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Nivolumab is an immune checkpoint inhibitor acting on programmed cell death protein 1 (PD-1) that has been used to treat a growing number of malignancies. Cutaneous side effects are common with nivolumab treatment, though they are typically self-limited. Here we present a case of persistent lichenoid dermatitis in a patient treated with nivolumab for renal cell cancer. The patient then developed Stevens-Johnson syndrome 9 months after initiation of nivolumab, with no other identifiable offending medication in the interim. Although an unusual presentation, a growing number of cases have reported delayed Stevens-Johnson syndrome/toxic epidermolytic necrosis-like reactions to immune checkpoint inhibitors. Awareness of this phenomenon is imperative for prompt recognition and treatment of potentially life-threatening cutaneous side effects.

We report three cases of methotrexate (MTX) -induced oral erosions and ulcers mimicking Stevens-Johnson syndrome (SJS) in older women with rheumatoid arthritis, although they did not had conjunctivitis. Furthermore, age, dehydration, and renal dysfunction could trigger adverse reactions of MTX, but one patient underwent dialysis, which is a contraindication for MTX. It is sometimes very difficult to differentiate the toxicity of MTX from SJS. Learning from the three cases, we propose that oral mucosal erosions without conjunctive mucosal inflammation, leukopenia, and thrombocytopenia differentiate MTX toxicity from SJS. Furthermore, our patients nearly recovered from myelosuppression within seven days and recovered from mucosal erosions characteristic of MTX toxicity within 14 days. These clinical courses could also be characteristic for MTX toxicity rather than SJS, although quick recovery does not happen in all cases. Therefore, physicians who prescribe MTX must accurately know MTX-induced adverse reactions to recognize them early. Furthermore, as seen in our patients, oral mucosal erosions occur often. Therefore, dermatologists or others who examine these symptoms should consider that mucosal erosions mimicking SJS could be an adverse reaction of MTX, regardless of whether or not SJS/toxic epidermal necrolysis is suspected.

Purpose Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis Syndrome (TENS) are severe and potentially lethal adverse drug reactions characterized by acute inflammation of the skin, mucous membranes, and ocular surface that typically occurs within weeks of a culprit drug ingestion. The purpose of this study is to report a retrospective trend analysis of SJS spectrum diagnoses and associated culprit drugs in patients admitted to the Loyola University Medical Center (LUMC) Burn Unit, the major referral center in the Chicagoland region for patients with SJS disease spectrum. Methods The electronic medical records (EMR) of 163 patients with a diagnosis of SJS/TENS admitted to the LUMC Burn Unit from 2000 to 2019 were reviewed. Clinical data in addition to the well-established algorithm of drug causality for epidermal necrolysis (ALDEN) allowed us to identify the single most probable culprit drug in 131 cases. Results From 2000 to 2019, the most common spectrum classification was TENS (48.1%), followed by SJS (33.6%) and SJS-TEN Overlap Syndrome (18.3%). Anticonvulsants were found to be the most probable culprit class in 30% of cases followed by Trimethoprim-Sulfamethoxazole in 19% of cases. Beta-lactams were the most probable culprit class in 11% of cases while NSAIDs and allopurinol were each the most probable culprit class/drug in 8.4% of cases. Conclusions This is one of the largest single center series of SJS/TENS cases in the United States. Further study into culprit drug distribution by region as well as continuous monitoring of trends is crucial in order to advise prescribing practices.

Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions.We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN).MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR).We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of50 and a mean score of 54.96 out of 77.Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile non-follicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug specific T-cells that mediate neutrophilic intracorneal, subcorneal, and/or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathological features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies such as cyclosporine, and intravenous immunoglobulin.

Background/purpose Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusions The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

Complications of hematopoietic stem cell transplant (HSCT) include acute graft-versus-host disease (aGVHD). Severe cutaneous aGVHD can present with generalized erythroderma, desquamation, and bullae which can mimic toxic epidermal necrolysis (TEN). TEN occurs in response to a culprit medication. Transplant patients are often on many medications, making it difficult to distinguish between the two conditions. Given that TEN-like aGVHD is rare, we describe a case series of pediatric patients and review the literature.This is a multi-institutional case series of children who developed TEN-like aGVHD following bone marrow transplantation. Demographic, clinical, and treatment information was collected.Ten patients were identified. Median age at transplantation was 8.5 years (range 0.12-17 years). Median time from transplant to first skin symptoms was 35 days (range 6-110 days) and to first TEN-like symptoms was 40 days (range 16-116 days). 7/10 had other organ GVHD involvement. All patients were on concurrent medications at time of first skin symptoms including immunosuppression for GVHD prophylaxis, infection prophylaxis or treatment, and pain medication. Treatments for TEN-like aGVHD included immunosuppression.We observe that patients withor equal to 50% BSA involvement of their skin with TEN-like aGVHD, extracutaneous GVHD, and lack of reepithelization tend to have poor outcomes. Given the rarity of this condition, multidisciplinary care of these patients is important for accurate and timely diagnosis and treatment.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse reactions to drugs and psychological sequelae are also observed to follow the trauma of widespread epidermal necrolysis. To delineate the association between SJS and TEN, and psychiatric disorders, we conducted a retrospective population-based cohort study by including 212 patients diagnosed with first-time SJS or TEN in Taiwan between 2000 and 2013 and 669 population controls. Adjusted hazard ratios were calculated after adjusting for sex, age, comorbidity in the form of Charlson comorbidity index, and facility level of care. Overall, SJS or TEN was associated with an increased risk of developing psychiatric disorders including schizophrenia, major depressive disorder, mania, anxiety, and bipolar with an adjusted hazard ratio of 1.392 (95% CI, 1.192-1.625; p 0.001). Particularly, the adjusted hazard ratios of psychiatric disorders were 1.290 (95% CI, 1.105-1.506; p 0.001) for SJS and 1.855 (95% CI, 1.587-2.167; p 0.001) for TEN.

