Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are among the most testable—and most dangerous—dermatologic emergencies on Step 1. The key is to recognize the timeline (often after a new drug), the painful mucosal erosions, and the sheet-like epidermal detachment that behaves like a severe burn. If you can quickly separate SJS/TEN from mimics (e.g., erythema multiforme, staph scalded skin syndrome), you’ll rack up easy points and—more importantly—know what to do clinically.
Where SJS Ends and TEN Begins (Definition + Cutoffs)
SJS and TEN are on a spectrum of the same disease process: immune-mediated keratinocyte apoptosis leading to epidermal necrosis and sloughing.
Body surface area (BSA) involvement:
| Condition | Epidermal detachment (BSA) |
|---|---|
| SJS | < 10% |
| SJS/TEN overlap | 10–30% |
| TEN | > 30% |
High-yield phrasing: “Life-threatening mucocutaneous reaction with epidermal necrosis and detachment.”
Pathophysiology (What’s Actually Happening?)
SJS/TEN is classically a type IV hypersensitivity reaction (T-cell mediated) to a medication (most commonly), leading to widespread keratinocyte apoptosis.
Mechanism you should be able to say out loud on exam day:
- Drug (or infection) triggers CD8+ cytotoxic T-cells and NK cells
- Release of granulysin, perforin/granzyme, and Fas–FasL signaling
- Keratinocyte apoptosis → full-thickness epidermal necrosis → sloughing
Why it’s so dangerous:
- Loss of skin barrier → massive fluid loss, electrolyte derangements
- Denuded skin → high risk of sepsis
- Mucosal involvement → airway/ocular/GI/GU complications
First Aid tie-in: This sits with Type IV hypersensitivity and severe drug reactions in the immunology/derm sections; also think “burn-unit physiology.”
Etiology & High-Yield Associations (The “Culprit List”)
Medications (most common, highest yield)
Memorize these drug classes—Step questions love them:
- Sulfonamides (e.g., TMP-SMX)
- Antiepileptics: lamotrigine, carbamazepine, phenytoin
- Allopurinol
- NSAIDs (especially oxicam derivatives)
- Nevirapine (HIV meds—less common but classic)
Timing clue (HY):
- Usually 1–3 weeks after starting the offending medication (can be faster with re-exposure)
Infections (classics)
- Mycoplasma pneumoniae (more associated with mucositis; can cause SJS-like pictures)
- Viral illnesses can be triggers, but drugs are the big one for exam purposes
Genetics (high-yield board association)
- HLA-B*1502: increased risk of carbamazepine-induced SJS/TEN (notably in many patients of Asian ancestry)
- HLA-B*5801: increased risk of allopurinol hypersensitivity (including SJS/TEN)
First Aid cross-reference: These HLA associations commonly appear near pharmacogenomics (carbamazepine, allopurinol) and adverse drug reactions.
Clinical Presentation (What You’re Looking For)
Prodrome (often precedes the rash)
- Fever
- Malaise
- Sore throat
- Cough, conjunctival irritation
Skin findings (high yield descriptors)
- Painful skin (pain is a big clue; often out of proportion)
- Dusky, atypical targetoid macules that coalesce
- Bullae → epidermal detachment
- Positive Nikolsky sign: gentle pressure causes epidermal sloughing
Mucosal involvement (very testable)
- Oral erosions (crusted lips)
- Ocular involvement (conjunctivitis → corneal damage)
- Genital/urinary erosions
HY pearl: SJS/TEN = prominent mucosal involvement + systemic toxicity.
Diagnosis (Step-Style Approach)
SJS/TEN is primarily a clinical diagnosis, but exams often ask what confirms it.
