|Ahead of print publication
US7 score in the subacute phase does not correlate with outcomes in Chikungunya arthritis
Benzeeta Pinto1, Anu Mohan Desai1, Farha Furruqh2, KN Sangeeta1, B Sheba Charles1, John Michael Raj3, Ramya Janardana1, Vineeta Shobha1
1 Department of Clinical Immunology and Rheumatology, St John's Medical College, Bengaluru, Karnataka, India
2 Department of Radiology, St John's Medical College, Bengaluru, Karnataka, India
3 Department of Biostatistics, St John's Medical College, Bengaluru, Karnataka, India
|Date of Submission||17-Sep-2020|
|Date of Acceptance||13-Jan-2021|
Department of Clinical Immunology and Rheumatology, St John's Medical College, Sarjapur Road, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Chikungunya fever is a remerging disease and may lead to postchikungunya inflammatory joint pain.
Objective: To study the clinical and ultrasound (US) features of chikungunya arthritis in the subacute phase and to determine if high disease activity on US on is associated with chronic disability.
Materials and Methods: We conducted a prospective observational study of all patients who presented with subacute chikungunya arthritis over 1 year duration. Chikungunya fever was diagnosed by consistent clinical picture with specific immunoglobulin M positivity. Disease activity assessments and US-7 score were performed at baseline. Indian Health Assessment Questionnaire (HAQ) and pain on numerical rating scale were done at baseline and 1 year of follow-up.
Results: We included 23 patients (18 females) with a median age of 43 years. Most (22/23) patients had polyarticular disease with negative rheumatoid factor and anticyclic citrullinated peptide. Ultrasound revealed synovitis in all and tenosynovitis in most patients. The median (interquartile range) US7 score, Disease Activity Score 28 erythrocyte sedimentation rate (DAS28-ESR) score, Indian HAQ, and pain at presentation were 15 (11), 4.4 (2), 0.92 (0.7), and 5 (6), respectively. Twenty patients were treated with a short course of glucocorticoids. One-year follow-up was available in 20 patients. The median HAQ and pain score at follow-up were 0.08 (0.21) and 1 (1), respectively . No correlation was found between US7 score, DAS28, swollen joint count, tender joint count, ESR, HAQ score, or pain at presentation with HAQ and pain at follow-up.
Conclusion: Disease activity at presentation as assessed by US7 score did not correlate with disability and pain at 1 year of follow-up in patients with chikungunya arthritis.
Keywords: Chikungunya arthritis, MSK, US-7
|How to cite this URL:|
Pinto B, Desai AM, Furruqh F, Sangeeta K N, Charles B S, Raj JM, Janardana R, Shobha V. US7 score in the subacute phase does not correlate with outcomes in Chikungunya arthritis. Indian J Rheumatol [Epub ahead of print] [cited 2021 Jun 18]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=313578
| Introduction|| |
Chikungunya fever is an acute febrile illness caused by an arbovirus of the Togaviridae family and is transmitted by the bite of infected Aedes mosquitoes. In India, surveillance data assimilated from the network of virology laboratories indicate continued transmission of this infection across all regions, with a peak between September and December, reporting 28 outbreaks between 2016 and 2018. The acute illness is characterized by fever and severe arthralgias and myalgias. This may be followed in a significant proportion of patients by a subacute and chronic phase predominated by rheumatic musculoskeletal manifestations. Up to 40% of patients may develop chronic inflammatory rheumatism following acute illness. The manifestations include arthralgias and arthritis, tenosynovitis, bursitis, frozen shoulder, and fibromyalgia like chronic pain. Chronic chikungunya arthritis may be oligoarticular or polyarticular closely resembling rheumatoid arthritis. Many patients with chronic chikungunya arthritis fulfil the ACR2010 criteria for RA. The risk factors for the persistence of joint symptoms are not clear. We hypothesized that higher inflammatory burden at presentation may be a factor determining the long-term outcome.
