Cutaneous Adverse Reactions Research Articles

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

Differential Effects of HLA-B∗15:11 and HLA-A∗31:01 on Carbamazepine-Induced Cutaneous Adverse Reactions

HLA-B*15:11 and HLA-A*31:01 would be used as biomarkers in predicting the risk of CBZ-induced cADRs in the populations where allele frequency of HLA-B*15:02 is extremely rare.

Acute Generalized Exanthematous Pustulosis: An Unusual Case due to Spider Bite

Acute generalized exanthematous pustulosis is an infrequent but severe pattern of cutaneous adverse reaction. It is characterized by the sudden appearance of sterile pustules on edematous-erythematous skin, which is mostly caused by the consumption of medications. However, it may also be associated with viral infections, toxins, or food allergens, although this is rare. We reported a case of AGEP in a 33-year-old male shortly after a spider bite, a rare cause of AGEP. It was improved by oral corticosteroid treatment after seven days.

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.

Adverse cutaneous reaction to hydroxychloroquine in a patient with anti-SAE-1-positive dermatomyositis and a history of diffuse large B-cell lymphoma

This case report details the cutaneous findings of a patient with a history of diffuse B-cell lymphoma and SAE-1–positive dermatomyositis who developed an adverse cutaneous reaction after initiation of treatment with hydroxychloroquine. This adds to the sparse literature available detailing the correlation between anti–SAE-1 autoantibodies in dermatomyositis and the unique adverse cutaneous reactions in patients taking hydroxychloroquine. Additionally, our patient developed dermatomyositis years after a diagnosis of lymphoma. This report highlights the utility of the myositis-specific antibody panel to guide diagnosis and management, as well as the potential for developing dermatomyositis years after a lymphoma diagnosis.

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.

Acute generalized exanthematous pustulosis induced by isoniazid and pyrazinamide in a child

An 8-year-old female with cervical lymph node tuberculosis, received rifampicin, isoniazid, pyrazinamide, and ethambutol. Two weeks later, she developed a fever and a generalized erythematous rash covered with pustules. Acute generalized exanthematous pustulosis diagnosis was confirmed by a skin biopsy. Antitubercular therapy was discontinued. Drug causality was found using oral provocation tests and patch tests. Cutaneous adverse drug reactions to first-line antituberculosis drugs are common. However, acute generalized exanthematous pustulosis is rare. It is a severe form of cutaneous drug reaction, primarily associated with beta-lactam antibiotics, and clinically characterized by non-follicular pustules on erythematous skin.

Clinical management of anti-tuberculosis related cutaneous adverse drug reactions based on reintroduction.

The prevalence of anti-tuberculosis related adverse cutaneous reactions is around 1%. The most frequent reaction is exanthema, then urticaria and DRESS. Sequential drug reintroduction helped identifying rapidly the main culprit drug with good outcome. Rifampicin and pyrazinamide were the two most culprit drugs. DRESS was attributable to ethambutol and rifampicin.

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.

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.

Farmacodermia em gato após uso de múltiplas medicações para tratamento de afecções sistêmicas

Drug eruption, also known as cutaneous adverse drug reaction, is a rare disease that is difficult to diagnose, requiring a combination of history evaluation, physical assessment, and histopathological examination. Clinically, it presents with variable signs, from mild urticaria to epidermal necrosis. Treatment consists of discontinuing the causative or similar medication; lesion management; and, sometimes, implementing systemic immunosuppressive treatments. The prognosis is generally good, except when there is systemic involvement or extensive skin necrosis. This study aims to describe the lesions, diagnosis, and evolution of a young cat presenting with drug eruption following the use of multiple medications for the treatment of systemic conditions. The patient underwent skin biopsy after showing progression of alopecic and localized lesions, which resulted in a suggestive diagnosis of superficial pustular drug eruption. Previous drug treatments were interrupted, but due to the lack of improvement in the lesion pattern, we chose to re-administer chlorambucil at a dose of 2 mg/cat every 48 h for therapeutic purposes. Up to the present time, the patient has been undergoing treatment and lesion management, with healthy-looking scar tissue and almost complete resolution of the skin lesions.

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.

Cutaneous adverse effects of antiepileptic drugs

Antiepileptic drugs (AED) are widely used in therapy. They are mainly indicated in the treatment of epilepsy and some psychiatric pathologies as well as for their analgesic action. Their cutaneous adverse effects (CAE) are common, often mild but sometimes serious. The aim of this work was to study the epidemiological and clinical features of CAE occurring in adults and elderly patients (aged over 20 years-old) and to identify the most implicated AED. We conducted a descriptive retrospective study over a period of five years from January 2017 to December 2022 about CAE of AED in adults and elderly patients notified to The National Center Chalbi Belkahia of Pharmacovigilance (Tunis,Tunisia). All cases were analyzed according to the updates French methods of imputability. We collected 71 cases of patients aged over 20 years old who presented CAE to AED. The age ranged from 20 to 79 years (mean age=44.8 years). The sex ratio F/M was 0.7. AED were indicated for neurological pathology in 70.5% of cases, for psychiatric pathology in 15.9% of cases and for their analgesic action in 12.9% of cases. Epilepsy was the first indication (51.1% of cases). The most notified CAE in our study were drug reaction with eosinophilia and systemic symptoms (DRESS syndrome; 34% of cases), maculopapular exanthema (MPE; 26% of cases), erythematous rash (8% of cases) and photosensitivity in 5% of cases. Severe cutaneous adverse reactions were accounted for 37% of all CAE. The most implicated AED were carbamazepine (52%), phenobarbital (24%) and lamotrigine (18%). However, further study with a larger number of patients and in collaboration with prescribing physicians are needed to better clarify features of CAE associated with AED intake and specify the risk factors, specific to our Tunisian population.

