Systemic insulin allergy is a rare condition and has usually been reported in adults. Human insulin analogs have been proposed for the treatment of insulin allergy (1,2). Here we report a 1-year-old infant with generalized allergy to insulin who has been successfully treated with the insulin analogs lispro and glargine. To our knowledge, this case subject is the youngest child reported with systemic insulin allergy and the only patient who was treated without any adverse event by glargine insulin in infancy.
A neonate girl, the first child of consanguineous parents, was born at full term after uneventful pregnancy. She was small for gestational age with a birth weight of 1,430 g. Although the infant had been fed properly from birth, she was presented with complaint of poor weight gain at 2 months of age. On admission, she weighted 1,700 g (below the third percentile) and appeared malnourished and dehydrated. The blood glucose concentration was 33.2 mmol, and there was no acidosis or ketonuria. HbA1c and C-peptide levels were 9.7% and <0.5 ng/ml, respectively. Anti-GAD and anti–islet cell antibodies were negative. The diagnosis of neonatal diabetes was established. The treatment with human NPH insulin (Humulin N; Lilly) was initiated. During subsequent 10-month follow-up, the patient demonstrated normal growth and development and HbA1c level decreased to 5.7%.
At 1 year of age, immediately after each insulin injection, she developed allergic reactions, including macular skin rush, pruritus, and dermographism, on her trunk and all injection sites. Although she had been treated with antiallergic drugs along with NPH insulin, the allergic reactions continued. Eosinophilia on peripheral blood smear was not detected, and the serum level of total IgE was 18 IU/ml (normal range <150 IU/ml). Unfortunately, tests for insulin-specific IgE and IgG were not performed. However, the patient demonstrated allergic reactions to different kinds of human insulin, including human regular insulin (Humulin R; Actrapid) and NPH insulin (Humulin N; Insulatard), not only following subcutaneous injection but also after intradermal test. Intradermal tests confirmed the insulin allergy.
Gradual insulin desensitization with low doses of regular insulin was not successful. We considered treating the patient with rapid-acting insulin analogs and examined skin reactions to lispro (Humalog; Lilly) and aspart (Novorapid; Novo Nordisk). Intradermal tests were negative for both. Lispro treatment was initiated, and no allergic reaction was observed. However, prolonged treatment of a 1-year-old infant with repeated injections of lispro four to five times a day was very difficult. We therefore decided to test the long-acting analog insulin glargine that would meet daily requirement of basal insulin. Skin tests were also negative with glargine insulin. Thus, the treatment with glargine insulin (Lantus; Aventis) was commenced with the permission of parents. The patient received bedtime glargine insulin (0.7 units · kg−1 · day−1) and, as needed, mealtime lispro insulin (0.1 units · kg−1 · day−1). This insulin regimen provided less hypoglycemic episodes than NPH insulin twice daily and achieved HbA1c values <7%. During the 6-month follow-up, we did not observe any allergic reaction or adverse event due to insulin glargine.
Insulin glargine has been used in the treatment of toddlers and children with type 1 diabetes (3). Because the systemic insulin allergy did not respond to the antihistaminic drug and desensitization therapies, we have inevitably used insulin glargine to treat the 1-year-old infant with neonatal diabetes. Once-daily dose of insulin glargine provided effective glycemic control and less hypoglycemic event and was well tolerated in our infant patient. This case indicates that the insulin analog glargine can be considered as a safe alternative treatment in very young children with allergic reactions to human recombinant insulin.