Abstract
Viruses produce a variety of cutaneous changes, including morbilliform (measles-like), papular, and vesicular eruptions. It is often difficult to distinguish viral exanthems from morbilliform drug eruptions; however, subtle distinguishing features may enable differentiation. This chapter provides an overview of the cutaneous manifestations associated with measles, rubella, erythema infectiosum, hand, foot, and mouth syndrome, herpangina, roseola infantum/exanthema subitum, Epstein–Barr virus, varicella-zoster virus, herpes zoster, herpes simplex virus, and cytomegalovirus.
Keywords
Cutaneous, Enanthem, Exanthema, Virus
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Measles is generally a benign, self-limited illness that presents with erythematous, confluent macules and papules that spread cephalocaudally and Koplik spots.
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Hand, foot, and mouth syndrome, caused by various Coxsackie viruses, is a self-limited illness that presents with oval to linear papules and vesicles on the dorsal and lateral fingers and toes as well as painful, oral mucosal vesicles and papules.
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Epstein–Barr virus infection can present with a variable exanthem on the trunk or upper arms, palatal petechiae, copper-colored morbilliform pruritic eruption (in patients treated with semisynthetic penicillins), or lichenoids papulovesicular exanthema on the extensor surfaces, gluteal area, and face (Gianotti–Crosti syndrome).
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Varicella infection (chickenpox) presents with crops of vesicles that evolve to pustules and, eventually, crusts on the body and palate.
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Herpes zoster presents with grouped vesicles, ulcers, and crust in a dermatomal distribution and can lead to secondary infection, scarring, and postherpetic neuralgia.
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Although herpes simplex virus can result in a wide variety of clinical syndromes, herpetic lesions present with grouped vesicles on an erythematous base and occasionally chronic ulcerations of vegetative lesions in the immunocompromised patients.
Viruses produce a variety of cutaneous changes, including morbilliform, papular, and vesicular eruptions. It is often difficult to distinguish viral exanthems from morbilliform drug eruptions; however, subtle distinguishing features may enable differentiation.
Measles (Rubeola)
Measles (rubeola) is caused by a single-stranded RNA paramyxovirus. Transmission occurs via respiratory secretions. Routine administration of live attenuated vaccine is currently recommended by the Centers for Disease Control and Prevention (CDC) for all infants, college entrants, and medical personnel without serologic evidence of past infection. The incidence of measles infection has decreased dramatically with the introduction of widespread vaccination; however, a gradual increase has occurred in recent years in the United States. Some of those affected were previously vaccinated, although more parents are choosing not to vaccinate, resulting in increasing numbers of small but significant local outbreaks. However, the health benefits of vaccinations far outweigh the unfounded concerns about the potential adverse effects based on scientifically discredited concerns with no medical basis. Two distinct forms of the disease are modified measles, which occurs when an individual is infected when they have passive immunity (during breastfeeding or with remaining transplacental antibodies), and atypical measles, which largely affects persons immunized with the killed vaccine during the 1960s.
Clinical Manifestations
After a 10-day incubation period, the viral prodrome phase consists of fever (may exceed 104° F), cough, coryza, conjunctivitis, photophobia, and myalgias, and lasts about 1 week. The classic exanthem consisting of erythematous confluent macules and papules is usually apparent at 2 weeks. The cutaneous eruption spreads cephalocaudally over 3 days, and resolves with fine desquamation and a brown hyperpigmentation. Koplik spots are pathognomonic and appear on the buccal, labial, and gingival mucosae just prior to the exanthem. They are 1- to 2-mm bluish macules on an erythematous base. Measles infection is usually benign and self-limited but has the potential to be fatal in malnourished and/or immunocompromised patients.
The most common complication of measles is secondary bacterial infection. Pneumonia occurs more frequently in children and is the most common cause of death associated with the virus. Atypical measles is a characteristic clinical syndrome seen in recipients of the killed vaccine that was used in the United States from 1963 to 1967. The cutaneous eruption begins on the wrists, arms, and soles, and then spreads centrally to the extremities and trunk. The lesions are initially morbilliform and then become vesicular, purpuric, or hemorrhagic. Koplik spots are rarely present.
Diagnosis
The clinical presentation is often classic; however, in countries with low measles prevalence, confirmation should be made with viral culture or serology (anti-measles IgM). Of note, atypical measles presents with a unique antibody titer pattern. Before the onset or at the onset of the exanthema, the titer is less than 1:5 but by day 10 the titer is greater than 1:1280.
