HLA‒B*58:01 and skin reactions in pediatric hematology and oncology patients treated with allopurinol

Allopurinol is widely used to prevent hyperuricemia in patients with tumor lysis syndrome. However, its use can trigger severe cutaneous adverse reactions (SCARs) with a mortality rate of approximately 11.39%. The human leukocyte antigen (HLA)-B*58:01 genotype is a major risk factor for SCARs. Although most studies to date have examined HLA-B*58:01 in Thai adults, data on pediatric patients are limited. Here we aimed to evaluate the association between HLA-B*58:01 and skin reactions in children with hematological or oncological diagnoses receiving allopurinol and determine its prevalence in this population. Pediatric patients (age≤18 years) with hematological or oncological diseases who received allopurinol were enrolled in this cross-sectional study of previously exposed and newly prescribed cases. HLA-B*58:01 genotyping was performed to assess its association with skin reactions. A total of 108 patients (mean age, 9.3 years) were included. Most patients (n=93, 86.1%) received allopurinol as prophylaxis for tumor lysis syndrome. Of them, 75 (69.4%) received allopurinol concomitantly with chemotherapy for malignancies, whereas the remaining patients received allopurinol during conditioning for hematopoietic stem cell transplantation. The prevalence of HLA-B*58:01 positivity was 17.6% (n=19 of 108 patients). The median exposure duration was 5 days (range, 1-19 days). No HLA-B*58:01-positive patients experienced a skin reaction. However, one patient who tested negative for HLA-B*58:01 developed a maculopapular rash on day 2 of the allopurinol therapy and required intravenous antihistamines. Short-duration allopurinol exposure likely mitigates the risk of SCARs regardless of HLA-B*58:01 status. Routine HLA-B*58:01 testing may not be warranted in pediatric patients receiving brief allopurinol courses. However, larger studies are required to confirm these findings.