Type IV hypersensitivity to subcutaneous heparin: A new case

A 71-year-old woman was seen for cutaneous lesions that appeared on her abdomen 15 days after the beginning of subcutaneous injection of nadroparin calcium (Fraxiparina(R)), a low molecular-weight heparin (LMWH). The lesions were very pruriginous, measured 0.5-3 cm, and appeared at and around the point of Fraxiparina(R) injection. Fraxiparina(R) treatment was stopped and the lesions subsided spontaneously in one week. The patient had been treated with intravenous heparin (H) one year before. A 6 mm punch biopsy showed spongiosis and a mild dermal superficial perivascular infiltrate composed of lymphocytes and eosinophils. A challenge test with a therapeutic dose of Fraxiparina(R) produced a lesion similar to those described above. Epicutaneous, prick and intradermal tests with undiluted samples of different H (both preservative-containing and preservative-free) were performed. Patch tests produced a mild erythematous reaction to all H at 48 hours and a (++) reaction at 96 hours. These reactions persisted for one week. Prick tests showed neither an immediate nor a delayed reaction. Intradermal tests with H did not produce an immediate reaction, but induced an infiltrated erythematous reaction at 48 hours that enlarged during the next 2 days and was transformed into pruritic plaques with vesicles. The lesions cleared in two weeks. Our findings confirm a delayed-type hypersensitivity to H and cross-reactivity between unfractioned and LMWH.