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Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, often triggered by medications, characterized by blistering and epithelial sloughing. We report the case of a 66‐year‐old male who presented with a 2‐day history of fluid‐filled lesions on his body. On examination, erosions were observed on the posterior and anterior trunk, as well as on both upper and lower limbs. Multiple vesicles and bullae were scattered bilaterally, involving 60%–70% of the body surface area. Co‐trimoxazole‐induced SJS was diagnosed. The patient was admitted to the ICU and treated with dexamethasone, hydrocortisone, imipenem, and azithromycin. Corticosteroids, combined with broad‐spectrum antibiotics, were effective in managing the condition. Early intervention and a multidisciplinary approach helped prevent complications and secondary infections. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by targeting immune checkpoints such as PD‐1, PDL‐1, and CTLA‐4, but concerns about severe immune‐related adverse events persist. The scarcity of literature on dermatologic implications, especially severe reactions such as Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), highlights the urgent need for investigation. Objective: Our systematic review aims to address the gap in relevant literature by extensively examining the epidemiologic risk factors and management of SJS/TEN‐like illnesses in ICI‐treated patients to provide insights for risk assessment and clinical care. Method s : We identified 158 case reports that detailed the incidence of SJS/TEN in patients being treated with ICIs, examining demographic patterns, type of malignancy, clinical characteristics, and treatments linked to onset. We assessed mortality rates, risk elements, and the effectiveness of interventions to help guide clinical care. Results: Analysis of 158 case reports revealed that SJS/TEN in ICI users is typically seen on average at the age of 63 and is more common in males. PD1 inhibitors such as nivolumab and pembrolizumab are often associated with various mucocutaneous patterns and significant risks with ICI use, especially TEN, which is linked to high morbidity and mortality rates. Limitations: Our study notes limitations due to the inclusion of case reports or case series, such as potential publication and reporting biases, leading to skewed findings. Additionally, because of the heterogeneous reporting standards, the retrospective nature limits phenotypic precision, control for confounding variables, and data completeness. Conclusion: Our study provides valuable insights into the epidemiology, clinical features, management strategies, and outcomes of ICI‐induced SJS/TEN, underscoring the importance of vigilant monitoring and personalized risk assessment in oncology practice. Continued research efforts are essential to optimize patient outcomes and enhance the safety profile of ICIs in cancer therapy. [ABSTRACT FROM AUTHOR]

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug‐induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti‐epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T‐cell therapy has demonstrated remarkable success in treating various B‐cell malignancies, redirecting T‐cell cytotoxicity toward cancer cells. Despite its efficacy, CAR‐T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69‐year‐old man with diffuse large B‐cell lymphoma treated with axicabtagene‐ciloleucel CAR‐T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol‐induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol‐induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol‐induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR‐T therapy‐related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: 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 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 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 speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy. [ABSTRACT FROM AUTHOR]

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)‐alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case–control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)‐8 and B‐cell lymphoma (Bcl)‐2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL‐2, IL‐6, TNF‐alpha, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), interferon‐gamma and matrix metalloproteinase‐2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL‐33, TGF‐beta‐1 and IL‐13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL‐13, IFN‐gamma, IL‐2 and IL‐5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Methods: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age‐ and gender‐matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. Results: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p <.0001), defensin (p <.0001), and matrix metalloproteinase 8 (p <.0001). The presence of neutrophils was confirmed by the upregulation of IL‐8 (p <.001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL‐36γ (p <.01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL‐36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p <.0001) and opiorphin (p <.002). Neutrophil elastase (p <.02) was significantly elevated in patients with severe eyelid margin keratinization. Conclusion: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL‐36γ, potentially mediated by neutrophils recruited via IL‐8. Future experimental studies are needed to test the role of therapies targeting IL‐8 and/or IL‐36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN. [ABSTRACT FROM AUTHOR]

ABSTRACT Radiotherapy is a rare cause of Stevens–Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN), especially in the pediatric age group. Most of the reported cases were concomitantly started on anti‐epileptic drugs. Herein, we present a case of radiotherapy induced SJS/TEN in an adolescent girl in the absence of anti‐epileptic drug use. Radiotherapy should be included as a potential cause for SJS/TEN, recognizing the important impact on management of the underlying malignancy. [ABSTRACT FROM AUTHOR]

Background. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and potentially life-threatening mucocutaneous blistering diseases that clinically can resemble autoimmune bullous diseases. Moreover, it has been shown that autoantibodies against epidermal proteins are present in SJS/TEN. Objectives. To establish the presence of antibodies against desmosomal and hemidesmosomal proteins in confirmed SJS/TEN patients. Methods. Serum of SJS/TEN patients diagnosed based on clinical criteria, e.g., epidermal detachment with erosions and severe mucosal lesions, (suspicion of) a culprit drug, and matching histologic results was evaluated by various techniques, e.g., indirect immunofluorescence on monkey esophagus, salt split skin and rat bladder, immunoblotting (IB) and immunoprecipitation (IP), ELISAs against desmogleins and BP180, keratinocyte footprint assay, and keratinocyte binding assay. Results. A total of 28 patients were included in this study, 15 men and 13 women with a mean age of 56 years. In most patients, none of the serological tests were positive. In two patients, an elevated DSG3 titer was found suspicious for pemphigus vulgaris. Three patients had elevated NC16a titers, suggesting bullous pemphigoid. However, in all these patients, no other tests were positive and in these patients, the biopsy for direct immunofluorescence showed no evidence for an autoimmune bullous disease. Three patients showed reactivity against rat bladder rat bladder; these were, however, completely negative for A2ML1, envoplakin, and periplakin in the IB as well as the IP. Conclusions. Serological analysis for desmosomal and hemidesmosomal antibodies is reliable to rule an autoimmune bullous disease in patients with suspected SJS/TEN. However, one should not rely on one single test method since false positive results can occur. Moreover, this study also makes it less plausible that antibodies against desmosomal and/or hemidesmosomal components are involved in the pathogenesis of SJS/TEN. [ABSTRACT FROM AUTHOR]

