Inflammatory markers in generalized pustular psoriasis (GPP): An immunohistochemical analysis

Summary: Abstract Body: GPP is a rare potentially life-threatening disease characterized by the presence of sterile pustules on erythematous skin. Although clinically different from psoriasis vulgaris (PV) it shares some features of PV such as the spongiform pustule. The cause of GPP is unknown; triggers include infections, corticosteroid withdrawal and genetic factors such as a mutation of the IL-36 RN antagonizing IL36-G and -A. Antibody treatment with the IL-36R antagonist spesolimab has shown efficacy. The role of other inflammatory factors is not well understood. To further elucidate the pathogenesis we performed an immunohistochemical study in 13 patients with GPP and in corresponding skin of 6 healthy control individuals. Skin biopsies were stained with antibodies against HLA-DR, IL-8 recruiting neutrophils, IL-17A, IL-17F, IL-23, IL-36 gamma, the chemokine CXCR3 (CD-183) in IFN-induced inflammation, tyrosine kinase (Tyk) phospho-di-esterase (PDE) 4B, and the T-cell transcription factor FOX-P3 and JAK-3. The stained slides were photographed in 20x enlargement with the Leica DFC 295 microscopic system and digitally analyzed with the ImageJ Plugin-IHC Profiler scanning 82364 square micrometers. Stained cells ranged from 50 to 365 per visual field. The two-sided t-test served for statistical analysis. In GPP compared to healthy controls, we found the following significant increased staining: Fox-P3 (p<0.00001), IL-36 gamma (p<0.001), IL-17F (p<0.004), IL-8 (p<0.03). By contrast, there was significantly increased staining for IL-23 in normal skin (p<0.009). The remaining differences failed to reach statistical significance. These results indicate that compared to normal skin there is a lack IL-23 in GPP, whereas IL-36 gamma, the transcription factor Fox-P3, IL-17-F and IL-8 are the dominant cytokines in the skin of GPP. Our results provide a basis for successful treatment in generalized pustular psoriasis. Rudolf Schopf¹ 1. Dermatology, Universitaetsmedizin, Mainz, RP, Germany. Clinical Research: Epidemiology and Observational Research