scholarly journals Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

2022 ◽  
Vol 2 ◽  
Author(s):  
Teodorikez Wilfox Jimenez-Rodriguez ◽  
Francisco Manuel Marco de la Calle ◽  
Inmaculada Lozano-Cubo ◽  
Rosa Ana Montoyo-Anton ◽  
Victor Soriano-Gomis ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Drug Exposure ◽  
Drug Hypersensitivity ◽  
Skin Tests ◽  
Hypersensitivity Reactions ◽  
Test Results ◽  
Drug Reactions ◽  
Immediate Hypersensitivity ◽  
Drug Hypersensitivity Reactions ◽  
Median Interval

Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.

Early Biomarkers for Severe Drug Hypersensitivity Reactions

2019 ◽  
Vol 25 (36) ◽  
pp. 3829-3839 ◽  
Author(s):  
Adriana Ariza ◽  
Maria J. Torres ◽  
Carmen Moreno-Aguilar ◽  
Rubén Fernández-Santamaría ◽  
Tahia D. Fernández
Keyword(s):  
Drug Exposure ◽  
Drug Hypersensitivity ◽  
Clinical Manifestations ◽  
Skin Tests ◽  
Time Interval ◽  
Hypersensitivity Reactions ◽  
Early Biomarkers ◽  
Immunological Mechanisms ◽  
Drug Hypersensitivity Reactions ◽  
Delayed Reactions

Drug hypersensitivity reactions (DHRs) are typically classified into immediate and delayed reactions based on the time interval between drug exposure and onset of symptoms. Clinical manifestations range from mild to severe and life-threatening reactions. The most severe clinical entities are anaphylaxis and anaphylactic shock for immediate reactions, and severe cutaneous adverse reactions such as Steven Johnson Syndrome and Toxic Epidermal Necrolysis for delayed reactions. The diagnosis is complex and challenging, as drug provocation tests and even skin tests can be very risky procedures, which makes them not recommended. Therefore, it is necessary to search for useful early biomarkers to manage the diagnosis of these reactions. These biomarkers could be useful to determine the clinical entity, but not to identify the culprit drug. Some of the currently available biomarkers are few genetic associations of drug allergy with polymorphisms of human leukocyte antigen (HLA), the detection of inflammatory and lipid mediators in serum, or the detection of cytokines, chemokines, and cytotoxic markers in skin biopsies. In this literature review, it has been summarize the immunological mechanisms involved in severe reactions, both immediate and delayed, and different early biomarkers: those currently used for the diagnosis of these reactions as well as possible early biomarkers that could be useful with further studies to standardize their clinical use.

Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions

2019 ◽  
Vol 25 (36) ◽  
pp. 3840-3854 ◽  
Author(s):  
Hakan Guvenir ◽  
Tugba Arikoglu ◽  
Emine Vezir ◽  
Emine Dibek Misirlioglu
Keyword(s):  
Adverse Drug Reactions ◽  
Drug Hypersensitivity ◽  
Stevens Johnson Syndrome ◽  
Facial Oedema ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
Cutaneous Manifestations ◽  
Clinical Phenotypes ◽  
Drug Eruptions ◽  
Drug Hypersensitivity Reactions

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

scholarly journals INVESTIGATION OF MEDICALLY INDUCED SKIN REACTIONS BASED ON THE ANALYSIS OF REPORTS OF ADVERSE DRUG REACTIONS IN THE REPUBLIC OF CRIMEA (FROM 2009 TO 2016)

2019 ◽  
Vol 7 (1) ◽  
pp. 32-41 ◽  
Author(s):  
A. V. Matveev ◽  
А. E. Krasheninnikov ◽  
E. A. Egorova ◽  
Е. I. Konyaeva
Keyword(s):  
Adverse Reactions ◽  
Drug Hypersensitivity ◽  
Clinical Manifestations ◽  
World Health ◽  
Report Cards ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
Skin Reactions ◽  
Drug Hypersensitivity Reactions ◽  
The Republic

