The association between HLA-B variants and amoxicillin-induced severe cutaneous adverse reactions in Chinese han population.

Background: Amoxicillin (AMX) is among the most prescribed and the best tolerated antimicrobials worldwide. However, it can occasionally trigger severe cutaneous adverse reactions (SCAR) with a significant morbidity and mortality. The genetic factors that may be relevant to AMX-induced SCAR (AMX-SCAR) remain unclear. Identification of the genetic risk factor may prevent patients from the risk of AMX exposure and resume therapy with other falsely implicated drugs. Methodology: Four patients with AMX-SCAR, 1,000 population control and 100 AMX-tolerant individuals were enrolled in this study. Both exome-wide and HLA-based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between AMX and risk HLA proteins. Results: Compared with AMX-tolerant controls, a significant association of HLA-B*15:01 with AMX-SCAR was validated [odds ratio (OR) = 22.9, 95% confidence interval (CI): 1.68-1275.67; p = 7.34 × 10-3]. Moreover, 75% carriers of HLA-B*15:01 in four patients with AMX-SCAR, and the carrier frequency of 10.7% in 1,000 control individuals and 11.0% in 100 AMX-tolerant controls, respectively. Within HLA-B protein, the S140 present in all cases and demonstrated the strongest association with AMX-SCAR [OR = 53.5, p = 5.18 × 10-4]. Molecular docking results also confirmed the interaction between AMX and S140 of the HLA-B protein, thus eliminating the false-positive results during in association analysis. Conclusion: Our findings suggest that genetic susceptibility may be involved in the development of AMX-SCAR in Han Chinese. However, whether the HLA-B variants observed in this study can be used as an effective genetic marker of AMX-induced SCAR still needs to be further explored in larger cohort studies and other ethnic populations.

Drug Reaction with Eosinophilia and Systemic Symptoms Induced by Diosmin and Hesperidin: A Case Report.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse reaction which exhibits a diverse range of presentations. We described a 48-year-old man diagnosed with acute generalized exanthematous pustulosis (AGEP)-like DRESS following the administration of diosmin and hesperidin. To our knowledge, diosmin and hesperidin-induced DRESS are exceptionally rare. This aims to raise awareness of potential severe cutaneous side effects in patients taking these agents.

Improving Clinical Practice Through Patient Registries in Allergy and Immunology.

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity (IEI), food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in IEI, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

Evaluation of the frequency and characteristics of drug hypersensitivity reactions in hospitalized children: Real life-cohort study.

Introduction: There are limited data regarding the characteristics and management of drug hypersensitivity reactions (DHR) in hospitalized children. This study aims to determine the prevalence, clinical features, and management of DHRs in pediatric inpatients. Methods: Children who had pediatric allergy consultation for suspected DHR during hospitalization in Ankara Bilkent City Hospital between August 1, 2020, and July 30, 2021, were included. Patient and reaction characteristics, culprit drugs, and management strategies were recorded. When possible, diagnostic tests (skin or provocation tests) were performed after discharge. Results: Among the 14,090 hospitalized children, 165 (72% male, median age: 106 months) underwent consultation for 192 suspected DHRs with 246 drugs. Cutaneous eruptions were the most common (94.3%). There was anaphylaxis in 40 patients and severe cutaneous adverse drug reaction in 4 patients (drug rash with eosinophilia and systemic symptoms in 3, acute generalized exanthematous pustulosis in 1). Antimicrobials were the leading cause (78.4%, n = 193/246). In 48 reactions, 60 (24%) culprit drugs could be readministered with close follow-up or desensitization (n = 12). In total, 186 suspected drugs were discontinued, and 115 were replaced with alternative drugs. After discharge, 38 provocation tests (2 positives) and 36 skin tests (1 positive prick test, 1 positive intradermal test, and 1 positive patch test) were performed. Discussion/conclusions: The incidence of suspected DHR among pediatric inpatients was approximately 1.1%. Skin symptoms were the most common manifestation. Twenty-four percent of suspected drugs could be continued during hospitalization. Patients with DHR during hospitalization should be evaluated with a drug allergy work-up unless there are contraindications to testing.

