Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics

Andrade, Pedro; Barros, Luísa; Gonçalo, Margarida

doi:10.1590/s0365-05962012000600018

Cited by 8 publications

(10 citation statements)

References 7 publications

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“…The importance of insulin allergy relies on its fundamental role as a lifelong treatment. Several cases have been documented on diabetic patients, allergic to Glargine [ 32 , 33 ], Detemir [ 34 , 35 ], Crystalline [ 14 , 36 ], NPH [ 14 , 37 ], Aspart [ 14 ], Lispro [ 33 ], all available insulins [ 8 , 12 , 15 , 38 ], and even components of such medications such as metacresol [ 24 ] and protamine [ 10 , 19 , 33 ], with or without presence of beta-lactam antibiotic allergy [ 12 ]. Clinical presentation varies, from local cutaneous lesions to anaphylactic shock, either IgE- or IgG-mediated [ 39 ]; see Figure 1 .…”

Section: Discussionmentioning

confidence: 99%

Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

Rojas

Villalobos

Martínez

et al. 2014

Case Reports in Immunology

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Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM). Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS), further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

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Section: Discussionmentioning

confidence: 99%

Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

Rojas

Villalobos

Martínez

et al. 2014

Case Reports in Immunology

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“…At subcutaneous injection sites, urticaria-like lesions, pain, erythema, and desquamation may occur within minutes (11,12). However, these may disappear in a few minutes to a few hours.…”

Section: Diagnosismentioning

confidence: 99%

“…A positive response may be obtained with provocation using a small dose, such as 2 U. Compared to insulins of animal origin, insulins produced by recombinant DNA technology have a lower risk of reaction (11).…”

Section: Diagnosismentioning

confidence: 99%

Insulin Allergy

Erdenen¹,

Kantarci²

2016

Istanbul Med J

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Insulin hypersensitivity reactions have been reported in both type 1 and type 2 diabetic patients. Some of these reactions stem from insulin itself, while some result from additive agents. Although reactions to all types of insulin can develop, reactions to human insulin and its analogues are rare. However, vital reactions can be observed. Previously used bovine and porcine insulins are known to be more immunogenic, and reactions to these types of insulin are more commonly observed. Due to the development of the purification process, the rate of these reactions has decreased considerably, from 30%-1% (1, 2). One-third of these reactions are associated with insulin, while the remaining reactions result from different substances that are added to the preparations. The allergic reaction types are named Type I, Type III, and Type IV (1-4). Skin reactions occurring at the injection site reduce the effects of exogenous insulin, stimulate insulin degradation, and/or impair insulin absorption. Thus, diabetes regulation also deteriorates (5).In addition to human insulins (NPH and regular insulins), analogues (lispro, aspart, glargine, detemir, glulisine, and degludec) may also induce allergic reactions. Stimulants may be an epitope of insulin itself and may also be changed by an antigenic epitope during production and purification. During subcutaneous degradation of insulin, different antigenic structures may be formed. Zinc and protamine are added to insulin to extend the duration of action, while metacresol and various contaminants are added as preservatives; these may cause reactions (1, 2). The commercially available insulin types and the additives they contain are presented in Table 1. Protamine is a cationic substance found in fish sperm; it is added to delay the release of insulin from the injection site. Exposure to protamine is a risk factor for allergy. Although fish allergies and vasectomy are believed to create risks in this regard, this situation was found to be only partly significant; no other relationships with other insulin types were observed, and no risk was found in a prospective study (3). However, protamine allergies and long-time use of insulin create risk for the production of insulin antibodies. In poorly controlled diabetes, this possibility should be considered. Although autoantibodies against protamine-heparin complex have been found, the relationship between insulin antibodies and protamine is not clear. This relationship is particularly significant in intermediate and rapid-acting insulins; the relationship between analogue insulins and autoantibodies was found to be contradictory. The time of insulin use, not the duration of diabetes, is significant. Protamine causes the formation of autoantibodies, probably by causing a change in the conformation of insulin. Also, cross-reactivity between human protamine and salmon protamine in insulin or the development of an immunologic response to salmon protamine can cause an allergic reaction. The amount of protamine found in NPH and insulin aspart is...

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“…There are various reports in the literature describing reactions that have been attributed to excipients within insulin (i.e. protamine, [14][15][16][17][18][19] meta-cresol 1,14,15,17,[20][21][22][23] and zinc [14][15][16][17][18][19]23,24 ). In addition, the bacteria utilized during the manufacturing process has been speculated to act as a potential antigen.…”

Section: Introductionmentioning

confidence: 99%

“…25 Due to the presence of case reports describing hypersensitivity reactions to specific excipients, clinicians may feel inclined to attribute hypersensitivity reactions from HIAs to these components, rather than considering the possibility that it may be the actual HIA itself. 17,25 Prior insulin exposure warrants consideration when discussing insulin hypersensitivity reactions as this may increase a patient's risk for developing a hypersensitivity reaction to HIAs. 14,28 The higher immunogenicity of older insulins and the potential for the development of higher antibody levels with long-term insulin use may affect tolerability of HIAs.…”

Section: Introductionmentioning

confidence: 99%

Hypersensitivity reactions to human insulin analogs in insulin-naïve patients: a systematic review

Bzowyckyj

Stahnke

2017

Therapeutic Advances in Endocrinology

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Objective: The objective of this study was to raise awareness of hypersensitivity reactions to human insulin analogs (HIAs) in insulin-naïve patients and encourage consistent and detailed reporting of HIA reactions. Data sources: A search of PubMed, MEDLINE and International Pharmaceutical Abstracts using the terms 'insulin' and 'hypersensitivity' was completed with English language, humans, and publication date after 1 January 1990 as limits. Study selection and data extraction: The initial search identified 598 articles. These titles and abstracts were reviewed for relevance (e.g. mention of HIA) resulting in the exclusion of 477 articles. The full texts of the remaining titles were evaluated in addition to each article's references to identify additional reports meeting criteria (n = 14). Upon extensive review, 118 articles were excluded for not meeting prespecified inclusion criteria, resulting in 17 articles. Data synthesis: Evidence supporting hypersensitivity reactions to HIAs was variable, potentially due to a variety of causes (e.g. difficulty identifying a true case of hypersensitivity reaction to HIAs). Inconsistencies were noted for the identification, confirmatory testing, management, and reporting of these reactions. Management strategies included use of insulin desensitization protocols, antihistamines, steroids, immunosuppressant/immunomodulator therapies, conversion to noninsulin therapies, and pancreas transplantation. Conclusions: Complete and consistent identification, evaluation, management, and reporting of these reactions is essential. Specific aspects of the patient's history should be reported, including previous insulin exposure, the specific HIAs used, duration of use prior to the reaction, a clear timeline of the reaction, and discussion of precipitating events or confounding factors.

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Type 1 Ig-E mediated allergy to human insulin, insulin analogues and beta-lactam antibiotics

Cited by 8 publications

References 7 publications

Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

Insulin Allergy

Hypersensitivity reactions to human insulin analogs in insulin-naïve patients: a systematic review

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