Stevens-Johnson syndrome and toxic epidermal necrolysis are severe, primarily drug-induced reactions of skin and mucosa. Since they differ in the extent of skin detachment but not in etiology, they are grouped together as epidermal necrolysis (EN). Due to nationwide registration, representative data are available at the German Center for the Documentation of Severe Skin Reactions (dZh). Here, an increasing number of case notifications in the context with new immuno-oncologic drugs, kinase inhibitors and biologics have been observed.Of 4,150 cases notifications between January 2003 and February 2019, 102 cases with exposure to these drug groups underwent systematic analysis, validation and causality assessment.Two cases of EN to vemurafenib were confirmed and one case to afatinib and pembrolizumab, respectively. In 14 EN cases other drugs - predominantly allopurinol or cotrimoxazole - were the causative agent. Fourteen cases were EN-like reactions: six bullous lichenoid drug eruptions (DE) to pembrolizumab (2), obinutuzumab, nivolumab, rituximab, infliximab/nivolumab, and eight multiforme-like DE to rituximab (2), adalimumab, ramucirumab, bevacizumab, vemurafenib, sorafenib (2). Lichenoid DE were differentiated from EN through histopathology and by the protracted course of EN, multiforme-like DE by variable skin manifestations with only sparse epidermolysis or mucosal involvement.A correct diagnosis is highly relevant in terms of prognosis and use of these drugs in malignoma treatment. Re-exposure is contraindicated in EN, but possible in other DE after rigorous risk-benefit evaluation.

RESUMO Introdução: A síndrome de Lyell é caracterizada por flictenas em mais de 30% de superfície corporal e acomete mucosas. Está relacionada à reação alérgica decorrente de medicamentos e apresenta alta mortalidade. Relato de caso: Mulher de 28 anos apresentou flictenas em 72% de superfície corporal após uso de diversos fármacos. Apesar da grande extensão, a paciente evoluiu de maneira satisfatória e recebeu alta sem sequelas. Conclusão: É fundamental o diagnóstico precoce, a estratificação e a conduta para reduzir a mortalidade da doença. ABSTRACT Introduction: Lyell’s syndrome is characterized by phlyctenas on more than 30% of the body surface and by involvement of the mucous membranes. It is related to the allergic reaction resulting from medications and has a high mortality. Case report: A 28-year-old woman presented phlyctenas on 72% of the body surface after using various drugs. Despite a great extent, the patient progressed satisfactorily and was discharged without sequelae. Conclusion: Early diagnosis, stratification, and management are essential to reduce mortality from the disease.

The purpose of this study was to analyze the clinical features, causative microorganisms, antibiotic susceptibility, and treatment outcomes in culture-proven microbial keratitis (MK) in patients with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and to analyze the potential risk factors.We reviewed the medical records of all patients with SJS/TEN who attended our department between 2009 and 2018. Patients with a diagnosis of MK who underwent corneal cultures were enrolled. Demographics; clinical characteristics including ocular findings, treatment, time between onset of SJS/TEN and keratitis; changes in visual acuity; culture results; and antibiotic susceptibility were analyzed. Culture results from prior conjunctival swabs and keratitis were also compared.Sixteen eyes from 12 patients (mean age 40.1 ± 27.7 years) with MK were identified. These patients had the most severe ocular involvement in the acute stage and had more severe ocular complications (SOCs) in the chronic stage compared with patients with SJS/TEN without MK. There were 26 infection episodes during 4.4 ± 6.9 (1.0-25.8) years of follow-up. Oral nonsteroidal anti-inflammatory drugs accounted for half of the causative drugs. Severe dry eye was the most common predisposing factor, followed by topical steroid use, trichiasis, and lid margin keratinization. Staphylococcus was the most common pathogen, and over half of the gram-positive bacteria were resistant to oxacillin/methicillin. Fungal infections (notably Candida ) accounted for nearly one-third of the causative microorganisms. Culture reports from periodic conjunctival swabs were not consistent with those from corneal scrapings. Recurrence of infection was associated with inferior visual outcome.Patients with SJS/TEN with SOCs are subject to recurrent corneal infections, which are responsible for deterioration of vision. Identifying the risk factors and aggressive treatment as early as possible is pivotal for infection control.

