Drug Eruptions: Stevens-Johnson Syndrome (SJS) & Toxic Epidermal Necrolysis (TEN)
Summary
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe, life-threatening cutaneous drug reactions representing a spectrum of disease characterised by mucosal erosions and widespread epidermal necrosis/detachment. They are defined by percentage of Body Surface Area (BSA) affected: SJS (<10%), SJS/TEN Overlap (10-30%), TEN (>30%). Common culprit drugs include Sulphonamides (Co-trimoxazole), Anticonvulsants (Lamotrigine, Carbamazepine, Phenytoin), Allopurinol, and NSAIDs. The hallmark is full-thickness epidermal necrosis with a positive Nikolsky sign (Epidermal detachment/blistering with lateral pressure). Mucosal involvement (Oral, Ocular, Genital) is universal. Management requires immediate drug withdrawal, supportive care in a Burns Unit (Fluid resuscitation, Wound care, Temperature control, Nutritional support), and urgent ophthalmology involvement (To prevent blindness). SCORTEN is a validated prognostic scoring system predicting mortality. Adjunctive therapies (IVIG, Ciclosporin) are used variably.
Key Facts
- Definition Spectrum (By BSA Detachment): SJS (<10%), SJS/TEN Overlap (10-30%), TEN (>30%).
- Main Cause: Drug-induced (>80%).
- Culprit Drugs: Sulphonamides, Anticonvulsants (Lamotrigine, Carbamazepine, Phenytoin), Allopurinol, NSAIDs.
- Nikolsky Sign: Positive (Epidermis separates with lateral pressure).
- Mucosal Involvement: Eyes (Pseudomembrane, Conjunctivitis, Blindness risk), Oral, Genital.
- Mortality: SJS ~5%. TEN ~25-35%.
- Management: Withdraw drug. Burns Unit. Ophthalmology. Supportive care.
Clinical Pearls
"Stop the Drug Immediately": The culprit drug must be identified and stopped within 24 hours to improve outcomes.
"Nikolsky Sign = Dangerous": Epidermal peeling with lateral pressure indicates full-thickness necrosis.
"Eyes, Eyes, Eyes": Ocular involvement can lead to permanent blindness. Daily ophthalmology input is essential.
"SCORTEN Predicts Mortality": Use SCORTEN within 24 hours to stratify prognosis.
Why This Matters Clinically
SJS/TEN are dermatological emergencies with high mortality. Early recognition, drug withdrawal, and supportive care save lives.
Incidence
- SJS: ~1-6 per million/year.
- TEN: ~0.4-1.2 per million/year.
Risk Factors
| Factor | Notes |
|---|---|
| HIV/AIDS | 100-fold increased risk. |
| HLA-B*15:02 (Han Chinese, SE Asian) | Strong association with Carbamazepine-induced SJS/TEN. Screen before prescribing. |
| HLA-B*58:01 | Association with Allopurinol-induced SJS/TEN. |
| Slow Acetylators | Increased risk with Sulphonamides. |
| Immunocompromised | |
| Prior SJS/TEN | Do NOT re-challenge with culprit drug. |
Drugs (Most Common Cause - >80%)
| Drug Class | Examples |
|---|---|
| Antibiotics | Sulphonamides (Co-trimoxazole), Penicillins, Quinolones. |
| Anticonvulsants | Lamotrigine, Carbamazepine, Phenytoin, Phenobarbital. |
| Allopurinol | |
| NSAIDs | Piroxicam, Others. |
| Others | Nevirapine (HIV), Sulfasalazine. |
Onset typically 1-3 weeks after starting drug (Up to 8 weeks for anticonvulsants).
Infections (Minority)
| Pathogen | Notes |
|---|---|
| Mycoplasma pneumoniae | Especially in children. "Mycoplasma-induced Rash and Mucositis" (MIRM). |
| HSV | Rare. |
Mechanism
| Step | Detail |
|---|---|
| Drug/Metabolite | Hapten or Pro-hapten. Binds to MHC. |
| T-Cell Activation | Cytotoxic CD8+ T-cells recognise drug-peptide-MHC complex. |
| Keratinocyte Apoptosis | Cytokines (Granulysin, Fas-FasL, Perforin/Granzyme) induce widespread keratinocyte apoptosis. |
| Full-Thickness Epidermal Necrosis | Epidermis separates from dermis. |
Key Cytotoxic Mediator
- Granulysin: Major secreted by cytotoxic lymphocytes. Directly induces keratinocyte apoptosis.
| Condition | BSA (Epidermal Detachment) |
|---|---|
| SJS | <10% |
| SJS/TEN Overlap | 10-30% |
| TEN | >0% |
BSA calculation: Rule of Nines or Palmar method.
