What is the overview, clinical manifestations, diagnosis, treatment, and prognosis of Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis (SJS-TEN)?

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Comprehensive Overview

Overview and Definition

SJS/TEN represents a spectrum of life-threatening mucocutaneous reactions characterized by extensive keratinocyte apoptosis and epidermal detachment, with mortality rates ranging from 1-5% for SJS to 25-35% for TEN. 1, 2

• SJS is defined as epidermal detachment <10% body surface area (BSA) plus widespread purpuric macules or flat atypical targets 3
• SJS/TEN overlap involves 10-30% BSA detachment 3, 4
• TEN is defined as >30% BSA detachment 3, 4
• Drugs are the primary cause in most cases, though Mycoplasma pneumoniae and HSV infections are well-documented triggers 1
• High-risk medications include allopurinol, sulfonamide antibiotics, aminopenicillins, carbamazepine, phenytoin, phenobarbital, and oxicam-type NSAIDs 1, 2

---

Clinical Manifestations

Prodromal Phase

• Fever, malaise, sore throat, and anorexia typically occur 4-28 days after drug exposure 5, 6
• Upper respiratory tract symptoms precede skin manifestations 5
• Document the index date (first symptom onset) and progression timeline 5

Cutaneous Manifestations

• Painful erythematous macules progress to atypical target lesions, blisters, and epidermal detachment 3, 6
• Dusky erythema represents detachable epidermis (impending necrosis) 3
• Positive Nikolsky sign (epidermal detachment with lateral pressure) 6
• Hemorrhagic erosions and denuded dermis at pressure areas despite careful handling 3

Mucosal Involvement

• Oral mucosa: Painful erosions, hemorrhagic crusting, difficulty eating 3
• Ocular: Conjunctival injection, erosions, pseudomembrane formation leading to potential corneal scarring 3
• Genital/perianal: Erosions, blistering, risk of subsequent strictures 3, 4
• Respiratory: Bronchial epithelial sloughing may occur, leading to respiratory compromise 3

Systemic Complications

• Sepsis is the most common cause of death, initially from Staphylococcus aureus, later from Gram-negative organisms including Pseudomonas aeruginosa 3, 7
• Pulmonary involvement with pneumonitis and potential respiratory failure 3, 4
• Hepatic dysfunction 4
• Renal impairment 4
• Gastrointestinal involvement with esophageal erosions 4

---

Diagnostic Approach

Clinical Assessment

Record all medications taken in the preceding 2 months, including over-the-counter drugs, complementary therapies, exact start dates, dose escalations, and stop dates. 3, 5

• Use the ALDEN algorithm (ALgorithm of Drug causality in Epidermal Necrolysis) to predict drug causality 3
• Assess airway patency immediately and involve anesthesia if intubation concerns exist 3, 5
• Perform full physical examination including vital signs, oxygen saturation, respiratory system assessment 3
• Map extent of erythema and epidermal detachment separately using Lund and Browder chart 3
• Examine mouth, eyes, and genitalia for mucositis, blisters, and erosions 3

Laboratory Investigations

Order the following investigations within 24 hours: 3

• Full blood count, C-reactive protein, urea and electrolytes, liver function tests, coagulation studies
• Glucose, magnesium, phosphate, bicarbonate, base excess, lactate
• Infection screening: Mycoplasma and Chlamydia serology, skin swabs for HSV and VZV PCR, chest X-ray 3
• Bacterial swabs from lesional skin for culture and sensitivity 3
• Conjunctival swabs for bacteria, Chlamydia, HSV, and adenovirus 3

Histopathology

• Skin biopsy shows full-thickness epidermal necrolysis with confluent keratinocyte apoptosis 1, 2
• Basal cell vacuolar degeneration and subepidermal vesicle/bulla formation 3
• Mild perivascular lymphocytic infiltrate in dermis 3
• Differentiates from staphylococcal scalded skin syndrome (more superficial cleavage) 3

