Pyodermatitis-Pyostomatitis Vegetans: The Role of Langerin Deficiency in Disease Pathogenesis.

Background/Objectives: Pyodermatitis-pyostomatitis vegetans (PPV) is a rare, chronic inflammatory mucocutaneous disorder. However, the etiology of PPV remains controversial. Methods: A review of online PPV case studies from PubMed, Wanfang database, Web of Science, and books has been performed. Comparative analysis of langerin expression has been conducted to verify the hypothesis summarized from the literature review by Immunohistochemistry (IHC). Results: A total of 63 patients were analyzed across 5 reviews, 44 case reports, and 1 book chapter. Our findings revealed distinct immunological alterations in PPV patients. Innate immunity was upregulated, marked by increased neutrophil and eosinophil counts and enhanced macrophage activity. Adaptive immunity was suppressed, with reduced dendritic cell (DC) numbers and activity and diminished adaptive immune responses. We hypothesize that langerin was a critical factor, contributing to adaptive immune suppression and a compensatory innate immune hyperactivation. Conclusions: We propose the hypothesis that langerin expression on Langerhans cells (LCs) plays a pivotal role in PPV pathogenesis by shifting the immune balance toward innate hyperactivation at the expense of adaptive immunity.