Arthus reaction to lepirudin, a new recombinant hirudin, and delayed‐type hypersensitivity to several heparins and heparinoids, with tolerance to its intravenous administration

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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.