title: Arthus reaction to lepirudin, a new recombinant hirudin, and delayed-type hypersensitivity to several heparins and heparinoids, with tolerance to its intravenous administration.
abstract: The pathogenesis of allergic reactions to heparin is poorly understood. Clinically, this phenomenon is relevant because of its increasing incidence and the resulting therapeutic challenges due to various cross-reactions between unfractionated and low-molecular weight heparins as well as between heparins and heparinoids. A 44-year-old female patient had developed a delayed-type hypersensitivity to certoparin-sodium. Diagnostic allergy testing revealed various cross-reactions between different heparins as well as an intolerance to heparinoids. After subcutaneous challenge with the recombinant hirudin lepirudin (Refludan) the patient developed a local Arthus reaction at the injection site. In general, recombinant hirudins do not cross-react with high- or low-molecular weight heparins and heparinoids because of a different molecular structure and are therefore an alternative in case of adverse reactions to heparins and heparinoids. Whereas a local Arthus reaction has already been described twice for low-molecular weight heparins, this is to the best of our knowledge the first observation of a superficial leukocytoclastic vasculitis due to s.c. applied lepirudin. Intravenous administration of heparins and heparinoids in case of hypersensitivity to these drugs following topical application risks a generalized eczematous reaction in patients with delayed-type allergy to both groups of substances. In our patient with delayed-type hypersensitivity to heparins and heparinoids and superficial vasculitis due to lepirudin, the intravenous challenge with heparin and a heparinoid was justified as an ultima ratio measure and proved to be the useful therapeutical alternative.
authors.affiliation: Department of Dermatology, Institute of Immunology, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany. Uta_Jappe@med.uni-heidelberg.de
authors.forename: U
authors.initials: U
authors.lastname: Jappe
authors.forename: D
authors.initials: D
authors.lastname: Reinhold
authors.forename: B
authors.initials: B
authors.lastname: Bonnekoh
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects*; D001183:Arthus Reaction / Q000209:etiology*; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects*; D006496:Heparinoids / Q000008:administration & dosage* / Q000009:adverse effects*; D006629:Hirudins / Q000009:adverse effects* / Q000031:analogs & derivatives*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D007262:Infusions, Intravenous; D011183:Postoperative Complications / Q000517:prevention & control; D011994:Recombinant Proteins / Q000009:adverse effects*; D013923:Thromboembolism / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D006496:Heparinoids; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; C083544:lepirudin