemic areas also appear at risk. The factors that determine why individuals are stung and the severity of injury after attacks remain uncertain. The presence of fire ants inside health care facilities and homes is a harbinger for fire ant attacks of disabled or infant occupants. We hypothesize that morbidity is determined by the number of stings, the condition of the patient and the type of treatment administered. Purpose: To determine if gender confers a risk for positive penicillin (PCN) skin test. Method: Rates of positive PCN skin tests, according to gender, were determined in patients with a history of PCN allergy undergoing an allergy pre-operative evaluation from June 2002 to June 2004. During this period, 19, 429 patients were seen in the pre-operative evaluation clinic in which 1921 had a history of PCN allergy and comprise our study population. A univariate logistic regression analysis was employed to calculate the odds ratio (OR) and the 95% confidence interval (CI) for gender differences in the rates of positive PCN skin test and a multivariate logistic regression analysis was used to adjust for age and history of multiple drug allergies. P-value of 0.05 or less was considered statistically significant. Results: Of the 1921 patients, 1759 underwent skin testing for PCN, 157 patients did not, and 5 charts were not available for review. The mean age of the study group was 60 years. Sixtyfour (3.6%) patients had a positive skin test to PCN. Of these, 53 (83%) were females and 11 (17%) were males (OR 3.6, 95% CI 1.9-7.2, p = 0.0001). Of those with a negative/equivocal PCN skin test, 960 (57%) were females versus 720 (43%) males. In a multivariate logistic regression analysis adjusted for age and history of multiple drug allergies, female gender again was more likely to have a positive PCN skin test (OR 4.7, 95% CI 2.3-10.5 p < 0.0001). 157 patients did not undergo PCN skin testing, 62 (40%) were male and 95 (60%) were female. Conclusion: This is the first report showing that a greater risk for a positive skin test to PCN exists in association with female gender. Age and a history of multiple drug allergies are unlikely to be confounding factors to the observed gender risk. Further studies are needed to identify other possible confounding factors and/or mechanisms that can explain this risk.
A. Fiocchi 1* , P.A. Restani 1 , S. Cucchiara 2 , G. Lombardi 3 , G. Magazzu' 4 , G.L. Marseglia 5 , K. Pittschieler 6 , S. Tripodi 2 , R. Troncone 7 , A. Vierucci 8 , 1. Milan, Italy; 2. Roma, Italy; 3. Pescara, Italy; 4. Messina, Italy; 5. Pavia, Italy; 6. Bolzano, Italy; 7. Napoli, Italy; 8. Firenze, Italy. Background: Cow milk substitutes for children allergic to cow milk proteins (CMP) include soy-based formula and cow s milk hydrolysates. Neither can rule out a sensitisation risk. Objective: Prospective assessment of clinical tolerance to a rice-based hydrolysate formula by children allergic to cow milk proteins (CMP) who consume rice openly. Patients and methods: Ninety-seven children aged 4 to 136 months with immediate reactions to cow milk confirmed during DBPCFC were assessed for clinical tolerance to cow milk by SPT with whole milk, -lactalbumin (ALA), -lactoglobulin (BLG), -and -casein ( -Cas, -Cas) (Sigma Chemical, St. Louis, Mo). Whole milk, ALA, BLG and Cas specific IgE determinations were performed using CAP test (Pharmacia, Uppsala, Sweden) . Similarly, sensitisation to rice and HRF were investigated by SPT and CAP test. Patients sera were investigated by immunoblotting for CMP, rice and HRF (Heinz-Plada, Milan, Italy). DBPCFC was carried our with 24 g RHF powder masked in Neocate TM (equivalent to 180 mL reconstituted formula). Results: SPT: all patients were positive to cow s milk and/or CMP fractions (>3 mm wheal diameter). IgE determinations gave positive results with cow milk and/or CMP fractions (72/84 patients tested), rice (16/81) and with HRF (2/85). Immunoblots (n=87) were positive for -Cas (n=46), -Cas (n=34), ALA (n=39), BLG (n=34) and bovine serum albumin (n=52). Similarly, although patients sera largely recognized rice (78/87), only one weakly reacted with RHF. Challenge with RHF was negative in all cases. Conclusions: We conclude that, despite their frequent sensitisation to rice, children with CMA tolerate both rice and RHF clinically. Hydrolyzed rice formulas may thus represent an alternative protein source for children with CMA.
R.C. Cartwright * , W.K. Dolen, Augusta, GA.
Introduction: Conventional treatment of human seminal fluid allergy includes abstinence, barrier protection, or subcutaneous immunotherapy with fractionated seminal fluid. Treatment using local intravaginal desensitization with unfractionated seminal fluid has recently been described, but experience with this desensitization method is still limited and little has been reported as to its long-term results. Methods: A 30-year-old woman with a history of allergic rhinitis and asthma experienced anaphylaxis following her first unprotected intercourse since the birth of her first child. IgE-mediated sensitization was demonstrated through the use of specific IgE testing (Pharmacia CAP System) and skin prick testing using undiluted seminal fluid obtained from the patient's husband. After approval from the Human Assurance Committee, the patient underwent rush intravaginal desensitization with steadily increasing concentrations of seminal fluid, beginning with a 1:10, 000 v/v concen-tration. Results: Her specific IgE level to human seminal fluid was 0.26 kU/L. Skin prick testing was positive with a wheal of 10 mm diameter with pseudopods and a flare of 25 mm diameter. Desensitization was successful and the patient tolerated local application of whole semen without significant reaction. Following desensitization, the patient reported that she and her husband engaged in unprotected intercourse without local or systemic symptoms. Over the last year since the desensitization, she has not experienced further anaphylaxis, but she has developed local symptoms if her exposure to seminal fluid was delayed past 5 days. The longest time period between exposures has been 2 weeks. She became pregnant 5 months ago and has not had any pregnancy complications. Conclusions: Local intravaginal desensitization was a safe and effective treatment for human seminal fluid allergy in this patient. A delay in seminal fluid exposure greater than 5 days was associated with the return of symptoms emphasizing the need for frequent seminal fluid exposure to maintain desensitization.
L. Terracciano, T. Sarratud, A. Fiocchi * , P. Restani, S. Guerci, Milan, Italy. BACKGROUND Kiwifruit allergy in children has been seldom reported and the reactions observed are usually mild. Anaphylaxis has not been described. We document the case of an infant who developed anaphylacic symptoms within minutes of his mother eating two kiwifruits and initiating breastfeeding. CASE HISTORY In his fourth month, the boy was admitted into an emergency department with dysphonia, breathing difficulties, generalised urticaria and angioedema of the lips and face. This episode was treated as an anaphylactic reaction with epinephrine, chlorpheniramine and hydrocortisone sodium succinate administered via a percutaneous catheter and symptomatic control was achieved within 30 minutes. After 15 days a second anaphylactic episode of similar severity occurred under the same circumstances. Neither episode required critical care. The boy presented two months later for clinical evaluation in our paediatric allergy unit. Skin prick tests (SPT) were positive only with egg white and yolk while negative to cow s milk (and protein fractions), beef, chicken, pork, codfish, rice, wheat, soybean, maize, potato, carrot, tomato, bean, pea, celery, peanut, Dermatophagoides pteronyssinus and D. farinae, grass and banana. SPT with kiwifruit was specifically ordered because exquisite contact was suspected, and induced a positive wheal (>3 mm diameter). Positive specific IgE determinations (CAP-FEIA from Pharmacia, Sweden) with kiwifruit (0.71 kU/L), cat dander (1.97 kU/L) and egg white (1.97 kU/L) were returned but determinations with other inhalant and food allergens were all below the cut-off point of 0.35 kU/L and total IgE levels were 155 kU/L. Strict avoidance of kiwifruit by the breastfeeding mother proved effective and nothing untoward happened in the intervening year. Currently aged 2.5 years, the boy is free from food-related symptoms. Prick-byprick tests with native allergens and SPT carried out with commercial extracts of allergens associated in the literature with kiwifruit allergy were all negative. COMMENT There are no reports of immediate reactions to kiwifruit under two years. In this case, severe reactions via breastmilk in an infant monosensitised to kiwifruit indicate that nursing may represent a hidden source of exposure. In older children monosensitisation without prior sensitisation to pollen has been described as the major risk associated with severity of symptoms.
M. Sikora * , J.W. Sleasman, N. Tangsinmankong, St. Petersburg, FL. Introduction: Treacher-Collins Syndrome (TCS) is an autosomal dominant disorder with an abnormality of craniofacial development during early embryogenesis. There is a known relationship between new bone formation and development of lymphocytes and cytokines. The association of TCS and humoral immunodeficiency has not yet been reported. We present a novel case of a 12 year-old Caucasian female patient with TCS and common variable immunodeficiency. Methods: Our patient presented with midface hypoplasia, micrognathia, microtia, conductive hearing loss and cleft palate with a history of recurrent upper and lower respiratory infections. Patient had a 10-year history of chronic sinusitis, recurrent otitis media and pneumoniae which resulted in bronchiectasis. Haemophilus influenza and Staphylococcus aureus were persistently isolated from bronchial fluids. Laboratory work-up for immunodeficiency was initiated. Results: Immunoglobulin analysis revealed low IgG 450 (528-2190 mg/dL); low IgA 42 (44-441mg/dL); IgM 65 (48-226mg/dL); IgG 1 354 (165-1440 mg/dL); low IgG 2 59 (71-460 mg/dL); IgG 3 85 (28-125 mg/dL); and low IgG 4 <8.1 (2-143 mg/dL). Patient had no detectable response to protein-derived vaccines (diphtheria and tetanus) and to polysaccharide-derived vaccines (pneumococcal) at baseline and at 4-6 weeks after immunization. T and B lymphocyte enumeration, CH50, AH50, and mannose-binding lectin were all within normal limits. Laboratory findings were consistent with the diagnosis of common variable immunodeficiency. Patient began receiving monthly doses of 550 mg/kg/dose of intravenous immunoglobulin resulting in clinical improvement. Our patient no longer requires antibiotic therapy for her respiratory infections; pulmonary function has improved and bronchiectasis resolved 6 months after initiation of IVIG. Conclusion: Our finding shows that TCS can be associated with common variable immunodeficiency which suggests a link between skeletal dysplasia and immunodeficiency.
A.S. Hartel * , J.W. Sleasman, N. Tangsinmankong, St. Petersburg, FL. Introduction: Streptococcus pneumoniae is the most common cause of invasive bacterial infection in humans. However, incidence of S. pneumoniae infections in healthy adolescents is low (5/100, 000 per year). Mannose-binding lectin (MBL) is a C-type lectin which plays a central role in the innate immune response by activating the classical complement pathway and acting as an opsonin by binding c1q receptors. Several studies have demonstrated an association between invasive bacterial infections, including S. pneumoniae and a homozygous mutation of the MBL gene. However, this association has not previously been described in patients with the heterozygous mutation. Methods: A 13-year-old Caucasian female presented with a second episode of meningitis over a 4-year span. Streptococcus pneumoniae was isolated from peripheral blood cultures on both occasions. Lumbar puncture revealed WBC 22, 600; 6% bands; 83% PMNs; glucose 3 mg/dL, protein 329 mg/dL; these results consistent with bacterial meningitis. Extensive evaluation for predisposing causes revealed benign Arnold-Chiari type1 malformation. Further immunological evaluation was initiated. Results: Evaluation revealed IgG 867 mg/dL (normal 528-2190); IgA 67 (44-441); IgM 181 (48-226), and normal IgG subclasses. Antibody responses to diphtheria and tetanus vaccines were adequate. Antibodies response to pneumococcal vaccine given 4 years prior were protective to all 10 common serotype tests (>1.4 mcg/mL). Lymphocyte subset analysis was within normal range. Howell-Jolly bodies were not detected from peripheral blood smear. Evaluation for secondary immunodeficiency was negative, including HIV antibody by ELISA. Complement analysis showed CH50 88 U/mL (65-95); AH50 71% (66-129%), and markedly low MBL of 74 ng/mL (>1000). Genetic analysis of her MBL revealed heterozygous mutation in codon 54 and mutations in two promoter regions (homozygous mutation on H/L variants and heterozygous mutation on P/Q variants). Conclusion: Heterozygous mutation of MBL codon when associated with mutation of promoter regions can result in severe impairment of MBL protein production, and may lead to increased susceptibility to invasive bacterial infections and meningitis.
Rationale: Patients with similar symptoms may have allergic, non-allergic, or mixed rhinitis triggers and can differentially respond to distinct medications. We assessed ST in our clinic patient population to characterize factors that influence appropriate diagnosis and treatment of rhinitis type. Methods: We used a validated commercial questionnaire and chart review of 230 patients seen in an academic allergy clinic, to assess the number of allergic vs. irritant ST and demographic and historical factors (including pharmacotherapy) associated with differences in symptoms. Results: The population (n=189: 138 female, 51 male) consisted of individuals with a mixed rhinitis history. Women had higher ST scores than men, including: total scores [10.44+/-0.51 vs. 7.20+/-0.65, p=0.0001 (unpaired t-test)]: allergen scores (4.56+/-0.30 vs. 3.51+/-0.37, p=0.0055); and irritant scores (5.58+/-0.29 vs. 3.69+/-0.41, p=0.0003). Further, patients treated with both azelastine (Az) and intranasal steroids (INS) had lower ST scores than patients treated with either alone (Total ST: Az 10.06+/-0.94, INS 10.3+/-0.97, both 8.0+/-0.88, p=0.0348; Allergen ST: Az 4.69+/-0.54, INS 5.05+/-0.37, both 3.11+/-0.50, p=0.0416; Irritant ST: no significant difference). Conclusions: Female patients have significantly higher symptom scores; total, allergic and irritant. Rhinitis monotherapy (INS or Az) is minimally effective in reducing ST but is more effective when used in combination. These data demonstrate rhinitis population heterogeneity and address differential responsiveness to similar medications. Increased response to combined drug therapy support the heterogeneous pathophysiology of mixed rhinitis features and may relate to a combination of multiple aeroallergen and air pollution exposure in the Houston area. Introduction: Interaction between eye & nose warrants attention with regard to the propagation and treatment of allergic reactions. The role of topical therapy for rhinitis and conjunctivitis is becoming more widely considered and questions of therapeutic route have been raised. Purpose: To elucidate the anatomic and pharmacokinetic interactions of conjunctival & nasal mucosa leading to more rational selection of routes of medication administration. Methods:Our studies have investigated the effect of ocularly instilled allergen inducing signs and symptoms of rhinoconjunctivitis. 1 study compared effects of allergen administered via conjunctival allergen challenge (CAC) or nasal allergen challenge (NAC) and analyzed tear & nasal secretions for ECP & tryptase. Studies have also used the ability of the CAC model to induce rhinitis signs & symptoms to evaluate the relative effects of medication routes: 1) ocular v. nasal spray v. systemic; 2) ocular + nasal spray v. systemic + nasal spray; 3) ocular v. placebo. Results: The NAC/CAC study revealed that, following CAC (N=34), significant ocular and nasal signs & symptoms were noted; following NAC (N=39), only nasal symptoms were clinically significant. Nasal symptom scores between CAC & NAC differed significantly at 1 timepoint, representing lag in allergen & mediator movement from eye to nose. Measurable levels of ECP & tryptase were found in tears and nasal secretions for CAC, but only in nasal secretions (with exception of 1 subject) for NAC. In CAC studies: 1) ocular therapy exhibited greater efficacy in ocular itching relief (N=73;P<0.05) and was not significantly different from nasal or systemic therapy in nasal symptom relief. 2) eyedrop+nasal spray combination exhibited significantly greater prevention of overall rhinoconjunctivitis signs and symptoms than nasal+systemic therapy (N=80). 3) ocular therapy offered greater protection from nasal signs & symptoms compared to placebo (N=32;P<0.05). Conclusion: NAC and CAC results support the unidirectional flow from eye to nose, the ability of CAC to yield nasal symptoms, and the efficacy of topical therapy. Tearing, due to inflammation of the inferior turbinate would be the only ocular symptom resulting from nasal challenge. These results offer insight to the nature of the connection between ocular and nasal mucosa and the efficacy of varied medication administration routes for management of rhinoconjunctivitis symptoms. Introduction: Asthma disease management programs frequently target high utilizers because they are responsible for a large amount of asthma costs. Once identified, such "frequent fliers" usually are offered interventions including case management. Programs using this approach usually demonstrate reductions in utilization. Though the interventions may cause this decline, it could also be due to regression to the mean (RTM) which is a tendency for outliers to become more like the mean over time. In this study we measured RTM in a Medicaid HMO asthma population to determine whether targeted case management is effective independent of this phenomenon. We hypothesized that directed case management provides additional utilization reduction beyond RTM. Methods: A weighted asthma utilization score was determined quarterly for members of an HMO with asthma from 2000 to 2004. RTM was measured by determining how many patients were persistent high utilizers quarterly for 1 year after baseline. To determine the effect of utilization-directed case management, the number of frequent fliers at baseline for each quarter also was determined. Results: A total of 296 asthma frequent fliers were identified on January 1, 2001. By September 1, 2001 only 15 of these individuals continued to be frequent fliers. Similar decreases in utilization were seen for frequent fliers identified at the beginning of each quarter of 2001. The mean decrease in the number of frequent fliers is shown in the Table. This represents a substantial regression to the mean. The total number of high utilizers at baseline decreased by 27% after implementation of utilization-directed case management in 2002 independent of regression to the mean. This also represented a decrease from 1.6% of health plan members with asthma to 0.6% by the start of 2004 suggesting that the decline is not a result of diminishing health plan membership. The benefit appears to be the result of early intervention with members before they become frequent fliers. Conclusions: Utilization-directed case management can reduce overall asthma utilization by preventing members from becoming high utilizers at an early stage. Programs that claim to intervene with plan members who already are high utilizers are likely to be taking advantage of regression to the mean. Studies indicate a high incidence of asthma(AS) among school-aged children. With the prevalence increasing, significant numbers remain unidentified. They experience morbidity, including school absenteeism, which may be preventable, in part, by adherence to National Asthma Guidelines. We implemented a pilot study to detect AS, AS control and initiation of appropriate health care among 7th grade students in a suburban population. The study was coordinated with the middle school staff and the local county health department. The screen parameters included: Student questionnaires, peak flows, exercise with peak flow assessment (FRAST)2, and Spirometry as indicated. Environmental tobacco smoke (ETS) was recorded. RESULTS: 196 students screened. 131 no AS history and negative screen (D). 31 AS history and negative screen (E). 5 AS history and positive screen (A). 23 no AS history with suggestive written screen and negative screen on exercise (B). 6 no AS history and positive screen (C). ETS in groups A, B, C: 40%, 32%, 60%. ETS in groups D, E: 23%, 16%. Individual student results were mailed home with medical follow-up recommended for a positive screen. Parents of the 34 children who failed the questionnaire or exercise screen (Groups A, B, C) were phoned at a 6-12 wk interval. No student in-group A or B had medical follow-up. 2(33%) students in Group C had medical follow-up. CONCLUSION: This AS screen of 7th grade students identified 6(3%) as having significant, undetected AS. 5(14%) with known AS had uncontrolled AS at the time of screen. 23(11.7%) students with strong suspicion of AS based on questionnaire had an acceptable exercise screen. Only 2 of the 34 children with a screen suggestive of AS or uncontrolled AS had medical follow-up. ETS was increased in the homes of students with a positive screen and remains a serious health issue. School screening for AS has merit, but mail and phone follow-up was insufficient to intervene or initiate acceptable AS treatment. References 1. Redline S. et. al. Development and validation of school-based asthma and allergy screening instruments for parents and students. Ann Allergy Asthma Immunol. 2003; 90: 516-528 2. Tsanakas.J.N., et al. Free Running Asthma Screening Test. Arch Diseases in Childhood.1988; 63:261-265 3. American College of Allergy, Asthma, and Clinical Immunology Screening test ages (8-14) ACAAI.org.
INTRODUCTION. Some laboratory evidence suggests that desloratadine is effective in inhibiting of inflammatory mediators, which play an important role not only in allergic but also in virally induced inflammation. The purpose of this study was to assess its efficacy in acute bronchiolitis developed in young children suffering from concomitant atopic dermatitis (AD). METH-ODS. Participants were 34 young boys and gilrs aged 18-36 who suffered from acute bronchiolitis as established by wheezing, rhinitis and fever. All patients also had concomitant AD as established by Hanifin and Rafka criteria. Patients were allocated to receive syrup formulation of desloratadine (Erius, Schering Plough) 1, 25 mg/day for 5 days (active group n=17) or no desloratadine treatment (control group n=17) using Quota Allocation System. We calculated physical global symptom score (combination of cough, wheezing, chest retractions, nasal flaring, blocked nose, runny nose, sore throat -0-5 scale) and Respiratory Distress Assessment Instrument (RDAI) to examine the patient at baseline and on day 5th after therapy was initiated, day of normalization of body temperature, respiratory rate, heart beat rate, and use of albuterol. RESULTS. Both group of patients were comparable on age, gender, family history of asthma, time of onset of the acute respiratory illness, extent of medication taken prior to entering the study, global symptom score and RDAI index. All children were evenly treated with oxygen, oral theophylline (10 mg/kg/day) and adequately rehydrated. On day 5th global symptom score of patients receiving desloratadine was 2, 51±0, 51 vs 3, 42±0, 62 in control group (p=0.035). On day 5th it was also significant difference between active and control groups on RDAI index (4, 44±1, 24 vs 7, 23±2, 30; p=0.046) especially for significant drop in wheezing score in active group. Day when respiratory/heart rate normalized, temperature returned to normal, use of albuterol did not differ significantly in these groups. CONCLUSIONS. Our preliminary study is the first to show that desloratadine is an effective agent in viral lower respiratory tract infections of young children suffering from AD. It encourages further GCP trials to explore action of desloratadine in infantile bronchiolitis and concomitant AD.
H.J. Su * , W.T. Lin, P.J. Tsai, C.Y. Huang, P.C. Wu, Tainan, Taiwan. Increasing prevalence of childhood asthma has been observed across the world, and found to be associated with, partly, indoor pollution, including bioaerosol exposure. Meanwhile, adequate ventilation is shown to be effective in diluting most indoor air pollutants, while only limited data are available addressing directly how the ventilation rate is implicated with childhood respiratory symptoms. This study aimed to examine the concentration distribution of selected indoor air pollutants, including bioaerosols, in domestic environment, and further to assess the effects of ventilation rate, characterized by a CO2 trace gas concentration decay method, on concentration variations of the above-mentioned air pollutants. Study subjects were chosen from a prior city-wide questionnaire survey based on positive response to inquiry for physician-diagnosed asthmatic status and wheezing symptoms in the past 12 months. Environmental assessments, including ventilation and air quality measurements, were conducted twice, 1 in early winter and the other on early summer. Respiratory health diary and PEFR (Peak Expiratory Flow Rate) were recorded for 1 week concurrent with the sampling activity. Increasing ventilation rate is statistically associated with decreasing indoor concentrations of CO2 and TVOCs. After adjustment for sex, age, and selected housing characteristics, the OR between TVOCs concentrations and reporting cough of study children is 9.47, and 12.84 between CO2 and nasal congestion. The OR between indoor bacterial concentration and the morning PEFR less 80% is 10.98 in the similar multivariate logistic regression for data collected from winter study. In summer, the only significant relationship is between ventilation rate and the morning PEFR less 80% of study children, OR= 0.17, in a multivariate logistic regression. This study has identified less reporting of childhood respiratory symptoms, especially for coughing and the morning PEFR less 80% are associated with increasing ventilation rate, and higher levels of indoor air pollution appear to be present with greater frequency of the above symptoms. This study suggest quantitatively that proper management of ventilation efficiency may be beneficial for the control of childhood respiratory illnesses.
*Adjusted for: sex, age, environmental tobacco exposure, use of incense and air conditioner **:p<0.05 NS:no statistical significance with whole model test Background: Moderate-to-severe allergic asthma can have a substantial impact on a patient's asthma-related quality of life (ARQL). In addition to asthma symptoms, allergic rhinitis, rhinosinusitis and other related comorbidities are often apparent in patients with more severe disease making it difficult to treat. Despite guideline-consistent care, many patients still experience variability in asthma control signaling an unmet need within this population. Omalizumab (Xolair®) has recently demonstrated clinical efficacy and safety in treating asthma. Objective: The aim of this paper is to summarize the ARQL outcomes associated with omalizumab therapy in moderate-to-severe allergic asthma. Methods: We performed a systematic review of ARQL data from the Clinical Study Reports and published clinical trials on omalizumab. ARQL was measured by the Juniper-Asthma Quality of Life Questionnaire (AQLQ). Results: Statistically significant results for ARQL endpoints consistently favored omalizumab over placebo. The magnitude of the changes in ARQL were consistently aligned with clinical endpoints. Moderate to large effect sizes in the omalizumab groups were maintained throughout the 28-week clinical trial program and during the 24-week double-blind extension phase. However, the placebo groups also experienced within-group improvements and moderate effect sizes. A meta-analysis indicated a 1.6 to 2.0 fold increase in large (>1.0 point) improvements in overall AQLQ scores in the omalizumab-treated group compared with placebo during the stabilization and steroid-reduction phases of the clinical trials. Conclusions: The consistently positive impact of omalizumab on ARQL outcomes during the clinical trial program provides evidence of its value as an adjunct therapy in patients with moderate-to-severe allergic asthma. Significant differences and large effect sizes were observed despite the fact that the control group received active, guideline-consistent treatment producing a substantial placebo effect. Improvements were observed in Overall, Symptom, Activity, Emotional and Environmental dimensions of the AQLQ indicating that omalizumab produced benefits in ARQL in patients with moderate-to-severe allergic asthma. Background: Omalizumab, a monoclonal anti-IgE antibody, significantly improves asthma-related quality of life (ARQL) for patients with moderatesevere allergic asthma who express symptoms despite moderate-high inhaled corticosteroids (ICS) doses. Mean scores can mask underlying variability in ARQL outcomes. This investigation examined variability in outcomes to elucidate the specific impact of omalizumab treatment. Methods: AQLQ data (n=948) from two randomized, double-blind, placebo-controlled clinical trials were pooled to assess underlying variability in the mean scores and to identify key drivers of ARQL treatment-effect differences (Juniper-Asthma Quality of Life Questionnaire (AQLQ)) between omalizumab and placebo (active control) patients. Results: Correlations between AQLQ and other clinical outcomes were low to moderate at best (r=0.14 to r=0.60). AQLQ assessment captures patient benefit that supplements clinical outcome measures. Across all component items of the AQLQ patients receiving omalizumab improved more than patients receiving placebo (active control) (p<0.05). Omalizumab patients reported the greatest improvement for reducing waking with symptoms in the morning (Symptoms domain: 2.06 vs. 1.50; p<0.001), limitations in all activities done (Activities domain: 1.18 vs. 0.68; p<0.001), the fear of not having medication available (Emotions domain: 0.99 vs. 0.60; p<0.01), and symptoms from being exposed to dust (Environment domain: 1.31 vs. 0.88; p<0.001), compared to placebo (active control) patients. Conclusion: ARQL assessment provides complementary and non-overlapping information on clinical benefit that is distinct from other clinical outcome measures. Examination of underlying variability in AQLQ mean scores and item-level response extend previously published results on omalizumab treatment effect by showing that aggregate ARQL improvements for omalizumab patients are strongly influenced by symptom and activity improvement.
A. Brimer 1 , K. Malhi, C. Adams, C. Dinakar, Kansas City, MO. INTRODUCTION: The desire to belong to a group is a very powerful motivator and is exceptionally strong in the adolescent population. Asthma is a disease that makes people feel different. This perception may impinge on patient adherence with medication regimens. We hypothesize that belonging to a club where every member has asthma may encourage identification of the adolescent asthmatic with their peers, and mitigate the perception of being different. OBJECTIVES: (1) To investigate the factors that make the asthmatic adolescent feel different (2) To explore the hypothesis that group activities, such as an asthma club, would help adolescent asthmatics feel less different. METHODS: As part of an ongoing survey, children with asthma between the ages of 8-18 years were offered an anonymous questionnaire in the primary care and adolescent clinics at our hospital. The questionnaire included both multiple-choice and open-ended questions designed to explore the feelings of the respondents. The responses were numerically tallied and reported as percentages. RESULTS: At the present time, 31 surveys out of a proposed 100 have been completed. One third of the youth with asthma answering the survey had negative feelings regarding their asthma. Nearly forty percent of the respondents reported that their diagnosis made them feel different from their healthy peers. Forty-five percent responded that they have felt restricted or excluded from school activities, athletics, and clubs due to their asthma. Over one-third of them feel uncomfortable taking their inhaler in front of their friends. Most respondents (93.6%) indicated that they enjoy group activities. The majority of respondents (89.7%) rated playing sports as their favorite group activity. CONCLUSION: Almost forty percent of asthmatic youth surveyed indicated that having asthma made them feel different and resulted in restriction/exclusion from school activities, athletics, and clubs. An overwhelming majority expressed a preference for participation in group activities, particularly recreational sports. This social preference towards group activities may be incorporated into an intervention, such as an asthma club, to help asthmatic youth adjust to the disease and its treatment regimen. INTRODUCTION: Airway hyperresponsiveness (AHR) is an exaggerated narrowing of the airways in response to stimuli, such as allergens, histamine, and cold air. AHR is a characteristic feature of asthma linked to chronic airway inflammation. Phosphodiesterase 4 (PDE4) is an enzyme found in key inflammatory cells involved in the pathophysiology of asthma. Inhibitors of PDE4 prevent the breakdown of cyclic adenosine monophosphate, a natural modulator of inflammation. Roflumilast is an investigational, oral, once-daily PDE4 inhibitor, which has shown anti-inflammatory activity in vitro and in vivo. This study examined the effect of a single dose of roflumilast on changes in AHR following allergen-induced asthmatic reactions in patients with mild asthma. METHODS: This double-blind, randomized, crossover study consisted of 2 treatment periods separated by a 2-to 5-week washout period. A total of 13 patients (forced expiratory volume in one second [FEV 1 ] 70% predicted) who were hyperresponsive to histamine (provocative concentration causing a 20% drop in FEV 1 [PC 20 FEV 1 ] 16 mg/mL) were randomized to receive a single dose of oral roflumilast 1000μg or placebo on Day 1 of each treatment period followed by an allergen challenge 60 min after medication. Histamine provocation was performed before and 24 h after intake of study drug. RESULTS: There was no change in FEV 1 60 min after roflumilast administration, suggesting the absence of direct or acute bronchodilation. Allergen challenge elicited early and late asthmatic reactions that were attenuated by a single dose of roflumilast 1000μg. The histamine PC 20 FEV 1 in patients treated with roflumilast decreased to a lesser extent than in those patients treated with placebo. The change in PC 20 FEV 1 from baseline after challenge was 2.51 ± 2.95 mg/mL (mean ± SD) with placebo and 1.23 ± 2.75 mg/mL with roflumilast. The magnitude of the change in PC 20 FEV 1 was statistically significantly different between the placebo and roflumilast treatment groups (p=0.002). Thus, roflumilast decreased the development of AHR by approximately 1.1 doubling-dilutions. CONCLUSIONS: A single dose of oral roflumilast 1000μg attenuated allergen-induced AHR. These data provide further evidence that roflumilast may provide anti-inflammatory activity in vivo and may be an effective treatment for patients with asthma.
INTRODUCTION For the past 7 years we have been tracking pediatric asthma admissions and evaluations at the Huntington Memorial Hospital. During the fall and winter months (Oct-March) from 1996 to 2002, we noted a 1.6 X increase in the number of asthma admissions and evaluations compared with the spring and summer (April -September; 4, 993 patient encoun-ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY ters in 7 years). We have analyzed potential causes for this increase. Diesel particulate was estimated in 1998-9, and a 2.5-fold increase in the fall versus spring was found in Burbank, a city adjacent to Pasadena. Pollutant particles from the combustion of fossil fuels may act as immuno-adjuvants to allergen exposure as has been demonstrated experimentally in mice and in human nasal exposure studies. METHODS Computerized analysis of asthma admissions and evaluations were calculated according to established codes for acute and chronic reactive airways disease. Infectious diseases in patients were analyzed by standard asthma questionnaire. Also, pollen and mold counts, as well as diesel particulates and meteorological conditions were studied. RESULTS Similar numbers of viral infections occurred in the fall of 2001 and spring of 2002. Among the most prevalent pollens and molds are Chinese Elm pollen (Sept -Oct) weed pollens (July -Dec), and a newly recognized Aureobasidium mold (Nov -March). Pollen grains can fragment and release respirablesized debris that are loaded with allergens (Taylor et al 2002 (Taylor et al , 2004 . The conidia of Aureobasidium are also of respirable size and were identified by sequence analysis. Fine particulate air pollution (PM2.5), containing diesel particles, is increased in the fall and winter in Southern California. CON-CLUSIONS The incidence of asthma outbreaks may vary with air pollution levels in the immediate environment. Pollen fragments and particles from fossil fuel combustion can deposit in similar regions of the lower airways. Rainfall increases in the fall and winter and this coincides with increased molds and Aureobasidium. Aureobasidium was recently discovered in high concentrations in Pasadena, is known to be allergenic and could be a factor in increased asthma. A mixture of pollens and molds and fine combustion particles may be relevant to this increased incidence of asthma in the fall and winter months in Pasadena. Background We have previously noted that tree and ragweed pollen grains can be airborne for most if not all daily periods during their respective seasons (AAAAI, 2003) , (ACAAI, 2003) . Because grass levels are lower than those of trees & weeds (AAAAI / NAB), we chose a longer daily interval to examine (six hours) that we had for trees (one hour) and ragweed (three hours). Methods Twenty-four hour microscope slide samples were collected using a Burkard 7 day air sampler from 05/01/04 to 06/30/04. The slides were examined @ 100 X along a single longitudinal traverse. The presence or absence of grass pollen was noted per six-hour segment (six successive fields). Results The presence of airborne grass pollen during the 4 daily segments was sparse the first two weeks of May. It gradually increased during the next 10 days, and then was detected during most of the daily segments through to the end of June.
# Ammophila arenaria (AA) is a highly resilient grass with habitat in Europe, North America, Australia, New Zealand, South Africa and the Mediterranean, used predominantly for dune stabilization. Patients with atopic diseases including allergic reactions to pollen are transferred to coastal regions in order to minimize pollen exposure. In spite of the presence of AA pollens, patients experience allergy relief at the coast. Our study examines the contradiction between the presence of strong grass allergens and the absence of allergic symptoms in atopic patients, and whether allergic cross-reactions among different types of grass pollen include AA pollen. 9 adult patients presenting symptoms of grass pollen allergy underwent prick testing and RAST testing to grass pollen mix and extracted AA pollen. 4 subjects showed positive results in prick and RAST testing to AA extracts and were subsequently tested via rhinomanometry for reactions to AA using prick test solutions. 2 subjects showed positive reactions to prick tests for AA extract and grass pollen mix, but did not show specific antibodies. All other sera showed elevated specific IgE levels, with specific reactions on 8 protein bands of AA. In sera incubated with grass pollen extract, almost all specific bands previously detected with AA were now inhibited. 3 patients with high levels of total and specific IgE to AA showed weak bands after inhibition, demonstrating the allergenicity of AA. Comparing data from coastal and mainland weather stations in June and July from 1961 to 1990, coastal wind speeds average 6.6 to 6.9 m/s while inland wind speeds average only 3.6 to 3.7 m/s. High wind speeds likely dilute pollen concentrations. Based on findings of an inverse relationship between wind speed and pollen concentration in the dispersion of ragweed pollen, we hypothesize that concentrations of AA pollens may be similarly influenced. No sensitized patient reported allergic symptoms in coastal areas inhabited by AA plants, indicating that under natural conditions, either the plant modifies its pollen allergenicity or that environmental conditions including salt aerosols, wind patterns, topography or light exposure cause the modification. As such patterns are likely to become more dramatic as the effects of global climate change transform the natural environment, these findings may also become relevant for other grass allergy types. Asthma is the most common chronic inflammatory disorders of the airways with increased prevalence in the past decade. It is characterized by airway obstruction, airway inflammation and airway hyperresponsiveness (AHR) to non-specific stimuli. In this study, we examined the effect of a novel class of molecule, OCID1001, in inhibiting antigen-induced early and late allergic response (EAR and LAR), AHR, and airway eosinophilia in mouse and guinea pig models of asthma. Pulmonary functions were measured in conscious unrestrained animals by whole-body plethysmography. Animals were sensitized with ovalbumin (OVA; 20mg, intraperitoneally) with 2mg alum followed by treatment with OCID1001 (120mg/kg, i.p. twice daily for 10 days). After the last dose, animals were challenged with ovalbumin. Pulmonary functions were recorded for EAR and LAR and 24 hrs later for AHR. This was followed by bronchoalveolar lavage, blood and lung tissue collection. Treatment with OCID1001 (120mg/kg) significantly attenuated LAR in OVA-sensitized and challenged mice or guinea pigs with no effect on EAR. AHR to methacholine in mice and to histamine in guinea pigs were prevented by treatment with OCID1001. OCID1001 attenuated the rise in total number of inflammatory cells in the lung and almost ablated the rise in BAL eosinophilia in the lung due to antigen sensitization and challenge. Effect of OCID1001 on pulmonary functions and airway inflammation in OVA-sensitized and challenged mice were comparable to that of dexamethasone in both models of asthma. These data suggest that OCID1001prevents the underlying pathophysiological changes in allergic airway inflammation and therefore could prove beneficial in the treatment of bronchial asthma. MA; 2. Madison, WI; 3. Portland, OR; 4. Milwaukee, WI; 5. Normal, IL; 6. Denver, CO; 7. Los Angeles, CA; 8. Fremont, CA. Introduction. Daclizumab (Zenapax®), a humanized monoclonal antibody directed against the IL-2 receptor chain (CD25), is approved for prevention of renal allograft rejection and is under evaluation for treatment of asthma. Daclizumab inhibits activation of human T lymphocytes by blocking IL2induced proliferation, and by reducing production of Th2-and Th1-associated cytokines. We recently reported that daclizumab improved pulmonary function in a phase II trial of patients with moderate to severe chronic persistent asthma (JACI, 2004, 113 (2):S286). We now report additional data from this trial on the possible role of daclizumab as an anti-inflammatory agent that affects asthma outcomes. Methods. 116 non-smoking asthmatics age 18-70 with baseline FEV1 50-80% predicted despite use of 1200 mcg daily inhaled triamcinolone (TAA) or equivalent were enrolled in a randomized, multi-center, double-blind, placebo-controlled trial. Patients were randomized (3:1) to i.v. daclizumab (2 mg/kg followed by 1 mg/kg every 2 weeks) or placebo added to stable dose TAA. Starting at week 12, patients underwent 25% reduction of TAA every 2 weeks while continuing study drug to week 20. Results. Patients on daclizumab demonstrated a prolonged time to exacerbation requiring systemic steroid rescue compared to placebo patients (p=0.024). Exacerbation rates were reduced in the daclizumab group compared to the placebo group for the 20-week steroid-stable and steroid-taper phases (11.6% vs. 28.6%, p=0.09). Patients on daclizumab demonstrated decreased peripheral eosinophil counts from baseline to week 20 (-30±20 /mm 3 vs. placebo +60±30 /mm 3 , p=0.004). Daclizumab-treated patients with elevated baseline serum eosinophil cationic protein (sECP) had a significant reduction in sECP from baseline to day 56 compared to placebo patients (p<0.01). Peripheral eosinophils decreased significantly in daclizumab patients who had no asthma exacerbations compared to an increase in daclizumab-treated patients with at least one exacerbation (p=0.032). Conclusions. Daclizumab reduces time to and frequency of exacerbation in treated asthmatics. The mechanisms of this effect remain to be fully elucidated, but initial findings suggest that associated reductions in circulating eosinophil and eosinophil products may play a role in these therapeutic effects. HAE is a genetic deficiency causing a decrease in C1 esterase inhibitor levels. It is a rare condition (approximate prevalence 1:10000 to 1:50000 individuals). It is manifest by acute attacks of swelling which can involve the larynx (a potentially life threatening condition), the GI tract (causing a syndrome similar to an acute abdominal catastrophe) or the skin and soft tissue of the patient including the limbs, face and external genitalia. There is no approved therapy for acute attacks in the USA. Pathogenesis of this potentially fatal condition is thought due to excessive activity of plasma kallikrein. DX-88 is a specific and highly active (Ki 40 pM) recombinant inhibitor of human plasma kallikrein undergoing evaluation in HAE and cardiopulmonary bypass. It is an animal free product. A double blind, randomised (5:1 drug to placebo) placebo controlled dose ascending study of DX-88 in acute attacks of HAE was run in the USA and the European Union. Four dose groups of 12 patients were to be included in the study. The doses were 5, 10, 20 and 40 mg/m2. The primary outcome variables were proportion of patients achieving a significant clinical response within 4 hours of administration of therapy, and safety. Secondary endpoints included site response, dose response, and median time to significant response by site and dose group. DX-88 met its primary endpoint; 72% of DX-88 patients had a significant improvement within 4 hours, (placebo response rate 25%, difference 47% p= 0.0169). Patients receiving DX-88 responded in a median time of 70 minutes. There was no difference in proportions of cases that responded within 4 hours between the three anatomical sites. Time to significant response did not significantly differ between dose groups and anatomical sites. The safety profile was comparable for patients treated with DX-88 and placebo, in terms of SAEs and AEs. In conclusion, DX-88 in this double blind study was shown to be statistically superior by 47% to placebo and to be at least as safe as placebo. The drug is effective at treating any HAE site, including the larynx. DX-88 represents an important advance in the management of HAE. AR is among the most common chronic childhood disorders, and is most effectively treated with intranasally inhaled glucocorticosteroids (ICS). Recent evidence suggests that intranasal ICS therapy may suppress HPA axis function and decrease growth velocity. This study reports 1-year follow-up data on 24 children (12 female, 9 African American), aged 6 to 14 years (mean 10.4 years) at entry, enrolled in a long-term growth trial of intranasal TAA for treatment of AR. Primary measures included height velocity, bone mineral density (BMD), serum osteocalcin and salivary cortisol levels. All subjects followed their expected age-appropriate growth velocities. Average growth velocities were 5.6 and 5.8 cm/year for girls and boys aged < 12 years, respectively, and 5.5 and 7.7 cm/year for girls and boys aged > 12 years, respectively. Mean (+ STD) BMD was 1.27 + 0.12 and 1.22 + 0.14 gm/cm2, mean serum osteocalcin levels were 89.1 + 25.5 and 114.5 + 32.7 ng/ml, and mean salivary cortisol levels were 16.7 + 8.0 and 11.5 + 6.5 nM/L at entry and 1-year follow-up, respectively. These results demonstrate no significant effect of one year of intranasal treatment with TAA on growth velocity or HPA function in children with AR. 13 patients 6 males, 7 females ranging in age from 66 years to 12 years, received (O) in doses ranging from 2 to 17 injections over 4 to 34 weeks. Patients were evaluated with symptoms scores, pulmonary function (PFT), blood eosinophil count (BEC), medication use, and allergy skin test. ST were initially performed by prick and if negative, by intradermal (ID) (1/1000 w/v) and if further negative by ID (1/500 w/v). Skin tests were performed immediately before and 20 minutes after the administration of O. There was no change in PFT or BEC. However there were significant reductions in symptom scores, including nocturnal asthma (<.0001), exercise tolerance (<.0001), sense of well being(<.0001). In addition, parenthetically there was a reduction in nasal symptoms (<.0001). There were also significant declines in medication use especially for albuterol (<.0001). ST declined in all patients evaluated and dramatically in many. For several individual allergens ST went from prick positive to ID (1/500 w/v) negative. Moreover ST declined in all instances further, 20 minutes after the administration of O except for 2 patients. In addition to asthma one of the patients had allergic bronchopulmonary aspergillosis and another had allergic fungal sinusitis. Three of the patients tested positive on prick test to mouse antigen and in each instance this became negative after administration of O with all 3 patients tolerating O without problem. We conclude: (1.) Administration of O is associated with an improvement in symptoms and decreased use of medications (2.) In addition there is a prominent decline in ST which is more marked 20 minutes after administration of O compared to immediately prior to administration the explanation of this finding is not apparent. (3.) O appears to be safe to administer to patients even if they demonstrate specific IgE to mouse antigen by ST
A.P. Baptist * , T.S. Tang, J.L. Baldwin, Ann Arbor, MI.
Introduction: Academic medical institutions are under pressure to shorten or eliminate resident elective rotations due to federal work-hour restrictions. It is unknown if this will affect knowledge and referral patterns for resident and faculty physicians. The objective of this study was to examine the factors associated with resident and faculty perceived knowledge and referral patterns towards allergy/immunology (A/I). Methods: A questionnaire was sent to 375 primary care physicians at one academic center. It addressed past history of A/I referrals, referral intentions for conditions that may be seen by allergists, and perceived A/I knowledge. Independent variables included history of an A/I rotation, gender, department, years in training/practice, and history of referral to an allergist. Results: 228 (61%) completed surveys were returned. Using logistic regression with forward selection, we found in the resident physician cohort those with advanced years in training or history of an A/I rotation were more likely to have increased past history of referral to an allergist (OR = 4.09, OR = 3.81), increased referral intention for chronic sinusitis to an allergist (OR = 3.51, OR = 5.18), and increased perceived A/I knowledge (OR = 2. . For the faculty physician cohort, those with a history of an A/I rotation were more likely to have an increased perceived knowledge about A/I (OR = 5.64-6.18). In addition, pediatric faculty physicians were more likely to refer asthma (OR = 5.62) and chronic eczema (OR = 17.09) to an allergist than faculty from other departments. Finally, faculty physicians with a past history of referral to an allergist were more likely to have refer asthma (OR = 10.64) and allergic rhinitis (OR = 9.78) to an allergist. Conclusion: The factors associated with resident and faculty physician perceived knowledge, referral history, and referral intentions towards A/I differ. For residents, senior training level and a history of an A/I rotation appear most important. For faculty, history of an A/I rotation, pediatric department, and past history of referral to an allergist appear most important. Given that a history of an A/I rotation may increase perceived knowledge and referral patterns towards A/I, eliminating A/I rotations in medical institutions may have important consequences for patients and the field of A/I. Because recent anecdotal reports suggest that HBV may be an effective treatment for patients with multiple sclerosis (MS), there has been a movement of patients to zealous lay practitioners to receive multiple and repeated bee stings. Since this practice has real risk of possible fatal allergic reactions as well as emotional and economic costs, properly conducted studies of safety and efficacy are needed. The purpose of the present Phase I pilot study was to evaluate the safety of HBV extract in patients with PFMS. A total of 9 evaluable bee venom non-allergic patients with PFMS (21-55 years) were enrolled and were randomly divided into 4 groups, each receiving an increasing allergen dose immunization schedule for one year. Hyperreactivity to HBV was evaluated by questionnaire, Px and hematologic, metabolic and immunologic tests including skin tests. Any possible beneficial responses to therapy were evaluated by questionnaire, functional neurologic tests (FNT) and changes in measurement of somatosensory-evoked potentials (SEPs) prior to and at the completion of the study. No serious adverse allergic reactions were observed in any of the 9 subjects even at the highest doses of bee venom therapy. Although 4 of 9 subjects had worsening of neurologic symptoms during the course of bee venom therapy, requiring termination, this response could not be ascribed to side effects of the HBV or to a spontaneous worsening of the neurologic disease independent of treatment since there was no correlation of these events with the bee venom injections. Of the remaining 5, 3 felt that the therapy was beneficial.There were no changes either in FNT or SEPs measured during the study. The present report represents the first controlled study evaluating the safety of HBV as a possible adjunctive treatment for multiple sclerosis. While this preliminary safety study suggests that administration of repeated injections of HBV in a step-up dosage regimen in appropriately selected non-HBV allergic patients with MS had no serious adverse allergic reactions, because of the small number of subjects studied, it does not permit conclusions regarding efficacy and therefore provides little evidence to support the use of HBV in the treatment of MS. Much larger carefully conducted multi-center studies would be required to establish efficacy.
I. Finegold * , New York, NY.
Rush immunotherapy (RIT) has benefits for inducing immunologic desensitization in shorter periods of time than conventional immunotherapy. However, there is an increased risk of systemic reactions utilizing accelerated schedules. In the past radiocontrast media reactions have been significantly reduced using a standardized protocol. A modification of this protocol was used prior to RIT. The oral premedication consisted of 50 mgm Prednisone 12 hours, 7 hours and 1 hour prior to RIT, Fexofenadine 180 mgm at 7 hours and again 1 hour prior to the procedure, and ranitidine 300 mgm, 7 hours prior to RIT. Patients tolerated the premedications well. A signed consent was obtained prior to RIT. Patients were desensitized in an office setting with appropriate therapy for anaphylaxis available without an indwelling intravenous line. Injections generally began with 1/100 dilution of the anticipated maintenance solu-tions and were doubled every 20-30 minutes for about 2-3 hours and then the patients were observed for 1 hour or more prior to discharge. In this manner patients were desensitized in 2-3 half day sessions. The patient was injected again in 1 week, 2 weeks and then 4 weeks. Doses were increased if they were not at a full maintenance dose. If reactions occurred this process was appropriately decreased. Utilizing this technique 46 patients were treated. The average age was 35.5 years old (14-56 years of age) 72 % were males.72% of patients had allergic rhinitis, 25% asthma, 3% insect allergy. Patients with complicated medical illnesses were excluded. Nine patients had systemic reactions requiring an injection of epinephrine. Among the symptoms experienced were wheezing, nasal congestion and flushing. No patient required a second injection of epinephrine, intravenous fluids, or hospitalization. The patient reaction rate was 21 % of patients treated or 9 in 1073 injections or 1% of all injections given during the rush protocol. These results are typical of the increased rate of reactions to RIT. However, these systemics were mostly very mild and responded to therapy and in only one case was there a delayed 4 hour reaction. Thus premedication while not preventing systemic reactions seemed to modify them to make RIT in an office setting a practical and effective therapy. We have previously shown that oligonucleotides consisting a novel 3'-3'linked structure and synthetic immunostimulatory motif CpR (R is a synthetic purine moiety), referred to as second-generation immunomodulatory oligonucleotides (IMOs), induce potent Th1 immune responses and prevent OVAinduced allergic asthma in mouse models. In the present study, we examined local and systemic immune responses of IMOs following intranasal (i.n.) administration to naive mice. These studies showed that IMOs produce higher levels of serum and local IL-12 compared with IL-6. We next examined the ability of s.c. and i.n. administrated IMOs to reverse OVA-induced Th2 immune responses in a murine model of asthma. Treatment of OVA-sensitized and challenged mice with IMOs by either route of administration suppressed IL-5 and IL-13 levels with an increase in IFN-gamma secretion in spleen cell cultures and lung homogenates. IMOs decreased levels of serum IgE and IgG1 and induced higher levels of total and OVA-specific IgG2a titers in serum and BALF. While both routes of IMO delivery showed similar efficacy on serum and BALF immunoglobulin levels, s.c. delivery resulted in stronger systemic effects on the spleen cell cytokine production and the i.n. route of administration produced stronger local effects on the lung cytokines. IMOs also decreased eosinophils in BALF and suppressed inflammatory cell infiltration and goblet cell hyperplasia in lungs. These effects in lung were superior with i.n. administration of IMO than did with s.c. administration. Further studies to understand the effect of low multiple doses against a single higher dose of i.n. administered IMOs in naive mice suggest that low multiple doses induce strong Th1 responses locally while the single higher dose produces higher systemic responses. These findings suggest that second-generation IMOs containing CpR dinucleotides potently reverse OVA-induced Th2 immune responses with strong Th1 type cytokine induction in OVA-sensitized and challenged mice and i.n. delivery is superior to s.c. delivery in reversing OVAinduced airway inflammation and mucosal secretion. showed AIT was medically inappropriate, lacked documentation of necessity for initiation or continuation and/or had strong contraindications in 12/18 (67%) of the reviewed records. METHOD: We audited a convenience sample of our own records for documentation of necessity for (continuing) AIT, using a checklist based on the OIG report which included the following 6 criteria: an appropriate diagnosis; specific justification; exclusion of strong contraindications; signed, informed consent; a written physician order, and at least annual re-evaluation for continuing AIT. RESULTS: The first 50 charts in our alphabetized file of 80 total AIT charts were reviewed. The patients (21 M, 29 F) ranged in age from 9-63 yr (mean, 40 yr). The mean duration of AIT was 2.3 yr (range, 0.25-12 yr). Indications for AIT included allergic rhinitis alone (68%) or with asthma (26%) or chronic sinusitis (2%), asthma alone (2%) and venom anaphylaxis (2%). All had initial documentation of necessity. Seven charts (14%) had no written order to initiate AIT. Nine (18%) lacked a signed consent form. No strong contraindication was found. (Peak flow documentation showed the asthma cases were well-controlled. Three episodes of AIT-induced anaphylaxis requiring epinephrine had occurred, but AIT was subsequently resumed and well-tolerated.) Seventeen (34%) charts had no documentation of re-evaluation during the preceding 6-12 months, including 3 with no documented re-evaluation during the previous 24 months or more, of AIT. Discontinuation of AIT was "considered" for 3 patients after 1.5, 7, and 10 yr of AIT, respectively, but all were still receiving maintenance doses. The estimated time for completing this review was 15-20 min per chart. INTER-PRETATION: An internal chart review for adherence to AIT practice parameters using a checklist such as ours can quickly and easily assess documentation for Medicare reimbursement and patient safety. Objective(s): Immunotherapy is an accepted mode of treatment for children suffering from allergic rhinitis and allergic asthma. This study demonstrates that rapid allergen vaccination (RAV) can be as safe as conventional allergen vaccination (CAV) in children. RAV may also improve patient adherence. Study design: 148 pediatric patients, 1-18 years of age, diagnosed with allergic rhinitis and/or mild to severe asthma underwent RAV over a 2 1/2 hour period in an office-based setting. All patients were premedicated with prednisone and H1 antagonists for 3 days prior to the procedure. Patients were monitored for reactions during the procedure and continued on a CAV schedule. Adherence was reviewed subsequently. Results: A total of 148 pediatric patients underwent RAV utilizing a 2 1/2 hour protocol. Of the 148 patients, 88 of them were male (59.5%) and 60 of them were female (40.5%). 143 (96.6%) of the patients had allergic rhinitis, 118 (79.7%) had asthma, and 23 (15.5%) had chronic sinusitis. During the procedure, 8 patients (5.4%) experienced systemic reaction, and none experienced true anaphylaxis. Seven of the eight patients who suffered a systemic reaction were patients with asthma on inhaled corticosteroids, three of the eight patients were male (37.5%) and five of the eight were female (62.5%). Every systemic reaction occurred within 15 minutes of the injection. Treatment usually included one or a combination of the following: nebulized breathing treatment with albuterol, two sprays in each nostril of azelastine, and diphenydramine taken orally or intramuscularly. Every patient that was treated was discharged within two hours, and no one required treatment with subcutaneous epinephrine, treatment for recurrent symptoms or hospitalization. All of the patients continued with a conventional allergen immunotherapy regimen following the rapid protocol to reach their maintenance dose. Typically, 6 months of build-up period was saved. Patients reached efficacious dosages almost immediately. Adherence rates were 95.3%, 90.5%, and 79.7% at 3, 6, and 12 months respectively. Conclusions: Effective doses of allergen vaccine can be safely reached using a 2 1/2 hour protocol ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY for children. Advantages of RAV over CAV include improved adherence with almost immediate clinical efficacy, and decreased costs. Introduction: Studies involving allergen immunotherapy (AIT) have furthered our understanding of cat allergen, proteases, and dust mite allergen. The impact of these data has not been assessed. Objective: To evaluate AIT prescribing trends over 12 years (1992) (1993) (1994) (1995) (1996) (1997) (1998) (1999) (2000) (2001) (2002) (2003) focusing on new prescriptions before and after published data regarding specific prescribing recommendations. Methods: A retrospective review of 38, 400 AIT prescriptions from a centralized allergy and extract laboratory database was performed with respect to published literature on findings and recommendations regarding the ubiquitous nature of cat allergen, effective dosing of cat antigen, combining protease containing extracts with those susceptible to degradation, dust mite antigen dosing, and the use of house dust versus dust mite antigen. Results: 1) In 1993, cat allergen was included in 10% of new allergy immunotherapy prescriptions reviewed; in 2003, it was included in 45% of new prescriptions, a statistically significant increase (p<0.00001). 2) Over the past 11 years, the mean quantity of cat antigen included in new prescriptions has been unchanged at 1mL/prescription. Only 5% of new prescriptions were written at the manufacturer recommended maintenance dose of 4ml, significantly less than those written below this level (p <0.00001).
3) There was no significant change in the percentage of extracts combining antigens with proteases with antigens susceptible to degradation. In 1992, 64% of prescriptions containing Alternaria and/or cockroach antigen were mixed with one or more antigens susceptible to degradation; in 2003, 56% of these extracts were still being combined. 4) The mean volume of dust mite mix contained in these prescriptions was between 2-2.99 ml/10ml. 5) Prescriptions containing dust mite rose from 20% in 1992 to 65% in 2003. The use of house dust was unchanged over the same period at 1.5% of prescriptions. Conclusions: Although the percentage of cat containing extracts has increased significantly, dosing of cat allergen has remained unchanged despite published literature recommending higher volumes. Protease-containing allergen prescribing patterns have not significantly changed from [1996] [1997] [1998] [1999] [2000] [2001] [2002] [2003] Young stage of life is a crucial period for aeroallergen sensitization, considering the immaturity of the neonatal immune system which may lead to T-cell anergy or a deviation towards Th2-type response in mice. The aim of this work was to evaluate the influence of oligodeoxynucleotides containing CpG motif (CpG-ODN) on ovalbumin (OVA) and Blomia tropicalis (Bt) immunization in early life compared to adult stage. Three days old A/Sn mice were immunized with OVA in Al(OH)3 and boosted on 10th and 30th day after immunization (dai) and bled on 37th dai. Groups of mice received 4mg of CpG-ODN or control-ODN associated with OVA on immunization and boost. Some animals from the three groups (OVA, OVA+CpG, OVA+Co) were killed at 20 days old and the spleen was collected and prepared to culture. Eight to 10 weeks old female A/Sn mice were immunized with OVA in Al(OH)3, boosted on 14th dai and bled on 21th dai. Groups of mice received 50mg of CpG-ODN or control-ODN associated with OVA on immunization. Animals from the three groups were challenged 3 months after immunization and bled 7 days later. Similar protocols were performed using Blomia tropicalis (Bt) extract in the place of OVA. Neonate and adult co-administration of CpG-ODN with OVA or Bt were able to significantly decrease specific IgE antibody levels and increase IgG2a production. Moreover, CpG-ODN decreased specific IgG1 levels in the Bt immunization. The co-administration of control-ODN in neonates decreased anti-OVA IgG1 production. After OVA-challenge 3 months later of adult immunization, a similar response was detected in the group that received CpG-ODN associated with OVA, which showed a decreased anti-OVA IgE and IgG1 and enhanced IgG2a levels. Analysis of cell division of neonate lymphocytes by flow cytometry showed a decreased proliferation in OVA+CpG mice group under OVA stimulation. This effect was seen either in B cells and T cells. The results showed that immunization with both allergens, OVA and Bt, associated with CpG-ODN decreased the type I hypersensitivity response. The pattern of antibody production suggests Th1-type response induced by CpG-ODN, and the establishment of memory Th1 response. This findings may imply that the use of CpG-ODN in early life seems to be beneficial as an strategy to modulate or to prevent the development of allergic diseases.
N. Horne * , A. Capetandes, M. Frieri, East Meadow, NY. INTRODUCTION: It has been shown that dust mite allergens can affect the functioning of airway epithelial cells (Winton et. al. Br J Pharm 124:1048 , 1998 . Previous experiments showed cA549 aggregate in the presence of Dermatophagoides pteronyssinus (Dp) (Capetandes et. al. Am J Clin Path, 121:25, 2004) . It is hypothesized that epithelial damage is associated with airway remodeling characterized by fibroblast dysregulation. To evaluate the response of fibroblasts to damaged airway epithelial cells, the bioactivity of serum-free conditioned media from Dp-treated cA549 cells (DpCM) was assayed with NHLF. METHODS: All experiments used insulin-transferrin-selenium supplemented DMEM (ITS). DpCM (generated with cA549 treated with 300 AU/ml Dp; Alk-Abello) was added to 50% confluent NHLF for 24 hours at 37oC and 5% CO2. ITS from cultured cA549 without Dp (ITS CM) was added to 50% confluent NHLF (control). Cell morphology and density were evaluated by microscopy and MTT assay, respectively. Data were analyzed by ANOVA followed by Student-Neuman-Keuls (SNK) at p<0.05 with power analysis. RESULTS: 50% confluent NHLF treated with DpCM showed decreased cell density (Figure 1) , and increased aggregation relative to ITS CM or ITS alone. NHLF in ITS alone or with direct addition of 300 AU/ml Dp to ITS (Dp ITS) showed no or weak aggregation. Aggregated NHLF showed 100% viability and grew to confluence when subcultured to serum-supplemented media. CONCLUSION: NHLF aggregation was greater, and cell density was lower with DpCM than with ITS, ITS CM, and Dp ITS. This suggests that Dp-treated cA549 cells release an unidentified factor or factors that contribute to NHLF aggregation and possible apoptosis. Identification of these factors would increase the understanding of the fibroblast response to epithelial cell exposure to Dp which may be involved in airway remodeling, a feature of chronic severe asthma.
J.T. Zimmermann * , Y.C. Huang, M. Frieri, East Meadow, NY. Introduction: Budesonide has been demonstrated to inhibit IL-8, TGF and GM-CSF in ragweed and dust-mite (DM) stimulated human alveolar epithelial cells (J Allergy Clin Immunol 209:3a, 2002; Ann Allergy Asthma Immunology 90: p79, 2003) . RANTES production and expression in DM and IL-1 -stimulated A549 cells has recently been shown to be inhibited by budesonide (Allergy Asthma Proc, In press 2004). Histamine is known to influence immune response by regulating cytokine synthesis (Allergy 47:024-1992) . In this study we examined the effect of budesonide in the presence of histamine on IL-8 production and expression by A549 cells. Methods: A549 pulmonary epithelial cells were cultured in DMEM for 24 hours in 5% CO2 in the presence of 1:20 of 10, 000 AU/ml DM, 10 -6 M histamine and 10 -7 M budesonide. IL-8 production was measured by a sensitive ELISA and IL-8 mRNA was measured by qualitative RT-PCR using standardized primers for IL-8 with a GAPDH control. Results: A549 cells were stimulated by DM (65-101 pg/ml) (p<0.01). Budesonide alone decreased IL-8 levels to 38 pg/ml (p<0.05), and in combination with histamine further decreased IL-8 levels to 23 pg/ml (p<0.001). Relative intensity of IL-8 mRNA expression was reduced 12-fold in DM-stimulated cells and 2-fold in control cells by budesonide. Conclusion: Budesonide in combination with histamine showed greater inhibition of IL-8 production by A549 cells than budesonide alone possibly by increasing cell membrane permeability.
C.R. Oliveira * , A.E. Fusaro, J.R. Victor, E.A. Futata, C.A. Brito, A.J. Duarte, M.N. Sato, São Paulo, Brazil. Antigen-driven bystander suppression induced by oral tolerance could be an interesting approach in the allergy field, considering the high incidence of new allergens sensitization in atopic individuals. To address the influence of non-related allergen exposure on the type I hypersensitivity response to the mite Blomia tropicalis (Bt) or ovalbumin (OVA) in mice and to verify oral tolerance effect in the Bt/OVA co-immunization model. Groups of mice were immunized with Bt extract and two weeks later submitted to OVA-immunization, or first immunized with OVA or co-injected with Bt and OVA. OVA feeding was performed five days prior co-immunization. IgE Abs were estimated by means of passive cutaneous anaphylaxis reaction and specific Ab and cytokines secretion by ELISA. Mice sensitized with Bt and then exposed to OVA developed an enhanced IgE response to itself and to OVA, but such response has not been observed when OVA-immunization was prior to Btimmunization. Co-injection of Bt and OVA led to a dominant IgE response toward OVA over Bt and vice-versa for the IgG1 response. OVA feeding prior co-immunization decreased IgE, IgG1 and IgG2a Ab levels against OVA in parallel to a bystander suppression, which avoided the outcome of Bt-sensitization. These mice showed increased IFN-?secretion levels induced by antigen-specific stimulus. Furthermore, effectiveness of oral tolerance was also related with OVA amounts employed in the co-immunization since OVA feeding prior co-immunization with low amounts of OVA led to inhibition of IgE Ab response to both allergens, whereas inhibition of specific and non-related antigen IgG Ab response was broken. The results evidenced that, depending on allergenic potential, new allergen exposure may exert an adjuvant effect on the primary sensitized allergen. The bystander effect to non-related allergen by oral tolerance should be an interesting mechanism to control new aller- Rationale. CD4 + CD25 + regulatory T cells from patients with atopic asthma undergo apoptosis when stimulated by specific allergen. Antihistamines are used to control allergic inflammatory diseases, but their influence on Treg cells is currently unknown. The present study investigates the influence of desloratadine (D) on apoptosis of CD4 + CD25 + regulatory T cells in atopic patients having dust mite induced allergic disease, including allergic asthma. Methods. Patients (n=6) with positive skin prick tests to house dust mite allergens and a clinical history of allergic upper and/or lower respiratory symptoms were treated with D 5mg (Schering-Plough, USA) once daily for 10 days. No patients used systemic corticosteroids, while theophylline and other medications were stopped at least 72 hours before blood collection. Blood was sampled before and after treatment with D. The control group was comprised of 6 individuals without allergic respiratory symptoms and with negative skin prick-tests. Peripheral blood mononuclear cells (PBMC) were isolated over a Ficoll density gradient and stimulated by specific allergen (Dermatophagoides farinae) and in a control series by phorbol myristate acetate (PMA). PBMC were labeled with anti-CD4, CD25, CD95, and Bcl-2 monoclonal antibodies. The annex-inV-propidium iodide (AnV-PI) test was done. Lymphocyte subpopulations and apoptosis were analyzed by flow cytometry. Results. After treatment with D, atopic patients had no significant differences in the number of CD4 + CD25 + cells. During co-culturing of PBMC from patients treated with D with specific allergen a significant increase in CD4 + CD25 + cells was observed. Simultaneously, treatment with D led to a significant increase in expression of the antiapoptotic protein Bcl-2 in CD4 + cells. This data paralleled the decrease of CD95 expression on CD4 + cells. There was also a decrease in Treg cells in the late stages of apoptosis (AnV + PI + cells) in D treated patients. Conclusions. The antihistamine preparation desloratadine prevented allergen-specific apoptosis of CD4 + CD25 + T regulatory cells in patients with atopic asthma. The type 1 histamine receptor may be involved in the regulation of apoptosis and/or survival of CD4 + CD25 + T cells.
A.G. Palma-Carlos * , M.L. Palma-Carlos, Lisboa, Portugal.
Introduction: Solar urticaria porphyrin corresponds to sun sensitivity to a 4000 A wavelengths and is due to disturbances of posphorin metabolism. Photosensitivity can cause urticaria, erythema, polymorphic solar eruption and in more severe cases vesicles and bullae. Photosensitivity was confirmed by light test. Methods: Protoporhyrin in RBC, uro and coproporphyrins in urines, copro and protoporhyrins in faeces and porphyrin precursors have been studied un all the cases of solar urticaria seen in the last few years. Results: In 10 patients, 8 female, 2 males, a diagnosis of porphyria has been confirmed by laboratory methods. Clinically 4 patients presented solar urticaria and 6 solar erythema or polymorphic solar eruption. 7 patients, 8 female, 2 males (21-54) presented also neuro visceral symptoms: abdominal pains (7) vomiting (4) asthenia (7) constipation (3) muscle pains and paresia (3) depression (2) anesthesic reactions (2). In 2 cases the symptoms were associated with anticonceptional drugs. The conjunction of clinical history with laboratory data has allowed to confirm the diagnosis of 2 cases of protoporphyria erytheropoietica, one triggered by anticonceptionals, 6 cases of coporporhyria hereditaria and 2 cases of porphyria variegata. This group comprises one case of erythropoietic protoporphyria induced by estrogens not previously reported. Conclusions: Research of porphyrins must be done in all the patients with solar urticaria and erythema. The incidence of sun sensitivity in mixed hepatic porphyriaalso presenting neuro-visceral symptoms which can be drug dependent suggests that porphyria study must be mandatory in suspected cases.
A.R. Narayan 1* , J. Kaplan 1 , V. Sirvan 1 , A. Chandrasekaran 2 , C. Goodwin 2 , L. Goodwin 2 , L. Guida 3 , M. Frieri 1 , 1. East Meadow, NY; 2. Manhasset, NY; 3. Bayshore, NY.
Rationale: Our division has reported that nitric oxide (NO) from tracheal epithelium can mediate induction of IL-8 (American Journal of Respiratory Critical Care Medicine 151:642a, 1995) . Increased levels of IL-8, LTB-4, and NO in mononuclear cells (MNC) from cystic fibrosis (CF) patients were noted.(Pediatric Asthma Allergy Immunology 10: 101-7 1996) . NO in MNC from CF was increased by stimulation with Aspergillus fumigatus (Asp) and rhDNAse (J. Clin Allergy Immunol 105:320P 2000). TNF-is produced from bronchial epithelial cells (BEC) in the presence of MNC of normal controls (NC). RANTES, a chemokine that facilitates leukocyte migration, is associated with airway inflammation in CF, and Asp sensitization in CF patients could amplify pro-inflammatory cytokines such as IL-8, TNF-, and RANTES. Methods: We studied the mRNA and protein expression of TNF-, IL-8 and RANTES in a 65 year-old CF patient and a NC. 1x10 6 MNCs from the patient and NC were stimulated with 21μg/ml of Asp with BEC at 10x10 5 and 10μg/ml rhDNAse. mRNA expression was studied by real time PCR (TaqMan chemistry ABI Prism 7700) and protein levels by ELISA. Results: TNF-production in supernatants of MNC with BEC from NC increased from 8 pg/ml to 64 pg/ml with rhDNAse. Whereas in CF patients the TNF-mRNA expression was greatly enhanced over NC but declined in the presence of rhDNAse (fold difference: 8.37-7.70). There was no difference in expression levels of NC (fold difference: 4.0-3.9) with rhDNAse treatment. IL-8 expression in MNC with BEC of patients increased 2.4 fold compared to NC (1.5 fold). rhD-NAse decreased Asp stimulated levels to 1.72 fold in patients compared to NC (2.9 fold). MNC and BEC RANTES production in patients increased from 49 to 1025 pg/ml and decreased to 570 pg/ml with rhDNAse, but increased from 1134 pg/ml to 1775 pg/ml in NC. In contrast, RANTES mRNA expression in all groups was higher in NC but decreased with rhDNAse in both CF and NC (37-26 fold vs. 14-10 fold). Conclusion: rhDNAse can increase NO and decrease pro-inflammatory TNF-and RANTES in CF patients stimulated with Asp. rhDNAse could lead to augmented bactericidal activity and epithelial defense by enhancing NO production and decreasing the expression and production of TNF-, IL-8 and RANTES. This is a case report of two steroid dependent atopic dermatitis patients who both responded to treatment with omalizumab. Patient A is a 39 year-old white male who presented with a history of severe atopic dermatitis for 10 years along with concomitant mild persistent asthma and allergic rhinitis. He had previously received monthly triamcinolone injections, methotrexate and doxycycline with limited response. On presentation he had mild improvement on a regimen of alternate day prednisone 30mg, fexofenadine 180mg bid, and zafirlukast 20mg bid. However, attempts at weaning prednisone were unsuccessful. omalizumab was initiated at a dosage of 150mg every four weeks. The Patient remains prednisone dependent yet free from atopic dermatitis. Patient A's diagnostic work up determined a total IgE of 33.1 ku/L. The patient's specific IgE tests were positive for grass mix, weed mix, maple, white pine, peanut, strawberry, gluten, soybean, wheat, oat, and dog dander. Specific IgE tests were negative for cat dander, egg white, milk, goose feathers, chicken feathers, mold mix, dust mix, and fish mix. Patient B is a 23 year-old white male who presented with a history of severe full body atopic dermatitis along with mild persistent asthma and allergic rhinitis. He also was receiving triamcinolone injections with limited success. He responded to alternate day prednisone 30mg, desloratidine 5mg bid, and zileuton 600mg bid. Attempts at weaning prednisone failed until initiation of omalizumab 375mg every two weeks. His atopic dermatitis is now under control with once daily desloratidine and omalizumab every two weeks. He was successfully weaned off of corticosteroid medication and has begun an immunotherapy regimen. Patient B's diagnostic work up determined a total IgE level of 1159 ku/L. Patient B's specific IgE tests were positive for weed mix, tree mix, maple, peanut, strawberry, dust mix, cat dander, dog dander, egg white, milk, oat, wheat, goose feathers, and chicken feathers. Specific IgE tests were negative for grass mix, white pine, mold mix, gluten, soybean, and fish mix. These two case reports reveal significant response to omalizumab in severe steroid dependent atopic dermatitis. Further research is strongly indicated considering the quality of life issues with severe atopic dermatitis and potential side effects to long-term corticosteroid treatment. Eosinophilic esophagitis (EE) has been described in children and is characterized by high levels of eosinophils (>20-24 eosinophils/high powered field [hpf]) in the esophageal mucosa. A recent report indicates that the combined prevalence of the eosinophilic gastrointestinal disorders may be higher than that of inflammatory bowel diseases (IBD). The presenting symptoms of EE mimick those of gastroesophageal reflux disease (GERD), and patients of all ages may experience a delay in time from onset of symptoms to diagnosis of EE. There is a paucity of data in the literature regarding the delay in time from symptom onset to diagnosis of EE. We report the data on four children three years of age and under with EE who experienced a significant diagnostic delay. Four young children were referred to the pediatric allergy clinic with a diagnosis of EE (Table) . Three of the patients were male and one was female. The patients were 17-36 months of age at the time of diagnosis, and the diagnostic delay was 15.5-33 months (average delay 23.6 months). The most common presenting symptom was vomiting, and three of the four patients had a history of respiratory obstructive symptoms. All of the patients had received conventional treatment for reflux disease, and one had undergone a Nissen fundoplication prior to diagnosis. In all four patients the esophageal biopsy revealed >20 eosinophils/hpf. Three out of four patients had a family history of atopy, and two patients had a known history of a food allergy. Skin tests to foods were positive in two patients and RAST (radioallergoabsorbent) testing to foods was positive in one patient. Recent data suggests that the diagnostic delay in IBD is decreasing as much as 50%. It is hypothesized that this may be due in part to an increased index of suspicion by health care providers. There is little data available regarding the diagnostic lag in children with EE. It is currently believed that chronic EE can lead to progressive esophageal scarring and dysfunction. Stricture formation has also been described in children less than two years of age. Given the reported increased incidence of this allergic gastrointestinal disease over the past decade, more data regarding the diagnostic delay of these conditions may be instrumental improving health care providers' awareness of this disorder.
