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Cureus Mar 2024The coronavirus disease 2019 (COVID-19) infection has led to accelerated development and utilization of vaccines to prevent its implications on health. One of these...
The coronavirus disease 2019 (COVID-19) infection has led to accelerated development and utilization of vaccines to prevent its implications on health. One of these vaccines is a vector-based, Oxford-AstraZeneca Vaccine (AZD1222). Frequently reported side effects are related to host-immune response. While dermatologic manifestation is peculiar in nature and denotes a serious eruption that might defer future vaccination. Herein, we present a case of a medically free 37-year-old female who developed clinical and histological evidence of pityriasis rosea (PR) after administration of a second-dose vaccination of AZD1222. The first dose of vaccination was administered as Pfizer BioNTech COVID-19 mRNA (BNT162b2) vaccine. This case is unique in nature as this patient developed AZD1222-induced PR, while some reports in the literature have linked PR to the BNT162b2 vaccine. This patient continued to receive a booster vaccination with BNT162b2 with no reportable side effects.
PubMed: 38628985
DOI: 10.7759/cureus.56310 -
PNAS Nexus Apr 2024Specific human leukocyte antigen (HLA) polymorphisms combined with certain drug administration strongly correlate with skin eruption. Abacavir hypersensitivity (AHS),...
Specific human leukocyte antigen (HLA) polymorphisms combined with certain drug administration strongly correlate with skin eruption. Abacavir hypersensitivity (AHS), which is strongly associated with HLA-B*57:01, is one of the most representative examples. Conventionally, HLA transmits immunological signals via interactions with T cell receptors on the cell surface. This study focused on HLA-mediated intracellular reactions in keratinocytes that might determine the onset of skin immunotoxicity by drug treatments. Abacavir exposure resulted in keratinocytes expressing HLA-B*57:01 exhibiting endoplasmic reticulum (ER) stress responses, such as immediate calcium release into the cytosol and enhanced HSP70 expression. In contrast, keratinocytes expressing HLA-B*57:03 (closely related to HLA-B*57:01) did not show these changes. This indicated that HLA-B*57:01 has a specific intracellular response to abacavir in keratinocytes in the absence of lymphocytes. Furthermore, abacavir exposure in HLA-B*57:01-expressing keratinocytes elevated the expression of cytokines/chemokines such as interferon-γ, interleukin-1β, and CCL27, and induced T lymphoblast migration. These effects were suppressed by ER stress relief using 4-phenylbutyrate (4-PB). HLA-B*57:01-transgenic mice also exhibited ER stress in epidermal areas following abacavir administration, and abacavir-induced skin toxicity was attenuated by the administration of 4-PB. Moreover, abacavir bound to HLA-B*57:01 within cells and its exposure led to HLA-B*57:01 protein aggregation and interaction with molecular chaperones in the ER of keratinocytes. Our results underscore the importance of HLA-mediated intracellular stress responses in understanding the onset of HLA-B*57:01-mediated AHS. We provide the possibility that the intracellular behavior of HLA is crucial for determining the onset of drug eruptions.
PubMed: 38628599
DOI: 10.1093/pnasnexus/pgae140 -
Journal of Medical Internet Research Apr 2024Early detection of adverse events and their management are crucial to improving anticancer treatment outcomes, and listening to patients' subjective opinions (patients'...
BACKGROUND
Early detection of adverse events and their management are crucial to improving anticancer treatment outcomes, and listening to patients' subjective opinions (patients' voices) can make a major contribution to improving safety management. Recent progress in deep learning technologies has enabled various new approaches for the evaluation of safety-related events based on patient-generated text data, but few studies have focused on the improvement of real-time safety monitoring for individual patients. In addition, no study has yet been performed to validate deep learning models for screening patients' narratives for clinically important adverse event signals that require medical intervention. In our previous work, novel deep learning models have been developed to detect adverse event signals for hand-foot syndrome or adverse events limiting patients' daily lives from the authored narratives of patients with cancer, aiming ultimately to use them as safety monitoring support tools for individual patients.
OBJECTIVE
This study was designed to evaluate whether our deep learning models can screen clinically important adverse event signals that require intervention by health care professionals. The applicability of our deep learning models to data on patients' concerns at pharmacies was also assessed.