Prodrome (1-3 Days)
| Feature | Notes |
|---|---|
| Fever | Often high. |
| Malaise / Fatigue | |
| Upper Respiratory Symptoms | May mimic viral illness. |
| Myalgia / Arthralgia | |
| Skin Tenderness | Preceding rash ("Burning skin"). |
Skin
| Feature | Description |
|---|---|
| Macular Rash | Initially erythematous macules. Atypical targets (Dusky centre, 2 zones). |
| Blisters | Flaccid. Coalesce. |
| Epidermal Detachment | Sheets of necrotic epidermis slough off. |
| Nikolsky Sign + | Lateral pressure on skin causes epidermal separation. |
| Asboe-Hansen Sign + | Lateral pressure on blister extends blister. |
| Distribution | Face, Trunk, Proximal limbs. Generalised. |
Mucosal Involvement (Always Present)
| Site | Features |
|---|---|
| Oral | Lip erosions, Mouth ulcers, Haemorrhagic crusting. Painful. Dysphagia. |
| Ocular | Conjunctivitis, Pseudomembranes, Corneal erosions. Risk of blindness (Symblepharon, Scarring). |
| Genital / Urethral | Erosions. Urinary retention. |
| Respiratory | Bronchial epithelium involvement (Rare, Severe). |
Systemic
| Feature | Notes |
|---|---|
| Fever | High, Persistent. |
| Fluid Loss | Like burns. Dehydration. Hypovolaemia. |
| Electrolyte Imbalance | |
| Secondary Infection | Sepsis major cause of death. |
Clinical Diagnosis
- Based on clinical presentation.
- Recent drug exposure.
- Mucosal involvement + Epidermal necrosis.
Skin Biopsy (Confirmatory)
| Finding | Notes |
|---|---|
| Full-Thickness Epidermal Necrosis | Apoptotic keratinocytes throughout epidermis. |
| Subepidermal Split | Separation at Dermo-Epidermal Junction. |
| Sparse Dermal Infiltrate | Lymphocytes. |
Frozen section can provide rapid diagnosis.
Investigations
| Test | Purpose |
|---|---|
| FBC | Anaemia. Neutropenia (Poor prognosis). |
| U&E | Dehydration. Electrolyte imbalance. |
| LFTs | Hepatic involvement. |
| Glucose | |
| Infection Screen | Blood cultures. Wound swabs. Mycoplasma serology. |
| HLA Typing | If relevant for future avoidance (HLA-B15:02, HLA-B58:01). |
| Parameter | Points |
|---|---|
| Age >0 | 1 |
| Heart Rate >20 bpm | 1 |
| Malignancy | 1 |
| BSA Detachment >0% (Day 1) | 1 |
| Serum Urea >0 mmol/L | 1 |
| Serum Bicarbonate <20 mmol/L | 1 |
| Serum Glucose >4 mmol/L | 1 |
Predicted Mortality
| SCORTEN | Mortality |
|---|---|
| 0-1 | 3% |
| 2 | 12% |
| 3 | 35% |
| 4 | 58% |
| ≥5 | 90% |
Calculate within 24 hours and Day 3.
Principles (EMERGENCY)
- Identify and Stop Culprit Drug Immediately.
- Admit to Burns Unit / Dermatology HDU / ICU.
- Supportive Care (Fluids, Wound care, Temperature, Nutrition).
- Ophthalmology Input (Daily if ocular involvement).
- Consider Adjunctive Therapies.
- Monitor for Sepsis.
- Pain Management.
Drug Withdrawal
- Stop ALL suspected drugs within 24 hours.
- Drugs with long half-lives (e.g., Allopurinol, Phenobarbital) carry worse prognosis.
Supportive Care (Burns Unit Principles)
| Intervention | Detail |
|---|---|
| IV Fluids | Replace losses. Less than standard burns formula (No capillary leak). |
| Wound Care | Non-adherent dressings. Avoid debridement of attached skin (Acts as biological dressing). |
| Temperature Control | Maintain warmth. High ambient temperature. |
| Nutritional Support | Early enteral feeding. High calorie/protein. |
| Mouth Care | Antiseptic mouth washes. Emollients. |
| Catheterisation | If genital involvement / urinary retention. |
| VTE Prophylaxis | |
| Analgesia | Often significant pain. |
Ophthalmic Care (URGENT)
| Intervention | Notes |
|---|---|
| Daily Ophthalmology Review | |
| Preservative-Free Lubricants | Frequent application. |
| Steroid Eye Drops | Reduce inflammation. |
| Symblepharon Release | Break adhesions forming between lid and globe. Use glass rod/spacer. |
| Amniotic Membrane Grafting | In severe cases. Prevents scarring. |
Ocular sequelae (Dry eyes, Symblepharon, Corneal scarring, Blindness) are common.
