Erythema Infectiosum

Overview

• Erythema infectiosum: illness caused by parvovirus B19, associated with fever and a characteristic rash
• Epidemiology:
  • Infection affects all ages but is more common in children between 3 and 15 years of age.
  • Outbreaks occur commonly in schools and childcare settings.
  • Occurrences of infection are more frequent in late winter and early summer.
• If a person is immunocompetent, immunity is usually conferred following infection.

Pathophysiology

Mode of transmission

• Respiratory secretions via:
  • Saliva
  • Mucus
  • Fomites
• Contact with infected blood or blood products
• Vertical/transplacental transmission in nonimmune women (can result in congenital infection)

Incubation

The incubation period is 4–21 days.

Pathogenesis

• Initial B19 viral infection: 
  • Entry into the upper respiratory tract → viremia (prodromal symptoms) 5–10 days from exposure
  • Virus spreads and is cytotoxic to rapidly dividing erythroid precursor cells in the bone marrow → transient ↓ reticulocytes and anemia
  • In healthy individuals: Bone marrow effect is not clinically significant.
  • In individuals with hematologic conditions: severe anemia/aplastic crisis occurs.
  • In immunocompromised patients, viremic state can be prolonged.
•  Rash:
  • 2–5 days later, erythematous malar rash with circumoral pallor (“slapped cheek”) appears.
  • Followed by lace-like erythematous rash on the trunk and extremities
  • Rash appearance represents resolution of viremia (appearance of immunoglobulin M (IgM)) → no more constitutional symptoms
  • May recur weeks later, triggered by sunlight, stress, or exercise

Clinical Presentation

Initial prodromal symptoms (viremia)

• Low-grade fever
• Headache
• Nausea
• Diarrhea
• Cold-like symptoms
• Pruritus

Later symptoms (viremia resolved)

• Days 2–5
• Rosy-red rash, mainly on cheeks
  • Classic slapped-cheek appearance
  • Rash extends over rim of the nose or mouth.
• Morbilliform → reticulated (lacey) rash:
  • Upper arms
  • Torso
  • Legs
• Rash more common in children

Complications

• Arthritis:
  • Acute symmetric joint pain (hands, knees, ankles)
  • More common in teenagers and adults (women > men)
  • Up to 10% of children may have stiff joints.
  • Can last 3 weeks or longer
  • No degenerative joint changes
• Transient aplastic crisis: 
  • Rapid decline in RBCs
  • Seen in patients with sickle cell disease, spherocytosis, and other hematologic diseases
  • Patients present with weakness/lethargy and pallor.
• Maternal infection and fetal effects: 
  • Rare but a serious infection (leading to fetal RBC destruction), especially when onset is in the 1st 20 weeks of pregnancy
  • Hydrops fetalis, miscarriage, intrauterine fetal death
• Chronic infection in immunocompromised patients:
  • These patients cannot mount an immune response to viremia, increasing the risk for chronic infection.
  • Results in pure red cell aplasia (giant pronormoblasts in the bone marrow) and severe anemia (reduced reticulocytes)

Diagnosis and Management

Diagnostic approach

• Diagnosis based on clinical features
• Additional test(s) in patients with signs and symptoms of anemia:
  • Complete blood count (hemoglobin drops by 2 g/dL from baseline)
  • Reticulocyte count decreased
•  IgG and IgM antibody testing: 
  • For pregnant women
  • Patients with hemoglobinopathies/hemolytic conditions
  • Severe or persistent arthropathy
  • Not utilized in immunocompromised patients, as they cannot produce detectable antibody levels
• In immunocompromised patients with pure red cell anemia: Polymerase chain reaction (PCR) for parvovirus B19 detects infection.

Treatment

• Generally, a self-limited illness and treatment is thus supportive.
• Severe transient aplastic crisis: Transfusion may be required.
• Immunocompromised patients with chronic infection and anemia may need:
  • Reduced dose of immunosuppressive agents
  • Intravenous immunoglobulin treatment
  • In severe cases, bone marrow transplantation

Prevention

• General infection-control practices
• High-risk individuals should be informed of measures to avoid exposure and when to seek medical attention.

Differential Diagnosis

• Hydrops fetalis: serious fetal condition that involves an accumulation of fluid in 2 or more fetal compartments including ascites, pleural effusion, pericardial effusion, and skin edema. The condition carries a poor prognosis for perinatal survival.
• Aplastic crisis: occurs with significant reduced production of RBCs resulting in a rapid decline in the hemoglobin level with reticulocytopenia. With parvovirus B19 infection, the marrow function generally returns spontaneously within 1 week.
• Arthritis: joint disorder characterized by joint pain and stiffness accompanied by other manifestations such as redness, warmth, swelling, and decreased range of motion in joints.