Dermatology · Severe Cutaneous Adverse Reactions
The facts most likely to be tested
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 pathognomonic 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; avoid systemic corticosteroids.
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 pathognomonic. 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 are contraindicated as they increase infection risk. 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