To study the cytokeratin profile and keratinization-related gene expression in keratinized lid margins of chronic Stevens-Johnson syndrome (SJS) patients.Posterior eyelid margins from 24 chronic SJS patients undergoing mucous membrane grafting and six healthy margins (orbital exenteration, fresh body donors) were studied using immunofluorescence staining (CK10, CK1, filaggrin, transglutaminase 1 (TGM1), (CK19, MUC5AC)) and quantitative PCR (keratinization-related genes-HBEGF, KGF, EGF, TGFα, TGFβ, and TNFα). The staining and gene expression were studied separately in the lid margin epidermis (LME) and lid margin conjunctiva (LMC).The expression of CK 1/10, filaggrin, and TGM1 in the LMC was similar to the LME in SJS patients. CK19 was expressed only in the basal epithelial layer of the LMC with loss of MUC5AC expression. Increased expression of KGF (p ≤ 0.056), TNFα (p ≤ 0.02), and TGFα (p ≤ 0.01) was observed in the LME of SJS patients compared to normal LME. LMC of SJS patients showed an increased expression of HBEGF (p ≤ 0.002), EGF (p ≤ 0.0002), KGF (p ≤ 0.02), TNFα (p ≤ 0.04), TGFα (p ≤ 0.003), and TGFβ (p ≤ 0.001) compared to normal LMC. Significant differences were observed in the expression of these genes between LME and LMC of SJS patients. These genes were validated using String analysis, which revealed the positive regulation of keratinization.In lid margins of SJS, there is an increased expression of keratinization-related genes compared to the normal lid margin. Keratinized LMC shares similar cytokeratin profile and keratinization gene expression as seen in cutaneous epithelium of SJS patients, indicating the possibility of the cutaneous epithelium as a source for keratinized LMC.

Lyell’s syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients’ outcome in TEN.

Allopurinol is known to cause severe cutaneous adverse drug reactions (SCAR) in Malaysia. However, the incidence of allopurinol-induced SCAR is unknown. Therefore, we aimed to determine the incidence of allopurinol-induced SCAR in Malaysia over 5 years from 2015 to 2019.This retrospective analysis was done in collaboration with the National Pharmaceutical Regulatory Agency (NPRA). All allopurinol-induced adverse drug reaction cases reported to NPRA from 2015 to 2019 were extracted. Allopurinol-induced SCAR cases were identified and the incidence over the 5 years was calculated.Incidence of allopurinol-induced SCAR averaged at 2.5 cases per 1000 new users over the 5-year period, with a reducing trend from 3.2 per 1000 new users in 2015 to 2.25 per 1000 in 2019; despite the increasing number of adverse drug reaction cases being reported over the years. Stevens-Johnson syndrome was the commonest form of allopurinol-induced SCAR reported, at 143 cases (46.8% of total SCAR reported). Among Malaysia's 3 main ethnicities, the Chinese had the highest percentages of allopurinol-induced SCAR when compared to the Bumiputera and Indians (3.18 × 10The estimated incidence of allopurinol-induced SCAR in Malaysia from 2015 to 2019 was 2.5 cases per 1000 new users. This figure is consistent with the incidence reported in other Asian countries, namely Taiwan and Thailand.

Background Mycoplasma pneumoniae (MP) infection is associated with extrapulmonary complications such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Objective We evaluated the differences in epidemiology, clinical characteristics, and disease outcomes between drug-induced and Mycoplasma-related SJS/TEN. Methods All patients with SJS/TEN admitted to our center between 2003 and 2016 inclusive were treated under a standardized protocol. Comparative analysis was made between patients who tested positive for MP versus a control group with negative MP serology in the presence of high-notoriety drugs defined by an algorithm for assessment of drug causality in epidermal necrolysis >5. Results Of 180 cases of SJS/TEN patients treated in our institution, 6 had positive MP serologies and were compared to a control group of 71 cases of drug-induced SJS/TEN with an algorithm for assessment of drug causality in epidermal necrolysis score of >5. There were no significant differences in baseline characteristics, disease classification, body surface area involved, and extent of mucosal involvement. We found significant differences in mortality rates between the Mycoplasma and control groups on discharge (0% vs 22.5%, P Limitations Retrospective design, small sample size. Conclusion Although recent studies have shown that MP-induced SJS/TEN is morphologically different and deserves a separate classification system, this would need to be borne out in larger prospective studies.

