Epidermal Necrolysis Research Articles

Immunohistochemical Expression of Immune Regulatory Proteins in Interface Dermatoses.

Cutaneous immune-related adverse events (irAEs) of immunotherapies, such as anti-programmed cell death protein-1 (PD-1), suggest that immune checkpoint factors may contribute to the pathobiology of lichenoid interface dermatitis in immunotherapy-naïve patients. Our study aimed to describe innate and adaptive immune markers via immunohistochemical (IHC) staining of lichenoid interface dermatoses. We studied the staining patterns of PD-L1, STING, IL-36 gamma, CD8, PD-1, and LAG-3 in five interface dermatoses: oral lichen planus (LP) (n = 10), cutaneous LP (n = 10), chronic cutaneous lupus erythematosus (CLE) (n = 11), erythema multiforme (EM) (n = 11), and toxic epidermal necrolysis (TEN) (n = 13), by immunohistochemistry (IHC) analysis. Expression was evaluated semi-quantitively according to the percentage of keratinocytes and dermal lymphocytes stained compared to keratinocytes and resident pericapillary lymphocytes in normal human skin. All interface dermatoses evaluated showed increased expression of PD-L1 on keratinocytes and LAG-3 in lymphocytes. STING was increased on the keratinocytes of most specimens. Expression of IL-36 gamma, in basal layer keratinocytes was more extensive in oral LP and cutaneous LP and varied in CLE, EM, and TEN. Lymphocytic infiltration expressing PD-1 was elevated in oral LP, cutaneous LP, and CLE. Current thinking is that interface dermatitis is the result of a cell-mediated immune reaction involving cytotoxic CD8+ T-cell-mediated apoptosis of keratinocytes. The findings of this study suggest that in addition to cell-mediated immunity, innate immune factors may contribute to pathobiology.

Systematic review and meta-analysis of non-SCORTEN predictors of mortality in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe cutaneous adverse reactions that result in in-hospital death in 12-49% of cases. The severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is the most widely used mortality prognosis score; however, it has been shown to have critical limitations. Other mortality predictors not incorporated in SCORTEN or other predictor tools are being increasingly reported. This systematic review and meta-analysis aimed to synthesize and evaluate the predictors of mortality in adults with Stevens-Johnson syndrome and toxic epidermal necrolysis not included in SCORTEN. It was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Potential bias was assessed using the National Institutes of Health (NIH) criteria. Forty articles describing results from 52,398 cases were included. Sixteen predictors were reported in five or more articles, and thirty-three were reported in two to four articles. Meta-analysis showed preexisting renal disease (odds ratio (OR): 3.14, 95% confidence interval (CI): 1.99-4.97, P < 0.0001, I2 = 21%), renal involvement (OR: 5.62, 95% CI: 2.29-13.77, P = 0.0002, I2 = 36%), respiratory involvement (OR: 3.14, 95% CI: 1.25-7.92, P = 0.015, I2 = 66%), diabetes mellitus (OR: 1.87, 95% CI: 1.21-2.89, P = 0.005, I2 = 19%), sepsis (OR: 5.64, 95% CI: 2.81-11.29, P < 0.0001, I2 = 63%), comorbidity (OR: 9.13, 95% CI: 4.60-18.12, P < 0.0001, I2 = 0%), and time to hospitalization (OR: 2.56, 95% CI: 1.15-5.65, P = 0.021, I2 = 93) increased risk of mortality. This systematic review and meta-analysis support several clinical and laboratory parameters not included in SCORTEN (preexisting renal disease, renal involvement, respiratory involvement, diabetes mellitus, sepsis, comorbidities, and time to hospitalization) as predictors of mortality in adults with SJS/TEN. The future utilization of these factors may improve mortality prognostication in adults with SJS/TEN.

