Allergy to Insulin Products May Occur in 2% of Patients

Insulin-related allergic reactions are rare (2%) but are very important because insulin is a life-saving medications for many patients.

Historical perspective

- The first insulin reaction was reported in 1922 - a callus at the injection site of insufficiently purified bovine insulin (from cow).

- Porcine insulin is less allergenic than bovine insulin.

- Recombinant insulin has the same amino sequence as human insulin and led to a large decrease in adverse reactions.

Insulin itself may not be the allergen

Prevalence of allergic reactions to insulin products is 2% but less than 30% of these are related to the insulin itself. Reactions occur due to the preservatives added to insulin such as zinc, protamine, and meta-cresol.

Types of allergic reactions

Allergic reactions can be:

- type I or IgE-mediated - most common and can, rarely, cause anaphylaxis
- type III or Arthus
- type IV or delayed-type hypersensitivity reactions occur after a delay of several days

Classification of adverse drug reactions (ADR)(click to enlarge the image).

Investigations include:

- skin prick testing
- patch testing
- intradermal testing
- skin biopsy

Desensitization protocol for insulin allergy

A negative skin test would be helpful in the evaluation of an immediate hypersensitivity reaction to insulin. Unfortunately, a positive skin test is not helpful because approximately 40% of patients on insulin therapy can have a positive response in the absence of clinical allergy.

IgE and IgG to insulin also play a diagnostic role in various protocols but have no definitive diagnostic significance.

This is a desensitization protocol for insulin allergy from the textbook, "Patterson's Allergic Disease," edition 6, 2002, edited by Grammer and Greenberger, pages 360-2:

Drug allergy management in 5 steps (click to enlarge the image).


Insulin allergy. Mohammad K. Ghazavi, MD, Graham A. Johnston, MBChB, FRCP. Clinics in Dermatology, Volume 29, Issue 3, Pages 300-305 (May 2011).
Successful desensitization with human insulin in a patient with an insulin allergy and hypersensitivity to protamine: a case report
Clinical and Molecular Allergy | Full text | Insulin allergy and resistance successfully treated by desensitisation with Aspart insulin
Desensitization for Insulin Allergy: A Useful Treatment Also for Local Forms
A rational clinical approach to suspected insulin allergy: status after five years and 22 cases - Bodtger - 2004 - Diabetic Medicine - Wiley Online Library
Insulin allergy: clinical manifestations and management strategies - Heinzerling - 2008 - Allergy - Wiley Online Library

Image source: Wikipedia, public domain.

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