Case series of a varied spectrum of drug reactions

Adverse drug reactions are an important cause of iatrogenic morbidity and mortality in the medical field across the globe. As newer drugs emerge into the market, newer adverse reactions are being reported. More than half of these new drugs have serious side effects. A distinction between numerous patterns of drug-induced reactions is potentially of critical importance because a delay even of several hours may make the difference between survival and death. Herein, we report five cases of severe cutaneous adverse drug reactions admitted at our dermatology ward. Key words: Adverse drug reaction, Iatrogenic morbidity

Dermatological Adverse Effects of Covid-19 Vaccine among Healthcare Workers: Findings from a Tertiary Care Hospital in Northern India

Objectives: The objective of this study was to identify the cutaneous manifestations that developed after covid-19 vaccination, with Covaxin and Covishield, in healthcare workers (HCW) and to identify any associated factors. Materials and Methods: A cross-sectional study was conducted over 3 months using an online and offline questionnaire that was circulated among the HCW working at a tertiary care hospital in Delhi. All the vaccinated HCWs who gave consent (n = 676) (n = number of participants) were included in the study. Data were summarised in an excel sheet and then analysed using SPSS, version 25. Results: Out of the 676 vaccine recipients, a higher number of participants were vaccinated with Covishield compared to Covaxin. Only 14 (2.0%) subjects developed new adverse dermatological manifestations following either vaccination. A higher incidence of adverse reaction was observed with Covaxin than with Covishield, but the difference was not significant. A significantly higher number of vaccinated paramedical workers developed new dermatological manifestations in the study period [P-value (probability value)] (P = 0.018). Conclusion: Our study demonstrated a low rate of cutaneous adverse reactions following vaccination with either Covaxin or Covishield. Further studies are hence needed to corroborate our findings.

P07 Pityriasis amiantacea: a unique presentation of psoriasis associated with tumour necrosis factor-α inhibitor therapy

Abstract Introduction Pityriasis amiantacea (PA) is a rare but distinctive scalp condition. It is characterised by thick, silvery scales that bind together causing matting of multiple hair shafts. This can ultimately result in temporary or permanent hair loss. PA is thought to be a reaction pattern rather than a specific diagnosis and common associated conditions include: scalp psoriasis, seborrhoeic dermatitis, tinea capitis and atopic dermatitis. We report a case of PA presenting in a patient with longstanding rheumatoid arthritis (RA), associated with tumour necrosis factor-α inhibitor (anti-TNF-α) therapy. Case description A 42-year-old was reviewed at her routine rheumatology follow up appointment. She has a 15-year history of seropositive, erosive RA managed with monthly golimumab injections for the last eight years. Prior to this she had been on etanercept for four years, but this lost efficacy. Unfortunately, she had poor disease control on methotrexate, leflunomide and sulphasalazine. She developed a sore area on her scalp nine months previously with accompanying itch. This then spread into an extensive confluent area of redness, associated with soreness, scale, matting onto hair and hair loss. She had been treated unsuccessfully with multiple antibiotic courses, including flucloxacillin, doxycycline and clarithromycin, oral fexofenadine, topical diprosalic and ketoconazole shampoo. The pruritic skin lesions continued to progress and even spread to behind the ears. This had been managed by her general practitioner (GP) as otitis externa. The patient was otherwise well with no joint pains, fever, weight loss or other systemic features. On examination, thickened, hyperkeratotic scaling plaques were seen with clumped hair shafts and underlying erythema of the entire scalp. There were no skin lesions over the rest of the body and nail changes were absent. Swab culture from the scalp was negative for fungal infection but Staphylococcus aureus and Psuedomonas aeruginosa were identified. Dermatology consult was sought, and she was diagnosed with extensive impetiginized pityriasis amiantacea associated with otitis externa. This was thought to be secondary to her anti-TNF-α therapy. Initial management was with scalp oils to soften the scales, Betnovate scalp ointment and a course of antibiotics. However, the mainstay of treatment was stopping the golimumab. Within one month of these interventions she made a dramatic improvement. Discussion The pathogenesis of PA is yet to be definitively established; however, it has been thought that PA may be a manifestation of an underlying inflammatory skin disease. Most commonly, PA is associated with psoriasis and seborrheic dermatitis. Drug induced cases have also been described. There are case reports of PA occurring in patients treated with valproic acid, vemurafenib and minoxidil. The skin symptoms seen in PA are likely a reaction of hair-bearing scalp to various inflammatory and microbial insults. Moreover, a study undertaken in Egypt found that over 96% of patients with PA had Staphylococcus isolates found in skin swabs taken from the affected scalp. Both S. aureus and S.epidermidis were identified; this could suggest incidental colonisation or that these bacteria play a part in development of PA. Multiple studies have looked at distinguishing microbial biofilms and their structure and physical properties. Resilient biological scaffolding of microbial biofilms, rich in polysaccharides, proteins, lipids, and nucleic acids, is triggered by the bacteria and develops on the scalp and hair shafts. As this continues it promotes accumulation of adherent scale and the hair shafts are increasingly bound together and matted to the scalp. TNF-a is an inflammatory cytokine produced by macrophages during acute inflammation. It causes a range of signalling events within cells, leading to necrosis or apoptosis, which contributes to the pathogenesis of many chronic inflammatory diseases, like psoriasis. However, in some cases TNF-a inhibition can paradoxically lead to new psoriasis or worsening of existing psoriasis. This has been observed with the three major anti-TNF-a agents (infliximab, etanercept and adalimumab). Often it is seen in patients receiving treatment for rheumatoid arthritis or inflammatory bowel disease. On average, cutaneous adverse effects are seen approximately 17 months after starting anti-TNF-a therapy. The most frequently seen presentations are of plaque psoriasis and palmoplantar pustulosis. Key learning points Inhibition of TNF-a causes increased production of interferon-a by dendritic cells, which has been associated with induction of psoriasis. Interleukin-1 (IL-1) has also been implicated in the development of psoriasis. Furthermore, TNF-a can activate apoptosis of potentially autoreactive T-cells. Blockade of this action could lead to T-cell mediated tissue and psoriatic pathology. Anti-TNF-a induced PA is a rare adverse reaction that usually requires drug discontinuation. The exact pathogenetic mechanism is unclear but an imbalance of the cytokine environment has been theorised. Our patient highlights the need to stay vigilant for cutaneous adverse reactions and the evolving diverse spectrum of psoriasiform conditions that can be seen secondary to anti-TNF-a therapy.

