Abstract

<h3>Introduction</h3> Drug reaction with eosinophilia and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS) represents a severe adverse drug reaction with a high mortality rate. Allopurinol-induced DRESS/DIHS can be associated with polymorphisms in human leukocyte antigen (HLA) genes, with higher prevalence of the HLA-B*58:01 allele in Asians (7.4%) and Africans (3.8%) compared to other ethnic populations. <h3>Case Description</h3> We report four cases (two of African and two of Asian descent) of severe allopurinol-induced DRESS/DIHS requiring hospitalization for treatment. All patients presented with a generalized, erythematous dermatitis and peripheral eosinophilia after recently starting allopurinol. RegiSCAR scoring ranged from 7-8. All cases were HLA-B*58:01 positive with skin punch biopsies consistent with DRESS/DIHS. Two patients had mucocutaneous involvement, while three had notable organ involvement and relapse of disease after tapering immunosuppressant therapies. Half of the patients had evidence of viral reactivation. One patient succumbed to infectious pulmonary complications and cyclosporine toxicity. Table 1 summarizes the characteristics, laboratory findings and clinical courses of these cases. <h3>Discussion</h3> Our case series demonstrated two African and two Asian patients with severe allopurinol-induced DRESS/DIHS with positive HLA-B*58:01 genotyping. This allele has been associated with an increased risk of DRESS/DIHS from allopurinol. Detection of HLA*58:01 has higher prevalence in Asians and Africans and may portend worse disease. Recent guidelines recommend screening for the HLA*58:01 allele in Southeast Asian and African patients prior to initiation of allopurinol. Our case series highlights the importance of recognizing populations with high HLA-B*58:01 allele frequency before introduction of allopurinol to prevent DRESS/DIHS.

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