Corticosteroids
Systemic corticosteroids (prednisolone) have been the mainstay of treatment for IH, for several decades. The mechanism of action of steroids is not entirely clear, though it is postulated to have an inhibitory effect on the production of vascular endothelial growth factor A (VEGF-A) by stem cells in haemangiomas.[1718] Steroids are most effective in the early proliferative phase. The usual recommended dose is 2-4 mg/kg/day, which should be continued until cessation of growth or shrinkage of haemangioma followed by gradual tapering.[19] Oral steroids at a dose of 2-3 mg/kg/day result in 75% response, >3 mg/kg/day show 94% response but with greater side effects while a lesser dose of <2 mg/kg/day results in poor response and a rebound phenomenon in 70% of the cases.[19] Bennett et al. in their meta-analysis on the efficacy of corticosteroids for IH included 184 children in a 10-case series. Statistical analysis revealed that a mean prednisone dose of 2.9 mg/kg (range, 1-4.5 mg/kg/day) was used over a mean period of 1.8 months (range, 0.5-5.4 months) before the dose was tapered. The overall response rate was 84% (range, 60-100%) and the mean rebound rate was 36% (range, 0-65%).[19] In a recent study on 20 children with IH, the lesions responded to oral prednisolone at a mean dose of 3.1 mg/kg/day given for a mean duration of 9.16 weeks (range, 3-15 weeks). The mean total duration of treatment including the tapering dose used was 29.9 weeks (range, 15-44 weeks). Overall, 90% of the cases showed >25% improvement with no case of rebound phenomenon during their follow up period of 6 months to 1 year.[20]
High dose pulse corticosteroids (methyl prednisolone 30 mg/kg/day infused over 1 hour daily for 3 days) may be useful in IH which need immediate therapeutic response (e.g. large peri-ocular IH with complete visual axis occlusion or large airway haemangioma with respiratory difficulty). Usually three or more monthly doses are required followed by shorter oral steroid regimen. Pope et al. in their randomized controlled trial of oral versus high dose pulse steroids in 20 children with problematic IH concluded that oral corticosteroids offer more clinical and biological benefit than pulsed steroids. However, patients in the oral steroid group had a higher frequency of side effects such as hypertension (18% vs. 13%), abnormal cortisol levels (78% vs. 60%) and growth retardation.[21] Figure 1a and b show good response (of hemangioma on the scalp) to steroids in one of our cases. The child also developed Cushingoid face.
Figure 1  (a-c) Serial photographs of haemangioma involving the scalp responded to steroid for 3 months. (a) baseline, (b) 3 months of treatment, c: showing cushingoid face Long term steroid use is associated with many side effects. Boon et al., in their study of complications of systemic corticosteroid therapy for haemangiomas, identified cushingoid facies in 44 of 62 children which began 1 to 2 months after starting at a dose of 2-3 mg/kg/day.[22] Although it was not statistically significant the authors observed that the cushingoid facies was higher in children who received therapy for more than 6 months. The cushingoid facies resolved spontaneously during the final few months of tapering steroids. Twenty-two (35%) children slipped off their growth curve for weight during the treatment, and 91% of these children returned to their baseline within 2 weeks to 16 months (mean, 7 months; median, 4 months) after treatment. They also observed a transient decrease in weight gain in 26 children (42%). Of these, 23 children returned to their pre-treatment weight curve within 2 years after therapy (mean, 7.4 months; median, 6 months). Three children remained at a lower percentile for a longer period of time. Children who received treatment for more than 6 months or who received the therapy during the first 3 months of life were found to be more likely to have this transient slowdown of gain in height. Personality changes such as irritability, depressed mood, euphoria, insomnia and restlessness was reported in 29% of their cases, appeared within 2 weeks of therapy and resolved immediately after stopping the drug. The other side effects reported were gastric irritation (21%, n = 13), oral and/or perineal candidiasis (6%, n = 4) and steroid myopathy (n = 1). The overall risk of bacterial infection was not increased. Serious complications such as aseptic necrosis of femoral head, osteoporosis and cataracts were not seen in any patient.[22] George et al., in a retrospective review, found that 16 (73%) of 22 children treated with systemic steroids had irritability, fussiness or insomnia. Hypertension was observed in 10 patients (45%), while abnormal morning cortisol levels were found in 13 of the 15 patients (87%) tested. In addition, low-dose corticotropin stimulation test results were abnormal in 2 of the 3 infants tested.[23] In a prospective study on 16 infants with haemangiomas treated with prednisolone at doses 2-3 mg/kg/day for 4 weeks followed by a tapering period (mean duration of steroid therapy 7.2 months), only one case (6%) was found to have adrenal insufficiency (on corticotropin stimulation test) after therapy completion, which normalised 3 months later. The authors concluded that there is a low risk of adrenal insufficiency following completion of steroid therapy in infants with haemangiomas. The authors commented that measuring morning serum cortisol levels, which is less specific than corticotropin stimulation test for assessing the HPA axis suppression, and measuring the cortisol levels while the patient is still on corticosteroid therapy could explain the higher incidence of adrenal insufficiency reported in the earlier studies.[24]