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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.

The 31-year-old female patient was admitted to the General Hospital of the Chinese People's Liberation Army for 3 days after the corneal transplantation of her right eye for 5 months.Four years ago, the patient developed red eyes, pain, dryness and photophobia after intravenous drip of cefuroxime sodium and metronidazole due to pelvic inflammation, accompanied by high fever, systemic rash and epidermal exfoliation, fingernail peeling, and mucosal ulceration in the eyes and mouth.Later, the patient received systemic hormone shock and point eye treatment in a local hospital, and the dry eyes gradually worsened. Despite continuous artificial tears and bandage mirror treatment, the corneal ulcer perforation in both eyes still occurred successively. After several penetrating keratografts and drug therapy, the ulcer and dissolution could not be prevented. He was admitted to our hospital due to corneal perforation in both eyes.Ophthalmic examination: visual acuity manual/15 cm in the right eye, intraocular pressure T-2, conjunctival sac stenosis, extensive corneal opacity and edema, ulcer about 8 mm, corneal perforation near the corneal limbus about 2 mm×5 mm below.The left eye had no light perception, a central corneal ulcer of about 8 mm, bulge of the posterior elastic layer, no anterior chamber, and atrophy of the eyeball.B-ultrasound showed choroidal detachment of the right eye.On the second day, the patient received right eye intraocular exploration, vitrectomy, ecotopic keratoscleral carrier Boston Ⅱ artificial keratoplasty, glaucoma valve implantation, autogenous ear cartilage implantation, conjunctival occlusion, and left eye lamellar keratoplasty, conjunctival occlusion.Postoperative visual acuity of right eye was -6.50 DS=0.12, intraocular pressure TN, ocular surface was stable.The left eye has no light perception and the ocular surface is stable.31岁女性因右眼角膜移植术后5个月热泪涌出3 d就诊。患者4年前因盆腔炎性反应静滴头孢呋辛钠及甲硝唑后出现双眼红痛、干涩、畏光，伴有高热及全身皮疹及表皮剥脱，指甲脱落，眼、口腔等多处黏膜溃烂。后患者于当地医院行全身糖皮质激素冲击及局部药物治疗，眼部干燥并逐渐加重，尽管局部给予持续人工泪液及绷带镜等治疗，仍先后发生双眼角膜溃疡穿孔。经多次穿透性角膜移植术和药物治疗无法阻止溃疡和角膜融解，因双眼角膜穿孔入院。眼科检查：右眼视力15 cm手动，眼压中度降低，结膜囊狭窄，角膜广泛混浊水肿，溃疡直径约8 mm，下方近角膜缘约2 mm×5 mm的角膜穿孔。左眼视力无光感，角膜中央溃疡直径约8 mm，后弹力层膨出，无前房，眼球萎缩。B超显示右眼脉络膜脱离。行右眼眼内探查、玻璃体切除、异位角巩膜载体BostonⅡ型人工角膜植入术、青光眼阀植入术、自体耳软骨植入术、结膜遮盖术，左眼板层角膜移植、结膜遮盖术。术后右眼-6.50 DS矫正至0.12，眼压正常，眼表稳定。左眼视力无光感，眼表稳定。.

Enfortumab vedotin is an antibody-drug conjugate used for treatment of urothelial cancer. It has recently been associated with several reports of Stevens Johnson syndrome/toxic epidermal necrolysis (TEN). In this report, we describe the case of a 63-year-old man who developed widespread, near full-thickness desquamation, clinically mimicking TEN but with histologic features of toxic erythema of chemotherapy. This distinction is significant because it may have implications for prognosis and treatment. Further investigation is needed to ascertain the incidence of true TEN versus clinical imitators in patients with enfortumab vedotin-related cutaneous toxicity.

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

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening disorders characterized by widespread epidermal necrosis of the skin and mucosa. The severity-of-illness scoring system for TEN (SCORTEN) was widely used since 2000 as a standard prognostic tool consisting of seven clinical values. Methods: To evaluate the prognosis using current treatments and risk factors for mortality, we retrospectively analyzed 59 cases of TEN, including SJS/TEN overlap treated in two university hospitals from January 2000 to March 2020. Results: The mortality rate of TEN was 13.6% (8/59). All patients treated with high-dose steroid administration in combination with plasma exchange and/or immunoglobulin therapy recovered. Logistic regression analysis showed nine clinical composite scores, namely: heart rate (≧120 bpm), malignancy present, percentage of body surface area with epidermal detachment (>10%), blood urea nitrogen (>28 mg/dL), serum bicarbonate level (252 mg/dL), age (≧71 years), the interval between disease onset and treatment initiation at the specialty hospital (≧8 days), and respiratory disorder within 48 h after admission. The receiver operating characteristic curves confirmed a high potential for predicting the prognosis of TEN. Conclusions: Recent developments in treatment strategies have contributed to the improved prognosis of TEN patients. A modified severity scoring model composed of nine scores may be helpful in the prediction of TEN prognosis in recent patients. Further large-scale studies are needed to confirm mortality findings to improve prognostication in patients with TEN.

Complications involving internal organs are usually present in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, pancreatic complications are rarely reported and studied.To summarize clinical characteristics of SJS/TEN-associated acute pancreatic injuries and to investigate underlying inflammatory mechanisms.Clinical records of 124 inpatients with SJS/TEN were reviewed. Serum levels of tumor necrosis factor α, interleukin (IL) 6, IL-18, IL-15, IL-12p70, and soluble CD56 were determined in 18 healthy donors and 17 patients with SJS/TEN, including 3 with acute pancreatic injuries.Acute pancreatic injury was diagnosed in 7.3% of patients (9/124) in the SJS/TEN cohort. Elevation of serum transaminase level and hypoalbuminemia occurred more frequently in patients with acute pancreatic injuries compared with those without pancreatic symptoms (P = .004 and .001, respectively). Although acute pancreatic injury did not alter mortality rate of SJS/TEN, it was associated with longer hospitalization stays (P = .008). Within the serum cytokines whose levels were elevated in SJS/TEN, only IL-18 was found to be selectively increased in patients with acute pancreatic injuries compared with those without them (P = .03).Cohort was small.Acute pancreatic injury is a gastrointestinal complication of SJS/TEN in which hepatotoxicity is more likely to occur. Overexpression of IL-18 might be involved in this unique entity.

Severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome/toxic epidermal necrolysis and drug-induced hypersensitivity syndrome, are rare and occasionally fatal. However, it is difficult to detect SCARs at the drug development stage, necessitating a new approach for prediction. Therefore, in this study, using the chemical structure information of SCAR-causative drugs from the Japanese Adverse Drug Event Report (JADER) database, we tried to develop a predictive classification model of SCAR through deep learning. In the JADER database from 2004 to 2017, we defined 185 SCAR-positive drugs and 195 SCAR-negative drugs using proportional reporting ratios as the signal detection method, and the total number of reports. These SCAR-positive and SCAR-negative drugs were randomly divided into the training dataset for model construction and the test dataset for evaluation. The model performance was evaluated in the independent test dataset inside the applicability domain (AD), which is the chemical space for reliable prediction results. Using the deep learning model with molecular descriptors as the drug structure information, the area under the curve was 0.76 for the 148 drugs of the test dataset inside the AD. The method developed in the present study allows for utilizing the JADER database for SCAR classification, with potential to improve screening efficiency in the development of new drugs. This method may also help to noninvasively identify the causative drug, and help assess the causality between drugs and SCARs in postmarketing surveillance.

Purpose To study the outcomes of cultivated oral mucosal epithelial transplantation (COMET) in eyes with chronic Stevens-Johnson syndrome (SJS) sequelae. Design Prospective interventional case series. Methods Forty-five eyes of 41 patients with chronic SJS sequelae were recruited and evaluated from 2013 to 2017 in an institutional setting. All patients underwent COMET, with an aim of fornix reconstruction and visual rehabilitation. Change in corrected distance visual acuity (CDVA), severity scores of various ocular surface parameters, and the occurrence of complications were documented during a follow up period of 2 years. Attainment and maintenance of a stable ocular surface, as assessed by change in the ocular surface severity scores was the primary outcome measure, while change in CDVA was the secondary outcome measure. Results The mean preoperative CDVA was 2.7± 0.5 logMAR, which improved to 1.5± 0.7 logMAR and 1.49± 0.98 postoperatively, at 1- and 2-year follow-up visit. Overall, 82.2% eyes (37/45) had improvement in visual acuity, 13.3% (6/45) experienced no change, whereas 2 eyes (4.4%) had worsening of visual acuity. The total ocular surface severity scores improved from a mean preoperative value of 29.1± 9.7 to 18.7± 7.2 postoperatively, at 2-year follow-up. Two eyes developed persistent epithelial defects, with progression to corneal melting requiring keratoplasty. Conclusions COMET allows successful and sustained restoration of ocular surface anatomy with functional improvement, in eyes with chronic sequelae of SJS.

Severe cutaneous adverse reactions (SCARs) are potentially lethal adverse drug reactions that involve the skin, mucous membranes, and internal organs, resulting in disability. SCARs include drug-induced epidermal necrolysis, which is Steven Johnson syndrome (SJS)/ Steven Johnson syndrome and toxic epidermal necrolysis overlap (SJS-TEN overlap)/ toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), generalised bullous fixed drug eruption (GBFDE), and acute erythroderma. Awareness of local epidemiology of SCARs plays an important role in prescribing practices by healthcare provider. Recognition of SCARs enables the offending drug to be withdrawn immediately, which is the definitive treatment of SCARs.This is a retrospective study reviewing SCAR cases reported to the Malaysian Adverse Drug Reactions Advisory Committee (MADRAC) registry at the Department of Dermatology, Hospital Melaka, for 5 years and 3 months from December 2014 to February 2020.A total of 41 SCARs cases were identified over the study duration. The incidence rate was 0.18%. All 41 cases require hospitalisations, with four cases (9.8%) managed in ICU and one mortality (2.4%) due to SJS-related complication. One patient had two episodes of SCARs. There were 22 male patients and 18 female patients. The majority were Malays (33, 80.5%), followed by Chinese (7, 17.1%) and Indonesian (1, 2.4%). There was no Indian patient with SCARs in this study. The mean age of patients was 47.2±17 years. Drug-induced epidermal necrolysis was the commonest type of SCARs (63.4%), and out of this, SJS accounted for the majority of cases (48.8%). Antibiotic was the main group of offending medication in this SCAR study (29.3%). The top five individual causative drugs of SCARs in sequence include allopurinol, phenytoin, carbamazepine, co-amoxiclav, and cephalexin. Allopurinol was the commonest culprit drug for drug-induced epidermal necrolysis and DRESS, phenytoin for acute erythroderma, and co-amoxiclav for AGEP.SJS was the most common manifestation and Allopurinol was the commonest culprit drug for SCAR cases in our cohort.

A 65-year-old male was admitted to our hospital with an abscess on his buttocks. Computed tomography (CT) on admission incidentally revealed left kidney cancer, and retroperitoneal nephrectomy was performed. Pathological examination confirmed a diagnosis of renal cell carcinoma. One month after surgery, CT showed findings suggesting primary liver cancer or liver metastasis along with retroperitoneal metastasis. Although metastatic kidney cancer was suspected, the possibility of primary liver cancer could not be ruled out. Therefore, we initiated treatment using sorafenib, which is indicated for both types of cancer, as first-line treatment for intermediate-risk based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification. After three months of sorafenib treatment, the patient showed hyponatremia, anemia, and hand-foot syndrome and was admitted to the hospital. CT showed an enlarged area that appeared to be a metastatic site, after which we suspended sorafenib. Four months after sorafenib treatment, nivolumab was initiated as a second-line treatment. However, on day 28 after the administration of nivolumab eruptions appeared all over the patient's body. The patient was diagnosed with Stevens-Johnson syndrome due to nivolumab. We initiated corticosteroid therapy, and the eruptions gradually improved. Prednisolone was gradually reduced to 5mg/day, after which the patient was discharged. Six months after discharge, the eruptions had generally become epithelialized and no metastatic lesions had grown. The patient remained under observation without proceeding to third-line treatment. It is crucial to carefully monitor the patient's condition, especially in cases involving serious immune-related adverse events.