Best confirmatory test
- Skin biopsy
Classic biopsy finding:
- Full-thickness epidermal necrosis with subepidermal separation (epidermis lifts off)
- Scant inflammation in epidermis; interface dermatitis may be seen
Key differentials (know how to separate)
| Condition | Key trigger/organism | Level of split | Mucosa? | Typical patients | Key clue |
|---|---|---|---|---|---|
| SJS/TEN | Drugs (TMP-SMX, lamotrigine, allopurinol, etc.) | Subepidermal due to necrosis | Yes, prominent | Any | Painful + systemic sx |
| Erythema multiforme | HSV most common | Epidermal changes but not massive necrosis | Minimal/variable | Younger | Target lesions on palms/soles, milder |
| SSSS | S. aureus exfoliative toxins | Intraepidermal (granular layer) | No (desmoglein-1 absent in mucosa) | Infants/children | Looks “scalded,” + Nikolsky |
| Pemphigus vulgaris | IgG vs desmoglein 3 | Intraepidermal (acantholysis) | Yes | Adults | Flaccid bullae; chronic |
| Bullous pemphigoid | IgG vs hemidesmosomes | Subepidermal | Rare | Elderly | Tense bullae, very pruritic |
SSSS vs SJS/TEN is a favorite trap:
- SSSS: toxin-mediated, kids, no mucosal involvement, superficial split
- SJS/TEN: drug-mediated, all ages, mucosal erosions, full-thickness necrosis
Management (What To Do First + What Matters Most)
Step 1: Stop the offending agent
- Immediate discontinuation is the single most important early intervention.
Step 2: Supportive care like a burn patient (core of treatment)
Most mortality comes from complications of skin failure, so management mirrors burn care:
- Airway assessment (especially if severe mucosal disease)
- IV fluids and electrolyte management
- Temperature control
- Wound care (non-adherent dressings; minimize skin trauma)
- Pain control
- Nutrition
- Infection surveillance (but avoid reflexive prophylactic antibiotics)
High-yield point: Treat in an ICU or burn unit when extensive.
Eyes are an emergency (don’t miss this)
- Early ophthalmology consult
- Prevent adhesions and corneal injury (lubrication, careful exams)
Immunomodulatory therapies (exam nuance)
Evidence varies by guideline and institution, but boards often test that these may be used in severe cases:
- IVIG (historically used; mixed evidence)
- Cyclosporine (increasing supportive data in some protocols)
- Systemic corticosteroids (controversial; may be used early in select cases)
Safe exam framing: Supportive care is the foundation; selected immunomodulators may be considered depending on severity/protocol.
Prognosis and Scoring (High-Yield Add-On)
Major causes of death
- Sepsis
- Multiorgan failure
- Severe fluid/electrolyte losses
TEN severity tool you might see
- SCORTEN predicts mortality (Step 1 doesn’t usually ask details, but Step 2 sometimes references risk stratification)
Classic USMLE Vignettes (What the Stem Looks Like)
You’ll typically see:
- “Started lamotrigine 2 weeks ago” or “recent TMP-SMX”
- Fever + malaise
- Painful erythematous rash → bullae
- Mucosal erosions
- Nikolsky positive
- Large areas of denuded skin (“like a burn”)
Correct next step questions:
- “Most appropriate next step?” → Stop drug + supportive/burn unit care
- “Best confirmatory test?” → Skin biopsy
- “Mechanism?” → Type IV hypersensitivity; CD8-mediated keratinocyte apoptosis
- “Likely complication?” → Sepsis, fluid loss, ocular scarring
First Aid Cross-References (How to Link It in Your Head)
While editions vary, SJS/TEN is typically clustered with:
- Dermatology: severe drug eruptions/blistering disorders; Nikolsky sign
- Immunology: Type IV hypersensitivity
- Pharmacology: adverse effects of sulfonamides, antiepileptics, allopurinol, NSAIDs; pharmacogenomics (HLA associations)
Memory hook:
“SJS/TEN = Sick + Sloughing + (new) Scripts.”
Sick (systemic), Sloughing (Nikolsky, detachment), Scripts (drug trigger).
Rapid-Fire High-Yield Summary (Exam-Day Checklist)
- SJS <10%, TEN >30% BSA detachment
- Drug reaction (often 1–3 weeks after starting): TMP-SMX, lamotrigine/carbamazepine/phenytoin, allopurinol, NSAIDs
- Painful rash + mucosal erosions + Nikolsky positive
- Path: CD8+ T-cell mediated keratinocyte apoptosis → full-thickness epidermal necrosis
- Confirm: skin biopsy
- Treat: stop offending drug, burn-unit supportive care, early ophtho
- Major mortality driver: sepsis