Characterizing Viral Exanthems

Joseph M Lam

Disclosures

Pediatr Health. 2010;4(6):623-635. 

In This Article

Macular & Maculopapular Exanthems

Measles

Measles is caused by a ssRNA virus belonging to the Paramyxoviridae family, genus Morbillivirus. It has an incubation period of approximately 10–12 days, and clinical disease begins with symptoms of fever, conjunctivitis, rhinorrhea, sore throat and a dry cough. Koplik spots (gray–white papules on the buccal mucosa) may be seen during this prodromal phase. Approximately 3–4 days after the prodromal symptoms, the typical exanthem of coalescing erythematous macules and papules erupts, beginning behind the ears and in the hairline area, and spreads over the rest of the skin over a period of a few days. The eruption typically resolves in the same order as its appearance, and will often desquamate.

The differential diagnosis includes other maculopapular exanthems, such as rubella, toxic shock syndrome, roseola, parvovirus B-19 infection and drug eruptions. Complications of measles include transient immunosuppression, acute postinfectious encephalitis and subacute sclerosing panencephalitis (SSPE). Transient immunosuppression occurs during the illness and lasts for approximately 6 weeks.[1] During this time, an infected individual is at risk for secondary bacterial infections, such as otitis media, pneumonia or gastroenteritis. Postinfectious encephalitis occurs in approximately one in 1000 patients, and manifests approximately 1 week after the onset of the exanthem.[4] Symptoms present during, or shortly after, acute infection, and include headache, fever and seizures. A lesser-known entity, known as measles inclusion-body encephalitis, can affect immunocompromised patients from weeks to months after acute infection.[5] SSPE affects approximately one in 100,000 patients, and manifests as a slow, progressive disease, which can present months or even years after resolution of the acute infection. The onset of SSPE is insidious, and psychiatric manifestations are prominent. Subsequently, myoclonic seizures usually lead to a final stage of akinetic mutism. In total, 95% of individuals with SSPE die within 5 years of diagnosis.[6] SSPE is caused by a persistent infection of the CNS with the virus, and early childhood infection with measles is a risk factor for SSPE.

An unusual variant of measles can be seen in previously vaccinated individuals, infants with maternal IgG antibodies and patients on immunoglobulin therapy.[1] In this modified form, the prodrome and exanthem are milder and of shorter duration. However, the disease is just as contagious in these individuals. Diagnosis is based on clinical presentation with laboratory confirmation, if necessary. Measles IgM can usually be detectable after the first 3 days of the exanthem.

Currently, there is no specific antiviral therapy for measles and treatment is symptomatic. More importantly, the longstanding availability of the measles vaccine makes the disease easily preventable. Despite, this, there is still poor uptake of the vaccine,[7–9] owing to, in part, a proposed causal relationship between receipt of the measles–mumps–rubella vaccine and autism, a claim that has been convincingly scientifically refuted.[10]

Rubella

Rubella, or German measles, is caused by an RNA virus in the Togaviridae family. Approximately 50% of infected individuals become symptomatic. After an incubation period of 2–3 weeks, symptomatic patients exhibit prodromal symptoms, which include low-grade fever, headache, sore throat and myalgias. A macular or maculopapular exanthem appears after approximately 2–5 days and spreads in a cephalocaudal pattern. Symmetrical lymphadenopathy is often seen, and often occurs in the postauricular and occipital areas. Arthralgias and arthritis are also common. The most serious complication of rubella is congential rubella syndrome, which classically presents with the triad of deafness, cataracts and cardiac disease.[11] The differential diagnosis includes other maculopapular exanthems, such as measles, roseola, parvovirus B-19 infection and drug eruptions. The diagnosis of rubella can be made with IgM antibody titers. Patients are contagious 1 week prior to the eruption of the rash until a week after the rash resolves. The treatment of rubella is supportive.

Erythema Infectiosum

Erythema infectiosum (EI) is a common childhood exanthematous illness caused by parvovirus B19 – a nonenveloped, ssDNA virus belonging to the Parvoviridae family. The name B19 comes from the bloodbank code, where the original positive serum sample was labeled (i.e., Row B, Sample 19).[12] It is the only parvovirus that has been linked directly to disease in humans.[13] Although parovirus B19 infection can have different clinical manifestations (see later), EI is the most commonly recognized.

