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

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S121-S121
Author(s):  
Robert Africa ◽  
Keyan Mobli ◽  
Taylor Hallman ◽  
Marc Schober ◽  
Mark Jason Torres ◽  
...  
Keyword(s):  
High Risk ◽  
Toxic Epidermal Necrolysis ◽  
Research Network ◽  
Stevens Johnson Syndrome ◽  
Global Health Research ◽  
Control Group ◽  
Factors Associated ◽  
Immune Mediated ◽  
Johnson Syndrome ◽  
Icd 10

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.

21 Navigating Controversial Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome Using Large Database Analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S19-S19
Author(s):  
Deepak K Ozhathil ◽  
Nicholas A Gore ◽  
Kayla Y Nguyen ◽  
George Golovko ◽  
Judy Pham ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Risk Reduction ◽  
Mortality Risk ◽  
Survival Advantage ◽  
Research Network ◽  
Stevens Johnson Syndrome ◽  
Control Group ◽  
Type Ii ◽  
Systemic Steroids ◽  
Johnson Syndrome

Abstract Introduction Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are part of a spectrum of autoimmune conditions, which cause epidermal detachment and keratinocyte necrosis. Due to the rare incidence, a dramatic heterogeneity in treatment algorithms and prolonged discussion of controversial therapies has ensued. We queried a large national data network to better understand how these therapies are actually implemented and the relative impact on survival. Methods The TriNetX Global Health Research Network (41 healthcare organizations) was queried using ICD-10 codes (L51.1 - 51.3) to identify patients diagnosed with SJS or TENS from 2000 to 2020. A treatment frequency map was constructed to determine the most common treatment groupings, and cohorts were indexed based on the most frequent isolated and combined therapy algorithms: systemic steroids (SS), diphenhydramine (DH), cyclosporine (CS), intravenous immunoglobulin (IVIG) and tumor necrosis factor alpha inhibitors (TNFαi). Cohorts were case matched for demographics against a restricted control group (RC; patients who did not receive any of the above-mentioned therapies) and an unrestricted control group (UC, all patients diagnosed with SJS or TENS) to evaluate mortality risk, survival probability, and to uncover Type II error. Results Cohorts were UC (6,196), RC (2,248), SS+DH (3,459), SS (1,269), SS+CS (1,554), DH (479), CS (52), IVIG (10) and TNFi (10). The treatment map showed 36.3% of patients did not receive any of the listed therapies. Of those that did 48.2% initially got SS, 24.3% got DH, 15.4% got SS+DH and 3% got SS+CS. Patients who received SS had a 8.51% mortality risk and 2.84% risk reduction compared to UC (p = 0.017). However, the Hazard Ratio (HR) was 0.80 (95% CI: 0.57, 1.23) showing no survival advantage. Compared to RC risk reduction decreased to 0.47% (p = 0.667). SS+DH showed a risk reduction of 1.13% compared to UC (p = 0.113; HR 0.89, 95% CI: 0.69, 1.16), but this advantage resolved when compared to RC. Similarly, SS+CS had a risk reduction of 2.12% compared to UC (p = 0.039; HR 0.80, 95% CI: 0.58, 1.09), which decreased to 0.07% (p = 0.947) when compared to RC. DH and CS had no significant risk reduction (p = 0.25 - 1.00) or survival advantage. IVIG and TNFαi were underpowered for analysis. Conclusions The most common treatments for patients diagnosed with SJS or TENS are systemic steroids, diphenhydramine, or a combination of the two. Unfortunately, none of the above therapies confer a significant survival advantage. Furthermore, some therapies raised concern for Type II errors when the control group is not adjusted for alternative therapies.

scholarly journals Stevens-Johnson syndrome and toxic epidermal necrolysis: a review

2016 ◽  
Vol 62 (5) ◽  
pp. 468-473 ◽  
Author(s):  
Anthony Wong ◽  
Andrey Augusto Malvestiti ◽  
Mariana de Figueiredo Silva Hafner
Keyword(s):  
High Risk ◽  
Early Diagnosis ◽  
Toxic Epidermal Necrolysis ◽  
Stevens Johnson Syndrome ◽  
Drug Reactions ◽  
Johnson Syndrome ◽  
Life Threatening ◽  
Inflammatory Drugs ◽  
Cutaneous Drug Reactions ◽  
Perilesional Skin

