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Allergy Jan 2023Virus infections and T-cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may... (Review)
Review
Virus infections and T-cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like β-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i): drugs tend to bind to proteins and may even bind to immune receptors. Without viral infections, this low affine binding may be insufficient to elicit T-cell activation. During a viral infection, immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T-cell activation and symptoms. There is a situation where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally activates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity by killing herpes peptide-expressing cells and releasing herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.
Topics: Humans; Drug Hypersensitivity; Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity, Delayed; Virus Diseases; Drug Hypersensitivity Syndrome
PubMed: 36264263
DOI: 10.1111/all.15558 -
Allergy Apr 2021
Topics: Drug Hypersensitivity; Humans; Hypersensitivity; Hypersensitivity, Immediate; Skin Tests
PubMed: 32780432
DOI: 10.1111/all.14555 -
Handbook of Experimental Pharmacology 2022Allergy or hypersensitivity to drugs often affects the skin and sometimes also mucosa. While immediate type reactions show a rather homogeneous pattern, delayed type...
Allergy or hypersensitivity to drugs often affects the skin and sometimes also mucosa. While immediate type reactions show a rather homogeneous pattern, delayed type reactions reveal a high variability. In both cases it may not always be easy to differentiate drug reactions from non-drug-induced skin conditions. Furthermore, the different types of cutaneous adverse reactions may be difficult to distinguish in the beginning. This accounts predominately for delayed hypersensitivity reactions that can occur after a variety of medications and present with manifold lesions. Most of these cutaneous adverse reactions are mild, but some are severe with high morbidity and mortality. In the clinical setting, it is important to recognize the signs that point to a more severe condition early on in order to initiate appropriate management. In addition, it is crucial to identify the potentially culprit medication on the basis of a detailed medication history and by evaluating the relevant exposure times of certain drugs that differ substantially between the various reaction types. After the acute stage of the adverse reaction is managed successfully, further allergologic testing may be undertaken to confirm the offending drug.
Topics: Drug Hypersensitivity; Humans; Skin; Skin Tests
PubMed: 34219202
DOI: 10.1007/164_2021_490 -
Current Opinion in Allergy and Clinical... Aug 2021Drug allergy management has previously not been emphasized in the elderly. However, the geriatric population poses several unique characteristics, challenges for drug... (Review)
Review
PURPOSE OF REVIEW
Drug allergy management has previously not been emphasized in the elderly. However, the geriatric population poses several unique characteristics, challenges for drug allergy testing and considerations in the management. Especially in the era of COVID-19, the elderly population is a vulnerable cohort and reviewing the management during this unprecedented time is both timely and relevant.
RECENT FINDINGS
In recent years, larger scale studies focusing on the epidemiology and prevalence trends of drug allergies among older adults has been summarized in this review. Emphasis on anaphylaxis in the older adults has been studied.
SUMMARY
There are many implications of these findings. Epidemiological studies are useful in realizing the burden and spectrum of drug allergies on our healthcare system. It has allowed us to identify certain barriers in drug allergy management and develop ways to overcome these challenges through. Lastly, we have proposed an approach to drug allergy management based on previous studies as well as from our perspective and local experience.
Topics: Age Factors; Aged; Aging; COVID-19; Desensitization, Immunologic; Drug Hypersensitivity; Drug Labeling; Global Burden of Disease; Humans; Prevalence; Risk Factors; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34101633
DOI: 10.1097/ACI.0000000000000761 -
Immunology and Allergy Clinics of North... May 2022The imagery of pigmented skin is underrepresented in teaching materials such as textbooks, journals, and online references, and this has resulted in poorer diagnostic... (Review)
Review
The imagery of pigmented skin is underrepresented in teaching materials such as textbooks, journals, and online references, and this has resulted in poorer diagnostic and management outcomes of skin pathology, including delayed cutaneous drug hypersensitivity reactions. In this review, we use clinical images to highlight factors that impact clinical presentations and sequelae of drug hypersensitivity reactions in pigmented skin compared with nonpigmented skin. We describe clinical features in some anatomic sites that aid diagnosis or are associated with more severe sequelae. Finally, we discuss strategies that may aid the diagnosis and management of these reactions in pigmented skin.
