Stevens-Johnson Syndrome Research Articles

Stevens-Johnson Syndrome Induced by Methotrexate, An Uncommon Adverse Drug Reaction: A Case Report

Adverse drug reactions (ADRs) can lead to severe consequences and increased mortality rates. This case report focuses on a 41-year-old woman, who developed methotrexate-induced Stevens-Johnson syndrome (SJS), emphasizing the importance of recognizing and managing such a patient. The patient exhibited recurrent vomiting, maculopapular rashes, erosions and ulcers in multiple locations, consistent with SJS. These symptoms highlight the severity of the adverse drug reaction. Treatment involved was the discontinuation of medications, oral ointments, gargles, prophylactic antibiotics, and blood transfusion. Significant improvement was observed after 15 days of treatment. This case report underscores the life-threatening nature of methotrexate-induced SJS. Early recognition, discontinuation of offending medications, and prompt intervention are crucial to mitigate harm. Raising awareness about ADRs and their management is vital for enhancing patient safety and outcomes.

Characteristics of adverse drug reactions due to nonsteroidal anti-inflammatory drugs: a cross-sectional study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for treating pain and inflammation. Spontaneous adverse drug reaction (ADR) reports represent a rich data source for the detection of unknown and rare ADRs. This cross-sectional study aimed to analyze the characteristics of ADRs due to NSAIDs in Thailand. All ADR reports of NSAIDs for systemic use from 2015 to 2019 were extracted from the national database in Thailand. Patient characteristics, drug use information, adverse event information, and source of senders in 32,857 reports were analyzed. The annual number of ADR reports due to NSAIDs decreased from 7,008 in 2015 to 5,922 in 2019. The most frequently reported drug was ibuprofen (n=12,645, 38.5%) followed by diclofenac (n=7,795, 23.7%), most patients were 40-59 years old, and the major adverse reaction was angioedema (n=7,513, 22.9%). Serious reactions were recorded in 20.7% (n=6,801) of the total ADRs. Most patients (n=20,593, 62.7%) recovered without sequelae, but there were 5,420 patients (16.5%) who could not recover and 3,109 patients (9.5%) who were recovering. Eight patients (0.02%) died of Stevens-Johnson syndrome (n=3), toxic epidermal necrolysis (n=4), and anaphylactic shock (n=1), which were possibly related to ADRs. The number of ADR reports due to NSAIDs decreased from 2015 to 2019 in Thailand. Serious ADRs and death cases accounted for 20.7% and 0.02%, respectively. Most fatal cases exhibited severe drug-induced skin reactions.

Stevens-Johnson syndrome: a case report of possible cephalosporin-induced cutaneous adverse reaction.

A severe medical condition known as Stevens-Johnson syndrome (SJS) is marked by a cutaneous and mucosal reaction from the use of specific medications. The prodromal illness is followed by severe mucocutaneous symptoms in this immune-mediated disease. We describe the clinical history of a 55-year-old Caucasian woman who was exposed to cephalosporins. In resource-constrained countries and hospitals where cutaneous biopsy is not readily available, it is not easy to diagnose Steven Johnson Syndrome. This is particularly true in countries where the incidence of infectious diseases such as scarlet fever and measles is high and the early symptoms of SJS can be mistaken for these conditions. We used the Naronjo scale to confirm the probable association of the drug with the syndrome. Physicians while writing prescriptions for their patients need to warn them of potential side effects and they should keep in mind conditions like Stevens-Johnson syndrome. This case report highlights the need for improved knowledge and understanding of SJS among healthcare practitioners in resource-limited communities where the prevalence of infectious diseases is high.

Osimertinib tolerance in a patient with Stevens Johnson syndrome during osimertinib therapy after treatment with pembrolizumab

BackgroundOsimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically.Case presentationWe present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it.ConclusionThis case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.

