Allergy to insulin has become rare with human recombinant insulin or its analogs, with an estimated incidence of <1%. The most common clinical situation is related to the type I allergic reaction in the Gell and Coombs classification and usually consists of a local wheal-and-flare eruption at injection site with induration, pruritus, and burning sensation that appear a few minutes after the injection and last for 1–2 h; this reaction is rarely systemic, with urticaria, angioedema, or anaphylactic shock. Insulin can also be infrequently responsible for a late type III Arthus’ reaction, characterized by the development of subcutaneous nodules at the injection site 2–6 h after administration (1). And last, insulin allergy may be rarely related to a type IV T-cell–mediated delayed reaction that appears 8–12 h after injection, peaks at 24 h, and lasts for several days with painful, itchy, local mononuclear infiltration.
To our knowledge, we report the first case of type III allergy to the new long-acting insulin analog detemir. A 31-year-old man with type 1 diabetes for 20 years was admitted for uncontrolled diabetes. He had no history of any allergy. He had been treated by glargine (Lantus; Sanofi-Aventis) once daily and aspart (Novorapid; Novo Nordisk) before each meal for 2 years. We decided to switch insulin glargine for detemir to optimize glycemic control. Six hours after the first injection of detemir, the patient presented a subcutaneous small, subdermal, nonpruriginous, slightly painful nonerythematous nodule with central hematoma at injection site (left arm). On the 2 following days, the same localized reaction occurred 4–6 h after the detemir injection (right arm, left thigh), although no reaction to aspart was noticed. Local factors such as poor injection technique, misuse of insulin injector, or use of impure alcohol were ruled out. Detemir was then switched back for glargine. The nodules spontaneously disappeared in ∼48 h.
We did not perform skin tests because of the explicit clinical presentation of a type III allergy and because of the potential risk of serum sickness after reintroducing detemir. However, we cannot exclude that an excipient rather than insulin detemir itself could be responsible for this allergy. Nevertheless, the only additive present in detemir preparation and not in glargine or aspart preparations is mannitol, and allergy to mannitol is exceptional and related to IgE-mediated anaphylaxis (type I reaction) (2). To our knowledge, we report here the first case of allergy with insulin detemir.
