Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is the most severe form of epidermal necrolysis, with detachment of over 30% of body surface area (BSA); SJS/TEN overlap involves 10 to 30%.

• Incidence is 0.4 to 1.2 per million per year. Mortality is 25 to 35% (higher with advanced age and comorbidity).
• Causative drugs overlap those for SJS: allopurinol, carbamazepine, lamotrigine, phenytoin, sulfonamides, nevirapine, oxicam NSAIDs, aminopenicillins, and immune checkpoint inhibitors.
• Pathogenesis: cytotoxic CD8+ T cells and NK cells releasing granulysin, FasL, perforin, and granzyme B.
• Long term sequelae are common: ocular (dry eye, symblepharon), cutaneous dyspigmentation, nail dystrophy, mucosal synechiae, and psychological sequelae.

• Prodrome followed by painful erythema, flaccid bullae, and sheets of epidermis that slough, leaving raw, weeping dermis ("scalded" appearance).
• Mucosal involvement of at least two sites in over 90%; oral and ocular pain, dysphagia.
• Fever, tachycardia, hypovolaemia, hypothermia risk, hyperglycaemia, and respiratory failure from bronchial epithelial necrosis.
• Complications: sepsis (Staphylococcus aureus, Pseudomonas), GI bleeding, renal injury, hypoalbuminaemia, and multiorgan failure.

• Clinical diagnosis with skin biopsy showing full thickness epidermal necrosis with minimal dermal inflammation.
• BSA assessment (Lund-Browder), SCORTEN at admission and day 3, and ALDEN for drug causality.
• Blood: cultures, lactate, creatinine, urea, glucose, bicarbonate, phosphate, albumin, liver tests, full blood count.
• Chest imaging, bronchoscopy if respiratory symptoms.
• Rule out SSSS, acute graft-versus-host disease, generalised bullous fixed drug eruption, and DRESS.

• Withdraw all potential culprit drugs (within the preceding 8 weeks, prioritising those with a 4 to 28 day onset).
• Transfer early to a burn or intensive care unit, and manage like a major burn: warmed room (30 to 32 degrees Celsius), fluid resuscitation (2 mL/kg/% BSA/24h, less than in thermal burns, monitored by urine output 0.5 to 1 mL/kg/h), early enteral feeding, insulin for hyperglycaemia, and stress ulcer prophylaxis.
• Wound care: non-adherent silver or silicone dressings, preserve detached epidermis as biological dressing, avoid adhesives, regular culture swabs, and systemic antibiotics only for suspected sepsis.
• Targeted therapy: ciclosporin 3 to 5 mg/kg/day for 7 to 10 days (lower mortality in several cohorts), or etanercept 50 mg SC single dose (comparable benefit), or IVIG 1 g/kg/day for 3 days (variable), or methylprednisolone 1 to 2 mg/kg/day for 3 days. Combination regimens are used in refractory cases.
• Daily ophthalmology review with amniotic membrane transplantation for severe ocular involvement; genitourinary, ENT, and respiratory care.
• Analgesia (including ketamine or opioids), thromboprophylaxis, psychological support, and long term follow up for dry eye and skin changes.
• Genetic testing and counselling (HLA-B) for family members of affected patients where relevant.