{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:12Z","timestamp":1786602432437,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Traditionally associated with Th17-mediated pathways, palmoplantar pustulosis (PPP) is a persistent inflammatory dermatosis limited to the palms and soles. However, therapeutic responses to IL-17\/IL-23 suppression are often limited, indicating significant immunological heterogeneity. There is growing evidence that type 2-associated immunological pathways may have a role in the persistence of disease in some patients. Herein, we report a 40-year-old woman with refractory PPP who had no personal or familial history of psoriasis or atopy. She was treated with stapokibart, an IL-4R\u03b1 monoclonal antibody that inhibits IL-4\/IL-13 signaling, and experienced a rapid and long-lasting remission. Previous treatments, such as topical corticosteroids, retinoids, and Tripterygium wilfordii, were ineffective. Lesional skin exhibited moderate phosphorylated STAT6 positivity in scattered inflammatory infiltrates, independent of CD4+ T-cell presence, indicating engagement of canonical IL-4\/IL-13 signaling at the tissue level, despite normal serum IgE levels and the lack of peripheral or tissue eosinophilia. The context-dependent clinical significance of Th2 pathway regulation in PPP is highlighted by a systematic literature review combined with our case. In non-atopic individuals, who frequently have noticeable pruritus despite unimpressive systemic atopic indicators, blockade of IL-4\/IL-13 signaling has resulted in significant clinical relief. On the other hand, it has also been observed that blocking Th2-related pathways, such as IL-4\/IL-13, IL-5, or IL-31, paradoxically causes PPP, highlighting the bidirectional and context-dependent significance of Th2 signaling in disease pathogenesis. Together with clinical characteristics like excessive pruritus, tissue-level Th2 activation may offer useful indicators to direct precision treatment in this diverse illness.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1851685","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:32:44Z","timestamp":1786599164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-4R\u03b1 antagonist (Stapokibart) in refractory palmoplantar pustulosis: a case report and literature review of Th2-targeted therapies"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rao","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]},{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-018-00745-6","article-title":"Clinical characteristics of Japanese patients with palmoplantar pustulosis","volume":"39","author":"Yamamoto","year":"2019","journal-title":"Clin Drug 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