Toxic Epidermal Necrolysis Patients Research Articles

Profile of Stevens-Johnson syndrome and toxic epidermal necrolysis patients in the inpatient hospital installation of Dr. Soetomo general hospital Surabaya from January 2019 – December 2021

Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis are significant health issues due to their severe complications. Factors like age, clinical symptoms, and underlying etiology play crucial roles in patient management. Therefore, it is important to review further the background or profile of the patients. This is the basis for conducting this study. This research aims to provide an overview of patients with SJS-TEN in the Inpatient Installation of RSUD Dr. Soetomo Surabaya, aiming to aid in prevention and management. Aim: Providing an overview of the profile of patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Inpatient Installation of Dr. RSUD. Soetomo Surabaya Methods: The study analyzed medical records of patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at RSUD Dr. Soetomo Surabaya from 2019-2021, analyzing parameters such as gender, age, symptoms, etiology, comorbidities, and length of stay. Results: The study found 28 cases of SJS-TEN, with 15 males (53.6%) and 13 females (46.4%). The highest prevalence was in the age group 19-44 years old as we called adult (35.7%). Most patients had multiple comorbidities, with common clinical symptoms including palpebral edema, multiple erythematous macules, conjunctival erythema, and fever. Most patients were classified as SCORTEN 1, with 71.4% taking multiple drugs. Most patients experienced multiple complications but experienced improvement and continued treatment through outpatient care (57.1%).

Oropharyngolaryngeal manifestations in severe toxic epidermal necrolysis: a single-center's retrospective case series.

Toxic epidermal necrolysis is a rare and life-threatening mucocutaneous disease. Although mucosal ear, nose, and throat (ENT) involvement is common, little is known about the characteristics, treatment modalities, and outcomes of these lesions. The aim of this study was to evaluate ENT mucosal lesions in severe toxic epidermal necrolysis patients and analyze their characteristics, treatment modalities, and outcomes, as well as proposing a management algorithm to prevent long-term debilitating sequalae of these lesions. This is a retrospective review of toxic epidermal necrolysis cases treated at the tertiary burns unit of the Lausanne University Hospital CHUV, Switzerland, between 2006 and 2019. Out of 19 patients with severe toxic epidermal necrolysis, 17 (89%) underwent a complete ENT examination at admission and 14 (82%) had ENT mucosal involvement. Five (26.3%) patients died during the stay in the intensive care unit. Of the 16 patients who received maximal care, 13 (81%) required orotracheal intubation for a median time of 16 (IQR: 14) days. Out of the 14 patients who survived, four (29%) had long-term ENT complications consisting of synechiaes necessitating subsequent endoscopic procedures. Those four patients all required mechanical ventilation with an orotracheal tube and suffered from hypopharyngeal synechiaes as well as oral and endonasal synechiaes in individual cases. This study suggests a high prevalence of ENT synechiaes in patients with severe toxic epidermal necrolysis and requiring orotracheal intubation. Periodic ENT examination could prevent mature synechiae formation in these patients. We propose an algorithm to prevent long-term sequalae in ENT mucosal involvement.

Key factors predicting the in-hospital mortality of patients with severe cutaneous adverse reactions in Thailand.

At present, no predictive models are available to determine the probability of in-hospital mortality rates (HMRs) in all phenotypes of severe cutaneous adverse reactions (SCARs). Our study explored whether simple clinical and laboratory assessments could help predict the HMRs in any phenotypes of SCAR patients. Factors influencing HMRs in 195 adults diagnosed with different SCAR phenotypes were identified, and their optimal cut-offs were determined by Youden's index. Predictive equations for HMRs for all SCAR patients and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) patients were determined using the exact logistic regression models. Acute generalized exanthematous pustulosis (AGEP) patients were significantly older, with a short time from drug exposure to reaction, and higher neutrophil count compared to SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS, p < 0.001). Peripheral blood eosinophilia, atypical lymphocytosis and elevated liver transaminase enzymes were significantly higher in DRESS. SJS/TEN phenotype, age ≥ 71.5 years, neutrophil-to-lymphocyte ratio ≥ 4.08 (high NLR) and systemic infection were factors predicting in-hospital mortality in all SCAR subjects. The ALLSCAR model developed from these factors demonstrated high-diagnostic accuracy for predicting HMRs in all SCAR phenotypes (area under the receiver-operator curve (AUC) = 0.95). The risk of in-hospital death was significantly increased in SCAR patients with high NLR after adjusting for systemic infection. The model derived from high NLR, systemic infection and age yielded higher accuracy than SCORTEN (AUC = 0.77) for predicting the HMRs in SJS/TEN patients (AUC = 0.97). Being older, having systemic infection, having a high NLR and SJS/TEN phenotype increases ALLSCAR scores, which in turn increases the risk of in-hospital mortality. These basic clinical and laboratory parameters can easily be obtained in any hospital setting. Despite its simple approach, further validation of the model is warranted.