SUMMARY Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are uncommon, acute and potentially life-threatening adverse cutaneous drug reactions. These pathologies are considered a hypersensitivity reaction and can be triggered by drugs, infections and malignancies. The drugs most often involved are allopurinol, some antibiotics, including sulfonamides, anticonvulsants such as carbamazepine, and some non-steroid anti-inflammatory drugs (NSAIDs). Necrosis of keratinocytes is manifested clinically by epidermal detachment, leading to scalded skin appearance. The rash begins on the trunk with subsequent generalization, usually sparing the palmoplantar areas. Macular lesions become purplish, and epidermal detachment occurs, resulting in flaccid blisters that converge and break, resulting in extensive sloughing of necrotic skin. Nikolsky's sign is positive in perilesional skin. SJS and TEN are considered to be two ends of the spectrum of one disease, differing only by their extent of skin detachment. Management of patients with SJS or TEN requires three measures: removal of the offending drug, particularly drugs known to be high-risk; supportive measures and active interventions. Early diagnosis of the disease, recognition of the causal agent and the immediate withdrawal of the drug are the most important actions, as the course of the disease is often rapid and fatal.

Stevens–Johnson syndrome and toxic epidermal necrolysis: a 10-year experience in a burns unit

2021 ◽  
Vol 30 (6) ◽  
pp. 492-496
Author(s):  
Khosrow S Houschyar ◽  
Christian Tapking ◽  
Mimi R Borrelli ◽  
Ina Nietzschmann ◽  
Behrus Puladi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Toxic Epidermal Necrolysis ◽  
Retrospective Review ◽  
Mortality Rates ◽  
Intravenous Immunoglobulins ◽  
Stevens Johnson Syndrome ◽  
Control Group ◽  
High Dose ◽  
Johnson Syndrome ◽  
Patient Reported

Objective: Stevens-Johnson syndrome (SJS) and its more severe counterpart, toxic epidermal necrolysis (TEN), are skin hypersensitivity reactions defined by epidermal blistering and necrosis. The exact pathophysiology of SJS/TEN is yet to be deciphered, but a number of risk factors have been identified including adverse drug reactions. The diagnosis of SJS/TEN is made on a clinical basis, and treatment consists of supportive care and occasionally immunosuppressants, such as cyclosporin, high-dose intravenous immunoglobulins and/or corticosteroids. Mortality rates can reach 20–25% in adults but are reduced with early intervention. To identify optimal treatment regimens, to better understand the patient cohort affected, and to help identify key risk factors for mortality, we report our experience with the treatment and management of SJS/TEN patients. Methods: A retrospective review of consecutive patients with SJS and/or TEN admitted to a single burns centre in Germany, between 2008 and 2018, was conducted. The primary outcomes of demographics, clinical course, treatment and patient-reported outcomes were recorded and compared with a control group of patients with burns without a diagnosis of SJS/TEN. Results: A total of 23 patients with SJS/TEN met the inclusion criteria: 17 (74%) with TEN; four (17%) with SJS/TEN overlap; and two (9%) with SJS. Of the patients, 14 (61%) were female and nine (39%) were male. Patient age ranged from 32–78 years (mean: 52 years). A matched cohort of 23 patients with burns served as the control group. All patients received standard of care with a multidisciplinary team. Compared with the control group, SJS/TEN patients had higher mortality rates (n=6, 26% versus n=8, 35%, respectively). The average age of death was 69 years in SJS/TEN patients versus 63 years in control group patients. Age and SCORTEN scores were significant predictors of mortality. Conclusions: SJS and TEN are rare but extreme reactions of the skin and mucosa, associated with high disease mortality rates. This 10-year single-centre retrospective review contributes to the bank of information for reviews evaluating the management of SJS/TEN patients.

Human Leukocyte Antigen Gene Testing and Carbamazepine-Induced Toxic Epidermal Necrolysis: A Study of Pediatric Practice

2020 ◽  
pp. 120347542095242
Author(s):  
Jessica M.S. Asgarpour ◽  
Lauren M. Lam ◽  
Tina K. Vogel ◽  
Helly R. Goez ◽  
Loretta Fiorillo
Keyword(s):  
At Risk ◽  
High Risk ◽  
Toxic Epidermal Necrolysis ◽  
Therapeutic Interventions ◽  
Stevens Johnson Syndrome ◽  
Drug Induced ◽  
Realistic Potential ◽  
Gene Testing ◽  
Johnson Syndrome ◽  
Standard Of Practice

