Stephen A. Paget, MD, FACP, FACR

Disclosures

February 28, 2003

Question

A 40-year-old woman presenting with a 12-month history of diffuse body aches was thought to have fibromyalgia. She responded to selective serotonin reuptake inhibitors (SSRIs) and then started becoming resistant to treatment. Salicylates were added to her therapy for 3 months but she again failed to respond and developed diffuse edema. She now needs 40 mg of torsemide (Demadex; Roche Laboratories Inc.; Nutley, New Jersey) daily. Her rheumatology panel is negative, C-reactive protein is 8 (nl < 0.5), IgG parvovirus B19 is 3 times normal level (IgM negative). Has anyone seen chronic parvovirus B19?

Response from Stephen A. Paget, MD, FACP, FACR

This 40-year-old woman poses an interesting clinical problem, initially presenting with diffuse body aches/fibromyalgia responsive to SSRI therapy and then becoming refractory to SSRIs and salicylates and evolving into a diffuse edematous state necessitating large doses of diuretic.

Addressing the main question of whether anyone has seen chronic parvovirus B19 infection, the answer brings up 2 more questions that need to be answered -- did this patient ever have acute parvovirus infection and, if so, what does the term "chronic" mean? Acute parvovirus B19 infection in an adult is often "caught" by a mother who is taking care of her child who has classic "fifth disease," also called erythema infectiosum, or "slapped cheek disease."

Usually, 2 weeks after a child has the acute exanthem manifested by high fevers the first day, which is followed by red (slapped) cheeks or a lacy rash on the extremities, the mother develops what appears to be acute rheumatoid arthritis (RA), with symmetrical polyarthritis of the small joints of the hands, and of the feet, knees, and elbows. The diagnosis is usually considered because of the acuteness of illness onset and the family history. Often the erythrocyte sedimentation rate will be elevated and a rheumatoid factor test may be positive in low titers.

During the first 2 months after illness onset, the patient will have elevated antibody titers to parvovirus B19 of the IgM type. Later, this switches to the IgG type. It must be remembered that this viral infection is common and often asymptomatic and thus IgG antibodies may be found to be elevated in the setting of many illnesses with which it has no cause-and-effect relationship. Also, elevated titers of many viruses can exist as part of a nonspecific "turn-on" of the immune system in various systemic inflammatory disorders such as RA.

The mean duration of RA-like arthritis due to parvovirus is 6 months with a rapid fall off after that time. Some patients can still have aches and pains after the initial synovitis phase but they do not usually have the redness, warmth, or swelling that is characteristic of the initial phase. The rheumatoid factor often clears when the joint symptoms resolve. Although there is still some debate, it is generally believed that parvovirus is not a cause of chronic RA.

Acute parvovirus infection can cause hemolytic anemia in fetuses and patients with hemolytic disorders such as sickle cell disease, and it also can lead to bone marrow aplasia in the setting of immunosuppression. Acute infections can also cause acute liver failure, aseptic meningitis, and exacerbations of already present systemic inflammatory disorders such as RA and juvenile RA.

So, did this patient ever have a parvovirus infection? Yes, of course. Do the elevated titers of IgG antibodies to this virus demonstrate a clear cause-and-effect relationship between the titers and her musculoskeletal or edematous problem? No, not necessarily. Could the elevated titers simply be "fellow travelers" and unrelated to her present illness? Yes. This movement from fibromyalgia to edema would be a very uncommon manifestation of parvovirus, making the linkage unlikely. Studies on patients with chronic fibromyalgia symptoms did not show a relationship between active viral infection and this diffuse pain syndrome. However, if you wanted to find out if this patient could have recurrent infection with this DNA virus, performing a polymerase chain reaction test could be helpful.

The elevated C-reactive protein is of concern and may reflect a systemic inflammatory, autoimmune disorder that is causing myocarditis and congestive heart failure, or proteinuria with the nephrotic syndrome or a capillary leak syndrome. Certainly a close look at those disorders that can cause this diffuse edematous state is mandatory.

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