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Frontiers in Immunology 2022Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and... (Review)
Review
Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and mechanisms. These reactions are classified into allergic drug hypersensitivity reactions and non-allergic drug hypersensitivity reactions. At present, the hapten theory, pharmacological interaction with immune receptors (p-i) concept, altered peptide repertoire model, and altered T-cell receptor (TCR) repertoire model have been proposed to explain how small molecule drugs or their metabolites induce allergic drug hypersensitivity reactions. Meanwhile, direct activation of mast cells, provoking the complement system, stimulating or inhibiting inflammatory reaction-related enzymes, accumulating bradykinin, and/or triggering vascular hyperpermeability are considered as the main factors causing non-allergic drug hypersensitivity reactions. To date, many investigations have been performed to explore the underlying mechanisms involved in drug hypersensitivity reactions and to search for predictive and preventive methods in both clinical and non-clinical trials. However, validated methods for predicting and diagnosing hypersensitivity reactions to small molecule drugs and deeper insight into the relevant underlying mechanisms are still limited.
Topics: Humans; Drug Hypersensitivity; Haptens; Drug-Related Side Effects and Adverse Reactions; Receptors, Immunologic
PubMed: 36439170
DOI: 10.3389/fimmu.2022.1016730 -
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 -
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 -
Current Opinion in Immunology Apr 2023Anaphylaxis is an acute life-threatening systemic allergic reaction that can have a wide range of clinical manifestations. The most common triggers for anaphylaxis... (Review)
Review
Anaphylaxis is an acute life-threatening systemic allergic reaction that can have a wide range of clinical manifestations. The most common triggers for anaphylaxis include food, medication, and venom. What is curious regarding anaphylaxis is how so many different agents can induce a severe systemic clinical response but only in a select subgroup of patients. Over the past decade, several important advances have been made in understanding the underlying cellular and molecular mechanisms contributing to anaphylaxis, with mast cells (MCs) being an essential component. Classically, cross-linked immunoglobulin E (IgE) bound to its high- affinity receptor induces MC mediator release. However, toll-like, complement, or Mas-related G-protein-coupled receptors also activate mouse and human MCs. While anaphylaxis secondary to foods historically has been more extensively characterized clinically and mechanistically, more recent studies have shifted focus toward understanding drug-induced anaphylaxis. The focus of this review is to highlight recent basic science developments and compare what is currently known regarding anaphylaxis to food, medications, and venom.
Topics: Humans; Mice; Animals; Anaphylaxis; Immunoglobulin E; Drug Hypersensitivity; Mast Cells; Receptors, G-Protein-Coupled; Allergens
PubMed: 36848746
DOI: 10.1016/j.coi.2023.102288 -
Current Opinion in Allergy and Clinical... Aug 2019Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives,... (Review)
Review
PURPOSE OF REVIEW
Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives, but the burden of specific drug IM-ADRs is population-specific; changing as new and fixed dose combinations enter the market, and drug-resistance patterns demand. This review considers recent literature on epidemiology, mechanisms, clinical management and prevention of IM-ADRs amongst persons living with HIV/AIDS.
RECENT FINDINGS
Epidemiological studies continue to describe high rates of delayed hypersensitivity to known offenders, as well as similar reactions in preexposure prophylaxis. IM-ADRs to oral and injectable integrase strand transfer inhibitors are reported with expanding use. The clinical spectrum and management of IM-ADRs occurring in HIV-infected populations is similar to uninfected; with exceptions such as a recently described severe delayed efavirenz DILI with high mortality. Furthermore, the context can be unique, such as the lower than expected mortality in a Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cohort from a HIV/TB high burden setting. Programmatic data showing the near complete elimination of Abacavir drug hypersensitivity syndrome following implementation of HLA-B57:01 screening is a stellar example of how prevention is possible with mechanistic insight.
SUMMARY
IM-ADRs remain a challenge in persons living with HIV. The complexities posed by polypharmacy, overlapping drug toxicities, drug interactions, overlap of IM-ADRs with other diseases, limited alternative drugs, and vulnerable patients with advanced immunosuppression with high mortality, necessitate increased use of drug provocation testing, treat-through and desensitization strategies. There is an urgent need for improved diagnostics and predictive biomarkers for prevention, or to guide treat-through, rechallenge and desensitization approaches.
