Paraneoplastic Pemphigus: A Comprehensive Review of Pathophysiology, Clinical Manifestations, Diagnostic Challenges, and Therapeutic Approaches

Abstract

Paraneoplastic pemphigus (PNP) is a rare and often fatal autoimmune blistering disorder associated with underlying malignancies, most commonly lymphoproliferative diseases. The condition is characterized by a complex interplay of immunological mechanisms that lead to a distinctive clinical presentation, including severe mucocutaneous lesions and a polymorphic skin eruption. The pathophysiology of PNP involves autoantibodies targeting desmosomal and hemidesmosomal proteins, as well as other epithelial adhesion molecules, resulting in widespread acantholysis and inflammation. Diagnosing PNP poses significant challenges due to its overlapping features with other pemphigus variants and autoimmune blistering diseases, necessitating a combination of clinical, histopathological, immunofluorescence, and serological evaluations. Therapeutic strategies for PNP are equally complex, requiring a multidisciplinary approach that addresses both the underlying malignancy and the severe autoimmune response. Despite advances in understanding the molecular underpinnings of PNP, the prognosis remains poor, with high mortality rates attributed to complications such as infections, respiratory failure, and the progression of the associated neoplasm. This review provides an in-depth analysis of the current knowledge on the pathophysiology, clinical manifestations, diagnostic challenges, and therapeutic approaches in paraneoplastic pemphigus, highlighting the need for early recognition and tailored treatment strategies to improve patient outcomes.