An alternative model for assessing mortality risk in Stevens Johnson syndrome/toxic epidermal necrolysis using a random forests classifier: A pilot study.

Mortality risk prediction is an important part of the clinical assessment in the Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) patient. The SCORTEN and ABCD-10 scoring systems have been used as predictive clinical tools for assessing this risk. However, some of the metrics required in calculating these scores, such as the total body surface area (TBSA) involvement, are difficult to calculate. In addition, TBSA involvement is calculated in a variety of ways and is observer dependent and subjective. The goal of this study was to develop an alternative method to predict mortality in patients with SJS/TEN. Data was split into training and test datasets and preprocessed. Models were trained using five-fold cross validation. Out of several possible candidates, a random forests model was evaluated as being the most robust in predictive power for this dataset. Upon feature selection, a final random forests model was developed which was used for comparison against SCORTEN. The differences in both accuracy (p = 0.324) and area under the receiver operating characteristic curve (AUROC) (p = 0.318) between the final random forests model and the SCORTEN and ABCD-10 models were not statistically significant. As such, this alternative method performs similarly to SCORTEN while only requiring simple laboratory tests from the day of admission. This new alternative can make the mortality prediction process more efficient, along with providing a seamless implementation of the patient laboratory tests directly into the model from existing electronic health record (EHR) systems. Once the model was developed, a web application was built to deploy the model which integrates with the Epic EHR system on the Fast Healthcare Interoperability Resources (FHIR) Application Programming Interface (API); this only requires the patient medical record number and a date of the lab tests as parameters. This model ultimately allows clinicians to calculate patient mortality risk with only a few clicks. Further studies are needed for validation of this tool.

Chronic kidney disease is potentially an independent prognostic factor for death in Stevens-Johnson syndrome and toxic epidermal necrolysis patients.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous conditions associated with high mortality and morbidity. Although several prognostic factors have been proposed, some may have yet to be identified. A 14-year retrospective cohort study of patients with SJS/TEN was conducted at a university-based hospital in Bangkok, Thailand, to explore additional prognostic factors for mortality of patients with SJS/TEN. Medical records of all patients aged ≥18 years who were diagnosed with SJS, SJS-TEN overlap, or TEN between 2007 and 2020 were reviewed. Univariate and multivariate analyses were performed to examine associations between death and potential prognostic factors. A total of 76 patients with a mean age of 52 years were enrolled. Among them, 46, 15, and 15 patients were diagnosed with SJS, SJS-TEN overlap, and TEN, respectively. Overall, 10 patients deceased, marking a mortality rate of 13.2%. Based on an algorithm for assessment of drug causality for epidermal necrolysis, drug was the major cause of disease (96.1%). Allopurinol and trimethoprim/sulfamethoxazole were the most frequent culprit drugs. Univariate analysis revealed nine prognostic factors related to death, i.e., age, malignancy, chronic kidney disease (CKD), coronary artery disease, heart rate >120 beats/min, diagnoses of SJS-TEN overlap and TEN, blood urea nitrogen (BUN) >10 mmol/L, hemoglobin <10 g/dL, and serum albumin <2 g/dL. Causality with regard to drug, drug notoriety, time interval from drug intake to onset of reaction, and timing of culprit drug withdrawal were not significantly associated with death. Four independent prognostic factors for mortality were identified from multivariate analysis, i.e., TEN (risk ratio [RR] 8.29, 95% confidence interval [CI]: 2.71–25.38), malignancy (RR 3.34, 95% CI: 1.68–6.69), BUN >10 mmol/L (RR 3.02, 95% CI: 1.28–7.14), and early-stage CKD (RR 4.81, 95% CI: 2.49–9.28). Our findings suggest that CKD is an independent prognostic factor for mortality of patients with SJS/TEN besides those from the SCORTEN.

