Predictive factors for therapeutic response and cluster analysis in syndrome of undifferentiated recurrent fever (SURF).

INTRODUCTIONSyndrome of undifferentiated recurrent fever (SURF) refers to a group of recurrent fevers without a clear monogenic cause. Clinical spectrum, treatment response predictors and management strategies remain unclear.OBJECTIVEThis study aims to longitudinally analyse a homogeneously selected cohort of 101 SURF patients, to identify factors associated with colchicine resistance and to evaluate the efficacy of interleukin-1 (IL-1) inhibitors.METHODSPatients were enrolled in the Eurofever Registry, carefully excluding those with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA); familial Mediterranean fever and other known monogenic recurrent fevers. Demographic, clinical and treatment data were analysed to identify predictors of colchicine resistance and define subgroups through cluster analysis.RESULTSCommon symptoms included fever, arthralgia, abdominal pain and myalgia, with PFAPA-like features (lymphadenopathy, tonsillitis, oral aphthae) observed in one-third of cases, sporadically. Colchicine efficacy, assessed in 77 patients, revealed complete response in the majority of patients (61%). Univariable analysis identified PFAPA-like features, including aphthous stomatitis (p=0.001), cervical lymphadenopathy (p=0.012) and exudative tonsillitis (p=0.004), as associated with colchicine resistance. Multivariable analysis confirmed aphthous stomatitis as an independent predictor of resistance (p=0.014). Tonsillectomy was ineffective. IL-1 inhibitors (anakinra, canakinumab) were beneficial in refractory cases. Cluster analysis revealed three distinct subgroups with varying symptoms and colchicine responses.CONCLUSIONSThese findings provide new insights into SURF, identifying predictors of colchicine resistance and supporting the efficacy of IL-1 blockade. Cluster analysis suggests the heterogeneity within SURF, reinforcing the need for refined diagnostic criteria and personalised treatment strategies.KEYWORDSBiological Therapy, Hereditary Autoinflammatory Diseases, Immune System Diseases, Inflammation© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.