A rare case report of diclofenac induced Steven Johnson syndrome

Stevens Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous diseases characterized by extensive necrosis involving the mucous membrane and epidermis. In this case, a 54-year-old female after intake of prescribed diclofenac tablet presented with multiple reddish maculopapular eruptions over face, abdomen, both limbs, over lips and oral cavity associated with pain and intense pruritus. This case is a rare presentation of drug induced SJS caused by commonly prescribed NSAID, diclofenac. Patient’s condition improved after withdrawal of offending drug and prompt treatment. This case suggests that emphasis on early detection, assessment and timely management of adverse drug reactions is of upmost importance. Thus, establishment of proper vigilance centre and regular monitoring is necessary and taking caution in prescribing drugs as well in elderly groups.

Toxic Epidermal Necrolysis Induced by Doxycycline: A Case Report and Literature Review

Toxic Epidermal Necrolysis Induced by Doxycycline: A Case Report and Literature Review

Deflazacort-induced Steven-Johnson syndrome: a case report and literature review

Objective: To summarize the clinical features and outcomes of deflazacort-induced Steven Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) to raise awareness among patients with Duchenne muscular dystrophy (DMD), neurologists as well as other deflazacort users. Methods: The clinical data of a boy with DMD who had SJS induced by deflazacort treated at the Department of Rheumatology & Clinical Immunology of Tianjin Children's Hospital in July 2024 was analyzed retrospectively. Taking "deflazacort" "Steven-Johnson syndrome" "toxic epidermal necrolysis" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2024. The clinical characteristics, treatment and outcomes of deflazacort-induced SJS-TEN were summarized. Results: A 12-year-old boy was admitted with a 3-day history of rash. He was diagnosed with DMD at the age of 3 and had been treated with prednisolone since the age of 8. Forty-four days before admission, the patient started deflazacort to replace prednisolone. Three days before admission, progressively worsening erythematous maculopapular rashes, blisters and skin peeling (8% body surface area), oral mucosal erosion, and exudative conjunctivitis occurred, thus deflazacort was discontinued. Complete remission of SJS was achieved after treatment with intravenous immunoglobulin (IVIG, total 1.4 g/kg), 2 doses of etanercept (0.9 mg/kg, once), subcutaneous injection and intravenous methylprednisolone (0.7 mg/(kg·d)). Based on the literature, there were 5 reports in English while none in Chinese, altogether 7 cases were reported. All the patients were male, aged 3-45 years. Duration of deflazacort exposure was 2-8 weeks. Dermatology diagnosis of our case was SJS, and 5 cases were TEN. One patient was diagnosed with exudative erythema multiforme, and subsequent deflazacort oral challenge test was positive. Treatment included methylprednisolone or dexamethasone in 5 cases, IVIG in 6 cases, etanercept in 3 cases and cyclosporine in 1 case. All patients recovered completely. Conclusion: The synthetic corticosteroid deflazacort can cause rare but severe adverse reactions such as SJS-TEN, which needs close monitoring and prompt recognition and management.

Infectious complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta-analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN. This review was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-six articles describing results from 1446 cases were included. Skin infection was the most commonly diagnosed infection. The pooled prevalence of sepsis, respiratory tract infection, skin infection, and urinary tract infection was 27.3%, 21.5%, 37.5%, and 21.8%, respectively. Staphylococcus aureus was the most commonly identified organism. The overall quality of the studies was suboptimal, and the level of heterogeneity was high. The skin, bloodstream, respiratory, and urinary tracts are most commonly infected in the course of adult SJS and TEN. During hospitalization, clinicians should closely monitor and promptly investigate for these as well as several other infectious complications. More research is needed, with greater attention to the risk factors and causative organisms that cause these infections.