METHODS
Pharmaceutical care records at community pharmacies were used for the evaluation of our deep learning models. The records followed the SOAP format, consisting of subjective (S), objective (O), assessment (A), and plan (P) columns. Because of the unique combination of patients' concerns in the S column and the professional records of the pharmacists, this was considered a suitable data for the present purpose. Our deep learning models were applied to the S records of patients with cancer, and the extracted adverse event signals were assessed in relation to medical actions and prescribed drugs.
RESULTS
From 30,784 S records of 2479 patients with at least 1 prescription of anticancer drugs, our deep learning models extracted true adverse event signals with more than 80% accuracy for both hand-foot syndrome (n=152, 91%) and adverse events limiting patients' daily lives (n=157, 80.1%). The deep learning models were also able to screen adverse event signals that require medical intervention by health care providers. The extracted adverse event signals could reflect the side effects of anticancer drugs used by the patients based on analysis of prescribed anticancer drugs. "Pain or numbness" (n=57, 36.3%), "fever" (n=46, 29.3%), and "nausea" (n=40, 25.5%) were common symptoms out of the true adverse event signals identified by the model for adverse events limiting patients' daily lives.
CONCLUSIONS
Our deep learning models were able to screen clinically important adverse event signals that require intervention for symptoms. It was also confirmed that these deep learning models could be applied to patients' subjective information recorded in pharmaceutical care records accumulated during pharmacists' daily work.
Topics: Humans; Deep Learning; Hand-Foot Syndrome; Prescriptions; Antineoplastic Agents; Neoplasms
PubMed: 38625718
DOI: 10.2196/55794 -
Malaysian Family Physician : the... 2024Buccal lichenoid lesions (BLLs) are characterised by a unique, linear whitish striation in the buccal region and can be accompanied by ulcers, plaques, erythemas,...
Buccal lichenoid lesions (BLLs) are characterised by a unique, linear whitish striation in the buccal region and can be accompanied by ulcers, plaques, erythemas, atrophies and blisters. They are distinguished from oral lichen planus (OLP) by the association of the administration of a drug or contact with a metal. Herein, we present the case of a 42-year-old woman with underlying hypertension with amlodipine-induced BLLs. She complained of a 1-month history of right buccal whitish streaks and oral ulcers 2 months after taking amlodipine. She visited a private otorhinolaryngology clinic, and a biopsy for the right buccal ulcer was conducted. The biopsy result showed features suggestive of OLP. The patient was then diagnosed with OLP. Her symptoms were persistent despite treatment, so a dental referral was made. Amlodipine was suspected as the cause of her condition and was therefore stopped. Her condition gradually resolved after amlodipine withdrawal. Hence, primary care physicians should be aware of BLLs as one of the adverse drug reactions of amlodipine so that prompt management can be taken to avoid further debilitating impacts on patients.
PubMed: 38623417
DOI: 10.51866/cr.531 -
The Israel Medical Association Journal... Apr 2024Group A Streptococcus (GAS) causes a wide spectrum of acute infections and immune-related diseases, most of which include a dermatological presentation. However,...
BACKGROUND
Group A Streptococcus (GAS) causes a wide spectrum of acute infections and immune-related diseases, most of which include a dermatological presentation. However, dermatological findings have a wide range of other possible etiologies. The diagnosis of GAS-related disease requires an indication of preceding GAS infection by direct culture or by measuring antistreptolysin O (ASLO) titer.
OBJECTIVES
To explore the correlation between ASLO positivity and dermatological diseases.
METHODS
We analyzed clinical data from all cases of patients over 18 years of age who underwent ASLO testing between the years 2016 and 2020 in the Department of Dermatology at Rambam Health Care Campus.
RESULTS
Of 152 adult patients with ASLO tests, 100 had diagnoses that were potentially related to streptococcal infection. Vasculitis and psoriasis were the most suspected diagnoses. Positive ASLO test was found in 44 (29%) patients. The diagnoses showing the highest ratio of positive ASLO were psoriasis (60%), erythema nodosum (46%), skin infections (43%), Sweet syndrome (33%), and vasculitis (15%). Psoriasis types included plaque psoriasis (8 patients), guttate psoriasis (3 patients), and palmoplantar pustulosis and erythroderma (2 patients each).
CONCLUSIONS
Although the applicability of ASLO for the spectrum of dermatological diseases remains unclear, our results enhance the practical relevance of the test. We showed a higher prevalence of positive ASLO tests in psoriasis and erythema nodosum cases and a lower prevalence in vasculitis. Notably, ASLO was positive in all psoriasis subtypes, suggesting high utility of the test for psoriasis.