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening drug-induced dermatologic conditions. SJS/TEN occurs in 1-10 per 10 000 patients taking carbamazepine (CBZ) (Pratt VM, McLeod HL, Rubinstein WS et al. Medical Genetics Summaries. National Center for Biotechnology Information US; 2018: 1-527). The development of SJS/TEN is associated with variable drug metabolism and presence of an at-risk HLA haplotype. HLA-B*15:02 and HLA-A*31:01 haplotypes can produce a hyperimmune response in the setting of CBZ use in patients of Asian and European descent, respectively (Schneider JA, Cohen PR. Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017; 34:1235-1244). Objective The US Food and Drug Administration (FDA) and the Canadian pharmacogenomics Network for Drug Safety (CPNDS) recommend that patients with high-risk ethnic backgrounds should be genetic tested before initiating CBZ (Sukasem C, Chaichan C, Nakkrut T et al. Association between HLA-B Alleles and Carbamazepine-induced maculopapular exanthema and severe cutaneous reactions in Thai patients. Journal of Immunology Research. 2018; 1-11).We sought out to assess the awareness of this in prescribing practitioners and their standard of practice. Materials and methods We created a 15-question survey and distributed to pediatric neurologists and pediatricians at the University of Alberta. We hypothesized that there was a discordance between the standard of practice and the recommendation by the FDA and CPNDS. Results The survey results indicated a lack of awareness of the at-risk ethnicities for CBZ-induced SJS/TEN. HLA gene testing was rarely done prior to initiation of CBZ in high-risk patients. In addition, there was a lack of awareness for standard of care for genetic testing in Canada and worldwide. Conclusions Our results demonstrate an evident gap between current prescriber practices and existing FDA and CPNDS recommendations to screen for HLA genotypes. We hope that this study captures the realistic potential to improve patient outcomes.

A European study of HLA-B in Stevens???Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs

2008 ◽  
Vol 18 (2) ◽  
pp. 99-107 ◽  
Author(s):  
Christine Lonjou ◽  
Nicolas Borot ◽  
Peggy Sekula ◽  
Neil Ledger ◽  
Laure Thomas ◽  
...  
Keyword(s):  
High Risk ◽  
Toxic Epidermal Necrolysis ◽  
Stevens Johnson Syndrome ◽  
European Study ◽  
Johnson Syndrome

Predictive Factors Associated With Acute Ocular Involvement in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

2015 ◽  
Vol 160 (2) ◽  
pp. 228-237.e2 ◽  
Author(s):  
Chie Sotozono ◽  
Mayumi Ueta ◽  
Eiji Nakatani ◽  
Amane Kitami ◽  
Hideaki Watanabe ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Predictive Factors ◽  
Stevens Johnson Syndrome ◽  
Ocular Involvement ◽  
Factors Associated ◽  
Johnson Syndrome

scholarly journals The Link between HLA-B Alleles and Causative Drugs in Vietnamese Patients with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

2020 ◽  
Vol 8 (B) ◽  
pp. 395-400
Author(s):  
Tran Thi Huyen ◽  
Pham Dinh Hoa ◽  
Trinh Minh Trang ◽  
Nguyen Ba Khanh ◽  
Tran Ngoc Que ◽  
...  
Keyword(s):  
Traditional Medicine ◽  
Toxic Epidermal Necrolysis ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Control Group ◽  
Laboratory Findings ◽  
Cross Sectional ◽  
Leukocyte Antigens ◽  
Johnson Syndrome ◽  
Culprit Drug

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Human leukocyte antigens (HLA) may play an important role in the pathogenesis of SJS/TEN. AIMS: This study aims to identify HLA-B alleles in Vietnamese patients with SJS/TEN and to investigate the possible link between HLA-B alleles and causative drugs. MATERIALS AND METHODS: Sixty patients including SJS (30 patients) and TEN (30 patients) were enrolled in a cross-sectional descriptive study at two hospitals in Hanoi, Vietnam, from July 2018 to July 2019. Clinical features and laboratory findings were noted, HLA-B alleles were analyzed by the polymerase chain reaction (PCR)-sequence-specific oligonucleotide assay and LuminexTM Multiplex Technology. RESULTS: The most common HLA-B allele was HLA-B*15:02 (41.7%) followed by HLA-B*58:01 (25%) and HLA-B*46:01 (15%). Of the 25 patients possessing HLA-B*15:02 allele, culprit medicines were carbamazepine (13 patients; 52%), traditional medicine (two patients; 8%), and unknown drugs (seven patients; 28%). Of the 15 patients carrying HLA-B*58:01 allele, there were 13 patients whose offending medicine was allopurinol. Of the eight patients whose culprit drug was traditional medicine, there were 6 patients (75%) carrying HLA-B*51:02. Patients who carry HLA-B*15:02 were found to have 4 times higher risk of developing carbamazepine-induced SJS/TEN as compared with the tolerant control group (OR=4.17; 95% CI=2.07–8.37; p < 0.001). CONCLUSION: HLA-B*15:02 was the most common HLA-B allele in Vietnamese patients with SJS/TEN. In traditional medicine-induced SJS/TEN patients, HLA-B*51:02 allele might play an important role. The link between the HLA-B genotypes and causative drugs may suggest physicians to avoid risk medications for certain patients.

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