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Current Opinion in Allergy and Clinical... Aug 2023Recent studies have been clarifying the pathogenesis and early diagnostic markers of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally,... (Review)
Review
PURPOSE OF REVIEW
Recent studies have been clarifying the pathogenesis and early diagnostic markers of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally, the efficacy of tumor necrosis factor alpha inhibitors is attracting attention. This review provides) recent evidence for the diagnosis and management of SJS/TEN.
RECENT FINDINGS
Risk factors for the development of SJS/TEN have been identified, particularly the association between HLA and the onset of SJS/TEN with specific drugs, which has been intensively studied. Research on the pathogenesis of keratinocyte cell death in SJS/TEN has also progressed, revealing the involvement of necroptosis, an inflammatory cell death, in addition to apoptosis. Diagnostic biomarkers associated with these studies have also been identified.
SUMMARY
The pathogenesis of SJS/TEN remains unclear and effective therapeutic agents have not yet been established. As the involvement of innate immunity, such as monocytes and neutrophils, in addition to T cells, has become clear, a more complex pathogenesis is predicted. Further elucidation of the pathogenesis of SJS/TEN is expected to lead to the development of new diagnostic and therapeutic agents.
Topics: Humans; Stevens-Johnson Syndrome; Immunologic Factors
PubMed: 37284785
DOI: 10.1097/ACI.0000000000000914 -
International Journal of Molecular... Jul 2023In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant... (Review)
Review
In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Acute Generalized Exanthematous Pustulosis; Drug Hypersensitivity Syndrome; Eosinophilia
PubMed: 37511017
DOI: 10.3390/ijms241411257 -
Danish Medical Journal Aug 2023About 10% of hospital inpatients are labelled with penicillin allergy in their electronic medical record (EMR). However, allergy is confirmed in less than 10% of these...
INTRODUCTION
About 10% of hospital inpatients are labelled with penicillin allergy in their electronic medical record (EMR). However, allergy is confirmed in less than 10% of these records. Consequently, 90% of patients are treated with broad-spectrum antibiotics, contributing to antimicrobial resistance. We aimed to explore experiences and practices of healthcare professionals that may explain incorrect labelling of penicillin allergy in Denmark and elucidate any consequences hereof.
METHODS
An electronic survey was distributed to physicians and nurses in six hospital units in Copenhagen and via social media. The survey was active from 19 March to 1 May 2020. Data were assessed using descriptive statistics and by thematic analysis.
RESULTS
The response rate was 44.6%. The survey had 369 participants; 152 physicians and 217 nurses. Half of the physicians and one in every five nurses had experienced problems treating patients with a penicillin allergy label. Physicians reported limited trust in allergy labels, and labelling practices varied. The risk that patients may be truly allergic was the main reason for not removing labels (72%), and a precautionary principle was identified related to penicillin allergy labelling.
CONCLUSIONS
The penicillin allergy label is an independent factor of medication errors. Solutions to enhance patient safety may include education of physicians in allergy labelling, decision support, standardisation of the allergy registration in the various EMR systems used, and ideally also a national drug allergy register, which is accessible from all sectors.
FUNDING
None.
TRIAL REGISTRATION
Not relevant.
Topics: Humans; Drug Hypersensitivity; Hypersensitivity; Anti-Bacterial Agents; Attitude of Health Personnel; Penicillins
PubMed: 37622646
DOI: No ID Found -
The Journal of Allergy and Clinical... Jan 2024Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences.
BACKGROUND
Diagnosing drug-induced allergy, especially nonimmediate phenotypes, is challenging. Incorrect classifications have unwanted consequences.
OBJECTIVE
We sought to evaluate the diagnostic utility of IFN-γ ELISpot and clinical parameters in predicting drug-induced nonimmediate hypersensitivity using machine learning.
METHODS
The study recruited 393 patients. A positive patch test or drug provocation test (DPT) was used to define positive drug hypersensitivity. Various clinical factors were considered in developing random forest (RF) and logistic regression (LR) models. Performances were compared against the IFN-γ ELISpot-only model.
RESULTS
Among the 102 patients who had 164 DPTs, most patients had severe cutaneous adverse reactions (35/102, 34.3%) and maculopapular exanthems (33/102, 32.4%). Common suspected drugs were antituberculosis drugs (46/164, 28.1%) and β-lactams (42/164, 25.6%). Mean (SD) age of patients with DPT was 52.7 (20.8) years. IFN-γ ELISpot, fixed drug eruption, Naranjo categories, and nonsteroidal anti-inflammatory drugs were the most important features in all developed models. The RF and LR models had higher discriminating abilities. An IFN-γ ELISpot cutoff value of 16.0 spot-forming cells/10 PBMCs achieved 94.8% specificity and 57.1% sensitivity. Depending on clinical needs, optimal cutoff values for RF and LR models can be chosen to achieve either high specificity (0.41 for 96.1% specificity and 0.52 for 97.4% specificity, respectively) or high sensitivity (0.26 for 78.6% sensitivity and 0.37 for 71.4% sensitivity, respectively).
