What is the updated protocol for the management of Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN), including approach to clinical examination, investigation, diagnosis, treatment, and FDA-approved medications?

Updated Protocol for Management of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

Immediate Life-Saving Actions

Immediately discontinue all suspected culprit medications and transfer patients with >10% body surface area (BSA) epidermal detachment to a specialized burn center or ICU within hours of diagnosis, as delayed transfer significantly increases mortality risk. 1, 2

• Calculate SCORTEN within the first 24 hours to predict mortality risk (scores range 0-7, with mortality from 1% to 99%) 1, 2, 3
• Transfer patients with lamotrigine-induced SJS/TEN immediately to a burn center or ICU with experience treating extensive skin loss 1
• Establish peripheral venous access and initiate intravenous fluid resuscitation immediately 1

Clinical Examination Approach

Initial Assessment

• Document the exact date of rash onset (index date) and progression pattern over hours to days 4, 3
• Record all vital signs including oxygen saturation with pulse oximetry, baseline body weight, and assess airway patency 4
• If any concerns regarding airway compromise, immediately involve anesthetic staff for potential intubation 4

Skin Examination

• Look for purpuric macules, flat atypical targets (not typical raised targets), flaccid blisters, and areas of epidermal detachment 4, 3
• Test for Nikolsky sign (lateral pressure extends epidermal detachment) 3
• Record extent of erythema and extent of epidermal detachment separately on a body map using Lund and Browder chart 4
• Estimate percentage of BSA involved for each parameter separately 4

Mucosal Examination

• Examine mouth, eyes, and genitalia (including perianal skin) for erosive and hemorrhagic mucositis, blisters, and erosions 4, 3
• Mucous membrane involvement is an early diagnostic hallmark and typically precedes skin findings 3

Respiratory Assessment

• Examine respiratory system to exclude pneumonia or respiratory compromise 4
• Respiratory symptoms and hypoxemia on admission require urgent intensivist discussion and rapid ICU transfer 2

Investigations

Mandatory Initial Laboratory Tests

• Full blood count, C-reactive protein, urea and electrolytes, liver function tests, coagulation studies 4
• Glucose, magnesium, phosphate, bicarbonate, base excess, lactate 4

Infectious Disease Workup

• Mycoplasma and chlamydia serology (particularly important in children and young adults) 4
• Skin swabs for HSV and varicella zoster virus PCR 4
• Chest X-ray if respiratory symptoms present 4
• Bacterial swabs from lesional skin for culture and sensitivity 4
• Conjunctival swabs for bacteria, chlamydia, HSV PCR, and adenovirus PCR 4

Diagnostic Confirmation

• Obtain two skin biopsies: first from lesional skin adjacent to a blister for histopathology, second from periblister lesional skin for direct immunofluorescence to exclude immunobullous disorders 1, 3
• Histopathology shows confluent epidermal necrosis, basal cell vacuolar degeneration, and subepidermal vesicle formation 1, 5

Drug History Documentation

• Record all medicines taken and vaccinations received over the preceding 2 months, including over-the-counter and complementary/alternative therapies 4, 1
• Document the date treatments were initiated, date of dose escalation, date when drugs were stopped, and any brand switches or medication errors 4
• Use ALDEN (ALgorithm of Drug causality in Epidermal Necrolysis) online tool to predict likely causality 4

Photography

• Take photographs of the skin for documentation and monitoring progression 4

Diagnosis

Clinical Diagnostic Criteria

The diagnosis requires the characteristic triad: painful skin lesions, mucous membrane involvement, and recent drug exposure (typically 4-28 days prior) 3, 6

Classification by Severity

• SJS: <10% BSA epidermal detachment 7, 6
• SJS/TEN overlap: 10-30% BSA epidermal detachment 7, 6
• TEN: >30% BSA epidermal detachment 7, 6

Differential Diagnoses to Exclude

• Erythema multiforme major (has typical raised target lesions, not flat atypical targets) 3
• DRESS syndrome 3
• Staphylococcal scalded skin syndrome (SSSS) - more common in children, spares mucous membranes 3, 5
• Acute generalized exanthematous pustulosis (AGEP) - has sterile pustules 3, 5
• Generalized bullous fixed drug eruption 3
• Linear IgA dermatosis, paraneoplastic pemphigus, pemphigus vulgaris, and bullous pemphigoid (excluded by direct immunofluorescence) 5