Immune-related toxic epidermal necrolysis affecting trachea mucosal epithelium: a case report and literature review

BackgroundMonoclonal antibodies against programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) have emerged as critical tools in cancer treatment. However, concerns regarding their potential cutaneous and mucosal toxicity, along with severe complications, have drawn clinical attention. Further research is warranted to investigate the adverse reactions and treatment strategies associated with PD-1 monoclonal antibodies.MethodsWe present a detailed case report of a laryngeal cancer patient who developed toxic epidermal necrolysis (TEN) after treatment with PD-1 monoclonal antibody. We analyzed the etiology, diagnosis, and treatment approaches by integrating clinical manifestations, pathological examinations, and literature research.ResultsAfter PD-1 monoclonal antibody therapy, the patient exhibited systemic rash, bullae, and epidermal detachment, which subsequently involved the tracheal and bronchial mucosa, resulting in dyspnea. The patient recovered after treatments with steroids, macrolides, immunoglobulins, and etanercept, along with repeated removal of scabs via bronchoscopy. Literature reviewing suggests a potential association between PD-1 monoclonal antibodies and the pathogenesis of Steven Johnson’s Syndrome (SJS) and Toxic epidermal necrolysis (TEN), possibly due to immune dysregulation. Treatment consists of immediate discontinuation of suspicious drugs, essential supportive therapy, and systemic corticosteroid administration, with the addition of immunosuppressants and/or immunoglobulins needed.ConclusionThe mucocutaneous toxicity induced by PD-1 monoclonal antibodies is not limited to the surface of the skin but also in deep mucosal layers, potentially leading to life-threatening complications. Therefore, when using PD-1 monoclonal antibodies, clinicians should closely monitor adverse events and apply appropriate treatments as soon as possible to prevent severe complications.

S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 2: Supportive therapy of EN in the acute and post-acute stages.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered as variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and of patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical specialties involved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. The second part is concerned with the topics of supportive therapy in the acute phase of EN and outpatient follow-up treatment.

Life-threating complications of immunotherapy: Stevens-Johnson syndrome and toxic epidermal necrolysis

Stevens–Johnson syndrome (SSD) and toxic epidermal necrolysis (TEN) are life–threatening conditions accompanied by skin lesions, as well as in some cases mucous membranes, manifested by necrosis and detachment of the epidermis. These conditions are considered urgent and require emergency hospitalization. Most often, these conditions develop when taking drugs, but in some cases it is not possible to find out the cause of the disease. In described case, we discovered this condition in a patient, who received immunotherapy with pembrolizumab, a monoclonal antibody to the PD-1 receptor, which generally used in the treatment of cancer patients.

Spatial proteomics identifies JAKi as treatment for a lethal skin disease.

Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1-3. 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 TEN4-6. 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 proteomics7,8. 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.

Implementation of HLA-related genotype-guided prescribing in Singapore.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To describe the implementation of human leukocyte antigen (HLA)-related genotype-guided prescribing in Singapore. Various HLA alleles have been implicated in drug hypersensitivity syndromes (DHS). These include HLA-B*15:02, which has been associated with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis, HLA-B*58:01, which has been associated with increased risk of severe cutaneous adverse reactions with allopurinol use, and HLA-B*57:01, which has been associated with increased risk of hypersensitivity reactions with abacavir use. Integrating pharmacogenomics into patient care through genotype-guided prescribing potentially optimizes use of these drugs by reducing DHS-related and healthcare costs. We describe the prevalence of HLA-related DHS in Singapore, the cost-effectiveness of genotype-guided prescribing, and local policies and guidelines, as well as the impact of genotype-guided prescribing where available. HLA-related genotype-guided prescribing has the potential to reduce the incidence of DHS and decrease healthcare costs, as seen in the success with carbamazepine. However, not all genotype-guided prescribing is cost-effective when implemented across the population, as was evident from local studies for allopurinol and abacavir. The cost-effectiveness of such measures may change over time with new data (eg, allele frequencies, test costs, drug prices, genotyping approach) and should be evaluated periodically and locally. Implementation of preemptive pharmacogenomics panel testing as part of routine clinical care may shift the threshold for cost-effectiveness and brings promise of further optimization of pharmacotherapy through precision medicine.

