30th July 2026

Erythema Multiforme

Background

Erythema Multiforme (EM) is an immune-mediated hypersensitivity reaction affecting cutaneous and mucosal membranes. The condition is characterised by typical targetoid lesions with concentric rings that develop in a symmetrical acral distribution with mucosal involvement in a small number of patients. The majority of cases are triggered by herpes simplex virus (HSV), but other triggers exist including drugs and vaccinations. It is self-limiting but has a tendency to recur in 30% of affected patients. Although historically believed to be part of the same disease process that causes Steven-Johnsons Syndrome(SJS)/Toxic Epidermal Necrolysis (TEN) , emerging research has provided evidence to suggest EM is its own disease entity. 

Epidemiology

The condition is relatively rare with an estimated annual incidence of 1%. EM has a male predominance of 3:2 and most commonly presents in the second and third decade of life. No association with race has been found. Specific HLA allotypes such as HLA-DQB1*0301 are thought to also increase risk of developing EM, particularly triggered by HSV. 

Aetiology

The exact pathogenesis of EM remains unclear but the underlying mechanism is proposed to be a type IV hypersensitivity reaction caused by cytotoxic T cells. A number of different causes exist, summarised in the table below.

Table 1: Causes of erythema multiforme

Diagnosis 

Classification

Table 2: Classification of Erythema Multiforme

Clinical features

Target lesions eruption over 72 hours over the distal, extensor surfaces. Prodromal symptoms are rare. 

Mucosal involvement includes oral blistering and genital ulceration. Symptoms usually heal within 2-3 weeks with minimal scarring although hyperpigmentation has been reported.

Target lesion on the dorsum of the hand.

Image Source: Wikimedia Commons (2009). Erythema Multiforme Minor of the Hand, Licensed under a creative commons licence. Available for free at https://commons.wikimedia.org/wiki/File:Erythema_multiforme_minor_of_the_hand.jpg (Accessed 19 May 2025)

Differential Diagnosis

• Rowell’s syndrome (targetoid lesions in Systemic Lupus Erythematosus)
• Pemphigus Vulgaris
• Urticaria
• Polymorphous light eruption
• Steven Johnson’s syndrome/Toxic Epidermal Necrolysis
• Paraneoplastic pemphigus

Investigations

• Full blood count 
• Urea & electrolytes
• Liver function tests 
• HSV serology and other infectious disease serology 
• Chest X-ray: to look for evidence of mycoplasma pneumoniae as a cause of EM 
• Skin biopsy: upper dermal oedema and epidermal keratinocyte necrosis. 
  • Biopsy is not usually required however may be considered to differentiate from other serious skin reactions.

Medical management 

• Omit offending agent or treat the underlying cause
• Emollient
• Prednisolone/methylprednisolone
• Analgesia
• Ocular involvement requires ophthalmology review 
• Recurrent disease: 6 months of anti-fungal treatment (vanciclovir/aciclovir) whether or not a clear trigger has been identified. 

Complications  

• Microstomia secondary to lip scarring
• Secondary bacterial infection