High-Risk Patients

Identify patients with likely drug trigger and underlying diseases associated with worse prognosis (malignancy, previous stem cell transplant) 4

Treatment Protocol

Specialized Care Environment

• Barrier nurse in a temperature-controlled side room (ambient temperature 25-28°C) with humidity control 1, 2
• Use pressure-relieving mattress 1, 2
• Coordinate care through multidisciplinary team led by specialist in skin failure (dermatology/plastic surgery), including intensive care, ophthalmology, and specialist skincare nursing 1, 2

Fluid Management

• Establish adequate intravenous fluid replacement guided by urine output and hemodynamic parameters 1, 2
• Consider using formula: body weight/% BSA epidermal detachment to determine replacement volumes 1
• Avoid overaggressive fluid resuscitation which causes pulmonary, cutaneous, and intestinal edema 1, 2
• Catheterize if clinically indicated for monitoring 1

Wound Care Protocol

• Handle skin with extreme care to minimize shearing forces that cause further epidermal detachment 1, 2
• Leave detached epidermis in situ to act as biological dressing 2
• Decompress blisters by piercing and expression or aspiration of fluid 2
• Regularly cleanse wounds by gently irrigating with warmed sterile water, saline, or chlorhexidine (1/5000) 1, 2
• Apply greasy emollient (50% white soft paraffin with 50% liquid paraffin) over entire epidermis including denuded areas every few hours 1, 2
• Consider aerosolized formulations to minimize shearing forces 1
• Apply nonadherent dressings (Mepitel™ or Telfa™) to denuded dermis 1, 2
• Use secondary foam or burn dressings to collect exudate 1, 2
• Consider silver-containing products/dressings for sloughy areas only 2

Pain Management

• Use validated pain assessment tools at least once daily 1, 2
• Provide adequate background simple analgesia with additional opioid analgesia for breakthrough pain 2
• Administer intravenous opioid infusions for those not tolerating oral medication 1
• Consider patient-controlled analgesia where appropriate 1
• Consider sedation or general anesthesia for patient handling, repositioning, and dressing changes 1

Infection Prevention and Management

Do not administer prophylactic systemic antibiotics as this increases skin colonization, particularly with Candida albicans 1, 2

• Take swabs for bacterial and candidal culture from three lesional areas on alternate days, particularly sloughy areas 1, 2
• Monitor for signs of systemic infection: confusion, hypotension, reduced urine output, reduced oxygen saturation 1
• Watch for monoculture of organisms on culture swabs from multiple sites (indicates increased likelihood of invasive infection) 1
• Institute targeted antimicrobial therapy only when clinical signs of infection are present 1, 2
• Monitor rising C-reactive protein and neutrophilia as indicators of sepsis 2

Ophthalmological Management

• Arrange examination by ophthalmologist experienced in ocular surface diseases within 24 hours of diagnosis 4, 1, 2
• Continue daily ophthalmological reviews throughout acute illness 2
• Apply preservative-free lubricant eye drops every 2 hours throughout acute illness 2
• Perform daily ocular hygiene by ophthalmologist or ophthalmically trained nurse to remove inflammatory debris and break down conjunctival adhesions 2
• Use topical antibiotics when corneal fluorescein staining or ulceration is present 2
• Consider topical corticosteroid drops under ophthalmologist supervision to reduce ocular surface damage 2
• Consider amniotic membrane transplantation (AMT) in acute phase for significantly better visual outcomes 2

Oral Care

• Apply white soft paraffin ointment to lips immediately, then every 2 hours throughout acute illness 2
• Use anti-inflammatory oral rinse containing benzydamine hydrochloride every 3 hours, particularly before eating 2
• Use antiseptic oral rinse twice daily to reduce bacterial colonization 2
• Apply topical anesthetics such as viscous lidocaine 2% or cocaine mouthwashes 2-5% for severe oral discomfort 2
• Treat candidal infection with nystatin oral suspension 100,000 units four times daily for 1 week, or miconazole 2
• Consider topical corticosteroids applied to oral mucosa 2