Toxic Epidermal Necrolysis: A Clinical Case Report with Emphasis on Diagnosis, Management, and Prognostic Implications

Toxic Epidermal Necrolysis: A Clinical Case Report with Emphasis on Diagnosis, Management, and Prognostic Implications

Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening cutaneous drug reaction mediated by human leukocyte antigen (HLA) class I-restricted CD8+ T cells. For unbiased assessment of cellular immunopathogenesis, here we perform single-cell(sc) transcriptome, surface proteome, and T cell receptor (TCR) sequencing on unaffected skin, affected skin, and blister fluid from 15 SJS/TEN patients. From 109,888 cells, we identify 15 scRNA-defined subsets. Keratinocytes express markers indicating HLA class I-restricted antigen presentation and appear to trigger the proliferation of and killing by cytotoxic CD8+ tissue-resident T cells that express granulysin, granzyme B, perforin, LAG3, CD27, and LINC01871, and signal through the PKM, MIF, TGFβ, and JAK-STAT pathways. In affected tissue, cytotoxic CD8+ T cells express private expanded and unexpanded TCRαβ that are absent or unexpanded in unaffected skin, and mixed populations of macrophages and fibroblasts express pro-inflammatory markers or those favoring repair. This data identifies putative cytotoxic TCRs and therapeutic targets.

REAÇÕES CUTÂNEAS GRAVES: UMA VISÃO ABRANGENTE SOBRE A SÍNDROME DE STEVENS-JOHNSON, SUA ETIOLOGIA, FISIOPATOLOGIA E ABORDAGENS TERAPÊUTICAS

Stevens-Johnson Syndrome (SJS) is a rare and severe condition characterized by epidermal detachment and mucosal lesions, primarily affecting the mouth, eyes, and genitals. Often triggered by adverse drug reactions, such as antibiotics and anticonvulsants, SJS can also be caused by viral infections and, rarely, neoplasms. SJS forms a spectrum with Toxic Epidermal Necrolysis (TEN), differing in the extent of skin involvement: in SJS, less than 10% of the body surface is affected, while in TEN, the involvement exceeds 30%. Although rare, with an incidence of 1.2 to 6 cases per million people, SJS carries high morbidity and mortality, leading to complications such as severe infections and permanent damage to the skin and mucous membranes. Early diagnosis is crucial, based on characteristic lesions and a recent history of medication use. In some cases, a biopsy is necessary to confirm the diagnosis. Treatment involves a multidisciplinary approach, including intensive care, immediate discontinuation of the causative drug, and immune modulation with corticosteroids or intravenous immunoglobulin. While new therapies, such as cyclosporine and special wound dressings, are being explored, there is still a need for consensus on the ideal treatment protocol, as well as advances in personalized diagnosis and treatment.

The role of intravenous immunoglobulin in autoimmune diseases with dermatological implications.

Intravenous immunoglobulin (IVIG) therapy has emerged as a promising treatment option for various dermatological autoimmune diseases due to its immunomodulatory potential and low incidence of severe side effects. Despite its widespread use, the mechanism of action of IVIG in treating autoimmune diseases remains a topic of debate. IVIG is derived from the plasma fractionation of a large pool of donors, primarily consisting of the IgG isotype. Its main mechanisms of action involve neutralizing circulating autoantibodies via the F(ab')2 portion, inhibiting complement-mediated tissue destruction, and reducing the half-life of circulating autoantibodies through the Fc portion. This paper explores the growing utilization of IVIG as an off-label therapy in dermatological autoimmune or immune-mediated diseases, including autoimmune bullous disease (AIBS), dermatomyositis (DM), lupus erythematosus (LE), systemic sclerosis, scleromyxedema, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), pyoderma gangrenosum (PG), and necrobiotic xanthogranuloma (NXG). In this context, the sole large prospective, randomized trial was the 2022 ProDERM study, which demonstrate efficacy of IVIG in improving cutaneous manifestations among 95 DM patients compared to the placebo group. Moreover, although considered off-label, the use of IVIG is regarded as the first-line therapy for patients with scleromyxedema. As a first line of therapy, IVIg is only approved for Kawasaki Disease (KD) in the setting of vasculitis. The treatment in all other indications is mostly considered as adjuvant therapy only after failure of immunosuppressive therapy or in the presence of contraindications.

