Evaluation of allergologic tests in exanthematous drug eruptions after application of mesna

Background: Serious adverse drug reactions (ADR) have been reported after application of mesna, used for the prevention of cyclophosphamide-induced urotoxicity. Methods: In a multicenter study, 12 patients who had developed exanthematous drug eruptions (EDE) in possible association with the application of mesna and 76 controls were evaluated allergologically by means of skin tests, in vitro lymphocyte transformation and cytokine secretion as well as oral provocation tests in selected patients. The 76 controls included patients with malignancies and autoimmune diseases with and without previous mesna application as well as atopic and normal controls. Results: Patients with mesna-associated EDE had developed pruritic macular, papular or urticarial rashes lasting several days. Positive skin test reactions to mesna were found in 4/12 patients with mesna-associated EDE in the patch test, and in 1/8 patients in the skin prick test. In the intradermal test, immediate reactions to mesna 1% were positive in 4/5 of patients with EDE but also in 7/16 normal controls, whereas delayed reactions (24-72 hrs) to mesna were only observed in patients with EDE (3/9). Single-blind oral provocation tests resulted in maculo-papular and urticarial rashes or gastrointestinal symptoms in 4/8 patients. After stimulation with mesna, laboratory tests revealed an increased lymphocyte proliferation (stimulation index >2) in 3/7 patients with EDE, however, positive reactions were also found in 17/58 controls, though with lower stimulation indices. Cytokine profiles of all Th₁, Th₂ and Th₀ subsets could be detected. Conclusions: From the results of this study it is concluded that delayed skin test reactions both in intradermal and patch tests are highly specific for patients with mesna-associated EDE. Skin testing may therefore be recommended for allergy diagnosis of mesna-associated EDE, which share features of type IV hypersensitivity reactions.