CONCLUSIONS
IFN-γ ELISpot assay was valuable in identifying culprit drugs, whether used individually or incorporated in a prediction model. Performances of RF and LR models were comparable. Additional test datasets with DPT would be helpful to validate the model further.
Topics: Humans; Middle Aged; Drug Hypersensitivity; beta-Lactams; Immunologic Tests; Enzyme-Linked Immunospot Assay; Patch Tests
PubMed: 37678574
DOI: 10.1016/j.jaci.2023.08.026 -
Allergy Mar 2024Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for... (Review)
Review
Drug allergy (DA) remains a complex and unaddressed problem worldwide that often deprives patients of optimal medication choices and places them at risk for life-threatening reactions. Underdiagnosis and overdiagnosis are common and due to the lack of standardized definitions and biomarkers. The true burden of DA is unknown, and recent efforts in data gathering through electronic medical records are starting to provide emerging patterns around the world. Ten percent of the general population engaged in health care claim to have a DA, and the most common label is penicillin allergy. Up to 20% of emergency room visits for anaphylaxis are due to DA and 15%-20% of hospitalized patients report DA. It is estimated that DA will increase based on the availability and use of new and targeted antibiotics, vaccines, chemotherapies, biologicals, and small molecules, which are aimed at improving patient's options and quality of life. Global and regional variations in the prevalence of diseases such as human immunodeficiency virus and mycobacterial diseases, and the drugs used to treat these infections have an impact on DA. The aim of this review is to provide an update on the global impact of DA by presenting emerging data on drug epidemiology in adult and pediatric populations.
Topics: Adult; Child; Humans; Quality of Life; Drug Hypersensitivity; Penicillins; Anti-Bacterial Agents; Anaphylaxis
PubMed: 38084822
DOI: 10.1111/all.15970 -
International Journal of Dermatology Dec 2023Chikungunya is a viral disease transmitted by female Aedes mosquitoes that has been increasingly reported in many parts of the world across the geographical borders. In... (Review)
Review
Chikungunya is a viral disease transmitted by female Aedes mosquitoes that has been increasingly reported in many parts of the world across the geographical borders. In addition to fever and joint pain, mucocutaneous manifestations of chikungunya have been reported in 40-75% of infected patients. Dermatological manifestations of chikungunya are often under-recognized and misdiagnosed as clinicians are not sensitized or educated regarding these. The early-onset cutaneous manifestations of chikungunya fever, occurring within 1 month of the fever, include maculopapular rashes, vesiculobullous eruptions, Steven-Johnson syndrome/toxic epidermal necrolysis-like eruptions, flagellate lesions, scrotal dermatitis, oro-genital ulcers, and exacerbation of preexisting dermatoses like psoriasis. Hyperpigmentation, lichenoid eruptions, diffuse hair fall, and exacerbation of acne usually occur as a late manifestation. Diagnosis of these mucocutaneous manifestations can be challenging as they often resemble other common dermatoses. This review article elaborates on various mucocutaneous manifestations of chikungunya fever, based on literature review and authors' clinical experience.
Topics: Humans; Female; Chikungunya Fever; Drug Eruptions; Stevens-Johnson Syndrome; Psoriasis; Fever
PubMed: 37781980
DOI: 10.1111/ijd.16853 -
Current Opinion in Allergy and Clinical... Aug 2024Drug allergy is responsible for a huge burden on public healthcare systems, representing in some instances a threat for patient's life. Diagnosis is complex due to the... (Review)
Review
PURPOSE OF REVIEW
Drug allergy is responsible for a huge burden on public healthcare systems, representing in some instances a threat for patient's life. Diagnosis is complex due to the heterogeneity of clinical phenotypes and mechanisms involved, the limitations of in vitro tests, and the associated risk to in vivo tests. Predictive models, including those using recent advances in artificial intelligence, may circumvent these drawbacks, leading to an appropriate classification of patients and improving their management in clinical settings.
RECENT FINDINGS
Scores and predictive models to assess drug allergy development, including patient risk stratification, are scarce and usually apply logistic regression analysis. Over recent years, different methods encompassed under the general umbrella of artificial intelligence, including machine and deep learning, and artificial neural networks, are emerging as powerful tools to provide reliable and optimal models for clinical diagnosis, prediction, and precision medicine in different types of drug allergy.
SUMMARY
This review provides general concepts and current evidence supporting the potential utility of predictive models and artificial intelligence branches in drug allergy diagnosis.
