Review of the current therapeutic landscape of pemphigus vulgaris: Targeting the type 2 and non-type 2 inflammatory pathways and novel upstream targets

Summary: Abstract Body: This study reviews the therapeutic potential of the inhibition of IL-33 and TSLP on type 2 and non-type 2 inflammatory pathways in the pathogenesis of pemphigus vulgaris (PV). Recent advances in biologic therapies have emphasized the role of the type 2 inflammatory pathway in the pathophysiology of PV. Through a review of the literature and analysis, we explore IL-33 and TSLP as important modulators of the type 2 inflammatory pathway via their activity in diseases such as asthma, atopic dermatitis, and bullous pemphigoid. In addition, we describe their impact on non-type 2 inflammation. Our analysis revealed that IL-33 and TSLP have essential roles in the pathogensis of PV, contributing to the activation of type 2 and type 17 T helper cells, eosinophils, and mast cells. In addition to having been implicated in the pathogenesis of PV, targeting of these cytokines can inhibit IL-4, IL-5, IL-13, IL-17, CCL17, CCL22, IFN-γ, and B-cell development. Targeting these cytokines may have a role in being pursued as monotherapy, or in conjunction with existing treatments. First-line therapies for PV, including oral corticosteroids and immunosuppressants, are often associated with systemic side effects and may not be suitable for all patients. Targeting upstream cytokines in PV presents a promising therapeutic avenue to reduce systemic side effects and improve patient outcomes in this chronic disorder. Gabriela Soto-Canetti^{1, 2}, Tammy Ehimwenma-Point Du Jour³, Jordan Talia¹ 1. Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2. School of Medicine, Ponce Health Sciences University, Ponce, Ponce, Puerto Rico. 3. School of Medicine, Meharry Medical College, Nashville, TN, United States. Clinical Research: Epidemiology and Observational Research