What is on the differential diagnosis for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis?

Key differentials include Erythema multiforme major, Staphylococcal scalded skin syndrome (SSSS), Drug-induced linear IgA bullous dermatosis, Acute generalized exanthematous pustulosis (AGEP), DRESS / DIHS, Paraneoplastic pemphigus, Generalized bullous fixed drug eruption.

What are the high-yield PANCE pearls for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis?

Painful skin disproportionate to visible findings + new drug exposure in past month = SJS/TEN until proven otherwise. Allopurinol is currently the most common single drug culprit in many series — never prescribe for asymptomatic hyperuricemia. HLA-B*15:02 testing is recommended before starting carbamazepine in patients of Han Chinese or Southeast Asian descent. Cyclosporine is the immunomodulator with the most consistent mortality benefit; IVIG and high-dose steroids are NOT routinely recommended. Survivors require lifelong ophthalmology follow-up and pharmacogenomic counseling for themselves and first-degree relatives.

Dermatology · PANCE / PANRE

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Drug-induced severe mucocutaneous reaction with widespread keratinocyte apoptosis and epidermal detachment; life-threatening.

Also known as: SJS, TEN, Stevens-Johnson syndrome, toxic epidermal necrolysis, Lyell syndrome, SCAR

Overview

A spectrum of severe cutaneous adverse drug reactions characterized by widespread keratinocyte apoptosis with full-thickness epidermal detachment and mucosal involvement. Classified by BSA detachment: SJS <10%, SJS/TEN overlap 10-30%, TEN >30%.

Epidemiology

Rare: SJS 1-7/million person-years; TEN 0.4-1.5/million person-years. Higher in HIV (1000x), SLE, hematologic malignancy. Mortality: SJS ~10%, SJS/TEN overlap ~30%, TEN ~30-50%. SCORTEN score predicts mortality.

Try a board-style Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis question

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1DermatologyMedium

A 58-year-old man presents with a 2-day history of fever, painful skin, and burning eyes followed by dusky red macules on the face and trunk that are beginning to blister and slough. He has erosions on the lips and oral mucosa and conjunctival injection. Nikolsky sign is positive. His clinician suspects Stevens-Johnson syndrome and reviews his medication list, noting several drugs started over the past month. Which of the following recently started medications is the strongest risk factor for this condition?

AAllopurinol
BAtorvastatin
CClopidogrel
DHydralazine

Reveal answer & full explanation

Correct answer: A — Allopurinol

AAllopurinol✓
BAtorvastatin
CClopidogrel
DHydralazine

Why Allopurinol is correct

Drugs cause more than 80% of SJS/TEN cases, and allopurinol is currently the single most common drug culprit in many series, particularly when started within the prior 4-28 days.
Other high-risk culprit classes include aromatic anticonvulsants (carbamazepine, lamotrigine, phenytoin, phenobarbital), sulfonamide antibiotics, oxicam NSAIDs, and nevirapine; the recent new-drug exposure plus painful skin and multisite mucosal involvement points to a high-risk culprit.
HLA-B*58:01 strongly predisposes to allopurinol-induced SJS/TEN in Han Chinese, Thai, and Korean patients, and allopurinol should never be prescribed for asymptomatic hyperuricemia.

Why the others are wrong

Atorvastatin: statins are very commonly prescribed but are not recognized high-risk SJS/TEN triggers, and their cutaneous reactions are rare and usually mild.
Hydralazine: classically causes drug-induced lupus rather than the keratinocyte apoptosis and full-thickness epidermal detachment of SJS/TEN.
Clopidogrel: an antiplatelet agent that is not a recognized cause of SJS/TEN.

🔒 Free preview limit reached

Keep reading — start your free trial

You've read your 2 free diagnosis previews. Create your free account to unlock the full Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.

