Patients with chikungunya meeting criteria for inflammatory rheumatic diseases: a systematic literature review and metaanalysis

de Souza, Viviane Angelina; Macedo, Deivson Mendes; Guimarães, Nathalia Sernizon; de Souza, Mariana Peixoto Guimarães Ubirajara e Silva; Kakehasi, Adriana Maria

doi:10.1186/s42358-025-00471-6

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Research • Adv. rheumatol. 65 • 2025 • https://doi.org/10.1186/s42358-025-00471-6 linkcopy

Patients with chikungunya meeting criteria for inflammatory rheumatic diseases: a systematic literature review and metaanalysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Background Chikungunya fever (CF) is marked by acute, subacute, and chronic phases, with a significant proportion of patients experiencing persistent joint and neuropathic pain. These symptoms may mimic those of rheumatic diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). There is currently no consensus on whether the infection directly causes chronic joint disease or serves as an immunological trigger for the development of rheumatic conditions.

Aim This study aims to evaluate the overall proportion of CF patients who progress to chronic arthropathy, and to identify how many of these patients meet the classification criteria for RA and SpA (including ankylosing spondylitis (AS) and psoriatic arthritis (PsA)).

Methods A thorough search was conducted in electronic databases, including PubMed, Embase, LILACS, and the Cochrane Library. The primary endpoint was the occurrence of chronic arthropathy, defined as joint signs and symptoms lasting more than six weeks following the acute phase of CF. The secondary endpoint involved the proportion of patients meeting the classification criteria for RA, SpA, AS, and PsA. A random-effects meta-analysis model was utilized to combine studies and determine the pooled frequency of persistent joint symptoms. Subgroup analyses were performed based on the fulfillment of classification criteria for rheumatic diseases. The risk of bias was assessed using the Joanna Briggs Institute critical appraisal tools. The study protocol was registered with PROSPERO (CRD42020211430).

Results A total of thirty-eight studies, comprising data from 12.524 individuals with CF published between 2008 and 2022, met the inclusion criteria. Of these, 4.324 (34.5%) patients developed chronic arthropathy; among them, 11.43% (240 in 2099) patients met the criteria for RA, 12.1% (86 in 711) patients for SpA, 3.42% (36 in 1052) patients for AS, and 2.05% (25 in 1220) patients for PsA.

Conclusion This study found that approximately one-third of CF patients experience persistent joint pain lasting over six weeks. However, only a minority of these individuals meet classification criteria for rheumatic diseases.

Keywords
Arbovirus; Chikungunya; Meta-analysis; Rheumatic diseases; Systematic review

