Cutaneous Adverse Reactions Research Articles

Prevalence, Pathophysiology, and Treatment of Urticaria post-COVID-19 Vaccination: A Systematic Review

Background: Vaccination for COVID-19 has been intensively developed since the end of 2020. Its use must also obtain an Emergency Use Authorization (EUA) permit. Some of the vaccines have been used including Sinovac, Astra Zeneca, Moderna, Pfizer, Johnson & Johnson, and Sinopharm. In fact, there are many effects that have developed after the COVID-19 vaccination administration like local reactions, systemic reactions, and other reactions. In addition, one of them is urticaria. However, the existing literature has focused poorly on urticaria caused by COVID-19 vaccines. Aims: This research explores the prevalence, pathophysiology, and treatment of urticaria post-COVID-19 vaccination. Methods: This study conducted a systematic review based on the guideline which is Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched Scopus, ProQuest, Ebsco, and Google Scholar databases from 2020 until 2022 for identifying the data regarding urticaria post-COVID-19 vaccination. In a nutshell, 9 studies were included in the systematic review. Results: Only 28% of urticarial rashes incident among all cutaneous adverse reactions after post-COVID-19, it was higher among females and people aged 45-49 years old, and people with allergy histories. The most frequent reaction is urticarial following the COVID-19 vaccine administration. This concerns hypersensitivity reaction related to Immunoglobulin E (IgE) mediated, Immunoglobulin G (IgG), and sensitizing excipients in COVID-19 vaccines. Conclusion: This systematic review raises the concern of hypersensitivity reaction that related to IgE-mediated, IgG, and sensitizing excipients in COVID-19 vaccines. Urticaria is the most frequent reaction after the COVID-19 vaccine administration. Attention to medical history and immunology/allergy consultation might be advantageous to assess the risk of allergy and the guidance of the vaccine. Received: 9 May 2023; Revised: 8 June 2023; Accepted: 18 July 2023

Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients" International Study.

The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. Seventy-nine patients (median age: 62.3 years; range 39-83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes.

Halo Nevi After Covid-19 Vaccination: Molecular Mimicry Attributed Cutaneous Side-Effect?

Covid-19 vaccination is a crucial component of the public health response to reduce the spread of Covid-19. Although well-tolerated, Covid-19 vaccination is associated with several cutaneous adverse reactions. Here, we document a case of a young man who developed numerous halo nevi at sites of pre-existing nevi following Covid-19 vaccination. Our patient is a 21-year-old male who presented to clinic after noticing a recent change in his moles. Three months after receiving the Johnson & Johnson (J&J) Covid-19 vaccine, the patient reported that he developed a ring of “vitiligo” surrounding each of his existing moles. He also received the Moderna Covid-19 booster 8 months after receiving the J&J vaccine and contracted Covid-19 two months later, with no additional change in his moles. The patient was otherwise well with no past medical or family medical history of skin cancer. On examination, the patient was found to have numerous halo nevi that had developed at sites of pre-existing nevi and were distributed over his face, neck, trunk, and extremities. Examination of his scalp revealed patches of white hair, underneath which were additional halo nevi. The development of vitiligo in the setting of Covid-19 vaccination is thought to be related to the activation of autoimmunity. Autoimmunity secondary to Covid-19 vaccination may be the cause of this patient’s halo nevi, given the patient’s age and absence of any systemic symptoms.

Adverse cutaneous reactions associated with MEK inhibitor therapy in a pediatric population

Adverse cutaneous reactions associated with MEK inhibitor therapy in a pediatric population

The pharmacogenomics of carbamazepine-induced cutaneous adverse drug reaction in the South of Vietnam.

Background: The relationship between HLA-B*15:02 and Severe Cutaneous Adverse Reactions was rigorously examined in Japanese, Han Chinese, Thais, and Caucasians. However, the number of studies about this topic in Vietnamese population is still limited and mostly focuses on the North of Vietnam. Objective: This study aims to clarify the genetic culprit of SCARs in Vietnamese population, particularly in the South of Vietnam, and to validate our result by a meta-analysis about this topic in Vietnamese. Method: A retrospective case-control study with 37 patients treated with carbamazepine monotherapy. Statistical calculation and meta-analysis were performed by R software. Result: HLA-B*15:02 increases the risk of SJS 12.5 times higher in CBZ-treated patients (p-value = 0.017). However, this allele has no impact on MCARs (Mild Cutaneous Adverse Reactions) of CBZ. The number needed to test and the number needed to genotype is two and nine patients respectively. Conclusion: This study recommends more investigations about the cost-effectiveness of this test to accelerate the protection of Southern Vietnamese from SCARs.

