Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Fleury Medicina e Saúde, São Paulo, Brazil.
PLoS Negl Trop Dis. 2023 Jan 6;17(1):e0011037. doi: 10.1371/journal.pntd.0011037. eCollection 2023 Jan.
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%).
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.
基孔肯雅热（CHIKF）仍然是一个主要的公共卫生问题。它在临床上分为三个阶段：急性、亚急性和慢性。慢性病例对应 25-40%的个体，尽管大多数病例仅表现为长期关节痛，但其中许多病例表现出持续或复发性炎症迹象，定义为基孔肯雅慢性炎症性关节病（pCHIKV-CIJD）。我们旨在确定急性和亚急性阶段向 pCHIKV-CIJD 演变的早期临床标志物。
方法/主要发现：我们研究了一个前瞻性队列，其中包括来自症状发作到 90 天的纵向临床数据收集的 CHIKF 确诊志愿者，包括 21 天的访问（D21）。在 169 例 CHIKF 患者中，86 例（50.9%）完成了随访，其中 39 例符合 pCHIKV-CIJD 的临床标准（45.3%）。与男性相比，女性慢性化的相对风险更高（RR=1.52；95%CI=1.15-1.99；FDR=0.03）。D0 时出现的任何症状或体征均未作为 pCHIKV-CIJD 的早期预测因子，而 D21 时出现症状是慢性化的危险因素（RR=1.31；95%CI=1.09-1.55；FDR=0.03）。关节痛（RR=1.35；95%CI=1.12-1.61；FDR=0.02）、报告的水肿（RR=3.61；95%CI=1.44-9.06；FDR=0.03）、报告的手和/或脚小关节水肿（RR=4.22；95%CI=1.51-11.78；FDR=0.02）以及体检时观察到的关节周围水肿（RR=2.89；95%CI=1.58-5.28；FDR=0.002）也具有统计学意义。此外，D21 时体检无异常的患者慢性演变风险较低（RR=0.41，95%CI=0.24-0.70，FDR=0.01）。29 例 pCHIKV-CIJD 患者进行了关节超声异常检查（检查的 90.6%）。最常见的发现是滑膜炎（65.5%）和关节积液（58.6%）。
该队列为 CHIKF 的预后评估提供了重要的见解。亚急性症状是向伴有滑膜炎的慢性关节炎演变的重要预测因子，关节痛、水肿、包括手和脚小关节在内的多个关节受累均提示慢性化的风险增加，尤其是女性。需要进一步研究以确定不良临床预后的准确和早期生物标志物，这将有助于更好地了解疾病的演变并改善患者的管理，从而减轻基孔肯雅热对全球公共卫生的负担。