The objective of this study was to investigate the clinical manifestations and pathologic appearances of the submandibular gland (SMG) in Stevens-Johnson syndrome (SJS).Patients with autologous transplantation of SMG for treatment of severe dry eye between March 1998 and May 2018 were divided into the SJS group (70 cases) and non-SJS group (50 cases) according to the history of SJS. The SMG weight and computed tomography volume and salivary flow rate were measured. The concentration index and secretion index were estimated using scintigraphy with technetium-99m-pertechnetate. Histopathology studies of SMG tissues were conducted, and the acini parameters were measured using a digital image analyzer.A decreased computed tomography volume and weight was observed in 48.57% the SJS group and 2% in the non-SJS group (P.01). The rest whole, acid-stimulated whole, and SMG rest salivary flow rates decreased in the SJS group (P.05). The normal SMG concentration index (37.5% vs 96.67%, P.001) and secretion index (35% vs 96.67%, P.001) rates were lower in the SJS group than in the non-SJS group. The glandular parenchyma was reduced, the acinar space was widened, and the fat content was increased in the SJS group.SMG atrophic and degenerative changes occurred in the SJS group, with a decrease in salivary secretion function in more than half of the patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Antiseizure medications (ASMs) with aromatic ring structure, including carbamazepine, are among the most common culprits. Screening for human leukocyte antigen (HLA) allele HLA-B*15:02 is recommended prior to initiating treatment with carbamazepine in Asians, but this allele has low positive predictive value.We performed whole genome sequencing and analyzed 6 199 696 common variants among 113 aromatic ASM-induced SJS/TEN cases and 84 tolerant controls of Han Chinese ethnicity.In the primary analysis, nine variants reached genome-wide significance (p 5e-08), one in the carbamazepine subanalysis (85 cases vs. 77 controls) and a further eight identified in HLA-B*15:02-negative subanalysis (35 cases and 53 controls). Interaction analysis between each novel variant from the primary analysis found that five increased risk irrespective of HLA-B*15:02 status or zygosity. HLA-B*15:02-positive individuals were found to have reduced risk if they also carried a chromosome 12 variant, chr12.9426934 (heterozygotes: relative risk = .71, p = .001; homozygotes: relative risk = .23, p .001). All significant variants lie within intronic or intergenic regions with poorly understood functional consequence. In silico functional analysis of suggestive variants (p5e-6) identified through the primary and subanalyses (stratified by HLA-B*15:02 status and drug exposure) suggests that genetic variation within regulatory DNA may contribute to risk indirectly by disrupting the regulation of pathology-related genes. The genes implicated were specific either to the primary analysis (CD9), HLA-B*15:02 carriers (DOCK10), noncarriers (ABCA1), carbamazepine exposure (HLA-E), or phenytoin exposure (CD24).We identified variants that could explain why some carriers of HLA-B*15:02 tolerate treatment, and why some noncarriers develop ASM-induced SJS/TEN. Additionally, this analysis suggests that the mixing of HLA-B*15:02 carrier status in previous studies might have masked variants contributing to susceptibility, and that inheritance of risk for ASM-induced SJS/TEN is complex, likely involving multiple risk variants.

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 case–control 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 (95% confidence interval):17.41 (1.31–230.72), 10.28 (3.61–29.31), 5.21 (2.95–9.19), 4.92 (1.88–12.85), 3.17 (1.77–5.66), 2.61 (1.26–5.41), and 1.98 (1.12–3.53), respectively. Conclusions Attention should be drawn to drugs assessed by high ALDEN scores that were associated with high absolute risks for SJS/TEN. Psoriasis, former drug allergies, in addition to systemic lupus erythematosus, malignancy, history of cerebrovascular accident, and diabetes mellitus were associated with increased SJS/TEN risk in our analysis. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00661-0.

Background: Case reviews of severe cutaneous adverse drug reactions (ADRs) such as SJS/TEN provide useful insights for clinical characteristics, putative drugs, and management protocols. Patients and Methods: Medical charts of 62 (m:f- 20:42) patients with SJS/TEN hospitalized between 2010 and 2019 were analyzed retrospectively for clinical attributes, putative drugs and their indications, extracutaneous complications, and therapeutic outcome. The diagnosis was clinical based on established criteria. WHO-UMC scale for reporting ADR and ALDEN algorithm score were used for causality assessment. Therapies were customized based on in-house resources and affordability. Results: Cases included were SJS (41.9%), SJS/TEN overlap (33.9%), and TEN (24.2%) aged 4–85 years. Complications included transaminitis (69.4%), lymphadenopathy (15.5%), septicemia (11.3%), and wound infections (4.8%). Aromatic anticonvulsants (37.1%), disease-modifying antirheumatic drugs (25.8%), antiretroviral drugs (12.9%), non-steroidal anti-inflammatory drugs (8.1%), antimicrobials (4.8%), and trihexyphenidyl (3.2%) were major putative drugs. The mean latent period was 16.6 days. The observed 8% mortality was because of primary comorbidities or multiorgan failure. Addition of fresh blood transfusion (BT, n = 11) or IVIg (n = 7) to systemic corticosteroids showed early relief in skin tenderness, improvement in general condition, and re-epithelialization. Only 16% of patients developed sequelae. Conclusion: Aromatic anticonvulsants, allopurinol, nevirapine, cotrimoxazole, paracetamol, and diclofenac remain the most implicated drugs. Sulfasalazine, leflunomide, ethambutol, and trihexyphenidyl were uncommon additions. A short course of high-dose dexamethasone in the early stage was useful. Addition of BT or IVIg provided rapid relief. Preexisting HIV disease, kidney disease, and sepsis remain important for in-hospital deaths. Retrospective study design and small number of cases remain major limitations.

