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The understanding of pembrolizumab-induced Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) primarily derives from case reports, leaving specific clinical features largely unknown. This study aims to investigate the clinical characteristics associated with pembrolizumab-induced SJS/TEN and to encourage the judicious use of pembrolizumab. Retrieve reports on pembrolizumab induced SJS/TEN before September 30, 2024 for retrospective analysis. Twenty-four (57.1%) and 18 (42.9%) patients were enrolled, with a median age of 65 years (range 32, 81). The median time to onset of SJS/TEN was 15 days (range 2, 180), and the median cycle was 1 cycle (range 1, 9). The most prevalent skin symptoms included erythema (66.7%), rash (64.3%), bullae/blisters (50.0%), and epidermal detachment (42.9%). Skin biopsy findings primarily revealed epidermal necrosis (42.9%), keratinocyte necrosis (35.7%), subepidermal bulla/blister (19.0%), and perivascular inflammatory cell infiltration (47.6%). Following the cessation of the drug and subsequent treatment, 85.7% of patients showed symptom improvement, while 14.3% succumbed to the condition. SJS/TEN represents a rare but potentially fatal adverse reaction to pembrolizumab. Clinicians should consider SJS/TEN in patients presenting with fever, erythematous rash, or mucosal involvement. Timely identification and management of SJS/TEN can significantly reduce morbidity and mortality.

Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at \"high\" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP), disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS). Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease.

Abstract Background Immune checkpoint inhibitors (ICIs) have demonstrated significant therapeutic benefits but are also associated with skin-related adverse reactions. The specific characteristics of severe adverse reactions caused by ICIs remain unclear. Objective To investigate the disease characteristics of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like reactions induced by ICIs. Methods Cases of ICI-induced SJS/TEN were collected from PubMed, CNKI, Wanfang Data Knowledge Service Platform, and Guangdong Provincial People’s Hospital, with a search time span ranging from March 2011 to January 31, 2024. Results A total of 110 cases of SJS, TEN, and overlapping SJS/TEN were analyzed, with a male predominance (62%). Mucous membrane involvement was observed in 71 patients (66%), though less frequently than in classic SJS/TEN. The mean latency period was 64 days, varying by subtype (105 days for SJS and 53 days for TEN). Combination therapy with ICIs was associated with a higher mortality risk (P = .029). Deceased patients exhibited shorter latency periods (mean 30.3 days) and more severe mucosal involvement (up to 100%), although the differences were not statistically significant. Systemic glucocorticoid therapy was the cornerstone of treatment for SJS/TEN-like reactions. The addition of immunoglobulin showed a trend toward improved outcomes but did not significantly affect mortality or cure rates compared to glucocorticoid monotherapy. The combination of systemic glucocorticoids and antibiotics demonstrated a promising trend, with a higher proportion of patients in the improvement/cure group using this regimen (P = .085). Conclusions This study summarizes the clinical characteristics of ICI-induced SJS/TEN-like reactions, providing insights into their features and potential treatment strategies for severe skin-related adverse events induced by ICIs.

Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue 1 – 3 . Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN 4 – 6 . Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics 7 , 8 . We analysed formalin-fixed, paraffin-embedded archived skin tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified more than 5,000 proteins in keratinocytes and skin-infiltrating immune cells. This revealed a marked enrichment of type I and type II interferon signatures in the immune cell and keratinocyte compartment of patients with TEN, as well as phosphorylated STAT1 activation. Targeted inhibition with the pan-JAK inhibitor tofacitinib in vitro reduced keratinocyte-directed cytotoxicity. In vivo oral administration of tofacitinib, baricitinib or the JAK1-specific inhibitors abrocitinib or upadacitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Crucially, treatment with JAK inhibitors (JAKi) was safe and associated with rapid cutaneous re-epithelialization and recovery in seven patients with TEN. This study uncovers the JAK/STAT and interferon signalling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAKi as a curative therapy. Cell-type-resolved spatial proteomics of the skin from patients with toxic epidermal necrolysis reveals that it is driven by JAK/STAT signaling, leading to successful treatment of this potentially fatal condition in patients using JAK inhibitors.

Stevens-–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe cutaneous adverse reactions. Recently, strong associations of and with carbamazepine- and allopurinol-induced severe cutaneous adverse reactions were found in Han Chinese patients, respectively, but ethnic differences in the associations have been reported. The objective of this study is to clarify the involvement of and in Japanese SJS/TEN patients. genotyping was performed on 58 Japanese SJS/TEN patients between July 2006 and April 2008 from multicenters in Japan. There were no carriers among 58 SJS/TEN patients. This patient group included seven carbamazepine-related and 11 aromatic anti-epileptic agent-related SJS/TEN patients. In addition, there were five carriers, which included four allopurinol-related SJS/TEN patients. While is unlikely to be associated with carbamazepine-related or aromatic anti-epileptic agent-related SJS/TEN, was significantly associated with allopurinol-related SJS/TEN in Japanese.

