title: The complex clinical picture of side effects to biologicals.
abstract: Biologicals are proteins used as drugs. Biologicals target clearly defined molecular structures, being part of established pathogenetic pathways. Therefore, their focused mode of action seems to render them superior to classic small molecular drugs regarding "off-target" adverse drug reactions (ADR). Nevertheless, the increasing use of biologicals for the treatment of different diseases has revealed partially unexpected adverse reactions. The often direct interaction of a biological with the immune system provides a clue to most side effects, which have consequently been subclassified, based on pathogenetic principles, into 5 subtypes named alpha, beta, gamma, delta, and epsilon, reflecting overstimulation (high cytokine values, type alpha), hypersensitivity (type beta), immune deviation (including immunodeficiency, type gamma), cross-reactivity (type delta), and nonimmune mediated side effects (type epsilon). This article presents typical clinical manifestations of these subtypes of ADR to biologicals, proposes general rules for treating them, and provides a scheme for a thorough allergological workup. This approach should help in future handling of these often very efficient drugs.
authors.affiliation: Department of Rheumatology, Clinical Immunology and Allergology, Inselspital, University of Bern, Bern 3010, Switzerland. oliver.hausmann@insel.ch
authors.forename: Oliver V
authors.initials: OV
authors.lastname: Hausmann
authors.forename: Michael
authors.initials: M
authors.lastname: Seitz
authors.forename: Peter M
authors.initials: PM
authors.lastname: Villiger
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Pichler
mesh_terms: D000328:Adult; D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001691:Biological Therapy / Q000009:adverse effects*; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E; D007155:Immunologic Factors / Q000009:adverse effects*; D018417:Th1 Cells; D018418:Th2 Cells; D015262:Xenobiotics / Q000009:adverse effects*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D007155:Immunologic Factors; D015262:Xenobiotics; D007073:Immunoglobulin E