Background/Objectives: The immune checkpoint inhibitors (ICIs) have been increasingly associated with severe cutaneous adverse reactions (SCARs). These reactions, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are uncommon but potentially lethal. Despite the severity of these reactions and growing association with the ICIs, their specific risk and mortality rates have been largely unexplored. Methods: A case/non‐case analysis was performed using data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to examine the reporting odds ratios (RORs) for ICI‐associated SCARs cases under two conditions: (1) ICIs compared with all drugs in FAERS and (2) ICIs compared with a reference group of pooled anticancer drugs to control for underlying malignancy. Results: A statistically significant ROR for SJS (ROR: 5.44), TEN (ROR: 5.81) and DRESS (ROR: 1.38) were identified under Condition 1. Under Condition 2, this significance was maintained for SJS (ROR: 7.31), TEN (ROR: 7.40) and DRESS (ROR: 3.90), and mild significance was identified for AGEP (ROR: 1.89). Mortality rates for the ICIs were increased compared with the anticancer medications (28.5% vs. 24.5% for SJS, 55.3% vs. 46% for TEN, 3.0% vs. 2.1% for AGEP and 7.1% vs. 6.1% for DRESS). Conclusions: Our results suggest an association between SCARs and the ICIs independent of cancer status. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ibuprofen single dose may rarely induce Stevens–Johnson Syndrome, emphasizing the vital need for heightened vigilance in healthcare and public awareness for safer medication practices. Stevens–Johnson Syndrome (SJS) is a severe and potentially life‐threatening skin disorder associated with certain medications, including ibuprofen. We present a case of a 45‐year‐old woman who developed SJS following a single dose of ibuprofen. Despite its rarity, this case underscores the importance of heightened vigilance in healthcare and public awareness regarding the potential risks of commonly used medications. Prompt recognition of SJS symptoms and immediate medical intervention are crucial for patient outcomes. Healthcare providers should exercise caution when prescribing ibuprofen, particularly in patients with a history of adverse drug reactions. This case emphasizes the need for ongoing monitoring, patient education, and informed decision‐making to promote medication safety and optimal patient care. [ABSTRACT FROM AUTHOR]

Background and Aims: Adverse cutaneous drug reactions (ACDRs) are common and potentially life‐threatening, while also hindering patient compliance to medications. Given the regional differences in patterns and prevalence of ACDRs, it is important to study the epidemiology, as well as the clinical and outcome patterns of patients with ACDRs in Iran. Methods: This cross‐sectional study on ACDRs was conducted among hospitalized patients in a referral university hospital in the city of Isfahan, Iran. The patients' demographics, clinical information, and outcomes, including age, gender, past medical history, medication history, drug reaction with eosinophilia and systemic symptoms (DRESS) diagnosis, Steven‐Johnson Syndrome (SJS) diagnosis, toxic epidermal necrosis (TEN) diagnosis, treatment regimen (steroids or intravenous immunoglobulin [IVIG]) and outcome information, including intensive care requirements, severe medical complications, or death, were obtained from medical records. Results: A total of 195 patients with a mean age of 40 years and consisting of 61% females were included. Carbamazepine, lamotrigine, sodium valproate, and phenytoin are the most commonly reported medications. Rate of complications was 45% with DRESS, SJS, and TEN diagnosed in 26%, 47%, and 19%, respectively. Treatment was carried out with steroids and IVIG in 81% and 19%, respectively. Among patients, 15% required intensive care and 5% died. Diagnosis of TEN, older age, and baseline heart disease were predictors of mortality. Patients with SJS were younger and more likely to be males, and they were more likely to have eye complications. On the other hand, patients with the diagnosis of TEN were more likely to receive IVIG and intensive care, and had a higher mortality rate. Conclusion: Our study provides insight into the demographics and clinical patterns of Iranian patients with ACDRs. This will help in predicting rates of complications, treatments, and outcomes in patients and therefore make proper management decisions. [ABSTRACT FROM AUTHOR]

This article discusses the risk factors for sulfamethoxazole/trimethoprim (SMX/TMP)-induced severe cutaneous adverse reactions (SCARs). The study found that the HLA-B*13:01 allele is significantly associated with SMX/TMP-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Additionally, a higher daily dose of SMX/TMP was identified as a risk factor for SMX/TMP-induced SCARs. The study suggests that HLA-B*13:01 could be used as a predictive marker for identifying individuals at risk of developing DRESS after SMX/TMP treatment. However, further research is needed to validate these findings and determine the clinical utility of HLA gene testing in predicting adverse reactions to SMX/TMP. [Extracted from the article]

This article presents the findings of a study conducted in South Indian children to investigate the relationship between certain HLA-B alleles and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) caused by aromatic anticonvulsants. The study concludes that there is no significant association between HLA-B alleles and SJS/TEN induced by these medications in South Indian children. The results suggest that genetic diversity within the Indian population may explain this lack of association. The article mentions the names of four authors involved in the research but does not provide any details about the specific topics or content of their reports. [Extracted from the article]

Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD. [ABSTRACT FROM AUTHOR]

