Skin Rash Appearing in a Patient with Gestational Diabetes Mellitus on Insulin Therapy

A 39-year-old woman, healthy by nature, was diagnosed with gestational diabetes mellitus (GDM) at 27 weeks of pregnancy. Despite dietary modifications and self-monitoring of blood glucose, glucose control was inadequate. Therefore, treatment with insulin detemir and insulin lispro injections was initiated at 30 weeks gestation. A few days after this, erythema and induration with pruritus appeared at the abdominal puncture site, and three weeks later spread on the bilateral lower legs (Figure. 1A, 1B). In blood tests, total IgE was at 25.8 IU/mL (<360), which was not appreciably elevated. However, at 10.1 U/mL (reference value: <0.4) and 1.19 UA/ml (FEIA method, reference value: <0.35), respectively, non-specific insulin antibody and human insulin-specific IgE titration were both high. Since switching from lispro to aspart did not improve symptoms, insulin detemir was changed to neutral protamine Hagedorn (NPH). Antihistamines were not used due to her refusal. The skin rash disappeared about one weeks after the change to NPH, and the baby was delivered by Cesarean section at 39 weeks gestation. Her blood glucose levels improved promptly after delivery, and insulin therapy was terminated. She was diagnosed with insulin allergy. Most insulin allergy is explained by an IgE-mediated type I allergy mechanism. Its frequency is relatively low: 0.1-3% of diabetic patients receiving insulin therapy [[1]Jacquier J. Chik C.L. Senior P.A. A practical, clinical approach to the assessment and management of suspected insulin allergy.Diabet Med. 2013; 30: 977-985https://onlinelibrary.wiley.com/doi/10.1111/dme.12194Crossref PubMed Scopus (32) Google Scholar]. Insulin allergy in GDM is extremely rare due to immune tolerance occurring during pregnancy [[2]Pazos M. Sperling R.S. Moran T.M. Kraus T.A. The influence of pregnancy on systemic immunity.Immunol Res. 2012; 54: 254-261https://link.springer.com/article/10.1007/s12026-012-8303-9Crossref PubMed Scopus (181) Google Scholar]. To our knowledge, there have only been about 10 cases so far. Insulin allergy rarely causes anaphylaxis, which has not been reported in GDM possibly due to immune tolerance. The causative agents of the allergy are thought to be insulin itself and the preservatives added to insulin, including zinc, protamine, and meta-cresol [[1]Jacquier J. Chik C.L. Senior P.A. A practical, clinical approach to the assessment and management of suspected insulin allergy.Diabet Med. 2013; 30: 977-985https://onlinelibrary.wiley.com/doi/10.1111/dme.12194Crossref PubMed Scopus (32) Google Scholar]. It has been reported that the average total IgE level is higher in GDM compared to uncomplicated pregnancy [[3]Sifnaios E. Mastorakos G. Psarra K. Panagopoulos N.D. Panoulis K. Vitoratos N. Rizos D. Creatsas G. Gestational Diabetes and T-cell (Th1/Th2/Th17/Treg) Immune Profile.Vivo. 2019 Jan-Feb; 33: 31-40https://iv.iiarjournals.org/content/33/1/31.longCrossref PubMed Scopus (0) Google Scholar], which may have triggered the present insulin allergy. In the present case, both nonspecific insulin antibodies and human insulin-specific IgE were elevated, leading to the diagnosis of insulin allergy. There are various treatments for allergic reactions to insulin [[1]Jacquier J. Chik C.L. Senior P.A. A practical, clinical approach to the assessment and management of suspected insulin allergy.Diabet Med. 2013; 30: 977-985https://onlinelibrary.wiley.com/doi/10.1111/dme.12194Crossref PubMed Scopus (32) Google Scholar]. Antihistamines and corticosteroids are used to relieve symptoms. It is also important to change the insulin to another type. In addition, subcutaneous insulin desensitization therapy may be considered in some cases [[1]Jacquier J. Chik C.L. Senior P.A. A practical, clinical approach to the assessment and management of suspected insulin allergy.Diabet Med. 2013; 30: 977-985https://onlinelibrary.wiley.com/doi/10.1111/dme.12194Crossref PubMed Scopus (32) Google Scholar]. Oral hypoglycemic agents, such as metformin, are available for GDM in only some countries, and insulin treatment is generally chosen. Therefore, for maternal and fetal safety, insulin allergy in GDM patients should be promptly diagnosed from precise visual examination and testing.