Trimethoprim/sulfamethoxazole-triggered drug-induced hypersensitivity syndrome in an HLA B*13:01-positive kidney transplant recipient: a case report with implications for HLA-severe cutaneous adverse reaction associations in transplant care.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe cutaneous adverse reaction (SCAR) with a reported mortality rate of approximately 2-10%. DIHS/DRESS typically develops 2-8 weeks after exposure to an offending drug. An important focus of contemporary SCAR research is the growing evidence that specific human leukocyte antigen (HLA) alleles confer a markedly increased risk of drug-specific hypersensitivity reactions. We report a case of a kidney transplant recipient who developed DIHS/DRESS after prolonged trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis and carried the HLA-B13:01 allele. HLA-B13:01 is a strong genetic risk factor for TMP/SMX-induced DIHS/DRESS, particularly in Southeast Asian populations. Herein, we highlight the potential clinical relevance of pre-transplant HLA typing in predicting SCAR risk in transplant recipients. TMP/SMX-associated DIHS/DRESS may be under-recognized in transplant settings, where awareness of HLA-associated risk remains limited despite robust evidence from non-transplant populations. Transplant clinicians should be aware that DIHS/DRESS can occur outside the typical latency period, especially during immunosuppressant tapering, highlighting the need to integrate pharmacogenomic risk assessments into transplant care.