A. Kohli-Pamnani * , E. Cooney, P. Huynh, F. Lobo, New Haven, CT. Introduction: Cutaneous hypersensitivity reactions to amprenavir, an HIV-1 protease inhibitor, are reported in up to 28% of treated patients, of whom 4% have severe or life-threatening rashes, with treatment discontinuation required in 3% of cases. We report a case of successful desensitization to amprenavir, for recurrent maculopapular exanthem, in an HIV-infected patient with late stage disease and limited antiretroviral (ARV) agent options. Methods: The patient is a 40 year-old Caucasian female with late stage HIV disease (absolute CD4 count 30 cells/mm 3 , HIV RNA 200, 000 copies/mL) and multiple ARV intolerances, who developed a severe generalized maculopapular eruption sparing mucous membranes six days following initiation of a regimen comprised of amprenavir, lopinavir/ritonavir, zidovudine, and lamivudine. A similar reaction occurred following re-challenge with amprenavir alone (600 mg oral formulation BID via percutaneous endoscopic gastrostomy (PEG) tube), despite concurrent administration of oral prednisone 20 mg/day and loratidine 10 mg/day. Results: Skin prick testing with amprenavir 0.01 mcg/mL was negative, whereas intradermal testing with 0.1 mcg/mL was positive with a 7 mm wheal and 20 mm flare. Percutaneous and intradermal testing with normal saline was nonreactive. The positive histamine control (skin prick only) yielded a 5 mm wheal and 20 mm flare. Subsequently, incremental doses of 0.025 mg, 0.1 mg, 0.25 mg, 1 mg, 2.5 mg, 7.5 mg, 25 mg, 50 mg, 100 mg, 300 mg, 600 mg, and 1200 mg of amprenavir oral solution were administered via PEG tube at 20 to 30 minute intervals (Table) . The patient successfully tol-erated amprenavir desensitization and has remained on therapy without recurrence of rash out to 16 months of follow-up. Conclusions: Desensitization may permit continued use of amprenavir in patients with a history of amprenavirinduced maculopapular eruptions who have limited alternate treatment options. Efforts aimed at characterizing the mechanism of amprenavir cutaneous hypersensitivity reactions seem warranted, given the frequency of reactions and the limited number of ARV agents available for patients with late stage HIV disease.
Doses of oral solution were administered by PEG tube at twenty to thirty minute intervals. Introduction: Beta-lactam (BL) allergy is the most common drug allergy. In most cases, IgE antibodies are specific to the BL nucleus. However, sidechain-specific IgE (SCSIgE) to BL has been described. Despite this, skin testing (ST) to BL other than penicillin (PCN) is not commonly performed. We report a case of a 31 year-old female with a selective allergy to PIP, and describe the utility of ST to this agent to confirm SCSIgE. Methods: ST to PrePen (PP) and PCN G was carried out with percutaneous (PC) testing followed by intradermal (ID) testing. ST was also carried out with ampicillin (AMP; 1 mg/ml), PIP (60 mg/ml at PC level; 1 mg/ml at ID level-a non-irritating concentration), and PIP/tazobactam (TBM; 60 mg/ml at PC level; 1 mg/ml at ID level) to exclude the possibility of selective allergy to TBM. Case Report: A 31 year-old white female with Crohn's disease was hospitalized for treatment of intra-abdominal abscesses. She had immediate flushing and urticaria during an infusion of PIP/TBM approximately 2 years prior. The Allergy/Immunology service was consulted for PCN ST because her primary service preferred to empirically treat with PIP/TBM. She had received imipenem approximately 8 months prior without untoward reaction. ST to PP and PCN G was performed with negative responses and adequate controls. She subsequently received PIP/TBM, but developed flushing and urticaria during her initial infusion, consistent with an IgE-mediated reaction. Two months later, ST to PP and PCN G was repeated. In addition, ST to AMP, PIP, and PIP/TBM was performed. She had positive responses to PIP and PIP/TBM with negative responses to PP, PCN G, and AMP, implying selective IgE-mediated potential to PIP. She tolerated an oral challenge with PCN VK 250 mg immediately following ST without untoward reaction. Conclusion: We have described a case in which ST to PIP was useful for diagnosing SCSIgE in our patient, who had 2 prior reactions consistent with IgE-mediated pathogenesis. This information will be helpful in identifying antibiotics she can safely receive in the future. This case supports the utility of ST to BL in addition to PCN, in evaluation and management of patients with a history of adverse reaction to BL that may reflect presence of SCSIgE.
A.R. Vaishnav * , B.S. Bochner, Baltimore, MD.
We report the case of a 39-year-old Caucasian male with a 15-year history of asthma, two episodes of eosinophilic pneumonia and chronic peripheral eosinophilia with baseline eosinophil counts around 1000/μL who developed amnesia and elevated cardiac enzymes in February 2004. Another physician had added montelukast in January 2004 and because of a good response advair was decreased from 500/50 to 250/50 BID. In February his eosinophil count increased to 3430/μL and soon he developed left arm numbness, diplopia as well as left arm and leg weakness. At his local hospital, he was found to have elevated troponins and CPKs. Cardiac catheterization showed normal coronary arteries and good left ventricular function. Soon after discharge, he developed confusion and global amnesia. Brain MRI showed diffuse uptake consistent with global inflammation and/or vasculitis. Upon hearing this story, we told him to take 60 mg of prednisone and urgently come to our hospital for admission. Within hours, his mental status and visual symptoms improved. Physical examination was unremarkable except for subungual splinter hemorrhages. Montelukast was stopped and 1 gm/day Solu-Medrol IV was started. Endomyocardial biopsy 2 days later showed mild hypertrophy and fibrosis without eosinophils. Repeat brain MRI and MRA were normal. Chest CT showed multiple patchy infiltrates with a new central cavitary lesion in the right lobe. Other labs included a negative ANCA, ANA of 1:40, normal complements and CSF. Our differential diagnosis included Churg-Strauss syndrome (CSS) versus hypereosinophilic syndrome (IHES) with myocardial, neurological and pulmonary involvement. Serum tryptase was normal as was fluorescent in situ hybridization for the FIP1L1-PDGFR fusion gene. Based on this, along with the new pulmonary cavitary lesion on chest CT, the diagnosis of CSS was made. After 3 days of IV steroids, he was switched to 60 mg/day of prednisone. Upon discharge his eosinophil count was 350/μL on 60 mg of prednisone. After all procedures were completed, he was also started on aspirin 325 mg daily to prevent thrombotic and thromboembolic complications. He was seen in follow-up in clinic and cytoxan 100 mg daily was started. His prednisone is being tapered. He is tolerating the treatment well and so far has had an excellent clinical and laboratory response. Introduction-C1-esterase inhibitor (C1-INH) deficiency is a rare disorder classified into acquired and hereditary forms. Both entities are distinguished by recurrent angioedema without pruritus or urticaria. The upper airway, head, neck, extremities and GI tract are typically involved. The inherited form usually presents in the first or second decade accompanied by a family history. The acquired form more commonly presents after the fifth decade. In acquired C1-INH deficiency, serological evaluation reveals low levels of C4, C1-INH, and C1q and a normal C3 level. Levels of C1q are normal in the hereditary form. The acquired form may be associated with lymphoproliferative disorders and autoimmune disease. Acquired C1-INH deficiency is typically recognized before the underlying malignant condition is diagnosed. Clinical regression has been reported in patients whose underlying disorder responds to treatment. Methods-A case report of a 57-year old female who developed repeated episodes of facial angioedema requiring hospitalization preceded by one year of vague abdominal pain and cramping. Data-Laboratory investigation of this patient revealed C4<10mg/dl (16-47 mg/dl), C1q<3.5mg/dl(5.0-8.6 mg/dl), CH50<20u/ml(31-66 u/ml), and C1-INH at 3 mg/dl(6-25 mg/dl) with a 51% activity (>68% normal). C3 was 138 mg/dl(90-180 mg/dl). Other laboratory evaluation was notable for a normal CBC with diff, comprehensive metabolic panel, amylase, lipase and SPEP pattern. IgE was elevated at 173 KU/L. Hematology was consulted. CT of chest, abdomen, and pelvis were nondiagnostic. Peripheral blood flow cytometry revealed a small distinct pop-ulation consistent with a clonal B-cell lymphoproliferative disorder. A repeat test showed skewing towards lamba light chain expression. Bone marrow biopsy and aspirate were essentially normal except for erythroid hyperplasia on Danazol treatment. The physical examination was without any masses or lymphadenopathy. The patient remained asymptomatic after beginning Danazol although elevations in RBC, Hgb, Hct and absolute lymphocyte count have developed. Conclusion-Acquired C1-INH deficiency is rare cause of recurrent angioedema that has been reported in small cohorts and case presentations. We report another case report that reinforces the need for physicians to evaluate for concomitant lymphoproliferative disorders. Chronic urticaria is a distressing condition usually associated with poor quality of life and poor response to symptomatic therapy. A wide variety of causes and mechanisms have been described and in some patients the cause remains unknown. Rare cases have been associated with thyroid antibodies and some responded to thyroxin, even in the absence of overt thyroid disease. CASE REPORT: A 54-yr-old obese white female presented with a history of persistent urticaria/angioedema for 4 mo. Urticaria involved various parts of the body and individual lesions usually lasted < 24 hr. It was often accompanied by facial edema. Oral diphenhydramine 25mg qid caused only little improvement. The patient could not suspect any offending factors. Review of systems and past medical history were unremarkable, except for hyperthyroidism at age 12 yr that was treated with "medication" for 3 yr. On physical examination there were several urticarial lesions though she has been taking diphenhydramine. The thyroid appeared normal regarding size, shape and texture. Various second generation antihistamines and doxepin were of little help. Laboratory evaluation revealed total serum IgE of 7 IU/ml (normal <200 IU/ml) and CH50 of 73 U/ml (normal 22-60 U/ml), but high TSH of 15.2 IU/ml (normal 0.4-5.0 IU/ml) and low free T4 of 0.58 ng/dl (normal 1.45-3.48 ng/dl). Her antithyroglobulin titer was 32 IU/ml (normal <100 IU/ml) but the antimicrosomal titer was highly elevated at 382 IU/ml(normal <20 IU/ml) consistent with Hashimoto's thyroiditis. Thyroxin therapy was initiated at a dose of 100 mcg/d which resulted in marked improvement within one week and the patient was able to discontinue doxepin and other antihistamines. Because of marked drop in TSH to 0.08 IU/ml, the thyroxin dose was reduced to 50 mcg/d. Her thyroid function tests became normal within two months. She did not experience any recurrence of urticaria or angioedema during over 6 mo of follow-up so far. CONCLUSION: Patients with chronic urticaria/angioedema, especially women, should be screened for thyroid autoantibodies and if positive, thyroxin therapy might bring impressive remission in urticaria. Hypersensitivity pneumonitis (HP) results from an abnormal immunologically mediated response to an environmental antigenic trigger. Typically patients with HP experience transient fever, hypoxemia, muscle and joint pain, difficulty breathing, fatigue, weight loss, and cough. There are two clinical presentations of HP differentiated by onset and resolution of symptoms. Patients experiencing acute HP experience the onset of symptoms 2 to 9 hours following exposure to a particular antigen and resolve in 1 to 3 days without specific treatment. However, patients with chronic HP experience symptoms that persist for months to years when exposed to a recognized cause of HP. A 55 year-old Caucasian male was referred to our practice with acute bronchitis. His referral was secondary to a history of allergic rhinitis, chronic asthma, gastro-esophageal reflux disorder, and sinus surgery. This non-smoking male was a machine operator at a local factory. He was doing well until he began working in the presence of a heat induction machine and metal lubricating spray called Multan EA20 (Hinkle Surface Technologies), I.D. No.: 238073. Multan EA20 is a product containing naphthenic petroleum distillates, amine salts, amine soap, triethanolamine hexyl, hexylene glycol, ethanol, sodium petroleum sulfonate, and triazine. This lubricant is known to irritate the eyes, skin, and respiratory tract. Recent studies indicate that thermal decomposition of triazine, which readily occurs during metalworking, results in the production of formaldehyde. Formaldehyde is a known carcinogen, as well as respiratory, skin, eye and digestive tract irritant. The patient developed serious respiratory health problems resulting in work absence and eventually hospitalization. While hospitalized he received a high resolution CT scan which showed diffuse ground glass appearance, and multiple attenuation areas of the lung which are consistent with hypersensitivity pneumonitis. The patient was treated with corticosteroids, and antibiotics with eventual normalization of lung parenchyma by chest CT. This represents the first reported case of hypersensitivity pneumonitis resulting from exposure to the metalworking fluid and respiratory irritant Multan EA20.
A.J. Ham Pong 1* , F. Chan 1 , S.L. Bahna 2 , 1. Ottawa, Canada; 2. Shreveport, LA.
Sexual intercourse has been known as the route for semen hypersensitivity reactions to the seminal fluid protein or to a contaminating drug or food. We report a case of anaphylaxis to cephalexin-containing semen by ingestion. HISTORY OF PRESENT ILLNESS: A 37-year-old woman developed a systemic reaction after swallowing semen. Since the couple frequently practiced fellatio without any reactions, her husband suspected cephalexin that he was taking over 2 days (500 mg qid). Her reaction began in less than 10 min and peaked over 50 min; first as itchy oral mucosa followed by wheezing, flushing of the face and upper chest, and nausea. Diphenhydramine 50 mg was administered po at 30 min and the reaction subsided over 1 hr. PAST MEDICAL HISTORY: She had generalized urticaria to oral penicillin more than 15 yr earlier and had positive penicillin skin test. She also had allergic rhinoconjunctivitis, mild intermittent asthma, and positive skin test to house dust mite, cat and dog epidermals, and pollens of grasses, trees, and ragweed. She also had oral allergy syndrome to certain fresh fruits and tree nuts; hazelnuts caused also diarrhea and colic. Neither the patient nor her husband ate any nut-containing food on the days preceding the reaction. FAMILY HIS-TORY: Allergic rhinoconjunctivitis in the mother, sister and brother. EVAL-UATION: The patient sought allergy evaluation about 2 yr after the reaction. She and her husband gave a consent. Her serum IgE was 108 IU/ml and skin test positive to penicilloyl polylysine 6x10-5 mol ID, but negative to cefazoline 10 mg/ml for prick and 3 mg/ml for ID. She had negative prick test to her husband's seminal plasma both before and after his intake of cephalexin 500mg qid for 2 days. Using a cephalexin bioassay sensitive down to 6.25 mcg/ml, the medication level in the husband's urine at 120 min post last dose was 2400 mcg/ml and in his serum at 135 min was 12 mcg/ml, but was undetectable in the semen collected at 90 min. CONCLUSION: This is probably the first case report of systemic reaction to ingested semen. The reaction occurred in an atopic, penicillin-sensitive woman and seems to be caused by cephalexin excreted in the semen or through urine contamination (1 drop = 120 mcg). In addition to her avoiding penicillin and cephalosporins, she was advised to avoid her husband's semen while him taking such drugs and for at least 3 days afterwards. BACKGROUND:Asthma causes serious morbidity & mortality all over yet most asthma educational evaluations and programs have an urban rather than rural focus.There is lack of data on rural North Dakota(ND). This ND survey aimed to study knowledge & awareness of management strategies for asthma like use of metered dose inhalers, spacer devices and peak flow meters. METHODS:The qualitative survey addressed attitudes and beliefs on asthma & its triggers;knowledge of medication delivery routes & use of hospitals and provider visits.A simple questionnaire was self-administered at 6 rural clinics in small towns in southeastern North Dakota.10 questions explored asthma knowledge, extent of family history of asthma & factors aggravating asthma.It was voluntary & the population surveyed included patients, family, teachers, employees at nursing homes, the local hospital & clinics. RESULTS:Of 297 surveys completed 61% had no asthma in the family.Of those with a family history(39%), 59% had 1 person with asthma, 28.6% had 2 & 12.3% had 3 or more.Respondents were aged 18-90 years & 81.1% were female.See Table. DISCUSSION:Our survey was rural & comparison with urban areas may help in planning for asthma education & resource allocation.61% denied asthma in their family. Similarly, nonurban Alaskan Natives have a lower incidence of asthma compared to nonnatives.Our results show a lack of awareness in our area.Grain dust exposure was perceived as an asthma trigger but without evidence, local research is needed.In our study smoking was considered a trigger by 91.5% & this may be real.There was lack of awareness of peak flow meters & their role in asthma care.A study showed that compared to other areas even rural nurses used peak flow meters less often to assess and monitor asthma.This suggests a need for comprehensive asthma educational programs in rural areas that are based on national guidelines.We had only a moderate followup rate at 60%.In comparison, one study had 21% missed scheduled follow-ups. Exercise induced asthma was known to only 50% of our group. CONCLUSION:The need for better patient-provider communication has been highlighted by the lack of awareness of proven strategies to combat asthma.The use of a simple survey has revealed many unknown facts about asthma awareness in rural ND.Further study to determine cost effective solutions to achieve national targets for asthma management are essential. Aim: In most studies of asthma, the emphasis was on changes in large and middle airways. The aims of this study:(1)to observe the morphologic changes in small airways and lung tissue(SALT) in guinea pig asthma models(GPAM);
(2)investigate the role of VCAM-1, eotaxin, NF-B and AP-1 in the inflammation of asthma; (3)explore the functional variation of alveolar type 2 cells in asthma; (4)evaluate the effects of inhaled Glucocorticoids on the above ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY parameters in SALT of asthma models. Methods: (1)The GPAM were established by ovalbumin challenge. Five groups were divided: control, asthma day 4 and day 14, intraperitoneal dexamethasone, and budesonide inhalation group.
(2)The expression of VCAM-1, eotaxin, NF-B and AP-1 was determined by immunohistochemical technology and RT-PCR; the DNA binding activity of NF-B and AP-1 by electropharetic mobility shift assay. (3)The BALF phospholipide concentration was measured by phosphorus detection. Results: (1)Significant inflammatiom with infiltration of eosinophils and lymphocytes in SALT was observed in asthma groups. (2)The protein levels of VCAM-1, eotaxin, NF-B and AP-1 expressed in the SALT were significantly elevated in asthma groups than those in control. (3)The mRNA expression of VCAM-1 and eotaxin of lung tissue homogenate was significantly increased in asthma group. (4)The DNA binding activity of NF-B and AP-1 of lung homogenate was significantly increased in asthma group. (5)The BALF surfactant represented by phospholipides was significantly decreased in asthma groups. (6)Glucocorticoids in different ways of intake provided significant effects on the inflammatiom of SALT. Conclusion: (1)Widespread and significant inflammation with eosinophilic infiltration existed in the SALT in GPAM, indicating asthma is a disease involving the whole airway and lung system. Not only there were structural changes, but also impaired function of alveolar cells. The role of small airway inflammatiom may be of great importance. (2)Eotaxin and VCAM-1 actively mediated the process of inflammatiom, NF-B and AP-1 played important roles in the regulation of VCAM-1 and eotaxin. The up-regulation of the above mediators in GPAM was expressed in SALT similar to that in central airways. We have recently reported that immunomodulatory oligonucleotides (IMOs) consisting of a novel structure and synthetic CpR or R'pG (R and R' are synthetic purine moieties) stimulatory motif effectively prevent OVAinduced asthma in mouse models. In the present study we examined whether these novel IMOs (HYB2055 and HYB2087) can reverse established allergic airway inflammation in mice. BALB/c mice sensitized and challenged with ovalbumin (OVA) were evaluated for airway hyperresponsiveness (AHR) to methacholine. Following OVA-sensitization, mice were randomized and treated with placebo or 30 mg or 60 mg/dose of HYB2055 or 2087 s.c. during the following 10 days. Two days after the final treatment, mice were rechallenged with OVA and pulmonary functions were recorded. Mice treated with either IMO were significantly protected from both early (EAR) and late (LAR) allergic response, airway hypersensitivity and hyperreactivity to methacholine, BAL and peribronchial eosinophilia, BAL and serum IL-5, and total serum IgE as compared to vehicle-treated OVA-sensitized and challenged animals. There was a significant increase in immature lung dendritic cells (CD11c+CD45R+) together with increase in serum IL-10 levels and significant decrease in lung DC2 type cells (CD11c+ CD11b+CD8a-) as compared to vehicle-treated ovalbumin-sensitized animals in the lungs following treatment with either IMO. These data suggest that both IMOs are effective and potent in attenuating key features of established allergic airway inflammation in bronchial asthma, and this effect could be mediated via decreasing lung DC2 cells and increasing immature dendritic cells. Additionally, IMOs contain a novel 3'-3'-attached structure that provides higher metabolic stability and may permit lower and/or less frequent dosing. HYB2055 was evaluated for its safety and immunopharmacology in a phase 1 clinical trial in healthy human volunteers. Introduction -Hemoglobinopathies are common in Southern Europe and Mediterranean area the more frequent being thalassemia and sickle cell disease. Aside of the major hematological diseases of homozygotic patients minor forms are frequent, thalassemia minor and sickle cell trait. In these cases mycrocytosis with decrease of red cell volume and mean corpuscular volume or abnormal erythrocytes are found and can lead to hemorheologic disturbances in bronchial circulation and bronchial hypereactivity. The rationale of this study is to evaluate the incidence of asthma in hemoglobinopatic patients allergic to house dust mites.Methods-From 4 000 patients seen in the last 4 years in an out-patient allergy clinic 44 cases of hemoglobinopathies have been confirmed by red cell count, hemoglobin electrophoresis, assays of hemoglobin A2, F, and S, and sickle cell test.All these patients had allergic disease characterized by clinical history, skin prick test to aeroallergens total and specific IgE (RAST-CAP-FEIA) and respiratory function evaluation. Results -Hemoglobinopathies: Betathalassemia 39 cases, Betadelta thalassemia 2, sickle cell trait 2, Hemoglobin C.1. Aside of 4 cases of urticaria, all the patients presented respiratory allergy, rhinitis in 12 cases of thalassemia and 1 hemoglobin C, asthma with or without rhinitis in 25 cases of thalassemia and 2 cases of sickle cell trait. Therefore asthma was present in 67, 5%. In a group 491 of respiratory allergic patients without hemoglobinopathies, 57% had asthma and 43% only rhinitis. Conclusions -The prevalence of asthma is higher in hemoglobinopathies.(p<005 Square chi test). Hemorheological changes probably greater rigidity of red blood cells and capillary bed can contribute to bronchial hypereactivity. Detection of hemoglobinopathies must be done in asthmatic patients with slight anemia or mycrocytosis. We investigated the role of aspirin-exacerbated respiratory disease (AERD) as a risk factor for the development of airway remodeling. Patients with aspirin intolerance develop hyperplastic sinusitis with fibrosis and nasal polyposis. We speculated that similar mechanisms could be acting in the lower airway and that these individuals would demonstrate more severe asthma and evidence for airway remodeling. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is a multicenter observational study of subjects with severe or difficult-to-treat asthma. Baseline data were compared between subjects 18 years who reported asthma exacerbation following aspirin ingestion and those who did not. The primary measure of asthma remodeling was the maximally achieved post-bronchodilator spirometry. Adult subjects with AERD (n=469) were compared with aspirin tolerant subjects (n=3009). Subjects with aspirin intolerance demonstrated evidence for airway remodeling as shown by lower post-bronchodilator predicted FEV 1 . In addition, they were more likely to have physician-assessed severe asthma, to have been intubated, and to have required high-dose inhaled corticosteroids or oral corticosteroids in the previous 3 months. We conclude that aspirin intolerance is associated with remodeling of both the upper and lower airways. Asthma is a complex and variable disease with two main components, airway inflammation and smooth muscle dysfunction. According to national and international asthma guidelines, subjects with persistent asthma can be classif ied into one of three categories (mild, moderate, or severe) based upon lung function, symptoms, nighttime awakenings, medications and exacerbations. Though it is widely believed that there is a high degree of variability in both pediatric and adult subjects with asthma, few studies have compared variability between them. Therefore, an analysis of previously conducted asthma studies was undertaken to evaluate pediatric subjects aged 4-11 years (n=276) and adult subjects (n=85) previously receiving short-acting beta 2 -agoinsts alone in seven double-blind, randomized, 12-week trials. The analysis is limited to subjects who were randomized to placebo in these trials. During the study, subjects exhibited marked fluctuations in asthma severity. Despite the fact that all subjects met criteria for moderate or severe asthma at baseline, 27%, 18%, 48% and 8% of weeks for pediatric subjects and 9%, 14%, 71%, and 6% of weeks for adults were spent in the intermittent, mild, moderate and severe categories, respectively. A summary of severity classification based upon symptoms and albuterol use is presented below. In addition, based upon PEF % predicted, 62% and 52% of weeks were spent in the intermittent/mild category for pediatric and adult subjects, respectively. However, fluctuations in PEF occurred frequently, with 46% of pediatric subjects and 30% of adult subjects experiencing 10 changes in severity based on PEF over 12 weeks, indicating more variability in pediatric subjects. This analysis clearly demonstrates that asthma is a variable condition and that both pediatric and adult subjects frequently move between severity categories. Furthermore, there are marked differences in severity classifications between pediatric and adult subjects. Asthma severity, and consequent optimal therapy, cannot adequately be assessed by discrete, point-intime assessments of lung function, frequency of albuterol use, or asthma symptoms, especially in the pediatric age group. Studies suggest that there may be an association between single nucleotide polymorphisms (SNPs) in the beta 2 -adrenergic receptor gene (ADRB2) and the response to beta 2 -adrenergic bronchodilators. Polymorphisms at codon 16 have been at the center of this debate. Therefore, a retrospective analysis of six large, randomized trials was conducted to evaluate clinical responses to salmeterol administered with fluticasone propionate (FSC) 100/50mcg BID for 12 weeks in patients ( 12 yrs) with moderate or severe asthma and differing ADRB2 polymorphisms at codon 16. Baseline demographics were similar for all genotype subgroups. All measures of asthma improved over baseline and were similar across Arg16/Gly subgroups at 12 weeks. Pairwise comparisons were conducted between genotypes and there were no differences other than FEV 1 as noted in the table. Findings from this retrospective analysis show that regardless of Arg16/Gly genotype, clinical response to salmeterol with an ICS was similar during chronic dosing. Although prospective studies are needed to fully understand the effect of ADRB2 polymorphisms on response to therapy with a long-acting beta 2 -agonist, this analysis suggests that therapy with salmeterol and an ICS together is appropriate for Caucasian patients with differing Arg16/Gly genotypes. Coronary artery disease(CAD) and asthma commonly coexist in adults. IV dipyridamole thallium scintigraphy is considered a safe non-invasive technique in the evaluation of CAD when patients can't exercise. Dipyrdamole is a purine that blocks reuptake of extracellular adenosine increasing serum adenosine levels after iv administration.This results in a transient coronary vasodilation increasing the sensitivity of the thallium study. Methylxanthines reverse the effects of endogenous adenosine by competitively antagonizing adenosine at local purinoreceptors. We report a case of a 69 yr.old female with a 30 year history of stable mild persistant asthma treated with daily salmeterol and low-dose fluticasone. She was referred to Cardiology for atypical chest pain. Within minutes of a standard iv dose of dipyridamole the patient reported chest tightness, cough, and wheezing. All these symptoms, typical of her past asthma flares, were abolished within 5 minutes of an aminophylline infusion and before albuterol was administered.The stress test was completed and was normal. Inhaled adenosine induces bronchconstriction and is used as a probe for bronchial hyper-responsiveness. Commercial iv adenosine preparations used in treating supraventricular tachycardia are reported to induce bronchospasm in known asthmatics. Since serum levels of adenosine are transiently increased following iv dipyridamole, bronchospastic symptoms during dipyridamole stress tests should not be unexpected. An earlier study found an increased incidence of wheezing in 39% of patients with known COPD/asthma undergoing dipyridamole stress tests despite pretreatment with beta agonists. The marked decline of theophylline use for chronic asthma in recent years may actually be increasing the incidence of this risk. Cardiologists performing thallium stress tests are familiar with the risk of asthma flares after dipyridamole. They use iv aminophylline frequently to reverse several types of clinical dipyridamole reactions, including bronchospasm. On the other hand, we are impressed that allergists are relatively unfamiliar with this association. Allergists and asthma specialists as well as asthmatic patients should be aware of risk of acute dipyridamole induced bronchospasm during elective cardiac stress testing. It has been shown that adhesive molecules are involved in inflammatory diseases of the lungs such as bronchial asthma. The purpose of the study was to measure and establish possible difference in serum levels of soluble ICAM-1 in 42 atopic patients (patients with allergic rhinitis and patients with bronchial asthma) in comparison with 28 patients without atopy (patients with asthma without rhinitis); whether there is a difference in sICAM-1 levels between groups of 26 patients with allergic rhinitis and asthma in comparison with group of 16 patients with allergic rhinitis only and also in comparison with 10 healthy controls. Results of the study have substantiated statistically significant difference in sICAM-1 levels between all groups of patients in comparison to healthy control, but no statistically significant difference in sICAM-1 levels between patients with and without atopy (Z=-1.738) or between patients with allergic rhinitis and bronchial asthma in comparison with group of patients with allergic rhinitis only (Z=0.00). Conclusion: ICAM-1 is an important marker of inflammation in patients with allergic rhinitis as well as in those with bronchial asthma. Atopic status does not influence differences in sICAM-1 levels. Although mean sICAM-1 levels were higher in patients with allergic rhinitis and bronchial asthma (312.71 ng/ml) in comparison with mean sICAM-1 levels in patients with allergic rhinitis only (279.69 ng/ml), no statistically significant difference was noted in sICAM-1 levels between these groups of subjects, i.e. asthma itself did not contribute to statistically significant increase of sICAM-1 levels.
K. Nadarajah * , G.R. Green, M. Naglak, Abington, PA.
Objective: To study the various clinical outcomes of penicillin skin testing (PST) in a community-based hospital and to determine the percentage of patients who have an antibiotic modification and the choice of antibiotic used following the result of PST. Method: This study is a retrospective chart review of all in-patients who were penicillin skin tested during a period of 6.6 years(Jan 1997 to July 2003). Information was collected on 101 patients using a detailed data collection form. Data was summarized using descriptive statistics including frequencies and percentages. Results: Of the 101 patients penicillin skin tested, 92 had a negative test, five had a positive test and in four patients the test was indeterminate(histamine controls were negative). Eighty six percent of the patients had a history of penicillin allergy, 7.9% had a history of cephalosporin allergy and 5.9% had a history of both penicillin and cephalosporin allergies. The duration of antibiotic prior to PST ranged from zero to 18 days. There was a 72.7% (67/92) reduction in the use of vancomycin, a 24.9% (23/92) reduction in the use of floroquinolones and a 7.6% (7/92) reduction in the use of aminoglycosides following PST. Aztreonam was used in 19.6% (18/92) of patients before PST and in zero patients after PST. Use of penicillin-based drugs was 49% (45/92) after PST and cephalosporin use increased from 4.4% (4/92 (all third generation cephalosporins)) to 47.8% (44/92( second and third generation cephalosporins)). i.e., 97% of patients with a negative PST received a penicillin or a cephalosporin. Vancomycin usage was higher among PST positive patients. Endocarditis was the diagnosis in 22% of all patients skin tested and Staphylococcus aureus (23.8%) and Enterococcus (16%) were the most common organisms on culture. There were no serious adverse reactions to the use of penicillins or cephalosporins when used following a negative PST, and there were no adverse reactions to penicillin skin testing. Conclusion: In the population studied, PST lowers the usage of vancomycin, floroquinolones and aminoglycosides and increases the use of penicillins. Third generation cephalosporin usage was increased by PST in our study. Overall, PST results in antibiotic modification that could lower the emergence of multi-drug resistant organisms and vancomycin resistant enterococcus. The aim of the study was to find a new marker which could be easily done to predict about possible allergy development in infants. Preventive procedure is always economically better than treatment itself.Food allergens are able to stimulate lymphocytes even in prenatal period. Immunological maturity of newborns is still in the center of our interest because its dependence on many different factors. The question was if CD30 activity in cord blood and in 1-year-old children correlates with development or not of allergy? The examined group consists of 120 newborns(58, 2% of boys). Breastfed were only 87 children until 3-months-old and 62 until they were 6-monthsold. Total IgE from cord blood and mothers' blood taken at delivery were measured using UniCAP. Immunological detection was done using fluorocytometry(Becton nad DAKO). Additionally parents were questionaired( family atopy). Our reaults show that positive family atopy history(group A) or elevated level of IgE( group B) or symptoms of allergy in first 3 months of life(group C) does not correlate with CD30 antigenicity. In all subgroups CD30 frequency was 1%. Our findings show unfortunately that CD30 cannot be a predictive marker for allergy development. Rationale: The etiology of eosinophilic esophagitis (EE) is unknown and the relationship to a type I allergic response is unclear. Comparison of patients with positive and negative type I allergy testing may further clarify EE and determine what are the most common food allergens. Methods: This is a retrospective chart review of medical records from January 2000 to January 2001 of children 1 year of age with biopsy confirmed EE (n = 42). EE was defined as having 15 eosinophils per high power field on esophageal mucosal biopsy. Patients were grouped according to positive (n = 26) and negative (n = 16) allergic responses on skin or radioallergosorbent testing (CAP RAST, Pharmacia). Skin testing with commercial extracts (Hollister-Stier Laboratories and Greer Laboratories) was performed in an allergist's office. A wheal of 3mm greater than the negative control on skin testing or IgE > 0.35 kU/L on RAST was considered positive. We performed Fisher exact analysis to determine if associations existed between a type I allergic response and factors such as age, symptoms, peripheral eosinophilia, and personal and family history of atopy (asthma, allergic rhinits, and atopic dermatitis). Results: EE patients with a positive type I allergic response were significantly younger than those with a negative response (mean 4.6 yo, median 4.5 yo, range 1 to 10.3 yo versus mean 8.5 yo, median 7.8 yo, range 1 to 21 yo; p = 0.0065). Vomiting as a presenting symptom was significantly increased in the allergic population (85%, 44%; p = 0.014) and abdominal pain as a chief complaint was significantly increased in the non-allergic population (31%, 69%; p = 0.026). Personal and family history of atopy and peripheral eosinophilia were similar between groups. The most common allergens were cow s milk (54%), peanut (46%), egg (42%), soybean (38%), and wheat (27%). Conclusion: Patients diagnosed with EE who present at a young age or who present with symptoms of vomiting may have a type I allergic response contributing to the esophageal eosinophilic inflammation. Consistent with food allergies in children, milk, peanut, egg, soybean, and wheat were the most common foods found with allergy testing. Because the positive predictive accuracy of food ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY testing is only about 50%, the challenge remains to develop a specific plan to confirm causative foods such as through oral challenges or elimination trials. Rationale: The relationship between specific IgE and IgG levels in atopic individuals is unknown. Increasing antigen exposure is expected to increase IgG production, however, the influence on IgE levels is unclear. To further clarify this relationship the following studies were conducted. Methods: Three hundred and sixty tandem determinations of specific IgE and IgG levels in 65 individuals were collected using the ImmunoCAP 100 instrument (Pharmacia Diagnostics) and commercially available reagents. Only subjects who had IgE levels > 0.35 kU/L and IgG determinations > 2 mg/l to the same specific allergenic species were included in the study. Specific IgE and IgG determinations were to Alternaria alternata, Aspergillus fumigatus, Penicillium notatum, Cladosporium herbarium, Felis domesticus, Canis familaris, Dermatophagoides farina, and Periplaneta Americana. Correlation coefficients were calculated using Excel (Microsoft). Results: The review of this data set yielded 55 tandem determinations of specific IgE and IgG levels in 25 atopic individuals. The most common IgE sensitization was to Alternaria. Sixtyfour percent of individuals had specific IgE directed against Alternaria. The lowest IgE response rate was for cat and roach. Only 20% of individuals had an IgE response to those specific species. Correlation coefficients (CC) were calculated between specific IgE and IgG levels and were positive for all eight species tested. The highest CC was for dog (n = 6, CC = 0.92) followed by Aspergillus (n = 13, CC = 0.71), Penicillium (n = 6, CC = 0.69), Alternaria (n = 13, CC = 0.62), Cladosporium (n = 8, CC = 0.35), cat (n = 5, CC = 0.31), and roach (n = 5, CC = 0.16). The lowest correlation was for Dermatophagoides farina (n = 7, CC = 0.03). Conclusion: When individuals with measurable specific IgE and IgG levels are considered, there appears to be a positive correlation between specific IgE and IgG levels for many allergenic species. Factors that influence the correlation are likely to be both genetic and environmental. Identifying this link and a clinical application are our next challenge. Recently, protein microarray tests are competing with traditional allergenspecific in vitro assays. While the advantages of microarrays in allergy testing are attractive, microarray analysis alone has not been very effective in reducing analysis time and automated microarray equipment typically is much larger than its benchtop counterparts. We have incorporated microarray technology into an automated microfluidic cartridge that provides rapid allergen testing using a compact, low-cost, desktop instrument. The injection molded microfluidic cartridge (Fig. A) contains arrays of miniature pumps and valves that direct reagents independently to a solid phase reaction area. Standard IgE (NIBSC) as well as allergens were immobilized within the cartridge to form a protein microarray. A small desktop analyzer actuated the pumps in the cartridge to automatically carry out a chemiluminescence-based ELISA reaction. Total IgE quantitation was performed in a 10 minute reaction. Fig.B shows the resultant image of a dilution series of immobilized IgE. Concentrations ranged from 0.625 to 1000 IU/ml corresponding to 1.9 fg to 3 ng IgE per spot. The average CV value for IgE quantitation was 12% showing good linearity (R2 = 0.99) and 6 fg sensitivity. This quantitative IgE curve is used to eliminate the effects of cartridge variability. Specific IgE detection was demonstrated using 3 extracts, D. pteronyssinu(Dp), A.fumigatus and B. verrucosa(Bv). A 2-step, 20 minute reaction ELISA technique was employed. Fig. C and D show the resultant images for Bv and Dp positive serum, respectively. The sensitivity of the Dp specific IgE test was further investigated using a positive class 1 serum sample confirmed by MAST. Dilution of the class 1 serum with negative control serum could then be detected on the cartridge down to an 8 fold dilution, resulting in a limit of detection in the range of 0.08-0.31 IU/ml for Dp specific IgE. We have demonstrated total IgE and allergen-specific IgE detection with total analysis times less than 30 minutes in a convenient, low cost system using a microfluidic-based microarray cartridge. Such rapid diagnosis allows physicians to provide treatment while the patient is still in the office. Background: Accurate allergen skin tests (AST) are the basis of optimal care of the allergic patient. Completing these tests on the first visit can expedite the diagnosis and treatment and offer patients(pts.) efficient use of their time and increase satisfaction. Appropriate pre-visit preparation is necessary to reduce the variables that affect AST outcomes. Both positive and negative skin test controls are necessary to assure the AST are reliable. Methods: We conducted a retrospective chart review of 1, 248 sequential pts. skin tested at an allergy practice, in order to examine the success of our pre-visit instructions and to identify other medications that may affect AST. Pts. were given verbal and written instructions to discontinue antihistamines and other histamine-1 receptor antagonist medications (H-1A) 5 days before their visit. They then underwent AST only if adequate positive (histamine) and negative (saline/vehicle) controls were obtained. Results: Only 53(4.2%) of the 1, 248 pts. had inadequate histamine response (IHR). Of these 53 pts., 23(1.8%) had used H-1A within the prior 5 days. 18(1.4%) pts. had taken H-1A in the recent past, but stopped them at least 5 days prior to testing. 12(1.0%) pts. had no exposure to H-1A. The use of psychiatric medications in the pts. with an IHR was also examined. Of the 18 pts. who discontinued H-1A for more than 5 days, 13(76%) were also taking various medications drugs used in the treatment of psychiatric disorders (SSRIs, benzodiazepines, atypical antidepressants & antipsychotics) which are not usually associated with H-1A. The group of 12 of the pts. with no prior use of H-1A included 10 (83%) who were also on various psychiatric medications. The high prevalence of psychiatric medication use in these two groups is in contrast to the to 23 pts. with recent use of H-1A in whom 43% were on psychiatric medications. Conclusion: Pre-visit patient education about discontinuation of H-1A can lead to successful first visit AST in the overwhelming majority of patients (95.7%).Failure to stop H-1A at the appropriate time occurred in only 1.8% of the pts. 1.4% of pts. discontinued H-1 A for the recommended 5 day interval, but still had IHR. Another 1% of pts. had an IHR yet no obvious use of H-1A. A few pts. taking psychiatric medications not normally associated with H-1A had IHR. Further investigation into this issue is warranted.
A. Blaziene * , A. Chomiciene, L. Jurgauskiene, N. Ciaponiene, Vilnius, Lithuania.
Background: Sublingual specific immunotherapy (SIT) is accepted as an alternative treatment to subcutaneous SIT of seasonal allergic rhinitis. The aim of this study was to evaluate changes in allergen-specific IgE and basophil degranulation test (BDT) before and after 1 year of SIT with a grass pollen mix. Methods: 6 patients (3 male and 3 female, aged 25-44 years) having sensitization to grass pollen with seasonal allergic rhinitis were treated with standardized grass pollen extracts. The blood samples were collected before and after 1 year of SIT assessing allergen-specific IgE using an ELISA method and BDT using a direct immunofluorescent method employing monoclonal antibodies. Results: The SIT was well tolerated by all patients. An increase in total IgE after SIT was observed in all patients. Specific IgE concentration was increased in 2 (33.3%) patients, while the BDT result was greater in 3 (50%) patients after 1 year of SIT. Conclusions: Allergen-specific IgE and BDT may serve as markers to indicate the clinical efficacy of SIT for seasonal allergic rhinitis patients.
A.G. Palma-Carlos * , S.L. Silva, M.L. Palma-Carlos, Lisboa, Portugal.
Introduction -The incidence of primary immunodeficiencies in patients attending an Out-Patient Center for Clinical Allergy and Immunology depends on the recruitment and on patients refered. Methods -In the last 3 years 3 000 patients have been observed in Lisbon Clinical Allergy Center reporting allergic diseases or repeated infections or refered by specialists (ENT, gynaecology, Internal Medicine, Pediatrics, or GP.). Screening for primary immunodeficiencies has been done by electrophoresis, assay of immunoglobulins and complement, IgG subclasses and flux-cytometry for T, B and NK cells. Results -102 cases (3, 4%) of primary immunodeficiencies have been diagnosed. Humoral: 13 deficits of IgA (12, 7% of immunodeficiencies), 7 of IgG (6, 8%) 16 of IgG subclasses (15, 7%) 11 of common variable immunodeficiency CVI-(10, 8%), 2 of IgM (2, 0%). Complement: 4 cases of C1 esterase inhibitor deficiency (3, 9%) Cellular: 45 cases of mucocutaneous Candidiasis (44, 1%) in fertile females, 2 cases of CD4 deficiency (1, 9%). Combined: 2 cases of deficiency of the couple CD40/C40 ligand with IgG deficiency (1, 9%).Conclusions -In the present series chronic mucocutaneous Candidiasis is the prevalent primary immunodeficiency, due to the number of patients refered by gynaecologists. Aside of this group where a decrease of NK cells was the more common immunologic pattern, humoral immunodeficiencies are frequent, mainly CVI, IgA, IgG and IgG subclasses deficiencies. The search for immunodeficiencies must be done in all patients with repeated infections attending immuno-allergology departments.
A CASE OF ATYPICAL C2 COMPLEMENT DEFICIENCY. C.C. Randolph * , Waterbury, CT.
Introduction:C2 complemennt deficiency occurs in 1 in 10, 000 individuals .It results in decreased opsonization and chemotaxis with increased prevalence ofSLE and other rheumatic disordersas well as enhanced vulnerability to pyogenic infection.There are two types of C2complement deficiency :type 1(90%associated with SLE)with no protein translation and type II with absence of protein secretion.We present a 15 year old white female otherwise healthy with recurrent urticaria and angioedema with C2 complement deficiency. Method:Case Report:A 15y/o w/f athlete presented with a two month history of recurrent hives and angioedema which she associated with ingestion of Halloween candy .One week before evaluation she had hives with Coconut as well.Her history was othewise unremarkable except for recurrent UTI'S, annual sinusitis, pneumonia in 1998 as well as migraines.She denied sexual activity.Her physical exam was normal.Results:An evaluation for autoimmune disease revealed normal ESR, ANA, DSDNA, mono and hepatitis serology as well as lyme titers however her CH50 was low17u/ml(normal 26-58U/ml)and evaluation of complement revealed c4 14mg/dl(normal 16-47mg//dl)and c2 <1.3mg/dl(normal 1.6-3.5mg/dl)with normal c3, c5-c9.Her father had nor-malc4 but c2 was 1.4mg/dl (normal 1.6-3.5mg/dl)Her sister had c2 of 1.5mg/dl and normal c4 and her mother had normal c2 and c4.Her workup included positive prick skin test to ragweed, ash and grass and she was started on Rhinocort and Clarinex seasonally.She has been followed for one year with resolution of hives and is asymptomatic.Her diagnosis had been confirmed by a pediatric rheumatologist.Conclusion;We present an atypical case of C2 complement deficiency in an currently asymptomatic individual. Background: We diagnosed a 10 month old male with CGD and aspergillus brain abscesses and pulmonary infiltrates. Review of the literature suggests he is one of the youngest cases of CGD complicated by cerebral aspergillosis. Case Report: A ten month old male previously seen for unexplained persistent pulmonary infiltrates since 4 month of age presented to our hospital with lethargy, fevers, and increased irritability. CT scan of the head revealed severe hydrocephalus. Multiple brain abscesses were found on surgical exam and cultured for aspergillus fumigatus. He had a history of failure to thrive and hypotonia since birth. Family history was significant for parents that were second cousins. There was no family history of recurrent infections or childhood deaths. Physical examination was significant for a child with weight and height in the 25% and 75%, respectively with persistent fevers >38.5 C, hypotonia, hepatosplenomegaly, and left lower lung field rales. Initial immune workup was normal except for elevated total IgE of 215 KU/L. CD4+ (526/m3) and CD8+ (332/m3) T cells were initially low, but later increased to normal levels without intervention. Neutrophil oxidase activity assessed by dihydrorotamine 123 (DHR) oxidation was 0% of control. Superoxide production assessed by cytochrome C reduction was zero. The patient was treated with interferon ? for presumed CGD. His aspergillus brain abscesses improved with intravenous voriconazole and caspofungun. The responsible organism for his recurrent pulmonary infections was not identified, but improved with antifungal therapy and broad spectrum antibiotics. The DHR test of both parents and siblings were normal. Antibody testing showed a complete deficiency of the p67 protein with normal levels of gp91, p22, and p47 proteins. Evaluation of the exons of the NCF-2 gene that encodes the p67 protein were normal. Conclusion: Mutations due to p67 protein deficiency are responsible for 3% of cases of CGD. There has been only one previously reported case of p67 deficiency without NCF-2 exon mutations in which a single point mutation in an intron of the NCF-II gene was identified. Fungal infections may complicate CGD, however cerebral aspergillosis is seldom encountered. This case ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY reports a 10 month old with CGD due to a p67 deficiency without exon mutations complicated by cerebral aspergillosis. INTRODUCTION: Lymphoid interstitial pneumonia is an uncommon condition which is considered both as a disease per se or as an inflammatory pulmonary reaction to various external stimuli or systemic diseases; however, at the present time most of the cases remain idiopathic. We present a case of an infant who developed a lymphoid interstitial pneumonia associated to a deficit of interferon-production. METHODS: We describe a clinical case and review the medical literature. RESULTS: We present the case of a five months old male with a history of cough, respiratory distress and four previous hospital admissions regarded as a 'pneumonic' events from two months of age and four siblings dead (two of them with 'abdominal disease' and one of them with candidiasis) during their first year of life. The parents referred no consanguinity. The physical examination showed a malnourished child with signs of bilateral lung consolidation. Oxygen supplementation and intravenous antibiotics were started. Our patient didn't have neonatal history related to the present compliant. The chest film revealed a diffuse bilateral interstitial pattern which was confirmed by pulmonary CT scan. Sweat chloride test, HIV and Epstein barr virus serology test were all negative. An initial immunologic evaluation reported slightly increased leukocytic count, hypergammaglobulinemia, lymphocityc flow citometry and nitro blue tetrazolium reduction test in normal parameters. The open lung biopsy showed a thicked pulmonar interstitium with moderate number of lymphocytes with not atypical pattern. Our patient was discharged with clinical improvement, ambulatory oxygen supplementation and inhaled fluticasone-salmeterol. In an ambulatory follow-up we evaluated lymphocytic production of cytokines and we found no levels of interferon-. We started weekly administration of oral transfer factor. The patient showed an excellent clinical improvement evidenced by no more oxygen dependence, weight gaining and absence of further hospital admissions. CON-CLUSIONS: Our patient represent a new linkage between lymphoid interstitial pneumonia and primary immunodeficiency characterized by interferonproduction deficit, maybe with a non previously described molecular defect and a probably autosomic recessive inheritance pattern; also we confirmed the transfer factor usefulness to induce gamma interferon endogeous production. Objective: Marijuana is a schedule class 1 psychoactive control substance more frequently used by the oriental societies( in the event of jubilation) causing altered state of conscience, euphoria, its prolonged use is followed by addiction and dependence.It contains more than 426 chemical entities with over 60 are of the cannabinoid i.e, cannabidiol (CBD), cannabinol (CBN), and delta-9, tetrahydrocannabinol (THC) The later on use has been associated with craving for further use of narcotics just to enhance the euphorient effects .The active ingredients i.e, Delta-9-TetrahydrocannabinolTHC) and other cannabinoids(THC) are liquid soluble at high concentrations which alters membrane function, resulting in alterations in immune cell response. cannabinoid has immunosuppressant properties causing impaired cell-mediated and humoral immune system activities, cytokine production, leukocyte migration and natural killer-cell(NK) activity resulting in reduction in the host resistance to bacterial and viral infection, (PMS)with HIV infection are at higher risk of developing AIDS, infection by opportunistic bacteria, fungi, or viruses (PMS), when compared to non marijuana smokers, have more respiratory ill-ness.Cannabinoids also characteristically as being immunomodulators i.e, generally suppressing but occasionally enhance some immunological responses, some have suggested that the immunosuppressive effects of cannabinoids might be useful clinically; for example, in treating multiple sclerosis.As per clinical response cannabinoids had been found exacerbating existing allergies from antigenic complex (eliciting formation of specific antibodies/metabolites as a hapten, combining with a body proteins). Methods .In the follow up studies including 18individuals(all males age25-60 years) with(PMS).of more than 6 months having serum level of TCH >10um, there have been 20 times reduction in the proliferation of T lymphocytes with a proportionate increase in the proliferation of B lymphocytes, reduction in the cytotoxic activity of T lymphocytes, reduction in macrophage activities i.e, phygocytosis RATIONALE: Patients with XLA are subject to arthritis and cellulitis. These three relatives have had similar courses, suggesting infectious etiology. METHODS: Two brothers and a cousin, from an African-American family known to carry XLA, have been diagnosed with XLA and chronically treated with IVIG. All three have developed arthritis and cellulitis of a lower extremity. The eldest, now 23 years old, had a 5-month waxing and waning arthritis and cellulitis that was refractory to the oral antibiotics attempted. His younger brother had not yet accomplished pubertal changes at the age of 16, and was below 3rd percentiles for weight and height. He also had several months waxing and waning arthritis and cellulitis refractory to oral antibiotics. He and his cousin have had esophogastroduodenoscopies that show gastritis and duodenitis with heavy growth of an organism visualized by specific staining for H. pylori. The cousin has also experienced more recent weight loss and arthritis/cellulitis. RESULTS: The younger brother had a blood culture that grew a curved gram-negative rod. A subsequent culture at the state lab grew a similar organism that was urease-negative. The two brothers are at or near completion of a six-month course of Ertapenem and Gentamicin; they have had resolution of their arthritis and cellulitis. The younger has gained 10.3 kg and experienced his pubertal changes at the age of 17 years. CON-CLUSIONS: There are prior reports of several different related organisms that can cause arthritis and cellulitis in patients with XLA. These include Helicobacter, Campylobacter, and Flexispira species. The urease-negative organism would not be Flexispira, but may be a Campylobactor species or Helicobacter canis. The results from this family suggest that long-term combination IV antibiotics may be indicated for patients with this syndrome. Slow virus infections have been reported to affect the Central nervous system. Parvovirus B19, Herpes and CMV are usually not included in the diagnosis of CNS diseases nor has been associated with CNS manifestation in an immuno-compromised patient. In this abstract, we report on a neurological manifestation that can be linked to Ebstein-Barr/Herpes Virus and Parvovirus-B19 in an immune deficient patient. A 50 year old female presented to our clinic with a history of chronic fatigue symptoms, daily arthralgias, frequent sinus infections and idiopathic tremors for the past 6 years. The patients neurological evaluation, including MRIs was found to be within normal limit, despite worsening tremors of her head and arms. A full clinical and labora-tory evaluation was performed which revealed IgG subclass, low T-cell numbers and functioning, low response to specific antibodies and positive IgM for EBV, Parvo and CMV. The patients Common Immune Deficiency coupled with chronic viral infection and worsening tremors led us to try high dose IVIG (2g/kg divided over 3 days on cycles of every 3 weeks). Within three months of starting IVIG, the patient had a large reduction in her tremors and negative IgMs for Parvovirus, Herpes and CMV. Given our findings, we suggest that IVIG may play a role as a neuro-immune modulator, as has been shown in other neuro-immune diseases. We further suggest that the interaction between Parvovirus B-19, Herpes and CMV as part of the slow viruses, combined with underlying immune disorder may lead to neurological presentation and high dose of IVIG can reverse the syndrome. Purpose: To date, only two patients older than fifty years of age have been diagnosed with Velocardiofacial Syndrome (VCFS); this case represents the third such patient. Methods: Physical and laboratory findings of the patient are presented as a case report. Results: We describe a sixty-six-year-old male, recently diagnosed with VCFS, confirmed by fluorescent in-situ hybridization (FISH), was referred by his psychiatrist for comprehensive care. He had a history of cleft palate and learning disabilities as a child, with the onset of psychiatric illness in his late teens. Although there was no history of cardiac disease, the patient had agenesis of the left renal artery as well as other vascular anomalies, including hypoplasia of the left A1 segement of the anterior cerebral artery. Other findings included hypothyroidism, hypoparathyroidism, sensorineural hearing loss, and typical facies. He also suffered from chronic candidiasis. Immunologic laboratory studies revealed over a 2:1 ratio of CD8:CD4 T cells with a decreased CD4 percentage, markedly diminished B cell percentage, decreased T cell mitogen responses, and markedly decreased B cell mitogen responses. Nevertheless, total serum IgG and specific antibody responses remained normal, with a low serum IgM. Conclusions: This patient meets the criteria for the diagnosis of VCFS; only the third reported case diagnosed over the age of fifty. Though his immunologic findings may be consistent with his diagnosis, they may be due in some part to immunologic senescence given his age. Background: The classic presentation for patients with XLA and mutations in the Btk gene includes marked hypogammaglobulinemia, absent B cells, and significant sinopulmonary infections beginning at 4-5 months of age. Typically, MDS presents with anemia, leukopenia, monocytosis, and thrombocytopenia with recurrent infections, skin rash, and hepatosplenomegaly. Many of these subjects demonstrate chromosomal abnormalities including monosomy 7. We describe a case of MDS presenting with some features of both conditions. Clinical History: We present a 2 year old male with a suspected diagnosis of XLA, chronic sinopulmonary disease beginning at 12 mo, diffuse bronchiectasis, and agammaglobulinemia with absent B cells. He had WBC =3750 cells/ul, with 60% monocytes and platelet count of 122, 000 /ul. He had no anemia, hepatosplenomegaly, or skin rash. Bone marrow biopsy showed MDS with absent plasma cells and monosomy 7 in 95 % of his cells. Btk expression and sequence analysis were normal. Conclusion: While XLA is the most likely primary immune deficiency that would present in a male with the clinical picture described above, this case illustrates the importance of maintaining an expanded differential diagnosis in patients with presumed primary immunodeficiency.
J. Wang * , L. Mayer, C. Cunningham-Rundles, New York, NY.
Background: Chronic granulomatous disease (CGD) usually results in acute or chronic infections with a defined spectrum of bacteria or fungi. Other characteristics include inflammatory disorders, including genitourinary or mucosal inflammation resembling inflammatory bowel disease. GM-CSF has been used in the treatment of mucosal inflammation in glycogen storage disease Ib and Crohn's disease with some success. Objective: To explore the use of a novel therapy in the treatment of mucosal inflammation associated with CGD. Methods: The patient was treated with daily GM-CSF (0.6 mcg/kg/dose subcutaneous injection) along with parenteral antibiotics and total parenteral nutrition. After 4 days on GM-CSF, hydrocortisone enemas were added due to continued pain and swelling. Results: Rectal and abdominal pain significantly improved, blood streaked stools decreased; he tolerated a regular diet and was discharged home 10 days after starting GM-CSF. He now has no rectal or abdominal pain and no blood in the stool. Conclusions: GM-CSF may be a useful therapy for the management of mucosal inflammation in CGD patients. It appears safe and well tolerated and permits avoidance of immune suppressive alternatives. Introduction: Management of autoimmune cytopenias in patients with cellular immunodeficiency may be very challenging. Treatment of these cytopenias with corticosteroids may potentiate the immune dysfunction leading to further infections. Methods: We describe a 15 month-old female with a cellular immunodeficiency and autoimmune thrombocytopenia / hemolytic anemia being treated with steroids and IVIG without improvement. Rituximab, a monoclonal antibody that binds to B-lymphocyte CD20 surface antigens, was initiated. Results: This patient presented at 11 months of age with failure to thrive, eczema and recurrent bacterial pneumonias. She was diagnosed with a T lymphocyte immunodeficiency with decreased absolute numbers of CD3 (493), CD4 (365), and CD8 (80) lymphocytes. T cell function was markedly decreased as measured by PHA, ConA, and PWM. She developed chronic thrombocytopenia with platelets of less than 20, 000 and Coombs positive anemia with hemoglobin of 6 g/dL. She was placed on 4mg/kg/day of prednisone with minimal improvement and continued to develop severe pneumonias. Rituximab 375 mg/m 2 /week was initiated for 5 doses. Her cytopenias improved with an increase in both platelet count (229, 000) and hemoglobin (15.1g/dL). Her absolute CD19 count fell from 1319 to 0. She was weaned off steroids permanently. She has also continued on IVIG, prophylactic antibiotics, and as needed rituximab pending bone marrow transplant. Conclusions: Rituximab, a monoclonal anti-CD 20 antibody, may be helpful in treating autoimmune cytopenias in patients with cellular immunodeficiency in which steroids need to be avoided. IVIG antibody replacement substitutes for the subsequent humoral antibody depletion due to induced secondary B cell lymphopenia. Introduction: The patient is a 3 month old male born at full term. During his prenatal course he was noted to have a pulmonary abnormality in his left lower lobe at approximately 12 weeks of age. Serial ultrasounds and fetal MRI were consistent with the diagnosis of congenital cystic adenomatoid malformation (CCAM). Histology from elective resection of the lesion performed at 2 months of age revealed no evidence of CCAM. Silver stain revealed florid Pneumocystis jiroveci (carinii) infection. The patient was completely asymptomatic. The differential diagnosis for this infection in the newborn period includes HIV infection, severe combined immunodeficiency, and x-linked hyper-IgM syndrome. The infection has also occurred in newborns with apparently normal immune systems. Methods: Immunology evaluation was performed to evaluate the patient for the listed diagnoses. A complete blood count was performed. Lymphocyte subsets were performed by flow cytometry. Quantitative immunoglobulins G,A, M and E were measured by nephelometry. Specific antibodies to tetanus and diptheria were determined by ELISA. HIV status was ascertained by western blot and DNA PCR. Dichlorofluorescein assay was performed. Fluorescenceactivated cell sorter technique was used to evaluate CD40 ligand. Lymphocyte stimulation to mitogens and tetanus were performed. Results: The patient had negative HIV1/2 antibodies and a negative HIV DNA PCR. The result of the complete blood count was normal with an absolute lymphocyte count of 6, 750. The patient had normal percentages and numbers of CD3, CD4, CD8, CD19, and natural killer cells. Lymphocyte stimulation to mitogens and tetanus was normal. DCF assay was normal. FACS revealed normal levels of CD40 ligand. At 5 months of age he had protective titers to diptheria and tetanus titers of 0.52 IU/mL (protective >0.6 IU/mL). At 5 months IgG, A, M and E were 235 (normal 218-636), <6, 36, and <5 respectively. Conclusion: Immunologic testing revealed no evidence of severe combined immunodeficiency, HIV infection or x-linked hyper-IgM syndrome. The patient remains well clinically with normal growth and development with no subsequent infections. Pneumocystis jiroveci pneumonia can be seen in infants with apparently normal immune systems. Commercial preparations of IgG produced for IV use (IVIG), must fulfill regulatory requirements. The method of preparation, however, may produce alterations in the content or function of IgG subclasses such as disturbed composition which can be reflected as a lowered clinical effectiveness of the product. We report 2 patients with specific IgG3 immunodeficiency, that, when changed to a new IVIG preparation, had lessening of clinical effectiveness of the new product but who also experienced recovery after they were changed to a different IVIG product. Case 1. A 53 y/o male with hx of cervical lymphadenopathy associated with recurrent URI, fatigue, cognitive alterations and hypercholesterolemia. He was Dx in 1993 with a specific IgG3 immunodeficiency for which he was started on IVIG infusions 400mgxkg q/4 w which brought his IgG3 levels to normal values 21 mg/dL, (18-95 mg/dL) with good clinical improvement. When he was changed to a different IVIG product with lower IgA content his initial symptoms returned with decrease of his IgG3 to 17 mg/dL (41-129 mg/dL) He was changed to a different IVIG product with higher IgA content with disappearance of all his previous symptoms. Case 2. A 47 y/o female with history of chronic yeast infection, fatigue, joint pain, asthma, GE reflux, depression, hypothyroidism and shunt for hydrocephaly. She was diagnosed with IgG1 and IgG3 immunodeficiency and started on IVIG 400 mg x kg x q/4 w. When changed to another IVIG with lower IgA content she experienced worsening of her symptoms during the 2 months that she was receiving it. She was changed to a different IVIG product with a higher IgA content with complete improvement of her symptoms. Although the content of IgA in Product 1 (50-150 ug/mL) was significantly lower than in Prod-uct 2 (720ug/mL), the total IgG and IgG subclass distribution (including IgG3) were comparable Therefore, the lack of clinical effectiveness of Product 1 would appear to be related to qualitative alterations in the product related to methodological preparation possibly in removal of the IgA or other physicochemical alterations affecting biologic activity which contributed to a lessened clinical efficacy of the product. We present these cases to alert the allergist-immunologist to these observations when treating patients with IgG or IgG subclass deficiencies. BACKGROUND: Development of atopy has been known to occur in nonatopic recipients of bone marrow transplants ( BMT) from atopic donors. The reverse condition, with atopic recipients losing evidence of specific IgE after BMT from non-atopic donors is quite unique. CASE REPORT: PH is a 37 year old male referred for recurrent nasal congestion. As a teenager, the patient was treated for chronic allergic rhinitis and asthma, atopic dermatitis diagnosed as severe, and multiple food allergy. Skin testing done as a teenager showed 3+ reactions to multiple pollen, dog, cat, most seafood, cashew, walnut and pecan. At 16 years of age, he underwent an allogeneic BMT from his non-atopic brother for acute myelogenous leukemia. Asthma and atopic dermatitis were observed to clear almost completely and allergic rhinitis improve after the BMT. His blood type changed from 0+ to 0-. Skin testing done on his current visit showed unremarkable responses to all pollen, cat, dog, dust mites and foods with good histamine control. DISCUSSION: The negative skin test results suggests that his current nasal symptoms are vasomotor in nature. Considering the past severity of his symptoms, it appears unlikely that he lost his specific-IgE sensitivity spontaneously. Transfer of atopy is known to occur in non-atopic recipients of BMT from atopic donors. In a study of 12 patients undergoing allogeneic BMT for hematologic malignancies, nonatopic recipients developed positive skin tests with profiles similar to atopic donors. 1 A possible mechanism is passive transfer of memory B-cells which initiate specific-IgE production with a donor pattern. A reverse of this mechanism could occur with the recipient gaining lymphoid precursors with no atopic tendency leading to clearing of atopy. The literature yielded one report of asthma resolving after high-dose chemotherapy and autologous stem cell transplantation The authors suggested that chemotherapy could have resulted in immune system reconstitution, normalization of the T-cell repertoire and resolution of asthma. INTRODUCTION: Primary central nervous system (CNS) lymphomas constitute only a small percentage of central nervous system tumors in adults and are seen more frequently in AIDS patients and immunodeficiency states. They are extremely rare in children, even those with primary immunodeficiency. We present a 4-year-old female with combined immunodeficiency who developed an EBER+ (EBV-associated) large B-cell lymphoma that was confined to the CNS. METHODS: The patient is a 4-year-old female that was being evaluated for combined immunodeficiency who presented to our institution with acute fever and seizure activity. RESULTS: The patient had a history of recurrent pneumonia, otitis media, sinusitis, and upper respiratory infections. She also exhibited failure to thrive, chronic diarrhea, and sen-sorineural deafness. She was found to have a combined immunodeficiency with severe neutropenia and lymphopenia, low IgA, low IgM, and poor specific antibody response to protein and polysaccharide antigens. She had no response to a Candida delayed hypersensitivity skin test. HIV tests were negative. She was thought to have acute meningoencephalitis causing the fever and seizure activity, however bacterial, viral, and fungal studies were negative. She received multiple anitbacterial, antifungal, and antiviral agents. She died secondary to brainstem compression due to severe cerebral edema. Autopsy revealed an EBER+ large B-cell lymphoma that involved about 80% of her brain and spinal cord. No tumor cells were found elsewhere. CON-CLUSIONS: This case represents a rare manifestation of combined immunodeficiency: the development of a primary CNS lymphoma. The tumor cells were found to be EBER+ (EBV-associated). EBV is known to be associated with lymphoma, especially in AIDS and immunocompromised patients. Only 6.5% of primary tumor sites in severe combined immune deficiency patients involved the CNS in the Immunodeficiency Cancer Registry that was instituted in the 1970s.
V. Litvinova * , G. Muzlaev, Krasnodar, Russian Federation.
Introduction: Glyoma is one of the most prevalent diseases among all brain tumors and more than 35% of them are malignant. In the previous investigations it has been shown the immune disorders in patients with glyoma tumor. At the same time it was suggested the possible anti-tumor activity of some proinflammatory cytokines (TNF, IL1, IL8), which can penetrate via haematoencephalic barrier and induce the lysis of tumor cells. The aim of this investigation was to study the serum and spinal fluid concentrations of one of the key immunoregulatory cytokines -gamma IFN and IL18 in patients with glyoma tumor. Methods: The concentrations of the gamma IFN and IL18 have been studied in serum and spinal fluid of 16 patients with glyoma by ELIZA method. In control, the same parameters have been studied in 6 patients with brain trauma. Results: It has been shown that concentrations of gamma IFN and IL18 in serum and spinal fluid was 1.5-2 times higher than in trauma patients (p<0.001). The serum levels of gamma IFN and IL18 in glyoma patients were 82.8 and 28.5pg/ml, accordingly. In trauma patients-44.3 and 16.3pg/ml. The concentration in spinal fluid of the studied cytokines was 1.8 time higher than in control patients. Conclusion: Proinflammatory cytokines gamma IFN and IL18 may be involved in pathogenesis of glyoma and can participate as possible anti-tumor factors of immunity in glyoma patients.
A. Arrey-Mensah * , R.U. Sorensen, New Orleans, LA.
Rationale: Immunodeficiencies need to be ruled out in infants that present with failure to thrive. Patients with T-cell lymphopenia, hypogammaglobulinemia and pancytopenia may have a primary immunodeficiency such as SCID, or a secondary immunodeficiency that may need to be managed differently. Methods: Evaluation of cellular and antibody-mediated immunity of a 15 month old AAF admitted with failure to thrive and chronic diarrhea. oHistory of duodenal atresia corrected by creating a blind duodenal loop and anastomosis of the stomach to the jejunum at birth. o Mass in hypogastrium. Results: Immunologic evaluation revealed: " Lymphopenia ranging 210 to 350cells/ul " Anemia: Hemoglobin 7.6g/dl, Retic 6.8 " ANCs ranging 700 to 2100 " Thrombocytopenia 54000L to 26500L " CD4+: 80 " CD8+: 50 " CD4/CD8R: 1.5 " CD19: 290 " CD56: 190 " MITOGEN RESPONSES were normal: " PHA 46, 397cpm " CON-A, 7, 690cpm " PWM, 36, 168cpm Immunoglobulins: IgG 102mg/dl IgA 80mg/dl IgM 55mg/dl IgE 20 IU/ml Total protein was 3.4g/dl, Albumin was 1.2g/dl The Immunoglobulin-G half-life study was 7 days in our patient: Metabolic imbalance: hypokalemia (1.8mmol/l) hyponatremia (127mmol/l) Hypocalcemia (4.6mg/dl) Blood, stool, urine cultures normal. Stool ova, parasite, virus were negative. HIV-PCR (-) Radiological evaluation: superior mesenteric vein thrombosis, chronic malrotation and volvulus, dilated duodenal blind loop with possible lymphatic obstruction. The patient improved clinically and all immunological markers normalized after surgical removal of adhesions and obstruction. Conclusion: The patient had a secondary immunodeficiency due to Lymphangiectasia. Lymphangiectasia should be considered in the presence of a lymphopenia with normal lymphocyte function and hypogammaglobulinemia accompanied by hypoproteinemia and hypoalbuminemia. Hypogammaglobulinemia and hypoproteinemia were secondary to gastrointestinal losses. The immunological component of 22q11.2 deletion syndrome (also known as DiGeorge syndrome;DGS), hypoplasia of the thymus, is quite variable among patients and provides the opportunity to determine the relationship between thymic function and T cell receptor (TCR) repertoire diversity. Using a novel measure of repertoire diversity based on CDR3 length polymorphism called Hamming Distance, TCRBV repertoire diversity in DGS was found to differ from control subjects by having an overall skewing of receptor expression. As expected from clinical outcomes, there was also great intra-individual variability in DGS TCR repertoires. The degree of repertoire diversity was directly correlated with thymic output as measured by T cell receptor excision circles (TRECS), i.e. greater thymic output resulted in more diverse repertoires (see figure below). This result demonstrates a quantitative relationship between thymic function and repertoire diversity in humans and may reflect the balance between thymic output and peripheral expansion to maintain an adequate TCR repertoire. In addition, it may suggest a basis wherein limited repertoire diversity mediates both immune deficiency and autoimmunity.
TCR repertoire diversity in DGS, as measured by Hamming distance, correlates with thymic output, as measured by TRECS (plotted on a logarithmic scale)
A. Sabra 1* , S. Sabra 1 , H.J. Castro 2 , J. Malka-Rais 2 , J.I. Mendez-Inocencio 2 , G. Santos 1 , J.A. Bellanti 2 , 1. Rio de Janeiro, Brazil; 2. Washington, DC.
