Davidson H. Hamer, MD; Lin H. Chen, MD
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1958.
Requests for Single Reprints: Davidson H. Hamer, MD, Center for Global Health and Development, 801 Massachusetts Avenue, Crosstown Third Floor, Boston, MA 02118; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Hamer: Center for Global Health and Development, 801 Massachusetts Avenue, Crosstown Third Floor, Boston, MA 02118.
Dr. Chen: Division of Infectious Diseases, Mount Auburn Hospital, 330 Mount Auburn Street, South 2, Cambridge, MA 02138.
Author Contributions:Conception and design: D.H. Hamer.
Analysis and interpretation of the data: D.H. Hamer, L.H. Chen.
Drafting of the article: D.H. Hamer, L.H. Chen.
Critical revision of the article for important intellectual content:D.H. Hamer, L.H. Chen.
Final approval of the article: D.H. Hamer, L.H. Chen.
Collection and assembly of data: D.H. Hamer, L.H. Chen.
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Tariq Al-Araimi, MD, Shikha Mittoo, MD, MHS, FRCPC
Department of Internal Medicine, University of Toronto, Mount Sinai Hospital, University of Toronto
October 18, 2014
Chikungunya and Autoantibody positive arthritis: what is the connection?
We read with great interest the article on Chikungunya by Hamer & Chen (1). However, chronic Chikungunya arthritis can persist for months post infection (2)(3). Among 47 travelers returning from the Indian Ocean island followed for a 14-month period, late arthropathy (after the 10th day), defined as having at least one of the following: symmetric oligo/polyarthritis accompanied by morning stiffness, non specific edema / tenosynovitis, worsening of mechanical pain in a pre-existing injured joint or bone was identified in 38 persons (2). In another series of 21 cases of newly diagnosed Chikungunya with a mean follow-up of 2 years, all of the 21 patients fulfilled the rheumatoid arthritis American College of Rheumatology (ACR) criteria with symptoms starting from the onset of viral infection to rheumatoid arthritis diagnosis (3). In our department, we recently had a confirmed case of Chikungunya who returned to Canada after travelling to the Dominican Republic & Jamaica after presenting with an inflammatory polyarthritis. The patient still complained of joint pain, one of the initial symptoms, after 3 months of presentation. We still pursued work up for a connective tissue disease (initial ANA was speckled pattern, titre of (1:80) persisting to (1:160) a month later, initial Anti-DsDNA was (38.7 IU/mL) while repeat was normal by Farr, RF and anti-CCP were negative). It remains unknown whether the virus can trigger an autoimmune event.
The main stay treatment in the acute phase is the use of analgesics or non-steroidal anti-inflammatory drugs as described by Hamer & Chen and allowing some time before considering starting immunosuppressive therapy. However, there is limited reports with regards resolution of symptoms by treating the chronic arthritic phase with hydroxichloriquine, methotrexate or steroids (3)(4).Research still ongoing on the mechanism of alpha viruses related arthritis, some data suggest presence of Chikungunya in synovial macrophages triggers release of pro-inflammatory mediators ( IL10 , IFN-alpha ) leading to activation of matrix metalloprotease (MMP), induction of apoptosis and fibroblast hyperplasia. This obviously suggests some similarity between the mechanism of Chikungunya arthritis and rheumatoid arthritis(5). In conclusion, consider work up for a connective tissue disease and follow-up among patients with prolonged arthralgias and/or arthritis.
1. Hamer DH, Chen LH. Chikungunya: Establishing a New Home in the Western Hemisphere. Ann Intern Med. [Epub ahead of print 23 September 2014] doi:10.7326/M14-1958.
2. Simon F, Parola P, Grandadam M, Fourcade S, Oliver M, Brouqui P, et al. Chikungunya infection: an emerging rheumatism among travelers returned from Indian Ocean islands. Report of 47 cases. Medicine. 2007;86(3):123-37.
3. 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(6):654-7.
4. Chopra A, Anuradha V, Lagoo-Joshi V, Kunjir V, Salvi S, Saluja M. Chikungunya virus aches and pains: an emerging challenge. Arthritis Rheum. 2008;58(9):2921-2.
5. Jaffar-Bandjee MC, Das T, Hoarau JJ, Krejbich Trotot P, Denizot M, Ribera A, et al. Chikungunya virus takes centre stage in virally induced arthritis: possible cellular and molecular mechanisms to pathogenesis. Microbes Infect. 2009;11(14-15):1206-18.