RETRACTED: Résultats à long terme de la kératoprothèse de Boston de type I au Canada

To evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure. Single surgeon retrospective cohort study including 85 eyes of 74 patients who underwent KPro implantation to treat severe ocular surface disease, including limbal stem cell deficiency, postinfectious keratitis, aniridia and chemical burns. Procedures were performed at the Centre hospitalier de l'Université de Montréal from October 2008 to May 2012. All patients with at least 5 years of follow-up were included in the analysis, including eyes with repeated KPro. Main outcome measures were visual acuity (VA), visual failure, defined as a sustained VA worse than the preoperative VA, postoperative complications, and device retention. Mean follow-up was 7.2±1.3 years (±SD). Mean VA was 2.1±0.7 (logarithm of minimal angle resolution) preoperatively and 1.9±1.2 at last follow-up. In total, 2.4% of patients had VA better than 20/200 preoperatively vs. 36.5% at last follow-up. Maintenance of improved postoperative VA was seen in 61.8% of eyes at 7 years. Preoperative factors associated with visual failure were known history of glaucoma (HR=2.7 [1.2 to 5.9], P=0.02) and Stevens-Johnson syndrome (HR=7.3 [2.5 to 21.4], P<0.01). Cumulative 8-year complication rates were 38.8% retroprosthetic membrane formation, 25.9% hypotony, 23.5% new onset glaucoma, 17.6% retinal detachment, 8.2% device extrusion and 5.9% endophthalmitis. The majority (91.8%) of eyes retained the device 8 years after implantation. Nearly two-thirds of patients exhibited improved VA 7 years after KPro implantation. Preoperative risk factors for visual failure were known glaucoma and Stevens-Johnson syndrome.

Stevens-Johnson syndrome: what do we know about it?

Introduction: Stevens-Johnson syndrome is characterized by hypersensitivity to the use of drugs, with adverse cutaneous reactions, such as macules, papules, etc., which may progress to more serious conditions, such as hypovolemic shock. It is considered a rare and serious mucocutaneous disease that affects both sexes and was discovered in 1922. Objective: The aim of the paper consists of a literature review on Stevens-Johnson Syndrome. Materials and Methods: For the present research, articles and case studies were selected in the Portuguese, English and Spanish languages between the years 2015 to 2023, available in the Google academic and PubMed databases. Results and Discussion: With this, it can be observed that these are skin reactions such as macules, papules, vesicles etc. The symptomatology of the presence is through fever, malaise and pruritus and can be caused by the use of drugs such as antibiotics, anti-epileptics, non-steroidal anti-inflammatory drugs and allopurinol and that their late suspension, can lead the patient to death. Conclusion: Thus, this study concludes the importance of early diagnosis, which allows for faster treatment, thus avoiding complications. Therefore, further studies on the subject are necessary.

Pharmacogenetics to prevent hypersensitivity reactions to antiepileptic drugs: is testing performed when indicated?

Extensive scientific evidence consistently demonstrates the clinical validity and utility of HLA-B*15:02 pre-screening in averting severe cutaneous adverse reactions (SCARs), namely Stevens-Johnson syndrome and toxic epidermal necrolysis, associated with carbamazepine or oxcarbazepine usage. Current practice guidelines and drug labeling actively advocate for pharmacogenetic pre-screening before initiating these antiepileptic drugs (AED), with particular emphasis on patients of Asian descent. However, there is a potential need to strengthen compliance with these recommendations. This retrospective study aimed to describe the pharmacogenetic pre-screening, documentation, and SCARs incidence for patients of Asian ancestry initiated on carbamazepine or oxcarbazepine at a large Northeastern USA healthcare system. Between 1 July 2016 and August 1, 2021, 27 patients with documented Asian heritage in the electronic health record (EHR) were included. The overall rate of HLA-B*15:02 pre-screening before carbamazepine or oxcarbazepine initiation was 4%. None who underwent pharmacogenetic pre-screening carried the associated HLA-B risk allele, and no SCARs were reported. Notably, pharmacogenetic results were not discretely entered into the EHR, and the results were only found as attached documents in the miscellaneous section of the EHR. There remains a significant opportunity for improving HLA-B*15:02 pre-screening for patients starting carbamazepine and oxcarbazepine to prevent SCARs in the USA.