A major investigative effort of our laboratory has been directed to the study of non-IgE mechanisms and their role in the immunopathogenesis of food allergy (FA). We have previously reported Th1 and Th2 cytokine alterations associated with several clinical entities that had overlapping disease manifestations affecting the mucosal-associated lymphoid tissues (MALT), of the GI tract (GALT), skin (SALT), nasal (NALT) and bronchial tissues (BALT). The objective of the present study was to evaluate specific immunologic alterations in a group of patients with non-IgE FA. Peripheral blood CD4 and CD8 lymphocyte subset analyses were performed in 10 patients with FA documented by double-blind placebo-control food-challenge (DBPCFC). All patients were treated with an amino-acid based formula (AABF) and then received an open challenge using a panel of commonly offending allergenic food allergens in a normal diet.The clinical picture of all 10 patients with FA were linked to MALT-related manifestations; 8 with GALT symptoms of diarrhea, vomiting, abdominal pain and FTT, 4 with BALT symptoms of asthma, 4 with SALT symptoms of eczema, 3 with NALT symptoms of rhinitis and 2 with edema, ascites and anaphylaxis. All subjects had normal serum IgE and eosinophil levels, negative IgE food RAST tests, normal CD4 (mean 1562 + 368) and very low CD8 (174 + 42) levels in peripheral blood. Abnormal CD4/CD8 ratios >3.5 were observed in all patients. Age-and gender-matched controls revealed CD4/CD8 ratios ranging from 1.5 to 2.5. Both patients with anaphylaxis had CD4/CD8 ratios >6. All patients responded well to AABF. Open challenge to common offending foods from a regular diet (milk, soy, wheat, egg, nuts, beef and chicken), revealed multiple food allergies. After two years of follow-up on an AABF regimen, the 10 patients remain well but allergic to multiple foods. Very low CD8 levels remain as the unique immunological alteration in all 10 patients.These studies suggest that abnormalities of very low CD8 distribution may play a pathogenetic role in non-IgE mediated FA. Since CD8 lymphocytes play a role in immunologic tolerance (IT), it is tempting to speculate that the very low CD8 levels may signal the failure of development of IT in our patients predisposing them to the development of allergies to multiple food components.
Background: Mixed connective tissue disease (MCTD) is a disease taht have caused controversy, while some authorities consider it a distinct rheumatic disease, others believe that it's an early stage of a fully defined autoimmune disease. The distinctive feature is the presence of the U1 small nuclear RNP autoantibodies. Clinical features involve Raynaud's is phenomenon, swollen hands, sclerodactyly, esophageal hypomotility, polyarthritis, and myositis, allof them can be present in others well deined rheumatic diseases. Only aew cases have been described in the pediatric population. Objetive: To determine the frecuency of mixed connective tissue disease in Mexican.Children in a tertiary level institution according to Kasakawa's criteria, Alarcon-Segovia's criteria and Sharp's criteria and establish if a diagnosis of a well defined autoimmune entity was made during the follow up. Methods:Medical charts were assessed with the diagnosis of MCTD between 1988 and 2003 in our hospital. Results: Between 1988 and 2004, 9 , 919 cases of autoinmune diseases were treated; 310 with systemic lupus erythematosus(SLE), 6544 with rheumatoid arthritis(RA), 1, 128 with scleroderma and 1, 937 with dermatomyositis. We found only four cases, 3 of them did not complete the Kasakawa's criteria but the diagnosis was probable according to Alarcon-Segovia and Sharp's criteria. One of them developed SLE after one year of follow up. The case that fulfilled the diagnosis criteria of MCTD; Raynaud's phenomenon, RNP antibody positive, arthritis, lymphadenopathy, restrictive pulmonary disease, sclerodactily and muscle weakness developed a full blown SLE at 10 years follow up. Discussion: The disease is extremely rare in children. We conclude that at least in pediatric age the disease may not exist by it's own, but it's an early stage of a defined autoimmune disease, and the terminology "un differentiated connective tissue disease" is more appropriate to define this cases.
A. Baysan * , H.Y. Song, S. Gupta, L. Yel, Irvine, CA.
Hereditary angioedema (HAE) is an autosomal dominant disease characterized by episodic angioedema of the skin or mucosa of the respiratory and the gastrointestinal systems. HAE is caused by a quantitative (Type I) and/or functional (Type II) deficiency of plasma protein C1 inhibitor, an early component of the classical complement pathway. Attacks of HAE may be lifethreatening and even cause death when the airway is involved. Here, we report a 67 year-old female patient with HAE Type II, who has seven affected family members, two of whom died of laryngeal angioedema. The patient had a history of recurrent swelling of the eyelids, lips, tongue and extremities, and respiratory distress since five years of age. She was hospitalized on several occasions one of which required intubation and assisted ventilation. Laboratory studies, between the attacks, revealed normal serum CH50 and complement C3 levels. Complement C4 level was decreased to 5 mg/dl (N:16-47 mg/dl). C1 esterase function was impaired, 46% (N: greater than 68%) in contrast to normal quantitative C1 esterase. The patient was on long-term danazol treatment for ten years and experienced side effects, most notably hirsutism. Currently, there are limited efficacious and safe treatment options for HAE. The treatment of choice for acute attacks and prophylaxis appears to be the C1 inhibitor concentrate, which is not yet licensed in the US. The present patient emphasizes the need to establish the correct diagnosis and an appropriate management plan in recurrent angioedema.
J. Hajsam * , L. Ponomarjev, Krasnodar, Russian Federation.
Background: The previous investigations indicate on the positive effects of NCIR in different chronic inflammatory and infectious diseases. Nevertheless, the mechanisms of the clinical efficacy of NCIR remain still unknown. The aim of this investigation is the study of the immune disorders in patients with chronic tonsillitis and the immunomodulatory effects of the complex treatment in combination with NCIR. Methods: 55 children with chronic tonsillitis in the age from 7 to 14 years old were under the observation. The T cell receptors (CD3+, CD4+, CD8+, CD16+, CD25+, HLA-DR+) have been studied using flow cytometry method. The cytokines (IL6, gamma IFN and IL18) have been investigated by ELIZA method. The treatment include traditional methods in combination with NCIR. Control group (without tonsillitis) consists of 56 children of the same age. Results: It has been shown that in chronic tonsillitis was dcrease of the number of CD3+, CD25+ and HLA-DR+ cells. The decrease of CD3+ cells was mainly due to decrease of CD4+ cells. At the same time it has been shown the increase in number of CD8+ cells. In chronic tonsillitis have been determined the increase in serum proinflammatory cytokine IL6 level in 3.6 times (p<0.001). At the same time the levels of gamma IFN and IL18 were lower than in control up to 3-4 times. The studied treatment method including NCIR resulted in increase in the number of CD4+ and CD25+ cells. The level of IL6 decreased from 95 pg/ml to 28.4 pg/ml. At the same time the serum concentration of gamma IFN and IL18 increased up to 2.4 and 1.9 times, accordingly. Conclusion: In chronic tonsillitis it has been shown the immune disorders in T cell's subpopulations and cytokine production. The efficacy of NCIR mainly depends on the normalisation in T cellular subpopulations and increase in the concentration of gamma IFN and IL18. Introduction: Viral hepatitis is characterized by suppression of CD4+Th1cell function related to disease severity. The aim of our research was the determination of total IgE concentration and anti-C1q-autoantibodies levels in patients with viral hepatitis C (VHC) and mixed viral hepatitis (VHB+C) and the investigation of their correlation with T cell parameters. Methods: 31 patients with VHC and 11 patients with VHB+C confirmed by PCR were examined. Evaluation of serum total IgE level was performed by ELISA kits produced by "Vector-Best", Russia. Immunophenotyping of peripheral blood mononuclear cells (PBMC) was done by cytometry with monoclonal antibodies to CD3, CD4, CD8, CD11b, CD16, CD20, CD25, CD95 and HLA-DR-antigens. Results: The level of serum total IgE in patients with VHC and VHB+C was significantly increased in all groups studied, especially in acute hepatitis C (526.8±129.4 MU/ml, P<0.05) compared with the control group. Analysis of PBMC subpopulations in patients with VHC and VHB+C was done related to the total IgE level: Group I -0-200 MU/ml; and Group II ->200 MU/ml. In patients with viral hepatitis and high total IgE level, the content of CD3+T-lymphocytes, CD4+T-cells and CD4/CD8 ratio were significantly decreased compared with the control group (P<0.05). More notable changes were found in patients with acute VHC and VHB+C. The increase in CD20+-cell content was seen in groups with both low and high levels of total IgE. The content of CD16+-cells in patients with high levels of total IgE was also increased (P<0.05). Conclusion: Patients with VHC and VHB+C had significantly greater levels of total IgE compared with the control group (P<0.05). The increase in total IgE levels in patients with viral hepatitis is associated with imbalances of T-lymphocyte subpopulations, including a decrease in CD4+T-cells, and an increase in B-and NK-cells. Title: Occupational airway allergy among health care workers (HCW) with latex allergy. Introduction: For the last years the frequency of latex allergy has increased. Health care workers (HCW) is the risk group of this diseases. Latex allergy symptoms occure in different organs -including skin, conjunctive, nose and bronchi. Study aim:The aim of this study was to estimate the incidence of airway allergy in group of HCW with latex allergy. Materials and methods: The investigations were carried out in a group of 252 HCW, aged 21-67 (average age 36, 3). There were two hundred and eight women and forty four men in the group. Investigation consisted of questionaire examinations, skin prick tests (latex), patch tests (rubber additives), sIgE (latex) and spirometry. Results: Seventy eight (31%) HCW reported undesirable effects after the contact with latex products. Fourty (15, 9%) HCW reported symptoms of airway (nose and bronchi). Latex allergy (SPT and/or sIgE and anamnesis positive) was diagnosed in 49 (19, 4%) cases. The symptoms concerned with: skin, nose and conjunctive (12 cases, 25%); skin and conjunctive (2 cases, 4%); nose and conjunctive (2 cases, 4%); nose and skin (5 cases, 10%); bronchi, skin, nose, and conjunctive (2 cases, 4%) and only skin in 26 cases (53%). Conclusions: The incidence of occupational airway allergy in group of health care workers with latex allergy is high (43% of all cases). Latex allergy symptoms usually affect skin, but sometimes it includes also other organs -conjunctive, nose and seldom with bronchi. The incidence of anaphylaxis is increasing. The Food Allergy and Anaphylaxis Network wishes to expand the use of injected epinephrine by first responders to allergic emergencies. In Indiana, there are 7, 500 First Responders, 14, 900 Basic EMTs, 1, 350 Advanced EMTs, and 2, 500 paramedics. The use of injected epinephrine was only permitted by paramedics and advanced EMTs (17% of all responders). In 2002 a bill was introduced to expand the use of injected epinephrine by EMS personnel in the event of an allergic emergency. It was sponsored by The Indiana Allergy Asthma and Immunology Society and the Emergency Medical Services Commission of Indiana. On July 1st 2003 Senate Bill No. 213 took effect permitting all first responders to administer, without restrictions, injected epinephrine. Once the legislation passed it became the responsibility of the Medical Director (MD) of each ambulance service in the state to implement the change. In an attempt to assess the impact of this legislation we surveyed each of the MDs in the state 9-12 months after the passage of the Bill. MDs were notified of the legislation by memo and public meetings. In addition each MD received a copy of the legislation. Of the 266 MDs, 56 (25%) responded to the survey. RESULTS: 1. Unaware of the Legislation: 14 (25%) 2. Aware of legislation but no implementation: 9 (16%) 3. Aware of legislation with implementation restricted to basic EMTs: 29 (52%) 4. Aware of legislation and implementation at all levels: 4 (7%) CONCLUSIONS: Twenty-five percent of MDs were unaware of legislation. Among those that implemented changes the majority (52%) permitted use by Basic EMTs only. Allergists, Lay organizations, and EMS commissioners need to assure implementation of legislation with all MDs within the state.
A. Khadavi 1* , B. Silverman 2 , A. Schneider 2 , 1. Great Neck, NY; 2. Brooklyn, NY.
Rabbit anaphylaxis is extremely rare, with one documented case upon inhalation only. We describe a patient with severe anaphylaxis upon consumption of a rabbit. A 6-year-old female with a 3-year history of asthma and allergic rhinitis was presented for evaluation. The patient complained of worsening asthma and rhinitis symptoms in the home and upon exposure to outdoor pollen. Further history revealed the family had a rabbit as a pet. Laboratory testing showed her total IgE was 865 kU/L, RAST results were normal for tree, ragweed and molds (<0.35 kIU/L). Positive results were found for ragweed, dust, cockroach, cat, dog, mouse, peanut and rabbit epithelium (8.43 kIU/L, class IV). Among other environmental control measures, the family was advised to eliminate the rabbit from the home environment, as it could be a potential trigger for their daughters allergy symptoms. Two days later, the patient presented to the emergency room with wheezing, coughing and angioedema of the hands and face. She was treated with albuterol, diphenhydramine and oral steroids. The parents said they followed all of our instructions and did not know why anaphylaxis occurred. Further questioning revealed that the family consumed the pet rabbit on the same night preceding the anaphylactic reaction. This was the first time the daughter ate rabbit. The parents assumed that only exposure to the live rabbit would worsen her allergy and asthma symptoms, never expecting an allergic reaction via ingestion. They were advised not to feed their daughter rabbit again and were given a prescription for self-injectable epinephrine. This demonstrates either complete identity, partial similarity or cross reactivity between inhaled and food allergens, as has been noted previously with certain other foods such as garlic and crustacean proteins. Physicians need to advise food allergic patients that an allergic reaction can develop upon inhalation of the food, as seen with peanuts. But also respiratory sensitization to an allergen can lead to allergic symptoms upon its ingestion.
T. Nsouli 1* , J. Scheiner 2 , J. Malka-Rais 2 , J.A. Bellanti 2 , 1. Burke, VA; 2. Washington, DC.
The safety of selective cyclooxygenase-2 (COX-II) inhibitors in patients with known NSAID-induced allergic reactions has not been definitely established and is still open to debate. In the present report, we describe two patients with hypersensitivity reactions to naproxen, the first characterized by a systemic anaphylactic reaction and the second by localized urticaria following ingestion of the drug. The first case was a 56 y/o WF with a history of osteoarthritis who, 15 minutes after the ingestion of 375 mg of naproxen, developed generalized pruritus, urticaria, laryngeal edema and hypotension. She was treated in the ER with epinephrine, diphenhydramine and IV corticosteroids. Epicutaneous and intradermal skin testing to celecoxib revealed negative results similar to a control. An oral challenge with celecoxib was well tolerated by the patient without any adverse responses. The second case was a 57 y/o WF with a known history of chronic urticaria and osteoarthritis requiring regular use of naproxen. A complete allergic and immunologic workup was negative. Upon discontinuation of the drug there was resolution of the urticaria. An oral challenge with celecoxib was well tolerated by the patient without adverse sequelae. These two case reports exemplify two extremes in the spectrum of adverse allergic reactions to naproxen, a non-selective COX-I and COX-II inhibitor, one systemic, the second localized and suggest that the pathogenesis of these symptoms was most likely pseudo-allergic in nature and not immunologically-mediated. The dissimilar chemical structures of naproxen and celecoxib together with their differing mechanisms of action suggest that the absence of allergic reactions to challenge with celecoxib, a COX-II inhibitor, may be related to a lack of cross-reactivity between the two drugs. Although these findings suggest that oral celecoxib could be a possible safe alternative in patients with naproxen-induced drug reactions, it would be prudent to first conduct careful challenges with the drug in a well-equipped medical setting where clinical acceptability and tolerability could be safely assessed. INTRODUCTION: Most fixed and removable dentures are made from casting alloys. Many orthodontic appliances are also fabricated from metallic biomaterials. It has been documented in vitro and in vivo, that metallic restorations release metal ions mainly due to corrosion. Those metallic ions may be distributed systemically and locally and could pay a significant role in the induction of oral or/and systemic immunoinflammatory conditions. This study determines the frequency of sensitization to metal salts and clinical characteristics in the group of patients with complaints related to adverse effects of dental alloys. METHODS: 31 patients (29 women and 2 men) aged 35-71 years with symptoms assumed to adverse effects of dental alloys were studied. All patients were studied with base metal salts, including Cu 2+ , Co 2+ , Cr 6+ , Mg 2+ , Mn 2+ , Ni 2+ , Ti 3+ , Zn 2+ using patch tests. All patch tests substances were 3% salts in petrolatum. The patch tests were conducted in accordance with recommendations of the ICDRG. Occlusion time was 2 days, and patch tests were read when removing the patches (Finn Chambers on Scanpor, Epitest Ltd Oy, Tulusa, Finland) and 2 to 4 days later. The total number, percentage of irritant and allergic patch test reactions were calculated. RESULTS: In 25 of 31 patients (80%) sensitivity to base metals used in dental restorations was noted. Symptoms included burning mouth (45%), metal taste (19%), electrical sensations (11%), dry mouth (9%), and taste irritation (12%), but 16/31 patients (54%) had no symptoms. Local gingivitis (19.3%), anomalies of the tongue (12%), stomatitis (12%) and lichenoid reactions (6%) were often seen. The most frequent patch test reactions were caused by Ni (45%), Cr (41%) and Co (19%) . CONCLUSION: This study demonstrated higher frequency of hypersensitivity reactions to Ni, Cr and Co in this group of patients often having symptoms such as burning mouth, metallic taste, electrical sensation, local gingivitis, and anomalies of the tongue.
W.Y. Mak * , S. Kearney, B. Silverman, A. Schneider, Brooklyn, NY.
The process of intravenous drug desensitization often involves simple but tedious calculations. Miscalculations may arise due to human error. For patients who are truly allergic to the drug in question, such errors can be life threatening, if not fatal. We propose the use of a spreadsheet to minimize such calculation errors. Spreadsheets, such as Microsoft Excel, IBM Lotus 1-2-3, and Corel Quattro Pro, are used extensively in finance for tedious and repetitive calculations. This property of a spreadsheet makes it an ideal tool to assist with any drug desensitization protocol. We chose Microsoft Excel for its availability at our institution. A general template was initially created with equations in specific cells which were based on the protocols listed in Patterson's Allergic Diseases, 6th Edition and Middleton's Allergy: Principles and Practice, 5th Edition. By inputting specific numbers, such as the amount of drug and volume of diluent into key cells of the spreadsheet, the program will automatically calculate the protocol for the given intravenous drug. An example of our Pipericillin protocol is listed below. We find that the use of a spreadsheet not only minimizes calculation errors and hence reduces the likelihood of avoidable reactions; but also decreases our preparation time for the desen-sitization protocol. We recommend its use for all allergists performing drug desensitizations.
States 25 years ago, the infestation of homes across the Northeast, Southeast and Midwestern states with these insects during the Fall and Winter months has become increasingly common. In the last 5 years, several investigators have published case reports of patients with allergic rhinitis, conjunctivitis and asthma symptoms associated with suspected inhalational exposure to high levels of proteins from these beetles. We report a series of 5 patients who presented with a spectrum of various allergy complaints ranging from symptoms of allergic rhinitis, asthma, urticaria, angioedema and acute anaphylaxis (with documented elevated serum tryptase) on exposure to high numbers of Multi-Colored Asian Ladybeetles(MALB.) METHODS: We performed Western blotting with the patients' serum and a whole-body ladybeetle extract made from confirmed H. axyridis obtained from one of the infested homes in that region. RESULTS: Blots with the patients' serum revealed IgE binding to 3 different proteins with molecular weights approximately 8, 28 and 78 kD. The serum from two patients bound a 28 kD protein possibly similar to the 30 kD protein previously identified by Yarbrough et al. JACI 1999; 104; 704-5 . IgE from four patients bound to an 8 kD protein not previously reported. Lastly, serum from two patients revealed IgE binding to a 78 kD protein possibly similar to the heavier proteins mentioned in an abstract by Magnan et al. JACI 2002; 109; 580 . CONCLUSION: We present five patients with specific IgE to MALB and allergic symptoms on exposure to high levels of MALB. We conclude that MALB are likely a significant source of several different allergenic proteins and that MALB are increasingly becoming a significant cause of a wide variety of hypersensitivity reactions across the United States. As multiple exposed subjects and several entomologists report that these beetles bite humans, we speculate that a wide range of IgE-mediated symptoms including urticaria, angioedema and anaphylaxis can occur by exposure to proteins by inhalation, direct contact and possibly by inoculation of these proteins into the skin by the bite or scratch of this beetle.
A CASE REPORT AND LITERATURE REVIEW. C.S. Taylor 1* , S. Ramesh 2 , 1. Getzville, NY; 2. Buffalo, NY.
Introduction: Lentils belong to the Legume family and are the staple ingredient of the ethnic Indian diet. Lentils have been shown to cause allergic reactions and even anaphylaxis. However, little research has been done to distinguish the types of lentils used commonly in the Indian diet and their various hypersensitivities. Some of these lentils include the black gram (Phaseolus mungo), mung bean and split chick peas (Bengal gram). Case Report: We report a 19-month-old Indian boy who presented with severe atopic dermatitis since the age of four months. His dermatitis was exacerbated by the ingestion of peas and beans and resolved with the avoidance of such. At nine months of age, the child was introduced to boiled mung beans and subsequently developed lip swelling within a few minutes. A similar reaction occured with split chick peas. Physical exam at consultation revealed severe eczema. Skin tests using commercial extract revealed 5+ response to peanut (he had never eaten peanuts), soybean, pea and egg. Subsequent skin tests at the follow up visit to prepared reagents revealed much greater than 5+ response to mung bean, chick pea, split chick peas, and black gram. The patient developed a systemic response during testing which required Epinephrine. Discussion: Legume allergy (other than peanut, soy and peas) is rare in the Unites States but has been reported in Asia and the Mediterranean area. It has been reported in one case series that patients with lentil allergy react to more than one lentil. There is a five percent cross reactivity between peanut and other legumes such as soy and peas. However, the extent of cross reactivity between peanut and the other legume sub-groups (ie. lentils) is not well documented. There also appears to confusion in the labeling of the various lentils used in ethnic diets. Conclusion: This case has been presented to make allergists aware that there are many differnt types of lentils that can cause hypersenstivity reactions and the importance of considering ethnicity and dietary habits in evaulating for food allergy. Background: Epinephrine is the drug of choice for the treatment of anaphylaxis however it is frequently underutilized. One possible reason is the fear of adverse cardiac effects. The most common side effects of epinephrine are palpitations, tachycardia, sweating, nausea, vomiting, respiratory difficulty, pallor, dizziness, weakness, tremor, headache, nervousness, anxiety and arrhythmias. A previous study showed that administration of epinephrine, in a small number of healthy adults did not cause any significant cardiac adverse events and vitals sign changes were not clinically significant. The purpose of this retrospective analysis is to determine the safety profile of epinephrine in a large number of patients that were administered epinephrine for treatment of anaphylaxis that occurred in a physician's office. Methods: All patients in an allergy office, that were administered epinephrine for acute anaphylaxis between 1999-2004 were selected for this retrospective analysis. A chart review for adverse events and vital was conducted. Vital signs and side effects had been monitored every 5 to 10 minutes for minimum of 30 to 90 minutes after the administration of epinephrine. Results: 105 patients between the ages of 8yrs to 55yrs received 128 injections of epinephrine. After an injections of epinephrine 60% of the patients had a pulse between 50-90, 27% between 72-100, and 13% between 102-110. Systolic blood pressure determined 81% of patients to be between 80-140, with 10%, between 142-160, and 7% between 162-170, and 2% between 172-180. Concurrently, diastolic blood pressure was found to have 94% between 50-90, 3% between 92-100 and 3% betweem 102-110. The most common reported side effects were tremor, headache and pallor. Any rise in blood pressure and heart rate after epinephrine was transient and returned to normal within 90 minutes of observation. There were no serious side effects. All patients responded to the epinephrine and were able to go home. Conclusions: This retrospective analysis revealed that the administra-tion of epinephrine is safe and effective for the treatment of acute anaphylaxis in an outpatient setting. The use of epinephrine for treatment of anaphylaxis is life-saving and its use to treat non-cardiac or elderly patients who have anaphylactic reactions should be encouraged. Purpose: A clinical pathway was established to decrease the use of vancomycin in surgical patients with self-reported penicillin (PCN) allergy. Methods: In 2001, our institution developed a preoperative evaluation (POE) clinic for elective surgical patients. In June 2002, on-site, same-day allergy consultation and penicillin skin testing was made available for preoperative patients with self-reported PCN allergy. We reviewed the antibiotic recommendations, the actual administration of vancomycin, and compliance by the surgeons with our recommendations from July 1, 2002-September 16, 2003. Results: During this time, 11, 819 patients were seen for their preoperative medical exam at the POE clinic, and 1204 were evaluated for PCN allergy. Of these, 1120 patients met IRB standards to participate in the study. The mean age of the patients was 60 years. The top three surgical specialties represented in the POE clinic were orthopedic (28.4%), urology (22%), and neurosurgery (15%). Of the 1120 patients, 1031 underwent skin testing for PCN allergy. Eighty-five percent (85%) or 951 of these patients with a history of PCN allergy were recommended to use -lactams such as cefazolin, and 164 (15%) were recommended to avoid -lactams. Forty-three (43) or 4% had one or more positive skin tests to PCN. Of the 1120 patients, 957 patients actually received pre-operative antibiotics. Of these 957 patients, 718 (75%) of those received cefazolin, 60 (6%) received clindamycin, 33 (3%) received ciprofloxacin, 25 (2%) received levofloxacin. Some patients received more than one antibiotic for prophylaxis. Only149 (16%) patients received vancomycin. Conclusions: Establishment of a clinical pathway in a preoperative clinic that includes allergy testing and consultation reduced vancomycin use to only 16% in surgical patients with a history of penicillin allergy.
H. Yarmohammadi * , A. Nowak-Wegrzyn, New York, NY.
Introduction: Anticonvulsant hypersensitivity syndrome is a potentially fatal drug reaction with cutaneous and systemic reactions to the arene oxideproducing anticonvulsants. In most cases, the hallmark features of fever, rash, and lymphadenopathy are accompanied by multi organ-system abnormalities. Fatal outcomes are most often associated with liver failure. Recognition of the syndrome, which may have variable presentations, is the key to prompt discontinuation of the drug, close monitoring, and management. Case 1: A 16y/o male received dilantin for seizure prophylaxis following craniopharyngioma resection. Fourteen days later he was readmitted for fever and CSF leak from surgical site. He was started on ceftriaxone and vancomycin empirically; an LP and pan culture was done. He continued to have low grade fever and, on the 6th day of admission, developed a maculopapular rash on trunk. On day 8th LFTs increased and CBC showed eosinophilia. Antibiotics were stopped but LFTs continued to rise. On Day 10, dilantin was stopped and LFTs normalized in 2 days, fever stopped and rash disappeared. Case 2: A 17 y/o girl was admitted to the hospital with generalized rash, facial edema and fever (39 degrees C). She developed a pruritic maculopapular erythematous rash over her trunk and face 2 weeks prior to admission. She then developed high fever. Three months prior to this visit she had been started on phenytoin (300mg/kg) for control of grand mal seizure. Physical exam revealed cervical and axillary lymphadenopathy. She had elevated WBC (13, 400), eosinophilia (20 %), and elevated LFTs. Phenytoin was stopped upon admission but 24 hours later she continued to have fever, elevated LFTs and devel-oped erythema in her mouth. Treatment with IVIG and prednisone was initiated and resolution of symptoms was seen within 2-3 days after therapy. Conclusions: The timely recognition of anticonvulsant hypersensitivity syndrome is important, because accurate diagnosis prevents potentially fatal re-exposure and influences subsequent anticonvulsant treatment options. IVIG and prednisone should be considered in situations where prompt improvement of the LFTs or clinical symptoms is not observed.
The recently published results of a telephone survey about the prevalence of seafood allergy in the US indicate that seafood allergy is a significant health concern. Aim of the present study was to retrospectively review our data on the topic. We have interviewed 7391 subiects attending our Allergy outpatients about any suspected food allergy. Over 95% were 14 years or older. Any reaction to food was reported by 33% of the patients, more frequently by women. Of these 2419 patients, 125 reported reactions to seafood (5%) with an overall prevalence of seafood reactions of 1.7%: 50 to fish (0.7%), 58 to shellfish (including mollusks) (0.8%) and 17 to both (0.2%). In the case of the reactions to fish it is quite possible that shellfish is also included, as the patients were often unable to tell the role of finfish from shellfish apart. This is most probably due to the fact that seafood dishes or a complete seafood meal in Italy generally include both shell and finfish. In only less than half cases there was a convincing relationship between the ingestion of seafood and the reaction. The reactions reported were: gastrointestinal (17), non life-threatening angioedema (15), mild oral allergy syndrome (13), acute urticaria (9), asthma (3), rhinoconjunctivitis (2). The gastrointestinal reactions might not all be true (IgE-mediated) allergic reactions, but also toxic. In conclusion, even in a selected population like that attending an Allergy Clinic and using a broad definition of adverse reaction, seafood allergy appears to be a rare phenomenon and of limited clinical impact, the prevalence of moderate to severe reactions (angioedema and asthma) in the whole selected population being 0.2%. Clopidogrel (Plavix) is an antithrombotic agent currently used to prevent thrombotic cardiovascular events by inhibiting adenosine diphosphate (ADP)dependent platelet activation. Clinically, it has been used in patients with aspirin intolerance or who developed neutropenia from ticlopidine. There have been reported cases of clopidogrel causing rash and urticaria. Often these patients are told they are allergic to clopidogrel and should not take it again, despite the fact that no workup was ever performed to elucidate whether the reaction was indeed immunologic in nature. A review of the literature revealed no reported attempts at desensitizing a patient to clopidogrel after a presumed immunologic drug reaction. We present the case of a 49 year-old female who initially took clopidogrel (75 mg. P.O. daily) for transient ischemic attacks. After tolerating the medicine for five days, it was replaced with an aspirin/warfarin combination, which she took for the next five days. Reintroduction of clopidogrel a week later was uneventful, until she developed a pruritic, maculopapular rash on the 5th, through 7th days of restarting therapy. At that time, she was not taking any other medications, and had no cardiopulmonary or gastrointestinal complaints. She had discontinued the clopidogrel and was asymptomatic during our consultation. Skin testing was done using clopidogrel prepared at concentrations of 1 mg/ml and 1/10 mg/ml. At the same time, control skin testing on three non-atopic subjects was performed and produced no reaction to either epicutaneous or intradermal testing. By contrast, the patient had a positive skin reaction at both concentrations on intradermal testing. The patient was hospitalized for an oral desensitization where clopidogrel dilutions were prepared by the hospital pharmacy. The patient tolerated an initial dose of 0.02 mg. Serial three-fold increases in concentration were given every 15 minutes, until a total cumulative dose of 77 mg. was reached. The patient tolerated the entire procedure and suffered no adverse reactions upon continuation of the treatment. This demonstrates the utility of oral desensitization to clopidogrel in patients with a positive skin test who require this medication. Lamotrigine is a non-aromatic anticonvulsant with desirable pharmacological profile. The most common idiosyncratic reaction in children is rash (10-20%). Severe cutaneous adverse reactions and systemic hypersensitivity reactions are uncommonly reported. Method: Case presentation An 11-yearold Caucasian female was prescribed lamotrigine in escalating dose for her first generalized seizure. A week later she developed a pink rash on her cheeks gradually progressing to her trunk, hands and feet. Three days later she was seen in the ER and treated for possible streptococcal-pharyngitis with fever and rash. Oral Penicillin-V treatment was initiated. The rash continued to spread all over her body with mild pruritis and sores on lips and mouth. Few blisters were noted in left ear, hands and feet. Later Lamotrigine was discontinued. Oral steroids were prescribed. She continued to develope new blisters, rash and hemorrhagic plaques and dysuria. She was later transferred to our institute. The physical examination was significant for afebrile girl without pallor and icterus. Bilateral conjunctivitis without keratitis evident. Tender cervical lymphadenopathy was palpable. Multiple ulcers on lips and gingiva were seen. Several targetoid lesions on trunk and extremity were noted along with few hemorrhagic plaques on extremities. Superficial sloughing of distal fingers and toes was noted. Nikolskys sign was not demonstrable. The systemic examination was unremarkable. Laboratory tests: Hemoglobin 14.2g/dl, WBC-Normal range without eosinophilia. Normal PT/aPTT and INR. Liver function tests showed elevated SGPT-1380iu/ml and SGOT-225iu/ml with normal bilirubin. Urine analysis was normal. Serology for CMV, EBV, HSV and Hepatitis A and B was negative. Skin biopsy showed full thickness epidermal necrosis and sub epidermal clefts. Aggressive supportive therapy was initiated. Corticosteroids were continued for five more days. Prior to being discharged from hospital the rash had dried and most lesions faded. The blisters and oral ulcers had healed. The liver enzymes had decreased. Conclusions: We report an occurrence of Stevens-Johnson syndrome with lamotrigine in a young child. In the literature severe reactions are associated with higher doses or rapid escalation of the dose, and concomitant use of valproate. Early recognition and withdrawal of medication is necessary to improve the outcome. Introduction: In patients with a history of penicillin (PCN) allergy and negative PCN skin tests to major and minor determinants, 97-99% of patients will tolerate PCN administration without risk of an immediate reaction. In fact, Middletons Allergy Principle & Practice reported that no life-threatening false-negative reactions have been reported when PCN was administered after a negative PCN skin test. We describe a case in which a patient with a history of PCN allergy and negative PCN skin tests to the major and minor determinants experienced life-threatening anaphylactic shock when administered piperacillin/tazobactam. Case History: A 38-year-old woman with Crohns disease was admitted for treatment of an enterocutaneous fistula. Three months before admission, the patient reported a severe reaction to either piperacillin/tazobactam or intravenous (IV) lorazepam needing respiratory support in the intensive care unit. In order to delineate this problem, an allergy consultation was obtained. Serum IgE antibodies to PCN, measured by a commercial CAP System radioallergosorbent test (RAST) fluoroenzymeimmunoassay (FEIA; Pharmacia and Upjohn, Uppsala, Sweden), and PCN skin tests to major and minor determinants were negative. A skin test (prick and intradermal) to piperacillin/tazobactam at 4.5mg/ml was also negative. Five minutes into receiving 3.375 grams of piperacillin/tazobactam IV, the patient reported feeling lightheaded, flushed, nauseated, and diaphoretic. The blood pressure decreased to 80/50 from a baseline of 110/60, heart rate 150/minute and appeared toxic. No wheezing or rash was noted on physical examination. Patient was treated with IV epinephrine, diphenhydramine, and dexamethasone and recovered without sequela. Serum tryptase, drawn 1 hour after the beginning of the reaction, was elevated at 56.3 ng/ml but decreased to 17.6 ng/ml 12 hours later. Complement levels were normal. Conclusion: Despite a very high negative predictive value of a negative PCN skin test to the major and minor determinants and reports that no life-threatening false-negative reactions have been reported when PCN is administered after a negative PCN skin test, physicians need to be very cautious in administering piperacillin/tazobactam and other b-lactams in patients with a history of severe reactions such as anaphylaxis to past PCN administrations.
A. Majmundar * , D.A. Khan, Dallas, TX.
Introduction: A variety of adverse drug reactions have been reported after therapy with allopurinol. Successful protocols for desensitization to allopurinol have been developed. We report a case of a patient who was successfully desensitized to allopurinol only to develop DRESS after four months of allopurinol therapy. Methods: A 57 year old man was referred to our department with a remote history of rash and fever resulting in hospitalization after initiation of allopurinol. Due to severe gouty arthritis unresponsive to colchicine and requirement of chronic steroids, it was recommended to attempt allopurinol desensitization. Based on the history of his prior reaction, a slow desensitization protocol was performed beginning with allopurinol 10μg and increasing the dose weekly to 25μg, 50μg, 100μg, 200μg, 500μg, 1mg, 5mg, 10mg, 25mg, 50mg, and 100mg. The patient tolerated the entire desensitization protocol without adverse reaction and was initiated on daily allopurinol at 200 mg per day. Results: Four months after desensitization and daily allopurinol use, the patient developed fevers and an acute maculopapular eruption on his back and abdomen without mucosal involvement. Laboratories demonstrated eosinophilia of 936 cells/mm 3 , elevated AST of 101, ALT of 102, and GGT of 163 U/L. He was treated with prednisone 80mg a day which was tapered weekly over 5 weeks with successful resolution of his symptoms, eosinophilia and transaminitis. Conclusion: While desensitization to allopurinol can be safely accomplished, allergists need to be cognizant of the potential for delayed serious drug reactions such as DRESS. Wiskott Aldrich Syndrome is an immunodeficiency characterized by eczema, pyogen infections, and mixed immunodeficiency.We describe a male seven-month old, perinatals antecedents without importance who had an ulcer in site of application of BCG. Non-blood relatives, healthy parents. At twomonths-old, he initiated with continuous fever, not quantified, treated with multiples antibiotics without resolution, he was hospitalized, plaquetopenia and anemia were diagnosed, he received a red globules and plateles transfusion, one week after he presented a disseminated dermatosis characterized by erythema and desquamation, at four-month-age presented right axillary adenomegaly, hepatoesplenomegaly and recurrent bilateral media otitis for what was hospitalized in our institute. He was malnutrition, bad general condition, febrile, with disseminated dermatosis affecting the head, trunk and extremities characterized by erythema and desquamation, in addition he had left ankle cellulitis, right axillary adenomegaly, hepatoespenomegaly. During his hospitalization he presented left hand cellulitis, hairy skin abscess, oral candidiasis, required surgical treatment by econdary compartimental syndrome because cellulitis of left ankle. Persistent hemogram reported thrombocytopenia with normal platelet volume, blood cultives were positive for grampositive bacterias, isoaglutinines, were normal. Immunoglobulines were elevated for the age range, He received antimicrobial and antifungic treatment. But he died. In the autopsy timic alymphoplasia was reported, cortical lymphoid depopulation in lymphatic ganglia and spleen, disease by disseminated cytomegalic inclusion, multifocal pulmonary pneumocystosis, BCGitis, disease graft versus guest. . With the previous features we concluded in a compatible mixed immunodeficiency with Wiskott-Aldrich syndrome with particular characteristics that make this case interesting. The patient course with cellular Immune deficiencie with thrombocytopenia and eczema, even when he didn't have platelet sizing diminished, we consider that the patient had a severe of Wiskott s Aldrich syndrome and at the moment we are Awaiting result of genetic study UASP gene. Background : Hypersensitivity to mosquito bites (HMB) is a disorder characterized by necrotic skin reaction and systemic generalized symptoms subsequent to mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer cell leukemia/lymphoma. We describe here a Korean child who had HMB associated with chronic EBV infection and natural killer cell lymphocytosis. Case : A 5-year-old male was admitted with well-demarcated necrotic skin lesions and severe swelling on right ear lobe developed after mosquito bites. He had suffered several similar symptoms since last summer, which complicated as deep scars on skin. Hepatosplenomegaly or peripheral lymphadenopathy was not detected. Laboratory tests showed WBC 7, 280/mm3 (neutrophil 39%, lymphocyte 56%), total eosinophil count 156/mm3, IgE by PRIST above 1, 000 IU/m. Immunoglobulin levels were normal. Specific IgE for Aedes communis by CAP was negative. Lymphocyte subset analysis demonstrated increased NK cells (CD16+CD56, 43%) and decreased CD3 and CD4 cells. IgM for anti-nuclear antigen (EBNA), IgM for viral capsid antigen (VCA) and IgM for anti-early antigen (EA) DR to EBV were negative. But the levels of anti-VCA IgG (> 200 U/mL), anti-EA DR IgG (> 150 U/mL) and anti-EBNA IgG (62 U/mL) were increased. Type A EB virus was demonstrated in blood mononuclear cells by DNA PCR method, and EBER in situ hybridization was negative in necrotic tissues. Immunostaining with NK-cell marker (CD56) revealed many immunoreactive cells with the perivascular inflammatory infiltrates in tissue. Skin patch tests for Mosquito allergen (Aedes togoi and Culex pipiens) showed positive response to C. pipiens. Introduction: Scimitar syndrome is a congenital anomaly resulting in anomalous pulmonary venous return from the right lung to the inferior vena cava.
Recurrent respiratory infections have been associated with Scimitar Syndrome. Methods: We report on a 16 year-old adolescent female who presented to Immunology Clinic with recurrent pneumonias. Results: The patient presented with numerous recurrent pneumonias, multiple ER visits, and hospitalizations. She complained of intermittent chest pain, cough, fatigue and exercise intolerance. The patient had a large secundum atrial septal defect surgically corrected at 5 years of age. A cardiac echo obtained at 7 years of age revealed RVH, but was normal at 9 years of age. She was a known atopic asthmatic. Previous immunologic workup was normal with IgA 183 (33-202), IgG 1290 (633-1280) and IgM 97 . At presentation to our clinic pulmonary functions were FVC of 79% and FEV1 of 78%. Review of previous chest radiographs showed chronic changes with an opacity partially obscuring the right hemidiaphragm. A high resolution chest CT-scan showed a large irregular venous structure extending through the right chest joining the inferior vena cava above the liver consistent with Scimitar Syndrome. The patient was referred to Pediatric Cardiology who recommended surgical correction. Conclusion: Scimitar syndrome may present as recurrent pneumonias and chronic lung disease. A high resolution chest CT scan may be useful in delineating this disorder. Background: Laryngomalacia is the most common cause of stridor in infants but only rare reports exist of clinically relevant laryngomalacia in adults. Objective: To present a case of laryngomalacia in an adult with significant respiratory symptoms initially attributed to asthma. Methods: An 18 year-old female with a history of allergic rhinitis and gastroesophageal reflux disease presented to the allergy clinic for further recommendations regarding a prior diagnosis of asthma poorly controlled on inhaled fluticasone, montelukast and albuterol. The patient was clinically diagnosed with asthma at age 13 due exercise related symptoms. The symptoms progressed and intermittent trials of various inhaled steroids provided minimal relief. On evaluation, the patient described constant wheezing which occurred only on inhalation and originated from the throat. Symptoms did not respond to albuterol use three to four times a day, rhinitis control and long-term, high-dose, antireflux therapy. Baseline spirometry was normal. Histamine bronchoprovacation and fiberoptic laryngoscopy were performed for further evaluation. Results: Histamine challenge was positive with a 33% decrease in FEV1 with 1 mg/ml histamine. However, laryngoscopy revealed redundant airway tissue most notable over the right arytenoid cartilage, consistent with laryngomalacia, which prolapsed into the laryngeal vestibule significantly obstructing the airway on inspiration only. The patient was referred to otolaryngology and surgical excision using a carbon dioxide laser was performed with subsequent improvement in symptoms and decreased asthma medication use. Conclusions: We report an unusual case of laryngomalacia in an adult presenting as asthma, which was successfully treated with laser surgical excision.
Laryngoscopy of the patient revealing redundant airway tissue most notable over the right arytenoid.
C. So 1* , S. Kuhl 2 , 1. Davis, CA; 2. Mather, CA.
C. So, S. Kuhl U.C. Davis Medical Center, Sacramento, CA & Sacramento VA Hospital, Mather, CA BACKGROUND: Wheezing is an uncommon manifestation of phrenic nerve dysfunction. OBJECTIVE: We offer a description of wheezing attributable to phrenic nerve dysfunction to remind clinicians that dyspnea and wheezing can be caused by cor pulmonale which can be caused by phrenic nerve dysfunction. METHODS: A 71-year old male non-smoker presented with chronic dyspnea and occasional wheezing for the last decade. The patient had a remote history of pericardial stripping for presumed tuberculous pericarditis. He also had a non-productive cough and orthopnea. Dyspnea was exacerbated by putting his hands over his head and bending over. He had been treated with inhaled corticosteroids and bronchodilators without relief. RESULTS: Repeated chest x-rays showed a chronically elevated right hemidiaphragm. Pulmonary function tests showed a restrictive pattern with: FEV 1 1.2 (40%), FVC 1.59 (36%), TLC 3.23 (49%), DLCO/VA 4.54 (125%) and no bronchodilator response. Left heart catheterization was normal while right heart catheterization showed elevated pulmonary artery pressures (56/20) and he was subsequently diagnosed with cor pulmonale. Cardiopulmonary exercise testing showed an increase in minute ventilation which was achieved predominantly by an increase in respiratory rate rather than to an increase in tidal volume suggesting restrictive or interstitial lung disease. Chest CT showed left ventricular enlargement and no evidence of interstitial lung disease. A fluoroscopic sniff test was performed and showed paradoxical movement of both diaphragms. He was diagnosed as having diaphragmatic dysfunction as a result of phrenic nerve injury from prior pericardial stripping. CONCLUSIONS: Wheezing and chronic dyspnea can be related to phrenic nerve dysfunction. A review and discussion of various causes of phrenic nerve dysfunction, including autoimmune causes, is offered. Patients with a history of prior cardiothoracic surgery who present with recalcitrant dyspnea and wheezing may benefit from evaluation for phrenic nerve dysfunction. Background: Sudden sensorineural hearing loss (SSNHL) is defined by a loss of at least 30 dB in 3 contiguous frequencies over a time course of 72 hours or fewer. Etiologies of SSNHL include viral infections, ototoxic drugs, autoimmune diseases, trauma, neoplasms, and vascular occlusion, but viral labyrinthitis is the most common cause. In cases of sudden hearing loss, herpes infections can be reported in approximately 70% of cases caused by viral infections. Typically, sensorineural hearing loss is not recurrent. We report a case of recurrent SSNHL is which oral herpes lesion preceded the onset of symptoms on three consecutive episodes. Case report: A 55-year-old male with a history of hypertension, hypothyroidism and chronic tinnitus of the left ear (since a gunshot wound 18 years prior) presented to clinic with a complaint of recurrent episodes of sensorineural hearing loss. The first episode of bilateral hearing loss occurred 14 months prior. An otolarnolgologist treated with a steroid taper and valacyclovir and the hearing loss resolved after one day of therapy. Since the initial presentation, the patient reports three subsequent episodes of SSNHL, with two of the episodes responding to prednisone and valacyclovir and one episode responding to steroids alone. Oral herpetic lesions preceded at least three of the episodes one day prior to the hearing loss. Laboratory data was significant for an elevation of varicella-zoster IgG, and of HSV IgG. HSV IgM was not performed. RPR was non-reactive and ANA was negative. A MRI of the head was normal. Audiogram demonstrated 30dB increase and speech discrimination improved from 80% to 100%. The rest of the laboratory data was unremarkable. The patient has been maintained on daily valacyclovir therapy and has had no further episodes of hearing loss. Conclusion: Our patient experienced hearing loss with concomitant evidence of HSV-1 stomatitis. This suggests a cause and effect relationship. We found that the antiviral therapy was effective for treatment of the SSNHL in this patient as demonstrated by the absence of further symptoms while on antiviral prophylaxis and conclude the most likely etiology of the recurrent hearing loss was secondary to the recurrent herpes simplex infections. Abstract The illness was described for the first time in 1937 in the Chinese literature by Kimm, and Szeto, the definitive histological description was published by Kimura in 1948, this illness is endemic in Asia, but rare, about 200 cases had been reported. Kimura Disease is extremely sporadic in the rest of the world. The etiology of this disease is ignored but it is believed that there is an aberrant immune reaction to an unknown antigenic stimulus, however Epstein Barr's virus, human herpes virus 8 and Candida albicans had been involved in certain cases. The mast cells had been implicated in its pathogenesis and a Th2 cytokine pattern with the production of interleukin 4, 5 and RANTES which regulate the synthesis of IgE and orchestrate the eosinophilic infiltration. On the other hand it is suggested that the eosinophils had undergone an accelerated apoptosis in this illnesS. Case Report. It is a 7 year-old boy with a 6 months evolution with the presence of bilateral subcutaneous nodules of 4x5 cm in parotid and submaxillary glands, presenting hypereosinophilia (8172 total eosinophils ) and high IgE ( 9187 total IgE), with normal renal function and negative mycotic and parasitic tests.The histopathologic findings revealed the presence of eosinophilic infiltrates with capillary proliferation and fibrosis. Discussion. For the clinical characteristics of the nodules together with the hypereosinophilia, extremely high IgE and the characteristic histological lesions the diagnosis is Kimura Disease. The usual clinical presentation consists on several indolent subcutaneous nodules that grow very slowly in volume, located in the neck and head, accompanied by satel-ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY lites adenophaties, and with increment in the salivary glands, there is renal affectation in half of the patients, and the laboratory detects hypereosinophilia and elevation of the total IgE. The histological lesions, shows hyperplastic lymphoid tissue with proliferative germinal centers, with infiltration of eosinophils in their interfollicular and perivascular zones sometimes forming an eosinophil abscess and proliferation of poscapillary venules. At the moment he have been treated with prednisone (1mgkdia), with great improvement in the clinical evolution. This is the first case reported in the literature in Mexico. Introduction: The incidence of cow's milk protein allergy (CMPA) is approximately 2-3% and presents primarily during the first year of life. Manifestations of CMPA in the neonatal period include gastroenteritis, colic, lethargy, metabolic acidosis, and hematochezia or melena and appear to be non-IgE mediated. IgE mediated reactions in the neonatal period, such as urticaria or angioedema, are unusual. Case: A 13-day-old African-American male presented with a 3 day history of rash, swelling, and erythema overlying multiple joints. There was no history of fever, diarrhea, or eczema. He had been on no medications prior to admission. Besides mother with a history of childhood asthma, there was no family history of atopy or food allergy. He had been fed cow's milk-base formula (Similac ® ) since birth exclusively. Physical examination revealed a diffuse erythematous, raised, macular-papular rash, with areas of duskiness and exfoliation. There was angioedema overlying the joints and periorbital areas (figure 1). Laboratory evaluation included CBC with diff, Hgb electrophoresis, lumbar puncture, urinalysis, C 1 q (qualitative and quantitative), C 2 , C 3 , C 4 , and cultures of the blood, CSF, and urine which were within normal. Percutaneous allergy skin testing for cow's milk allergy was performed revealing a 3 + reaction to cow's milk extract (Greer, Lenoir, NC) with positive histamine and negative saline controls. RAST testing showed 8.23 KU/L for -lactoglobulin and 5.10 KU/L for cow's milk. He was placed on an elemental formula. Skin lesions and swelling resolved completely within 36 hours. At 2 week follow-up the patient was thriving without complaint. Conclusion: Early sensitization to cow's milk protein in the neonatal period may occur, resulting in IgE mediated urticaria and angioedema. The rashes may be misdiagnosed as erythema multiforme or anaphylactoid purpura, since hemorrhagic lesions and cockade pattern are common. Physicians should be aware that these reactions may occur so that early recognition and management may be initiated.
Neonate with periorbital angioedema and exfoliating, urticarial rash. Rationale: Two patients, presenting with invasive fungal CNS infections, were found to have NK cell dysfunction and hypogammaglobulinemia. Methods: Case reports Results: Patient #1: A 47 year old Caucasian male presented with headache, double vision, periorbital swelling, and bilateral sinus disease on CT scan. Biopsies showed invasive rhinocerebral mucormycosis. He continued to deteriorate in spite of IV and intrathecal amphotericin B, hyperbaric oxygen, many debridement procedures, and a left orbital exenteration. Immune evaluation revealed low IgG, low IgM and a barely detectable NK cell killing activity. Neutrophil respiratory burst was normal. He continued to worsen despite IVIG replacement. He had intolerable side effects to IFN-a. GM-CSF (500 mcg QOD) was initiated, in order to boost NK cell activity. This resulted in stabilization of his infection. He was discharged on oral anti-fungal therapy (posaconazole), IVIG, and GM-CSF. Sixteen months later, he continues to remain stable clinically and radiographically on IVIG and GM-CSF. Patient #2: A 62-year-old Caucasian male presented with headache, mental status changes, and ataxia. A head CT scan showed a left mass effect and edema. He underwent surgical debridement for ventriculitis and Zygomycetes (the same family as mucormycosis) was found. He was started on IV amphotericin B and oral posaconazole. His immune evaluation revealed low IgG and IgM and low NK cell activity. Neutrophil respiratory burst was normal. He was started on IVIG and GM-CSF after which his NK cell function improved significantly. He remains clinically stable on IVIG and GM-CSF with persistent radiographic evidence of enlarged ventricles. Conclusion: Hypogammaglobulinemia is usually not associated with invasive CNS fungal infections, suggesting that NK cell dysfunction was likely responsible for the clinical courses of these patients. NK cell deficiency has been reported to be associated with recurrent mucosal candidiasis, suggesting an important role for these cells in the control of some fungi. The spectrum of the clinical presentations of NK cell deficiency is not known since it is not normally included in immune system evaluations. These patients illustrate the importance of including functional NK cell assessment in any evaluation of immune function. Introduction: To report a case of successful systemic hydrocortisone desensitization, since allergic reactions and systemic desensitization to corticosteroids have rarely been documented. Method: We present a patient with multiple medical problems who has a history of both radiocontrast induced anaphylactoid reaction and corticosteroid allergy. This patient had to undergo cardiac catheterization and corticosteroid desensitization was performed prior to the procedure. Results: Skin testing to radiocontrast is not considered helpful, therefore patients with suspected reactions to radiocontrast are generally premedicated with corticosteroids and antihistamines to decrease the risk and severity of a reaction. 1, 2 Since this patient experienced an allergic reaction to a corticosteroid previously, she was skin tested to two different corticosteroids. The least reactive skin test revealed a 3+ positive immediate reaction to hydrocortisone. Cardiac catheterization with contrast was considered absolutely necessary in this case and corticosteroid desensitization was performed. The half-life of hydrocortisone is the shortest among the tested corticosteroids (80-118 minutes), so a protocol was developed with short intervals of escalating doses. Each dose was diluted yielding a total volume of 75mL to avoid fluid overload because patient has renal failure. During desensitization, patient developed pruritus and erythema between the 3 rd and 4 th dose that resolved immediately with 50mg diphenhydramine. After desensitization, the patient continued to be on hydrocortisone 200mg intravenously every four hours. One hour prior to the procedure, the patient was premedicated with hydrocortisone and diphenhydramine and was administered radiocontrast without any adverse reactions. Conclusion: We successfully desensitized our patient to a corticosteroid and premedicated her with hydrocortisone and diphenhydramine before administering radiocontrast. This case illustrates that intravenous desensitization may be a suitable approach to therapy in corticosteroid allergic patients who require systemic corticosteroids administration. Autoimmune neutropenia is defined as a decrease in the absolute number of peripheral neutrophils caused by an immunologically-mediated mechanism. Autoantibodies directed to neutrophils can lead to the peripheral destruction of neutrophils and/or inhibit myelopoesis in the bone marrow. Although recurrent aphthous stomatitis is often the heralding sign of neutropenia, the diagnosis of AIN requires the demonstration of specific antineutrophil antibody which acts by promoting the immune destruction and clearance of neutrophils by mononuclear phagocytes. The present case report describes the rare clinical association of RAS in an adult. A 66 yr-old black male presented with a 3 year history of recurrent and repeated painful multiple oral ulcers. Initially the oral ulcers occurred on a monthly basis then over time the ulcerations on the oral mucosa and tongue began to appear weekly and later continuously. Past medical history revealed no drug allergies but a positive history of hypertension. Physical exam revealed an otherwise healthy male with no lymphoadenopathy or splenomegaly. Laboratory workup revealed : HIV negative, viral culture for H. simplex negative, mild increase in CD8, cyroglobulins negative, anti dsDNA negative anti-Smith and RNP negative, WBC count 3300/mL, neutrophils 29% (ANC 957), lymphocytes 54%, monocytes 11%, and platelets: 243, 000. Bone marrow biopsy revealed a normal production of neutrophils. A direct neutrophil antibody assay: revealed an elevated value of 6, 576 (N= <4, 000). Although following initiation of prednisone (60 mg) an immediate increase in ANC was seen, the levels fell as the dosage was tapered. The figure below shows the time course and dose-response relationship of ANC and prednisone dosage. This case report illustrates the importance of recognition of the relationship of RAS and neutropenia, an association that can masquerade as other clinical entities. Background: Dyspnea, wheezing, and decreased FEV1 are suggestive of asthma. It is essential for the clinician to consider a broad differential diag-nosis as the outcome could be catastrophic if the correct diagnosis is missed. Case Presentation: We present a case of a 48 y.o. Filipino female who was referred to our clinic for the evaluation of cough, shortness of breath, and wheezy respiration associated with changes in voice quality, nasal and palatal pruritus, and postnasal drainage. Her initial evaluation revealed mold spore hypersensitivity by prick puncture testing and spirometry with an obstructive pattern with FVC-3.05 L (99%) and FEV1-1.25 L (50%) predicted and a 15% reversibility post nebulized albuterol. An initial diagnosis of allergic rhinitis with adult onset asthma was made and she was started on salmeterol, budesonide, montelukast, and pirbuterol. Her symptoms persisted and rabeprazole was added to treat possible laryngopharyngeal reflux. Repeat spirometry revealed FEV1-0.84 L prompting treatment with systemic corticosteroids again with no improvement. Fiberoptic laryngoscopy was within normal limits. A high resolution computed tomography was obtained and showed a mass in the left side of the trachea which was obstructing 60% of the airway. Bronchoscopy revealed a tumor 4-5 cm below the vocal cords with the appearance of adenoid cystic carcinoma which was confirmed by pathology. The tumor was resected by removal of 7 cm trachea with re-anastomosis, followed by a 6 week course of radiation therapy. All medications were discontinued. Her symptoms of wheezing, dyspnea, and cough completely resolved. Repeat spirometry was within normal limits and she remained asymptomatic. Surveillance bronchoscopies have been negative for any recurrence. Discussion: Adenoid cystic carcinoma (ACC) is an uncommon form of malignant neoplasm that occurs within the salivary glands. Tracheobronchial ACC typically presents with symptoms of cough, dyspnea, and hoarseness. Due to its slow growth, ACC has a relatively indolent course. In a recent study of a cohort of 160 ACC patients, survival was 89% at 5 years but only 40% at 15 years. Standard therapy is surgical resection often followed by radiotherapy. Conclusion: In patients who fail conventional therapies for asthma it is important to entertain other diagnosis and have a systematic approach to establish the correct diagnosis. IPEX is an extremely rare, hereditary condition characterized by Immune dysfunction, Polyendocrinopathy, Enteropathy and X-linked recessive inheritance that leads to death without prompt diagnosis. Patients usually present by 4 months with severe diarrhea, failure to thrive, and early onset IDDM. Most children die by one year without a bone marrow transplant. Immunologic evaluation is typically normal except for elevated IgE, eosinophilia, and autoantibodies. We report a case of IPEX in an infant who presented at birth and died at 79 days of multi-organ system failure. This male infant was born at 30 weeks due to chorioamnionitis and PROM. At birth, copious green fluid appeared from his rectum and NG tube which evolved into a secretory diarrhea. Workup for fistula was negative. At 2 weeks, the patient developed ascites and explorative laparotomy revealed an inflamed appendix. After the laparotomy, the patient had no further stool output and never tolerated enteric feeds. He remained intubated and had problems with apnea and coagulapathy. Pathology of the appendix showed an excess of lymphocytes. Immune system investigation showed elevated IgE (5320) and IgG (979). Serum anti-enterocyte IgG antibody was positive in the patient and negative in his mother. Based on this data, IPEX was suspected which autopsy seemed to confirm. Autopsies are scarce in patients with IPEX. The findings revealed many organs affected by fibrosis but lymphocyte infiltration of only the pancreas and GI tract. The pancreas revealed almost complete loss of the exocrine structure, with invasion of fibrosis and chronic inflammatory cells. The mucosa of the GI tract from the stomach to rectum showed columnar epithelium taken over by fibrosis, capillaries and chronic inflammation. These inflammatory cells were CD3+ lymphocytes and plasma cells on immunochemistry. The lymphoreticular system was consistent with lymphoid paucity in the thymus, lymph nodes and spleen. Preliminary data suggests this patient has a splice mutation of the FOXP3 gene. IPEX is an extremely rare disease, often difficult to diagnose while a patient is alive. Infants will present in early infancy with diarrhea and endocrinopathies. Without prompt diagnosis, death is inevitable. As a result, one must be aware of atypical presentations and considered in patients with total villous atrophy and one other clinical feature such as IDDM or autoimmunity. Introduction: DiGeorge syndrome (DGS) is characterized by thymic hypoplasia, parathyroid hypoplasia, and conotruncal cardiac defects, but has a wide variety of clinical manifestations. There is also an increased risk for autoimmune phenomena in later life due to thymic hypoplasia. Case report:
A 13 year-old AA girl with Tetralogy of Fallot (repair at age 2), developmental delay, asthma, recurrent sinopulmonary infections/skin abscesses, GERD, arthralgias and seizure disorder (due to hypoxic encephalopathy during cardiac surgery) presented to Allergy/Immunology clinic for immune workup. There was no history of documented hypocalcemia. At age 10, she developed persistent annular patches on her left leg. A skin biopsy appeared consistent with sarcoid dermatitis. There was no other evidence of sarcoidosis except for slightly elevated ACE level. Given lack of systemic involvement, the skin lesions were not treated, but resolved spontaneously. At age 12, she developed swelling of the right mandible, and a bone biopsy revealed Garre's osteomyelitis (sterile hyperproliferative osteomyelitis), likely triggered by dental caries, with elevated ESR (40) and polyclonal hypergammaglobulinemia (IgG 2640), but normal CRP. Immune workup revealed a decrease in CD4 and CD8 cells (CD4/CD8 ratio 2.44), slightly elevated B cells, high-normal range NK cells, normal range T cell cytokine production in response to mitogens and IL-12, but excessive production of proinflammatory cytokines in responses to LPS. In conjunction with facial dysmorphism, DGS was suspected, and FISH analysis revealed 22q11.2 microdeletion. A repeat workup did not reveal evidence of systemic sarcoidosis, and autoantibody screening was negative including lupus anticoagulant. She was treated with a COX-2 inhibitor, secondary to GERD and mild thrombocytopenia, and her joint symptoms resolved with a concurrent decline in ESR (to 30) and IgG level (to 2390) after 2 months. Conclusion: Recurrent infections with fragmented care and resultant chronic inflammation (hence overstimulation of the immune system) may have led this DGS patient to develop atypical autoimmune phenomena and other unusual clinical manifestations. This case illustrates the importance of recognizing the phenotypic features of DGS early in life, and of providing close monitoring and coordinated care. Rationale: We report a case of a patient with Celiac Disease who continues to have symptoms of fevers, nausea, vomiting, night sweats and fatigue despite being on a gluten free diet whose symptoms have been responsive to antihistamines. Methods: Case report. Results: In 1998, this 41 year-old white male suffered from mononucleosis and episodes of prostatitis. He began suffering from fatigue and fevers and was followed at a Chronic Fatigue Syndrome center in 1999. In November 2000, patient was placed on famvir alleviating his sore throat. He was later placed on Interferon gamma which was discontinued due to increased fevers, nausea and vomiting. After stopping medication, symptoms abated for sometime. In 2002, patient's father was diagnosed with Celiac Sprue. In April of 2003, the patient developed a pruritic rash on his right arm. Biopsy revealed subepidermal vesicles with PMN's at the tips of dermal papillae. In May of 2003, he developed oral ulcers as well as joint pains. Patient underwent endoscopy with biopsies revealing intraepithelial lymphocytosis in the duodenum. Patient has been on a strict gluten free diet since October 2003. He reports that some symptoms have improved: skin lesions, itchy eyes, and oral ulcers. However, he has begun to suffer from constipation and continues to intermittently have night sweats, fevers, nausea and vomiting. In February of 2004, he had pruritus that was not alleviated by hydroxyzine. A regimen of Benadryl and Pepcid was started to aid with the pruritus. The patient reported in the improvement of his symptoms of pruritis, sweats, and emesis. Conclusions: Diagnosis: Celiac Disease(CD) patient with persistent nausea, vomiting, sporadic fevers, and fatigue despite maintaining a strict gluten free diet has shown improvement of symptoms with antihistamines. Patient has history of chronic infections: prostatitis and chronic EBV. Patient also reported alleviation of symptoms after interferon therapy suggesting some autoimmune component to his current illness. CD prevalence in the United States is much higher than once thought 0.5-1% of the U.S. Celiac disease has been associated with increased risk of lymphoma and malabsorption leading to neurological diseases. This is a rare case of CD associated pruritus responding to antihistamines. Rationale: Eosinophilic cystitis is a relatively rare condition in children and adults with a varied course. It usually responds to short-term NSAID and steroid therapy. We report a man with a severe case who responded to prolonged oral steroids. Case Report: A 54 year old Caucasian man with a prior esophageal cancer s/p esophagectomy, diabetes, hypertension, allergic rhinitis and chronic obstructive pulmonary disease presented with suprapubic pain, urinary frequency, dysuria, and hematuria. Urinalysis showed numerous red blood cells and bacteria but no malignant cells or eosinophils. He was treated with antibiotics with resolution of symptoms. Several weeks later he experienced severe suprapubic pain and hematuria resulting in a symptomatic drop in his hemoglobin. He underwent a cystoscopy and biopsy that revealed a chronic cystitis with an inflammatory infiltrate containing numerous eosinophils. He was unresponsive to treatment with NSAID and intravesicular DMSO and was then referred to our service. We started prednisone 20 mg/day but the dysuria and hematuria persisted. Prednisone was doubled plus a third generation quinolone was added. Three weeks later the hematuria and dysuria resolved and he was asymptomatic. The antibiotic was stopped and prednisone was gradually tapered over several weeks. Whenever his steroid dose dropped below 20 mg/day he experienced an exacerbation of his symptoms. Over the last three years this dose of prednisone has kept his symptoms abated and his renal function stable. Conclusion: Eosinophilic cystitis is an uncommon diagnosis of unknown etiology. We describe a patient with debilitating suprapubic pain and symptomatic anemia from the hematuria associated with eosinophilic cystitis. For over three years since we first saw him, continued therapy with 20 mg of prednisone/day has prevented exacerbations. This case is unique in the severity of the hematuria experienced and the prolonged relatively low steroid dose needed to suppress exacerbations. We propose that in eosinophilic cystitis patients with severe hematuria who may otherwise be candidates for a cystectomy, a trial of prolonged oral prednisone may be beneficial. Rationale: Allergic reactions to insulin occurred more frequently in the past, with porcine and bovine preparations. In contrast, allergic reactions to human insulin preparations are now reported in <1% of patients treated with insulin. Insulin allergy may be manifested as an immediate-type 1 IgE-mediated reaction, delayed type hypersensitivity or as serum sickness, varying in severity from mild discomfort to life-threatening events. We present a case to illustrate that an insulin allergy may complicate hospitalization and often be misdiagnosed. Methods: A 66 y.o. diabetic female with a history of "Insulin Allergy" was evaluated. The patient is a long standing diabetic controlled on oral hypoglycemics but required insulin during acute illnesses and hospitalizations. The patient was unable to recall previous types of insulin she had received. During previous hospitalizations, the patient complained of vague symptoms of fatigue, parasthesia, sweating, anxiety, and palpitations. On one occasion the patient had a syncopal episode with hypotension and on another occasion the patient developed a rash and dyspnea after receiving SQ insulin. The physcian intrepreted the findings may be due to hypoglycemic. An allergic reaction was not suspected and the patient never underwent any testing. During a recent hospitalization, the patient's history was reviewed and a formal allergy consult was obtained. She underwent epicutaneous and intradermal testing to human insulin preparations. Insulin antibody levels were also obtained. Results: The patient had negative epicutaneous testing to all human insulin preparations. However, on intradermal testing, the patient had positive reactions to lispro, NPH, and lente and negative intradermal tests to insulin glargine and regular insulin. IgG and IgE insulin antibody test results were < 1. Conclusion: Hospitalized patients receiving multiple medications commonly experience pharmacologic, adverse and/or allergic reactions. It is necessary to obtain a thorough history and document all reactions that patients experience to determine what type of event occurred. With a suspicion of drug allergy, skin testing and/or RAST assay may provide insight into possible IgE mediated reactions. In this case we advised the patient that she may use regular insulin during hospitalizations and that insulin glargine can be used to help achieve optimal glycemic long term control. Background: Hereditary angioedema type III (HAE III) is a recently described form of angioedema occurring exclusively in females and characterized by normal C4, C1 inhibitor (C1 INH) protein and function. HAE III is thought to have an X-linked or autosomal dominant mode of inheritance. We evaluated a 13 year old female with recurrent facial swelling, abdominal pain and laryngeal edema with a family history of similar symptoms in several female relatives. Case Report: A 13 year old African American female presented with a two year history of recurrent lip, tongue and facial swelling. She also had abdominal pain, diarrhea and shortness of breath. Episodes were not associated with hives. Her symptoms predated menarche and did not correlate with her menstrual cycle. At the time of presentation she described an increase in frequency of her symptoms that did not respond to antihistamines (diphenhydramine, cetirizine) or prednisone. The patient had no other medical problems. Family history was significant for recurrent episodes of facial, lip and tongue swelling in a maternal aunt, grandmother and great grandmother. The patient's great grandmother required tracheal intubation with ventilator support for upper airway compromise. The patient's physical exam was unremarkable. Laboratory values drawn during an acute episode of swelling revealed: C1 INH function = >68% (normal >68%), C1 INH protein = 323mg/mL (normal 158-413 mg/mL), C4= 21.70 mg/dL (normal 20-59 mg/dL). DNA sequencing at exon 8 to investigate the possibility of an unusual C1 INH mutation with normal C1s binding but abnormal kallikrein inhibition was negative. Other lab tests included a normal mast cell tryptase of 2.9 mcg/L, a negative RF and ANA, a normal angiotensin converting enzyme of 62 U/L (normal 6-64 U/L) and positive skin prick tests to a variety of foods which the patient tolerates. Based on two case reports of treatment of HAE III with androgens, the patient was started on Danazol 200mg daily with symptomatic improvement. Conclusion: HAE III is a rare disease that affects females exclusively. Clinically it is indistinguishable from C1 INH deficiency. The mechanism of inheritance remains to be elucidated. It is unclear why Danazol appears to ameliorate symptoms even though there is no evidence for C1 ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY inhibitor dysfunction in this disorder. We believe this to be the first kindred of HAE III reported in the United States.
R. Dworski * , M. Peters, Nashville, TN.
A four-month-old female identical twin was evaluated for noisy breathing and recurrent cyanosis. She was delivered at 32 weeks of an estimated gestational age after an uncomplicated pregnancy. At birth she was intubated for 3 hours for respiratory distress but the remainder of her neonatal period was uneventful. At age 3 weeks she developed a noisy breathing often associated with cyanosis, particularly in a supine position or while crying. Treatments with inhaled albuterol and prednisolone were ineffective. She had no respiratory infections or symptoms of gastroesophageal reflux disease. Her growth was normal. Her twin sibling was well. The family history was negative for allergies or respiratory conditions. Initially she was diagnosed with tracheomalacia. However, the history of cyanotic episodes prompted a search for a definitive diagnosis. She underwent bronchoscopy which showed tracheomalacia when breathing spontaneously and circumferential narrowing of lower trachea likely due to compression. Echocardiogram revealed a double aortic arch. The finding was confirmed by computed tomography angiography which demonstrated the presence of a vascular ring composed of double patent aortic arches, each giving rise to the ipsilateral carotid and subclavian arteries. The airway was normal at the aortic inlet, but narrowed markedly at the level of the two arches. A surgical division of the ductus ligamentous and distal anterior vascular arch was performed. Aortic arch abnormalities should be suspected in all infants with hoarse coughing or noisy breathing, especially during inspiration but sometimes also during expiration. The diagnosis should also be considered in older children with recurrent bronchitis or pneumonia. Respiratory symptoms are more frequent than gastrointestinal manifestations. Diagnosis usually occurs in the first year of life. A surgery is often the treatment of choice. Postoperative complications are relatively rare. Outcome of surgery should be judged after 12 months, including at least one winter season. Malacia can delay extubation and recovery following surgery. Surgical cure occurs in approximately 70% of patients. Surgery is probably less successful in children with double arches and malacia.