Reference, location	Study design	Sample (n)	Sex (female)	CF + Chronic Arthropathy	Mean age±SD or median (range)	Objective	Results	Study duration (weeks)
Abella et al., 2019, Colombia	cross-sectional	94	72	94	57 ± 14.99	To identify the clinical and immunological characteristics, functional disabilities, and quality of life decline in a sample of Colombian patients with chronic arthropathy associated with chikungunya virus.	Significant functional and quality of life involvement of the affected patients, with almost one third presenting with arthritis in the first 9 months following the acute infection. Synovitis was identified in 29.8% of the cases at the time of the assessment, with a mean of 2.21 ± 1.26 swollen joints.	NA.
Genaro et al., 2020, Brazil	cross-sectional	106	98	106	51.63 ± 12.52	To identify possibly fast, simple low-cost biomarkers to monitor chronic CF-induced articular disease. A case was defined as arthritis in 4 joints for more than 6 weeks associated with laboratorial confirmation of recent acute CF infection.	Negative association between the disease duration at the first medical evaluation after initial infection and the persistence of joint symptoms in these individuals. The presence of risk factors for chronic disease was detected in our samples; however, there was no evidence of correlation with the intensity of musculoskeletal manifestations.	NA.
Banerjee et al, 2018, India	case-control	65	37	25	55 (35-76)	To evaluate the status of several standard oxidative stress markers and their correlation in chikungunya patients suffering with polyarthralgia. Persisting polyarthralgia was determined by clinical signs and symptoms presented from 10 to 30 days of infection.	Patients suffering from persisting polyarthralgia post-CF infection generates higher amount of intracellular ROS along with altered oxidative damage parameters and Siglec-9 expression on monocyte.	139
Bertolotti et al., 2020, French West Indies	prospective cohort	193	N.I.	87	N.I.	To assess the prevalence of chronic CF arthritis (CCA) at 48 weeks and to search for acute phase factors significantly associated with chronicity.	The overall prevalence of CCA was 52.1%. The reduced frequency of intravenous rehydration was associated with the development of CCA in univariate analysis. Thus, initial dehydration is one of the potential factors leading to the development of CCA. Enthesitis and tenosynovitis are risk factors significantly associated with CCA in univariate analysis.	48
Blettery et al., 2016, Martinica	prospective cohort	128	N.I.	47	64.1 (34-88)	To describe chronic CF manifestations seen during the outbreak in the Caribbean from December 2013 to January 2015.	21.1% of the patients progressed to a chronic form of seronegative RA; Thirteen/45 of the patients met criteria for PsA; 7/45 met modified New York criteria for AS; 6/45 had nonradiographic SpA; 19/45 had nonclassified forms of SpA, meeting the European Spondyloarthropathy Study Group criteria; 9 patients (7.0%) fibromyalgia according to American College of Rheumatology criteria.	52
Bouquillard et al., 2018, France	retrospective cohort	307	255	243	54 ± 12.6	To analyse the characteristics and progression of rheumatic manifestations in patients with post-CF joint pain.	Joint manifestations (arthralgia and arthritis) occurred preferentially in the extremities. Inflammatory involvement of the ankle seems to be particularly suggestive of CF infection, given its frequency and intensity. In some cases, the clinical presentation suggested the onset of RA. 13 (4%) patients, of the 328 patients initially examined, and 6.2% of the patients who presented with clinical signs of synovitis were diagnosed with RA(ACR 1987 criteria).	139
Chang et al., 2018, Colombia	cross-sectional	33	27	25	56 ± 10.0	To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis.	Initial symptoms of GF included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly.	NA.
Chang et al., 2018, Colombia	prospective cohort	485	388	123	49 ± 16	To estimate the frequency of chronic joint pain after GF in a Latin American cohort.	After 20 months, one-fourth of the participants had persistent joint pain. The most commonly affected joints were the small joints, including the wrists, ankles, and fingers. A multivariable analysis indicated that significant predictors of persistent joint pain included college graduate status, initial symptoms of headache or knee pain, missed work, normal activities affected, >4 days of initial symptoms, and >4 weeks of initial joint pain.	87
Chopra et al., 2012, India	prospective cohort	509	N.I.	202	N.I.	To evaluate long-term pain and chronic musculoskeletal rheumatic pain after GF.	Fifty-nine cases (12%;CI: 8.9-14.7) and 24 cases (5%, Cl: 3.0-6.9) suffered from musculoskeletal pains and arthritis at 1 and 2 years, respectively. Thirteen cases tested seropositive only for rheumatoid factor: 11 nonspecific arthralgias), one known RA and one OA.	104
