Erythema multiforme (EM) is an acute, self-limited, immune-mediated condition characterized by distinctive target-like lesions on the skin. It predominantly affects young adults and is often precipitated by infections, particularly herpes simplex virus (HSV), or, less commonly, by medications. The disorder manifests in two primary forms: erythema multiforme minor and erythema multiforme major, distinguished by the extent of mucosal involvement and severity.
Etiology and Pathogenesis
Infectious Triggers
The most common precipitant of EM is infection, with herpes simplex virus (HSV) being the primary agent. Studies indicate that HSV infection precedes a significant number of EM cases, suggesting a strong association between the two conditions. Other infectious agents, such as Mycoplasma pneumoniae, have also been implicated, particularly in pediatric populations.
Drug-Induced Erythema Multiforme
Although less common, certain medications can trigger EM. Drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics, and anticonvulsants have been associated with the onset of EM. It is imperative to identify and discontinue the offending agent to prevent recurrence.
Immunopathogenesis
EM is considered a type IV hypersensitivity reaction. The pathogenesis involves a cell-mediated immune response, where antigen-specific T cells recognize viral or drug-related antigens presented by keratinocytes, leading to an inflammatory cascade and subsequent skin and mucosal manifestations.
Clinical Manifestations
Skin Lesions
The hallmark of EM is the presence of target or “iris” lesions. These lesions are typically symmetrical, well-defined, and exhibit three concentric zones: a central dusky or necrotic area, a middle pale edematous zone, and an outer erythematous ring. Lesions commonly appear on the extensor surfaces of the extremities, particularly the palms and soles, and may spread centripetally.
Mucosal Involvement
In erythema multiforme major, mucosal surfaces are affected in addition to the skin. This can involve the oral cavity, eyes, and genitalia, leading to symptoms such as painful erosions, conjunctivitis, and genital ulcers. Mucosal involvement distinguishes EM major from EM minor, where mucous membranes are typically spared.
Diagnosis
The diagnosis of EM is primarily clinical, based on the characteristic appearance of the lesions and patient history. A thorough assessment to identify potential triggers, such as recent infections or new medications, is essential. In atypical cases, a skin biopsy may be performed to confirm the diagnosis, revealing features such as necrotic keratinocytes and a perivascular lymphocytic infiltrate.
Management
General Measures
Management of EM involves identifying and eliminating the underlying cause. For HSV-associated EM, antiviral therapy may be beneficial in reducing the frequency and severity of episodes. In drug-induced cases, discontinuation of the offending medication is crucial.
Symptomatic Treatment
Symptomatic relief can be achieved through the use of topical corticosteroids to reduce inflammation and antihistamines to alleviate pruritus. For patients with significant mucosal involvement, mouthwashes and topical anesthetics may provide relief from oral lesions.
Severe Cases
In severe cases of EM major, hospitalization may be required for supportive care, including fluid management and wound care. Systemic corticosteroids are sometimes employed, although their use remains controversial due to potential side effects and lack of definitive evidence regarding efficacy.
Prognosis
Erythema multiforme is generally a self-limiting condition, with lesions resolving within two to four weeks. However, recurrence is common, especially in cases associated with HSV. Prophylactic antiviral therapy may be considered in patients with frequent recurrences to reduce the likelihood of future episodes.
