Can lamotrigine cause Stevens-Johnson syndrome?

Lamotrigine and Stevens-Johnson Syndrome

Yes, lamotrigine is a known cause of Stevens-Johnson syndrome (SJS) and is specifically listed as one of the most common drugs causing SJS/toxic epidermal necrolysis (TEN) in clinical guidelines. 1

Risk Factors and Incidence

• Lamotrigine is recognized as a high-risk medication for SJS/TEN with an estimated frequency of approximately 1/1000 2
• The risk is highest during the first 8 weeks of treatment 3
• The relative risk of developing SJS/TEN within the first 8 weeks of lamotrigine use is approximately 25 times higher than in the general population 3
• Risk factors that increase the likelihood of lamotrigine-induced SJS include:
  • Rapid dose escalation 4
  • Concomitant use of valproic acid 5
  • Genetic predisposition (HLA-B*15:02 in Han Chinese populations) 1

Clinical Presentation

SJS/TEN due to lamotrigine typically presents with:

• Prodromal symptoms: fever, malaise, and upper respiratory symptoms
• Mucocutaneous manifestations:
  • Well-defined erythematous lesions
  • Targetoid macular lesions
  • Oral erosions and mucosal involvement
  • Progressive skin detachment (varies by severity)
• Symptoms typically begin 3-28 days after starting lamotrigine 2

Management Approach

1. Immediate discontinuation of lamotrigine upon first signs of rash or mucosal involvement 4
2. Assessment of severity using SCORTEN (SCORe of Toxic Epidermal Necrolysis) 1
3. For severe cases with extensive epidermal detachment (>10% BSA):
   • Admission to specialized intensive care unit or burn center 1
   • Multidisciplinary team approach including dermatology, intensive care, ophthalmology, and specialist nursing 1
4. Supportive care:
   • Fluid management
   • Wound care
   • Pain control
   • Monitoring for complications

Prevention Strategies

• Start with low doses of lamotrigine and follow recommended slow titration schedules 6
• Avoid concurrent use with valproic acid when possible 5
• Consider HLA-B*15:02 screening before initiating treatment in patients of Han Chinese descent 1
• Patient education about early warning signs and symptoms
• Regular monitoring during the initial treatment period

Important Caveats

• Lamotrigine should not be reintroduced after SJS/TEN has occurred due to risk of recurrence
• Cross-reactivity with other aromatic anticonvulsants (carbamazepine, phenytoin) may occur
• The risk of SJS/TEN with lamotrigine appears higher than with many other anticonvulsants 2
• Documentation and reporting to pharmacovigilance authorities is essential 1

For patients requiring mood stabilization or seizure control who have experienced lamotrigine-induced SJS/TEN, alternative medications should be considered based on the specific indication, with careful monitoring for cross-reactivity.