Identifying clinical and molecular phenotypes in bullous pemphigoid and immune checkpoint inhibitor-induced bullous pemphigoid: A hierarchical clustering on principal components analysis identifies unique phenotypes and treatment refractory subsets.
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Abstract Body: Understanding of disease heterogeneity is limited in classic and immune checkpoint inhibitor (ICI) induced Bullous Pemphigoid (BP); herein, we identify clinical and molecular phenotypes.1,2 Hierarchical clustering on principal components (HCPC) analysis was performed on 446 patients with a diagnosis of definitive BP (BP=417 & ICI-BP=29) at the Mayo Clinic between 1998-2024. ICI-BP required BP diagnosis during or within 12 weeks of ICI treatment. Four clusters were identified with a difference in treatment refractory and non-treatment refractory cases (N=272 & 174; p=0.040), defined as using two or more systemic treatments. Clusters had similar gender, age, race, ethnicity, smoking, comorbidities, and ICI-BP. Cluster 1 (N=281; ICI-BP=20) had minimal oral involvement (3.6%), highest upper extremity (UE) (92.5%) and trunk (100%) involvement, and highest BP180+/BP230+ (29.5%). Cluster 2 (N=65; ICI-BP=3) had highest lower extremity (LE) (87.7%), and lowest head/neck (10.8%) and trunk (0%) involvement. Cluster 3 (N=27; ICI-BP=2) all had mucosal involvement (100%), highest anogenital (81.5%) and head/neck (48.1%) involvement, and highest BP180+/230- (55.6%). Cluster 4 was the only cluster with eye involvement (12.3%), had lowest UE (9.6%) and LE (16.4%) involvement, and highest BP180-/230- (52.1%). Cluster 3 patients had more refractory treatment (81.5%) compared to cluster 1 (62.6%), cluster 2 (52.3%) and cluster 4 (54.8%). We identified novel phenotypes that have differences in treatment response which further our knowledge for a personalized approach to BP treatment. Zachary Leibovit-Reiben<sup>1</sup>, Alyssa L. Stockard<sup>1</sup>, Nan Zhang<sup>2</sup>, Alysia Hughes<sup>1</sup>, Xing Li<sup>3</sup>, Julia S. Lehman<sup>4</sup>, Mark Pittelkow<sup>1</sup>, Johann E. Gudjonsson<sup>5</sup>, Aaron R. Mangold<sup>1</sup> 1. Department of Dermatology, Mayo Clinic Arizona, Scottsdale, AZ, United States. 2. Department of Quantitative Health Sciences, Mayo Clinic Arizona, Scottsdale, AZ, United States. 3. Mayo Clinic Department of Health Sciences Research, Rochester, MN, United States. 4. Department of Dermatology, Mayo Clinic Minnesota, Rochester, MN, United States. 5. Department of Dermatology, University of Michigan, Ann Arbor, MI, United States. Clinical Research: Interventional Research