What disorder is most commonly associated with Stevens-Johnson syndrome?

Herpes Simplex Infection is Most Commonly Associated with Stevens-Johnson Syndrome

Herpes simplex infection is the most commonly associated disorder with Stevens-Johnson syndrome (SJS), particularly in children where infections rather than medications are the predominant triggers.

Etiology of Stevens-Johnson Syndrome

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent a spectrum of severe mucocutaneous reactions characterized by widespread epithelial keratinocyte apoptosis and necrosis. While both conditions share similar pathophysiology, they differ in the extent of skin detachment:

• SJS: <10% body surface area involvement
• SJS/TEN overlap: 10-30% body surface area involvement
• TEN: >30% body surface area involvement

Common Causes by Population:

1. Children and Young People:

   • Infections (predominant cause - up to 50% of cases) 1
     • Herpes simplex virus (most common infectious trigger)
     • Mycoplasma pneumoniae (up to 50% of infection-related cases)
   • Medications (less common than in adults)

2. Adults:

   • Medications (predominant cause) 1
     • Anticonvulsants
     • Antibiotics (particularly sulfonamides)
     • Allopurinol
     • NSAIDs (particularly oxicams)

Why Herpes Simplex is the Most Common Trigger

The British Association of Dermatologists' guidelines clearly identify that in children, infections rather than drugs are the most common precipitants of SJS 1. Among these infections, herpes simplex virus is particularly significant:

1. Recurrence patterns: SJS recurrence is more common in children (up to 18% of cases), primarily because infections like herpes simplex can recur, whereas drug-induced cases can be prevented by avoiding the culprit medication 1.

2. Pathophysiological mechanism: Herpes simplex triggers immune-mediated cytotoxic reactions against keratinocytes, leading to the characteristic epidermal necrolysis seen in SJS 2.

3. Clinical distinction: Herpes-associated SJS has been recognized as a distinct clinical entity, with specific management approaches including acyclovir and corticosteroids 2.

Differential Diagnosis

When considering the association between various disorders and SJS, it's important to distinguish from other conditions:

• Systemic lupus erythematosus (SLE): While SLE can present with mucocutaneous manifestations, it is not a common trigger for true SJS.

• Sarcoidosis: Not typically associated with SJS.

• Herpes zoster infection: Less commonly associated with SJS compared to herpes simplex.

• Celiac disease: Not a recognized trigger for SJS.

Clinical Presentation of SJS

SJS typically presents with:

• Prodromal symptoms (fever, malaise, upper respiratory symptoms)
• Painful cutaneous and mucosal lesions
• Ocular inflammation (may precede skin manifestations)
• Widespread epidermal detachment
• Positive Nikolsky sign (epidermis slides with gentle lateral pressure)

Management Considerations

For SJS associated with herpes simplex:

• Early recognition and prompt management are critical
• Consider antiviral therapy (acyclovir) for active herpes infection
• Supportive care remains the cornerstone of management
• Multidisciplinary approach involving dermatology, ophthalmology, and intensive care as needed

Key Pitfalls to Avoid

1. Misdiagnosis: Confusing SJS with other bullous disorders like staphylococcal scalded skin syndrome (SSSS), which lacks mucosal involvement.

2. Delayed recognition: Cutaneous pain is an early feature that should prompt consideration of SJS.

3. Overlooking infectious triggers: While medications are often blamed, particularly in children, infectious causes like herpes simplex should be actively investigated.

4. Failure to anticipate recurrence: Patients with herpes-associated SJS are at higher risk for recurrence and may benefit from prophylactic antiviral therapy.