Incidence, In-Hospital and Long-Term Mortality, and Sequelae of Epidermal Necrolysis in Adults

The incidence of epidermal necrolysis (EN), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), varies across studies. While in-hospital mortality rates range from 15% to 20%, contributors to long-term mortality have been rarely evaluated and remain unknown. To assess the incidence of and compare factors associated with in-hospital mortality and postdischarge mortality and sequelae among patients with EN. This cohort study used French Health System data from January 1, 2013, to December 31, 2022, and included all adult patients (aged ≥18 years) with EN identified using International Statistical Classification of Diseases, Tenth Revision codes combined with a validated algorithm. Epidermal necrolysis. Incidence, in-hospital mortality, postdischarge mortality, and sequelae were assessed as main outcomes. Factors associated with mortality were assessed using a multivariable Cox proportional hazards model. A total of 1221 adult patients with EN (median [IQR] age, 66 [49-79] years; 688 females [56.3%]) were included. Incidence was 2.6 (95% CI, 2.5-2.7) cases per million person-years. The in-hospital mortality rate was 19% (95% CI, 17%-21%) and postdischarge mortality rate, 15% (95% CI, 13%-17%) for an overall mortality of 34% (95% CI, 31%-36%). In multivariable analysis, factors associated with in-hospital mortality were age (adjusted hazard ratio [AHR], 1.03 per year of age; 95% CI, 1.02-1.04 per year of age), history of cancer (AHR, 2.04; 95% CI, 1.53-2.72), dementia (AHR, 1.85; 95% CI, 1.12-3.07), liver disease (AHR, 1.81; 95% CI, 1.24-2.64), and EN severity (TEN vs SJS: AHR, 2.14; 95% CI, 1.49-3.07). Cancer, liver disease, and dementia remained associated with postdischarge mortality (AHR, 3.26 [95% CI, 2.35-4.53], 1.86 [95% CI, 1.11-3.13], and 1.95 [95% CI, 1.11-3.43], respectively). Conversely, EN initial severity was not associated with mortality after hospital discharge (TEN vs SJS: AHR, 0.95; 95% CI, 0.60-1.47), but acute complications remained associated (AHR, 2.14 [95% CI, 1.26-3.63] and 2.44 [95% CI, 1.42-4.18] for acute kidney injury and sepsis, respectively). The main sequelae were ophthalmologic and mood disorders. The findings of this cohort study suggest that although EN is a rare condition, it is associated with high rates of in-hospital and postdischarge mortality among patients who are older and have comorbid conditions. However, in contrast with in-hospital mortality, postdischarge mortality is not associated with EN initial severity but with acute in-hospital complications (eg, acute kidney injury and sepsis). Future studies are needed to construct models to estimate long-term outcomes and sequelae in patients with EN.

Suprathel® and water-filtered infrared-A radiation (wIRA) as a new treatment strategy for toxic epidermal necrolysis (TEN): A prospective study

Toxic epidermal necrolysis (TEN) is a life-threatening condition with a mortality rate of approximately 25% to 30%. Early and adequate wound coverage is necessary due to largescale skin defects. Suprathel® is a modern wound dressing that shows promising results when treating superficial wounds such as scald, burns and abrasions. Previous reports on wound care in TEN patients using Suprathel® have described radical debridement of the entire affected body surface prior to the application of Suprathel®. However, the heavy wound secretion frequently results in the loss of a significant portions of Suprathel® over time. Prolonged operation time increases the risk of hypothermia. In addition, the large open wound areas result in an increased risk for hypovolemic shock, wound infection, and subsequent sepsis. This study presents a new strategy that involves serial hydrotherapeutic wound debridement and the stepwise application of Suprathel® to the affected areas. Water-filtered infrared A light (wIRA) was used to keep the Suprathel®-covered areas dry. Retrospective data from patients who received polyhexanide gel treatment (control group 1) and those who only received Suprathel® (control group 2) were collected for matched-pair analysis. The length of stay in the intensive care unit (ICU) and the need for catecholamines were compared among the three groups. By using serial debridement and combining wIRA treatment with Suprathel® dressings, we were able to significantly reduce the need for catecholamines, lower the risk of hypothermia and infection, and shorten ICU stay compared to the two control groups. We propose incorporating this methodology into the standard of care to promote wound closure and healing when treating TEN patients.

