Insulin Allergy: The Allergist's Updated Approach to Evaluation and Management

The transformative discovery of insulin in the early 20th century followed by its rapid clinical implementation was initially complicated by high rates of hypersensitivity reactions. Improvements in purification methods and the transition from animal-derived sources to human insulin products has significantly lowered, although not eliminated, hypersensitivity reactions to insulin. Although considered rare adverse reactions to insulin, hypersensitivity reactions and immune-mediated manifestations continue to occur in patients requiring insulin treatment. This has broad implications given that approximately 11.6% of the US population has a diagnosis of diabetes and 8.4 million Americans rely on insulin for survival. Because of the scope and impact of insulin as a life-saving treatment for patients with diabetes, it is important for allergists to evaluate, provide a diagnose for, and manage patients with hypersensitivity reactions to insulin appropriately. Recognizing early manifestations of insulin hypersensitivity is the first step in providing prompt and targeted management in these complex cases. The following article aims to summarize the allergist's recommended approach to insulin hypersensitivity reactions, including type I IgE-mediated and type III immune-complex mediated reactions, type IV T-cell mediated hypersensitivity reactions, as well as additional immune-mediated manifestations of insulin therapy such as lipoatrophy and insulin autoantibodies. Furthermore, the authors emphasize approaching insulin hypersensitivity cases with a broad differential diagnosis, which includes hypoglycemia, anaphylaxis mimics, hypersensitivity to excipients and medical devices, and cutaneous manifestations of diabetes.