Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN)

• Definition: SJS and TEN are severe mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis and mucous membranes. They are now considered variants of the same condition, with differences in the extent of skin involvement.
• Prevalence: SJS occurs at an estimated rate of 1–2 cases per million people per year, while TEN occurs at 0.4–1.2 cases per million people per year.
• Etiology: Nearly always caused by medications, although infections and vaccines are rare triggers.

Demographics

• Age and Gender: Can affect all age groups and races. Slightly more common in females than males.
• HIV: SJS/TEN is 100 times more common in individuals with HIV.
• Genetics: HLA associations and specific gene polymorphisms (e.g., CYP2C coding for cytochrome P450) are risk factors, particularly with certain drugs like anticonvulsants and allopurinol.

Causes

• Medications: Over 200 medications have been associated with SJS/TEN. Common culprits include:
  • Antibiotics:
    • Sulfonamides (e.g., cotrimoxazole)
    • beta-lactams (e.g., penicillins, cephalosporins).
  • Anticonvulsants:
    • Lamotrigine
    • carbamazepine
    • phenytoin
    • phenobarbital.
  • Others:
    • Allopurinol
    • acetaminophen
    • nevirapine
    • NSAIDs (especially oxicam type).
• Other Triggers: Rarely, vaccines and infections such as mycoplasma and cytomegalovirus.

Clinical Features

• Prodromal Phase:
  • Resembling an upper respiratory infection with symptoms like high fever (> 39°C)
  • sore throat
  • difficulty swallowing
  • runny nose
  • cough
  • red and sore eyes (conjunctivitis)
  • general aches and pains.
• Skin Involvement:
  • Early Rash: Begins with tender, painful red macules or diffuse erythema, starting on the trunk and spreading to the face and limbs.
  • Blisters: Flaccid blisters that coalesce to form large sheets of skin detachment.
  • Nikolsky Sign: Positive; gentle rubbing of the skin causes it to peel away.

• Mucosal Involvement:
  • Eyes: Conjunctivitis, corneal ulcers, uveitis.
  • Mouth: Cheilitis, stomatitis with painful ulcers.
  • Genital and Urinary Tract: Erosions, ulcers, urinary retention.
  • Respiratory and GI Tract: Tracheal/bronchial involvement causing respiratory distress, diarrhea.

Complications

• Acute Phase Complications:
  • Dehydration and Malnutrition: Due to extensive fluid loss and difficulty in oral intake.
  • Infections: Risk of skin and mucosal infections, pneumonia, sepsis.
  • Respiratory Distress: Acute respiratory distress syndrome (ARDS).
  • GI Issues: Ulceration, perforation, intussusception.
  • Multi-Organ Failure: Including renal failure, shock, disseminated intravascular coagulation (DIC).

Diagnosis

• Clinical Suspicion: Based on the extent of skin detachment and typical mucocutaneous features.
• Classification:
  • SJS: <10% body surface area (BSA) detachment.
  • Overlap SJS/TEN: 10–30% BSA detachment.
  • TEN: >30% BSA detachment.
• Histopathology: Skin biopsy showing keratinocyte necrosis, full-thickness epidermal necrosis, minimal inflammation. Direct immunofluorescence is negative.
• Blood Tests: Anemia, leucopenia (especially lymphopenia), neutropenia (poor prognosis), mildly raised liver enzymes, proteinuria.

Differential Diagnoses

• Other Severe Cutaneous Adverse Reactions (SCARs): Drug hypersensitivity syndrome.
• Infections: Staphylococcal scalded skin syndrome, toxic shock syndrome.
• Autoimmune Diseases: Erythema multiforme, bullous systemic lupus erythematosus, paraneoplastic pemphigus.

Treatment

• Drug Cessation: Immediate discontinuation of the suspected causative drug.
• Hospitalization: Preferably in an intensive care or burns unit.
• Supportive Care: Fluid and nutritional support, temperature regulation, pain management, and sterile handling.
• Skin Care:
  • Gentle removal of necrotic skin/mucosal tissue
  • Daily assessment for infection.
  • Topical antiseptics (e.g., silver nitrate, chlorhexidine).
  • Non-adherent dressings.
• Eye Care:
  • Frequent eye drops/ointments.
  • Ophthalmologist assessment.
• Mouth and Genital Care:
  • Mouthwashes, topical anesthetics.
  • Prevent vaginal adhesions with steroid ointments.
• Respiratory Care: Aerosols, physiotherapy, possible intubation.
• Urinary Care: Catheterization, urine cultures.
• Psychiatric and Physiotherapy Support: Address anxiety and maintain joint movement.
• Systemic Treatments: Controversial use of corticosteroids, ciclosporin, anti-TNFα antibodies, IVIG, plasmapheresis.
• Antibiotics: Only if infection is present; prophylactic antibiotics not recommended.

Prevention

• Avoiding Causative Drugs: Education on avoiding the offending drug and structurally related medications.
• Genetic Screening: Potential future tool for predicting SJS/TEN risk.
• Careful Prescription Practices: Particularly with allopurinol and anticonvulsants.

Outlook

• Acute Phase: Lasts 8–12 days; re-epithelialization takes weeks.
• Long-term Sequelae: Pigment changes, skin scarring, nail loss, genital scarring, joint contractures, lung disease.
• Eye Complications: Potential for severe vision problems and blindness.

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