{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T05:06:59Z","timestamp":1779426419270,"version":"3.53.1"},"reference-count":117,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening inflammatory dermatosis increasingly recognized as a distinct disease entity rather than a variant of plaque psoriasis. Emerging evidence indicates that GPP is primarily driven by dysregulation of the interleukin-36 (IL-36) signaling axis, leading to amplification of proinflammatory cascades in keratinocytes and a predominantly innate, neutrophil-driven immune response. This promotes rapid neutrophil recruitment, sterile pustule formation, and abrupt cutaneous and systemic inflammation. Consistent with this, GPP demonstrates a greater predominance of innate immune and neutrophil-driven inflammation, whereas plaque psoriasis is more strongly associated with IL-23\/Th17-mediated adaptive immune responses. Transcriptomic and genetic studies further support this distinction, demonstrating enrichment of IL-36-associated and neutrophil-related signatures, activation of MyD88-dependent pathways, and mutations in genes regulating the IL-36 axis, including IL36RN, AP1S3, and CARD14. Consequently, conventional systemic therapies and biologics targeting TNF-\u03b1, IL-17, and IL-23 pathways show variable efficacy and may act more slowly in GPP. In contrast, IL-36 receptor inhibitors represent a more mechanism-aligned approach and have demonstrated rapid and clinically meaningful responses in acute flares. However, important gaps remain, including the lack of validated biomarkers and limited data on long-term treatment outcomes. This review provides an integrated perspective on IL-36-driven inflammation in GPP, including comparison with plaque psoriasis, and outlines its implications for mechanism-based therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms27104441","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-36-Driven Inflammation in Generalized Pustular Psoriasis: Immunological Insights from Plaque Psoriasis and Implications for Targeted Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5660-2143","authenticated-orcid":false,"given":"Klara","family":"Andrzejczak","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Wybrzeze L. Pasteura 1, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9100-9321","authenticated-orcid":false,"given":"Emilia","family":"Kucharczyk","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Wybrzeze L. Pasteura 1, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Sternak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Wybrzeze L. Pasteura 1, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7879-8305","authenticated-orcid":false,"given":"Karol","family":"Bili\u0144ski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Wybrzeze L. Pasteura 1, 50-367 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Maj","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Ponikowska","sequence":"additional","affiliation":[{"name":"University Centre of General Dermatology and Oncodermatology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"m1590","DOI":"10.1136\/bmj.m1590","article-title":"National, Regional, and Worldwide Epidemiology of Psoriasis: Systematic Analysis and Modelling Study","volume":"369","author":"Parisi","year":"2020","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.abd.2021.05.011","article-title":"Generalized Pustular Psoriasis (von Zumbusch)","volume":"97","author":"Romiti","year":"2022","journal-title":"An. 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