Case N3 - FJM

A previously healthy 65-year-old woman went to her primary care physician in late
August, seeking evaluation of a “spot” that had appeared on her right leg 3 weeks
earlier. She felt completely well and recalled no trauma or tick bites. Her physical
examination was notable only for a low-grade temperature elevation (37.7°C) and a
7-to-8-mm erythematous macule on her right leg. She had no lymphadenopathy or
articular abnormalities and was told that the lesion was most likely the result of an
insect bite; still, she was advised to follow up if its appearance changed.
One week later, the skin lesion had resolved, but the patient returned, reporting
malaise and diffuse arthralgias that had progressively worsened, with intense, disabling
pain and stiffness in her neck, shoulders, wrists, hands, knees, and ankles.
She also reported a transient occipital headache and scalp tenderness when brushing
her hair. In addition, she noted pain in the left anterior part of her chest that had
awakened her from sleep, was exacerbated by respiration, and was partially relieved
by sitting up.

The white-cell count was 4600 per cubic millimeter
(72% neutrophils, 20% lymphocytes, 4%
monocytes, 3% eosinophils, and 1% basophils).
The hematocrit was 38.2%, and the platelet count
227,000 per cubic millimeter. The creatinine level
was 0.9 mg per deciliter (79.6 μmol per liter). The
levels of sodium, potassium, and glucose were
normal. The aspartate aminotransferase level was
25 units per liter, and the alanine aminotransferase
level 33 units per liter. The thyrotropin level
was 1.9 μU per milliliter. Tests for Lyme disease
— enzyme-linked immunosorbent assay (both
IgM and IgG antibodies) and Western blotting —
were negative. The erythrocyte sedimentation rate was
40 mm per hour



The patient had persistent arthralgias and sought
care from another internist. She reported no fever,
rash, visual changes, jaw claudication, sore
throat, cough, dyspnea, nausea, vomiting, diarrhea,
or dysuria. Her chest pain had resolved. Her
medical history was notable for osteoporosis, for
which she was taking raloxifene. She was taking
no other medications. There was no personal or
family history of psoriasis or other rheumatologic
illness. She reported extensive international travel,
including travel to Africa, but her most recent trip
had been several years ago. She noted no recent
contact with anyone who was sick and had last
seen her grandchildren 6 weeks earlier. She also
reported no risk factors for hepatitis B or C infection
or for sexually transmitted diseases.

On physical examination, the patient appeared
pale. Her temperature was 36.5°C, pulse 88 beats
per minute and regular, and blood pressure
125/80 mm Hg. She had no mucocutaneous or
nail abnormalities, lymphadenopathy, or ocular
inflammation. Temporal-artery pulses were present
and symmetrical, and there was no overlying
tenderness. The results of cardiac and pulmonary
examinations were normal, with no pleural or
pericardial rubs, and an abdominal examination
revealed no abnormalities. Examination of her
joints revealed notable swelling, tenderness, and
palpable warmth in several proximal interphalangeal
joints and the second and third metacarpophalangeal
joints of her hands. The range of
motion of her neck, shoulders, and wrists was
limited by mild-to-moderate pain, but there was
no appreciable synovitis in these joints.

¿What is the Diagnosis?

No imaging studies were performed. Consultation with a
rheumatologist confirmed the presence of synovitis in
the small joints of the patient's hands. A repeat white-cell
count was 4130 per cubic millimeter, with the differential
count revealing 70% neutrophils, 20% lymphocytes, 6%
monocytes, 2% eosinophils, and 2% basophils. The
hematocrit was 39.2%, and the platelet count 242,000
per cubic millimeter. The urinary sediment was unremarkable.
The erythrocyte sedimentation rate was 40 mm per hour.
Antinuclear antibodies were not detected, nor was rheumatoid
factor. An electrocardiogram was normal.

The IgG index for parvovirus B19 was 1.9 units, and the IgM index 10.4 units (normal value, <0.9).

The elevated parvovirus IgM titer is diagnostic of acute parvovirus infection. Parvovirus B19 infection can have a polyarticular presentation that affects both large and small joints in a symmetrical fashion, resembling rheumatoid arthritis. In contrast to rheumatoid arthritis, however, parvovirus-associated arthritis is generally self-limited.

The patient's inflammatory articular symptoms resolved over a period of several months. On routine evaluation 1 year later, she had no residual synovitis.

