Exanthems and Drug Reactions

Description

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  An exanthem is a rash that occurs as a sign of a systemic disease. A viral exanthem is a rash that arises because of a viral infection.

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  Most viruses produce similar rashes, leading to the term nonspecific viral rash .

History

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  Nonspecific viral rashes are the most common viral exanthems and are challenging to diagnose.

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  Historic elements such as season, exposure history, and local and regional epidemiology are important in the evaluation of a patient with a suspected viral exanthem.

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  Most nonspecific viral exanthems in the winter are due to respiratory viruses; in the summer and fall they are due to the enteroviruses.

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  Examples of viruses capable of causing nonspecific viral exanthems include nonpolio enteroviruses (enterovirus, coxsackievirus, echovirus), Epstein–Barr virus, human herpesvirus 6, human herpesvirus 7, parvovirus B19, and respiratory viruses (rhinovirus, adenovirus, parainfluenza virus, respiratory syncytial virus, influenza virus).

Skin Findings

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  Nonpolio enterovirus can produce generalized erythematous macules and papules.

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  Sometimes these viruses produce petechial rashes that can mimic meningococcemia.

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  Epstein–Barr virus causes pharyngitis, morbilliform (5%–15%), vesicular, urticarial, and petechial rashes. Periorbital edema occurs in 35% of patients with this virus.

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  All respiratory viruses can cause diffuse pink macules and papules that coalesce to plaques. Many patients with adenovirus infection develop keratoconjunctivitis that is highly contagious.

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  Papular acrodermatitis of childhood (Gianotti–Crosti syndrome) is a viral exanthem characterized by monomorphic, discrete papules and vesicles coalescing on the face, extremities, and buttocks.

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  Unilateral laterothoracic exanthem (asymmetric periflexural exanthem) is a rash occurring on the lateral thorax, near the axilla. Sometimes this viral exanthem will spread to the other hemithorax and the extremities.

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  Papular−purpuric gloves and socks syndrome is an acute self-limiting rash characterized by petechial erythema on the palms and soles. Patients with this may have fevers and flu-like symptoms. Most cases are caused by parvovirus B19.

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  Severe coxsackievirus A6 may cause erosive vesicles and bullae mimicking widespread herpes simplex infection (“eczema coxsackium”).

Nonskin Findings

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  Nonskin findings vary according to the specific virus. Most nonspecific viruses are associated with fever and constitutional symptoms.

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  Nonpolio enteroviruses cause fever, abdominal pain, and vomiting. There can be multiorgan involvement, including the central nervous system and the pulmonary and cardiac systems. These viruses can mimic serious bacterial illness.

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  Epstein–Barr virus can produce fever, sore throat, lymphadenopathy, abdominal pain, myalgias, and hepatosplenomegaly.

Laboratory and Biopsy

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  The laboratory evaluation should be focused and directed by the history and physical examination.

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  Skin biopsy findings are not specific but can be helpful to distinguish between staphylococcal scalded skin syndrome and drug hypersensitivity reaction.

Differential Diagnosis

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  Drug hypersensitivity reaction

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  Kawasaki disease

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  Staphylococcal scalded skin syndrome

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  Toxin-mediated erythema (toxic shock syndrome, staphylococcal toxic shock syndrome)

Course and Prognosis

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  Most nonspecific viral exanthems are self-limited and resolve in 1 to 2 weeks.

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  The rash of Gianotti–Crosti syndrome can last up to 8 weeks.

Pediatric Considerations

• Viral exanthems are common in childhood and can be difficult to distinguish from morbilliform drug reactions.

• Measles vaccination exanthem occurs in 5% of those receiving the vaccine.

• Kawasaki disease should be considered in small infants with exanthems and prolonged fever.

Description

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  Roseola infantum is a viral exanthem characterized by high fever followed by the abrupt appearance of a diffuse rash as the fever resolves.

History

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  Roseola infantum occurs in infants from the ages of 6 months to 3 years, with a peak incidence at 6 months.

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  It is caused by human herpesvirus 6 and human herpesvirus 7.

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  Most cases occur during early spring, although roseola infantum can occur anytime during the year.

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  The incubation period is 12 days (range, 5–15 days).

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  Infants appear well, except for a high fever (38.3°–41.1° C).

Skin Findings

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  Within 2 days of defervescence, small, pink, almond-shaped macules occur on the neck, trunk, proximal extremities, and face.

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  The rash is not itchy and fades within several days to a week.

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  Eyelid edema is seen in 30% of children.

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  Most patients have pink papules on the uvula and soft palate.

Nonskin Findings

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  Irritability can occur in up to 14% of patients.

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  Posterior cervical, occipital, and posterior auricular adenopathy are common.

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  Open fontanels are sometimes bulging.

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  Complications include febrile seizures, aseptic meningitis, hemiplegia, and encephalitis or encephalopathy.

