Make the Diagnosis

Make the Diagnosis - October 2016

A healthy 30 year old female with a history of herpes simplex virus on the lips presented with three days of pruritic targetoid lesions on the arms and legs. She reports similar episodes in the past.

A healthy 30 year old female with a history of herpes simplex virus on the lips presented with three days of pruritic targetoid lesions on the arms and legs.  She reports similar episodes in the past.


Acute Febrile Neutophilic Dermatosis (Sweet's Syndrome)

Erythema Multiforme

Acute Urticaria

Erythema multiforme

Erythema multiforme (EM) is a hypersensitivity reaction. Cutaneous lesions generally occur symmetrically on the extensor surfaces of the acral extremities and spread centripetally. Lesions are polymorphous and may be macular, papular, or bullous, with or without mucosal involvement. Classic targetoid lesions have a dusky central area, a paler edematous ring, and an erythematous outermost ring. EM can be triggered by multiple causes. 90% of cases are infectious, with herpes simplex virus infection most common and mycoplasma pneumoniae second. Medications (sulfonamides, anticonvulsants, etc), malignancy, autoimmune disease, immunizations, radiation, and sarcoidosis may also cause EM.

The differential diagnosis for EM includes urticaria, Stevens-Johnson syndrome, fixed drug eruption, bullous pemphigoid, paraneoplastic pemphigus, acute febrile neutophilic dermatosis (Sweet's syndrome), polymorphous light eruption (PMLE), and cutaneous small vessel vasculitis. The lesions of EM are fixed and all arise within 72 hours of onset, which can help distinguish between urticaria. The distribution of the lesions can help rule out Stevens-Johnson syndrome, which classically begins centrally and spreads distally and often will involve mucosal surfaces. Fixed drug eruption generally presents with fewer lesions and a preceding medication history. Bullous pemphigoid and paraneoplastic pemphigus are both chronic in their course and have distinguishing histopathologic characteristics that will not be present in erythema multiforme. Sweet's syndrome is also associated with infection; however, histology reveals a dense neutrophilic infiltrate with dermal edema on biopsy. History can be useful in distinguishing EM from PMLE: preceding infection strongly suggests EM, while ultraviolet radiation exposure is more likely to result in PMLE. Lastly, EM differs from cutaneous small vessel vasculitis through both histopathologic examination and direct immunofluorescence.

EM is usually a self-limited condition of about two weeks without significant sequelae, however, it may vary in both the length and severity of its course. A small subset of patients may experience episodic eruptions over a period of years, in what is known as recurrent EM. An even smaller subset of patients may continuously suffer from the lesions for months or even years, which is termed persistent EM. Treatment is aimed at the underlying condition or cause. Offending medications should be discontinued. Patients with mild cases of EM generally fare well with symptomatic treatment alone; however, more severe cases may require hospitalization for hydration, analgesia, and antiviral therapy. The use of systemic corticosteroids for EM is controversial and is generally reserved for severe cases with mucosal involvement. Prophylactic antiviral therapy is indicated for those with recurrent erythema multiforme of viral origin who suffer from six or more episodes per year. Very rarely, erythema multiforme may include ocular involvement leading to serious long-term sequelae, so patients with ocular symptoms should be immediately referred to an ophthalmologist for evaluation.

The patient's biopsy revealed necrotic keratinocytes and exocytosis of lymphocytes and was consistent with EM. She improved with oral antiviral therapy and topical steroid cream.

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