Bullous pemphigoid induced by anti-IL-23 monoclonal antibody in a psoriatic patient: a case report.

Psoriasis, a chronic immune-mediated inflammatory skin disorder, is increasingly managed with anti-IL-23 biologics, such as guselkumab. Nevertheless, their rare adverse effects remain poorly understood. This study presents the case of a 78-year-old woman with moderate-to-severe psoriasis who presented with bullous pemphigoid (BP) 2 weeks after initiating guselkumab therapy. The clinical presentation was characterized by generalized bullae with epidermal-dermal separation and eosinophilic infiltration, despite negative anti-BP180 or BP230 antibodies. Single-cell RNA sequencing (scRNA-seq) of psoriatic versus BP lesions exhibited distinct cellular profiles: BP lesions were enriched in epidermal stem cells (44.32%) and endothelial cells (21.38%), in contrast to keratinocyte predominance (77.3%) noted in psoriasis. Differential gene analysis revealed the upregulation of keratinocyte stress markers (KRT6B and MMP7) and interferon-related genes (IFI6) in BP. Immune dysregulation was reflected in the activation of macrophages/T cells expressing pro-inflammatory factors (SPP1 and GZMB). Tissue stem cells demonstrated PTX3 upregulation, linking complement activation and extracellular matrix remodeling to epidermal damage. Collectively, these findings reveal dual mechanisms of guselkumab-induced BP: immune imbalance and defective epidermal repair. Future studies should validate these pathways in larger cohorts and investigate IL-23/interferon signaling crosstalk.