Key words: rubella, vaccinia, pediatric exanthema, erythema infectiosum, herpangina
Few clinical scenarios engender as much anxiety as the sudden onset of rash and fever in a child. However, the diagnostic possibilities can be quickly narrowed—and the likelihood of potentially serious disease can be assessed—with a triage system that involves classifying the presenting symptoms into 1 of 3 groups:
• Group 1 includes children with symptoms of serious illness who require immediate intervention.
• Group 2 includes children with a clearly recognizable—and usually benign—viral syndrome.
• Group 3 includes children who present early in the course of the disease, when the clinical picture and physical findings are nonspecific, and those with undifferentiated rashes with fever. (Most febrile children with a rash fall into this group.)
In the first 2 articles in this series (see Part 1 and Part 2), I focused on various classes of disorders in group 1: those that manifest with fever and petechiae or purpura, with fever and blanching rash, or with fever and vesicular or bullous lesions. Here, in part 3, I offer the last presentation of fever and rash requiring immediate attention—fever accompanied by pharyngitis and a "sandpaper" rash. I then go on to discuss the clearly recognizable viral syndromes that normally present with fever and rash; I describe the typical presentations and recommendations for initial management. Finally, I provide clues for differentiating the various viral infections characterized by umbilicated lesions.
FEVER AND SANDPAPER RASH: SCARLET FEVER
Scarlet fever is simply pharyngitis caused by group A β-hemolytic streptococcus (GAS) with an associated rash. The rash has characteristic features that make it easy to identify, which in turn facilitates the diagnosis of streptococcal pharyngitis. In fact, at least 1 study has shown that children with sore throat were more likely to receive antibiotics if the child received a diagnosis of scarlet fever.1
The rash of scarlet fever is caused by an erythrogenic toxin in persons who lack antibodies that protect against this toxin. The rash begins within 1 or 2 days of onset of the pharyngitis or other symptoms of an upper respiratory tract infection. It is first seen around the neck and then spreads to the trunk. The rash consists of small papules with a rough sandpaper quality. The cheeks may be erythematous, but the perioral region is typically spared. The rash is especially prominent at skin creases; the red lines that often form in these areas are referred to by the eponym "Pastia sign." In addition, patients often have a "strawberry" tongue, the result of prominent red papillae surrounded by a white tongue coating. After a few days, fine peeling may develop on those areas of the face affected by the rash, followed by heavier peeling of the trunk and extremities.
As with all cases of GAS infection, children with scarlet fever require antibiotic therapy within 9 days of symptom onset to prevent rheumatic fever. However, there is no evidence that antibiotics prevent poststreptococcal glomerulonephritis or change the course of the rash with scarlet fever.2,3
RECOGNIZABLE VIRAL ILLNESSES
In most children with clearly recognizable viral syndromes (eg, varicella, measles, rubella, erythema infectiosum, and the Enterovirus infections of herpangina and hand-foot-and-mouth disease), the diagnosis is made clinically. Remember, however, that while viral syndromes usually present typically, atypical presentations do occur infrequently. The only therapy required is parental education and reassurance, comfort measures, and appropriate follow-up.
Important safety precautions to take when treating children with these "classic" febrile rashes include requesting a return visit and providing good access to follow-up care. Good infection-control measures (eg, hand washing and not sharing eating utensils) are always recommended. If possible, women of childbearing age should avoid contact with children who have rubella or erythema infectiosum.
Varicella. Varicella presents with mild systemic symptoms and lesions that progress from papules to pustules, with significant pruritus. The rash begins on the trunk and spreads to the extremities. Most of the lesions are clustered on the trunk; they emerge in various asynchronous crops. Thus, multiple degrees of progression exist simultaneously. The rash typically lasts 12 to 21 days. Patients remain contagious until the last lesion to appear has completely crusted over.
No antiviral medications are used in healthy children in whom varicella develops. Symptomatic therapies include topical preparations, oral antihistamines, and trimming the child's fingernails. Topical preparations that contain pramoxine hydrochloride 1% are particularly helpful in relieving the intense itching. Acetaminophen is recommended for fever. (Never give aspirin or aspirin-containing products to children with varicella because of the risk of Reye syndrome.)
Children with chronic heart, lung, or immune disorders should be seen by a physician immediately if there is any suspicion of varicella. Children with varicella lesions on the tip of their nose in whom eye pain or redness develops should also be seen immediately to rule out ocular involvement.
Measles (rubeola). This disease has an incubation period of 7 to 14 days. Its communicable period begins 2 to 4 days before the rash appears and continues until the fever has resolved.
