Stevens-Johnson Syndrome Research Articles

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.

Sequential Development of Immune Checkpoint Inhibitor-Induced Acute Tubulointerstitial Nephritis (ICI-ATIN) following Stevens-Johnson Syndrome (SJS)-Like Reaction in Patient on Pembrolizumab and Meropenem: A Common Drug Trigger?

Sequential Development of Immune Checkpoint Inhibitor-Induced Acute Tubulointerstitial Nephritis (ICI-ATIN) following Stevens-Johnson Syndrome (SJS)-Like Reaction in Patient on Pembrolizumab and Meropenem: A Common Drug Trigger?

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

Oseltamivir-Induced Steven Johnson Syndrome, Case Report

First described in 1922, Steven Johnson Syndrome (SJS) is an acute mucocutaneous disease with conjunctivitis, stomatitis, purple macules and skin necrosis in which an acute inflammatory process followed by the action of immune complexes has been identified. In the middle hypersensitivity, it should involve less than 10% of the total body surface. Its annual incidence in the world is unknown, it is estimated 1-2 cases per million in a year of which 20% will be pediatric patients; this can be triggered by drugs, infectious agents and biological agents. It manifests as lesions in the skin and mucous membranes of which it can involve ocular conjunctiva, oral, nasal, vaginal, urethral and perianal mucosa

Unusual Presentation of Stevens-Johnson Syndrome Induced by Trimethoprim-Sulfamethoxazole: A Case Report

Unusual Presentation of Stevens-Johnson Syndrome Induced by Trimethoprim-Sulfamethoxazole: A Case Report

Stevens–Johnson syndrome in an Asian man after receiving the third dose of COVID-19 vaccine

Stevens–Johnson syndrome in an Asian man after receiving the third dose of COVID-19 vaccine

A case of Stevens–Johnson syndrome after influenza a virus infection

A case of Stevens–Johnson syndrome after influenza a virus infection

Post-marketing safety concern of PI3K inhibitors in the cancer therapies: an 8-year disproportionality analysis from the FDA Adverse Event Reporting System

ABSTRACT Background The Phosphoinositide 3-kinases (PI3Ks) family plays a crucial role in tumorigenesis. Alpelisib (inhibiting PI3Kα), copanlisib (inhibiting PI3Kα andPI3Kδ), duvelisib (inhibiting PI3Kδ and PI3Kγ), and idelalisib (inhibiting PI3Kδ) were developed to target the PI3K pathway. However, the toxicity limits their application to some extent. It’s necessary to investigate the adverse effects (AEs) of these inhibitors. Research design and methods We conducted a comparative analysis of the safety signals of AEs in PI3K inhibitors using disproportionality analysis in the FDA Adverse Event Reporting System database(FAERS). Results Our study identified significant safety signals for metabolic disorders with all PI3K inhibitors. Notable safety signals for gastrointestinal disorders were observed with most PI3K inhibitors, with the exception of copanlisib. Common AEs shared among all PI3K inhibitors included colitis and dehydration. Alpelisib displayed unique AEs associated with metabolic disorders, whereas copanlisib exhibited idiosyncratic AEs linked to cardiac and vascular disorders. Stevens-Johnson syndrome emerged as a common severe adverse event (SAE) among alpelisib, copanlisib, and idelalisib, while febrile neutropenia was prevalent among copanlisib, duvelisib, and idelalisib. Intestinal perforation was solely associated with alpelisib. Conclusions The safety profiles of the five PI3K inhibitors vary concerning adverse events. These findings could guide drug selection and inform future prospective research.

Stevens-Johnson syndrome and toxic epidermal necrolysis-like eruptions in patients treated with immune checkpoint inhibitors: a systematic review.

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. 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. 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. 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. 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. 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.

