Chronic Chikungunya Arthritis Research Articles

Chikungunya Arthritis Treatment with Methotrexate and Dexamethasone: A Randomized, Double-blind, Placebo-controlled Trial.

Chikungunya fever is a reemerging epidemic disease caused by a single-stranded RNA alphavirus transmitted throughout by Aedes mosquitoes. Chikungunya virus infection is a biphasic disease in which 72% to 95% of affected individuals manifest acute chikungunya fever. Following the acute phase, more than 40% of affected individuals develop arthritis, often lasting more than 3 months, referred to as chronic chikungunya arthritis, which frequently mimics rheumatoid arthritis. This study aimed to evaluate the efficacy and safety of treatment of chronic chikungunya arthritis with methotrexate and dexamethasone in a randomized, double-blind, placebo-controlled clinical trial. The patients were reassessed for treatment response by the DAS28-ESR, tender joint count and swollen joint count, Patient Global Assessment, and for secondary measures, including the Health Assessment Questionnaire Disability Index and Pain Visual Analog Scale. Thirty-one subjects were randomized (placebo, n = 16; methotrexate, n = 15); 27 completed treatment and 4 discontinued during the 8-week blinded period. Among the participants, 96.8% were female, with mean ± SD age was 52.9 ± 13. The mean ± SD disease duration prior to treatment was 220.9 ± 51.2 days. At 8 weeks, methotrexate-treated subjects showed a greater numerical trend towards improvement, but there were no significant differences between methotrexate- dexamethasone group and dexamethasone (placebo) group. In this relatively small cohort, all of whom received background dexamethasone, there was a greater numerical improvement trend in prespecified outcome measures, but methotrexate in combination with dexamethasone was not superior to dexamethasone in chronic chikungunya arthritis.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial

BackgroundChikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. ObjectiveTo evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. MethodsIn this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. ResultsThere was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. ConclusiontDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. Trial RegistrationBrazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.

Incidence and factors associated with chronic chikungunya arthritis following chikungunya virus infection.

Chikungunya virus infection is a mosquito-borne illness. First-phase symptoms include fever, malaise, rash, and arthritis (self-limiting). Some patients can have chronic-phase symptoms, including chronic tenosynovitis, bursitis, and arthritis. This study aimed to determine the incidence and risk factors of chronic arthritis in patients with chikungunya infection. This retrospective cohort study analysed all adults diagnosed with chikungunya infection between 2015 and 2020 at our centre. Baseline and follow-up symptoms were evaluated in serologically confirmed cases. Chronic chikungunya arthritis was persistent arthritis >3 months after the onset. Patients who had preexisting chronic inflammatory arthritis and were lost to follow-up before 3 months from diagnosis were excluded. This study enrolled 120 patients. The median age was 51 (IQR 14) years, and 78% were female. The median number of joints with arthritis was 4 (IQR 8). The initial visual analog scale (VAS) score was 50 mm (IQR 40). Small joints of the hands, wrist, and knee (44.2%, 43.3%, and 42.3%, respectively) were the most affected. The incidence of chronic chikungunya arthritis was 40.4%. From the multivariable logistic regression, the initial number of joints with arthritis, initial VAS scores, and female sex were independently associated with chronic chikungunya arthritis with odds ratios of 1.09 (95% confidence interval [CI] 1.01-1.18), 1.03 (95% CI 1.01-1.06), and 4.17 (95% CI, 1.05-16.67), respectively. Chronic chikungunya arthritis is common in patients with chikungunya virus infection. Its predictive factors include the initial number of joints with arthritis, initial VAS scores, and female sex.

Pathogenesis of chronic chikungunya arthritis: Resemblances and links with rheumatoid arthritis.

Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.

