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.

scholarly journals Human leukocyte antigen B*0702 is protective against ocular Stevens–Johnson syndrome/toxic epidermal necrolysis in the UK population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gibran F. Butt ◽  
Ali Hassan ◽  
Graham R. Wallace ◽  
Shigeru Kinoshita ◽  
Sajjad Ahmad ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Toxic Epidermal Necrolysis ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Ocular Complications ◽  
Leukocyte Antigen ◽  
Asian Populations ◽  
Risk Alleles ◽  
Johnson Syndrome ◽  
The Uk

AbstractStevens–Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) are part of a disease continuum of vesiculobullous mucocutaneous reactions affecting the skin and mucous membranes including the ocular surface. Manifestations of disease range from mild dry eye to progressive conjunctival cicatrisation, limbal epithelial stem cell failure and corneal blindness. In Far Eastern and South East Asian populations where SJS/TEN is prevalent, numerous human leukocyte antigen (HLA) gene variants at the A, B and C loci have been identified as risk factors for developing SJS/TEN with severe ocular complications (SOC). By contrast, the incidence of SJS/TEN with SOC in European countries is relatively low. To date, ocular SJS/TEN risk altering alleles have not been widely investigated in European populations. In this study, we analysed the association of HLA -A, -B and -C alleles with SJS/TEN in 33 patients residing in the UK with age matched controls. The data showed statistically significant novel negative allele association with HLA-B*0702 and a trend with HLA-C*0702 in the patient group, indicating these alleles are protective. Further characterisation of protective and risk alleles in other ethnic groups is required to fully elucidate the putative role of these alleles in the susceptibility of SJS/TEN with or without severe ocular complications in patients in the UK.

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.

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.

Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis

2017 ◽  
Vol 74 (9) ◽  
pp. e183-e192 ◽  
Author(s):  
Xingang Li ◽  
Zhigang Zhao ◽  
Shu-Sen Sun
Keyword(s):  
Human Leukocyte Antigen ◽  
Toxic Epidermal Necrolysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Strong Association ◽  
Human Leukocyte ◽  
Stevens Johnson Syndrome ◽  
Leukocyte Antigen ◽  
Johnson Syndrome ◽  
Population Controls

Abstract Purpose The association between human leukocyte antigen (HLA) variants and allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) was evaluated through a pooled analysis of published studies. Methods A comprehensive search was performed in multiple databases, including PubMed, MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials, and Science Direct. Studies investigating the association between HLA alleles with allopurinol-induced SJS or TEN were retrieved, and the data were independently extracted. The overall odds ratios (ORs) with corresponding 95% confidence intervals were calculated to determine the association between the presence of HLA variant in at least one allele and allopurinol-induced SJS or TEN. To test the robustness of the meta-analysis results, a sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies. The fixed-effects and random-effects models were used to pool the collected data. Results A total of 4 studies with 81 allopurinol-induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or population controls (general population) were identified. SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls. All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results. Conclusion A strong association was found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or TEN, especially in an Asian population.

scholarly journals Analisis Cost of Illness Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN)

2020 ◽  
Vol 7 (1) ◽  
pp. 84
Author(s):  
Qarriy Aina Urfiyya ◽  
Dyah Aryani Perwitasari ◽  
Sri Awalia Febriana
Keyword(s):  
Linear Regression ◽  
Length Of Stay ◽  
Toxic Epidermal Necrolysis ◽  
Cost Of Illness ◽  
Stevens Johnson Syndrome ◽  
Cross Sectional ◽  
Total Cost ◽  
Median Total Cost ◽  
Johnson Syndrome ◽  
Cross Sectional Design

