Acute polyarthritis associated with hantavirus infection
Eun Young Lee,
Chang Ho Song and
Seung Ok Choi
Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
Correspondence and offprint requests to:
Eun Young Lee MD PhD, Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Kangwon-Do 220701, Korea.
Keywords: haemorrhagic fever with renal syndrome; hantavirus; polyarthritis
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Introduction
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Haemorrhagic fever with renal syndrome (HFRS) is the most common clinical manifestation of hantavirus infection. The major clinical findings are fever, headache, lumbar pain, and abdominal pain. However, a wide variety of additional symptoms can also occur since multiple organ systems are involved in HFRS, for example, the kidneys, the gastrointestinal tract, the respiratory tract, and the central nervous system [1,2]. But acute polyarthritis as a clinical manifestation of HFRS has not been previously reported.
We report the case of a 63-year-old Korean man who developed fever, chills, pharyngitis, and acute polyarthalgia with renal failure. To our knowledge, this is the first report of acute polyarthritis in HFRS.
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Case
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A 63-year-old Korean male had been well until 5 days before admission, when abrupt fever, chills, pharyngitis, nausea, vomiting, and polyarthralgia including hands, shoulders, and hips developed, followed by generalized oedema and decreased urine output. The multiple joint pain were persistent in a wax-and-wane pattern. There was no history of tuberculosis, diabetes mellitus, hypertension, hepatitis, arthritis, or other autoimmune disease. Three years ago the patient was diagnosed with a duodenal ulcer and then cured. He was on no regular medication. He was a farmer. The temperature was 37.8°C, blood pressure 140/90 mmHg, and pulse rate 64 beats/min. On physical examination, the patient appeared ill, with a puffy face and conjunctival injection. Coarse breathing sounds with rales on the entire lung fields and decreased breathing sounds on right lower lung fields were heard on auscultation. There was bilateral costovertebral angle tenderness. Marked pretibial pitting oedema was also noted. There were swelling and tenderness on the proximal interphalangeal joint of both 2nd fingers and the left 5th finger, and tenderness on the right shoulder and both hip joints. Morning stiffness, which persisted over 1 h, was noted. There were no rheumatoid nodules.
Laboratory findings were as follows: haematocrit 35.4%, white blood cell count 14 900/mm3, platelet count 12 000/mm3, anti-platelet Ab (-), reticulated platelet 1.2%, erythrocyte sedimentation rate 36 mm/h, C-reactive protein 5.44 mg/dl, rheumatoid factor <20.0 IU/ml, blood urea nitrogen 77 mg/dl, creatinine 8.8 mg/dl, uric acid 10.9 mg/dl, aspartate aminotransferase 101 U/l, alanine aminotransferase 70 U/l, total protein 5.1 g/dl, albumin 2.4 g/dl, cholesterol 157 mg/dl, total calcium 6.4 mg/dl, inorganic phosphate 5.4 mg/dl, total bilirubin 0.3 mg/dl, serum sodium 114 mEq/l, potassium 4.8 mEq/l, carbon dioxide 15.5 mEq/l, chloride 82 mEq/l. Urinalysis revealed a specific gravity of 1.010, pH 7.5, protein (3+), glucose (+) with red blood cells 2530/HPF on microscopic examination. Arterial blood gases breathing ambient air revealed the following values: pH 7.423, pCO2 21.7 mmHg, pO2 93.7 mmHg, bicarbonate 14.2 mmol/l, and O2 saturation 97.7%. A coagulation profile revealed a prothrombin time of 10.9 s (123% of control) and activated partial thromboplastin time of 12.5 s. HBsAg (-), anti-HBs (+) and anti-HCV (-). Fibrinogen level and fibrinogen degradation products were 221 mg/dl and >40 µg/ml respectively. The D-dimer test was >1.0 µg/ml. A serologic test for antibodies to hantaviruses (indirect immunofluorescence antibody test) was positive with a high titre (1 : 512). Polarizing microscope examination revealed no crystals in the joint fluid from the 2nd proximal interphalangeal joint of the hand. Radiographs of the hands revealed only soft-tissue swelling without bony erosions.