Subacute cutaneous lupus erythematosus in a patient of pancreatic cancer secondary to novel albumin-bound paclitaxel chemotherapy

Paclitaxel is commonly used for the treatment of breast, ovarian, gastrointestinal, and carcinoma of the head and neck. Paclitaxel treatment is often associated with hair loss, myalgia, acral erythema, scleroderma and Stevens–Johnson syndrome, peripheral neuropathy, nausea, vomiting, bone marrow suppression, and rarely cardiac electroconductive pathway abnormalities. However, its association with cutaneous/systemic lupus erythematosus has been sparsely described. In this case report, we are discussing a case of nab-paclitaxel-induced subacute cutaneous lupus erythematosus which has been described only once in the published literature.

Genotypic and Phenotypic Characteristics of Co-Trimoxazole-Induced Cutaneous Adverse Reactions

Background: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs). Methods: The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated. Results: Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04–8.75), HIV infection (OR = 3.48, 95% CI: 1.13–10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54–15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57–22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE. Conclusions: Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Tata Laksana Terintegrasi Sindrom Stevens-Johnson (SJS) dan Nekrolisis Epidermal Toksik (NET)

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous reactions characterized by extensive epidermal necrosis and epidermal detachment. The incidence of SJS in Japan is 2.3 cases/100,000 people/per year. The mortality rate of SJS-TEN in Saudi Arabia is 1 per 10 cases (10%). SJS-TEN can be caused by drugs, idiopathic, infection, post-bone marrow transplant, immunization, radiotherapy, and genetics. The pathogenesis of SJS-TEN is suspected as a result of a cytotoxic reaction to keratinocyte cells which causes massive apoptosis. Clinical manifestation begins with prodromal symptoms followed by erythematous macular lesions and atypical target lesions that may confluence, then develop into bullous, oozing erosions with mucosal involvement. Vital sign observation is important to predict prognosis. A diagnostic procedure is necessary if another diagnosis is being considered. Management of SJS-TEN includes cessation of suspected drugs, early treatment such as fluid resuscitation, early nutrition, treatment and evaluation of eyes and skin lesions. Multiorgan involvement can occur in SJS-TEN so multidisciplinary management is needed for optimal therapy. Corticosteroids and cyclosporin A provide beneficial effects on SJS-TEN. SCORTEN is used to evaluate prognosis.

Development and Validation of a Novel Score to Predict Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: CRISTEN.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests. This study aimed to present a novel score that predicts mortality in patients with SJS/TEN in the early stages based on only clinical information. We retrospectively evaluated 382 patients with SJS/TEN in a development study. A clinical risk score for TEN (CRISTEN) was created according to the association of potential risk factors with death. We calculated the sum of these risk factors using CRISTEN, and this was validated in a multinational survey of 416 patients and was compared with previous scoring systems. The significant risk factors for death in SJS/TEN comprised 10 items, including patients' age of ≥65 years, ≥10% body surface area involvement, the use of antibiotics as culprit drugs, the use of systemic corticosteroid therapy before the onset, and mucosal damage affecting the ocular, buccal, and genital mucosa. Renal impairment, diabetes, cardiovascular disease, malignant neoplasm, and bacterial infection were included as underlying diseases. The CRISTEN model showed good discrimination (area under the curve [AUC]= 0.884) and calibration. In the validation study, the AUC was 0.827, which was statistically comparable to those of previous systems. A scoring system based on only clinical information was developed to predict mortality in SJS/TEN and was validated in an independent multinational study. CRISTEN may predict individual survival probabilities and direct the management and therapy of patients with SJS/TEN.

Stevens-Johnson syndrome secondary to massive inflammatory hyperplasia of bilateral lingual margins: a case report and literature review.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.

Cyclosporine Monotherapy in Pediatric Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: Preserving Sepsis Indicators While Promoting Recovery

Abstract Stevens–Johnson syndrome and toxic epidermal necrolysis are severe skin reactions seen commonly following exposure to drugs. The quest for the ideal drug to treat these conditions faces significant challenges. There is an absence of head-to-head, comparative, clinical, double-blinded trials comparing the various disease-modifying agents, owing to the rarity and severity of these conditions, along with ethical issues. In such a scenario, gathering data through clinical experiences can provide valuable insights for formulating future guidelines and improving the quality of care. The following case highlights the potential of cyclosporine A to preserve sepsis signs while demonstrating therapeutic efficacy, adding to the growing body of evidence in its favor.

