Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review

Abstract

BackgroundChikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because little is known about interventions for treating CHIKV-related illness, we conducted a systematic review.MethodsWe used Cochrane methods. We searched PubMed, EMBASE, Cochrane Library, LILACS and other sources from the earliest records to March 2016. We had no language restrictions. We included randomized controlled trials assessing any intervention for treating acute or chronic CHIKV-related illness. Our primary outcomes were pain relief, global health status (GHS) or health related quality of life (HRQL), and serious adverse events (SAEs). We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality.ResultsWe screened 2,229 records and found five small trials with a total of 402 participants. Patients receiving chloroquine (CHQ) had better chronic pain relief than those receiving placebo (relative risk [RR] 2.67, 95% confidence interval [CI] 1.23 to 5.77, N = 54), but acute pain relief was marginally not different between groups (mean difference [MD] 1.46, 95% CI 0.00 to 2.92, N = 54). SAEs were similar (RR = 15.00, 95% CI 0.90 to 250.24, N = 54). Comparing CHQ with paracetamol (PCM), CHQ patients had better pain relief (RR = 1.52, 95% CI 1.20 to 1.93, N = 86). Compared with hydroxychloroquine (HCHQ), disease-modifying anti-rheumatic drugs (DMARDs) reduced pain (MD = -14.80, 95% CI -19.12 to -10.48, N = 72). DMARDs patients had less disability (MD = -0.74, 95% CI -0.92 to -0.56, N = 72) and less disease activity (MD = -1.35; 95% CI -1.70 to -1.00; N = 72). SAEs were similar between DMARDs and HCHQ groups (RR = 2.84, 95% CI 0.12 to 67.53, N = 72). Comparing meloxicam (MXM) with CHQ, there was no difference in pain relief (MD = 0.24, 95% CI = -0.81 to 1.29; p = 0.65, N = 70), GHS or HRQL (MD = -0.31, 95% CI -2.06 to 1.44, N = 70) or SAEs (RR = 0.85, 95% CI 0.30 to 2.42, N = 70). Finally, a four-arm trial (N = 120) compared aceclofenac (ACF) monotherapy to ACF+HCHQ, ACF+ prednisolone (PRD), or ACF+HCHQ+PRD. Investigators found reduced pain (p<0.001) and better HRQL (p<0.001) in the two patient groups receiving PRD, compared to those receiving ACF monotherapy or ACF+HCHQ. Trials were at high risk of bias. GRADE evidence quality for all outcomes was very low.ConclusionResults from these small trials provide insufficient evidence to draw conclusions about the efficacy or safety of CHIKV interventions. Physicians should be cautious in prescribing and policy-makers should be cautious in recommending any intervention reviewed here. Rigorous trials with sufficient statistical power are urgently needed, with results stratified by disease stage and symptomology.

Review: Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management

“…In addition to a potent type I IFN response, the acute stage of chikungunya virus infection (<21 days after the onset of infection) is associated with elevated patient plasma levels of multiple soluble factors, including proinflammatory cytokines and chemokines (CCL2, macrophage migration inhibitory factor, CCL4, CXCL10, IL‐6, IL‐8, and IL‐16), antiinflammatory cytokines (IL‐1 receptor A, IL‐10, and IL‐13), growth factors (granulocyte colony‐stimulating factor [G‐CSF], granulocyte–macrophage colony‐stimulating factor [GM‐CSF], vascular endothelial growth factor, and stem cell growth factor β) and other mediators (IFNγ, IL‐4, IL‐7, and CXCL9) . This results in intense monocyte trafficking to the infected tissues , along with strong activation of both CD8+ T and natural killer (NK) cells to assist in clearing the virus .…”

Global Emergency Medicine: A Review of the Literature From 2017

“…A systematic review on chikungunya virus infection-related rheumatic and musculoskeletal disorders identified chloroquine, hydroxychloroquine, disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal anti-inflammatory drugs as therapeutic options, but also highlights the lack of high-quality data to guide treatment decisions. 23 Tickell et al 28 performed a systematic review of Shigella infection in children. Dysenteric Shigella infections are often clinically obvious and are treated with antibiotics, but Shigella infections without symptoms of dysentery can be very difficult to detect.…”

A Case Report of Chikungunya Fever, Rheumatoid Arthritis, and Felty’s Syndrome

“…Considering the safety and effectiveness of MTX in the treatment of RA and related disorders and its widespread availability and relative cost-effectiveness, it is not surprising [20,21]. Ravindran and Alias evaluated two regimens in 62 patients, triple therapy of MTX (15 mg/week), HCQ (400 mg/day), and SSZ (1 g/day) compared to HCQ (400 mg/day) monotherapy.…”