Ultrasound (US) is a sensitive tool for detecting synovitis and tenosynovitis in the joints and can pick up activity that is missed on routine clinical examination. Other advantages include absence of ionizing radiation, ability to perform dynamic and comparative examination of multiple joints, low cost, and good tolerability by patients. The US7 score is a comprehensive disease activity tool that incorporates synovitis, tenosynovitis, and erosions. It is a validated disease activity measure in RA and is sensitive to change., Since chikungunya arthritis closely resembles RA,, we used the US-7 score to measure disease activity in patients with subacute chikungunya arthritis and to assess if high disease activity at onset is associated with persistent disability at follow-up of 1 year.
| Materials and Methods|| |
This was a prospective observational study conducted in a tertiary care referral center from December 2017 to December 2018. All patients with a recent history of viral fever followed by joint pains of <12 weeks in duration who presented to the rheumatology outpatient clinic were screened for the study. The case definition of chikungunya arthritis was as follows: clinical illness consistent with chikungunya fever with laboratory confirmation with chikungunya serology (specific anti-CHIKV immunoglobulin M [IgM] antibodies positive) and synovitis of at least one joint either on clinical examination or US. Antichikungunya virus IgM antibodies were detected using a qualitative lateral flow immunoassay (CTK biotech Inc). Patients with diffuse pain or other musculoskeletal complaints without synovitis were excluded from the study. Patients with any other form of inflammatory arthritis or connective tissue disease were excluded from the study. All patients underwent detailed clinical examination and relevant laboratory investigations. Serologies for rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP), human immunodeficiency virus, hepatitis B surface antigen, and hepatitis C were done in all patients.
Disease activity was assessed with disease activity score 28 joints-erythrocyte sedimentation rate (DAS28 ESR), swollen joint count (66), and tender joint count (68). Disability assessment was done at baseline and last follow-up using the Indian version of the Health Assessment Questionnaire (HAQ). Pain was documented on a numerical rating scale (NRS). Treatment of patients was as per discretion of a treating physician. Patients were followed up for at least 1 year after recruitment and HAQ and NRS for pain were assessed at the last follow-up. All clinical assessments were done by a rheumatologist (BP).
Ultrasound disease activity assessment
Musculoskeletal US was performed using GE Logiq E US machine with a 12-20 Hz hockey stick probe. US was done by a radiologist trained in musculoskeletal US (FF) who was blinded to the clinical findings. We used the US7 score to measure disease activity. US7 score is a validated tool for the measurement of disease activity in rheumatoid arthritis. It includes the assessment of 7 joints for synovitis, tenosynovitis with both gray scale and power Doppler (PD) ultrasonography, and erosions with GS. The joints of the clinically dominant hand and foot were included, namely, wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis was scored semiquantitatively (Grade 0-3) by gray scale (GS) and PD-US. Tenosynovitis was scored for its presence on gray scale and semiquantitatively (0–3) for vascularity on PD. Erosions were scored as present or absent. Definitions of synovitis, tenosynovitis/paratenonitis, and erosions were as per OMERACT definitions.
Statistical tests were performed using the StataCorp. 2019. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC. Quantitative variables were described as mean ± standard deviation or median (interquartile range [IQR]) as appropriate. Categorical variables were described as frequencies. Normality of the data was checked using Shapiro–Wilk test. Correlations were analyzed using Spearman's or Pearson's coefficient as applicable. P < 0.05 was considered statistically significant.
Ethical clearance was obtained from the institutional ethics committee. Bioethics guidelines set by the Indian Council of Medical Research 2017 and the Helsinki declaration 2013 were adhered to.
| Results|| |
Twenty-three patients (18 females) with a median age of 43 years (IQR: 13; range, 25–65) were included in the study. The median duration of joint pain at presentation was 2 months (IQR: 1.5; range, 0.5–3 months). The pattern of joint involvement was similar to rheumatoid arthritis; 22 patients had polyarticular disease. RF was positive in 1 patient in low titer, and anti-CCP was negative in all [Table 1]. US revealed synovitis on gray scale in all patients and tenosynovitis in 21/23 patients [Figure 1]. PD showed increased vascularity in the synovium in 22 patients. In 15 patients, Doppler signal was noted in the tenosynovium. The median DAS28 ESR score, Indian HAQ, and US7 score at presentation were 4.4 (2), 0.92 (0.7), and 15 (11), respectively [Table 1]. Six patients had low disease activity (DAS28 ESR < 3.2), 11 moderate (DAS28 ESR 3.2–5.1), and 6 high disease activity (DAS28 ESR > 5.1) based on DAS28 scores. Thirteen patients reported mild disability (HAQ < 1) and 10 patients moderate disability (HAQ 1–2) at presentation. The median pain score at presentation was 5 (6). US7 score did not show a good correlation with other parameters of disease activity and HAQ-DI at presentation [Table 2]. Synovitis score on gray scale showed a significant correlation with CRP, ESR, and swollen joint counts. Twenty patients were treated with a short course of glucocorticoids in the first 3 months of illness. Fifteen and three patients were treated with methotrexate and hydroxychloroquine, respectively. One-year follow-up was available in 20 patients. Only two patients continued to be on methotrexate. All the other patients had stopped treatment after a variable duration of 3–6 months. The median HAQ score at follow-up was 0.08 (IQR: 0.2; range, 0–0.41). The HAQ score was less than 1 in all patients. Nine patients reported no disability (HAQ-0) and the rest reported mild disability (HAQ 0–1). The NRS pain at follow-up was 1 (IQR: 1; range, 0–3). No correlation was found between US7 score at presentation and DAS28, swollen joint count, tender joint count, ESR, US7 score, HAQ score, or NRS pain at presentation with HAQ and pain NRS at follow-up [Table 3].
