title: Complement activation-related pseudoallergy caused by liposomes, micellar carriers of intravenous drugs, and radiocontrast agents.
abstract: 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.
authors.affiliation: Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington DC 20307, USA.
authors.forename: J
authors.initials: J
authors.lastname: Szebeni
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D003287:Contrast Media / Q000009:adverse effects*; D016503:Drug Delivery Systems / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000276:immunology*; D006801:Humans; D007275:Injections, Intravenous / Q000009:adverse effects; D008081:Liposomes / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology; D008823:Micelles; D012307:Risk Factors; D012997:Solvents / Q000009:adverse effects
chemical_list: D003287:Contrast Media; D008081:Liposomes; D008823:Micelles; D012997:Solvents