A. Thatayatikom * , A.J. White, St. Louis, MO. Background: Common variable immunodeficiency (CVID) is the commonest symptomatic primary antibody deficiency syndrome in which B lymphocytes produce low levels of immunoglobulin, leading to recurrent bacterial infection. Although hypogammaglobulinemia and susceptibility to the recurrent infection are seen in all patients, other associated conditions such as a non-infectious granulomatous disease have been well described in CVID. Corticosteroid therapy has been used with improvement in a subset of CVID with granulomatous disease; however, its treatment remains problematic and a new therapeutic agent is needed. Tumor necrosis factor (TNF ) has been demonstrated as a primary mediator in granuloma formation and maintenance. Therefore, anti-TNF medications are potentially therapeutic agents of the granulomatous disease. Case Report: A 22-year-old Caucasian male with CVID and severe granulomatous disease was treated successfully with infliximab, a chimeric anti-TNF monoclonal antibody. The patient initially presented with high fever, chills and abdominal pain; subsequently, he developed acute respiratory failure and adult respiratory distress syndrome. The patient was hospitalized and he required intensive care with ventilatory support. His diagnostic tests revealed elevated sedimentation rate and positive Epstein-Barr virus (EBV) capsid IgM antibody. Imaging studies demonstrated bilateral diffuse pulmonary infiltrates and hepatosplenomegaly. Open lung and liver biop-sies revealed non-caseating granulomatous lesions without evidence of EBV or other infections. High dose corticosteroid therapy was given with partial improvement, then high dose infliximab (10mg/kg) was given weekly with remarkable improvement. The patient was able to wean off ventilator successfully within 3 weeks and his prednisone dose was dramatically decreased. Infliximab infusion (5mg/kg) every 8 weeks and low dose prednisone were continued. A follow-up liver biopsy after 6 months of the infliximab showed no granulomatous lesions. Infliximab was discontinued after 12 months of the treatment. There was no serious infection or complication during the period of treatment. Conclusion: Anti-TNF therapy may be a safe and effective treatment and may allow corticosteroid dose reduction. Future clinical studies of anti-TNF therapy in CVID with granulomatous disease are warranted. Background: Chrug-Strauss syndrome is a disorder characterized by hypereosinophilia and systemic vasculitis occurring in individuals with asthma. Objetive: To present a pediatric case suffering from a systemic vasculitis. This case fulfilled the Churg-Strauss syndrome clinical criteria and the histophatology findings were compatible with the diagnosis. Case: a 14 year female came to our institution with the diagnosis of severe asthma, chronic sinusisits and polyps requiring high doses of steroids. There was no history of administration of antileukotriene receptor antagonists. 2 months before her admission she presented weight loss, fatigue, cephalea and cough. On physical examination, pallor, respiratory difficulty and signs of bronchospasm were evident. Tachycardia and hepatomegaly were also documented. The laboratory test showed anemia, eosinophilia 1300/dl, ANCA+, SGOT 246, STGOP 253, IgE elevated 1345 UI/ml. The chest-X ray showed patchy opacities in both lungs and cardiomegaly. Pulmonary scintigraphy reported low perfusion in both lungs, predominantly in the left lung.Echocardiography demonstrated signs of myocarditis and eyection fraction of 32%. An open lung biopsy was executed and vasculitis with fibrinoid changes affecting small and medium vessels was reported. Treatment was started with oral prednisone 2 mg/kg/d and cyclophosphamide pulses with a satisfactory evolution. Discussion: To our Knowledge this is the first pediatric case of CSS reported in Mexico. She fulilled the following criteria. asthma, eosinophilia and systemic vasculitis involving the heart, liver and lungs. The disease is extremely rare, specially in Mexico. Aggressive treatment is necessary as in this case, with a favorable outcome. Introduction "All that wheezes is not asthma" is a well-known aphorism among physicians. This same principle exists for patients that present with lip swelling in the allergist's office. We describe a patient who presented with fluctuating lip swelling who was ultimately found to have cheilitis granulomatosa. Case History A 26-year-old male with a history of allergic rhinitis and asthma presented to the allergy clinic with lower lip swelling and occasional upper lip swelling. He was receiving allergen immunotherapy for dust mites and trees. The swelling had been waxing and waning for 13 years, but became more persistent for the previous six months. He denied tongue/throat swelling, dysphagia, respiratory distress, or any triggers for the swelling. ChapStick® and Vaseline® were used topically on his lips. Failed treatments included loratadine, ranitidine, cetirizine, fexofenadine, and montelukast. He was placed on a one-week course of prednisone, which decreased his lip swelling, but it recurred after completion of the treatment. Physical exam was significant for diffuse, firm lower lip edema to 3-4 times the normal size. There were no oral lesions or tongue swelling. Patch testing to a standard panel, preservatives, oral flavors, and dental acrylate was negative. Punch biopsy revealed a noncaseating epithelioid granulomatous inflammation consistent with granulomatous cheilitis. He was placed on minocycline 100 mg by mouth twice daily with little benefit. An 8-week course of oral prednisone resulted in improvement of the lip swelling. Conclusion Melkersson-Rosenthal syndrome (MRS) is a rare syndrome that is characterized by a triad of recurrent facial paralysis, chronic edema of the face and lips, and hypertrophy and fissuring of the tongue. Cheilitis granulomatosa is considered a monosymptomatic form of MRS and manifests as a chronic swelling of the lips caused by granulomatous inflammation. The swelling is typically not tender and may be either soft or firm. Allergists are often consulted for lip swelling thought due to angioedema. However, as this case illustrates, not all lip swelling is angioedema and one must consider other diagnoses such as Melkersson-Rosenthal syndrome and cheilitis granulomatosa. Progressive multifocal leukoencephalopathy (PML) is a disorder of the nervous system that affects individuals with immune suppression. It has been associated with HIV infection and is present in nearly 10% of patients with acquired immune deficiency syndrome. The JC virus, a common human polyomavirus, causes this demyelinating disorder. Progressive symptoms reflect the multifocal distribution of brain lesions, and include mental deterioration, vision loss, speech disturbances, ataxia, paralysis, and, ultimately, coma. In rare cases, seizures may occur. There is no known treatment for PML. We report a 21 year-old (y/o) male with 6 months weight loss and a sudden onset of confusion, lethargy, and progressive loss of cognition requiring hospitalization. Upon questioning he was found to have had recurrent upper respiratory tract infections since infancy successfully treated with antibiotics. As a child he had atopic dermatitis, exercise induced asthma, and myringotomy tubes placed twice. At 12 y/o, he underwent a nasal polypectomy. In 2002, at 19 y/o, a squamous cell carcinoma was removed, and he developed benign cervical lymphadenopathy and common warts. A year later he developed HSV esophagitis. The remainder of his history was unremarkable with normal development and growth and no history of drug abuse, multiple sexual partners, or homosexual contacts. On physical examination, he was thin, ill appearing, with oral ulcers, generalized scanty lymphoadenopathy, multiple common warts on both feet, and occasional ronchi. A brain MRI showed a demyelinating process consistent with PML. PCR for JC virus was positive, while HIV PCR was negative; total immunoglobulins and CD4 counts were low ( We are reporting a 47 year old female with a 10 year history of moderate persistent asthma, who was started on Xolair 150mg SQ q 4 wks., and who then presented with a presumed allergic reaction. Three hours after her second Xolair injection, patient reported developing dizziness, shortness of breath, and felt like she was having an allergic reaction. She was evaluated and observed for two hours in an emergency department. The treating physician reported no wheezing and felt there was no need for treatment. To rule out psychogenic factors, she was given a placebo injection at the next scheduled visit. Ten minutes later she reported developing throat tightness and shortness of breath. She had no changes in her peak flows and her lungs were clear. Her "symptoms" resolved completely within 5 minutes of receiving placebo epinephrine and nebulized normal saline. Patient was informed she had reacted to a placebo injection, as well as placebo epinephrine and albuterol, and counseled. The patient returned to the office every week for the next three weeks to receive blinded injections. She subsequently did not react to either doses of placebo or Xolair. She has since tolerated her monthly Xolair injections without incident. This case illustrates the importance of ruling out psychologic causes of presumed allergic reactions. Introduction :Latex allergy, type I IgE mediated hipersensitivity, occurs specially in high risk populations, like in patients that have undergone various surgeries. Case: a 10 year old boy with asthma and allergic rhinitis since 1996, penicillin allergy and retrospectively, his mother refers lip edema with balloon inflating.At 4 years of age (1998): left orchiorrhaphy because of cryptorchis. Between 1999-2004: 4 surgeries because of sacral giant melanocitic naevus.During the fourth surgical intervention (0ct 8 -2004) to collocate a tissue expander, the patient presents perioral and fingertip cyanosis, generalized cutaneous rash and severe bronchospasm.AP:40/22 mmHg, HR 140 x/min. He was treated with IV fluids, steroids, antihistamines and inhaled racemic epinephrine.At the ICU his final outcome is satisfactory. Laboratory: Total Ige :27.4IU/L, skin prick test with glove extract, raw and natural latex extract and purified latex proteins(pseudoeveine, molecular hevein, Hev b 6.02 and modified hevein)all positive +++. Western Blot with protein extract of latex positive and ELISA with purified latex proteins ( same as above) positive. The last surgery to withdraw the tissue expander was performed with latex free surgical equipment without any problems. Discussion: The patient's risk factors for latex allergy are atopy and repetitive exposure to latex articles because of surgery. He presents mild manifestations of latex allergy, till he finally develops full-blown anaphylaxis. Diagnosis was made based on clinical history, skin prick test, Western Blot with protein extract and Elisa with purified latex protein. He had a favorable outcome withdrawing latex during the last surgery. Introduction: Churg-Strauss Syndrome (CSS) is a form of primary vasculitis that is a rare diagnosis in an elderly patient. Case Report: A 75 year old woman presented with a 3 week history of fatigue, vomiting, diarrhea, abdom-inal pain, and right lower leg paresthesia. Prior to admission she was being treated for left neck erythema and adenopathy presumed to be cellulitis. She was in good health with no history of atopy until the age of 72, when she developed both chronic sinusitis, requiring bilateral sinus surgery and polypectomy, * and new onset asthma, * that required systemic steroid control. Prednisone was tapered 1 month prior to admission. Objective findings included coalescent non-blanching petechiae on her abdomen, peripheral eosinophilia of 4800(50%), * normochromic normocytic anemia, RF=124, ESR=90, IgE=232, IgG=1645. ANA, P and C-ANCA were negative. CT showed ascites and pleural effusions. EGD revealed duodenitis with ulceration and eosinophilic infiltration on biopsy. ECHO showed pericardial effusion and septal motion abnormality. Troponin of 31 without CAD was consistent with subepicardial myocarditis. EMG confirmed right peroneal neuropathy.* Skin biopsy revealed a dense superficial and mid-dermal perivascular and interstitial eosinophilic infiltrate. Additional evaluation excluded malignancy, infection, and ABPA. Treatment with Prednisone, 1mg/kg/day was initiated. A rapid clinical improvement ensued and has persisted. {*ACR criteria for CSS}. Discussion: Churg-Strauss Syndrome is a rare form of vasculitis with mean age of onset within the third and fifth decades. It is an uncommon cause (<5%) of systemic vasculitis in patients older than 65. The Formes Frustes of CSS is a variant in which early manifestations of the syndrome are hidden by oral and systemic steroids employed in the treatment of worsening asthma often associated with CSS. This variant makes expedient identification of CSS more challenging. Delayed recognition contributes to a relentless progression of this entity resulting in a systemic vasculitis with multi-organ involvement. Early diagnosis, especially in the prodromal and eosinophilic phases, is essential. Untreated, CSS has a high rate of morbidity and mortality. Therefore, CSS and the Formes Frustes variant must be an integral component in the differential diagnosis of patients presenting with adult onset asthma and/or recurrent sinusitis. Common variable immunodeficiency (CVID) is the most prevalent of the primary immunodeficiency diseases. CVID is a heterogeneous group of immunologic disorders of unknown etiology, characterized by impaired antibody responses, hypogammaglobulinemia with normal B cells. The common immunologic defect in patients with CVID is defective antibody formation, and many different immune system defects have been reported in this group of patients. Most patients, really, have no identified molecular diagnosis. CVID consists of several different genetics defect. The immunologic defect in CVID is a failure of B-lymphocyte differentiation into plasmacells. B lymphocytes from these patients failed to differentiate into Ig-producing cells when stimulated with pokeweed mitogen in vitro, even when cocultured with normal T cells. An overwhelming body of literature suggests that most patients with CVID have intact B lymphocytes of immature phenotype. However the functional classification of CVID patients on the basis of in vitro ig production is time consuming. Recently has been proposed a new classification based on the quantitative repartition of memory B cell according to the dual expression of IgD and CD27. We present a case of a 14 yr old boy. He presented soon in his life frequent infections, of particular severity: pneumonia, meningoencefalitis, sepsis, bronchitis, otitis, linfoadenitis. He also had a -thalassemia intermedia. This clinical manifestations suggested an immunodeficiency. For this reason at 2 years of age serum immunoglobulin and antibody detection showed a reduction in IgG2 subclass and in CD19+ cells, with normal total IgG, IgA, IgM, normal CD4/CD8 ratio, normal CD3, isohemagglutinins and in vitro T cell function. There was also a defective antibody production after Tetanus, Diphtheria, Pertussis immunization. These laboratory findings did not allow, however, a sure diagnosis for CVID. A new immunological evaluation at the age of 11 years old, after the onset of splenomegaly, and enlarged lymph nodes, demonstrated a B memory defect, with a severe deficit of T lymphocytes function in vitro. It was also possible to find a severe deficiency of CD 27 + cells, meaning a defect in memory B cells: we can therfore label this condition as a CVID. In the past two decades there have been conflicting views regarding the clinical importance of IgG subclass deficiencies in children. IgG2 subclass plays a vital role in the immune response to polysaccharide antigen. Isolated IgG2 subclass deficiency may be widespread and often asymptomatic in children. However, in association with other subclasses and/or other immunoglobulin classes, there may be a significant, symptomatic outcome. The reported patient was diagnosed with familial dysautonomia (FD) at the age of five weeks, presenting with severe hypotonia and tachypnea. Hindered by poor pulmonary function, he was hospitalized over fifteen times for recurrent pneumonias, including four lengthy intensive care admissions. Daily inhaled-corticosteroids and brochodilator therapies were initiated, along with chest therapy via a high frequency chest wall oscillator. Immunoglobulin levels were measured recently and point to low levels of IgG2, IgG4 and total IgA antibodies: IgG1 443 mg/dL (N 330-1065), IgG2 57 mg/dL (N 57-345), IgG3 50.5 mg/dL (N 7.5-125.6), IgG4 <2.0 mg/dL (N 1.8-115.5), and total IgA 28 mg/dL (N 33-235). Since receiving monthly IVIG therapy he had no further recurrence of pulmonary infections and was slowly weaned off daily brochodilator therapy. The currently accepted theory is that low IgG2 subclass levels may be associated with increased risk of bacterial infections only in selective groups. FD patients may be in a distinctively susceptible population in which IgG2 levels are critical. The older brother, who was also diagnosed with FD, demonstrated IgG2, IgG4 and IgA levels that were slightly higher but nevertheless on the lower end of the normal range. He suffers from less invasive and less frequent bacterial infections. This may support a genetic association between the FD and hypogammaglobulinemia. Alternatively, it may signal that FD patients may have a prolonged variant of transient hypogammaglobulinemia of infancy. Follow-up immune profile studies, post-IVIG trough levels and broader investigations of the FD population are necessary to determine the severity and prevalence of these findings. Pulmonary failure is the dominant cause of death in patients with FD. Prompt diagnosis and effective treatment of the associated immune deficiency may be proven essential in the effort to enhance and prolong their lives.
S. Hassan * , J.A. Grant, Galveston, TX.
Rationale: Common variable immunodeficiency (CVID), a rare primary immunodeficiency presenting in young adults with repeated sinopulmonary infections as a result of profound hypogammaglobulinemia, was first described by Suri et al. (Ann Acad. Med. Singapore, 1988) . We describe a young man with diagnosed but untreated CVID and its eventual course. Case description: A 27-yr-old Caucasian male hospitalized secondary to chronic pneumonia and respiratory failure was noted to have non-existent levels of immunoglobulins. History revealed IVIG treatment at age 12, stopped after a year due to non-compliance. Although untreated, he denied recurrent sinusitis, otitis media, or bronchitis for almost 14 years but notes a recent inability in keeping up with baseball practice. He is the last of ten healthy siblings. Patient started monthly IVIG infusions but was noted to have hypertension (150/90), tachycardia (120-130), tachypnea (25-30) on the 4th month with O2 saturation of 87-93% and PO2 of 49% on room air. With a 2-day history of acute dyspnea, calf muscle and right abdominal pain, he was admitted to the hospital and pulmonary thromboembolism was ruled out. Laboratory Data: Humoral functions (Pneumococcal, Tetanus toxoid, and Hepvac) -undetectable T cell function (Mumps, Candida, PPD) -normal Immunoglobulin (IgG, IgA, IgM) -undetectable Flow cytometry -B and NK cell markers normal, mild decrease in the CD4/CD8 ratio High resolution CT thorax -bronchiectasis, bronchial wall thickening, and obstructive changes with airtrapping. 6 minute walk -desaturation to 78% on 4L O2 by NC BNP -462 Echocardiogramestimated EF 40-45%; severe pulmonary hypertension. Cardiac catheterization -normal coronary arteries, severe pulmonary hypertension (PA pressure 70/40). Conclusion: CVID patients have a reasonably good prognosis on treatment. Untreated CVID is associated with chronic lung infections, bronchiectasis, pulmonary hypertension and right heart failure. Although, lung transplant became available during the early eighties (NEJM 1982), this extremely invasive but life saving procedure was undertaken in a patient with CVID and end-stage pulmonary hypertension in 1998 (Thorax 1998). Lung transplant may be the only way of ensuring survival for this patient. Introduction Chronic Eosinophilic Pneumonia (CEP) is a rare disorder of unknown etiology characterized as a chronic and relapsing interstitial lung disease with blood or tissue eosinophilia. CEP occurs more often in women with preexisting atopic disease. Patients with CEP respond rapidly to systemic corticosteroids, but often relapse with short, low-dose courses of therapy. While uncommon, extrapulmonary involvement, such as arthralgia, cutaneous purpura, pericarditis, and hepatitis, have been reported. We present a case of a patient who has CEP with pericardial effusion. Case Report The patient is a non-smoking 60-year-old woman with a past medical history significant for allergic rhinitis and asthma who initially presented with a four-month history of worsening shortness of breath, dyspnea on exertion, dry, non-productive cough, and weight loss (approximately five pounds). Her symptoms were refractory to increased dosages of inhaled fluticasone. She then developed intermittent fever up to 102°C. Chest x-ray revealed bilateral apical infiltrates. Treatment with levofloxacin for seven days resulted in no improvement of symptoms or roentographic findings. Thereafter, she presented with chest and abdominal pain, hypotension, and hypoxia. Blood work revealed a white cell count of 6800 c/mm 3 with a differential significant for 34% eosinophilia (absolute eosinophil count of 2300 c/mm 3 ). Chest CT showed dense consolidation predominantly along the peripheral aspect of the upper and superior segment of the lower lobes, and pericardial effusion. Moderate pericardial effusion without evidence of tamponade was confirmed on echocardiogram. Left upper lobe wedge biopsy findings included significant tissue eosinophilia, scattered foci of active organizing exudates, and no evidence of granulomatous or necrotizing vasculitis. The patient was treated for CEP with a six-month course of prednisone, starting at 60 mg daily, resulting in rapid improvement of her pulmonary and systemic symptoms. Background: Immunologists are consulted for evaluation of immunodeficiency in patients with recurrent skin infections. Disorders of the phagocyte system may be associated with cutaneous infections. Methods: Case report Case: A 15-month-old African American girl (twin A) presents with recurrent skin abscesses. At 13 months of age, she had her first buttocks abscess, which required incision and drainage with oral antibiotics. A month later, she developed another abscess and was found to be neutropenic, with an absolute neutrophil count (ANC) of 264/μL. Cyclic neutropenia was considered and her pediatrician monitored CBCs, which all showed persistent neutropenia (ANCs between 68 and 264). At 15 months of age, she was hospitalized for fever with neutropenia. Immunology was consulted for evaluation of neutropenia. The rest of the past medical history was unremarkable. She was healthy appearing and growth parameters were appropriate for age. Her physical examination was unremarkable. Immunoglobulins, B-and T-cell markers, nitroblue tetrazolium, complement assay, hemoglobin, platelets and the peripheral smear were normal. Antibodies for HIV, CMV, EBV and parvovirus were undetectable. Anti-neutrophil antibodies were positive, establishing the diagnosis of primary autoimmune neutropenia (AIN). The abscess healed with oral antibiotics. Severe neutropenia (ANC 0-280) persisted for three subsequent months without further infections. Twin (B) was also found to have persistent severe neutropenia without morbidities, suggestive of primary AIN. Primary AIN is less known among physicians and is typically diagnosed after extensive investigations that exclude other causes of neutropenia. The exact incidence of AIN is unknown. It is usually seen in children between 5 and 38 months of age, often with severe neutropenia and self-limiting bacterial infections. The clinical course and presence of antibodies to neutrophil antigens (NA1, NA2 or CD11b/18) is diagnostic. Familial occurrence of primary AIN is not reported in the literature. Conclusion: Primary AIN may remain under diagnosed due to lack of characteristic clinical features. Although a benign clinical course is likely, severe infections, including pneumonia, sepsis and meningitis, have been reported. Genetics may play a role in this disease, as we present primary AIN in twins. Background: Atopic Dermatitis (AD) is a chronic inflamatory disease of skin that affects 5% of the wordl population.The natural history of AD in some patients, evolve to the coexistence with other allergic diseases: allergic rhinitis, allergic conjunctivitis and asthma. The sublingual immunotherapy has demonstrated utility in some patients; however, semi-rush immunotherapy to pollens has only showed utility in one animal case published few years ago. Case report: A 2-year-old infant was referred to us. He began one year before with skin lesions compatible with AD, six months later began perennial rinhorrea and nasal itching. Multiple treatments with topic corticosteroids, moisturizing, antihistamines and topic/systemic antibiotics did not demonstrate utility. Our evaluation revealed AD lessions that affected 60% of the total body surface and clinical features of Allergic Rhinitis (AR).The lab tests revealed eosinophylia (600cell/mm3) in blood cell count, normal levels of total IgE but specific IgE to Dermatophagoides pteronissinus (DPT) was high. The skin prick test reveales the same results. We added environmental control, oral costicosteroids and Transfer factor. Despite our treatment no improvement was observed. We considered DPT as the principal factor in the maintenance of AD lessions and AR episodes. In the absence of sublingual immunotherapy in our hospital, we decided for semi-rush immunotherapy schedule. We began from 0.1 ml of 1:10, 000 w/v concentrations of DPT until 0, 5 ml of 1:100 w/v concentrations in two months receiving three doses per week. No local or systemic adverse events was reported and the AD lesions and AR symptomatology disappeared in the first month of treatment. At this time, no exacerbations have been documented. Conclusion: The semi-rush immunotherapy can be useful and safe for treatmente of AD in some patients in whom specific IgE to aeroallergens has been demonstrated. Introduction: Eosinophilic gastrointestinal disorders are a rare group of disorders that can involve the entire gastrointestinal tract. Presentations are varied but may include vomiting, dysphagia, abdominal pain, diarrhea and failure to thrive. The diagnosis is made by endoscopic biopsies which reveals eosinophil rich inflammation in the absence of known causes for eosinophilia. Peripheral eosinophils and IgE may be elevated but can be normal. We report a patient with eosinophilic gastroenteritis associated with an ampullary tubulovillous adnenoma. Methods:A 71-year-old white male with allergic rhinitis and a family history of atopy was admitted for profuse watery diarrhea. He denied any new medications, eating raw foods or recent travels. Eosinophils were elevated to 2.4(29% of WBC) and IgE was elevated to 3259. Multiple stool specimens were negative for ova & parasites and enteric pathogens. Serology was negative for Strongyloides, Trichinella, E. Histolytica and Toxocara. AST, ALT & bilirubin were elevated and a CT scan showed dilated billiary ducts with a possible ampullary mass. Biopsy of the ampullary mass revealed a tubulovillous adenoma. Biopsies of the duodenum, terminal ileum, colon and rectum were remarkable for focal eosinophilic cryptitis & chronic inflammation in the lamina propria consisting of eosinophils, scattered lymphocytes and histiocytes. All specimens were negative for parasitic infections including duodenal aspirates. He was empirically started on metronidazole and singulair with gradual improvement of symptoms, eosinophils and liver tests. Two months after discharge, the patient remained diarrhea free with a normal eosinophil count. Conclusion: We report a patient with eosinophilic gastroenteritis and an ampullary tubulovillous adenoma with obstruction of the biliary system. This unique presentation illustrates the diverse nature of gastrointestinal manifestations seen in eosinophilic gastroenteritis. Background: Zonisamide is an anti-seizure medication chemically classified as a sulfonamide and unrelated to other ant seizure agents. We report a case of hypersensitivity to this agent in a child. Method: Case Report Results: This patient is a 22-month-old girl who developed "peeling of her lips" three weeks after starting Zonisamide. One week later she developed a rash that began on her face and generalized over several days to her neck, trunk and extremities. There was no respiratory distress, joint complaints and no angioedema associated with the episode, but fever to 103 prompted referral to our hospital on day 6 of the rash. The rash was macular-papular without discrete urticarial lesions. The rash coalesced with underlying erythema on face, chest and neck. The patient has a known history of seizure disorder, asthma, mild eczema, gastro esophageal reflux, development delay, lactose intolerance and failure to thrive. Her other medications were, lansoprazole, topiramate, and Albuterol. Labs revealed a normal white cell count, an elevated sed rate ( 51) and elevated LFT's, i.e. SGOT 80 and SGPT 180. The only new medication was Zonisamide that was discontinued. She was treated with IV steroids and hydroxyzine. The rash started fading by day 2 and the patient's fever resolved by the third hospital day. Liver enzymes returned to normal by day 7. Conclusion: This relatively new anti-seizure agent can be associated with hypersensitivity reactions in children. Introduction: Kawasaki disease (KD) is an acute chilhood vasculitis. In addition to the diagnostic criteria a broad range of nonspecific clinical features may be observed including aseptic meningitis, vomiting, diarrhea, abdominal pain, sterile pyuria, arthralgia and arthrtis, pulmonary infiltration, pleural effusion and nonspecific paralytic ileum as manifestation of gastrointestinal vasculitis. We describe a child who developed all features of Kawasaki disease included the most rarely reported. Patient report: A 2 year-old female presented 15 days of high fever, nonsuppurative cervical lymphadenopathy, petequial rash in legs, swelling of feet, distended abdomen, vomiting, obnubilated and hypoactive, incongruent speech, fisured lips and distended abdomen. Lab tests showed: anemia (9.8g/dl), high WBC count (24, 200cells/mm3), thrombocytopenia (47, 000/mm3), hypoalbuminemia (1.1g/dl), lactate dehydrogenase (LDH) 209mcg/l, glutamin transferase (GGT) 190. CSF total proteins 129, glucose 60, cells 23, PM 5%, mn 95%, seric complement 88, cultures were negatives. She developed myocarditis, aneurysms in the right and left coronary arteries. On the 25th day presented cardiac failure, pleural effusion, paralytic ileum, hydrops vesicular, mechanic ventilatory assistance was required. The first dose of intravenous immunoglobulin (IVIG) (2g/k) was infused, heparin and hydrocortisone. On 45 day a second doses of IVIG was infused, because of fever, and abdominal vasculitis. Steroids ware discontinued, heparin was suspended and aspirin was added as antiaggregant. Discussion: our patient presented an unusual and severe presentation of KD with pleural effusion, nonspecific ileum, cardiac failure secondary to myocarditis, aseptic meningitis and thrombocytopenia; all those manifestations had rarely been reported at the same time. She presented with a devastating evolution. complications were resolved. The lastest studies have shown that treatment with IVIG plus corticosteroids significantly reduce serum concentrations of proinflamatory cytokines. In this case antiinflamatory doses of aspirin were contraindicated and steroids were used with satisfactory outcome. Limited data is available for nonresponding patients to guide therapy. Although multiple doses of IVIG are sufficient in some patients, some of them remain refractory to therapy and they need corticosteroids to control the vasculitis process Eosinophilia is defined by an absolute eosinophil count above 0.7 X 10 9 and can be seen in association with a broad spectrum of disorders ranging from allergic to malignant. Idiopathic hypereosinophilic syndrome (HES) should be considered in any patient with an eosinophil count above 1.5 X 10 9 for more than 6 months without commonly recognized causes of eosinophilia and with evidence for organ damage not otherwise explained in the clinical setting. It is potentially an aggressive disease with mean survival of less than a year without treatment. We present a 39 year old male horse breeder, with eosinophilia lasting more than 10 years. Prior to coming to our institution, he underwent extensive medical evaluation including bone marrow and GI biopsies, multiple imaging studies with MRI and CT scans of the chest and the head as well as detailed evaluation of his cardiac status. All these tests were normal and the patient was empirically started on treatment for possible HES including trials of prednisone, hydroxyurea, interferon alfa, and imatinib, all without lasting resolution of his eosinophilia and causing significant side effects with profound depression of his immune status. Finally, in light of the patient's profession, a Strongyloides enzyme immunoassay was done and found to be remarkably positive. Duodenal drainage confirmed the infestation with this nematode. Within a week of starting treatment with ivermectin, his eosinophil count came down by 50% and eventually normalized. We learn that one should be persistent in excluding all common causes of eosinophilia before considering HES. In case of parasite infestation, premature treatment with immunosuppressors can result in worsening of the infection with potential for poor and even fatal outcome. Stool evaluation might not be sensitive enough for detection of parasites and it is therefore necessary to complete a diagnostic work up with appropriate serology. Doxil is the pegylated liposomal form of doxorubicin and has been used successfully as a cancer chemotherapy agent in many types of tumors. A hypersensitivity reaction can occur, usually during the first infusion, and appears to be rate related. The symptoms include dyspnea, tachypnea, facial swelling, chills, hives, chest pain, and back pain. We report a case of a hypersensitivity reaction to Doxil in a 26 year-old woman with Hodgkin's lymphoma. During her first outpatient Doxil infusion at 1 mg/min, she developed urticaria, chest tightness, dyspnea, and back pain. These reactions persisted despite being medicated with antihistamines and steroids and immediately resolved during pauses in the infusion. After 23 mg of Doxil, the infusion was discontinued. Six days later, she was admitted to complete the other half of the dose. She had a negative intradermal skin test to a 1:100 dilution of Doxil. She was then premedicated with diphenydramine, dexamethasone, acetaminophen, and famotidine. The Doxil infusion was started at 0.4 mg/min and was soon stopped due to flushing of the hands and face. The infusion was decreased to 0.2 mg/min. She was able to tolerate this slow infusion with only mild and tolerable symptoms. When her symptoms worsened, the infusion was stopped for 30 to 60 minutes. She completed the 23 mg infusion of Doxil after 13 hours. Pre-infusion and post-infusion complement levels were drawn during this second administration of Doxil. Her pre-infusion C2, C3, C3a, C4, C5, C5a, and Bb levels were all normal. Her pre-infusion C4a and SC5b-9 levels were high, indicating that she might have had some residual or persistent complement activation caused by her first Doxil infusion. Her post-infusion C2, C3, C3a, C4, C5, C5a, and Bb levels were all normal. However, her post-infusion SC5b-9 levels significantly increased, suggesting complement was activated during the second Doxil infusion. Given her reaction during her first Doxil infusion and a negative skin test to Doxil, it is highly unlikely that her Doxil hypersensitivity was an IgE-mediated process. Therefore, in patients with a similar Doxil hypersensitivity, we suggest a slow rate of infusion of 0.1-0.2 mg/min, toleration of mild symptoms, 30 to 60 minute pauses during more severe symptoms, and continuation of premedication during the entire lengthy infusion. Introduction Eosiniphilic esophagitis (EE) is an isolated, severe esophageal eosinophilia. Patients are usually young males presenting with vomiting, epigastric or chest pain, dysphagia and obstructive respiratory problems. They are often initially misdiagnosed with and treated for gastroesophageal reflux disease (GERD). Distinction between the two diseases can be made with biopsies of the esophageal mucosa. While any eosinophils in the esophageal mucosa indicate pathology, GERD typically presents with up to 7 eosinophils per high powered field (HPF, 400X) while EE most often presents with greater than 20-24 eosinophils per HPF. Case Report The patient is a 3 and one half year old boy who has experienced severe symptoms of GERD from the age of 6 months. He vomits after meals at least 1-2 times per day. He coughs when he lies down at night and regurgitates phlegm in the early morning. He has complained of discomfort in his lower chest after eating. His weight has remained at 35 pounds for the last six months. The patient was diagnosed with asthma at age 2 and a half; however, there is no family history of asthma or allergies. The patient initially experienced improvement on lansoprazole, but his symptoms recurred when the medication was discontinued and subsequent courses were ineffective. His physical exam was normal barring slightly edematous nasal turbinates. An endoscopic biopsy showed "numerous eosinphils" (later clarified to 38 eosinophils per HPF) in his distal esophagus. The patient showed allergy to milk and wheat on radioallergosorbent (RAST) testing. The patient was started on swallowed fluticasone 2 puffs twice daily and advised to see a nutritionist regarding a wheat and milk elimination diet. Conclusion EE is an important differential of GERD-like symptoms in childhood. To avoid misdiagnosis it is critical to evaluate the number of eosinophils present in a biopsy specimen to help differentiate between GERD and EE. Children with EE are at increased risk of developing esophageal dysmotility and esophageal strictures. Patients often have positive skin prick or RAST tests to foods and aeroallergens. Alternative treatments such as food elimination diets and glucocorticoids (systemic or topical) are effective in treating symptoms which may not respond to reflux medications.
Introduction In 1992 Asherton introduced the term catastrophic antiphospholipid syndrome (CAPS) to describe patients sharing clinical evidence of multiple (three or more) organ involvement and/or histopathological evidence of multiple vessel occlusions. Case Report We present a 13 year old female, with lumbar pain, arthralgias, weight loss, fever, malaise, Raynaud phenomenom, alopecia, oral ulcers and hepatomegaly. On arrival, she was polypneic with tachycardia, basal hypoventilation, and hepatomegaly was evident. Hb: 8.8, Leucocytes: 39.300, Total Lymphocyctes: 8, 300, Total Neutrophyles: 28, 700, Platelets 393, 000. Coombs positive. Urin exam: proteinuria, leucocyturia and erythrocyturia. Creatinine 1.3. Diagnosed as SLE with pericarditis, cardiac failure and acute pulmonary edema, urinary tract infection and pneumonia, requiring mechanical ventilation and inotropic support, intravenous gammaglobulin and hydrocortisone. Acute renal failure and hemodialysis was begun with improvement. Suddenly she presented seizures crisis, stuporous, livido reticularis skin and acrocyanosis, external opthamalplexia, bilateral facial diplexia, ocular fundus with arteriolar vasospasm. Right facio-corporal hemiparesia, cortical and progressive medular ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY segment changes. CT showed multiple left fronto-occipital parietal hypodensities suggestive of lacunar infarcts. Diagnosed as neurolupus and CAPS. Initially anti b2 GLP1 and anti CLP were negative with later positivization. Urinary tract infection contraindicated high doses of steroids and, intravenous gamaglobulin and anticoagulation were started. With significant improvement. Currently the patient is evolving in a satisfactory way. Discussion The literature establishes that catastrophic APS is characterized by elevated mortality. In this patient damage was evident to the CNS, PNS, kidneys and the skin. With the presence of positive antiphospholipid antibodies with an energic antiinflamatory, immunoregulatory and immunosupressive therapy, the function of each affected organ completely recovered. This case exemplifies that the therapy of CAPS should be undertaken in a sufficient and early manner given the elevated mortality of this syndrome. Patient, a 70-year-old white, male non-smoker physician on high-dose regimen of Advair and Singulair presents with an 8-day history of progressive chest tightness. Pulmonary function tests showed normal (FEV 1 of 96%) lung function. In the past, whenever inhaled steroid dosages were lowered, patient experienced a reoccurrence of asthma symptoms, despite consistently normal lung function results. To rule out the possibility of a psychologically induced asthma exacerbation, the patient's fractional concentration of exhaled nitric oxide (FENO) levels were measured. The patient's FENO level was elevated at 48.9 ppb. Values greater than 30 ppb have been described as consistent with airway inflammation. With an increase in the patient's inhaled steroids, the patient had a remission of symptoms within a week. This case is illustrative of an increasingly common clinical picture where a symptomatic asthmatic may have normal spirometry but elevated FENO. As devices for measuring FENO become more available in the outpatient clinic setting, elevated FENO may be an excellent diagnostic marker in assessing whether airway inflammation is being adequately treated in situations where spirometry values are within normal ranges.
Introduction The autoimmune thrombocytopenic purpura (ATP) is characterized by thrombocytopenia and megakaryocytic hyperplasia. The first choice of treatment consists of intravenous gamma globulin (IVIG), corticosteroids and anti-D antibodies and the second line measures are immunosuppressant drugs, splenectomy and Danazol. Case Report A 4 years old male presented in the first year of life ecchymosis in several parts of the body intermittently. In April 2003 he presented ephistaxis and lower gastrointestinal bleeding. Complete blood count showed platelet count of 45, 000/uL. Prednisone was started (2 mg/kg) with no improvement. At that time, Danazol, anti-D antibodies, and IVIG (2 g/kg) were added. Subsequently, the platelet average count diminished to 5, 000. The patient was transferred to our hospital. At his admission he presented Cushingoid habitus (figure 1) and acanthosis nigricans. The immunological tests (AAN, CH50, C3, C4, immunoglobulins, anticardiolipins and B2 glycoprotein) showed no alterations. Bone marrow aspirate demonstrated megakaryocytic hypercellurarity. Prednisone dose was tampered when the patient presented secondary glaucoma. Patient continued his treatment with Danazol and IVIG (2 dosages of 2g/kg each), hydroxychloroquine and cyclophosphamide with no improvement. Thus, 3 months after the immunosuppressant treatment, splenectomy was performed, obtaining partial improvement. At that time ranitidine and hydroxychloroquine were suspended and cyclophosphamide was changed to Azathioprine. Last platelet count was 106, 000/uL. Conclusion Chronic ATP in childhood as the present case account for approximately 4-5% of the total ATP patients. Chronic ATP that does not respond to conventional treatment is a therapeutic challenge. In this patient we used first choice and second choice drugs with no improvement, consequently a splenectomy was indicated, not obtaining the desired response at first. The use of immunosuppressant drugs is not common for this disease, but it could be a good alternative for ATP resistant to conventional treatment.
This are the most important laboratory test of our patient. Background: Budesonide is the only corticosteroid available for inhalation by jet nebulizer and is indicated for the treatment of asthma in children. Objective: To evaluate the distribution and clinical efficacy of inhaled budesonide administered by nebulization with a modified commercial device. Methods: A 23 year old male with severe persistent asthma underwent a LeFort procedure for multiple craniofacial abnormalities. The external device maintained his mouth open impeding the proper use of controller medications. As a result he developed an increase in his asthma symptoms. He was subsequently treated with nebulized budesonide delivered with a modified jet nebulizer through the end of a plastic tube in a flow-by manner. We then performed dynamic ventilation imaging after administering 33.40 mCi of nebulized technetium 99m-DTPA diluted in two mL of normal saline. Images were obtained for five minutes at three seconds per frame. Spirometry monitoring was not possible given the obstructive nature of the facial device. Results: The patient demonstrated improvement of his asthma symptoms. The ventilation scan showed that the patient breathed the technetium DTPA through the specialized device with delivery to his full lung volumes within 12 seconds. Conclusions: We report the successful treatment of a patient unable to use the commercially available methods for administration of inhaled steroids. Rationale: HP is a non-IgE mediated inflammatory response in the lungs due to a variety of organic antigens, including metal working fluids. The wideranging clinical features include acute, subacute, and chronic forms. Elevated antineutrophilic cytoplasmic antibodies and platypnea, defined as dypsnea induced by the upright position and relieved with recumbency, have not been previously reported in patients with HP. Case: 35-year-old white male tool and dye machinist presented with progressive cough, weakness, dyspnea on exertion, and platypnea. Symptoms began 15 weeks earlier with coryza and diffuse myalgias. He had lost 12% of his body weight since symptom onset. Examination revealed a pulse of 140, respiratory rate 18, and right basilar crackles. Resting pulse ox on room air was 95%, but dropped to 91% upon ambulation. PFT's revealed severe obstruction (FEV1 42% predicted) with significant reversibility (FEV1 +19%), and a DLCO of 82% (adjusted for VA and Hemoglobin). Hemoglobin was 17.5 with a normal leukocyte count and differential. C-ANCA (anti-PR3) was 19.3 (<5), and P-ANCA (anti-MPO) was 15.9 (<15), both performed by ELISA. Echocardiogram showed an EF of 50-55% with mild pulmonary hypertension; no shunt was present. Chest roentogram was normal, but a chest CT revealed a diffuse ground-glass pattern with scattered centrilobular opacities. Biopsy was consistent with HP. He was removed from his work exposure to metal working fluids with full recovery of lung function and resoulution of symptoms. Conclusions: HP presents as a constellation of symptoms without a single, unique identifying pattern. Platypnea and elevated ANCA's have been observed in a wide range of disorders, all of which were excluded in this patient. Platypnea has been associated with hereditary hemorrhagic telangiectasia, pulmonary AVM, hepatopulmonary syndrome, recurrent pulmonary emboli, and patent foramen ovale. Elevated ANCA's has been associated with Wegener's granulomatosis, Goodpasture's syndrome, Churg-Strauss vasculitis, drug-induced vasculitis, inflammatory bowel disease, and others. ELISA is a more specific modality for ANCA's than indirect immunofluorescence, but it is less sensitive. The possibility of HP should be considered in patients with either of these two abnormalities. Rationale: Heart disease is the leading cause of death in America and 70% of persons between 70 and 80 years of age have coronary athersclerosis at autopsy. The presentation in the elderly is commonly atypical. 45% of myocardial infarctions were silent or unrecognized in the Framingham cohort. In patients 65 and older, it is estimated that 8-25% will present with dyspnea without any associated chest pain. We present a case of unstable angina presenting as exercise-induced asthma. Case: An 81 year-old white male with moderate persistent asthma, hypertension, dyslipidemia, and a long history of allergic rhinitis presented having had an abrupt increase in his usual exercise-induced asthma symptoms four weeks prior. Asthma had been diagnosed at age 69 with spiromety showing moderate obstruction and significant but incomplete reversibility. He had a remote history of pipe and cigar smoking, but had quit at age 50. He had been well-controlled since that time with his most recent regimen consisting of fluticasone 100 mcg/salmeterol 50 mcg diskus, one inhalation twice daily. His typical exercise-induced asthma symptoms included dyspnea on exertion and chest tightness without radiation, and were relieved with rest and albuterol. The amount of exertion needed to trigger his symptoms, however, was much less than he had previously experienced, and this remained constant during the four weeks prior to his presentation. One week prior he had a normal ECG evaluation by his primary care provider. Six months prior he had a normal nuclear cardiac stress test. Physical examination was unremarkale except for moderately decreased aeration and 1+ pitting edema of his lower extremities. Cardiology performed a nuclear stress test the next day which was abnormal. Catheterization revealed 99% steonsis of his proximal LAD. He succefully underwent CABG and is doing well on follow-up. Conclusion: The elderly present many challenges to the diagnostician; these include multiple co-morbidities as well as atypical and often late disease presentations. The key to raising suspicion for cardiac involvement in this case was the recognition of the patient's cardiac risk factors in the setting of an abrupt onset of exercise symptoms while lacking other asthma symptoms such as nocturnal cough. Cold urticaria is an uncommon form of physical urticaria. This case of a 9-year-old with cold urticaria and angioedema provides additional information regarding an unusual disorder in the pediatric population. An otherwise healthy 9-year-old female presented with a complaint of urticaria precipitated by cold exposure over the preceding 5 weeks. She had no recent illnesses and a past medical history significant only for cat allergy. On multiple occasions the patient noted erythema and pruritus of her arms and face after walking through the freezer aisle of a grocery store. Urticaria would then develop on regions where she scratched, spontaneously resolving in 2-3 hours. On one occasion, urticaria appeared diffusely while taking a shower after the patient had been swimming. The urticaria resolved within a few hours after the patient was given diphenhydramine by her mother. Three days prior to presentation the patient experienced upper lip angioedema with erythema, globus sensation and difficulty swallowing after drinking a strawberry slushy. The patient denied any respiratory complaints at that time and her symptoms again ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY resolved spontaneously. Family history was significant for a maternal history of seasonal allergies. Upon physical exam the patient was well appearing. She had 2-3 discrete urticaria on each calf. The patient's mother noted that recently these would appear on "cold and rainy" days, attributing them to the fact that the patient's pants left her lower legs exposed. The remainder of her exam was normal and dermatographism was absent. Laboratory evaluation consisted of cryoglobulins and strawberry RAST, both of which were negative. Application of an ice cube to the patient's forearm for 5 minutes resulted in a 9x6 centimeter wheal noted 3 minutes after ice removal. A diagnosis of cold urticaria with associated angioedema was made. The patient's mother opted to use diphenhydramine as needed and an epinephrine autoinjector was dispensed. By 3 months after symptom onset, the patient's only complaint was pruritus of her hands if they became too cold. No urticaria were noted. At 6 month follow-up the patient denied any symptoms for the preceding 2 months and had a negative ice cube test. Cold urticaria in the pediatric population is a rare entity and not well understood. This case of a 9-year-old with cold urticaria and angioedema offers additional insight into this unusual disorder.
A. Khuntia * , M. McMorris, Ann Arbor, MI.
INTRODUCTION: Chronic granulomatous disease(CGD) is a heterogeneous group of disorders characterized by genetic defects in the ability of phagocytes to generate microbicidal reactive superoxide anions and its metabolites. It manifests early in life, primarily as recurrent infections, caused by catalase-producing bacteria such as Staphylococcus aureus, Burkholderia cepacia, and Serratia Marcescens and fungus such as Aspergillus fumigatus. The disease may be inherited in an X-linked or autosomal recessive manner, with X-linked disease accounting for 65-70% of cases. The US incidence of CGD is 1/250, 000 live births with an average age at presentation of 3 years for Xlinked and 7.8 years for autosomal recessive disease. CASE REPORT: 18 year old male with history of three separate episodes of pneumonia beginning at age 16. Each episode resulted in a hospital admission and intravenous antibiotic therapy after failed oral antibiotic therapy. An extensive pulmonary evaluation was initiated after the third episode of pneumonia, including a chest CT, viral, bacterial and immunodeficiency studies. CBC, complement, immunoglobulins, flow cytometry, viral and bacterial studies were all normal. The CT scan revealed dense nodular opacities in the right upper lobe with surrounding ground-glass opacification and mild bronchiectasis. A subsequent bronchoscopy demonstrated necrotizing granulomatous inflammation. Open lung biopsy grew Burkholderia cepacia on tissue culture. The clinical history, tissue histopathology and atypical organism found on culture were all suggestive of an underlying immunodeficiency. A neutrophil oxidative burst assay was performed which demonstrated minimal neutrophil activity upon stimulation, suggestive of the diagnosis of CGD. A chemilluscence assay verified the diagnosis of CGD, with minimal fluorescence noted on flow cytometry after neutrophil stimulation. DNA analysis demonstrated a p47-phox deficiency, resulting in one of the autosomal recessive and less clinically severe forms of the disease. CONCLUSIONS: This case of CGD is unusual because of the delayed presentation. It demonstrates the importance of a complete immunological evaluation including an evaluation for neutrophil disorders such as CGD in patients of all ages who present with recurrent and recalcitrant episodes of pneumonia, especially when atypical organisms such as Burkholderia cepacia are found on culture. Autoimmunity may play a role in the development of premature ovarian failure (POF), but the exact mechanism is not well understood. POF is mainly diagnosed after 19 years of age and most women complain of secondary amenorrhea. POF has been reported in combination with presence of ANA and autoimmune diseases, but rarely with JRA. Here we report two cases of POF and positive ANA in pediatric patients, one with clinical features of JRA. The first patient, an African American 17-year-old girl, height in 50th percentile, weight in 10th percentile, with tenosynovitis of wrists and arthritis of knees and elbows for the past two years, was referred for further evaluation and management. She did not have her menarche yet and laboratory investigation revealed positive ANA. The second patient, an African American 17-year-old girl, 50th percentile for height and weight, was referred to the immunology clinic with chief complaint of primary amenorrhea and delayed development of secondary sexual characteristics and was found to have positive ANA without clinical findings of JRA. Both patients were Tanner stage 2 for breasts and Tanner stage 2-3 for pubic and axillary hair. Both had elevated FSH and LH, karyotype 46XX and small uterus and small ovaries on pelvic ultrasound. Antiovarian antibody was not detected in any of the two patients. The bone age was significantly delayed. POF in karyotypically normal women is frequently seen in combination with elevated serum ANA. The clinical spectrum of rheumatoid disease associated with POF ranges from asymptomatic ANA positivity to typical presentation of JRA. Women with POF should be monitored for the emergence of autoimmune disorders including JRA, and women with JRA should be followed for menstrual irregularities and signs of POF. Introduction: Many U. S. military personnel deployed to the Middle East continue to develop infection with Leishmaniasis, a parasite transmitted by the sand fly. Pentavalent antimonials have been used as an effective treatment for Leishmaniasis for many years. In the United States, Sodium Stibogluconate (Pentostam) is the pentavalent antimonial of choice, and is currently being administered under an IND protocol. Side effects of therapy include myalgias, arthralgias, rash, malaise, abdominal pain, pancreatitis, and hypersensitivity reactions. The true incidence of hypersensitivity reactions is not currently known. Case reports: Two U. S. soldiers receiving Pentostam for the treatment of cutaneous Leishmaniasis were evaluated in our clinic at Walter Reed Army Medical Center after experiencing urticaria, angioedema, wheezing and dyspnea after medication infusion during the 20-day course of daily therapy. Due to the concern of a potential IgE-mediated reaction, skin testing was performed. After informed consent, skin testing included a prick test at full strength, followed by intradermal (ID)testing. Soldier #1 was a 23-year old male reporting lip swelling, throat tingling, dyspnea and chest pain 7-8 hours after treatment #10/20. Skin testing to both lots used during the treatment course showed positive values of 8x20mm and 9x14mm respectively at ID 1:1000. Soldier #2 was a 28-year old male reporting diffuse pruritus, hives, dyspnea, and chest pain 15 minutes after infusion #16/20. Skin testing showed positive values of 7x14mm and 8x12mm respectively at ID 1:1000. Due to clinical symptoms and positive skin testing, therapy was discontinued in each case. One control individual showed negative testing to prick at full strength, ID 1:1000, and ID 1:100. Conclusion: Skin testing with Pentostam may provide an objective tool for accurate classification of adverse reactions as IgEmediated. Reliance on skin prick testing alone may not be sufficient to detect Pentostam skin test reactivity, as both of these patients reacted to ID testing only. A prospective study including pre-and post-treatment skin testing should provide more information on the value of skin testing in providing objective evidence for an IgE-mediated process and determining the incidence of hypersensitivity to Pentostam. Introduction: A 3-year-old girl with a history of multiple infections was hospitalized with respiratory distress and hypoxia. Her past medical history was significant for hypothyroidism, psoriasis, asthma and multiple pneumonias. A CBC revealed an absence of lymphocytes. Laboratory: T and B cell subsets showed no B-cells and very low T cells (<100 cells). Inadequate lymphocytes were present for mitogen and antigen studies. Serum immunoglobulins were normal and she had antibodies to Streptococcus Pneumoniae and Tetanus. Antibodies to RSV, Influenza and Mycoplasma were absent. Chest x-ray revealed interstitial infiltrates bilaterally. A High resolution CT scan revealed septal thickening and confirmed interstitial infiltration. Open lung biopsy was consistent with non-specific inflammation with extensive lymphocytic infiltration. BAL fluids and biopsy were negative for bacteria, fungi and opportunistic pathogens. Clinical Course: The patient did not improve with antibiotics and steroids were started. The patient improved rapidly and was discharged to home. Biochemical analysis demonstrated a deficiency of adenosine deaminase (ADA), a form of severe combined immune deficiency (SCID). The patient was started on replacement ADA, Adagen. A repeat high resolution CT scan showed some improvement. However, the patient continues to be steroid dependant to control her pulmonary symptoms. Lymphocyte numbers remain low despite effective ADA replacement and the absence of serum dATP. She remains clinically stable and receives Adagen injection twice weekly. Discussion: ADA deficiency is a condition, which leads to accumulation of the metabolite dATP, which is toxic to lymphocytes. This disease most commonly presents in the first year of life as SCID and is fatal unless treated. Our case is unusual due to the late onset of severe disease, normal serum immunoglobulin and the presence of some protective antibodies. Despite adequate replacement of ADA the patient continues to be profoundly lymphopenic, most likely due to steroids. Although we do not yet completely understand the underlying lung disease we suspect that the patient has an autoimmune process causing interstitial inflammation. Background: Atopic dermatitis has a broad range of differential diagnoses. Human sarcoptic infestation is characterized by severely pruritic lesions of variable appearance and distribution and may masquerade as eczema. Infestation may be difficult to confirm and eradicate. Animal transmission has been reported as a source of human infection. Objective: To report a case of persistent sarcoptic infestation masquerading as eczema and associated with delusional parasitosis. Methods: A 58-year-old female was referred to Allergy Clinic for evaluation with a two year history of recurrent, pruritic rash thought to be refractory atopic dermatitis. Previous ineffective treatments included topical steroid creams, Lindane, topical anti-fungals and multiple OTC antiitch preparations. At initial evaluation, she had widespread excoriated papules in various stages of healing over 70% of her body. She reputed her dog was diagnosed with recalcitrant mange, which necessitated giving him medicated baths twice daily. Results: A clinical diagnosis of subacute sarcoptic infection was made and the patient was prescribed two courses of Elimite followed by oral Ivermectin. Her rash quickly resolved except for post-inflammatory hyperpigmentation. Three weeks after resolution of primary lesions, she again complained of pruritic eruptions occurring on easily accessible areas and began bringing in medicine bottles of skin debris and scabs for examination. Scrapings, KOH preparation and skin biopsy examined microscopically showed no evidence of sarcoptic re-infestation. A diagnosis of delusional parasitosis was made. Conclusions: The animal to human transmission of sarcoptic infection seen in this patient is rare and responded quickly to appropriate treatment. Despite eradication of the infection, she developed delusional parasitosis, a rare psychiatric disorder characterized by fixed, false belief of an infestation by insects or other creatures. She displayed the classic matchbox sign in which samples of skin, scabs and other detritus are brought in for examination. She is currently receiving psychiatric care. Background: Thimerosal is a mercury derivative that has been used since the 1930s. It is a commonly used preservative in ophthalmic solutions, otic drops, and vaccines due to its bactericidal property. Objective: To report the first case of a generalized reaction to thimerosal found in an influenza vaccine. Methods: We present a patient who developed a generalized maculopapular eruption after receiving a thimerosal containing influenza vaccine. Patch testing was performed to determine if there was an allergy to thimerosal. Results: Patch testing confirmed a Type IV (T cell mediated) sensitivity to thimerosal, further supported by the prior history of a reaction to a thimerosal containing contact lens solution. The patient was asked to avoid thimerosalcontaining products, including vaccinations, unless the benefit clearly outweighed the potential risk of a reaction. Conclusion: Physicians need to be aware that thimerosal is found in many products including vaccinations. Clinicians should also be aware that allergic reactions do occur with exposure to thimerosal even in vaccines. This is the first case report in the literature of a generalized reactions to thimerosal from an influenza vaccine Angioedema is a rare condition that has been described in the literature and exists in both inherited and acquired forms. A defect of the innate immune system, more particularly the complement system, is the inciting culprit. The acquired form of C1 esterase inhibitor deficiency has been divided into two classes and is generally not commonly seen until after the forth decade of life. Type 1 acquired angioedema has been described in association with lymphoproliferative disorders, while type 2 is related to excessive complement activation and consumption due to autoantibodies. Our case is a 67-year old man referred from an outside physician for further management of idiopathic edema. He first experienced facial edema in April 2002 attributed to sweet myrrh root ingestion. Subsequently, in November 2002 he developed diffuse swelling of his upper extremities and tongue without airway compromise. A minimal work-up at that time was inconclusive. He fortunately remained asymptomatic until January 2004 at which time he experienced two episodes of tongue swelling without etiology. He was seen in his local emergency department and treated with diphenhydramine, corticosteroids, and epinephrine on both occasions with gradual improvement of his symptoms. The patient was not on medications commonly associated with angioedema and did not report insect envenomation. Subsequently, he was seen by his primary care physician who ordered a number of laboratory tests including a CH50, which was significantly suppressed. In light of this finding, he was referred to our clinic for further evaluation. At the time of presentation to our office, the patient was symptom free. His physical exam was within normal limits. Further laboratory evaluation was essentially unremarkable with the exception of comple-ment studies, which are listed in the table. Our case demonstrates an elderly patient with evidence of idiopathic swelling. We arrived at our diagnosis of acquired angioedema based on clinical presentation and confirmatory serum complement levels. A low CH50 at time of presentation allowed us to further delineate the etiology of complement deficiency. The fact that our patient did not present with swelling until after age 60 and the paucity of a family history of idiopathic angioedema makes the diagnosis of acquired angioedema probable. Measure of serum C1q level confirmed the diagnosis. INTRODUCTION: Certain diseases, widely believed to be of allergic etiology, including atopic dermatitis and episodes of wheezing might be the result of interplay of genetic and environmental factors, at least partially. We describe a child with a rare chromosomal disorder presenting with typical features of atopic dermatitis and recurrent mild wheeze. MATERIALS AND METHODS: A new born African-American male was noted to have unusual facial features immediately after birth. The baby was born naturally, without antenatal and neonatal problems. On physical examination, the infant had unusual facial characteristics with tight and taut facial skin, relatively diminished facial pad of fat, pointed chin, and markedly hypertonic extremities. Additionally, cardiac exam revealed mumur consistent with uncomplicated ASD. Frequent reassessments of the infant in the outpatient clinic were done. The child had repeated bouts of wheezing attacks, and facial rashes compatible with the diagnosis of atopic dermatitis. The wheezes were treated in the clinic with nebulaized bronchodilators, and the atopic dermatitis responded reasonably to topical steroid applications and moisturizers as needed. Chromosomal analysis of the peripheral blood of the chid confirmed the diagnosis of deletion of long arm (q) of chromosome 1 [46, XY, del (1)(q42q43)]. Karyotypic analyses of the mother and father were normal. The child exhibited features of developmental delay, and seizure activities. Anti-epileptic drugs (AED) were instituted. Initial EEG was normal and the subsequent EEG showed findings of static encephalopathy. CT scan of the brain revealed absent corpus callosum. Neurologic evaluations and physiotherapies were requested for improvement of fine motor skills. He did not seem to suffer from any serious infectious or immunodeficient illnesses. His CBC was normal. He continued to have fair gains in his weight, height, and head circumference. His atopic dermatitis and wheezing episodes remained under control. There were a few hospitalizations for break-through seizures and dehydration from gastroenteritis. A subsequent echocardiography confirmed closure of ASD. CON-CLUSION: A child with chromosomal anamoly, atopic dermatitis, and mild intermittent wheeze is reported. Despite multiple congenital problems, the child continued to have a stable clinical course. Etoposide is a chemotherapeutic agent used to treat many solid tumor malignancies. Hypersensitivity reactions have been well described and there are a few reported deaths from anaphylaxis. Some suggest that the hypersensitivity is an anaphylactoid type reaction as it may occur during the first dose. Case reports of cutaneous complications include Stevens-Johnson syndrome, radiation recall and diffuse erythema. There are four cases in which diffuse erythematous papules developed after etoposide therapy. All rashes spontaneously resolved within three weeks and biopsies demonstrated keratinocytes in a starburst pattern. We report the first case of an immediate etoposide induced skin reaction that evolved into long lasting hyperpigmented plaques. Pretreatement was able to prevent this immediate and late reaction on subsequent exposure to etoposide. A 27 year old female with ovarian cancer was treated with bleomycin, etoposide and vinblastine. Three hours after initiation of the third dose of etoposide, patient developed pruritic, erythematous macules on her chest, abdomen, face and extremities. The infusion was stopped and decadron administered. Over forty-eight hours, the pruritic macules became hyperpigmented plaques on her chest, abdomen, extremities and face. Pruritus resolved after a slow taper of prednisone. The darken plaques were treated with multiple topical preparations but persisted for about three months. Biopsies demonstrated superficial perivascular infiltration of lymphocytes and a few eosinophils suggestive of a drug eruption. Etoposide was considered essential for this patient so allergy was consulted. The literature supports cautious readministration of etoposide with pretreatment and slower infusion rate to prevent immediate hypersensitivity. We could not guarantee prevention of the late hyperpigmented reaction. The patient was pretreated with prednisone and cetirizine. Etoposide was administered in an ICU with a slower rate of infusion. Etoposide was tolerated without immediate pruritus or erythematous reaction. The patient did not develop the delayed darkened plaques. Cautious administration of etoposide after premedication and a slow rate of infusion prevented both the immediate and late reaction previously experienced by this patient. Eosinophils normally comprise 1-3% of peripheral white blood lymphocytes. Peripheral blood eosinophilia is defined as an absolute eosinophil count >500 cells/mm3 and is most often caused by atopy, helminth infections, or collagen vascular diseases. Less common causes include adrenal insufficiency and neoplastic processes. Eosinophilia can be characterized as mild (<1500 cells/mm3), moderate (1500-5000 cells/mm3) or severe (> 5000 cells/mm3). Although severe eosinophilia has been reported in association with adult HIV infection, studies of HIV-infected children have not shown peripheral blood eosinophilia to be a feature of pediatric HIV infection. We report an unusual case of severe peripheral blood eosinophilia in an adolescent male who was subsequently found to be HIV-infected. A previously healthy 15-year-old male presented with 2 week history of fever, diarrhea, cough, vomiting, abdominal pain, anorexia and a 5lb weight loss over the previous 2 months. The patient had recently emigrated from Guyana and denied sexual activity, intravenous drug abuse, or other HIV risk factors. There was no known maternal HIV infection. Repeated stool specimens were negative for ova and parasites. Serologies for E. histolytica, T. canis, and S. stercoralis were negative. An abdominal ultrasound, chest X-ray, serum electrolytes, and liver function tests were all within normal limits. Total white blood cell was 16, 500 with 59% eosinophils (absolute eosinophil count of 9, 735 cells/mm3). ELISA and Western Blot were positive for human immunodeficiency virus (HIV-1). CD4+ Tlymphocyte count was 1277 cells/mm3 with an HIV-1 RNA level of 11, 000 copies/ml. The patients symptoms resolved over the next 10 days without treatment. He was started on combination antiretroviral therapy (zidovudine, lamivudine, abacavir, and efavirenz). Absolute eosinophil count continues to slowly decrease with the last count of 3, 605 cells/mm3 three months following the introduction of antiretroviral therapy. Severe peripheral blood eosinophilia may be a presenting feature of HIV infection in adolescents. HIV testing should be considered in cases where more common causes of eosinophilia such as atopy and parasitic infections are excluded. Triad asthma is well described in adults but not in the pediatric literature. This case highlights the successful treatment of a severe pediatric asthmatic with nasal polyps and aspirin sensitivity. A 13 year-old female presented with severe persistent asthma, EIB, allergic rhinitis, chronic sinusitis, nasal polyps, and a history of pneumonia. Her asthma symptoms were minimal from age 2 until age 9. She then started Flovent and required increasing amounts of inhaled and oral steroids. She required 6 courses of oral steroids per year by age 13. In addition, she had snoring, fatigue, chronic nasal congestion, rhinorhea, and sneezing despite treatment withAllegra and Rhinocort. She had received immunotherapy from age 8 to 10 with no clinical improvement. Since age 8 she had recurrent sinusitis and had required 2 polypectomies. She noted aspirin caused nasal stuffiness and mild wheezing and therefore avoided it. On exam she had allergic shiners, Dennie lines, boggy turbinates, nasal polyps, and diffuse wheezing. On evaluation she had severe airway obstruction. Her FEV1 increased from 36% to 51% with albuterol. Her chest CT had a mosaic pattern due to severe air trapping, and her NO level was 177. A sleep study showed severe hypopneas, and she had pan-sinusitis on CT. She had multiple positive SPTs, an eosinophil count of 1100 and an IgE of 700. She had a normal sweat chloride and pH probe.The differential diagnosis included Churg-Strauss, ABPA, cystic fibrosis, bronchiolitis obliterans, and triad asthma. After a thorough evaluation, she was diagnosed with triad asthma. With 6 weeks of treatment with oral prednisone, her FEV1 improved from 36% to 83%. Her inhaled controller therapy was increased and she was placed on Xolair. She had a polypectomy and then underwent aspirin desensitization. One year after starting treatment her FEV1 remains 83%. She requires albuterol 1x/month and has not required prednisone. Her EIB, allergic rhinitis and congestion are markedly improved. She has had no further episodes of sinusitis, and a repeat sleep study was normal. In conclusion, we treated a severe pediatric asthmatic with nasal polyps and aspirin sensitivity. This is not frequently reported in the pediatric population, and raises questions about the incidence, optimal long term treatment of triad asthma, and the differences from the adult onset of this disease.
A.A. White * , R.A. Simon, La Jolla, CA.
Background: Human disease from mold has traditionally been isolated to infection, allergic disease, or hypersensitivity pneumonitis. Specific diseases or pathologic findings other than those listed above have not been well described. We report a case of acute eosinophilic pneumonia related to mold exposure. Case Presentation: A 50 year old woman developed dry cough and shortness of breath after Stachybotrys mold was discovered in her home. A chest radiograph showed bilateral upper lobe infiltrates which worsened two weeks later. Treatment with macrolide and flouroquinolone antibiotics was ineffective. A white blood cell count was 12, 000/cumm with 35% eosinophils. An erythrocyte sedimentation rate was 99 mm/hr. Aspergillus IgE was negative. Treatment with prednisone led to complete resolution of the chest radiographic abnormalities and improvement in pulmonary function testing. This patient was given a diagnosis of acute eosinophilic pneumonia with mold as a likely causal factor. Discussion: There is dispute amongst health care professionals regarding the significance of environmental mold contamination in the etiology of human disease. This case represents well characterized disease occurring in the setting of mold exposure. While a causal relationship cannot be established, the temporal relationship of mold contamination, symptom onset, and disease progression is compelling. Interestingly, a recent report of mold contamination leading to nonspecific interstitial pneumonia/fibrosis has been described. We have observed a patient in our clinic with similar pathology on biopsy and temporal relationship to mold exposure. To our knowledge, acute eosinophilic pneumonia has not been reported in conjunction with mold exposure. Conclusion: This case highlights a new condition in which mold may have a causal role. The mechanism is unknown, but likely is through a non-IgE mediated immunologic pathway. Public awareness of mold as a health concern is increasing. Perhaps similar cases will emerge as a history of mold exposure is offered by patients at the time they are evaluated for lung disease. A stronger correlation may then emerge. Scuba diving is a commonly practiced activity which normally carries only minimal risks. Any severe allergic reaction such as anaphylaxis, however, occurring during this activity could be a particularly dangerous not only because the swimmer is submerged but also because of the lack of proximity to medical care. We report a case of anaphylaxis occurring during scuba diving resulting from an unsuspected hypersensitivity to a latex component of the scuba diving suit. A 21 yr-old white male developed a severe generalized urticarial rash with angioedema of his lips and eyelids, and difficulty breathing within 5 minutes of his applying the suit and entering the water. After being rescued, he was transported to a nearby emergency department where he received epinephrine, antihistamines, corticosteroids and IV fluids with gradual improvement over a 4 hour period. The patient denied being stung by a marine aquatic organism and there was no prior history of allergy or medications usage prior to his reaction. Since subsequent investigation revealed that the scuba diving suit contained latex (Brazilian rubber), a specific IgE RAST was found to be strongly positive (Class V) to latex. Therefore, the patient was advised to use a suit made of Neoprene synthetic rubber (polychloroprene) which is a nonlatex containing product. This case report illustrates the importance of a diligent search for hidden sources of latex products which can produce life-threatening allergic reactions in sensitized patients. There has been considerable debate concerning the safety of immunizing egg-allergic children with the combined MMR vaccine. This concern derives from the possibility of an anaphylactic reaction since the MMR vaccine is prepared from attenuated viruses grown on chick embryo fibroblast cell cultures. We have previously reported the safe administration of the MMR vaccine to 6 severe egg-allergic children without development of an adverse reaction (Nsouli, TM, et al. Ann Allergy Asthma Immunol. 2004; 90:163) , a finding consistent with the current Report of the Committee on Infectious Diseases, American Academy of Pediatrics, 2003. The present case report describes an anaphylactic reaction in an egg allergic 4 yr-old-white male consisting of generalized urticaria, angioedema, wheezing immediately following the administration of a second MMR vaccine. The history of hives following ingestion of eggs was confirmed by positive specific IgE RAST testing. The patient's anaphylactic reaction necessitated emergency treatment including epinephrine, diphenhydramine, and corticosteroids in addition to IV fluids. Although the administration of MMR vaccine in egg-allergic children is not considered as an absolute contraindication, the present case report suggests that caution should be observed when administering the MMR vaccine in such patients and that careful medical observation be included together with the ready availability of emergency medical equipment.
P. Buddiga * , R. Turbin, A. Baisre, L. Bielory, Newark, NJ.
Introduction: Sarcoidosis is a chronic granulomatous disease of unknown etiology that may have a multi-organ system manifestation and is characterized by the histopathological evidence of nonnecrotizing granulomas. Case Report: A 53 year old African American woman with a 10 year history of Type II Diabetes mellitus, hypertension and sinusitis recalcitrant to multiple courses of antibiotics over 3 months was admitted to the hospital with complaints of right eye proptosis, diplopia, headache and right facial numbness.Her exam was consistent with an ipsilateral mild optic neuropathy, complete sixth (VI)nerve palsy, trigeminal, ophthalmic and maxillary division numbness.CT and MRI of the face, orbit and brain revealed an extensive process infiltrating ethmoid, maxillary and frontal sinuses;orbits and deep facial structures.Chest CT revealed bilateral interstitial nodules and symmetric hilar adenopathy. Differential diagnoses included sarcoidosis, lymphoma/tumor, Wegener's granulomatosis or fungal infection.Labs-Purified protein derivative test=negative(neg), Antineutrophil cytoplasmic Autoantibodies=neg. Angiotensin converting enzyme=83[8-52 U/L], Fungal & Anaerobic and Acidfast bacilli culture of sinus secretions=neg.Ethmoid, adenoid and maxillary sinus biopsies=multiple nonnecrotizing granulomas. On the basis of compatible clinical and radiographic findings, histopathological evidence and exclusion of other diseases with similar findings, the diagnosis of sarcoidosis was established. She was started on parenteral methylprednisolone and subsequently tapered to oral prednisone after 5 days.Concomitantly she was started on methotrexate as a steroid sparing agent.Most recent chest x-ray after 4 months of treatment reveals near complete resolution of the hilar lymphadenopathy.At 5 months her optic neuropathy and facial dysesthesia had resolved, and she was left with mild persistent VI nerve dysfunction. Conclusion:Sarcoidosis that manifests itself as sinusitis is an uncommon presentation and the mechanism involved is thought to be a consequence of the destruction of cilia and mucus producing glands by the granulomatous process.Review of the literature indicates that this is the eighth case reported and illustrates that a high index of suspicion of other etiologies must be maintained when there is a refractory response to multiple courses of antibiotics in the treatment of sinusitis.
J.B. Hein * , P. Patel, L. Bielory, Newark, NJ.
