PMC:4631427 / 6766-13487 JSONTXT

{"project":"TEST0","denotations":[{"id":"26604803-237-243-1382644","span":{"begin":275,"end":277},"obj":"[\"20004784\"]"},{"id":"26604803-237-243-1382645","span":{"begin":278,"end":280},"obj":"[\"15536426\"]"},{"id":"26604803-114-120-1382646","span":{"begin":597,"end":599},"obj":"[\"18589838\"]"},{"id":"26604803-113-119-1382647","span":{"begin":1613,"end":1615},"obj":"[\"24229825\"]"},{"id":"26604803-98-104-1382648","span":{"begin":1711,"end":1713},"obj":"[\"21272928\"]"},{"id":"26604803-230-236-1382649","span":{"begin":1861,"end":1863},"obj":"[\"22738678\"]"},{"id":"26604803-192-198-1382650","span":{"begin":2056,"end":2058},"obj":"[\"24991453\"]"},{"id":"26604803-229-235-1382651","span":{"begin":2422,"end":2424},"obj":"[\"17602945\"]"},{"id":"26604803-233-239-1382652","span":{"begin":2824,"end":2826},"obj":"[\"24991453\"]"},{"id":"26604803-236-242-1382653","span":{"begin":2827,"end":2829},"obj":"[\"6204202\", \"1294076\", \"3549903\"]"},{"id":"26604803-232-238-1382654","span":{"begin":3161,"end":3163},"obj":"[\"2840522\"]"},{"id":"26604803-235-241-1382655","span":{"begin":4538,"end":4540},"obj":"[\"2809025\"]"},{"id":"26604803-231-237-1382656","span":{"begin":4541,"end":4543},"obj":"[\"2918186\"]"},{"id":"26604803-234-240-1382657","span":{"begin":4834,"end":4836},"obj":"[\"2715549\"]"},{"id":"26604803-237-243-1382658","span":{"begin":4837,"end":4839},"obj":"[\"4056964\"]"},{"id":"26604803-149-155-1382659","span":{"begin":5188,"end":5190},"obj":"[\"2715549\"]"},{"id":"26604803-232-238-1382660","span":{"begin":5488,"end":5490},"obj":"[\"10469035\"]"},{"id":"26604803-237-243-1382661","span":{"begin":5580,"end":5582},"obj":"[\"16095141\"]"},{"id":"26604803-231-237-1382662","span":{"begin":6128,"end":6130},"obj":"[\"8616415\"]"},{"id":"26604803-234-240-1382663","span":{"begin":6131,"end":6133},"obj":"[\"9651458\"]"}],"text":"Diagnosis\nAll patients with a history of clinical reaction to peanut or tree nuts should be referred to an allergist for further evaluation. OFC remains the gold standard for diagnosis of any food allergy but is not always used given the risk of severe anaphylactic reaction.23,29 More often, the diagnosis of peanut or tree nut allergy is based upon a convincing clinical history, positive testing via skin prick or serum food-specific IgE, and rarely, if needed, confirmatory OFC. Specific IgE testing, either by skin prick or serum food-specific IgE, is not always sensitive or highly specific,30 especially in the absence of convincing clinical history of anaphylaxis to the food in question. It is also important to note that allergy testing correlates only with the risk of reactivity to foods but does not predict severity of future reactions. Intradermal skin testing to foods can induce severe reactions and should not be performed. Other diagnostic methods such as the atopy patch test remain controversial and are generally not recommended for the diagnosis of food allergy.31\nFor peanut specifically, there has been recent development in component testing for diagnosis. This includes serum-specific IgE for various peanut proteins such as Ara h 1, 2, 3, and 8. The clinical utility of component testing remains yet to be fully determined, but testing to these proteins in patients allergic to peanut has been shown to be more specific and may correlate with various clinical phenotypes. For example, IgE to Ara h 2 was shown to be more specific than testing to whole peanut IgE when confirmed by OFC.32 IgE to storage proteins, Ara h 1, 2, and 3, has been associated with severe allergic reactions,33 whereas Ara h 8 seems to correlate with milder, oral-allergy symptoms, likely due to structural similarities to the major allergen in birch pollen.34\nTo verify acute anaphylaxis triggered by nuts or other foods, serum total tryptase level can be utilized, though may be less sensitive than in cases of drug or hymenoptera-induced anaphylaxis.35 Tryptase is abundant in mast cell secretory granules and the levels immediately increase, peaking ~1–2 hours after onset of symptoms. Importance of obtaining a timely sample makes clinical utilization difficult. Ideally, a serum tryptase level should be obtained within 3 hours of symptom onset, as levels return to baseline within 24 hours of symptom resolution.36 In