Erythema infectiosum manifests in three overlapping stages. After an incubation period of 1–2 weeks, patients present with fiery-red facial erythema, which has been described as having a 'slapped cheeks' appearance (Figure 1). In the second stage, patients develop a reticulate macular or urticarial exanthem 1–4 days after the slapped cheek eruption, and this second rash is mainly seen over the proximal extremities. In the third stage, the exanthem recurs intermittently in response to stimuli, such as local irritation, high temperatures and emotional stress.[12] Arthropathy may occur in up to 60% of adults with EI,[14] whereas it will only occur in approximately 10% of children with joint symptoms. In children, the arthropathy affects larger joints, such as the knees, wrists and ankles, and in an asymmetric pattern.[12]

Figure 1.

A child with the classic 'slapped cheek' appearance of erythema infectiosum.

The differential diagnosis includes a drug reaction, measles, rubella and enterovirus infection, and roseola infantum. Complications of EI are owing to the affinity of parvovirus B19 for erythroid precursors. Parvovirus B19 infection can suppress red blood cell production, causing transient aplastic crisis, chronic red cell aplasia, hydrops fetalis or congenital anemia. This is even more likely in patients with illnesses that have already shortened the lifespan of erythrocytes, such as iron-deficiency anemia, HIV, sickle cell disease, thalassemia and spherocytosis. Although treatment is supportive, at-risk patients may require transfusions or intravenous immunoglobulin therapy.[15,16]

The diagnosis of EI is usually made clinically. An ELISA is commercially available with high sensitivity, although false-positive results may recur owing to crossreaction to other viruses or the rheumatoid factor.[17] PCR can detect viral DNA in clinical samples of urine, respiratory secretions, body tissues and serum.[18]

Roseola Infantum

Roseola infantum is caused by human herpesvirus (HHV) types 6 and 7, and belongs to the Roseolovirus genus in the subfamily of Betaherpesvirinae.[19]

Both HHV-6 and -7 are highly prevalent in the healthy population, and establish latency in macrophages and T lymphocytes. They are frequently shed in saliva of healthy donors, and the pathogenic potential of reactivated virus ranges from asymptomatic infection to severe diseases in transplant recipients. By the end of the second year of life, approximately 75% of all children are seropositive for HHV-6 and approximately 24% of all children with HHV-6 infection will manifest clinical symptoms of roseola.[20,21] HHV-7 infection usually occurs later, with approximately 65% of British children infected by the age of 3 years.[22]

In roseola, after an incubation period of 5–15 days, infected children develop high fevers that last 3–5 days. This is followed by the acute onset of a rosey pink, nonpruritic macular rash, predominantly on the neck and trunk. Owing to the presence of high fevers, patients are often worked up for an occult bacterial infection.

Roseola infection can cause leukopenia[23] and, rarely, thrombocytopenia and hepatitis.[22] Patients generally recover without sequelae. However, approximately 22% of patients with roseola may develop febrile seizures.[24] The differential diagnosis includes measles, rubella and other viral exanthems.

The diagnosis of roseola is made clinically. Laboratory diagnosis of HHV-6 and -7 infections is difficult owing to the limited availability of antibody tests, problems with antigenic crossreaction and lack of understanding of the clinical relevance and epidemiology of these two viruses. However, the development of standardized quantitative real-time PCR, and the use of antibody tests based on recombinant proteins, may aid in the diagnosis of HHV-6 and -7 infection in the future.[22]

Epstein–Barr Virus & Aminopenicillins

Epstein–Barr virus (EBV) is a member of the Herpesvirus family, belonging to the genus Lymphocryptovirus. While only approximately 5–10% of children infected with EBV manifest an exanthem,[2] if amoxicillin or ampicillin is administered, a characteristic bright-red morbilliform eruption almost always occurs.[25–27] This eruption begins 5–9 days after exposure to the medication, starting on the trunk before becoming generalized as confluent macules and papules. The eruption most likely results from ampicillin–antibody immune complexes as a consequence of polyclonal B-cell activation. This consistently occurs in adolescents and adults with infectious mononucleosis administered ampicillin, but resolves without specific measures. This reaction is not considered a 'true' drug allergy and, in most children, re-exposure to the antibiotic after the EBV infection will not trigger a similar response. However, since antimicrobial therapy is not necessary for infectious mononucleosis, the antibiotic should be discontinued during the acute EBV infection.

Although approximately 7% of mononucleosis-like illnesses are caused by cytomegalovirus (CMV), CMV does not appear to give this drug-related exanthem.[28]

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