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

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

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.

<p>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 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref060" target="_blank">60</a>]. 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 [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref054" target="_blank">54</a>]. ⁷RAPID 3 is significantly correlated with disease activity score (such as DAS28), and easily calculated in 10 second [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref055" target="_blank">55</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref056" target="_blank">56</a>].</p

Characteristics of patients referred to a rheumatologist for rheumatic pains persisting after a confirmed chikungunya infection, Saint Denis, Reunion Island, 2006–2012.

<p>* Age in 2006 (at the acute stage);</p><p>** prolonged acute CHIK when fever >10 days or symptoms > 3 weeks.</p><p>CHIK: chikungunya;</p><p>pCHIK: post-CHIK;</p><p>CIR: chronic inflammatory rheumatism;</p><p>MSD: musculoskeletal disorders;</p><p>RA: rheumatoid arthritis;</p><p>RMSD: rheumatic musculoskeletal disorders;</p><p>SA: spondyloathropathy,</p><p>UP: undifferentiated polyarthritis.</p><p>Characteristics of patients referred to a rheumatologist for rheumatic pains persisting after a confirmed chikungunya infection, Saint Denis, Reunion Island, 2006–2012.</p

Definitions of chronic inflammatory rheumatisms (CIR): rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria [37]; spondyloarthritis according the European Spondyloarthropathy Study Group (ESSG) Classification [38]; undifferentiated polyarthritis (own study criteria).

<p>* Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. DIP, first CMC, and first MTP are excluded from assessment. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement. “Large joints” refers to shoulders, elbows, hips, knees, and ankles. “Small joints” refers to the MC, PIP, second through fifth MTP, thumb IP joints, and wrists.</p><p>** In this category, at least 1 of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed (e.g., temporomandibular, acromioclavicular, sternoclavicular…).</p><p>*** Negative refers to international unit (IU) values that are less than or equal to the upper limit of normal (ULN) for the laboratory and assay; low-positive refers to IU values that are higher than the ULN but ≤ 3 times the ULN for the laboratory and assay; high-positive refers to IU values that are > 3 times the ULN for the laboratory and assay. Where RF information is only available as positive or negative, a positive result should be scored as low-positive for RF.</p><p>****Normal/abnormal is determined by local laboratory standards.</p><p>IP = interphalageal;</p><p>PIP = proximal interphalangeal;</p><p>DIP = distal interphalangeal;</p><p>CMC = carpometacarpal;</p><p>MCP = metacarpophalangeal;</p><p>MTP = metatarsophalangeal;</p><p>CRP = C-reactive protein;</p><p>ESR = erythrocyte sedimentation rate;</p><p>ACPA = anti-citrullinated protein antibody.</p><p>Definitions of chronic inflammatory rheumatisms (CIR): rheumatoid arthritis according to the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref037" target="_blank">37</a>]; spondyloarthritis according the European Spondyloarthropathy Study Group (ESSG) Classification [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003603#pntd.0003603.ref038" target="_blank">38</a>]; undifferentiated polyarthritis (own study criteria).</p

Treatment history of patients referred to a rheumatologist for rheumatic or musculoskeletal pains persisting after a confirmed chikungunya infection, Saint Denis, Reunion Island, 2006–2012.

<p>* No relapse 3 months after the termination of corticotherapy.</p><p>pCHIK: post-chikungunya;</p><p>MSD: musculoskeletal disorders;</p><p>CIR: chronic inflammatory rheumatism;</p><p>RA: rheumatoid arthritis;</p><p>SA: spondylarthropathy;</p><p>UP: undifferentiated polyarthritis;</p><p>DMARDs: disease-modifying antirheumatic drugs.</p><p>Treatment history of patients referred to a rheumatologist for rheumatic or musculoskeletal pains persisting after a confirmed chikungunya infection, Saint Denis, Reunion Island, 2006–2012.</p

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

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

Clinical characteristics and specific treatments of patients consulting for musculoskeletal pain (multiple joint inflammation excluded) persisting after a confirmed chikungunya infection, Saint-Denis, Reunion Island, 2006–2012.

<p><i>One patient may have several MSD</i>.</p><p>MCP: metacarpophalangeal;</p><p>PIP: proximal interphalangeal;</p><p>MTP: metatarsophalangeal;</p><p>NSAIDs: non steroidal anti-inflammatory drugs.</p><p>Clinical characteristics and specific treatments of patients consulting for musculoskeletal pain (multiple joint inflammation excluded) persisting after a confirmed chikungunya infection, Saint-Denis, Reunion Island, 2006–2012.</p

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.

<p>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.</p