Profile of Stevens-Johnson syndrome and toxic epidermal necrolysis patients in the inpatient hospital installation of Dr. Soetomo general hospital Surabaya from January 2019 – December 2021

Background: Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis are significant health issues due to their severe complications. Factors like age, clinical symptoms, and underlying etiology play crucial roles in patient management. Therefore, it is important to review further the background or profile of the patients. This is the basis for conducting this study. This research aims to provide an overview of patients with SJS-TEN in the Inpatient Installation of RSUD Dr. Soetomo Surabaya, aiming to aid in prevention and management. Aim: Providing an overview of the profile of patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the Inpatient Installation of Dr. RSUD. Soetomo Surabaya Methods: The study analyzed medical records of patients with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis at RSUD Dr. Soetomo Surabaya from 2019-2021, analyzing parameters such as gender, age, symptoms, etiology, comorbidities, and length of stay. Results: The study found 28 cases of SJS-TEN, with 15 males (53.6%) and 13 females (46.4%). The highest prevalence was in the age group 19-44 years old as we called adult (35.7%). Most patients had multiple comorbidities, with common clinical symptoms including palpebral edema, multiple erythematous macules, conjunctival erythema, and fever. Most patients were classified as SCORTEN 1, with 71.4% taking multiple drugs. Most patients experienced multiple complications but experienced improvement and continued treatment through outpatient care (57.1%).

Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study

Anti-SS-A antibody is a potential predictor of severe Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study

Gene expression signatures of human senescent corneal and conjunctival epithelial cells.

This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.

Self-Retained, Sutureless Amniotic Membrane Transplantation for the Management of Ocular Surface Diseases.

Amniotic membrane (AM) has anti-inflammation, anti-fibrotic, and regenerative effects. Sutureless cryopreserved AM transplantation, ProKera® (Bio-Tissue, Inc., Miami, FL, USA), is easily applied by ophthalmologists in the treatment of ocular surface diseases. This retrospective study included patients with ocular surface diseases who received ProKera® between January 2022 and May 2023. Six patients (9 eyes) with a mean age of 56.8 ± 20.8 years old (range 25-74) and a mean follow-up period of 7.8 ± 4.1 months (range 1-12) were included, including 2 of recurrent conjunctival tumors with limbal and corneal involvement (cases 1-2), 1 of pterygium with marked astigmatism (case 3) and 3 of Stevens-Johnson syndrome (SJS, cases 4-6). ProKera® was inserted after the lesion excision and deep keratectomy in cases 1-3, and no recurrence or corneal complication was noted. Cases 4-5 were discharged from the intensive care unit and presented with severe chronic SJS. Most ocular manifestations improved significantly after symblepharon release and ProKera® insertion, except for corneal conjunctivalization in 1 eye (case 5). Case 6 involved early ProKera® use at the bedside during acute SJS, resulting in complete resolution. We concluded that the adjunctive application of ProKera® can be effective for ocular surface reconstruction and provides options to intervene earlier for outpatients or patients unstable for invasive surgical intervention.

Analysis of circRNA profiles and clinical value in Stevens-Johnson syndrome and toxic epidermal necrolysis.

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.

Association between HLA alleles and beta-lactam antibiotics-related severe cutaneous adverse reactions.