Topics: Allergens; Anti-Infective Agents; Anti-Retroviral Agents; Biomarkers; Dideoxynucleosides; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; Genetic Testing; HIV Infections; HIV-1; HLA-B Antigens; Humans; Immunization
PubMed: 31145192
DOI: 10.1097/ACI.0000000000000545 -
Journal of Immunological Methods Jun 2021
Topics: Drug Hypersensitivity; Humans
PubMed: 33684438
DOI: 10.1016/j.jim.2021.113004 -
Turkish Journal of Medical Sciences Oct 2021Coronavirus Disease 2019 (COVID-19) affected the whole world in a short time. One of the most influential public health initiatives modern medicine has to offer, the... (Review)
Review
Coronavirus Disease 2019 (COVID-19) affected the whole world in a short time. One of the most influential public health initiatives modern medicine has to offer, the vaccine has become even more important as the COVID-19 pandemic continues to worsen worldwide. Many vaccine trials were launched during the COVID-19 pandemic, and these vaccines were widely used around the world, offering realistic hope for ending the pandemic. Allergic reactions to vaccines were reported shortly after their approval. These reactions, in general, are rare, but, in some circumstances, they can be serious. Allergy to vaccines can occur because of either the active vaccine component or vaccine ingredients. The spectrum of the reactions may be just a local hypersensitiviy reaction or may be as severe as an anaphylaxis, which is an acute severe, life-threatening systemic hypersensitive reaction, and it requires quick intervention. If an allergy is suspected, a correct examination followed by algorithms is important for true diagnosis, treatment, and decision regarding revaccination. Patients who experience an allergic reaction with the first dose of covid 19 vaccine should be directed to the allergy-immunologist, and the evaluation of at-risk patients should be individualized. Finally, we should point out that the benefits of current COVID-19 vaccines go far beyond the side effects, and that the vaccine is the most important way to recover from the pandemic.
Topics: Algorithms; COVID-19 Vaccines; Drug Hypersensitivity; Humans
PubMed: 34333906
DOI: 10.3906/sag-2104-329 -
Asian Pacific Journal of Allergy and... Dec 2023Drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced liver injury (DILI) can hamper therapeutic strategy, contribute to multiple drug... (Review)
Review
Drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced liver injury (DILI) can hamper therapeutic strategy, contribute to multiple drug resistance and serious public health burden. Diagnosis (including allergy assessment) and management of these two severe hypersensitivity reactions in clinical practice are somewhat difficult and published scientific evidence is rather weak and limited. The first step is always represented by stopping all anti-tuberculosis (TB) drugs, treating reaction with systemic corticosteroids, and identifying the offending drug, even if it is often complicated by the patient's simultaneous intake of antibiotics. Patch tests and in vitro tests, such as lymphocyte transformation test, could bridge this diagnostic gap, but the available data are scarce and their sensitivity low. The re-challenge test is often necessary but places patients at risk for serious adverse reactions. The desensitization protocols are quite varied and not universally accepted. In this narrative review, we provide an update to the literature data on the management of DRESS and DILI with particular attention to the allergological work-up in the last decade.
Topics: Humans; Antitubercular Agents; Drug Hypersensitivity Syndrome; Eosinophilia; Hypersensitivity
PubMed: 37874314
DOI: 10.12932/AP-010423-1582 -
Current Opinion in Allergy and Clinical... Aug 2021Understand how the clinical history has been used to risk stratify patients reporting a beta-lactam allergy, both in clinical care pathways and predictive models. (Review)
Review
PURPOSE OF REVIEW
Understand how the clinical history has been used to risk stratify patients reporting a beta-lactam allergy, both in clinical care pathways and predictive models.
RECENT FINDINGS
Drug allergy clinical care pathways have emerged as a safe and effective method of stratifying patients with a reported beta-lactam allergy into risk categories, with 'low-risk' patients able to proceed straight to direct challenges or test doses. These methods have streamlined antibiotic stewardship policies and penicillin allergy de-labeling. However, how to define 'low-risk' has been subject to much debate. New research has developed predictive models that utilize the clinical history to assess a patient's true risk of beta-lactam allergy.
SUMMARY
The clinical history has long been an essential part of drug allergy evaluation and has proven invaluable within the past decade in the development of drug allergy clinical pathways. Evidence-based predictive models that use the clinical history to assess a patient's true risk of beta-lactam allergy offer tremendous promise, but differ in crucial areas such as the populations they study, the predictor variables they use, and the ultimate accuracy they attain. These models highlight key aspects of the drug allergy history and pave the way for future large-scale research.
Topics: Anti-Bacterial Agents; Drug Hypersensitivity; Humans; Penicillins; Skin Tests; beta-Lactams
PubMed: 34054028
DOI: 10.1097/ACI.0000000000000758