ABSTRAK SJS/TEN merupakan reaksi yang melibatkan kulit dan mukosa yang berat dan mengancam jiwa. SJS dan TEN merupakan kejadian yang jarang terjadi, yaitu 1,4 – 12,7 kasus per 1 juta orang per tahun mengalami SJS dan TEN, dengan angka mortalitas 5% pada SJS dan 30-35% pada TEN. Obat merupakan penyebab utama SJS (50-80% dari kasus) dan TEN (80%). Tujuan: Mengetahui median total biaya per hari pasien SJS/TEN, serta pengaruh lama rawat inap terhadap total biaya SJS/TEN. Penelitian observasional analitik dengan sudut pandang masyarakat. Pengambilan data secara retrospektif menggunakan total sampling pasien rawat inap SJS dan TEN di RSUP Dr. Sardjito Yogyakarta tahun 2014-2018. Analisis data dengan menghitung median (range) dan regresi linear pada SPSS IBM versi 22.0 untuk mengetahui pengaruh lama rawat inap terhadap biaya SJS/TEN. Terdapat 29 pasien yang dianalisis. Median total biaya per hari pasien SJS/TEN Rp 1.139.963 (Rp 665.294-Rp 8.776.895), dengan Rp 1.139.963 (Rp 740.267-Rp 8.776.895) pada SJS dan Rp 1.166.084 (Rp 665.294-Rp 1.514.607) pada TEN. Hasil signifikansi uji regresi linear lama rawat inap terhadap total biaya SJS/TEN adalah 0,093 (p>0,05). Median biaya per hari SJS/TEN adalah Rp 1.139.963 (Rp 665.294-Rp 8.776.895), dan lama rawat inap tidak mempengaruhi total biaya SJS/TEN.  Kata Kunci—Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, analisis biaya, cost of illness  ABSTRACT SJS/TEN is a reaction that involves heavy and life-threatening skin and mucosa. SJS and TEN are rare events, 1,4 – 12,7 cases per 1 million people per year experiencing SJS and TEN, with a mortality rate of 5% in SJS and 30-35% in TEN. Drugs are the main cause of SJS (50-80% of cases) and TEN (80%). Objective: To determine the median total cost per day of SJS and TEN patients, and the effect of length of stay on the total cost of SJS/TEN. This study used an observational analytic with cross sectional design and societal perspective. The data was collected retrospectively using total sampling of SJS and TEN inpatients at RSUP Dr. Sardjito Yogyakarta in 2014-1018. The data was analyzed by calculating the median (range) and linear regression in IBM SPSS version 22.0, to determine the effect of length of stay on SJS/TEN costs . There were 29 patients analysed. The median total cost per SJS/TEN patient was IDR 1.139.963 (IDR 665.294-8.776.895), with IDR 1.139.963 (IDR 740.267-8.776.895) on SJS and IDR 1.166.084 (IDR 665.294-1.514.607) on TEN patients. The significance linear regression of the length of stay in SJS/TEN was 0,093 (p> 0,05). The median cost per SJS/TEN day was IDR 1.139.963 (665.294-8.776.895), and the length of stay does not affect the total cost of SJS/TEN. Keywords— Stevens Johnson Syndrome, Toxic Epidermal Necrolysis, cost analysis, cost of illness

741 Trends in Offending Medications in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis in a Large Academic Burn Center

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S202-S203
Author(s):  
Michael Duplisea ◽  
Lori Chrisco ◽  
Felicia N Williams ◽  
Rabia Nizamani ◽  
Sarah L Laughon ◽  
...  
Keyword(s):  
Toxic Epidermal Necrolysis ◽  
Severity Of Illness ◽  
Stevens Johnson Syndrome ◽  
Burn Center ◽  
Emerging Trends ◽  
Johnson Syndrome ◽  
Culprit Drug ◽  
Specialized Care ◽  
Burn Units ◽  
Causative Agents

Abstract Introduction Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a rare, severe mucocutaneous eruption caused by medications and resulting in diffuse epidermal detachment. Patients are often referred to burn units for specialized care. This study assesses trends in precipitating medications over 10 years at our Burn Center. Methods We performed a single-site, retrospective review at our burn center using the institutional burn registry and patient charts. Patients admitted from January 1, 2009 to December 31, 2018 identified as having SJS/TEN were eligible for inclusion. Demographics, comorbidities, diagnosis, treatment, inciting agents, and severity-of-illness score for TEN (SCORTEN) were evaluated. Statistical analysis was performed using the Mann Whitney U test using SAS version 9.4 (SAS Inc., Cary, NC). Results Biopsy-proven SJS, SJS/TEN overlap, or TEN was confirmed in 168 patients. Of these, 103 had a single identified offending drug. Of these patients, 36% had been exposed to sulfamethoxazole-trimethoprim (SMX-TMP), 11% to allopurinol, and 10% to lamotrigine. Trends in culprit drug by year are shown in Figure 1. The majority of SMX-TMP and penicillin cases occurred early in the period of study; lamotrigine and pembrolizumab cases occurred more recently. Patients exposed to allopurinol presented with higher SCORTENs than patients exposed to SMX-TMP, 2.9 vs 1.9, respectively (p&lt; 0.035). Conclusions SMX-TMP once accounted for a large portion of SJS and TEN cases at our center. In recent years, lamotrigine has become a more common offending drug, prescribed in our cohort for psychiatric indications. Also notable, in the past year we have treated three patients with TEN due to immunotherapy (pembrolizumab) for metastatic or unresectable cancer. Paralleling the increasing use of immunotherapy has been a rise of immune-related adverse events, including severe skin toxicities. Further study is warranted to determine what can be done to prevent SJS/TEN from occurring in patients treated with these drugs. Applicability of Research to Practice Understanding emerging trends in causative agents of SJS/TEN will allow the burn community to focus education efforts for providers who prescribe these medications frequently. The psychiatric and oncology communities may benefit from increased awareness of the risk of SJS/TEN in patients receiving lamotrigine and immunotherapy, respectively.

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