cases of food-induced anaphylaxis, however, often serum tryptase is not elevated, even when sent within an appropriate time frame. This may be due to the activity of mucosal mast cells and basophils involved in food-induced anaphylaxis, which contain less tryptase compared with cutaneous mast cells that are more frequently activated in other causes of anaphylaxis, such as drugs or hymenoptera.35,37–39\nOther laboratory markers that have been studied in anaphylaxis include serum histamine, urinary histamine metabolites, and concentration of angiotensin-converting enzyme (ACE). ACE is an enzyme involved in bradykinin catabolism, and angioedema is a known side effect for up to 0.7% of patients taking ACE-inhibiting medications.40 Regarding ACE levels, one study of peanut- and tree-nut-allergic individuals found an increased risk of severe pharyngeal edema in those patients having ACE concentrations in the lowest quartile (\u003c37.0 mmol/L).28 Serum histamine is a less practical marker as it peaks within 10 minutes of anaphylaxis onset and returns to baseline values within 1 hour. Urinary histamine metabolites may be of better utility as these can remain elevated up to 24 hours following an episode of anaphylaxis; however, their utility in clinical practice is limited.\n\nCross-reactivity between nuts\nAlthough clinical cross-reactivity between nuts may be difficult to establish, the possibility of exhibiting symptoms of food allergy to multiple nuts plays an important role in the management of patients allergic to nut, especially for children who are of an age where identification of individual nuts is incomprehensible. The summary of nut cross-reactivity is given in Table 1. It is common to find positive testing (skin prick or serum-specific IgE) to other legumes in those patients with history of clinical reaction to peanut. A study of 62 children with legume allergy found 79% of patients with serologic evidence of IgE binding to at least one additional legume and 37% had IgE binding to all six legumes tested, including peanut, soybean, lima bean, pea, garbanzo bean, and green beans.41,42 Despite this common finding of cross-sensitization, the rate of clinical allergy to multiple legumes is much lower. This has been demonstrated in multiple studies of children with peanut allergy, in which double-blind, placebo-controlled OFCs were used to assess clinical reactivity to soy.43,44 Although a good proportion (up to 31%) of patients allergic to peanut exhibited a positive skin test result to soy, significantly fewer children had clinical reactivity to both legumes (only 1%–3%). Another study of children with atopic dermatitis showed no reaction to any other legumes tested in children sensitive (skin test positive) to peanut.43\nCo-sensitization between peanut and tree nuts is common; however only one-third of patients with peanut allergy also exhibit clinical allergy to one or more tree nuts.31 For example, one study in the UK found 59% of peanut-sensitized patients were also sensitized to hazelnut, Brazil nut, or both.45 Other studies have found limited serologic cross-reactivity between peanut and tree nuts.46 For patients with an allergy to peanut, it is important to consider age, risk of cross-contamination, and implications of dietary restrictions before recommending a peanut versus completely nut-free diet.\nSimilarly, patients allergic to tree nut frequently exhibit sensitization to other tree nuts. In particular, associations between certain nuts, for example, cashew–pistachio and walnut–pecan, are particularly strong. Clinical cross-reactivity to multiple nuts has been reported in up to one-third of patients evaluated for tree nut allergy.47,48 In general, only foods that have elicited reactions should be avoided, and in tree-nut-allergic individuals, previously tolerated individual tree nuts that were negative in skin test can likely be continued. In special circumstances, such as for young children, it is not uncommon to suggest avoidance of all tree nuts as to avoid accidental exposure. Individual tree nuts that have not yet been introduced can be done so by OFC in the office, if necessary. Again, this decision should be made based on clinical history, risk of cross-contamination, age of the patient, and test results."}