Chopra et al., 2008, India	prospective cohort	156	105	95	N.I.	To evaluate the characteristics of musculoskeletal disorders of patients with GF.	Seventy-two patients (73%) had inflammatory arthritis. No classic erosions of RA on radiographs of the hands and feet of patients with inflammatory arthritis.	21
Chow et al., 2010, Singapore	case-control	30	26	4	39	To investigate the profiles of clinical disease, viral load, and immune mediators in patients with GF.	Arthralgia or joint pains persisted at the chronic phase (month 2-3 after illness onset) in 4 patients (13.3%). Persistent arthralgia was associated with higher levels of IL-6 and granulocyte macrophage colony stimulating factor.	7
Ganu et al, 2009, India	prospective cohort	16	9	16	50	To study clinical features and laboratory findings in patients with GF chronic arthritis.	Most commonly affected joints were wrists, MCPs, PIPs, elbows, shoulders, knees, ankles and MTPs. Out of 16 patients 2 were positive for RF (12.5%) and 9 were positive for anti-CCP (56.5%). X-Rays of hands and other affected joints revealed reduced joint space and periarticular osteopenia. Erosions developed in 5/16 patients (31.25%).	104
Gutierrez-Rubio et al, 2014, Philippines	prospective cohort	70	53	37	39.2 ±13.50	To describe the course and outcome of musculoskeletal manifestations in patients with GF seen over a three-month period.	The most common joint areas involved were the ankles (60.0%), the wrists (40.0%) and the small joints of the hand (51.4%). Twenty-seven (47.3%) had symmetric arthritis. Thirty-seven cases (52.9%) had arthralgia or arthritis for at least six weeks. By the end of the follow-up period, only four (5.7%) had persistent musculoskeletal symptoms. Age and sex were not found to be factors in determining chronicity of arthritic symptoms.	12
Hayd et al., 2020, Brazil	cross-sectional	120	98	40	49	To describe the duration, severity, an characteristics of CF arthritis in comparison with local controls to further understand the long-term rheumatologic impact.	Four patients in the CF arthritis group were diagnosed with RA using the ACR criteria and did not have a pre-existing diagnosis of RA nor arthritis symptoms.	NA.
Hoarau et al., 2010, France	prospective cohort	49	30	9	60 (19-90)	To identify prognostic markers of arthritis-like pathology after CF disease.	A polarized inflammatory immune response is engaged in the acute phase of CF although only weak circulating levels of proinflammatory Th 1 effectors and immunoregulatoryTh2 molecules were detected. This response persisted in some patients who went on to develop chronic arthralgia.	52
Javelle et al., 2015, France	retrospective cohort	159	121	112	51	To retrospectively document the clinical and therapeutic courses of rheumatic and musculoskeletal CF over a 6-year period.	Ninety-four patients (59%) who were free of any articular disorder prior to CF met the chronic arthropathy criteria: RA (n = 40), SpA (n = 33), undifferentiated polyarthritis (n = 21).	288
Manimunda et al., 2010, India	prospective cohort	203	107	100	35 (25-44)	To describe the acute (first month) and chronic (10th month) clinical features of CF disease, as well the nature of chronic arthritis.	Thirty four (36%) patients in the cohort met the ACR criteria for RA.	43
Mathew et al., 2011, India	prospective cohort	5277	313	437	48.37 ± 13.62	To describe the clinical profile of chronic rheumatic musculoskeletal pain and disorders, captured inadvertently about 15 months following a CF epidemic.	The most freguent diagnosis was chronic postviral polyarthralgia (57%). RA and seronegative SpA were observed in 6 and 11 patients, respectively. PsA was the commonest SpA, comprising 2.5% of the diagnoses.	60
Nayak et al., 2020, India	prospective cohort	184	6	30	46.1 (20-70)	To assess the antibody response patterns in CF acute febrile patients from India and then evaluated the impact of these febrile antibody response patterns on the downstream outcome of protection versus progression to chronic arthritis.	Thirty (100%) presented with arthralgias and 27 (90%) polyarthritis.	86
O’Sullivan et al., 2018, Jamaica	cross-sectional	306	153	215	47.6 ± 18.5	To report demographic and self-reported clinical characteristics associated with persistent and severe arthralgia 8-12 months post CF infection.	70.3% (215) of patients reported arthralgia. Females and previous arthritis showed a greater likelihood for severe arthralgia as well as persistent arthralgia.	48.
Paul et al., 2011, India	prospective cohort	150	90	135	N.I.	To study the clinical profile of acute CF, chronic sequelae and response of these patients to treatment.	Rheumatoid factor was done in 44 (44%) patients with symptoms lasting more than 6 months and 15% (15 patients) had elevated values. Five patients turned out to have RA clinically and with anti-CCP positivity. Synovial biopsy was done for three patients with persistent arthritis and all showed features of chronic synovitis.	78
