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Critical Reviews™ in Therapeutic Drug Carrier Systems
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ISSN Druckformat: 0743-4863
ISSN Online: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v18.i6.50
40 pages

Complement Activation-Related Pseudoallergy Caused by Liposomes, Micellar Carriers of Intravenous Drugs, and Radiocontrast Agents

Janos Szebeni
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue Silver Spring, MD 20910-7580


There is growing awareness that numerous drug-induced immediate hypersensitivity reactions (HSRs) do not fit in Gell and Coombs’ Type I category of drug allergies, characterized by the pivotal pathogenic role of allergen-specific IgE. Such non-IgE-mediated “pseudoallergic” reactions are primarily caused by (1) certain liposomal formulations of intravenous drugs and imaging agents, (2) infusion liquids containing micelle-forming amphiphilic lipids or synthetic block-copolymer emulsifiers, and (3) iodinated radiocontrast media with limited solubility in water. Common features of the latter “pseudoallergens” include the capacity to activate the complement (C) system; also, the symptoms they cause are often typical manifestations of excessive anaphylatoxin generation in blood. Hence, these reactions have been called “C activation-related pseudoallergy” (CARPA). The present review surveys the experimental and clinical evidence for the involvement of C activation in HSRs caused by pseudoallergens in the above three categories. To fit CARPA within the classical scheme of HSRs, a subdivision of Type I allergy is proposed on the basis of the mechanism of mast cell (and basophil) activation. The new scheme distinguishes direct and receptor-mediated HSRs, with the latter category subdivided to true IgE-mediated allergy; anaphylatoxin-mediated CARPA; and IgE plus anaphylatoxin double-triggered reactions. Further issues addressed in the review include animal models, risk factors, laboratory predictive tests, and pharmacological prevention of CARPA.

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