Treatment
The treatment is supportive. Immune serum globulin may be given to exposed susceptible persons who are immunocompromised. Some studies suggest the use of ribavirin in immunocompromised hosts may be beneficial.
Rubella
Rubella (German measles) is a self-limited childhood infection caused by a single-stranded RNA togavirus. The incidence of rubella has decreased dramatically since the introduction of a live attenuated vaccine in 1968. Transmission occurs by inhalation of infected respiratory droplets, with increased incidence during the spring months.
Clinical Manifestations
After a 2- to 3-week incubation period, illness begins with a mild prodrome consisting of malaise, anorexia, fever, headache, and coryza. The cutaneous eruption appears first on the forehead and rapidly spreads inferiorly to involve the face, trunk, and extremities. The lesions consist of pink macules and papules, which may become confluent, creating a scarlatiniform eruption (scarlet fever-like macular erythema). Pruritus may be present. The time course of the rubella exanthem is 3 days, which is a differentiating point from the usual 6-day course of the rubeola exanthem. The exanthem of rubella also does not desquamate. There may be symmetric, tender, postauricular, suboccipital, and posterior cervical lymphadenopathy. Petechiae on the soft palate, or Forschheimer spots, may also be present. Arthritis and arthralgia are common complications of infection, especially in females.
Widespread vaccination against rubella was developed largely for the prevention of congenital rubella syndrome. Maternal infection during the first 16 weeks of gestation results in a 65% risk for congenital rubella. Manifestations of congenital rubella syndrome include extramedullary hematopoiesis (blueberry muffin baby), thrombocytopenia, cataracts, deafness, and patent ductus arteriosus. The impact of maternal infection on the fetus drops precipitously after 20 weeks of gestation.
Diagnosis
The diagnosis of rubella is made clinically and confirmed serologically. The virus can be isolated by culture from the oropharynx or joint aspirate.
Treatment
Treatment is supportive care.
Erythema Infectiosum
Erythema infectiosum (fifth disease) is an acute childhood exanthem caused by human parvovirus B19. Most cases develop during the winter or spring, and transmission is by respiratory droplets.
Clinical Manifestations
Most infections due to parvovirus B19 are asymptomatic; however, in school-aged children erythema infectiosum is common. A mild prodrome of low-grade fever, coryza, malaise, and headache may present initially during viremia. Soon thereafter the characteristic asymptomatic bilateral erythema of the cheeks with circumoral pallor, often referred to as a “slapped cheek,” appears. This may be accompanied by pharyngitis, myalgia, diarrhea, nausea, or conjunctivitis. Within a few days the exanthem extends to the body and is described as an evanescent reticulated erythema of the trunk and extremities. Oftentimes, the exanthem recedes and recurs with high temperatures, exercise, or stress. A unique cutaneous manifestation of parvovirus B19 infection is the papular purpuric “gloves and socks” syndrome. This affects young adults and results in symmetric swelling and pain in the distal feet and hands, followed by the purpuric eruption. Complications are much more common in adults, and include arthritis, hemolytic anemia, encephalopathy, and aplastic crisis. Parvovirus infection during pregnancy can cause spontaneous abortion and hydrops fetalis.
Diagnosis
The diagnosis is usually made on clinical grounds. Serum parvovirus-specific immunoglobulin M can be measured.
Treatment
Treatment is supportive care. Joint symptoms typically respond to nonsteroidal anti-inflammatory medications. Chronic anemia and aplastic crises may require treatment with immunoglobulin or blood transfusion.
Hand, Foot, and Mouth Syndrome
Hand, foot, and mouth (HFM) syndrome is a combination of an exanthem and enanthem that primarily affects toddlers. The etiologic agent is a Coxsackie virus, most commonly A16, but also A5, A10, B1, or B3, and other enteroviruses can cause the eruption. Several recent reports document Coxsackie virus A6 (CVA6) as the cause of an atypical, often more severe HFM syndrome in adults. Coxsackie viruses are small RNA viruses of the picornavirus family. Outbreaks are characteristically limited to the summer and early fall months.