Rodriguez-Morales et al. [ ³⁰ ], Colombia	retrospective cohort	283	173	283	29 (17-42)	To study the proportion of patients evolving to chronic polyarthralgia post CF.	Of the CF infected subjects, 152 (53.7%) reported persistent rheuma- tological symptoms. All of these patients reported Joint pains (chronic polyarthralgia, 49.5% morning stiffness, 40.6% Joint edema, and 16.6% Joint redness.	26
Segura-Charry et al., 2020, Colombia	retrospective cohort	410	363	280	57.3 ± 11.7	To evaluate symptomatic and serological behaviour in patients suffering from CF infection, and to describe the comorbidities associated with the chronic phase of the disease.	46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination. 20.3% (87 patients) were diagnosed de novo post-CF RA (58.6% of whom were seropositive and 11 patients (13.4%) were doubly seropositive for the RA test/antiCCP positive, and remarkably 14 patients (17%) were anti-CCP positive with a negative RA test); 7.3% (31 patients) were diagnosed with axial and/or peripheral SpA (15 patients with peripheral involvement, 11 patients with axial involvement and five patients with development of PsA), with the presence of HLA-B27 positive in 46.7%, 45.5% and 0% of cases, respectively.	195
Sissoko et al., 2009, France	retrospective cohort	147	102	84	52.0 ± 15.0	To assess the course of late rheumatic manifestations and investigating potential risk factors associated with the persistence of these rheumatic manifestations.	Age >45 years, severe initial Joint pain, and presence of underlying OA were predictors of nonrecovery.	15
Tritsch et al., 2019, Colombia	prospective cohort	485	N.I.	123	51.0 ± 14.0	To determine the frequency of chronic Joint pain and stiffness 3 years after infection with CF.	54% of those patients reported continued Joint pain 40 months after infection. Two patients with persistent Joint pain developed RA after CF infection.	173
Alam et al., 2018, Pakistan	cross-sectional	52	37	52	45.0 ± 5.0	To study clinical and laboratory features associated with persistent arthralgia in patients with CF.	Mean duration of arthralgia was 2.6 months. Symmetrical arthralgia and asymmetrical was described in 76.9% and 23.1% of cases respectively. Small Joint involvement was in 21.2%, large Joint in 20.8% while both small and large involvement was seen in 48.1 % of patients.	NA.
Fuentes-Silva et al., 2017, Venezuela	prospective cohort	168	150	168	55.33 ± 12.72	To examine how many patients with CF evolve to chronic rheumatic diseases.	Thirty patients (17.85%) evolved into the following rheumatic diseases: RA (12.50%), PsA (2.38%), SpA (1.79%) and systemic lupus erythematosus (0.60%). There was a statistically significant association between positivity of RF, anti-CCP or both with development of the de novo rheumatic diseases.	104
Gutierrez-Rubio et al, 2014, Philippines	prospective cohort	70	53	37	39.2 ± 13.50	To describe the course and outcome of musculoskeletal manifestations in patients with CF seen over a three-month period.	The most common joint areas involved were the ankles (60.0%), the wrists (40.0%) and the small joints of the hand (51.4%). Twenty-seven (47.3%) had symmetric arthritis. Thirty-seven cases (52.9%) had arthralgia or arthritis for at least six weeks. By the end of the follow-up period, only four (5.7%) had persistent musculoskeletal symptoms.	12
Gupta et al., 2018, India	prospective cohort	882	484	568	53.64 ± 15.82	To study the rheumatological manifestations of CF infection.	Fourty (5.4%) patients developed new onset knee OA, 38 (5.14%) met ACR/EULAR 2010 criteria for RA, 28 (3.78%) met modified New York criteria for AS, 29 (3.92%) developed undifferentiated arthritis, 17 (2.3%) patients developed various enthesitis and tenosynovitis, 1 (0.14%) patients fulfilled ACR 1997/SLICC 2012 criteria for SLE, 20 (2.7%) patients fulfilled ACR 2010 criteria for fibromyalgia, 5 (0.67%) patients fulfilled CASPAR criteria for PsA, 3 (0.4%) patients fulfilled 2015 classification criteria for gout.	47
Alam et al., 2018, India	cross-sectional	112	81	37	N.I.	To study clinical and laboratory features associated with persistent arthralgia in patients with CF.	Symmetrical arthritis was reported in 85 (75.9%) patients, while asymmetrical arthritis was seen in 27 (24.1%) patients. 75 (66.9%) had polyarthralgia involving small, medium and large joints. Morning stiffness was reported in 68 (60.7%) of patients. Three patients later after 6 months of follow-up had anti-CCP positive, while 2 were negative. They were treated as inflammatory arthritis with DMARDS.	24