Rapid and Reliable HLA-B*59:01 Genotyping to Prevent Carbonic Anhydrase Inhibitor-Induced Severe Cutaneous Adverse Reactions.

OBJECTIVE: Carbonic anhydrase inhibitors (CAIs) are intraocular pressure-reducing medications used in ophthalmology. Human leukocyte antigen-B*59:01 (HLA-B*59:01) is strongly associated with CAI-induced severe cutaneous adverse reactions (SCARs). This study aimed to develop and validate a rapid and economical screening method for HLA-B*59:01 to prevent carbonic anhydrase inhibitor-induced SCARs. METHODS: Duplex allele-specific polymerase chain reaction (PCR) with an internal control was performed for HLA-B*59:01 genotyping. The accuracy of duplex allele-specific PCR for HLA-B*59:01 genotyping was evaluated in 200 blood samples, using sequence-based typing (SBT) as the reference method. RESULTS: In total, 50 HLA-B*59:01-positive and 150 HLA-B*59:01-negative results obtained using duplex allele-specific PCR were in complete agreement with the SBT results. CONCLUSION: Duplex allele-specific PCR is a rapid, reliable, and economical assay for screening the HLA-B*59:01 allele.

Clinical Presentation and Diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.

Severe vitamin D deficiency increases the risk of severe cutaneous adverse reactions.

Vitamin D deficiency has been reported to be associated with allergic diseases and dermatological disorders. We investigated the role of vitamin D in drug-induced non-immediate hypersensitivity reactions by measuring serum vitamin D levels in 60 patients diagnosed with non-immediate drug hypersensitivity reactions and in 60 patients who tolerated the same medication without any allergic reactions. The results showed that serum vitamin D levels were significantly lower in patients with severe cutaneous adverse reactions (SCARs) (13.56 ± 6.23 ng/mL) compared to patients with mild reactions (17.50 ± 7.49 ng/mL) and the drug-tolerant control group (17.42 ± 7.28 ng/mL), with p values of 0.031 and 0.015, respectively. The proportion of severe vitamin D deficiency (< 10 ng/mL) was much higher in SCAR patients compared to drug-tolerant subjects (36.7% vs. 11.7%, p value = 0.005). After adjusting for age, gender, region of residence, and concurrent illnesses, patients with severe vitamin D deficiency had significantly increased in-hospital mortality (odds ratio 16.04; 95% CI, 1.25-206.12, p value = 0.03). In conclusion, the risk of developing SCARs and in-hospital mortality was increased in patients with severe vitamin D deficiency. Further investigations should be conducted to elucidate the role of vitamin D in the development of SCARs.

Immune checkpoint inhibitor-induced epidermal necrolysis: A narrative review evaluating demographics, clinical features, and culprit medications.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune-related adverse events (irAEs). Severe cutaneous irAEs, including epidermal necrolysis, are rare but potentially life-threatening. There is limited understanding of the clinical features and management of ICI-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), so we aimed to analyze 95 cases of ICI-induced SJS/TEN (35 cases of SJS, 26 cases of TEN, two cases of SJS/TEN overlap, and 32 cases of unspecified) to increase knowledge of this condition among oncologists and dermatologists. We conducted a comprehensive search of PubMed for all relevant case reports published until the end of December 2022, and collected data on patient demographics, cancer type, ICI regimen, time to onset of SJS/TEN, clinical presentation, management strategies, and outcomes. PD-1 inhibitors were the most common ICIs associated with SJS/TEN (58.9%), followed by the combination of PD-1 and CTLA-4 inhibitors (11.6%), and PD-L1 inhibitors (6.3%). Lung cancer and melanoma were the most frequent malignancies treated (35.8% and 25.4%, respectively). SJS/TEN occurred most frequently within the first 4 weeks (51.7%), and corticosteroid monotherapy was the most commonly chosen systemic treatment (56.4%). The overall mortality rate of ICI-induced SJS/TEN was 30.8%. Our findings highlight the frequency and severity of ICI-induced SJS/TEN and the urgent need for predictive molecular biomarkers aimed at preventive measures and early intervention.

