Dermatology · Severe Cutaneous Adverse Reactions
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Toxic Epidermal Necrolysis is defined by full-thickness skin detachment involving >30% of total body surface area.
The most common triggering medications include allopurinol, anticonvulsants (phenytoin, carbamazepine, lamotrigine), sulfonamides, and nevirapine.
A positive Nikolsky sign, where the epidermis detaches with lateral pressure, is a characteristic clinical finding.
The disease process involves widespread keratinocyte apoptosis mediated by CD8+ T-cells and granulysin release.
Patients typically present with a prodrome of fever and flu-like symptoms followed by painful, dusky-red macules that rapidly progress to flaccid bullae.
Involvement of mucous membranes (oral, ocular, or genital) occurs in nearly all cases and is a critical diagnostic feature.
The immediate management priority is the discontinuation of the offending agent and transfer to a burn unit for supportive care.
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A 42-year-old male is brought to the emergency department with a widespread, painful rash that started 3 weeks after initiating medication for gout. Physical examination reveals diffuse erythema and large areas of epidermal sloughing involving the trunk, face, and extremities, estimated at 45% of his body surface area. He has crusted erosions on the lips and conjunctival injection. Lateral pressure on the skin causes immediate shearing of the epidermis. His temperature is 101.8°F (38.8°C).
What is the most likely diagnosis?
Toxic Epidermal Necrolysis (TEN)
The patient's presentation of >30% body surface area involvement, positive Nikolsky sign, and mucosal involvement following the initiation of a high-risk medication (allopurinol) is diagnostic for TEN.
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High yield triage
Etiology / Epidemiology
Severe drug-induced hypersensitivity reaction; most commonly triggered by sulfonamides, allopurinol, and anticonvulsants.
Clinical Manifestations
Diffuse full-thickness skin necrosis with Nikolsky sign; involves >30% of total body surface area.
Diagnosis
Clinical diagnosis confirmed by skin biopsy showing full-thickness epidermal necrosis.
Treatment
Immediate drug withdrawal and supportive care in a burn unit; systemic corticosteroids remain controversial; cyclosporine or etanercept may be considered.
Prognosis
High mortality rate; use SCORTEN score to predict mortality; sepsis is the leading cause of death.
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Epidemiology & Etiology
TEN is a rare, life-threatening reaction typically occurring 1–3 weeks after drug initiation. High-risk agents include SATAN drugs: Sulfonamides, Allopurinol, Tetracyclines, Anticonvulsants, and NSAIDs. It represents the severe end of the spectrum compared to Stevens-Johnson Syndrome.
Pertinent Anatomy
The condition involves the dermo-epidermal junction. Destruction of the basement membrane leads to massive epidermal detachment and exposure of the underlying dermis.
Pathophysiology
TEN is a Type IV hypersensitivity reaction mediated by cytotoxic T-cells. Massive keratinocyte apoptosis is triggered by Fas-ligand and granulysin release. This results in widespread blistering and sloughing of the skin and mucous membranes.
Clinical Manifestations
Patients present with a prodrome of fever and malaise followed by painful, dusky erythema. The Nikolsky sign (lateral pressure causing skin detachment) is a characteristic finding. Mucosal involvement of the eyes, mouth, and genitals is present in >90% of cases, leading to corneal scarring and strictures.
Diagnosis
Diagnosis is primarily clinical, but a skin biopsy is the gold standard to differentiate from other dermatoses. Histology reveals full-thickness epidermal necrosis with minimal dermal inflammation. The SCORTEN score is used to calculate mortality risk based on seven clinical variables.
Treatment
The first-line intervention is immediate discontinuation of the offending agent. Patients must be transferred to a burn unit for fluid resuscitation and wound care. Systemic corticosteroids remain controversial — potential benefit is offset by infection and impaired wound healing; cyclosporine and etanercept have the strongest current mortality data. IVIG or cyclosporine may be considered, but evidence remains controversial.
Prognosis
Mortality is high, often exceeding 30%. Major complications include sepsis, fluid/electrolyte imbalance, and multi-organ failure. Survivors often suffer from long-term ocular sequelae and scarring.
Differential Diagnosis
Stevens-Johnson Syndrome: <10% body surface area involvement
Staphylococcal Scalded Skin Syndrome: spares mucous membranes
Erythema Multiforme: targetoid lesions, usually HSV-associated
Pemphigus Vulgaris: intraepidermal bullae, positive Nikolsky
Bullous Pemphigoid: subepidermal bullae, negative Nikolsky