EP12 Chikungunga arthritis mimicking acute seronegative spondyloarthritis

Case report - IntroductionChikungunya is a tropical arbovirus transmitted by female Aedes Aegypti or Aedes Abopitus mosquitos. It is not indigenous to UK but occurs in epidemics in Africa and Asia. It often presents with pyrexia, arthralgia or arthritis, myalgia and a maculopapular rash and can mimic both peripheral and axial inflammatory arthritis as well as more common forms of viral arthritis. It can also become chronic leading to disabling symptoms. The diagnosis should be considered in all patients presenting with early inflammatory arthritis who have travelled to affected areas. Case report - Case descriptionA 57-year-old female developed sudden onset fever along with a macular rash whilst visiting South East Asia. She then developed widespread joint pains and severe inactivity stiffness, particularly affecting her ankles. The rash and fever settled after a few days, but her arthralgia persisted in her cervical spine and both small and large joints. She had a history of recurrent episcleritis and had been investigated for axial spondyloarthropathy two years previously, but MRI imaging of the spine and sacroiliac joints did not show any inflammatory changes.Examination in the rheumatology clinic confirmed right medial epicondylitis, bilateral shoulder tenderness, tenderness over the extensor tendons of the feet and painful cervical spine movement.Investigations revealed high inflammatory markers; CRP 29 (0-10 mg/L) and ESR 48 (0-15 mm/hr), a positive rheumatoid factor but negative anti CCP antibodies and a normal white cell count.Acute seronegative spondyloarthropathy was suspected but Chikungunya serology was requested at the suggestion of the patient, because of the history of a mosquito bite. IgM and IgG antibodies were positive on immunofluorescence, confirming recent infection.She was initially given intramuscular depomedrone and non-steroidal anti-inflammatory drugs (NSAIDs) with a short response but required oral prednisolone 20mg daily to suppress the inflammation in her feet. An MRI confirmed an ankle effusion and peroneal tenosynovitis. After 6 months her symptoms improved, and she was able to stop prednisolone completely and she remains well 9 months after the initial infection.Case report - DiscussionChikungunya infection causes musculoskeletal symptoms in all affected patients, but the clinical presentation can highly variable, from mild joint pain to erosive arthritis. It can be divided into three phases: incubation phase, acute phase, and chronic phase. The incubation phase varies between one to twelve days after the mosquito bite. The acute phase begins with high fever, headache, polyarthralgia/arthritis, lymphadenopathy, and anorexia. Joint involvement is often distal and symmetrical affecting the hands, wrists, shoulders, knees, ankles, and feet. A maculopapular rash is common. Dengue virus and Zika virus infection can present similarly. Treatment for acute Chikungunya fever is supportive. Analgesic, anti-pyretic and NSAIDs are used for symptom relief. During the chronic phase, infected people develop symmetrical, migratory, oligoarticular or polyarticular arthritis with morning stiffness and joint oedema, which can last from months to years.Our patient had a previous history which was consistent with seronegative spondyloarthropathy, an acute presentation of inflammatory arthritis and results and imaging which supported this diagnosis. The correct diagnosis could easily have been missed if a travel history had not been taken and the patient’s suspicions ignored.The best treatment for chronic Chikungunya arthritis is unclear. NSAIDs are often the first treatment but, as in this case systemic steroids are often necessary. Conventional synthetic DMARDs have also been reported efficacious. Biologic DMARDS have been used in resistant cases.Case report - Key learning pointsChikungunya has emerged as a global disease affecting millions of people with significant musculoskeletal morbidity. Any patient has travelled to endemic areas including Africa and Asia, with fever and joint pain should be screened for Chikungunya virus as well as Dengue virus, and Zika virus.Diagnosis is either by RT PCR (positive 0-7 days of infection or Immunoglobulin M (detectable after 5 – 10 day of infection and persists for few months).Treatment is supportive in acute phase, may require low doses of steroids to aid resolution of symptoms. Conventional DMARDS have shown benefit in chronic phase with ongoing synovitis/tenosynovitis. Patients may know more about rare, endemic diseases than their European doctors and their suspicions about potential diagnoses should always be considered.

Prevalence of chronic chikungunya and associated risks factors in the French West Indies (La Martinique):A prospective cohort study.

BackgroundThe chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity.Methodology/Principal findingsA total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5–59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4–32.2, p = 0.04).ConclusionsThis cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders.Trial registrationclinicaltrials.gov (NCT01099852).

