{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:17:04Z","timestamp":1789604224925,"version":"build-2803163510"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Dermatol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Importance: Wells syndrome (eosinophilic cellulitis) is a rare inflammatory dermatosis characterized by erythematous, edematous plaques and dermal eosinophilic infiltration. Understanding its evolving triggers and treatment options is critical for optimizing management, particularly in corticosteroid-refractory cases. Objective: To systematically review newly reported immunologic and iatrogenic triggers of Wells syndrome, as well as emerging therapies, with the goal of updating clinical guidance. This review focuses on diagnosis and therapy, emphasizing outcomes in patients with refractory or relapsing disease. Evidence review: A systematic literature search was conducted following PRISMA 2020 guidelines across six databases for English-language studies published between January 2016 and May 2025. Studies were eligible if they described new triggers or treatments for Wells syndrome. Article selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Joanna Briggs Institute and Newcastle-Ottawa tools. Findings: Twenty-four studies met inclusion criteria: 21 case reports, 2 case series, and 1 retrospective cohort study. Newly identified triggers included COVID-19 infection, SARS-CoV-2 and influenza vaccines, aluminum- and gelatin-containing pediatric vaccines, and biologic therapies such as ustekinumab and tumor necrosis factor-alpha (TNF-\u03b1) inhibitors. In vaccine-related cases, causality was supported by positive patch testing. Novel therapies trialed in corticosteroid-refractory or relapsing patients included dupilumab, topical ruxolitinib, abrocitinib, and mepolizumab. Most patients experienced complete or near-complete resolution. However, recurrences were common, particularly in idiopathic cases or upon re-exposure to known triggers. Conclusions and relevance: Recent literature expands the clinical spectrum of Wells syndrome, highlighting new immunologic and iatrogenic triggers. Targeted treatments, especially biologics and Janus kinase inhibitors, demonstrate promising results and may offer steroid-sparing alternatives for patients with refractory disease. Clinicians should consider emerging triggers in differential diagnosis and evaluate newer therapies in recurrent or treatment-resistant cases. Further prospective and registry-based studies are warranted to validate efficacy and support development of evidence-based management guidelines.<\/jats:p>","DOI":"10.1007\/s00403-025-04305-9","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:37:49Z","timestamp":1749461869000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Wells syndrome: emerging triggers and treatments\u2013 an updated systematic review"],"prefix":"10.1007","volume":"317","author":[{"given":"Areeba","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Cahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Haber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"4305_CR1","doi-asserted-by":"crossref","unstructured":"Wolff L, Horisberger A, Moi L\u2026 MKI journal of, 2023 undefined. Polyarteritis nodosa: old disease, new etiologies. mdpi.com [Internet]. [cited 2025 May 5]; Available from: https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16668","DOI":"10.3390\/ijms242316668"},{"key":"4305_CR2","doi-asserted-by":"crossref","unstructured":"Mcmullan P, Kristin| S, T| G,| S, Lu W, Torre J, Santiago S, Weston G J LuSkin Health and Disease, 2023\u2022academic.oup.com [Internet]. 2023 [cited 2025 May 5];3. Available from: https:\/\/academic.oup.com\/skinhd\/article-abstract\/3\/3\/ski2.206\/7755655","DOI":"10.1002\/ski2.206"},{"key":"4305_CR3","doi-asserted-by":"crossref","unstructured":"Heelan K, Ryan J, NS\u2026 of DC (2013) undefined Wells syndrome (eosinophilic cellulitis): Proposed diagnostic criteria and a literature review of the drug-induced variant. pmc.ncbi.nlm.nih.govK Heelan, JF Ryan, NH Shear, CA EganJournal of Dermatological Case Reports, 2013\u2022pmc.ncbi.nlm.nih.gov [Internet]. [cited 2025 May 5]; Available from: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3888780\/","DOI":"10.3315\/jdcr.2013.1157"},{"key":"4305_CR4","unstructured":"Cureus DS (2023) undefined Revolutionizing dupilumab treatment in refractory eosinophilic cellulitis: a case report and comprehensive literature review. cureus.comD ShahCureus, 2023\u2022cureus.com [Internet]. 2023 [cited 2025 May 5]; Available from: https:\/\/www.cureus.com\/articles\/210459-revolutionizing-dupilumab-treatment-in-refractory-eosinophilic-cellulitis-a-case-report-and-comprehensive-literature-review.pdf"},{"key":"4305_CR5","unstructured":"Heinig B, Vojvocic A, Lotti T\u2026 MT\u2026 MJ of, 2019 undefined. Wells syndrome\u2013an Odyssey. pmc.ncbi.nlm.nih.govB Heinig, A Vojvocic, T Lotti, M Tirant, U WollinaOpen Access Macedonian Journal of Medical Sciences, 2019\u2022pmc.ncbi.nlm.nih.gov [Internet]. [cited 2025 May 5]; Available from: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC6910816\/"},{"key":"4305_CR6","doi-asserted-by":"crossref","unstructured":"Tirado-S\u00e1nchez A\u2026 IS\u00c1Med cl\u00edn (Ed, 2021 undefined. Wells syndrome (eosinophilic cellulitis). A retrospective study in 35 adult patients. pesquisa.bvsalud.org [Internet]. [cited 2025 May 5]; Available from: https:\/\/pesquisa.bvsalud.org\/portal\/resource\/pt\/ibc-215988","DOI":"10.1016\/j.medcli.2021.01.026"},{"key":"4305_CR7","doi-asserted-by":"publisher","unstructured":"R\u00e4\u00dfler F, Luk\u00e1cs J, Elsner P Treatment of eosinophilic cellulitis (Wells syndrome)\u2013a systematic review. Wiley Online LibraryF R\u00e4\u00dfler, J Luk\u00e1cs, P ElsnerJournal of the European Academy of Dermatology and Venereology, 2016\u2022Wiley Online Library [Internet]. 