Treatment of Toxic Epidermal Necrolysis with Etanercept in a Pediatric Patient.
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SUBMITTER: Zander E
PROVIDER: S-EPMC8475798 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLittle is known about the epidemiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in children.ObjectiveWe sought to determine the morbidity, mortality, and comorbid health conditions of SJS and TEN in US children.MethodsThis was a cross-sectional study of the 2009 to 2012 Nationwide Inpatient Sample, which contains a representative 20% sample of all US hospitalizations. Sociodemographics, inflation-adjusted cost, length of stay, comorbidities, and mortality were analyzed using descriptive statistics and multivariate regression analyses.ResultsThe incidences of SJS, SJS-TEN, and TEN were a mean 5.3, 0.8, and 0.4 cases per million children per year in the US, respectively. Prolonged length of stay and higher costs of care (SJS: 9.4 ± 0.6 days, $24,947 ± $3171; SJS-TEN: 15.7 ± 1.5 days, $63,787 ± $8014; TEN: 20.4 ± 6.3 days, $102,243 ± $37,588) were observed compared with all other admissions (4.6 ± 0.1 days, $10,496 ± $424). Mortality was 0% for SJS, 4% for SJS-TEN, and 16% for TEN. In regression models, predictors of mortality included renal failure (adjusted OR [aOR] 300.28, 95% confidence interval [CI] 48.59->999.99), malignancy (aOR 54.33, 95% CI 9.40-314.22), septicemia (aOR 30.45, 95% CI 7.91-117.19), bacterial infection (aOR 20.38, 95% CI 5.44-76.36), and epilepsy (aOR 5.56, 95% CI 1.37-26.2).LimitationsData regarding treatment were not available. Date of diagnosis of comorbidities was not present, precluding temporal analysis.ConclusionsPediatric SJS/TEN poses a substantial health burden in the United States.
| S-EPMC5502094 | biostudies-literature
Project description:Toxic epidermal necrolysis (TEN) is a rare, severe cutaneous adverse drug reaction with average mortality 25-35%, especially among elderly multimorbid patients. Established therapeutic guidelines do not exist and controversies underlie many of the presently suggested treatment regimens. Herein we present the use of the recently described combination scheme of methylprednisolone (500 mg methylprednisolone bolus i.v.) followed by infliximab (5 mg/kg i.v.) and high-dose intravenous immunoglobulin (2 g/kg over 5 days) to treat an elderly, 74-year-old female patient with TEN (SCORTEN 3) within the premises of a district hospital. Already from the second day of hospitalization the skin condition markedly stabilized and the patient's status improved rapidly thereafter. She was discharged after 19 days in stationary care in excellent general condition and remained without any sequels 9 months afterwards. The present paper further supports the feasibility, efficacy, and safety of the proposed combination modality for the treatment of elderly patients with TEN, a population susceptible to more severe TEN.
| S-EPMC3505931 | biostudies-literature
Project description:IntroductionA wide spectrum of cutaneous adverse reactions ranging from simple maculopapular rashes to more severe and life-threatening reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis(TEN) have been described after exposure to many antiepileptic drugs. Although the adverse effect following lamotrigine has been reported after a low initial dosage, the risk of developing TEN is relatively rare.Case reportWe present a 23-year-old female, 6 months post-partum, a case of complex partial seizure, who developed TEN after 14 days of monotherapy with lamotrigine. She was put on steroids and other supportive management. After a tempestuous course of 9 days in ICU, she made an eventful recovery.DiscussionLamotrigine, a chemically different newer antiepileptic, if rapidly titrated and used in conjunction with valproate can cause exfoliative dermatitis-like TEN, but at lower doses and as a monotherapy, female, post-partum, probably due to hormonal factors and strong association between HLA-B*1502 and AED (Antiepileptic drug)-induced SJS/TEN in patients of Asian ethnicity could be other contributing cause. Also, lesser use of lamotrigine in developing nations might have led to a lesser incidence of serious cutaneous adverse reactions. The SCORTEN (Severity-of-illness score for toxic epidermal necrolysis) is the most widely used system to standardize the evaluation of risk and prognosis in patients with TEN.ConclusionThough rare but TEN can occur following lamotrigine monotherapy. Prompt diagnosis, withdrawal of offending agent, and timely proper supportive care might help in lowering the mortality.