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.

Higher Odds of Adverse Cutaneous Reactions in Patients With Dermatomyositis Treated With Hydroxychloroquine Compared With Methotrexate.

Hydroxychloroquine (HCQ) use for the treatment of dermatomyositis (DM) has been associated with adverse cutaneous reactions. We applied a new user, active comparator, retrospective design to assess differences in adverse cutaneous reactions or hospitalizations between HCQ and methotrexate (MTX) use among patients with DM. We used a national network of data from insurance registries (TriNetX), enrolling patients with two International Classification of Diseases (ICD) codes for DM separated by 6 months or more who had a prescription for either (but not both) HCQ or MTX on or after DM diagnosis. Outcomes were adverse cutaneous reactions (ICD codes) or hospital admission (Current Procedural Terminology (CPT) codes) within 4 months from the prescription dispense date. Logistic regression was used to produce adjusted odds ratios (aORs) and 95% confidence intervals (CIs) comparing outcomes in the HCQ group (n=1364) and the MTX group (n=1400), adjusted for age at first DM diagnosis, year of birth, sex, and time from DM diagnosis to first prescription. Overall, we found no significant difference in odds of hospitalization in those taking HCQ (aOR 1.05; 95% CI: 0.79-1.39) compared with those on MTX. Patients with DM on HCQ had 30% higher odds of adverse cutaneous reaction diagnosis compared with patients on MTX (aOR 1.30; 95% CI: 1.02-1.59). Age at DM diagnosis was an effect modifier of this association, with higher odds of adverse cutaneous reaction among patients taking HCQ who were younger at diagnosis. Compared with MTX use, HCQ use, especially in younger patients, may result in higher odds of adverse cutaneous reactions.

Chronic Spontaneous Urticaria Following mRNA COVID-19 Booster Vaccination at a Military Academy.

Several adverse cutaneous reactions have been reported in the literature after SARS-CoV-2 vaccination with emerging reports on chronic spontaneous urticaria (CSU). However, there is little literature of chronic urticaria after COVID-19 boosters in a military population and the impact on operational readiness. We present a retrospective case series of CSU following Moderna COVID-19 booster vaccinations at the US Naval Academy (USNA). Demographics, clinical features, and impact on readiness were evaluated. Forty-nine students from the USNA were evaluated for urticaria after their third COVID-19 booster vaccination. Seventeen individuals were diagnosed with CSU. The median age was 20 years and predominantly male; the median time interval between vaccination and the onset of urticaria was 11 days. Out of 13 referred to Allergy, 7 patients had CU index performed and 2 were positive. Four patients received a second booster vaccination subsequently and did not have any exacerbation of symptoms. Symptoms were controlled with antihistamines, and none required immunomodulator or immunosuppressive therapies. All students were able to complete their commissioning, and none were referred for a medical board. In this series, USNA students who developed CSU after the mRNA COVID-19 Moderna booster vaccine did not have limitations from commissioning, duty status, or issues with subsequent COVID-19 vaccinations.

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.