Patel et al., 2019, India	case-control	400	N.I.	24	N.I.	To evaluate the prevalence of post CF chronic arthritis among 400 consecutive acute coronary syndrome patients.	This study is an abstract and does not provide further details about the joint involvement of patients, only the occurrence of chronic arthropathy following CF infection.	N.I.
Rahim et al., 2010, India	retrospective cohort	342	N.I.	122	N.I.	To study the factors associated with persistence of pain post CF attack.	Major sites of persistent pain were noted to be knee, ankle, wrist and elbow with predisposition to the right side of the body.	32
Salgado et al., 2018, Brazil	cross-sectional	76	65	76	57.17 (standard deviation not informed)	To evaluate the prevalence of rheumatologic manifestations in 76 patients with CF infection, during an epidemic that occurred in 2016 in the city of Rio de Janeiro, Brazil.	Polyarthralgia occurred with higher prevalence (39 patients, 51,31%), affecting wrists, ankles, shoulders, knees and hands. Twenty six patients had arthritis (34,21%),Tendinopathy in 27 regions, being more common in shoulders, ankles and wrists and including De Quervain. Paresthesias occurred in 7 patients, prevailing carpal tunnel syndrome and one patient presented dactylitis.	NA.
Benjama-nukul et al., 2021, Thailand	cohort	164	121	91	48,2 ± 14.0	To describe the rheumatic manifestations in CF infection, estimate the prevalence of enthesitis in CF infected patients, and determine the factors associated with CF induced enthesitis.	48 patients (52.7%) had post-CF chronic inflammatory rheumatism, including 7 (14.6%), 11 (22.9%), and 30 (62.5%) who were classified as having RA, SpA, and undifferentiated arthritis, respectively. Forty-three patients (47.3%) had post-CF muskuloskeletal disorder. Of these, 14 (32.6%) displayed diffuse symptoms (polyarthralgia in 12 patients and polyenthesitis in 2). Twenty-nine (67.4%) patients had locoregional symptoms (monoarthralgia ou oligoarthralgia in 18 patients, neuropathic pain in 6, enthesitis in 4, and tendinitis in 1).	NA.
Bossy et al., 2020, French Carribean	cross-sectional	61	51	61	N.I.	To describe the clinical profile in a cohort of patients in Guadeloupe with chronic clinical manifestations 36 months after CF infection.	Beside arthralgiajoint stiffness and general symptoms (asthenia, sleep disorders) contribute to the impairment of QoL lasting years after chikungunya.	144
Hossain et al., 2022, Bangladesh	prospective cohort	143	60	60	43,3 ± 11,5	To identify the clinical patterns and consequences of post-CF arthritis.	Among the 60 chronic CF patients, 35 had undifferentiated arthritis, where polyarthralgia was present in 21 (60.0%) patients, and polyarthritis was present in 8 (22.8%) patients. Ten patients had SpA where polyarthralgia was present in 6 (60.0%) patients, and seven patients had RA where 5 (71.4%) had polyarthritis.	52
Medina-Cintron et al., 2021, Puerto Rico	case-control	61	41	33	52,5 ± 10,5	To evaluate the clinical features and correlates in DMARD-naive patients with chronic CF arthritis.	Joints of upper extremities were more commonly involved than those of lower extremities. Joint tenderness was most common in MCP Joints (54.6%), shoulders (51.5%), PIP (45.5%), and knees (39.4%). Joint swelling was more commonly observed in PIP Joints (15.2%), MCP Joints (12.1%), shoulders (9.1%), wrists (6.1%), and ankles (6.1 %). Nineteen (57.6%) patients with chronic CF arthritis had moderate to high disease activity.	24
Watson et al., 2021, Brazil	cross-sectional	40	36	40	49.5 (42-55)	To compare the relevance of Joint counts and symptoms to clinical outcomes in RA and chronic CF disease.	Only stiffness was significantly associated with disability in CF patients. In CF arthritis, tender Joint counts were significantly correlated only with one quality of life domain, while pain intensity score correlated with impaired mobility, self-care and pain/discomfort domains, and stiffness was associated with the mobility, usual activity and anxiety/depression domains.	108

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[TFN1] N.A. = not applicable; N.I. = not informed; CF: chikungunya fever; pCHIK-CIR=post-CHIKV chronic inflammatory rheumatism; pCHIK-MSD= post-CHIKV musculoskeletal disorders; RA: rheumatoid arthritis; SpA: spondyloarthritis; PsA: psoriatic arthritis; OA: osteoarthritis; CCP: cyclic citrullinated peptide; MCP: metacarpophalangeal; PIP: proximal interphalangeal joints; MTP: metatarsophalangeal

[TFN2] Spondyloarthritis (SpA). Undifferentiated polyarthritis (UP). Patients who had not previously displayed, rheumatic symptoms and developed CIR immediately after CF were classified as de novo pCF, CIR. Patients who had not previously displayed rheumatic symptoms and developed SA immediately after, CF were classified as de novo pCF-SpA

[TFN3] σ² = 1108,64/22

[TFN4] σ² = 50,39

[TFN5] σ² = 7,09