Background Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. Objectives We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. Methods Participants were sent a survey via the online tool “Survey Monkey” consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. Results Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index Conclusions Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

Stevens-Johnson syndrome (SJS) is a delayed hypersensitivity reaction, lasting approximately two to four weeks. It is a rare disease, with an incidence of 1 to 6 cases per million inhabitants. Despite the low prevalence, it manifests itself as a result of drug interactions resulting from practices that are not so rare as polypharmacy and the use of medications without a professional prescription. The methodology of the present study is based on Scoping Review of virtual search platforms. It is expected, at the end of the work, to have an updated compilation of information, in order to contribute to the dissemination of the state of the art on the subject, since the occurrence of SSJ is directly associated with the knowledge that the community has about it.

Possible biases in pharmacovigilance reporting may impact epidermal necrolysis (EN) and drugs associations.To assess biases associated with EN-reporting.Using VigiBase, the World Health Organization-pharmacovigilance database, among drugs associated with EN between 2016 and 2020, we used an unsupervised clustering including reports characteristics, that is, reporter quality, time from drug intake to EN onset, and only one suspected drug in the report.Among 152 drugs, three clusters were identified. Cluster 1 (n = 41) exhibited drugs frequently reported within a time from intake to onset longer than 4 days, in 57 ± 13% of reports. It corresponded to well-reported drugs and was composed mainly of antivirals and antiepileptics. Cluster 2 (n = 42) exhibited drugs frequently reported within a time from drug intake to onset shorter than 4 days, in 31 ± 12% of reports. It corresponded to drugs with a high risk of protopathic bias and was composed of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, and antibiotics. Cluster 3 (n = 69) exhibited drugs frequently reported with an unavailable time from drug intake to reaction, in 66 ± 11% of reports, and reported by a high frequency of consumers (9 ± 9%). It corresponded to drugs reported with a high risk of classification bias, and was composed of anticancer therapies and cardiovascular drugs.Protopathic and classification biases impact EN-reporting and should be considered regarding associations with antibiotics, NSAIDs, analgesics, anticancer therapies, and cardiovascular drugs.

Toxic epidermal necrolysis (TEN) is a drug-mediated disease process that mimics a partial-thickness thermal injury. It has long been treated with frequent wound dressing changes and supportive care. There has been minimal efficacious systemic therapy. The pathophysiology is poorly understood but causes necrosis of keratinocytes at the dermal–epidermal junction leading to sloughing of the epidermis. The disease is rare with high mortality rates associated with long hospital stays. This case report describes the application of autologous skin cell suspension to a patient with TEN after antihypertensive and hyperglycemic therapy. This was associated with minimal wound care and efficacious arrest of patient disease process and timely closure of wound.

Background: The newly described ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area [BSA]) is a 5-item mortality prediction model for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). It was developed in the United States, has at present been externally tested only in the United States, Spain, and Singapore, and remains to be validated in resource-restricted settings. We sought to compare the accuracy of ABCD-10 and Score of Toxic Epidermal Necrolysis (SCORTEN) in predicting in-hospital mortality in a cohort from central China. Due to disease progression affecting the accuracy of the prediction model during hospitalization, for example, higher predictive accuracy of SCORTEN based on parameters collected on day 3 of hospitalization, we also assessed the overall predictive value of ABCD-10 on days 1 and 3, respectively. Methods: A retrospective study was performed over a 10-year period (2010–2020) from 3 medical institutions in Wuhan. The performance of predictive models was assessed by both discrimination and calibration. Receiver-operating characteristic (ROC) curves, Hosmer-Lemeshow goodness-of-fit tests and calibration plots were used to evaluate the model discrimination and calibration. Results: Of 84 included patients, 11 (13.1%) did not survive. The discrimination power of ABCD-10 was not significantly different from that of SCORTEN (area under the curve: day 1, p > 0.05; day 3, p > 0.05). Although the calibration of ABCD-10 was good, it was inferior to SCORTEN as it underestimated total mortality (Hosmer-Lemeshow goodness-of-fit test: day 1, p = 0.17 vs. p = 0.63; day 3, p = 0.35 vs. p = 0.93). Besides, the performance of ABCD-10 was slightly better on day 3 relative to day 1. During hospitalization, bacteremia developed in 21 (25.0%) patients, which was associated with a higher risk of death in our cohort (odds ratio, 22.88; 95% CI, 4.38–119.40; p < 0.001). Conclusion: ABCD-10 showed acceptable overall performance, but revealed mortality underestimation and was inferior to the performance of SCORTEN. In consistence with SCORTEN, ABCD-10 was a better model when using values collected at day 3 of hospitalization relative to day 1.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious adverse cutaneous drug reactions, characterized by epidermal detachment and mucous membrane involvement. SJS/TEN is more common in female patients, with unique findings in the ocular and vulvar regions. Early recognition and intervention, as well as long-term follow-up, are crucial to prevent devastating scarring and sequelae. This review examines the vulvar and ocular manifestations of SJS/TEN and describes the current treatment recommendations for female patients, requiring close consultation and collaboration among dermatology, ophthalmology, and gynecology.

