Journal of General and Family Medicine
2015, vol. 16, no. 3, p. 204–207.
Case Reports
Chikungunya Virus Infection Presenting with Persistent Arthralgia without Fever Yosuke Sasaki, MD, Satoru Manda, MD, Takahiro Sato, MD, Tadashi Maeda, MD, PhD, Taito Miyazaki, MD, Kazushige Nakanishi, MD, PhD, and Yoshihisa Urita, MD, PhD Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan Chikungunya virus infection (CVI) typically manifests via a “two-phase” presentation: most patients develop acute fever and some patients subsequently develop arthralgia that can persist for years. Many patients visit clinics during the second phase, for relief of the arthralgia, but not during the acute febrile phase. We report a 25-year-old Japanese man infected with CVI in Jamaica who presented with chronic disabling peripheral-dominant symmetric polyarthralgia without fever, which affected the neck, knees, elbows, wrists, and fingers. Given the recent emergence of dengue fever in Japan, clinicians should consider CVI as a differential diagnosis of dengue fever when examining travelers complaining of persistent arthralgia, regardless of their countries of origin. Keywords: chikungunya fever, dengue fever, arthralgia, arthritis, Jamaica
Introduction Chikungunya virus infection (CVI) is caused by the chikungunya virus (CV), an RNA virus belonging to the alphavirus family. CVI typically manifests as acute fever and rash that is often followed by chronic arthralgia.1,2 CV is transmitted primarily by Aedes aegypti (A. aegypti) and Aedes albopictus (A. albopictus), mosquitoes that also transmit dengue virus.3 CVI has been endemic in Sub-Saharan Africa, India, and Southeast Asia. However, since December 2013, it has expanded to countries in the Western Hemisphere.1,4
We treated an afebrile case of CVI presenting with arthralgia. Given the recent emergence of dengue fever (DF) in Japan, our report should highlight the importance of persistent arthralgia due to CVI as a differential point from DF. Clinicians should consider CVI when they examine travelers complaining of persistent arthralgia, even if they are from the Western Hemisphere and currently afebrile.
Case Presentation A 25-year-old Japanese man visited our department
Corresponding author: Yosuke Sasaki, MD Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541, Japan E-Mail:
[email protected] Received for publication 9 February 2015 and accepted in revised form 27 March 2015 © 2015 Japan Primary Care Association
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after experiencing disabling polyarthralgia for a month. Symptoms started with a rash and subsequent systemic arthralgia at the end of August, two months prior to visiting our department, during his stay in Jamaica for training in Jamaican folk dance. During his fourth week in Jamaica, he noticed a centrifugally spreading itchy rash that persisted for several days. Although he did not developed fever or chills, he subsequently complained about disabling peripheral-dominant symmetric polyarthralgia without joint swelling at the neck, knees, elbows, wrists, and fingers that made it impossible to walk. After his four-week stay in Jamaica, he returned to Japan and visited several hospitals. However, the laboratory tests and joint Xrays were unremarkable. He finally visited our department five weeks after the onset. The patient was a carpenter and an avid student of Jamaican folk dance. His past medical history and family history were noncontributory. He had visited Jamaica several times in recent years. During his last visit, he stayed in Kingston for the majority of the time, but he also visited an eastern suburb, for a few days. During his stay, he had protected sexual intercourse with a female Jamaican national. He also noticed frequent mosquito bites throughout his stay in Jamaica. On physical examination, he complained of arthralgia during times of motion. His blood pressure was 96/ 60 mmHg, his heart rate was regular at 60 beat per minute, and his body temperature was 37.4°C. Despite careful examination, the head, neck, heart, lungs, abdomen, skin, and lymph nodes were unremarkable, and despite the joint pain, there were no objective arthritic findings. Given his travel history and joint pain, we considered DF and CVI, but initially excluded them because of the lack of fever. We also suspected sexually transmitted infection, rheumatic diseases including reactive arthritis, or adrenal insufficiency, for which laboratory testing revealed no abnormalities (Table 1). Considering his persistent arthralgia, we reconsidered CVI, and a positive result of the IgM antibody confirmed this diagnosis. Although the patient needed regular administration of loxoprofen for three months, the symptoms gradually improved and completely improved four months after the onset.