Psychotherapeutic interventions for burns patients and the potential use with Stevens-Johnson syndrome and toxic epidermal necrolysis patients: A systematic integrative review.

The existing evidence demonstrates that survivors of SJS/TEN have reported long-lasting psychological effects of their condition. Burns patients experience similar psychological effects. It is important to look at ways to help allay the psychological complications of SJS/TEN. As there is an absence of evidence on SJS/TEN psychotherapeutic interventions, it was judged to be beneficial to determine the evidence underpinning psychotherapeutic interventions used with burns patients. The aim of this systematic integrative review was to synthesize the evidence relating to psychotherapeutic interventions used with adult burns patients and patients with SJS/TEN. The systematic review was guided by Whittemore and Knafl's integrative review process and the PRISMA guidelines. Nine databases were searched for English and French language papers published January 2008 to January 2021. The protocol for the review was registered with PROSPERO. Following a screening process, 17 studies were included in the review. Two themes were identified using content analysis, (i) Empirically supported psychotherapeutic treatments, (ii) Alternative psychotherapeutic treatments. This review revealed no evidence on specific psychotherapeutic interventions for patients with SJS/TEN. Some of the interventions used with burns patients, viz. relaxation therapy, hypnosis and cognitive behavioral therapy showed some significant benefits. However, the evidence for burns patients is mainly focused on pain and pain anxiety as outcomes. Following further research, some of the interventions deployed in burns patients may be applicable to SJS/TEN patients, particularly stress reduction techniques. In addition, the caring behaviours such as compassion, respect, and getting to know the patient as a person are important components to psychological care.

WGCNA-Based DNA Methylation Profiling Analysis on Allopurinol-Induced Severe Cutaneous Adverse Reactions: A DNA Methylation Signature for Predisposing Drug Hypersensitivity.

Background: The role of aberrant DNA methylation in allopurinol-induced severe cutaneous adverse reactions (SCARs) is incompletely understood. To fill the gap, we analyze the DNA methylation profiling in allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients and identify the DNA methylation signature for predisposing allopurinol hypersensitivity. Methods: Genome-scale methylation analysis was conducted using the Illumina® HumanMethylation450 BeadChip. Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to analyze the data. Results: A total of 21,497 annotated promoter regions were analyzed. Ten modules were identified between allopurinol hypersensitivity and tolerance, with turquoise and yellow modules being the most significant correlation. ATG13, EPM2AIP1, and SRSF11 were the top three hub genes in the turquoise module. MIR412, MIR369, and MIR409 were the top three hub genes in the yellow module. Gene Ontology (GO) analysis revealed that the turquoise module was related to the metabolic process in intracellular organelles and the binding of various compounds, proteins, or nucleotides. The yellow module, however, was related to stimulus sensory perception in cytoskeletal elements and the activity of the receptor or transducer. Conclusion: DNA methylation plays a vital role in allopurinol-induced SCARs. DNA methylation profiling of SJS/TEN is significantly related to autophagy and microRNAs (miRNAs).

The Profiles of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) Patients in Tertiary Hospital

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe eruptive skin reactions that can cause death. The incidence of SJS and TEN cases in the United States is 1.5–9.6 per 1,000,000 per year. Drugs are the primary etiology of SJS and TEN. Some drugs are at high risk and used frequently. The SJS and TEN mortality rates were relatively high, with SJS 4.8%, SJS / TEN overlap 19.8%, and TEN 14.8%. In Indonesia, there are lack of studies on the SJS and TEN. This study is needed to determine the epidemiological profile of SJS and TEN. Purpose: This study aimed to describe SJS and TEN patients' profiles. Methods: Drug-induced SJS and TEN cases from January 2016 to December 2019 were evaluated from the medical records patients' profile, incidence, suspected drugs, risk factors, and comorbidities of SJS and TEN were described. Result: There were 28 SJS and TEN patients, comprising of 24 SJS patients (85.7%), 3 TEN patients (10.7%), and 1 SJS overlapping TEN patients (3.5%). The most common suspected drugs were paracetamol (22.2%), carbamazepine (20.4%), cefadroxil (8.8%), and ciprofloxacin (8.8%). Women (53.5%) experienced more severe drug eruptions than men (46.4%). The largest age group was 25–44 years (35.7%). Most comorbidities were epilepsy (21%), diabetes (15.7%), hypertension (15.7%), and stroke (15.7%). Conclusion: The most common manifestation was SJS with paracetamol as the most common suspected drug, followed by carbamazepine.