Severe cutaneous adverse drug reactions, including Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are challenging to be early diagnosed and evaluate their prognoses. This investigation aimed to analyse the expression profiles of SJS/TEN in peripheral blood mononuclear cells (PBMC) and assess the correlation between circular RNA (circRNA) and disease severity. Sixteen SJS/TEN patients and sixteen controls were enrolled and serum samples of both groups were obtained. CircRNA expression profiles in three SJS/TEN patients and three controls were detected by RNA sequencing and bioinformatic analyses were then performed. The differentially expressed circRNAs were verified by quantitative polymerase chain reaction (qPCR). Then, analysing the correlation of circRNAs with the toxic epidermal necrolysis‐specific severity of illness score (SCORTEN) and the epidermal detachment area. A total of 134 circRNAs were differentially expressed in the PBMCs of SJS/TEN individuals, according to our results. The qPCR showed that three circRNAs (hsa_circ_0000711, hsa_circ_0083619 and hsa_circ_0005615) were down‐regulated, and one circRNA (hsa_circ_0003028) was up‐regulated, which were compatible with the sequencing findings. The concentration of hsa_circ_0083619 was closely associated with the SCORTEN scale (r = −0.581, p = 0.037) and the epidermal detachment area (r = −0.576, p = 0.039). The circRNA‐miRNA‐mRNA prediction network was used to construct the hsa_circ_0083619/miR‐18a‐5p/BCL2L10 axis. The hsa_circ_0083619 could serve as a disease severity indicator for SJS/TEN. Through bioinformatics analysis, we speculated that hsa_circ_0083619/miR‐18a‐5p/BCL2L10 axis might play a role in SJS/TEN pathogenesis. [ABSTRACT FROM AUTHOR]

Aims: Despite the availability of newer antiseizure medications, carbamazepine (CBZ) remains the gold standard. However, patients of Asian ancestry are susceptible to CBZ‐related severe cutaneous adverse reactions. Universal HLA‐B*15:02 screening is a promising intervention to address this. With the increasing recognition of integrating real‐world evidence in economic evaluations, the cost‐effectiveness of universal HLA‐B*15:02 screening was assessed using available real‐world data in Malaysia. Methods: A hybrid model of a decision tree and Markov model was developed to evaluate 3 strategies for treating newly diagnosed epilepsy among adults: (i) CBZ initiation without HLA‐B*15:02 screening (current practice); (ii) universal HLA‐B*15:02 screening prior to CBZ initiation; and (iii) alternative prescribing without HLA‐B*15:02 screening. The model was populated with real‐world inputs derived from the Malaysian population. From a societal perspective, base‐case analysis and sensitivity analyses estimated the costs and outcomes over a lifetime. Incremental cost‐effectiveness ratios were calculated. Results: In the base‐cases analysis, universal HLA‐B*15:02 screening yielded the lowest total costs and the highest total quality‐adjusted life years (QALYs) gained. Compared with current practice, universal screening was less costly by USD100 and more effective by QALYs increase of 0.1306, while alternative prescribing resulted in 0.1383 QALYs loss at additional costs of USD332. The highest seizure remission rate (56%) was estimated for universal HLA‐B*15:02 screening vs. current practice (54%) and alternative prescribing (48%). Conclusion: Our study suggests that universal HLA‐B*15:02 screening is a cost‐effective intervention in Malaysia. With the demonstrated value of real‐world evidence in economic evaluations, more relevant standardization efforts should be emphasized to better inform decision‐making. [ABSTRACT FROM AUTHOR]

Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life‐threatening reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)‐B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.62 to 580.3 for mild to severe reactions, respectively). In addition to the parent drug, the metabolite oxypurinol (OXP) is implicated in triggering T cell‐mediated immunopathology via a labile interaction with HLA‐B*58:01. To date, there has been limited information regarding the T‐cell receptor (TCR) repertoire usage of reactive T cells in patients with ALP‐induced SJS or TEN and, in particular, there are no reports examining paired αβTCRs. Here, using in vitro drug‐treated PBMCs isolated from both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors, we show that OXP is the driver of CD8+ T cell‐mediated responses and that drug‐exposed memory T cells can exhibit a proinflammatory immunophenotype similar to T cells described during active disease. Furthermore, this response supported the pharmacological interaction with immune receptors (p‐i) concept by showcasing (i) the labile metabolite interaction with peptide/HLA complexes, (ii) immunogenic complex formation at the cell surface, and (iii) lack of requirement for antigen processing to elicit drug‐induced T cell responsiveness. Examination of paired OXP‐induced αβTCR repertoires highlighted an oligoclonal and private clonotypic profile in both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors. [ABSTRACT FROM AUTHOR]

Mucocutaneous eruptions are associated with numerous infectious processes and can present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME), Stevens Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). Limited reports have detailed the association of these eruptions with SARS‐CoV‐2 infection. We present a series of eight cases of severe mucocutaneous blistering eruptions associated with SARS‐CoV‐2 infection. A retrospective case series was performed at six tertiary medical centers from March 1, 2020 to August 1, 2022. Inclusion criteria were met with a clinical diagnosis of EM, RIME, SJS, or TEN and a positive SARS‐CoV‐2 test (rapid antigen or polymerase chain reaction) less than 4 weeks prior to onset of dermatologic manifestation. Data was collected at time of each patient encounter. Eight patients met criteria with six pediatric patients (<18 years of age) having a median age of 15 years and two adult patients (>18 years of age) having a median age of 36 years. Patients were found to have a clinical diagnosis of RIME in 85.7% of cases. Oral mucosal involvement was the most common clinical finding (100%), followed by ocular (50.0%), urogenital (50.0%), and skin (37.5%) involvement. Evaluation did not reveal any additional infectious triggers in four patients. Evidence of possible concurrent or previous infectious triggers were identified in four patients. This case series highlights the development of severe mucocutaneous eruptions in association with COVID‐19 infection, as well as the potential contributing role of concurrent or prior infections. [ABSTRACT FROM AUTHOR]

