What are the clinical manifestations, diagnosis, and management of adenovirus and parvovirus B19 infections, particularly in children, immunocompromised individuals, and pregnant women?

Adenovirus and Parvovirus B19: Clinical Manifestations, Diagnosis, and Management

Adenovirus Infections

Clinical Manifestations

Adenoviruses typically cause mild, self-limited infections affecting the respiratory tract, gastrointestinal system, or conjunctiva, but can cause severe disseminated disease in immunocompromised patients with fatality rates exceeding 50% if untreated 1.

Common Presentations

• Respiratory tract infections are the most frequent manifestation, particularly in young children who lack humoral immunity 1
• Conjunctivitis and pharyngoconjunctival fever occur commonly 1
• Gastroenteritis with diarrhea, especially in pediatric populations 1

Severe/Rare Manifestations

• Hemorrhagic cystitis, particularly in immunocompromised patients 2, 1
• Hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis represent uncommon but serious complications 1
• Myocarditis/perimyocarditis with borderline myocarditis being the most common histological pattern associated with adenovirus 2
• Disseminated disease occurs primarily in organ transplant recipients and HIV-infected individuals, with mortality exceeding 50% without treatment 1

High-Risk Populations

• Immunocompromised patients (transplant recipients, HIV infection) face significantly higher risk of severe disease and dissemination 2, 1
• Military recruits and individuals in closed/crowded settings are at increased risk for epidemic spread 1
• Young children are more susceptible due to lack of pre-existing immunity 1

Diagnosis

Definitive diagnosis of adenoviral pericarditis or myocarditis requires PCR or in-situ hybridization of pericardial fluid and/or peri-/epicardial tissue biopsies, as serological testing is futile 2.

• Viral nucleic acid detection by quantitative PCR is the gold standard for identifying adenovirus in affected tissues 2
• Adenovirus DNA is rarely detected in pericardial biopsies compared to other viruses like parvovirus B19 2
• Throat or rectal swabs and serum antibody testing do not correlate with tissue-based molecular detection and should not be relied upon 2
• Endomyocardial biopsy in children is reasonable for unexplained cardiomyopathy, as adenovirus is associated with the worst prognosis among viral causes 2

Management

For severe adenovirus infections, cidofovir is the drug of choice, though not all patients require treatment 1.

Treatment Approach

• Supportive care is appropriate for mild, self-limited infections in immunocompetent hosts 1
• Cidofovir should be used for severe pneumonia or disseminated disease, particularly in immunocompromised patients 1
• Intravenous immunoglobulin (IVIG) at 10g IV on days 1 and 3 for 6-8 hours is under investigation for adenovirus perimyocarditis 2
• Corticosteroids are contraindicated in viral pericarditis as they reactivate viral infections and promote ongoing inflammation 2, 3

Special Considerations

• Children with PCR-confirmed adenovirus after transplantation have only 66% 5-year survival versus 95% in PCR-negative patients 2
• Involvement of infectious disease specialists is recommended for severe cases 2
• Live oral vaccines are highly efficacious for prevention in military populations but are not currently available to civilians 1

---

Parvovirus B19 Infections

Clinical Manifestations

Parvovirus B19 causes a wide spectrum of disease from mild erythema infectiosum in children to life-threatening complications in high-risk populations including pregnant women, immunocompromised patients, and those with hemolytic disorders 4, 5.

Immunocompetent Children and Adults

• Erythema infectiosum (Fifth disease) presents with the classic "slapped-cheek" rash in children, appearing after the infectious period has passed 5, 6
• Arthralgia and arthropathy occur in 62% of adults, typically presenting as peripheral, symmetrical polyarthralgia 7, 8
• "Gloves and socks" syndrome with papular, purpuric eruptions on hands and feet 5
• Fever (65%), skin rash (58%), and constitutional symptoms are common 8

Hematologic Complications

• Transient aplastic crisis occurs in patients with chronic hemolytic anemias (sickle cell disease, thalassemia, spherocytosis, iron deficiency anemia) due to acute cessation of red blood cell production 9, 5
• Chronic red cell aplasia develops in immunocompromised patients 5
• Laboratory abnormalities include thrombocytopenia (43%), lymphopenia (38%), elevated liver enzymes (37%), and increased acute phase reactants (73%) 8

