Publication date: Jun 09, 2025

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. 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. 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. 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-α) 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. 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.

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