Pathogenesis of chikungunya arthritis: A scoping review

Chikungunya virus (CHIKV) is a mosquito borne alphavirus that causes chikungunya disease, which is characterized by debilitating arthritis. While the acute phase is marked by fever and joint pain, many patients develop chronic arthritis that persists for years. The pathogenesis of chikungunya arthritis (CA) is not fully understood, prompting us to perform an updated review of the literature to describe the mechanisms contributing to this condition. A comprehensive search was conducted on numerous electronic databases for all studies relating to pathogenesis of CA. The search strategy included the key word search "pathogenesis", "chikungunya", "arthritis". Two reviewers independently determined eligibility, rated study quality, and extracted data. The methodology followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. The data from included articles were charted and a qualitative thematic analysis formulated. A total of 623 records were identified from the electronic database search. This was narrowed to 63 records which were eligible after excluding by title and then by abstract. Following the surveying of 58 available full texts, 35 articles were eligible for inclusion, from which data was extracted. Key mechanisms identified for chronic CA included host risk factors, viral component persistence in joints, a robust pro-inflammatory cytokine response, the resulting joint destruction from pannus formation and the activation of matrix metalloproteases (MMPs) and osteoclasts. This scoping review extrapolates factors that contribute to the pathogenesis for developing chronic CA. Namely host factors and the ability of CHIKV to establish persistence within synovial fibroblasts. The inflammatory mediators and signalling pathways triggered by the host fibroblast synoviocytes, the secretion of MMPs, and promoting of osteoclastogenesis, contribute to ongoing inflammatory immune response and joint destruction. Thus, this review synthesizes evidence for a multifactorial pathogenesis of chronic CA, paralleling mechanisms of rheumatoid arthritis and highlighting targets for potential therapeutic intervention.