Measles is a "triphasic" illness. The first phase is a prodrome that is usually marked by nonspecific anorexia and malaise. The second phase is heralded by the development of Koplik spots; these 1- to 3-mm gray or blue-gray spots on an erythematous base appear on the oral mucosa, usually opposite the second molars on the buccal mucosa. Koplik spots are pathognomonic for measles; they slough before or during the onset of the rash. Phase 2 usually lasts 1 to 3 days. Phase 3 is denoted by the sudden onset of high spiking fever, cough, coryza, conjunctivitis, and rash. The rash consists of erythematous macules that begin near the hairline and spread from the face and neck to the rest of the body; the palms and soles are usually spared. Unlike with varicella, the rash is only mildly pruritic.
The fever, rash, conjunctivitis, and cough reach peak intensity between days 2 and 4 after the onset of these symptoms. At maximum intensity, the rash assumes a dark red, almost purple hue. Between days 3 and 4 after the onset of the rash, the lesions begin to fade from the face and neck and then from the rest of the body. There may also be a fine desquamation.
Management consists of helping the child feel comfortable, preventing the spread of the virus, and watching for secondary bacterial infections. The World Health Organization recommends vitamin A supplementation in patients who are deficient in this nutrient.
Mortality related to measles can be high in some populations, especially in young children. Complications can include pneumonia and postinfectious encephalitis, which carries a high mortality rate. In addition, it can cause a delayed disorder, subacute sclerosing panencephalitis (SSPE), which causes blindness and other permanent neurological deficits and which has a high mortality rate.
Vaccination is the key to the prevention of this disease. SSPE has not been documented to occur in immunized children.4,5 Countries with low rates of measles vaccination have witnessed measles outbreaks with fatalities and with permanent neurological deficits in some survivors.6,7
Distinguishing Among Viral Infections Characterized by Umbilicated Papules or Pustules
Centrally umbilicated lesions occur in molluscum contagiosum, varicella, vaccinia, and monkeypox and smallpox. These conditions vary greatly in severity. The following information can assist with making crucial distinctions between these diseases.
Molluscum contagiosum. This benign disorder, caused by the poxvirus molluscum contagiosum, involves rapidly spreading, small pearly topped papules with central umbilication. The lesions can occur on any part of the body. In adolescents and young adults, lesions in the genital area have often been sexually transmitted. There is no history of fever or associated symptoms, although the lesions may be mildly pruritic.
The lesions can be treated to hasten resolution, but spontaneous resolution over time is the norm. Treatment options include topical medications and cryotherapy. The goal of therapy is to cause the tops of the pearly papules to slough. Because touching the papules and then touching uninfected skin can spread the infection, a new crop of lesions often appears while older lesions are being treated.
Varicella. This disease presents with mild systemic symptoms (low-grade fever, anorexia, and headache). The rash begins on the trunk and spreads to the extremities. Most of the lesions are clustered on the trunk. Lesions emerge in various asynchronous crops; thus, multiple degrees of progression exist simultaneously.
Vaccinia. Since the eradication of smallpox in 1977, the poxvirus that causes smallpox has existed only in a limited number of research centers. The live virus used in the smallpox vaccine is a separate virus, called vaccinia. Because the smallpox vaccine is a live virus vaccine, it can cause vaccinia infection in new vaccinees and others.
Vaccination against smallpox had been discontinued after the disease was eradicated. However, use of the vaccine was resumed after the 2003 monkeypox outbreak in the United States. Because of fears of possible use of smallpox as a biological weapon, an active vaccination program for military personnel, certain medical providers, and first responders was reinstated.15
Pediatric patients can become infected with the vaccinia virus after coming in contact with an adult who was recently vaccinated for smallpox. (Accidental vaccinia is estimated to occur in 42.1 patients per 1 million vaccinees.16) With vaccinia, the prodrome is mild or absent: manifestations may include lowgrade fever, anorexia, myalgia, and headache. The rash is usually limited to a single lesion; however, satellite lesions and generalized vaccinia may occur. In vaccinia, maculopapular lesions appear first and develop into discrete papules, which evolve into vesicles on an erythematous base—and eventually into pustules. The eye is a frequent site of accidental inoculation. If there are lesions near the eyes, or patients complain of eye pain or redness, they should be evaluated immediately. Children with ocular vaccinia require the attention of a pediatric ophthalmologist for evaluation and management of possible vaccinia keratitis.17
Smallpox and monkeypox. The clinical features of smallpox and monkeypox readily distinguish them from varicella. In both smallpox and monkeypox, a 2- to 4-day prodrome usually occurs that involves high fever, lymphadenopathy, anorexia, and myalgia. The lesions begin in the mouth and then spread to the face and the extremities, where most of the lesions are clustered; all are at the same stage of progression. The poxvirus rash of smallpox and monkeypox often involves the palms, which is rare in varicella. The papules are deeper than those of varicella.
Monkeypox is clinically very similar to smallpox but with milder symptoms and fewer lesions. Also, cough has been noted to be a prominent feature in about a third of patients with monkeypox. In the US monkeypox outbreak, only 80% of patients had the typical clustering of lesions with all the lesions at the same stage of development.15 In atypical cases, only confirmatory laboratory tests can differentiate monkeypox from varicella. Association with prairie dogs was a helpful epidemiologic clue during the 2003 outbreak; however, other mammals may serve as vectors. A high index of suspicion and confirmatory testing are mandatory in all cases of possible monkeypox.
