Viral exanthems: Rubella, roseola, rubeola and enteroviruses

Rubella

Rubella (German measles, 3-day measles) is caused by a member of the Togaviridae family; it is a usually benign infection characterized by a short prodrome of fever, cervical, suboccipital or postauricular lymphadenopathies and arthralgias, followed by a maculopapular erythematous rash that begins on the face and spreads centrifugally, lasting up to 5 days. A petechial enanthem called Forchheimer spots can be also seen. Thrombocytopenia and encephalitis are extremely rare complications.

Management Strategy

It is usually a benign disease; however, if the infection occurs in the first weeks of pregnancy, up to 85% of neonates might die in utero or be born with congenital rubella syndrome (CRS; growth restriction and major birth defects). CRS can lead to ocular involvement, auditive disorders, and cardiac and neurologic manifestations, as well as extramedullary hematopoiesis (blueberry muffin lesions; see figure). Those that survive the neonatal period may have an increased risk for developmental delay and endocrinopathies.

Differential diagnosis includes measles virus, parvovirus B19, and other rash etiologies. Suspected cases, especially during pregnancy, should be confirmed by laboratory testing.

The standard method for laboratory diagnosis is the detection of rubella-specific immunoglobulin M (IgM) in serum. These antibodies may not be detectable until 4 days after rash onset and persist for at least 8 weeks after infection and even more after vaccination. False-positive IgM results may be found. Seroconversion or a significant increase in rubella immunoglobulin G (IgG) titer in paired acute and convalescent phase sera tested in the same assay are also indicative of an acute infection. Distinguishing primary infections from persisting IgM antibodies is essential, especially during pregnancy.

The treatment is generally supportive .

Rubella vaccine is a live virus vaccine administered as a two-dose series in the United States as part of the measles-mumps-rubella (MMR) with or without varicella (MMRV) vaccine (MMR or MMRV at 12–15 months of age with a second dose at 4–6 years). Rubella is another vaccine-preventable viral disease, with life-long immunity after natural infection or vaccination. In the absence of vaccination, the mean age of rubella infection is 5–9 years of age.

According to the US guidelines, if a non-immune pregnant woman (in whom termination is not an option) is identified within 5 days of exposure, passive immunization with 20 mL intramuscular immune globulin (IMIG) within 72 h of exposure should be considered. This intervention has shown an excellent safety profile and it has proved to be of benefit for preventing rubella, although evidence directly in relation to the prevention of CRS is scarce.

Roseola

Roseola infantum (exanthem subitum, sixth disease) is a common disease caused by a primary infection with human herpesviruses HHV-6A, HHV-6B, or HHV-7. It mainly affects children aged 6–36 months. It consists of two phases: high fever for 3–7 days, followed by a fast defervescence and an exanthem starting on the neck and chest lasting for 2 days. It is a self-limiting illness and, as with other viruses belonging to the herpes family, it usually remains latent in immunocompetent patients with the possibility of reactivation.

Other dermatologic manifestations of these viruses are pityriasis rosea and HHV-7 and drug-induced hypersensitivity syndrome (DIHS/DRESS) with HHV-6B reactivations favored by certain drugs.

Management Strategy

Detecting genomic DNA by PCR is the technique of choice as it is specific, sensitive, and accessible. Other tests such as culture techniques and immunofluorescence for viral antigen detection can also be performed but are not recommended.

Detection of specific IgG and IgM antibodies by immunofluorescence is restricted due to cross-reactions between HHV-6A, HHV-6B, HHV-7, and cytomegalovirus (CMV) antibodies.

Ganciclovir, cidofovir, and foscarnet have shown to inhibit HHV-6 and -7 replication in vitro. Individual case reports have suggested benefit from these agents in immunocompetent patients with end-organ disease.