Drug hypersensitivity reactions are among the most important problems that arise when using drugs. The occurrence of such reactions in the population is at least 7% and tends to a constant increase. The most frequent manifestations of drug hypersensitivity reactions are medically induced skin lesions.The aimof this research was to study and analyze the cases of development of skin drug reactions on the basis of the reports on the adverse reactions (ADRs) of the drugs, registered in the Republic of Crimea in the period from 2009 to 2016.Materials and methods.The objects of the research were report cards about the adverse reactions, registered in the regional base (registry) of spontaneous messages called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2009 to 2016. During the analysis of the report cards, 2,698 cases of the development of skin drug reactions arising in response to the use of drugs in patients were selected. The study of the frequency of occurrence of skin drug reactions in the application of various groups of drugs was carried out taking into account the codes of the Anatomical Therapeutic Chemical (ATC) Сlassification System of drugs of the World Health Organization (WHO).Results.Of the study showed that the development of skin drug reactions was most often associated with the use of antimicrobial agents for internal use, nonsteroidal anti-inflammatory drugs (NSAIDs), drugs for the treatment of diseases of the gastrointestinal tract and agents that affect the nervous system. Among the clinical manifestations of skin drug reactions, generalized and localized rashes prevailed, and itching and hyperemia of the skin were much less common in patients. The analysis of age categories showed that the most frequently medically induced reactions occurred in children from birth to 3 years, as well as in the age group of patients from 46 to 60 years. The risk factors identified in the course of the analysis, were female gender, early childhood and old age, as well as the presence of aggravated drug allergy history.Conclusion.Drug hypersensitivity reactions create certain difficulties in clinical practice related to the diagnosis, treatment and prophylaxis, and may also cause danger to health or life of patients. In this connection, the study of such adverse reactions is the most important task of practical health care and requires direct participation of doctors of all specialties.

Drug Allergies

2018 ◽  
Author(s):  
James L Baldwin ◽  
Aimee L. Speck
Keyword(s):  
Adverse Drug Reactions ◽  
Skin Testing ◽  
Drug Hypersensitivity ◽  
Type A ◽  
World Health ◽  
Hypersensitivity Reactions ◽  
Type B ◽  
Drug Reactions ◽  
Drug Hypersensitivity Reactions

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

Drug Allergies

2018 ◽  
Author(s):  
James L Baldwin ◽  
Aimee L. Speck
Keyword(s):  
Adverse Drug Reactions ◽  
Skin Testing ◽  
Drug Hypersensitivity ◽  
Type A ◽  
World Health ◽  
Hypersensitivity Reactions ◽  
Type B ◽  
Drug Reactions ◽  
Drug Hypersensitivity Reactions

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

scholarly journals Variability of the Genes Involved in the Cellular Redox Status and Their Implication in Drug Hypersensitivity Reactions

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 294 ◽  
Author(s):  
Pedro Ayuso ◽  
Elena García-Martín ◽  
José A. G. Agúndez
Keyword(s):  
Drug Hypersensitivity ◽  
Thioredoxin Reductase ◽  
Redox System ◽  
Redox Status ◽  
Current Evidence ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
Glutathione S Transferase ◽  
Drug Hypersensitivity Reactions ◽  
Inflammatory Processes

Adverse drug reactions are a major cause of morbidity and mortality. Of the great diversity of drugs involved in hypersensitivity drug reactions, the most frequent are non-steroidal anti-inflammatory drugs followed by β-lactam antibiotics. The redox status regulates the level of reactive oxygen and nitrogen species (RONS). RONS interplay and modulate the action of diverse biomolecules, such as inflammatory mediators and drugs. In this review, we address the role of the redox status in the initiation, as well as in the resolution of inflammatory processes involved in drug hypersensitivity reactions. We summarize the association findings between drug hypersensitivity reactions and variants in the genes that encode the enzymes related to the redox system such as enzymes related to glutathione: Glutathione S-transferase (GSTM1, GSTP, GSTT1) and glutathione peroxidase (GPX1), thioredoxin reductase (TXNRD1 and TXNRD2), superoxide dismutase (SOD1, SOD2, and SOD3), catalase (CAT), aldo-keto reductase (AKR), and the peroxiredoxin system (PRDX1, PRDX2, PRDX3, PRDX4, PRDX5, PRDX6). Based on current evidence, the most relevant candidate redox genes related to hypersensitivity drug reactions are GSTM1, TXNRD1, SOD1, and SOD2. Increasing the understanding of pharmacogenetics in drug hypersensitivity reactions will contribute to the development of early diagnostic or prognosis tools, and will help to diminish the occurrence and/or the severity of these reactions.