An association study of HLA with levofloxacin-induced severe cutaneous adverse drug reactions in Han Chinese

Levofloxacin-induced severe cutaneous adverse drug reactions (LEV-SCARs) remain unexplored. An association study of human leukocyte antigen (HLA) alleles with LEV-SCARs among 12 patients, 806 healthy subjects, and 100 levofloxacin-tolerant individuals was performed. The carrier frequencies of HLA-B∗13:01 (odds ratio [OR]: 4.50; 95% confidence interval [CI]: 1.15-17.65; p= 0.043), HLA-B∗13:02 (OR: 6.14; 95% CI: 1.73-21.76; p= 0.0072), and serotype B13 (OR: 17.73; 95% CI: 3.61-86.95; p= 4.85×10-5) in patients with LEV-SCARs were significantly higher than those of levofloxacin-tolerant individuals. Molecular docking analysis suggested that levofloxacin formed more stable binding models with HLA-B∗13:01 and HLA-B∗13:02 than with non-risk HLA-B∗46:01. Mass spectrometry revealed that nonapeptides bound to HLA-B∗13:02 shifted at several positions after exposure to levofloxacin. Prospective screening for serotype B13 (sensitivity: 83%, specificity: 78%) and alternative drug treatment for carriers may significantly decrease the incidence of LEV-SCARs.

Integrating real-world data in cost-effectiveness analysis of universal HLA-B*15:02 screening in Malaysia.

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

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

Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap syndrome are rare severe cutaneous adverse reactions associated with high mortality. 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. 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. 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). Lack of standardization for diagnostic criteria. Risk factors identified in this study lay the groundwork for improvement in SJS/TEN mortality prediction scoring.

Carbamazepine-Induced Severe Cutaneous Adverse Drug Reactions: A 21-Year Comparison Between Children and Adults in Malaysia.

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

Cutaneous adverse reactions to antiepileptic drugs: 17 cases at the Dermatology Department of the Arrazi Hospital in Marrakech

Cutaneous adverse reactions to antiepileptic drugs: 17 cases at the Dermatology Department of the Arrazi Hospital in Marrakech

Evaluation of Cutaneous Adverse Drug Reactions Reported in a Teaching Hospital of Coastal Andhra

Adverse drug reactions (ADR) can be manifested in different forms, among these cutaneous adverse drug reactions (CADRs) are the commonest. They have been steadily gaining importance and constitute a major proportion of all ADRs. As available data on CADRs is very less, more research is required to have reliable data, hence the current study was undertaken. This prospective study was carried out to evaluate the age and gender distribution, presenting complaints, spectrum of CADRs, causative drugs, causality, severity, and outcomes in patients with or suspected CADRs attending the department of Dermatology of Konaseema Institute of Medical Sciences &amp; Research Foundation Hospital between January 2014 and June 2015. In cooperation with the Dermatologist, patients’ reactions were analyzed based on morphology, and laboratory investigations. Causality was assessed as per the World Health Organization- Uppsala Monitoring Centre (WHO-UMC)causality assessment scale. Modified Hartwig and Siegel Scale was used for the severity assessment of reactions. CADRs occurred most commonly in the 31-40 years age group (32%) with no sign of the difference in both sexes. The most common complaint of CADRs by the patients was skin rash (42%) anddiagnoses were Erythematous drug eruption (ERDE) and Fixed drug eruption (FDE) (28%). The commonest causative drug categories were antimicrobials (52%) and Non-Steroidal Anti-inflammatory Drugs (NSAIDs) (24%).Among antimicrobials, ciprofloxacin, and in NSAIDs, diclofenac were the commonest causative drugs. In causality, majority of the cases were under possible category(42%). Most of the reactions were mild (46%), and moderate (46%) in severity. The majority of the cases showed good recovery without any mortality or disability. The limitations of this study were the relatively small sample size, inability to confirm the particular causative drug in majority of the patients. Future research should focus on the genetic factors concerning to CADRs and molecular-level evaluation should be done for a better understanding of the pathophysiology of various ADRs.

