Girl’s blistering rash spreads to eyes and face

The Case

A healthy 9-year-old female presents with a 1-day history of fever, progressive rash, conjunctivitis, and superficial oral ulcers.

Diagnosis: Erythema multiforme

When initially described in 1860, erythema multiforme (EM) was considered part of a spectrum of diseases, including EM minor, EM major, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).¹ This disease grouping was redefined in 1993 to delineate clear definitions and diagnostic criteria for each condition.² Erythema multiforme is now considered a separate entity from SJS/TEN with a distinct pathophysiology and clinical course. It is an immune-mediated disorder presenting with cutaneous or mucosal lesions, or both.

Epidemiology and clinical findings

The exact incidence of EM is unknown, however, and is thought to be less than 1% but greater than 0.01%.³ It predominantly affects young adults with a slight female predominance without racial predilection. Causes of EM include infections, medication use, malignancy, autoimmune disease, radiation, immunizations, and menstruation. Infections represent the majority of cases with herpes simplex virus (HSV) being the most common. Medication-associated EM represents less than 10% of cases. Common disease-precipitating medications are nonsteroidal anti-inflammatory drugs, sulfonamides, antiepileptics, and antibiotics.

More: Mucositis and rash in a 9-year-old boy

Erythema multiforme typically does not present with prodromal symptoms such as fever, malaise, or myalgias, but when mucosal involvement occurs, prodromal symptoms are common. It is characterized by acrally distributed, distinct targetoid lesions with concentric color variation, sometimes accompanied by oral, genital, or ocular mucosal erosions or a combination of these.³ Targetoid lesions have a central portion of epidermal necrosis appearing as a dusky area or blister. Outside the central portion is a dark red, inflammatory zone surrounded by a lighter edematous ring. Mucosal involvement occurs in 25% to 60% of cases.

Differential diagnosis

Imitators of EM include urticarial multiforme, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, Sweet syndrome, Rowell syndrome, and polymorphous light eruption (Table).³ The potentially life-threatening conditions of SJS and TEN are differentiated from EM by lesion morphology and extent of epidermal detachment.² Desquamation is a clear clinical differentiator of EM and SJS with desquamation in EM limited to 1% to 2% of body surface area and higher, but less than 10% in SJS and greater than 30% in TEN.⁴

Laboratory findings

No laboratory tests are necessary in making the diagnosis of EM; however, certain labs and skin biopsy may assist in confirming the diagnosis, determining the inciting factor, and excluding other conditions. Lesions can be swabbed for Tzanck smear, polymerase chain reaction (PCR) studies, or viral cultures for HSV. Serologic tests can be performed for Mycoplasma pneumoniae. Erythrocyte sedimentation rate, white blood cell count, and liver function enzymes may be elevated in severe cases of EM.

Treatment

Clinical erythema multiforme is a self-limiting skin disease. Some patients have multiple outbreaks over several years (recurrent EM) while others may experience continuous uninterrupted disease (persistent EM). Lesions appear over 3 to 5 days and resolve in 1 to 2 weeks. Disease onset to resolution is less than 4 weeks but may last 6 weeks in severe cases with mucosal involvement.³ Skin lesions typically do not scar.

Treatment mainly is supportive and involves discontinuing the inciting factor and ensuring adequate nutrition and hydration. Disease management depends on the severity and mucosal involvement. Topical antiseptics and oral antihistamines are helpful in mild cases, whereas high-potency topical corticosteroids, oral steroids, and specialists’ help are beneficial when severe disease and mucosal involvement is present. Antibiotics are usually withheld as these may worsen SJS, which is commonly on the differential.⁴ In severe cases, systemic corticosteroids may be used, although controversy exists regarding this therapeutic option. Currently, no randomized clinical trials demonstrate treatment that alters the course of EM or reduces the risk of complications.

Patient outcome

The patient was hospitalized for 2 weeks with worsening of her skin findings and mucosal involvement. The initial acral distribution of the rash with class target appearance eventually involved the trunk of the body and face. Progression of the disease and mucosal involvement raised concern for SJS. A skin biopsy was performed and results were consistent with EM. Laboratory testing for causative agents, HSV, Mycoplasma serology, and enterovirus PCR all were negative.

Next: Toddler with lesions on cheeks, ears, and arms

Because of the severity of the girl’s presentation, she was treated with intravenous steroids, topical triamcinolone, and a nasogastric tube for nutrition. Corneal epithelial defects that developed from EM-associated conjunctivitis required amniotic membrane grafts by ophthalmology. Pediatric dermatology recommended an extended oral prednisone taper with close follow-up after discharge. She has had no recurrences of EM.

REFERENCES

1. Siedner-Weintraub Y, Gross I, David A, Reif S, Molho-Pessach V. Paediatric erythema multiforme: epidemiological, clinical, and laboratory characteristics. Acta Derm Venereol. 2017;97(4):489-492B.

2. Read J, Keijzers G. Pediatric erythema multiforme in the emergency department: more than “just a rash.” Pediatr Emerg Care. 2017;33(5):320-324.

3. Sokumbi O, Wetter DA. Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist. Intl J Dermatol. 2012;51(8):889-902.

4. Hidajat C, Loi D. Drug-mediated rash: erythema multiforme versus Stevens-Johnson syndrome. BMJ Case Rep. September 22, 2014.

5. Emer JJ, Bernardo SG, Kovalerchik O, Ahmad M. Urticaria multiforme. J Clin Aesthet Dermatol. 2013;6(3):34-39