Fatigue is a frequent symptom. Many disorders may cause fatigue. Fatigue usually disappears when these disorders improve, but it occasionally persists. Some patients continuously show fatigue without apparent disorder, and they are diagnosed as having chronic fatigue syndrome (CFS) (1) or fatigue syndrome (2). Many factors are associated with prolonged or chronic fatigue. Concerning infectious agents, Epstein-Barr virus is associated with prolonged or chronic fatigue (3), but other infectious agents may be associated with prolonged or chronic fatigue.

We encountered a female who showed various symptoms similar to those of CFS. The diagnoses of acute parvovirus B19 and major depressive disorder were ultimately made. It is well known that acute parvovirus B19 infection develops various symptoms including polyarthropathy and skin rash (4, 5). The association between parvovirus B19 and prolonged or chronic fatigue have also been reported (5–7). However, the relationship remains uncertain. Here we describe a clinical characteristics and the course of this patient.

A 39-year-old Japanese female had been well until May 2001 when neck and shoulder pain, headache, pyrexia, insomnia, poor sleep, generalized weakness, and anorexia developed. Her symptoms improved after administration of analgesics. However, these symptoms recurred in late June, and persisted despite further analgesic treatment. Moreover, weight loss, diarrhea, and systemic lymphadenopathy also developed. She was referred to our hospital in mid July 2001. Physical examinations disclosed pyrexia and emaciation. Tender cervical and axillary lymph nodes were palpable. Urinalysis, complete blood count, renal and thyroid function were normal. Mild elevation of alanine aminotransferase (51 IU/l, normal 0–40) was found, but neither hepatitis B surface antigen nor hepatitis C virus antibody was negative. Antinuclear antibody and rheumatoid factor were also negative. Histopathologic diagnosis of the biopsied lymph node was necrotizing lymphadenitis (Fig. 1). Chest roentgenography, abdominal ultrasonography, and gastrotract fiberscope did not detect any sign of malignant disease. Serological tests for Epstein-Barr virus were negative, but both IgM and IgG antibodies to parvovirus B19 were positive in her serum. One thousand copies of parvovirus B19 per microliter was detected in her serum by real time polymerase chain reaction (Fig. 2). She was ultimately diagnosed as having acute parvovirus B19 infection. The diagnosis of major depressive disorder was also made by a psychiatrist according to the diagnostic criteria of DSMIII-R (8), although she had not previously been diagnosed as having psychiatric disorder. She received paroxetine hydrochloride hydrate and oriental herbal therapy was started in August, and her symptoms gradually improved. IgM antibody to parvovirus B19 disappeared in December 2001. However, one hundred copies of parvovirus B19 per microliter was still detected in her serum by real time polymerase chain reaction on March 2002 (Fig. 2). The patient reports that she feels no clinical symptoms now.

CFS is characterized by chronic unexplained fatigue and clinical symptoms including impairment in short-term memory, sore throat, tender cervical or axillary lymph nodes, muscle pain, multijoint pain, headache, unrefreshing sleep, and postexertional malaise (1). Almost all of these symptoms were found in the course of the present patient, and closed examinations did not disclose any malignant disease or hormonal abnormalities. These findings suggested that the diagnosis of our patient was CFS, although these symptoms persisted for two months only. It has been reported that some infectious agent is associated with CFS (3, 5, 6), and thus we investigated the association of a virus. This patient demonstrated acute parvovirus B19 infection.

It is well known that parvovirus B19 causes erythema infectiosum in children and many types of clinical symptoms in adults. These symptoms include polyarthropathy, anemia, skin rash, and edema (4, 5). Many reports have demonstrated a close association between parvovirus B19 and rheumatoid arthritis (9). The association with systemic lupus erythematosus (10), Wegener's granulomatosis and polyarteritis nodosa (11) have also been reported. These findings suggest that many clinical symptoms are caused by parvovirus B19 infection. Concerning CFS, the association between parvovirus B19 and CFS remains uncertain (6, 7). Recently, Kerr et al reported that 13 percent of patients with acute parvovirus B19 infection develop CFS (5). They reported that chronic fatigue is associated with acute fatigue caused by parvovirus B19 infection, but no other factors are associated with chronic fatigue (5). In this report, the clinical symptoms, blood examination of parvovirus B19, and autoantibodies were investigated in patients with acute parvovirus B19 infection. However, the association with life stressors has not been investigated. It has been reported that many predisposing and maintaining cofactors are associated with the outcome of post infectious fatigue (3). The husband of our patient was admitted to our hospital because of duodenal ulcer in April 2001, and she reported sleeping poorly. Moreover, she had a dispute with a neighbor in May, and felt depressed. We consider that these life stressors, depressive mood, and acute parvovirus B19 infection caused prolonged fatigue in this patient. It is noteworthy that parvovirus B19 viral genome existed in her serum in March 2002 when her clinical symptoms had completely disappeared. These findings suggest that the presence of parvovirus B19 does not necessarily always cause prolonged fatigue. We consider that acute parvovirus infection is merely a trigger and this agent causes prolonged fatigue only in patients experiencing life stressors or other cofactors that maintain and promote CFS. However, the viral load in serum may be associated with prolonged fatigue. It is also possible that the immune response against parvovirus B19 may cause prolonged fatigue, but this hypothesis could not be confirmed in this study.