Prognostic Assessment: SCORTEN

Calculate SCORTEN score on admission and at 24 hours to predict mortality: 3

SCORTEN parameters (1 point each):

• Age >40 years
• Malignancy
• Heart rate >120 bpm
• BSA detachment >10%
• Serum urea >10 mmol/L
• Serum glucose >14 mmol/L
• Serum bicarbonate <20 mmol/L

Predicted mortality by SCORTEN score: 3

• 0-1 points: 1-4% mortality
• 2 points: 12% mortality
• 3 points: 32% mortality
• 4 points: 62% mortality
• 5 points: 85% mortality
• ≥6 points: 95-99% mortality

---

Treatment Guidelines

Immediate Management

Immediately discontinue all potential culprit drugs—this is the single most critical intervention. 3, 5

Transfer patients with >10% BSA epidermal detachment without delay to a burn center or ICU with experience managing SJS/TEN. 3, 5 Delayed transfer significantly increases mortality 5.

Multidisciplinary Team Coordination

Care must be coordinated by a specialist in skin failure (dermatology or plastic surgery) with an MDT including: 3, 5

• Intensive care physicians
• Ophthalmology (examination within 24 hours mandatory) 3, 5
• Specialist skincare nursing
• Additional input from respiratory medicine, gastroenterology, gynecology, urology, oral medicine, microbiology, pain team, dietetics, physiotherapy, and pharmacy as needed 3

Supportive Care Environment

Barrier-nurse patients in a side room with: 3

• Humidity control
• Pressure-relieving mattress
• Ambient temperature raised to 25-28°C 3
• Antishear handling techniques to minimize epidermal detachment 3, 5

Wound Management

Conservative approach (first-line): 3

• Frequent application of bland emollient to support barrier function and reduce transcutaneous water loss 3
• Appropriate dressings on denuded dermis to reduce fluid/protein loss, limit microbial colonization, and control pain 3
• Re-epithelialization typically begins once active blistering ceases, taking days to weeks 3

Surgical approach (consider if conservative management fails): 3

• Debridement of detached epidermis followed by biosynthetic xenograft or allograft application 3
• Indications: clinical deterioration, extension of detachment, local sepsis/subepidermal pus, delayed healing, wound conversion 3

Fluid Resuscitation

• Fluid requirements are lower than predicted by Parkland formula for burns 3
• Avoid overaggressive resuscitation to prevent pulmonary, cutaneous, and intestinal edema 3
• Monitor urine output, vital signs, and end-organ perfusion 3

Infection Management

Do NOT use prophylactic systemic antibiotics—this increases colonization risk, particularly with Candida albicans. 3, 5

Institute antimicrobial therapy only when clinical signs of infection are present: 3

• Monitor for confusion, hypotension, reduced urine output, reduced oxygen saturation
• Rising C-reactive protein and neutrophilia suggest sepsis 3
• Monoculture on swabs from multiple sites indicates predominant organism and increased invasive infection risk 3
• Consider HSV reactivation in slow-healing erosions, particularly genital and oral sites 3
• For Mycoplasma-triggered cases, consider targeted antibiotics (e.g., azithromycin) 3

Respiratory Management

If respiratory symptoms or hypoxaemia on admission, urgently discuss with intensivist for rapid ICU transfer. 3

• Fibreoptic bronchoscopy to identify bronchial involvement, evaluate prognosis, and sample for bacterial infection 3
• Bronchoscopy may prevent atelectasis by removing sloughed bronchial epithelium 3
• Monitor with pulmonary function testing and high-resolution CT if ongoing symptoms 3

Ophthalmologic Care

Arrange examination by an ophthalmologist experienced in ocular surface diseases within 24 hours of diagnosis. 3, 5 Failure to provide early ophthalmologic care results in permanent visual impairment 5.

Active Immunomodulatory Therapy

No active therapeutic regimen with unequivocal benefit exists for SJS/TEN. 3 The evidence for immunomodulatory agents is conflicting and based on observational studies only.