We describe here the case of a 7-year-old male patient with Stevens-Johnson syndrome (SJS), which was suspected to be caused by treatment with tipepidine hibenzate (Asverin

Background Therapeutic plasma exchange (TPE) is an effective means of treating systemic lupus erythematosus in children and is safe for most pediatric patients with systemic lupus erythematosus, but severe complications such as toxic epidermal necrolysis (TEN) may occur, which is a life-threatening condition. Methods In this study, three systemic lupus erythematosus (SLE) children developed toxic epidermal necrolysis after TPE. We analyzed their medical history, clinical manifestations, SLEDAI scores, and immunological characteristics, compared to 117 cases of SLE patients without TEN after TPE, trying to find the possible risk factors. Results The three children with TEN after plasma exchange appeared to have a higher proportion of male (male: female = 2:1), fever (100% Vs 32.5%), erythema on the cheek (100% Vs 54.7%), itching rash (100% Vs 54.7%), ruptured rash (100% Vs 54.7%), oral ulcer (100% Vs 54.7%) and higher LDH level (1826.0 ± 1113.1 Vs 721.1 ± 799.5 U/L), but lower white blood cell count (5.5 ± 3.3 Vs 7.2 ± 4.2 × 109/L), neutrophil count (4.7 ± 3.7 Vs 5.2 ± 3.6 × 109/L), lymphocyte count (0.6 ± 0.5 Vs 1.5 ± 0.8 × 109/L), platelet count (133.7 ± 58.1 Vs 178.5 ± 103.1 × 109/L) and C-reactive protein (all normal Vs 47.9% elevated). Autoantibody spectrum revealed that positive anti-SSA seemed more common (100% Vs 42.7%) in the three children. Relative risk analysis revealed that male (OR 21.4, 95%CI 1.78–257.186), ruptured skin rash (OR 56.5, 95%CI 4.199–760.196) and rash with itching (OR 24, 95%CI 1.98–290.896) are the risk factors of SLE patients developing TEN after plasma exchange. Conclusions We should pay particular attention to TEN after plasma exchange in SLE patients (3/120, 2.5%). This condition may be related to male, ruptured skin rash and rash with itching. For SLE patients with risk factors. We should arrange plasmapheresis more carefully.

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. Objectives To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. Methods We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. Results A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. Conclusions Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

Objective Previous studies have found an association between HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS)/ toxic epidermal necrosis (TEN) spectrum in Han Chinese populations. This study aims to investigate the association between HLA-B*1502 and lamotrigine- or phenytoin- induced SJS/TEN in an Iranian population. Methods The medical records of twenty-eight lamotrigine-induced SJS/TEN patients and twenty-five lamotrigine-tolerant controls as well as eight phenytoin-induced SJS/TEN and twelve phenytoin-tolerant controls were extracted between March 2013 to March 2019 from the university hospitals in Mashhad, Iran. The presence of HLA-B*1502 allele was determined using real-time polymerase chain reaction (PCR). Results Among lamotrigine-induced patients with SJS/TEN, 11 (39.3%) patients tested positive for the HLA-B*1502 while only 3 (12.0%) of the lamotrigine-tolerant controls tested positive for this allele. The risk of lamotrigine-induced SJS/TEN was significantly higher in patients with HLA-B*1502, with an odds ratio (OR) of 4.74 [95% confidence interval (CI) 1.14-19.73, p = 0.032]. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HLA-B*1502 for lamotrigine-induced SJS/TEN was 39.29%, 88.00%, 78.57% and 56.41%, respectively. The HLA-B*1502 allele was present in 2 (25.0%) of phenytoin-induced SJS/TEN cases and 5 (41.7%) of the phenytoin-tolerant controls tested positive for HLA-B*1502 allele. The risk of phenytoin-induced SJS/TEN was not higher in the patients with HLA-B*1502 (OR = 0.467 [95% confidence interval (CI) 0.065-3.34, p = 0.642]). Significance Lamotrigine-induced SJS/TEN is associated with HLA-B*1502 allele in an Iranian population but this is not the case for phenytoin-induced SJS/TEN.

Objective Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs. Methods Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM. Results The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use. Significance This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.

Thermal burns can occur during seizure. This diagnosis can be difficult in case of atypical lesions, even more if the epilepsy is unknown and in case of seizures with loss of consciousness and/or an unwitnessed epileptic attack. We report two cases of cutaneous bullous lesions initially misdiagnosed as severe acute cutaneous adverse reactions (generalized bullous fixed drug eruption and Stevens–Johnson syndrome). In the two cases, the clinical aspect, necrotic evolution, and absence of obvious attributable medication allowed to revert to the diagnosis of burns due to boiling water revealing previously unknown epilepsy. For both, surgical management with skin graft was performed, and antiepileptic treatment was introduced. Facing unexplained burns, occult epilepsy should be investigated. Questioning of patient and relatives is crucial.

To detect the immunohistochemical changes in the main lacrimal glands of patients suffering from chronic ocular sequelae of Stevens-Johnson syndrome (SJS).Histological sections of biopsies from the lacrimal gland of three chronic SJS patients (mean age, 33 years; 2 males) with severe dry eye disease (Schirmer = 0 mm) were assessed using double immunofluorescence techniques. Changes in the expression of secretory proteins lactoferrin (Lf), lysozyme (Ly), aquaporin 5 (AQP5), S-100, and early apoptosis marker (Annexin V) were studied.Different morphological expressions of secretory proteins were present in the three samples. One sample had maintained the immunoreactivity for Lf, Ly, S-100, similar to healthy controls. Two samples had significantly reduced immunoreactivity for anti-Lf, anti-Ly, and S-100, the weakest being in the sample with distorted lobular architecture and mild interlobular fibrosis. AQP5 had a distinct vesicular intracytoplasmic immunoreactivity suggesting defective trafficking and integration of the protein to the apical membrane. There was no S-100 immunostaining in the acinar or ductal epithelium, whereas interstitial nerve fibers scattered in the periacinar region showed reduced immunoreactivity for S-100. There was strong Annexin V immunoreactivity in the nuclei of epithelial cells in the majority of acinar and ductal epithelia of all the samples, with distorted nuclear morphology in one sample.Defective trafficking of AQP5 and variable expression of Ly, Lf, S-100 are the notable findings in the lacrimal glands of chronic SJS patients along with signs of early apoptosis. It suggests that the palpebral lobe of the lacrimal gland is involved in the pathological processes occurring in the conjunctiva of SJS patients.

