Eosinophilic fasciitis: a comprehensive systematic review of clinical, histologic, and therapeutic perspectives

BACKGROUND: Eosinophilic fasciitis (EF) is a rare autoimmune disorder within the sclerodermatous disease spectrum, characterized by inflammation and fibrosis of the subcutaneous fat and fascia, often accompanied by peripheral eosinophilia. Although its exact etiology remains uncertain, potential triggers include intense physical exertion, infections, malignancies, and drug exposure - most recently, immune checkpoint inhibitors such as anti-PD-1/PD-L1 agents. Histopathological findings consistently reveal eosinophilic infiltration and fibrosis of subcutaneous fat and fascia. Corticosteroids remain the cornerstone of treatment, often supplemented with immunosuppressants in refractory cases. Emerging therapies, such as anti-IL-5 agents (mepolizumab and benralizumab), offer targeted approaches for corticosteroid-resistant EF by directly modulating eosinophilic inflammation. METHODS: A systematic review of PubMed and Ovid was conducted according to PRISMA guidelines until October 2024, including studies on clinical, histological, or therapeutic aspects of eosinophilic fasciitis. RESULTS: The mean age was 45.95 years, with balanced sex distribution (51.1% females). Most cases involved both upper and lower limbs (56.2%), followed by lower limbs (11.2%) and upper limbs alone (9.8%). Eosinophilia was present in 92.4% of patients, hypergammaglobulinemia in 19.9%, and elevated CRP in 13.5%. Histology showed eosinophilic infiltration in 68.9%. Identifiable triggers included intense exercise (8.7%), drugs - especially anti-PD1 checkpoint inhibitors (5.6%) - infections (2.8%), and paraneoplastic causes (2.3%). Treatments included corticosteroids (89.3%), methotrexate (27.5%), cyclosporine (6.7%), hydroxychloroquine (3.6%), azathioprine (3.9%), and rituximab (1.7%). Anti-IL5 agents (N.=7) were used in refractory cases, with full resolution in 2 and mild improvement in 5. CONCLUSIONS: This review provides a systematic analysis of the clinical, biological, and histological characteristics of EF, its associated triggers, and therapeutic strategies based on a comprehensive review of reported cases. We found that poor prognostic factors include diagnostic delay (>6 months), trunk involvement, early-onset disease (<12 years), and morphea-like skin lesions.