Lamotrigine Emerging as a Driver of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: An 8-Year Retrospective Study.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) represent severe manifestations of a potentially life-threatening spectrum defined by a desquamating rash of the skin and mucous membranes. This study was prompted by the observed increase in the off-label use of lamotrigine as a causal agent in SJS/TEN in our regional burn center.

Methods: A retrospective cohort of 48 patients presenting to the Connecticut Burn Center from 2015-2022 with suspicion for SJS/TEN were reviewed for age, sex, causative drug, presenting symptoms, hospital course, biopsy confirmation, length of stay, comorbidities, and 30-day mortality. Descriptive statistical analysis was conducted to identify trends in causative agent, clinical presentation, and mortality.

Results: Thirty patients in our cohort received a final diagnosis of SJS/TEN. While antibiotics remain the most frequent cause of SJS/TEN across the study period (33.3 %, n = 10), the incidence of cases attributable to lamotrigine increased from 1 case between 2015 and 2018 (6.7 %) to 6 cases between 2019 and 2022 (40 %). In 2020 alone, 50 % of all cases were attributable to lamotrigine (n = 4). Of the patients where lamotrigine was implicated, 71.4 % (n = 5) were prescribed lamotrigine for off-label use in the treatment of non-bipolar mood disorders. The average lamotrigine-associated SJS/TEN patient was younger (p < 0.001), had fewer comorbidities, and was more likely to be female than the general SJS/TEN population.

Conclusion: Off-label use of lamotrigine is emerging as a major driver of SJS/TEN with notable changes in patient demographics. Further research is necessary to understand how changing trends in the patient population will impact clinical course and optimal management.