The chronic sequelae of Stevens-Johnson syndrome cause severe ocular morbidity. Among the various manifestations, including dry eye, cicatrization causing forniceal shortening, adnexal disorders, lid margin keratinization, and limbal stem cell deficiency, keratinization of the lid margin leads to progressive ocular surface damage through constant blink-induced microtrauma. This damage induces corneal punctate keratopathy and neovascularization and can produce epithelial defects leading to corneal infection or perforation. Management strategies for chronic ocular sequelae are broadly categorized into ocular surface stabilization procedures, tectonic procedures, and visual rehabilitation procedures. Interventions in the acute stage of the disease include amniotic membrane grafting. Timely intervention helps to prevent deterioration of the ocular surface in these eyes.

Background Toxic epidermal necrolysis (TEN) is a severe, potentially lethal drug reaction for which no standard treatment is available. Objective To describe 17 consecutive TEN patients treated with a single dose of etanercept, a TNF-alpha inhibitor. Materials & methods Comorbidities and any drug treatment initiated within the previous month were recorded on admission. Patients received 50 mg etanercept in a single subcutaneous injection. The clinical severity of the disease was computed using the SCORTEN scale. The expected number of deaths was calculated based on the probability of death associated with each SCORTEN score level. Healing was defined as complete re-epithelialization. Time to healing was analysed using the Kaplan-Meier estimator. Results The lowest SCORTEN score was 2, and seven patients scored in the most severe risk category (i.e., =>5). A comparison between observed (2/17) vs. expected deaths (10/17) was statistically significant (p=0.012). Fifteen patients promptly responded to treatment and achieved complete re-epithelization (median time to healing: 8.5 days), without complications or side effects. The two observed deaths were due to other causes, although re-epithelization had initiated in both patients. Conclusion These preliminary results add to our initial observations indicating that etanercept may effectively control TEN, a potentially lethal skin condition for which there is currently no effective cure. Where funding is available, randomized controlled trials on etanercept for TEN should be conducted.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening immune-mediated hypersensitivity reactions. Various drugs, such as Non Steroidal Anti-inflammatory drugs (NSAIDS), allopurinol, anticonvulsants and antibiotics, have been implicated as triggering agent of SJS/TEN. Levamisole is frequently used as an antihelminthic and as an immunomodulator in cases of nephrotic syndrome. However, levamisole has not been reported as a trigger for SJS/TEN. The current case describes levamisole-induced TEN in a 15-year-old male who presented to emergency with erythematous lesions, blistering and denudation of skin involving up to 30% of body surface area. Algorithm of drug causality for epidermal necrolysis scoring was applied for causality assessment and a relationship was found to be "possible". Immediate withdrawal of levamisole along with a short course of corticosteroids and cyclosporine led to improvement in signs and symptoms. Clinicians should be aware of the possible association of levamisole and SJS/TEN.

Aim: To examine gene expression in different clinical phenotypes of allopurinol-induced severe cutaneous adverse reactions (SCARs). Materials & methods: Gene expression profiling was performed using microarray on 11 RNA samples (four controls, three hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms, four Stevens–Johnson syndrome/toxic epidermal necrolysis) followed by quantitative real-time PCR in a total of 11 SCARs patients and 11 controls. Results: The biological pathways which were significantly enriched in differentially expressed genes in Stevens–Johnson syndrome/toxic epidermal necrolysis compared with hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms patients included; cell surface interactions at the vascular wall, immunoregulatory interactions at the immunological synapse and MyD88 signaling pathways. Overexpression of miR146a occurred in allopurinol-tolerant HLA-B*58:01 carriers. Conclusion: Biological pathways are identified which appear to be implicated in determining clinical phenotypes in allopurinol-induced SCARs. Overexpression of miR146a is potentially important for allopurinol tolerance in HLA-B*58:01 carriers.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of vesiculobullous disorders affecting skin and mucous membranes. Although rare, they are associated with a high mortality rate of up to 35% in adults and up to 17% in children.1 2 Ocular involvement is common and is present acutely in 43–81% of hospitalised patients.3 4 This ranges from conjunctival injection and membrane formation to epithelial sloughing of eyelid, conjunctiva and cornea. Chronic ocular complications occur in 20–79% of patients.1 Fusion between bulbar conjunctiva and fornices leads to symblepharon, while tarsal conjunctival scarring is associated with lid keratinisation and cicatricial lid changes including entropion, trichiasis and distichiasis.5 All of these changes contribute to corneal complications including limbal stem cell deficiency (LSCD) and eventual ocular surface failure with poor visual prognosis.6 Prompt treatment during the acute inflammatory stage of SJS/TEN is important in preventing chronic sequelae.1 Use of amniotic membrane transplantation (AMT) to suppress inflammation and promote healing during the acute phase was first reported by John et al in 2002.7 Amniotic membrane contains anti-inflammatory cytokines and suppresses innate immunity, thus having anti-inflammatory as well as anti-scarring effects.8 Its effectiveness has also been demonstrated in other ocular surface disorders such as chemical burns, persistent epithelial defect and ocular cicatricial pemphigoid.9–12 Since then, AMT has been shown to reduce inflammation and promote healing in the acute stage of SJS/TEN in several case series.8 13–15 In a large retrospective study, Hsu et al have showed the benefit of early AMT in patients with moderate and severe ocular involvement from SJS/TEN compared with medical management alone.16 Recently, Shanbhag et al reported that patients who received AMT in the acute period had significantly reduced vision-threatening complications; however, complications still occurred in this group mostly …

Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) or drug-induced liver injury (DILI) are severe drug-induced reactions, known as idiosyncratic drug reactions. It is believed that immune response can lead to these severe adverse drug reactions. Our previous analysis of the Japanese Spontaneous Drug Reaction database suggested that the onset of SJS/TEN and DILI was strongly associated with infection. Hence, we conducted a matched, nested case-control study to elucidate the association between concurrent infection and the onset of SJS/TEN or liver injury in patients prescribed antipyretic analgesics. We extracted 4 112 055 patients who were prescribed antipyretic analgesics between January 2014 and December 2015. Amongst them, 553 (0.01%) were diagnosed with SJS/TEN and 12 606 (0.3%) with liver injury. In a matched, nested case-control study, 131 and 2847 cases matched for SJS/TEN or liver injury, respectively. For each case, 3 controls were randomly matched with the case for age at index date and sex. In the conditional logistic regression analysis, there was a significant association between the combination of infection and antipyretic analgesics and the onset of SJS/TEN or liver injury (SJS/TEN: adjusted OR, 5.59; 95%CI, 2.01-15.51; liver injury: adjusted OR, 2.79; 95%CI, 2.24-3.46). Although it was not possible to distinguish whether the associations were caused by the infection or were a direct consequence of the antibiotic agents, our findings may help to increase awareness of the possibility of the increased onset of idiosyncratic drug reactions (SJS/TEN and liver injury) in antipyretic analgesic users because of infections.

What is known and objective To investigate the general characteristics, economic burden, causative drugs and medical errors associated with litigation involving severe cutaneous adverse drug reactions (SCADRs) in China, with the aims of improving rational medication use and reducing the extent of damage from SCADRs. Methods This study analysed 150 lawsuit judgements involving SCADRs from 2005 to 2019, collected from China Judgments Online. Results and discussion In total, 50% of lawsuits stemmed from SCADRs occurring in general hospitals. The average time elapsed from the date of occurrence of the SCADRs to the end of litigation procedures was 1055 days. Of the patients involved, 51% were female and more than two thirds (69%) were under 60 years old. The most common outcome of SCADRs was death (39%), followed by disabilities (30%). The average responsibility of the medical provider was 48 ± 29%. The average amount of compensation was $43 424. Of the cases studied, 51% of SCADRs were Stevens-Johnson syndrome or toxic epidermal necrolysis, which together accounted for 75% of cases with known clinical subtype. The overall average economic burden of SCADRs was $99 178, of which indirect costs made up the largest proportion (more than 60%). The most common causative drug groups were antimicrobial drugs (49%), Chinese patent medicine and Chinese herbal medicine (17%), and antipyretic analgesics (16%). Finally, 61% of medical errors were found to stem from violation of duty of care, 20% from violation of informed consent and 18% from violations related to the medical record writing and management system. What is new and conclusion Severe cutaneous adverse drug reactions not only severely affect patient survival and quality of life, but also impose a heavy economic burden in terms of health care and societal costs. Medical providers should be better educated on strategies to reduce risk to patients and establish mechanisms of risk sharing and management.

The ojective of this study was to describe the reasons for admission to the burn center of patients with autoimmune rheumatic diseases (ARD), identify their clinical characteristics, and assess their outcomes relative to the non-ARD patients. We conducted a retrospective study of ARD patients admitted to a burn center from 2011 to 2018, and they were compared with a non-ARD group of patients. Medical records were reviewed for patients’ clinical characteristics, including demographics, ARD diagnosis, laboratory studies, and APACHE II score. Additionally, we evaluate the reason for admission in the burn center, management during the burn center stay, complications, outcomes including length of stay, and mortality during the hospital stay. Among the 1094 adult patients admitted during the study period, 30 (2.7%) had a new or prior diagnosis of ARD. The most common ARD associated with admission in the burn center was rheumatoid arthritis (RA) (37%, n = 11) followed by systemic lupus erythematosus (SLE) (33%, n = 10). Burn injuries (47%, n = 14), and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (30%, n = 9) were the most frequent admission reasons. Compared with the non-ARD group (n = 52), ARD patients were more likely to be females (60% vs. 24%, P = 0.004), to receive glucocorticoids (50% vs. 6.9%; P

Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and Stevens–Johnson/TEN overlap syndrome (SJS/TEN) are severe exfoliative skin disorders resulting primarily from allergic drug reactions and sometimes from viral causes. Because of the significant epidermal loss in many of these patients, many of them end up receiving treatment at a burn center for expertise in the care of large wounds. Previous work on the treatment of this disease focused only on the differences in care of the same patients treated at nonburn centers and then transferred to burn centers. We wanted to explore whether patients had any differences in care or outcomes when they received definitive treatment at burn centers and nonburn centers. We queried the National Inpatient Sample database from 2016 for patients with SJS, SJS/TEN, and TEN diagnoses. We considered burn centers as those with greater than 10 burn transfers to their center and fewer than 5 burn transfers out of their center in a year. Multivariable logistic regression assessed factors associated with treatment at a burn center and mortality. Using the National Inpatient Sample, a total of 1164 patients were identified. These were divided into two groups, nonburn centers vs burn centers, and those groups were compared for demographic characteristics as well as variables in their hospital course and outcome. Patients treated at nonburn centers were more likely to have SJS and patients treated at burn centers were more likely to have both SJS/TEN and TEN. Demographics were similar between treatment locations, though African-Americans were more likely to be treated at a burn center. Burn centers had higher rates of patients with extreme severity and mortality risks and a longer length of stay. However, burn centers had similar actual mortality compared to nonburn centers. Patients treated at burn centers had higher charges and were more likely to be transferred to long-term care after their hospital stay. The majority of patients with exfoliative skin disorders are still treated at nonburn centers. Patients with SJS/TEN and TEN were more likely to be treated at a burn center. Patients treated at burn centers appear to have more severe disease but similar mortality to those treated at nonburn centers. Further study is needed to determine whether patients with these disorders do indeed benefit from transfer to a burn center.