Laboratory and Biopsy

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  Leukocytosis develops at the onset of fever.

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  Leukopenia with a granulocytopenia and relative lymphocytosis appears as the temperature increases and persists until the eruption fades.

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  Serologic testing is available, but typically is not helpful.

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  Skin biopsy findings are not specific.

Differential Diagnosis

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  Other viral exanthems (e.g., parainfluenza virus, parvovirus B19, rubella, enterovirus)

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  Drug eruptions

Course and Prognosis

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  Prodromal symptoms include a sudden onset of high fever of 39.4° to 41.1° C.

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  Most children appear to be inappropriately well, given the high fever.

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  Roseola is a major cause of visits to the emergency department, of febrile seizures, and of hospitalizations.

Treatment

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  Acetaminophen and ibuprofen are effective antipyretics.

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  Immunocompromised hosts or children with a severe illness may require antiviral treatment (valganciclovir, ganciclovir, cidofovir, foscarnet).

Pearls

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  Infections by herpesvirus types 6 and 7 should be suspected in infants with febrile convulsions—even those without the exanthem.

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  People with AIDS can have disseminated multisystem involvement, and transplant recipients can have reactivation of latent virus.

Description

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  Erythema infectiosum, also known as fifth disease or slapped cheek disease , is a common viral exanthem that causes bright-red cheeks and lacy erythema of the arms.

History

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  Erythema infectiosum occurs in the winter and spring and is associated with community outbreaks.

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  It is caused by parvovirus B19 and is transmitted through respiratory secretions or blood, or vertically from mother to fetus.

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  Peak attack rates occur in children aged 5 to 14 years.

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  During outbreaks, 60% of susceptible schoolchildren and 30% of susceptible adults acquire the infection.

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  Asymptomatic infection is common.

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  The incubation period is 4 to 14 days.

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  Prodromal symptoms are usually mild or absent. Pruritus, low-grade fever, malaise, and sore throat precede the eruption in approximately 10% of cases. Lymphadenopathy is absent. Older persons may complain of joint pain.

Skin Findings

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  There is facial erythema—the slapped cheek appearance. Red papules on the cheeks rapidly coalesce in hours, forming red, slightly edematous, warm, erysipelas-like plaques that are symmetric on both cheeks and spare the nasolabial fold and the circumoral region (circumoral pallor). The slapped cheek appearance fades in 4 days.

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  Approximately 2 days after the slapped cheek rash, lacy erythema in a “fish net” pattern begins on the proximal extremities and extends to the trunk and buttocks, fading in 6 to 14 days.

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  For the next 2 to 3 weeks, the eruption fades and reappears in previously affected sites. Factors such as sunlight, hot water, and physical and emotional exertion exacerbate the rash.

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  The rash fades without scaling or pigmentation, and the palms and soles are spared.

Nonskin Findings

Pregnancy

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  Approximately 50% to 60% of reproductive-age women are immune to parvovirus B19.

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  Exposure to household members carries a 50% risk for seroconversion, whereas exposure from daycare or classroom work carries a 20% to 50% risk for seroconversion.

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  When infection occurs during pregnancy, only 30% to 44% report signs (arthralgias and rash) of acute infection.

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  The overall risk for fetal loss is 8% to 17% when infection occurs before 20 weeks and 2% to 6% after 20 weeks.

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  An affected fetus can develop anemia, high-output cardiac failure, pleural effusions, polyhydramnios, and nonimmune hydrops fetalis.

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  Overall, most parvovirus B19−infected mothers deliver healthy term infants.

Laboratory and Biopsy

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  Detection of serum immunoglobulin M antibodies to parvovirus B19 using enzyme immunoassay is the most sensitive indicator of acute parvovirus B19 infection in immunocompetent hosts. These antibodies persist for up to 6 months.

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  Polymerase chain reaction is the most sensitive method to detect parvovirus B19 and is the preferred method in immunocompromised hosts. These studies can be used to test fetal and maternal blood and amniotic fluid.

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  Exposed pregnant women should have serologic or other diagnostic testing.

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  Serial fetal ultrasounds should be performed on all pregnant women infected with parvovirus B19.

Differential Diagnosis

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  Scarlet fever

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  Enterovirus infection

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  Rubella

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  Rheumatoid arthritis (when there are joint symptoms)

Course and Prognosis

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  Patients are not considered infectious after the rash develops.

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  Most infections are self-limited without adverse sequelae.

Treatment

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  Nonsteroidal anti-inflammatory drugs (NSAIDs) can control joint symptoms for most patients.

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  Patients should be assured that this unusual eruption will fade and does not require treatment.

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  If a fetus is affected, intrauterine evaluation and treatment are available at tertiary care centers.

Pediatric Considerations

• Children can return to child care and school when the rash appears.