What is Stevens-Johnson syndrome?

Stevens-Johnson Syndrome (SJS)

Stevens-Johnson Syndrome (SJS) is a rare, severe mucocutaneous reaction characterized by blistering and epithelial sloughing of skin and mucous membranes, usually triggered by medications or infections, with potentially life-threatening complications and long-term sequelae. 1

Clinical Features

SJS presents with:

• Prodromal phase: Fever, malaise, and upper respiratory tract symptoms typically precede the eruption by several days 1

• Cutaneous manifestations:

  • Early, prominent cutaneous pain (an important warning sign) 1
  • Atypical target lesions or purpuric macules, initially on upper torso, proximal limbs and face 1
  • Progressive spread to trunk and distal limbs, often involving palms and soles 1
  • Positive Nikolsky sign (epidermis slides over dermis with gentle lateral pressure) 1
  • Blistering with flaccid bullae as necrotic epidermis separates from dermis 1
  • Epidermal detachment affecting <10% of body surface area (BSA) in SJS 1, 2

• Mucosal involvement: Early and prominent involvement of mucous membranes of eyes, mouth, nose, and genitalia, leading to erosive and hemorrhagic mucositis 1

Disease Spectrum

SJS is part of a spectrum of severity:

• SJS: <10% BSA epidermal detachment
• SJS/TEN overlap: 10-30% BSA epidermal detachment
• Toxic Epidermal Necrolysis (TEN): >30% BSA epidermal detachment 1, 2

Etiology

The most common causes include:

1. Medications: Primary cause in adults 1

   • Anticonvulsants
   • Antibiotics (particularly sulfonamides)
   • Allopurinol
   • NSAIDs 3

2. Infections: More common trigger in children 1, 2

   • Herpes Simplex Virus
   • Mycoplasma pneumoniae 2

Pathophysiology

SJS/TEN is characterized by widespread epithelial keratinocyte apoptosis and necrosis initiated by:

• Drug-induced cytotoxic T lymphocytes 1
• Granulysin as the key mediator of apoptosis 1
• Proapoptotic molecules including TNF-α, IFN-γ, and inducible nitric oxide synthase 1, 4

Diagnosis

Diagnosis is primarily clinical, supported by:

• Characteristic clinical presentation with skin and mucosal involvement
• Skin biopsy showing subepidermal cleavage (to differentiate from similar conditions) 1
• History of exposure to potential triggers (medications or infections) 1

Differential Diagnosis

Important conditions to distinguish from SJS include:

• Staphylococcal Scalded Skin Syndrome (SSSS) - lacks mucosal involvement 1
• Erythema Multiforme Major (EMM) - typically caused by HSV with target lesions on extremities 2
• Immunobullous disorders (pemphigus, pemphigoid) 1

Management

Management requires a multidisciplinary approach:

1. Immediate interventions:

   • Stop the suspected culprit drug immediately 1, 2
   • Refer to specialized center with experience in managing SJS/TEN 1, 5
   • Transfer to burn unit or ICU for severe cases (>10% BSA involvement or with comorbidities) 1

2. Supportive care (cornerstone of management):

   • Fluid and electrolyte management
   • Wound care
   • Nutritional support
   • Pain management 2, 5

3. Specific treatments:

   • No consensus on immunomodulatory therapy 1
   • Systemic corticosteroids remain controversial - may help in early stages but increase infection risk 3
   • Cyclosporine and TNF-α inhibitors show promise in reducing mortality 4
   • For infection-triggered SJS (e.g., HSV), appropriate antimicrobial therapy 2

4. Specialized care:

   • Ophthalmology consultation for ocular involvement 1, 2
   • Multidisciplinary team approach 1

Complications and Prognosis

• Mortality: <10% for SJS, rising to 30% for TEN 1
• Acute complications: Sepsis, multiorgan failure 1, 5
• Long-term sequelae:
  • Skin: Pigmentation changes, scarring
  • Ocular: Vision impairment, blindness
  • Mucosal: Oral, dental, respiratory, and urogenital problems 1, 3

Recurrence Risk

Recurrence is more common in children (up to 18% of cases), particularly when triggered by infections that may recur 1, 2. Prophylactic strategies may be considered for recurrent HSV-associated SJS 2.

Key Pitfalls to Avoid

• Delayed recognition of early warning signs (cutaneous pain, mucosal involvement)
• Failure to promptly discontinue the culprit medication
• Inadequate monitoring for systemic complications
• Lack of appropriate specialist referral
• Insufficient long-term follow-up for sequelae 5, 6