Drug hypersensitivity reactions can result in life-threatening epidermal necrosis caused by cytotoxic T lymphocytes and natural killer cells. Chung et al . show that an unusual form of granulysin secreted from these cells is largely responsible for the cell death ( pages 1311–1313 ). Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell—mediated cytotoxicity that does not require direct cellular contact.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases; however, it is hard to estimate their incidence due to the rarity of these diseases. We evaluated the incidence of SJS and TEN using a nationwide administrative database. We used a national medical insurance review system (Health Insurance Review and Assessment) database which contained the claim data of the entire nation from 2009 to 2013 to estimate the accurate incidence of SJS and TEN in Korea. The diagnostic codes of L511 (SJS) or L512 (TEN) from the International Classification of Diseases-10th revision were used to define the target study population. We also retrospectively followed up a 2011 SJS and TEN cohort for 24 months in order to assess the in-hospital mortality, related complications and total claims cost due to SJS and TEN. A total of 1,167 (938 SJS and 229 TEN) cases were newly diagnosed from 2010 to 2013. The age- and sex-standardized annual incidences estimated in this study were 3.96 to 5.03 in SJS and 0.94 to 1.45 in TEN per million. There was no significant change in annual incidence throughout the study periods. When analyzed by 10-year age groups, the annual incidence was the lowest in group 20-29 years and the highest in group 70 for both SJS and TEN. Based on the 2011 cohort analysis, the in-hospital mortality were 5.7 and 15.1% for SJS and TEN, respectively. The mortality increased with age, particularly, after 40 years of age. Among the complications related with SJS or TEN, ocular sequelae was the most common (43.1 and 43.4% of SJS and TEN patients, respectively) followed by urethral sequelae (5.7 and 9.4% of SJS and TEN patients, respectively). Overall, our data suggest that SJS, and TEN are infrequent but constantly arise throughout the years.

Essays by Herman Beavers, Gena Chandler, Marc C. Conner, William Gleason, William R. Nash, Linda Selzer, Gary Storhoff, and John Whalen-Bridge InCharles Johnson: The Novelist as Philosopher, leading scholars examine the African American author's literary corpus and major themes, ideas, and influences. The essays explore virtually all of Johnson's writings: each of his novels, his numerous short stories, the range of his nonfiction essays, his many book reviews, and even several unpublished works. These essays engage Johnson's work from a variety of critical perspectives, revealing the philosophical, cultural, and political implications of his writings. The authors seek especially to understand \"philosophical black fiction\" and to provide the multifocal, \"whole sight\" analysis Johnson's work demands. Johnson (b. 1948)--author ofDreamer,Oxherding Tale, and the National Book Award-winningMiddle Passage--draws upon influences as diverse as Richard Wright, Herman Melville, Thomas Aquinas, Franz Kafka, W. E. B. Du Bois, and Ralph Waldo Emerson. He combines rigorous training in western philosophy with a lifelong practice in eastern religious and philosophical traditions. He has repeatedly told interviewers that he became a writer specifically to strengthen the interplay between philosophy and fiction. Marc C. Conner is associate professor of English at Washington and Lee University. William R. Nash is associate professor of American studies and director of African American studies at Middlebury College.

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions, predominantly drug induced. The mortality rates for SJS and TEN are as high as 30 %, and short- and long-term morbidities are very common. SJS/TEN is one of the few dermatological diseases that constitute a true medical emergency. Early recognition and prompt and appropriate management can be lifesaving. In recent years, our understanding of the pathogenesis, clinical presentation, and management of SJS/TEN has improved. Nevertheless, in 2015, there are still no internationally accepted management guidelines. This review summarizes up-to-date insights on SJS/TEN and describes a protocol for assessment and treatment. We hope these suggested guidelines serve as a practical clinical tool in the management of SJS/TEN. The classic manifestation of SJS/TEN consists of initial “flu-like” symptoms (malaise, fever, anorexia) in the prodromal phase, followed by cutaneous and mucous membrane (ocular, oral, and genital) inflammation and pain, and other systemic involvement. Symptoms usually begin 4–28 days after the onset of drug intake. Treatment is multidisciplinary and includes identification and withdrawal of the culprit drug, transfer to a specialist unit, supportive care, medical treatment, communication, and provision of appropriate information and emotional support.