Rubella (German measles). Rubella has a milder prodrome than measles; this typically consists of low-grade fever and anorexia. The rash is not as intense, but it usually follows the same pattern (first the face and neck, then the rest of the body; not palms or soles). Generally, the rash fades in the same sequence; however, it can resolve all at once.
Congenital rubella syndrome can cause deafness, eye defects (cataracts), and heart defects primarily in infants born to women who had primary infection in the first trimester.8 In addition, it has been associated with other abnormalities, including duodenal stenosis.9 The prevalence of rubella has decreased dramatically with the vaccination programs in developed countries but remains high in third world countries.
Erythema infectiosum. Popularly referred to as "fifth disease" (a reference to the old nomenclature that identified pediatric exanthemas by number), erythema infectiosum is caused by parvovirus B19. The only known hosts for the virus are humans. Erythema infectiosum is most commonly a disease of children aged 5 to 15 years, but it can occur at any age.
Patients are most contagious during the mild prodromal phase, which lasts for 2 to 5 days and consists of low-grade fever, headache, and malaise. Prodromal symptoms may also include arthralgia, arthritis, pharyngitis, conjunctivitis, cough, and diarrhea. The child is no longer contagious once the rash appears.10
This variable prodrome is followed by brilliant red patches on the cheeks, referred to as the "slapped cheek" sign. The erythema fades within hours to a few days, after which a generalized maculopapular rash on the neck, body, and extremities develops. As the rash resolves, it has a lacy, reticular pattern (Figure 1 A and B). The rash is more prominent with increased skin perfusion, such as occurs in a warm environment, with sunlight exposure, with feeding, or with exertion. When the patient is in a cooler environment or at rest, the rash appears to fade. The rash can wax and wane for weeks to months; however, it usually lasts 1 to 2 weeks. Rarely, the rash may be mildly pruritic or may be petechial.11
The appearance of the characteristic rash makes the diagnosis clear. In addition, once the rash has appeared, the patient is no longer contagious and the earlier symptoms have usually resolved fully.
Although a benign disorder in most children, erythema infectiosum can cause a significant aplastic crisis in patients with hemoglobinopathies (ie, sickle cell anemia), hemolytic anemia, or immunodeficiency. The infection can also cause fetal hydrops in susceptible pregnant women.
There is no specific antiviral therapy for erythema infectiosum. The symptoms of the prodrome are usually treated with acetaminophen or ibuprofen( to relieve fever and discomfort.
Herpangina. This Enterovirus infection is usually caused by a coxsackievirus. Herpangina presents with low-grade fever, malaise, anorexia, and shallow vesicles or ulcerations of the posterior pharynx (including the uvula, soft palate, and tonsillar pillar). Like most enteroviral illnesses, herpangina tends to occur during the spring and fall.
Home therapy includes antipyretics and adequate fluid intake.12
Hand-foot-and-mouth disease. Like herpangina, this disease usually results from coxsackievirus infection. It begins with low-grade fever, malaise, anorexia, and posterior pharyngeal ulcerations. The oral lesions may involve the entire palate and tongue; the gingival mucosa is spared. Maculopapular lesions subsequently appear on the hands and feet (Figure 2); these progress to vesicles and then ulcerations.
Hand-foot-and-mouth disease is usually benign. However, many other enteroviruses can cause outbreaks of disease with similar features. One in particular, enterovirus 71 infection, has been associated with serious pulmonary and CNS complications.13 The identification of serological markers of hand-foot-and-mouth disease may be needed during an outbreak of enterovirus 71 infection. Therapy is usually the same as that for herpangina.
Figure 2. These maculopapular lesions are characteristic of hand-footand-mouth disease. The rash appears on the hands and feet after a prodrome of low-grade fever, malaise, anorexia, and posterior pharyngeal ulcerations.
Roseola. Occasionally children present who recently had a high fever but now feel better—yet who have a new rash. This presentation is typical of roseola, a syndrome characterized by several days of high, unremitting fever followed by defervescence with the abrupt onset of a diffuse macular or maculopapular rash. Generally the child's clinical condition greatly improves with the onset of the rash.
Roseola is caused by herpesvirus 6 and rarely by herpesvirus 7. It typically occurs in children between 6 and 15 months of age. Infection with herpesvirus 6 can also present similarly to rubella and rubeola.
Patients with roseola often experience febrile seizures. Herpesvirus 6 can cause encephalitis as well.14 No therapies have been proven to prevent these febrile seizures, nor is any specific antiviral therapy available for roseola. Symptomatic therapy with antipyretics (other than aspirin), maintenance of good hydration, and reassurance are helpful.
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