Introduction: CID may result in opportunistic infections such as cryptococcal meningitis. We present an unusual case of cryptococcal meningitis in an HIV-negative patient with severe CD4 lymphocytopenia. Case: A 40 yearold male with a three year history of sarcoidosis presented with acute onset of right-sided body numbness. The patient had been on prednisone 40 mg/day for 5 months prior to presentation. CT and MRI scanning showed no vascular defects, meningeal enhancement, hydrocephalus or mass lesions. Gallium scanning revealed normal uptake in the liver and spleen, mild uptake in the lungs and nasopharyngeal region, and asymmetric uptake in bilateral kidneys. The patient's initial WBC was 8, 000 cells/mm 3 , composed of 6970 neutrophils/mm 3 , 50 eosinophils/mm 3 , 50 basophils/mm 3 , 530 lymphocytes/mm 3 , and 400 basophils/mm 3 . Repeat studies revealed the total lymphocyte count decreased at 240 cells/mm 3 with CD19 (Pan B) cells decreased at 29 cells/mm 3 and CD3 (Pan T) cells decreased at 189 cells/mm 3 . CD4 count was 144 cells/mm 3 and CD8 count 50 cells/mm 3 with a CD4/CD8 ratio of 2.9. IgG levels were normal at 716 mg/dl. ELISA was negative for HIV, and HIV-1 RNA by PCR was not detected. Serum ACE level was 19 u/l and CSF ACE level was 23 u/l. CSF obtained by lumbar puncture stained positive with India ink and culture revealed Cryptococcus neoformans. The patient responded to Amphotericin B lipid complex 5 mg/kg/day, and his neurological status eventually returned to baseline. Conclusions: The severe lymphopenia in this patient caused predisposition to infection with Cryptococcus neoformans. The etiology of the profound lymphopenia likely was multifactorial, including mild sarcoidosis activity (lung uptake on gallium scan) and chronic corticosteroid therapy. However, once Cryptococcus became entrenched in the patient's CSF, the infection itself likely depressed peripheral lymphocyte numbers even further. This case demonstrates the importance of exploring a broad differential diagnosis when faced with lymphocytopenia. Background: Isosulfan blue 1% is a common dye used in sentinel lymph node dissection. The usage of the procedure and dye has increased in numbers, and although rare, several cases of anaphylactic reaction have been reported. Objective: We are reporting a patient who had an anaphylactic reaction to isosulfan blue while undergoing breast cancer excision with sentinel lymph node biopsy. Methods: The patient is a 44 year-old woman with breast cancer. She underwent breast mass excision with sentinel lymph node biopsy using the Lymphazurin 1% blue dye (isosulfan blue). She has a history of penicillin induced hives but has no other drug allergy. As soon as the dye was injected, she became flushed, hypotensive, and tachycardic. Hypotension was refractive to fluid challenge. She was then treated with epinephrine as well as intravenous steroids and cimetidine with relief of symptoms. Subsequently, she was evaluated in Allergy and skin tests with isosulfan blue 1% at 1:100, 1:10 dilution, and undiluted were performed using histamine as positive control and saline as negative control. This procedure was also performed on two control subjects. Results: The patient had a positive skin test (wheal and flare) to isosulfan blue 1% (undiluted) with the control being appropriately positive for histamine and negative for saline. Control subjects had negative response to dye and saline and positive response to histamine. Conclusions: Isosulfan blue 1-% dye may cause anaphylactic reactions in patients undergoing sentinel lymph node dissection. . The positive skin test result to the dye plus the negative skin test responses in the controls suggests that the reaction may be immunoglobulin E (Ig E) mediated. Eosinophilic duodenitis (ED) and gluten-sensitive enteropathy (GSE) or Celiac disease (CD) are distinct clinical entities with well-defined clinical and laboratory parameters. ED is a rare condition of unknown etiology, which is manifest by eosinophilic infiltration of the gastrointestinal tract and peripheral eosinophilia. GSE or CD is a form of non-IgE food allergy caused by immune hypersensitivity to ingested gluten. The simultaneous occurrence of the two entities, however, is a rare event. The following presentation is a case report in which both entities were found in the same patient. An 11 y/o white hispanic male presented with severe, chronic, colicky abdominal pain and headache of 5 months duration. Hematologic and immunologic studies were within normal limits. Serum IgE levels were 356 IU/mL (n= < 200 IU/mL), Anti-endosomial Ab (+), IgG Antigliadin: 16 U/mL (n=: 0-12 u/mL), Skin tests for food and inhalant allergens were weakly positive (1+). Biopsy of the inferior third of esophagus revealed chronic moderate esophagitis; biopsy of gastric antrum revealed lymphatic hyperplasia; duodenal biopsy showed shortening of the villi with the presence of eosinophils. Following treatment with esomeprazole 40 mg BID, famotidine 20 mg QD, montelukast 20 md QD, lactobacillus, a diet free of gluten, rofecoxib 25 mg QD and betamethasone for 15 days, betamethasone the patient improved with partial resolution of symptoms. The presence of duodenal eosinophils persisted despite a gluten free diet, and continued to require repeated bursts of prednisone. Since to our knowledge this is rare finding in which ED occurred in association with GSE, a high index of suspicion for simultaneous occurrence of ED should be raised in any case of GSE that fails to respond to a conventional gluten free regimen. We report the evaluation of a 6 month old male presenting with a pustular rash and choking episodes from birth. By age 6 weeks, he had experienced two pneumonias, one with fleeting infiltrates requiring intubation. Persistent eosinophilia (5000-9000/ml) and eosinophils on pustule biopsy were noted. Persistence of these and subsequent RSV pneumonia and recurrent draining otitis media led to referral. Physical examination showed a thriving male infant with multiple erythematous papules and pustules along the scalp, face, axilla, and trunk. Eosinophilia was confirmed. Quantitative immunoglobulins were abnormal for IgG 179 and IgE 255 IU/ml. Peanut CAP RAST was 23 kUA/L. HIB post-vaccination titer, T cell enumeration/stimulation, and NBT were normal. HIV testing, stool eosinophils, O&P, and hemoccult were negative. CXR, HRCT, EKG, and echocardiogram were normal. Pustule cultures for bacteria, virus, and fungus were negative. Skin biopsy revealed numerous eosinophils in the pustule, dermis, epidermis, and perifollicular region. CD1a+ and S-100 staining were negative for histiocytic infiltration. NEMO defect/incontinentia pigmenti were considered but testing was negative and karyotype 46, XY. Bone marrow biopsy revealed numerous eosinophils at different stages of maturation, and no myeloproliferative or neoplastic changes. Bronchoscopy was remarkable for 15% eosinophils on BALF. 24-hour pH probe and impedence evaluation was negative. EGD with biopsy was normal except for mild eosinophilic infiltration of the proximal and distal esophagus. With the clinical picture of recurrent pruritic crops of sterile pustules and characteristic skin biopsy demonstrating eosinophil infiltration, the diagnosis of eosinophilic pustulosis (EP) of childhood was made. Despite no longterm sequelae or other end-organ involvement in EP, the degree and duration of eosinophilia, and presence of eosinophils in the airways and esophagus, raises the concern for other eosinophilic syndromes. Following cardiac, CNS, pulmonary, and GI systems is warranted. The infants pneumonias were felt to be due to aspiration, and ear infections the result of humoral immunity nadir or draining pustules in the external auditory canals. Immunoglobulin levels will be monitored. This case illustrates the heterogeneity of eosinophilic diseases and raises the question of what drives the mechanisms behind malignant and benign disease. INTRODUCTION: Behcet's disease is a chronic, relapsing vasculitic disease characterized by recurrent oral, genital, and gastrointestinal ulcerations, a wide variety of skin lesions, uveitis, and arthritis. Pediatric cases of Behcet's disease are uncommon with an estimated prevalence of 1 in 600, 000 children under the age of 15. Although the disease in children shows similar characteristics as adults, the diagnosis of Behcet's disease in the pediatric population remains a challenge. This report describes an 18 year old girl referred to our pediatric immunology clinic for evaluation of recurrent painful oral ulcerations since the age of 7 with no genital ulcerations. The oral ulcers would last for two weeks and heal spontaneously but would reappear 2 to 3 weeks later. The patient had a history of Raynaud's Phenomenon for the last 6 to 7 years and the recent onset of joint pain. Physical examination revealed 4-5 white elliptoid lesions 5-7 mm in diameter on an erythematous base on the tongue and soft palate. Skin examination was significant for hyperpigmented patches over the neck, abdomen, and back. There were erythematous, serpigenous lesions on the palms and punctuated necrotic lesions on the finger-tips. Pathergy test was positive. Laboratory investigation was unremarkable and cultures from the oral ulcers remained negative. The patient was diagnosed with Juvenile Behcet's disease. She was started on immunosuppressive therapy with low dose prednisone and responded. CONCLUSION: Behcet's disease is a difficult diagnosis to make in the pediatric population. This case demonstrates that in children, recurrent oral ulcerations may be the only initial manifestation of Behcet, and an important clinical marker for the disease. Rationale: Relapsing polychondritis is an uncommon severe inflammatory condition with unknown etiology that can present in a variety of manners. We report a 14 year old patient who initially presented with signs and symptoms of anaphylaxis to shellfish and was later diagnosed with relapsing polychondritis. Case Report: A 14 year old African-American boy with a 6 year history of asthma and fish and shrimp allergy presented to the Pediatric Intensive Care Unit on 4/23/03 after an episode of severe shortness of breath. His symptoms started shortly after accidental exposure to shrimp. In the intensive care unit, he was noted to be wheezing and stridorous. An initial chest Xray as well as subsequent fiber optic laryngoscopy showed sub-glottic stenosis. He was intubated and received mechanical ventilation for greater than a week. After extubation, he stated that he felt fine, but continued to demonstrate audible stridor. Pulmonary function tests demonstrated extra-thoracic obstruction, laryngoscopy continued to show sub-glottic stenosis, and esophagogastroduodenoscopy showed erosive esophagitis consistent with reflux. Initial lab tests demonstrated a normal eosinophil count, elevated IgE (969 IU/ml), and positive immunocaps testing to multiple foods. The patient was discharged home with minimal stridor and no wheezing. Over the next nine months, the severity of his stridor waxed and waned, but in general it worsened in spite of a strict elimination diet and anti-reflux therapy. On 9/25/03 he received an emergency tracheostomy. On 1/26/04, the patient was again admitted to the hospital. At this time he complained of bilateral knee pain as well as significant weight loss. Physical exam demonstrated arthritis with effusions of both knees as well as unilateral auricular chondritis and bilateral episcleritis. Antibodies against type II collagen were positive (42.1 EU/ml). The diagnosis of relapsing polychondritis was suggested. Conclusion: Relapsing polychondritis is a rare inflammatory disorder of the cartilage and connective tissue with an unknown etiology. The wide array of presenting complaints as well as the relapsing nature of this disorder often causes significant delay in diagnosis and treatment. In our case there was a period of nine months between the initial presentation and the time when the diagnosis of polychondritis could be made.
D.K. Geller * , M. Ballow, Buffalo, NY.
Introduction: An 11 yo male previously diagnosed with PANDAS presented to our immunology clinic for IVIG. The patient was healthy until age 8 when he developed facial motor tics associated with group A beta hemolytic strep pharyngitis. He was treated with antibiotics and the tics resolved completely. He has had multiple recurrences associated with strep and other viral infections. The tics improve or resolve completely when he is infection free. He has no history of vocal tics, attention deficit/hyperactivity disorder, or obsessional thinking or compulsive behaviors. Laboratory: Multiple throat cultures positive for group A beta hemolytic strep, positive antistreptolysin and antideoxyribonuclease B titers. Discussion: PANDAS identifies a subgroup of children with an obsessive compulsive disorder and/or tic disorder whose symptoms seem to be triggered by streptococcal infections. The proposed pathophysiology is an immune-mediated mechanism in which antistreptococcal antibodies, antistreptolysin and antideoxyribonuclease B, cross react with the basal ganglia of genetically susceptible hosts. A few studies have looked at immunomodulatory therapies including IVIG for neuropsychiatric symptoms including tic disorders secondary to post-streptococcal autoimmunity. We plan a trial of IVIG for this patient given the recurrent nature of his tics and the relation to streptococcal and other viral infections. Introduction: The Chronic Granulomatous Disease (CGD) is an inheritable disorder of phagocyte cell respiratory burst that result in life-threatening infections. The pulmonary infection is the primary cause of death in greater that 50% of the cases and the role of surgery in management of this entity remains undefined. Case report: A lobectomy was performed in a 2 year-old male who presented a persistent opacity of the medial right lobe with fever, cough, malaise an rapid onset of respiratory failure; skin abcesses were concomitant. His familiar history was unremarkable. A chest tube was placed in a first instance in order to drain empyema, but no progress was observed. A CT scan showed necrotizing pneumonia of the right lung, mediastinal and retroperitoneal limphadenopathy and bronchopleural fistula. A second surgical intervention was undertaken to correct the fistula and pleural debridement was done. At this time, Serratia marcenses was isolated from blood culture and lung; a primary immunodefiency was suspected. Our evaluation showed NBT reduction on 0% and Dyhidrorhodamine assay (DHRA) didn't demonstrate and effective oxidative burst. The subsecuent management was based on specific antibiotic to Serratia and prophylaxis with TMP-SMZ and Itraconazole. Transfer Factor to improve the IFN levels was initiated. The patient's mother showed on DHRA two granulocyte populations, with and without oxidative burst. A X linked CGD was consistent. Medical progress was observed in the next days. Conclusion: Despite the poor utility showed by the surgical procedures in the complicated pneumonia in CGD patients in many series, attending to the unusual nature of the pulmonary infections and the high mortality and morbidity associated with thoracic surgery; the management of this case showed that an aggressive approach in the diagnosis combined with some procedures used in immunocompetent patients pneumonia may improve the clinical condition in CGD patients. Background: Takayasu arteritis is a large vessel vasculitis primarily affecting the aorta and its branches. It is most prevalent in women in the second and third decades of life. Initial symptoms are systemic and often self-limited, but the disease may progress undetected over years until signs of vascular insufficiency develop. Arteritis is commonly seen in the aortic arch and its branches, although the disease is a panarteritis and vascular compromise can occur in many organs. Pathologically, involved vessels show intimal proliferation and fibrosis, and scarring of the elastic lamina. Case Report: We report the case of a 31 year old Southeast Asian woman who presented with diplopia, ptosis, dizziness, and progressive dyspnea. Past medical history was significant for rheumatic fever complicated by aortic valve insufficiency and hypertension. Physical findings on admission included hypertension, asymmetric upper extremity blood pressure (left arm 95/50mm Hg, right arm 200/50 mm ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY Hg), wide pulse pressure and a harsh diastolic murmur. Admission labs showed anemia (hemoglobin: 11g/dL, hematocrit 33%) and an elevated erythrocyte sedimentation rate of 31mm/hr. Transesophageal echocardiography revealed severely dilated aortic root aneurysm with secondary severe chronic aortic valve insufficiency and calcified aortic leaflets not typical of rheumatic heart disease. Resection of the aortic valve and aneurysm was performed. Pathologic examination of the aortic aneurysm revealed intimal and adventitial fibrosis with focal chronic inflammation and partial loss and fibrosis of media, findings compatible with healed Takayasu arteritis. The patient was started on prednisone 100mg by mouth daily for Takayasu arteritis and discharged in stable condition. Discussion: This is a case of Takayasu arteritis masquerading as rheumatic heart disease. The episode of rheumatic fever was likely the initial presentation of Takayasu arteritis, as the systemic symptoms of these diseases can overlap. Takayasu arteritis is an insidious disease that often leads to a delayed diagnosis with considerable morbidity for the patient. Since Takayasu arteritis may go undiagnosed until ischemic symptoms develop, physicians should be alert to the possibility of this disease in young women to avert end organ damage and achieve early remission with drug therapy. We present a fifteen year old boy with disseminated papillomatosis and idiopathic CD4+ lymphocytopenia (ICL). The warts have been present since he was one year old and have progressively worsened. There are more than fifty warts on each of his hands. His legs have multiple warts and about ten warts recently appeared on his lips and around his mouth. His past medical history is significant for no hospitalizations and no blood transfusions. He has never had problems with other infections, and he had a benign course of chicken pox that spontaneously resolved. He has been on cimetidine for six months without improvement. Several topical therapies, including imiquimod, have failed. He has a total lymphocyte count of 1484/uL (normal range, 1288-4512/uL) and a CD4+ count of 301/uL (normal range, 361-1715/uL). The CD8+, Natural Killer Cells, and CD19+ cells were normal. His HIV test is negative. The serum immunoglobulins were normal as well. Lymphoctye proliferation studies reveal an absent response to antigens (Candida and Tetanus) with a normal response to mitogens. Further studies showed no other cause of CD4+ lymphocytopenia. This case shows that the diagnosis of Idiopathic CD4+ lymphocytopenia should be considered in any patient with widespread viral infection whose HIV test is negative. Appropriate evaluation of the CD4+ count should be pursued.
J. Ko * , A. Nowak-Wegrzyn, New York, NY.
INTRODUCTION: Approximately 40% of children with moderate to severe atopic dermatitis (AD) have food allergies. Complementary and alternative medicine (CAM) is utilized by an estimated 16-27% of patients with allergies. We present a case of a 4 year-old boy with AD referred after receiving a diagnosis of food allergy by a CAM practitioner. METHODS/CASE: A 4 year-old boy was referred for evaluation of mild AD and possible food hypersensitivity. His AD started at 1 year of age and was limited to the face. He was initially breast-fed and was switched to milk-based formula at 4 months of age. Solids were introduced at 5 months of age without difficulty. He had no immediate reactions or noted worsening of AD due to foods. The patient presented to a naturopath for allergy evaluation. Based on electrodermal skin testing results, he was reported to be allergic to milk, egg, peanut, rice, and beef (all of which he had tolerated previously). He was restricted from milk and egg for 4 weeks without noticeable change in his AD, which was limited to the cheeks and controlled on topical pimecrolimus. RESULTS: His weight and height were both 75th percentile. Physical exam was normal except for 2-3 cm dry, erythematous patches on both cheeks and mildly dry skin on flexor/extensor surfaces of both arms. Skin prick testing revealed negative tests to milk, egg, peanut, and dust mite. Serum IgE testing was also negative. Since he had no evidence of IgE sensitization to commonly allergenic foods, he was recommended to continue an unrestricted diet and discontinue use of a "Sippy" cup. His AD subsequently improved on a skin care regimen of postbathing moisturization and topical pimecrolimus prn. Asthma and allergies are the #2 reason for CAM use in the US. Electrodermal skin testing is a method utilized by naturopathic doctors to detect allergen "sensitivity". However, in two double-blinded trials examining atopic and non-atopic patients, electrodermal testing did not correlate with skin prick testing results, regardless of inter-operator variability. CONCLUSIONS: Allergy patients are seeking CAM treatment, and it is important for physicians to be aware of the safety and efficacy of alternative medical practices. The use of electrodermal skin testing has not been proven to detect allergen sensitivity and use of this modality should be discouraged.
E.E. McGintee * , K.E. Sullivan, Philadelphia, PA.
Introduction: Hematopoietic stem-cell transplantation causes profound Tcell immunodeficiency due to the rigorous conditioning involved. Following transplant, the T-cell compartment is initially reconstituted through expansion of mature donor-derived T-cells. However, thymopoiesis is necessary to generate naive T-cells with a diverse repertoire. Factors affecting thymic function impact the ability of the body to reconstitute the immune system. We report a case of severe T-cell immunodeficiency after two stem-cell transplants for neuroblastoma in a patient with a history of thymic hemorrhage secondary to mediastinal surgery. Case: A 5-year-old female with a history of high-risk neuroblastoma was referred for immunologic evaluation due to a significant infectious history since completing her neuroblastoma therapy. She initially presented at 21 months of age with a right atrial mass that was presumed to be an atrial myxoma. She underwent mediastinal surgery to resect the tumor, which was found to be neuroblastoma extending from her right adrenal gland along the vena cava. A CT scan following her surgery revealed an area of hemorrhage in her right thymus. She subsequently received high-dose chemotherapy and two autologous stem-cell transplants. Her infection history was significant for multiple episodes of upper respiratory illnesses, sinusitis, and otitis media requiring myringotomy tube placement on two occasions. Immunologic evaluation revealed a dramatically low absolute lymphocyte count with deficits primarily in the T-cell compartment, and reduced proliferation in response to mitogens. Immunoglobulin levels were normal; she formed protective titers to diphtheria and tetanus but not to any of 14 pneumococcal serotypes. Conclusion: Stem-cell transplantation often results in severe T-cell immunodeficiency. The thymus plays an important role in reconstituting the T-cell compartment with naive T-cells generated from hematopoietic stem-cells, which restores TCR diversity. As this case illustrates, damage to the thymus can significantly impair the ability to reconstitute the T-cell compartment.
A.K. Knight * , C. Cunningham-Rundles, New York, NY.
Rationale: This is the first case report of oxcarbazepine induced immunoglobulin deficiency. Methods: A 49 y/o white female was referred for further investigation of low serum immunoglobulin found as part of an evaluation for chronic bacterial vaginitis. She was taking oxcarbazepine for chronic pain. This was discontinued and immunoglobulin levels and B cell numbers were tested at intervals. Specific antibody responses to pneumococcal vaccine were tested. Results: At presentation, on oxcarbazepine, immunoglobulin levels were low [IgG 576, IgA <11, and IgM <4 mg/dL] and she had a B cell deficiency [1%, 18 B cells (normal 5-15%, 75-375 cells/cu mm)]. Antibody response one month after pneumococcal vaccine was poor (protective antibody to 2/12 serotypes). (7%)] with protective antibody responses to 5/12 pneumococcal serotypes. She continued to have IgA deficiency. Conclusions: The patient's initial evaluation suggested the diagnosis of Common Variable Immune Deficiency with hypogammaglobulinemia and specific antibody deficiency. However, these defects reversed when oxcarbazepine was discontinued. It is unclear if persistent IgA deficiency was a pre-existing condition, possibly predisposing her to this adverse reaction to oxacarbazepine, or induced by the oxacarbazepine. Immunoglobulin deficiency is a known, though rare, reaction to carbazepine, the parent drug of oxacarbazepine; this adverse reaction can occur with its derivative oxcarbazepine as well. Secondary hypogammaglobulinemia should be considered before diagnosing primary immunodefiencies such as CVID and committing the patients to lifelong immunoglobulin therapy. INTRODUCTION: Interferon and glatiramer acetate (Copaxone) are indicated for the treatment of relapsing-remitting multiple sclerosis (MS). Anaphylactic reaction has been reported as a rare complication of interferon and Copaxone use. We report a case of interferon -1a (Rebif) and Copaxone hypersensitivity associated with positive skin tests and desensitization to interferon -1b (Betaseron). CASE REPORT: The patient is a 28 year-old woman with asthma and allergic rhinitis who was diagnosed with MS in Oct '04 after an uncomplicated pregnancy and was subsequently placed on Rebif. One month after starting therapy, patient developed wheezing and generalized urticaria after receiving a dose of Rebif. The symptoms recurred the next day. Her neurologist stopped the Rebif and started her on Copaxone. Two months later she developed episodes of generalized urticaria. The patient was then evaluated in our center and underwent skin testing with interferon -1a intramuscular (Avonex), interferon -1a subcutaneous (Rebif), Betaseron, and Copaxone.
She had a positive skin prick reaction to Copaxone and positive intradermal skin tests to Avonex (1:10 strength), Rebif (1:1), and Betaseron (1:1) after 24 hrs. The intradermal reactions to all 3 interferon formulations continued to progress upto 48 hrs. Her neurologist felt that she would benefit from Betaseron therapy. The positive intradermal skin test to Betaseron was sufficient to warrant desensitization to prevent immediate hypersensitivity reactions. She underwent subcutaneous desensitization as shown in the Table. The desensitization was halted at 240 minutes after the patient developed itching of the hands.* She returned in 24 hrs and we restarted by administering 0.1 mL of 1:1 strength Betaseron. Increasing doses were given until the patient received a full therapeutic dose (0.3 mg in 1 mL). She has since done well with daily doses of Betaseron (4.5 mil units). CONCLUSION: We report a MS patient who developed urticaria and asthma exacerbation in response to Rebif and urticaria to Copaxone. Skin tests confirmed an IgE-mediated allergic reaction. She underwent successful desensitization to Betaseron. To our knowledge, this is the 1st report of desensitization to Betaseron as well as extension to previous reported cases of systemic reaction to interferon and Copaxone. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that has been used for ischemic vascular disease because of its effects on red blood cells and platelets. It has been used for systemic inflammatory diseases such as sarcoidosis because of its ability to inhibit production of cytokines such as tumor necrosis factor (TNF-a). We decided to offer a trial to a patient with chronic urticaria since agents that increase intracellular cAMP have been shown to inhibit mast cell degranulation. We report a case of a 50 year-old female with a history of allergic rhinitis, hypothyroidism, and diabetes mellitus with recurrent episodes of chronic urticaria since adolescence. She had known allergies to various antibiotics but otherwise had an unremarkable history, family history and social history. She was being treated with fexofenadine 180mg qd, azelastine nasal spray, zafirlukast 20mg bid, hydroxychloroquine 200mg bid, levothyroxine 25mcg qd, doxepin 25mg qHS, metformin 500mg bid, and spironolactone 25mg qd at the time of her initial evaluation. Her physical exam was notable only for scattered 2-3 cm urticarial skin lesions as well as areas of hypo and hyperpigmentation from previous excoriations. Her nasal turbinates were mildly congested with dull membranes. A previous skin biopsy showed only urticaria with increased numbers of mast cells. Her workup included normal CBC, urinalysis, SPEP and complete chemistry profile, as well as negative ANA and anti-thyroid antibodies. Pentoxifylline 400mg tid was added to the patient`s regimen. Her urticaria resolved within 2-3 weeks and was no longer visible at 2 months follow-up. Pentoxifylline is a safe medication with few side effects that may benefit patients with chronic urticaria via several mechanisms, including the inhibition of mast cell degranulation and secretion of various cytokines and chemokines. The beneficial effects of pentoxifylline in the treatment of this patient`s urticaria have been seen in other patients. Further study is indicated to determine which patients with urticaria are most likely to benefit from pentoxifylline, as well as elucidate the mechanisms of action by which pentoxifylline ameliorates symptoms of chronic urticaria.
C.M. Mjaanes * , M. Boguniewicz, Denver, CO.
We report the case of an 11-year-old male who since the age of 6 years has suffered from recurrent episodes of left tongue swelling. Onset of the swelling is usually abrupt, and generally occurs during the night, awakening him from sleep. He describes a sensation of pain in his tongue but denies any pruritus, throat, lip or eyelid swelling. He has no cough, dyspnea, wheezing, rash, or itchy/watery eyes. The episodes occur infrequently, approximately once every spring . They tend to resolve spontaneously within 4 to 6 hours, however, on 2 occasions, the swelling has lasted for 7-21 days. The patient's current episode has been present for 3 weeks and is progressing. Today he reports more pain and increased swelling. The child reports no benefit from oral antihistamines. He was treated with dexamethasone during his initial episode and experienced gradual resolution of the swelling. He has never been treated with topical or systemic epinephrine, or additional courses of systemic steroids. There is no family history of angioedema. The child was referred for evaluation of an immunologic/allergic etiology of his unilateral tongue swelling. Laboratory studies obtained early in the course of his current episode revealed the following: C3 level 84 mg/dL; C4 level 14.4 mg/dL; C2 level 22.5 mug/mL; C4D level 0.94 mug/mL; C1 esterase inhibitor function 115% of normal. C1 esterase inhibitor level 17.4 mg/dL; CH50 223 units/mL; ANA 1:40, negative; beta-tryptase < 1.0 ng/mL; total tryptase 7.0 ng/mL (all normal). Initial evaluation revealed marked swelling along with erythematous and violaceous discoloration of the left lateral and anterior portions of the child's tongue. The remainder of his examination was normal. The patient was referred to the pediatric otolaryngology clinic with a presumptive diagnosis of a glossal hemangioma versus lymphangioma. He underwent a magnetic resonance imaging study which revealed a poorly defined, mass-like enlargement of the anterior and left aspect of the tongue. He was treated with a five day course of prednisolone. After initial regression of the lesion a planned surgical excision was carried out without any complications. In conclusion, this rare case illustrates the unique presentation of glossal hemangioma presenting as recurrent angioedema. Highlighted are the differential diagnoses, laboratory studies and clinical features of oropharyngeal swelling.
Severe tongue swelling. Rare skin conditions such as leprosy need to be considered in the differential diagnosis of apparent urticaria and angioedema that is atypical in appearance or response to therapy. A 28 year old male originally from Laos presented with chronic recurrent nonpruritic indurated plaques on his face and trunk, and was referred to allergy by his primary physician with a diagnosis of urticaria and angioedema to rule out an allergic reaction to foods. He was otherwise healthy and on no medication, and had a negative personal and family history of atopy. He had moved to the United States from Southeast Asia in 1990, and visited for several weeks again in 2003. He was treated with prednisone and hydroxyzine without benefit; skin testing to foods was negative, and CBC, differential, sedimentation rate, antinuclear antibody, and liver function testing was normal or negative. A skin punch biopsy from an indurated area on the back showed granulomas with clusters of acid-fast organisms on AFB stain consistent with tuberculoid leprosy. As the patient was G6PD deficient, he could not be treated with dapsone and was treated alternatively with minocycline 100mg, rifampin 600mg, and clofazimine 50 mg daily. He was subsequently started on prednisone as he was determined to be having a reversal reaction; his lesions continue to improve. This patient had a rare condition, leprosy, which was confused with urticaria and angioedema. In patients presenting with atypical apparent urticaria or angioedema, especially if response to standard pharmacologic treatment is poor, a skin biopsy is indicated, and may be diagnostic as in this case. Introduction: Cutaneous flushing about the face of a toddler within minutes of eating specific foods prompts parents and clinicians alike to pursue food allergy testing. Auriculotemporal Syndrome, also known as Frey Syndrome, is an isolated and transient facial erythema about the distribution of the auriculotemporal nerve following mastication. We report a child who was referred for food allergy testing and was diagnosed with Auriculotemporal Syndrome. Case History: A 2 yo WF, prior full-term forceps-assisted delivery, has a history of facial flushing within minutes following ingestion of specific foods. The flushing can be induced by a variety of foods, specifically spaghetti, crackers, potato chips and hard candies, and typically resolves within minutes after eating. The child has no respiratory or gastrointestinal distress during the flushing episode. There is no angioedema, urticaria, or other rash elsewhere on her body. Within ten minutes of eating a lollipop in clinic, an erythematous, warm macular eruption appeared in a band-like region anterior to her ear extending from her temporal bone to her mandible. This response occurred bilaterally, with a mildly greater intensity on the right side of her face. No sweating or other symptoms developed, and the flushing began to diminish after thirty minutes of observation. Discussion: Auriculotemporal Syndrome is commonly seen in patients who have undergone facial surgery, specifically about the parotid gland. It is believed to be secondary to a disruption in the fibers of the auriculotemporal nerve. It is theorized that the nerve regeneration following an injury may join the parasympathetic fibers of the salivary gland with sympathetic fibers of eccrine sweat glands. Mastication then could result in flushing and sweating over the cutaneous distribution of the auriculotemporal nerve that extends from the temporal region to the mandible, anterior to the ear. Although rare in children, auriculotemporal syndrome has been associated with forceps delivery. Therapy is seldom of benefit or needed, and the syndrome often resolves spontaneously over many years. Conclusion: Auriculotemporal Syndrome leads to a cutaneous eruption temporally related to the ingestion of foods. Allergists should maintain an awareness of this rare syndrome to minimize food allergy testing or eliminate unnecessary food provocation challenges or restrictive diets.
M. Al-Ahmad * , S.S. Mace, Toronto, Canada.
Introduction: Ranitidine is a well-known H2-receptor antagonist. Anaphylactic reactions are seldom reported despite widespread use of the drug. We report a patient with anaphylactic reaction to ranitidine Methods: We report a case of anaphylactic reaction with Ranitidine. Results: A 45-year-old female with a history of urticaria over one year period, presented with 4 episodes of anaphylactic reactions of increasing severity over 1 year, after ranitidine ingestion. The first two episodes, occurred one hour after ranitidine ingestion, began with a sensation of burning, and itching in the head followed by dizziness, hypotension and near loss of consciousness. The patient had no significant pulmonary or laryngeal symptoms. The fourth episode, occurred 12 minutes after taking ranitidine tablet, was characterized by severe hypotension. Two episodes were managed at the emergency department. A skin prick test with a crushed ranitidine tablet demonstrated a positive 20 mm wheal response, which was negative in a control. Investigations for carcinoid syndrome and systemic mastocytosis were negative. Conclusion: An IgE mediated allergy to ranitidine is possible. Anaphylactoid reaction to ranitidine is a well recognized entity. However, to our knowledge, few cases of anaphylactic reaction to ranitidine have been described. Hypersensitivity reaction to ranitidine should be considered in patients suspected of having drug-related allergy. Introduction: Severe Combined Immune Deficiency(SCID) and Cystic Fibrosis(CF) may both present in infancy with a history of failure to thrive, diarrhea, and recurrent respiratory infections. Although CF is the most common genetic disease occurring in Caucasians with an incidence of 1 in 2500 births, SCID is a rare condition estimated to occur between 1 in 50, 000 to 1 in 500, 000 births. We report a case of X-linked SCID where the diagnosis of CF was originally entertained due to similar presentation and misleading laboratory results. Case: 5-month-old Caucasian male with 3 month history of recurrent respiratory illnesses, fever, loose stools, thick nasal discharge and failure to thrive. This was his second admission for a respiratory infection. Relevant lab results consisted of cultures which grew parainfluenza A virus on NP wash and Pseudomonas aeruginosa on deep throat culture, Chest Xray showed patchy infiltrates and a borderline sweat test of 51 MMOL/L. Despite being treated with broad spectrum antibiotic coverage, albuterol and pulmozyme, his respiratory symptoms were not improving. Physical exam revealed a thin infant with palpable though small lymph nodes cervical and groin, diffuse scattered rhonchi and liver edge palpable 3 cm below the costal margin. Quantative Immunoglobulins were obtained and resulted as an IgG of 75, IgA of <10, and IgM of 13. Review of his chest x-ray was significant for absent thymic shadow. Lymphocyte count since admission ranged from 400-1000. Flow cytometry revealed a CD3/CD4 count of 0%, CD3/CD8 count of 0%, CD56 of 1% and CD19 of 99% of all lymphocytes. T-cell stimulation tests were markedly diminished to both antigen and mitogen. A presumed diagnosis of X-linked SCID was made and patient undrewent haploidentical bone marrow transplantation. Subsequently, CF gene analysis resulted as negative. Discussion: As outlined in the case it is essential to recognize the similarities between the presenting symptoms of CF, a relatively common genetic disease and SCID, an uncommon one. Although Pseudomonas is seen in increased frequency in patients with CF, it is essential to recognize that it is also a leading pathogen affecting patients with antibody deficiency. Review of the literature did not reveal any previous cases of individuals with SCID reported as having an increased sweat chloride, nor any explanations of why this would occur. While immunodeficiency has previously been associated with some forms of dwarfism, we report the first described case of Common Variable Immune Deficiency in a patient with Seckel Syndrome (Bird Headed Dwarfism). The diagnosis of Seckel Dwarfism, an autosomal recessive disorder, was made at 6 months of age in this boy based on intrauterine growth retardation, proportional dwarfism, microcephaly, micrognathia, and narrow face with "bird-like" large eyes and beaking of the nose. Hematologic abnormalities are reported in an estimated 15% of such patients, and this child developed thrombocytopenia at the age of 3 years. By age 7, he had pancytopenia with hypocellular bone marrow. A low CD4 count (117/uL) was noted and both Bactrim and Neupogen were begun. His only significant infections, rotavirus and salmonella gastroenteritis, occurred at that time along with frequent otitis leading to PE tube placement at ages 7 and 8 but which subsequently resolved. He has never had opportunistic infections or thrush. By the age of 10 years, he required monthly red cell transfusions for severe anemia. After several months of transfusions, the blood bank reported that he no longer had detectable blood group antibodies during crossmatch; this led to measurement of immunoglobulins. IgM was undetectable with low IgA (35 mg/dL) and low IgG (545 mg/dL). He demonstrated no protective titers to any Pneumococcal serotypes after either conjugated or unconjugated Pneumococcal vaccines. Response to diphtheria, tetanus, rubeola, and influenza vaccines was adequate. Total hemolytic complement was normal. He remains lymphocytopenic (ALC = 552/uL) with low CD4 (211/uL). After five doses of IVIG at 400mg/kg monthly, platelets have remained between 15-20 K/uL and there has not been any improvement in the anemia. Although the mechanism for the bone marrow failure in these patients is presumed to be chromosomal breakage, this has not been demonstrated in this child. His karyotype is 46XY with no chromosomal fragility or deletions detected to date. Hypogammaglobulinemia should be investigated in any patient undergoing frequent transfusions who loses blood group antibodies, and suspicion of immune deficiency should remain particularly high in patients with severe growth retardation or dwarfism.
N.L. Rider * , T. Craig, Hershey, PA.
The objective of this study was to assess the effectiveness of physicians at a university primary care clinic in diagnosing and managing adult patients with asthma. A retrospective chart review of 63 adult patients from this clinic was performed. Each chart was evaluated using a survey instrument developed from the National Asthma Education and Prevention Program (NAEPP), which consisted of 22 queries. Of the charts evaluated 50 met our entry criteria. Overall compliance with the NAEPP recommendations was 34%. Adherences to the asthma guidelines in the following areas were: diagnosis (42%), treatment/disease control (60%), monitoring (15%), and education (18%). These data suggest that there is an opportunity to improve the care provided to patients with asthma, especially in the areas of asthma education and monitoring, even in a university outpatient facility. These data also suggest that NAEPP guidelines have not been effectively incorporated into primary care practices.
B.M. Wahlers * , L. Sherwood, T. Craig, Hershey, PA.
Objective: Our aim was to evaluate adherence to the National Heart Lung and Blood Institute (NHLBI), National Asthma Education and Prevention Program (NAEPP) diagnosis and management guidelines, regarding asthma admissions at a teaching hospital. Methods: A retrospective chart review of 197 patients over the age of 18 years admitted to the Hershey Medical Center between 1997 and 2002 with a primary diagnosis of asthma or asthma exacerbation was conducted using a 21-item questionnaire focused on key aspects of asthma care as outlined in the NAEPP guidelines. Results: Overall compliance to the guidelines was 61.5%. Maximal areas of compliance were noted in regards to pharmacologic treatments utilized (99%, 95%). Much lower levels of compliance were noted in areas of patient education (58%), instruction in written action plan prior to discharge (11%), provision of peak flow meter for home use (47%), assessment of asthma symptoms and severity (58%), and inhaled steroid prescription on discharge (69%). Conclusion: Adequate care in terms of pharmacologic treatments is being given but sub-optimal cares in other areas of the guidelines exist. There continues to be room for improvement in regards to asthma management, most notably in the area of education, documentation of triggers, and preparation for discharge with adequate tools to monitor and control symptoms. Background: Asthma is one of the most common problems of childhood, responsible for a significant proportion of absence from school because of chronic illness. Objective: This study was carried out among the school-aged children (7-18 years) in Tehran schools during 2002-2003, in order to determine the frequency of asthma. Methods: According to the recommendation of WHO, a questionnaire was designed, containing 8 standard questions, and the students were given necessary information to complete the questionnaires. The guidance and high school students completed the questionnaires but the parents of primary school students completed them by themselves. Results: Seven hundred and eight children out of 2000 children had asthma (35.4%); this prevalence was higher in the boys (37.1%), when compared to the girls (33.5%). The prevalence of this disease has been estimated about 39.5% in guidance schools, 35.4% in high schools and 31.6% in primary students. Based on this survey, the most common clinical manifestations in asthma were included: prolonged cough lasting more than 10 days (22.4%), and exerciseinduced wheezing or dyspnea (16.9%), followed by repeated dyspnea or wheezing (6.4%). Based on the drug responses after receiving solbutamol, the prevalence of asthma was evaluated in the range of 32.2% in primary schools, 16.7% in guidance schools and 22.9% in high schools. Conclusions: The prevalence of asthma is high among the students of Tehran schools and it needs more careful screening programmes and either more information given to the patients and parents about the disease. In the US, asthma is the most common chronic disease of childhood and affects approximately 5 million children. Reasons for inadequate asthma control include: inappropriate therapy, incorrect inhaler technique, poor compliance with treatment, and exposure to environmental triggers. Rates for asthma prevalence, hospitalization, and death are highest among children residing in inner cities, and important risk factors for asthma-related mortality include being poor and black. The communities of Braddock, North Braddock and Rankin are among the poorest in Allegheny County and are designated areas of greatest health risk. Recent statistics have demonstrated an increase in the number of asthma hospitalizations in these communities: 13.6 children per 1000, which is double the average for Allegheny County and greater than seven-times the overall US rate of asthma hospitalizations. Our goals were to assess asthmatic severity and appropriateness of treatment, provide asthma education, and to ensure access to healthcare for asthmatic children living in these medically underserved and predominantly African-American communities. Twenty-seven asthmatic children were identified. Of the children assessed 7% were under the age of 2 years, 19% were aged 2-5 years, and 74% were 6-14 years of age. Based on NHLBI guidelines the severity of each child's asthma was determined: 41% had mild-intermittent asthma, 15% had mildpersistent asthma, 26% had moderate-persistent asthma, and 18% had severepersistent asthma. The appropriateness of treatment based on severity was also determined. We found that 27% of the children with mild-intermittent asthma, 50% of children with mild-persistent asthma, 60% of children with moderate-persistent asthma and 100% of children with severe-persistent asthma were receiving inappropriate treatment. Furthermore, of the inappropriately treated children 92% were undertreated. Following the assessment, patients and parents were educated with regard to asthma triggers, pathophysiology, use of peak flow meters, inhaler technique and pharmacologic treatment. Patients were also scheduled for outpatient follow-up care. These results demonstrate that inappropriate treatment, especially undertreatment, may be a significant cause of the increased asthma morbidity in this population and underscore the need for aggressive education and innovative methods of ensuring health care.
W. Li-Ling * , T. Keng-Leong, F.C. Stephanie, E. Philip, Singapore.
BACKGROUND: Asthma admission is an important indicator of asthma morbidity. Little is known about the risk factors associated with asthma admission among high-risk asthmatics. PURPOSE: 1) To characterise the profile of high-risk asthmatics who had previous asthma hospitalization. 2) To identify predictors and risk factors that are associated with asthma hospitalization. METHODS: Data for consecutive high-risk asthmatics who were enrolled into our asthma program from October 2001 to May 2004 were retrieved from our prospective database. High-risk asthmatics were defined as patients who had a clinical diagnosis of asthma and who had at least one hospital admission for exacerbation of asthma in the preceding 12 months or at least one severe exacerbation of asthma in the preceding 6 months requiring unscheduled visit for beta2-agonist nebulisation. A comparison was made among high-risk asthmatics who had at least one or more hospitalization for asthma in the past 12 months prior to the asthma program enrolment with those who were not hospitalized. Statistical analyses were performed using SPSS Version 10.1 for Windows. RESULTS: Among 521 high-risk asthmatics, 252 (48.4%) had at least one or more asthma hospitalization in the past 12 months prior to the enrolment into the asthma program. Hospitalization was significantly associated with female gender (63.1% with asthma admission v 43.1% without asthma admnission). A significantly higher proportion of asthmatics with no formal education (19.4% v 17.7%), primary education (23.8% v 16.6%) and secondary education (32.1% v 29.3%) were hospitalized for asthma as compared to the those who had tertiary education (24.6% v 36.5%). Those admitted were predominantly in lower income group, had poor inhaler technique and have no ownership of an asthma action plan (33.3% v 76.6%). Those hospitalized were also younger, median age 37years (19, 62) v 35years (15, 84) and had a lower first peak flow reading, 260L/Min (130, 500) v 300L/Min (150, 480) . CONCLUSION: Among high-risk asthmatics, certain population subgroups are at greater risk for hospitalization for asthma. Intervention aimed to reduce asthma morbidity should take the above findings into consideration. Introduction An association between asthma symptoms and air quality is well established, but controversy exists concerning the role of various air quality indicators. The association of San Antonio air quality with emergency department (ED) visits for asthma at our military medical center has not been defined. The objective of this study is to determine the correlation of selected air quality indicators in San Antonio with ED visits for asthma for both the general population and for the pediatric population. Methods Selected air quality indicators were the 8-hr air quality index (AQI) for ozone, 24-hr AQI for particulate matter < 2.5 μm, pollen counts, mold spore counts, and daily high temperature. The number of daily ED visits coded for asthma was obtained retrospectively. Pediatric visits (patients < 18 years-old) were evaluated as a subgroup. Pearson correlation coefficients (r) were calculated for all data pairs. Results During the 331 days of the study period, there were 491 visits for asthma. Of these visits, 151 were pediatric. The number of daily visits ranged from 0 to 6 for all visits and from 0 to 3 for the pediatric visits. R values for all visits were -0.067, -0.069, 0.110, -0.011, and -0.218; for pediatric visits, -0.055, -0.036, 0.033, -0.010, and -0.074 for the 8-hr AQI for ozone, 24-hr AQI for particulate matter < 2.5 μm, total pollen grains/m 3 , mold spores/m 3 , and daily high temperature, respectively. In addition to calculating r values for same-day air quality indicators and ED visits, r values were also calculated for a 3-day average of air quality indicators with the ED visits. For the 3-day averages, r values for all visits were -0.113, -0.117, 0.127, -0.071, and -0.267; for pediatric visits, -0.081, -0.011, 0.025, 0.017, and -0.063 for the 3-day averages of the 8-hr AQI for ozone, 24-hr AQI for particulate matter < 2.5 μm, total pollen grains/m 3 , mold spores/m 3 , and daily high temperature, respectively. Conclusion There was no significant correlation between the selected air quality indicators and ED visits for asthma, either for the general population or for pediatric visits. This study provides no evidence that air quality is linked to ED visits for asthma in San Antonio but the degree to which air quality in San Antonio affects asthma symptoms remains unclear. Introduction: The aim of this study was to evaluate the level of NO in the exhaled air of patients suffering from chronic cough. Methods: The study was performed on 213 young (mean age 28.5 +/-8.2 years), nonsmoking patients with chronic cough referred to the Allergy Clinic for evaluation. Bronchial provocation challenge with histamine was performed according to the method of Ryan. Exhaled NO was measured on-line using a chemiluminescence analyzer (Sievers, USA). All patients had resting spirometry within normal values. Results: Significant bronchoconstrictive response to histamine at a concentration equal to or lower than 8 mg/ml (PC20 8mg/ml) was found in 65 patients (30.5%). These patients had a significantly greater mean concentration of NO in the exhaled air (80.6+/-59.4 ppb) than those with a PC20>8mg/ml (28.4 +/-29.2 ppb; p<0.0001). Receiver Operating Characteristic (ROC) curve analysis revealed that it is possible to identify from among patients suffering chronic cough those who have significant bronchial hyperreactivity (PC20 8mg/ml). Using 40 ppb as a cut-off value for the exhaled NO concentration, the specificity for bronchial hyperreactivity was 86.5% and sensitivity 72.3%. Conclusion: Assessment of NO concentration is helpful in the assessment of bronchial hyperreactivity in patients having chronic cough.
L. Abetz 1* , J. Bousquet 2 , E. Juniper 3 , E. Bateman 4 , H. Boushey 5 , W. Busse 6 , T. Clark 7 , R. Pauwels 8 , S. Pedersen 9 , 1. Manchester, United Kingdom; 2. Montpelier, France; 3. Ancaster, Canada; 4. Cape Town, South Africa; 5. San Francisco, CA; 6. Madison, WI; 7. London, United Kingdom; 8. Ghent, Belgium; 9. Kolding, Denmark. Introduction: The ACQ has been developed as a measure of asthma control for use in clinical practice or in clinical trials. The reliability, validity and responsiveness have previously been demonstrated for the original 7 item ACQ, the 6 item (minus FEV1 question) and 5 item (minus FEV1 and short acting bronchodilator use questions) versions. Data from the 1-year Gaining Optimal Asthma controL (GOAL) study was used to assess the predictive value of the ACQ s 7, 6, and 5 item versions in determining asthma control status. Method: Receiver operating characteristic curves (ROC curves), plotting true positive rates versus false positive rates for different ACQ cut-points, were used to determine optimum cut points for Totally Controlled and Well-Controlled asthma. Scores for the 7, 6, and 5 item versions of the ACQ were examined at 0.25 intervals. Results: When predicting Totally Controlled asthma, the areas under the ROC curves (AROCC) were 0.88/0.88/0.86 for the 7, 6 and 5 item versions, respectively; and when predicting Well-Controlled asthma the AROCC were 0.86/0.86/0.84 for the 7, 6 and 5 item versions. In both predictive models, the 7 and 6 item versions provided the best AROCC. For the 7 and 5 item versions, the best cut-off point to predict Totally Controlled asthma was <=0.75, with AROCC of 0.81/0.79, and corresponding sensitivity of 0.74/0.71 and specificity of 0.89/0.88, respectively. For the 6 item version the best cut-off point was <=0.5, with AROCC of 0.82, sensitivity of 0.76 and specificity of 0.87. The best cut-off points for predicting Well-Controlled asthma were <=1.25 for the 7 item version (AROCC=0.77; sensitivity=0.70; specificity=0.83), and <=1 point for the 6 and 5 item versions (AROCC=0.77/0.75; sensitivity=0.70/0.69; specificity=0.83/0.81, respectively). Conclusion: Results indicate the sensitivity and specificity of the ACQ in predicting asthma control status. A 29 yo black male with asthma and allergic rhinitis developed gradually worsening cough productive of clear to yellow sputum despite treatment with high dose fluticasone, salmeterol, monteleukast, and PRN albuterol. Asthma history was significant for an intubation at age 10 and pneumonia at age 28. Physical exam revealed pale turbinates and expiratory wheezes. Pulmonary function test showed a severe obstructive lung defect with FEV1 1.52 (38%), improving by 4% after bronchodilator and FEV1/FVC ratio 54%. A chest CT revealed significant bronchiectasis in the right middle lobe, lingula and both lower lobes. Evaluation for bronchiectasis showed normal quantitative immunoglobulins, subclasses, and humoral responses, rendering innate immunodeficiency less likely. The diagnosis of allergic bronchopulmonary aspergillosis was entertained, but IgE was 500kU/L and aspergillus titers were negative. A sinus CT failed to show active disease, yet the patient reported chronic yellow nasal discharge despite courses of antibiotics. Although he was sexu-ally active with several male partners, HIV testing was negative 2 times, 6 months apart. Evaluation for cystic fibrosis (CF) showed no symptoms of malabsorption and a negative sweat test. Other tests revealed normal -1 antitrypsin level, P-ANCA, ESR, ACE level, and negative sputum for AFB and mycobacteria, helping to exclude other conditions such as 1-antitrypsin deficiency, vasculitis, sarcoidosis, and chronic infection. With no definitive answer, the diagnosis of CF was pursued, but genetic screening as well as mapping were negative. The diagnosis of primary ciliary dyskinesia was then entertained; however, a mucosal biopsy of the nose did not reveal any structural abnormalities. Finally, a sperm analysis revealing azoospermia confirmed the diagnosis of Young's syndrome, a rare disease with features similar to CF including bronchiectasis, chronic sinusitis and azoospermia. In Young's syndrome however, there is an obstructive process rather than a lack of vas deferens resulting in azoospermia and normal sweat chloride, genetic, and pancreatic testing. This case demonstrates the importance of investigating a persistently productive cough in an asthmatic patient and the differential diagnosis as well as the appropriate work up for bronchiectasis. A final diagnosis is important since appropriate management in each situation may affect long term outcome.
A.G. Palma-Carlos * , M.L. Palma-Carlos, Lisboa, Portugal.
Introduction: Bronchial challenges are currently done in allergic asthma with allergen, histamine or metacholine.Bronchial reactivity to allergens and histamine can probably be variable. Purpose to evaluate if the dose of allergen and histamine triggering a significant bronchial obstruction are always correlated in asthmatic patients. Methods: A Vitalograph model Compact has been used throughout the study. Allergen challenge has been done with an acqueous solution of house dust mite. Bronchial challenges with placebo (sodium chloride) histamine or allergens have been done in all patients. For the provocations with histamine or allergens the threshold dose, inducing a decrease in FEV1 greater than 15% has been determined in all the cases, as well for histamine as for allergens. A second challenge has been done in all patients with a supra-threshold dose of histamine or allergen corresponding to the double of the threshold. Results: 30 provocations have been done in 10 patients either with histamine or allergen. 6 were allergic and 4 non allergic. The threshold dose for histamine were between 5 and 25 ug. in allergic patients and 250 and 500 ug. in non allergic patients.In allergic patients after histamine threshold challenge mean decrease was for FEV1 19, 2% and for FEV1/VC 17, 3%. For supra-threshold dose FEV1 decreases 37, 8% and FEV1/VC 32, 8%. After allergen challenge FEV1 decreases 20, 3% and FEV1/VC 15, 8%. With supra threshold doses FEV1 decreases 28, 6% and FEV1/VC 29, 3%. In 4 non allergic patients there was no changes after allergen challenge. A good correlation in constriction induced by histamine or allergen either for threshold or supra threshold doses (p<0.001) was observed but not between the threshold doses of histamine and allergen. Conclusions: These results confirm that bronchial obstruction can be triggered by allergens and mediators that the sensitivity of FEV1 and FEV1/VC for evaluation are roughly comparable after challenge and points to a better sensitivity of a supra threshold dose of allergen or mediators. Allergen and histamine challenges don't give the same information. Introduction: Peak expiratory flow rate (PFR) and forced expiratory volume in the first second (FEV1) are currently used in functional evaluation of asthmatic patients but his degree of correlation in obstructive, restrictive and mixed spirometric ventilatory patterns are not well known. The purpose of this study was to evaluate if the correlation between PFR and FEV1 2 markers of global airways obstruction is comparable in asthmatic patients with obstruction restriction or both. Methods: 152 asthmatic patients, 69 males, 83 females have been studied by spirometry with a Vitalograph Compact in absence of bronchodilatory or anti-inflammatory therapy. Patients have been classified in 4 functional patterns according to VC, and FEV1/CV: Normal : VC greater than 90% of expected value and FEV1/VC greater than 70%, obstructive:VC greater than 90% and FEV1/VC greater than 70% restrictive VC, less than 90% and FEV1/VC greater than 70% and mixed VC less than 90% and FEV1/VC less than 55% presenting a so called functional emphysema. Results: According to these criteria 15 patients were normal, 44 restrictive, 15 obstructive and 78 mixed. In all the group the correlation between PFR and FEV1 was statiscally significant (P<001) but the correlation coefficient variable. In functionally normal patients r =+0, 74 in restrictive patients + 0, 67 in obstructive + 0, 66 in mixed + 0, 84 and in the sub-group with functional emphysema + 0, 96. For this sub-group the correlation coefficient R allows to define FEV1 = 91 + 5, 6 PFR. Conclusions: The report between the two most usual assays of global bronchial obstruction depends on the balance between restriction, (either by interstial fibrosis or hyperinflation) and obstruction and is more close when a more marked obstruction coexist with a restrictive pattern (functional emphysema). In practice PFR has the same value that FEV1 only in more severe cases of ventilatory failure. The dispersion of values and the standard error or regression do not allow to correlate both data in most patients. Introduction: The TENOR study longitudinally observes the natural history of subjects with severe or difficult-to-treat asthma. This analysis assessed the association between previous and future asthma exacerbations in TENOR. Methods: Subjects eligible for this analysis were 12 years of age at baseline and had at least one follow-up assessment in year 1 and year 2. Recent asthma exacerbations in the past 3 months were defined as: asthma-related emergency room (ER) visits, nights of hospitalization, unscheduled physician office contacts; or as a composite measure of at least one of the previous exacerbation events. Relative risks (RRs) and 95% confidence limits (95%CI) were generated comparing exacerbations in year 2 relative to year 1. Exacerbation rates were defined as the number of events divided by total patient follow-up time.
No adjustment was performed for baseline characteristics. Results: 2826 subjects were eligible for this analysis. RRs in year 2 vs. year 1 were: 3.9 (95%CI: 3.3-4.6) for unscheduled office contacts, 4.1 (95%CI: 3.48-4.82) for the composite exacerbation measure, 10.2 (95%CI: 7.8-13.4) for ER visits and 15.1 (95%CI: 9.8-23.3) for nights of hospitalization. Over 37% of subjects with 5 or more exacerbations (composite measure) in year 1 had a similarly high rate in year 2 compared to 3% of patients without an event in year 1 who went on to have 5 or more exacerbations in year 2 (see Table) . Conclusion: TENOR subjects who experienced an asthma exacerbation in year 1 were at statistically significantly increased risk of subsequent exacerbations the following year compared to subjects not experiencing an exacerbation in year 1. This increased risk was consistent for all asthma exacerbation outcomes and most elevated for hospitalizations due to asthma. Assessment of recent asthmarelated healthcare use is a critical component of the clinical evaluation of subjects with severe or difficult-to-treat asthma. Funded by Genentech Inc. and Novartis Pharmaceuticals Corp. BACKGROUND: Preliminary studies investigating yoga and breathwork for asthma have been promising. Several randomized controlled trials have shown a benefit from yoga postures and/or breathing versus control, but the control in these cases involved no intervention other than usual care. This study advances the field by providing an active control. METHODS: A randomized, controlled, double-blind clinical trial was conducted from October 2001 to March 2003 to determine the effectiveness and feasibility of a yoga and breathwork intervention for improving clinical indices and quality of life for adult patients with mild to moderate asthma. Random assignment was made to either a 4-week yoga intervention that included both postures and breathwork, or a stretching control condition. Outcome measures were assessed at 4, 8, 12 and 16-weeks and included the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), rescue inhaler use, spirometry, symptom diaries, and health care utilization. RESULTS: Sixty-two participants were randomized into the intervention and control groups, and 45 completed the final follow-up measures. Intention-to-treat analysis was performed. Significant within-group differences in post-bronchodilator FEV1 and morning symptom score were apparent in both intervention and control groups at 4 and 16 weeks; however, no significant differences between groups were observed on any outcome measures.CONCLUSIONS: Iyengar yoga conferred no appreciable benefit in mild to moderate asthma. Circumstances under which yoga is of benefit in asthma management, if any, remain to be determined. In order to investigate asthma mortality trends for the U. S. Hispanic population, I have collected and graphed data from the National Center for Health Statistics. Mortality data for the Hispanic population have been available for the entire United States only since 1997 and readily available for asthma only since 1999. These data indicate decreases in deaths from asthma (J45-J46) from 320 in 1999 to 274 in 2001 with decreases in the non-Hispanic population from 4324 in 1999 to 3976 in 2001. Rates of death from asthma decreased for the Hispanic population from 1.0 per 100, 000 in 1999 to 0.7 in 2001, while that for the non-Hispanic population decreased from 1.84 to 1.6. Rates for non-Hispanic whites decreased from 1.5 to 1.4 in 2001. Rates of death from asthma have been twice as high among Hispanic women as men. Rates of death from asthma for non-Hispanic blacks have been more than twice as high as those for non-Hispanic whites. (National Center for Health Statistics data dictate racial terminology). Data for people of Hispanic origin include people of any race. These data are affected by both underreporting of Hispanic origin on death certificates and undercoverage in the census and resultant population estimates for a net correction of 1.6%. Thus, rates of death from asthma have been lower and have been decreasing faster among Hispanics than the rest of the population in the United States. Allergic rhinitis and asthma are both highly prevalent diseases and often coexist in patients. Rhinitis symptoms have been shown to impact the lower airway. As such, the impact of rhinitis on asthma control may be the greatest in patients with the most severe rhinitis symptoms. Therefore, this analysis was performed to determine the impact of baseline rhinitis severity on asthma control in patients with both asthma and allergic rhinitis who received either fluticasone propionate aqueous nasal spray (FPANS) or montelukast (MON) added to fluticasone propionate/salmeterol 100/50 mcg (FSC). A total of 863 patients (>15 years) with persistent asthma and seasonal allergic rhinitis received FPANS 200mcg QD, MON 10mg QD or placebo (PBO) in addition to FSC 100/50mcg BID for 4 weeks. At baseline, total nasal symptom scores (TNSS) ranged from 44 to 400. The analysis was restricted to patients whose pre-enrollment asthma therapy did not include FSC. Regardless of baseline rhinitis severity, in patients with both asthma and allergic rhinitis, MON added to FSC resulted in no additional improvements in overall asthma control compared with FSC alone. These data suggest that optimal treatment of the individual conditions should be the goal of treatment for patients with coexistent allergic rhinitis and asthma. (SAM40066) Introduction Recent studies have demonstrated that parainfluenza and coronaviruses are as important triggers of asthma. Parainfluenza viruses are one of the main triggers of virus-induced asthma at summer. Parainfluenza viruses often cause severe low respiratory tract infections in immuncompromised patients and in patients with bone marrow transplantation. A retrospective study found that 41% of pediatric BMT patients with HPIV infection (47% of viral respiratory infections) developed pneumonia and 6% died. Both viruses contributed to fatal asthma. Materials and methods For amplification of these viruses, primers which anneal to specific regions of viral genomes: HN-gene for PIV1, PIV2 and PIV3 and spike glycoprotein gene for coronavirus OC43 and nucleocapsid glycoprotein gene for coronavirus 229E were used. PCRdiagnostics was performed on nasal and throat swabs taken from children with atopic asthma exacerbation. Results From 02/04 to 05/04 a total of 56 samples (including 28 negative controls) were tested by PCR. 11 positive for respiratory viruses samples noted in children having asthma exacerbations including 23.9% of all tested samples. PIV3 was detected in 54.5% of all positive samples, PIV2 in 18.2%, and coronavirus OC43 in 27.3%. PIV2 and coronavirus 229E were not detected during this study. For negative controls samples were taken from children with atopic asthma in remission. All 10 controls were found to be negative by viral PCR. Conclusions Respiratory viruses are an important factor in asthma exacerbations in children. PIV3 was the most frequently detected among the positive samples. Although HPIV-2 was less often positive than HPIV-1 and HPIV-3 infections in this study, the frequency of the detected coronaviruses may have been influenced by the seasonal activity of these viruses. Introduction. In Budapest all children come under the regular supervision of a specially trained paediatrician. Each paediatrician is responsible for an average of 950 children, often seen up to the age of 18 years. Methods. A questionnaire was sent to the district paediatricians of Budapest in 1995 Budapest in , 1999 Budapest in and 2003 . The total number of children in their practice and the number of the asthmatics was assessed. The diagnosis of asthma in every case was established in a paediatric hospital, or a special allergy or pulmonology outpatient clinic. Results. In 1995, replies were received from 118 paeditricians, who were responsible for the supervision of 104, 087 children, of which 1.88 ± 0.87% had been diagnosed as having asthma. In 1999 replies were sent by 153 physicians, who had a total of 142, 684 children under their care, including 3, 228 asthmatics, a prevalence of 2.26 ± 0.95%. At the end of 2003, 151 paediatricians having 141, 276 children answered, noting 3, 831 asthmatics, a 2.71 ± 1.2% prevalence of asthma. Conclusion. The current survey of prevalence of asthma in childhood is by far the largest that has been made. An increasing prevalence of the diagnosis of asthma based on clinical investigations was noted, the differences between the investigated years being highly significant.
Panel Report Guidelines for the Diagnosis and Management of Asthma have been available since 1991, to standardize and improve the quality of asthma care. However, asthma remains the leading cause of hospitalization for New York City children. Implementation of the guidelines has not been fully embraced in the primary care setting. We attempted to increase primary care practitioners' compliance with the guidelines through extensive training. A hospital based pediatric clinic and 4 school based health clinics in the Brooklyn inner city, participated from April 2002 to March 2003 in the program as part of New York City's Education and Quality Improvement Project (EQuIP). Initially an asthma physician specialist and asthma educator trained the primary care physicians and nurse practitioners in the guidelines. The training was reinforced during monthly luncheon sessions. Clinical exam rooms were also supplied with asthma education materials, peak flow meters, and asthma action plans. Goals were to identify asthmatics, document asthma severity, give persistent asthmatics written management plans, and utilize appropriate controller medications. Compliance was measured by tracking asthma visits with an asthma intake form. Prior to this project no consistent attempt had been made in the clinics to regularly classify asthmatic severity, provide written asthma action plans or to place patients on controller medications. After onset of the project a total of 216 asthma visits were evaluated; 104 were from school based health centers and 113 from hospital based pediatric clinic. Severity was classified in 83%(179/216) of asthma visits. Patients classified as persistent received updated written management plan during 90%(100/110) of asthma visits and 92%(102/110) were placed on controller medications. This asthma management program demonstrated success in improving primary care practitioners' compliance with the NAEPP Asthma guidelines. Further studies are needed to determine if compliance with the guidelines persisted after cessation of the extensive training and if such compliance improves asthma outcomes. Numerous studies have associated asthma and obesity. Although obesity has been identified as a risk factor for asthma, there is limited information on the impact of obesity on childhood asthma. This study examines the effect of body composition on asthma severity and pulmonary function in children. We retrospectively reviewed charts from asthmatic children ages 5 to 18 years, referred to a community-based pediatric pulmonology practice between 1999 and 2003. Data were included if asthma was the the primary diagnosis and a baseline spirometry was available. Asthma severity was classified and body mass Index(BMI) was classified as normal, overweight and obese. Spirometry results were reviewed. Eighty-five patients were reviewed. Thirtyone(36.5%) patients were normal weight; 21(24.7%) were overweight and 33(38.8%) were obese. Baseline characteristics such as age, gender and race/ethnicity were similar. Asthma severity classification did not differ between normal, overweight and obese children. Overall, 34% were classified as intermittent, 53% as persistent mild asthma and 13% as persistent moderate-severe asthma. 21% of children with intermittent asthma were receiving controller therapy compared to 62.5% with persistent mild and 81.8% with moderate-severe asthma(p=0.0001). Although healthcare utilization for asthma(emergency room visits/admissions) were significantly different between children with intermittent, persistent mild and moderate-severe asthma(p=0.0004), there was no difference when normal, overweight and obese children were compared. Spirometry results showed comparable peak expiratory flow rates(PFR) in all groups; 75% of predicted in normal weight and 79% of predicted in both overweight and obese. Mean forced vital capacity(FVC) was 93.9%, 88.5% and 95% and the mean forced expiratory volume in 1 second(FEV1) was 85.9%, 81.2% and 86.6% respectively. There was no difference in FEV1/FVC; 82.3%, 83.1% and 81.8% and forced expiratory flow in mid-lung volumes (FEF25-75); 74.4%, 73% and 76.9% of predicted. In this study we retrospectively reviewed asthmatic children and compared BMI, asthma severity and spirometry. We found no difference in asthma severity classification between normal and overweight/obese patients. Regardless of the BMI, all indices of spirometry were similar. Further studies are needed to examine the impact of obesity on different asthma related disease outcomes. Our objective is to further investigate the effect of budesonide, formoterol, and levalbuterol, alone, and in combination, on TGF-1 production and expression in ragweed (RA) stimulated A549 cells. METH-ODS: A549 cells were cultured in duplicate for 24 hours at 37 degrees celcius with 5% CO 2 in serum free DMEM with or without the following: 10μg/ml of RA, 1.0 x 10 -7 M of budesonide, 1.3 x 10 -7 M formoterol, and 1.0 x 10 -5 M levalbuterol. TGF-1 production and expression was measured by a sensitive ELISA and mRNA assay in cell supernatants and pellets. RESULTS: TGF-1 production and expression from A549 cells rose markedly in the presence of RA (952.35 -1268 pg/ml) (59 -71 amol/ml) with significant inhibition following the addition of budesonide, and the combinations of budesonide and formoterol, budesonide and levalbuterol, and budesonide, formoterol, and levalbuterol (p<0.05). Combined treatment with budesonide and levalbuterol versus budesonide alone reached significance for production and expression (p<0.05). Budesonide and formoterol compared with budesonide alone reached significance for TGF-1 production (p<0.05). CONCLUSION: Combination therapy with budesonide and a long or short acting beta-agonist showed greater effect of TGF-1 inhibition compared with budesonide alone. This synergistic effect on the distal airways may prevent a subset of asthmatics from developing airway remodeling.
G. Tamura 1* , Y. Sano 2 , K. Hirata 3 , S. Ishioka 4 , M. Nakashima 5 , T. Miyamoto 2 , 1. Sendai, Japan; 2. Tokyo, Japan; 3. Osaka, Japan; 4. Hiroshima, Japan; 5. Hamamatsu, Japan. Tulobuterol tape is the world's first long-acting transdermal preparation of a beta2-agonist designed to release tulobuterol in an optimal fashion. When it is applied once daily at bedtime, the blood concentration of tulobuterol peaks early in the morning and is kept at effective levels for 24 hours. Tulobuterol tape has milder and less frequent adverse events than conventional oral tulobuterol preparations, and when used at bedtime can prevent marked drop in peak expiratory flow (PEF) early in the morning. Consequently, tulobuterol tape has been commonly used in Japan as a long-acting beta2-agonist. In the present study, to evaluate its efficacy as a long-acting beta2-agonist and to compare its effects at two different doses, we administered tulobuterol tape at doses of 1 or 2 mg/day to patients with persistent asthma already using inhaled corticosteroids. This study was a randomized, double-blind, double-dummy, parallel-group, multicenter trial of 4-week duration. Mean PEF in the 1 and 2 mg/day groups were significantly increased from the baseline value by 15.1 and 28.2 at week 1, 19.5 and 32.6 at week 2, 22.6 and 35.3 at week 3 and 23.8 and 35.9 L/min at week 4, respectively. The increase in mean morning PEF in the 2 mg/day group was significantly higher than that in the 1 mg/day group at every point of determination. The mean evening PEF was significantly increased in both treatments groups compared with baseline values at every point of determination. Although the increase in the 2 mg/day group was greater than that in the 1 mg/day group at each point of determination, the difference between groups was statistically significant only at week 1. The safety profiles of the two treatments were similar. In patients with persistent asthma who require inhaled short-acting beta2-agonists while receiving inhaled corticosteroids, tulobuterol tape 2 mg/day significantly improved PEF compared with tulobuterol tape 1 mg/day. Introduction: On an average, 4% of the 1500 children admitted annually for asthma to Children s Hospital require admission to the Pediatric Intensive Care Unit (PICU). These admissions are highest in the months of August, September and October. Aeroallergens such as Alternaria and ragweed predominate during this season, and allergies to these allergens may account for the increased number of PICU admissions for asthma. Objective: We hypothesized that the seasonal increase in the admission rate could be related to allergen sensitivity, particularly to Alternaria and/or to ragweed that predominate during late summer and fall. Method: Data was collected from a retrospective chart review of all patients admitted to the PICU for asthma exacerbation between 1997 and 2003. Skin prick testing (SPT) within one year of PICU admission was the criteria for inclusion in this study. Results: There was a higher prevalence of admissions to the PICU for asthma exacerbation during August, September and October (168 out of 416 admissions = 40% of all admissions, p<0.001). Sixty-one subjects met the one-year SPT criteria for analysis. Subjects admitted during August, September and October were categorized as Group A, and all others were categorized as Group B. Sensitivity to a total of 11 aeroallergens (tress, grasses, weeds, ragweed, outdoor molds, indoor molds, Alternaria, cat, dog, roach and dust mites) was compared between the two groups. There was no statistical significance in aeroallergen sensitivity to Alternaria or ragweed between subjects admitted to the PICU in August, September and October (group A) and subjects admitted during the other months of the year (Group B). Conclusion: Asthma exacerbation requiring PICU admissions is more prevalent during the months of August, September and October. The increased rated of PICU admissions did not correlate with the aeroallergen sensitivity to the prevalent allergens during August, September and October. Therefore we suspect other factors such as, viral upper respiratory infections, in addition to aeroallergen sensitivity, which may contribute to severe asthma exacerbation during the late summer and fall months.
K. Kuzume * , Shigenobu, Ehime, Japan.
Infantile wheezing may be the result of different phenotypes. The aim of this study was to evaluate the risk factors for allergies and the results of allergyrelated blood tests among infants with different types of allergy symptoms. 2130 infants were examined physically at birth and at 1, 3, 6, 9, and 12 months of age, and questionnaires about number of siblings, the family history of allergy, and feeding methods were given. Allergic diseases were diagnosed at 12 months of age, and the subjects were divided into 4 groups: infants with atopic dermatitis (AD) only (A group, n=447), infants with both AD and wheezing (A/W group, n=175), infants with wheezing only (W group, n=155), and infants without allergic symptoms (C group, n=1353). Risk factors were then evaluated. 332 patients (198 from the A group, 109 from the A/W group, and 25 from the W group) were given allergy-related blood tests, total serum IgE levels, and RAST with egg white, milk, and house dust mites at 6 and 12 months of age. The results of the blood tests in 36 control subjects at 6 months of age were compared to the other groups. As shown in Table1, there were more male infants in the A/W and A groups than in the C group (p<0.001, A/W vs. C; p<0.01, A vs. C). Numbers of siblings were greater in the W and A/W group than in the A or C group (p<0.0001, W vs. A and W vs. C; p<0.01, A/W vs. A; p<0.05, A/W vs. C). The rate of positive family history of allergic diseases was high in the A and A/W groups, compared to the W or C group (p<0.0001, A vs. C and A/W vs. C; p<0.05, A/W vs. W). The rate of breastfeeding at 3 months of age was high in the A group compared to the others (p<0.0001, A vs. C). Patients in the W group had lower levels of total serum IgE at 12 months of age, compared to patients in A or A/W (p<0.01, W vs. A/W and W vs. A). Also patients in the W group had lower levels of RAST with egg white at 12 months of age, compared to patients A or A/W (p<0.0001, W vs. A/W and W vs. A). The median of total serum IgE levels at 6 months of age was higher in A and A/W but not in W, compared to C (p<0.001, A/W vs. C and A vs. C). In conclusion, there were two different phenotypes of wheezing in infants before 12 months of age. Wheezing with AD might be "allergy-related", while wheezing without AD may be related to other factors.
As compared to C group: a), p<0.05; b), p<0.01; c), p<0.001; d), p<0.0001 As compared to A group: 1), p<0.05; 2), p<0.01; 3), p<0.001; 4), P<0.0001 As compared to A/W group: f), p<0.05; g), p<0.01; h), p<0.0001 A group, infants with atopic dermatitis only; A/W group, infants with atopic dermatitis and wheezing; W group, infants with wheezing only; C group, infants without allergic symptoms. RAST, radioallergosorbent test, N/A, data not available
R. Amelio 1* , C. Capristo 1 , A. Capasso 1 , M. Miraglia del Giudice 2 , N. Maiello 1 , F. Decimo 1 , 1. Naples, Italy; 2. Napoli, Italy.