{"project":"2_test","denotations":[{"id":"26604803-20004784-55579339","span":{"begin":275,"end":277},"obj":"20004784"},{"id":"26604803-15536426-55579340","span":{"begin":278,"end":280},"obj":"15536426"},{"id":"26604803-18589838-55579341","span":{"begin":597,"end":599},"obj":"18589838"},{"id":"26604803-24229825-55579342","span":{"begin":1613,"end":1615},"obj":"24229825"},{"id":"26604803-21272928-55579343","span":{"begin":1711,"end":1713},"obj":"21272928"},{"id":"26604803-22738678-55579344","span":{"begin":1861,"end":1863},"obj":"22738678"},{"id":"26604803-24991453-55579345","span":{"begin":2056,"end":2058},"obj":"24991453"},{"id":"26604803-17602945-55579346","span":{"begin":2422,"end":2424},"obj":"17602945"},{"id":"26604803-24991453-55579347","span":{"begin":2824,"end":2826},"obj":"24991453"},{"id":"26604803-6204202-55579348","span":{"begin":2827,"end":2829},"obj":"6204202"},{"id":"26604803-1294076-55579348","span":{"begin":2827,"end":2829},"obj":"1294076"},{"id":"26604803-3549903-55579348","span":{"begin":2827,"end":2829},"obj":"3549903"},{"id":"26604803-2840522-55579349","span":{"begin":3161,"end":3163},"obj":"2840522"},{"id":"26604803-2809025-55579350","span":{"begin":4538,"end":4540},"obj":"2809025"},{"id":"26604803-2918186-55579351","span":{"begin":4541,"end":4543},"obj":"2918186"},{"id":"26604803-2715549-55579352","span":{"begin":4834,"end":4836},"obj":"2715549"},{"id":"26604803-4056964-55579353","span":{"begin":4837,"end":4839},"obj":"4056964"},{"id":"26604803-2715549-55579354","span":{"begin":5188,"end":5190},"obj":"2715549"},{"id":"26604803-10469035-55579355","span":{"begin":5488,"end":5490},"obj":"10469035"},{"id":"26604803-16095141-55579356","span":{"begin":5580,"end":5582},"obj":"16095141"},{"id":"26604803-8616415-55579357","span":{"begin":6128,"end":6130},"obj":"8616415"},{"id":"26604803-9651458-55579358","span":{"begin":6131,"end":6133},"obj":"9651458"}],"text":"Diagnosis\nAll patients with a history of clinical reaction to peanut or tree nuts should be referred to an allergist for further evaluation. OFC remains the gold standard for diagnosis of any food allergy but is not always used given the risk of severe anaphylactic reaction.23,29 More often, the diagnosis of peanut or tree nut allergy is based upon a convincing clinical history, positive testing via skin prick or serum food-specific IgE, and rarely, if needed, confirmatory OFC. Specific IgE testing, either by skin prick or serum food-specific IgE, is not always sensitive or highly specific,30 especially in the absence of convincing clinical history of anaphylaxis to the food in question. It is also important to note that allergy testing correlates only with the risk of reactivity to foods but does not predict severity of future reactions. Intradermal skin testing to foods can induce severe reactions and should not be performed. Other diagnostic methods such as the atopy patch test remain controversial and are generally not recommended for the diagnosis of food allergy.31\nFor peanut specifically, there has been recent development in component testing for diagnosis. This includes serum-specific IgE for various peanut proteins such as Ara h 1, 2, 3, and 8. The clinical utility of component testing remains yet to be fully determined, but testing to these proteins in patients allergic to peanut has been shown to be more specific and may correlate with various clinical phenotypes. For example, IgE to Ara h 2 was shown to be more specific than testing to whole peanut IgE when confirmed by OFC.32 IgE to storage proteins, Ara h 1, 2, and 3, has been associated with severe allergic reactions,33 whereas Ara h 8 seems to correlate with milder, oral-allergy symptoms, likely due to structural similarities to the major allergen in birch pollen.34\nTo verify acute anaphylaxis triggered by nuts or other foods, serum total tryptase level can be utilized, though may be less sensitive than in cases of drug or hymenoptera-induced anaphylaxis.35 Tryptase is abundant in mast cell secretory granules and the levels immediately increase, peaking ~1–2 hours after onset of symptoms. Importance of obtaining a timely sample makes clinical utilization difficult. Ideally, a serum tryptase level should be obtained within 3 hours of symptom onset, as levels return to baseline within 24 hours of symptom