scholarly journals In-Vitro Approaches to Predict and Study T-Cell Mediated Hypersensitivity to Drugs

2021 ◽  
Vol 12 ◽  
Author(s):  
Sean Hammond ◽  
Paul Thomson ◽  
Xiaoli Meng ◽  
Dean Naisbitt
Keyword(s):  
Chemical Reactivity ◽  
Drug Hypersensitivity ◽  
Poor Performance ◽  
Preclinical Studies ◽  
Hypersensitivity Reactions ◽  
Clinical Use ◽  
Lead Compound ◽  
Drug Hypersensitivity Reactions ◽  
Compound Selection

Mitigating the risk of drug hypersensitivity reactions is an important facet of a given pharmaceutical, with poor performance in this area of safety often leading to warnings, restrictions and withdrawals. In the last 50 years, efforts to diagnose, manage, and circumvent these obscure, iatrogenic diseases have resulted in the development of assays at all stages of a drugs lifespan. Indeed, this begins with intelligent lead compound selection/design to minimize the existence of deleterious chemical reactivity through exclusion of ominous structural moieties. Preclinical studies then investigate how compounds interact with biological systems, with emphasis placed on modeling immunological/toxicological liabilities. During clinical use, competent and accurate diagnoses are sought to effectively manage patients with such ailments, and pharmacovigilance datasets can be used for stratification of patient populations in order to optimise safety profiles. Herein, an overview of some of the in-vitro approaches to predict intrinsic immunogenicity of drugs and diagnose culprit drugs in allergic patients after exposure is detailed, with current perspectives and opportunities provided.

scholarly journals In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children

2016 ◽  
Vol 117 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Wei Yann Haw ◽  
Marta E. Polak ◽  
Carolann McGuire ◽  
Michel Erlewyn-Lajeunesse ◽  
Michael R. Ardern-Jones
Keyword(s):  
Diagnostic Tests ◽  
Drug Hypersensitivity ◽  
Rapid Diagnostic Tests ◽  
Hypersensitivity Reactions ◽  
Drug Hypersensitivity Reactions

scholarly journals Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions

2020 ◽  
Vol 10 (4) ◽  
Author(s):  
Yuttana Srinoulprasert ◽  
Ticha Rerkpattanapipat ◽  
Mongkhon Sompornrattanaphan ◽  
Chamard Wongsa ◽  
Duangjit Kanistanon
Keyword(s):  
Drug Hypersensitivity ◽  
In Vitro Tests ◽  
Hypersensitivity Reactions ◽  
Clinical Value ◽  
Drug Hypersensitivity Reactions

Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions

2019 ◽  
Vol 369 ◽  
pp. 39-48 ◽  
Author(s):  
S.S. Ahmed ◽  
J. Whritenour ◽  
M.M. Ahmed ◽  
L. Bibby ◽  
L. Darby ◽  
...  
Keyword(s):  
Skin Test ◽  
Drug Hypersensitivity ◽  
Hypersensitivity Reactions ◽  
Drug Hypersensitivity Reactions

Skin testing and drug challenge in the evaluation of drug hypersensitivity reactions

2021 ◽  
Vol 42 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Anna R. Wolfson ◽  
Aleena Banerji
Keyword(s):  
Negative Impact ◽  
Skin Testing ◽  
Drug Hypersensitivity ◽  
Clinical History ◽  
Hypersensitivity Reactions ◽  
Causative Drug ◽  
Care Assessment ◽  
Drug Hypersensitivity Reactions ◽  
Drug Challenge ◽  
Drug Challenges

Immediate hypersensitivity to drugs is characterized by symptoms such as hives, swelling, and wheezing. To prevent a negative impact on care, assessment by an allergist is important. Evaluation requires a clear clinical history, but it is often lacking or vague, which makes a diagnosis difficult. Allergists instead can use skin testing and drug challenge to evaluate drug hypersensitivity reactions, which help the patient and provider understand the causative drug(s) and, more importantly, enables the use of the exonerated drug(s). Although penicillin skin testing is standardized, well described, and widely used, skin testing for most other drugs requires the use of a nonirritating skin testing concentration that can have a low negative predictive value. Drug challenges are the criterion standard for confirming tolerance. The allergist must obtain an in-depth clinical history and then follow with skin testing and/or drug challenges when indicated to determine which drugs can be de-labelled and which should be avoided. In this review, we focused on the evaluation of drug hypersensitivity reactions to antibiotics, perioperative agents, biologics, and chemotherapeutics.

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.

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.

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