Intravenous immunoglobulin (IVIg): 3

• Pooled data shows no mortality benefit (OR 1.00,95% CI 0.58-1.75) 3
• Pediatric patients may have lower mortality than adults (0% vs 21.6%) 3
• If used, high-dose IVIg (≥2 g/kg over 3-5 days) shows lower mortality than low-dose in adults 3
• Evidence quality is poor with major methodological limitations 3

Systemic corticosteroids: 3

• Conflicting evidence; no randomized controlled trials demonstrate benefit 3
• Some observational studies suggest benefit, but results did not reach statistical significance 3

Cyclosporine: 3

• Limited case series suggest potential benefit at 3 mg/kg/day for 10 days 3
• No control group data; evidence quality is low 3

The British Association of Dermatologists recommends that immunomodulatory interventions should ideally be practiced under specialist MDT supervision in the context of clinical studies or case registries. 3

---

Course and Prognosis

Acute Phase

• Active blistering and epidermal detachment typically cease within days 3
• Re-epithelialization may occur within days or take several weeks 3
• Septicemia is the leading cause of death in the acute phase 7, 4

Mortality Risk Factors

• Age >65 years 7
• Mechanical ventilation requirement 7
• Antibiotic-triggered SJS/TEN has highest mortality risk 7
• Underlying malignancy and previous stem cell transplant 3
• Higher SCORTEN scores 3

Long-Term Sequelae (>50% of TEN survivors experience complications) 1

Ocular complications (most disabling): 3, 5

• Corneal scarring, ocular surface disease
• Eyelid abnormalities, trichiasis, meibomian gland dysfunction
• May develop weeks to months after acute episode 3

Cutaneous sequelae: 3

• Scarring, dyschromia, dyspigmentation
• Nail dystrophy

Genital complications: 3

• Phimosis, adhesions, meatal scarring
• Vaginal strictures

Other organ systems: 3, 4

• Esophageal strictures
• Bronchiolitis obliterans (rare)
• Chronic fatigue (major problem for weeks post-discharge) 3, 5
• Psychological problems including depression 3

---

Critical Pitfalls to Avoid

Delayed transfer to specialized care significantly increases mortality. 5 Transfer patients with >10% BSA involvement immediately 3, 5.

Failure to discontinue the culprit drug immediately worsens prognosis. 5 Stop all potential triggers without delay 3, 5.

Indiscriminate prophylactic antibiotic use increases colonization risk, particularly with Candida. 3, 5 Only use antibiotics when clinical infection is evident 3.

Neglecting ophthalmologic care within 24 hours results in permanent visual impairment. 3, 5 This is a non-negotiable early intervention.

Overaggressive fluid resuscitation causes pulmonary and tissue edema. 3 Use conservative fluid management compared to burn formulas 3.

Rough handling of skin causes further epidermal detachment. 3, 5 Use antishear techniques and warn unfamiliar clinicians before examination 3.

---

Discharge Planning and Follow-Up

Provide written information about drugs to avoid, including related medications that may cross-react. 3, 5 Encourage wearing a MedicAlert bracelet 5.

Document drug allergy prominently in patient's medical records and inform all healthcare providers. 5

Send discharge letter to GP outlining: 3

• The culprit medication and drugs to avoid
• Potential chronic complications requiring monitoring
• Follow-up plan with specialist services 3

Refer to specialist drug allergy service for expert review. 3

Report adverse drug reaction to pharmacovigilance authorities (MHRA in UK). 3

Arrange follow-up monitoring for: 3, 5

• Ocular complications (ophthalmology)
• Cutaneous scarring and dyspigmentation (dermatology)
• Genital complications (gynecology/urology)
• Psychological support and fatigue management 3
• Quality of life assessment 3

Counsel patients and families about expected convalescence period and chronic fatigue lasting weeks to months. 3, 5