What is Stevens-Johnson syndrome?

Stevens-Johnson Syndrome (SJS)

Stevens-Johnson Syndrome is a rare, severe mucocutaneous reaction characterized by blistering and epithelial sloughing of skin and mucous membranes, typically triggered by medications or infections, with potentially life-threatening complications and mortality rates of up to 10%. 1

Clinical Presentation

Stevens-Johnson Syndrome presents with a characteristic pattern:

• Prodromal phase: Fever, malaise, and upper respiratory symptoms typically precede skin eruption by several days 1
• Cutaneous manifestations:
  • Early and prominent cutaneous pain
  • Atypical target lesions or purpuric macules
  • Progressive spread to trunk and distal limbs, often involving palms and soles 1
  • Rapid confluence of lesions with positive Nikolsky's sign (skin sloughing with gentle pressure) 2
• Mucosal involvement:
  • Early and prominent erosive and hemorrhagic mucositis
  • Affects mucous membranes of eyes, mouth, nose, and genitalia 1, 3
• Body surface area (BSA) involvement:
  • SJS: <10% BSA
  • SJS/TEN overlap: 10-30% BSA
  • Toxic Epidermal Necrolysis (TEN): >30% BSA 1

Etiology

The primary triggers for SJS include:

• Medications (most common cause):
  • Anticonvulsants
  • Antibiotics (especially sulfonamides)
  • Allopurinol
  • NSAIDs
  • Antimalarials 1, 2
• Infections:
  • Herpes simplex virus
  • Mycoplasma pneumoniae 1, 4
• Other less common causes:
  • HIV infection
  • Cancer
  • Genetic factors 4

Pathophysiology

SJS is primarily an immune-mediated reaction:

• Cell-mediated cytotoxic reaction against keratinocytes leading to massive skin necrolysis
• Immune synapse composed of cytotoxic T cells with drug-specific HLA class I restriction
• Various cytotoxic proteins and cytokines (granulysin, perforin, granzyme B, IL-15, Fas ligand, IFN-γ, TNF-α) mediate the pathogenesis 5

Diagnosis

Diagnosis is primarily clinical, based on:

• Characteristic clinical presentation with skin and mucosal involvement
• History of exposure to potential triggers
• Skin biopsy showing:
  • Variable epidermal damage from individual cell apoptosis to confluent epidermal necrosis
  • Basal cell vacuolar degeneration
  • Subepidermal vesicle or bulla formation
  • Mild perivascular infiltrate of lymphocytes and histiocytes 1

Important differential diagnoses include:

• Staphylococcal Scalded Skin Syndrome (SSSS)
• Erythema Multiforme Major (EMM)
• Immunobullous disorders (pemphigus, pemphigoid) 1

Management

Management requires a multidisciplinary approach:

1. Immediate interventions:

   • Stop the suspected culprit drug immediately
   • Transfer to a specialized center with experience in managing SJS/TEN 1, 3

2. Supportive care (cornerstone of management):

   • Fluid and electrolyte management
   • Wound care
   • Nutritional support
   • Pain management
   • Airway and breathing stabilization
   • Treatment of superimposed infections with broad-spectrum antibiotics 1, 3

3. Specific treatments (controversial):

   • Systemic corticosteroids: May suppress progression but increase infection risk
   • Cyclosporine: Emerging evidence for decreased mortality
   • TNF-α inhibitors: Emerging evidence for decreased mortality
   • Intravenous immunoglobulins: May block Fas ligand-mediated apoptosis 1, 2, 5

4. Special considerations:

   • For SJS associated with herpes simplex: Consider antiviral therapy (acyclovir) 1

Prognosis and Complications

• Mortality rates:

  • SJS: <10%
  • TEN: up to 30% 1

• Acute complications:

  • Sepsis
  • Multiorgan failure 1, 3

• Long-term sequelae:

  • Skin: Pigmentation changes, scarring
  • Ocular: Vision impairment, blindness
  • Mucosal: Oral, dental problems
  • Respiratory issues
  • Urogenital problems and strictures 1, 2

Recurrence

• More common in children (up to 18% of cases)
• Particularly when triggered by infections that may recur
• Management strategies include:
  • Prophylactic antiviral therapy for HSV-associated SJS
  • Early intervention with higher-dose antivirals and prednisone at first sign of HSV reactivation 1

Important Clinical Pearls

• SJS/TEN is a true dermatological emergency requiring immediate recognition and intervention
• Symptoms typically begin 4-28 days after drug initiation 6
• No reliable laboratory test exists to determine the offending drug; diagnosis relies on patient history and empirical risk of drugs 2
• Provocation tests are contraindicated as re-exposure may trigger a more severe episode 2
• Recovery is usually slow, taking 3-6 weeks depending on extent, severity, and complications 2