Fecha de publicación: -- Fuente: PubMed "hive" Eur J Intern Med. 2026 Sep 30:107224. doi: 10.1016/j.ejim.2026.107224. Online ahead of print.ABSTRACTBACKGROUND: Undifferentiated systemic autoinflammatory diseases (USAID) comprise a heterogeneous group of disorders characterized by recurrent systemic inflammation without an identifiable monogenic cause.OBJECTIVE: To describe the phenotypic and therapeutic features of adult USAID and identify phenotypic clusters.METHODS: We conducted a retrospective single-center study at the French Reference Center for Autoinflammatory Diseases between 2010 and 2025. USAID was defined as recurrent systemic attacks with ≥3 documented C-reactive protein (CRP) elevations and no pathogenic variant identified. Therapeutic response was classified as complete (CR) or partial (PR). Hierarchical cluster analysis included clinical and biological variables.RESULTS: Among 150 patients (65.3% women; median age at onset 14 [0-64] years), recurrent attacks occurred in 87.3%. The most frequent manifestations were cutaneous (87.3%), fever (84%), asthenia (80%), musculoskeletal (79.3%), and abdominal involvement (63.3%). Colchicine was prescribed in 56.7% (CR 8.2%, PR 44.7%). Biologic therapies included anti-TNFα (n = 32; CR 21.9%, PR 31.3%), anti-IL-1 (n = 24; CR 25%, PR 16.7%), anti-IL-6 (n = 22; CR 31.8%, PR 31.8%), and JAK inhibitors (n = 16; CR 18.8%, PR 37.5%). Four clusters were identified: Cluster 1 (15.3%): fever, aphthous ulcers, pharyngitis, abdominal pain and lymphadenopathy. Cluster 2 (27.3%): brief attacks, urticaria and abdominal pain. Cluster 3 (19.3%): prolonged attacks, prominent arthralgia, arthritis, and myalgia. Cluster 4 (38%): predominantly men, older age at onset, frequent neutrophilic dermatoses. Treatment responses did not differ significantly between clusters.CONCLUSION: Adult USAID patients can be subdivided into four clusters. Phenotypic stratification may help structure diagnostic reasoning and guide future therapeutic research.PMID:42816246 | DOI:10.1016/j.ejim.2026.107224