Topics: Humans; Drug Hypersensitivity; Artificial Intelligence; Precision Medicine; Neural Networks, Computer; Deep Learning
PubMed: 38814733
DOI: 10.1097/ACI.0000000000001002 -
JAMA Network Open May 2024β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug...
IMPORTANCE
β-lactam (BL) allergies are the most common drug allergy worldwide, but most are reported in error. BL allergies are also well-established risk factors for adverse drug events and antibiotic-resistant infections during inpatient health care encounters, but the understanding of the long-term outcomes of patients with BL allergies remains limited.
OBJECTIVE
To evaluate the long-term clinical outcomes of patients with BL allergies.
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal retrospective cohort study was conducted at a single regional health care system in western Pennsylvania. Electronic health records were analyzed for patients who had an index encounter with a diagnosis of sepsis, pneumonia, or urinary tract infection between 2007 and 2008. Patients were followed-up until death or the end of 2018. Data analysis was performed from January 2022 to January 2024.
EXPOSURE
The presence of any BL class antibiotic in the allergy section of a patient's electronic health record, evaluated at the earliest occurring observed health care encounter.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause mortality, derived from the Social Security Death Index. Secondary outcomes were defined using laboratory and microbiology results and included infection with methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, or vancomycin-resistant Enterococcus (VRE) and severity and occurrence of acute kidney injury (AKI). Generalized estimating equations with a patient-level panel variable and time exposure offset were used to evaluate the odds of occurrence of each outcome between allergy groups.
RESULTS
A total of 20 092 patients (mean [SD] age, 62.9 [19.7] years; 12 231 female [60.9%]), of whom 4211 (21.0%) had BL documented allergy and 15 881 (79.0%) did not, met the inclusion criteria. A total of 3513 patients (17.5%) were Black, 15 358 (76.4%) were White, and 1221 (6.0%) were another race. Using generalized estimating equations, documented BL allergies were not significantly associated with the odds of mortality (odds ratio [OR], 1.02; 95% CI, 0.96-1.09). BL allergies were associated with increased odds of MRSA infection (OR, 1.44; 95% CI, 1.36-1.53), VRE infection (OR, 1.18; 95% CI, 1.05-1.32), and the pooled rate of the 3 evaluated antibiotic-resistant infections (OR, 1.33; 95% CI, 1.30-1.36) but were not associated with C difficile infection (OR, 1.04; 95% CI, 0.94-1.16), stage 2 and 3 AKI (OR, 1.02; 95% CI, 0.96-1.10), or stage 3 AKI (OR, 1.06; 95% CI, 0.98-1.14).
CONCLUSIONS AND RELEVANCE
Documented BL allergies were not associated with the long-term odds of mortality but were associated with antibiotic-resistant infections. Health systems should emphasize accurate allergy documentation and reduce unnecessary BL avoidance.
Topics: Humans; Drug Hypersensitivity; Female; Male; beta-Lactams; Retrospective Studies; Middle Aged; Aged; Anti-Bacterial Agents; Longitudinal Studies; Pennsylvania; Adult; Urinary Tract Infections; Risk Factors; Electronic Health Records
PubMed: 38758551
DOI: 10.1001/jamanetworkopen.2024.12313 -
Allergologia Et Immunopathologia 2023Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to...
BACKGROUND
Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting.
METHODS
We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines.
RESULTS
Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs.
CONCLUSIONS
While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.
Topics: Humans; Adult; Retrospective Studies; Single-Blind Method; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Angioedema; Urticaria
PubMed: 37695234
DOI: 10.15586/aei.v51i5.946 -
The Journal of Allergy and Clinical... Oct 2023An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug...
An accurate diagnosis of IgE-mediated allergies is necessary to inform risk management for severe allergic reactions including anaphylaxis for food, venom, and drug allergies. The most widely available laboratory test for allergy is serum-specific IgE testing, which is routinely used for food allergy and insect sting allergy. Testing for specific IgE is limited by high sensitivity and low specificity, resulting in concern regarding overdiagnosis. Testing of allergen components has led to improved diagnosis for some food and venom allergens. Additional options for laboratory tests, such as epitope analysis, basophil activation, and mast cell activation, are being investigated for their potential to optimize diagnosis and provide predictors for reaction severity and treatment response. In contrast, laboratory testing for drug allergy is more limited because to date, there are no well-validated commercial assays in the United States. Furthermore, it is important to diagnose delayed reactions to medications, because these also significantly affect decision-making regarding therapeutic options for infectious disorders. Reliable tests for both immediate and delayed drug hypersensitivity are much needed, because drug allergy labels can significantly limit treatment options for patients. Research in this area is emerging.
Topics: Humans; Immunoglobulin E; Allergens; Anaphylaxis; Drug Hypersensitivity; Wasp Venoms
PubMed: 37343922
DOI: 10.1016/j.jaip.2023.06.021