Corticosteroid Pulse Therapy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Patients With Acute Ocular Involvement

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. Retrospective, comparative case series. 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. 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. In SJS/TEN patients with acute ocular involvement, CPT initiated within 4 days from disease onset may help reduce severe ocular sequelae.

Nursing care for a toxic epidermal necrolysis patient to recover from total pain: A case study in the intensive care unit

Nursing care for a toxic epidermal necrolysis patient to recover from total pain: A case study in the intensive care unit

Effect of older age on complications and mortality in inpatients with Stevens-Johnson syndrome or toxic epidermal necrolysis

To the Editor: The prognoses for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) patients are known to be affected by old age.1 However, the effect of older age on hospital complications and inpatient mortality is primarily limited to results from small studies of SJS/TEN patients.1,2

Quality of Life of Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) and Stevens-Johnson Syndrome (SJS) and/or Toxic Epidermal Necrolysis (TEN) Patients.

PurposeDrug Reaction With Eosinophilia and Systemic Symptom (DRESS), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) are acute hypersensitivity reactions with the potential to reduce the quality of life of exposed individuals. This study aims to determine the quality of life of patients suffering from DRESS, SJS, SJS/TEN.Patients and MethodsA cross-sectional approach was used to get the quality of life data from DRESS, SJS, and/or TEN patients at Dr. Sardjito general hospital, Yogyakarta. The utility index and VAS score differences of EQ-5D-5L were analyzed based on the diagnosis.ResultsWe recruited 58 patients. Most of the patients were female (63%). The mean value of utility index was 0.61, 0.08 and 0.03 for DRESS, SJS and SJS/TEN patients, respectively (p value <0.01). Furthermore, the mean of VAS score was 73.36, 57.93 and 50.00 for DRESS, SJS and SJS/TEN patients, respectively (p value <0.01).ConclusionIn general, the quality of life of DRESS patients is better than the quality of life of SJS and/or TEN patients.

The effects of systemic cyclosporine in acute Stevens-Johnson syndrome/toxic epidermal necrolysis on ocular disease

PurposeTo evaluate the effect of systemic cyclosporine (CsA) on ocular disease in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients. MethodsIn this retrospective, comparative cohort study at a single center, patients with a diagnosis of SJS/TEN and with at least 3 months of follow up were divided into two groups: those who received systemic CsA and those who did not receive systemic CsA. Best-corrected visual acuity (BCVA) and chronic ocular surface complications score (COCS) at final follow-up were compared between the two groups. ResultsThe median age and follow-up period of patients was 29 years (range, 1.5–71 years) and 16.8 months (range, 3.67–91.58 months), respectively. BCVA, COCS, meibomian gland dysfunction, limbal stem cell deficiency, and the need for mucous membrane grafting and scleral lenses were not significantly different between patients who received systemic CsA as compared to patients who did not receive systemic CsA. ConclusionsIn this small cohort of patients with SJS/TEN, we could identify no association between the use of systemic CsA as a component of their initial therapy and chronic ocular complications.

Association of Cytokines With the Development of Complications in Burn and Toxic Epidermal Necrolysis (TENS) Patients

Association of Cytokines With the Development of Complications in Burn and Toxic Epidermal Necrolysis (TENS) Patients

Effect of diabetes mellitus on hospital complications of Stevens-Johnson syndrome and toxic epidermal necrolysis patients

Effect of diabetes mellitus on hospital complications of Stevens-Johnson syndrome and toxic epidermal necrolysis patients

Investigating the “July effect” in Stevens-Johnson syndrome and toxic epidermal necrolysis patients

Investigating the “July effect” in Stevens-Johnson syndrome and toxic epidermal necrolysis patients

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Patients Admitted to Sina Hospital in Hamadan, Iran: A 16-year study

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Patients Admitted to Sina Hospital in Hamadan, Iran: A 16-year study

