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Journal of Investigational Allergology... 2020The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions... (Review)
Review
The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.
Topics: Disease Management; Disease Susceptibility; Drug Compounding; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Hypersensitivity, Delayed; Pharmaceutical Preparations
PubMed: 32376520
DOI: 10.18176/jiaci.0562 -
Swiss Medical Weekly Feb 2023Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate... (Review)
Review
BACKGROUND
Corticosteroids, which are anti-inflammatory and immunosuppressive agents used for the treatment of various diseases including allergic disorders, can induce immediate and delayed hypersensitivity reactions. Although these reactions are not common, due to the wide usage of corticosteroid medications, corticosteroid hypersensitivity reactions are clinically important.
OBJECTIVE
In this review, we summarise the prevalence, pathogenetic mechanism, clinical manifestations, risk factors, diagnostic and therapeutic approach for corticosteroid-induced hypersensitivity reactions.
METHODS
An integrative review of the literature was conducted using PubMed searches (mainly large cohort-based studies) regarding the different aspects of corticosteroid hypersensitivity.
RESULTS
Hypersensitivity reactions to corticosteroids can be immediate or delayed and can follow all modes of corticosteroid administration. Prick and intradermal skin tests are useful diagnostic tools for immediate hypersensitivity reactions, patch tests are useful for delayed hypersensitivity reactions. According to the diagnostic tests an alternative (safe) corticosteroid agent should be administered.
CONCLUSION
Physicians of all medical disciplines should be aware that corticosteroids can cause (paradoxically) immediate or delayed allergic hypersensitivity reactions. The diagnosis of such allergic reactions is challenging since it is often difficult to distinguish between hypersensitivity reactions and deterioration of the basic inflammatory disease (e.g., worsening of asthma or dermatitis). Thus, a high index of suspicion is needed in order to identify the culprit corticosteroid.
Topics: Humans; Prevalence; Drug Hypersensitivity; Adrenal Cortex Hormones; Hypersensitivity, Immediate; Hypersensitivity, Delayed; Skin Tests
PubMed: 36800886
DOI: 10.57187/smw.2023.40025 -
Immunology and Allergy Clinics of North... Nov 2017Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be... (Review)
Review
Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics.
Topics: Allergens; Anti-Bacterial Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Skin; Skin Tests
PubMed: 28965638
DOI: 10.1016/j.iac.2017.07.002 -
Current Allergy and Asthma Reports Mar 2016Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids... (Review)
Review
Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Skin Tests
PubMed: 26857016
DOI: 10.1007/s11882-016-0596-7 -
Immunology and Allergy Clinics of North... May 2022In evaluating adverse drug reactions (ADRs), patch tests (PTs), skin prick tests (SPTs), and intradermal tests (IDTs) are useful tools for identifying responsible drugs... (Review)
Review
In evaluating adverse drug reactions (ADRs), patch tests (PTs), skin prick tests (SPTs), and intradermal tests (IDTs) are useful tools for identifying responsible drugs and finding safe alternatives. Their diagnostic value depends on the clinical features of the ADR and on the drug tested. PTs have a good sensitivity in assessing acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms. SPTs done with all drugs except opiates are used for immediate hypersensitivity reactions. IDTs seem sensitive for immediate hypersensitivity reactions to beta-lactam antibiotics, iodinated contrast media, heparins, general anesthetics, and platinum salts.
Topics: Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Patch Tests; Skin Tests
PubMed: 35469620
DOI: 10.1016/j.iac.2022.01.003 -
Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.Contact Dermatitis Nov 2023Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are...
BACKGROUND
Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients.
OBJECTIVES
To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative.
METHODS
Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative.
RESULTS
A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it.
CONCLUSIONS
In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.