Overlapping Stevens-Johnson Syndrome and DRESS Syndrome Caused by Phenobarbital: A Vietnamese Case Report.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome and Stevens-Johnson Syndrome (SJS) are severe cutaneous adverse reactions to drugs. Those reactions which are rare in children can be especially severe and challenging to diagnose and manage. Herein we present a 59-month-old male who presented with a rash, fever, and multiple organ dysfunction initiation of Phenobarbital for epilepsy. Diagnosis of ovelaping SJS and DRESS syndrome had been made based on clinical manifestations accompanied with skin biopsy according to RegisSCAR diagnostic criteria. A therapy with intravenous immune globulin (IVIG), corticosteroids and supportive care was given successfully for the patient. This case underscored the significance of promptly and effectively recognizing and managing these intricate reactions.

Acute generalized exanthematous pustulosis: Analysis of cases managed in a Tunisian tertiary hospital.

Acute generalized exanthematous pustulosis (AGEP) is a severe and life-threatening cutaneous adverse reaction. Drug-induced AGEP is mainly related to antibiotics. More recently, AGEP following spider bites has been increasingly described. Treatment includes withdrawal of the offending drug and supportive care. In Tunisia, data concerning severe cutaneous adverse reactions (SCARs) in general and especially AGEP is lacking. Herein, we conducted a retrospective study to investigate the epidemiological, clinical characteristics and etiologies of AGEP referred to the Dermatology department. Our study included 32 cases of AGEP. AGEP cases occurred in overall 8.9% of all SCARs referred to the department during the same period study. The majority were females (24 women and 7 men). The median age of the patients was 33 years. A history of psoriasis was reported in 16.1% of patients. All patients presented with an extensive erythematous rash with pinhead pustules. Neutrophil hyperleukocytosis (greater than 7000/mm3) was noted in 17 patients (63% of cases). It was associated with hypereosinophilia exceeding 500 elements/mm3 in 8 cases (29.6%). Drug-induced AGEP was reported in 53% of cases. Antibiotics were implicated in the majority of cases. Delay in onset ranged from 15hours to 7 days, with an average of 2.8 days. A non-drug-induced etiology was considered if the pharmacological investigation was negative, or if a clear non-drug trigger was found. It was retained in ten cases (48.4% of all observations). Spider bites were revealed in 8 cases. AGEP represents a severe, usually drug-related skin reaction. It is classified as a type IVd reaction mediating T cell-related sterile neutrophilic inflammatory response. It typically occurs within 24-48 h of ingestion of the offending drug. Antibiotics are the most common drug family to cause AGEP. Spider bites were involved in 25.8% of cases in our study, as important as antibiotic-induced AGEP. Analysis of the particularities of AGEP according to etiology, whether drug-induced or not, revealed the presence of an initial escarotic lesion (P=0.01) and the finding of blood hypereosinophilia (P=0.014) in the non-drug AGEP group were the distinguishing features. Blood hyperesoniophilia, more frequent in the non-drug AGEP group, suggests a pathophysiology probably different from that of the drug AGEP group. Clinicians should be aware of both etiologies. Our study focuses on the importance of AGEP associated with spider bite as a potential triggering factor in Tunisia.

Severe cutaneous adverse reactions due to antibiotics therapy: a pharmacovigilance analysis of FDA adverse event reporting system events.

