Differential Diagnosis of Target Skin Lesions

Primary Differential Considerations

The British Association of Dermatologists identifies erythema multiforme (EM) as a condition that presents with classic "iris" or target lesions, consisting of three distinct concentric zones, and is most commonly triggered by herpes simplex virus (HSV) infection, followed by Mycoplasma pneumoniae and drugs 1, 2
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) features flat atypical targets or purpuric macules, demonstrates a positive Nikolsky sign, and is predominantly drug-induced, with a prodrome of fever and malaise 1, 3, 4

The British Association of Dermatologists identifies immunobullous disorders, such as pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA bullous dermatosis, as conditions that can mimic target lesions, and recommends direct immunofluorescence to exclude these disorders 1, 4
Leukocytoclastic vasculitis shows palpable purpura rather than true target lesions, and Sweet syndrome demonstrates tender erythematous plaques or nodules with neutrophilic infiltrate on histology 5, 6

The British Association of Dermatologists and Infectious Diseases Society of America recommend a clinical assessment that includes documenting lesion morphology precisely, mapping distribution pattern, assessing for epidermal detachment, and examining all mucosal surfaces for erosions and hemorrhagic crusting 1, 4, 5, 6
Essential investigations include skin biopsy from lesional skin, perilesional biopsy for direct immunofluorescence, HSV PCR or serology, and medication history documenting all drugs taken in the preceding 2 months 1, 3, 5, 6