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Toxic epidermal necrolysis pathology

Author: Harriet Cheng (BHB, MBChB), Dermatology Unit, Waikato Hospital; Duncan Lamont, Pathologist, Waikato Hospital; A/Prof Patrick Emanuel, Dermatopathologist, Auckland, New Zealand, 2014.


Toxic epidermal necrolysis (TEN) is a severe cutaneous drug reaction characterised by a prodromal 'flu-like illness followed by the rapid appearance of a painful erythematous rash and desquamation of skin and mucous membranes. TEN is at the severe end of a spectrum with Stevens-Johnson syndrome defined by >30% body surface area skin detachment.

Histology of toxic epidermal necrolysis

In TEN, there are subepidermal bullae (Figures 1–3) with widespread epidermal necrosis and subsequent separation or loss of the entire epidermis. Apoptotic keratinocytes may be seen at the periphery (Figure 2, arrow). There is minimal inflammatory infiltrate.

Toxic epidermal necrolysis pathology

Differential diagnosis of toxic epidermal necrolysis

Erythema multiforme: Apoptotic keratinocytes with less prominent necrosis (may be seen at the centre of established lesions), inflammatory infiltrate is more prominent with lymphocytic perivascular infiltrate.

Phytophototoxic reaction: Marked oedema and subepidermal blistering with apoptotic keratinocytes and epidermal necrosis. Minimal inflammatory infiltrate. Clinical features will easily differentiate from TEN.

Chemotherapy-induced acral erythema: If severe can progress to subepidermal blistering with epidermal necrosis. Clinically distinct from TEN.

Differential diagnosis of cell-poor subepidermal blistering includes variants of epidermolysis bullosa, porphyria cutanea tarda, cell-poor type bullous pemphigoid, burns, suction blisters and some bullous drug reactions.



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  • Weedon’s Skin Pathology (Third edition, 2010). David Weedon
  • Pathology of the Skin (Fourth edition, 2012). McKee PH, J. Calonje JE, Granter SR

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