Forced oscillation technique (FOT) is considered a sensible and specific method to estimate breathing functionality in asthmatic children aged 3 to 6 years, because it doesn't need special collaboration. The aim of our study was to value baseline respiratory resistances with the FOT in preschool-aged children with asthma under high dose of Budesonide and Flunisolide treatment. At this purpose, 40 asthmatic children aged 3 to 6 years were selected: at a first examination (T0) all the patients showed basal value FOT at 6Hz frequency (Rr6) changes major or equal than 35% under 200 mcg of salbutamol treatment. 30 days before the study, children selected didn't take systemic and inhaled steroids, cromons, leukotrienes antagonists, teophylline or anti-histamines and they didn't present upper and lower airways infections; then, two weeks before run-in, all selected patients took beta-2-agonists at least 3 times per week. All the patients were divided in two groups: Group I (20 children) under inhalation of Flunisolide 40mcg/Kg/dose + Salbutamol 1500 mcg b.i.d. for 7 days and, for the following two weeks, under inhalation of Flunisolide 20 mcg/Kg/dose + Salbutamol 200 mcg by pMDI+Spacer prn.; Group II (20 children) under inhalation of Budesonide 0, 5 mg b.i.d. + Salbutamol 1500 mcg b.i.d. for 7 days, and for the following two weeks, under inhalation of Budesonide 0, 25 mg b.i.d. + Salbutamol 200 mcg by pMDI+Spacer prn. Moreover, we gave diary-card with a simple symptoms score (at T0 and T7 ), to get the real perception of the symptoms in the course of study. However, during the treatment, 4 children have ritired from the study. The results obtained were statistically analysed (t Student's test). Significant Rr6 pre beta-2-agonists and ? value reduction was obtained at T7 and T21 vs. T0. Group I had (at T7) such a quick action than Group II reducing airways resistances (p<0, 01). Children treated with Flunisolide had lower frequency of breathless and nocturnal cough at T7 and lower salbutamol use from T7 to T21 than Budesonide group (p=N.S.). In conclusion, FOT is actually a safety method to value efficacy of inhaled steroids in preschool-aged children with asthma. Introduction: Approximately 7.5% of U.S. adults and 6.0% of Louisiana (LA) adults have current asthma, and over 25% currently smoke cigarettes, according to the 2002 Behavioral Risk Factor Surveillance System (BRFSS). The purpose of this study is to compare asthmatic smokers vs. nonsmokers in LA and the U.S. Here we address whether asthmatic smokers utilize more medical care services in the ER and outpatient clinics, and whether they were able to fully participate in activities of daily living compared to nonsmoker asthmatics. Methods: BRFSS is a state-based, telephone survey of U.S. adults. The survey collects self-reported information about modifiable risk factors for chronic diseases. This study analyzed data from the 2002 BRFSS survey using SAS software. Data: Out of the current asthmatics, 25% are cigarette smokers in the U.S. In Louisiana, 31% of asthmatics are currently smoking, which is significantly higher than the national average (p<0.0001). Within the past year, the average number of emergency room visits due to asthma was similar for both locations (LA 0.53, US 0.48, p=0.46) . Nationally, smokers visited the ER significantly more frequently than nonsmokers (S 0.61, NS 0.43, p<0.01). In LA, smokers visited the ER twice as often as nonsmokers (S 0.80, NS 0.40, p<0 .01) The number of annual routine outpatient checkups for asthma was similar based on location (LA 1.39, US 1.66, p=0.06). Smokers and nonsmokers had a similar number of checkups nationally (S 1.74, NS 1.64, p=0.32) and in Louisiana (S 1.79, NS 1.21, p=0.06). The number of days where asthmatics were unable to perform their usual activities was significantly fewer in LA than nationally (LA 3.6, US 11.6, p<0.001). Smokers had a significantly higher number of missed days nationally (S 17.8, NS 9.6, p<0.0001). In LA, there was not a significant difference in the number of missed days based on smoking status (S 4.9, NS 2.9, p=0.47). Conclusion: Even though Louisiana has a lower prevalence of asthmatics compared to the national average, significantly more of our asthmatics are smokers. Asthmatic smokers in LA and the U.S. utilized the ER more than their nonsmoking counterparts. Smokers and nonsmokers had similar numbers of routine outpatient visits. Asthmatic smokers missed more days, but this was only significantly different at the national level. Other research has shown that young age is highly associated with improper use in children using a MDI and holding chamber (Arch Pediatr Adolesc Med 2002; 156:378) . The objective of this study was to compare health outcomes achieved by children with asthma using inhaled corticosteroids (ICSs) delivered by a nebulizer compared with outcomes of children using ICSs delivered by non-nebulized device. Methods: Using a managed care organization database (PHARMetrics Integrated Outcomes Database), we identified children aged 8 years with an asthma diagnosis and asthmarelated hospitalization/emergency department (ED) visit (July 2000 -June 2002 and with a prescription claim for an ICS within 30 days of discharge. We compared relative risk of hospitalization/ED recurrence from day 31-180 (Cox proportional hazards regression, covariates=sex, age, current and prior asthma medications, prior oral corticosteroid and short-acting 2 -adrenergic agonist use, initial type of index event) for patients receiving nebulized ICS vs other ICS by age groups (0-4 years and 5-8 years). Results: Of 1552 patients with claims for ICS, 729 received nebulized ICS, of which 480 were aged 4 years; 823 received non-nebulized ICS, of which 292 were aged 4 years. Postindex hospitalization/ED rates were 12.4%. Refill rate was higher for patients using nebulized ICS. After model risk adjustment, patients using nebulized ICS had a 53% risk reduction for hospitalization/ED recurrence vs those not using nebulized ICS (HR: 0.47, 95% CI: 0.28, 0.78). In the 0-to 4-year age group, patients on nebulized ICS had a 62% risk reduction compared with patients not using nebulized ICS (HR: 0.38, 95% CI: 0.21, 0.69). In the 5-to 8-year age group, patients on nebulized ICS had a 52% risk reduction (HR: 0.48, 95% CI: 0.16, 1.46). Conclusion: In actual practice, treatment with nebulized ICS after an asthma exacerbation is associated with a significant reduction of recurrent hospitalization/ED visits in young children, possibly due to improved technique and compliance. Introduction: TENOR is a 3-year, multi-center, cohort study of patients with severe or difficult-to-treat asthma. The objective of the TENOR study is to better understand the natural history of patients with severe or difficult-totreat asthma. This analysis assessed the frequency of skin testing in this population and characterized the differences between the positive (ST+) and negative (ST ) subjects. Methods: Subjects were asked whether they had ever been skin tested and, if so, the test results. Those who were ST+ were compared to both ST and those never tested (STND) using clinical and other asthma-related characteristics. Subjects 12 years of age were included in this analysis. Results: 2985 subjects were eligible for this analysis. 85.8% were skin tested in the past, with STND frequency of 5.1% from allergist sites and 33% from pulmonologist/other sites. Of those tested, 93.5% were positive (allergist 95.7%, pulmonologist/other 87.3%). Baseline IgE for ST+ subjects was 104.6 IU/ml vs. 32.4 IU/ml for ST ; p<0.0001 (Table) . As shown, the age at asthma onset, duration of asthma, rate of atopic disorders, and the rate at which asthma was triggered by aeroallergens differentiated the ST+ from the ST group. Disease severity as evaluated by FEV 1 , healthcare utilization, and medication use, however, was similar between the two groups. In general, STND were more likely to have values closer to the ST+ group, suggesting that the majority of those not tested would have been ST+, if administered a test. Conclusions: The prevalence of ST+ subjects from both allergy and pulmonary practices was high, demonstrating that the majority of these severe or difficult-to-treat patients have allergic asthma. ST+ patients showed differences in clinical characteristics compared to ST , including a greater likelihood of their asthma symptoms being triggered by aeroallergens. These data also show that the clinical profile of STND patients may be similar to that of ST+ patients, suggesting the utility of a more universal allergic evaluation in severe asthmatics. Funded by Genentech and Novartis Pharmaceuticals Corp. Background Current national guidelines for the diagnosis and management of asthma such as the NAEPP EPR 2002, classify asthma severity based on frequency of asthma symptoms, medication use, and measurements of lung function by spirometry or peak expiratory flow variability. Recently, the utility of spirometry measurements for assigning asthma severity has come into question. Here we evaluate the correlation of spirometry measurements with asthma severity in school-aged children who are mostly naive to anti-inflammatory therapy. Methods Children were participants in a school-based lowincome asthma mobile van program, the Breathmobile. Recruitment was through referrals by school nurses and community public health clinics, parental response to flyers, and asthma screening questionnaires. Spirometry was performed on all children greater than 4 years of age as part of a comprehensive asthma evaluation. Asthma severity was assigned based on symptoms only, according to the NAEPP EPR 2002 . Results From April 2002 to April 2004 of the 620 children evaluated on the Breathmobile, 540 patients were diagnosed with asthma. Classification of severity by symptom frequency according to NAEPP EPR guidelines resulted in 28% as mild intermittent (MI), 28% as mild persistent (MiP), 32% as moderate persistent (MoP), and 12% as severe persistent (SP). The percentage of patients and their mean lung functions at baseline evaluation without bronchodilator challenge are shown in the table. There were statistically significant differences (p<.05) between severity groups which was most pronounced for the FEF25-75% when comparing the severe persistent group and the intermittent group. However, mean values appear to be "normal" for all degrees of asthma given current accepted cut-off values, FVC 80%, FEV1 80%, FEV1/FVC 80%, and FEF25-75 60%. Conclusion In our study, airflow impairment did correlate with asthma severity, although it was "normal" (FEV1 80%) even in children with severe persistent asthma. Therefore, a "normal" lung function measurement may be misleading as sole criteria for asthma severity classification. Perhaps a higher cutoff point (FEV1<90%) might be a better indicator of asthma severity in children. Asthma is the most frequently chronic disease in childhood.Our main was to know the prevalence of bronchial asthma in children (6-7 and 13-14 years) in the north zone of Mexico City and to compare the prevalence obtained by the written questionnaire versus the video questionnaire in the group of 13 to 14 years, according to methodology proposed by ISAAC. Material and Methods: By means of a validated and standardized questionnaire (ISAAC) that was applied to 3500 children from 6 to 7 years and 3899 from 13 to 14. The questionnaires of 6 and 7 years were filled out by their parents. The group from 13 to 14 years answered a questionnaire and a video questionnaire. According to ISAAC specification and based on a studied population, it was calculated by STATcal program the size of the sample. It was choose a haz-ardous sample of 3000 children between 6-7 years and 3000 of the 13-14 group years, both sexes in elementary and high school. Measures of central tendency and Chi2 were used. Results: The final sample size for both groups was 7110 children (3211 of 6-7 and 3899 adolescents), 51.5% men and 48.5% women. The prevalence of the asthma diagnosis for teenagers was of 8 % (p<0.05 IC 7.1-8.7) and it was 4.5% in children (p<0.05 IC 3.8-5.2), wheezing in the last 12 months was 6.8% (p<0.05 IC 5.9-7.6) in children and of 9.9% (p<0.05 IC 9-10.8) for 13-14 years. wheezing induced exercise appeared in 13.1% (p<0.05 IC 12-14.1) in teenager and 3.4 % (p<0.05 IC 2.7-4) in the other group. The severity of asthma showed by nocturnal awakness was 4.3% and 2.6% (p<0.05), number of crisis in the last year 6.3% and 9.3% for children and teenagers respectively (p<0.05). In the video questionnaire of teenagers 7.3% (IC 6.5-8.1) answered affirmative on have displayed a shaken breathing on the last year resting and only 6.8% (IC 6-7.6) in the last month. About exercise question 16.5% confirmed have displayed symptoms, 14.6%(IC 13-15.8) in the last year and 11.1% (IC 10.1-12.1) in the last month. Wide-awake at night 7.5% (IC 6.7-8.3) in the last year and 5.2% ) in the last month. Conclusions: The prevalence of asthma by diagnosis was higher in teenagers group than in children group. The prevalence of asthma was higher also in this group. Rationale: We investigated the relationship of pet exposure and healthcare utilization (HCU) in a cohort of pediatric patients with severe or difficult-totreat asthma in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) observational study. We hypothesized that pet exposure would increase HCU due to increased airway inflammation. Methods: TENOR is a 3-year multicenter cohort study of patients with severe or difficult-to-treat asthma. Children ages 6-12 were interviewed at baseline regarding asthma-related HCU in the previous 3 months. Patients with pet exposure (PPE, n=370) were compared with patients with no pet exposure (PNPE, n=382). Responses were analyzed using Fisher's exact test. Results: PPE were less likely to have severe asthma by physician assessment (32% vs. 40%; p=0.01). In addition, PPE were less likely to have an emergency room (ER) visit (18% vs. 26%; p=0.006) or to have been hospitalized (7% vs. 12%; p=0.02) in the previous 3 months. More PNPE had an IgE level >100 IU/ml (74% vs. 63%; p=0.001). PPE and PNPE were similar with regard to presence of allergic rhinitis and skin test positivity. Compared with PNPE, fewer PPE with two or more pets had ER visits and hospitalizations (Table) . Among PPE, there were no differences in IgE levels or in asthma severity related to the number of pets. Conclusions: Pet exposure was associated with reduced HCU in the TENOR pediatric cohort, with the most pronounced effect seen in reduced ER visits and hospitalizations needed by those with multiple pets. PPE had significantly lower IgE levels compared to PNPE, regardless of the number of pets. These data support the hypothesis that exposure to pets may paradoxically protect individuals from the development of severe asthma. Alternatively, these data may reflect a self-selection in patients with severe or allergic asthma who are likely to avoid having a pet. However, there may be other confounding factors in families with pets that confer a protective effect on asthma severity. INTRODUCTION: In asthma and other chronic obstructive airway diseases, phosphodiesterase 4 (PDE4) is involved in the pathophysiology of the disease and is expressed abundantly in key inflammatory cells. Inhibitors of PDE4 are investigational, anti-inflammatory agents that prevent the breakdown of cyclic adenosine monophosphate, a natural modulator of inflammation. Roflumilast is an investigational, oral, once-daily PDE4 inhibitor with demonstrated in vitro and in vivo anti-inflammatory activity, which may translate into clinical efficacy in asthma therapy. This study examined the ability of roflumilast to exert direct or acute bronchodilatory activity in patients with mild to moderate asthma. METHODS: This was a double-blind, randomized, placebo-controlled, crossover study consisting of three treatment periods of one day each, separated by a 7-to 14-day washout period. During each treatment period, 15 patients with a forced expiratory volume in one second (FEV 1 ) of 50% to 90% of predicted received either oral roflumilast 1000 μg, roflumilast 500 μg, or placebo. The FEV 1 was measured twice prior to administration and periodically up to 6 h following treatment. After 6 h, patients inhaled 200 μg salbutamol from a metered-dose inhaler; FEV 1 was measured 15 min later. Adverse events, vital signs, and electrocardiogram results were monitored throughout the study. RESULTS: Median baseline FEV 1 was similar for the three treatment periods. Both doses of roflumilast did not lead to statistically significant differences versus placebo in the time-averaged FEV 1 over the first or up to 6 h after drug intake (p > 0.05). Thus, there was no evidence of a direct or acute bronchodilatory effect with either single doses of roflumilast 1000 μg or 500 μg. In contrast, inhalation of the short-acting bronchodilator salbutamol led to a distinct improvement in FEV 1 versus baseline in all treatments groups with median FEV 1 increases of 19%, 21%, and 14% in the roflumilast 1000 μg, roflumilast 500 μg, and placebo groups, respectively. Roflumilast was well tolerated. CONCLUSIONS: Oral, once-daily roflumilast exhibits no direct or acute bronchodilatory activity in patients with mild to moderate asthma as could be achieved with short-acting 2 -agonists. These data support the proposed mechanism of action of roflumilast as an antiinflammatory agent. South Africa; 2. Guadalajara, Spain; 3. Munich, Germany; 4. Weinheim, Germany; 5. Budapest, Hungary; 6. Konstanz, Germany. INTRODUCTION: Phosphodiesterase 4 (PDE4) is found in key inflammatory cells involved in the pathophysiology of chronic obstructive pulmonary disease and asthma. Inhibitors of the PDE4 enzyme are anti-inflammatory agents that prevent the breakdown of cyclic adenosine monophosphate, a natural modulator of inflammation. Roflumilast is an investigational, oral, oncedaily PDE4 inhibitor with demonstrated in vitro and in vivo anti-inflammatory activity. This study examined the dose-related efficacy of roflumilast in patients with asthma. METHODS: Patients with stable asthma (forced expiratory volume in 1 second [FEV 1 ] 50% to 85% of predicted) were enrolled in this randomized, double-blind, dose-range finding study. After a single-blind placebo run-in period of up to three weeks, patients received oral roflumilast 100 μg, 250 μg, or 500 μg once daily (N = 229, 228, and 233, respectively) for 12 weeks. Efficacy was assessed by change from baseline in spirometric lung function FEV 1 and forced vital capacity (FVC), as well as morning and evening peak expiratory flow (PEF) recorded in patient diaries. Safety and tolerability parameters were monitored throughout the study. RESULTS: Treatment with roflumilast led to dose-dependent and statistically significant increases in FEV 1 , FVC (both p < 0.0001), and in morning PEF (p < 0.01). At last visit, FEV 1 improved from baseline by 260 mL (11%), 320 mL (13%), and 400 mL (16%) in patients treated with roflumilast 100 μg, 250 μg, and 500 μg once daily, respectively. Similarly, dose-dependent improvements of 10 L/min, 12 L/min, and 20 L/min in morning PEF from baseline were reached. Roflumilast was well tolerated at all dose levels tested. The most frequent drug-related adverse events were headache followed by gastrointestinal disorders such as diarrhea and nausea. There were no clinically relevant changes in vital signs, electrocardiogram, or laboratory parameters. CONCLUSIONS: Oral, once-daily roflumilast was associated with dose-dependent, clinically relevant improvements of lung function in patients with stable asthma. Roflumilast was well tolerated.
J.L. Izquierdo 1* , E.D. Bateman 2 , P. Magyar 3 , U. Harnest 4 , P. Hofbauer 5 , A. Varga 6 , C. Schmid-Wirlitsch 7 , D. Bredenbroeker 7 , T.D. Bethke 7 , 1. Guadalajara, Spain; 2. Cape Town, South Africa; 3. Budapest, Hungary; 4. Munich, Germany; 5. Weinheim, Germany; 6. Tatabanya, Hungary; 7. Konstanz, Germany. INTRODUCTION: Phosphodiesterase 4 (PDE4) inhibitors are a new class of anti-inflammatory agents for therapeutic use in inflammatory airway diseases. In several studies, the investigational, oral, once-daily PDE4 inhibitor roflumilast has provided clinically meaningful improvements in patients with chronic obstructive pulmonary disease and asthma. This study examined the long-term safety and tolerability of roflumilast over 40 weeks in patients with asthma. METHODS: Patients with persistent, stable asthma (FEV 1 50% to 85% of predicted at randomization) participated in a double-blind, randomized dose-range finding study and were treated with oral roflumilast 100 μg, 250 μg, or 500 μg once daily for 12 weeks. Patients completing the 12-week study per-protocol, then continued treatment in this open-label 40-week extension study. All patients received oral roflumilast 500 μg once daily during the extension period. Adverse events (AEs), clinical laboratory parameters, vital ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY signs, and ECG were assessed throughout the extension period. RESULTS: A total of 456 patients were enrolled in the 40-week extension study. Overall, the most common AEs were related to the respiratory system. Only a small number of patients (6%) experienced AEs that were assessed as at least likely related to study medication. The most frequent drug-related adverse events were headache, diarrhea, and nausea as reported by 3%, 1%, and 1% of patients, respectively. Most AEs were mild to moderate in intensity and transient in duration; 6% of patients discontinued the study due to AEs. Most (60%) of these AEs leading to discontinuation were assessed as not related or unlikely related to study drug. Out of 456 patients, 16 reported serious AEs, which were all assessed as not related or unlikely related to roflumilast. No clinically relevant changes in clinical laboratory parameters, vital signs, ECG, or physical examination occurred. CONCLUSIONS: Oral, once-daily roflumilast 500 μg administered for 40 weeks was well tolerated in patients with persistent, stable asthma. This study provides evidence that roflumilast is associated with a low incidence of AEs, which are mostly mild to moderate in intensity and transient in nature, thus, supporting the potential therapeutic use of roflumilast in asthma. Paris, France; 3. Madrid, Spain; 4. Guadalajara, Spain; 5. Harrow, United Kingdom; 6. Weinheim, Germany; 7. Augsburg, Germany; 8. Munich, Germany; 9. Kaufbeuren, Germany; 10. Konstanz, Germany. INTRODUCTION: In asthma, inhaled corticosteroids (ICS) have been the mainstay of maintenance treatment. New therapeutic agents are needed that target key inflammatory processes in asthma as effectively as ICS but overcome known limitations of ICS. Phosphodiesterase 4 (PDE4) inhibitors are anti-inflammatory agents that prevent the breakdown of cyclic adenosine monophosphate, a natural modulator of inflammation. Roflumilast is an investigational, oral, once-daily PDE4 inhibitor for potential use in anti-inflammatory asthma therapy. This study compared the standard corticosteroid treatment of twice-daily, inhaled beclomethasone dipropionate (BDP) with oral, once-daily roflumilast in patients with asthma. METHODS: In a randomized, double-blind, double-dummy study, patients (forced expiratory volume in one second [FEV 1 ], 50% to 85% of predicted) received either oral roflumilast 500μg once daily (N=207) or inhaled BDP 200μg twice daily (400μg/day; N=214) for 12 weeks. Mean change (LSMean and SEM) in lung function parameters FEV 1 , forced vital capacity (FVC), and morning and evening peak expiratory flow (PEF) from baseline was determined after 12 weeks of treatment. Further, symptom score and rescue medication use were assessed. RESULTS: Both roflumilast 500μg and BDP 400μg improved FEV 1 from baseline to clinically meaningful levels (300 ± 40mL and 370 ± 30mL, respectively; both p<0.0001). Similarly, roflumilast and BDP improved FVC (300 ± 40mL and 360 ± 40mL, respectively; both p<0.0001) as well as morning and evening PEF (p 0.0003). Roflumilast 500μg was statistically non-inferior to BDP 400μg. Roflumilast and BDP led to statistically significant and comparable improvements in asthma symptoms and use of rescue medication. Adverse events were generally mild to moderate; the most common drugrelated adverse events reported in the roflumilast group were nausea, headache, and diarrhea. There were no clinically relevant changes in vital signs, ECG, or laboratory parameters. CONCLUSIONS: Roflumilast 500μg provided clinically meaningful improvement of lung function parameters, reduced asthma symptoms, and decreased the need for rescue medication. Oral, once-daily roflumilast was as effective as inhaled, twice-daily BDP in the treatment of asthma. Oral roflumilast 500μg was well tolerated. Rationale: Evaluation of medical claims from commercial health plans permits assessment of therapeutic interventions on resource utilization. This study investigated the impact of controller therapy in children starting asthma maintenance medications. The risk of obtaining prescriptions for oral corticosteroids (OCS), short-acting beta-agonists (SABA) or adding another asthma therapy was evaluated. Methods: This was a retrospective observational study utilizing medical and pharmacy claims from a large representative managed care plan from 1/1/2000-5/31/2003. Children aged 4-17 years old with an asthma diagnosis (ICD-9, 493.xx) and an initial pharmacy claim for one of the following regimens: fluticasone/salmeterol in a single inhaler, n=1, 168 (FSC), fluticasone propionate alone, n=2, 473 (FP), montelukast, n=4, 246 (MON), any inhaled corticosteroid plus montelukast, n=1, 009 (ICS+MON), and an ICS plus salmeterol from separate inhalers, n=296 (ICS+SAL) were included in the analysis. Subjects were excluded if they had received any asthma controller medication in the 6 months prior to the initiation of therapy. Regression was used to estimate the incidence rate ratio (IRR) for OCS and SABA use (negative binomial) and the odds ratio (OR) of adding a controller (ADD) and an ED or hospitalization (IP) event (logistic). All models controlled for demographics, pre-controller asthma-related medications and events, and baseline total health care costs. Results: The ratios in the table with a confidence interval excluding unity indicate significantly increased use or likelihood of an event compared to the FSC cohort. Controller naïve children started on FSC were less likely to add another controller than MON, FP or ICS+SAL, and had less use of OCS or SABA than the 4 cohorts when studied for 12 months after the initiation of controller therapy. In addition, children treated with ICS + MON had a significantly greater OR of an ED/IP visit compared to FSC. Conclusion: Use of FP + SAL (FSC) in a single inhaler assures that children are getting more optimal inhaled corticosteroid therapy as well as the benefits from the long acting bronchodilator while avoiding the potential for selective discontinuation of ICS in the 2 multiple controller cohorts.
A.S. Nayak 1* , R. Nathan 2 , J. Williams 3 , S. Kundu 3 , M. Lloyd 3 , D. Banerji 3 , 1. Normal, IL; 2. Colorado Springs, CO; 3. Bridgewater, NJ.
INTRODUCTION: Inhaled corticosteroids (ICS) are recommended firstline therapy for severe, persistent asthma. Systemic exposure to ICS may suppress hypothalamic-pituitary-adrenal (HPA)-axis function, particularly at doses required to control severe asthma. Ciclesonide (CIC) hydrofluoroalkane (HFA) metered dose inhaler (MDI) is a novel and effective ICS that is converted in the lungs to its active metabolite, desisobutyryl ciclesonide (des-CIC). Previously, in short-term studies, CIC has been shown to have no effect on serum or urinary cortisol levels, which may be attributed to the low oral bioavailability, high serum protein binding and high clearance rate of CIC and its active metabolite. This HPA axis analysis was part of a long-term study evaluating the safety of CIC and beclomethasone dipropionate (BDP) HFA-MDI in patients with severe persistent asthma. METHODS: This was a multicenter, double-blind, parallel-group, 12-month extension of a 12-week double-blind trial of patients 12 years with severe persistent asthma. Patients were randomized in a 2:1 ratio (CIC:BDP) to receive CIC (320 g bid) exactuator or BDP (320 g bid) ex-actuator. After 2 weeks, the doses of both medications could be titrated to 160 g bid as needed for asthma control. HPA-axis function was assessed at selected centers in a subset of patients at baseline and end of study (at month 12 or early termination) by measuring both peak serum cortisol induced by low dose (1-μg) cosyntropin and 24-hr urinary free cortisol corrected for creatinine. RESULTS: Data were available for a small number of patients at 13 centers evaluating HPA-axis (Table) . Mean baseline levels and change from baseline to end of study values in low-dose cosyntropin peak serum cortisol levels for CIC and BDP were comparable. Likewise, baseline levels and mean change from baseline to end of study values in 24-hr urinary free cortisol corrected for creatinine were comparable among the two treatment groups. CONCLUSION: These findings demonstrate that CIC 320 to 640 μg daily for 12 months is safe and has no significant effect on HPA-axis function.
A. Long 1* , A. Rahman 2 , 1. Boston, MA; 2. Wilmington, DE.
INTRODUCTION: Little information is available regarding the relationships between asthma severity, disease control, and compliance with medications. METHODS: Physicians' perceptions regarding these variables were determined by Internet-based general asthma medication usage survey and patient-specific asthma medication usage surveys between December 18 and 29, 2003, for 406 physicians (100 PCPs, 106 pediatricians, 100 allergists and immunologists, and 100 pulmonologists). The patient-specific surveys were based on chart information of 3 randomly chosen patients per physician on controller medication. RESULTS: Of 1218 patients, 12%, 31%, 43%, and 14% were categorized by their physicians as having mild intermittent or mild, moderate, or severe persistent asthma, respectively. Overall, 45% of patients were categorized as having "very controlled" asthma and 58% as being "very compliant" with their current regimen. Worse asthma control, decreased compliance, and increased physician visits were all associated with increased asthma severity classification. Physicians reported that only 5% of patients with severe persistent disease (n=169) had "very controlled" asthma in contrast to 77% of patients with mild intermittent asthma (n=143). Patients with mild intermittent asthma, and mild, moderate, and severe persistent asthma, had a mean of 2.9, 3.4, 4.5, and 5.5 physician visits for asthma, respectively, within the past year. Physician perception of patient compliance varied less across the groups, with 55% of patients with severe persistent asthma and 66% of patients with mild intermittent asthma being rated as "very compliant." The incidence of allergic rhinitis was similar among all severity levels (range: 50%-56%), but patients with severe persistent asthma were more likely to have comorbid conditions, including hypertension, chronic obstructive pulmonary disorder, chronic bronchitis, and osteoporosis, compared with patients in other asthma severity levels. CONCLUSIONS: Decreased asthma control and rates of com-pliance, as well as increased physician visits and comorbid medical conditions, may be associated with increased asthma severity classification. Rationale: Children with asthma frequently have co-morbid allergic conditions requiring medications. The purpose of this study was to assess whether the controller asthma medication selected would reduce the utilization of intranasal steroids (INS) and prescription nonsedating antihistamines (NSA) for children treated for co-morbid allergy. Methods: This was an observational retrospective study that utilized the PharMetrics Integrated Outcomes Database that contains administrative medical and pharmacy claims data from over 30 managed care plans across the United States. Children age 4-17 years old with a new diagnosis of asthma (ICD-9, 493.xx) were identified and observed for 12 months after their initial diagnosis and treatment of asthma (post-index). Four cohorts were established based on their controller medication dispensed: montelukast, n=1906 (MON), fluticasone propionate, n=2455 (FP), FP+MON n=287, FP/salmeterol in a single inhaler, n=599 (FSC). Results: Baseline comorbid diagnosis of allergic rhinitis was observed in 14-20% of the children. The patterns of use of INS and NSA were similar in the 12 months before and the 12 months after the initial asthma diagnosis and treatment. Children with a diagnosis of allergic rhinitis were nearly twice as likely to receive a NSA or INS. All 4 treatment cohorts used a similar amount of each allergy medication. The presence or absence of a diagnosis of allergic rhinitis did not alter the findings. The adjusted odds ratio (95%CI) of using a NSA or INS relative to the use of FSC in the post-index period was MON: 0.989 (0.809, 1.208); FP: 0.828 (0.682, 1.007); FP+MON: 1.095 (0.804, 1, 489 ). The table below shows the percent of children dispensed a NSA and/or an INS. The number of units of each allergy medication was also similar across all 4 cohorts. Conclusion: The use of MON, FP, FP+MON or FSC for asthma did not alter the rate or quantity of either intranasal corticosteroid or nonsedating antihistamines dispensed to children over the 12-month period. Although allergic rhinitis is a common comorbidity of pediatric asthma, the selection of a regimen containing montelukast did not reduce the use of either NSA or INS compared to asthma treatments with FP or FSC. Rationale: Medication compliance is recognized as a significant challenge in pediatrics.The purpose of this study was to compare inhaled corticosteroid (ICS) persistence in pediatric patients using a single inhaler, containing both an inhaled corticosteroid (fluticasone propionate, FP) and an inhaled long-acting beta-agonist (salmeterol, SAL) (FSC), to patients receiving FP alone, FP + SAL from separate inhalers, or ICS + montelukast (MON). Methods: Retrospective 24-month pre-post database study utilizing medical and pharmacy claims. A total of 4946 subjects 4-17 years of age with a diagnosis of asthma (ICD9 493) were grouped into 4 cohorts: FSC [n=1168]; FP only [n=2473] ICS+SAL [n=296]; and ICS+MON [n=1009]. Patients were controller naïve for 6 months prior to the index event (the first prescription of the medication of interest). Subjects were required to have continuous enrollment of 6 months pre-and 12 months postindex. Subjects with cystic fibrosis, COPD, bronchopulmonary dysplasia or respiratory distress syndrome were excluded. ICS refill rates, as a measure of persistence, were compared between FSC and the ICS components of the other cohorts over a 12-month follow-up period. Results: Mean refill rates over the 12-month follow-up period was significantly greater (p=< 0.05) for FSC (4.48) compared with the mean ICS refill rate in the FP alone (3.39) cohort, the ICS + SAL (3.61) and the ICS + MON (3.92) cohort. Patients on FSC filled 32% more ICS prescriptions than patients on FP alone, 24% more than ICS+SAL and 14% more than ICS + MON. Mean refills were generally higher than the median fills as a considerable number of children had only one fill: FSC (35.6%), FP (49.1%), ICS (48.3%) + SAL (50.0%), ICS (36.0%) + MON (18.6%). Conclusion: Patients using FSC, are likely to fill their inhaled corticosteroids more often over 12-months compared with patients using ICS + SAL in 2 separate inhalers, ICS+MON, and FP as monotherapy. Improved persistence with ICS has been shown in other studies to decrease morbidity and mortality of asthma. Use of FSC, a single inhaler, assures that children are getting more optimal inhaled corticosteroid therapy as well as the benefits from the long acting bronchodilator while avoiding selective discontinuation of ICS that may occur when two medications are dispensed. The National Health Interview Survey (NHIS) estimates 14.5 million United States residents with asthma. Noncompliance with treatment has been estimated as between 20 and 80%. The consequences of noncompliance include absences from work or school, increased emergency room visits, more severe attacks, increased drug side effects, greater cost of care, and death. We questioned compliance in a 47yo man with severe, prednisone dependent eosinophilic asthma because he had persistent symptoms despite treatment with fluticasone propionate/salmeterol xinafoate 500/50 bid, prednisone 20mg to 40mg qd, and budesonide (200 mcg/puff) 2 puffs bid. After discontinuation of budesonide and prednisone and initiation of methylprednisolone 16mg bid for 24 hours and then 16mg qd and beclomethasone dipropionate 2 puffs (80mcg) HFA bid with a spacer, clinical improvement was unexpectedly abrupt. FEV1 increased from 58% to 90% of predicted. Sputum eosinophil counts decreased from 78% to 2%. Because of the sudden improvement with the change to methylprednisolone, compliance to prednisone and fluticasone was questioned. To evaluate compliance, the patient's blood, urine, and sputum were tested for synthetic corticosteroids, without his knowledge, using mass spectrometry. The blood level of methylprednisolone was 2.6mcg/dl and prednisolone was 0.35mcg/dl, documenting use of methylprednisolone and the recently discontinued prednisone. The urine levels were 13mcg/dl of methylprednisolone, 1.3mcg/dl of prednisolone and 0.74mcg/dl of prednisone that further confirmed recent use of prednisone. The sputum testing revealed 0.8mcg/dl beclomethasone, 33mcg/dl fluticasone and 1.8mcg/dl methylprednisolone confirming compliance to inhaled fluticasone and beclomethasone at the time of the test. Thus, contrary to our clinical suspicion, the patient was indeed compliant with his inhaled glucocorticoids and prednisone and subsequently with the methylprednisolone. To our knowledge, this is the first case report to document compliance to inhaled and oral corticosteroids by analysis of synthetic corticosteroid concentrations in blood, urine, as well as sputum. If compliance could be documented with certainty, it could potentially minimize the adverse effects of needless escalating steroid doses, reduce the cost of treatment, and minimize morbidity and mortality as well. Rationale:The burden of pediatric asthma extends beyond those children with an asthma diagnosis. Children with wheezing frequently have a delay in the diagnosis of asthma that may impede instituting appropriate therapy and reducing disease morbidity. This observational study was designed to assess the treatment patterns of children 4-17 years old receiving asthma medication(s) without a diagnosis of asthma compared with children diagnosed with asthma and children without claims for asthma. Methods:This was a retrospective cross-sectional study that utilized the PharMetrics Integrated Outcomes Database containing administrative medical and pharmacy claims data from over 30 managed care plans across the United States. Three cohorts were selected: children with an asthma diagnosis (ICD-9, 493.xx) (Dx cohort), children with prescription claims for asthma controllers or rescue medications without an asthma diagnosis (Rx cohort) and children with neither an asthma diagnosis nor prescription claims for asthma medications (Control cohort). Utilization of asthma medications, asthma specific costs and total costs of care were assessed. Results: A total of 295, 000 children were identified: 6.7% in the Dx cohort, 4.4% in the Rx cohort and 88.9% in the control cohort. The potential asthma cohort was 11.1%. Total annual non-asthma related costs for the Dx cohort was $1, 642 for the Rx cohort was $1, 306 and for the control was $802. Only 19% and 5% of the total healthcare charges in the Dx and Rx cohorts retrospectively were asthma related. Non-asthma charges were significantly higher in both the Dx and Rx cohorts compared with the control cohort. In the Rx cohort, the ratio of SABA prescription claims to asthma controller claims were 1.85-fold higher than in the Dx cohort. Conclusion: Children treated with asthma medications without an asthma diagnosis consume greater health care resources resembling the pattern of health care utilization of children with an asthma diagnosis more closely than controls. Further, children with treatment in the absence of an asthma diagnosis appear to be under-treated with controller therapy as recommended by national and international guidelines. BACKGROUND: A recent retrospective study assessed asthma variability in inner-city patients 6 months before and 6 months after enrollment into an NAEPP guidelines-directed clinical management and educational program. While guidelines-directed care improved asthma symptoms and outcomes, significant variability in disease indices were observed over the 6-month period.
The present analysis evaluates resource utilization associated with this variability. METHOD: Economic end points, including hospital/emergency department (ED) visits, total unscheduled office visits, sick visits, and days lost from work or school, were collected from 125 inner-city patients aged 18 years (74% female, 69% minority, 80% treated by primary care physicians) enrolled in a guidelines-directed asthma clinical management and education program aimed at minimizing barriers to adherence. Patients were stratified into 2 groups: those with high variability in asthma (n=62) and those with low variability in asthma (n=63), with variability defined as number of fluctuations in NAEPP symptom class in the 6-month postintervention period (high variability = patients with fluctuations higher than the mean; low variability = patients with fluctuations lower than the mean). RESULTS: Guidelines-directed therapy was associated with improvements in asthma during the 6-month treatment period for both groups. Patients in the high-variability group had more ED visits, sick visits, total unscheduled visits, and office visits compared with patients in the low-variability group (see table) . CONCLUSIONS: Despite guidelines-directed therapy and overall improvement in asthma control, patients experienced variability in asthma, indicating that even when their disease is stable, their symptoms continue to fluctuate. As a result, asthma variability may contribute to increased resource utilization. INTRODUCTION: Inhaled corticosteroids (ICS) are considered first-line therapy for patients with persistent asthma. ICS can lead to oropharyngeal adverse events, which may affect treatment outcomes and adherence. The occurrence of these local adverse events is dependent upon several factors, including dosage and duration of ICS treatment. Ciclesonide (CIC) hydrofluoroalkane (HFA)-metered dose inhaler (MDI) is a novel and effective ICS, with relatively low oropharyngeal deposition. CIC is converted in the lungs to its active metabolite, desisobutyryl-ciclesonide (des-CIC). Furthermore, CIC undergoes limited conversion in the oropharynx, which may account for its improved safety profile. This oropharyngeal safety profile analysis was part of a long-term study evaluating the safety of CIC HFA-MDI vs beclomethasone dipropionate (BDP) HFA-MDI in patients with severe persistent asthma. METHODS: This was a multicenter, double-blind, parallelgroup, 12-month extension of a 12-week double-blind study of patients 12 years with severe persistent asthma. Patients were randomized in a 2:1 ratio (CIC:BDP) to receive CIC (320 g bid) or BDP (320 g bid) (both ex-actuator). After 2 weeks, the doses of both medications could be titrated to 160 g bid as needed for asthma control.) Oropharyngeal adverse events were monitored, and suspected oral fungal infections were verified by positive culture. RESULTS: The incidence of oral candidiasis was lower in subjects receiving CIC (4.1%), compared with those receiving BDP (10.4%) ( Table) . The incidence of pharyngitis and hoarseness was 3.6% and 2.5%, respectively, for the CIC group, and 5.2% and 1.0%, respectively, for the BDP group. All local adverse events resolved without sequelae, and there were no withdrawals due to oropharyngeal treatment-emergent adverse events. CONCLUSION: After 12-months of treatment with CIC 160 μg or 320 μg twice-daily, the incidence of oropharyngeal adverse events was low. CIC treatment resulted in a much lower incidence of oral candidiasis, compared with similar doses of BDP, reflecting a better local tolerance. Objective: To determine the prevalence of asthma and asthma-related morbidity, treatment and asthma-risk factors in a selected population. Method: A routine health screening, including tests for asthma, was conducted at the New Orleans Center for Creative Arts High School. Participants (204) identified their medications and asthma tools in addition to completing the ISAAC questionnaire. Prevalence data included lifetime wheezing, 12 month wheezing, and previous asthma diagnosis. Asthma-related morbidity included sleep disturbance, wheezing with exercise, asthma attack rate and night awakening. Results: " Participants were aged 13-9 years (50.5% African American, 45.1% white) with 31.4% male, 68.6% female. " Cumulative asthma prevalence was 18.8%, lifetime wheezing (24%), 12-month wheezing 12.7% with girls reporting 3.36 times more often (95% CI: 1.54, 7.36), and wheezing more than 4 times in 12 months 4.7%. " There was a significant association between race and wheezing in the last 12 months (p < 0.024) with whites reporting 3.78 times more often (95% CI: 2.01, 7.10). Asthma morbidity was reported as follows: a. Night cough -10.5% b. Wheezing with exercise -10.9% " Parents with a less education (high school or less) were 8.33 times more likely (95% CI: 7.46, 9.30) to have children who developed wheezing in the past 12 months. " Higher Body Mass Index (BMI = 25) was associated with wheezing after exercise (p < 0.008) with a 3.27-fold increase (95% CI: 2.46, 4.31). " Among those with current asthma (15/204), 4 were not on any medication, 10 were using bronchodilators, and 5 were on anti-inflammatory medications. Three reported using a spacer and 6 reported using a peak flow meter. Conclusion: Asthma prevalence is higher in this school population than the national average. Less parental education, female gender, and BMI = 25 were associated with greater asthma morbidity. The majority of the participants with current asthma reported receiving episodic and inadequate treatment with inhaled corticosteroids. Objectives: To determine the prevalence of asthma and asthma related symptoms; to assess its severity among New Orleans school children. Methods: Seven elementary, middle, and high schools in New Orleans participated in the screening of 1511 students, 54% female, 45% male, ages 5-18 in the Fall, 2000. The 8-item questionnaire was designed by the International Study of Asthma and Allergies in Childhood (ISAAC) to determine asthma prevalence and severity in children. The ISAAC questionnaire is a validated protocol used on over 500, 000 children in 56 countries. Asthma is defined as cur-rent wheezing for the purposes of this study. Data was entered using SPSS 10 and SAS 8 software for analysis. Results: Table: Presence of asthma symptoms by ethnicity Conclusion: Asthma prevalence is significantly higher in inner-city school children in New Orleans when compared to the national prevalence (24.6% to 26.4% vs. 7.5%). Asthma prevalence and severity do not differ significantly between African-American and Caucasian children in New Orleans even after removing the effect of gender and age. Video is an effective method of teaching pollen identification. Projected digital images offer three-dimensional views of unique pollen detail similar to focusing a microscope. The National Allergy Bureau™(NAB) currently provides pollen counts to the media. These reported levels are obtained by standardized counting methods rather than forecasts based on historical pollination predictions and weather patterns. The American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology have an interest in ensuring consistent counting and accurate reporting practices. Both organizations offer pollen identification training in conjunction with their annual meetings and have used the video for initial training sessions and for experienced counters in advanced courses. There are 112 certified pollen counting stations in the United States and Canada with approximately 80 currently active locations. The NAB requires the demonstration of ability to count and accurately identify pollen on test slides. An updated recertification process using an interactive web site is currently being developed. Ongoing pollen identification training is essential for the continued success of this aeroallergen network. Most observers found that the video provided a quality emulation of microscopic viewing and enhanced the depth and detail of individual pollen characteristics. The video received the highest possible ratings by course attendees. In conclusion the video plays a positive role in pollen identification training and the continuing education of experienced counters. The diagnosis and treatment of mold allergies are complicated by the genetic diversity of individual fungal species and the influence of endogenous fungal proteases on extract compositions and potencies. Studies examining the biochemical comparability of mold extracts from different sources and their compatibility with other allergens in immunotherapy mixtures are essential to the clinical effectiveness of these products. Compositional comparisons of extracts prepared from Alternaria, Aspergillus and Penicillium source materials by 7 U.S. allergen manufacturers revealed variable SDS-PAGE protein banding patterns and noticeable differences in total protein and carbohydrate concentrations. Alt a 1 levels in Alternaria extracts did not correlate closely with total protein levels or with IgE-binding potencies measured by ELISA inhibition. Immunoblot profiles of fungal extracts were more closely related to one another compared to SDS-PAGE patterns, suggesting that similar allergenic or antigenic epitopes may be retained in molecules of varying size. Parallel ELISA inhibition dose-response curves provided statistical evidence that a repertoire of IgE epitopes is conserved in many of these products. Variations in the potencies of fungal extracts from different manufacturers may result from differences in source materials and/or conditions of extraction and storage. The stability and compatibility of allergen mixtures containing mold extracts were assessed after storage for up to 6 months at 2-8°C using specific immunoblot and ELISA procedures. Grass and mite allergens compromised by mixing with mold extracts were stabilized by glycerin. Alternaria extracts from different sources produced similar effects on grass allergens when added at comparable strengths. Degradative effects caused by Aspergillus or Penicillium products were more closely related to total fungal protein concentrations than to extraction ratios. Structural epitopes on cat, ragweed and fungal allergens were stable after mixing with protease-containing mold extracts, indicating the presence of natural protease inhibitors or allergenic protein sequences distinct from those recognized by these enzymes. Allergenic extracts labeled as weight/volume or by PNU have no regulatory requirement for determination of activity. Alum-adsorbed allergenic extracts are labeled in PNU and are felt to be depot formulations. The purpose of this study was to develop methods to measure important allergen proteins and specific IgE binding capability of these alum-adsorbed allergenic extracts and to begin to assess the potency of these non-standardized extracts. Allergen proteins are adsorbed to alum particles making their measurement difficult. In this study allergens were released from Center-Al ® alum precipitated allergenic extracts using 0.3 M Citrate buffer, pH 5. The major allergen contents of several lots of each product were measured using monoclonal antibody ELISAs for Group 5 grasses, Cyn d 1 Bermuda, Bet v 1 birch, Ole e 1 olive, and Pla l 1 English plantain. These assays were developed and validated by ALK-Abello and optimized for the citrate releasing buffer. Direct binding IgE was performed by immobilizing serial dilutions of extract to microtiter plates and then adding specific atopic sera and enzyme labeled anti-IgE. The methods used were able to measure in vitro allergen activity in the alum-adsorbed extracts. Major allergen content was successfully measured in the extracts and the amount was related to the PNU content. As expected, the variability of the major allergens within a particular extract species was higher than in standardized extracts that are adjusted for potency. The extracts demonstrated specific IgE binding ability in the binding assay. The IgE binding capability at various dilutions was related to the major allergen content. In conclusion, methods were developed to release adsorbed allergen proteins from alum extracts. The extracts were then analyzed for major allergen pro-teins and the ability to bind IgE. Major allergen content is currently used to monitor the activity of aqueous and glycerinated extracts and this study demonstrates that implementing these testing procedures will improve the consistency and quality of alum-adsorbed extracts.
Introduction There are over 5000 species of smut and rust fungi. Ustilago maydis, or corn smut, is a basidiomycete fungus that infects ears of corn. It is responsible for a percentage of grain loss in the United States but eaten as a delicacy in Mexico. It grows into large tumor-like structures, called galls, dispersing soot-like spores responsible for the common name, "smut." It is readily airborne and believed to be a causal agent for allergic rhinoconjunctivitis. "Corn smuts" was added to the standard screening panel for patients presenting for evaluation of rhinitis in the region of middle Tennessee. Methods Using Greer Laboratories™ Corn Smut Extract 1:20 w/v, patients were tested by prick/puncture method with the Hollister-Stier Quintip™ device. If negative, intradermal testing was performed. Positive and negative controls were assessed. Based on current national recommendations, wheals 3 mm greater than negative control were considered positive for prick/puncture testing and wheals 8 mm greater than negative control were considered positive for intradermal testing. Results 105 patients were tested between November, 2003 and March, 2004 . 14/105 (13.3%) met criteria for prick/puncture positivity. 52/105 (49.5%) met criteria for intradermal positivity. Patients prick positive to corn smut had the following prick positive tests: dust mites 12/14 (85.7%); cat 11/14 (78.6%); local grass mix 10/14 (71.4%); local tree mix 10/14 (71.4%); local weed mix 10/14 (71.4%), mold mix 8/14 (57.1%); cockroach 7/14 (50%); and dog 4/14 (28.6%). Discussion Allergy testing for aeroallergens is available to a limited number of antigens, of which, only a few are standardized. As time passes, relevant antigens are discovered and their importance further elucidated. This assessment reveals a significant presence of corn smut IgE largely accounted for by intradermal positivity which may or may not reflect clinical sensitivity. These numbers are provided so that other clinicians may compare to prevalence in their geographical area. Further studies are needed to determine the association of corn smut IgE with clinical symptoms. H 1 antihistamines are the mainstay of therapy for allergic disorders, including skin diseases. The most common side-effect of marketed antihistamines is sedation, especially when the clinical symptoms require a higher dose than recommended, a condition commonly encountered in dermatological disorders. The present study describes the pharmacology of a new non-sedating H 1 antihistamine, R129160 (Hivenyl™). R129160 binds to the cloned human H 1 receptor with a similar affinity (Ki: 19 nM) as the reference antihistamines cetirizine (Ki: 50 nM) and loratadine (Ki: 37 nM). In vivo, R129160 protects rats and guinea pigs from lethal shock, induced by compound 48/80 and histamine, respectively (ED 50 : 0.06 and 0.055 mg/kg respectively). The compound is at least as effective as cetirizine and loratadine. In rats, R129160 inhibits the histamine-and allergen-induced cutaneous reactions (ED 50 : 1.4 and 2.3 mg/kg) with a similar potency as cetirizine (ED 50 : 0.7 and 2.7 mg/kg) and loratadine (ED 50 : 1.8 and 1.6 mg/kg). Even so, in guinea pigs the compound inhibits the histamine-and allergen-induced skin reactions (ED 50 : 0.14 and 1.2 mg/kg) to a similar extent as loratadine and cetirizine. However, in dogs R129160 is more potent in inhibiting the Ascaris allergen-induced wheal reaction (ED 50 : 0.024 mg/kg) than cetirizine (ED 50 : 0.14 mg/kg) or loratadine (ED 50 : 0.20 mg/kg). R129160 fails to occupy central H 1 receptors in the guinea pig cerebellum up to 40 mg/kg, in contrast to loratadine (ED 50 : 2.2 mg/kg). In vitro and in vivo cardiovascular safety experiments indicate that R129160 lacks the intrinsic capacity to prolong the QT-interval, even at high doses. As such, R129160 (Hivenyl™) is characterized as a potent, non-sedating and cardiosafe H 1 antihistamine. It has been selected for further clinical development, mainly in the field of dermatology. The compound will be a suitable tool to explore the activity of a selective H 1 antihistamine in various indications, without the contamination of the sedative activity often observed with other marketed antihistamines when increasing the dose. CIU represents one of the most clinically perplexing disorders which the allergist-immunologist is faced with. We have previously reported the clinical efficacy of FXT (Prozac), an SSRI widely used for the treatment of depression, in the management of CIU (Nsouli TM, et al. Ann Allergy Asthma Immunol 2002; 88:60) . In this presentation we report 2 additional cases of CIU which responded dramatically following the use of FXT. A 41 yr-old female and a 21 yr-old male presented with CIU of 18 and 24 months duration, respectively, requiring oral corticosteroid (CS) therapy for control of their CIU after failure of high dose anti-H1 (hydroxyzine) and anti-H2 (ranitidine) agents (Table) . Testing for food and latex allergy, viral hepatitis, autoimmune thyroid disease and parasitic infection were all negative. A skin biopsy performed in subject #1 was consistent with an urticarial vasculitis. Following one week of oral FXT (40 mg qd [Subject #1] 20 mg qd [Subject #2]) a striking and complete resolution of urticaria in each patient was observed within 7 to 10 days during which time it was possible to successfully taper the CS. Both patients have been maintained on FXT therapy with complete control of their CIU. The very favorable response to FXT therapy in these 2 patients in addition to our first case report suggests that this drug may have a new therapeutic application in the management of recalcitrant CIU. Background: Ipratropium bromide nasal spray (IB) is indicated for treatment of rhinorrhea caused by common cold (CC), seasonal and perennial allergic rhinitis (AR) in adults and children age 5 and up. Symptoms of rhinorrhea from CC or AR in children are similar to those in adults, yet there is little data on the use of IB in children under 5 years of age. Objective: Evaluate the safety and efficacy of IB nasal spray 0.06% in 2-5 year-old children with symptoms of rhinorrhea from CC or AR. Methods: A total of 230 children (43 CC and 187 AR) were treated in an open-label, multi-center study. The CC patients received IB nasal spray (84 mcg per nostril) tid for 4 days, the AR patients received IB nasal spray (42 mcg per nostril) tid for 14 days. Effectiveness was measured using a global assessment questionnaire and daily symptom scores reported by the parent. Results: From the global assessment questionnaire, 91% and 90% of the parents found IB either "very useful" or "somewhat useful" in the CC and AR groups respectively. Regarding effectiveness, 98% (CC) and 87% (AR) of the parents reported that IB had either a "good effect" or "excellent effect" in treating rhinorrhea. Moreover, 67% (CC) and 91% (AR) of parents found administration of a nasal spray either "extremely easy" or "very easy." Eighty-one percent (CC) and 89% (AR) of the parents reported they would use IB again for their child's allergy symptoms. The daily symptom score (0 = none to 5 = unbearable) for rhinorrhea decreased from 2.9 to 1.3 (-55%, p<0.0001) for CC and from 2.1 to 1.1 (-48%, p<0.0001) from baseline compared to the average on-treatment score, with decreases also seen for stuffy nose and sneezing. The nasal spray was well tolerated with adverse events (AE) reported in 28% of CC and 35% of AR patients. The AEs were mostly mild to moderate and no potentially systemic anticholinergic or serious AEs were reported. Conclusions: IB nasal spray 0.06% administered at a dose of either 42 or 84 mcg per nostril tid is an easy to use, safe, and effective therapy for control of rhinorrhea in children 2 to 5 years of age with common cold or allergic rhinitis. Chronic idiopathic urticaria (CIU) represents one of the most clinically perplexing disorders which the allergist-immunologist is faced with. The pathogenesis of the condition derives from the release of potent vasoactive substances including histamine, and products of arachidonic acid metabolism, e.g., prostaglandins and thromboxanes formed by the action of the enzymes cyclooxygenase (COX) of which COX-2 is responsible for pseudoallergic and other inflammatory responses. Although a number of therapeutic options exist owing to the plethora of mediators produced, treatment has focused largely on the use of H1 antihistamines and, unsurprisingly, at times without complete resolution of symptoms. In this presentation we report the successful use of a COX-2 inhibitor for the treatment of chronic urticaria. A 10 y/o white hispanic female presented with a 4 month history of chronic urticaria predominantly on the soles of the feet, with unknown precipitating factors, and fail-ure to respond to prior treatment with: cetirizine, steroids, benadryl, ebastine and epinastine. The patient received a blood transfusion 3 years ago and there was no prior history of allergies. Skin testing revealed 3+ reactions to dust mite, pollen, cockroach, shellfish, 2+ reactions to corn, milk and IgE = 262 IU (NV < 90 IU), ASO = 400 UI (NV < 200 UI). After 2 weeks of treatment with Rofecoxib (Vioxx) 25 mg, and benadryl, the rash resolved. Vioxx was continued for 2 more weeks until complete resolution of symptomatology. This case illustrates that the addition of a selective COX-2 inhibitor (i.e., Rofecoxib) with an H1 antihistamine may be a more effective regimen for patients with CIU who fail to respond adequately to conventional therapy. Introduction: Elderly asthmatic patients whose symptoms are controlled by inhaled corticosteroid (ICS) therapy may still have breathlessness on exertion. We randomized elderly asthmatic patients stabilized by medium-dose ICS therapy into two groups, treated one group with medium-dose ICS therapy plus montelukast, a leukotriene receptor antagonist, and the other with increased-dose ICS therapy, and compared the effects of the treatment regimens on exercise tolerance. Methods:The subjects were 24 patients with bronchial asthma (16 males and 8 females, 70.6±3.9 years) stabilized by ICS therapy (with fluticasone proprionate, FP; 400 mg/day) for three months or more with low peak expiratory flow (PEF) rates (<80%predicted, variability<15%). They were randomly divided into two groups (12 patients each) to be treated with ICS therapy plus montelukast (400 mg/day FP + 10 mg/day montelukast; M group) or with increased-dose ICS therapy (600 mg/day FP; F group). Pulmonary function tests, a six-minute walking test, respiratory gas analysis during incremental (15W/min) cycle ergometer exercise were conducted, and exhaled nitric oxide (NO) levels were measured before and after two weeks of the study treatment. Results: Pulmonary function tests showed significant increases in maximal mid-expiratory flow (MMF) and forced expiratory flow at 50% vital capacity (V50) in the M group (p<0.01) but no significant changes in the F group. Exhaled NO levels decreased significantly in both groups (40.7±13.9 to 27.5±9.1 ppb in the M group and 53.1±17.6 to 38.0±10.4 ppb in the F group; p<0.01). The six-minute walking distance extended from 531±64 to 575±58 m in the M group and from 553±60 to 570±58 m in the F group.The peak oxygen uptake (peakVO2) increased significantly in the M group (%peakVO2/W from 76.2±12.7 to 84.4±14.6%; p<0.01) but not in the F group (%peak VO2/W from 76.2±10.7 to 76.4±10.3%). The peak exercise load also increased significantly in the M group (76.6±22.0 to 96.1±23.1 W; p<0.01) but not in the F group (81.2± 16.2 to 82.2±14.3W). Conclusions: The results indicate that concomitant administration of montelukast is more effective than dose escalation of ICS on exercise tolerance in elderly asthmatic patients under medium-dose ICS therapy.
E. Meltzer 1* , Y. Luo 2 , L. Shen 2 , Z. Guo 2 , C. Schemm 2 , Y. Huang 2 , K. Chen 2 , P. King 2 , R. Nave 3 , D. Banerji 2 , S. Rohatagi 2 , 1. San Diego, CA; 2. Bridgewater, NJ; 3. Konstanz, Germany.
Introduction: Inhaled corticosteroids (ICS) are first-line treatment for persistent asthma. Ciclesonide (CIC) is a novel and effective ICS under development. Freely circulating, unbound ICS is available to cause systemic adverse effects, such as hypothalamic-pituitary-adrenal (HPA) axis suppression. Hence, it is important to determine the free fraction of ICS in plasma. In separate studies, the protein binding of the active metabolite of CIC, desisobutyryl-ciclesonide (des-CIC), was evaluated, and the effects of inhaled CIC on HPA axis function were determined. Methods: Human plasma protein bind-ing of des-CIC (0.5-500 ng/mL) was determined using equilibrium dialysis. Dialyzed samples were analyzed by liquid chromatography with tandem mass spectroscopy to determine free and bound des-CIC. In 3 separate clinical studies, the effects of CIC (HFA; 320-1280 μg daily) and placebo (PBO), via metered-dose inhaler (ex-actuator doses), over 9 days, 4 or 12 weeks, on basal HPA axis function (24-hour area-under-the-curve [AUC0-24h] serum or urinary cortisol corrected for creatinine) or stimulated (low-dose [1 μg] cosyntropin) serum cortisol were investigated in patients ( 18 years) with persistent asthma. Results: The mean % of human plasma protein binding for des-CIC was 99%. In 2 studies measuring serum cortisol AUC0-24h, there was no difference between PBO and CIC (320-1280 μg). Similar results were observed for 24-hr urinary cortisol corrected for creatinine. In the 3rd study measuring low-dose (1 μg) cosyntropin-stimulated peak serum cortisol, after 12 weeks of treatment, there was no significant difference in the mean change from baseline versus placebo for either CIC320 (P=0.383) or CIC640 (P=0.911). Conclusions: The favorable pharmacokinetic profile of CIC, in particular the high protein binding of des-CIC, may explain the lack of HPA-axis suppression. This appears to result in greater systemic safety. Purpose: Unscheduled office and ED visits for urgent asthma care are an ongoing point of concern. Determining preventive variables regarding these unscheduled visits could have a significant impact on asthma costs and quality of life. Objective(s): This research addresses the following question: when stratifying by race, gender, age, metropolitan/rural place of residence and comorbidity, do adults with asthma have fewer ED or unscheduled office visits for urgent asthma care if they: a) have an identified primary care provider, or b) have health insurance? Method(s): Univariate and stratified bivariate contingency table analyses were performed on weighted 2001 Behavioral Risk Factor Surveillance Survey (BRFSS) data. Result(s): Adults with asthma who had an identified primary care provider were more likely to have no unscheduled office visits (OR=1.87) or ED visits (OR=2.07) for urgent asthma care. This was also true for adults with asthma who had health insurance (OR=1.38 for no unscheduled office visits and OR=1.71 for no ED visits). These relationships held when stratifying by race, gender and age. The relationships also held for metropolitan residents. The analysis was inconclusive for rural residency and the existence of co-morbidities. Conclusion(s): Despite race, gender, age and metropolitan residency, having a primary care provider or having health insurance impact whether or not adults with asthma are more likely to have unscheduled office or ED visits for urgent asthma care. Further investigations are needed to examine how these factors impact adults with asthma who are rural residents or who have co-morbidities.
D. Bukstein 1* , G.A. Cherayil 2 , 1. Madison, WI; 2. Brookfield, WI.
Introduction: Costs for plans to process prior authorizations for non-formulary medications, has been estimated to be $20 to $25 per request. Costs for physicians to process these requests has not been extensively studied. Methods: Dr.Bukstein, board certified allergist, developed a data collection tool. The form was utilized by physicians and nurses to document time spent on processing prior authorizations. Data collected included, class of medicines requiring the PA, nursing time spent on calling the patient, pharmacist, health plan, nursing time spent completing forms, nursing time clarifying the information for the PA, as well as physician time spent completing PA activities. Results: Data was collected over 8 weeks in 2003 and 117 requests were processed.The class of medicines most often processed was antihistamines, comprising 66% of requests. Nursing calls were tracked and calls to and from patients were the most common call documented. They averaged 5.6 +/-6.5 calls per day per nurse. The nurses spent an average of 17 minutes per patient call. Calls to health plans averaged 1.8 +/-1.5 calls per nurse per day and time spent on these call was 8.4 +/-9.5 minutes per call. Physician calls documented included 154 calls averaging 1.9 +/-1.2 calls per physician per day. These calls averaged 5.8 +/-5.0 minutes per call.Often the results of the prior authorizations were not known on the day of the request. Originally 30.8% of requests were granted the same day. Retrospective review revealed 98.7% were approved the first time they were processed. Salary and benefits were calculated for nurses and physicians. The hourly rate was defined as $21.50 per hour for nurses and $150 per hour for physicians. The costs for the time spent on the 117 prior authorizations were calculated. During the 8 week study period, over 40 hours was spent by nurses on 231 calls and over 8 hours was spent by physicians on 154 calls during the same time period. The total nursing and physician cost in this specialty practice was $17.77 per prior authorization. Conclusion: There are substantial costs with processing of prior authorization requests for non-formulary drugs on the physician office side of managed care as well as on the insurance side of the process. Specialty physicians should have a different process for obtaining non-formulary medications since almost 100% of their requests are granted. Introduction: Diabetes mellitus can adversely impact the course and outcome of myocardial infarction (MI). One of the mechanisms underlying this phenomenon is alteration of the course of inflammation and the reparative process following myocardial necrosis. Abnormal wound healing, tissue reparation and immune responses in diabetic patients have been intensively studied, but the cellular and the molecular mechanisms are still unclear. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine which plays a critical role in coordination of the course of inflammation and reparation, acting as a potent depressor of inflammation and a stimulator of regeneration. This study investigates the dynamics of serum concentrations of the active form of TGF-beta1 during the period up to the 20th day after the onset of a MI in diabetic and non-diabetic patients. Results: In non-diabetics a significant increase was observed in TGF-beta1 on day 2 (5-fold greater than in controls; 1370.0±306.2 and 269.3±214.5 pg/ml respectively) with further increases reaching a peak on day 7 (1723.1±127.6 pg/ml). On day 20 TGF-beta1 decreased to levels less than on day 2, but was still greater than in healthy controls (1265.3±369.8 pg/ml). In diabetics, concentrations of TGF-beta1 on days 2 (939.7±155.2 pg/ml) and 7 (965.8±150.4 pg/ml) after MI were similar to diabetics without MI (724.6±233.5 pg/ml). Only on day 20 was TGF-beta1 increased to levels (1502.8±285.6 pg/ml) which were 2 fold greater than in diabetics without an MI. Thus, in diabetic patients serum concentrations of the active form of TGF-beta1 are much greater than in non-diabetics. MI in patients with diabetes mellitus is associated with a reduced and significantly delayed increase in TGF-beta1. Conclusion: TGF-beta deficiency may be a factor associated with low activity of tissue reparation after MI in diabetic patients.
Introduction Helicobacter pylori (HP) is the most common gastrointestinal infection worldwide, but only 10-15% of those infected develop chronic gastritis or peptic ulcer disease. The pathogenesis of ulceration, mechanisms of HP lifelong persistence in gastric mucosa and local immune disturbances induced by this infection are well known, but the mechanisms of resistance and elimination of this infection have not been extensively studied. Most study is based only on phenomenological findings, such as absence or low HP colonization in subjects spontaneously producing high levels of IL-2. The aim of this investigation was the analysis of the efficacy of the recombinant Interleukin (rIL-2) Roncoleukin (Biotech, Russia) in treatment of HP-associated gastric ulcer disease. Methods 108 patients were randomly divided into two groups. The first group of patients was treated with standard therapy including of two antibiotics (Claritromycin and Amoxicillin), proton pomp inhibitors and H2 receptor antagonists. Patients of the second group were treated with the same therapy, but instead of antibiotics they received 0.1 mg Roncoleukin into four to six areas submucously using a gastroscopic method and 0.4 mg Roncoleukin dissolved in 400 ml of 0.9% NaCl with 4 ml 10% human albumin infused intravenously. This procedure was performed three times at an interval of 72 hours. Results Immunological findings demonstrated that Roncoleukin results in an increase of CD25+, HLA-DR+ and CD16+CD56+ cell levels. There was an increase in the serum concentrations of IL1 (3 fold), IL6 (4 fold) and IFN (more than 20 fold) while the level of TNF and IL8 profoundly decreased. One month after the end of treatment, the group treated with rIL-2 had HP eradication achieved in 95.4% in comparison to 81.5% of the control patients. In the rIL-2 treated group, the ulcer epithelization period was 10.79±0.46 days while in the normal treatment control group it was 35.23±1.58 days (p<0.001). Conclusion Immunotherapy with rIL-2 is a more effective method of treatment of Helicobacter pylori-associated gastric ulcer disease when compared with traditional methods of treatment employing only antibiotics. INTRODUCTION The role of different cytokines and the growth factors is now appreciated in progression of essential hypertension. The participation of ET-1 and TGF 1 in pathogenesis of essential hypertension especially in the process of fibrosis, hypertrophia of vascular smooth muscular fibers, and cardiomyocytes, and the activation of renin-angiotensin system is now recognized, in addition to effects on myocyte cultures. The aim of the investigation was the study of serum ET-1 and TGF 1 levels in patients with essential hypertension. MATERIALS AND METHODS 60 patients with essential hypertension (40 males and 20 females) with average age 54.0 ± 5.3 years were studied. All patients suffered from left ventricle hypertrophy documented by echocardiography. The control group consisted of 20 healthy volunteers similar to the investigated patients in sex and age. In all patients the serum concentrations of ET-1 and TGF 1 were determined using ELISA (Biomedica, Biosource). RESULTS An increase in the serum concentrations both growth factors were noted in the studied group when compared with the control group. The average concentration of ET-1 in patients with essential hypertension was 0.64 (0.32-0.91) pmol/l. The level of ET-1 in the control group was 0.1 (0.05-0.17) pmol/l (p=0.04). The concentration TGF 1 in essential hypertension patients was 224.2 (125.4-314. 3) pg/ml and in control group was 68.2 (42.5-81.8) pg/ml (p=0.02). There was a positive correlation between the concentrations (Spearmen's rank coefficient of correlation was 0.42; p=0.01). CON-CLUSION The increase of the serum concentration of growth factors ET-1 and TGF 1 and their co-influence in patients with essential hypertension, suggests a role of these growth factors in the pathogenesis of arterial hypertension.
U. Kaza 1* , C. Lauter 2 , 1. Bloomfield Hills, MI; 2. Royal Oak, MI.
Introduction: Few studies have examined the referral patterns for allergy and immunology inpatient consultations in a community hospital. Consequently, an invaluable part of physician and housestaff education is missing. Our objective was to examine the number of inpatient allergy and immunology consultations, the reasons for consultations and the outcome of the patients in order to improve physician education. Methods:We performed a retrospective chart review of all inpatient allergy and immunology consultations in the years 1996-1997 and in 2002-2003 to determine the reasons for consultation, the recommendations made and if they were followed and the outcomes of the patient. Results:We reviewed a total of 408 inpatient allergy and immunology consultations. In the 1996-1997 time period 26% of inpatient consults were for asthma, 22% for drug allergy, 12% for rash. In the 2002-2003 time period 25% of inpatient consults were for rash, 21% for drug allergy, 16% for asthma. The top three reasons for consultations remained the same although the order changed. Consultations for immune deficiency, angioedema and rashes increased, whereas consultations for asthma and allergies decreased. There were a total of 202 consultations in 1996-1997 and 206 in 2002-2003 . The number of consultations remained the same despite an increase in overall number of hospital admissions from 44, 677 in 1996 to 58, 348 in 2003 . In greater than 95% of consultations, allergists' recommendations were followed. In both of the time periods studied, greater than 70% of patients improved, with less than 9% having no improvement, in the remainder of cases improvement was not applicable. Conclusion:In conclusion, we believe that identifying the reasons for inpatient allergy and immunology consultations and examining the most common recommendations, as well as the outcomes of patients will be a valuable guide in the education of our physicians. By incorporating this information into grand rounds and resident conferences, physicians will benefit from learning about when an allergist can be helpful and how to manage some of the more common allergic and immunologic problems in patients that are hospitalized. The high percentage of providers who follow the advice of allergists indicate that allergists have a great deal of educational value to offer other physicians. While Complementary and Alternative Medicine (CAM) has generally experienced increased popularity, its utilization by allergy/asthma patients remains uncertain. Our private allergy practice surveyed the use of CAM in allergy/asthma patients in 1998(1). Using a similar questionnaire, we assessed the current interest in CAM with our allergy/asthma patients and compared the data to our 1998 survey. We analyzed 103 completed questionnaires from 113 sequential surveys administered. The results were compared to 113 questionnaires reported in 1998. They indicated that in both study periods (1998 & 2004) , the majority of patients wanted to discuss CAM (65 and 69% respectively). An equal number (18%) in each study period discussed CAM with their primary care provider. Sixteen percent (16%) of our respondents sought a CAM practitioner for general medical needs in 1998 vs. 19% in 2004. However, there was an increase from 4% to 10% of our patients seeing a CAM practitioner for their allergies and/or asthma from 1998 to 2004. Sixty-two percent (62%) would like to consider pursuing CAM through our allergy spe-cialty practice or other provider. When asked regarding preferred treatment, 62% stated combination traditional with CAM, 8% preferred traditional only, 3% CAM only, and 27% did not know/doctor s choice. More patients are now seeking chiropractic care (36% to 52%) compared to our 1998 results. Acupuncture was the first choice CAM modality at 48% in 2004 surpassing vitamin/mineral therapy in 1998. Currently, the second and third choices were vitamin/mineral therapy and deep tissue massage. While these numbers were small, we were impressed that currently 10% (two and a half times more since 1998) of patients in our practice were seeking CAM allergy/asthma care from outside of our practice. These results demonstrated that more than half of our patients were interested in pursuing traditional with CAM options within our office. Given this trend, we have begun discussing the concept of Integrative Allergy, which to us means Integrating evidenced-based CAM modalities within our traditional allergy/asthma practice. (1) Introduction: Clinical immunization knowledge is complex and demands ongoing training. Nationally, basic immunization and vaccine safety education is limited within traditional medical, nursing, and provider education. Project Immune Readiness (PIR), a peer-reviewed, web-based, interactive course, was developed in response to this deficit and the need for standardized resources to provide initial and sustainment training for safe and effective immunization services. It is designed for medical personnel with diverse educational preparation. Currently, PIR offers 21 course modules addressing 42 hours of instruction on specific vaccines, their respective diseases, and general information on immunization healthcare and vaccination procedures. Methods: Users completed a pre-test (establishes baseline knowledge), an interactive module, followed by a post-test (to observe change from baseline) for each course in sequence. Anonymous user and score data were collected as part of a quality assurance and course validation process. Learning Gain Indices (LGI) were calculated based on average mean pre-test and post-test scores for each module LGI of all modules demonstrated substantial increases in user vaccination knowledge. Comparing pre and post-testing is an effective method to assess learning gains. The findings support PIR as a successful and valid distance-learning tool that establishes and documents core knowledge of medical personnel administering vaccinations. Further research is needed to assess the effectiveness of knowledge acquisition and retention, in addition to variance in vaccine delivery after training. This approach to learning may have value as a resource that supports smallpox and influenza pandemic emergency preparedness plans for just in time training. Introduction: Variances from practice guidelines for the prescription of auto-injectable epinephrine are well documented among practicing physicians, families, and patients. Effective patient education requires provider competency. The current study was designed to survey resident physician perceptions regarding auto-injectable epinephrine education, use, and patient education requirements. Methods: Residents from primary care disciplines at a tertiary care medical center were invited to complete a voluntary, anonymous questionnaire. A total of 58 surveys were distributed and returned: 22 Emergency Medicine, 11 Family Practice, 9 Internal Medicine, and 16 Pediatric residents completed the questionnaire. Due to the small sample size, responses from physicians in various disciplines were reviewed as a whole. Results: 40 respondents (69%) reported that they had previously prescribed auto-injectable epinephrine for allergic emergencies. The majority (63%) of these prescribers reported that their training was inadequate. 14 respondents (35%) reported no training, while 11 respondents (28%) reported that their training was less than that needed to ensure proficiency. 15 respondents (37%) reported that their training was adequate to ensure proficiency. None reported expertise. Only 7 of 40 prescribers (17.5%) reported that either they or their staff always demonstrated proper medication use to the patient. Interestingly, 2 of these 7 providers reported they had not been trained on proper use. The table below summarizes resident training and patient education practices. Additional physician knowledge deficits included the proper site of medication administration, the proper interval for replacing medication, and the proper place for medication storage. Conclusions: Of the residents surveyed, who have previously prescribed auto-injectable epinephrine, 63% identified training deficiencies. Only 17.5% of prescribers reported that the standard of care requirement to demonstrate proper medication use was always met. There is a clear need to improve auto-injectable epinephrine education in all residency training programs.