Urogenital Care

• Examine urogenital tract regularly during acute illness 2
• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours 2
• Catheterize when urogenital involvement causes dysuria or retention, or to monitor output 2
• Consider vaginal dilators or tampons wrapped in Mepitel to prevent vaginal synechiae formation 2

Respiratory Management

• Perform fibreoptic bronchoscopy to identify bronchial involvement, evaluate prognosis, investigate pneumonitis, and mechanically remove sloughed bronchial epithelium 2
• Urgent intensivist discussion required if respiratory symptoms or hypoxemia present 2

Nutritional Support

• Provide continuous enteral nutrition throughout acute phase 2
• Deliver 20-25 kcal/kg daily during catabolic phase 2
• Increase to 25-30 kcal/kg daily during anabolic recovery phase 2
• Consider nasogastric feeding when oral intake is precluded by buccal mucositis 2

Additional Supportive Measures

• Administer low molecular weight heparin as prophylactic anticoagulation for immobile patients 2
• Provide proton pump inhibitor if enteral nutrition cannot be established 2
• Consider recombinant human G-CSF for neutropenic patients 2

Systemic Immunomodulatory Therapy

First-Line Options (Start Within 72 Hours)

Cyclosporine 3 mg/kg daily for 10 days, tapered over 1 month, has shown benefit in multiple studies with reduced mortality compared to predicted rates 2

• Alternative: Systemic corticosteroids, particularly early IV methylprednisolone pulse therapy (prednisolone 1-2 mg/kg/day or equivalent), may be beneficial if started within 72 hours of onset, tapered rapidly within 7-10 days 2, 8
• Cyclosporine may be used alone or in combination with corticosteroids 8
• High-strength topical corticosteroids may be applied to affected skin areas 2

Therapies with Equivocal or Negative Evidence

• IVIg has equivocal evidence: pooled analysis showed no mortality benefit (OR 1.00,95% CI 0.58-1.75) 2
• Thalidomide should be avoided: associated with excess deaths in one randomized trial 2

FDA-Approved Medications

There are currently no FDA-approved medications specifically for the treatment of SJS/TEN. The management relies on supportive care and off-label use of immunomodulatory agents (cyclosporine, corticosteroids) based on clinical evidence 2, 8

Special Considerations for Pediatric Patients

• Infection causes up to 50% of pediatric SJS/TEN cases (particularly mycoplasma, HSV, chlamydia) 2
• Test for infective triggers and consult infectious disease team in all pediatric cases 4, 2
• Consider targeted antibiotics as appropriate (e.g., azithromycin for mycoplasma) 4
• Manage in age-appropriate specialist units with pediatric intensivists and skin loss specialists 2
• High-risk children need quicker transfer to specialized care 2

Discharge Planning and Follow-up

• Provide written information about culprit drug(s) to avoid and any potentially cross-reactive medications 1, 2
• Encourage wearing MedicAlert bracelet bearing name of culprit drug 1, 2
• Document drug allergy in patient's medical records and inform all healthcare providers 1, 2
• Report adverse drug reaction to national pharmacovigilance authorities 1, 2
• Inform patients about potential fatigue and lethargy for several weeks following discharge 2
• Arrange follow-up with dermatology and ophthalmology within weeks of discharge 1
• Consider referral to support groups such as SJS Awareness U.K. 2

Common Pitfalls to Avoid

• Delayed recognition and transfer to specialized care significantly increases mortality 1, 2
• Indiscriminate prophylactic antibiotics increase resistant organism colonization, particularly Candida 1, 2
• Overaggressive fluid resuscitation causes pulmonary, cutaneous, and intestinal edema 1, 2
• Failure to involve ophthalmology within 24 hours leads to permanent visual impairment 1, 2
• Continued use of culprit medication worsens condition and increases mortality 2
• Neglecting infectious causes (particularly mycoplasma in children/young adults) worsens prognosis 1

Outcome Measures for Monitoring

Critical outcomes (ranked 7-9 for decision-making): survivorship/survival, internal organ dysfunction (PELOD, modified SOFA or MODS score), no residual impairment (eyes, skin, genital), and quality of life/psychosocial well-being 4