Background Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial. Methods A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG). Results The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection. Conclusion The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life-threatening hypersensitivity conditions associated with epidermal detachment and mucositis. The indication for flexible nasoendoscopy (FNE) and overall predictive factors for early intubation are unclear.To describe the incidence of airway involvement and the key indicators for intubation in our SJS or TEN patient cohort. To determine the association between FNE findings and early intubation.A retrospective review of 45 patients with biopsy proven SJS or TEN admitted to an Australian tertiary burns centre from 2010 to 2017.Thirty-five patients were diagnosed with TEN (77.8%), followed by overlap syndrome (SJS-TEN) (n = 6, 13.3%) and SJS (n = 4, 8.9%). Twenty (44.4%) patients were intubated; and all 20 had a diagnosis of TEN (100.0%) (p 0.05). Intubated patients had a higher increase in total body surface area percentage(%) from day 1-3 [10.0% (IQR 0.0-23.8%)] and a longer length of stay [26.0 days (IQR 12.5-34.0)], compared to non-intubated patients [0.0% (IQR 0.0-4.0%)], [10.0 days (IQR 6.0-14.0)] (p 0.05) respectively. The main indications for intubation were to facilitate operative and dressing management (47.4%) followed by airway involvement (26.3%). FNE was performed on 32 patients (71.1%), however FNE findings did not significantly influence intubation rates.More than half (n = 20, 57.1%) of the 35 patients diagnosed with TEN underwent intubation, mainly to facilitate operative and dressing management. FNE was performed on most patients, however there was no clear association between FNE findings and early intubation.

Background/objectives Stevens-Johnson syndrome and toxic epidermal necrolysis represent important sources of potential mortality and morbidity in children. There is a need for more clinical data in this population to determine whether specific treatments preferentially improve outcomes. Methods This was a single-center retrospective review of children admitted with drug-induced Stevens-Johnson syndrome, toxic epidermal necrolysis or Stevens-Johnson syndrome/toxic epidermal necrolysis overlap at a tertiary care pediatric institution in North America from 2008 to 2018. Patients without a dermatology assessment and diagnosis were excluded. Demographic, clinical, and treatment information were abstracted and reviewed for all included patients. Results Sixteen patients were identified, 43% female (7/16), with a mean age at presentation of 10.4 ± 5.2 years. Antibiotics were implicated in 56.3% of patients (9/16) and anticonvulsants in 31.3% (5/16). Sulfamethoxazole-trimethoprim was the triggering antibiotic in 31.3% of patients. The majority of patients were treated with intravenous immunoglobulin alone (50%, 8/16) or intravenous immunoglobulin with steroids (25%, 4/16). Etanercept was added to intravenous immunoglobulin and corticosteroid in a 2-year-old patient, resulting in clinical stabilization and halting of epidermolysis. No patients died. Clinical sequelae were noted in five patients, including ocular complications (n = 4), labial adhesions (n = 1), and persistent skin dyspigmentation (n = 3). Conclusions Our results highlight that sulfamethoxazole-trimethoprim is an important cause of Stevens-Johnson syndrome-toxic epidermal necrolysis in children. Mortality was reassuringly low, but ocular sequelae were an important cause of morbidity. More data are needed to help determine whether specific treatments including etanercept may provide mortality or morbidity benefit in pediatric populations.

Purpose To investigate the details of the long-term progression of ocular surface cicatrization in eyes with ocular sequelae caused by Stevens-Johnson syndrome (SJS)/toxic epidermal necrosis (TEN). Methods In 105 eyes of 66 patients with SJS/TEN, the severity of ocular sequelae was retrospectively evaluated using an ocular surface grading score (OSGS) at 2 time points separated by a greater than 5-year interval. The OSGS included 7 ocular surface components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening) evaluated into grades 0 to 3 (maximum total OSGS: 21), with the worsening of each component and total OSGS evaluated at the greater than 5-year interval. Moreover, we evaluated whether upper-tarsus and lid-margin scarring are factors that affect ocular surface cicatrization progression. Results In 35 (33.3%) of 105 eyes, the total OSGS worsened during the follow-up period. Partial conjunctivalization (score 1-2) progressed more frequently to total conjunctivalization (score 3) than to no conjunctivalization (score 0) (OR [95% CI]; 5.6 [1.6-20.3]). Partial keratinization (score 1-2) also had a high risk of progression into total keratinization (41.0 [6.3-266.5]). In all cases, keratinization progressed only in the eyes with total conjunctivalization (conjunctivalization score 3). Severity of upper-tarsus scarring or lid-margin scarring affected the worsening of the total OSGS. Conclusions In 66 patients with chronic-phase SJS/TEN, ocular surface cicatrization progressed in 33.3% of the 105 eyes during the long-term follow-up period of over 5 years. More than 50% of the partial conjunctivalization eyes progressed toward total conjunctivalization. The partial keratinization eyes had a high possibility of progressing to total keratinization; that is, the so-called "end-stage" status.

Background The predictors of readmission in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have not been characterized. Objective To determine the variables predictive of 30-day readmission after SJS/TEN hospitalization. Methods We performed a cross-sectional study of the 2010-2014 Nationwide Readmissions Database. Bivariate and multivariable logistic regression was used to evaluate associations of patient demographics, comorbidities, and hospital characteristics with readmission. Aggregate and per-readmission costs were calculated. Results There were 8837 index admissions with SJS/TEN reported; of these, 910 (10.3%) were readmitted, with diagnoses including systemic infection (22.0%), SJS/TEN (20.6%), and cutaneous infection (9.1%). Associated characteristics included age 45 to 64 years (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.43-2.49), Medicaid insurance (OR, 1.83; 95% CI, 1.48-2.27), and nonmetropolitan hospital admission (OR, 1.67; 95% CI, 1.31-2.13). Associated comorbidities included HIV/AIDS (OR, 2.48; 95% CI, 1.63-3.75), collagen vascular disease (OR, 2.38; 95% CI, 1.88-3.00), and metastatic cancer (OR, 2.16; 95% CI, 1.35-3.46). The median per-readmission cost was $10,019 (interquartile range, $4,788-$16,485). Limitations The Nationwide Readmissions Database lacks the ability to track the same patient across calendar years. The diagnostic code lacks specificity for hospitalizations Conclusions Thirty-day readmissions after SJS/TEN hospitalizations are common. Dedicated efforts to identify at-risk patients may improve peridischarge continuity.

