French referral center management of Stevens–Johnson syndrome/toxic epidermal necrolysis

Drug-induced adverse reactions represent major health problems, with the skin being one of the most common targets. Approximately 2% of all drug-induced skin reactions are considered serious. Stevens–Johnson syndrome/toxic epidermal necrolysis corresponds to rare and acute life-threatening mucocutaneous reactions characterized by extensive necrosis and epidermal detachment. This review focuses on the management of these severe cutaneous reactions in the French Referral Center for Toxic Bullous Diseases. Early referral to a specialized unit, early diagnosis of severe cutaneous adverse reactions, prompt withdrawal of the culprit drug, improved symptomatic management, and specific dermatological care have contributed to better survival in the past 10 years and also has limited sequelae.     

Epidermal necrolysis (Stevens–Johnson syndrome and toxic epidermal necrolysis): Historical considerations

ObjectiveTo describe the history of toxic epidermal necrolysis, before and after the original report by the British dermatologist Alan Lyell in 1956.MethodsSubjective expert choice of key advances in the comprehension of the nosology, classification, causality, and mechanisms of epidermal necrolysis (EN) over more than a century.ResultsEpidermolysis had been reported long before Lyell's paper, but most cases had likely been staphylococcal scalded skin syndrome in children. Concerning non-Staphylococcus EN, confusion with erythema multiforme dissipated and its relation to Stevens–Johnson syndrome was clarified. Tremendous advances were made in understanding the causes and mechanisms, with increased acceleration in the last 10 years.ConclusionThe next decade should be devoted to improve the prevention and management of a disease that is the most terrible form of drug hypersensitivity.     

Accuracy of SCORTEN and ABCD-10 to predict mortality and the influence of renal function in Stevens–Johnson syndrome/toxic epidermal necrolysis

Epidermal necrolysis (EN) compromises a spectrum of life-threatening dermatoses (Stevens–Johnson Syndrome [SJS], overlap syndrome and toxic epidermal necrolysis [TEN]). Currently, no active therapeutic regimen with unequivocal benefit exists for SJS/TEN. SCORTEN is the widely-used prognostic scale specific for SJS/TEN. Nevertheless, a new prognostic scale, the ABCD-10, has been recently proposed. In this context, acute renal failure (ARF) seems to be an important comorbidity that could influence prognosis in SJS/TEN patients more than it is assumed by these two scales. Our objectives were to compare the accuracy of the SCORTEN and ABCD-10 scales in predicting the mortality in SJS/TEN, and to investigate the influence of renal failure on prognosis. The prognostic results of 18 patients with EN treated in two referral centers between 2013 and 2018 are presented. SCORTEN, ABCD-10 and renal function values were retrospectively collected for all patients. Out of the 18 patients who were analyzed, nine (50%) received only supportive therapy, four were treated with etanercept 50 mg in a single dose (22.2%) and five with corticosteroids (27.8%). Five patients developed ARF. Predicted mortality was 3.48 for SCORTEN and 2.33 for ABCD-10. Eventually, four patients died (22.2%), all had ARF and none of them received active treatment. Despite study limitations and in the absence of active treatment of choice, SCORTEN behaved as a reliable predictor of mortality in patients with EN, outperforming the newer ABCD-10. ARF was an early event associated with a poor prognosis, which could represent a prognostic marker to consider in the future.     

British Association of Dermatologists' guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis in children and young people, 2018

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are urgent, serious immune reactions in which there is skin loss and severe ulcers in the mouth, eyes and genital areas. It affects about 5-6 people per million under 18 years of age in the U.K. each year. It has a mortality of (causes death in) 5-10% and re-occurs in up to 18% of survivors. The British Association of Dermatologists led a group of relevant experts to examine the evidence in developing guidelines to aid diagnosis and management of SJS/TEN in children and young people. As with many rare conditions, there are few high-quality trials comparing one treatment with another. Most of the evidence comes from patient examples reported in the medical literature (i.e. medical journals). The research reveals some important differences between children and adults in terms of the cause and outcomes of SJS/TEN. Infections are a more common cause in children and young people although medication can be the cause in all ages. Children are less likely to die from SJS/TEN than adults. Preventing long-term complications is of key importance. Management in the early stages should ensure the identification of the cause, stopping any possible medications that might be the cause, and consideration of infection as the trigger. The best evidence for improved outcomes is good supportive care in the right clinical environment. This requires admission to appropriate specialist units with experience in managing skin loss, and a team of hospital specialists who can address all potential clinical complications. Longer-term management involves supporting patients and their families with any resulting complications including those affecting the eyes, skin, lungs and psychological impact. The guidelines highlight that there is still much that is unknown about the best way to manage this potentially devastating reaction, and identifies the need for better routine data collection, diagnosis and standardised treatment, as well as a multi-disciplinary (involving different types of healthcare workers) approach to management.     

