Chikungunya virus infection is generally a self-limiting disease that usually recovers spontaneously without sequelae. Some patients may evolve into a chronic condition with polyarthritis and systemic manifestations. The relative frequency of these manifestations is highly variable ranging between 14% and 87%.[53]Rodriguez-Morales AJ, Cardona-Ospina JA, Villamil-Gómez W, et al. How many patients with post-chikungunya chronic inflammatory rheumatism can we expect in the new endemic areas of Latin America? Rheumatol Int. 2015 Dec;35(12):2091-4.
http://www.ncbi.nlm.nih.gov/pubmed/26045218?tool=bestpractice.com
Death is rare. The highest case fatality rate was during the Réunion Island outbreak with 1 in 1000 cases.[103]Mavalankar D, Shastri P, Bandyopadhyay T, et al. Increased mortality rate associated with chikungunya epidemic, Ahmedabad, India. Emerg Infect Dis. 2008 Mar;14(3):412-5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570824
http://www.ncbi.nlm.nih.gov/pubmed/18325255?tool=bestpractice.com
Chronic rheumatologic manifestations
Patients may develop symmetric polyarthritis that is usually incapacitating and resembles rheumatoid arthritis, but chronic monoarthritis or oligoarthritis can also occur following the acute infection. The course can be continuous or relapsing. Overall, the pain associated with these arthritides tends to decrease with time, but can persist for months and years. Radiologic imaging can show focal bony erosions, joint effusions, and bursitis. The clinical manifestations may be associated with persistence of immunoglobulin M (IgM) antibodies and interleukin-6 levels in serum and, occasionally, with positive rheumatoid factor or anti-cyclic citrullinated peptide antibodies.
There is currently no evidence of a definitive link between initial infection and the development of chronic arthritis.[104]Goupil BA, Mores CN. A review of chikungunya virus-induced arthralgia: clinical manifestations, therapeutics, and pathogenesis. Open Rheumatol J. 2016 Nov 30;10:129-40.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204064
http://www.ncbi.nlm.nih.gov/pubmed/28077980?tool=bestpractice.com
However, 3 factors were associated with progression toward chronic disease in one study: age 45 to 59 years (adjusted odds ratio [OR]: 6.4, 95% confidence interval [CI]: 1.8, 22.1) or ≥60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial joint involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8), and high chikungunya virus IgG titers at the start of the disease (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per 1 unit increase).[5]Marimoutou C, Ferraro J, Javelle E, et al. Chikungunya infection: self-reported rheumatic morbidity and impaired quality of life persist six years later. Clin Microbiol Infect. 2015 Jul;21(7):688-93.
https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(15)00316-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25752222?tool=bestpractice.com
[105]Schilte C, Staikowsky F, Couderc T, et al. Chikungunya virus-associated long-term arthralgia: a 36-month prospective longitudinal study. PLoS Negl Trop Dis. 2013;7(3):e2137.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605278
http://www.ncbi.nlm.nih.gov/pubmed/23556021?tool=bestpractice.com
[106]Gérardin P, Fianu A, Michault A, et al. Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study. Arthritis Res Ther. 2013 Jan 9;15(1):R9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672753
http://www.ncbi.nlm.nih.gov/pubmed/23302155?tool=bestpractice.com
[107]Couturier E, Guillemin F, Mura M, et al. Impaired quality of life after chikungunya virus infection: a 2-year follow-up study. Rheumatology (Oxford). 2012 Jul;51(7):1315-22.
https://academic.oup.com/rheumatology/article/51/7/1315/1798829
http://www.ncbi.nlm.nih.gov/pubmed/22427407?tool=bestpractice.com
A systematic review found that more than half of those infected will go on to experience chronic articular symptoms.[108]Edington F, Varjão D, Melo P. Incidence of articular pain and arthritis after chikungunya fever in the Americas: a systematic review of the literature and meta-analysis. Joint Bone Spine. 2018 Jul 24 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/30053609?tool=bestpractice.com
Chronic systemic manifestations
In addition to rheumatologic symptoms, patients may exhibit neuropathic pain affecting the upper and lower limbs, chronic headache, fatigue, asthenia, and depression up to 6 years after the acute infection, in association with significant poor scores in different scales of quality of life (such as the 36-item short-form health survey [SF-36], Arthritis Impact Measurement Scales 2 [AIMS2-SF], and the General Health Questionnaire [GHQ-12]).[67]Mahendradas P, Avadhani K, Shetty R. Chikungunya and the eye: a review. J Ophthalmic Inflamm Infect. 2013 Feb 11;3(1):35.
http://www.ncbi.nlm.nih.gov/pubmed/23514031?tool=bestpractice.com
[107]Couturier E, Guillemin F, Mura M, et al. Impaired quality of life after chikungunya virus infection: a 2-year follow-up study. Rheumatology (Oxford). 2012 Jul;51(7):1315-22.
https://academic.oup.com/rheumatology/article/51/7/1315/1798829
http://www.ncbi.nlm.nih.gov/pubmed/22427407?tool=bestpractice.com