Culprit Medications and Risk Factors Associated with Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Population-Based Nested Case–Control Study

Abstract

Objective Our objective was to describe the incidence of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in a large unselected cohort, to validate the culprit drugs involved and the frequency of SJS/TEN for each drug, and to analyze the clinical risk factors for SJS/TEN. Methods Using the computerized database of Clalit Health Services, we identified all adult patients with a new SJS/TEN diagnosis between 1 January, 2008 and 30 June, 2019 and validated each case. Cumulative incidence of SJS/TEN for each culprit drug was calculated by dividing the number of valid cases by the total number of new users of the drug in the study period. Using risk-set sampling, 20 controls were matched to each case by sex and age on the index date for a nested casecontrol analysis. Multivariable conditional logistic regression was used to estimate the odds ratio and 95% confidence interval for the association of incident SJS/TEN with chronic diseases. Results We identified 87 adult cases of true/probable SJS/TEN between 1 January, 2008 and 30 June, 2019. Culprit drugs [with ALDEN scores ascertained as at least probable (≥ 4)] associated with the highest absolute risks were phenytoin, lamotrigine, and allopurinol with 3.56, 2.82, and 1.10 SJS/TEN cases/10,000 new users, respectively. Additional drugs with mean ALDEN scores ≥ 4 were sunitinib, sulfasalazine, carbamazepine, etoricoxib, etodolac, and cefuroxime, cumulative incidence: 13.57, 0.72, 0.32, 0.05, 0.02, and 0.02/10,000 new users, respectively. Previous diagnosis of systemic lupus erythematosus, psoriasis, previous drug allergies, epilepsy, malignancy, history of cerebrovascular accident, and history of diabetes mellitus were associated with an increased risk for SJS/TEN, odds ratios (

Risk factors and drugs that trigger the onset of Stevens–Johnson syndrome and toxic epidermal necrolysis: A population-based cohort study using the Shizuoka Kokuho database

“…In this study, we showed that 3 underlying diseases were associated with the development of SJS/TEN, namely systemic autoimmune disease and type 2 diabetes, as previously shown, 9 and peripheral vascular disease. In autoimmune disease, disturbed regulatory immunity augments cytotoxic reactions, which are associated with the induction of SJS/TEN.…”

“…Patients with SJS/TEN were defined as those with a medical claim with the disease code, which is the code used for billing medical fees for SJS/TEN (SJS: 6951003, TEN: 8845586). In this study, the candidate risk factors were age, sex, and the presence of comorbidities using the Elixhauser comorbidity index 20 and previously reported risk factors and candidate risk factors 8 , 9 , 21 , 22 (as defined using the ICD-10, Supplementary Table I, available via Mendeley at https://data.mendeley.com/datasets/yd63zxsgxy/1 ).…”

“… 6 , 7 Previous studies have reported risk factors associated with SJS/TEN, such as skin disease, liver disease, 8 diabetes, psoriasis, systemic lupus erythematosus, and previous drug allergies. 9 However, these previous studies did not examine the risk factors using a cohort in the general population as a riskset.…”

Stevens-Johnson Syndrome From Combined Allopurinol and Angiotensin-Converting Enzyme Inhibitors: A Narrative Review

“…Patients ceased the suspected drug upon SJS/TEN diagnosis in this study [ 20 ]. Other studies found the culprit drugs that were at high risk for triggering SJS were phenytoin, lamotrigine, and allopurinol [ 21 , 22 ]. An increased risk for developing SJS is associated with factors such as age, autoimmune disease, previous drug allergies, epilepsy, or a history of cerebrovascular accident [ 23 - 25 ].…”

Macrophage Activation Syndrome Complicated by Toxic Epidermal Necrolysis Following SARS-CoV-2 mRNA Vaccination

“…Although our patient responded appropriately to MAS treatment, she was exposed to multiple medications during the early, uncontrolled phase of MAS, which may have increased her risk of developing TEN. The presence of inflammatory disorders, such as autoimmune disease, increases the risk of TEN, particularly in the early stages before the disease is controlled [ 4 ]. Inflammation promotes antigen presentation and activation of T cells and NK cells, leading to drug-specific CD8 + T cell and NK cell-mediated epidermal damage [ 5 ].…”