-
International Journal of Molecular... Jul 2017Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate... (Review)
Review
Drug provocation test (DPT) is the controlled administration of a drug to diagnose immune- or non-immune-mediated drug hypersensitivity and the last step for accurate recognition of drug hypersensitivity reactions when the previous diagnostic evaluations are negative or unavailable. A DPT is performed only if other conventional tests fail to yield conclusive results. In each clinical presentation, "to provoke or not to provoke" a patient should be decided after careful assessment of the risk-benefit ratio. Well-defined benefits of DPT include confirmative exclusion of diagnoses of drug hypersensitivity and provision of safe alternatives. However, disadvantages such as safety, difficulty in interpretations of results, lack of objective biomarkers, risks of resensitization, efficiency in daily practice, and lack of standardized protocols, are poorly debated. This review summarizes the current published research concerning DPT, with particular emphasis on the advantages and disadvantages of DPT in an evidence-based manner.
Topics: Anaphylaxis; Bronchial Provocation Tests; Cross Reactions; Disease Management; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Prevalence; Reproducibility of Results
PubMed: 28677662
DOI: 10.3390/ijms18071437 -
Allergology International : Official... Jul 2021Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the... (Review)
Review
Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns. Current analyses provided by the Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of mRNA-1273 and BNT162b2 vaccines administered, respectively. Although rather low, such rates could have importance due to the uncommon fact that a large majority of the world population will be subjected to vaccination with the aforementioned vaccines in the following months and vaccination will most likely be necessary every season as for influenza vaccines. Health regulators have advised that any subject with a previous history of allergy to drugs or any component of the vaccines should not be vaccinated, however, certain misunderstanding exists since allergy to specific excipients in drugs and vaccines are in occasions misdiagnosed due to an absence of suspicion to specific excipients as allergenic triggers or due to inaccurate labeling or nomenclature. In this review, we provide an updated revision of the most current data regarding the anaphylactic reactions described for BNT162b2 vaccine, mRNA-1273 vaccine, and AZD1222 vaccine. We extensively describe the different excipients in the vaccines with the potential to elicit systemic allergic reactions such as polyethylene glycol (PEG), polysorbates, tromethamine/trometamol, and others and the possible immunological mechanisms involved.
Topics: 2019-nCoV Vaccine mRNA-1273; Anaphylaxis; Animals; BNT162 Vaccine; COVID-19 Vaccines; ChAdOx1 nCoV-19; Drug Compounding; Drug Hypersensitivity; Excipients; Humans; Patient Safety; Risk Assessment; Risk Factors; Vaccination
PubMed: 33962863
DOI: 10.1016/j.alit.2021.04.003 -
Journal of Investigational Allergology... 2020The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since... (Review)
Review
The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since it was first reported in Wuhan, China in December 2019. Its severe clinical manifestations, which often necessitate admission to intensive care units, and high mortality rate represent a therapeutic challenge for the medical community. To date, no drugs have been approved for its treatment, and various therapeutic options are being assayed to address the pathophysiological processes underlying the clinical manifestations experienced by patients. New and old drugs administered as monotherapy or in combination to immunologically compromised patients may favor the development of adverse drug reactions, including drug hypersensitivity reactions, which must be identified and managed accordingly. Given the lack of herd immunity and the high rate of viral contagion, new cases are expected to emerge in the coming months. Thus, the probability of more adverse reactions or even new clinical manifestations may increase in parallel. Allergists must receive updated information on these treatments, as well as on the management of possible drug hypersensitivity reactions.
Topics: Antiviral Agents; COVID-19; Cytokines; Diagnosis, Differential; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunologic Factors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32700681
DOI: 10.18176/jiaci.0588 -
Acta Medica Portuguesa Oct 2018Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms... (Review)
Review
Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.
Topics: Drug Hypersensitivity; Humans; Immunogenetic Phenomena
PubMed: 30387427
DOI: 10.20344/amp.10092 -
British Journal of Clinical Pharmacology Sep 2017Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on... (Review)
Review
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system, and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programmes for their prevention. In this review, genetic associations of off-target drug-induced ADRs that have a clinical phenotype suggestive of an immunologically mediated process and their mechanisms are highlighted. A significant proportion of these reactions lack immunological memory and current data are informative for these ADRs with regard to disease pathophysiology, therapeutic targets and biomarkers which may identify patients at greatest risk. Although many serious delayed immune-mediated (IM)-ADRs show strong human leukocyte antigen associations, only a small subset have successfully been implemented in screening programmes. More recently, other factors, such as drug metabolism, have been shown to contribute to the risk of the IM-ADR. In the future, pharmacogenomic targets and an understanding of how they interact with drugs to cause ADRs will be applied to drug design and preclinical testing, and this will allow selection of optimal therapy to improve patient safety.
Topics: Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Humans
PubMed: 28345177
DOI: 10.1111/bcp.13294 -
Allergy May 2021Our understanding of IgE-mediated drug allergy relies on the hapten concept, which is well established in inducing adaptive reactions of the immune system to small... (Review)
Review
Our understanding of IgE-mediated drug allergy relies on the hapten concept, which is well established in inducing adaptive reactions of the immune system to small molecules like drugs. The role of hapten-carrier adducts in re-challenge reactions leading to mast cell degranulation and anaphylaxis is unclear. Based on clinical observations, the speed of adduct formation, skin and in vitro tests to inert drug molecules, a different explanation of IgE-mediated reactions to drugs is proposed: These are (a) A natural role of reduced mast cell (MC) reactivity in developing IgE-mediated reactions to drugs. This MC unresponsiveness is antigen-specific and covers the serum drug concentrations, but allows reactivity to locally higher concentrations. (b) Some non-covalent drug-protein complexes rely on rather affine bindings and have a similar appearance as covalent hapten-protein adducts. Such drug-protein complexes represent so-called "fake antigens," as they are unable to induce immunity, but may react with and cross-link preformed drug-specific IgE. As they are formed very rapidly and in high concentrations, they may cause fulminant MC degranulation and anaphylaxis. (c) The generation of covalent hapten-protein adducts requires hours, either because the formation of covalent bonds requires time or because first a metabolic step for forming a reactive metabolite is required. This slow process of stable adduct formation has the advantage that it may give time to desensitize mast cells, even in already sensitized individuals. The consequences of this new interpretation of IgE-mediated reactions to drugs are potentially wide-reaching for IgE-mediated drug allergy but also allergy in general.
