<p>Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease characterized by autoantibodies targeting desmogleins 1 and 3, resulting in painful bullae and mucosal erosions. Increasing evidence suggests a role for type 2 inflammation in the pathogenesis of PV. While the relationship between bullous pemphigoid (BP) and atopy has been well studied, the association between PV and atopic diseases remains unclear, with limited data available. This study aimed to evaluate the burden of type 2 comorbidities among patients with PV using a large, multi-institutional global dataset.</p><p>We performed a retrospective case-control study utilizing the TriNetX Global Collaborative Network. Adults aged 18 years or older with a diagnosis of PV were compared to healthy controls identified by two or more general medical exam visits. We examined the prevalence of various atopic comorbidities, including atopic dermatitis, chronic spontaneous urticaria, prurigo nodularis, alopecia areata, and others.</p><p>Compared to matched healthy controls, PV patients displayed a significantly increased risk of chronic spontaneous urticaria, prurigo nodularis, and atopic dermatitis. Conversely, PV patients displayed a significantly decreased risk of moderate-to-severe asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). There was no difference in the risk of eosinophilic esophagitis, alopecia areata, allergic contact dermatitis, or allergic conjunctivitis between PV patients and healthy controls. These findings suggest that PV is selectively associated with certain T helper 2 (Th2) cell-driven atopic conditions, while inversely associated with others, possibly due to differing immunologic pathways. Nevertheless, the observed associations support the involvement of Th2 inflammation in PV and may have therapeutic implications. Further prospective studies are warranted to validate these associations and clarify their mechanistic and clinical relevance.</p>