Topics: Adult; Humans; Adolescent; Antistreptolysin; Dermatology; Erythema Nodosum; Psoriasis; Streptococcal Infections; Vasculitis
PubMed: 38616666
DOI: No ID Found -
Journal of Family Medicine and Primary... Feb 2024Drug-induced lichen planus is a cutaneous adverse effect that manifests as a systemic eruption of flat-topped, erythematous, or violaceous papules resembling lichen...
INTRODUCTION
Drug-induced lichen planus is a cutaneous adverse effect that manifests as a systemic eruption of flat-topped, erythematous, or violaceous papules resembling lichen planus on the trunk and extremities. Although antitubercular therapy has been linked to cutaneous hypersensitivity reactions, the literature on such cases is scarce. Here, we present a case to contribute to this field, reporting on its presentation and management, and reviewing previous case studies.
CASE REPORT
Our patient, a 63-year-old male, presented with black pigmented patches on the skin, having been diagnosed with pulmonary tuberculosis and on antitubercular therapy for the past two months. A diagnosis of ATT-induced lichen planus was made, and all ATT was stopped. The patient was treated with antihistamines, apremilast, tacrolimus, and corticosteroids, and rechallenge of each drug was performed consecutively. No new lesions appeared after rechallenge with isoniazid and rifampicin. However, ethambutol was not reintroduced due to strong suspicion, by exclusion, that it was the offending agent, whereas on rechallenge with isoniazid and rifampicin, the patient's skin lesions gradually improved with eventual resolution of hyperpigmentation.
DISCUSSION AND CONCLUSION
Lichenoid drug eruptions are characterized by type IV hypersensitivity reactions, and rechallenge is required to ensure safer treatment since the risk of disseminated and multi-drug-resistant tuberculosis increases with the cessation of antitubercular therapy.
PubMed: 38605770
DOI: 10.4103/jfmpc.jfmpc_499_23 -
The World Allergy Organization Journal Apr 2024There are limited data regarding the characteristics and management of drug hypersensitivity reactions (DHR) in hospitalized children. This study aims to determine the...
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.
PubMed: 38601275
DOI: 10.1016/j.waojou.2024.100893 -
Case Reports in Dermatological Medicine 2024Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases...
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem.
PubMed: 38596598
DOI: 10.1155/2024/9547206 -
Indian Journal of Dermatology,... Apr 2024Background The paradoxical occurrence of psoriasis triggered by Interleukin-17 (IL-17) inhibitors is notable due to its prominent symptoms and the therapeutic dilemma it...
Background The paradoxical occurrence of psoriasis triggered by Interleukin-17 (IL-17) inhibitors is notable due to its prominent symptoms and the therapeutic dilemma it presents for follow-up care. Objective To describe cases in our clinic, perform an in-depth literature review, and suggest the most probable mechanisms of action. Method We conducted a literature review on published cases of IL-17 inhibitor-induced psoriasis. Results We found 22 articles reporting 30 cases of IL-17 inhibitor-induced paradoxical psoriasis, primarily observed in patients with a previous psoriasis history. Almost 60% of cases showed a change in lesion morphology, with the plaque or pustular type being prevalent. About 73.3% of patients had to discontinue the implicated drug, leading to partial or complete symptom resolution. The mechanism behind this response seemed to involve IL-17 inhibitors downregulating Tumour Necrosis Factor alpha (TNF-α), subsequently upregulating plasmacytoid dendritic cells and triggering unopposed IFN-alpha (IFN-α) production. Limitation Data are confined to case reports and case series. Conclusion More assertive measures are recommended for treating paradoxical psoriasis induced by IL-17 inhibitors than those caused by TNF-α inhibitors. Reintroducing an IL-17 inhibitor is not advised, as patients did not show improvement.
PubMed: 38594973
DOI: 10.25259/IJDVL_719_2023 -
Allergology International : Official... Apr 2024Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly...
BACKGROUND
Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs.
METHODS
A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016-2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019-2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined.
RESULTS
The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4-8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3-63.7; P = 0.001). The in vitro BAT showed higher activation of CD63 basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE.
CONCLUSIONS
This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.
PubMed: 38594174
DOI: 10.1016/j.alit.2024.03.003