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Toxic epidermal necrolysis (TEN) is an immune mediated, severe cutaneous adverse drug reaction characterized by epidermal detachment affecting greater than 30% body surface area. The mortality rate of TEN exceeds 20% and is usually caused by infection and respiratory compromise. Withdrawal of the causative drug, supportive care, and adjuvant therapy improve prognosis. Over the past decade, randomized controlled trials and meta-analyses have supported a role for cyclosporine, tumor necrosis factor alpha inhibitors, and combination therapy with intravenous immune globulin and corticosteroids. This review summarizes the medical management of TEN in adult patients.

Severe cicatricial entropion in Stevens-Johnson syndrome (SJS) patients is difficult to treat and is associated with a higher recurrence rate. Also, entropion in the presence of lid margin mucous membrane graft (MMG) further complicates the surgical anatomy and approach.To report a modified surgical technique of repairing severe upper eyelid cicatricial entropion in an SJS patient with history of lid margin MMG.Cicatricial entropion in patients with SJS is entirely different from trachomatous cicatricial entropion. The involvement of the lid margin with keratinization, tarsal scarring, persistent conjunctival inflammation, and unhealthy ocular surface affects the surgical approach and outcomes. Conjunctiva-sparing surgery with reconstruction of the lid margin using MMG, flattening and repositioning the anterior lamella, and covering the bare tarsus with MMG rather than leaving it raw are the necessary modifications in this technique from conventional anterior lamellar recession. The video demonstrates the surgical technique for harvesting and preparation of a labial MMG, the splitting of the anterior and posterior lamella of the lid margin, scar tissue release between the lash line and the tarsus, repositioning of the anterior lamella, and anchoring of the labial MMG.Anterior lamellar recession combined with MMG wrapping the lid margin and bare tarsus offers good cicatricial entropion repair outcomes. Removal of fat and submucosa from the mucosal graft should be done for better cosmesis. Adequate separation of the scar tissues from the lash line and the tarsus is essential.https://youtu.be/6HsKgeZQCyY.

Purpose To investigate the long-term effects of corticosteroid pulse therapy (CPT) for the treatment of acute-stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients with severe ocular involvement. Design Retrospective, comparative case series. Methods This study retrospectively reviewed the medical records of 116 SJS/TEN patients who developed the disease between 2002 and 2018. Patients with severe ocular disorders (ie, ocular surface epithelial defect, pseudomembranous formation, or both) at the acute stage and who were followed for >1 year post SJS/TEN onset were enrolled. In those patients, the treatments administered for acute-stage SJS/TEN and associated ocular sequelae were examined, including the best-corrected visual acuity (BCVA) in the patient's worse eye and the incidence of the ocular complications at the final follow-up examination. Results A total of 85 patients were enrolled. Of those, 36 received CPT within 4 days post disease onset (group A) and 49 patients did not receive CPT within 4 days post disease onset (group B). The percentage of eyes with a BCVA in the worse eye of ≥ 1.0 were 52.8% in group A and 14.3% in group B. Severe ocular sequelae (ie, a worsening of BCVA and corneal and conjunctival complications) were significantly less in group A than in group B. Conclusions In SJS/TEN patients with acute ocular involvement, CPT initiated within 4 days from disease onset may help reduce severe ocular sequelae.

Background Stevens-Johnson syndrome is a rare medical condition with severe mucocutaneous lesions due to adverse drug reactions characterized by exudative multiform erythema, stomatitis, and conjunctivitis. Long-term oral consequences of such cases include xerostomia, caries, impactions, and multiple dental developmental aberrations as short root anomalies. Aim and objective To highlight the role of pedodontist in early diagnosis and treatment planning of dental abnormalities due to Stevens-Johnson syndrome (SJS) using a cone-beam computed tomography (CBCT). Case description A 16-year-old male reported a chief complaint of decayed posterior teeth. Past medical history revealed adverse reactions to an unknown drug at the age of 4 to 5 years. In addition to carious teeth, clinical examination revealed that all canines were missing along with mandibular incisors. On CBCT examination, abnormal short, plump roots with normal crown were seen in all permanent first molars and incisors along with impacted canines and mandibular incisors. This condition was diagnosed as a "Short root anomaly" (SRA) due to SJS. He was found positive to allergy tests for NSAIDs such as ibuprofen and paracetamol. Conclusion NSAIDs can cause a severe adverse reaction resulting in SJS. If this hypersensitivity reaction occurs early during the development of a permanent tooth it may cause dental anomalies such as short roots, root dysmorphia, agenesis, and multiple impacted teeth. Clinical significance This report highlights a unique case of multiple dental aberrations due to SJS and the role of a pedodontist in the early diagnosis and treatment planning of such cases with the help of CBCT. Short root anomalies can be misdiagnosed as root resorption or immature apex. Medical history, clinical and CBCT findings are essential for diagnosis and treatment in SJS patients. Careful orthodontic treatment planning is required in cases of short root anomalies. How to cite this article Katyal S, Yadav V. Diagnostic and Treatment Approach in the Management of Dental Anomalies Associated with Stevens-Johnson Syndrome: A Case Report. Int J Clin Pediatr Dent 2021;14(4):569-574.