Topics: Anaphylaxis; Animals; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Humans; Immunoglobulin E; Mast Cells; Pharmaceutical Preparations
PubMed: 32780486
DOI: 10.1111/all.14554 -
International Archives of Allergy and... 2020Drug hypersensitivity is one of the most frequent causes of anaphylaxis, particularly in adults and in hospitalized patients. Drug-induced anaphylaxis (DIA) is also... (Review)
Review
Drug hypersensitivity is one of the most frequent causes of anaphylaxis, particularly in adults and in hospitalized patients. Drug-induced anaphylaxis (DIA) is also associated with more severe outcomes than other anaphylaxis triggers, and drugs are responsible for the majority of deaths due to anaphylaxis. We here review the current knowledge on the incidence, prevalence, drugs involved, mortality, and mortality risk factors for DIA. The incidence of both anaphylaxis and DIA seems to be increasing worldwide. Antibiotics and analgesics are the most frequently reported triggers of DIA. However, the importance of other drug groups should be taken into account, especially in particular settings (e.g., peri-operative and oncology). The identification of risk factors, geographical variables, and drugs associated with higher risk for DIA may improve the outcomes of this entity.
Topics: Anaphylaxis; Drug Hypersensitivity; Humans; Incidence; Prevalence
PubMed: 32396909
DOI: 10.1159/000507445 -
International Journal of... 2011The most common agents that are responsible for intraoperative anaphylaxis are muscle relaxants. In fact, neuromuscular blocking agents (NMBAs) contribute to 50-70... (Review)
Review
The most common agents that are responsible for intraoperative anaphylaxis are muscle relaxants. In fact, neuromuscular blocking agents (NMBAs) contribute to 50-70 percent of allergic reactions during anaesthesia. The main mechanism of hypersensitivity reactions to NMBAs is represented by acute type I allergic reactions and the most severe form is anaphylaxis. The rate of non IgE mediated immediate hypersensitivity reactions usually varies between 20 percent and 35 percent of the reported cases in most large series. In a recent report, non allergic suspected reactions to NMBAs occurred with almost the same frequency as did those with an allergic component. Although the precise mechanisms of these reactions remain difficult to ascertain, they usually result from direct non specific mast cell and basophil activation. After diagnostic procedures, regardless of the specific IgE results, NMBAs are contraindicated if the skin tests were positive. In view of the constantly evolving anesthesiologic practices, and of the complexity of allergy investigation, an active policy to identify patients at risk and to provide any necessary support to anaesthetists and allergologists should be promoted. The high frequency of IgE anaphylactic reactions and the feasibility of skin tests in children justify systematic allergy testing whenever hypersensitivity reaction occurs during general anaesthesia.
Topics: Anesthesia; Drug Hypersensitivity; Humans; Muscle Relaxants, Central; Perioperative Period; Risk Factors
PubMed: 22014924
DOI: 10.1177/03946320110240s306 -
International Journal of Occupational... Nov 2023On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as...
OBJECTIVES
On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests.
MATERIAL AND METHODS
The authors included 113 children, aged 4-18 years, referred to Pediatrics and Allergy Clinic in Łódź, Poland, due to incidence of adverse reaction during treatment. Medical history regarding allergies to drugs was taken in accordance to the form developed by the United States Food and Drug Administration Adverse Event Reporting System. Skin prick tests, intradermal test and drug provocation test were performed in all patients.
RESULTS
In all 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to β-lactams, nonsteroid anti-inflammatory drugs, local anesthetics in 19 patients (16.8%). Previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash.
CONCLUSIONS
Drug allergy is a difficult problem in the practice of a doctor and is difficult to diagnose, especially in the pediatric population. It seems that too often isolated symptoms reported during infection or disease are taken as a symptom of drug allergy, and not as a symptom resulting from the course of the disease. Int J Occup Med Environ Health. 2023;36(5):632-42.
Topics: Child; Humans; Drug Hypersensitivity; Hypersensitivity; Skin Tests; beta-Lactams; Risk Factors; Anti-Bacterial Agents
PubMed: 37750429
DOI: 10.13075/ijomeh.1896.02227 -
International Journal of... 2011Perioperative allergic reactions manifest in various ways. The majority of systemic reactions occur during anesthesia within minutes of intravenous induction; however,... (Review)
Review
Perioperative allergic reactions manifest in various ways. The majority of systemic reactions occur during anesthesia within minutes of intravenous induction; however, agents which are administered via other routes may cause reactions after more than 15 minutes. Anaphylaxis during anesthesia may present in many different ways and the signs and symptoms, which do not vary from those of anaphylactic reactions in general, may be masked by hypovolemia, light, deep anesthesia or extensive regional blockade. Recommendations for treatment are based on available evidence in the literature. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline and fluid therapy as first-line treatment. Increased focus on this subject will hopefully lead to prompt diagnosis and rapid, correct treatment.
Topics: Anesthesia; Child; Drug Hypersensitivity; Epinephrine; Humans; Hypersensitivity; Perioperative Care; Vasoconstrictor Agents
PubMed: 22014932
DOI: 10.1177/03946320110240s314