Infections / Exanthems: Viral
Prior to 1963, measles was the most common viral exanthem of childhood, but in the U.S., measles became a relatively rare disease, with a precipitous decline with vaccine licensure.50-52 However, epidemics began to reoccur in the late 1980’s, with 17,000 cases reported in 1989. To address this issue, a two-vaccine schedule for measles (15 months and four to six years of age) is recommended. Anders51 et al documented the “failure rate” of live attenuated measles vaccination administered to 2031 children older than 12 months of age to be less than 0.2% (95% CI 0 - 0.147%). Measles occurs in winter and spring with an incubation period of one week. Illness is manifested by a prodrome of three days with systemic toxicity, prostration, high fever, coryza, headache, photophobia, dry hacking cough, and impressive conjunctivitis. Koplik’s spots, the pathognomonic enanthem of measles, appear on the buccal mucosa opposite the molars during the prodromal period and fade within three days after the onset of the rash. This nonpruritic exanthem begins behind the ears and rapidly spreads caudad. As the rash spreads, the discrete macules coalesce to produce a confluent rash. After one week, the rash fades. Attenuation of the illness occurs in children with partial immunity (those who received a vaccine).
In the U.S., rubella has remained a relatively rare disease, though sporadic outbreaks do occur. It produces a relatively mild illness associated with an exanthem. It’s real danger lies in severe fetal infection that can develop if infection occurs during early pregnancy. In the first few weeks of pregnancy, the chance of transmission is 30 to 50%; at five to eight weeks, it is 25%, and from nine to 12 weeks, the risk is 8%. Incubation is two to three weeks and typically occurs during the spring. The prodrome consists of malaise, cough, sore throat, low grade fever, headache, and a pink maculopapular rash that begins on the face with caudal progression. The rash tends to fade as it spreads and is typically gone by day four. Other clinical findings include suboccipital and postauricular adenopathy and arthralgia (in 25% of affected patients). Neutropenia is often present and serologic tests are used to confirm diagnosis. Unlike measles, where systemic toxicity and fever are the rule, fever is less common in rubella.
Erythema Infectiosum (Fifths Disease)
Erythema infectiosum is a mildly contagious disease caused by human parvovirus B19. It typically affects school aged children (5 to 15 years of age).53-61 The incubation period is usually one to two weeks with a prodrome consisting of low grade fever, malaise, and headache. A fiery red macular rash soon appears on the cheeks (“slapped cheek”), lasts one to four days, and is followed by a more generalized rash which evolves into a distinctive, lacy, reticular pattern most prominent on the extensor surfaces of the extremities. The rash may wax and wane for up to three weeks. Children with erythema infectiosum typically feel well but constitutional symptoms, such as headache, fever, sore throat, and coryza, occur in 5 to 15% of patients. Arthritis58-65 is the most common complication in adults but is unusual in children. Lastly, this infection is associated with transient aplastic crisis63,68 in patients with hemolytic anemias, hemoglobinopathies (particularly sickle cell disease),69 or idiopathic thrombocytopenic purpura,57,62,70 as well as intrauterine infection and fetal death71 (risk ranges from 3 to 10%) in pregnant women infected during the first 20 weeks of gestation. Yoto et al72 reported epidemiological evidence suggesting that parvovirus B19 may be the cause of acute hepatitis. It should be noted that, when children have the rash of fifth’s disease, they are no longer infectious.
Roseola is caused by human herpes virus 6 (the other five human herpes viruses, herpes simplex 1 and 2, varicella-zoster, cytomegalovirus, and Epstein-Barr virus are also known causes of skin eruptions). Roseola is the most common exanthem in children under age three. Virtually all cases occur between six months and three years of age, with most cases occurring before age one. It is estimated that 30% of children will develop this infection. The incubation period is one to two weeks and the illness classically presents with a fever of up to five days followed by precipitous defervescence and the appearance of a pink maculopapular rash on the neck and trunk. Despite the elevated temperature, affected children are brighteyed and do not appear to be acutely ill. Roseola cases have also been documented without a preceding febrile illness. The duration of the rash lasts one to two days. Mild coryza, headache, and occipital/cervical/ post-auricular adenopathy is common. Periorbital edema, when present in a febrile otherwise non-toxic child, is a useful clue during the pre-exanthematous stage. A common complication (seen in approximately 6% of cases) is febrile seizures.
