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Purpose of Review: Antimicrobials are a leading cause of severe T cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in-vitro, in-vivo, and ex-vivo diagnostics for T cell-mediated ADRs., Recent Findings: Recent literature has evaluated the efficacy of traditional antibiotic allergy management, including patch testing, skin prick testing, intradermal testing, and oral challenge. Although patch and intradermal testing are specific for the diagnosis of immune-mediated ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex-vivo diagnostics, especially enzyme-linked immunospot, has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous immune-mediated ADRs., Summary: In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct 'allergy label' is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction, is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T cell-mediated ADRs via personalized approaches, including human leukocyte antigen-typing, may pave future pathways to safer antimicrobial prescribing guidelines., Competing Interests: None

Purpose of Review: This article provides an update on hypersensitivity reactions to heparins and novel oral anticoagulants, with special emphasis on diagnostic methods and management of patients., Recent Findings: Although heparins are drugs widely used, hypersensitivity reactions are uncommon. Cutaneous delayed hypersensitivity reactions after subcutaneous administration affects up to 7.5% of patients. Heparin-induced thrombocytopenia is another unusual but severe condition in which early recognition is crucial. Immediate hypersensitivity reactions to heparins have been also reported, but with the novel oral anticoagulants are much more uncommon, although reports of exanthemas have been notified.Skin tests and subcutaneous provocation test are useful tools in the diagnosis of hypersensitivity reactions, except in heparin-induced thrombocytopenia in which biopsy of lesional skin and in-vitro tests are the modalities of choice to confirm the diagnosis.Management of hypersensitivity reactions includes finding an alternative depending on the type of reaction. Fondaparinux and novel oral anticoagulants may be safe alternatives., Summary: Delayed skin lesions after subcutaneous heparin are the most common type of hypersensitivity reactions, followed by life-threatening heparin-induced thrombocytopenia. Immediate reactions are uncommon. Allergologic studies may be useful to find an alternative option in patients with skin lesions in which heparin-induced thrombocytopenia has been previously excluded, as well as in heparin immediate reactions.

Anticonvulsant hypersensitivity syndrome is a potentially life-threatening delayed hypersensitivity reaction characterized by the triad of fever, rash and multiorgan involvement, which usually occurs within the first weeks of introduction of an antiepileptic drug. It mimics several life-threatening diseases, which makes it potentially difficult to recognize. We describe the case of a 6-year-old boy admitted with anticonvulsant hypersensitivity syndrome after the association of lamotrigine treatment with sodium valproic acid for reluctant epilepsy.

Purpose of Review: A number of studies over recent years have shown the relevance of nonimmediate immunological reactions to drugs and emphasized the need for these reactions to be studied in greater depth, including both in-vivo and in-vitro tests and provocation studies., Recent Findings: Several clinical entities are involved, ranging from mild to severe reactions. Nonimmediate reactions have a special tropism for the skin, although other organspecific or systemic reactions may also occur. In the affected organ, the drug acts as a hapten or protohapten, originating an immunological stimulus that is followed by recruitment of T lymphocytes and other types of cells, depending on the reaction. This involves a trafficking phenomenon in which these cells use different receptors that interplay with their corresponding ligands in the tissue. In addition, a number of activation and cytotoxic markers are also expressed, which are related with disease severity., Summary: Current studies provide overwhelming evidence of the interaction between the organ involved, very often the skin, and immunocompetent cells. This is of relevance for diagnostic and therapeutic approaches.

Purpose of Review: Nonimmediate reactions to beta-lactams include several clinical entities, from maculopapular rash to severe reactions such as Steven-Johnson syndrome. Toxic epidermal necrolysis and organ-specific reactions may also occur., Recent Findings: Progress has been made in understanding the role of the immunological system in nonimmediate reactions to beta-lactams. Different T-cell subsets recognize beta-lactams after haptenation of serum or cell proteins in the context of major histocompatibility complex. Studies using T-cell lines and clones have shown that a heterogeneous response is generated, with the expression of different cytokine profiles. Betalactams also act on dendritic cells, inducing changes that enable them to interact with naïve lymphocytes, becoming memory T cells. Tissue-activated CD4 and CD8 cells express perforin and other cytotoxic mediators that elicit the lesions. Studies on the clinical course of these entities indicate that cells migrate, establishing a recirculation with homing to the skin and back to the circulation. These cells thus participate not only in skin lesions but probably also in the repair process., Summary: Understanding the immunological mechanisms involved in nonimmediate reactions to beta-lactams has improved over the last few years, with better definition of the different T-cell subpopulations involved. Experimental studies and monitoring of the response support the implication of different cell subsets.

Purpose of Review: The present review addresses the most recent literature regarding the diagnosis of drug hypersensitivity reactions, which can be classified as immediate or nonimmediate according to the time interval between the last drug administration and the onset. Immediate reactions occur within 1 h; nonimmediate ones occur after more than 1 h., Recent Findings: Clinical and immunological studies suggest that type-I (IgE-mediated) and type-IV (cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. New diagnostic tools, such as the basophil activation test and the lymphocyte activation test, have been developed and are under validation., Summary: In diagnosis, the patient's history is fundamental; the allergologic examination includes in-vivo and in-vitro tests selected on the basis of the clinical features. Prick, patch, and intradermal tests are the most readily available forms of allergy testing. Determination of specific IgE levels is still the most common in-vitro method for diagnosing immediate reactions. The sensitivity of allergologic tests is not 100%; in selected cases, therefore, provocation tests are necessary. The routine use of the basophil activation test and the lymphocyte activation test could increase the sensitivity of diagnostic work-ups, thus reducing the need for drug provocation tests.

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.