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Chikungunya Viral Polyarthritis

To the Editor:

Chikungunya virus (CHIKV) polyarthritis can mimic rheumatoid arthritis (RA) by joint distribution and possible chronicity. It should be suspected in patients with RA-like features who have a history of travel to endemic areas, viremic symptoms, and rash. We describe one such case.

A 59-year-old previously healthy Canadian man was referred in mid-2006, with a 6-week history of symmetrical polyarthritis that was nonresponsive to nonsteroidal antiinflammatory drugs (NSAID). While visiting Mauritius 6 weeks earlier, he had developed fever, rigors, sweats, and intense polymyalgia. Over the ensuing 48 hours he developed severe polyarthralgia of his hands and feet, and an erythematous rash on his legs and feet. Except for the polyarthralgia, all symptoms abated in 4–5 days. On examination, he had synovitis at the metacarpophalangeal (MCP) joints, proximal interphalangeal joints, metatarsophalangeal (MTP) joints, and both wrists and ankles, and enthesitis at the insertions of both Achilles tendons (Figure 1).

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Figure 1. Affected joints (in black) in a patient with CHIKV polyarthritis presenting 6 weeks after onset of illness.

Investigations revealed negative rheumatoid factor and antinuclear antibody, erythrocyte sedimentation rate 24 mm/h, C-reactive protein 3 mg/dl, and normal complete blood count, creatinine, electrolytes and liver function tests. CHIKV hemagglutination inhibition titer was elevated at 1:2560, and Dengue virus serology was negative. Hand radiographs showed no erosive changes.

Given his travel history, transient febrile illness, and positive CHIKV serology, he was diagnosed with CHIKV polyarthritis. He received 2 doses of 80 mg methylprednisolone intramuscularly 4 weeks apart, with good response. When reviewed 8 weeks after initial consultation, he had improved significantly, but synovitis of the wrists and MTP joints persisted. He was then given hydroxychloroquine 200 mg orally twice daily and prednisone orally 7.5 mg daily, the latter tapered in 6 weeks. On last followup, about 16 months after the acute illness, he was still having stress pain at the wrists and MCP, and was continued on hydroxychloroquine, with intermittent NSAID use. Repeat hand radiographs at that time showed no erosions, and anti-citric citrullinated peptide antibody was negative.

CHIKV is a mosquito-borne RNA virus, transmitted primarily by the Aedes aegypti and Aedes albopictus species¹. The illness is characterized by 3–7 days of high fever, headache, rash, myalgia, and severe arthralgias/arthritis, the hallmark of the disease. Arthropathy can be debilitating, accounting for the name "Chikungunya," which, in the language of the Makonde (northern Mozambique), means "that which bends up." It is mainly distal and symmetric, and can be persistent, with 12% of patients affected for 3–5 years in one study².

After many years of quiescence, CHIKV reemerged in early 2005 with an outbreak in the Comoros Islands. It subsequently spread to other Indian Ocean islands, including Reunion, where 255,000 cases were reported in just over one year following an outbreak in March 2005³. CHIKV was implicated in 228 deaths in the Reunion outbreak (about 1 per 1000 clinical cases)⁴. Several states in India were also affected throughout 2006, with more than 1.25 million clinical cases and attack rates reaching 45% in some areas⁵.

CHIKV infection has been reported in travelers returning from known outbreak areas to Europe, the United States, Canada, the Caribbean, and parts of South America⁶. It is now apparent that returning viremic travelers can precipitate local outbreaks. In late August 2007, authorities reported an outbreak in the Emilia Romagna region of Italy, with 254 potential cases reported as of mid-September 2007⁷. That outbreak was traced to a traveler returning from India. The globalization of A. albopictus to most tropical and temperate areas¹, including the Americas up to southern areas of Canada, renders pandemic potential to CHIKV.

Suspected cases should be confirmed by serology. Reverse transcription-polymerase chain reaction (RT-PCR) is useful during the initial viremic phase (Day 0 to Day 7), but classic serological methods are simpler (hemagglutination inhibition titer, complement binding, immunofluorescence, and ELISA)⁸. IgM is detectable (1–12 days) by ELISA immunofluorescent assay and persists up to 3 months. IgG is detected in convalescent samples and persists for years. The sensitivity and specificity of these tests are poorly established, however.