Discussion Our patient did not develop fever (the most common symptom of CVI) and only sought out medical assistance in Japan due to arthralgia. CVI develops in a “two-phase” presentation:5 most patients develop acute fever after an incubation period averaging 3–7 days (range, 1–12 days),6,7 and some patients subsequently develop persistent joint symptoms.8 Reportedly, 86.5–100% of patients develop fever8,9 accompanied by arthralgia, headache, and rash. Fever may reach as high as 38.5–40°C and typically lasts 3–5 days (range, 1–10 days).8–10 Rash involves 40–75% of patients.8,9,11 A common manifestation is macular/maculopapular exanthema that predominantly affects the thorax, the face, and limbs. Approximately 25–50% of patients also develop pruritus.8,11 Polyarthralgia begins 2–5 days after onset of fever and usually resolves within 7–10 days.8,10–12 It is typically symmetric and migratory and involves more than 10 (predominantly peripheral) joints (90%).8,10–12 Hands/ fingers (50–76%), wrists (29–81%), ankles (41–68%), elbows, toes, and knees are frequently affected. The axial skeleton is affected in 34–52% of cases.8,10,12 Previously injured joints are particularly susceptible.7 Although most symptoms subside within two weeks, arthralgia can persist for years in some patients (5– 60%), probably as a result of abnormal inflammatory regulation.3,13 Persistent joint symptoms include arthralgia without arthritis, edematous polyarthritis, morning stiffness, and tenosynovitis.5,7,8 The risk factors of chronic symptoms include age (Ú40–45 years old),7,13 underlying disorder (e.g., osteoarthritis), and severity at the onset.7 As the name “chikungunya,” a word in the Kimakonde dialect meaning “to become contorted” or “to walk bent over,” describes, the arthralgia is so severe that it interferes with daily activities.1,2 Notably, many patients seek out medical assistance during the second phase for relief of the persistent arthralgia, but not at the acute febrile phase.5 Differential diagnoses of CVI are listed in Table 2.3 Rheumatologic conditions are important differential diagnoses.3 DF makes for a troubling differential diagnosis because both diseases share a similar
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Journal of General and Family Medicine
Table 1. Laboratory findings Complete blood count Leukocyte (/mm3) Basophil (%) Eosinophil (%) Segmental (%) Lymphocyte (%) Atypical lymphocyte (%) Monocyte (%) Hemoglobin (g/dL) Hematocrit (%) Platelet (©104/mm3) Chemistry Sodium (mEq/L) Potassium (mEq/L) Chloride (mEq/L) Calcium (mg/dL) Phosphorus (mg/dL) BUN (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) HbA1c (%) Uric acid (mg/dL) AST (U/L) ALT (U/L) LDH (U/L) ALP (U/L) CK (U/L) CRP (mg/dL) ESR (mm/h) TP (mg/dL) Albumin (mg/dL) Fe (µg/dL) Ferritin (ng/mL)
2015, vol. 16, no. 3
Continued:
Urinalysis Protein Glucose Occult blood Leukocyte Erythrocyte Cast Serological study HIV-RNA Anti HTLV-1 Ab Malaria TPHA STS Anti-C. trachomatis IgG Anti-C. trachomatis IgA Hormonal study ACTH (pg/mL) TSH (µIU/mL) Cortisol (U/mL)
6000 1 1 50 44 1 3 13.6 40.1 23.5 143 4.5 113 9 3.6 10 0.87 103 5.8 3.3 17 15 203 241 98 0 1 6.7 4.1 69 66.9
(—) (—) (—) (—) (—) (—) (—) (—) (—) (—) (—) (—) (—) 33.3 1.64 12.3
Abbreviations: ACTH, adrenocorticotrophic hormone; ALT, alanine aminotransferase; ALP, alkaline phosphatase; AST, aspartate aminotransferase; aPTT, activated partial thromboplastin time; BUN, blood urea nitrogen; CK, creatinine kinase; CRP, C-reactive protein; C. trachomatis, Chlamydia trachomatis; ESR, erythrocyte sedimentation rate; Hb, hemoglobin; HIV, human immunodeficiency virus; Ht, hematocrit; HTLV-1, human T lymphotropic virus-1; LDH, lactate dehydrogenase; TPHA, Treponema pallidum hemagglutination; STS, serologic test for syphilis; TP, total protein; TSH, thyroid stimulating hormone.
