Unveiling Clinical Phenotypes in Chronic Chikungunya Disease: Insights from a Brazilian Observational Study

Chronic chikungunya disease (CCD) affects approximately 30-50% of infected individuals and is associated with persistent inflammatory arthritis, chronic pain, and long-term functional disability. We conducted a prospective observational cohort study including 584 patients with laboratory-confirmed chikungunya infection, evaluated between 3 and 12 months after acute infection, to better understand the natural history, risk factors, clinical presentation, and treatment patterns of CCD. Here, we present a cross-sectional analysis derived from this cohort. Older age, female sex, and higher body mass index were identified as major risk factors for CCD. Four distinct clinical phenotypes were identified: Axial (12.2%), defined by inflammatory axial pain regardless of peripheral manifestations; Oligoarthritis (18.1%), defined by fewer than four swollen joints; Polyarthritis (10.6%), defined by four or more swollen joints; and Pain without Swelling (70.4%), characterized by myalgia and/or arthralgia in the absence of objective inflammatory findings on physical examination. The axial phenotype could overlap with peripheral phenotypes, whereas oligoarthritis, polyarthritis, and pain without swelling were mutually exclusive categories. These phenotypes differed substantially in symptom burden and clinical impact. Patients with the Pain without Swelling phenotype had longer symptom duration, whereas Axial and Polyarthritis phenotypes were associated with greater functional impairment and higher disease burden. These findings reinforce the clinical heterogeneity of CCD and support the potential value of phenotype-based approaches for clinical management and future therapeutic research.