Evaluation of Suspected Hypersensitivity Reactions to Oral Iron Preparations in Children

INTRODUCTION: Oral iron preparations are widely used in the treatment of iron deficiency anemia globally, including children. Although adverse reactions are occasionally reported, true hypersensitivity to oral iron is considered uncommon. However, suspected reactions may lead to unnecessary discontinuation of iron therapy and referral to allergy clinics. To evaluate the clinical characteristics and diagnostic yield of drug provocation testing in children with suspected hypersensitivity reactions to oral iron preparations. METHODS: This retrospective study included children referred to a tertiary pediatric allergy clinic for suspected hypersensitivity to oral iron preparations. Clinical characteristics, reaction phenotypes, timing of reactions, and drug provocation test (DPT) outcomes were analyzed. Hypersensitivity was confirmed when objective symptoms were reproduced during culprit drug provocation. Children aged 0-18 years who underwent culprit or alternative drug provocation testing were included. RESULTS: A total of 28 children were included in the analysis. The median age at the index reaction was 2.5 years (IQR: 0.5-9.3), and 18 patients (64.3%) were female. Allergic diseases were present in 12 patients (42.9%). Maculopapular eruption was the most frequently reported index reaction (11/28, 39.3%), followed by other cutaneous rashes (6/28, 21.4%), urticaria (5/28, 17.9%), and angioedema (1/28, 3.6%) while non-cutaneous manifestations were reported in 5 patients (17.9%). The median time from drug intake to symptom onset was 6.75 hours (IQR: 4.12-9.00). Culprit drug provocation testing was performed in 14 patients, confirming hypersensitivity in 2 cases (2/14, 14.3%). Twelve patients (12/14, 85.7%) had negative provocation tests. Alternative iron provocation was performed in 14 patients; all of which were tolerated. CONCLUSION: True hypersensitivity to oral iron preparations appears to be uncommon in children. Appropriate allergy evaluation, including drug provocation testing when indicated, may help clarify suspected reactions and prevent unnecessary avoidance of iron therapy.