resolution.36 In cases of food-induced anaphylaxis, however, often serum tryptase is not elevated, even when sent within an appropriate time frame. This may be due to the activity of mucosal mast cells and basophils involved in food-induced anaphylaxis, which contain less tryptase compared with cutaneous mast cells that are more frequently activated in other causes of anaphylaxis, such as drugs or hymenoptera.35,37–39\nOther laboratory markers that have been studied in anaphylaxis include serum histamine, urinary histamine metabolites, and concentration of angiotensin-converting enzyme (ACE). ACE is an enzyme involved in bradykinin catabolism, and angioedema is a known side effect for up to 0.7% of patients taking ACE-inhibiting medications.40 Regarding ACE levels, one study of peanut- and tree-nut-allergic individuals found an increased risk of severe pharyngeal edema in those patients having ACE concentrations in the lowest quartile (\u003c37.0 mmol/L).28 Serum histamine is a less practical marker as it peaks within 10 minutes of anaphylaxis onset and returns to baseline values within 1 hour. Urinary histamine metabolites may be of better utility as these can remain elevated up to 24 hours following an episode of anaphylaxis; however, their utility in clinical practice is limited.\n\nCross-reactivity between nuts\nAlthough clinical cross-reactivity between nuts may be difficult to establish, the possibility of exhibiting symptoms of food allergy to multiple nuts plays an important role in the management of patients allergic to nut, especially for children who are of an age where identification of individual nuts is incomprehensible. The summary of nut cross-reactivity is given in Table 1. It is common to find positive testing (skin prick or serum-specific IgE) to other legumes in those patients with history of clinical reaction to peanut. A study of 62 children with legume allergy found 79% of patients with serologic evidence of IgE binding to at least one additional legume and 37% had IgE binding to all six legumes tested, including peanut, soybean, lima bean, pea, garbanzo bean, and green beans.41,42 Despite this common finding of cross-sensitization, the rate of clinical allergy to multiple legumes is much lower. This has been demonstrated in multiple studies of children with peanut allergy, in which double-blind, placebo-controlled OFCs were used to assess clinical reactivity to soy.43,44 Although a good proportion (up to 31%) of patients allergic to peanut exhibited a positive skin test result to soy, significantly fewer children had clinical reactivity to both legumes (only 1%–3%). Another study of children with atopic dermatitis showed no reaction to any other legumes tested in children sensitive (skin test positive) to peanut.43\nCo-sensitization between peanut and tree nuts is common; however only one-third of patients with peanut allergy also exhibit clinical allergy to one or more tree nuts.31 For example, one study in the UK found 59% of peanut-sensitized patients were also sensitized to hazelnut, Brazil nut, or both.45 Other studies have found limited serologic cross-reactivity between peanut and tree nuts.46 For patients with an allergy to peanut, it is important to consider age, risk of cross-contamination, and implications of dietary restrictions before recommending a peanut versus completely nut-free diet.\nSimilarly, patients allergic to tree nut frequently exhibit sensitization to other tree nuts. In particular, associations between certain nuts, for example, cashew–pistachio and walnut–pecan, are particularly strong. Clinical cross-reactivity to multiple nuts has been reported in up to one-third of patients evaluated for tree nut allergy.47,48 In general, only foods that have elicited reactions should be avoided, and in tree-nut-allergic individuals, previously tolerated individual tree nuts that were negative in skin test can likely be continued. In special circumstances, such as for young children, it is not uncommon to suggest avoidance of all tree nuts as to avoid accidental exposure. Individual tree nuts that have not yet been introduced can be done so by OFC in the office, if necessary. Again, this decision should be made based on clinical history, risk of cross-contamination, age of the patient, and test results."}