A Case of Insulin Allergy Due to Zinc

Local cutaneous hypersensitivity reactions (erythema, induration and pruritis) after injection of Lente insulin in a 43-year-old female were investigated using semisynthetic human insulin (Novo) and its vehicle. Intradermal skin tests for any of the commercially available insulin preparations including human Monotard insulin and its vehicle were positive. The degree of erythema and induration parallelled the zinc contenet of the insulin preparations. The patient's insulin allergy was thus indicated to be caused by the zinc in the insulin preparations. Intradermal skin tests also suggested that her local pruritis was ascribable to phenol and glycerol in the insulin preparations. The erythema and pruritis disappeared following application of ointment containing diphenhydramine and hydrocortisone, and using N.P.H.-insulin whose zinc content is the lowest among intermediate I insulin preparations. However, the induration was not ameliorated by these treatments. The dose of intermediate insulin to normalize the patient's blood glucose (30 units/day) was relatively high compared to usual Japanese noninsulin dependent diabetics, and 16 units day of Lente insulin was sufficient to normalize her blood glucose before a local cutaneous reaction appeared. These findings suggested insulin malabsorption and/or degradation at the injection site. However, measurements of the plasma IRI and glucose after subcutaneous insulin injection with or without aprotinin and intramuscular insulin injection (N.P.H.-insulin, 20 u) did not explain this possibility.