Erythema Multiforme

Introduction | Aetiology and Risk Factors | Clinical Presentation | Diagnosis | Management and Treatment | Prevention | When to Refer | References

Introduction

Erythema Multiforme (EM) is an acute, immune-mediated condition characterised by the sudden onset of erythematous, target-like lesions primarily on the skin and mucous membranes. It is often self-limiting but can be recurrent. EM is classified into two main types: Erythema Multiforme Minor and Erythema Multiforme Major. EM minor typically presents with mild skin involvement and no or minimal mucosal involvement, whereas EM major involves more extensive mucosal involvement and systemic symptoms. The condition is most commonly triggered by infections, particularly herpes simplex virus (HSV), but can also be associated with certain medications and other underlying conditions.

Aetiology and Risk Factors

Several factors can trigger the immune response that leads to erythema multiforme:

• Infections:
  • Herpes Simplex Virus (HSV): The most common trigger, particularly for recurrent EM.
  • Mycoplasma Pneumoniae: Often associated with more severe forms of EM, particularly in children.
  • Other infections: EM can be triggered by various viral, bacterial, or fungal infections, though less commonly than HSV.
• Medications:
  • Antibiotics (particularly penicillins and sulfonamides), anticonvulsants (e.g., phenytoin, carbamazepine), and NSAIDs are common drug triggers.
  • Medications are more commonly associated with severe forms like Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) but can also cause EM.
• Other Triggers:
  • Vaccinations, autoimmune diseases, and malignancies are less common triggers.

Clinical Presentation

EM is characterized by distinctive skin and mucosal lesions:

• Target Lesions:
  • These are the hallmark of EM, consisting of concentric rings of erythema, often with a central blister or dark centre. The lesions are typically symmetric and can appear on the palms, soles, extensor surfaces of the limbs, and face.
• Mucosal Involvement:
  • In EM major, mucous membranes, including the mouth, eyes, and genitalia, can be involved, leading to painful erosions and ulcers.
• Prodromal Symptoms:
  • Some patients, particularly those with EM major, may experience flu-like symptoms such as fever, malaise, and sore throat prior to the appearance of skin lesions.
• Duration:
  • The lesions typically appear over several days and can persist for 1-4 weeks before resolving without scarring, although hyperpigmentation can occur.

Diagnosis

The diagnosis of erythema multiforme is primarily clinical, supported by the characteristic appearance of the lesions and patient history:

• History: Take a detailed history of recent infections (especially HSV), medication use, and any previous episodes of similar lesions.
• Physical Examination: Look for the presence of typical target lesions and assess the extent of skin and mucosal involvement. Examine for signs of systemic illness.
• Laboratory Tests: While not routinely required, certain tests may be helpful in specific cases:
  • Viral Swabs: HSV PCR testing can be done if HSV is suspected as a trigger.
  • Blood Tests: A full blood count (FBC), liver function tests, and inflammatory markers (CRP, ESR) can help assess the severity and rule out other conditions.
• Skin Biopsy: A biopsy is rarely needed but may be performed in atypical cases or to rule out other conditions. Histopathology typically shows epidermal necrosis with lymphocytic infiltration.

Management and Treatment

The management of erythema multiforme depends on the severity of the condition and the identification of the underlying trigger:

1. General Measures

• Identify and Remove the Trigger: If a specific drug or infection is identified as the trigger, it should be discontinued or treated accordingly. For example, antiviral therapy for HSV or antibiotics for Mycoplasma pneumoniae.
• Symptomatic Treatment:
  • Antihistamines can help manage itching.
  • Analgesics and antipyretics (e.g., paracetamol) can be used for pain and fever.

2. Topical Treatments

• Topical Corticosteroids: Mild to moderate potency topical corticosteroids can be applied to affected areas to reduce inflammation and discomfort.
• Mouthwashes: Antiseptic mouthwashes such as chlorhexidine or topical anaesthetic gels can help with oral lesions and reduce pain, allowing for easier eating and drinking.

3. Systemic Treatments

• Antivirals: For recurrent EM associated with HSV, prophylactic antiviral therapy (e.g., aciclovir or valaciclovir) can reduce the frequency and severity of episodes.
• Systemic Corticosteroids: These are sometimes used in severe cases of EM major, although their use remains controversial due to potential side effects and the lack of strong evidence supporting their efficacy.
• Immunomodulatory Therapy: In cases of recurrent or severe EM that do not respond to standard treatment, immunosuppressive agents such as azathioprine or dapsone may be considered under specialist supervision.

4. Hospital Management

• Severe Cases: Patients with extensive skin involvement or significant mucosal involvement (EM major) may require hospitalisation for supportive care, including fluid management, pain control, and wound care.

Prevention

Preventing erythema multiforme, particularly recurrent cases, involves managing the underlying triggers and maintaining good overall health:

• HSV Suppression: In patients with recurrent EM triggered by HSV, long-term antiviral therapy may be indicated to prevent future episodes.
• Avoidance of Known Triggers: Patients should be advised to avoid medications that have previously triggered EM and to inform healthcare providers of their history of the condition.
• Monitoring for Recurrence: Regular follow-up and early intervention at the first sign of recurrence can help mitigate the severity of future episodes.

When to Refer

Referral to a specialist may be necessary in the following situations:

• Severe or Recurrent Cases: Patients with severe EM or those experiencing recurrent episodes should be referred to a dermatologist for further evaluation and management.
• Diagnostic Uncertainty: If the diagnosis is unclear or if there is concern for other conditions, a referral for a skin biopsy or further investigation may be warranted.
• Complications: Referral to other specialists, such as ophthalmologists for severe eye involvement or a rheumatologist for associated systemic diseases, may be necessary.

References

1. British Association of Dermatologists (2024) Guidelines for the Management of Erythema Multiforme. Available at: https://www.bad.org.uk (Accessed: 26 August 2024).
2. National Institute for Health and Care Excellence (2024) Erythema Multiforme: Diagnosis and Management. Available at: https://www.nice.org.uk/guidance/ng203 (Accessed: 26 August 2024).
3. British National Formulary (2024) Treatments for Dermatological Conditions. Available at: https://bnf.nice.org.uk/ (Accessed: 26 August 2024).