Anaphylaxis to intravenous cyclosporine and tolerance to oral cyclosporine: case report and review

Background: Hypersensitivity reactions to cyclosporine are rare. The mechanism of the reaction and guidelines for subsequent use of cyclosporine are not well defined. Objective: To investigate the mechanisms involved in hypersensitivity reactions to cyclosporine and determine the feasibility of future cyclosporine use. Methods: We report a patient who had an anaphylactic reaction during the intravenous infusion of cyclosporine. Skin-prick tests were performed for the antibiotics he received earlier in the day and the cyclosporine. A MEDLINE search identified all the reported cases of hypersensitivity reactions to cyclosporine. Each was analyzed to determine a mechanism of the hypersensitivity reaction and subsequent management outcomes. Results: Intradermal tests to intravenous cyclosporine formulation (1 mg/mL) were positive in the patient and negative in two controls. There was no reaction to the antibiotics. The Literature search revealed 22 cases of hypersensitivity reaction to cyclosporine. The clinical setting and diagnostic evaluation suggest multiple mechanisms for the hypersensitivity response. All seven patients who were given an oral formulation of cyclosporine tolerated it well after a reaction to the intravenous infusion. Two patients who initially reacted to an oral solution formulation subsequently tolerated the corn oil-based soft gelatin capsule. Conclusions: Hypersensitivity reactions to cyclosporine are due to Cremophor EL. There is direct and indirect evidence for various immunologic and nonimmunologic pathways precipitating the reaction. This case suggests a role for IgE in the hypersensitivity reaction. Fortunately, a hypersensitivity reaction to one formulation of cyclosporine does not preclude use of a different formulation. The corn oil-based soft gelatin capsule appears to be the safest formulation.