What is the differential diagnosis of target skin lesions?

Differential Diagnosis of Target Skin Lesions

The differential diagnosis of target skin lesions primarily includes erythema multiforme (EM), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), urticaria, fixed drug eruption, and various immunobullous disorders, with the key distinguishing feature being the morphology of the target lesion itself—true targets with three concentric zones favor EM, while flat atypical targets or purpuric macules suggest SJS/TEN. 1, 2

Primary Differential Considerations

Erythema Multiforme

• Classic "iris" or target lesions consist of three distinct concentric zones: a dark red or dusky center, a pale edematous middle ring, and an outer erythematous ring with well-defined borders 2, 3
• Lesions are predominantly distributed on extremities (hands, feet, elbows, knees) with acral preference, and remain fixed for a minimum of 7 days 2, 4
• Most commonly triggered by herpes simplex virus (HSV) infection, followed by Mycoplasma pneumoniae (especially in children) and drugs 2, 3, 4
• EM minor involves skin with minimal or no mucosal involvement, while EM major includes mucosal surfaces 5, 6

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

• Features flat atypical targets or purpuric macules rather than raised, well-defined targets 1
• Demonstrates positive Nikolsky sign (lateral pressure causes epidermis to slide over dermis) indicating epidermal necrolysis 1
• Predominantly drug-induced (sulfonamides, anticonvulsants, allopurinol, NSAIDs) rather than infection-related 1, 2
• Characterized by painful skin, multisite mucositis, and systemic disturbance with prodrome of fever and malaise 1
• Lesions begin on face, chest, and proximal limbs, then spread with confluent erythema 1

Additional Differential Diagnoses

Immunobullous Disorders

The British Association of Dermatologists identifies the following conditions that can mimic target lesions 1:

• Pemphigus vulgaris and mucous membrane pemphigoid present with flaccid blisters and mucosal erosions
• Bullous pemphigoid shows tense blisters on erythematous or normal skin
• Linear IgA bullous dermatosis demonstrates annular or targetoid lesions
• Direct immunofluorescence is essential to exclude these disorders, showing characteristic immunoreactant deposition patterns 1

Drug Eruptions and Vasculitis

• Fixed drug eruption presents with solitary or few round erythematous plaques that recur in the same location with drug re-exposure 5
• Leukocytoclastic vasculitis shows palpable purpura rather than true target lesions 1
• Sweet syndrome demonstrates tender erythematous plaques or nodules with neutrophilic infiltrate on histology 1

Other Mimickers

• Urticaria has individual lesions that resolve within 24 hours (versus EM lesions fixed for ≥7 days) and demonstrates dermal edema without epidermal necrosis 2, 5
• Viral exanthems lack the characteristic three-zone target morphology 2
• Tinea corporis shows annular scaling plaques with central clearing but lacks the dusky center of true targets 3

Critical Diagnostic Approach

Clinical Assessment

• Document lesion morphology precisely: count the number of concentric zones, assess for raised versus flat configuration, and note color distribution 2
• Map distribution pattern: acral/extremity predominance suggests EM, while truncal/facial involvement with spread suggests SJS/TEN 1
• Assess for epidermal detachment: calculate percentage of body surface area involved and test for Nikolsky sign 1
• Examine all mucosal surfaces (eyes, mouth, nose, genitalia) for erosions and hemorrhagic crusting 1

Essential Investigations

The British Association of Dermatologists and Infectious Diseases Society of America recommend 1:

• Skin biopsy from lesional skin adjacent to a blister for routine histopathology showing variable epidermal damage from individual keratinocyte apoptosis to confluent necrosis 1
• Perilesional biopsy sent unfixed for direct immunofluorescence to exclude immunobullous disorders 1
• HSV PCR or serology and Mycoplasma serology when EM is suspected 2, 4
• Medication history documenting all drugs taken in the preceding 2 months with start dates 1

Key Pitfalls to Avoid

• Do not confuse atypical targets with true targets: atypical targets in SJS/TEN are flat with only two zones and poorly defined borders, while EM has raised lesions with three distinct zones 1, 2
• Mycoplasma-induced SJS in children may present with predominantly mucosal involvement and minimal skin lesions ("Mycoplasma pneumoniae-associated mucositis"), requiring high clinical suspicion 1, 2
• Immunocompromised patients require broader differential including bacterial, fungal, viral, and parasitic infections, graft-versus-host disease, and malignancy-related infiltrates 1
• Early biopsy is critical before lesions evolve, as delayed sampling may show nonspecific findings 1