Treatment of CHIKV infection and arthritis has been primarily supportive with fluids, rest, NSAID, and other analgesics. A small, open, pilot study (1984) suggested improvement in the Ritchie articular index and morning stiffness with chloroquine phosphate⁹. To date, no vaccine or antiviral agent is available⁸. Infection is thought to confer lifelong immunity¹⁰.

In summary, CHIKV polyarthritis can mimic RA by joint distribution and possible chronicity. It should be suspected in patients with RA-like features who have a history of travel to endemic areas, viremic symptoms, and rash. Suspected cases should be confirmed via serology.

Although treatment is primarily supportive, our case suggests that patients with persistent arthropathy may benefit from corticosteroids and longer-term treatment with hydroxychloroquine. Intuitively, other disease-modifying antirheumatic drugs may be of benefit as well. This area would require controlled study, especially as the epidemic continues.

With continued travel to and immigration from areas with CHIKV outbreaks, the number of affected patients seen in non-endemic areas is likely to increase. Of greater concern is the pandemic risk posed by vector globalization. The emergence and rapid spread of West Nile virus in 1999 in the United States testify that arboviruses are a threat to developed countries with a temperate climate. Clinicians should be aware of viremic symptoms in travelers returning from endemic areas. Suspected cases of CHIKV should be immediately reported to public health authorities, and measures taken to avoid local outbreaks.

RAJ J. CARMONA, MBBS, Rheumatology Fellow; SAEED SHAIKH, FRCPC, Assistant Clinical Professor, Rheumatology; NADER A. KHALIDI, FRCPC, Associate Clinical Professor, Rheumatology, Department of Rheumatology, McMaster University, 240 James St. South, Hamilton, Ontario L8P 3B3, Canada. Address reprint requests to Dr. Carmona. E-mail: rajcarmona@hotmail.com

REFERENCES

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2. Brighton SW, Prozesky OW, de la Harpe AL. Chikungunya virus infection — a retrospective study of 107 cases. S Afr Med J 1983;63:313-5. [MEDLINE]

3. Public Health Agency of Canada. Travel health advisory. Outbreak of chikungunya virus: south west Indian Ocean and India. May 2006. [Internet. Cited February 28, 2008.] Available from: http://news.gc.ca/web/view/en/index.jsp?articleid=215809&keyword=chikungunya.

4. Institut de Veille Sanitaire. Chikungunya outbreak on Reunion: update on June 1 2006 [French]. June 2006. [Internet. Cited February 28, 2008.] Available from: http://www.invs.sante.fr/presse/2006/le_point_sur/chikungunya_reunion_020606/index.html.

5. World Health Organization. Epidemic and pandemic alert and response — Chikungunya in India. October 17 2006. [Internet. Cited February 28, 2008.] Available from: http://www.who.int/csr/don/2006_10_17/en/index.html.

6. Warner E, Garcia-Diaz J, Balsamo G, et al. Chikungunya fever diagnosed among international travelers — United States, 2005-2006. MMWR Morbidity and Mortality Weekly Report. 2006 September 29. [Internet. Cited February 28, 2008.] Available from: www.cdc.gov/MMWR/preview/mmwrhtml/mm5538a2.htm.

7. World Health Organization Regional Office for Europe. Communicable disease surveillance and response. Chikungunya in Emilia Romagna Region, Italy. 2007 September 16. [Internet. Cited February 28, 2008.] Available from: http://www.euro.who.int/ surveillance/outbreaks/20070904_1.

8. Pialoux G, Gauzere B, Jaureguiberry S, et al. Chikungunya, an epidemic arbovirus. Lancet Infect Dis 2007;7:319-27. [MEDLINE]

9. Brighton SW. Chloroquine phosphate treatment of chronic Chikungunya arthritis. An open pilot study. S Afr Med J 1984;66:217-8. [MEDLINE]

10. Centers for Disease Control and Prevention. Division of Vector-Borne Infectious Disease. Chikungunya fever fact sheet. November 29, 2007. [Internet. Cited February 28, 2008.] Available from: www.cdc.gov/ncidod/dvbid/Chikungunya/chikvfact.htm.