Development of a concise clinical index for predicting chronic chikungunya arthritis

ObjectiveTo evaluate the performance of an instrument for predicting chronic chikungunya arthritis (CCA) in adult patients. MethodsA diagnostic test study was conducted and data from 217 confirmed cases of chikungunya virus (CHIKV) illness were analyzed. Two chronic chikungunya arthralgia scales (3-item CCAS-3 and 4-item CCAS-4) were constructed. ResultsModest performance of the CCAS-3 scale was documented at the two given cut-off points. A CCAS-4 score ≥3 showed high sensitivity and specificity for predicting the persistence of CCA at 12 months after acute disease. ConclusionsIf replicated in other populations, these results could be useful in the medical management of patients with symptomatic CHIKV infection.

Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review.

Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis. A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov. Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non-controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001). The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo-controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.

Need for Accurate and Consistent Definition of Chronic Chikungunya Arthritis: Comment on the Article by Chang et al

Need for Accurate and Consistent Definition of Chronic Chikungunya Arthritis: Comment on the Article by Chang et al

Emergence and treatment of chikungunya arthritis.

To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis. Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used. CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.

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

Chronic chikungunya (CHIK) arthritis, an inflammatory arthritis, often follows acute CHIK fever (CHIKF), a viral infection. The pathogenesis of chronic CHIK arthritis is poorly characterized, but may resemble other forms of inflammatory arthritis. Clinically, chronic CHIK arthritis sometimes mimics rheumatoid arthritis (RA). We report a patient with well-characterized CHIKF followed 2months later by chronic CHIK arthritis not only resembling RA clinically, but also associated with RA biomarkers and extra-articular features, including Felty's syndrome (FS). We describe this patient's excellent response to methotrexate and discuss the implications her case provides in understanding this important emerging rheumatic disease.

Regulatory T cells and IL-10 as modulators of chikungunya disease outcome: a preliminary study.

Regulatory T (Treg) cells hold centre stage in regulating the immune responses in most viral infections. However, their involvement in chikungunya infection is unexplored. In the current study, the frequencies and functionality of peripheral Treg and T effector (Teff) cells were assessed during different phases of chikungunya by flow cytometry and in-vitro cytokine assays. Treg cells were also studied in rheumatoid arthritis (RA) patients, whose symptoms closely mimic chronic chikungunya arthritis patients. Frequency of Treg cells was lower in acute and chronic chikungunya arthritis patients than in recovered individuals and controls, and comparable among recovered individuals and controls. Treg/Teff ratio was lower in acute than in chronic chikungunya arthritis patients, recovered individuals and controls. Higher secretion of CHIKV specific IL-10 was observed in recovered individuals than in acute, chronic chikungunya arthritis patients and controls. Frequencies of Treg and Teff cells were higher and Treg/Teff ratio was lower in RA patients than in chronic chikungunya arthritis patients. The results indicate that reduction of Treg cells was associated with ongoing CHIKV infection and normalization of Treg cells with resolution of disease. Contrasting phenotypic data in RA and chronic chikungunya arthritis suggest an altogether different mechanism of Treg-mediated pathology in both arthritis conditions. Overall, our preliminary study, suggesting an association of peripheral Treg cells and IL-10 with recovery from chikungunya, may provide insight into chikungunya disease prognosis and warrants further study.

Impaired NK cell functionality and increased TNF-α production as biomarkers of chronic chikungunya arthritis and rheumatoid arthritis

The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3−CD56+) and NK-like T (CD3+CD56+) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-α and IFN-γ-secreting NK-like T cells were high in both chronic arthritis patients than in controls. Percentage of TNF-α+ NK cells was higher in RA patients than in controls. Percentage of perforin+ NK cells was low in both chronic arthritis patient groups. Among the patient groups, expressions of perforin+ and IFN-γ+ NK-like T cells were higher in RA. Overall, our data show reduced frequency of NK-like T cells, lower expression of perforin+ NK, higher expression of TNF-α+ NK-like T and IFN-γ+ NK-like T cells as the markers of chronic arthritic diseases. In the absence of any specific treatment for chronic chikungunya induced arthritis and promising results of anti-TNF-α therapy against RA, current data may form the basis for future in vivo studies and has scope as possible therapeutics against chikungunya.

