Immune-checkpoint inhibitor-induced bullous pemphigoid in patients with metastatic renal cell carcinoma: two case reports and systematic review of the literature

BACKGROUND AND PURPOSE: Immune-checkpoint inhibitors (ICIs) improve outcomes in renal cell carcinoma (RCC) but may cause immune-related adverse events (irAEs), including cutaneous toxicity. Bullous pemphigoid (BP) is a rare but clinically significant irAE that can require ICI discontinuation. Patient/material and methods: We report two cases of BP in patients with metastatic RCC treated with ICIs at Karolinska University Hospital, Stockholm, Sweden. In addition, a systematic review was conducted in Medline, Embase, Cochrane Library, and Web of Science to identify published cases of ICI-associated BP in metastatic RCC. Data on patient characteristics, treatment, clinical presentation, diagnostics, management, and outcomes were extracted and descriptively analysed. RESULTS: Twenty-eight publications describing 30 cases were identified. Median age at BP onset was 69 years (interquartile range [IQR] 65-73), and 86.7% were male. Nivolumab was the most commonly reported ICI monotherapy. Median time from ICI initiation to BP onset was 35 weeks (IQR 16-76). Typical manifestations included tense bullae and vesiculobullous eruptions on the trunk and extremities. Diagnosis was confirmed by skin biopsy and immunological testing in 80% of cases. Management mainly involved corticosteroids, while ICI interruption or discontinuation was required in over half the cases. Both patients from our center improved after immunosuppressive treatment. INTERPRETATION: ICI-associated BP is a rare but important irAE in metastatic RCC, often occurring after prolonged ICI exposure and potentially requiring treatment modification. Early recognition may improve multidisciplinary management.