Advances in understanding of the pathogenesis and therapeutic implications of drug reaction with eosinophilia and systemic symptoms: an updated review.

Drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome (DRESS/DIHS) is one type of severe cutaneous adverse reaction (SCAR). It is featured by fever, widespread skin lesions, protracted clinical course, internal organ involvement, and possibly long-term autoimmune sequelae. The presence of high-risk human leukocyte antigen (HLA) alleles, hypersensitivity reaction after culprit drug ingestion, and human herpesvirus reactivation may all contribute to its complex clinical manifestations. Some recent studies focusing on the roles of involved cytokines/chemokines and T cells co-signaling pathways in DRESS/DIHS were conducted. In addition, some predictors of disease severity and prognosis were also reported. In this review, we provided an update on the current understanding of the pathogenesis, potential biomarkers, and the relevant therapeutic rationales of DRESS/DIHS.

BI24 Cutaneous pseudolymphoma secondary to pembrolizumab

Abstract A 35-year-old man presented with a 7-week history of itchy, nontender, indurated erythematous plaques and nodules on his forehead and upper back, with no discriminatory clinical features. He was systemically well. Three months previously, he had completed a 12-month course of adjuvant pembrolizumab for stage IIIC melanoma. The primary melanoma had been excised from his left cheek, with involvement of left parotid and supraclavicular lymph nodes, treated with clearance via superficial parotidectomy and left neck dissection. Clinical and imaging surveillance revealed no evidence of melanoma recurrence. Incisional biopsies of the lesions on his back and forehead both demonstrated a superficial and deep dermal perivascular and periadnexal infiltrate of small- and medium-sized lymphoid cells. There was no epidermotropism and B- and T-cell clonality studies were negative. Morphological appearance and immunophenotype favoured a CD4+-reactive lymphoid process in keeping with cutaneous pseudolymphoma (CPL), secondary to pembrolizumab. The conspicuous forehead lesion was unresponsive to clobetasol propionate under occlusion. A single course of intralesional triamcinolone acetonide 10 mg mL–1 resulted in significant improvement within days, with subsequent complete resolution. The lesion on the back resolved spontaneously. Drug-induced CPL describes an adverse cutaneous drug reaction mimicking B- or T-cell lymphomas clinically and/or histologically. It has been described with anticonvulsants, antidepressants and biologic agents, often with resolution on cessation of the responsible drug (Etesami I, Kalantari Y, Tavakolpour S et al. Drug-induced cutaneous pseudolymphoma: a systematic review of the literature. Australas J Dermatol 2023; 64:41–9). It has been proposed that the drugs affect immune surveillance, leading to an abnormal cutaneous lymphocyte response. A case report (Ayoubi N, Haque A, Vera N et al. Ipilimumab/nivolumab-induced pseudolymphoma in a patient with malignant melanoma. J Cutan Pathol 2020; 47:390–3) has described drug-induced CPL secondary to ipilimumab and nivolumab in a 38-year-old man presenting with erythematous plaques on the hands and face, similar to the presentation of our patient, which responded to prednisolone. As with the other adverse effects of immunotherapy, it is likely that CPL in this cohort is due to an iatrogenic immune dysregulation leading to T-cell overactivity. We present the first reported case of CPL secondary to pembrolizumab and highlight the successful use of intralesional steroid as a treatment option. It is important to recognize CPL as an adverse cutaneous effect of immunotherapy and be aware that it can present after completing treatment due to an ongoing immune response.

Risk-conferring HLA variants in an epilepsy cohort: benefits of multifaceted use of whole genome sequencing in clinical practice

BackgroundWhole genome sequencing is increasingly used in healthcare, particularly for diagnostics. However, its clinically multifaceted potential for individually customised diagnostic and therapeutic care remains largely unexploited. We used existing whole...

