Continuous Subcutaneous Insulin Infusion to Resolve an Allergy to Human Insulin

Insulin allergy has increasingly decreased with the use of human recombinant insulin and is now reported in <1% of diabetic patients treated with insulin (1,2). Different methods have been used in the treatment of insulin allergy, such as the use of oral antihistaminics, the addition of glucocorticoids to insulin, the change to lispro insulin, which has proven to be less allergenic in several cases (3), as well as different models of desensitization. We report a patient with generalized allergy to insulin who was successfully treated with a continuous subcutaneous insulin infusion system.

A 43-year-old man (weight 65 kg, BMI 21.9 kg/m²) was diagnosed as having type 1 diabetes in October of 1998. He had no other diseases and no history of any allergy. He began treatment with human insulin (regular and NPH). Shortly after initiating treatment, he developed a local reaction at the injection site (pruritus, erythema, and swelling) 15–20 min after the injection, which subsided within 1–2 h. This reaction appeared 4–5 times a week and was tolerated without treatment. In June 2000, he developed a systemic reaction 5 min after insulin injection (generalized urticaria), which resolved with an H1 antihistamine. In July 2000, he used lispro insulin sporadically, and the same reaction ensued. Systemic reaction reappeared on two other occasions in September and December 2000. In January 2001, he was admitted to our hospital to evaluate a possible insulin allergy. Physical examination was normal. Leukocytes were within the normal range (6.10 × 109/l), but there was eosinophilia (0.73 × 109/l). Total IgE was 20.1 KU/l (n <100). The specific human insulin IgE antibody (CAP-SYSTEM; Pharmacia, Upssala, Sweden) was 123 KU/l (n <0.35). Skin-prick tests (5 UI/ml) were performed with human insulin and insulin lispro, as well as with additives of insulin preparations (protamine, paraben, metacresol, phenol, zinc, and isophane) using the Novo Insulin Allergy Kit (Novo Nordisk). The patient tested positive for all types of insulin and negative for additives and was thus diagnosed with insulin allergy. Because the local reactions were moderate and he had not received previous treatment, daily oral antihistamine therapy (mizolastine) was initiated. During the first week with mizolastine, the local reaction improved, but it reappeared with every injection during the second week. At the beginning of February 2001, systemic reaction recurred (generalized urticaria with facial and periorbital angioedema), coinciding with an omission of the mizolastine. Because of the increase in the intensity of the local reaction, despite the antihistaminic, treatment with an insulin pump with insulin lispro was started to achieve insulin tolerance by continuous insulin infusion. This therapy schedule involved a basal line (0.7 IU/h for 2–8 h, 0.3 IU/h for 8–13 h, 0.6 IU/h for 13–18 h, 0.8 IU/h for 18–21 h, and 0.6 IU/h for 21–22 h) and an additional bolus (6IU before breakfast, 5IU before lunch, and 6IU before dinner). The allergic reaction immediately disappeared, and optimal metabolic control was achieved. Skin-prick tests remained positive 3 months later, although the patient remained clinically asymptomatic.

To date, two cases of allergy to human insulin treated with an insulin pump have been reported (1,2). In one case, previous desensitization with human insulin injected every 2 h failed. In the other case, desensitization was achieved with an insulin pump. In our case, the insulin allergy was successfully treated with the insulin pump at therapeutic doses without previous desensitization. Continuous basal infusion may therefore induce tolerance of additional doses of preprandial insulin, despite these doses being similar to those that previously produced allergic reaction upon subcutaneous injection. Thus, the insulin pump may be useful as an alternative treatment in insulin allergy.