Key Facts

SJS and TEN represent a spectrum of severe cutaneous adverse reactions (SCARs) characterised by epidermal necrosis and detachment. They are dermatological emergencies requiring immediate drug withdrawal and multidisciplinary care.

Epidemiology

• Incidence: SJS ~1–6 per million/year; TEN ~0.4–1.2 per million/year
• All ages; increased risk with HIV (100× higher incidence)
• Mortality: SJS ~5%, TEN ~25–30%

Aetiology

• Drugs (>80%): onset typically 1–3 weeks after drug initiation
  • Allopurinol (most common single cause)
  • Anticonvulsants: carbamazepine, lamotrigine, phenytoin, phenobarbital
  • Antibiotics: sulfonamides (co-trimoxazole), penicillins, cephalosporins, quinolones
  • NSAIDs: piroxicam (oxicam class)
  • Antiretrovirals: nevirapine
• Infections: Mycoplasma pneumoniae (especially in children — often SJS without clear drug cause)
• HLA associations: HLA-B5801 (allopurinol), HLA-B1502 (carbamazepine — SE Asian populations)

Pathophysiology

• CD8+ cytotoxic T-cells and NK cells → massive keratinocyte apoptosis via Fas-FasL, granulysin, and perforin/granzyme pathways
• Granulysin: key cytotoxic molecule — serum levels correlate with severity
• Full-thickness epidermal necrosis → sheet-like detachment → exposed dermis (like burn)
• Mucosal epithelial necrosis → oral, ocular, genital, respiratory tract involvement

Prodromal Phase (1–3 Days)

• Fever >39°C, malaise, myalgia
• Sore throat, painful swallowing, stinging eyes
• May mimic upper respiratory infection

Mucocutaneous Phase

• Skin: dusky red/purple macules with central necrosis (atypical targetoid lesions)
  • Positive Nikolsky sign: lateral pressure → epidermal separation
  • Confluent areas of epidermal detachment — skin sloughs off in sheets
  • SJS: <10% BSA; SJS-TEN: 10–30%; TEN: >30%
• Oral mucosa (90%): painful erosions of lips, buccal mucosa, tongue → difficulty eating/drinking
• Ocular (80%): conjunctival erosions, photophobia, pseudomembrane formation
• Genital (50–70%): erosions of vulva, penis, urethra → urinary retention
• Respiratory tract: cough, dyspnoea (bronchial epithelial involvement)

Red Flags

• Rapidly increasing BSA of detachment → transfer to burns unit
• Respiratory compromise → ITU
• Ocular involvement → urgent ophthalmology (risk of symblepharon, blindness)
• Sepsis from exposed dermis — leading cause of death

Bedside

• Nikolsky sign: positive — epidermal detachment with lateral pressure
• BSA assessment: calculate percentage of detached/detachable epidermis
• SCORTEN score: calculate within 24 hours of admission — predicts mortality

Bloods

• FBC: lymphopenia, neutropenia (common)
• U&Es: urea >10 mmol/L (SCORTEN parameter); renal function for fluid management
• LFTs: transaminitis common
• Glucose: >14 mmol/L (SCORTEN parameter)
• Bicarbonate: <20 mmol/L (SCORTEN parameter)
• Blood cultures: if sepsis suspected (exposed dermis = high infection risk)
• Mycoplasma serology/PCR: especially in children without clear drug trigger

Biopsy

• Skin biopsy: full-thickness epidermal necrosis with minimal dermal inflammation — characteristic
• Frozen section: can differentiate TEN from SSSS rapidly (subcorneal split in SSSS vs full-thickness necrosis in TEN)

Special Tests

• Ophthalmology assessment: urgent — assess for conjunctival erosion, pseudomembranes
• Chest X-ray: if respiratory symptoms
• Drug causality assessment: ALDEN algorithm — identifies causative drug by timing, known risk, rechallenge data

Immediate

• STOP the causative drug immediately — single most important intervention; delay increases mortality by ~3–5% per day
• Transfer to burns unit/ITU: for TEN (>10% BSA); SJS may be managed on dermatology ward
• Calculate SCORTEN within 24 hours

Supportive Care (Burns Unit Principles)

• Fluid resuscitation: less than typical burns (~70% of Parkland formula); replace losses through exposed dermis
• Wound care: non-adherent dressings; minimise handling; leave detached epidermis in situ as biological dressing if possible
• Temperature regulation: heated room (30–32°C)
• Nutrition: high-calorie, high-protein; NG feeding if oral intake compromised
• Infection prevention: strict asepsis; avoid prophylactic antibiotics (only if signs of sepsis)
• Pain management: opioid analgesia usually required
• DVT prophylaxis: LMWH

Eye Care

• Ophthalmology review: daily in acute phase
• Preservative-free lubricating drops: hourly
• Topical corticosteroid eye drops (dexamethasone 0.1%)
• Break symblepharon: daily lysis of adhesions with glass rod
• Amniotic membrane transplant: for severe ocular involvement

Pharmacological

• Ciclosporin 3–5 mg/kg/day: increasing evidence of benefit — may halt disease progression; used in many UK centres
• Systemic corticosteroids: controversial — may be used early in disease; avoid in established TEN
• IVIg: evidence equivocal; used in some centres at 2 g/kg over 3 days
• Etanercept 50 mg SC single dose: some trial evidence (Paradisi trial)

Long-Term

• Document drug allergy comprehensively — patient, notes, GP, allergy card
• Avoid structurally related drugs: cross-reactivity (e.g. aromatic anticonvulsants)
• Ophthalmology follow-up: chronic dry eye, symblepharon, corneal scarring
• Dermatology follow-up: scarring, pigmentary changes
• Psychological support: PTSD, depression common after TEN

Referral Criteria

• Burns unit/specialist dermatology: all SJS-TEN
• Ophthalmology: all cases (even without initial eye symptoms)
• ICU: respiratory involvement, haemodynamic instability
• Psychology: long-term follow-up for psychological sequelae

• SJS: mortality ~5%
• SJS-TEN overlap: mortality ~10–15%
• TEN: mortality ~25–30%
• SCORTEN predicts mortality accurately (see table)
• Sepsis: leading cause of death
• Long-term complications: chronic dry eye/blindness (~20%), urogenital strictures, skin scarring, psychological trauma
• Mycoplasma-induced SJS (children): generally better prognosis

SCORTEN Prognostic Score

SJS vs TEN vs EM