2016 Sep 1 [cited 2025 May 5];30(9):1465\u201379. Available from: https:\/\/onlinelibrary.wiley.com\/doi\/abs\/https:\/\/doi.org\/10.1111\/jdv.13706","DOI":"10.1111\/jdv.13706"},{"key":"4305_CR8","doi-asserted-by":"crossref","unstructured":"Moseley I, Yang E, Mathieu R, Reports CEJC (2022) undefined Wells syndrome as a presenting sign of COVID-19 in the setting of allergic rhinitis and iron deficiency anemia. ElsevierI Moseley, EJ Yang, RJ Mathieu, C Elco, CM MassoudJAAD Case Reports, 2022\u2022Elsevier [Internet]. [cited 2025 May 5]; Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2352512622001035","DOI":"10.1016\/j.jdcr.2022.02.018"},{"key":"4305_CR9","doi-asserted-by":"crossref","unstructured":"Yu AM, Ito S, Leibson T, Lavi S, Fu LW, Weinstein M et al Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature. Pediatr Dermatol [Internet]. 2018 Sep 1 [cited 2025 May 5];35(5):e262\u20134. 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[cited 2025 May 5]; Available from: https:\/\/search.ebscohost.com\/login.aspx?direct=true%26;profile=ehost%26;scope=site%26;authtype=crawler%26;jrnl=00119059%26;asa=N%26;AN=164632995%26;h=3yb3JFHAjRzTMahTuxNWCC0H8WIQOS39NE4Z7QYAW6VNhvS7t9OYp19MxbOiTZF6Gnim3dB37zNFFvUy2QhfFQ%3D%3D%26;crl=c"},{"key":"4305_CR16","doi-asserted-by":"publisher","unstructured":"Traidl S, Angela Y, Kapp A, Suhling H, Schacht V, Werfel T Dupilumab in eosinophilic cellulitis (Wells\u2019 syndrome)\u2013case report of a potential new treatment option. Wiley Online LibraryS Traidl, Y Angela, A Kapp, H Suhling, V Schacht, T WerfelJDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2021\u2022Wiley Online Library [Internet]. 2021 Nov 1 [cited 2025 May 5];19(11):1653\u20135. 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Actas Dermosifiliogr [Internet]. 2020 Nov 1 [cited 2025 May 6];111(9):804\u20135. Available from: https:\/\/www.actasdermo.org\/en-eosinophilic-panniculitis-associated-with-covid-19-articulo-S157821902030278X","DOI":"10.1016\/j.adengl.2020.10.003"},{"key":"4305_CR28","doi-asserted-by":"crossref","unstructured":"\u0160ajn M, Luzar B, Zver S Wells\u2019 syndrome possibly caused by hematologic malignancy, influenza vaccination or ibrutinib: A case report. World J Clin Cases [Internet]. 2022 Oct 26 [cited 2025 May 6];10(30):10997. Available from: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC9631159\/","DOI":"10.12998\/wjcc.v10.i30.10997"},{"key":"4305_CR29","doi-asserted-by":"crossref","unstructured":"Heelan K, Ryan JF, Shear NH, Egan CA (2013) Wells syndrome (eosinophilic cellulitis): Proposed diagnostic criteria and a literature review of the drug-induced variant. J Dermatol Case Rep [Internet]. Dec 30 [cited 2025 May 6];7(4):113. 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Wiley Online LibraryD Terhorst-Molawi, S Altrichter, J R\u00f6wert, M Magerl, T Zuberbier, M Maurer, KC BergmannJDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2020\u2022Wiley Online Library [Internet]. 2020 Jul 1 [cited 2025 May 6];18(7):737\u20139. Available from: https:\/\/onlinelibrary.wiley.com\/doi\/abs\/https:\/\/doi.org\/10.1111\/ddg.14151","DOI":"10.1111\/ddg.14151"},{"key":"4305_CR33","doi-asserted-by":"crossref","unstructured":"Brun J, Chiaverinia C, Bessis D, Bourrat E, Lasek-Duriez A, Hadj-Rabia S et al (2015) Syndrome de Wells de l\u2019enfant et atopie: \u00c9tude r\u00e9trospective de 11 cas et revue de la litt\u00e9rature. Ann Dermatol Venereol [Internet]. [cited 2025 May 6];142(5):320\u201331. 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Wiley Online Library [Internet]. 2024 Jan 1 [cited 2025 May 6]; Available from: https:\/\/onlinelibrary.wiley.com\/doi\/abs\/https:\/\/doi.org\/10.1111\/1346-8138.17417","DOI":"10.1111\/1346-8138.17417"},{"key":"4305_CR36","doi-asserted-by":"crossref","unstructured":"\u0160ajn M, Luzar B, Zver S Wells\u2019 syndrome possibly caused by hematologic malignancy, influenza vaccination or ibrutinib: A case report. World J Clin Cases [Internet]. 2022 Oct 26 [cited 2025 May 6];10(30):10997\u20131003. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/36338211","DOI":"10.12998\/wjcc.v10.i30.10997"},{"key":"4305_CR37","doi-asserted-by":"crossref","unstructured":"Herout S, Bauer WM, Schuster C, Stingl G Eosinophilic cellulitis (Wells syndrome) successfully treated with mepolizumab. JAAD Case Rep [Internet]. 2018 Jul 1 [cited 2025 May 6];4(6):548\u201350. 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Therefore, ethical approval was not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"805"}}