Unsupervised clustering of undifferentiated systemic autoinflammatory diseases (USAID)
First author: Jeanne Chauffier
Journal: European Journal of Internal Medicine
Article link: https://doi.org/10.1016/j.ejim.2026.107224
Summary author: Jeanne Chauffier
Background:
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, frequent urticaria and abdominal pain.
Cluster 3 (18.7%): prolonged attacks, prominent arthralgia, arthritis, and myalgia.
Cluster 4 (38%): predominantly men, higher age at the 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.
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