A case of Mycoplasma pneumoniae‐induced rash and mucositis with recent influenza vaccination

AbstractA 33‐year‐old female presented with coryzal symptoms, facial swelling, severe haemorrhagic stomatitis, blistering oral mucositis, conjunctival injection and a sparse targetoid rash on the back and face, requiring admission to hospital. She had received the seasonal influenza vaccination 3 days prior to feeling unwell. Differential diagnosis included erythema multiforme major (EMM) secondary to the influenza vaccine or Mycoplasma pneumoniae‐induced rash and mucositis (MIRM). Oropharyngeal swabs were negative on PCR for cutaneous viruses and Mycoplasma pneumoniae (MP). A skin biopsy from a targetoid lesion on the body showed full thickness epidermal necrosis with epidermal–dermal clefting, numerous civatte bodies and a moderate perivascular infiltrate of lymphocytes and plasma cells in the papillary dermis. She was successfully treated with oral prednisolone and azithromycin. Following discharge from hospital, the paired serological testing for MP returned positive, confirming a diagnosis of MIRM. Our case highlights the difficulties in detecting MP as two diagnostic methods yielded different results, and so we advocate performing both MP PCR and serology to maximise the yield and speed of diagnosis. Secondly, our case highlights the clinical challenge in differentiating MIRM from EMM or Stevens–Johnson syndrome, particularly if there is a potential drug trigger (in our case the influenza vaccine), as all these conditions can feature a severe mucositis with often indistinguishable histological findings. Correct diagnosis of MIRM is important for appropriate and timely administration of anti‐MP antibiotic therapy to facilitate recovery and minimise complications.

Update on Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Diagnosis and Management.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the most severe cutaneous adverse reactions that are typically drug-induced in adults. Both SJS and TEN have high morbidity and mortality rates. SJS/TEN imposes clinical challenges for physicians managing patients suffering from this condition, both because it is rare and because it is a rapidly progressing systemic disease with severe cutaneous, mucosal, and systemic manifestations. Although many cases of SJS/TEN have been reported in the literature, there is no consensus regarding diagnostic criteria or treatment. Significant progress has been made in understanding its genetic predisposition and pathogenesis. This review is intended to provide physicians with a comprehensive but practical SJS/TEN roadmap to guide diagnosis and management. We review data on pathogenesis, reported precipitating factors, presentation, diagnosis, and management SJS/TEN focusing on what is new over the last 5 years.

Management of Vulvovaginal Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is an autoimmune process resulting in painful epidermal sloughing that can involve the vulva and vagina. Current guideline recommendations are based on expert opinion and may not reflect modern management of SJS/TEN in burn centers. We performed a retrospective chart review of 34 female patients treated for SJS/TEN at our burn center from 2015 to 2023. Cases frequently involved the vulva (83.3%) and vagina (56.0%), though pelvic examination often was limited. For eight patients with confirmed vulvovaginal lesions, there were no direct sequelae of SJS/TEN requiring intervention. In the modern era of SJS/TEN management in burn centers, interventions such as steroids may not be needed.

A case report of Stevens-Johnson syndrome caused by omeprazole.

Stevens-Johnson syndrome (SJS) is a rare but severe skin-mucosal reaction with a high mortality rate. It is characterized by sudden, painful blistering lesions on the skin, often accompanied by high fever and systemic toxicity. Lesions typically appear on the dorsal surfaces of the hands, feet, forearms, legs, and soles of the feet. They can also affect the conjunctiva, oral mucosa, labial mucosa, and vaginal mucosa. Patients may experience complications such as pneumonia, severe comorbidities, and liver and renal failure. A 51-year-old female patient was admitted to the hospital due to "abdominal distention and skin yellowing for 20 days." After using omeprazole, she developed a rash all over her body, and her liver function further deteriorated, ultimately leading to chronic acute liver failure. The diagnosis included fever, rash suspected to be drug-induced, chronic and acute liver failure, and decompensation of post-Hepatitis B cirrhosis. During hospitalization, suspected adverse drug reactions were discontinued, and symptomatic supportive treatment with methylprednisolone and fluid replacement was promptly provided. The patient's symptoms and follow-up showed that the rash disappeared and liver and kidney function improved significantly after treatment. We explored how chronic acute liver failure can cause immune system abnormalities and immune paralysis in patients, manifested as susceptibility to infection. This case report describes a drug-induced allergic reaction - SJS - in patients with chronic acute liver failure, as well as subsequent treatment, including hormone dosage and treatment duration. I hope this report will help enrich the relevant literature on drug-induced SJS combined with chronic and acute liver failure, laying the foundation for improving the survival rate of patients with the disease.