Diverse ethnic genetic populations display variability in the risk regarding anti-seizure medicine (ASM)-induced severe cutaneous adverse reactions (SCARs). However, clinical and epidemiological data on ASM-induced SCARs in Asians is limited.We conducted a retrospective, post-market study until April 30, 2020 using VigiBase® for demographic characteristics, causative ASMs, complications and mortality. The study included adverse events as classified by Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries of SCARs, mainly Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and SJS/TEN overlap reported for ASMs.A total of 694,811 adverse events were reported across the world while using ASMs. Of this, skin and subcutaneous tissue adverse events were 122,885 (17.6%). Among ASM-induced skin and subcutaneous tissue adverse events, SJS, TEN, DRESS and SJS/TEN overlap represented 11,181 (9.1%), 3,645 (3.0%), 5,106 (4.1%) and 6 (0.004%) cases, respectively. Female SJS/TEN/DRESS patients were 54.1%, and 75% of them were adults (18Y). Nearly 64% of the ASM-induced SCARs were serious and culminated in death (3.5%), life-threatening conditions (11.5%), and hospitalization/prolonged hospitalization (43.5%) of patients on ASM therapy. Carbamazepine (31.6%), phenytoin (29.6%), lamotrigine (24.3%), valproic acid (6.4%) and phenobarbital (5.7%) are the most commonly used ASMs linked with SCARs. ASMs associated with significantly higher risk of SCARs in Asians were carbamazepine [n = 3265, ROR 3.55 (95% CI 3.38-3.72, P 0.0001)], lamotrigine [n = 1253, ROR 3.90 (95% CI 3.63-4.18, P 0.0001)], gabapentin [n = 85, ROR 3.58 (95% CI 2.79-4.60, P 0.0001)], pregabalin [n = 68, ROR 3.16 (95% CI 2.40-4.16, P 0.0001)], clonazepam [n = 53, ROR 3.19 (95% CI 2.31-4.41, P 0.0001)], lorazepam [n = 31, ROR 3.07 (95% CI 2.06-4.59, P 0.0001)] and acetazolamide [n = 28, ROR 3.90 (95% CI 2.45-6.21, P 0.0001)].Based on our study, carbamazepine, lamotrigine, gabapentin, pregabalin, clonazepam, lorazepam, and acetazolamide are the most common causative ASMs for SCARs in the Asian population.

Importance Immune checkpoint inhibitors (ICIs) have emerged as active therapies for a variety of cancers. Cutaneous toxicities are common immune-related adverse events and patients will often be referred to dermatologists for evaluation. Observations Cutaneous adverse events to ICIs can have a variety of clinical presentations. Among the more common are eczematous, morbilliform, and lichenoid dermatoses, as well as vitiligo and pruritus. Less common adverse events include psoriasiform dermatoses, bullous disorders, and severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. Because of the immunologic mechanism of ICIs, there are also a variety of rheumatologic adverse reactions with cutaneous manifestations, such as scleroderma, dermatomyositis, cutaneous lupus erythematosus, and various vasculitides. These cutaneous reactions often respond to topical or systemic steroids, although specific toxicities may have alternative treatments available. Conclusions and relevance As they become more widely prescribed, dermatologists will see an increasing number of patients with cutaneous adverse events caused by ICI therapies. Accurately diagnosing and treating these toxicities is paramount to achieving the most favorable outcomes for patients.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Aim: To provide a comparison of genotyping for HLA risk alleles versus patch testing to determine which of these two tests is a better diagnostic tool for cutaneous hypersensitivity reactions caused by anti-seizure medication.Methods: A literature study was performed in PubMed to assess the sensitivity and specificity of HLA genotyping and patch tests for identifying anti-seizure medication induced cutaneous hypersensitivity reactions.Results: This study shows that HLA-B*15:02 genotyping shows high sensitivity for carbamazepine-induced SJS/TEN, especially in Han Chinese and Southeast Asian patients (66.7–100.0%) whereas the sensitivity of patch tests (0.0–62,5%), HLA-A*31:01 (0–50%) and HLA-B*15:11 (18.2–42.9%) are lower. On the contrary, for carbamazepine and phenytoin induced DRESS, patch tests (respectively 70.0–88.9% and 14.3–70.0%) show higher sensitivity than HLA tests (0–66.7% and 0–12.7%). Also for lamotrigine-induced DRESS patch tests perform better than HLA-B*15:02 (33.3–40.0 versus 0%). For anti-seizure medication induced MPE and for oxcarbazepine-induced SCARs more studies are needed.Conclusion: Use of HLA-B genotyping may aid clinicians in the diagnosis of carbamazepine, phenytoin, lamotrigine and oxcarbazepine induced SJS/TEN, particularly in Han Chinese and Southeast Asian patients. On the other hand, patch tests seem to perform better in the diagnosis of carbamazepine and phenytoin induced DRESS.