Topics: Female; Humans; Contrast Media; Drug Hypersensitivity; Dermatitis, Allergic Contact; Skin Tests; Iodine Compounds; Exanthema; Hypersensitivity, Delayed
PubMed: 37394777
DOI: 10.1111/cod.14372 -
Annals of Allergy, Asthma & Immunology... Jan 2021
Topics: Aged; Drug Hypersensitivity; Factor Xa Inhibitors; Female; Humans; Hypersensitivity, Delayed; Male; Pyridines; Thiazoles
PubMed: 32866622
DOI: 10.1016/j.anai.2020.08.027 -
Acta Clinica Belgica Aug 2022Following intravenous contrast medium (CM) injection, a small proportion of patients acquires hypersensitivity reactions that occur either immediately or non-immediately...
Following intravenous contrast medium (CM) injection, a small proportion of patients acquires hypersensitivity reactions that occur either immediately or non-immediately (delayed). Although it is now claer that even oral applied CMs are able to cause adverse reactions, many radiologists as well as physicians of other disciplines, still believe that CM-application via the gastrointestinal route does not induce hypersensitivity reactions. Since this kind of misinterpretation may harm the patient, education on this topic is still necessary. Therefore, we describe a case who acquired a delayed hypersensitivity reaction following the oral intake of a non-ionic iodinated CM.
Topics: Contrast Media; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate
PubMed: 34556010
DOI: 10.1080/17843286.2021.1982217 -
Annals of Internal Medicine Oct 2003Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity... (Review)
Review
Immune reactions to small molecular compounds, such as drugs, can cause a variety of diseases involving the skin, liver, kidney, and lungs. In many drug hypersensitivity reactions, drug-specific CD4+ and CD8+ T cells recognize drugs through their alphabeta T-cell receptors in an MHC-dependent way. Drugs stimulate T cells if they act as haptens and bind covalently to peptides or if they have structural features that allow them to interact with certain T-cell receptors directly. Immunohistochemical and functional studies of drug-reactive T cells in patients with distinct forms of exanthema reveal that distinct T-cell functions lead to different clinical phenotypes. In maculopapular exanthema, perforin-positive and granzyme B-positive CD4+ T cells kill activated keratinocytes, while a large number of cytotoxic CD8+ T cells in the epidermis is associated with formation of vesicles and bullae. Drug-specific T cells also orchestrate inflammatory skin reactions through the release of various cytokines (for example, interleukin-5, interferon) and chemokines (such as interleukin-8). Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema). Taken together, these data allow delayed hypersensitivity reactions (type IV) to be further subclassified into T-cell reactions, which through the release of certain cytokines and chemokines preferentially activate and recruit monocytes (type IVa), eosinophils (type IVb), or neutrophils (type IVd). Moreover, cytotoxic functions by either CD4+ or CD8+ T cells (type IVc) seem to participate in all type IV reactions.
Topics: Cross Reactions; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Immunity, Innate; T-Lymphocytes
PubMed: 14568857
DOI: 10.7326/0003-4819-139-8-200310210-00012 -
Allergy Apr 2020Delayed-type, T cell-mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human... (Review)
Review
Delayed-type, T cell-mediated, drug hypersensitivity reactions are a serious unwanted manifestation of drug exposure that develops in a small percentage of the human population. Drugs and drug metabolites are known to interact directly and indirectly (through irreversible protein binding and processing to the derived adducts) with HLA proteins that present the drug-peptide complex to T cells. Multiple forms of drug hypersensitivity are strongly linked to expression of a single HLA allele, and there is increasing evidence that drugs and peptides interact selectively with the protein encoded by the HLA allele. Despite this, many individuals expressing HLA risk alleles do not develop hypersensitivity when exposed to culprit drugs suggesting a nonlinear, multifactorial relationship in which HLA risk alleles are one factor. This has prompted a search for additional susceptibility factors. Herein, we argue that immune regulatory pathways are one key determinant of susceptibility. As expression and activity of these pathways are influenced by disease, environmental and patient factors, it is currently impossible to predict whether drug exposure will result in a health benefit, hypersensitivity or both. Thus, a concerted effort is required to investigate how immune dysregulation influences susceptibility towards drug hypersensitivity.
Topics: Alleles; Drug Hypersensitivity; Humans; Hypersensitivity, Delayed; Incidence; T-Lymphocytes
PubMed: 31758810
DOI: 10.1111/all.14127