When did Steven's Johnson's syndrome (SJS) become a separate entity from erythema multiforme (EM) with mucosal involvement?

Historical Separation of Stevens-Johnson Syndrome from Erythema Multiforme with Mucosal Involvement

Stevens-Johnson Syndrome (SJS) was definitively recognized as a separate entity from erythema multiforme with mucosal involvement in 1993, when the first international consensus classification was published. 1

Evolution of Classification

The distinction between these conditions has evolved significantly over time:

Pre-1993 Classification

• SJS was historically considered to be a severe form of erythema multiforme with mucosal involvement
• The terminology was inconsistent and overlapping, with terms like "erythema multiforme major" often used interchangeably with SJS 2
• This created significant diagnostic confusion and treatment inconsistencies

The 1993 Consensus Classification

• The first international consensus classification in 1993 formally separated these conditions based on:
  • Morphology of individual lesions
  • Pattern of distribution
  • Etiology
  • Clinical course

Key Differences Established by the Classification

1. Morphological Differences:

   • EM: Typical or raised atypical target lesions primarily on extremities and/or face
   • SJS: Flat atypical targets or purpuric macules that are widespread or distributed on the trunk 3

2. Etiological Differences:

   • EM: Primarily caused by infections (especially herpes simplex virus and Mycoplasma pneumoniae)
   • SJS: Predominantly triggered by drugs (80% of cases) 3

3. Clinical Course Differences:

   • EM: Generally self-limited with good recovery and rare long-term complications
   • SJS: Higher mortality and significant risk of long-term sequelae 4

Evidence Supporting the Separation

A landmark 1995 study by Bastuji-Garin et al. provided strong evidence for this separation. Their research showed:

• A strong correlation (K = 0.87, P < .001) between clinical classification and probable cause
• EM was mostly related to herpes (17 of 28 cases) or other non-drug causes (8 of 28)
• EM was rarely related to drugs (only 3 of 28 cases)
• SJS was nearly always related to drugs (28 of 33 cases) and never to herpes 3

Current Understanding

The British Association of Dermatologists' guidelines (2019) clearly state:

• "Erythema multiforme is regarded as a reactive mucocutaneous disorder that is distinct from SJS/TEN."
• "EMM does not progress to SJS/TEN; typically, patients are constitutionally well, make a good recovery and are rarely affected by long-term complications." 4

Clinical Implications of the Separation

The separation of these entities has important implications for:

• Prognosis: SJS has significantly higher mortality than EM with mucosal involvement
• Treatment approach: EM generally requires only supportive care, while SJS may benefit from immunomodulatory therapy 1
• Follow-up care: SJS patients require more intensive monitoring for long-term sequelae, particularly ocular complications 5

Common Pitfalls in Diagnosis

• Historical literature before 1993 often used these terms interchangeably
• Some older case reports and studies may have misclassified these conditions
• The British Association of Dermatologists notes that "previous publications and reports of SJS/TEN in children and young people may have been biased by misclassification of diseases" 4

The formal separation of these conditions in 1993 has significantly improved diagnostic accuracy, treatment approaches, and our understanding of the distinct pathophysiological mechanisms underlying each condition.