Introduction: Beta-lactam antibiotics are one of the most common causes of antibiotics-related severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reactions with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Recent evidence demonstrated that the human leukocyte antigen (HLA) polymorphisms play important roles in the development of drug-related SCARs. This study aimed to extensively characterize the associations between HLA genetic polymorphisms and several phenotypes of SCARs related to beta-lactam antibiotics. Methods: Thirty-one Thai patients with beta-lactam antibiotics-related SCARs were enrolled in the study. A total of 183 unrelated native Thai subjects without any evidence of drug allergy were recruited as the control group. Genotyping of HLA class I and class II alleles was performed. Results: Six HLA alleles including HLA-A*01:01, HLA-B*50:01, HLA-C*06:02, HLA-DRB1*15:01, HLA-DQA1*03:01, and HLA-DQB1*03:02, were significantly associated with beta-lactam antibiotics-related SCARs. The highest risk of SCARs was observed in patients with the HLA-B*50:01 allele (OR = 12.6, 95% CI = 1.1-142.9, p = 0.042), followed by the HLA-DQB1*03:02 allele (OR = 5.8, 95% CI = 1.5-22.0, p = 0.012) and the HLA-C*06:02 allele (OR = 5.7, 95% CI = 1.6-19.9, p = 0.011). According to the phenotypes of SCARs related to beta-lactam antibiotics, the higher risk of SJS/TEN was observed in patients with HLA-A*03:02, HLA-B*46:02 (OR = 17.5, 95% CI = 1.5-201.6, p = 0.033), HLA-A*02:06, HLA-B*57:01 (OR = 9.5, 95% CI = 1.3-71.5, p = 0.028), HLA-DQB1*03:02 (OR = 7.5, 95% CI = 1.8-30.9, p = 0.008), or HLA-C*06:02 (OR = 4.9, 95% CI = 1.1-21.4, p = 0.008). While eight HLA alleles including HLA-A*02:05, HLA-A*02:11, HLA-B*37:01, HLA-B*38:01, HLA-B*50:01, HLA-C*06:02, HLA-C*03:09, and HLA-DRB1*15:01 were associated with AGEP, the highest risk of AGEP was observed in patients with the HLA-B*50:01 allele (OR = 60.7, 95% CI = 4.8-765.00, p = 0.005). Among the four HLA alleles associated with DRESS including HLA-C*04:06, HLA-DRB1*04:05, HLA-DRB1*11:01, and HLA-DQB1*04:01, the HLA-C*04:06 allele had the highest risk of beta-lactam antibiotics-related DRESS (OR = 60.0, 95% CI = 3.0-1202.1, p = 0.043). However, these associations did not achieve statistical significance after Bonferroni's correction. Apart from the HLA risk alleles, the HLA-A*02:07 allele appeared to be a protective factor against beta-lactam antibiotic-related SCARs (OR = 0.1, 95% CI = 0.0-0.5, p = 3.7 × 10-4, Pc = 0.012). Conclusion: This study demonstrated the candidate HLA alleles that are significantly associated with several phenotypes of beta-lactam antibiotics-related SCARs. However, whether the HLA alleles observed in this study can be used as valid genetic markers for SCARs related to beta-lactam antibiotics needs to be further explored in other ethnicities and larger cohort studies.

Stevens-Johnson syndrome and toxic epidermal necrolysis: 11-year retrospective experience in a high-complexity tertiary hospital in Milan, Italy

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced hypersensitivity reactions characterized by widespread epidermal necrosis, mucous membrane erosions, and systemic findings. We have provided our 11-year experience from a Milan, Italy tertiary hospital managing SJS/TEN, evaluating the clinical and histopathologic features plus the impact on mortality. We retrospectively analyzed 28 patients diagnosed with SJS/TEN based on the clinical and histopathologic findings, according to the classification criteria of multiple studies. We assessed the dermatographics, comorbidities, drug history, lesion characteristics, clinical findings, treatments, blood tests, and outcomes. Severity scores (SCORTEN, Re-SCORTEN, ABCD-10) were used for treatment evaluation and mortality prediction. Data were statistically analyzed, and significant factors associated with mortality were identified. We found that among the 28 patients, 89.2% had comorbidities, mainly cardiovascular diseases, and 21.4% had autoimmune disorders. All patients had received systemic therapy (46.6% monotherapy, 53.6% combination therapy), with systemic steroids (71.4%) and intravenous immunoglobulins (67.8%) being common treatments. There were complications, including systemic infections (67.9%) and septic shock (10.7%). The overall mortality rate was 17.8%. The statistical analysis indicated that malignancy, a high ABCD-10 score, and a high neutrophil-to-lymphocyte ratio were significantly associated with mortality. The extent of affected body surface area did not correlate significantly with mortality. This study provides insights into SJS/TEN management, revealing factors influencing mortality in a high-complexity tertiary hospital setting.