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

SJS presents with a characteristic pattern:

• Prodromal phase: Fever, malaise, and upper respiratory symptoms typically precede skin eruption by several days 1
• Cutaneous manifestations:
  • Early, prominent cutaneous pain
  • Atypical target lesions or purpuric macules
  • Progressive spread to trunk and distal limbs, often involving palms and soles 1
• Mucosal involvement: Early and prominent erosive and hemorrhagic mucositis affecting:
  • Eyes
  • Mouth
  • Nose
  • Genitalia 1

SJS is defined by less than 10% body surface area (BSA) involvement, while SJS/TEN overlap involves 10-30% BSA, and Toxic Epidermal Necrolysis (TEN) involves greater than 30% BSA 1.

Etiology

The primary triggers of SJS include:

• Medications: Most common cause, particularly:
  • Anticonvulsants
  • Antibiotics (especially sulfonamides)
  • Allopurinol
  • NSAIDs 1, 2
• Infections:
  • Herpes simplex virus
  • Mycoplasma pneumoniae 1

Diagnosis

Diagnosis is primarily clinical, based on:

• Characteristic clinical presentation with skin and mucosal involvement
• History of exposure to potential triggers
• Skin biopsy showing subepidermal cleavage 1

Histopathology reveals:

• 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

Pathophysiology

SJS/TEN is primarily a cell-mediated cytotoxic reaction against keratinocytes:

• Immune synapse composed of cytotoxic T cells with drug-specific HLA class I restriction
• Various cytotoxic proteins and cytokines involved:
  • Soluble granulysin
  • Perforin
  • Granzyme B
  • Interleukin-15
  • Fas ligand
  • Interferon-γ
  • Tumor necrosis factor-α 3

Management

Immediate Interventions

1. Stop the suspected culprit drug immediately 1
2. Refer to a specialized center with experience in managing SJS/TEN 1, 2
3. Transfer to a center with burn surgery, critical care, and dermatology capabilities 2

Supportive Care (Cornerstone of Management)

• Fluid and electrolyte management
• Wound care
• Nutritional support
• Pain management 1
• Airway and breathing stabilization
• Treatment of superimposed infections with broad-spectrum antibiotics 2

Specific Treatments

The following treatments may be considered, though their use remains controversial:

• Systemic corticosteroids: Commonly used but efficacy remains uncertain 3
• Immunomodulatory therapy:
  • Cyclosporine
  • TNF-α inhibitors (increasing evidence showing decreased mortality) 1, 3
• Intravenous immunoglobulins: May block Fas ligand-mediated apoptosis 4
• Antiviral therapy (acyclovir) for SJS associated with herpes simplex 1

Prognosis and Complications

Mortality

• SJS: Less than 10% mortality
• TEN: Up to 30% mortality 1

Acute Complications

• Sepsis
• Multiorgan failure 1

Long-term Sequelae

• Skin: Pigmentation changes, scarring
• Ocular: Vision impairment
• Mucosal: Oral, dental, respiratory, and urogenital problems 1
• Other: Nail deformities 1

Recurrence

• More common in children (up to 18% of cases)
• Particularly when triggered by infections that may recur
• Can be managed with prophylactic antiviral therapy in HSV-associated cases 1

Prevention

For patients with a history of SJS:

• Avoid all medications that previously triggered the reaction
• Consider genetic testing for HLA associations with certain drug reactions
• For recurrent HSV-associated SJS, consider prophylactic antiviral therapy 1

Pitfalls and Caveats

1. Delayed recognition: Early recognition is critical for improved outcomes
2. Failure to discontinue culprit medication: Immediate withdrawal is essential
3. Inadequate supportive care: Requires multidisciplinary approach in specialized centers
4. Underestimating severity: Even cases with limited skin involvement can have severe mucosal involvement
5. Inappropriate outpatient management: Outpatient treatment is unacceptable for SJS/TEN 4