On the 2nd day of hospitalization, orthopnoea developed. The urine volume was 320 ml/day, blood urea nitrogen 105 mg/dl, creatinine 11.8 mg/dl. Chest PA revealed cardiomegaly, pulmonary congestion, and right pleural effusion, therefore haemodialysis was performed via a temporary jugular-vein catheter. The urine volume increased to 1690 ml/day after 10 days of hospitalization. Renal function gradually improved and the patient was discharged on the 23th day with a blood urea nitrogen of 16 mg/dl, serum creatinine 2.9 mg/dl, serum sodium 137 mEq/l, potassium 3.9 mEq/l, carbon dioxide 30.1 mEq/l, chloride 105 mEq/l. The polyarthralgia and joint swelling improved with the ingestion of methotrexate, hydroxychloroquine, low-dose steroid and non-steroidal anti-inflammatory drugs.
Three months later, the patient was in excellent condition. The polyarthralgia was much improved. Haematocrit was 26.4%, white blood cell count 8720/mm3, platelet count 324 000/mm3, mean corpuscular volume 94.2 fl, mean corpuscular haemoglobin 30.2 pg, mean corpuscular haemoglobin concentration 32.1 g/dl, erythrocyte distribution width 13.6%, erythrocyte sedimentation rate 102 mm/h, blood urea nitrogen 12 mg/dl, creatinine 0.8 mg/dl, fasting blood sugar 92 mg/dl. Urinalysis revealed normal findings.
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Discussion
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Viruses are attractive candidates for infectious aetiological agents or cofactors in the development of rheumatic diseases. A wide variety of viruses has been associated with acute rheumatic illness, most of which seem to be self-limiting [3]. Common agents include the rubella virus [4] and hepatitis B virus [3]. Others have also been occasionally implicated, including coxsackieviruses and adenoviruses [3,5]. Recently, the roles for parvovirus B19 in vasculitis and erosive rheumatoid arthritis have been reported. The rheumatic disease manifestations of hepatitis C virus infection included polyarthritis [6]. Venuta et al. [7] also reported a case of acute EBV infection with polyarthritis. Ross River virus and Barmah Forest virus have been commonly recognized as causes of epidemic polyarthritis and polyarticular disease in Australia [8]. Viral infections are important in rheumatic disease not only because of the acute and subacute syndromes they cause, but also because of their potential importance as aetiological factors in common chronic diseases such as rheumatoid arthritis. Despite the failure to obtain firm evidence of viral infection in most patients with rheumatoid arthritis and other connective diseases, this theory should not be discarded, firstly because several mechanisms have been discovered by which virus infections can persist in lymphocytes and other tissue, thereby provoking inflammation without the production of complete readily detectable virus particles; secondly there are numerous ways in which host resistance to virus can be subverted with an infective aetiology. The main problem is proving whether a primary pathogenetic role can be attributed to any isolated virus or is the virus just a passenger virus that has been activated by the disease process.
The lymphotrophic nature of the virus is probably ultimately responsible for the rheumatic disease manifestations. We described here a patient with HFRS who also had many features suggestive of seronegative inflammatory polyarthritis. Both hands were involved symmetrically with more than three joints involvement, and there was morning stiffness. Seronegative arthritides may be linked to antigen presentation to CD8 cells in association with class I MHC alleles (e.g. HLA-B27) [9]. In patients with HFRS, there is evidence of T-cell activation, for example increased numbers of CD8-positive cells and a concomitant decrease of CD4-positive cells occurring at a very early stage in the course of HFRS [10]. Functional testing of suppressor T cells has shown a decreased activity in spite of increased numbers of CD8-positive cells [10]. These findings suggest similar pathogenetic roles of T cell in both HFRS and seronegative polyarthritis.
In summary, in our case, fever, pharyngitis, and renal failure caused by acute hantavirus infection developed, and active polyarthritis developed simultaneously in the patients with HFRS. We suggest that hantavirus may cause acute rheumatic illness such as polyarthritis, so hantavirus infection should be considered in the differential diagnosis of acute polyarthritis.
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Received for publication: 27. 4.99
Accepted in revised form: 30. 4.99