William Rodriguez-Cintron, MD
Pulm/CCM VA Caribbean Healthcare System
December 16, 2014
Chikugunya in the Caribbean
Read with great interest the manuscript by Hamer and Chen (1) regarding Chikungunya. The manuscript however failed to mention and address the incidence of the disease in the Caribbean located US Commonwealth of Puerto Rico (PR). Though, this is eloquently addressed by the US Center for Diseases Control (CDC) in the latest Morbidity and Mortality Weekly Report (2). The first locally acquired, laboratory-confirmed chikungunya case was detected in PR in early May 2014 and 10,201 suspected cases (282 per 100,00 residents) had been reported by August 12, 2014. Certainly, there have been and there will be implications locally in terms of public health. However, because of the known shunt with the mainland USA, physicians within the mainland USA should become more aware of chikungunya when advising someone who is to travel to PR and/or treating an ill patient that is coming from PR.
William Rodriguez-Cintron, MD, MACP
Chief, Pulmonary/CCM VACHS
10 Casia St, SJ, PR 00921
1. Hamer D, Chen L : Chikungunya: Establishing a new Home in the western hemisphere; Ann Int Med 2014;161:827-828
2. Tyler S, et al, Chikungunya cases identified through passive surveillance and household investigations-Puerto Rico-, May 5-August 12, 2014; Centers for Disease Control and Prevention, Morbidity and Mortality Weekly Report; Vol 63, No 48: December 5, 2014
Davidson H. Hamer, MD, Lin H. Chen, MD
Boston University School of Public Health
January 27, 2015
We agree with Dr. Rodriguez-Cintron regarding the importance of chikungunya virus infections in Puerto Rico. Due to the large numbers of islands and countries affected by this widespread outbreak, our commentary on chikungunya in the Americas was unable to include a comprehensive list of all those with autochthonous transmission (1); however, the Pan American Health Organization (PAHO) regularly provides updated case numbers and incidence rates for each island and country (2). As of January 23, 2015, Puerto Rico has reported 21,518 suspected and 4,278 confirmed cases, with an incidence rate of 700 cases/100,000 population. According to PAHO, the chikungunya outbreaks in Dominican Republic and Saint Martin (French part) are even more dramatic, with over 500,000 suspected cases in the former, and an incidence rate of 18,246 cases/100,000 population in the latter (2). Because of the high volume of travel between the United States and all infected areas, it is imperative that we raise awareness of clinicians practicing in the contiguous United States regarding chikungunya in the Americas – all Caribbean islands, and most countries in Central and South America.
We appreciate the comment from Drs. Al-Araimi and Mittoo regarding the similarity in presentation of chikungunya arthritis and rheumatoid arthritis, and that work-up is warranted for connective tissue disease in patients diagnosed with chikungunya who experience persistent or recurrent arthritis. Following the chikungunya epidemic in La Reunion in 2005, a cohort study of 147 chikungunya-infected patients found that 57% reported rheumatic symptoms at 15 months (nearly 2/3 with persistent symptoms and 1/3 were recurrent/relapsing) (3). These findings are similar to the patient described by Drs. Al-Arami and Mittoo.
As noted by Drs. Al-Araimi and Mittoo, it is not yet known whether chikungunya virus triggers an autoimmune process, although some immunologic findings suggest inflammatory mechanisms (4). In chikungunya-infected patients who later are diagnosed with rheumatoid arthritis, the utility of therapy with disease-modifying anti-rheumatic drugs such as methotrexate, tumor necrosis factor blockers, hydroxychloroquine, and corticosteroids, has not yet been established (5). Finally, since persistent or relapsing arthralgia/arthritis may present to rheumatologists as well as primary care providers for evaluation, specialists should remain vigilant about assessing for chikungunya virus infection. Longitudinal natural history studies and randomized controlled trials of interventions for chikungunya patients with persistent arthritis are critically needed.
Davidson H. Hamer, MD
Center for Global Health and Development, Boston University School of Public Health, Boston, MA, USA
Lin H. Chen, MD
Mt. Auburn Hospital, Cambridge, MA, USA
1. Hamer DH, Chen LH. Chikungunya: Establishing a new home in the Western Hemisphere. Ann Intern Med. 2014;161:827-828.
2. Pan American Health Organization; World Health Organization. Chikungunya. Available at www.paho.org. Last accessed January 21, 2015.
3. Sissoko D, Malvy D, Ezzedine K, Renault P, Moscetti F, Ledrans M, Pierre V. Post-epidemic chikungunya disease on Reunion Island: course of rheumatic manifestations and associated factors over a 15-month period. PLoS Negl Trop Dis. 2009;3:e389. doi: 10.1371/journal.pntd.0000389.
4. Roques P, Gras G. Chikungunya fever: focus on peripheral markers of pathogenesis. J Infect Dis. 2011;203:141-3.
5. Simon F, Javelle E, Oliver M, Leparc-Goffart I, Marimoutou C. Chikungunya virus infection. Curr Infect Dis Rep. 2011;13:218-28.
Hamer DH, Chen LH. Chikungunya: Establishing a New Home in the Western Hemisphere. Ann Intern Med. ;161:827–828. doi: 10.7326/M14-1958
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Published: Ann Intern Med. 2014;161(11):827-828.
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