Summary Background Toxic epidermal necrolysis (TEN) is a devastating exfoliative disorder with life-changing complications. This study aimed to identify acute complications and long-term sequelae of TEN and to highlight the importance of a multidisciplinary management follow-up. Methods A 19-year (1998–2016) retrospective review of all patients with TEN admitted to Cruces University Hospital´s Burns Unit was performed. Demographic and admission data were collected. Survivors were contacted for a follow-up multidisciplinary assessment involving dermatological, ocular, ENT, urological, gynecological, and psychological examination. Results Within the total cohort of patients analyzed (22), 6 survivors agreed to be interviewed. The patients presented with both physical and psychological sequelae, including dermatological (100%), oropharyngeal (50%), and ophthalmologic sequelae (50%), with corneal damage and severe dry eye as the most frequent. The only male patient underwent phimosis surgery due to mucosal adhesions. Psychometric scales captured symptoms of post-traumatic stress disorder (33.33%), and quality of life was affected in 66.67% of the patients by skin sequelae. Conclusion Quality of life can be severely impaired by multiple long-term complications. It is important to emphasize the need for multidisciplinary awareness during their acute stay at Burns Unit. Furthermore, long-term follow-up might prevent or limit the progression of the chronic sequelae.

BACKGROUND: Since the last review of vaccine safety surveillance data for erythema multiforme (EM), Stevens Johnson syndrome (SJS), SJS/TEN, and toxic epidermal necrolysis (TEN) (EM/SJS/TEN), over 37 new vaccines have been introduced in the United States. We sought to describe reported EM/SJS/TEN after vaccines during 1999–2017. METHODS: We identified U.S. reports of EM/SJS/TEN received by the Vaccine Adverse Event Reporting System (VAERS) during 1999–2017. We stratified analysis by condition (EM, SJS, or TEN), and analyzed reports by serious or non-serious status, sex, age group, time from vaccination to symptom onset, exposure to known causes of EM/SJS/TEN, and vaccines administered. We used Empirical Bayesian data mining to detect vaccine-AE pairs reported more frequently than expected. RESULTS: Of 466,027 reports to VAERS during 1999–2017, we identified 984 reports of EM, 89 reports of SJS, 6 reports of SJS/TEN, and 7 reports of TEN. Few reports of EM (9%), and most reports of SJS (52%), SJS/TEN (100%), and TEN (100%) were serious. Overall, 55% of reports described males, 48% described children aged < 4 years; 58% of EM/SJS/TEN occurred ≤ 7 days after vaccination. Few reports (≤5%) described exposure to known causes of EM/SJS/TEN. Overall, childhood vaccines (e.g., combined measles, mumps, and rubella vaccine) were most commonly reported. We identified 6 deaths; 4 were exposed to medications associated with EM/SJS/TEN. EM after smallpox vaccine was reported disproportionately among people aged 19–49 years. CONCLUSIONS: EM/SJS/TEN were rarely reported after vaccination; data mining identified a known association between EM and smallpox vaccine.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty-seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1-17 years); 51.1% were male. Thirty-three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often-implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3-42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long-term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post-inflammatory hypo-/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long-term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long-term sequelae requiring regular follow-up.

Blisters and subsequent desquamation of the skin in the presence of acute edema is a well-known clinical phenomenon. In this case report, we describe a new variant that we have termed anasarca-induced desquamation in a 50-year-old man with molting of the entire cutaneous surface after acute edema, in a setting of 40-lb weight gain over 5 days. Laboratory workup for infectious causes and punch biopsies of skin lesions ruled out Stevens-Johnson syndrome and staphylococcal scalded skin syndrome, which have a similar clinical presentation to anasarca-induced desquamation. In patients with diffuse superficial desquamation in the setting of acute edema, anasarca-induced desquamation is worth investigating to avoid the use of corticosteroids and intravenous antibiotics in this inherently benign condition.

Despite poor evidence, the antiparasitic ivermectin has been advocated as a potential COVID-19 therapy. This has led to a rise in calls to poison-control centers by people self-medicating with ivermectin, which is sold over the counter for veterinary uses. We aimed to investigate the association between severe cutaneous adverse reactions (SCARs) and ivermectin. Postmarketing data from the FDA Adverse Event Reporting System (FAERS), gathered between 2014 and 2021, was employed to detect disproportional signals of SCARs following systemic ivermectin therapy. The reporting odds ratio (ROR) was used to quantify the strength of association, while adjusting for age, sex, and region. The search yielded 517 reports of systemic ivermectin (median age 54 years, 46.8% female), of which 25 (4.8%), 81 (15.7%), and 411 (79.5%) were classified as SCARs, nonsevere cutaneous adverse events (AEs), or noncutaneous AEs, respectively. The regional distribution differed between SCAR reports (32.0% from Africa and 12.0% from North America) compared with other AEs, which originated from North America in over half of cases. The most common SCARs were toxic epidermal necrolysis (seven cases), Stevens-Johnson syndrome (seven cases), and drug reaction with eosinophilia and systemic symptoms (four cases). Five SCAR cases (20.0%) resulted in death and 12 (48.0%) lead to hospitalization. There was a strong safety signal for any SCAR (adjusted ROR 3.34, 95% confidence interval [CI] 2.17-5.12) and toxidermias (adjusted ROR 7.08, 95% CI 4.23-11.84). This study suggests that ivermectin is associated with SCARs on rare occasions. Dermatologists should be aware of this given the increase in ivermectin misuse.

BACKGROUND: Stevens‐Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary‐level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N‐acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions. OBJECTIVES: To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome. SEARCH METHODS: We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN‐specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re‐epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE. MAIN RESULTS: We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta‐analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow‐up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor‐alpha (TNF‐alpha) inhibitors, cyclosporin, thalidomide, N‐acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease‐specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low‐certainty evidence). Time to complete re‐epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease‐specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re‐epithelialisation (mean difference (MD) −2.93 days, 95% CI −4.4 to −1.46); or length of hospital stay (MD −2.00 days, 95% CI −5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low‐certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF‐alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly "until skin lesions healed") may reduce disease‐specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day "until skin lesions healed") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low‐certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re‐epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re‐epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease‐specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low‐certainty evidence). Time to complete re‐epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay. AUTHORS' CONCLUSIONS: When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease‐specific mortality is very low: corticosteroids versus no corticosteroids, IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN.