Topics: Drug Hypersensitivity; Humans; Skin
PubMed: 35469616
DOI: 10.1016/j.iac.2022.01.005 -
The Journal of Allergy and Clinical... Feb 2023
Topics: Humans; Drug Hypersensitivity; Anaphylaxis; Receptors, G-Protein-Coupled; Mast Cells; Receptors, Neuropeptide; Cell Degranulation; Nerve Tissue Proteins
PubMed: 36089079
DOI: 10.1016/j.jaci.2022.09.004 -
The Journal of Allergy and Clinical... May 2024Immediate drug-induced hypersensitivity reactions (IDHSRs) have conventionally been attributed to an immunoglobulin E (IgE)-mediated mechanism. Nevertheless, it has now... (Review)
Review
Immediate drug-induced hypersensitivity reactions (IDHSRs) have conventionally been attributed to an immunoglobulin E (IgE)-mediated mechanism. Nevertheless, it has now been acknowledged that IDHSRs can also occur independently of IgE involvement. Non-IgE-mediated IDHSRs encompass the activation of effector cells, both mast cell-dependent and -independent and the initiation of inflammatory pathways through immunogenic and nonimmunogenic mechanisms. The IDHSRs involve inflammatory mediators beyond histamine, including the platelet-activating factor, which activates multiple cell types, including smooth muscle, endothelium, and MC, and evidence supports its importance in IgE-mediated reactions in humans. Clinically, distinguishing IgE from non-IgE mechanisms is crucial for future treatment strategies, including drug(s) restriction, readministration approaches, and pretreatment considerations. However, this presents significant challenges because certain drugs can trigger both mechanisms, and their presentations can appear similarly, ranging from mild to life-threatening symptoms. Thus, history alone is often inadequate for differentiation, and skin tests lack a standardized approach. Moreover, drug-specific IgE immunoassays have favorable specificity but low sensitivity, and the usefulness of the basophil activation test remains debatable. Lastly, no biomarker reliably differentiates between both mechanisms. Whereas non-IgE-mediated mechanisms likely predominate in IDHSRs, reclassifying most drug-related IDHSRs as non-IgE-mediated, with suggested prevention through dose administration adjustments, is premature and risky. Therefore, continued research and validated diagnostic tests are crucial to improving our capacity to distinguish between these mechanisms, ultimately enhancing patient care.
Topics: Humans; Drug Hypersensitivity; Immunoglobulin E; Hypersensitivity, Immediate; Basophils; Mast Cells; Animals; Platelet Activating Factor
PubMed: 38423288
DOI: 10.1016/j.jaip.2024.02.019 -
Archives of Disease in Childhood May 2023
Topics: Humans; Penicillins; Drug Hypersensitivity; Hypersensitivity; Anti-Bacterial Agents
PubMed: 36963812
DOI: 10.1136/archdischild-2022-325200 -
Allergology International : Official... Apr 2022Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory... (Review)
Review
Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory disorders caused by antigens, including drugs or pathogenic microorganisms present prior to immune recovery, or by the exacerbation of an inflammatory disorder that was already present. Drug-induced hypersensitivity syndrome is a prototype of IRIS, and the pathophysiology of non-HIV IRIS can be recognized in several disorders treated with corticosteroids, immunosuppressants, molecular-targeted drugs, TNF-α antibody drugs, immune checkpoint inhibitors, and dipeptidyl peptidase-4 inhibitors. This review focuses on the relationship between the immune mechanism of non-HIV IRIS and drug allergies, especially severe drug eruption. The antigen recognition mechanism in drug allergy varies depending on the clinical type and the causative drug. The p-i concept is the main mechanism in severe drug eruption such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Lymphocytes activated by an antigen other than a drug, such as a virus, can also develop drug allergy by the loose binding of drugs with immune receptors of T cells or human leukocyte antigen. Therefore, fluctuations in the immune environment affect the onset of severe drug eruption. Novel agents that cause major changes in immunity have been marketed mainly for autoimmune diseases and malignant tumors; therefore, it is necessary to consider their effects when treating severe drug eruptions. Moreover, although a list of diagnostic criteria for this syndrome has been drafted, predictive and diagnostic biomarkers for this syndrome needs to be urgently developed.
Topics: Adrenal Cortex Hormones; Drug Hypersensitivity Syndrome; Eosinophilia; Humans; Immune Reconstitution Inflammatory Syndrome; Stevens-Johnson Syndrome
PubMed: 35236619
DOI: 10.1016/j.alit.2021.12.002 -
Pediatric Allergy and Immunology :... May 2023
Topics: Humans; Child; Drug Hypersensitivity; Anti-Bacterial Agents
PubMed: 37232287
DOI: 10.1111/pai.13957