scholarly journals Diagnosing and Managing Patients with Reactions to Radiocontrast Media

2021 ◽  
Vol 8 (3) ◽  
pp. 210-221
Author(s):  
Knut Brockow
Keyword(s):  
Skin Testing ◽  
Drug Hypersensitivity ◽  
Skin Tests ◽  
Hypersensitivity Reactions ◽  
Positive Skin ◽  
Provocation Tests ◽  
Ring Molecules ◽  
Allergic Skin ◽  
Drug Hypersensitivity Reactions ◽  
Drug Provocation Tests

Abstract Purpose of the review Iodinated radio contrast media (RCM) belong to the most common elicitors of drug hypersensitivity reactions (HR). Urticaria or anaphylaxis may occur ≤ 1(−6) hour(s) (immediate HR) and exanthems (non-immediate HR) develop > 6 h after application of RCM. Evidence for an immunologic mechanism of RCM HR against the different RCM benzene ring molecules and the benefit of allergological testing in patients with previous hypersensitivity reactions is progressively increasing. Recent findings Positive skin tests can confirm allergy in patients with previous reactions to RCM and help to select alternative better tolerated RCMs. Severe hypersensitivity reactions are mainly caused by an allergic mechanism, whereas the majority of non-severe reactions appear to be non-allergic. Skin testing is highly recommended to help identify allergic hypersensitivity reactions and to select alternatives. Using structurally different RCM is more effective than premedication for the prevention of future reactions. Drug provocation tests to RCM have been increasingly used, but are not yet standardized among different centers. Summary In patients with previous severe hypersensitivity reactions to RCM, skin testing is recommended. For future RCM-enhanced examinations in patients with previous reactions, structurally different, skin test-negative preparations should be applied. Drug provocation tests do confirm or exclude RCM hypersensitivity or may demonstrate tolerability of alternative RCMs.

Drug Allergies

2015 ◽  
Author(s):  
James L Baldwin ◽  
Aimee L. Speck
Keyword(s):  
Skin Testing ◽  
Drug Hypersensitivity ◽  
Public Health Problem ◽  
Type A ◽  
World Health ◽  
Hypersensitivity Reactions ◽  
Type B ◽  
Drug Reactions ◽  
Drug Hypersensitivity Reactions

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This chapter contains 8 highly rendered figures, 3 tables, 83 references, 5 MCQs, and 1 teaching slide set.

scholarly journals Model Based Evaluation of Hypersensitivity Adverse Drug Reactions to Antimicrobial Agents in Children

2021 ◽  
Vol 12 ◽  
Author(s):  
Abdelbaset A. Elzagallaai ◽  
Michael J. Rieder
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Adverse Drug Reactions ◽  
Current Knowledge ◽  
Drug Hypersensitivity ◽  
High Morbidity ◽  
Hypersensitivity Reactions ◽  
Drug Reactions ◽  
Model Based ◽  
Drug Hypersensitivity Reactions

Drug use in children is–in most cases–supported by extrapolation of data generated from clinical trials in adult populations. This puts children at higher risk of developing adverse drug reactions (ADRs) due to “off-label” use of drugs and dosing issues. Major types of ADRs are drug hypersensitivity reactions, an idiosyncratic type of ADRs that are largely unpredictable and can cause high morbidity and mortality in a hard-to-identify specific population of patients. Lack of a complete understanding of the pathophysiology of DHRs and their unpredictive nature make them problematic in clinical practice and in drug development. In addition, ethical and legal obstacles hinder conducting large clinical trials in children, which in turn make children a “therapeutic orphan” where clear clinical guidelines are lacking, and practice is based largely on the personal experience of the clinician, hence making modeling desirable. This brief review summarizes the current knowledge of model-based evaluation of diagnosis and management of drug hypersensitivity reactions (DHRs) to antimicrobial drugs in the pediatric population. Ethical and legal aspects of drug research in children and the effect of different stages of child development and other factors on the risk of DHRs are discussed. The role of animal models, in vitro models and oral provocation test in management of DHRs are examined in the context of the current understanding of the pathophysiology of DHRs. Finally, recent changes in drug development legislations have been put forward to encourage drug developers to conduct trials in children clearly indicate the urgent need for evidence to support drug safety in children and for modeling to guide these clinical trials.

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