R. Bloebaum 1* , R.K. Calabrese 2 , M. 1. Houston, TX; 2. New York, NY. Introduction: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in patients with AIDS. Adverse reactions occur frequently to the most effective medication for both the prevention and treatment of PCP, trimethoprim-sulfamethoxazole (TMP-SMX). We looked at the immediate safety and efficacy of three protocols for desensitization in AIDS patients. Methods: By retrospective chart review, we identified 49 patients with AIDS who had experienced previous mild to moderate hypersensitivity reactions to TMP-SMX and required desensitization. Patients received one of three desensitization protocols based on illness severity or ward attending preference: a 6-hour intravenous (IV) desensitization, an 8-day oral desensitization, or a 10-day oral desensitization. Results: Of the 49 patients that received desensitization, 38 (77.5%) completed successfully. Of these, 33 subjects had no reaction during the desensitization process; however, seven of these subjects were on steroids for treatment of other diseases. The remaining five successful patients had mild reactions which were treated symptomatically with acetaminophen, antihistamines or both. Eleven patients failed to complete the desensitization: six stopped by the attending physician and four dropped out voluntarily. One patient expired during desensitization from extensive disease complications related to the admitting diagnosis. All protocols were equally successful when comparing the immediate success rates, 6/7 (86%) of the 6hour protocol, 4/5 (80%) of the 8-day protocol and 28/37 (75.7%) of the 10day protocol. The 6-hour IV desensitization protocol was most frequently used in the Intensive Care Unit on critically ill patients. Two of these patients, counted as successfully desensitized, died 5 and 28 days post protocol completion secondary to extensive comorbid conditions unrelated to the desensitization. Conclusion: Given the insignificant differences between the success of the 6hour IV desensitization and the oral desensitization protocols, we believe that either may be used effectively. Further, in patients with mild to moderate hypersensitivity reactions to TMP-SMX, an oral desensitization protocol may be used safely in the outpatient setting if given appropriate lab follow up.
A. Morales * , E. Gonzalez, A. Contreras, D. Lopez, G. Lopez, Mexico City, Mexico. INTRODUCTION In 1966 Davis describes Job Syndrome in two women, in 1971 Dr Buckley reports two children, being known as Hyper-IgE syndrome (Job's syndrome or Buckley's syndrome). Defined as a primary immunodeficiency, dominant autosomic, characterized by multi-systematic alterations (immunological, skeletal, dermal and dental). It's diagnostic criteria are levels of IgE 2000 UI/ml, chronic dermatitis, recurring respiratory infections, cold abscesses, pneumatoceles, infections caused by candida, and finally craniofacial alterations. On another front, extraordinary high levels of IgE have been reported in patients with allergic illnesses that increase the risk of anaphylaxis, but do not have the Job's syndrome criteria. OBJETIVE To determine if allergic patients with IgE levels higher than 2000 UI/ml have diagnostic of Job's syndrome. MATERIAL AND METHODS A retrospective revision was realized from May 2001 to April 2004 in files of 27 patients treated in allergy services at the Instituto Nacional de Pediatria with a total IgE greater than 2000 UI/ml, by means of a page with recollected dates. RESULTS Nine women and 18 men were included with an age range of 3 to 18 years, and an average age to 9 years; 22 (81.5%) were diagnosed with allergies; of which 55.6% rhinitis allergy, 51.9% asthma, and 40.7% topical dermatitis of which co-existed in patients. 51.9% presented hereditary antecedents of atopic. The cutaneous tests were positive in 11 (40.7%) with a greater reactivity of dermatophagoids. One syndrome of hyper IgE was detected. Others diagnosed were found as not allergic were Hunter's syndrome and toxocariasis. CONCLUSION There are patients with allergies that have total levels of IgE as elevated as 49, 560 UI/ml without correspond to Job's syndrome. By which a multi-allergic clinical entity is proposed with levels greater than 2000 UI/ml. Introduction Home monitoring of lung function in asthmatic patients is used extensively in both clinical and research settings, however, little attention is given to device quality control. Objective The purpose of this study was to determine the accuracy, precision and usefulness of the AirWatch System (ENACT Health Management Systems, Palo Alto, CA, USA). Methods The subjects included in this study were submitted to spirometry following American Thoracic Society guidelines (ATS 1995), using Collins GS 4G PFT System. Afterwards, peak expiratory flow rate (PEF) and forced expiratory volume in one second (FEV1) were determined using AirWatch. FEV1 and PEF measures from both devices were compared, by using two sample t-test and Pearson correlation coefficient. Results A total of 115 patients (75 females) were enrolled, and their mean age was 43.7 years (9 to 76 years). FEV1 measures ranged from 0.54 to 5.81 L (mean 2.43 L), and from 0.62 to 7.44 L (mean 2.51 L), in Collins and AirWatch, respectively. PEF ranged from 107 to 871 L/min (mean 384 L/min) in Collins and from 61 to 794 L/min in AirWatch (mean 353 L/min). Significant difference was noted for PEF measures (p< 0.05 and Pearson correlation R= 0.61) between the two devices; however, we did not observe this difference when FEV1 measures were concerned. Regarless the degree of obstruction (high or low flow rates), these results did not change. Conclusion AirWatch showed great utility for FEV1 measures when compared to Collins spirometer. Although AirWatch is able to assess lung function at home, on a daily basis, it is not reliable for PEF measures. Introduction: Epidemiologic data show that poorly controlled asthma is a serious public health problem. The degree of implementation of the NAEPP Guidelines in primary care practice remains to be defined. The objective of this survey was to determine if introduction of an assessment tool into primary care practices along with a specially designed program to implement the Guidelines would improve diagnosis and therapy. Methods: The Asthma Care Network (ACN), a program designed to assist healthcare providers in the assessment and management of their patients with asthma, employs a team of specially trained Respiratory Care Associates (RCAs), 100 RNs and RTs, who visit primary care offices to inform staff about various components of the NAEPP Guidelines and assist in their implementation. .A total of 4901 primary care providers in 2876 sites were recruited as part of the ACN program. Data from more than 60, 000 patient visits were collected and analyzed between March 2002 and January 2004. The program assessment tool surveyed asthma control and medication prescribing patterns. Outcome measures included degree of symptom control, limitation of activity, sleep disruption, use of rescue medication and utilization of urgent care services. These data were collected on an Office Visit Assessment Form (OVA) completed by both patient and physician. The RCAs provided information, education, device training in the use of inhalers and spacers, and a CE course for the staff discussing pathophysiology, assessment and management of asthma. Results: A total of 60, 248 OVA forms were completed. Among all patient including adults (older than 18 years of age) and children (<4-17 years of age), 74% (range 69% to 81%) reported symptoms consistent with lack of asthma control. Approximately 70% of the survey group had more than 2 markers of uncontrolled asthma. As a result of this assessment, controller medication use increased by over 30%, 52% of which was an ICS-containing medication. Conclusion: The information provided to the primary care health care providers resulted in a considerable increase in prescription of controller therapy, and in particular, increased use of ICS controller medication consistent with NAEPP guidelines. Background: Patients with allergic rhinitis (AR) demonstrate symptoms of allergy to fruits, vegetables and nuts in 48-72% of cases. Oral allergy syn-drome (OAS), typical for hypersensitivity to plant food, is based on cross-reaction of pollen-allergen specific immunoglobulin E (IgE) antibodies with homologous food proteins. The production of Th1 and Th2 cytokines in allergic rhinitis patients with or without sensitization to food (fruits and vegetables) allergens was assessed. Methods: Fifty five patients aged 18-38 years with allergic rhinitis were observed. Group I -20 patients with AR; Group II -35 patients with AR and OAS. Sensitivity to pollen allergens was tested by skin prick tests. The allergic reaction to food in patients with OAS was proved by a positive history of oral symptoms caused by eating fruits and vegetables and a positive skin prick test with respective food allergens. Blood eosinophil counts and total IgE levels were determined during the peak of allergic rhinitis symptoms. IL-5, IL-10 and -interferon levels were measured by ELISA. Results: 24.5% of patients were sensitized only to grass pollen, 23.3% only to tree pollen and 52.2% reacted to pollens of grasses, trees and weeds. In patients with OAS, skin tests were more often positive to birch (57.8%), alder (46.3%), and mugwort (26.7%). The most common food products implicated in OAS were hazelnut (69.3%), apple (29.2%), carrot (16.4%), and peanut (12.7%). The allergy to fruits and vegetables was confirmed by positive prick test in 78.4%. During the season blood eosinophil count and total IgE levels were elevated in all patients. There was an increase in the production of IL-5 to 187.3±5.4 pcg/ml in Group I and to 221.5±6.2 pcg/ml in Group II (nor-mal=74.3±3.3 pcg/ml). The levels of IL-10 increased to 186±12 pcg/ml in Group I and to 197±10 pcg/ml in Group II (normal=5.8±0.25 pcg/ml); the level of -IFN decreased to 287.6±7.4 pcg/ml in Group I and to 272.6±5.2 in Group II (normal=331±35 pcg/ml). After SIT with pollen allergens the clinical manifestations of allergic rhinitis and OAS decreased in 84.6% of patients. Conclusion: Allergic rhinitis patients' sensitivity to food allergens may cause OAS in these patients associated with increased functional activity of Th2 responses.
PATIENT KNOWLEDGE AND IMPROVEMENT WITH ALLER-GEN IMMUNOTHERAPY. C.C. Randolph * , Waterbury, CT.
Introduction: There is no consensus on objective parameters for improvement in immunotherapy. Similarly little is known regarding patient knowledge of immunotherapy. Utilizing two published questionnaires (1-2), we assessed clinical improvement based on symptom and medication scoring and knowledge of immunotherapy. Methods: The charts of 219 patients of an estimated 530(41%), 109(50%) with allergic rhinitis only and 116 (53%) with concomitant asthma, were retrospectively or prospectively reviewed who had been on immunotherapy to inhalants for 6 months to 6 years, mean 2.7 years, age range 7y-64y, mean 25y, 108 male(49%), 111 female(51%) with 213 caucasian (97%), 2 oriental (1%) and 4(2%) Afroamericans .They completed symptom and medication survey (1) every 6 months with range of improvement using a decline in Likert scale (+)20 to (-)104, mean 24. 186 (85%) indicated improvement in their symptoms and/or medication .111(50%) completed (2) a 7 question survey of knowledge of immunotherapy. There were 7 questions regarding the outcome of immunotherapy, the years to onset of immunity, the duration until onset of immunity, the danger of immunotherapy and the extract in the vial. The correct responses were recorded to 2/7 (2/111=1.8%), 11(9.9%) 3/7, 19(17%)4/7, 10(9%)5/7, 18(16%)6/7.39(35%) had a perfect response to all questions. 12(11%) had no correct responses. Conclusion: The majority of immunotherapy patients improved (85%) by symptom and medication scoring over the mean of 2.7 years but only 35% had complete knowledge of the rationale for immunotherapy. Further education and repeated surveying of patients on immunotherapy to assure comprehensive knowledge of immunotherapy and achieve better outcomes is recommended by this investigation. As is unique in this study symptom and medication scoring using the Rhinitis /Sinusitis questionnaire approved by the ACAAI and a comprehensive questionnaire assessing knowledge should be conducted periodically ie every 6 months to provide objective parameters for improvement. References: 1.Santilli J, Nathan R, Glassheim J .Patient receiving immunotherapy report it is effective as assesses by rhinitis outcomes questionnaire(RAQ) in private (42)) is a protein involved in the parasite invasion of host erythrocytes and is a leading vaccine candidate for the erythrocyte stage of malaria infection. An increasing number of vaccine clinical trials are being undertaken using various formulations of MSP-1(42). Comparison of humoral responses among these trials has been limited by the lack of a universal reference standard for specific antibody. The purpose of this study was to develop a human reference standard for MSP-1(42) antibody measured in absolute quantity units that could facilitate comparison of interstudy vaccine response. Method: We formulated the reference standard by pooling human plasma samples known to contain high titers of MSP-1(42) antibody. The specific antibody within the pooled plasma was captured by MSP-1(42) adsorbed to nickel resin in a process of immobilized metal affinity chromatography (IMAC). The intact MSP-1(42) antibody-antigen complexes were separated from the nickel resin and total IgG in the complexes measured by enzyme-linked immunosorbent assay (ELISA). Results: Our antibody quantitation method yielded a concentration of 48.3 mcg/ml of MSP-1(42) antibody in the reference standard. Conclusion: The reference standard characterized in this study may be useful as a quantitative working standard for MSP-1(42) antibody response in future vaccine clinical trials involving MSP-1(42). This standardization may facilitate the clinical development of MSP-1(42) as a candidate vaccine for malaria infection. Background. Specific immunotherapy (SIT) is currently one of the most effective and widely used treatment methods of allergic diseases including asthma. Efficacy of SIT depends on the correct choice of patients, severity of asthma and patient's condition when the SIT is begun. According to WHO recommendations, SIT is approved for use in patients with mild to moderate asthma. Methods. SIT with a saline extract of house dust allergen was administered to 30 patients with mild persistent allergic asthma. Injections were performed subcutaneously 2-3 per day. The course consisted of 6766 PNU of allergen and lasted 12-14 days. Patients were repeatedly surveyed at 3, 6 and 12 months after SIT was completed. Dyspnea attacks occurring during daytime and at night were assessed, as was the influence of physical exertion on dyspnea and lung function, and also the number of utilizations of short-acting beta-agonists per day. Pulmonary function measurements were performed as was assessment of concomitant allergic rhinitis. 50% of patients received treatment including cromones, and 30% utilized inhaled corticosteroids among whom 13.3% had a dose of 400 mcg per day and 16.7% 200 mcg per day. SIT efficacy was assessed by clinical symptoms, pulmonary function measurements and amount of concomitant therapy received. Results. The number of daytime dyspnea attacks reduced from 10.70 ± 3.40 per month to 1.20 ± 0.09 during the 3 months following SIT, and 76.7% of patients reduced concomitant asthma therapy. At 6 months, dyspnea attacks increased to 2.90 ± 0.75 per month, still significantly less then prior to SIT. Nocturnal symptoms followed the same pattern, occurring 7.20 ± 1.62 per month prior to SIT, 1.01 ± 0.01 per month 3 months after SIT and 1.99 ± 0.25 per month at the end of the sixth month after SIT. 26.7% of patients had no symptoms of bronchial obstruction during the 6 months after SIT and their pulmonary function approached normal values, although 36.7% of patients returned to asthma therapy. Nasal congestion decreased from 3.28 ± 1.20 points to 1.98 ± 0.08 (p<0.05), clinical improvement still present for 3 months after SIT, but recurring at 6 months after SIT. Conclusion. SIT may be an effective treatment method that improves both asthma and allergic rhinitis for more than 3 months following a brief course, allowing a decrease in the amount of symptomatic treatment. A safe therapeutic vaccine that can alter the allergic response to peanuts would serve a serious unmet medical need. Peanut allergy responses are largely associated with downstream events related to antigen specific IgE crosslinking of IgE receptors and subsequent degranulation of mast cells and basophils. Our clinical studies with ragweed have shown that linking immunostimulatory DNA (ISS) to allergens can decrease IgE recognition of the allergen and generate an immunogen that generates protective Th1 responses and reduces harmful Th2 responses. To test this approach to peanut immunotherapy, we focused on the clinically relevant allergen, Ara h 2, as a proof of concept. ISS oligonucleotides were linked to Ara h 2 at two different ratios: PIC (2 ISS per protein) and HPIC (4 ISS per protein). Immunogenicity of PIC and HPIC was evaluated in C3H/HeJ female mice immunized twice with 5 ug of PIC, HPIC, or Ara h 2. Sera were analyzed for anti-Ara h 2 IgG1 and IgG2a responses. Spleens were harvested and Ara h 2-specific IFNg and IL-5 responses were measured in vitro. Mice were immunized with Ara h 2 elicited predominantly IgG1 and IL-5 responses, indicative of a Th2-type response. Animals immunized with PIC showed significantly enhanced IgG2a responses and strong IFNg responses, indicative of Th1-type responses. HPIC immunized mice elicited little antibody response, presumably due to ISS blocking B cell epitopes, but did induce IFNg responses. To assess allergenicity of PIC and HPIC, histamine release was measured in blood from peanut allergic donors treated in vitro with PIC, HPIC, and Ara h 2. Histamine release was detected at very low concentrations of Ara h 2 (0. 01 ng/ml), 10-fold higher concentrations for PIC (0.1 ng/ml) and was undetectable at concentrations up to 1000fold higher for HPIC (10 ng/ml). An IgE binding competition assay also confirmed reduction in allergenicity following the same trend for the ISS-linked allergens. Linking ISS to Ara h 2 increases Th1 responses to the allergen, blocking IgE recognition of epitopes on Ara h 2. Thus, ISS-linked Ara h 2 appears to be a promising candidate for a safe immunotherapy product for treating peanut allergic subjects. Introduction: Immunotherapy has been studied for its adverse effects in some sensitive patients as with worsening of therapeutic response in some amounting to withdrawal of the later. Methods: In the allergy center therapeutic trials of Immunotherapy(house dust, mixmite) had been undertaken since 1998, in therapeutic dose of 0.02Pnu/ml, 0.2Pnu/ml, 2Pnu/ml, 20Pnu/ml, 200Pnu/ml2000Pnu/ml, 4000Pnu/ml(Housedust), 0.01Au/ml, 0.1Au/ml, 1Au/ml10Au/ml 100Au/ml 1000Au/ml 2000Au/ml(mixmite).Patients age 2-65 years, both sex after diagnostic scratch/prick tests with appropriate antigenic preparations reported for local/systemic adverse effects the details of which were as under, Results: Please see the attached table for details, In some cases worsening of the existing allergic status was noted, which on analysis revealed initially a slow rise in the allergen -specific IgE to be later on fol-lowed by rise of IgG1 & IgG4 & gradual fall of IgE.Only 1/100 patient could not complete immunotherapy for fear of adverse effects. Conclusions: With utmost care/follow-up, no incidence of mortality outcome was reported from 1998to late 2003 The incidence of adverse effects were significantly lowered on pre-medication with anti-histamines significantly more with elderly than younger age. Even with all these documented hazards the beneficial effects far exceeded the harmful effects. Background: The prevalence of allergic disease in most human population is steadily increasing. Seafood allergy is a serious food allergy, although hypersensitive reactions caused by seafood has long been know, biochemical and Immunological studies on seafood allergies had only begun lately. Shrimp and abalone are the most frequently reported causes early asthmatic response. Objective: To investigate cross-reactivity of shrimp, abalone and Derp1. Methods: Shrimp and abalone extracts were prepare from raw seafood. Sera from 17 patients from HongKong were studied who had asthma after consumption of seafood. IgE ELISA analyses comfirmed the combined sensitization to shrimp, abalone and Derp1. Specific-IgE ELISA assays were accomplished for shrimp and abalone extracts inhibited by Derp1 and Derp1 ELISA and Immunoblot assays inhibited by shrimp and abalone extracts. Results: ELISA inhibition showed that most IgE antibodies against shrimp and abalone were cross-reactive with Derp1 and the same time, Derp1 ELISA was inhibition by shrimp and abalone extract. The ELISA inhibition percent (%)of shrimp extract (GM:53.28%) and abalone extract(GM:36.75%) by Derp1 were significantly higher than Derp1 by shrimp extract(GM:26.64%) and abalone extract (GM:17.59%). (P<0.01). Furthermore, and there was a significant correlation of ELISA inhibition percent between shrimp extract, abalone extract and Derp1 inhibited by each other; SDS-PAGE and immunoblot of shrimp and abalone is the 38 and 49kD allergen respectively. Conclusion: This indicates that Derp1 was the sensitive agent. Shrimp, abalone and Derp1 demonstrate significant cross-reactivity. These findings confirm that the primary crossreactive allergen of shrimp and abalone is the 38 and 49kD allergen respectively.
B. Sun 1* , A. Wu 2 , N. Zhong 1 , 1. Guangzhou, China; 2. Hong Kong.
Background: The house dust mites (Dermatophagoides farinae (Derf) are a major source of aeroallergens implicated in the expression of atopic disorders, including asthma, allergic rhinitis, and atopic dermatitis . In particular, strong circumstantial evidence suggests that house dust mites antigens are important precipitating factors of Asthma. Many house duse mite allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines in bronchial epithelial cells. Objectives: we have investigated whether Der f allergen proteases induced cytokine production from the epithelial cell line BEAS-2B. Methods: Cells were exposed to four different concentrations with serial additions of Der f (0.02, 0.2, 2, 20ug/ml) were incubated for 24h to 96h. and compare with those without incubation of allergen. Cytokine in the supernatants were assayed by ELISA, Reverse transcription?PCR was also performed. Results: Cells treated with Der f allergen showed serial changes in the cohesiveness of the monolayer. There was a significant increase in the level of cytokine production compared with the untreaed sample. Statistically Significantly increased with addition of Der f caused the release of IL-6 and IL-8 in time and concentration-dependent manner (p<0.05, respectively). Levels of IL-6 and IL-8 were elevated 24 h and 48 h after allergen exposure, increasing with time, continued increased levels to be present of IL-6 and IL-8 in the supernatants at 72 h and 96 h. At the same time show the concentration dependence of induction of IL-6 and IL-8 expression as well as an increase in the expression of IL-6 and IL-8mRNA. Conclusion: HDM-induced airway inflammation may include Der f-mediated release of inflammatory mediators, and the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium. Suggesting that IL-6 and IL-8 production by bronchial epithelial cells may play a role in the pathogenesis of allergic asthma. The purpose of this study is to delineate the immune injury mechanisms that involved in the autoimmune inner ear disease by introducing plasmid DNA encoding of TH1 cytokines (INF-g) into the inner ear. b-tubulin is a microtubular protein which we found as an important autoantigenic in Meniere's Disease as well as other autoimmune hearing loss. Hearing loss was induced in mice and guinea pigs when they are immunized with the tubulin molecules. Autoimmune hearing loss could be the results of TH1 cytokine responses from autoimmune injury. To test the hypothesis, guinea pigs were immunized with 200mg of tubulin in CFA and boosted once more. Two weeks later, we introduced 100ug (5ul) of naked DNA encoding INF-g was injected into the left side inner ear through round window. Same volume of 0.1M PBS was injected into right side as control. ABR was recorded before and after the injection. 15 weeks after the injection, the animals were sacrificed and temporal bones were examined with H-E and INF-g immunocytochemical staining. The ears injected with the plasmid DNA-INF-g had an enhanced hearing loss (30 dB), and degeneration of the spiral ganglion was found in these ears. However, the injection of the naked DNA encoding INF-g did not change the expression of the INF-g in the inner ears. These results suggest that autoimmune hearing loss could be the result of TH1 responses to inner ear autoantigens. -Tubulin is an important molecule in the hair cells supporting cells within the sensory epithelium of organ of corti and found to be an auto autoantigen in autoimmune hearing loss including Mèniére's disease. The object of the study is to induce hearing loss in mice with varying doses of antigen and evaluate the pathogenesis of autoimmune hearing loss induced by -tubulin in mice. Mice were immunized with 100, 200 or 300 μg of -tubulin and hearing was evaluated by auditory brainstem responses (ABR) and distortion product of otoaccoustic emission (DPOAE). All mice had hearing loss by ABR and DPOAE tests and morphological study of temporal bone showed spiral ganglion degeneration and TUNEL staining positive cells were noted in these immunized mice. Thus this study showed that -tubulin is an autoantigen for hearing loss in animal model as in human autoimmune hearing loss patients including Mèniére's disease. Supported by NIH R0DC005010-01 Introduction: Oral Polio Vaccination (OPV) in the United States is currently being replaced with Inactivated Polio Vaccination (IPV) given parentrally. While past studies have looked into the relationship of vaccination and asthma prevalence, none have investigated this relationship with regards to vaccination route namely orally versus parentrally. This study investigates the relationship between vaccination rates for the live attenuated orally administered Polio vaccine and parentrally administered vaccines(DTP, MMR)and two potentially dependent factors; asthma prevalence rate and asthma-caused death rate. Methods: We looked at data from the National Center for Health Statistics yearly publications of Health, United States (1983 -1999 and the Morbidity and Mortality Weekly Report Surveillance Summaries . Two databases were compiled to cover the 0-4 age population in the United States since this is the primary period of childhood vaccination. One database contained information for asthma related deaths and vaccination rate (DTP, MMR, OPV) covering the years 1970-1999 and the other database compiled information for self reported asthma prevalence and vaccination rates(DTP, measles, rubella, OPV) covering the period 1983-1999. A T-test was used for statistical analysis. Results: Statistically significant correlation was found between vaccination rates and asthma prevalence rates. Data for DTP (p = 0.012), measles (p = 0.024), and rubella (p = 0.023) indicated a statistically significant positive correlation with asthma prevalence. The Oral Polio Vaccine was the only one of the vaccines that failed to display a significant relationship with asthma prevalence rates (p = 0.133). Statistical analysis proved that a correlation between vaccination rates of United States children ages 0-4 and asthma-caused deaths was insignificant (p > 0.05). Conclusions: The OPV, which is administered orally rather than parentrally, displayed no relationship with asthma prevalence. This could be due to the fact that live attenuated orally administrated polio vaccine may induce mucosal immunity, simulating a normal pathogen route of entry into the body. Childhood vaccination had no relationship with asthma-caused death rates.
A.S. Alfrayh * , Riyadh, Saudi Arabia.
introduction: heredity plays a major role in asthma and other allergic diseases, mechanisms underlying the inheritance of these disorders are poorly understood. this study therefore analyzed the risk conferred by family history of asthma and atopy for having childhood asthma. Methods : A total of 1601 children between 1-16 yrs selected randomly in three cities in Saudi Arabia ( Hail, Taif and Gizan )in 1995-1996 . The questionnaire which is similar to the one used in the international study of allergy and asthma in childhood ISAAC. were self administerd under medical supervision.Apart from the demogrphic details, the questionnaire included questions on symptoms and physician diagnosis of asthma, rhinitis, eczema and family history of these conditions. the family members were grouped as immediate family and relatives. Asthma and atopy were defined as ever having had physician diagnosis of such conditions information was also available about exposure to cigarette somke at least one member was a smoker in the household and having pets. Relative risk for developing asthma was estimated in terms of odds ratio by bivariate analyses using Chi square test and P value was considered significant when less than 0.05. Results : History of asthma in the immediate family and relatives conferred a 4 fold and 3 fold risk for development of childhood asthma odd ratio ( OR )=4.2, 95% confidence interval(CI)=3.3 to 5.5, p=0.00001 and OR=3.3, 95%CI=2.5 to 4.3, p=0.00001 respectively. Rhinitis in immediate family and the relatives was associated with 3 folds increased risk for childhood asthma OR = 3.0, 95% CI = 2.2 to 4.0, p=0.0001 respectively whereas history of eczema conferred over 3 folds risk OR=3.4, 95% CI = 2.4 to 4.7, p=0.00001 for childhood asthma when present only in the immediate family. history of eczema in relatives was not associated with any risk. of the environmental factors, exposure to cigarette smoke conferred 2 folds risk of developing childhood asthma OR = 2.6, 95% CI = 2.0 to 3.3, p= 0.0001, whereas exposure to pets was not a significant risk foctor. Conclusion : Presence of asthma and atopy either in the biological parents or relatives constitute a significant risk for childhood asthma.Paricularly in the presence of evironmental risk factors. The murine local lymph node assay (LLNA) has been developed as an alternative to guinea pig models for the assessment of the contact sensitization potential. However, there is a need to develop a non-radioisotopic endpoint for the LLNA, because of the radioisotopic method's requiring the use of special facilities. In this study, we investigated to evaluate the lymphocyte subpopulations in the lymph node cells following allergen and irritant treatment. Female Balb/c mice were treated by the topical application on the dorsum of both ears with sensitizers, 2, 4-dinitrochlorobenzene (DNCB), toluene diisocyanate (TDI), and a-hexylcinnamaldehyde (HCA), and an irritant, sodium lauryl sulfate (SLS), once daily for three consecutive days. The lymph node (LN) cells were harvested 72h after the final treatment. Phenotypic analysis of lymphocytes subsets was performed with a flow cytometry. The allergens DNCB, TDI, and HCA and an irritant, SLS increased cell number compared to the vehicle. There was an increase in the percentage of B220+ cells in mice treated with DNCB and TDI compared to the vehicle control, but not in those treated with SLS. Mice were treated with DNCB, HCA and TDI showed a preferential increase in the percentage of B220+CD40+ cells compared with vehicle and irritant-treated mice. There was an increase in B220+CD86+ cells of mice treated with DNCB, TDI and HCA, but no significant increases were observed in mice treated with SLS. Mice were treated with DNCB, and TDI showed an increase in the percentage of B220+CD23+ cells compared with vehicle and irritant-treated mice. These results suggest that analysis of B cell activation marker, CD40 on B cells may be useful in differentiating allergen and irritant responses in the draining lymph nodes of chemically treated mice.
M. Frieri * , Y.C. Huang, East Meadow, NY. Introduction: Nitric oxide (NO) is an important biomarker for inflammation in airway epithelial cells and in exhaled breath of asthmatic subjects. We have previously demonstrated NO production in antigen-stimulated human bronchial epithelial cells and an effect of omalizumab (monoclonal anti-IgE antibody) on NO production in those cells [Leyko BT et al. J Allergy Clin Immunol 2004; 113(suppl 193) :A668]. In this study, we investigated the potential role of IgE and its receptors on A549 cells by characterizing the effect of omalizumab on antigen, EGF, and IL-1 stimulation of A549 cells in a medium containing atopic serum. Methods: A549 human alveolar epithelial cells were stimulated with 100 IU/mL of IL-1 , 10 μg/mL of ragweed (RA), 1000 AU of dust mite (DM), and 40 ng/mL of EGF, and exposed to either 10 -7 M budesonide or 0.1 μg/mL omalizumab for 6 or 24 hours. NO production was measured in duplicate by a highly sensitive ELISA. Results: Omalizumab but not budesonide inhibited NO production at 6 hours in A549 cells stimulated with IL-1 (17-13μM, p<.05)and IL-1 +DM (18-14μM, p=.08), but not with RA alone. However, at 24 hours omalizumab and budesonide each significantly inhibited NO production stimulated by IL-1 (29-9μM; 29-17μM), IL-1 +DM (22-12μM; 20-14μM), and EGF (17-9μM; 17-13μM) (p<.05). Conclusion: NO production is a marker for inflammation. Omalizumab demonstrated a significant anti-inflammatory effect in distal alveolar cells by inhibiting NO production stimulated by antigen, IL-1 , and EGF in a medium containing atopic serum. As persistent inflammation in asthma may play a role in airway remodeling, treatment with omalizumab may have a beneficial effect on chronic airway inflammation in patients with asthma. Oral tolerance trigger regulatory mechanisms able to down-modulate antigen-specific T and B cell response. To address the lasting effect of several regimens of oral tolerance to ovalbumin, in naive or antigen primed mice, B-cell function has been focused. Furthermore, we analyze specific antibody response up to eight months of post-immunization, proliferative response, B7 (CD80/CD86) expression on B cells and T cell CTLA-4 involvement in oral tolerance. A/Sn mice were immunized by intraperitoneal route with 50μg of OVA/0, 1 mg-alum and boost 10 days after priming (dap). OVA feeding was done with 25mg at different days before or after antigen priming. In others protocols, mice were fed twice, before and after priming with a total of 50mg of OVA. All groups were boosted at 60 or 120 or 180 or 240 dap. The results showed that only mice fed at naive status and those fed twice before and after immunization demonstrated a long lasting of IgE Ab response inhibition up to 8 months of immunization. These mice showed a marked inhibition of antigen-specific proliferative response that was restored with anti-CD28 mAb in vitro stimulation. Evaluation by flow cytometry of spleen cells cultured for 48 hours upon OVA stimulation, showed an important decrease of B 7.2 expres-sion on B cells of naive fed mice, which remained inhibited until 8 months of immunization. After addition of anti-CTLA-4 mAb an enhancement of B7.2 expression was detected on B cells of naive fed mice. CTLA-4 molecules expression on CD4+ T cells of naive fed mice remained unchanged following OVA stimulation while a peak of expression was detected at 96h of OVA stimulation in control group. This finding reinforce the T cell anergic status of naive fed mice, due to the less cell division and consequently a low rate of CD4+/CD44high activated cells. The results showed that antigen feeding before immunization induce a long lasting anergy mediated by an impaired T-B cell cooperation and Ab production due to the decrease of costimulatory molecules expression on B cells and negative signaling effects by CTLA-4 expression. Introduction: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and fibronectin (FN) can promote angiogenesis, a putative component of airway remodeling. (S)-albuterol can exacerbate airway hyperresponsiveness, bronchospasm and release pro-inflammatory cytokines from small airway and smooth muscle cells. Our study evaluated the effects of (S)-albuterol ((S))-and (R)-albuterol ((R)) on secretion of these factors on normal human lung fibroblasts (NHLF) and myofibroblasts (myoNHLF) in the presence or absence of TGF 2, IL-1 , or allergens. Methods: NHLF were stimulated to differentiate to myoNHLF with 1000 pg/mL TGF . Dose-dependent effects of (S) and (R) [10 -8 to 10 -4 M] were evaluated for secretion of VEGF, bFGF and FN by NHLF and myoNHLF with and without 1000 AU/ml D. pteronyssinus (Dp), 1000 PNU/ml ragweed (RA), 100 U/ml IL-1 , or 1000 pg/mL TGF 2 into serum-free media (ITS) at 37 o C with 5% CO 2 collected at 24 hr and assayed by ELISA. Results: In NHLF the following was observed: VEGF secretion was 2-fold higher with 10 -7 M (R) relative to (S), p<0.05; bFGF secretion was increased 50%-100% by 10 -5 M (S) relative to (R), p<0.05. A lower concentration of (S) (10 -6 M) in the presence of either Dp or IL-1 caused a 2-fold increase in secretion of bFGF relative to (R), p=0.02. In the presence of myoNHLF the following was observed: 10 -7 and 10 -5 M (S) caused a 50%-100% increase in secretion of FN relative to (R). At 10 -7 M (S), this effect was further increased with the addition of IL-1 , p=0.022). Conclusion: In a dose-dependent manner, (S)-albuterol stimulated the release of bFGF and FN by NHLF and myoNHLF, respectively. This was enhanced by dust mite and/or IL-1 , potentially contributing to the matrix remodeling observed in chronic asthma. VEGF over-expression can have a protective effect against chronic hypoxia and can recruit immune cells to the alveoli. Increased VEGF by (R)-albuterol could contribute to such an effect in vivo in asthmatics. bFGF, in BAL and sputum of asthmatics, and FN which contributes to subepithelial fibrosis, can promote angiogenesis. Increased bFGF and FN by (S)-albuterol could be detrimental over time by enhancing matrix deposition and remodeling in a subset of asthmatics.
O. Ozdemir 1* , C. Moore 2 , Y. Ravindranath 1 , S. Savasan 1 , 1. Detroit, MI; 2. New Orleans, LA.
Background: Mast cells (MC) have been shown to demonstrate natural cytotoxicity against mouse fibrosarcoma cell line in culture when incubated for 24-48h. This effect has been postulated to be mediated through soluble and/or membranous TNF-. More recently; FasL, MC chymase and serine protease granzyme H with its chymase activity were proposed as mediators of mast cell-mediated cytotoxicity. Thus, both 'granule-exocytosis' through chymase, granzyme H and soluble TNF-and 'death receptors' through membrane-bound TNF-and FasL pathways appear to be operative in this process. Aims: Following our earlier observations on long-term liquid culture-grown human bone marrow mast cell cytotoxicity against human leukemia cells in 24-48h co-incubation experiments, we investigated mast cell-mediated cytotoxicity against natural killer/lymphokine-activated killer cell-sensitive cells in short term (12h) cultures without any stimulation for the first time. Methods: Human bone marrow mononuclear cells were cultured in methyl cellulose supported with IL-3, IL-6 and SCF. Mast cell colonies that developed in six weeks were transferred to liquid medium and maintained for 18 weeks before experiments. Cytotoxicity was investigated against K562, Raji and Daudi cells at 12, 24 and 48 hours of co-incubation by our established flow cytometric cell-mediated cytotoxicity assay. Results: After 12h co-incubation, 61% (11% early apoptotic and 50% late apoptotic or necrotic death) and 29% (21% early apoptotic and 8 % late apoptotic or necrotic death) target cell kill was demonstrated in Daudi and Raji cells, respectively. Daudi cell killing has stayed stable at 24h (67%; 27% early apoptotic and 40% late apoptotic). Despite a small numbers of experiments, Daudi cell kill was statistically significant at 12h (p:0.011) and 24h (p:0.011) compared to control. However, K562 cell elimination (18%) has not occurred until 48h. Mast cell-Daudi cell conjugates were seen on the Wright/Giemsa slides (Figure) . Conclusion: Our results demonstrate that human MC can cause cell-mediated cytotoxicity against certain cells in relatively short-term. This further suggests possible contribution of 'granule-exocytosis' pathway to MC natural cytotoxicity, indicating a faster MC response in immune surveillance.
O. Ozdemir 1* , M. Buyukavci 2 , Y. Ravindranath 1 , S. Savasan 1 , 1. Detroit, MI; 2. Erzurum, Turkey.
Background: The effect of melatonin (MLT) on cellular immunity has been controversial. Recently, MLT has been demonstrated to activate T and NK cells through its membrane or nuclear high affinity receptors. It was also shown that pharmacological concentrations of MLT (>nM) could be cytotoxic against different human cancers. Aims: Our aim was to investigate the effect of MLT alone or in combination with IL-2 on peripheral blood lymphocytes (PBL), lymphokine activated killer (LAK) cell generation and its cytotoxicity. Methods: PBL were cultured for 7 days in the presence of MLT at different concentrations (10 -3 , 10 -5 , 10 -7 M) with or without IL-2 (100 U/ml). Cell viability was determined by trypan blue exclusion test. Cell-mediated cytotoxicity of lymphocytes/LAK cells against K-562 and Daudi cells was studied using our established flow cytometric cell-mediated cytotoxicity assay. Results: Although 10 -3 M concentration of MLT did not affect cell proliferation much on day 3, it significantly inhibited proliferation by day 7 (p<0.05) consistent with known anti-proliferative effect of MLT. 10 -5 and 10 -7 M concentration of MLT also mildly inhibited proliferation on day 3; however there was a minimal rebound with 10 -7 M concentration by day 7. Consistent with the reported MLT-treated PBL's reduced response to mitogens, IL-2 and MLT (10 -3 M) combination suppressed proliferation on days 3 and 7; however, with 10 -5 M MLT concentration PBL counts increased gradually from day 3 to 7. Although MLT treatment alone did not enhance cell-mediated cytotoxicity, IL-2 and MLT combinational treatment at both concentrations (10 -3 and 10 -5 M) increased it significantly compared to baseline activity (Figure) . Conclusion: IL-2 and MLT combination at 10 -5 M concentration resulted in superior lymphocyte proliferation and LAK cell-mediated leukemia cell kill. MLT-induced increase in IL-2R-expression of PBL shown earlier might be the mechanism for our observations. MLT can be considered in immunotherapy as an adjunct to IL-2 treatment.
A.E. Fusaro * , J.R. Victor, C.R. Oliveira, C.A. Brito, E.A. Futata, M. Maciel, A.J. Duarte, M.N. Sato, São Paulo, Brazil. The maternal exposure to allergens during pregnancy or even in postnatal period may influence the allergy onset to newborns, through antigen or antibody transmission. We sought to verify the effect of maternal antigen exposure before conception, during gestation or in the breastfeeding period on the offspring type I hypersensitivity response. Female Balb/c mice were immunized or not with OVA extract/alum, boosted twice at 10th and 20 th and mated with normal Balb/c male on the 21th day after sensitization (das). Others groups of immunized mothers also received oral administration with OVA along pregnancy, or non-immunized mothers received OVA only during breastfeeding. Offspring from immunized or normal mice were immunized intraperitoneally with OVA at 25 do and boosted on the 10th das. The results showed a important decreased of TGF-levels in the amniotic fluid and milk from immunized mothers before mating in comparison to obtained from normal mothers. OVA exposure during pregnancy of immunized mothers decrease significantly the transference of TGF-by breastfeeding, while both TGF-isoforms were founded at high levels in the amniotic fluid. Similar levels of TGF-transference by placenta to the newborn was detected in both immunized mother groups. Pups from mothers exposed with Ag during pregnancy showed an increased spleen cell number, whereas did not produced IL-2, IL-4, IL-10 e IFN-secretion induced by antigen neither altered responsiveness to anti-CD3 or mitogen. Maternal OVA-immunization induced a marked inhibition of spe-cific IgE antibody response in the immunized pups, contrasting to the enhancement of IgE responsiveness detected in the immunized pups from mothers which were exposed to OVA only at postnatal period. These results showed that preconceptional immunization exert a protective effect on the offspring IgE development and an exacerbation of IgE responsiveness due to mother antigen exposure during breastfeeding. The findings suggest that rather than in utero antigen priming occurrence, postnatal period may contribute to offspring early life sensitization. Financial support: FAPESP and LIM56-FMUSP INTRODUCTION: The reasons for the increased incidence of allergic diseases in westernized countries are still unknown. Mercury is an important pollution factor to which humans are increasingly exposed. Prior studies on the effect of mercury on mitogen stimulated human lymphocytes indicated a TH2weighted immune response, but the results were inconsistent and difficult to reproduce. Phorbol myristate acetate (PMA) is a direct activator of protein kinase C, which has been shown to play a role in mercury induced IL-4 production in animals. Therefore we investigated the effect of mercury on PMAactivated human peripheral blood mononuclear cells (PBMC). METHODS: PBMC from 8 individuals were cultured for 4 days in culture medium containing PMA and ionomycin in the presence or absence of mercuric chloride (HgCl2). IL-4 and gamma-IFN concentrations were measured by ELISA of culture supernatants. Cell death and apoptosis were determined by 7-AAD and annexin staining and fluorescence activated cell sorting (FACS). Cell-proliferation was assessed by 3H-Thymidin-incorporation. RESULTS: After 4 days of culture, PMA/ionomycin-stimulated a small amount of IL-4 compared to untreated PBMC (1.7 +/-0.92 pg/ml versus 0.36 +/-1.0 pg/ml). However, mercury induced a more than 30 fold increase in IL-4 production when added to PMA-activated cells (57.4 +/-45.2 pg/ml, p<0.01). Gamma IFN production was strongly increased in PBMC that were treated with PMA/ionomycin (>3500 pg/ml versus 417 +/-1045 pg/ml in unstimulated cells) but dropped markedly in cells treated with mercury plus PMA/Ionomycin. In addition, mercury induced increased cell death, apoptosis and reduced cell proliferation. CONCLUSIONS: HgCl2 strongly stimulates IL-4 production in PMA/ionomycin treated PBMC while cell viability and gamma-IFN production drop significantly. These preliminary results suggest that human exposure to mercury may be playing a role in the observed increased incidence of allergic disease in the industrialized world Background: Mast cells (MC) have been shown to induce natural cellmediated cytotoxicity in long-term (24-48 hrs.) in vitro assay systems. The cytotoxicity is mediated by at least two pathways: secretory via exocytosis of MC granules containing serine proteases such as granzymes, chymase and soluble TNF-and nonsecretory (cell-to-cell contact) via membranous TNFand FasL. Chymase induces apoptosis in neonatal rat cardiomyocytes and human vascular smooth muscle cells. The objective of this study was to investigate MC mediated cytotoxicity against NK/LAK-sensitive cells in short term (12 hrs.) unstimulated cultures. Methods: Human bone marrow mononuclear cells were cultured in methylcellulose supported with IL-3, IL-6, and Stem Cell Factor. Mast cell colonies developed at 6 weeks and were transferred to liquid IMDM and maintained for 18 weeks. A flow cytometric cytotoxicity assay was used to determine cytotoxicity against Daudi, Raji, and K562 cell lines at 12 hrs., 24 hrs., and 48 hours. The controls consisted of cell lines without Mast cells at 12 hrs., 24 hrs., and 48 hours. Results: Rationale: To establish the antibody response rate in children with recurrent infections and fully immunized with the Pneumococcal 7-valent Conjugate vaccine. Methods: We have analyzed 39 patients referred to our clinic with recurrent infections despite complete immunization with the Pneumococcal 7-valent Conjugate vaccine for age, according to ACIP guidelines. We assessed the patients by checking their immunization status and the antibody titers to all 7 Streptococcus pneumoniae serotypes included in the vaccine (4, 6B, 9V, 14, 18C, 19F, 23F) assessed by standardized ELISA. The patients were assembled into 3 groups, a non-immunized group with laboratory data prior to the vaccine, and an immunized group consisting of responders and nonresponders according to their antibody titer (<1.3 or >1.3 IU/ml respectively). The data were analyzed using Epi Info and SPSS. Results: The mean age was 3.3 years for non-responders and 3.8 years for responders. There was no significant statistical difference between the groups regarding age, race and sex. Ten patients were identified who failed to respond to all 7 serotypes included in the Pneumococcal 7-valent Conjugate vaccine. There was no significant statistical difference between the non-immunized and the immunized nonresponders to all 7 serotypes. Conclusions: We have identified a special immunological phenotype of specific antibody deficiency (SAD) patients with normal total immunoglobulins and normal responses to protein antigens, but who failed to respond to conjugate pneumococcal polysaccharides.
A. Yates 1* , R. deShazo 1 , J. Butler 1 , G. Howell 1 , J. Farley 1 , H. Liu 1 , N. Nanayakkura 2 , G.B.Yi 1 , R. Rockhold 1 , 1. Jackson, MS; 2. Oxford, MS.
INTRODUCTION: Venom from S. invicta consists of 95% disubstituted piperidine alkaloids and is toxic to insects, birds and farm animals. Recent reports of morbidity and mortality in elderly patients after massive fire ant stings suggest the potential for systemic mammalian toxicity. We evaluated the toxic responses to systemic administration of two structurally verified, synthetic S. invicta venom alkaloids, solenopsin A (trans-2-methyl-6-n-undecylpiperidine) and its cis-isomer, isosolenopsin A, in rats. METHODS: Sprague Dawley rats were anesthetized with isoflurane, paralyzed with gallamine, artificially ventilated and instrumented to record arterial blood pressure (BP; mm Hg), heart rate (HR; bpm) and % change in left ventricular contractility (LVC; P/ t). In addition, a group of rats was chronically instrumented to record BP and HR while the animals were conscious and freely-moving. RESULTS: Solenopsin A at 3 to 30 mg/kg IV dose-dependently lowered BP, HR and LVC. At 30 mg/kg IV, hypotension (-40±12 mmHg), bradycardia (-27±8 bpm) and decreased LVC (-41±17 P/ t) were marked. Isosolenopsin A, 15 mg/kg IV, produced responses similar to solenopsin A 15 mg/kg IV. Solenopsin A 30 mg/kg IV elicited tonic-clonic convulsions and respiratory arrest in conscious, freely-moving rats. Hematuria was seen with solenopsin A, but not isosolenopsin A. Superfusion of a working, isolated, perfused rat heart with 10 uM of solenopsin A elicited a marked, reversible decrease in LVC, and cardiac arrest occurred with 100 uM of solenopsin A. CONCLUSION: The results demonstrate that these alkaloids possess significant depressant activity on the cardiac and respiratory systems of rats. The neurologic and cardiorespiratory effects can account for lethality to small mammals in the wild, and may contribute to adverse cardiovascular effects noted in humans after massive fire ant stings. Introduction: During asthma attacks, the pH of exhaled breath condensate (EBC) decreases two log orders (pH=5.0), returning to normal levels after corticosteroid therapy (pH=7.0). Ion channels, once thought to participate only in the transport of ions, are now suspected of mediating airway inflammation in asthma as well. To determine whether allergen directly alters airway mucosal pH and ion function, we measured nasal pH and nasal potential difference (PD) before and after nasal allergen challenge (NAC). Methods: Ten allergic rhinitic subjects (mean±SEM age 28.3 years±2.9, 7 females) underwent a crossover, single-blinded, placebo-controlled study, where they were challenged with allergen (dust mite, grass, cat) and control diluent in two different occasions in random order via nasal spray. Nasal pH was measured on the surface of nasal mucosa with a pH probe. Nasal mucosa PD was measured between nasal mucosa and forearm skin. Subjects also filled out a nasal symptom scale. Measurements were taken at baseline, 1 hour, 4 hours, and 24 hours after NAC. Results: The nasal symptom score increased significantly immediately after allergen compared to control challenge (13.0±2.4 vs. 3.7±1.1 respectively, p=0.003). There were no statistically significant differences in the nasal pH at 1h and 4h, but a significant decrease at 24h compared with baseline (-0.2±0.1 vs. +0.14±0.1, p=0.02). The change in pH from 0h to 24h correlated significantly and inversely with change in symptoms (r=-0.59, p=0.007) and number of sneezes (r=-0.65, p=0.002) after challenges. Nasal PD did not change significantly after challenges. Conclusion: Allergen decreases nasal mucosal pH in the very late phase after challenge in allergic rhinitic subjects. Decrease in airway mucosal pH during asthma exacerbations may be caused by aggravation of allergic inflammation. Nasal potential difference does not change after allergen challenge. Funding: NIAID, ACAAI Foundation Introduction: UV induces differentiation of T-and B-lymphocytes, suppresses natural killer cells, renders a tolerogenic effect and induces apoptosis resulting in local and system immunosuppression. Methods: Lymphocytes were studied using indirect immunofluorescence methods employing monoclonal antibodies to CD-markers CD4, CD8, CD16, CD25, CD95, HLA-I, and HLA-II, from the blood of 14 volunteers (aged 18-24 years) before UV exposure (control), after an exposure of blood in vitro to a dose 1.12 kJ, and after 24 hours of exposure of the medial surface of the elbow joint in vivo (S=200 cm2), to a dose of 1.12 kJ. Results: The direct exposure of blood results in a significant reduction in the number of lymphocytes, probably due to direct phototoxic effects. Significant modifications both of the aggregate number of lymphocytes and amount of T-helpers after UV exposure of the skin were not seen. After UV the number of cells which express the marker CD8 is sig-nificantly increased. Exposure to UV in vitro induces reduced number of cells bearing CD16. However on in vivo exposure, a significant increase in number of cells which express CD16 was observed. UV exposure of blood reduced significantly the HLA-I (9.67±0.72 reduced to 0.32±0.54) and HLA-II (DR) (21.56±1.19 reduced to 18.45±1.15) expression. UV exposure of skin increased significantly HLA-I to 11.56±0.81, while HLA-II (DR) was insignificantly decreased to 20.65±2.01. CD95 expression increased from 22.43±1.12 to 25.95±1.08 due to blood UV exposure, while there were insignificant reductions in CD4 (39.33±2.14 reduced to 36.62±2.34) and CD8 (36.50±2.03 reduced to 25.75±2.74) expression. Conclusion: UV starts a cascade-like response, including apoptosis, leading to changes in NK cell, helper and suppression lymphocyte numbers consistent with an immunomodulating effect of UV radiation. Background: Previous investigations have shown the involvement of histamine and histamine receptors (H 1 , H 2 , H 3 , H 4 ) in IgE synthesis in atopic and lymphoproliferative diseases. IgE responses may depend on the concentrations of histamine and histamine receptor antagonists and agonists. The goal of this investigation was to evaluate the role of the concentration of histamine and H 3 /H 4 antagonists along with the importance of pre-existing levels of IgE in determining IgE responses. Methods: IgE synthesis was studied in MNC cultures of patients (7-14 years old) having mild atopic asthma and rhinitis. All patients had high levels of total IgE and specific IgE to ragweed pollen, house dust mite, epidermal or mold allergens. Patients were divided into two groups according to the serum IgE and levels of spontaneous IgE synthesis: group A -with low levels (4.8±1.2 IU/ml) and group B -with high levels (9.7±1.4 IU/ml). The serum level of total IgE in group A was 426.1±24.3 IU/ml and in group B was 570.2±26.5 IU/ml. FUB 181 hydrogenmaleate was used as an H 3 /H 4 specific antagonist. Results: Histamine in high concentrations (10 -5 M) suppressed and in low concentrations (10 -8 M) stimulated spontaneous IgE synthesis. The H 3 /H 4 antagonist FUB 181 activity depends on the pre-existing levels of IgE. In high concentrations (10 -5 M), the antagonist increased IgE synthesis only in group A, but not in group B having high spontaneous levels of IgE synthesis. The synthesis in group A increased 1.36 fold (p<0.001), but H 3 /H 4 blockade cancelled the IgE suppressive effect of high concentrations of histamine (10 -5 M). The addition of histamine into the MNC culture stimulated IgE synthesis 1.56 fold. FUB 181 had no effect on IgE-stimulatory effects of low concentrations of histamine (10 -8 M). In allergen (ragweed)-stimulated MNC culture, FUB 181 had a co-stimulatory effect on IgE synthesis induced by histamine. Conclusions: The IgE stimulating response depends on the concentrations of histamine and the H 3 /H 4 antagonist as well as pre-existing levels of serum IgE and IgE spontaneous synthesis. Introduction: Preliminary data has shown that oral contraceptives can precipitate or worsen attacks of hereditary angioedema (HAE). It is thought that estrogens affect the synthesis and degradation of bradykinin with resulting edema. Objective: Our objective is to determine if there is a difference among the various oral hormonal preparations, namely, combined monophasic, combined multiphasic, progesterone only, and hormone replacement therapy, in regards to their effect on frequency of HAE exacerbations. Methods: Patients in this study consisted of women over the age of 18 diagnosed with HAE who receive their care at our institution and women meeting the same criteria who are active in the HAE Foundation and have access to this association's web page. All patients answered a sixteen item questionnaire about past or present birth control pill or hormone replacement therapy usage and its impact on the frequency of exacerbations. Results: Of the patients who completed the questionnaire, 94% had taken or were currently taking oral contraceptive pills or hormone replacement therapy. Of the women whom had taken monophasic birth control pills, 100% worsened with increased number and severity of exacerbations. However, only 75% of the women that had used combined multiphasic birth control pills worsened. All of the women who had tried progesterone only birth control pills worsened. Of those on isolated estrogen for hormone replacement, 67% had an increased number of exacerbations. When androgens were used concurrently with oral contraceptive pills or hormone replacement therapy, exacerbations decreased to 60%. Conclusion: We are not able to demonstrate a statistical benefit of one oral contraceptive pill preparation over another because of our sample size. However, our preliminary data supports that the oral contraceptive pill which produces less exacerbations and less symptoms is a combined multiphasic pill with concurrent androgen treatment. INTRODUCTION Atopic dermatitis (AD) is associated with multiple immunological abnormalities including imbalances in the subsets of blood circulating lymphocytes forming cellular infiltrates in inflamed skin. Many studies of the functional and phenotypic properties of lymphocytes in AD have been limited to either peripheral blood or skin-infiltrating lymphocytes. The purpose of our study was to evaluate and compare the content and phenotypic properties of CD4+ lymphocytes from blood and inflamed skin of AD patients. MATERIALS AND METHODS 15 adult (age 18-43 years) patients with chronic AD were selected by the criteria of Hanifin. All patients gave written informed consent. The CD4+ lymphocytes of peripheral blood were phenotyped by flow cytometry. Skin biopsies were obtained from eczematous areas, then cryosected and double immuno-histochemistry was performed. For phenotyping of lymphocytes in blood and skin a panel of monoclonal antibodies was used including CD3, CD4, CD8, CD25, HLA-DR and CLA. RESULTS Immunophenotype analyses of the peripheral blood lymphocytes showed a predominance of CD3+CD4+ cells (86%±21.3). Most cells were CD4+HLA-DR+ (14%±12.6) and CD4+CD25+ phenotype (26%±13.5). Double immunohistochemistry of the skin biopsies revealed in the epidermis rare but constant presence of CD4+CD25+cells (1.0±6.4 cells/mm 2 ) and CD4+HLA-DR+ cells (1.2±1.3 cells/mm 2 ). In the dermal inflammatory infiltrates the predominant cells were CD4+CD25+ (21.0±9.7 cells/mm 2 ) and CD4+HLA-DR+ (45.0±6.7 cells/mm 2 ). The dominant inflammatory infiltrate consisted of CD4+CLA+ phenotype (62.9±23.5 cells/mm 2 ) cells. CONCLUSION In AD skin inflammation is associated with the appearance in the circulation of CD4+ lymphocytes in activated form (CD4+HLA-DR+) and lymphocytes with regulatory properties (CD4+CD25+). These lymphocytes are recruited from the circulation, having the skin homing properties (CD4+CLA+), and form the main constituent of the dermal inflammatory infiltrate. Contact dermatitis (CD) comprises a spectrum of inflammatory skin reactions usually caused by exposure to non-immunogenic low molecular weight substances (haptens). Failure to diagnose the condition may result in a chronic and disabling condition with impaired quality of life. A 28 yr-old white male presented with a severe, symmetrically distributed facial maculopapular rash with secondary excoriated lesions. Prior to the appearance of the rash, the patient had been applying Lubriderm as a skin moisturizer for dry skin. A standardized thin layer rapid use epicutaneous (TRUE) test containing 23 chemical agents suspended in a vehicle and attached to an adhesive backing was applied to the patient's back. At 48 hrs, a positive reaction was observed at the skin site of the paraben mix application. The Lubriderm preparation used by the patient contained paraben, in contrast to a newer preparation, Advanced Therapy Lubriderm, which is paraben-free. Complete resolution of the facial lesions occurred following discontinuation of the Lubriderm and the use of oral and topical corticosteroid therapy. This case report illustrates how a commonly used moisturizer can contain a sensitizing agent that could be detected by standardized patch testing which should be a part of the diagnostic armamentarium of every allergist-immunologist. We report how a commonly used and effective moisturizer (Lubriderm) can cause severe allergic CD and that the use of a standardized thin layer rapid use epicutaneous (TRUE) patch test panel can be an effective diagnostic tool for the detection of the offending agent. Rationale: This study aimed to establish the possible differences of cutaneous sensitization to common aeroallergens in children under 1 years old. Methods:The study was conducted between 2003-2004 and included 120 infants from Silesia/southern part of Poland/.These infants were refered to our allergy unit due to respiratory symptoms like rhinitis, otitis, pharyngitis, cough, bronchitis recurring;eye's symptoms/ conjunctivitis/ and oral symptoms. The skin prick test/ SPT/ to major aerollergens in our environment(HDII, Birch, Alternaria, Cladosporium and trees)were done to 6-months-old and 1-yearold children. A SPT of 3 mm or larger was considered as positive. Patients were classified into three groups: I:positive family atopy II:smoking ciggarettemother/ or father III:cat or dog at home IV: coexisting food allergy Results:58, 8 % of examined children were boys. The prevalence of sensitisation found were as follows:latex 38, 1%, birch 32, 8%, DPII-28, 6%, grass pollen 28, 1%, Alternaria-8, 4%. Positive SPTs to latex were first seen in the 6-months-old group and this prevelance doubled until they finished 1 year. Conclusion: In our study, cutaneuos sensitisation start to appear in 6-months-old chlidren. Background: Propylene glycol (PG) may induce allergic contact dermatitis (ACD) and skin irritant reactions. Topical formulations frequently contain PG. It is present in low concentration (5%) in pimecrolimus cream 1%, a non-steroid inflammatory cytokine inhibitor. Objectives: This study was designed to assess the incidence of cutaneous responses to pimecrolimus cream in patients allergic to PG and to determine their nature (ACD or irritation) and severity. Methods: In this double-blind, randomized, vehicle-controlled, withinpatient study, 20 subjects allergic to PG underwent 48-hour patch-testing (PG 30 and 100%, pimecrolimus cream and vehicle) followed by a 7-day repeated open application test (ROAT). Application sites were assessed by the investigator using a scale ranging from 0 (no reaction) to 7 (spreading bullous reaction) at 0, 48, and 120 hours after patch removal and at the completion of the ROAT. Results: PG allergy was confirmed by patch-testing in 16 patients. Two patients showed a positive patch-test reaction with pimecrolimus cream and vehicle, indicating an ACD. In contrast, no patient demonstrated signs of ACD when pimecrolimus cream was applied under normal conditions, i.e. without occlusion (ROAT). The statistical analysis showed that there were significantly less reactions at pimecrolimus patch-test sites than at the PG patch-test sites (p<0.01 for both PG concentrations, one-sided exact binomial test) and that the median severity was lower with pimecrolimus cream vs. PG (p=0.02 and p<0.01 for PG 30% and 100% respectively, Wilcoxon signed-rank test). Conclusions: This pilot study suggests that pimecrolimus cream 1%, when applied under normal conditions, can be used safely in patients with PG allergy. Introduction: Chronic idiopathic urticaria is not always responsive to antihistamine therapy. Multiple alternative agents have been tried. We report two cases where tacrolimus has been successful in treating this condition. Methods: This is a case report of two patients who have chronic idiopathic urticaria and have been treated with tacrolimus. Patient #1 is a 27 y/o WM who pre-sented with urticaria that had been going on several months. The duration of his urticarial lesions was <24 hours His urticaria was treated with several medications including: hydroxyzine, cyproheptadine, ceterizine, montelukast, colchicine, and dapsone. He was intolerant to hydroxychloroquine. Montelukast seemed to provide some modest benefit but he continued to have daily urticaria with >50 lesions/day after two months of therapy. Tacrolimus was added to montelukast at 1mg BID. Patient #2 is a 64 y/o WF with a history of biopsyproven urticaria. She had suffered from episodic urticaria since the age of six that was responsive to systemic steroids. After thirty years of having no urticaria, she developed recurrent urticaria at age 62. At this time, she was treated with hydroxyzine, doxepin, montelukast, loratadine, ceterizine, fexofenadine, colchicine, dapsone, and even prednisone with very little improvement in symptoms. She was then started on tacrolimus 1mg BID as monotherapy while she was having daily urticaria. Results: After one month of treatment with tacrolimus 1mg BID, patient #1 had a decrease in the number of urticaria. His dose of tacrolimus was increased to 3mg/day, and after four weeks, his urticaria resolved. He remained on tacrolimus for a total of six months which was tapered and discontinued. He continues to be in remission from urticaria. Patient #2 had complete resolution of her hives after just two doses of tacrolimus. After two months, she remains free of urticaria on tacrolimus 1mg BID. Conclusion: For patients with severe chronic urticaria unresponsive to multiple therapies, tacrolimus, like cyclosporine, may be efficacious. Tacrolimus may also be truly immunomodulatory and capable of inducing remission of urticaria.
S.V. Gerasimov * , Lviv, Ukraine.
INTRODUCTION. Recent studies suggest that probiotics can be useful in prevention and treatment of atopic dermatitis (AD) in children. As clinical effect of probiotics varies greatly depending on the specific strain, we are currently conduct a search for the most promising probiotic to be used as complementary therapy in infants and young children with AD. METHODS. We studied 23 infants aged 25-51 weeks (36±8) with AD established using Hanifin and Rafka criteria. Patients were evenly allocated among probiotic (n=11) and nonprobiotic (n=12) treatment groups using Quota Allocation System. Severity of AD was defined using SCORAD index and infant`s quality of life was assessed using IDQOL index. Patients were examined before and 4 weeks after the treatment with/without probiotic powder formulation (B. infantis, L. acidophilus DDS-1, 10 billion CFU/day, DDS-Junior, UAS Laboratories). We compared pre/posttreatment values of indices above and amount of mometasone furoate (0, 1%) used employing a paired or unpaired t-test. RESULTS. At baseline, infants in either groups were comparable on age, gender, duration of the disease, SCORAD and IDQOL indices, and medication taken for the previous 4 weeks. Before entering the study all patients were maintained on allergen elimination diet due to milk and egg white allergy. After the treatment with/without probiotics the mean SCORAD index decreased from 42, 2 to 32, 7 (p=0, 14) and from 51, 5 to 31, 3 (p=0, 06), respectively. However, the mean amount of mometasone furoate used in non-probiotic treatment group was significantly greater (7, 8 g vs 2, 1 g, p=0, 03), despite the same recommendation on the use of the drug was given. Additionally, parents of children taking probiotics reported an improvement in infant`s quality of life as seen on the decrease of IDQOL index from 21, 1 to 12, 0 (p=0, 04). In non-probiotic group decrease in IDQOL was not significant (24, 2 to 19, 5; p=0, 14) . There were no adverse events in any of the treatment groups. CONCLUSIONS. Our preliminary results suggest that some probiotics may have a corticosteroid-sparing effect and improve quality of life of infants with AD. There is a clear trend towards reduction of SCORAD index, which did not change significantly, probably due to a limited number of patients involved. Introduction : The aim of this study was to analyze the risk factors of severe atopic dermatitis(AD) in the first 6 months of life. Methods : The children aged less than 6 months with AD were divided into two groups according to Six Area Six Sign in Atopic Dermatitis(SASSAD) Score. Children with score less than 14 was classified as Mild AD(n=90) and those with score above 15 as severe AD(n=44). These patients were fed with breast milk or cow's milk formula, and no allergenic food was given except rice and some vegetables. We analyzed the gender, feeding patterns, family history of allergy, number of siblings, total IgE and specific IgE to common food allergens (egg white, cow's milk, wheat, soy) by CAP-FEIA assay. Total eosinophil count was 1863±2032 /ul in severe AD and 686±539 /ul in mild AD(p<0.001). Results : 1) Total IgE was 180.6±245.1 U/mL in severe AD and 32.2±50.7 U/mL in mild AD(p=0.002). Specific IgE to Egg white, wheat and soy (19.03±29.72 U/mL, 4.68±10.62 U/mL, 7.07±22.01 U/mL in severe AD; 1.78±3.54 U/mL, 0.15±0.99 U/mL, 0.09±0.30 U/mL in mild AD; p<0.05) were associated with severe AD, but cow milk(4.34±16.6 U/mL in severe AD, 0.80±4.17 U/mL in mild AD) showed no difference. 2) Gender, feeding patterns, family history of allergy and the number of siblings were not significantly associated with severe AD. Conclusion : Severe AD is associated with sensitization to food allergens in the first 6 months of life, although they are not fed with those foods. BACKGROUND: Atopic dermatitis (AD), an inflammatory skin disease diagnosed primarily in children, has been shown to have a negative impact on quality of life (QoL). Pimecrolimus cream 1% is a non-steroid, topical calcineurin inhibitor with demonstrated efficacy in the acute treatment and longterm management of pediatric and adult AD. In a 24-week, double-blind, vehicle-controlled study, a secondary aim was to evaluate the impact on parent's quality of life of a pimecrolimus-based or corticosteroid (CS)-based treatment regimen of children with AD. METHODS: 275 children aged 3 months to 11 years (mean 5 years) with mild to severe AD were randomized 2:1 to receive treatment with pimecrolimus or vehicle cream. Emollients for dry skin and pimecrolimus or vehicle bid were applied at the first signs of AD. For severe flares, a mid-potency topical CS (fluticasone or mometasone) indicated for once-daily use in AD replaced the evening study drug application for a maximum of 3 weeks or until all AD resolved. Parents completed the Parent's Index of Quality of Life-Atopic Dermatitis (PIQoL-AD), a 28-item validated questionnaire, which measures parent's needs-based QoL, at baseline, week 12, and study completion. Change in PIQoL-AD scores at baseline and week 24 were compared between treatments. A negative change indicated improvement. RESULTS: Parents of patients in both groups reported improvement in PIQoL-AD scores at week 24, with greater improvement for the pimecrolimus group. The mean change in PIQoL-AD score from baseline to week 24 was -3.3 in the pimecrolimus group vs. -2.6 in the CS-based treatment group (37.6% vs. 26.8% improvement, respectively). ANCOVA analysis, using treatment and center as main effects and baseline score as a covariate, compared the change in PIQoL-AD score in two treatment groups. Pimecrolimus treatment demonstrated a more favorable change (-1.2) which approached statistical significance [p=0.056; 95%CI= (-2.5, 0.0)]. CONCLUSION: A treatment regimen utilizing pimecrolimus cream 1% had a beneficial effect on parent's quality of life compared to a corticosteroid-based regimen. This benefit was consistent with other measures of efficacy studied. Introduction: Atopic dermatitis is a chronic, inflammatory and recurrent skin disorder . Its prevalence has increased in recent decades but little is known about it in Mexico city. The aim of this study was to evaluate the prevalence and severity of atopic eczema in a pediatric population. Methods: A cross-sectional questionnaire survey (ISAAC phase I questionnaire) was conducted on random samples of schoolchildren aged 6 to 7 years and 13 to 14 years from educational centers of four northern counties from Mexico city. Those children with a positive response to being questioned about the presence of an itchy relapsing skin rash in the last 12 months were considered to have atopic dermatitis. Children whose symptoms resulted in sleep disturbance for 1 or more nights per week were considered to have severe atopic eczema. Statistical analyses were done with SPSS 6.0 for Windows, chi square . The size of the sample was determined folowing the ISAAC specifications and calculated with the STATcal program. Results: Complete data was available for 3211 children aged 6 to 7 years in 45 schools and 3899 children aged 13 to 14 years in 47 high schools. 51.5% males and 48.5% females. Response rates were high ( 91.4 % for those aged 6 to 7 years and 100% for those aged 13 to 14 years). The prevalence of symptoms of atopic dermatitis in the last 12 months was 9.6 % at age 6 to 7 and 9 % at age 13 to 14 years. Medical diagnose of atopic eczema was 4 % and 2.4 % for children aged 6 to 7 years and 13 to 14 years, respectively. Reported eczema accounted for 12.4 % and 11.3 % at age 6 to 7 and 13 to 14 years, respectively. Children with symptoms of severe atopic dermatitis accounted for 1 % of all those with symptoms of atopic dermatitis. We also found that the majority of the children begun with skin manifestations of atopic dermatitis before the age of 4 years old. Conclusions: The prevalence of atopic eczema was very similar for both groups of ages. Our results agree with those found in other two studies acomplished in other mexican cities (Cuernavaca and Chihuahua) and with those from other countries of Latin America like Brazil, Chile and Costa Rica. Although, we found lowest values than those from Sweden, Japan and Australia. Studies that include objective skin examination are required to confirm these findings.
A. Kaplan 1* , S. Meeves 2 , Y. Liao 2 , S.T. Varghese 2 , G. Georges 2 , 1. Charleston, SC; 2. Bridgewater, NJ.
Introduction: The symptoms of chronic idiopathic urticaria (CIU) can have a profound impact on patient health and quality of life. The safety and efficacy of fexofenadine (FEX) BID for the treatment of CIU has been previously established in two multicenter, double-blind, randomized, placebo-controlled trials. This study evaluated the efficacy and safety of a QD dose of FEX HCl 180 mg, as this dosing schedule could offer advantages in terms of patient compliance and convenience. Methods: This multicenter, randomized, double-blind, parallel-group, placebo-controlled study consisted of a single-blind placebo run-in period of 2-5 days, followed by a 28 (±4)-day treatment period. Males and females aged 12 years with a diagnosis of CIU and with active disease were enrolled. Patients were randomized 2:1 to receive either FEX HCl 180 mg QD or placebo QD. The primary endpoints were change from baseline in Mean daily Number of Wheals (MNW score) and mean daily severity of pruritus (measured on a 5-point scale) over the 28-day treatment period, as assessed reflectively by the patient. Secondary efficacy measures included a modified total symptom score (MoTSS), comprising sum of number, frequency, size and duration of lesions, and severity of pruritus. MNW and pruritus severity were also assessed instantaneously at trough drug levels (immediately prior to dosing). Results: Over the 28-day treatment period, patients treated with FEX (n=167) experienced significantly greater improvements in MNW and pruritus scores compared with the placebo group (n=92) (p<0.0001 for both). Similarly, over the treatment period, and at individual weekly timepoints, the mean reductions in AM reflective, PM reflective and mean daily MoTSS were significantly greater for patients in the FEX group compared with those in the placebo group (p 0.0052 for all comparisons). The mean reductions in instantaneous MNW and pruritus scores were greater with those who received FEX than those who received placebo (MNW: p=0.0154; pruritus score: p=0.00088). There were no significant differences in the frequency of treatment emergent adverse events between the two treatment groups, and no clinically relevant changes were observed with respect to clinical laboratory data, vital signs or ECGs. Conclusion: This study demonstrated that a QD dose of FEX HCl 180 mg offers effective and well-tolerated relief from the symptoms of CIU. Introduction: The wheals and pruritus associated with chronic idiopathic urticaria (CIU) are often so debilitating that they have a profound impact on patient quality of life. Specifically, CIU has been shown to negatively affect patient mobility, sleep, energy levels, social interaction and emotional wellbeing. The purpose of this study was to examine the impact of treatment with fexofenadine HCl (FEX) 180 mg on health-related quality of life (HRQL) among patients with CIU. Methods: As part of a multicenter, randomized, double-blind, parallel-group, placebo-controlled study, designed to evaluate the efficacy and safety of a once-daily dose of FEX 180 mg in CIU, the impact of treatment on HRQL was also examined. Patients were asked to complete the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Questionnaire (WPAI) at baseline and at Weeks 2 and 4 (final visit or early termination). The primary endpoint was mean change from baseline in DLQI total score, using the mean data of evaluations performed at Weeks 2 and 4 as the post-baseline measure. Secondary endpoints included change from baseline in individual DLQI domains and WPAI scores. Additional analyses were conducted to examine the reliability, validity and responsiveness of the HRQL measures. Results: A total of 254 patients were included in the HRQL population: n=163 FEX, n=91 placebo. Patients in the FEX group experienced significantly greater improvements in the mean DLQI total score than those in the placebo group (p=0.0029). This pattern was repeated with respect to the individual domains of symptoms and feelings (p=0.0071), daily activities (p=0.013), leisure (p=0.0425) and personal relationships (p=0.0023). Both treatment groups reported improvements in productivity, as measured by change from baseline using the WPAI. Patients randomized to FEX experienced significantly less impairment while working (p=0.0455) and performing activities (p=0.0088) than those who received placebo. The DLQI was demonstrated to be reliable (Cronbach's alpha=0.87); both the DLQI and WPAI were found to be valid and responsive instruments in this CIU population. Conclusion: This study demonstrated that a once-daily dose of FEX 180 mg improves the HRQL of patients with CIU, as assessed by change in DLQI total score.
