Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 cases in Reunion Island from 2006-2012

Abstract

Background: Since 2003, the tropical arthritogenic chikungunya (CHIK) virus has become an increasingly medical and economic burden in affected areas as it can often result in long-term disabilities. The clinical spectrum of post-CHIK (pCHIK) rheumatic disorders is wide. Evidence-based recommendations are needed to help physicians manage the treatment of afflicted patients.

Patients and methods: We conducted a 6-year case series retrospective study in Reunion Island of patients referred to a rheumatologist due to continuous rheumatic or musculoskeletal pains that persisted following CHIK infection. These various disorders were documented in terms of their clinical and therapeutic courses. Post-CHIK de novo chronic inflammatory rheumatisms (CIRs) were identified according to validated criteria.

Results: We reviewed 159 patient medical files. Ninety-four patients (59%) who were free of any articular disorder prior to CHIK met the CIR criteria: rheumatoid arthritis (n=40), spondyloarthritis (n=33), undifferentiated polyarthritis (n=21). Bone lesions detectable by radiography occurred in half of the patients (median time: 3.5 years pCHIK). A positive therapeutic response was achieved in 54 out of the 72 patients (75%) who were treated with methotrexate (MTX). Twelve out of the 92 patients (13%) received immunomodulatory biologic agents due to failure of contra-indication of MTX treatment. Other patients mainly presented with mechanical shoulder or knee disorders, bilateral distal polyarthralgia that was frequently associated with oedema at the extremities and tunnel syndromes. These pCHIK musculoskeletal disorders (MSDs) were managed with pain-killers, local and/or general anti-inflammatory drugs, and physiotherapy.

Conclusion: Rheumatologists in Reunion Island managed CHIK rheumatic disorders in a pragmatic manner following the outbreak in 2006. This retrospective study describes the common mechanical and inflammatory pCHIK disorders. We provide a diagnostic and therapeutic algorithm to help physicians deal with chronic patients, and to limit both functional and economic impacts. The therapeutic indication of MTX in pCHIK CIR could be approved in future efficacy trials.

Fig 1. Nosologic flow-chart of patients referred to a rheumatologist for post-chikungunya (pCHIK) persistent rheumatic musculoskeletal pain, Saint-Denis, Reunion Island, 2006–2012.

Fig 2. Time elapsed between chikungunya (CHIK) infection and the first visit to a rheumatologist for rheumatic or musculoskeletal disorders, Saint-Denis, Reunion Island, 2006–2012: musculoskeletal disorders versus chronic inflammatory rheumatisms.

Fig 3. Proposal for a diagnostic and therapeutic algorithm to manage rheumatic and musculoskeletal disorders persisting after acute chikungunya (CHIK) infection, with the following abbreviations: ACPA = anti-citrullinated protein antibody; CHIK = chikungunya; CIR = chronic inflammatory rheumatisms; CPK = creatine phosphokinase; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; Ig = immunoglobulin; Pi = post-infection; MSD = musculoskeletal disorders; RF = rheumatoid factors; RMSD = rheumatic musculoskeletal disorders; TSH = Thyroid Stimulating Hormone; ¹NSAID = non-steroidal anti-inflammatory drugs; ²DN4 = “Douleur Neuropathique 4” questionnaire.

Neuropathic pain if ≥4/10 (sensitivity = 83% and specificity = 90%): use of tricyclic antidepressants, anti-epileptic drugs. ³Corticosteroids = [5–40] mg/day, short course (decrease and withdrawal within 6 months), associated with calcium and vitamin supplementation. ⁴MTX = methotrexate [7.5–25] mg/week orally or injected (notably if > 15mg/week); in the absence of contraindication (hepatic, pulmonary); in association with vitamin B9 (folate as folic acid or folinic acid) 5 to 10 mg/week 48 hours after MTX is taken; with weekly monitoring of complete blood count and monthly monitoring of liver and renal functions [60]. ⁵Immune-modulating biologic agents = rheumatologist prescription among anti-TNF (etanercept 25mg twice a week, infliximab 3–5 mg/kg/ 6–8 weeks, adalimumab 40 mg/ 2 weeks, golimumab 50mg/month), abatacept (inhibition of T-lymphocyte activation, 500–1000 mg/ 4 weeks), rituximab (depletion of B-lymphocytes, 1000 mg repeated at 2 weeks) and tocilizumab (inhibition of interleukin-6 receptor, 8 mg/ kg/ 2 weeks). ⁶MDHAQ = Multi-Dimensional Health Assessment Questionnaire [54]. ⁷RAPID 3 is significantly correlated with disease activity score (such as DAS28), and easily calculated in 10 second [55,56].