Western Hemisphere was reported in Saint-Martin/Sint Maarten in 2013, it rapidly spread to other Caribbean
Continued on next column:
manifestation, geographic distribution, and vector
islands and American countries.1,3,4 Genetic adaptation (E1-226V mutation) promoting transmission by
mosquitos, with co-infection occasionally occurring.3
A. albopictus may explain the recent spread because
However, CVI tends to cause a high fever, polyarthralgia, rash, and lymphopenia, whereas DF tends
A. albopictus has a broader distribution than does A. aegypti, a former vector in Asia.1,14
to cause neutropenia, thrombocytopenia, hemorrhage, shock, and death.3
Although only several cases involving travelers have been reported in Japan,15 given the recent emergence of
Since it was first isolated in Tanzania in 1952, CVI has
DF and CVI, clinicians should consider CVI when they
caused epidemics in Africa and Asia. However, since 2004, CVI has spread to islands in the Indian Ocean,
examine travelers complaining of persistent arthralgia, even if they are from the Western Hemisphere and
Italy, and France.1 Once the first outbreak in the
currently afebrile.
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Chikungunya Virus Infection Presenting with Persistent Arthralgia without Fever
Table 2. Differential diagnoses of chikungunya virus infection
4 Mansuy J-M, Grouteau E, Mengelle C, Claudet I, Lzopet J: Chikungunya in the Caribbean as threat to
Infectious diseases Malaria Leptospirosis Borrelia infection (especially relapsing fever) Rickettsia infections (especially African tick bite fever) Bacterial infections Enteric fever Group A streptococcus Meningococcal infection Viral infections: Dengue fever Measles Rubella Epstein-Barr virus Parvovirus Enteroviruses Adenovirus Primary HIV infection Other alpha virus infections Mayaro Ross River Barmah Forest O’nyong-nyong Sindhis Non-infectious diseases Post-infection arthritis Rheumatologic conditions
Europe find information on. Emerg Infect Dis. 2014; 20(8):1423–1425.
Note: This table was created based on information found in Reference 3.
5
Parola P, Simon F, Oliver M: Tenosynovitis and
vascular disorder associated with Chikungunya virusrelated rheumatism. Clin Infect Dis. 2007;45:801–802. 6 Hamer DH, Chen LH: Chikungunya: Establishing a new home in the western hemisphere. Ann Intern Med. 2014;161:827–828. 7 Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT: Chikungunya: a re-emerging virus. Lancet. 2012;379(9816):662–671. 8 Taubitz W, Cramer JP, Kapaun A, et al: Chikungunya fever in travelers: clinical presentation and course. Clin Infect Dis. 2007;45(1):e1–e4. 9 Queyriaux B, Simon F, Grandadam M, Michel R, Tolou H, Boutin J-P: Clinical burden of chikungunya virus infection. Lancet Infect Dis. 2008;8:2–3. 10 Lakshmi V, Neeraja M, Subbalaxmi MVS, et al: Clinical features and molecular diagnosis of Chikungunya fever from South India. Clin Infect Dis. 2008; 46(9):1436–1442. 11 Caglioti C, Lalle E, Castilletti C, Carletti F, Capobianchi MR, Bordi L: Chikungunya virus infection: an overview. New Microbiol. 2013;36:211–227. 12
Parola P, de Lamballerie X, Jourdan J, et al: Novel
chikungunya virus variant in travelers returning from Indian Ocean islands. Emerg Infect Dis. 2006;12(10): 1493–1499. 13 Dupuis-Maguiraga L, Noret M, Brun S, Le Grand
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