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Erythema Multiforme, Stevens–Johnson Syndrome, and Toxic Epidermal Necrolysis

CRITICAL — Systemic

Symptoms

flu-like prodrome: fever, malaise, arthralgia, dysphagia

ocular: red eyes, pain, burning

cutaneous: skin rash with target lesions, dusky macules, or blisters

Clinical Findings

Disease spectrum

  • erythema multiforme (em) minor and major
  • stevens–johnson syndrome (sjs): <10% body surface area (bsa) detached
  • sjs/ten overlap: 10–30% bsa detached
  • toxic epidermal necrolysis (ten): >30% bsa detached
  • eye findings present in 50–80% of patients

Mucocutaneous hallmarks

  • target lesions: three concentric zones (central dusky, pale edema, erythematous rim)
  • nikolsky sign: positive (epidermal sliding on lateral pressure)
  • oral stomatitis with pathognomonic hemorrhagic lip crusting

Acute ocular phase (<2 weeks)

  • bilateral severe mucopurulent conjunctivitis and thick tarsal pseudomembranes
  • conjunctival sloughing and large corneal epithelial defects
  • eyelid margin ulceration and eyelash shedding
  • high risk of corneal melt or perforation

Chronic cicatricial phase

  • severe dry eye (schirmer near zero) due to loss of goblet cells and lacrimal ductules
  • symblepharon, ankyloblepharon, and keratinized lid margins
  • limbal stem cell deficiency (lscd): causes conjunctivalization and neovascularization
  • lid malposition: cicatricial entropion and trichiasis

Prognostic tools

  • scorten: predicts mortality based on age, hr, bsa, and bun
  • sotozono grading: grade 3 (pseudomembrane + epithelial defect) mandates immediate amt

Etiology

Pathophysiology

  • t-cell–mediated hypersensitivity activating cd8+ cytotoxic t cells
  • granulysin drives widespread keratinocyte apoptosis

Triggers

  • em: infection-triggered (hsv most common, mycoplasma, adenovirus)
  • sjs/ten: drug-triggered (satan mnemonic: sulfa, allopurinol, tetracyclines/anticonvulsants, nsaids, nevirapine)

Pharmacogenomics

  • hla-b*15:02 (carbamazepine), hla-b*58:01 (allopurinol), hla-b*57:01 (abacavir)

Red Flags

acute ocular surface involvement in sjs

fever with mucosal ulcers and skin rash

suspected drug trigger (stop immediately)

late-stage limbal stem cell deficiency

Investigations

Ocular evaluation

  • slit-lamp exam with eyelid eversion for fornix inspection
  • document epithelial defects and assign sotozono grade

Systemic evaluation

  • calculate scorten score and obtain skin biopsy
  • dermatology and internal medicine consults
  • cultures if secondary infection is suspected

Treatment

Acute systemic

  • supportive care (hydration, wound care, nutrition) in burn unit
  • adjuncts: consider ivig or cyclosporine

Acute ocular

  • topical steroids: prednisolone acetate 1% or difluprednate 4–8x daily
  • aggressive preservative-free lubrication (tears, gels, and ointments)
  • prophylactic topical antibiotics for epithelial defects

Surgical intervention

  • amniotic membrane transplant (amt) over lid margins, conjunctiva, and fornix (<72 hours)
  • daily manual pseudomembrane peeling

Clinical Pearl

sjs is an ophthalmic emergency on day one — amniotic membrane transplant within the first week dramatically reduces long-term cicatricial complications, so involve ophthalmology at the first mucocutaneous sign.

Differential Diagnosis

  • mucous membrane pemphigoid
  • pemphigus vulgaris
  • bullous pemphigoid
  • staphylococcal scalded skin syndrome

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