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

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From the Guidelines

Erythema multiforme is a distinct reactive mucocutaneous disorder, usually precipitated by infection, characterized by typical target lesions that start on acral surfaces and progress proximally, and is important to differentiate from Stevens-Johnson syndrome and toxic epidermal necrolysis for the USMLE. The key points to understand about erythema multiforme include its typical presentation with symmetric, targetoid lesions, and its common triggers such as HSV infection and medications 1. Some important characteristics of erythema multiforme are:

  • Typically starts on acral surfaces and progresses proximally
  • Characterized by target lesions with three zones: a central dusky area, a pale edematous ring, and an outer erythematous halo
  • May involve mucous membranes, but this is usually confined to the mouth in erythema multiforme major (EMM)
  • Patients are typically constitutionally well and make a good recovery with rare long-term complications 1. It's essential to distinguish erythema multiforme from more severe conditions like Stevens-Johnson syndrome and toxic epidermal necrolysis, which have greater mucosal involvement and systemic symptoms 1. Management of erythema multiforme involves identifying and removing the trigger, providing supportive care, and treating any underlying HSV infection with antivirals like acyclovir, and immediate discontinuation of the offending drug in medication-induced cases 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

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Current Perspectives on Erythema Multiforme.

Clinical reviews in allergy & immunology, 2018

Research

Recent Updates in the Treatment of Erythema Multiforme.

Medicina (Kaunas, Lithuania), 2021

Research

Erythema Multiforme: Recognition and Management.

American family physician, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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