Significance of HLA-B15 in three pemphigus patients with rituximab-triggered severe cutaneous drug reactions

Rituximab, a CD20 inhibitor, has swiftly become the primary treatment for pemphigus patients. We present 3 cases of pemphigus patients who had undergone rituximab treatment. After the second intravenous administration of rituximab, the primary rash developed into severe cutaneous drug reactions. Peripheral blood was collected from the aforementioned 3 patients for the detection of susceptibility genes by using second-generation sequencing. Notably, a significant resemblance was observed in the HLA profiles of these 3 patients, particularly regarding high-risk alleles associated with rituximab-induced severe cutaneous drug reactions (CDRs). This rare occurrence of severe CDRs post-rituximab administration may be HLA-dependent and linked to HLA-B*15:02:01, HLA-B*15:12 and HLA-B*15:27:01. This pioneering laboratory trial shows the pathological background of rituximab-induced severe cutaneous drug reactions. Our findings contribute to the expanding catalogue of potential HLA-B*15 linked to severe CDRs and underscore the importance of vigilance regarding such reactions in pemphigus patients undergoing rituximab therapy.