CD12 Citalopram-induced drug reaction with eosinophilia and systemic reaction confirmed by patch testing

Abstract A 46-year-old man was referred for investigation of an acute widespread rash and fever that started 4 weeks after commencing citalopram. Clinical and histological features were consistent with drug reaction with eosinophilia and systemic reaction (DRESS). He was not on any other medication, had no known allergies and had not previously taken a selective serotonin reuptake inhibitor (SSRI). Six months after resolution, he was patch tested to the extended British Baseline Series and citalopram (crushed tablet in 50% petrolatum). Readings on days 2 (D2) and 4 (D4) were positive for citalopram (D2 ++ and D4 +++). To investigate possible crossreactivity, he was subsequently patch tested to fluoxetine, paroxetine and sertraline (crushed tablets in 50% petrolatum), which showed a positive reaction to paroxetine [D2 (–) and D4 (+)]. Patch tests to citalopram and paroxetine were negative with no irritancy in a normal volunteer. SSRIs are extensively and increasingly used for depression and other mental health problems; 45 000 000 UK prescriptions were issued in the last financial year. Despite such widespread use, cutaneous adverse drug reactions (CADRs) appear to be rare. From 1998 to 2022, the Medicines and Healthcare products Regulatory Agency recorded 16 586 adverse reactions to citalopram, of which only 1077 (6.5%) were cutaneous. Various rashes have been reported to arise from SSRI treatment, ranging from maculopapular eruptions to toxic epidermolysis necrolysis/Stevens–Johnson syndrome. There have been isolated reports of DRESS from fluoxetine, sertraline and escitalopram (the S-enantiomer of citalopram). To our knowledge, this is the first reported case of citalopram-induced DRESS. The sensitivity and specificity of patch tests in the diagnosis of delayed CADR varies according to the drug and rash. We have found case reports of positive patch tests to sertraline and paroxetine following maculopapular exanthems. Our findings highlight a diagnostic role for patch tests with an extemporaneous preparation in SSRI-induced DRESS. SSRIs have diverse chemical structures, and we speculate that patch tests may be of benefit in identifying a safer alternative should further SSRI treatment be needed.

Aripiprazole-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Case Study.

The use of medications in management of disease is an integral part of treatment to patients in both the inpatient and outpatient setting; however, these medications often have risk of adverse effects associated with their benefits of use. Adverse cutaneous reactions are one of the most frequent types of adverse drug reactions. Two major phenotypes of cutaneous adverse drug reactions are toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS). Aripiprazole is an antipsychotic drug with a well-documented profile of adverse effects for physicians to be aware of; however, SJS/TEN is not known to be included in that profile. The authors encountered a case of aripiprazole-induced SJS/TEN and used the electronic medical records from this encounter to summarize this novel case in detail. Existing literature was reviewed using public databases for evaluation of similar cases. We present a case of SJS/TEN induced by aripiprazole use for bipolar disorder, type 1, which is not an adverse effect of the drug that has been documented in the literature. We include patient history, hospital course, images, and treatment of disease throughout admission as well as a thorough discussion of the topic. We present a case of an adverse drug reaction that has not previously been documented in the literature with the goal of informing readers of the potential for this life-threatening atypical effect and the severity of disease it may cause.

Drug-Induced Hypersensitivity Reaction and Re-Introduction of Anti-Tubercular Drugs (ATT): A Case Report and Review of Literature

Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis and is the leading cause of death by a single infectious agent overall. According to the WHO Global TB Report, India contributes to 26% of the global burden of TB. Currently, a four-drug regimen comprising Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol is approved for the treatment of drug-sensitive TB. The management of cutaneous adverse drug reactions to anti-tubercular drugs is akin to a double-edged sword, with discontinuation of ATT increasing the risk of developing disseminated and drug-resistant tuberculosis, and continuation leading to persistence or exacerbation of the adverse drug reaction (ADR). The risk of developing an ADR to anti-tubercular therapy (ATT) varies from 8 to 85% in various studies [10]. The prevalence of rashes associated with ATT shows that the maculopapular rash (42.5%) is the most frequently observed type, followed by urticarial, lichenoid, DRESS, AGEP, and exfoliative dermatitis (17). The drugs associated with Cutaneous ADRs from the lowest to the highest risk are Isoniazid, Rifampicin, Pyrazinamide, Ethionamide, Cycloserine, Ethambutol, Para-aminosalicylic acid (PAS), and Streptomycin (25). We present a case and approach to the re-introduction of first-line anti-tubercular drugs after hypersensitivity with fixed-dose combinations.&#x0D; Keywords: Tuberculosis, Mycobacterium tuberculosis, adverse drug reaction, anti-tubercular therapy

Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01

Allopurinol, widely used in gout treatment, is the most common cause of severe cutaneous adverse drug reactions. The risk of developing such life-threatening reactions is increased particularly for HLA-B*58:01 positive individuals. However the mechanism of action between allopurinol and HLA remains unknown. We demonstrate here that a Lamin A/C peptide KAGQVVTI which is unable to bind HLA-B*58:01 on its own, is enabled to form a stable peptide-HLA complex only in the presence of allopurinol. Crystal structure analysis reveal that allopurinol non-covalently facilitated KAGQVVTI to adopt an unusual binding conformation, whereby the C-terminal isoleucine does not engage as a PΩ that typically fit deeply in the binding F-pocket. A similar observation, though to a lesser degree was seen with oxypurinol. Presentation of unconventional peptides by HLA-B*58:01 aided by allopurinol contributes to our fundamental understanding of drug-HLA interactions. The binding of peptides from endogenously available proteins such as self-protein lamin A/C and viral protein EBNA3B suggest that aberrant loading of unconventional peptides in the presence of allopurinol or oxypurinol may be able to trigger anti-self reactions that can lead to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

A real-world pharmacovigilance study of severe cutaneous adverse reactions associated with antiepileptic drug combination therapy: data mining of FDA adverse event reporting system

ABSTRACT Background The aim of this study was to evaluate the association between antiepileptic drug combination regimens and severe cutaneous adverse reactions (SCAR). Research design and methods We gathered cases indication with epilepsy based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2021. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results Out of 128,262 reports were collected from the FAERS database, 104,278 cases were in the antiepileptic drugs group, and 23,984 cases were in the other primary suspected drugs group. A total of 20 combination regimens were associated with increased association of SCAR, top five of them were topiramate-phenytoin (ROR 57.62, 95% CI 30.93–107.34), lamotrigine-valproic acid (ROR 52.93, 95% CI 47.09–59.49), diazepam-phenobarbital (ROR 39.61, 95% CI 20.01–78.38), zonisamide-valproic acid (ROR 36.57, 95% CI 19.16–69.80), lamotrigine-diazepam (ROR 35.22, 95% CI 15.70–79.00). Conclusion The antiepileptic agent combinations may increase the incidence of SCAR and should be carefully evaluated in clinical practice. It is recommended to choose the combination regimens which have lower SCAR reporting rate for patients.

Cutaneous Adverse Events After COVID-19 Vaccination.

The morphology and timing of cutaneous reactions after Coronavirus disease (COVID-19) vaccines have been well described; however, data on the rates and risk factors are limited. Therefore, this study aimed to measure the incidence of cutaneous adverse reactions (CARs) after COVID-19 vaccination in Thailand, describe the rash characteristics according to the doses or types of vaccine, and assess the risk factors for developing CARs. This was a prospective observational study of adults who received COVID-19 vaccination and provided informed consent. Cutaneous diagnoses were made by expert dermatologists with supporting skin biopsies, as needed. Data were analyzed using descriptive statistics and logistic regression to examine the independent risk of developing a CAR. Between July 2021 and January 2022, 7505 participants were vaccinated. Vaccine-related CARs occurred in 92 patients with an overall risk of 1.2%. CARs occurred after the first (n=41), second (n=23), third (n=27), and fourth (n=1) doses. Among the 92, 75 (81%) developed CARs within 7 days and 61 (66%) resolved within 7 days. Urticaria, injection site reaction, and a delayed (≥ 3 days post vaccine) local reaction were the three most common CARs occurring in 59 cases (64%). In total, 51 (55%) patients received only symptomatic and supportive treatment. Underlying urticaria and psoriasis were the independent factors for developing a CAR: adjusted odd rations of 15.63 (6.02-40.57, p < 0.001) and 5.36 (1.57-18.36, p = 0.007), respectively. A total of 6/34 (17%) and 4/31 (12%) patients developed urticarial and psoriasis flare post vaccine. Our study found superficial perivascular and intraepidermal eosinophil infiltration, which may be unusual pathological findings in vaccine-induced pemphigus foliaceous. CARs after COVID-19 vaccination had a low incidence and were mostly mild in severity and transient in nature. Underlying urticaria and psoriasis were risk factors for CAR development.