|Table 1: Clinical features and disease activity parameters in chikungunya arthritis|
Click here to view
|Table 2: Correlation of ultrasound 7 score with other parameters of disease activity at baseline|
Click here to view
|Table 3: Correlation of ultrasound 7 scores with disability and pain at 1 year of follow-up|
Click here to view
| Discussion|| |
The clinical features and joint distribution of chikungunya arthritis in our study were very similar to rheumatoid arthritis with symmetric small and large joint involvement and sparing of axial skeleton. However, only one patient was positive for RF and all were negative for anti-CCP. Bouquillard et al. reported 21 cases with chronic chikungunya arthritis who fulfilled the ACR criteria for rheumatoid arthritis. Unlike our series, 57% of the patients in this series were positive for RF and 28.6% positive for anti-CCP. None or our patients had axial or entheseal involvement. Javelle et al. found that among 94 with chronic inflammatory rheumatism following chikungunya fever, the pattern of joint involvement included rheumatoid arthritis (n = 40), spondylarthritis (n = 33), and undifferentiated polyarthritis (n = 21). RHUMATOCHIK study included 307 patients with joint pains following chikungunya fever. In this study, synovitis was found in 64% of the patients. The joint involvement was symmetric and most commonly involved the wrists, the proximal interphalangeal joints of the fingers, and the ankles. Very few patients in this study were treated with glucocorticoids and disease-modifying antirheumatic drugs. At 32 months of follow-up, 83% of the patients continued to have joint pains.
The US features of chikungunya arthritis in our study were similar to RA with prominent synovitis and tenosynovitis. A study that evaluated the US features of acute chikungunya arthritis noted joint effusions in over 90%; however, unlike our study, tenosynovitis was rare. We found that tenosynovitis/paratenonitis was very prominent in the subacute phase and contributed to the disease activity. Similar findings were noted by Mogami et al. in four patients with subacute chikungunya arthritis. Erosions were uncommon as expected due to the short duration of symptoms. Mogami et al. studied the ankle joints using US in 52 patients of chikungunya arthritis with a mean duration of symptoms of 4 months. Joint effusion (69%) followed by tenosynovitis (59%) were the most common findings noted in this study.
The treatment and outcomes of chikungunya arthritis are not well studied. In our series, most patients were treated with steroids and methotrexate. A randomized open-label study found that triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine was superior to hydroxychloroquine in patients with chronic persistent chikungunya arthritis of >1 year duration. Few other retrospective series have also reported the efficacy of methotrexate. However, the effect of early treatment has not been examined., All our patients were recruited into the study within 3 months of onset of symptoms. Early treatment may have modified the outcome positively since most patients had no/mild disability at 1 year of follow-up and only 2 patients continued to be on treatment. This was much lower than that reported from previous observational studies. A meta-analysis that included 18 studies found that the prevalence of chronic inflammatory rheumatism was 40% and chronic arthritis was 13%. Based on our observations, we believe that institution of steroids/DMARDs in the acute/subacute stage may prevent chronic arthritis postchikungunya fever.