T. Algozzine 1* , A. Lee 2 , S. Wong 3 , L. Anzisi 4 , 1. Manchester, NH; 2. Centerport, NY; 3. Syosset, NY; 4. Mamaroneck, NY. Symptoms of allergic and non-allergic rhinitis may significantly impact a patient's quality of life, by causing fatigue, headache, cognitive impairment and other systemic symptoms. Appropriate management of allergic rhinitis is important in the effective management of coexisting or complicating respira-tory conditions (e.g. asthma, sinusitis, or otitis media). In addition, many commonly used over-the-counter (OTC) antihistamines can cause performance impairment that may impact daily activities. We designed a brief ten-question allergy survey in an attempt to determine how patients were being treated for their allergies, evaluate a patient's self-assessed impact of their allergies on their daily activities, and identify any difference in treatment outcomes between primary care and allergist practices. Patients were invited to complete the surveys anonymously. Completed surveys were collected and entered into a Microsoft Access database for evaluation. Minitab was utilized for statistical calculations. Four hundred and thirty seven patients completed the survey. Fifty-eight percent of survey respondents were women and 89% were adults (age >18). Of those patients surveyed, 53% (n=233) were under the care of an allergist. Compared to primary care, patients treated by allergists reported more allergies (3.4 vs. 1.8, p <0.001) and received more medications on average (2.3 vs. 1.4, p<0.001). Pollen was the most common allergy type reported among all patients. While the majority of all patients (69%) received prescription medications, more primary care patients received no therapy or only OTC treatment when compared to allergist patients (46% vs. 17%, p<0.001). Seventy-four percent of primary care patients reported their allergy symptoms were controlled compared to 63% of allergist patients (p<0.05). Patients receiving treatment from an allergist reported less impact of their allergies on daily activities (a lower score signified less impact) compared to patients seen in primary care (2.27 vs. 3.84, p<0.001). The results of our survey suggest that allergists treat more complex patients. These patients had multiple allergies, more uncontrolled symptoms, and utilized more prescription medications. Despite these findings, patients treated by allergists reported less impact of allergies on their daily activities. INTRODUCTION The patogenic mechanism of nasal polyps are unknow.They frecuently are associated with aspirin intolerance, intrinsic asthma, chronic sinusitis, Young sindrome, cystic fibrosis, Kartagener syndrome and Churg-Strauss syndrome.Chemical mediators found in nasal polyps are as follows: histamine, serotonin, leukotrienes, norepinefrine and possibly PGD2.Recently, leukotrienes have been implicated in mediation of bronchoconstriction and inflammatory Leukotriene levels have also been shown to be elevated in some patients with sinonasal polyposis (Figure 1 ) HYPOTHESIS Antileukotrienes might play a significant role in controlling polyposis and symptoms secundary to sinonasal disease, and they might viable alternative to longterm, oral steroid therapy and repeat surgical debridement PURPOSE This study was undertaken to evaluate the potential role of leukotriene receptor antagonist on recurrent polyposis associated with asthma and improvement of some factor implicated with them DESIGN OF STUDY:Clinical assay, prospective, triple blind. MATERIALSAND METHODS:The study involved 30 patients 12 (40%) males and 18 (60%) women, mean age 20.7 years, with a range 16-45 years selection criteria:INCLUSION CRITERIA: Nasal polyps associated with astha, allergic or non allergic.EXCLUSION CRITERIA: Patients with any concurrent illness, use of sistemic or local corticosteroidsor any kind of antileukotriene within 1 month prior to the beggining of the study.We made an alleatory selection 10 patients recived Montelukast (10 mgs/day), and nasal steroids, beclometasone (600 mgs/day) for 6 months.10 patients recived loratadine plus pseu-doefedrin5mgs/120 mgs/day and nasal steroids, beclometasone, 10 patints were operated of FEES and transnasal endoscipic polypectomy plus Montelukast and nasal steroids, beclometasone IgE serum levels 2.Skin Prick test 3.Sensitivity in vitro 4.CT Scan 5. Celullarity on nasal lavage (Eosinophils and Neutrophils)6.Proinflamatory cytokines (IL4-IL5-IL8) on nasal lavege by ELISA test. RESULTS Ther was a tendency for more improvement of the group 3 ( Surgery-Montelukast-local steroid) of symptoms and objective measurments, in second place of improvement the group 1 Montelukast-local steroid) and the worse on improvement subjective and objetive was group 2 local steroid and loratadine-pseudoefedrine use as placebo Introduction: Sensory perceptions of intranasal corticosteroids (INS) vary among products and can be unpleasant and affect adherence to therapy. Methods: We conducted a cross-sectional study of 120 patients across 4 allergy and immunology clinics in the United States. Respondents were asked to choose between pairs of hypothetical INS that differed by sensory attribute composition. Based on prior research, we measured 6 salient sensory attributes: smell, taste, aftertaste, throat rundown, nose runout, and feel of spray in nose/throat. Each attribute was described in 3 intensity levels, such as "no taste" (low), "weak taste" (moderate), and "strong taste" (high) ( Table) . Other outcomes included an importance score for each sensory attribute and patients' willingness to adhere to an INS having the lowest levels of each sensory attribute compared to one with moderate levels. Results: Preferences decreased with increasing intensity level of each sensory attribute. The most important attribute was aftertaste in 28% of patients, taste in 19%, throat rundown in 18%, nose runout in 12%, smell in 11%, and feel of spray in 7%. Only 5% had more than one attribute tied for most important. If instructed to take INS daily for 3 months, 77% of patients stated that they would definitely be able to follow their doctor's advice (willing to adhere) if given an INS containing the lowest level of each sensory attribute compared with 4% for one having moderate levels (P<0.01). Conclusions: Patients' preferences decrease with increasing intensity levels of each sensory attribute and affect patients' willingness to adhere. Tailoring INS to patient preferences may lead to improved treatment satisfaction and adherence. Introduction:A high prevalence of rhinitis and asthma comorbidity has been persistently noticed in epidemiological studies in last years. Our objective was to evaluate the prevalence of rhinitis and asthma comorbidity in a Portuguese population including both atopic and non-atopic patients. Methods: A retrospective study was performed. Clinical records from patients attending an immunoallergology outpatients'clinic during 39 months (from January 1998 until June 2001) were reviewed. Data were collected concerning clinical history of rhinitis and/or asthma, aeroallergens'skin prick tests and respiratory function evaluation. Results: Among the 3582 patients attending an appointment during the study period, 2448 (68.3%) had rhinitis and/or asthma (56.2% F; 43.8% M;mean age 26 +/-19 years). Patients with respiratory disease included 1983 atopic (81.0%) and 465 non-atopic 19%). Diagnosis of asthma, rhinitis or of both diseases was made in 170 (8.6%), 581 (29.3%) and 1232 (62.1%), respectively, in atopic patients and in 56 (12.0%, 265 (57.0%) and 144 (31.0%), respectively, in non-atopic patients. Rhinitis was diagnosed in 87.9% of atopic asthmatic and in 72-0% of non-atopic patients with asthma. In patients with rhinitis, asthma was also diagnosed in 67.9% of atopic patients and 35.2% on non-atopic patients. Conclusions: In this study population rhinitis was frequently diagnosed in patients with asthma and vice-versa, thereby leading to a high prevalence of this comorbodity. This association was more frequent in atopic patients. Our data are comparable to those we found in recent literature. These results suggest that clinical investigation of asthma should be mandatory in management of patients with rhinitis as well as asthmatic patients should be routinely submitted to clinical evaluation of rhinitis. Introduction: Cetirizine HCl (C) has been shown to be more effective than fexofenadine HCl (F) in controlling seasonal allergic rhinitis (SAR) symptoms at 21-24 hr post-dose, however, the efficacy of C and F was comparable between 0-5 hr post-dose. Response to treatment in the middle of the dosing interval needed to be addressed. Methods: This randomized, double blind, placebo (P)-controlled study was designed to compare the efficacy and tolerability of a single dose of C 10 mg, F 180 mg, and P between 5-12 hr postdose in ragweed-sensitive SAR subjects. Subjects meeting entry criteria were exposed to pre-determined controlled levels of ragweed pollen in the EEU during priming and double blind treatment. Subjects assessed rhinitis symptoms at half hr intervals during pollen exposure; at priming, at the qualifying period, at baseline, and from 5-12 hr post-dose. The primary efficacy endpoint was the change from baseline in Total Symptom Severity Complex (TSSC) score at 12 hr post-dose. TSSC score was the sum of severity ratings (0=absent to 3=severe) for 4 symptoms: runny nose, sneezing, itchy nose/palate/throat and itchy/watery eyes. Results: A total of 599 subjects (mean age 32.8 y; 58.9% females) were randomized: C, 249; F, 250; P, 100. Baseline characteristics were comparable among groups; TSSC: C=9.2, F=9.2, P=8.9. C produced a 26% greater reduction in TSSC score at 12 hr (-4.3, p=0 .001) and a 14% greater reduction overall (i.e., average over the 5-12 hr post-dose period) (-5.0, p=0.006) compared with F (-3.4, -4.4, respectively). Both C and F reduced TSSC score more than P (12 hr, -1.9; overall, -2.3, p<0.001) including all individual symptoms (p<0.05). C however, was more effective than F for runny nose and sneezing at 12 hr and overall, itchy/watery eyes at 12 hr, and itchy nose/throat/palate overall (p<0.05). Rates of discontinuation due to adverse events (AEs) were low: C, 0.4%; F, 0%; P, 1.0%. The incidence of treatmentemergent AEs was similar: C, 25.3%; F, 29.6%; P, 35.0%. Somnolence occurred in 0.8% of subjects on C, and 0% on F or P. Conclusion: C produced a greater improvement in rhinitis symptoms compared with F and P, at 12 hr post dose and over the 5-12 hr post-dose period. All treatments were safe and well tolerated. Background: Medication utilization patterns of patients suffering from seasonal allergic rhinitis (SAR) are not well documented, and although many anti-allergic medications are prescribed for daily use, actual usage is unknown, but recognized to be quite variable. Methods: 1821 subjects with positive ragweed skin tests were mailed a survey during the third week of ragweed season, soliciting the nature and severity of SAR symptoms, usage patterns and reasons for choice of anti-allergic medication. Results: 550 subjects completed the survey (30.2%). The prevalence of symptoms were, in decreasing order: sneezing (91.5%), runny nose (82.4%), itchy/gritty eyes (80.4%), stuffiness (78.5%), itchy nose (71.3%), watery eyes (64.7%), itchy palate/throat (56.9%), post-nasal drip (55.6%), red/burning eyes (49.1%), headache (36.5%), itchy ears (34.0%), cough (30.0%), shortness of breath (15.7%), and wheeze (15.5%). SAR patients used antihistamines most frequently (94.7%), followed by decongestants (63.1%), combination (antihistamine/decongestant) products (52.0%), and intranasal corticosteroids (42.5%). Medications were mostly taken intermittently rather than daily (antihistamines 68.0%; nasal corticosteroids 71.8%), Conclusion: A constellation of nasal symptoms were the most common seasonal allergic manifestations, followed by ocular, palatal and ear irritation. Antihistamines were the most frequently used medication to treat symptoms, succeeded by decongestants (alone or in combination). A significant proportion of subjects took their allergy medication, including nasal corticosteroids, intermittently rather than regularly, underscoring the relevance of single-dose evaluations of drug efficacy.
A.K. Ellis * , E. Rafeiro, J.D. Ratz, J.H. Day, Kingston, Canada. Background: Traditional assessment of seasonal allergic rhinitis (SAR) medication efficacy utilizes randomized controlled trials over 2-4 weeks in season. An additional study method employs single-dose responses using controlled allergen challenge such as the Environmental Exposure Unit (EEU). A comparison of allergic symptoms generated by controlled allergen challenge to those occurring in ragweed season symptoms has not been done. Methods: 1821 subjects with known SAR to ragweed were mailed a survey during the third week of ragweed season, soliciting the nature and severity of SAR symptoms. Subjects participating in a subsequent controlled allergen challenge study using the EEU, were again asked to complete a similar survey that documented symptoms generated in this model. Those who completed both surveys comprised the primary analysis group. Results: 550 subjects completed the ragweed season survey, 516 subjects completed the EEU survey, and 270 completed both. Symptoms generated by EEU exposure were similar to those elicited during ragweed season, with the exception of cough (68% vs. 27%, respectively, p <0.01). Subjects reported that symptoms were more severe in the EEU than those experienced on a typical ragweed season day, but less severe than those during peak ragweed season days. Conclusion: Allergic upper respiratory tract symptoms produced during controlled ragweed pollen exposure in the EEU were similar in nature and degree to those expe-rienced during ragweed season, supporting evidence that the EEU is a valid model for studying SAR.
R. Nave 1 , M.A. Wingertzahn 2* , S. Brookman 3 , S. Kaida 4 , T. Shah 2 , 1. Konstanz, Germany; 2. Florham Park, NJ; 3. Princeton, NJ; 4. Tokyo, Japan. RATIONALE: Ciclesonide (CIC) is a new corticosteroid under development for treatment of allergic rhinitis (AR). CIC is a pro-drug that is hydrolyzed to the active metabolite desisobutyryl-ciclesonide (des-CIC) in the target tissue. CIC has low oral bioavailability and is highly bound to plasma proteins; therefore CIC administered as a nasal spray is expected to have minimal local and systemic effects. OBJECTIVE: The primary objective was to evaluate the safety and tolerability of repeated escalating doses of CIC (50-800 mcg/day) given as a nasal spray for 14 days to healthy and asymptomatic subjects with SAR. Secondary objectives were to determine PK of CIC and des-CIC and to evaluate the effect of CIC on endogenous cortisol. METHODS: This was a single-center, randomized, placebo-controlled, double blind, modified sequential dose study. Six cohorts were randomized. Cohorts I-V consisted of healthy subjects given doses of CIC up to 400 mcg BID. Cohort VI (asymptomatic SAR subjects) received 400 mcg BID. Each cohort was comprised of 6 subjects who received CIC and 2 subjects who received placebo. Safety assessments were conducted by recording adverse events (AEs), clinical laboratory, eye, and nasal examination findings. Serum and urine samples were taken for evaluation of cortisol levels. CIC and des-CIC serum concentrations were determined by LC-MS/MS. RESULTS: No trend was observed for AEs when comparing CIC and placebo treatment. Additionally, no subject experienced a serious AE or withdrew from the study due to an AE during the trial. Cortisol levels showed no differences between the dose groups or between activetreated subjects and placebo-treated subjects. Additionally, serum concentrations of CIC and des-CIC in the majority of serum samples were shown to be below the lower limit of quantification (LLOQ; 25 pg/ml for CIC and 10 pg/ml for des-CIC), therefore no descriptive statistics could be calculated. CON-CLUSIONS: Ciclesonide nasal spray, at the doses evaluated, was safe and well tolerated in healthy and asymptomatic SAR subjects with no detectable effects of CIC on serum or urinary free cortisol concentrations. Additionally, no PK parameters could be calculated for CIC nasal spray, as it was virtually undetectable in serum despite the use of a sensitive assay. The preferred treatment for allergies is avoidance. Air filtration is logical but room air purifiers have been of limited efficacy. ZEPHYR™ is a new device which creates an envelope of air 99% free of allergenic particles around the head of the sleeping person. Allergic rhinitis frequently causes daytime somnolence. This is a pilot study of the effectiveness of ZEPHYR on symptoms of seasonal allergic rhinitis (ragweed hay fever) and on daytime sleepiness. Methods: Subjects age 12 to 45 with ragweed hay fever were studied in the ragweed season using each subject as his/her own control. Usual allergy medicines were not allowed, except loratadine for rescue. Outcome measures were a symptom score, Juniper Rhinitis Quality of Life Questionnaire, a tolerability rating, and Epworth Sleepiness Scale. During the first week subjects qualified by symptom scores, then entered the one-week treatment period with ZEPHYR. The third week was a post-treatment observation period. Results: Of 13 participants, 10 (77%) showed symptom improvement. The whole group averaged 26% reduction in morning symptoms and 24% reduction in evening symptoms. Sleepiness scores improved 29%. Rhinitis QOL improved 33%. The ZEPHYR system was well tolerated as evidenced by the response to several statements regarding ZEPHYR use and tolerability: (Scoring: 1 = Strongly Disagree, 5 = Strongly Agree) "The system did not bother me while I was sleeping." (Mean Score 4.8) "The noise level did not affect my ability to sleep." (Mean Score 4.7) "The temperature was just fine for me." (Mean Score 4.8) "The system did not get in my way during sleep." (Mean Score 5.0) Conclusions: ZEPHYR significantly reduced seasonal hay fever symptoms and daytime sleepiness, improved quality of life, and was well-tolerated by subjects. ZEPHYR may provide maximal environmental control of bedroom allergen exposure irrespective of ambient airborne allergen levels in the room. Nasal congestion is an important symptom that is associated with significant morbidity in the rhinitis sufferer. Disrupted sleep leading to daytime fatigue, loss of concentration, and decreased productivity are potential results of this symptom. A study employing online interviews with 1200 rhinitis sufferers from Harris Interactive's online database was conducted in order to understand the symptoms they identify with most and to determine the impact nasal congestion had on their daily activities. Respondents were at least 18 years of age and experienced nasal congestion from seasonal allergic, perennial allergic, and/or perennial non-allergic rhinitis. The results showed that 60% of the respondents agreed nasal congestion is the most bothersome symptom of rhinitis; 37% experienced nasal congestion daily, while 35% experienced it several times per week. Not surprisingly, sleep was the most important factor affected by nasal congestion. Two-thirds (66%) of the respondents felt their sleep had been moderately or significantly impacted by nasal congestion, and more than half (56%) felt it was difficult to get a good night's rest because of congestion. Sleep was interrupted or disturbed by nasal congestion approximately 3 nights per week, on average. Furthermore, sleep disruption from nasal congestion contributed to daytime fatigue; 62% of the respondents indicated that they were typically tired or fatigued during the day when they experience nasal congestion. In addition, 42% felt that activities requiring concentration, such as reading, were moderately or significantly impacted by nasal congestion. This study confirms that nasal congestion causes the rhinitis sufferer significant problems beyond that of just a stuffy nose. Consequently, healthcare providers need to ensure that their rhinitis patients who have nasal congestion as their primary complaint are managed effectively. Desloratadine (DL, Clarinex ® ) is a non-sedating oral antihistamine that is metabolized to 3-OH DL. However, a phenotypic polymorphism has been observed in some patients that results in reduced formation of 3-OH DL. The prevalence and safety profiles of such poor metabolizers of DL were examined in pharmacokinetic and clinical trials. A poor metabolizer was defined as a subject having a 3-OH DL to DL AUC ratio of <0.10, or a DL half-life of 50 hours. In pediatric studies, where a sparse sampling approach was uti-lized to screen for poor metabolizers, a plasma concentration ratio of 3-OH DL to DL of <0.10 at 12 hours classified a subject as a poor metabolizer. A total of 3, 748 adult and pediatric subjects (2-70 years old) were phenotyped with a single dose of DL or loratadine. The overall prevalence of the poor metabolizer phenotype was 6% (228/3748). This prevalence was comparable for adult (70/1194, 6%) and pediatric subjects (158/2554, 6%), and greater in both populations among Blacks (16% pediatric, 18% adult) than Caucasians (3% pediatric, 2% adult). Pharmacokinetic analysis found that exposure to DL was approximately 6-times higher in poor metabolizers than in normal metabolizers. There was no apparent difference in DL exposure among poor metabolizers in different age groups (6-months to <2-years, 2-to <6-years, 6-to <12-years, and 12-years) when treated with age-appropriate doses. The multiple-dose (7-35 days) safety profile of DL was examined in pediatric poor metabolizers (2-11 years) in 5 placebo-controlled trials, and in adult poor metabolizers (20-70 years) in pharmacokinetic trials. Pooled AE rates were low and comparable between the poor metabolizer and placebo subjects, as shown in the table below with all AEs that appeared in >2% of subjects in any treatment group (or >3% in adult poor metabolizers). There was no difference in cardiovascular safety profile or ECG results (including QTc interval) among these groups. In conclusion, (1) expression of the DL poor metabolizer phenotype is independent of age, but higher in Blacks than in Caucasians, (2) exposure to DL in poor metabolizers is independent of age when administered at age-appropriate doses, (3) the safety profile of DL poor metabolizers is not different from that of placebo at all ages down to at least 2-years old. These results are consistent with the high therapeutic index of DL. Desloratadine (DL, Clarinex®) is extensively metabolized to 3-OH DL and subsequently glucuronidated. The enzyme responsible for the formation of this active metabolite is unknown. Poor metabolizers of DL represent a subset of the population that has a reduced ability to form 3-OH DL. A poor metabolizer was defined as a subject having a 3-OH DL to DL exposure ratio of <10%, or DL half-life of 50 hr. PK parameters from adult and pediatric poor metabolizers following repetitive administration of DL were characterized in Clinical Pharmacology trials and are summarized in the table below. Exposure to DL [AUC(0-24hr)] in poor metabolizers was approximately 6-fold greater than the corresponding values in normal metabolizers; Cmax was 3to 4-fold greater. The magnitude of the reduction in the formation of 3-OH DL and the concurrent increase in exposure to DL associated with the poor metabolizer phenotype was similar in pediatric and adult subjects at age-appropriate doses. Despite the increased exposure to DL in poor metabolizers, there was no increase in adverse event frequency or changes in electrocardiographic parameters.
a: Dose normalized to 5 mg. b: Least Squares Mean Ratio: ANOVA of log-transformed data extracting sources of variation due to age group and metabolizer status. The ratio is a contrast of metabolizer status. c: Lower and upper 90% confidence interval based on log-transformed data. INTRODUCTION: Many patients with seasonal allergic conjunctivitis (SAC) complain of symptoms of dry eyes. We have previously reported that patients with SAC experience discomfort from dry eyes anywhere between 2 to 6 days per week and that the overall severity of the dry eye symptoms tend to range from mild to severe. This preliminary cross over study evaluated the benefits of Nedocromil sodium 2% ophthalmic solution used twice daily, compared with Nedocromil sodium 2% ophthalmic solution used with Refresh (ocular lubricant), for the treatment of dry eye symptoms in association with SAC during 8 weeks. METHODS: Patients who had a minimum of two-year history of SAC and dry eyes, a positive skin prick test towards grass pollen and between the ages of 18 to 65 were enrolled. Patients were evaluated on four visits and completed a daily diary, which included scales for grading allergic conjunctivitis and dry eye symptoms. At each clinic visit they completed the OSDI and the RQLQ (Rhinitis Quality of Life Questionnaire). The OSDI (ocular surface disease index) was developed to assess dry eye symptoms and the impact on vision related functioning. The RQLQ evaluates quality of life in patients with allergic conjunctivitis. At the last visit, both the patient and the physician assessed the treatment and the effectiveness, if any, of the addition of Refresh to Nedocromil sodium 2% ophthalmic solution. Daily grass pollen counts were preformed using a Burkhard sampler. RESULTS: 19 patients (7 male and 12 female) were enrolled and 3 dropped out. Patients experienced minimal symptoms at the start of the season due to low concentration of grass pollen. Preliminary analysis carried out using a paired t-test was preformed on the ocular average scores for the two treatment periods. There was no significant difference between the 2 treatment groups for redness, light sensitivity and tearing of the eyes. A reduction in dry eye symptoms was reported in all patients using Refresh eye drops and the number of drops required varied between patients. During the treatment periods there was improvement in patients RQLQ. CONCLUSION: Patients preferred the addition of Refresh eyedrops in alleviating SAC and dry eye symptoms. Further studies need to be carried using Refresh eye drops in larger number of patients with SAC and dry eye symptoms.
C. LaForce * , Raleigh, NC.
Introduction: The objective of this study was to determine the ability of azelastine nasal spray to improve rhinitis symptoms and quality of life parameters in seasonal allergic rhinitis patients remaining symptomatic after treatment with fexofenadine. Methods: This placebo-controlled, double-blind study began with a 1-week, open-label lead-in period, during which patients received fexofenadine 60 mg bid. After 7 days, patients who improved less than 25% to 33% on fexofenadine were randomized to treatment for 2 weeks with: (1) azelastine nasal spray, (2) azelastine nasal spray plus fexofenadine, or (3) placebo. The primary efficacy variable was the change from baseline to Day 14 in theTotal Nasal Symptom Score (TNSS), which consisted of runny nose, sneezing, itchy nose, and nasal congestion scores recorded twice daily in patient diary cards. In addition, quality of life was assessed using the Rhinitis Quality of Life Questionnaire (RQLQ). Results: After 2 weeks of treatment, azelastine nasal spray (P<.01) and azelastine nasal spray plus fexofenadine (P<.01) significantly improved theTNSS compared to placebo. Based on 90 patients with complete TNSS and RQLQ data, the overall RQLQ score also was significantly (P<.01) improved compared to placebo. Conclusions: Azelastine nasal spray was an effective treatment for patients with seasonal allergic rhinitis who did not respond well to fexofenadine and significantly improved quality of life parameters compared to placebo. The results of this study indicate that azelastine nasal spray is an important alternative to oral antihistamines and should be considered in the initial management of seasonal allergic rhinitis.
W. Berger * , Mission Viejo, CA.
Objective: To evaluate improvement over time with azelastine nasal spray in the treatment of patients with moderate-to-severe seasonal allergic rhinitis (SAR) who remained symptomatic after treatment with loratadine or fexofenadine. Methods: The studies were 2-week, multicenter, double-blind, placebo-controlled trials that began with a 1-week, open-label lead-in period in which patients received either loratadine 10 mg qd (Study No. 1) or fexofenadine 60 mg bid (Study No.2). Patients who improved <25%-33% with loratadine were randomized to treatment with: (1) azelastine nasal spray 2 sprays/nostril bid, (2) azelastine nasal spray 2 sprays/nostril bid plus loratadine 10 mg qd, (3) desloratadine 5 mg qd, or (4) placebo. Patients who improved <25%-33% with fexofenadine were randomized to treatment with: (1) azelastine nasal spray 2 sprays/nostril bid, (2) azelastine nasal spray 2 sprays/nostril bid plus fexofenadine 60 mg bid, or (3) placebo. The primary efficacy variable was the change from baseline to Day 14 in the Total Nasal Symptom Score (TNSS), consisting of runny nose, sneezing, itchy nose, and nasal congestion. Symptom severity was recordedAM and PM in diary cards on a 4-point scale (0=none; 1=mild; 2=moderate; 3=severe). Results: In both studies, patients treated with azelastine nasal spray experienced increasing improvement inTNSS over 14 days of treatment.The improvements were approximately 2-fold greater than placebo at each day of the study, and the differences from placebo were statistically significant (P<.05) at Days 2, 7, 14, and overall. In Study No. 1, 33% of patients treated with azelastine had >30% improvement in TNSS compared to 17% in the placebo group. In Study No. 2, 29% of patients treated with azelastine had >30% improvement in TNSS compared to 12% in the placebo group. Conclusions: Azelastine nasal spray was effective in treating patients with moderate-to-severe SAR who remained symptomatic after treatment with either loratadine or fexofenadine. Azelastine demonstrated first-day effectiveness, and patients treated with azelastine experienced increasing improvements in rhinitis symptoms over the 14-day study periods.Azelastine nasal spray is an effective treatment alternative to oral loratadine or fexofenadine and an appropriate first-line therapy in the management of SAR. Introduction: A large, open-label, azelastine (Astelin) nasal spray patient experience trial was conducted in patients with SAR, VMR, or mixed rhinitis (allergic rhinitis with nonallergic triggers). This analysis evaluated the effect of azelastine nasal spray in treating rhinitis symptoms in a subset of patients with a history of asthma or sinusitis. Methods: Patients were entered into an open-label protocol and treated for 2 weeks with azelastine nasal spray at a dosage of 2 sprays per nostril bid. After 2 weeks, the patients completed a questionnaire that assessed onset of action, symptom improvement, satisfaction with therapy, and quality of life. Results: From a total of 4364 rhinitis patients who received azelastine monotherapy during the 2-week study period, data were analyzed for patients with asthma (n=260) or sinusitis (n=346). A greater percentage of these patients had severe rhinitis compared to the overall population. Nasal congestion and postnasal drip were reported as the most bothersome rhinitis symptoms. After 2 weeks of treatment with azelastine nasal spray, >80% of patients with asthma and >85% of patients with sinusitis reported some or complete control of congestion and postnasal drip. In addition, >62% of patients with asthma reported chest tightness, shortness of breath, and wheezing were somewhat or completely controlled, and >77% of patients with sinusitis reported that headache and facial pain were somewhat or completely controlled during treatment with azelastine nasal spray. Conclusion: Azelastine nasal spray provided effective control of rhinitis symptoms, including nasal congestion and postnasal drip, in patients with a history of asthma or sinusitis. Introduction: Epinastine is an antihistamine with mast cell stabilization and anti-inflammatory properties. Epinastine 0.05% ophthalmic solution was evaluated for treatment of allergic signs and symptoms elicited by feline dander in a cat exposure room. Methods: Participants (n=30) were aged 18 years, with a history of ocular allergy to cats, a positive skin prick reaction to cat dander, and an ocular itching score of 2 (on a 0-4 scale) within 30 minutes of entering the cat room. Subjects wore a TB mask while in the cat room to reduce the effects of inhaled allergen. After 30 minutes of exposure, 1 drop of epinastine HCl 0.05% was instilled in one eye, and olopatadine 0.1% was instilled in the fellow eye. Environmental exposure to cat dander continued for another 60 minutes. Prior to instillation, and at 5, 15, 30, 45 and 60 minutes after instillation, conjunctival hyperemia and chemosis (scales of 0-3), and ocular itching, tearing, ocular burning, nasal itching and rhinorrhea (scales 0-4) were assessed. Results: Instillation of a single drop of ophthalmic epinastine significantly reduced ocular itching from a mean pre-instillation score of 2.27 to a mean score of 0.37 at 60 minutes after instillation (P<.001), despite continuous exposure to cat dander during the entire period. Similarly, ocular burning, tearing, and hyperemia were significantly reduced by epinastine treatment (P<.002). Chemosis was only weakly induced by cat room exposure, with a mean pre-instillation score of 0.167; however, epinastine treat-ment decreased that to 0 (P=.023). Instillation of epinastine also significantly reduced nasal itching and rhinorrhea scores (P<.043). Results for olopatadine were not statistically different; however, the change from baseline in itching scores in the epinastine-treated eyes was greater than that seen in the olopatadine-treated eyes at the majority of timepoints. Conclusion: Ophthalmic epinastine is indicated for the prevention of itch associated with allergic conjunctivitis.This study shows that treatment of cat-sensitive subjects with ophthalmic epinastine following environmental exposure to cat dander significantly reduced ocular itching and other signs and symptoms of allergic conjunctivitis. Objective: The objective of this study was to evaluate azelastine (Astelin®) nasal spray, cetirizine (Zyrtec®), fluticasone (Flonase®), and placebo in the treatment of patients with symptomatic seasonal allergic rhinitis. Methods: This was a double-blind placebo-controlled pilot trial in 60 patients with seasonal allergic rhinitis. The study began with a 1-week, placebo lead-in period, followed by a 1-week blinded treatment period (Day 1 to Day 7). Efficacy variables were: (1) change from baseline to Day 7 in the total nasal symptom score (TNSS; consisting of rhinorrhea, sneezing, itchy nose, and nasal congestion);
(2) onset of action based on TNSS over the 4 hours following initial administration of study drugs; and (3) change from baseline to Day 2 (24-hour change) in TNSS. TNSS was scored twice daily (AM and PM) on a 4-point rating scale (0=none, 1=mild, 2=moderate, 3=severe). Patients recorded a minimum 12-hour TNSS of 8 on at least 3 days during the lead-in period, and a congestion score of 3 on at least 3 days to qualify for entry. Qualified patients were randomized to treatment with: (1) azelastine nasal spray 2 sprays per nostril bid plus placebo capsules qd; (2) cetirizine 10-mg tablets qd plus placebo nasal spray; (3) fluticasone 2 sprays per nostril qd plus placebo capsules qd; or (4) placebo nasal spray plus placebo capsules. Results: Azelastine significantly (P<.05) improved the TNSS compared to cetirizine, fluticasone, and placebo beginning 30 minutes after initial administration; cetirizine significantly improved TNSS versus placebo at 150 minutes; fluticasone showed no significant differences from placebo over the 4-hour evaluation period. Azelastine significantly (P<.05) improved the TNSS at Day 2 (24-hour change from baseline) compared to cetirizine, fluticasone, and placebo. Conclusions: Azelastine nasal spray improved the TNSS in patients with moderate-to-severe seasonal allergic rhinitis. In addition, azelastine nasal spray demonstrated a 30-minute onset of action and significantly improved TNSS versus cetirizine, fluticasone, and placebo 24 hours after initial administration. Introduction: Epinastine, an antihistamine with mast cell stabilization and anti-inflammatory properties, has been developed for the treatment of allergic conjunctivitis. The efficacy and tolerability of epinastine was assessed and compared with levocabastine. Methods: Eligible patients for this randomized, double-masked, parallel-group, active-controlled environmental clinical trial were 18-65 years old with a recent diagnosis of seasonal allergic conjunctivitis. Patients instilled 1 drop epinastine HCl 0.05% or levocabastine 0.05% ophthalmic solution in each eye BID for 6 weeks. Patients and investigators assessed efficacy and tolerability at study visits on Days 0 (baseline), 7, 14, 28, and 42, and assessed overall efficacy and tolerability at study exit. Adverse events were monitored.
Results: Epinastine provided superior itch relief compared with levocabastine (P=.048; see figure) ; mean ocular itch scores over 4 treatment visits were 0.79 for epinastine and 0.97 for levocabastine (0-3 scale; 3=worst; baseline scores were 2.08 for epinastine and 2.06 for levocabastine). The mean summed score (ocular itching, tearing, and foreign body sensation) over 4 treatment visits was significantly better for epinastine than levocabastine (P=.010).At study exit, 53% of epinastine-treated patients rated overall efficacy "very good" (the highest possible rating), versus 34% of levocabastine-treated patients. At 5 minutes postinstillation, 77% of epinastine-treated and 75% of levocabastine-treated patients rated tolerability "very good". At study exit, 80% of epinastine-treated and 75% of levocabastine-treated patients rated overall tolerability "very good", with investigator ratings being similar. Treatment-related adverse events occurred in 7.1% of epinastine-treated patients (most frequent: eye pain and skin itching, 1.2% each) and 10.3% of levocabastine-treated patients (most frequent: double vision, 3.4%; influenza-like symptoms, 2.3%); most AEs were mild or moderate. Conclusion: Our results confirm the therapeutic potential for epinastine as an efficacious treatment suitable for long-term use throughout the allergy season. Ophthalmic epinastine was superior to levocabastine for relief of ocular symptoms in patients with allergic conjunctivitis and was well-tolerated. Since chronic inflammation is the histopathologic landmark of otitis media with effusion, clinical observations have led us to believe that the combination of a cysteinyl leukotriene receptor antagonist Montelukast with an oral antibiotic may be more efficacious than monotherapy with an oral antibiotic in the treatment of serous otitis media. We studied twenty pediatric patients (age 3 years to 6 years) in a randomized open labeled 2-week trial to compare the efficacy of the combination Montelukast (4 mg or 5 mg chewables tablets QD dosed according to patient's age) with an oral antibiotic Amoxicillin/Clavulanate potassium (90 mg/kg/day in 2 divided doses every 12 hours) to a monotherapy with an oral antibiotic Amoxicillin/Clavulanate potassium for the treatment of otitis media with effusion. The efficacy of treatment options was assessed using pneumatic otoscopy, impedance tympanometry, and audiometry to monitor the clinical course of the middle ear effusion in both treatment groups. In the combination group Montelukast and antibiotic a resolution of otitis media with effusion occured at the 7th day. In contrast in the group treated with monotherapy with the oral antibiotic the resolution of otitis media with effusion occured on the 14th day. In conclusion, the combination of Montelukast plus an oral antibiotic is more effective than monotherapy with an oral antibiotic.The combination of Montelukast plus an antibiotic may be a safer and shorter therapy given the safety issues with long term use of systemic antibiotics. Introduction: A randomized, double-blind, placebo-controlled study was conducted in an environmental exposure chamber (EEC) to compare the efficacy of three doses of olopatadine nasal spray, a topical anti-allergy treatment for Seasonal Allergic Rhinitis (SAR), versus placebo spray. Methods: Patients aged 17-65 years old with a history of SAR were screened, consented, evaluated for a positive skin test to ragweed allergen, and enrolled in this IRBapproved study. A total of 320 "primed" patients were exposed to ragweed allergen in the EEC and randomized to olopatadine 0.2% (N=80), olopatadine 0.4% (N=80), olopatadine 0.6% (N=80), or placebo (vehicle) (N=80) spray, 2 sprays/nostril once in the morning. Symptoms were self-assessed using a 4point scale (total nasal symptom score, TNSS, comprised of sneezing, runny, itchy and stuffy nose) via diaries at periodic intervals during the 12-hour study period. Safety was also assessed. Results: Obvious trends indicated a dosedependent response to olopatadine 0.2%, 0.4% and 0.6%, though concentrations were not statistically different from each other. All three concentrations of olopatadine were clearly more efficacious than placebo spray at the first time point, 30 minutes, continuing to the end of the 12-hour session. Olopatadine exhibited a safety profile comparable to placebo. Conclusions: Olopatadine nasal spray 0.2%, 0.4% and 0.6% exhibited dose-dependent responses. Onset of action for all three concentrations of olopatadine was apparent at the first post-dose timepoint, 30 minutes, and efficacy was maintained throughout the next 12 hours. Olopatadine nasal spray was safe, well-tolerated, and effective for the treatment of SAR in the EEC chamber.
C. Slonim * , Tampa, FL.
OBJECTIVE: To assess patient subjective responses to the treatment of allergic conjunctivitis using azelastine hydrochloride ophthalmic solution. METHODS: Participating physicians selected 20 patients from their practice to receive azelastine hydrochloride 0.05% ophthalmic solution 1 drop per affected eye twice daily for 5 days. Patients on prior ocular allergy medications were allowed to participate. After 5 days of treatment with azelastine hydrochloride, patients (n=2, 887) rated their experiences with azelastine hydrochloride via a self-administered survey. Not all questions were answered by each patient. RESULTS: At baseline, 88% of patients reported that their ocular itching affected their work, school, and/or leisure activities at least "somewhat". After using azelastine hydrochloride, 70% of patients achieved either "moderate" or "complete" relief from ocular itching, including 30% who reported "complete" relief from itching. Seventy-one percent (71%) of patients had been treated previously with a topical prescription anti-allergy medication for their ocular itching. Seventy percent (70%) of patients (n=836) who had not been previously treated with a topical prescription anti-allergy medication treatment and 71% of previous medication users (n=2, 192) experienced at least "moderate" relief of itching when treated with azelastine hydrochloride. Sixty-five percent (65%) of the previously-treated patients rated azelastine hydrochloride as "somewhat better" or "much better" than their previous medication. CONCLUSIONS: Results suggest that azelastine hydrochloride ophthalmic solution is an effective treatment for the ocular itching associated with allergic conjunctivitis as rated by the patient, regardless of whether they had been treated previously with a topical prescription anti-allergy medication. Objective: To determine an association between food allergy and acid reflux in adults. Method: We conducted a retrospective chart review of 60 atopic adult patients in an academic otolaryngic allergy practice. 30 adults who tested positive and 30 adults who tested negative for food allergy were included in the study. Charts were reviewed for a diagnosis of gastroesophageal reflux disorders (GERD). This included a history of laryngopharyngeal reflux (LPR) and peptic ulcer disease (PUD). Population prevalence (19.8%; CI 17.7-21.9) of acid reflux was estimated from a historical study (Locke GR et al. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmstead County, Minnesota. Gastroenterology 1997; 112:1448-56) that had a similar subject population. The prevalence of GERD in each study arm, as well as in the total study group of atopic adults, was compared to the historical control. Results: Subjects testing positive for food allergy had a diagnosis of GERD in 26.7% (95% CI 11.8-41.6) of cases. Those subjects who did not demonstrate a food allergy were positive for GERD in 40% (95% CI 25.1-54) of cases. In the total study group, the prevalence of GERD was 33.34% (95% CI 22.8-43.8). On Chi square analysis, the prevalence of GERD was significantly higher in the total study group when compared with the historical control (p=0.013). Those subjects who tested negative for food allergy had a statistically significant higher prevalence of GERD than the control population (p=0.003). The prevalence of GERD between the group testing positive and the historical control did not show a significant difference (p=0.41). When comparing the study arms to each other, there was no significant difference in the prevalence of GERD (p=0.27). Conclusions: The prevalence of acid reflux disorders was not higher in subjects with food allergy when compared to a historical control. Although a statistical significance was noted between adults who tested negative for food allergy and the control population with regards to the prevalence of GERD, this may reflect the fact that individuals examined in an Otolaryngologist's office are more likely to have acid reflux disorders than the general population. Overall, the atopic subjects did have a higher incidence of acid reflux disorders, but there was no statistical significance between subjects with and without food allergy.
A. Suryadevara * , D.L. Hamilos, Boston, MA.
Introduction: Recent studies suggest that CRS without nasal polyposis (CRSsNP) and CRS with nasal polyposis (CRScNP) represent distinct pathologic entities. We wished to determine whether these conditions differed in their clinical presentation. Methods: Over a two-year period, new patients coming to a University based specialty clinic meeting criteria for CRS were enrolled in an outcomes study. Patients indicated which of four major (facial pain/pressure/headache, nasal obstruction, nasal purulence/discharge, and hyposmia/anosmia) and four minor (fever, halitosis, dental pain, cough) criteria for CRS they were experiencing. Rhinoscopy was performed to look for nasal polyps or polypoid tissue in any sinus area. The prevalence of each symptom was compared in the groups by chi square analysis. Results: The population (N=126) had a mean age of 46 +/-13.6 and was 59% female, 86% Caucasian, 8.7% African-American, 1.6% Asian and 1.6% Hispanic. Most patients (87%) were non-smokers. All had at least 2 major criteria or 1 major + 1 minor criteria for CRS at enrollment. Forty-one patients (32.5%) had CRScNP. The mean number of major criteria was greater in the CRScNP than CRSsNP (3.27 vs 2.91, P=0.017). Nasal obstruction and hyposmia/anosmia were more prevalent in CRScNP (P= 0.05, 0.025 respectively). Facial pain/pressure/headache was more prevalent in CRSsNP (P=).025). The most prevalent symptoms in CRScNP were: nasal purulence/discharge (97.6%)>hyposmia/anosmia (85.4%)>facial pain/pressure/headache (82.9%)>nasal obstruction (61%). In contrast, the most prevalent symptoms in CRSsNP were: facial pain/pressure/headache (95.3%)>nasal purulence/discharge (88.2%)>hyposmia/anosmia (64.7%)>nasal obstruction (42.4%). None of the symptoms were absolutely distinguishing of these conditions. No differences were found between the two groups for fever, halitosis, dental pain or cough. Conclusion: We conclude that patients with CRScNP have a greater burden of symptoms of CRS and a much higher prevalence of hyposmia/anomsia. These findings are consistent with other studies showing that, in comparison to CRSsNP, CRScNP tends to be more difficult to treat and have a higher rate of relapse after intensive medical therapy (Subramanian et al, Am J Rhinology 2002;16:303).
L.E. Mansfield 1* , E.E. Philpot 2 , C. Posey 1 , 1. El Paso, TX; 2. Research Triangle Park, NC.
Daytime sleepiness is a common complaint in SAR. Patients often complain of mental slowness, difficulty in concentrating, and thinking. The present study evaluated whether effective therapy of SAR would decrease DSS and improve an objective measure of CP. DSS was measured using the Epworth Sleep Scale (ESS). Objective CP was measured using the Test of Variables of Attention (TOVA), a validated test. Thirty two adults (15 Males, 17 Females with a 2 year history of SAR, a compatible physical exam, and corresponding positive allergy testing) volunteered for this 3 week randomized double blind placebo controlled study. After a one week INF placebo (Pl) baseline, the subjects received either active INF or continued Pl. They maintained daily nasal symptom dairies and ESS. The subjects took the TOVA test at the end of Week1 and Week3. Weekly Nasal Symptom Scores significantly improved with the INF, but not the Pl. W1 vs. W3 Nasal Congestion INF 29, 24 p=.03, Pl 29, 26 p=ns; Runny Nose INF 22.5, 19.9 p=ns; Pl 21.75, 21.38 p=ns; Sneezing INF 26.5, 19 p=.01; Pl 24.9, 21.1 p=ns. Total weekly ESS was abnormal and decreased significantly in the INF group, but not in PL group. W1 vs. W3 INF 60.5, 46.5 p=.001, Pl 52.6, 46.8 p=ns. Response time of the TOVA testing, initially somewhat slow, significantly decreased in INF but not PL treatment. W1 vs. W3 INF 435 msec, 385 msec p=.02; Pl 360 msec, 359 msec p=ns. These results demonstrate that SAR is associated with DSS and CP problems. The mechanism is likely to be sleeping disordered breathing associated with nasal congestion and obstruction. Effective treatment of nasal congestion with INF led to decreased DSS and improved cognitive performance.
L.E. Mansfield 1* , C. Graham 2 , 1. El Paso, TX; 2. New York, NY.
There is increasing recognition that sleep disturbance and daytime tiredness occur during active AR. The mechanism appears to be nasal congestion and obstruction leading to sleep disordered breathing and resultant poor quality of sleep. In our practice, as part of the initial history, questions regarding fatigue, snoring, sleep problems, and tiredness are addressed. Sleep problems and Tiredness are graded according to the following scale: Effect on Daily Activity ; 0=not troubled;1= a little trouble; 2=somewhat troubled ;3= trou-bled a lot ; 4= total disruption. We reviewed 272 consecutive charts of patients with allergic rhinitis documented by history, physical examination and allergy testing. There were 169 females and 103 males; age range 5y to 84y. 127 (47%) of patients or parents recognized they commonly snored. 40 (15%) stated they were chronically fatigued. The graded answers concerning sleep problems and tiredness were even more revealing of AR patient's perception of their problems See Table In general, the higher sleep problem responses were associated with higher tiredness scores. National surveys of unselected populations suggest that about 10 percent of adults consider themselves to have sleep problems. The high frequency of sleep related problems and tiredness in our sample has prompted us to add more detailed questions regarding sleep related events to our intake history. It is our opinion that questions specifically related to sleep and daytime tiredness should be included in all evaluations for allergic rhinitis. We conclude that sleep related problems and tiredness may be more common in patients with allergic rhinitis than previous reported.
R.W. Weber 1* , J. Garcia 2 , R. Faruqi 2 , D. Banerji 2 , G. Georges 2 , The Study 405 Investigator Group 3 , 1. Denver, CO; 2. Bridgewater, NJ; NJ. Introduction: The intranasal glucocorticosteroid triamcinolone acetonide (TAA) is a safe and effective treatment for persistent allergic rhinitis (PAR). A new hydrofluroalkane-134a (HFA) propellant delivery system (TAA-HFA) has recently been developed. This study primarily assessed the long-term safety of TAA delivered via this new device, as well as its long-term efficacy. Methods: 396 patients aged 12-69 yrs (mean=32) with PAR enrolled in this 1-yr, open-label study at 10 centers in the US. Patients received TAA-HFA 220 μg once daily for a 2-week run-in period before adjusting the dose to 440 μg or 110 μg once daily based on symptom severity. Doses were standardized to 440 μg once daily across all patients at ~4 months to ensure sufficient long-term safety data at the maximum dose. Physical exams, including measurement of vital signs and laboratory measurements were taken at baseline, 6 months and study end. Independent patient and physician global symptom evaluations were performed at baseline, week 2 and months 1-12 thereafter. Patients recorded any adverse events (AEs) on daily diary cards. Results: Of the 396 patients included in the study, 349 (88.1%) reported AEs. The incidence of AEs was similar to that of other comparable allergic rhinitis long-term studies. The most frequently reported AEs were pharyngitis, rhinitis, local reactions, headache, epistaxis and sinusitis (Table 1) . Most AEs were mild-to-moderate in intensity; 34 patients withdrew from the study due to AEs. There were no clinically relevant changes in physical exams, vital signs or laboratory measurements. A total of 4 serious AEs (SAEs) were reported; breast carcinoma (n=1), depression (n=1), post-operative spinal fluid leak (n=1) and staphylococcal infection (n=1). SAEs were thought to be not related to the study drug. At final visit, 83% of patients had either moderate or marked/complete relief of symptoms using global symptom scores. Similarly, 86% of physicians rated their patients as having either moderate or marked/complete relief. Conclusions: Long-term administration of TAA-HFA 440 μg exhibited a good safety and tolerability profile, while providing moderate-to-complete symptom relief in more than 80% of patients treated for PAR. Introduction: Second-generation, 'non-sedating' antihistamines (AHs) have lower tendency to cross the blood-brain barrier and cause central nervous system side effects than first-generation agents. However, studies have suggested differences between second-generation AHs regarding cognitive function impairment. Methods: A MEDLINE literature search was performed using the search terms 'antihistamine AND impairment', 'antihistamine AND psychomotor' and 'antihistamine AND central effects', as well as with individual AH names (acrivastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine and mizolastine). The findings for second-generation AHs were reviewed and well-designed, placebo-and positive-controlled studies in humans using objective measures of cognitive impairment were included. Results: 43 publications were identified as the inclusion criteria. All included objective assessments such as driving performance, critical flicker fusion and divided attention tasks. There was a large variation in the numbers of available well-designed studies; the most rigorously assessed agents were fexofenadine and cetirizine. A number of the AHs (ebastine, acrivastine, loratadine, mequitazine and mizolastine) were not impairing at recommended doses, but were at higher doses. In a small number of available studies, the newer AHs desloratadine and levocetirizine produced no impairment at recommended doses (5 mg); however, higher doses were not investigated. Cetirizine studies were variable; impairment at the recommended 10 mg dose or higher was seen in a number of studies. In contrast, fexofenadine HCl, up to a dose of 360 mg, was non-impairing in a large number of studies. Only one study indicated impairment in one task (critical tracking) and this was only observed with the first doses of fexofenadine HCl (120 and 180 mg) and not subsequent doses; however, the authors concluded that doses up to 240 mg/day should be safe for patients who drive. Conclusion: While second-generation AHs are less impairing than the first-generation, some newer AHs produce impairment at or above the recommended dose. These differences become important to the patient when agents cause sedation or if patients over use beyond the recommended dose. In conclusion, Fexofenadine was the only AH found to be non-impairing in all studies, even at double the recommended US dose.
S. Shaver 1 , R.B. Berkowitz 1* , C. Lutz 1 , P. Jones 1 , C. Qiu 2 , S. Meeves 2 , S.T. Varghese 2 , G. Georges 2 , 1. Woodstock, GA; 2. Bridgewater, NJ.
Introduction: Fexofenadine (FEX) is a H1-receptor antagonist, with proven efficacy in the treatment of allergic rhinitis (AR). To date, no live cat-room challenge studies have assessed the efficacy of FEX in cat-allergen induced AR. This study assessed the efficacy of a single dose of FEX HCI 180 mg in preventing and controlling cat-allergen induced AR using the cat-room challenge model. Methods: This single-center, prospective, randomized, doubleblind, placebo-controlled, two-way crossover study consisted of a screening visit, one or two priming visits and two treatment periods, separated by a 14 (±3)-day wash-out. Qualifying subjects were randomized to treatment Sequence 1 (placebo followed by FEX) or 2 (FEX followed by placebo). Baseline endpoints were obtained prior to study drug administration, and 5 minutes before entering the cat challenge room for allergen challenge. Allergen challenges were initiated 1.5 hours post-dose, for both treatment periods. The primary endpoint was the change from baseline in total symptom score (TSS; sum of rhinorrhea, itchy nose/palate/throat, sneezing and itchy/watery/red eyes) after 30 minutes of allergen exposure at 2 hours post-dose, compared with placebo. Other endpoints included changes in individual symptom scores, including nasal congestion. Levels of airborne Felis domesticus allergen 1 (Fel d 1) were determined. Results: Of 211 subjects screened, 66 were randomized and 63 completed the study; 32 and 31 in Sequence 1 and 2, respectively. Mean change in TSS from baseline was significantly less with FEX compared with placebo at 30 minutes after initiation of the cat allergen challenge (p=0.0327). Significantly greater percentage reductions in the individual symptom scores for sneezing (p=0.0037) and nasal congestion (p=0.0455) were observed with FEX compared with placebo, 30 minutes after challenge. Although levels of Fel d 1 varied widely, they were balanced between treatment groups. The overall incidence of treatment-emergent adverse events (AEs) was low and comparable between groups; no serious AEs occurred. Conclusion: This study demonstrated that a single dose of FEX HCI 180 mg is effective and well tolerated as a prophylactic agent for alleviating the AR symptoms induced by exposure to cat allergen. Further large-scale clinical trials are warranted to confirm these findings. Rationale: Allergic rhinitis in children is thought to be associated with several co-morbid disorders. We conducted the following study to assess whether children with diagnosed hypertrophy of tonsils and/or adenoids evaluated by an allergist were more likely to demonstrate objective evidence of allergen sensitization than children similarly evaluated without evidence of these upper airway obstructions. Methods: Records from the past ten years were identified in the hospital database by presence of an Allergy clinic visit and an ICD-9 code for hypertrophy of adenoids and/or tonsils. We reviewed these records to confirm that the diagnosis was accurate. We included subjects if reliable skin prick or in vitro testing for specific IgE to aeroallergens was performed. For comparison, we randomly obtained an age and testing-type similar sample. First group subjects were excluded from the second group. Skin testing was performed with commercial allergen extracts applied with a Dermapik©. In vitro testing was by UniCAP© FEIA. Positive skin testing had at least a wheal 3 mm or flare 10 mm greater than the negative control. Positive in vitro values were 0.7 KU/L or greater or a positive pollen mix. Additionally, we performed a search in an insurance database to determine how many local children had a code for allergic rhinitis. Results: Of 202 pediatric Allergy patients with adenoid/tonsillar hypertrophy tested, 41.6% (95% CI +/-6.8%) had at least one positive test. In 802 without adenoid/tonsillar hypertrophy, 50.7% (95% CI +/-3.5%) had at least one positive test. The observed difference was 9.1 % (95% CI +/-7.6%). The Standard error of the difference in percentage was 3.94; the Z score was 2.3. The corresponding P value is 0.02. The percentage of 70, 356 children with an allergic rhinitis ICD-9 was 15.6% (95% CI +/-0.3%). Conclusion: The number of allergist-referred children with adenoid and/or tonsillar hypertrophy testing positive for an aeroallergen is slightly less than the number of similar children without these diagnoses testing positive. It is not clear that adenoid/tonsillar hypertrophy is associated with a higher risk of allergic rhinitis. A prospective study with allergy testing of all children with adenoid and/or tonsillar hypertrophy might provide information that could alter referral patterns.
W.E. Berger 1* , W. Storms 2 , S. Kimura 3 , M. Beck 4 , S. Galant 5 , T. Westbrook 3 , 1. Mission Viejo, CA; 2. Colorado Springs, CO; 3. Pensacola, FL; 4. Miami, FL; 5. Orange, CA. Background: Patients having allergic rhinoconjunctivitis are often treated with nasal spray or systemic allergy therapy, forgoing therapy specifically targeting ocular symptoms. The rhinitis quality of life questionnaire (RQLQ) and allergic conjunctivitis quality of life questionnaire (ACQLQ) instruments can be used to quantify the relative benefit of varying medication regimens. Objective: To determine the extent of benefit gained in quality of life when an eye drop treatment for ocular allergy (olopatadine) was added to rhinitis patients' preexisting regimen of nasal or systemic allergic treatment. Methods: This was a four week prospective, multi-center, open-label crossover, quality of life study occurring during allergy season. At visit 1, patients completed the RQLQ and ACQLQ questionnaires to assess baseline quality of life. Patients were randomized to receive ocular allergy therapy (olopatadine, Patanol BID) concomitant with their systemic or nasal rhinitis treatment(s) for 2 weeks between either visit 1 and Visit 2 (Group A) or between Visit 2 and Visit 3 (Group B). At Visit 2 and Visit 3, patients completed the RQLQ and ACQLQ. Results: A total of 200 patients completed this study: 97 in Group A, 103 in Group B. Of these, 181 (90.5%) experienced eye allergy symptoms at least 1 day during the previous week as reported in the baseline ACQLQ. Baseline scores of the RQLQ and ACQLQ for both groups were comparable. Clinically significant improvement from baseline in global RQLQ and ACQLQ was seen following addition of ocular therapy for both groups (RQLQ: -1.07, -0.94; ACQLQ: -1.2, -1.2). Similar improvement was seen across all domains of both questionnaires. The ACQLQ correlated with the RQLQ in the applicable domains. Conclusion: Many allergic rhinitis patients using nasal or systemic medication also suffer from ocular allergic symptoms. For these patients, quality of life improvement is not maximized; the addition of a topical antiallergy eye drop can result in beneficial effects on quality of life. In this study, the addition of olopatadine eye drops to these patients' medication regimens resulted in significant improvement in not only eye symptom related quality of life domains but in overall quality of life.
H. Milgrom 1* , R. Lanier 2 , F.C. Hampel 3 , B. Kittner 4 , 1. Denver, CO; 2. Fort Worth, TX; 3. New Braunfels, TX; 4. Bridgewater, NJ. Introduction: Fexofenadine, a non-sedating, selective H1-receptor antagonist, is currently indicated for use in children aged 6-11 years with seasonal allergic rhinitis in a number of countries, including the US, and has an excellent safety profile in this age group. This study was designed to assess the safety and tolerability of fexofenadine in children aged 2-5 years with allergic rhinitis (AR). Methods: The study had a multicenter, double-blind, randomized, placebo-controlled, parallel-group design. Children aged 2-5 years (n=453) with AR were randomized 1:1 to either placebo twice daily (BID; n=231) or fexofenadine HCl 30 mg BID (n=222), for 2 weeks. Both treatments were given orally as granulated powders (capsule content) mixed with two teaspoons of apple sauce. Treatment-emergent adverse events (TEAEs) were recorded for all subjects by parents/caregivers and assessed by investigators. Clinical laboratory variables, physical examinations, vital signs and ECG evaluations were also assessed in a subgroup of children (placebo, n=79; fexofenadine, n=71). Results: Baseline demographics were similar in both treatment groups. While approximately 50% of children in both groups experienced at least one TEAE, no unusual or unexpected TEAEs were observed in the fexofenadine group. When the total group was analyzed for TEAEs by body system, or assessed separately by age groups of 2-, 3-, 4-and 5-year-olds, no clinically meaningful differences were observed between the two treatment groups. In both treatment groups, the majority of subjects overall and in each age group experienced TEAEs rated as mild or moderate in intensity. Few subjects experienced TEAEs considered possibly related to study medication (placebo: 8.2% [19/231]; fexofenadine: 9.5% [21/222]). The percentage of discontinuations due to TEAEs was also comparable between treatment groups (placebo: 6.9% [16/231]; fexofenadine: 5.0% [11/222] ). In the subgroup assessment, no clinically relevant changes were seen from baseline for laboratory variables, vital signs, ECGs or physical examinations in either treatment group. Introduction: The efficacy and safety of fexofenadine HCl 30 mg BID has been proven in two large Phase III studies in pediatric subjects aged 6 to 11 years with seasonal allergic rhinitis. In addition, the safety of fexofenadine has been demonstrated in pediatric subjects 2 to 5 years of age with allergic rhinitis (AR). Subsequently, two studies (T/3001; T/3002) have assessed the pharmacokinetics, safety and tolerability of fexofenadine 15 and 30 mg BID in pediatric subjects 6 months to 2 years of age. Methods: Both studies were of multicenter, randomized, double-blind, placebo-controlled, parallelgroup design and enrolled pediatric subjects aged 6 months to <1 year weighing 10.5 kg and aged ±1 year to <2 years weighing >10.5 kg. All subjects had a diagnosis of AR as assessed by previous medical history, pattern, or suggestive physical findings. Subjects were randomized to receive fexofenadine HCl 15 mg (T/3001), or 30 mg (T/3002) granulation powder twice-daily, or placebo for a minimum of 7 days. Safety was evaluated based on adverse events (AEs), vital signs, 12-lead electrocardiograms (ECGs), and physical examinations. Results: A total of 174 and 218 subjects were randomized in studies T/3001 (fexofenadine HCl 15 mg BID: n=85, placebo: n=89) and T/3002 (fexofenadine HCl 30 mg BID: n=108, placebo: n=110), respectively. In T/3001, 40.0% (34/85) of children receiving fexofenadine and 42.7% (38/89) receiving placebo experienced at least one treatment-emergent AE (TEAE). In T/3002, the incidences of TEAEs were 35.2% (38/108) and 52.7% (58/110), respectively. In both studies, most of the TEAEs experienced were mild or moderate in intensity. The incidence of possibly-related TEAEs was also similar for both treatments in each study. No clinically relevant changes from baseline to study end were observed for vital signs, ECGs and physical examinations. Conclusions: The findings of this study show that fexofenadine 15 mg and 30 mg BID are well tolerated and have a safety profile comparable to placebo in pediatric subjects aged 6 months to 2 years. For Seasonal Allergic Rhinitis (SAR) patients that remain symptomatic on an H1-receptor antagonist, Cetirizine, and a nasal glucocorticosteroid, Mometasone furoate, the addition of Omalizumab, a recombinant, humanized, chimeric, anti-IgE monoclonal antibody, may provide additional efficacy in sub-optimally controlled Seasonal Allergic Rhinitis patients. In this open labeled 12week trial, 20 patients with symptomatic SAR currently using Cetirizine, 10 mg QD, + Mometasone furoate, 100 mcg/nostril QD, were randomized to continue the existing therapy Cetirizine + Mometasone or to add-on Omalizumab subcutaneously (every 2 weeks to 4 weeks) dosed according to patient's weight, and baseline IgE levels to the existing therapy Cetirizine + Mometasone furoate. The endpoints of the trial include: rhinomanometry, nasal symptom score (composite score of nasal congestion, rhinorrhea, sneezing, post nasal drip and itching) and flexible rhinopharyngolaryngoscopy examination. Mean efficacy measurements at the end of the 12-week trial revealed a significant improvements in all parameters examined in the treatment group receiving Omalizumab (as add-on to the existing therapy), compared to the other group. In conclusion, the addition of Omalizumab to the combination of Cetirizine plus Mometasone furoate, is more effective than the combination of cetirizine plus Mometasone furoate, for the treament of Seasonal Allergic Rhinitis patients. It appears that when Omalizumab is added to the combination H1receptor antagonist, Cetirizine, and nasal corticosteroid, Mometasone furoate, the primary end points (rhinomanometry and symptom scores) are significantly improved. Background: Based on the official statistic data, the prevalence of allergic diseases in Russia has increased more than 3 times during the past 10-15 years, but still the lowest of all European countries. In some studies done in some regions of Russia based on ISAAC program, it has been shown that the prevalence allergies is significantly higher than indicated in official statistics of health departments. The goal of this investigation was to study the prevalence of allergic diseases, in children of South Russian region. Meth-ods: This study was done in two steps according to ISAAC program guidelines. In the first step a questionnaire was given to a total of 6558 school children, ages 7 to 8 (group A) and 13 to14 years old (group B), from the two cities of Krasnodar and Novorossiysk in Southern Russia. In the second step a physical exam, skin prick tests with different allergens (pollens, molds, cat, dust mites, foods etc.), and pulmonary function tests were performed. Results: Wheezing was reported in 12.9% of group A and 15.3% of group B children within the past 12 months. The severity of asthma reported was mild in 72% (group A)-84% (group B); moderate in 16.7% (group A)-10.7% (group B) and severe in 3.4% (group A)-5.8% (group B) in studied children). Majority of the cases of asthma was noted to be allergic asthma. In both groups of children there was a high incidence of allergies to perennial allergens such as dust mites, cats, molds and other indoor allergens, 18.7% (group A) and 77.3% (group B). The percentage of allergies to pollens was 19.1% and 33.0%, accordingly. Allergic rhinitis symptoms were noted in 26.6% (group A) and in 38, 6% (group B). Atopic dermatitis symptoms with skin itching observed in 8.3% (7-8 years old)and 5.3% (13-14 years old). Family history of atopy was noticed in 34.6% of group A and 41.6% of group B children. Conclusions: The prevalence of allergic diseases in South Russia is similar to the ones in most of the European countries. The prevalence of asthma has been associated with increased incidence of allergies, due to indoor and pollen allergens. The prevalence in rhinitis and atopic dermatitis in South Russia is parallel to asthma. Acknowledgement: We would like to thank Hollister-Stier Lab., Greer and Antigen Lab. for allergen samples. Objective: To examine the cost and effectiveness of telithromcyin vs. azithromycin for treatment of mild acute sinusitis under current levels of antimicrobial resistance. Methods: We considered an adult with mild acute sinusitis, and symptom duration of 7 days. A decision analytic model was created to compare 2 strategies of 1st-, 2nd-and 3rd-line therapies: azithromycin/amoxicillin-clavulanate/levofloxacin (AZI/AMC/LEV), and telithromycin/amoxicillin-clavulanate/levofloxacin (TEL/AMC/LEV). We considered 3 outcomes: response to initial therapy, cost, and time to completion of all antibiotic therapy. Clinical resolution was due to response to antibiotic, or to spontaneous resolution. We assumed bacteria that were resistant in vitro would only be resistant in vivo 50% of the time. Resistance levels were based on the 2000-2001 US PROTEKT surveillance study. Model parameters, such as prevalence of bacterial infection, frequency of causative pathogens, and rates of spontaneous resolution, were based on the published literature. Those failing to improve after 5 days were switched to next line therapy. We analyzed claims data from 8 managed care organizations to estimate non-drug charges for initial and follow-up care, and applied a 60% cost-to-charge ratio. Drug costs were estimated using the wholesale acquisition cost plus $8 for overhead and dispensing. All costs were adjusted to year 2004 $US. Results: The model predicted the TEL/AMC/LEV strategy would result in 71.8% improving by 5 days compared to 65.4% for AZI/AMC/LEV. The telithromycin strategy had lower mean cost, $172 vs. $176. Although telithromycin cost more than azithromycin, the TEL/AMC/LEV strategy had slightly lower total drug costs ($95 vs $96) due to less need for additional antibiotic courses. Mean time to completion of therapy was 8.4 days for TEL/AMC/LEV and 9.1 days for AZI/AMC/LEV. Sensitivity analyses showed that TEL/AMC/LEV had superior health outcomes even when only 5% of in vitro resistant organisms were also resistant in vivo. TEL/AMC/LEV also had lower cost if at least 30% of cases were bacterial, or if in vitro resistant organisms were at least 30% resistant in vivo. Conclusion: Based on results obtained using this decision analytic model, initial treatment of mild acute rhinosinusitis with telithromycin may result in improved outcomes and lower cost than initial treatment with azithromycin. Rationale: "Delta crud" is the term used to describe rhinosinusitis syndromes in the Mississippi Delta region. Local perception is that it is associated with chemical crop dusting, regional produce, especially cotton, or high rates of mold allergy. The climate is extreme with mild winters, hot humid summers, and large volume rain. Thirty-five percent of inhabitants live below the poverty level, 62% are African American. Patients from the agriculturally intensive Delta suffer from asthma at almost twice the rate of those in the neighboring hills. Rates of pesticide use are among the highest in the nation. There are no prevalence estimates for rhinosinusitis in this region. "Delta Crud" is chronic in many patients with exacerbations occurring in the summer and fall, especially during chemical spraying and defoliation. We conducted this cross-sectional questionnaire based pilot study to begin characterization of rhinosinusitis in this population. Method: The Sinusitis Treatment Outcome Questionnaire, with two modifications, was given to consecutive patients presenting to the North Sunflower regional hospital ER and the Sunflower outpatient clinic one month prior to the beginning of summer crop dusting. The question, "Do you have Delta Crud?" was added. The survey was anonymous, allowing IRB exemption. RESULTS: 91 consecutive patients returned completed questionnaires. 46(50%) admitted to having "Delta Crud". Patients who claimed to have Delta Crud had significantly more sinus headache, nasal pruritus, conjunctivitis, and chest symptoms (see table) . There was no significant difference in antibiotic prescriptions, ER visits, and missed work. Six patients with Delta Crud had been hospitalized for "allergy reasons" compared with three patients without Delta Crud. Despite severe symptoms just 4 patients received sinus CT scans. Only 10/46 patients were prescribed intranasal corticosteroids. Conclusion: In our pilot study, the prevalence of chronic rhinosinusitis symptoms (Delta Crud) is 50%, with severe sinus, pulmonary and ocular symptoms. Evaluation and treatment may be suboptimal in this economically disadvantaged rural region. Further characterization of "delta crud", pollen counts, IgE mediated disease, environmental contributions and comparative studies of related regions are needed. Introduction: Patients with rhinitis commonly experience sinus pain and pressure (SP+P). Many patients with recurrent acute bacterial sinusitis (RABS) base the presence of a recurrence on the severity of SP+P and other nasal symptoms. The ability of patients to differentiate between rhinitis and RABS was evaluated by reviewing the subject screening logs of 4 previously reported clinical trials of Flonase (fluticasone propionate) Nasal Spray, 50 mcg (FP).
Methods: The efficacy of FP was studied in two trials in subjects with SP+P due to allergic rhinitis and in two trials of subjects receiving cefuroxime axetil to treat an acute episode of RABS. SP+P screening logs were examined to determine how many subjects who thought they had SP+P were excluded from the study for an upper respiratory or sinus infection. RABS screening logs were examined to determine how many subjects with symptoms of an acute episode of RABS were excluded from the study for a negative sinus x-ray or CT scan. RABS symptoms experienced at the screening visit by subjects who qualified for the study were also evaluated. Results: Of 505 subjects screened in the SP+P studies, only 4 (0.8%) were excluded for evidence of sinus or upper respiratory tract infections, as clinically diagnosed by the investigator. Out of 1502 subjects with screening log data in the RABS studies, 649 (43.2%) were excluded for a negative sinus x-ray or CT scan. Of the 704 subjects who qualified for the RABS study, the most prevalent symptoms included nasal congestion (100%), mucopurulent discharge (97%), facial pain or tenderness in the sinus area (93%), sinus headache (90%) and malaise (90%). Only 15% of subjects had a fever. Only one symptom, nasal congestion, was rated by clinicians as severe for greater than 40% of subjects in either study (46% and 43%). Conclusions: While most subjects can determine when SP+P is due to allergic rhinitis, many cannot determine when symptoms progress to a sinus infection. Symptoms experienced by subjects with RABS were consistent with inflammation, but did not include fever as may be expected with an untreated bacterial sinus infection. Under appreciation by patients for the role of inflammation in sinus disease may result in over self-diagnosis of sinus infection and the demand for antibiotics. Liposomes are small particles consisting of lipid bilayer membranes, which are used to deliver drugs including amphotericin B, more efficiently and with less toxicity. Very few cases of allergy to liposomal amphotericin B (LAB) have been reported to date. Although there is a report on conventional amphotericin B (CAB) desensitization, to our knowledge no case of LAB desensitization has been described yet. A 75 y/o patient with lymphoma was treated with LAB for pulmonary aspergillosis. Within 30 minutes of infusion he developed urticaria, hypotension and tachycardia for which he was treated with the appropriate drugs for anaphylaxis. A second attempt to re administer LAB resulted in a similar anaphylactic reaction. Desensitization to LAB was then successfully completed using a modified protocol based on desensitization to CAB (JACI 1995; 96:425-7) : 0.0005 mg infusion over 10 minutes 0.005 mg infusion over 10 minutes 0.05 mg infusion over 10 minutes 0.5 mg infusion over 30 minutes 5 mg infusion over 30 minutes 50 mg infusion over 30 minutes 100 mg infusion over 30 minutes 200 mg infusion over 120 minutes Conclusion: desensitization to LAB, a lifesaving drug for invasive fungal diseases, can be performed successfully.
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