A case of insulin allergy: the crystalline human insulin may mask its antigenicity.

We report an unusual case of insulin allergy. A 48-year-old man with non-insulin-dependent diabetes mellitus receiving biosynthetic isophane human insulin (Humulin N) developed itchy wheal-and-flare reactions at the sites of injection. When Humulin N was changed to a semi-synthetic crystalline human insulin zinc (Novolin U), the allergic reactions completely disappeared. Evaluation of his serum showed a high level of insulin-specific IgE. Skin testing with all commercially available insulins showed immediate local reactions to all agents tested except for Novolin U. In addition, decrystallized Novolin U prepared by lowering the pH with acetic acid also induced a positive reaction. These observations suggest that the crystallized structure of human insulin may mask its antigenicity for allergic reactions.