Varicella is a common and highly contagious systemic illness caused by the varicella-zoster virus. In the U.S., approximately 3.5 million people contract varicella each year. Half of the cases occur before age five and 90% by 15 years, with peak incidence in late winter and spring. After an incubation period of two to three weeks, the illness begins with a low grade fever and malaise. The characteristic skin eruption begins as red macules that progress to discrete vesicles surrounded by erythema. The eruption typically begins on the face and trunk and spreads in successive crops centrifugally to the extremities over a week long period. It is often accompanied by significant pruritis. Lesions eventually crust over in five to ten days. The presence of lesions in varying stages of evolution and minimal distal extremity involvement helps to differentiate chickenpox from smallpox. Severe presentations of varicella may occur in children receiving steroids and immunocompromised patients. Such children are more likely to suffer extensive eruptions and varicella pneumonia. The Tzanck smear can demonstrate multinucleated giant cells and, in questionable cases, can be used to confirm the diagnosis. In most cases, management of varicella is directed at symptomatic relief of constitutional symptoms and ameliorating pruritis. Secondary bacterial infections, if present, should be treated with antibiotics directed against Staphylococcus aureus. Acyclovir may be effective in treating varicella and has been shown to prevent visceral dissemination in immunocompromised children. A trial using oral acyclovir in otherwise healthy children produced modest results in terms of defervescence and lesion healing time.73-75 In a search of three articles on this topic, acyclovir was associated with a reduction in the number of days with fever (- 1.1 days, 95% CI -1.3 to -0.9) and in reducing the number of lesions (-76 lesions, 95% CI - 145 to -8 lesions). Results were less supportive with respect to the number of days to the relief of itching, and there was no clinically important difference between acyclovir and placebo with respect to complications associated with chickenpox. In summary, the clinical importance of acyclovir treatment in otherwise healthy children remains uncertain. Children with a history of chickenpox in the first year of life have a much higher incidence of zoster (shingles) in childhood (relative risk 2.8). The calculated incidence rate of zoster by 12 years of age in children who acquired varicella by one year of age in the Rochester study was 4.1 cases per 1000. A higher rate was noted in children who acquired varicella in the first two months of life: 12 cases per 1000.74 An important point to consider is the association between vesicular lesions noted on the tip of the nose (involvement of the nasociliary branch of the trigeminal nerve) and possible ocular involvement.
The most common presentation of primary herpes simplex in children (one to five years of age) is herpetic gingivostomatitis (HSV-1), but infection may also involve the eye (herpetic keratoconjunctivitis), the external genitalia (HSV-2), and fingers (herpetic whitlow). It should be noted, however, that oral HSV-2 and genital HSV-1 infections have become increasingly more common. Wrestlers are prone to spread herpes infection to one another, a condition called herpes gladiatorum.
Treatment76-77 is usually symptomatic, though acyclovir may be prescribed to shorten the course of more severe or recurrent disease. Recurrent HSV presents as grouped vesicles near the site of primary infection, and are often preceded by a burning or tingling sensation in the affected area. Triggering mechanisms responsible for reactivation include febrile illness, menses, stress, sunburn, or local trauma. Recurrent infection differs from primary infection in the smaller size of vesicles, their close grouping, and the usual absence of constitutional symptoms. Neonatal herpes usually develops when infants are delivered vaginally to mothers who have genital herpes. About half of these infected infants will have skin manifestations, and half of these, if untreated, will either die or suffer serious neurologic or ocular sequelae. Again, the Tzanck smear can demonstrate multinucleated giant cells and, in questionable cases, can be used to confirm diagnosis. Harel77 et al conducted a randomized, double blind, placebo controlled study exploring the efficacy of acyclovir (15 mg/kg five times daily for seven days) in 72 children (ages one to six years) with confirmed H. simplex gingivostomatitis. Children who received acyclovir had oral lesions for a shorter period of time verses placebo (four vs. ten days, 95% CI 4 - 8) and earlier disappearance of fever (one vs. three days, 95% CI .8 - 3.2). Viral shedding was significantly shorter in the group treated with acyclovir (one vs. five days, 95% CI 2.9 - 5.1).76-77
Enteroviral Exanthems 48,49
Enteroviral exanthems are the most common summertime exanthems. This group of viruses was previously divided into coxsackie, echo, and polioviruses, but has now been unified within the picornavirus family. The age of the child at the time of infection appears to be significant in disease expression; exanthems are more common in younger children, whereas aseptic meningitis is more prominent in older children. The cutaneous manifestation is typically morbiliform, though vesicular and urticarial rashes have been reported. The incubation period typically lasts about one week and a prodrome is usually absent. Fever, upper respiratory infection, conjunctivitis, and vomiting/diarrhea are frequently seen. Common complications include pericarditis, myocarditis, pleurodynia, parotitis, hepatitis, pancreatitis, and encephalitis. Hand-foot-mouth disease, also caused by enteroviruses (most commonly coxsackie A16), is manifested by malaise and fever with oral vesicles (severe odynophagia with associated anorexia), followed by vesicles on the hands and feet. The diaper area may be affected in infants.
In young children, an exanthem is seen in as many as one-third of infected patients. Eighty to ninety percent of adolescents with mononucleosis develop a rash if amoxicillin/ampicillin is administered. After an incubation period of one to two months, acute infection begins insidiously with a high fever, congestion, odynophagia, adenopathy, and hepatosplenomegaly. The associated exanthem is usually maculopapular and facial; peripheral/periorbital edema may be present (in 50% of cases). The mono-spot test is unreliable in children younger than four years of age and if symptoms have been present for less than five days. Acute and convalescent EB viral titers and the finding of atypical lymphocytosis (seen in 70%) are supportive. It is purported that up to a quarter of children with EBV may have concurrent beta-hemolytic streptococcal infection. Prescribe a macrolide in this situation to avoid precipitating a rash.