Parvovirus infection

Management Strategy

Erythema infectiosum is typically a self-resolving exanthema transmitted via respiratory droplets. Outbreaks occur in the winter and spring and typically affect school-aged children between 5 and 15 years of age. After a short variable prodrome of fever, malaise, diarrhea, and pharyngitis, the classic features of the exanthem appear. Bright pink macular erythema of the cheeks (‘slapped cheek’ sign) together with nasal bridge and circumoral pallor precedes an evanescent macular, reticulated, or ‘lacelike’ rash over the trunk and proximal limbs. The rash may last for up to weeks to months (rarely years) and subsequently recurs after exposure to sun, warm temperature, and intense physical activity. In the majority of cases, supportive care and reassurance are all that is required. The rash of erythema infectiosum is immune complex–mediated so patients are no longer infectious by the time it appears and HPB19 IgG is detectable in the blood once the eruption occurs. Patients can be reassured and advised on simple supportive measures such as antipyretics, fluids, and bland emollients for the rash.

Parvovirus should be suspected with all petechial rashes whose origin is undetermined. PPGSS is the most common, presenting with pruritic to painful edema, erythema, and petechiae of the hands and feet with a classic sharp demarcation at the wrist and ankles. The ‘slapped cheek’ sign and an enanthem (palatal, pharyngeal, labial, and lingual erythema, petechiae, and ulcerations) may accompany the rash along with fever, and other non-specific viral symptoms. PPGSS typically occurs in spring and summer and in adolescents and young adults. Unlike erythema infectiosum, patients with PPGSS are viremic while the rash is present and are thus contagious. The eruption typically resolves within 1–2 weeks with non-specific supportive measures. The acropetechial syndrome involves the perioral skin in addition to the hand and foot involvement classically seen in PPGSS. A petechial eruption in a bathing trunk distribution, sometimes associated with pustules, as well as a cellulitis-like presentation, has also been described. Postviral disorders, including asymmetric periflexural exanthema (unilateral lateral thoracic syndrome), papular acrodermatitis of childhood (Gianotti–Crosti syndrome), and Kawasaki disease, have occurred after HPB19 infection. HPB19 is also in the differential diagnosis of the ‘blueberry muffin’ baby and TORCH infections, and should be considered in any newborn with multiple blue to purple cutaneous lesions. Other secondary associations include erythema nodosum, erythema multiforme, livedo reticularis, vasculitis, and Sweet syndrome.

HPVB19 infection may cause a symmetric arthropathy in up to 50% of adults, most commonly women, and in up to 10% of children. It is similar to rheumatoid arthritis involving the wrists, ankles, knees, and metacarpophalangeal and proximal interphalangeal joints. Arthropathy may accompany the cutaneous eruption but frequently follows it. The arthritis is usually self-limiting, requiring only non-steroidal antiinflammatory drugs for symptomatic relief. In about 20% of patients, the arthritis may become chronic, and it has been suggested that infection with HPB19 may be a trigger for autoimmune arthritis and connective tissue disease. HPVB19 infection can induce autoantibody formation, including antinuclear antibody and numerous subsets, rheumatoid factor, and ANCA.

In predisposed individuals with underlying disorders of hemolysis, decreased erythrocyte production, or active bleeding, HPB19 infection can cause a transient aplastic crisis. This acute anemia may be self-limited and asymptomatic, but transfusion may be required if severe. In addition to anemia, there may be moderate neutropenia and thrombocytopenia. Severe, recalcitrant cases of aplastic anemia may require intravenous immunoglobulin (IVIG) or bone marrow transplantation. Chronic HPB19 infection in immunosuppressed patients can result in pure red blood cell aplasia, a form of chronic anemia that results from the inability to create neutralizing antibodies to the virus. Children who are already anemic due to other causes, such as malaria, malnutrition, or parasites, can become profoundly anemic with HPB19 infection.

Patients with AIDS and chronic anemia secondary to HPB19 infection, who are treated with highly active antiretroviral therapy ( HAART ), with recovery of CD4 counts, have had resolution of their anemia. AIDS patients started on HAART can experience an immune reconstitution syndrome with overwhelming systemic involvement of parvovirus, resulting in encephalitis, severe anemia, or other severe sequelae.

Fetal infection with parvovirus B19 may result in mild-to-severe anemia, thrombocytopenia, high-output congestive heart failure, non-immune hydrops fetalis, and fetal death. Fetal stroke and other neurologic sequelae have also been reported. Fetal infection occurs usually during the first 20 weeks of pregnancy, although third trimester hydrops-related and spontaneous non-hydrops-related fetal demise has been reported. One-third or more of women of childbearing age do not have IgG antibodies to HPB19 and are susceptible to primary infection. Testing maternal serum for IgM and IgG titers and/or HPB19 DNA with polymerase chain reaction (PCR) analysis should be performed in pregnant women who develop symptoms of HBP19 infection or are in contact with children with a known parvovirus infection. If they have serologic evidence of primary infection, serial fetal ultrasonography should be performed to evaluate for signs of fetal anemia and hydrops fetalis.

Rarely, additional systemic involvement, including renal, neurologic, hepatic, cardiac, respiratory, ocular, and endocrine manifestations, has been reported during acute infection with HPB19. Immunosuppressed patients are at greatest risk for systemic involvement due to both primary infection with, and reactivation of, HPB19. Liver and spleen enlargement can be pronounced, mimicking leukemia. HPB19-associated hemophagocytic lymphohistiocytosis has been reported in patients with underlying malignancy on chemotherapy. Viral myocarditis can cause ventricular dysfunction and heart failure. Neurologic sequelae include neuritis and Guillain–Barré syndrome. HPB19 infection can mimic various connective tissue disorders, in particular systemic lupus erythematosus, dermatomyositis, and vasculitis. Infection with HPB19 has been linked to a multitude of chronic conditions, including hepatitis, nephritis, neurologic disease, and malignancy. However, a causal relationship has not been established. Reactivation of HPB19 has also been reported in adults with DRESS (drug reaction with eosinophilia and systemic symptoms) presenting with the classic reticular rash seen with parvovirus.

Although most parvovirus infections are diagnosed clinically, atypical presentations with systemic concerns or new-onset arthropathy of unknown cause warrant diagnostic testing. Serologic testing includes analysis for IgM and IgG antibodies using enzyme-linked immunoassay (ELISA), radioimmunoassay, or immunofluorescence. IgM to HPB19 indicates recent infection. HPB19-specific IgG antibodies indicate past exposure and may be positive in over half the adult population. In at-risk patients or those who have symptoms of anemia, a complete blood count will establish whether there is any significant level of anemia requiring transfusion.

It is possible to detect parvovirus DNA in both the blood and lesional skin. PCR techniques are extremely sensitive and may be useful in the following clinical scenarios: patients with an atypical presentation of HPB19 infection, where the clinical suspicion of infection is high and antibody studies are negative, and in immunocompromised patients who cannot mount an appropriate immunoglobulin response. In addition, a window period exists during the first 7 days after exposure when IgG and IgM are negative, and a second period exists where IgM has become undetectable. PCR may also be helpful during these periods.