Regulation of RIP3 protein stability by PELI1-mediated proteasome-dependent degradation

Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a serine-threonine kinase largely essential for necroptotic cell death; it also plays a role in some inflammatory diseases. High levels of RIP3 are likely sufficient to activate necroptotic and inflammatory pathways downstream of RIP3 in the absence of an upstream stimulus. For example, we have previously detected high levels or RIP3 in the skin of Toxic Epidermal Necrolysis patients; this correlates with increased phosphorylation of MLKL found in these patients. We have long surmised that there are molecular mechanisms to prevent anomalous activity of the RIP3 protein, and so prevent undesirable cell death and inflammatory effects when inappropriately activated. Recent discovery that Carboxyl terminus of Hsp 70-Interacting Protein (CHIP) could mediate ubiquitylation- and lysosome-dependent RIP3 degradation provides a potential protein that has this capacity. However, while screening for RIP3-binding proteins, we discovered that pellino E3 ubiquitin protein ligase 1 (PELI1) also interacts directly with RIP3 protein; further investigation in this study revealed that PELI1 also targets RIP3 for proteasome-dependent degradation. Interestingly, unlike CHIP, which targets RIP3 more generally, PELI1 preferentially targets kinase active RIP3 that has been phosphorylated on T182, subsequently leading to RIP3 degradation.

PELI1 Selectively Targets Kinase-Active RIP3 for Ubiquitylation-Dependent Proteasomal Degradation

Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is a central protein in necroptosis, but posttranslational processes that regulate RIP3 activity and stability remain poorly understood. Here, we identify pellino E3 ubiquitin protein ligase 1 (PELI1) as an E3 ligase that targets RIP3 for proteasome-dependent degradation. Phosphorylation of RIP3 on T182 leads to interaction with the forkhead-associated (FHA) domain of PELI1 and PELI1-mediated K48-linked polyubiquitylation of RIP3 on K363. Thissame phosphorylation event is also important forRIP3 kinase activity; thus, PELI1 preferentially targets kinase-active RIP3 for degradation. PELI1-mediated RIP3 degradation effectively prevents cell death triggered by RIP3 hyperactivation. Importantly, upregulated RIP3 expression in keratinocytes from toxic epidermal necrolysis (TEN) patients is correlated with low expression of PELI1, suggesting that loss of PELI1 may play a role in the pathogenesis of TEN. We propose that PELI1 may function to control inadvertent activation of RIP3, thus preventing aberrant cell death and maintaining cellular homeostasis.

Management and outcome of Stevens–Johnson syndrome and toxic epidermal necrolysis in patients admitted to Kenyatta National Hospital

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous drug reactions requiring intensive care and protracted hospitalization. Local data on their characteristics, management and outcomes are minimal. Our objective was to identify the complications of SJS/TEN and the management strategies employed and the effect of these on patient mortality. We conducted a retrospective cross-sectional study to determine the characteristics, management strategies and patient mortality associated with SJS/TEN in patients admitted to Kenyatta National Hospital from June 2006 to June 2016. Total population sampling was used to identify 115 patients with SJS/TEN. Data on disease complications, management strategies employed and mortality status as an outcome of therapy were extracted. Patients were predominantly managed using antimicrobials (16.4% of patients, 21.8% of whom received topical mupirocin). Fluid and electrolyte replacement, skin emolliation with liquid paraffin, temperature regulation and corticosteroids were used to treat 15.3, 13.4, 11.1 and 9.4% of patients, respectively. The mortality rate was 21.7%. Significantly (p ≤ 0.05) higher mortality was associated with patients’ area of residence, disease subclass, disease severity score, hypokalaemia, dyspnoea, haematological disturbance, sepsis and dehydration. Conversely, use of total parenteral nutrition, anticoagulants for deep venous thrombosis prophylaxis and prolonged duration of therapy were associated with significantly (p ≤ 0.001) lower mortality. Mortality was not associated with administration of corticosteroids or antibiotics. Independent predictors of mortality were hypokalaemia, dyspnoea, haematological disturbance and sepsis (all p ≤ 0.05). The main management strategy used to treat SJS/TEN was antimicrobial prophylaxis, but this was not correlated with mortality. Mortality was high and was attributed to distant patient residence, severe disease and complications, suggesting that early recognition of these signs could avert mortality.