March 1996
MIAMI BEACH, Fla.—When you make the diagnosis of erythema multiforme (EM), you are almost always wrong. So says William L. Weston, MD, who insists that it is really urticaria, and not EM, which is the culprit in most instances.
An acute, self-limited condition characterized by the abrupt onset of symmetrical, fixed red papules, some of which evolve into target lesions, EM is often overdiagnosed, Weston said, here at the Masters of Pediatrics annual meeting.
Etiology and
pathogenesis
The majority of children with EM have a history of herpes simplex virus (HSV) infection. A preceding herpes labialis is seen in 50% of children with EM, said Weston, Chair and Professor, Department of Dermatology, University of Colorado Health Sciences Center, Denver. The episode of herpes labialis usually precedes EM by 7 to 10 days; the herpes labialis can last 1 day to up to 21 days.
"Herpes simplex type I virus DNA can be detected within the early red papules or the outer zone of a target lesion in 80% of children with EM by molecular diagnosis," he said.
The inflammation within skin lesions is part of the HSV-specific host response.
"Other infections associated with EM are histoplasmosis and Orf virus. Histoplasmosis in endemic areas has occasionally been responsible for EM, especially when both EM and erythema nodosum lesions are present during infection," Weston said.
Pathology
The keratinocyte, Weston continued, is the target of the inflammatory insult in EM with individual keratinocyte necrosis as the earliest pathologic finding. A perivascular infiltrate of mononuclear leukocytes and T-lymphocytes with exocytosis into the epidermis is seen. Spongiosis and focal liquefication degeneration of basal keratinocytes are apparent as lesions evolve.
"A histology, which excludes lupus erythematosus and vasculitis and is compatible with EM, is sometimes helpful to the clinician," he said, "although immunofluorescent findings are nonspecific."
In contrast with Stevens-Johnson syndrome or toxic epidermal necrolysis, large sheets of epidermal necrosis are not seen in EM.
Clinical features
Although the exact incidence of EM is unknown, it is believed to be relatively uncommon in childhood: 20% of all cases occur in childhood, usually with no prodrome.
Abrupt onset of skin lesions accompanied by itching or burning are characteristic. The primary lesion is a round, red papule that remains fixed at the same skin site for 7 days or more.
At least some of the red papules evolve into "target lesions," characterized by concentric zones of color change, with a central dusky or purple zone and an outer red zone.
"Target lesions will often develop a blister or crust in the central zone after several days," he said. Target lesions appear predominantly on the upper extremities, as do most of the total number of lesions. Involvement of the dorsa of the hands and the forearms are the most frequent skin sites, but the palms, neck, face, and trunk are also frequently involved; lesions on the legs are less frequently seen.
"Although there is considerable variation from child to child, usually over 100 lesions are present in each patient. The Koebner phenomenon may be seen, with target lesions appearing within an area of cutaneous injury, such as scratches," he said.
Additionally, EM skin lesions tend to be grouped, especially around the elbows and knees. They also may be found within areas of sunburn. A few discrete oral erosions are present in more than half of children and are mildly symptomatic. Occasionally large bullous target lesions may involve the lips and mimic the crusted lips seen in Stevens-Johnson syndrome. Other mucosal sites are not involved, and fever, lymphadenopathy, and organomegaly are absent, he said.
Prognosis
Most pediatric bouts last 2 weeks and heal without sequelae. Except for burning and stinging of the skin, the child is usually otherwise healthy. "Children affected by EM have an uncomplicated course although recurrences are the rule. Most children have one or two recurrences a year, except when immunosuppressive drugs are given, and then five or six flares can occur. Secondary infections and more frequent and longer EM episodes may be associated with the use oral steroids," he said.
Differential diagnosis
Many pediatricians overdiagnose EM by identifying children with giant urticaria as having EM. To be sure of an EM diagnosis, the physician should look for definite clinical criteria.
They include symmetric, fixed red papules, some of which evolve into typical target lesions. The duration of individual lesions at the skin site and epidermal damage in the center of the target lesion warrant particular attention. Erythema multiforme papules are fixed to the same skin site for at least 7 days. Urticarial lesions, however, last less than 24 hours in one site, he explained.
"The center of EM lesions demonstrates epithelial damage in the form of crusting or blisters, whereas the center of giant urticaria reveals normal skin. Administration of subcutaneous epinephrine will clear urticaria within 20 minutes, but will not change EM lesions. Edema of the hands and feet are associated with urticaria, not EM," Weston said.
Treatment
For the usual EM attack, symptomatic treatment will suffice, Weston believes. Oral antihistamines given for 3 to 4 days reduce the stinging and burning; oral antacids may be required for discrete oral ulcers. In children with HSV-associated EM who have frequent recurrences, a 6- to 12-month prophylactic course of oral acyclovir at 10 mg/kg/day may be helpful.
Presented at the Fifth Annual Masters of Pediatrics meeting, Miami Beach, Fla., Jan 25-29, 1996.