What are the key points of Erythema Multiforme for the United States Medical Licensing Examination (USMLE)?

From the Guidelines

Erythema multiforme is a reactive mucocutaneous disorder distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), typically precipitated by infection and characterized by target lesions that start on acral surfaces and progress proximally. For USMLE preparation, key points to focus on include its association with infections, such as herpes simplex virus (HSV), and its characteristic target-like skin lesions. The presentation of erythema multiforme major (EMM) includes mucosal erosions and ulceration, usually confined to the mouth, but it does not progress to SJS/TEN 1.

Key Characteristics

• Typically precipitated by infection, with HSV being a common trigger
• Characterized by target lesions that start on acral surfaces and progress proximally
• Mucosal involvement is limited in erythema multiforme minor but extensive in the major form
• Histologically, characterized by lymphocytic infiltrate at the dermal-epidermal junction with necrotic keratinocytes

Management and Treatment

• Management primarily involves treating the underlying cause, such as antivirals for HSV
• Discontinuing offending medications and providing supportive care with antihistamines and topical steroids for symptomatic relief
• Recurrent erythema multiforme may require prophylactic antivirals like acyclovir 400mg twice daily

Differential Diagnosis

• Distinguish erythema multiforme from SJS/TEN, which have more extensive mucosal involvement and skin detachment
• Understand that erythema multiforme is a distinct entity from SJS/TEN, with different outcomes and management approaches 1.

From the Research

Erythema Multiforme Key Points

• Erythema multiforme (EM) is an immune-mediated condition that presents with discrete targetoid lesions and can involve both mucosal and cutaneous sites 2, 3, 4, 5, 6
• The diagnosis of EM is based on its typical clinical picture of targetoid erythematous lesions with predominant acral localization as well as histological findings 2
• EM can be differentiated into isolated cutaneous and combined mucocutaneous forms, with atypical manifestations including lichenoid or granulomatous lesions 2
• Herpes simplex virus infection is the most common cause of EM, while other infectious agents and drugs can also trigger the condition 2, 3, 4, 5, 6
• Treatment of EM is highly variable, depending on the etiology, the involvement of mucosal sites, and the chronicity of the disease 3
• Symptomatic treatment with topical steroids or antihistamines is commonly used, while recurrent EM may require antiviral prophylaxis or other systemic therapies 3, 4, 5

Causes and Triggers

• Herpes simplex virus infection is the most common cause of EM 2, 3, 4, 5, 6
• Other infectious agents, such as Mycoplasma pneumoniae, hepatitis C virus, Coxsackie virus, and Epstein Barr virus, can also trigger EM 2
• Drugs, including allopurinol, phenobarbital, phenytoin, and others, can cause EM 2
• Vaccination, immunotherapy, and topical drugs like imiquimod have also been linked to EM 2

Diagnosis and Differential Diagnosis

• EM can be confused with other conditions, such as Stevens-Johnson syndrome, urticaria, and fixed drug eruption 3, 4, 5
• Histopathologic testing and other laboratory investigations can help confirm the diagnosis of EM and differentiate it from other clinical imitators 5
• The duration of individual lesions can help differentiate EM from urticaria, with EM lesions typically fixed for a minimum of seven days 4

Treatment and Management

• Treatment of EM involves symptomatic treatment with topical steroids or antihistamines and treating the underlying etiology, if known 3, 4, 5
• Recurrent EM associated with herpes simplex virus should be treated with prophylactic antiviral therapy 4, 5
• Severe mucosal EM can require hospitalization for intravenous fluids and repletion of electrolytes 4