Comparative Clinical and Histological Analysis of Bullous Pemphigoid: Immunotherapy-Associated vs. Spontaneous Onset Cases

Introduction: Immune checkpoint blockade (ICB) therapy can be associated with the development of bullous pemphigoid (BP). To characterize clinical, histological and serological characteristics, we compared immune-related BP (irBP) and spontaneous BP (sBP) considering clinical, serological and histopathological character. Methods: 149 BP patients treated at the University Hospital Zurich between 2015 and 2024 were identified retrospectively. Demographic and serological data were obtained from electronic records. Hematoxylin-eosin (HE)-stained biopsies were semi-quantitatively evaluated for immune cell infiltrates, split formation, and infiltration patterns. Results: From the total of 149 cases, 17 were irBP and 132 were sBP. Patients affected by irBP were predominantly males (94%), females were slightly overrepresented in sBP (51.5%) and BP was less often suspected at presentation (59% vs 85% in sBP). Anti-BP230 antibodies were more frequently elevated in sBP (64.4% vs 23.5% in irBP). Histologically, irBP cases showed denser neutrophilic, eosinophilic, and lymphocytic infiltrates, as assessed by semi-quantitative scoring. Conclusion: irBP differs from sBP by showing denser immune-infiltrates, lower rates of elevated anti-BP230 antibodies and predominantly affect males. These observations suggest that irBP represents a distinct subtype and highlight the need for diagnostic awareness in the setting of ICB therapy.