Subacute Disease (3-To-11 Weeks) Predicts Post-Chikungunya Chronic Inflammatory Rheumatism (> 12 Weeks): Findings Of An Ambispective Cohort In La Virginia, Risaralda, Colombia

Background: Much of the clinical research on chikungunya (CHIK) has been focused on the acute disease (<3 weeks) (>500 publications on PubMed) and the post-CHIK chronic inflammatory rheumatism (pCHIK-CIR) (≥12 weeks) (>200 publications on PubMed), but subacute stage (3-11 weeks) have been neglected (6 publications on PubMed). Relevance, relationship and predictability of pCHIK-CIR based on the occurrence of subacute disease has not been properly addressed. Methods & Materials: In a cohort study, with data analyzed at occurrence (acute phase, <3 weeks), subacute (3-11 weeks) and chronic phases (≥12 weeks, 12 months and 2 years), of cases serologically diagnosed in La Virginia, Risaralda, Colombia, the risk of pCHIK-CIR according the progression to the subacute phase (from the acute phase), was analyzed. Phases were classified according WHO/PAHO (2015) chikungunya criteria. Incidence according exposition (risk difference, RD and relative risk, RR) and proportions (χ2) with their respective 95% confidence intervals (95%CI), were calculated using Stata IC 14.0® licensed, p significant <0.05. Those with other arboviroses during follow-up were excluded. Results: At the end of this follow-up, 62 patients were valid for analyses, 43 (69.4%) corresponding to those that progressed to the development of pCHIK-CIR+ and 19 (30.6%) that were free of disease after 2 years (pCHIK-CIR-). From the total, 83.9% had subacute disease and 16.1% not. From those patients that developed pCHIK-CIR, all of them had subacute disease first. Among those free of disease (pCHIK-CIR-), 9 presented subacute disease. Among patients that presented subacute disease 82.7% developed pCHIK-CIR+, compared to 0% of those that did not progressed to subacute disease, RD = 83/100 (95%CI 58-100) (p = 0.0076). Among those with subacute phase polyarthralgia 84% developed pCHIK-CIR+ (vs 16.7% without it) (RR = 5.208; 95%CI 2.51-10.797). The median number of joints affected during subacute disease was 8 (reaching up to 16 simultaneously). Conclusion: Based on the current findings, once a patient reaches the subacute phase (presenting rheumatological persistent symptoms, such as polyarthralgia, rigidity and/or edema), interventions to mitigate the impact of pCHIK-CIR should be performed. These results would be also in the current consideration of immunomodulatory therapeutics, since cytokines, among other factors, appear to be related to the progression to chronic disease.