52907 Enhancing Prognostic Accuracy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Mortality with Machine Learning

52907 Enhancing Prognostic Accuracy for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Mortality with Machine Learning

Oral Complications Due to Medication in Stevens-Johnson Syndrome Patient with Systemic Involvement

Background: Stevens-Johnson Syndrome (SJS) is a drug-induced hypersensitivity reaction involving mucocutaneous with various trigger factors including drugs and herpes simplex virus. Objective: This case report aimed to discuss oral complications due to medication in SJS patients with systemic disease involvement. Case: A 51-year-old man was referred to the Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, at Hasan Sadikin Hospital from the dermatology and venereology department complaining of pain in the oral cavity, especially when eating and drinking two months before, with a history of phenytoin, salbutamol and theophylline therapy. Extraoral examination showed erosive lesions and tended to bleed serosanguinolenta crusts on the lips. Intraoral there were erosive lesions and white plaque on the tongue, buccal mucosa, labial mucosa, and palate, as well as dental caries and calculus. Blood examination showed low hemoglobin, hematocrit, erythrocytes, lymphocytes, monocytes, SGOT, and sodium levels, while HbA1c, random, fasting, and 2 HPP glucose levels were high. Reactive Anti-HSV-1 IgG and rheumatoid factor. KOH examination showed positive spores, hyphae, pseudohypha, and budding cells. The diagnosis was SJS-associated oral lesions with HSV-1 virus infection, oral candidiasis accompanied with diabetes mellitus. For diabetes mellitus treatment, he was referred to the internal medicine department. Case Management: The therapy was 0.9% NaCl for lip compress, acyclovir tablet, nystatin oral suspension, chlorhexidine digluconate 0,12% mouthwash, folic acid, and vitamin B12. Oral lesions were improved significantly after diabetes mellitus was treated. Conclusion: The SJS patient was susceptible to complications in the oral cavity, especially fungal and viral infections due to the received medication.

Erythema Multiforme and Epidermal Necrolysis Following COVID-19 Vaccines: A Systematic Review.

The outbreak of COVID-19 pandemic has raised urgent vaccine development to prevent viral transmission. Cutaneous adverse events such as erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been observed following COVID-19 vaccination. In this systematic review, we aimed to investigate the clinical features and outcomes of EM/SJS/TEN following COVID-19 vaccination. A comprehensive literature search was conducted in PubMed, Embase, Web of Science, and Cochrane databases up to July 3, 2022. We included studies reporting patients who developed EM, SJS, or TEN following COVID-19 vaccination. A total of 47 studies involving 90 patients with EM and 16 patients with SJS/TEN were reviewed and outlined. EM predominantly occurred after the messenger ribonucleic acid vaccines (70.4%), mostly after the first (47.5%) and second doses (42.4%), with delayed onsets ranging from 1 day to 30 days. SJS/TEN were observed following either the first (55.6%)- or second-dose (33.3%) vaccination, with onset times ranging from 6 hours to 14 weeks. Three EM cases and 1 SJS case showed recurrence upon reexposure to the same vaccines. No mortality was reported. Most patients exhibited improvement or resolution after treatment, with resolution times ranging from 6 days to 8 weeks. In conclusion, EM and epidermal necrolysis, including SJS and TEN, have emerged as potential cutaneous adverse events following COVID-19 vaccine administration. Further research is warranted to elucidate the pathogenesis and casual relationship between COVID-19 vaccines and EM/SJS/TEN.

Lamotrigine: A Safe and Effective Mood Stabilizer for Bipolar Disorder in Reproductive-Age Adults.

Lamotrigine belongs to the group of antiepileptic drugs and mood stabilizers, and its action is based on the selective blocking of voltage-deficient sodium channels. The effect of this mechanism is the stabilization of the presynaptic part of the neuronal membrane and subsequent inhibition of the secretion of the neurotransmitters glutamate and aspartate into the postsynaptic part of the neuron. Lamotrigine has been approved by the Food and Drug Administration for the maintenance treatment of adults with bipolar disorder since 1994. In the field of psychiatry, this medicine is also used off-label in the treatment of acute bipolar depression. Studies show promising effects of the use of lamotrigine in bipolar disorder type II with rapid phase change. Bipolar disorder is a common psychiatric problem that most often affects young adults. Lamotrigine is most effective in bipolar disorder in preventing depressive episodes, which dominate the clinical picture of this disease. The latest research focuses on extending its action, to include manic episodes. Lamotrigine, through an unexplained mechanism, can affect the immune system, causing Stevens-Johnson syndrome, hemophagocytic lymphohistiocytosis, and drug reaction with eosinophilia and systemic symptoms syndrome. These are rare, life-threatening adverse effects that require urgent intervention in the form of drug discontinuation and immunosuppressive treatment. Strict contraindications to the use of lamotrigine include sensitivity reactions accompanied by systemic symptoms. Phenotype testing enables screening of patients predisposed to serious hypersensitivity reactions. The aim of the article is to review the indications, contraindications, and adverse effects of lamotrigine in the treatment of bipolar disorder and depression.

