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Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort - PubMed

  • ️Sun Jan 01 2023

Clinical markers of post-Chikungunya chronic inflammatory joint disease: A Brazilian cohort

Carolina Dos Santos Lázari et al. PLoS Negl Trop Dis. 2023.

Abstract

Background: Chikungunya-fever (CHIKF) remains a public health major issue. It is clinically divided into three phases: acute, post-acute and chronic. Chronic cases correspond to 25-40% individuals and, though most of them are characterized by long-lasting arthralgia alone, many of them exhibit persistent or recurrent inflammatory signs that define post-Chikungunya chronic inflammatory joint disease (pCHIKV-CIJD). We aimed to identify early clinical markers of evolution to pCHIKV-CIJD during acute and post-acute phases.

Methodology/principal findings: We studied a prospective cohort of CHIKF-confirmed volunteers with longitudinal clinical data collection from symptoms onset up to 90 days, including a 21-day visit (D21). Of 169 patients with CHIKF, 86 (50.9%) completed the follow-up, from whom 39 met clinical criteria for pCHIKV-CIJD (45.3%). The relative risk of chronification was higher in women compared to men (RR = 1.52; 95% CI = 1.15-1.99; FDR = 0.03). None of the symptoms or signs presented at D0 behaved as an early predictor of pCHIKV-CIJD, while being symptomatic at D21 was a risk factor for chronification (RR = 1.31; 95% CI = 1.09-1.55; FDR = 0.03). Significance was also observed for joint pain (RR = 1.35; 95% CI = 1.12-1.61; FDR = 0.02), reported edema (RR = 3.61; 95% CI = 1.44-9.06; FDR = 0.03), reported hand and/or feet small joints edema (RR = 4.22; 95% CI = 1.51-11.78; FDR = 0.02), and peri-articular edema observed during physical examination (RR = 2.89; 95% CI = 1.58-5.28; FDR = 0.002). Furthermore, patients with no findings in physical examination at D21 were at lower risk of chronic evolution (RR = 0.41, 95% CI = 0.24-0.70, FDR = 0.01). Twenty-nine pCHIKV-CIJD patients had abnormal articular ultrasonography (90.6% of the examined). The most common findings were synovitis (65.5%) and joint effusion (58.6%).

Conclusion: This cohort has provided important insights into the prognostic evaluation of CHIKF. Symptomatic sub-acute disease is a relevant predictor of evolution to chronic arthritis with synovitis, drawing attention to joint pain, edema, multiple articular involvement including small hand and feet joints as risk factors for chronification beyond three months, especially in women. Future studies are needed to accomplish the identification of accurate and early biomarkers of poor clinical prognosis, which would allow better understanding of the disease's evolution and improve patients' management, modifying CHIKF burden on global public health.

Copyright: © 2023 Lázari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart showing the progress of the CHIKF cohort.

Gray frames represent patients who were excluded from the analysis. Green frames represent the two study groups analyzed. n = number of patients; D21 = Follow–up visit 21 days after inclusion; D90 = Follow–up visit 90 days after inclusion; pCHIKV–CIJD = post–Chikungunya chronic inflammatory joint disease; non–pCHIKV–CIJD = patients who did not met criteria of pCHIKV–CIJD.

Fig 2
Fig 2. Evoltution of volunteers’ symptoms and signs along the follow–up.

A. Any symptom. B. Joint pain. C. Reported joint edema. D. Peri–articular edema in physical examination. Yes: With symptom; No: Without symptom; Missing: Patient did not return and was not contacted in the period.

Fig 3
Fig 3. CHIKV genome sequencing and phylogenetic analysis.

A. Number of reads of CHIKV sequences per sample. To the left of the dotted line are samples with a number of reads enough to cover CHIKV complete genome. B. The phylogenetic tree was obtained by comparing pCHIKV–CIJD, non–pCHIKV–CIJD, and other publicly available samples from Rio de Janeiro and other states.

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