Continuing Education Activity

Erythema infectiosum, also known as 5th disease, is a common viral exanthem caused by parvovirus B19. The condition primarily affects children aged 5 to 15 years, especially during the spring and summer months. Being 1 of the 6 most common viral rashes in children, erythema infectiosum is usually self-limited. Adults may also be affected, though less commonly.

The primary mode of transmission is through droplets from respiratory secretions, although hematogenous spread can also occur. Symptom control and supportive care form the basis of treatment. However, when the disease affects pregnant individuals, complications such as transient aplastic crisis or hydrops fetalis become significant concerns, and heightened surveillance is warranted.

Diagnosis is typically clinical but may be confirmed through serologic testing for immunoglobulin M and immunoglobulin G antibodies or through polymerase chain reaction testing in high-risk cases. No specific antiviral therapy is available. Management remains supportive, focusing on symptom relief.

This activity for healthcare professionals is designed to enhance learners' competence in evaluating and managing erythema infectiosum. Participants will deepen their understanding of the condition's epidemiology, genetics, and clinical presentation. Current diagnostic and therapeutic approaches will also be explained. Improved skills will empower clinicians to collaborate within an interprofessional team caring for affected individuals.

Objectives:

• Identify clinical and diagnostic features indicative of erythema infectiosum.

• Select the appropriate diagnostic tests to evaluate erythema infectiosum.

• Apply best management practices for erythema infectiosum.

• Implement interprofessional team strategies for improving care coordination and communication to improve outcomes in patients with erythema infectiousum. 

Introduction

Erythema infectiosum, also known as 5th disease, is a common viral exanthem primarily affecting children. The disorder is 1 of the 6 classic viral rash illnesses of childhood.[1] This febrile disease typically occurs in children aged 5 to 15 years, though adults may also be affected, albeit less frequently (see Image. Fifth Disease, Arm Rash). The causative agent is human parvovirus B19, which is also implicated in conditions such as aplastic anemia, polyarthropathy, and hydrops fetalis. The infection characteristically progresses through 3 distinct cutaneous phases.[2]

Transmission occurs mainly through respiratory droplets, though hematogenous spread is also possible. Cases are most common in the spring and early summer. Treatment is supportive and focused on symptom management. However, in pregnancy, complications such as transient aplastic crisis or hydrops fetalis warrant special consideration.[3]

Etiology

Parvovirus B19, the causative agent of erythema infectiosum, is a nonenveloped, single-stranded DNA virus belonging to the Parvoviridae family.[4] The virus exhibits a strong tropism for erythroid progenitor cells, leading to its characteristic clinical manifestations. The mechanism of spread most commonly involves inhalation of respiratory droplets. However, vertical transmission from mother to fetus and transfusion-related exposure via infected blood or blood products are also documented routes of infection.

Epidemiology

Erythema infectiosum occurs worldwide and most often affects school-age children aged 5 to 15.[5] Adult cases are less frequent. The infection is most commonly reported during the spring months.[6]

Parvovirus B19 infection during pregnancy may result in severe fetal complications.[7] These conditions include miscarriage, intrauterine fetal demise, and hydrops fetalis.[8] The estimated risk of fetal loss following acute maternal infection is approximately 5%. Pregnant individuals in the 2nd trimester have the highest risk of complications, though adverse outcomes have been documented throughout all stages of pregnancy.[9]

Individuals with sickle cell disease or other chronic hemolytic anemias face increased susceptibility to severe outcomes.[10] Parvovirus B19 infection targets and destroys reticulocytes, leading to reduced or transiently disrupted erythropoiesis. Affected patients may develop transient aplastic crisis, resulting in significant anemia. These individuals often appear acutely ill, with symptoms such as fever, malaise, and lethargy. Clinical findings of aplastic crisis include pallor, tachycardia, and tachypnea, reflecting the severity of the anemia.[11]