Chikungunya disease and chloroquine treatment

In a recent issue of the Journal of Medical Virology, Khan et al. [2010] presented an “assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against Chikungunya virus in Vero cells.” This article mentions the fact that chloroquine, a well-known drug developed for the treatment of malaria in the 1930s, was considered previously as a potent antiviral drug in a number of viral diseases (HIV, HBV, influenza A virus, SARS, and others) but makes no reference to previous studies of the antiviral activity of chloroquine against alphaviruses (and more specifically Chikungunya virus) suggesting that the authors had identified a new and promising field of investigation. Their presentation deserves significant qualification. First, the in vitro antiviral effect of chloroquine is not a recent discovery. It was first reported some 40 years ago [Inglot, 1969; Shimizu et al., 1972]. A clinical antiviral application of the molecule has been assessed over time for a number of viral pathogens, and the concrete benefits or risks of such treatment is still debated [Boelaert et al., 1999; Seth et al., 1999; Fredericksen et al., 2002; Savarino et al., 2006]. Regarding alphaviruses, in cellulo inhibition of Sindbis and Semliki Forest virus replication was reported 30 years ago [Coombs et al., 1981; Helenius et al., 1982], but these results were balanced by those obtained from a mouse model, which suggested that chloroquine may enhance viral replication in vivo and aggravate the disease [Maheshwari et al., 1991]. Soon after the beginning of the Chikungunya outbreak in 2005, in the Indian Ocean, the question of the possible use of chloroquine was raised. It is a matter of fact that, in many tropical areas, chloroquine is used as a symptomatic treatment of febrile illnesses and thus, the health authorities had to face its actual—non-evaluated—use during the acute phase of Chikungunya disease. The (confusing) reasons why a part of the local population utilized chloroquine also possibly included the fact that immunomodulatory effects of chloroquine have been used for a long time in autoimmune and rheumatological diseases [Cooper and Magwere, 2008], including chronic Chikungunya arthritis [Brighton, 1984]. Early studies of the emerging Indian Ocean Chikungunya virus (CHIKV) variant demonstrated in vitro inhibition of virus replication by chloroquine [Charrel, 2006; de Lamballerie et al., 2008, 2009; Gould et al., 2010]. Sourisseau et al. [2007] reported that chloroquine inhibited potently the appearance of CHIKV-positive cells and CHIKV-associated cytopathic effect and noted that the therapeutic (antiviral) index of chloroquine in cell cultures is rather narrow and thus, one should be cautious when proposing the use of chloroquine as an antiviral treatment in infected individuals. These early results led to the careful design of a clinical trial in the French Reunion Island (Indian Ocean) (CuraChik, http://clinicaltrials.gov/ct/show/NCT00391313), which was performed at the end of the 2006 outbreak [de Lamballerie et al., 2008]. In this double-blind placebo-controlled randomized trial, 27 patients (diagnosed within <48 hr) received chloroquine and 27 other patients received a placebo treatment. The chloroquine treatment consisted of 600 mg at day 1, 600 mg at days 2 and 3, and 300 mg at days 4 and 5 (and not 250 mg daily as reported by Savarino et al. [2007]). The results did not provide justification for the use of chloroquine to treat acute Chikungunya infections. In conclusion, the issue of chloroquine treatment of Chikungunya virus infection has been examined for years. Whilst in vitro inhibition of CHIKV replication is strongly established, the narrow therapeutic index and the absence of obvious biological or clinical improvement during a clinical trial do not argue in favor of a curative use in non-complicated cases. Whether chloroquine may be useful as a prophylactic treatment, or in the case of severe, sustained Chikungunya infections deserves further investigations that could take advantage of the availability of a relevant non-human primate animal model [Labadie et al., 2010].