Non-IgE-mediated drug-induced hypersensitivity reactions in pediatrics.

Despite their prevalence and potential severity, non-IgE-mediated drug-induced hypersensitivity reactions (DHRs) are under-researched and poorly defined, particularly in children. Presentations range from mild cutaneous reactions to severe systemic diseases, with pathophysiological mechanisms and reliable diagnostic markers not well established. The lack of validated tests often leads to permanent drug restrictions, reliance on second-line drugs, and increased costs. Focusing on recent advancements and areas needing further research, this review aims to enhance children's recognition, diagnosis, and management of non-IgE-mediated DHRs. Recent studies have enhanced the understanding of immediate and delayed non-IgE-mediated drug reactions. Key findings include the Mas-related G protein-coupled receptor X2 in mast cells and the identification of HLA alleles linked to severe cutaneous adverse reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Improved diagnostic techniques, including skin testing, show promise in identifying immediate and delayed non-IgE DHRs. Additionally, research highlights the impact of cofactors, drug metabolites, and co-infections on these DHRs and explores potential biomarkers for predicting reaction severity. Non-IgE-mediated DHRs are a significant cause of morbidity and treatment changes in pediatric patients. Recent research underscores their clinical presentations and mechanisms, paving the way for more precise diagnostic and therapeutic strategies to improve patient outcomes.

Acute and chronic ocular outcomes in SJS/TEN patients treated with oral ciclosporin vs intravenous immunoglobulin.

To evaluate differences in ocular complications of Stevens Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) patients receiving either systemic IVIG or Ciclosporin (CsA) as initial treatments. Retrospective review of consecutive patients admitted for SJS/TEN at the Singapore General Hospital (SGH) from 2011 to 2017 who received either IVIG or Ciclosporin at the onset of the disease and had ophthalmological follow-up of at least 6 months were included. Acute ocular severity of SJS/TEN was graded using the Gregory grading score; chronic ocular complications were graded using the Sotozono system. A total of 18 subjects were included for analysis, with eight in the IVIG group and 10 in the CsA group. There were no significant differences in acute Gregory severity grading between the two groups. The CsA group had a trend towards worse overall chronic Sotozono grading scores compared to the IVIG group (median [IQR]: 2 [0-3] vs. 1 [0-6.5], p = 0.27), with a higher incidence of acute severe cornea involvement (60% vs. 25%, p = 0.93) and chronic corneal and eyelid involvement in the former than the latter. SJS/TEN patients with worse acute ocular involvement were more likely to have TEN and perianal mucosal involvement (50% vs. 0, p = 0.01). Compared to those who received IVIG, SJS/TEN patients who received CsA at the acute disease stage, seemed to have worse acute corneal and chronic corneal and eyelid complications. Larger studies are needed to confirm this finding.

Prognostic significance of the Systemic Immune-Inflammation Index in Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (SJS/TEN) patients.

Inflammatory markers such as neutrophil-lymphocyte ratio (NLR) and eosinophil count are known prognostic indicators for SJS/TEN severity. This study explored the correlation of systemic immune-inflammatory index (SII), platelet-lymphocyte ratio (PLR) and NLR with SCORTEN and patient outcomes. A retrospective audit of 34 SJS/TEN patients (25 SJS, 3 SJS/TEN overlap, 6 TEN) was conducted from 2018 to 2022 revealed mean admission values of SII 1597 (standard deviation (SD) 1904.18), NLR 6.52 (SD 5.99) and PLR 201.74 (SD 135.01). Cut-off values for predicting mortality were SII 1238.25 (area under ROC (AUROC) 0.82), NLR 8.32 (AUROC 0.8) and PLR 284.66 (AUROC 0.78). Multiple logistic regression using a backward stepwise method identified SCORTEN as a significant factor associated with mortality (p=0.029) after adjusting for SII, NLR and PLR. None of the inflammatory markers significantly predicted mortality, although admission PLR may be a potential risk factor (p=0.053).