Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors

Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study

BACKGROUND: Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. METHODS: Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. RESULTS: Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. CONCLUSIONS: These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors

Clinical practice: Drug desensitization in children

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids

Diclofenac Hypersensitivity: Antibody Responses to the Parent Drug and Relevant Metabolites

Background: Hypersensitivity reactions against nonsteroidal antiinflammatory drugs (NSAIDs) like diclofenac (DF) can manifest as Type I-like allergic reactions including systemic anaphylaxis. However, except for isolated case studies experimental evidence for an IgE-mediated pathomechanism of DF hypersensitivity is lacking. In this study we aimed to investigate the possible involvement of drug-and/or metabolite-specific antibodies in selective DF hypersensitivity. Methodology/Principal Findings: DF, an organochemically synthesized linkage variant, and five major Phase I metabolites were covalently coupled to carrier proteins. Drug conjugates were analyzed for coupling degree and capacity to crosslink receptor-bound IgE antibodies from drug-sensitized mice. With these conjugates, the presence of hapten-specific IgE antibodies was investigated in patients' samples by ELISA, mediator release assay, and basophil activation test. Production of sulfidoleukotrienes by drug conjugates was determined in PBMCs from DF-hypersensitive patients. All conjugates were shown to carry more than two haptens per carrier molecule. Immunization of mice with drug conjugates induced drug-specific IgE antibodies capable of triggering mediator release. Therefore, the conjugates are suitable tools for detection of drug-specific antibodies and for determination of their anaphylactic activity. Fifty-nine patients were enrolled and categorized as hypersensitive either selectively to DF or to multiple NSAIDs. In none of the patients' samples evidence for drug/metabolite-specific IgE in serum or bound to allergic effector cells was found. In contrast, a small group of patients (8/59, 14%) displayed drug/metabolite-specific IgG. Conclusions/Significance: We found no evidence for an IgE-mediated effector mechanism based on haptenation of protein carriers in DF-hypersensitive patients. Furthermore, a potential involvement of the most relevant metabolites in DF hypersensitivity reactions could be excluded

Early members of ‘living fossil’ lineage imply later origin of modern ray-finned fishes

Modern ray-finned fishes (Actinopterygii) comprise half of extant vertebrate species and are widely thought to have originated before or near the end of the Middle Devonian epoch (around 385 million years ago). Polypterids (bichirs and ropefish) represent the earliest-diverging lineage of living actinopterygians, with almost all Palaeozoic taxa interpreted as more closely related to other extant actinopterygians than to polypterids. By contrast, the earliest material assigned to the polypterid lineage is mid-Cretaceous in age (around 100 million years old), implying a quarter-of-a-billion-year palaeontological gap. Here we show that scanilepiforms, a widely distributed radiation from the Triassic period (around 252–201 million years ago), are stem polypterids. Importantly, these fossils break the long polypterid branch and expose many supposedly primitive features of extant polypterids as reversals. This shifts numerous Palaeozoic ray-fins to the actinopterygian stem, reducing the minimum age for the crown lineage by roughly 45 million years. Recalibration of molecular clocks to exclude phylogenetically reassigned Palaeozoic taxa results in estimates that the actinopterygian crown lineage is about 20–40 million years younger than was indicated by previous molecular analyses. These new dates are broadly consistent with our revised palaeontological timescale and coincident with an interval of conspicuous morphological and taxonomic diversification among ray-fins centred on the Devonian–Carboniferous boundary. A shifting timescale, combined with ambiguity in the relationships of late Palaeozoic actinopterygians, highlights this part of the fossil record as a major frontier in understanding the evolutionary assembly of modern vertebrate diversity

Global Priorities for Conserving the Evolutionary History of Sharks, Rays, and Chimaeras

In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates—the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct—further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life