Commentary

Human parvovirus B19 is a single-stranded DNA virus that was identified in 1975. The cell-surface receptor — P antigen, or globoside (Gb4) — mediates tropism for the primary target of the virus, erythroid precursor cells. Gb4 is also expressed on granulocytes; platelets; heart, lung, liver, and kidney cells; vascular endothelial cells; smooth-muscle cells; and, notably, synovial cells.

Outbreaks of parvovirus B19 infection typically occur from late winter to early summer. Careful questioning may elicit a report of contact with a sick child, but as this case illustrates, the absence of known contact with someone who is sick does not rule out infection with this virus. Transmission commonly occurs through aerosolized droplets, but other means of transmission are possible, including transfusion of contaminated blood products.

The incubation period is 6 to 18 days, and clinical manifestations vary with the host. Infection in children is often asymptomatic or mild. The most common clinical presentation in childhood is erythema infectiosum, or fifth disease, which presents with a characteristic facial rash (“slapped cheek” appearance) and a reticular rash on the torso and limbs. In contrast, adults with parvovirus B19 infection often present with a more debilitating, influenza-like illness. The facial rash is rare in adults, and the reticular rash, which is common in children, is present in only a minority of adults. Whereas joint symptoms develop infrequently in children with parvovirus, as many as 60% of adults present with clinically significant arthralgias or arthritis. Joint symptoms are twice as likely to develop in women as in men. Articular involvement is symmetrical and most commonly affects the wrists, hands, knees, and ankles, a pattern mirroring that seen in rheumatoid arthritis, certain forms of psoriatic arthritis, and systemic lupus erythematosus. The diagnostic process may be further complicated by the occasional presence of autoantibodies, including rheumatoid factor and antinuclear antibodies, which may be found in the presence of viral infections, albeit at a low titer.

Parvovirus-associated arthritis is usually self-limited, resolving in 1 to 3 weeks. However, in as many as 20% of infected women, articular symptoms persist for months to years. It has been suggested that parvovirus B19 infection may precipitate the development of rheumatoid arthritis, systemic lupus erythematosus, or juvenile rheumatoid arthritis. However, this view remains controversial. Elevated levels of interleukin-6, tumor necrosis factor α, and granulocyte–macrophage colony-stimulating factor have been found to be negatively associated with the development of acute parvovirus-associated arthritis.7 Expression of antibodies to the 77-kD nonstructural parvovirus B19 protein, NS1, found in 15 to 30% of those infected, is associated with the development of chronic arthritis but not acute arthritis.

Although acute arthritis is the usual clinical manifestation of parvovirus B19 infection in healthy adults, other manifestations may occur, including anemia and leukopenia. Intrauterine infection is a major cause of hydrops fetalis. The estimated risk of fetal infection when a woman is infected with parvovirus during pregnancy is 30%, with a 5 to 9% risk of fetal loss. Infection during the second trimester appears to pose the greatest risk of hydrops fetalis.

In patients who have chronic hemolysis, such as sickle cell anemia, infection may be manifested as a transient aplastic crisis.In other patients with immunosuppression, such as organ-transplant recipients, chronic anemia may develop as a result of persistent viral suppression of erythrocyte production.

The presence of the IgM antibody to parvovirus B19, as in the patient described, indicates acute infection. This antibody appears 10 to 12 days after infection and persists for 1 to 3 months. IgG-antibody expression, found in 40 to 80% of adults, follows and confers lifelong immunity. Although infection commonly occurs early in life, a substantial number of middle-aged and older adults remain susceptible.

This case illustrates the importance of considering parvovirus B19 infection in the differential diagnosis of acute-onset arthritis, regardless of the patient's age. This is particularly important in cases of symmetrical polyarthritis that may otherwise suggest other rheumatic diseases, especially rheumatoid arthritis and systemic lupus erythematosus. As many as 15% of new cases of inflammatory arthritis may be caused by parvovirus infection.Including parvovirus B19 infection in the differential diagnosis of new-onset polyarthritis and ordering appropriate serologic testing to confirm the diagnosis can eliminate the need for expensive additional testing and consultation, avoid inappropriate treatment, and enable the physician to reassure the patient that the arthritis is likely to be self-limited.

Source

1. No respect for age - NEJM

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