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.
ABSTRACT: Children who present with rash and fever can be divided into 3 groups: those with features of serious illness who require immediate intervention, those with clearly recognizable viral syndromes, and those with early or undifferentiated rash. The morphology of lesions among children with symptoms of serious illness offers clues to the underlying cause. Fever accompanied by pharyngitis and a "sandpaper" rash that begins around the neck suggests scarlet fever. In most children with fever and rash who have clearly recognizable viral illnesses, such as measles or erythema infectiosum, diagnosis is clinical and therapy includes parental education and reassurance with appropriate follow-up. Viral illnesses characterized by the presence of umbilicated lesions include several relatively benign conditions (eg, molluscum contagiosum, varicella) but also the more severe monkeypox and smallpox. The lesions of monkeypox and smallpox are all in the same stage of development-unlike those of varicella, which appear in synchronous crops.
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 Î²-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
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.
Figure 1 – The generalized maculopapular rash of erythema infectiosum develops on the neck, trunk, and extremities (A). As the rash fades, it has a lacy, reticular pattern (lesions on day 2, B).
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.
REFERENCES:1. Benin AL, Vitkauskas G, Thornquist E, et al. Improving diagnostic testing and reducing overuse of antibiotics for children with pharyngitis: a useful role for the electronic medical record. Pediatr Infect Dis J. 2003;22:1043-1047.
2. Gerber MA. Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am. 2005;52:729-747.
3. Alcaide ML, Bisno AL. Pharyngitis and epiglottitis [published correction appears in Infect Dis Clin North Am. 2007;21:847-848]. Infect Dis Clin North Am. 2007;21:449-469, vii.
4. Ruocco E, Donnarumma G, Baroni A, Tufano MA. Bacterial and viral skin diseases. Dermatol Clin. 2007; 25:663-676, xi.
5. Weisberg SS. Measles. Dis Mon. 2007;53:471-477.
6. Yu X, Wang S, Guan J, et al. Analysis of the cause of increased measles incidence in Xinjiang, China in 2004. Pediatr Infect Dis J. 2007;26:513-518.
7. Das P. Infectious disease surveillance update. Lancet Infect Dis. 2006;6:402.
8. Badilla X, Morice A, Avila-Aguero ML, et al. Fetal risk associated with rubella vaccination during pregnancy. Pediatr Infect Dis J. 2007;26:830-835.
9. Diamanti A, Pietrobattista A, Bevivino E, et al. Duodenal stenosis, a new finding on congenital rubella syndrome: case description and literature review. J Infect. 2006;53:e207-e210.
10. Young NS, Brown KE. Parvovirus B19. N Engl J Med. 2004;350:586-597.
11. McNeely M, Friedman J, Pope E. Generalized petechial eruption induced by parvovirus B19 infection. J Am Acad Dermatol. 2005;52(5 suppl 1):S109-S113.
12. Bernius M, Perlin D. Pediatric ear, nose, and throat emergencies. Pediatr Clin North Am. 2006;53:195-214.
13. Ho M, Chen ER, Hsu KH, et al. An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group. N Engl J Med. 1999;341:929-935.
14. Vianna RA, de Oliveira SA, Camacho LA, et al. Role of human herpesvirus 6 infection in young Brazilian children with rash illnesses. Pediatr Infect Dis J. 2008;27:533-537.
15. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis [published correction appears in Lancet Infect Dis. 2004;4:251]. Lancet Infect Dis. 2004;4:15-25.
16. Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970;122:303-309.
17. Tom WL, Kenner JR, Friedlander SF. Smallpox: vaccine reactions and contraindications. Dermatol Clin. 2004;22:275-289, vi.