Background: Acute rheumatic fever (ARF) is a significant public health concern in resource-limited settings, but its clinical presentation remains inadequately described. This study leverages data from the ARF Diagnostic (ARC) Network to provide a global overview of ARF characteristics.

Methods: Children aged 3–18 years from Brazil, Malawi, Pakistan, and Timor-Leste were enrolled based on clinical signs of joint pain, suspected rheumatic carditis, chorea, or known rheumatic heart disease (RHD) with suspected ARF recurrence. A standardized enrollment protocol was used across all sites.

Results: A total of 202 children with definite ARF were included: Brazil (n=17), Malawi (n=36), Pakistan (n=129), and Timor-Leste (n=20). Most cases (93%) occurred within the 5–14-year age group, with site-specific median ages ranging from 8 to 11 years. Males comprised 57% of the cohort. First-episode ARF accounted for 74% of cases, while 26% were recurrent episodes. The breakdown of major manifestations among these cases included 72% with joint symptoms (5.5% polyarthritis, 90% polyarthralgia, 4% monoarthritis), 82% with carditis (77% moderate/severe, 23% mild), 2.5% subcutaneous nodules,  0.5% erythema marginatum, and 22% with chorea. Regional variation was notable: 47% of Brazilian patients presented with chorea, 83% had carditis in Pakistan, and joint involvement was common in Malawi (78%) and Timor-Leste (90%).

Conclusion: These findings highlight regional variation in ARF manifestations and the need for improved diagnostic and management strategies in high-burden areas. It remains unclear whether differences in clinical presentation reflect variations in care-seeking behavior or true disease prevalence.