Start your 7-day free trial → Sign in

Free to start · No credit card · Cancel anytime

Risk factors

Drugs (>80% of cases): allopurinol, anticonvulsants (lamotrigine, carbamazepine, phenytoin, phenobarbital), sulfonamide antibiotics (TMP-SMX, sulfasalazine), NSAIDs (especially oxicams — piroxicam, meloxicam), nevirapine, abacavir, sertraline, immune checkpoint inhibitors
Genetic predisposition (pharmacogenomic): HLA-B*15:02 with carbamazepine (Han Chinese, Southeast Asian); HLA-B*58:01 with allopurinol (Han Chinese, Thai, Korean); HLA-B*57:01 with abacavir
HIV (1000x increased risk)
Active malignancy, autoimmune disease, recent radiation therapy + phenytoin (EMPACT syndrome)
Mycoplasma pneumoniae and rare other infections (more often produce MIRM)

Pathophysiology

Drug or drug metabolite presented by HLA molecules → activation of cytotoxic CD8+ T-cells specific for drug-MHC complex → release of granulysin, perforin/granzyme, FasL → widespread keratinocyte apoptosis at the dermal-epidermal junction → full-thickness epidermal necrosis and detachment. Onset 4-28 days after starting offending drug.

Clinical presentation

Symptoms

Prodrome 1-3 days: fever ≥38°C, malaise, sore throat, photophobia, dysphagia, cough
Painful skin (burning, stinging) — often precedes visible rash
Eye discomfort, conjunctival injection
Oral, genital, respiratory pain

Signs / physical exam

Initial: dusky red/purple macules and atypical flat targets on face and trunk → centrifugal spread to extremities (NOTE: opposite distribution to EM)
Progression to flaccid bullae and full-thickness epidermal sloughing — wrinkles like 'wet cigarette paper' under pressure
Positive Nikolsky sign (lateral pressure shears epidermis) and Asboe-Hansen sign (bullae extend with pressure)
Severe mucosal involvement (≥2 sites in 90%): hemorrhagic crusted lips, painful oral erosions, purulent conjunctivitis with pseudomembranes/symblepharon, genital ulceration, urethritis, esophagitis, tracheobronchitis
Detachment: SJS <10% BSA, SJS/TEN overlap 10-30%, TEN >30%

Classic findings

Skin pain disproportionate to visible findings; widespread dusky targets; mucosal involvement at multiple sites; positive Nikolsky.

Differential diagnosis

Erythema multiforme major — Acral typical 3-zone targets, HSV-triggered, no significant skin detachment, low mortality
Staphylococcal scalded skin syndrome (SSSS) — Young children, no mucosal involvement, cleavage in granular layer (superficial), positive Nikolsky on inflamed skin only
Drug-induced linear IgA bullous dermatosis — String-of-pearls bullae, less systemic; DIF linear IgA at BMZ
Acute generalized exanthematous pustulosis (AGEP) — Sterile pustules on erythema, fever, neutrophilia; resolves in days after drug stopped
DRESS / DIHS — Drug Reaction with Eosinophilia and Systemic Symptoms — fever, facial edema, morbilliform rash, lymphadenopathy, eosinophilia, hepatitis; 2-8 weeks after drug
Paraneoplastic pemphigus — Painful mucositis, polymorphous skin lesions, underlying malignancy; positive desmoplakin antibodies
Generalized bullous fixed drug eruption — Recurs at same sites with rechallenge, fewer mucosal sites, lower mortality

Diagnostic workup

Diagnostic criteria

Clinical + histopathologic confirmation; SJS/TEN spectrum defined by BSA epidermal detachment.

Labs

CBC (cytopenias common), CMP (renal/hepatic dysfunction), CRP, glucose, bicarbonate, urea
Calculate SCORTEN within 24 h and at 72 h (7 variables: age >40, malignancy, HR >120, BSA >10%, BUN >10 mmol/L, glucose >14 mmol/L, bicarbonate <20 mmol/L) — predicts mortality
Skin biopsy: full-thickness epidermal necrosis with subepidermal blister; minimal dermal inflammation
Direct immunofluorescence (negative — helps distinguish from autoimmune bullous diseases)
Cultures (blood, skin, urine) to identify sepsis
Mycoplasma serology and HIV testing

Imaging

Chest X-ray — pneumonitis or aspiration
Bronchoscopy if airway involvement suspected

Diagnostic algorithm

Parameter	SJS	SJS/TEN Overlap	TEN
BSA detachment	<10%	10-30%	>30%
Typical mortality	~10%	~30%	~30-50%
Lesion morphology	Atypical flat targets + macules + bullae	Mixed	Confluent erythema with sheet-like detachment
Mucosal involvement	Severe, ≥2 sites	Severe	Severe, ≥2 sites
Main triggers	Drugs (>80%) — allopurinol, anticonvulsants, sulfa, NSAIDs	Drugs	Drugs
Setting of care	Specialized burn/ICU	Burn/ICU	Burn/ICU

SJS / SJS-TEN overlap / TEN spectrum classification.