Clinical Manifestations
This syndrome is characterized by the abrupt onset of sore mouth, cutaneous eruption, and fever. Malaise, diarrhea, joint pains, and lymphadenopathy may be present. The typical acral lesions are few in number and consist of oval to linear or football-shaped red papules and vesicles located over the dorsal and lateral aspects of the fingers and toes. The palmar and plantar surfaces may also be involved ( Fig. 31-1 ). An exanthem or red papules over the proximal extremities may also be present. Oropharyngeal lesions consist of painful papules and vesicles that become erosions scattered over the soft palate, tonsillar pillars, and posterior pharynx. In children, buttock involvement is a common finding. Of note, incomplete forms of HFM syndrome can occur, where the exanthema does not manifest at all body sites. HFM syndrome due to CVA6 can present in an atypical distribution, involving the scrotum, ear, scalp, and chin. HFM syndrome is generally a self-limited disease lasting less than 1 week.
Diagnosis
The eruption is usually characteristic. In some cases, viral culture of the stool or throat washings can be used to confirm the diagnosis. Acute and convalescent sera can also be assessed for Coxsackie viral titers.
Treatment
Treatment is supportive care.
Herpangina
The etiologic agent in herpangina is a Coxsackie virus: A2, A4, A5, A6, A8, and A10 are the most frequently identified culprits. It commonly occurs in children from ages 3 to 10.
Clinical Manifestations
Herpangina is characterized by the abrupt onset of fever, sore throat, anorexia, dysphagia, and vomiting. The exanthem is a morbilliform erythema with generalized pink papules, most prominent on the buttocks. Occasionally, petechiae are present. Oral lesions consist of 1- to 8-mm, painful erosions with erythematous borders located on the soft palate, uvula, posterior pharyngeal wall, tongue, or anterior tonsillar pillars. Genital ulcerations are noted occasionally. Herpangina is a mild illness, lasting only a few days. Rarely, the course is complicated by parotitis.
Diagnosis
Viral culture of stool or throat washings can be used to confirm the diagnosis. Acute and convalescent sera can also be assessed.
Treatment
Treatment is supportive care.
Roseola Infantum/Exanthem Subitum (Human Herpesvirus 6)
Human herpesvirus 6 (HHV 6) is genetically and pathogenetically similar to cytomegalovirus. HHV 6 has been demonstrated to be the cause of exanthem subitum (also known as roseola infantum, or sixth disease). Exanthem subitum can sometimes be caused by HHV 7 as well. By age 2, nearly 100% of children are seropositive for HHV 6. HHV 7 usually causes exanthema subitum much later in life. The presumed route of transmission is by respiratory tract secretions.
Clinical Manifestations
A prodromal syndrome with a sudden high fever typically occurs 7 to 15 days after exposure to this virus. Constitutional symptoms, including malaise, coryza, sore throat, headache, anorexia, and nausea, appear with the exanthem in a few days. The exanthem consists of discrete pink macules and papules distributed primarily over the trunk, buttocks, and neck, which may coalesce to confluent erythema. A ring of pallor surrounds the individual lesions. Complete resolution occurs in 1 to 4 days. Infection is benign and self-limited with infrequent complications, the most common being febrile seizures in 10% of patients.
Diagnosis
The classic feature of an isolated high fever preceding the eruption of the exanthem is usually sufficient to make the diagnosis. Serologic studies are available for absolute confirmation.
Treatment
Treatment is supportive care.
Epstein–Barr Virus
Epstein–Barr virus (EBV), a herpesvirus, is the primary etiologic agent in the clinical syndrome infectious mononucleosis. Infection with EBV usually occurs in childhood or adolescence and is generally mild and self-limited.
Clinical Manifestations
The incubation period of EBV is long: 3 to 7 weeks. Following this, acute infection is characterized by fever, pharyngitis, severe fatigue, and symmetric posterior cervical lymphadenopathy. Eyelid edema and hepatosplenomegaly are often prominent. Mucocutaneous manifestations are more common in younger children. There may be an exanthem on the trunk and upper arms consisting of macules, urticarial plaques, petechiae, or purpura. An enanthem consisting of palatal petechiae at the border of the soft and hard palate is common. A distinctive and pathognomonic copper-colored morbilliform pruritic eruption may develop in infected patients treated with ampicillin or other semisynthetic penicillins ( Fig. 31-2 ). Gianotti–Crosti syndrome, often associated with EBV, manifests as symmetric lichenoid papules or papulovesicular exanthem on the extensor surfaces of the distal, extremities, gluteal areas, and face, which resolve after 1 month. EBV infection is usually self-limited. Late manifestations of EBV-related disease include lymphoproliferative disease, which might affect the skin on rare occasions.