Pathophysiology

Parvovirus B19 spreads primarily through respiratory droplets, entering cells within the respiratory tract. Transmission can also occur through exposure to infected blood. Viremia typically develops 5 to 10 days after exposure, and infected individuals remain contagious for approximately 5 days following the onset of viremia. Immunocompetent individuals may remain asymptomatic, experience a nonspecific flu-like illness, or present with the classic facial rash and arthralgias. Patients with aplastic anemia often exhibit markedly elevated viral loads. Once arthralgias and rash appear, patients are no longer contagious and cannot transmit the virus. In fetal infections, hydrops fetalis develops due to impaired red blood cell production, leading to high-output cardiac failure.[12]

History and Physical

The most common and classic presentation of erythema infectiosum is a mild febrile illness with a rash. Initial symptoms of infection can include fever, malaise, myalgias, diarrhea, vomiting, and headache. After initial viremia, the classic erythematous malar rash involving the cheeks with surrounding oral pallor develops. This rash does not appear early in the disease process. The lesion is classically described as a “slapped-cheek rash” and may be the only clinical diagnostic finding (see Image. Fifth Disease, Slapped-Cheek Rash). This facial rash lasts 4 to 5 days. By the time the facial rash develops, the patient usually feels well, and the viremia has resolved. This rash is thought to be immune-mediated (see Image. Fifth Disease, Reticular Facial Rash).

Days after the facial rash develops, a maculopapular rash usually appears on the trunk and limbs. This rash is nonpruritic and typically lasts about 1 week. As it resolves, the rash may take on a lacy or reticular appearance, often more prominent on the extensor surfaces. The palms of the hands and soles of the feet are typically unaffected.[13] Exposure to sunlight or heat may exacerbate the rash.

The infection may also present with arthralgias. Joint symptoms, which are thought to be immune-mediated, occur more commonly in adults than in children, with women being more affected than men. Affected joints are usually symmetric and include the hands, feet, wrists, knees, and elbows. Patients often complain of joint stiffness. No signs of physical joint destruction are observed. Joint involvement typically occurs later in the disease course and resolves after about 3 weeks of symptom onset. When joint symptoms are present, the patient is not considered infectious.

Immunocompromised individuals typically do not exhibit rash or joint symptoms, which are believed to be immune-mediated. Due to an inadequate immune response, these individuals may not develop the typical symptoms of erythema infectiosum. Instead, these patients may experience chronic parvovirus B19 infection, which can lead to neutropenia, thrombocytopenia, or complete bone marrow suppression. Key characteristics of the rash include its potential to cause pruritus in adults, frequent appearance in children (with less than 50% of adults affected), and cessation of infectiousness once it manifests.

Evaluation

Diagnosis of parvovirus B19 infection generally does not require testing due to the self-limiting nature of the disease and its mild symptoms. However, blood tests for specific antibodies may be conducted. Immunoglobulin M antibodies can confirm acute infection, typically appearing 7 to 10 days after virus exposure. These antibodies may remain detectable for 2 to 3 months following infection. Immunoglobulin G antibodies begin to rise about 2 weeks after exposure and provide lifelong immunity once measurable.[14]

Testing is particularly useful in diagnosing aplastic crisis to confirm causality from acute parvovirus B19 infection. Additionally, testing for immunoglobulin G antibodies is common in prenatal care to assess immunity status and evaluate the risk of potential congenital disabilities.

Treatment / Management

The disease process typically resolves without intervention. Symptom control and supportive care form the foundation of treatment for erythema infectiosum. Acetaminophen or nonsteroidal anti-inflammatory drugs may be used to manage fever, arthralgias, and headache when present. Serial hemoglobin and hematocrit monitoring should be conducted if an aplastic crisis is identified on evaluation. Red blood cell transfusions must be administered as needed throughout the course of infection. Close follow-up with an obstetrician is essential when a pregnant patient is diagnosed with acute parvovirus B19 infection early in gestation, including serial ultrasounds to monitor for fetal complications such as hydrops fetalis.