| S-EPMC7691122 | biostudies-literature
Project description: Not available
| S-EPMC8354840 | biostudies-literature
Project description: Not available
| S-EPMC9900641 | biostudies-literature
Project description:BackgroundToxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment.Methods/designThis split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment.DiscussionTopical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology.Trial registrationClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037.
| S-EPMC4546316 | biostudies-literature
Project description:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. Cytotoxic T cells and associated effector molecules are known to drive SJS/TEN pathophysiology, but the contribution of innate immune responses is not well understood. We describe a mechanism by which neutrophils triggered inflammation during early phases of SJS/TEN. Skin-infiltrating CD8+ T cells produced lipocalin-2 in a drug-specific manner, which triggered the formation of neutrophil extracellular traps (NETs) in early lesional skin. Neutrophils undergoing NETosis released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1 expression caused keratinocytes to be vulnerable to necroptosis that caused further release of LL-37 by necroptotic keratinocytes and induced FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. The NETs-necroptosis axis was not observed in less severe cutaneous adverse drug reactions, autoimmune diseases, or neutrophil-associated disorders, suggesting that this was a process specific to SJS/TEN. Initiation and progression of SJS/TEN keratinocyte necroptosis appear to involve a cascade of events mediated by innate and adaptive immune responses, and understanding these responses may contribute to the identification of diagnostic markers or therapeutic targets for these adverse drug reactions.
| S-EPMC9392155 | biostudies-literature
Project description:Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is one of the most devastating of adverse drug reactions (ADRs) and was, until recently, essentially unpredictable. With the discovery of several risk alleles for drug-induced SJS/TEN and the demonstration of effectiveness of screening in reducing incidence, the stage is set for implementation of preventive strategies in populations at risk. Yet much remains to be learned about this potentially fatal complication of commonly used drugs.
| S-EPMC5805563 | biostudies-literature
Project description:Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients' skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.
| S-EPMC10832423 | biostudies-literature
Project description:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases characterized by detachment of the epidermis and mucous membrane. SJS/TEN are considered to be on the same spectrum of diseases with different severities. They are classified by the percentage of skin detachment area. SJS/TEN can also cause several complications in the liver, kidneys, and respiratory tract. The pathogenesis of SJS/TEN is still unclear. Although it is difficult to diagnose early stage SJS/TEN, biomarkers for diagnosis or severity prediction have not been well established. Furthermore, optimal therapeutic options for SJS/TEN are still controversial. Several drugs, such as carbamazepine and allopurinol, are reported to have a strong relationship with a specific human leukocyte antigen (HLA) type. This relationship differs between different ethnicities. Recently, the usefulness of HLA screening before administering specific drugs to decrease the incidence of SJS/TEN has been investigated. Skin detachment in SJS/TEN skin lesions is caused by extensive epidermal cell death, which has been considered to be apoptosis via the Fas-FasL pathway or perforin/granzyme pathway. We reported that necroptosis, i.e. programmed necrosis, also contributes to epidermal cell death. Annexin A1, released from monocytes, and its interaction with the formyl peptide receptor 1 induce necroptosis. Several diagnostic or prognostic biomarkers for SJS/TEN have been reported, such as CCL-27, IL-15, galectin-7, and RIP3. Supportive care is recommended for the treatment of SJS/TEN. However, optimal therapeutic options such as systemic corticosteroids, intravenous immunoglobulin, cyclosporine, and TNF-? antagonists are still controversial. Recently, the beneficial effects of cyclosporine and TNF-? antagonists have been explored. In this review, we discuss recent advances in the pathophysiology and management of SJS/TEN.
| S-EPMC7308994 | biostudies-literature