545 Pharmacologic and Comorbid Factors Associated with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome

Abstract

Abstract Introduction Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis syndrome (TENS) share immune-mediated etiology for epidermal detachment and pharmacologic triggers. Both conditions are on a spectrum of diseases of varying severity, with TENS representing the graver end of the continuum. The demographics and comorbidities of this population remain relatively unknown due to their rare incidence. Comorbidities determine the causative drugs used, but also afford triggers for the autoimmune cascade resulting in SJS or TENS. We analyzed the trends of comorbid and pharmacologic risk factors associated with these diseases in over 3,000 patients. Methods We used the TriNetX Global Health Research Network from 2009–2020 to identify 3,515 patients diagnosed with SJS or TENS (ICD-10 codes L51.1–51.3). We then obtained annual demographic and comorbidity data. We indexed patients into cohorts that were prescribed a high-risk drug as previously reported in the literature to be associated with SJS and TENS development. Our control cohort consisted of patients that did not take these high-risk drugs. These cohorts were analyzed to identify the relative risk of developing SJS or TENS 4 to 56 days after taking a high-risk drug. Similarly, we excluded co-medication of the other high-risk drugs and compared these patients to our control group. Results The mean age was 46 with a female predominance (59.8%). The most common comorbidities were hypertension (20.2–21.3%), mood affective disorders (12.4–15.8%), or kidney disease (11.6–12.8%), and the prevalence of these have remained constant. Phenobarbital had the highest risk for these diseases (RR: 20.2, CI: 13.58–29.93), with carbamazepine second (RR: 14.1, CI: 8.68–22.85). After excluding other high-risk medication, phenobarbital continued to be associated with the highest risk (RR: 30.3, CI: 16.12–56.73), followed by phenytoin (RR: 25.3, CI: 13.51–47.53) and carbamazepine (RR: 24.7, CI: 13.74–46.34). Well reported triggers like sulfamethoxazole, allopurinol, and sertraline only represented moderate risk (RR: 7.7, CI: 6.11–9.83; RR: 5.2, CI: 2.77–9.73; RR: 1.7, CI: 0.90–3.16) even after excluding co-founding factors. Conclusions This study suggests that seizure disorder medications such as phenobarbital, carbamazepine, and phenytoin demonstrate the highest risk for developing SJS and TENS.