Differential Diagnosis

Several other viral exanthems fall within the differential diagnosis of erythema infectiosum, including measles, rubella, roseola, and scarlet fever. In adults, where arthralgias occur more frequently, the differential may also include influenza and mononucleosis. Noninfectious conditions such as drug hypersensitivity, rheumatoid arthritis, and juvenile idiopathic arthritis should also be considered. Arthritic diagnoses are typically ruled out once joint pain and stiffness resolve, which usually occurs about 3 weeks after symptom onset.[15]

Prognosis

Symptoms of erythema infectiosum are typically mild and self-limited in immunocompetent individuals, with some patients remaining asymptomatic. In contrast, immunocompromised individuals or those with hematologic disorders may experience more severe symptoms. Chronic infection and persistent anemia can develop in immunocompromised patients. Acute infection during pregnancy can lead to fetal complications, including fetal death. The risk of fetal loss is highest when infection occurs before 20 weeks of gestation.[16]

Complications

Complications of erythema infectiosum primarily affect high-risk populations, including immunocompromised individuals, patients with hematologic disorders, and pregnant women. In people with hemolytic anemias such as sickle cell disease or hereditary spherocytosis, parvovirus B19 can trigger transient aplastic crisis, marked by severe anemia and reticulocytopenia that often necessitate transfusion. Immunocompromised individuals, including those with human immunodeficiency virus or undergoing chemotherapy, may develop chronic infection, resulting in persistent anemia or pure red cell aplasia.

In pregnancy, vertical transmission can lead to hydrops fetalis, severe fetal anemia, or intrauterine fetal demise, especially when infection occurs during the 1st or 2nd trimester.[17] A postviral arthropathy resembling rheumatoid arthritis may develop in adults, presenting as symmetric polyarthritis of the hands, wrists, and knees. Rare neurologic complications, such as encephalitis, myocarditis, and vasculitis, have also been reported.

Deterrence and Patient Education

Deterrence and patient education for erythema infectiosum emphasize limiting transmission, recognizing complications in high-risk groups, and managing symptoms. Parvovirus B19 spreads through respiratory droplets, so proper hand hygiene, respiratory etiquette, and avoiding close contact with symptomatic individuals are essential preventive strategies. However, subclinical infections can make prevention difficult.

Most patients may be reassured that the illness is self-limiting. Supportive care with antipyretics and analgesics addresses fever and joint discomfort.

High-risk individuals, including pregnant women, those with hemolytic disorders, and immunocompromised patients, should be counseled to seek medical attention after known exposure. Early evaluation may help prevent complications such as hydrops fetalis or aplastic crisis.

Healthcare providers and caregivers should recognize that the period of highest infectivity occurs before the appearance of the facial rash. No vaccine is currently available, highlighting the importance of education and timely risk assessment.

Pearls and Other Issues

Important pointers about erythema infectiosum to communicate to patients and caregivers include the following:

• This common viral exanthem typically affects children, especially during the spring months.
• The classic diagnostic feature is a bright red rash on the cheeks with perioral pallor, often described as a "slapped cheek" appearance.
• Extra precautions are necessary for individuals who are pregnant due to the risk of fetal complications, such as hydrops fetalis.
• Patients with sickle cell disease or other hemolytic conditions are at risk for aplastic crisis and require closer monitoring.

Although the illness is generally mild, certain populations face serious risks. Empowering families with this knowledge is essential for prevention.

Enhancing Healthcare Team Outcomes

Erythema infectiosum is a generally benign viral illness in children and is often managed by pediatricians, emergency medicine physicians, internists, and nurse practitioners. When the infection is diagnosed in a pregnant patient, an obstetrics consultation should be obtained due to the risk of complications such as aplastic crisis and hydrops fetalis. These patients require close monitoring throughout the remainder of the pregnancy.

Nursing staff should ensure that immunocompromised individuals are appropriately isolated and monitored. Patient education should emphasize the importance of proper hand hygiene and standard infection control practices. Parents should be reassured that the rash is not contagious, and children do not need to be excluded from school once the rash has appeared.

Pharmacists play a role in counseling families that no specific antiviral treatment is available and that the rash typically resolves without intervention. In cases involving immunocompromised individuals or pregnant patients, timely referral to the appropriate specialists is strongly recommended to optimize outcomes.