The complexities of insulin allergy: a case and approach

Abstract

Background Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). Case presentation A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. Conclusions Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective.

Case report: Insulin desensitization as the only option for managing insulin allergy in a Sudanese patient

“…Omalizumab (an anti-IgE monoclonal antibody) has been used to induce tolerance to insulin in a number of cases ( 7 ). Pancreatic transplantation has been reported as a last resort.…”

“…The more recent insulin analogs showed even fewer reactions ( 5 ). While impurities were the main cause of insulin-related allergies in the past, in the era of modern insulin analogs, allergic reactions can result from protamine sulfate, preservatives like cresol and phenol, or the insulin molecule itself ( 6 , 7 ).…”

“…Systemic steroids have been used, but the evidence is slightly weak. Omalizumab is a monoclonal antibody that has been approved for use in some IgE-mediated conditions and may be used in difficult cases of insulin allergy ( 7 ).…”

Research progress on albumin-based hydrogels: Properties, preparation methods, types and its application for antitumor-drug delivery and tissue engineering

“…There is a large body of research on albumin-based hydrogels, but very little of the research has been translated into clinical application. Nowadays, there are many albumin products on the market, such as Abraxane ® , Fyarro ® , Idelvion ® , Tresiba ® , Victoza ® , Levemir ® and so on ( Yardley, 2013 ; Aberumand and Jeimy, 2021 ; Li and He, 2022 ; Pasca and Zanon, 2022 ; Zhou et al, 2022 ). But, very few albumin-hydrogel products are listed among them.…”

Rituximab Therapy for Insulin Allergy in Type-1 Diabetes Mellitus

“…However, up to 2.4% of insulin-treated patients can still be affected, with varied presentations from immediate type-1 IgE-mediated reactions to delayed type-3 immune complex-mediated and type-4 IgG-mediated reactions. 1 Interestingly, less than one-third of these reported events are related to the insulin molecules, with the remainder attributed to the noninsulin components such as zinc, protamine, and metacresol in the preservatives. In particular, type-4 reactions seem to occur with the noninsulin components, whereas the type-1 reactions seem to occur with both insulin and noninsulin elements.…”