The article discusses an external validation study of the Re-SCORTEN scoring system in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. The study found that the ratio of red cell distribution width (RDW) to hemoglobin (Hb) showed similar accuracy in predicting mortality compared to SCORTEN. The study supports the predictive value of RDW/Hb in mortality, but after adjusting for SCORTEN, the association was not significant. The findings suggest that using RDW/Hb and SCORTEN together (Re-SCORTEN) may improve prognostic performance without statistical significance. [Extracted from the article]

Severe cutaneous adverse drug reactions (SCARs) are a life‐threatening condition. We aimed to identify all carbamazepine‐induced SCARs voluntarily reported to the Malaysian pharmacovigilance database and to compare between children and adults. Adverse drug reaction reports for carbamazepine were extracted from 2000 to 2020, and divided into 2 groups, that is, children (aged 0–17 years) and adults (aged 18 years and above). Age, sex, race, and carbamazepine dose were analyzed using multiple logistic regression. Of 1102 carbamazepine adverse drug reaction reports, 416 reports were SCARs (99 children, 317 adults). Stevens–Johnson syndrome and toxic epidermal necrolysis were the main SCAR types for both age groups. Median time‐to‐onset for any type of SCAR was 13 days, regardless of age. In children, Malay individuals were 3.6 times more likely to report SCARs (95% confidence interval, 1.356–9.546; P =.010) compared to the Chinese population. In adults, carbamazepine‐induced SCARs were reported as 3.6 times higher in those with a daily dose of 200 mg or less as compared to a daily dose of 400 mg or more. (95% confidence interval, 2.257–5.758; P <.001) Carbamazepine‐induced SCARs reported in Malaysia were predominantly Stevens–Johnson syndrome or toxic epidermal necrolysis, with the majority in Malay individuals. Initiation therapy needs close monitoring between 2 weeks and 1 month. [ABSTRACT FROM AUTHOR]

Objective: The HLA‐B*1502 allele is strongly associated with carbamazepine (CBZ)‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA‐B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA‐B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. Methods: Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score‐based stabilized weighting (PSSW) ensured well‐balanced covariates. The difference in 3‐month SCAR and SJS/TEN rates between phase 2 (2011–2017) and phase 1 (2000–2009) was examined using a one‐sample Z‐test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA‐B*1502 genotyping. Results: CBZ prescriptions reduced from 7% (2000–2003) to 6% (2004–2010) and 4% (2011–2017). The screening rates of CBZ nonusers and CBZ users increased from 0%,.5% in 2011 to.8%, 16% in 2017, respectively. After PSSW, the mean 3‐month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p <.0001) and nonusers (1.96 vs. 1.65, p <.0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p <.0001) but not for nonusers (.71 vs..74, p =.1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = −.38, p =.0342) and nonusers (r = −.80, p <.001). No significant correlation was found between SJS/TEN incidence rates and screening rates. Significance: Recognizing HLA‐B*1502 allele and avoiding CBZ therapy in HLA‐B*1502‐positive patients is critical for preventing CBZ‐induced severe adverse events. [ABSTRACT FROM AUTHOR]

In this observational case–control study, 107 cutaneous adverse reaction (CAR) cases (CAR+) manifesting up to 12 weeks after the start of treatment with antiseizure medication (ASM) were identified. Control groups consisted of 98 epilepsy patients without a history of CAR (CAR‐) and 3965 healthy individuals in the Brazilian National Registry of Bone Marrow Donors. All participants were HLA typed by high‐resolution Next Generation Sequencing for HLA‐A, B, C, DQB1 and DRB1; HLA‐DPA1, DPB1, DQA1, DRB3, DRB4 and DRB5 were also sequenced in samples from CAR+ and CAR‐ individuals. The relationship between the carrier frequency of each allele, CAR type and ASM for all participants was investigated. The ASMs most frequently associated with CAR were carbamazepine (48% of CAR+ subjects), lamotrigine (23%), phenytoin (18%), phenobarbital (13%) and oxcarbazepine (5%). The main alleles associated with a risk of CAR were HLA‐A*02:05 (OR = 6.28; p = 0.019, carbamazepine or oxcarbazepine); HLA‐DPA1*02:02 (OR = 4.16, p = 0.003, carbamazepine); HLA‐B*53:01 (OR = 47.9, p = 0.014, oxcarbazepine), HLA‐DPA1*03:01/DPB1*105:01 (OR = 25.7, p = 0.005, phenobarbital); HLA‐C*02:10 (OR = 25.7, p = 0.005, phenobarbital) and HLA‐DRB1*04:02 (OR = 17.22, p = 0.007, phenytoin). HLA‐A*03:01 increased the risk for phenytoin‐induced maculopapular exanthema 4.71‐fold (p = 0.009), and HLA‐B*35:02 was associated with a 25.6‐fold increase in the risk of carbamazepine‐induced Stevens‐Johnson syndrome (p = 0.005). None of the 4170 subjects carried the HLA‐B*15:02 allele, and HLA‐A*31:01 was not associated with CAR. Hence, HLA‐A*31:01 and HLA‐B*15:02 were not associated with CAR in this population. Although other HLA class I and II alleles tested were associated with a risk of CAR, none of these associations were strong enough to warrant HLA testing before prescribing ASM. [ABSTRACT FROM AUTHOR]

