What are the clinical differences between Stevens‑Johnson syndrome and toxic epidermal necrolysis and how should each be managed?

Stevens-Johnson Syndrome vs Toxic Epidermal Necrolysis: Clinical Differences and Management

Defining the Spectrum

The fundamental distinction between SJS and TEN is the percentage of body surface area (BSA) with epidermal detachment: SJS involves <10% BSA, overlap SJS-TEN involves 10-30% BSA, and TEN involves >30% BSA. 1, 2

Classification Criteria

• SJS: Epidermal detachment <10% BSA plus widespread purpuric macules or flat atypical targets 1, 2
• Overlap SJS-TEN: Detachment of 10-30% BSA with the same lesion morphology 1, 2
• TEN: Detachment >30% BSA, with or without purpuric macules or target lesions 1, 2

Critical documentation point: Epidermal detachment includes both already detached epidermis (visible erosions and blisters) AND detachable epidermis (areas with positive Nikolsky sign that appear as dusky erythema). 2, 3 Document both erythema extent and actual detachment separately on a body map, as only detachment determines classification and prognosis. 2, 3

Mortality Differences

The mortality rates differ dramatically based on extent of involvement:

• SJS mortality: 0-3.1% in adults, 0% in children 1, 2
• Overlap SJS-TEN mortality: 14.3% in adults, 3.9-25% in children 1, 2
• TEN mortality: 17-25% in adults, 8.5-14.7% in children 1, 2, 4, 5

Clinical Presentation (Identical Between SJS and TEN)

Prodromal Phase (4-28 days after drug initiation)

• Fever, malaise, and flu-like upper respiratory symptoms 3
• Severe cutaneous pain preceding visible skin changes is a critical red-flag symptom demanding immediate evaluation 3
• Ocular inflammation may develop before cutaneous lesions 3

Cutaneous Evolution

• Initial lesions: Dark red macules with central dark red spot surrounded by pink ring (atypical flat targets) 3
• Distribution: Begins on upper torso, proximal limbs, and face, then spreads to trunk and distal extremities 3
• Palms and soles are prominently involved early 3
• Lesions expand and coalesce over 5-7 days to maximum extent 3
• Positive Nikolsky sign: Gentle lateral pressure causes epidermal peeling 1, 3
• Flaccid blisters form as necrotic epidermis separates from dermis 3
• Extensive sheet-like epidermal detachment exposes denuded dermis that exudes serum, bleeds readily, and is prone to secondary infection 3

Mucosal Involvement (Early and Severe)

• Erosive and hemorrhagic mucositis affecting eyes, mouth, nose, and genitalia is an early diagnostic hallmark 1, 3, 6
• Purulent keratoconjunctivitis with eyelid edema develops early 6
• Oral mucositis with painful erosions may require nasogastric tube feeding 6
• In Mycoplasma-associated cases, mucosal involvement may predominate with minimal cutaneous lesions 1, 6

Management Algorithm

Immediate Actions (All Severity Levels)

1. Stop the culprit drug immediately—this is the single most important intervention to improve prognosis 2
2. Identify the causative agent: Most commonly allopurinol, sulfonamide antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital, and oxicam NSAIDs 5
3. Obtain skin biopsy to confirm diagnosis and exclude other blistering dermatoses 1

Transfer and Level of Care Decisions

For SJS (<10% BSA):

• Transfer to center with multidisciplinary team experienced in managing SJS/TEN 1
• Intensive care or burn unit admission if comorbidities present or requiring ventilation 1

For Overlap SJS-TEN (10-30% BSA) or TEN (>30% BSA):

• Immediate transfer to burn unit or intensive care unit is mandatory 1, 2, 7
• Patients with >30% BSA detachment and clinical deterioration may require surgical intervention in addition to supportive care 1, 2

Multidisciplinary Consultation (Immediate)

Consult the following specialties promptly to prevent sequelae:

• Ophthalmology (for all cases—ocular complications are common and severe) 1, 7
• Dermatology 7
• Ear, nose, and throat surgery 7
• Urology 7
• Gynecology 7
• Colorectal surgery 7

Supportive Care

• Precise fluid, electrolyte, protein, and energy supplementation 4
• Expert wound care with modern dressings (nanocrystalline dressings may be kept in situ for longer periods) 7
• Moderate mechanical ventilation if required 4
• Pain management (cutaneous pain is prominent) 3, 7

Immunomodulating Therapy (Controversial)

The evidence for specific immunosuppressive treatments remains controversial and has not shown improved outcomes in most studies. 4, 5

• High-dose intravenous immunoglobulin therapy may be considered but lacks consensus 5
• Systemic corticosteroids remain controversial in SJS/TEN 6, 8
• Novel therapies targeting TNF-α inhibitors and specific pathogenic mechanisms (necroptosis, specific immune cell pathways) are emerging but not yet standard of care 8

Critical Pitfalls to Avoid

• Do not dismiss early cutaneous pain as a nonspecific symptom—it precedes visible skin changes and should trigger urgent evaluation 3
• The Nikolsky sign is helpful but not specific for SJS/TEN—it can also be positive in pemphigus 3
• Do not confuse with erythema multiforme major: EMM has raised target lesions predominantly on limbs/extremities, while SJS has flat atypical targets more widely distributed 1, 3
• Paracetamol and ibuprofen have unclear causality—they are often confounders given their use for prodromal symptoms, though reports of both causing SJS exist 1
• Document detachable epidermis (dusky erythema with positive Nikolsky) as part of total detachment percentage—not just frank blisters and erosions 2, 3

Histopathology

• Variable epidermal damage ranging from individual keratinocyte apoptosis to confluent full-thickness epidermal necrosis 1, 5
• Basal cell vacuolar degeneration and subepidermal vesicle/bulla formation 1
• Mild predominantly perivascular lymphocytic and histiocytic infiltrate in dermis 1
• Occasional adnexal structure involvement 1