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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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Immediate drug hypersensitivity reactions (DHR) constitute an important health condition, with serious consequences of inadequate diagnosis. In this article, some of the most important issues related to in vitro diagnosis of IgE-mediated allergies are discussed. In vitro diagnostics will benefit from expanded and novel insights and understandings in drug chemical reactivity, protein binding, biotransformation, degradation, identification of (cross-reactive) drug antigenic determinants, and deeper understanding of sensitization routes. Collective efforts should be undertaken to activate fundamental and clinical investigations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Intraoperative anaphylaxis and hypersensitivity reactions in the setting of anesthesia contribute significantly to the morbidity and mortality of surgeries and surgical procedures. Because multiple medications and products are given in a short period of time, identifying the specific cause can be difficult. Neuromuscular blocking agents, antibiotics, and latex are the most common causes of anesthesia-related reactions, though other medications or exposures could be involved. Careful review of anesthetic charts and allergy testing can help identify the underlying cause. The identification of the cause and subsequent prevention of reactions are critical to reduce overall mortality and morbidity related to anesthesia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The incidence of immune-mediated anaphylaxis during anesthesia ranges from 1 in 10,000 to 1 in 20,000. Neuromuscular blocking agents represent the most frequently involved substances, followed by latex and antibiotics, but every drug or substance used may be involved. Diagnosis relies on tryptase measurements at the time of the reaction and skin tests and specific IgE or basophil activation assays.

Diagnosis of drug allergy involves first the recognition of sometimes unusual symptoms as drug allergy and, second, the identification of the eliciting drug. This is an often difficult task, as the clinical picture and underlying pathomechanisms are heterogeneous. In clinical routine, physicians frequently have to rely upon a suggestive history and eventual provocation tests, both having their specific limitations. For this reason both in vivo (skin tests) and in vitro tests are investigated intensively as tools to identify the disease-eliciting drug. One of the tests evaluated in drug allergy is the basophil activation test (BAT). Basophils with their high-affinity IgE receptors are easily accessible and therefore can be used as indicator cells for IgE-mediated reactions. Upon allergen challenge and cross-linking of membrane-bound IgE antibodies (via Fc-epsilon-RI) basophils up-regulate certain activation markers on their surface such as CD63 and CD203c, as well as intracellular markers (eg, phosphorylated p38MAPK). In BAT, these alterations can be detected rapidly on a single-cell basis by multicolor flow cytometry using specific monoclonal antibodies. Combining this technique with in vitro passive sensitization of donor basophils with patients' serum, one can prove the IgE dependence of a drug reaction. This article summarizes the authors' current experience with the BAT in the diagnostic management of immediate-type drug allergy mediated by drug-specific IgE antibodies.

Radiocontrast media can cause immediate (1 hour) and nonimmediate (>1 hour) hypersensitivity reactions that remain unpredictable and a cause of concern for radiologists and cardiologists. Immediate hypersensitivity reactions resemble anaphylaxis, whereas nonimmediate ones clinically are predominated by exanthemas. Increasing evidence indicates that immediate reactions and nonimmediate skin exanthemas may be allergic reactions involving either contrast media-reactive IgE or T cells, respectively. Skin testing is a useful tool for the diagnosis of contrast media allergy. It may have an important role in the selection of a safe product in previous reactors, although validation data are still lacking. In vitro tests to search for contrast media-specific cell activation are currently under investigation.

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and clinical symptoms of delayed-type non-IgE-mediated allergic hypersensitivity (DTH) to heparin. For diagnosis, intradermal, patch, and subcutaneous challenge tests with heparins are suitable. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Hirudin polypeptides, which exhibit a different chemical structure, are a safe therapeutic alternative for subcutaneous application, however. Importantly, despite DTH to subcutaneously injected heparins, most patients tolerate heparin intravenously. Moreover, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration without prior testing may be justified.

Drug desensitization is the induction of temporary clinical unresponsiveness to drug antigens to which patients have presented severe hypersensitivity reactions. It is typically achieved by gradual reintroduction of small doses of drug antigens at fixed time intervals, and it is aimed at providing increased safety and protection from side effects, including anaphylaxis. Delivery of full therapeutic doses is achieved during desensitization, allowing patients to receive firstline chemotherapy, antibiotics, or monoclonal antibodies, as well as other drugs such as insulin, aspirin, and iron. Desensitizations are high-risk interventions. Inhibition of cellular activation mechanisms occurs during drug desensitization, allowing for the protective clinical outcomes and lack of side effects in the majority of cases, but the cellular and molecular inhibitory mechanisms are incompletely understood. The indication for desensitization protocols can only be done by trained allergists and immunologists and should be implemented as standard of care because of their high success rates and outcomes-demonstrated safety profile.

Skin tests with drugs help determine the cause and mechanism of drug hypersensitivity reactions. The diagnosis of adverse drug reactions is based primarily on history and clinical presentation. In type I, IgE-mediated allergic drug reactions, skin prick test and intradermal testing may provide rapid and supportive evidence for diagnosis or exclusion of IgE-mediated reactions. These tests often are more sensitive than laboratory assays for IgE antibodies to drug allergens, which are available only for a few drugs. Because intradermal skin tests occasionally induce adverse events, they should be performed by experienced personnel in an adequate environment.