Background: At present, no predictive models are available to determine the probability of in‐hospital mortality rates (HMRs) in all phenotypes of severe cutaneous adverse reactions (SCARs). Objectives: Our study explored whether simple clinical and laboratory assessments could help predict the HMRs in any phenotypes of SCAR patients. Methods: Factors influencing HMRs in 195 adults diagnosed with different SCAR phenotypes were identified, and their optimal cut‐offs were determined by Youden's index. Predictive equations for HMRs for all SCAR patients and Stevens‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) patients were determined using the exact logistic regression models. Results: Acute generalized exanthematous pustulosis (AGEP) patients were significantly older, with a short time from drug exposure to reaction, and higher neutrophil count compared to SJS/TEN and drug reaction with eosinophilia and systemic symptoms (DRESS, p < 0.001). Peripheral blood eosinophilia, atypical lymphocytosis and elevated liver transaminase enzymes were significantly higher in DRESS. SJS/TEN phenotype, age ≥ 71.5 years, neutrophil‐to‐lymphocyte ratio ≥ 4.08 (high NLR) and systemic infection were factors predicting in‐hospital mortality in all SCAR subjects. The ALLSCAR model developed from these factors demonstrated high‐diagnostic accuracy for predicting HMRs in all SCAR phenotypes (area under the receiver‐operator curve (AUC) = 0.95). The risk of in‐hospital death was significantly increased in SCAR patients with high NLR after adjusting for systemic infection. The model derived from high NLR, systemic infection and age yielded higher accuracy than SCORTEN (AUC = 0.77) for predicting the HMRs in SJS/TEN patients (AUC = 0.97). Conclusions: Being older, having systemic infection, having a high NLR and SJS/TEN phenotype increases ALLSCAR scores, which in turn increases the risk of in‐hospital mortality. These basic clinical and laboratory parameters can easily be obtained in any hospital setting. Despite its simple approach, further validation of the model is warranted. [ABSTRACT FROM AUTHOR]

Decreased epidermal high‐mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Etanercept, an anti‐tumor necrosis factor therapeutic, is effective in the treatment of SJS/TEN. The objective was to characterize antitumor necrosis factor‐alpha (TNF‐α)‐mediated HMGB1 keratinocyte/epidermal release and etanercept modulation. HMGB1 release from TNF‐α treated (± etanercept), or doxycycline‐inducible RIPK3 or Bak‐expressing human keratinocyte cells (HaCaTs) was determined by western blot/ELISA. Healthy skin explants were treated with TNF‐α or serum (1:10 dilution) from immune checkpoint inhibitor‐tolerant, lichenoid dermatitis or SJS/TEN patients ± etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF‐α induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF‐α or SJS/TEN serum resulted in significant epidermal toxicity/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole‐slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre‐blistered SJS/TEN versus control (P < 0.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF‐α is a key mediator of epidermal HMGB1 release, other cytokines/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS/TEN that could be utilized for further mechanistic studies and targeted therapy screening. [ABSTRACT FROM AUTHOR]

Background: Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS) are both severe cutaneous adverse reactions. Keratinocyte death is much more prominent in SJS/TEN compared to DRESS. Objective: This study aimed to investigate the role of exosomal miRNAs on keratinocyte death in SJS/TEN. Methods: Peripheral blood mononuclear cells (PBMCs) from SJS/TEN and DRESS patients were stimulated with the culprit drugs. The exosomes released in cell supernatants were co‐incubated with HaCaT cells to study the cytotoxic effects on keratinocytes. Exosomal miRNA sequencing analysis was performed to compare the expression patterns between SJS/TEN and DRESS subjects. HaCaT cells were then transfected with miRNA mimics and inhibitors to explore the functions of miRNAs on keratinocyte cell death. Results: Cytotoxic effects of PBMC‐derived exosomes on keratinocytes were demonstrated in SJS/TEN and could be neutralized with exosome inhibitors. Cytotoxic effects of PBMC‐derived exosomes from SJS/TEN subjects were higher after incubating PBMCs with the culprit drugs than those incubating with irrelevant drugs and unstimulated controls. The sequencing data revealed differential expressions of 61 exosomal miRNAs between SJS/TEN and DRESS. Exosomal miR‐4488 was upregulated while miR‐486‐5p, miR‐96‐5p and miR‐132‐3p were downregulated in SJS/TEN compared to DRESS as determined by quantitative real‐time PCR. The increased percentage of apoptotic cells upon transfection of HaCat cells was 36.3% and 34.9% with miR‐4488 mimic and miR‐96‐5p inhibitor, respectively. Conclusion: This study illustrated the regulatory functions of exosomal miRNAs in controlling keratinocyte death in SJS/TEN. Exosome inhibitors might have a therapeutic role in SJS/TEN. [ABSTRACT FROM AUTHOR]

Since the outbreak of COVID-19, various vaccines have been developed to prevent viral transmission. We included studies reporting at least one patient who developed SJS, TEN, AGEP, and DRESS after at least one dose of a COVID-19 vaccine. Meanwhile, COVID-19 vaccines have been reported potentially to induce severe cutaneous adverse reactions (SCARs).[[1], [3]] SCARs, encompass several disease entities including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). [Extracted from the article]

Background: Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but potentially life‐threatening cutaneous adverse reactions. There is still no consensus on adjuvant treatments, and little is known about their effects on systemic inflammation in SJS/TEN. Our aim was to characterize the systemic and cutaneous immune profiles of SJS/TEN patients and to investigate whether/how intravenous immunoglobulins (IVIG), cyclosporine A (CSA), and best supportive care only (BSCO) affected the systemic immune signature and clinical outcome (6 week‐mortality, complications, hospitalization stay). Methods: We included 16 patients with SJS/TEN, treated with high‐dose IVIG (n = 8), CSA (n = 4) or BSCO (n = 4). Serial serum samples were obtained prior‐, 5–7 days, and 21 days after treatment onset. Serum levels of inflammation−/immune response‐associated proteins were measured by high‐throughput proteomics assay (OLINK) and cytotoxic molecules by ELISA. RNA extracted from skin biopsies collected prior treatment was analyzed by Nanostring. Results: Serum inflammatory profiles in SJS/TEN patients were notably characterized by massive upregulation of type 1 immune response and proinflammatory markers. Surprisingly, there was limited overlap between cutaneous and serum immune profiles. Serial serological measurements of immune response markers showed very diverse dynamics between the different treatment groups. IVIG‐treated patients showed completely different dynamics and most significant proteomic changes in an early phase (Day 5–7). In all treatment groups, type 1−/inflammatory response markers were dampened at day 21. Clinically, there were no outcome differences. Conclusion: Our study demonstrates that BSCO, CSA, and IVIG have very diverse biological effects on the systemic inflammatory response in SJS/TEN, which may not correlate with clinical outcome differences. [ABSTRACT FROM AUTHOR]