Clinical Features of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Induced by Immune Checkpoint Inhibitor versus Non-Immune Checkpoint Inhibitor Drugs in China: A Cross-Sectional Study and Literature Review.

Immune checkpoint inhibitors (ICIs) can cause life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Large-scale original research on ICI-induced SJS/TEN is limited. This study aimed to explore the unique clinical characteristics and potential pathophysiological mechanisms of SJS/TEN induced by ICIs. This cross-sectional study compared the clinical features of SJS/TEN induced by ICIs and non-ICIs, and reviewed the case characteristics of ICI-induced SJS/TEN. Clinical features were analyzed using independent t-tests, Mann-Whitney U-tests, and multivariable regression models. This study enrolled 41 cases of ICI-induced SJS/TEN and 107 non-ICI-induced cases from January 22, 2015, to May 28, 2024. ICI-induced SJS/TEN patients exhibited a trend towards a longer latency period (β: 17, 95% CI: -1.49 to 35.48), a smaller affected body surface area (BSA) (β: -40.68, 95% CI: -71.59 to -9.77), and milder oral and ocular mucositis than non-ICI-induced cases. A literature review identified PD-1 inhibitors as the primary ICIs involved and systemic corticosteroids as the most frequent intervention. No statistically significant difference in mortality rate was observed between patients treated with systemic corticosteroids alone and those receiving combination therapies (P= 0.85). The mortality rate for ICI-induced SJS/TEN was 24.5%. This study offered the largest comparative analysis to date, highlighting the unique clinical features of ICI-induced SJS/TEN, including a smaller affected BSA, a prolonged latency period trend, and milder oral and ocular mucositis. We described the epidemiology, clinical presentation, and therapeutic strategies for ICI-induced SJS/TEN. These findings not only contribute to a deeper understanding of the complex immune-inflammatory pathways in severe immune-related cutaneous adverse events (ircAEs) but also may inform the development of more targeted and effective treatments.

A carbamazepine metabolite activates NLRP3 and controls skin homing of CD8+ T-cells in SJS/TEN

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with extensive keratinocyte death. Carbamazepine (CBZ), the most commonly implicated drug in SJS/TEN, is metabolized by the cytochrome P450 enzyme 3A4 (CYP3A4) into carbamazepine-10,11-epoxide (CBZE) in the liver. While CD8+ cytotoxic T cells play an important role in SJS/TEN, the underlying mechanism of exuberant immune response by CD8+ T cells in these conditions remains incompletely understood. ObjectivesTo examine the expression of NLRP3 inflammasome and their skin migration in CBZE-induced SJS/TEN. MethodsThe expression of the NLRP3 inflammasome complex in skin lesions, sera, and blister fluids of SJS/TEN patients were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay. NLRP3 formation and CD8+ T cell activation status and their functions were examined by immunoblotting, immunofluorescence, and chemotaxis assays. ResultsThe expression of the NLRP3 inflammasome complex was greatly increased in skin lesions of SJS/TEN patients. Moreover, IL-1β and IL-18 levels in sera and blister fluids of SJS/TEN patients were approximately 3-fold higher than those in healthy individuals, with a linear correlation between IL-1β levels and disease activity. CBZE induced NLRP3 inflammasome formation, upregulated CXCL9/CXCL10 levels, and activated CD8+ cytotoxic T cell functions via IL-1β/IL-1R or IL-18/IL-18R signaling in SJS/TEN keratinocytes, which promoted CD8+ cytotoxic T cell migration in SJS/TEN patients. ConclusionThis study showed that CBZE promoted NLRP3 inflammasome formation and strengthened the activation and function of CD8+ cytotoxic T cells in the skin, which contributed to the initiation and progression of SJS/TEN.

63 Incidence and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Following Completion of COVID-19 Vaccination: A Retrospective Analysis

63 Incidence and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Following Completion of COVID-19 Vaccination: A Retrospective Analysis