In this case-control study, class І and ІІ human leukocyte antigen (HLA) alleles in Iranian patients with benign and severe cutaneous adverse drug reactions (CADRs) due to aromatic anticonvulsants and antibiotics were evaluated. Patients diagnosed with CADRs (based on clinical and laboratory findings) with a Naranjo score of ≥ 4 underwent blood sampling and HLA-DNA typing. The control group comprised 90 healthy Iranian adults. Alleles with a frequency of more than two were reported. Deviations from Hardy-Weinberg equilibrium were not observed. Eighty patients with CADRs including 54 females and 26 males with a mean age of 41.49 ± 16.08 years were enrolled in this study. The culprit drugs included anticonvulsants (lamotrigine, carbamazepine, and phenytoin) and antibiotics (ciprofloxacin and co-trimoxazole). The comparison of allele frequencies in the Iranian healthy control group and the group with benign CADRs revealed that HLA-Cw*04, and HLA-A*24 were significantly associated with lamotrigine-induced maculopapular CADRs. Furthermore, HLA-B*51 showed a significant correlation with carbamazepine-induced maculopapular CADRs. Significant associations were also detected between ciprofloxacin-induced urticarial CADRs with HLA-B*40, and HLA-DRB1*14. In the severe group, HLA-B*38 and HLA-DRB1*13 were significantly associated with lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Moreover, HLA-A*31 and HLA-Cw*04 were significantly correlated with carbamazepine-induced drug reactions with eosinophilia and systemic symptoms (DRESS). HLA-B*08 also showed a significant correlation with ciprofloxacin-induced acute generalized exanthematous pustulosis (AGEP). In conclusion, Lamotrigine-induced MPE was significantly correlated with HLA-Cw*04, and HLA-A*24. Similarly, lamotrigine-induced SJS/TEN was significantly associated with HLA-B*38 and HLA-DRB1*13. Additionally, HLA-A*31 was associated with DRESS caused by carbamazepine. The most frequent CADR-inducing drugs were anticonvulsants.

Toxic erythema of chemotherapy is an umbrella term encompassing a range of reactions characterized by symmetric erythematous to dusky patches, which can develop oedema, desquamation and/or purpura. We describe an elderly patient with prostate cancer who developed this complication while receiving docetaxel chemotherapy, presenting with prominent mucosal and periorificial involvement, along with epidermal necrosis, closely mimicking toxic epidermal necrolysis.

A 52-year-old male presented to Beijing Tongren Hospital with a 5-year history of bilateral dry eyes. He had been diagnosed with Steven-Johnson syndrome due to allergy to cold medication. On examination, the Schirmer I test value was 0 mm, the tear break-up time was 0 s, and corneal fluorescein staining showed corneal epithelial erosion with partial fusion in both eyes. The clinical diagnosis was dry eyes (severe) and Steven-Johnson syndrome. No significant effect was observed after use of artificial tears and anti-inflammatory eye drops and tear punctal embolization. Then an insular infraorbital neurovascular pedicle labial salivary gland transplantation was performed in the right eye. During the 1-year postoperative follow-up, the symptoms and signs were significantly improved in the operated eye, and the surgical results were satisfactory.1例52岁男性患者因双眼干涩5年，就诊于首都医科大学附属北京同仁医院北京同仁眼科中心。既往因感冒药物过敏诊断为Steven-Johnson综合征。眼部检查双眼泪液分泌试验结果为0 mm，泪膜破裂时间为0 s，角膜荧光素染色可见角膜上皮糜烂，部分融合。临床诊断为双眼干眼（重度）；Steven-Johnson综合征。常规人工泪液、抗炎滴眼液及泪小点栓塞治疗无明显效果后，行具有创新性的岛状眶下神经血管蒂唇腺移植术。术后随访1年，患者术眼干眼症状及体征均明显改善，手术效果满意。（

To report a unique case of Stevens-Johnson syndrome (SJS) with severe ocular complications induced by pembrolizumab, an immune checkpoint inhibitor.A 64-year-old man with urothelial cancer presented with bilateral corneal epithelial defect and conjunctival pseudo-membrane formation with erythematous patches on the four extremities, abdomen, and back. He had urothelial cancer with multifocal lesions in the renal pelvis and left ureter, and para-aortic metastatic lymph nodes. Accordingly, pembrolizumab treatment was planned. Generalized skin eruption occurred 4 days after the first cycle of pembrolizumab treatment, and ocular symptoms occurred 2 weeks after the first cycle. The patient's symptoms improved after cessation of pembrolizumab treatment and administration of steroids systemically.Immune checkpoint inhibitors, including pembrolizumab, have been developed recently and are widely used in the treatment of various cancers. However, it should be noted that the drugs may cause adverse events such as SJS with severe ocular complications.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are infrequent mucocutaneous diseases, rapidly progressive and life-threatening. The clinical aspects and the management of TEN are exposed following a case.A man in his 40s presented to the emergency department with severe odynophagia, poor general condition and fever. His medical history was significant for HIV stage AIDS, and the treatment was discontinued 5 years before the present diagnosis. He was admitted for cerebral toxoplasmosis and discharged the previous 14 days with sulfadiazine. Erythematous-bullous lesions in the oral cavity, diffuse erythematous maculopapular rashes over his neck and chest, acute bilateral conjunctivitis and purulent urethritis was observed. The diagnostic suspicion was SJS/TEN due to sulfadiazine in immunosuppressed patients.This entity is infrequent but is a life-threatening dermatological emergency that requires immediate medical attention. Its diagnosis is mainly clinical, with a new drug history, prodromal symptoms and characteristic cutaneous–mucous lesions. Early diagnosis and rapid withdrawal of the drug improve the prognosis.