Radiation dermatitis, limited to the irradiated site, is the most common cutaneous adverse reaction due to radiotherapy. There are scattered reports of erythema multiforme‐like rash, Stevens–Johnson syndrome, and toxic epidermal necrolysis associated with radiotherapy. Some of these reports include cases without remarkable drug history, which suggests rashes induced by radiotherapy. The lack of a large cohort study, however, makes it difficult to ascertain the time course, severity, and outcome of the cases. We aimed to evaluate the potential association between radiotherapy and erythema multiforme‐like rash in a larger sample of patients. We examined the records of patients at our institute who received radiotherapy and developed a rash from 2010 to 2021. We present 30 patients with erythema multiforme‐like rash, which arose during or after radiotherapy. We describe the background, details of radiotherapy, and clinical course of the patients including the cutaneous and extracutaneous symptoms. Radiotherapy was the most likely cause of rash, and in most cases, the rash was relieved by conservative management and radiation could be continued. When erythema multiforme‐like rash arises in patients under cancer treatment, radiotherapy should be considered a potential trigger. [ABSTRACT FROM AUTHOR]

Reactive infectious mucocutaneous eruption (RIME) is an eruptive mucositis with varying degrees of cutaneous involvement presumed to be due to an immunologic response to various infectious pathogens. Most reported cases occur after a prodromal upper respiratory illness. We present a patient with a particularly severe case mimicking drug‐induced epidermal necrolysis found to be triggered by asymptomatic norovirus infection, a virus not previously reported in association with RIME. [ABSTRACT FROM AUTHOR]

The article discusses immune cutaneous reactions in orf and pseudocowpox viruses, both caused by Parapoxviruses. Orf primarily affects sheep and goats, while pseudocowpox infects calves. The diagnosis is mainly clinical and epidemiological, with self-resolving manifestations but potential complications. Treatment includes supportive therapy, and clinicians should be aware of these infections to avoid misdiagnosis and unnecessary treatments. [Extracted from the article]

This article discusses the clinical applicability of an artificial intelligence (AI)-based prognosis prediction model for a rare ocular surface disease called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The rarity of cases and the lack of a standardized prediction system make medical treatment services for SJS/TEN highly dependent on the experience of each clinical institution. The study created an AI model that accurately predicts the severity of ocular surface symptoms at more than 5 years after the first diagnosis. The AI model showed comparable performance to an empirical model based on the expertise of experienced physicians. Further research is needed to explore the feasibility of using AI for standardized prognosis prediction of SJS/TEN ocular symptoms. [Extracted from the article]

Osteopontin (OPN) was initially described as a protein involved in bone metabolism, but the roles played by OPN in the immune system and allergic reactions have attracted increasing attention. Here, we clarify the OPN‐related dynamics of severe cutaneous adverse drug reactions, and assess whether the OPN level has utility for classifying such reactions and serving as a biomarker of severity. Serum OPN levels in patients with drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme‐type drug reaction (EM‐DR) were quantified by ELISA. The OPN sources were analyzed by dual immunofluorescence assay of DIHS, SJS/TEN and EM‐DR biopsy specimens. The serum OPN levels of DIHS/DRESS patients (489.1 ± 37.0 ng/mL) and SJS/TEN patients (508.5 ± 47.8 ng/mL) were significantly higher compared with controls (314.4 ± 14.3 ng/mL; p < 0.001). After treatment, the serum OPN level of DIHS/DRESS patients decreased to that of controls. In addition, OPN levels in DIHS/DRESS patients and SJS/TEN patients were higher than in patients with EM‐DR (Mann–Whitney U test, p < 0.05). However, when the Kruskal–Wallis test was used to compare the OPN levels among the three groups of patients, the difference was not significant (p = 0.055). Dual immunofluorescence assay revealed that T lymphocytes and macrophages were the main OPN sources in DIHS, SJS/TEN and EM‐DR patients. These data suggest that the OPN level can be used to evaluate the severity of inflammation in patients experiencing drug reactions. [ABSTRACT FROM AUTHOR]

Aim: To appraise the current evidence on the efficacy and safety of lamotrigine (LAM) in the treatment of pediatric mood disorders (PMD) (i.e., Major Depressive disorder [MDD], bipolar disorder [BD]). Methods: Major databases were searched for randomized controlled trials (RCTs), open‐label trials, and observational studies reporting on pediatric (age < 18 years) patients treated with LAM for mood disorders. Results: A total of 3061 abstracts were screened and seven articles were selected for inclusion. Seven studies (319 BD and 43 MDD patients), including one RCT (n = 173), three prospective (n = 105), and three retrospective (n = 84) studies, met the study criteria with a study duration range from 8 to 60.9 weeks. The mean age of this pooled data is 14.6 ± 2.0 years. LAM daily dosage varied from 12.5 to 391.3 mg/day among the studies. In an important finding, the RCT reported favorable outcomes with LAM (HR = 0.46; p = 0.02) in 13‐ to 17‐year‐old age group as compared with 10‐ to 12‐year‐old age group (HR = 0.93; p = 0.88). In addition, time to occurrence of a bipolar event trended toward favoring LAM over placebo. All the studies identified LAM as an effective and safe drug in PMDs especially, BDs. Overall, LAM was well tolerated with no major significant side effects and no cases of Stevens–Johnson syndrome. Conclusions: Most studies suggested that LAM was safe and effective in pediatric patients with mood disorders. However, the data regarding the therapeutic range for LAM are lacking. Based on the data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM dosage for mood improvement in the pediatric population. Further studies including larger sample sizes are required to address this relevant clinical question. [ABSTRACT FROM AUTHOR]