Post-traumatic stress disorder in Stevens–Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients

Epidermal necrolysis is a rare and severe syndrome, mainly caused by a reaction to a medication, which causes severe blistering and sloughing of skin and mucous membranes. It includes two syndromes, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), depending on the percentage of body surface area involved. Incidence in France is one to two cases per million people. Multiple long-term consequences of this violent and acute disorder are known about, mostly affecting skin and eyes, but also psychological distress, called post-traumatic stress disorder (PTSD). However, commonness and risk factors of PTSD are still largely unknown. The present study was conducted by the research team of the national reference centre for toxic bullous diseases, based in Henri Mondor hospital, Créteil, France. We aimed to assess the prevalence and the risk factors of PTSD. We included 31 adult patients admitted at the acute phase (i.e. at its most severe) of SJS/TEN from 2009 to 2013. All of them were evaluated by a psychiatrist with several psychologic scores at the acute phase and were prescribed an anti-anxiety drug, hydroxyzine, if necessary, then patients were checked again at two, six and 12 months. The degree of post-traumatic stress was defined by a PTSD Checklist score of greater than 44. At six months, the PTSD prevalence was 23%. Three patients developed a late PTSD at 12 months. We conclude that a systematic psychiatric evaluation is warranted at the acute phase and must be followed by a prolonged and repeated evaluation of the patients for at least one year.     

Genetic association of IFN-γ +874T/A polymorphism in Mexican patients with drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, but potentially life-threatening diseases, characterized by widespread epidermal necrosis and are predominantly drug induced. There is a paucity of data regarding the role of cytokine and cytokine receptors polymorphisms in the pathoimmunology of SJS/TEN. The aim of this study was to investigate the role of TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg gene polymorphisms in SJS/TEN in Mexican Mestizo patients. Twenty-nine unrelated SJS/TEN patients and 128 unrelated healthy individuals were studied. Genomic extraction was carried out from complete blood samples using the salting out method. The PCR–RFLP method was used to amplify the following polymorphisms: TNF-α-308, IFN-γ +874, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg. TNF-α-308, IL-10-1082, IL-13 Arg130Gln, and IL-4R Gln551Arg polymorphisms were not associated with the genetic susceptibility to SJS/TEN. The distribution of TT, TA, AA genotypes of IFN-γ +874 was significantly different in SJS/TEN patients compared with controls (pC = 0.012). TA and AA genotypes were grouped to highlight the differences between patients and controls given by the absence of the AA genotype in the group of patients (pC = 0.03, OR = 3.61 95 % CI 1.20–11.6). This preliminary study suggests that IFN-γ +874 T/A polymorphism is associated with SJS/TEN.     

The psychological impact of Stevens-Johnson syndrome and toxic epidermal necrolysis on patients’ lives

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions (affecting 1-2 people per million per year) usually caused by a severe immune reaction to certain medications and, in some cases, the cause may be linked to particular infections. Those affected are likely to have a loss of skin and mucous membranes. People who get these conditions become very ill quickly and experience severe pain. SJS and TEN can have long-term physical effects such as skin, eye, breathing and stomach problems. Little is known about the psychological effects on patients’ lives. This research was inspired by a man diagnosed with TEN. Because he appeared anxious and fearful, the authors questioned how SJS/TEN affected patients’ lives. The authors systematically searched for research papers regarding SJS and TEN, to help understand the psychological impact of these conditions on patients’ lives, and they found six relevant studies. The findings highlight that some healthcare practitioners lacked information about the conditions, leading to fear and anxiety in patients. Some patients had symptoms of post-traumatic stress disorder (PTSD), anxiety and depression. The findings conclude that SJS/TEN impacts psychologically on patients’ lives. The authors suggest that, if healthcare practitioners are educated about SJS/TEN, this should assist them to provide patients with the information and support which they need in order to be less anxious. In addition, on discharge, patients should have a follow up appointment with a relevant healthcare practitioner to reduce the possibility of PTSD occurring. Linked Article:   O’Reilly et al. Br J Dermatol 2020; 183 :452–461 .     

Tegafur/gimeracil/oteracil (TS-1) induced Stevens–Johnson syndrome: Case report

TS-1 is an oral fluoropyrimidine anticancer drug that contains tegafur, gimeracil, and oteracil. A 78-year-old Japanese male who was diagnosed with carcinoma of the oral floor (rT4aN0M0) was prescribed a standard dose of TS-1 (80 mg/day). On Day 8 after administration of TS-1, an eruption developed. There was erythema, along with vesicles and erosions involving the lip, face, neck, trunk, limbs, and genitals. The drug-induced lymphocyte stimulation test (DLST) for TS-1 was negative on the 23^rd day, but positive on the 43^rd day (20 days after discontinuing prednisolone). The condition was diagnosed as Stevens–Johnson syndrome due to TS-1 because of the clinical course and laboratory results. This case and 24 cases previously reported in the literature were analyzed. The types of drug eruption were drug-related lupus (9 cases), acral erythema (7 cases), scleroderma-like skin lesion (2 cases), Stevens–Johnson syndrome (2 cases), lichenoid eruption (1 case), purpura (1 case), lichen planus (1 case), erythema multiforme (1 case), hypopigmentation (1 case) and toxic epidermal necrolysis (1 case), respectively. In view of the increasing usage of TS-1 in several common cancers, clinicians should be aware of drug eruptions due to TS-1.