Clinical profile and long-term sequelae of Chikungunya fever

Objectives 1. Primary objective: To study the clinical profile of acute Chikungunya fever. 2. Secondary objectives: To study the clinical profile of chronic sequelae and response of these patients to treatment. Methods One hundred and fifty adult patients who presented with a triad of fever arthralgia and rash during the period of June-December 2007 to the outpatient department of Medical College Calicut were considered for the study. They were followed up for 18 months or till symptoms subsided by direct examination as well as telephone interviews. There were no drop outs. Further follow-up of those in whom symptoms persisted was done, Exclusion of other rheumatologic disorders was done clinically and by relevant investigations Data was analyzed using SPSS statistical package. Results One hundred and thrity-four patients had typical clinical features of Chikungunya and 122 tested positive for IgM chik V capture ELISA. Hundred of them who were traceable were included in follow-up group with an age range of 20–60 years; 60% of them were females. A biphasic pattern was noted for the disease with first surge during July-September (60% of cases) and second surge during December (15% of cases). Fever was present in 96% Arthralgia was present in 100% of the patients and arthritis in 78%. Acute arthritis resolved within seven days in most of the patients. Ankle and small joints of hand were the joints most commonly affected. Ninty percent of the patients had symptoms beyond three months. In 14% of patients arthralgia persisted for 3–6 months, in 32% for 6–9 months, in 22% for 9–12 months, and in 22% for more than 1 year. Antimalarials were effective in decreasing the duration of disease; 5% of chronic Chikungunya arthritis evolved into rheumatoid arthritis. Conclusions In our study causes arthralgia was present in 100% of Chikungunya patients, arthritis in 78%, skin rash in 68%, and 22% had persistent symptoms. Antimalarials and short courses of steroids may be useful in a subset of them. Chikungunya arthritis evolved into rheumatoid arthritis in 5% of our patients.

Methotrexate and hydroxychloroquine combination therapy in chronic chikungunya arthritis: a 16 week study

Objective To study the clinical profile of patients of chronic chikungunya arthritis presenting to a rheumatology OPD in the Western part of India and to judge the treatment response to the disease modifying drugs (methotrexate and hydroxychloroquine) used to treat them. Materials and methods The diagnosis of chronic chikungunya arthritis was based on clinical criteria only. All patients giving a history of fever with arthritis starting during the epidemic of chikungunya in the Western part of India (August–September 2006) and having had the arthritis for > 3 months since then were included in the study. Baseline clinical characteristics were calculated. Most patients received methotrexate (15 to 20 mg weekly) and hydroxychloroquine for their chronic arthritis and their ACR 20, 50 and 70 responses and EULAR remission and EULAR good response based on DAS 28 ESR were calculated. Results A total of 305 patients presented to the OPD till March 2008. Mean age of the patients was 49 years. Female to male ratio was 2.8:1 (223:82). The other mean baseline values were: patients global 6 (0 to 10, 0 best), physician's global 5.8 (0 to 10, 0 best), HAQ score 1.6 (0 to 3), swollen joint count 8.8 (28 joint count), tender joint count 14 (28 joint count), ESR 52 mm first hour (Westergren). About one-third of the patients had parasthesias in the carpal tunnel distribution. Rheumatoid factor was positive in 76 out of 256 when it was done (29.7%) and anti-CCP was positive in 6/73 when it was done. Data needed for judging treatment response was available in 149 patients at a mean follow up of 16 weeks period and they received combination of methotrexate and hydroxychloroquine. ACR 20 was achieved in 73/149 (48.9%), ACR 50 in 28/149 (18.8%) and ACR 70 in 6/149 (4%). Only one of the patients achieved EULAR remission (DAS 28 ESR < 2.6) and four others achieved EULAR good response (DAS 28 ESR < 3.2) at the end of 16 weeks. None of the patients had any adverse effect to the DMARDs used. Conclusion Chronic chikungunya arthritis is a significant cause of morbidity in this part of the world. In this analysis most patients were middle aged and female to male ratio was 3:1. About one-third of the patients reported carpal tunnel symptoms. About half of the patients who received the combination of methotrexate and hydroxychloroquine achieved an ACR 20 response at 16 weeks.