Background Toxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material. Methods A retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose. Results The sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation. Conclusion Our data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

AIMS Carbamazepine (CBZ) is one of the most common causative drugs of severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms. Although genetic polymorphisms of the human leucocyte antigens (HLA) are well recognized key elements for the susceptibility to CBZ-induced SCARs, some evidence suggest that polymorphisms of microsomal epoxide hydrolase 1 (EPHX1) may also contribute to the risk of these SCARs. This study investigated the association between the HLA and EPHX1 polymorphisms on CBZ-induced SCARs in large sample sizes and well-defined SCARs patients. METHODS Ninety-one CBZ-induced SCARs Thai patients and 144 CBZ-tolerant patients were enrolled in the study. The genotypes of HLA-A, HLA-B and EPHX1 were determined. RESULTS Only 2 HLA alleles including HLA-B*15:02 and HLA-A*24:07 were statistically significant association with CBZ-induced SJS/TEN. The highest risk was observed in patients with HLA-B*15:02 allele (OR = 44.33, 95% confidence interval = 20.24-97.09, corrected P-value = 6.80 × 10-29 ). Moreover, HLA-B75 serotypes were significantly associated with CBZ-induced SJS/TEN groups with an odds ratio of 81.00 (95% confidence interval = 32.39-202.56, corrected P-value = 3.84 × 10-34 ). There is no association between EPHX1 c.337 T > C polymorphism and all phenotypes of CBZ-induced SCARs. CONCLUSION The HLA-B*15:02 allele is the strongest genetic marker for the prediction of SJS/TEN induced by CBZ in Thai population. Screening for other alleles in the HLA-B75 serotype increases sensitivity for prediction of a life-threatening SCARs caused by CBZ.

Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are life-threatening conditions best approached with multidisciplinary burn-equivalent care. There is a lack of consensus on wound management, in particular, whether to debride detached epidermis. Our center instituted “antishear” wound therapy 35 years ago, where detached skin is left in situ as a biologic dressing and a standardized protocol avoids shear forces to prevent further desquamation. Our center’s initial results showed outcomes comparable to SCORTEN predictions, but advancements in burn critical care necessitate a reevaluation of the antishear approach. A retrospective chart review was conducted for all patients admitted between June 2004 and May 2020 with a dermatologist-confirmed diagnosis of SJS/TEN (N = 51). All patients were treated with burn-equivalent critical care and antishear wound therapy. Standardized mortality ratios were calculated using the established SCORTEN, and newly developed ABCD-10, prediction models. Mean SCORTEN, ABCD-10, and %TBSA were 2.6, 2.0, and 28%. Overall mortality was 22%; SCORTEN score (P < .001), ABCD-10 score (P < .01), %TBSA involved (P = .02), and development of multisystem organ failure (P < .001) correlated with increased mortality. Cohort-wide standardized mortality based on ABCD-10 was 1.18 (P = .79). Standardized mortality based on SCORTEN was 0.62 (P = .20) and 0.77 (P = .15) for patients with scores ≤3 and >3; across the cohort it was 0.71 (P = .11), representing a 29% mortality reduction. Incorporating the antishear approach as part of burn-equivalent care for SJS/TENs led to outcomes comparable to those predicted for surgical debridement via SCORTEN. However, the antishear approach has the advantage of avoiding painful dressing changes, sedation, and general anesthesia required for surgical debridement.

Drug hypersensitivity reactions (DHR) are heterogeneous in their pathomechanisms, clinical presentation, severity, and outcomes. Novel DHR mechanisms, phenotypes, and endotypes have been described. The key to prevention from further exposure to the culprit drugs involves correct identification of the putative drug through a combination of in vitro and/or in vivo tests, accurate drug allergy labeling and reporting, and electronic decision support systems within electronic medical records to prevent future accidental prescribing. Prescreening and premedication, the focus of this review, may be a useful adjunct to preventive measures in certain situations. After an index immediate drug hypersensitivity reaction, prescreening may be useful in perioperative anaphylaxis, and iodinated (ICM) and gadolinium-based contrast media (GCM) where the culprit and potential alternative agents are skin tested. In certain nonimmediate DHR, pharmacogenomic prescreening may be used before prescribing high-risk drugs (eg, carbamazepine and allopurinol) where specific human-leukocyte antigen genotypes are associated with severe cutaneous adverse reactions. Premedication with antihistamine and systemic corticosteroids is another therapeutic strategy to prevent infusion reactions for certain biologicals and chemotherapeutic agents, in cases of perioperative anaphylaxis, ICM and GCM DHR, and clonal mast cell disorders. Rapid drug desensitization may also be used to induce temporary tolerance in situations where there are limited alternative drugs. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE vol:9 issue:8 pages:2958-2966 ispartof: location:United States status: published

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

INTRODUCTION The distinction between epidermal necrolysis [EN; including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and overlap syndrome] and erythema multiforme major (EMM) in children is confusing. We aimed to better describe and compare these entities. MATERIALS AND METHODS This French retrospective multicentre study included children ≤18 years old referred for EN or EMM between 1 January 2008 and 1 March 2019. According to pictures, children were reclassified into TEN/overlap, SJS or EMM/unclassified (SJS/EMM) groups and compared for epidemiological and clinical data, triggers, histology and follow-up. RESULTS We included 62 children [43 boys, median age 10 years (range 3-18)]: 16 with TEN/overlap, 11 SJS and 35 EMM. The main aetiologies were drugs in EN and infections (especially Mycoplasma pneumoniae) in EMM (P