Pregnancy-Related Complications

• Fetal hydrops, spontaneous abortion, and fetal anemia are serious risks, particularly with infection between 9-20 weeks gestation 4
• Intrauterine transfusion may be required for severe fetal anemia or hydrops 9

Other Organ System Involvement

• Cardiac manifestations including myocarditis and pericarditis 4, 8
• Neurological complications such as cranial nerve palsies and distal paresthesias 8
• Hepatic and renal involvement can occur 4

Immunologic Phenomena

• False-positive serologies for anti-CMV and anti-EBV IgM occur in 27% of cases 8
• Autoantibodies including ANA (19%), anti-DNA (28%), anti-phospholipid antibodies (14%), and hypocomplementemia (32%) may be present 8

Diagnosis

Clinical diagnosis can be made without laboratory confirmation if erythema infectiosum is present; when laboratory confirmation is needed, serum IgM testing is recommended for immunocompetent patients, while viral DNA testing is recommended for aplastic crisis and immunocompromised patients 5.

Diagnostic Approach

• Parvovirus B19 IgM serology is the test of choice for immunocompetent patients with suspected acute infection 5
• PCR for viral DNA should be used in patients with aplastic crisis, immunocompromised status, or when IgM may be unreliable 5
• Parvovirus B19 DNA is detected at high copy numbers (up to 7 × 10⁶ genome equivalents/μg DNA) predominantly in epicardial tissue 2
• Four-fold rise in serum antibody levels is suggestive but not diagnostic 2

Distinguishing from Rheumatoid Arthritis

• Anti-CCP antibodies and rheumatoid factor are typically negative in B19 arthritis, unlike rheumatoid arthritis 7
• B19 arthritis is non-erosive and does not cause joint destruction 7
• Rheumatoid nodules never occur in B19-associated disease 7
• Consider B19 as a mimicking disease in patients with apparent difficult-to-treat inflammatory arthritis 7

Management

The American Academy of Pediatrics recommends supportive care with antipyretics and analgesics for immunocompetent individuals, while transient aplastic crisis requires prompt recognition and red blood cell transfusions 9.

Immunocompetent Patients

• Supportive care including antipyretics for fever and analgesics for joint pain is the mainstay of treatment 9
• NSAIDs provide symptomatic relief for arthralgia 7
• Reassess at 2-3 months to confirm resolution of arthritis 7
• Avoid escalating to DMARDs unless inflammatory activity persists beyond the expected self-limited course 7

Patients with Hemolytic Disorders

• Red blood cell transfusions are often needed to manage severe anemia in transient aplastic crisis 9
• Monitor siblings and close contacts with hemolytic disorders for concurrent or subsequent aplastic crisis 9

Pregnancy Management

• Intrauterine transfusion for cases of fetal hydrops or severe anemia 9
• Close monitoring with ultrasound and middle cerebral artery Doppler studies to detect fetal anemia 9

Immunocompromised Patients

• Intravenous immune globulin (IVIG) therapy may be required for chronic red cell aplasia 5
• Corticosteroids are generally not recommended as they may worsen viral infections through further immunosuppression 3

Persistent Arthritis

• Low-dose glucocorticoids may be considered if NSAIDs are insufficient, though evidence is limited 7
• Hydroxychloroquine can be considered for persistent non-erosive polyarthritis 7
• Avoid methotrexate and leflunomide unless definitive RA diagnosis is established 7

Prevention and Infection Control

Isolation of infected individuals, particularly from pregnant women, immunocompromised patients, and those with hemolytic disorders, is essential to prevent transmission 9.

• Respiratory droplet precautions as the virus spreads mainly through respiratory droplets 5
• By the time the rash appears, the patient is no longer infectious 5
• No specific vaccine is currently available, though one is under investigation 6

Critical Pitfalls to Avoid

• Do not initiate DMARD therapy for B19 arthritis, as this leads to apparent failure of multiple DMARDs, unnecessary immunosuppression, and inappropriate escalation to biologics 7
• Do not use corticosteroids for viral pericarditis/myocarditis, as they reactivate infections and worsen outcomes 2, 3
• Do not rely on serology alone for diagnosis in immunocompromised patients or those with aplastic crisis—use PCR 5
• Do not miss the diagnosis in pregnant women, as early detection allows for monitoring and intervention to prevent fetal complications 9, 4