Stevens‐Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are rare and life‐threatening mucocutaneous diseases that occur almost exclusively as a result of adverse drug reactions, although there are rare cases attributed to infection, immunization, or malignancy.1,2 Given the low incidence of these diseases as well as the high level of morbidity and mortality, randomized controlled clinical trials are difficult to perform, making it difficult to establish a "gold‐standard" treatment. To date, there are only five published articles in the literature detailing evidence‐based guidelines for the treatment of SJS and TEN, one of which is specifically tailored to pediatric and young adult patients.3–7 These guidelines have significant overlap in regards to the importance of prompt discontinuation of the offending drug and the need for supportive care, but there are differences in regards to the ideal supportive care measures. Additionally, there is still no clear consensus agreement on the pharmacological treatment of SJS and TEN.4–7 Herein, we aim to compare the international treatment guidelines for management of SJS and TEN as well as promote continued discussion and a multidisciplinary approach to establish consensus recommendations for these mucocutaneous emergencies. [ABSTRACT FROM AUTHOR]

Hyperuricemia has become a global problem and is one of the four basic metabolic diseases after hypertension, hyperlipidemia, and hyperglycemia. However, the existing drugs have undesired or serious adverse effects, such as the high risk of Stevens‐Johnson syndrome for allopurinol, and the cardiovascular side effects induced by febuxostat. Therefore, it is an urgent need to develop an effective and safety agent for the treatment of hyperuricemia. The urate transporter 1 (URAT1) inhibitors have been considered as a promising uric acid‐lowering agents. To improve adverse reactions caused by excessive lipophilicity and large molecular weight of existing drugs, five novel low‐molecular‐ weight URAT1 Inhibitors were designed and synthesized by molecular hybridisation. Among them, although compound 4 showed less potent activity than the classic URAT1 inhibitor benzbromarone in vitro, compound 4 exhibited better uric acid‐lowering activity than benzbromarone in vivo, which may be related to the fact that compound 4 has lower lipophilicity than benzbromarone to facilitate drug absorption. In addition, compound 4 cherishes some merits, which have a smaller molecular weight and lower lipophilicity, and superior in vitro activity than lesinurad. Generally, the results indicate that compound 4, with a good therapeutic effect, is a prospective candidate for the treatment of hyperuricemia. [ABSTRACT FROM AUTHOR]

Stevens‐Johnson Syndrome (SJS) is a rare but severe skin reaction characterized by blistering and peeling of the skin and ulcerations of mucous membranes; toxic epidermal necrolysis (TEN) is a subset of SJS characterized by the involvement of >30% of the skin. Though previously associated with drugs and infections, discussions on the association between TEN/SJS and COVID‐19 have been limited. We present a review of TEN/SJS after COVID‐19 infection and vaccination. Literature searches were conducted on PubMed and Google Scholar from 2019 to 8/2022. Thirty‐eight articles were selected based on subject relevance, and references within selected articles were also screened for relevance. As of 8/2022, there have been 34 published cases of TEN, SJS, and SJS‐TEN overlap after COVID‐19 infection and vaccination, including 12 cases after vaccination and 22 cases after infection. Multiple authors hypothesize that virotopes or excipients in COVID‐19 vaccines can activate T‐cells or cytokines to induce TEN/SJS. Meanwhile, some hypothesize that COVID‐19 infection induces immune activation that can trigger TEN/SJS or increase susceptibility to drug‐induced TEN/SJS. Treatments for post‐infection and post‐vaccination TEN/SJS vary significantly. We recommend remaining vigilant for this rare and severe potential complication. [ABSTRACT FROM AUTHOR]

Atypical presentations of Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN)-like eruptions[1] have been observed in association with immune checkpoint inhibitors (ICIs), and the term progressive immunotherapy-related mucocutaneous eruption (PIRME) has been proposed for this condition.[2] PIRME presents with a milder disease course, rare ocular involvement, involvement of a second drug trigger, and a generally favorable response to treatment.[2] Current guidelines advise permanent ICI discontinuation after an SJS/TEN-like reaction.[3] We describe a patient who developed PIRME in the setting of pembrolizumab and azithromycin exposure who successfully tolerated pembrolizumab rechallenge after azithromycin discontinuation. Rechallenge with ICI may be considered in the appropriate clinical setting in patients who experience PIRME or atypical SJS/TEN-like presentations following ICI therapy. The patient had an identifiable second drug trigger, experienced mild symptoms associated with her eruption, and improved with topical steroid therapy, and there was a lack of other viable treatment options for her cancer. [Extracted from the article]

Most of the patients (7 patients, 53.8%) developed SJS/TEN after the first dose of the COVID-19 vaccine, similar to our case. Stevens-Johnson syndrome/toxic epidermal necrolysis overlap case possibly induced by COVID-19 vaccine Stevens-Johnson syndrome (SJS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap syndrome and TEN are considered to be a part of continuous spectrum of life-threatening mucocutaneous necrolysis.[[1], [3]] Drugs are the most common triggers. [Extracted from the article]