BACKGROUND: The aim of this study was to monitor, identify and evaluate severe cutaneous adverse reactions (SCAR) induced by antibiotics in patients. METHODS: Disproportionality algorithms were performed in data mining to screen suspected SCAR after using nine categories of antibiotics based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to December 2022. The drug information and demographic characteristics of antibiotic-associated SCAR were also investigated. RESULTS: The FAERS database received 12,212 antibiotic-associated SCAR cases. Approximately half of the SCAR patients were females, the majority of them were adults aged 18-65 years (48.35%), and 47.68% of SCAR patients required hospitalization. The highest SCAR signals RORs (95% CI) for antibiotics were: sulfonamides 23.30 (22.05-24.62), glycopeptides 21.27 (20.26-22.33), penicillins 16.00 (15.44-16.59), carbapenems 10.46 (9.57-11.44), and cephalosporins 13.27 (12.57-14.00). Cefotaxime, sulfamethoxazole/trimethoprim, cefixime, vancomycin, piperacillin, ceftriaxone, amoxicillin, and meropenem had stronger associations with the SCAR than the other antibiotics. However, sulfonamides-associated SCAR cases had the lowest fatality rate (6.23%), penicillin-associated SCAR cases had the highest hospitalization rate (54.16%), and carbapenem-associated SCAR cases seemingly resulted in the highest risk of death (19.03%). CONCLUSION: Data mining of FAERS identified 30 antibiotic-associated SCAR signals, and provided a referable evidence of the occurrence, characteristics and prognosis of antibiotic-related SCARs.

Analysis of clinical features of oxcarbazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis.

Background: Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN. Methods: Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023. Results: A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported. Conclusion: Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.

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.

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.

Cost-effectiveness analysis of HLA-B*13:01 screening for the prevention of co-trimoxazole-induced severe cutaneous adverse reactions among HIV-infected patients in Thailand.

Studies found a strong association between HLA-B*13:01 allele and co-trimoxazole-induced severe cutaneous adverse reactions (SCARs). Genetic screening before initiation of co-trimoxazole may decrease the incidence of co-trimoxazole-induced SCARs. This study aims to evaluate the cost-effectiveness of HLA-B*13:01 screening before co-trimoxazole initiation in HIV-infected patients in Thailand. A combination of a decision tree model and a Markov model was used to estimate lifetime costs and outcomes of two strategies including 1) HLA-B*13:01 screening before co-trimoxazole initiation and 2) usual practice from a societal perspective. Alternative drugs are not considered because dapsone (the second-line drug) also presents a genetic risk. Input parameters were obtained from literature, government documents, and part of the TREAT Asia HIV Observational Database (TAHOD). One-way sensitivity analyses and probabilistic analyses were performed to determine robustness of the findings. HLA-B*13:01 screening resulted in 0.0061 quality-adjusted life years (QALYs) loss with an additional cost of 370 THB ($11.84). At the cost-effectiveness threshold of 160,000 THB ($5,112.85), the probability of the genetic screening strategy being cost-effective is 9.54%. This analysis demonstrated that HLA-B*13:01 allele screening before initiation of co-trimoxazole among HIV-infected patients is unlikely to be cost-effective in Thailand. Our findings will help policymakers make an evidence-informed decision making.

Severe cutaneous adverse reactions associated with immune checkpoint inhibitors therapy and anti-VEGF combination therapy: a real-world study of the FDA adverse event reporting system.

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy combined with anti-vascular endothelial growth factor (anti-VEGF) regimens showed new hope for cancer patients and considered as future pillar of cancer therapy. However, severe cutaneous adverse reactions (SCARs) in patients with ICIs and anti-VEGF combined therapy raise a serious concern and remain thoroughly assessed in clinics. RESEARCH DESIGN AND METHODS: Data retrieved from the first quarter of 2004 to the third quarter of 2022 in FAERS database underwent disproportionality analysis and Bayesian analysis were utilized to detect and assess the SCAR signals of ICIs and ICIs and anti-VEGF combined therapy for comparison. RESULTS: In total, 854 (1.10%) and 80 (1.06%) reports on SCARs associated with ICIs and a combination of ICIs and anti-VEGF therapy, respectively, were analyzed. Most of SCARs reports were associated with the use of pembrolizumab (36.01%), nivolumab (23.97%) and a combination of ipilimumab and nivolumab (19.71%). A use of atezolizumab and bevacizumab combined therapy (60.00%) caused the most SCARs records out of ICIs and anti-VEGF combined therapies. CONCLUSIONS: Treatment with joint therapy of ICIs and anti-VEGF agents may cause severe cutaneous adverse events. It is vital to identify ICI-related SCARs early, and to manage them appropriately.

Epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the United States and factors predictive of outcome.

Background: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap syndrome are rare severe cutaneous adverse reactions associated with high mortality. Objectives: To estimate incidence and describe trends of SJS/TEN hospitalizations in the United States and to describe the clinical, demographic, and geographic characteristics of affected patients and risk factors for mortality. Methods: We utilized hospitalization data from the 2010 to 2020 National Inpatient Sample. SJS, SJS-TEN overlap syndrome, and TEN were identified by International Classification of Diseases, 9th Revision and International Classification of Diseases, 10th Revision codes and analyzed by logistic regression. Results: We identified 51,040 hospitalizations involving SJS/TEN. Amog those, 37,283 (73.0%) were for SJS only, 7818 (15.3%) were for SJS-TEN overlap syndrome, and 7160 (14.0%) were for TEN only. Overall, SJS/TEN hospitalization rates declined over time, 2010 to 2020 (P < .05). Mortality rates of the SJS group, SJS-TEN overlap syndrome group, and TEN group were 5.4%, 14.4%, and 15.3%, respectively. Increasing age, chronic kidney disease, pneumonia, sepsis, and malignant neoplasm were all significantly associated with increased odds of mortality (P < .05). Non-Hispanic White racial/ethnic identification was associated with decreased odds of mortality (P < .05). Limitations: Lack of standardization for diagnostic criteria. Conclusions: Risk factors identified in this study lay the groundwork for improvement in SJS/TEN mortality prediction scoring.

Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions are a diverse group of reactions mediated by the immune system after exposure to a drug. The Gell and Coombs classification divides immunologic DHRs into 4 major pathophysiologic categories based on immunologic mechanism. Anaphylaxis is a Type I hypersensitivity reaction that requires immediate recognition and treatment. Severe cutaneous adverse reactions (SCARs) are a group of dermatologic diseases that result from a Type IV hypersensitivity process and include drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). Other types of reactions are slow to develop and do not always require rapid treatment. Emergency physicians should have a good understanding of these various types of drug hypersensitivity reactions and how to approach the patient regarding evaluation and treatment.

Severe cutaneous adverse reactions to drugs: A real-world pharmacovigilance study using the FDA Adverse Event Reporting System database.

Background: Sound drug safety information is important to optimize patient management, but the widely recognized comprehensive landscape of culprit-drugs that cause severe cutaneous adverse reactions (SCARs) is currently lacking. Objective: The main aim of the study is to provide a comprehensive landscape of culprit-drugs for SCARs to guide clinical practice. Methods: We analyzed reports associated with SCARs in the FDA Adverse Event Reporting System database between 1 January 2004 and 31 December 2021 and compiled a list of drugs with potentially serious skin toxicity. According to this list, we summarized the reporting proportions of different drugs and drug classes and conducted disproportionality analysis for all the drugs. In addition, the risk characteristic of SCARs due to different drugs and drug classes was summarized by the positive-negative distribution based on the results of the disproportionality analysis. Results: A total of 77,789 reports in the FDA Adverse Event Reporting System database were considered SCAR-related, of which lamotrigine (6.2%) was the most reported single drug followed by acetaminophen (5.8%) and allopurinol (5.8%) and antibacterials (20.6%) was the most reported drug class followed by antiepileptics (16.7%) and antineoplastics (11.3%). A total of 1,219 drugs were reported as culprit-drugs causing SCARs in those reports, and the largest number of drugs belonged to antineoplastics. In disproportionality analysis, 776 drugs showed at least one positive pharmacovigilance signal. Drugs with the most positive signals were lamotrigine, acetaminophen, furosemide, and sulfamethoxazole/trimethoprim. Conclusion: Our study provided a real-world overview of SCARs to drugs, and the investigation of SCAR positive-negative distribution across different drugs revealed its risk characteristics, which may help optimize patient management.