Treatment

First-line

IMMEDIATELY discontinue all suspected offending medications — single most important intervention
Transfer to specialized burn unit or ICU — improved survival vs general ward
Supportive care (analogous to severe burns):
• Fluid resuscitation (less than burn formulas; ~2/3 of standard burn fluids) — central line, urine output 0.5-1 mL/kg/h
• Temperature regulation (ambient 28-30°C)
• Nutritional support — enteral feeding preferred
• Wound care: non-adherent dressings, avoid debridement of detached epidermis (acts as biologic dressing)
• Pain control
• Prevent infection — surveillance cultures; antibiotics ONLY if documented infection, not prophylactic
• Ophthalmology consultation daily — lubrication, topical steroids, amniotic membrane
• Urology/gynecology consultation for genital involvement

Immunomodulatory therapy (controversial, evidence limited)

Cyclosporine 3-5 mg/kg/day for 7-10 days — most evidence-supported; reduces mortality in observational studies
Etanercept 50 mg SC × 1-2 doses — emerging evidence; possibly improved time to re-epithelialization
IVIG — formerly used, evidence mixed; no longer routinely recommended
Systemic corticosteroids — controversial; high-dose pulse early may benefit, prolonged courses associated with sepsis and worse outcome

Second-line / adjunct

Document the offending drug clearly in medical record and provide patient with allergy alert/MedicAlert bracelet
Pharmacogenomic counseling for family members (HLA-B*15:02, HLA-B*57:01, HLA-B*58:01)
Counsel patient to AVOID re-exposure to the offending drug and structurally related compounds (e.g., aromatic anticonvulsant cross-reactivity)

Complications

Acute (days to weeks):
• Sepsis and bacteremia (leading cause of mortality)
• Pneumonia, ARDS
• Hypovolemic shock, acute kidney injury
• GI hemorrhage, intestinal perforation
• Thromboembolism, hepatic dysfunction
Chronic (months to lifelong):
• Ocular: chronic dry eye, symblepharon, trichiasis, corneal scarring, vision loss (occurs in 35% of TEN survivors)
• Cutaneous: post-inflammatory dyspigmentation, scarring, nail dystrophy, alopecia
• Mucosal: oral synechiae, esophageal/vaginal strictures, urethral stenosis, anal stenosis
• Pulmonary: bronchiolitis obliterans
• Psychiatric: PTSD, depression, anxiety

PANCE pearls

Painful skin disproportionate to visible findings + new drug exposure in past month = SJS/TEN until proven otherwise.
Allopurinol is currently the most common single drug culprit in many series — never prescribe for asymptomatic hyperuricemia.
HLA-B*15:02 testing is recommended before starting carbamazepine in patients of Han Chinese or Southeast Asian descent.
Cyclosporine is the immunomodulator with the most consistent mortality benefit; IVIG and high-dose steroids are NOT routinely recommended.
Survivors require lifelong ophthalmology follow-up and pharmacogenomic counseling for themselves and first-degree relatives.

References

FDA / AAAAI — Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Clinical Practice Statements (AAD/AAAAI guidance)
Bastuji-Garin SCORTEN — SCORTEN: A Severity-of-Illness Score for Toxic Epidermal Necrolysis (Bastuji-Garin et al., J Invest Dermatol 2000)
BAD 2016 — UK Guidelines for the Management of Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis in Adults (Creamer et al., Br J Dermatol 2016)
AAD 2024 — Severe Cutaneous Adverse Reactions to Drugs (AAD work group)

Practice Dermatology questions on FirstPassPA

Turn this outline into retention. 6,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.

Answer the free question above → Get today's free question →

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.