Adjunctive Systemic Therapies (Controversial – Limited Evidence)
| Therapy | Notes |
|---|---|
| IVIG (Intravenous Immunoglobulin) | May neutralise Fas-FasL interaction. Variable evidence. |
| Ciclosporin | Inhibits T-cell activation. Some favourable data. |
| Systemic Corticosteroids | Controversial. May increase infection/delay healing. |
| Etanercept (Anti-TNF) | Some case series. |
No single adjunctive therapy has strong evidence. Supportive care is paramount.
| Complication | Notes |
|---|---|
| Sepsis | Leading cause of death. |
| Respiratory Failure | Bronchial epithelium involvement. |
| Ocular Sequelae | Dry eyes, Symblepharon, Corneal damage, Blindness. |
| Hypovolaemia / Electrolyte Imbalance | Fluid loss. |
| Genital Scarring / Stenosis | |
| Oesophageal / GI Strictures | |
| Psychological | PTSD, Depression. |
| Long-Term Skin Changes | Pigmentation, Scarring. |
| Condition | Mortality |
|---|---|
| SJS | ~5-10% |
| SJS/TEN Overlap | ~10-30% |
| TEN | ~25-35% |
Use SCORTEN for individualised prediction.
| Feature | DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) |
|---|---|
| Timing | 2-8 weeks after drug. |
| Rash | Morbilliform. Facial oedema. NOT epidermal necrosis. |
| Systemic | Fever. Lymphadenopathy. Hepatitis. Nephritis. Pneumonitis. |
| Bloods | Eosinophilia. Atypical lymphocytosis. Raised LFTs. |
| Drugs | Anticonvulsants (Carbamazepine, Phenytoin), Allopurinol, Sulphonamides, Minocycline, Vancomycin. |
| Treatment | Withdraw drug. Systemic corticosteroids. |
Key Guidelines
| Guideline | Organisation | Notes |
|---|---|---|
| BAD Guidelines (SJS/TEN) | British Association of Dermatologists | UK standard. |
| EDF Guidelines | European Dermatology Forum | European guidance. |
Scenario 1:
- Stem: A patient started on Carbamazepine 2 weeks ago presents with fever, oral ulcers, and widespread blistering. Nikolsky sign is positive. Skin detachment is 15% BSA. What is the diagnosis?
- Answer: SJS/TEN Overlap (Carbamazepine-induced). 10-30% BSA.
Scenario 2:
- Stem: What prognostic scoring system is used in SJS/TEN?
- Answer: SCORTEN.
Scenario 3:
- Stem: What is the most important initial management step in SJS/TEN?
- Answer: Immediate withdrawal of the culprit drug.
| Scenario | Urgency | Action |
|---|---|---|
| Suspected SJS/TEN | Emergency | A&E -> Burns Unit / Dermatology HDU/ICU. |
| Ocular Involvement | Emergency | Ophthalmology same day. |
| DRESS Syndrome | Urgent | Dermatology admission. Steroids. |
What is SJS/TEN?
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are very serious skin reactions, usually caused by medications. The skin blisters and peels off, like a severe burn. It also affects the mouth, eyes, and genitals.
What causes it?
Usually a reaction to a medication, especially certain antibiotics, seizure medications, or gout medications. It can start 1-4 weeks after starting the drug.
How is it treated?
- Stop the medication immediately.
- Hospital care (Often in a burns unit).
- Eye care (To protect vision).
- Fluids and wound care.
Key Counselling Points
- Never Take That Drug Again: "You must avoid this drug (and related ones) forever. Carry a list/alert card."
- Tell All Doctors: "Inform every healthcare professional about your allergy."
- Report Symptoms Early: "If you ever develop a rash with mouth sores and fever after starting a new medication, seek help immediately."
| Standard | Target |
|---|---|
| Culprit drug identified and stopped within 24 hours | 100% |
| SCORTEN calculated within 24 hours | 100% |
| Ophthalmology review within 24 hours (If ocular involvement) | 100% |
| Transfer to Burns Unit / Appropriate setting | 100% |
- Stevens & Johnson (1922): Described 2 children with febrile mucocutaneous eruption ("Stevens-Johnson Syndrome").
- Lyell (1956): Described TEN ("Lyell Syndrome").
- SCORTEN (2000): Bastuji-Garin et al. developed and validated the prognostic score.
- BAD Guidelines. SJS/TEN. bad.org.uk
- Bastuji-Garin S, et al. SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis. J Invest Dermatol. 2000. PMID: 10998259
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. SJS/TEN is a medical emergency – seek immediate medical attention if suspected.