The strengths of our study were the assessment of disease activity both clinically and with the aid of US. The US assessments were done systematically and by a single blinded observer as per the US7 score. Our study had several limitations. The sample size was small. In the absence of any valid disease activity tools for chikungunya arthritis, we used outcome measures validated for use in rheumatoid arthritis. We were unable to repeat an US at follow-up to assess disease activity and response to treatment. Other rheumatic manifestations of chikungunya fever like carpal tunnel syndrome and bursitis were not assessed.
| Conclusion|| |
Chikungunya arthritis in the subacute phase is characterized by synovitis and tenosynovitis in a distribution similar to rheumatoid arthritis. It closely mimics seronegative rheumatoid arthritis. High disease activity as documented clinically and with US7 score did not correlate with disability at 1 year of follow-up. Further studies are required to understand the natural history and risk factors for chronic arthritis. A short course of steroids and DMARDs early in the disease may modify the course and lead to favorable outcomes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Murhekar M, Kanagasabai K, Shete V, Joshua V, Ravi M, Kirubakaran BK, et al
. Epidemiology of chikungunya based on laboratory surveillance data—India, 2016-2018. Trans R Soc Trop Med Hyg 2019;113:259-62.
Rodríguez-Morales AJ, Cardona-Ospina JA, Fernanda Urbano-Garzón S, Sebastian Hurtado-Zapata J. Prevalence of post-chikungunya infection chronic inflammatory arthritis: A systematic review and meta-analysis. Arthritis Care Res (Hoboken) 2016;68:1849-58.
Javelle E, Ribera A, Degasne I, Gaüzère BA, Marimoutou C, Simon F. Specific management of post-chikungunya rheumatic disorders: a retrospective study of 159 cases in Reunion Island from 2006-2012. PLoS Negl Trop Dis. 2015 Mar 11;9(3):e0003603. doi: 10.1371/journal.pntd.0003603.
Ohrndorf S, Backhaus M. Advances in sonographic scoring of rheumatoid arthritis. Ann Rheum Dis 2013;72 Suppl 2:ii69-75.
Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W et al
. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009;61:1194-201. doi: 10.1002/art.24646.
Backhaus TM, Ohrndorf S, Kellner H, Strunk J, Hartung W, Sattler H, et al
. The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy. Ann Rheum Dis 2013;72:1163-9.
Bouquillard E, Combe B. A report of 21 cases of rheumatoid arthritis following Chikungunya fever. A mean follow-up of two years. Joint Bone Spine 2009;76:654-7.
Bouquillard E, Fianu A, Bangil M, Charlette N, Ribéra A, Michault A, et al
. Rheumatic manifestations associated with Chikungunya virus infection: A study of 307 patients with 32-month follow-up (RHUMATOCHIK study). Joint Bone Spine 2018;85:207-10.
Marques CD, Duarte AL, Ranzolin A, Dantas AT, Cavalcanti NG, Guimarães Gonçalves RS, et al
. Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2-treatment. Rev Bras Reumatol English Ed 2017;57 Suppl 2:438-51.
Kumar A, Malaviya AN, Pandhi A, Singh R. Validation of an Indian version of the Health Assessment Questionnaire in patients with rheumatoid arthritis. Rheumatology (Oxford) 2002;41:1457-9.
Blettery M, Brunier L, Banydeen R, Derancourt C, de Bandt M. Management of acute-stage chikungunya disease: Contribution of ultrasonographic joint examination. Int J Infect Dis 2019;84:1-4.
Mogami R, de Almeida Vieira A, Junqueira Filho EA, Lopes AJ. Chikungunya fever outbreak in Rio de Janeiro, Brazil: Ultrasonographic aspects of musculoskeletal complications. J Clin Ultrasound 2017;45:43-4.
Mogami R, Vaz JL, Chagas Y de FB, Torezani RS, Vieira AA, Koifman AC, et al
. Ultrasound of ankles in the diagnosis of complications of chikungunya fever. Radiol Bras 2017;50:71-5.
Ravindran V, Alias G. Efficacy of combination DMARD therapy vs. hydroxychloroquine monotherapy in chronic persistent chikungunya arthritis: A 24-week randomized controlled open label study. Clin Rheumatol 2017;36:1335-40.
Pandya S. Methotrexate and hydroxychloroquine combination therapy in chronic chikungunya arthritis: A 16 week study. Indian J Rheumatol 2008;3:93-7. [Full text]
Amaral JK, Sutaria R, Schoen RT. Treatment of chronic chikungunya arthritis with methotrexate: A systematic review. Arthritis Care Res (Hoboken) 2018;70:1501-8.
[Table 1], [Table 2], [Table 3]