Carbamazepine has been described as a cause of SCARs in approximately 1 in 5000 patients.[5] DRESS is a hyperinflammatory syndrome[6] that occurs after a relatively prolonged exposure (e.g. >4 weeks) to triggering medications such as carbamazepine. Anti-epileptic drugs (AEDs) are known to be associated with dermatological and systemic reactions, usually grouped as "drug hypersensitivity reactions", "drug-induced hypersensitivity syndromes" or "severe cutaneous adverse reactions" (SCARs).[1], [2], [3] This group of reactions, which includes Stevens-Johnsons syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP) are severe and can lead to organ damage, long-term sequelae and even death if not managed correctly (especially if the offending drug is not discontinued promptly).[4] Carbamazepine seems to be the drug most frequently associated with SCAR in children, possibly due to its common use as an effective AED, paired with its relatively rare and benign adverse event profile. Keep drug reaction in the differential diagnosis forpatients presenting with fever, rash and liver injury. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). [Extracted from the article]

What Is Known and Objective: Allopurinol, the first‐line medication for hyperuricemia is well‐known for its association with severe cutaneous adverse reactions, especially Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). In the current study, we analysed the Vietnamese spontaneous reporting database to identify signals and preventability of allopurinol‐induced SJS/TEN in Vietnam from 2010 to 2019. Methods: Signal generation was assessed using the case/non‐case method. Reporting odds ratios (RORs) and 95% confidence intervals (95% CI) were calculated. Results: Among 72,822 spontaneous ADR reports submitted to the Vietnam National Drug Information and Adverse Drug Reaction Monitoring Centre, 392 reports were on SJS/TEN, of which, 65 cases (16.6%) were related to allopurinol. The signals of allopurinol‐induced SJS/TEN in Vietnam started in 2014 (ROR of 3.531, 95% CI: 1.830–6.810) and annually increased until 2019 (ROR of 11.923, 95% CI: 8.508–16.710). The preventability assessment showed that no allopurinol‐induced SJS/TEN case was definitely unpreventable. 61.6% of the SJS/TEN cases were avoidable because they were associated with inappropriate prescribing such as unapproved indications, too high initial dose and even rechallenging in patients with a history of allopurinol allergy. What Is New and Conclusion: The signals of allopurinol‐induced SJS/TEN in Vietnam started in 2014 and annually increased until 2019. Our first report specifically focusing on the ADR preventability of allopurinol showed that correction of medical errors relating to prescription could prevent more than 60% of SJS/TEN cases in Vietnamese allopurinol users. This is a feasible and practical solution, provided that there would be a systematic change in both healthcare systems and public awareness. [ABSTRACT FROM AUTHOR]

Oral care is an often difficult and an unappreciated part of hospital life. Patients who are unable to provide their own care rely on assistance from hospital personnel. Most sequelae from suboptimal oral care often present over months if not years, in the form of dental caries and periodontal disease. We present an exception, where a 66-year-old patient who experienced widespread ulceration and necrosis from Capnocytophaga-related sepsis received suboptimal oral care, resulting in their tongue being fused to their lip. This was later divided by the oral and maxillofacial team resulting in restoration of full function. Future cases can be avoided in patients with similar symptoms, such as Stevens-Johnson syndrome or erythema multiforme, if rigorous oral care can be provided. [ABSTRACT FROM AUTHOR]

Background/Objectives: Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening mucocutaneous hypersensitivity reactions that carry significant morbidity and mortality. While clinical features are well documented in adult and pediatric patients, infantile cases are rarely reported. Our objective was to synthesize clinical features and outcomes in this population. Methods: A literature search was performed from three large databases (PubMed, EMBASE, and Web of Science) to systematically identify reports of SJS/TEN in the infantile period (defined as less than 12 months of age) between 1962 and 2019. Cases determined to represent SJS/TEN based on defined criteria were included. Each case was scored based on Quality Rating Scheme for Studies and Other Evidence. The initial search yielded 4856 publications, of which 19 (n = 26) met final inclusion criteria. Results: All cases for which body surface area (BSA) involvement was available or able to be approximated (n = 18/26) met criteria for TEN. All cases (n = 26) had mucous membrane involvement, with the oral mucosa most commonly affected (85.7%). Mortality was high within our population with 39.1% of infants expiring, 77.8% secondary to bacterial sepsis. The most common triggers were medications (52.4%), infections (33.3%), and vaccinations (14.3%). Conclusions: This review highlights several unique clinical findings amongst infants with SJS/TEN, including increased BSA involvement, higher rates of bacterial sepsis, and higher mortality rates compared to older children and adults. Infants are more likely to present as TEN over SJS. More research is needed to identify triggers, successful treatments, and specific outcomes in this population. [ABSTRACT FROM AUTHOR]

Toxic epidermal necrolysis and Stevens‐Johnson Syndrome describe a spectrum of severe cutaneous skin reactions constituting a medical emergency, and no formal treatment guidelines exist to direct systemic immunosuppressive therapy although referral to a burns unit and wound management remains a mainstay of treatment. We performed a retrospective chart review on all patients at a single centre with TEN between 2017 to 2021 to compare clinical characteristics and outcomes of those treated with the tumour necrosis factor‐alpha (TNF‐α) inhibitor adalimumab against non‐TNF‐α immunosuppressants such as glucocorticoids, intravenous immunoglobulin and cyclosporine. All patients treated with adalimumab had successful resolution of their TEN, resulting in a mean duration of hospital admission of 22.5 days compared to 33 days for patients treated with non‐TNF‐α inhibitors. We highlight adalimumab as a promising systemic immunomodulator in the treatment of TEN with efficacy comparable to other immunosuppressive agents and associated with a shorter duration of hospital admission. [ABSTRACT FROM AUTHOR]