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Evaluation of autoantibodies to common and neuronal cell antigens in Chronic Fatigue Syndrome
Suzanne D Vernon  and William C Reeves

Since the onset of acute parvovirus B19 infection, she had experienced persistent abdominal pain and diarrhea that remained undiagnosed despite extensive investigation, including colonoscopy, and she was being treated with carbamazepine and imipramine. Although she was able to continue working, her illness necessitated frequent time off from work, and eventually she had reduced her work commitment to part time. In addition, her social life had also been markedly curtailed by this illness. She had been treated with physiotherapy that had provided minimal benefit, and so she was referred for rheumatology assessment after a 24-month illness.

The findings of history, examination, and laboratory investigations performed immediately before commencement of IVIG therapy are summarized in table 1. At this time, the patient had had a 26-month history of fatigue, arthralgia, and other symptoms. During the examination, she appeared to be flushed and had no evidence of synovitis. She had pain on external rotation of her left hip, and 7 of 18 tender points were present.

The findings of routine blood investigations, including a complete blood cell count, determination of urea and electrolyte levels, liver function tests, and determination of the erythrocyte sedimentation rate (ESR), were normal. The patient was found to be positive for serum parvovirus B19 DNA, serum antiparvovirus B19 VP1/2 IgG and antiparvovirus B19 NS1 IgG, and rheumatoid factor (RF), and she was found to be negative for leukocyte parvovirus B19 DNA and antinuclear antibody (ANA). The findings of Schirmer's test were normal. Skeletal radiography findings were normal.

In January 2001, the patient was admitted to hospital for IVIG therapy (Sandoglobulin; Novartis Pharmaceuticals) at a dosage of 400 mg/kg per day for 5 days, after which her symptoms resolved during the next 2 weeks, with a more gradual improvement during the next 2 months. At the time of this writing, her condition remains in remission. The patient subsequently returned to work without sick leave and was able to participate again in family and social activities that were not possible during her illness. Serial serum samples obtained at intervals from the onset of illness were tested for parvovirus B19 markers and cytokines.

Patient 8, as described elsewhere [9], was a 34-year-old Italian woman who was employed as a schoolteacher and was the mother of 2 young children. She presented in the summer of 1998 with a 3-week history of fever, skin rash, and polyarthralgia. She also complained of pain, a sensation of heat, and swelling in her elbows, shoulders, hands, back, neck, knees, ankles, and feet. Serum samples obtained in June 1998 were found to be positive for antiparvovirus B19 IgM.

After the acute phase, the arthralgia persisted in her elbows, knees, back, neck, fingers, and wrists; it occurred in regular bouts lasting 12 weeks and was associated with feeling feverish and shivery and with recurrence of cold sores. Fatigue was also a prominent feature of the acute phase and persisted throughout the follow-up period until June 2000. Additional symptoms included deterioration in memory and concentration, sore throat, painfully aching muscles, new headaches, difficulty sleeping, unrefreshing sleep, postexertional malaise, increased tendency to sweat, dizzy spells, and blurred vision.

In April 2000, she presented with a 2-month history of palpitations; physical examination revealed bilateral exophthalmos and a diffuse goiter. Serum testing revealed a high level of thyroxine, which confirmed a diagnosis of hyperthyroidism. This illness was brought under control with propranolol and carbimazole therapy, and treatment with carbimazole (60 mg per day) was maintained. The fatigue and related symptoms had necessitated giving up her teaching career, and she was able to socialize only rarely. She was referred for rheumatology assessment after a 24-month illness.

The findings of history, examination, and laboratory investigations performed immediately before commencement of IVIG therapy are summarized in table 1. At this time, the patient had had a 26-month history of fatigue, arthralgia, and other symptoms. During the examination, she was flushed and had no evidence of synovitis, and 7 of 18 tender points were present. The findings of routine blood investigations, including a complete blood cell count, determination of urea and electrolyte levels, liver function tests, and determination of the ESR, were normal.

At follow-up, the patient tested positive for serum parvovirus B19 DNA and serum antiparvovirus B19 VP1/2 IgG but negative for leukocyte parvovirus B19 DNA and antiparvovirus B19 NS1 IgG. She also tested positive for RF and ANA (homogenous ANA titer, 300).

In January 2001, the patient was admitted to the hospital for IVIG therapy (Sandoglobulin) at a dosage of 400 mg/kg per day for 5 days. Within 2 weeks, she felt much improved, and during the next 2 months, she recovered completely. This treatment has enabled her to again participate in family and social activities that were not possible during her illness. Serial serum samples obtained at intervals from the time of onset of illness were tested for parvovirus B19 markers and cytokines.

Patient 32, as described previously [9], was a 46-year-old white salesman who presented in January 1998 with acute pain and swelling in his hands, knees, and ankles associated with a flulike illness; he tested positive for serum antiparvovirus B19 IgM. Fatigue was present from the beginning of this illness. He had been in very good health before the development of this illness. During the next 2 years, he experienced joint pain in the hips, knees, ankles, wrists, and metacarpal joints.

There was also intermittent swelling in the fingers. Fatigue had increased from the time of acute parvovirus B19 infection until it was necessary for him to sleep for several hours during the day. Although he was able to continue his work as a salesman, his social activities were severely restricted. He also reported a deterioration in memory and concentration, painful aching muscles, new headaches, difficulty sleeping, unrefreshing sleep, postexertional malaise, and an increased tendency to sweat. He was referred for rheumatology assessment after a 24-month illness.

 

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Autoantibodies to neuronal cell antigens in Chronic Fatigue Syndrome