Insulin allergy is an increased sensitivity of the immune system to insulin and protein impurities present in the drug, manifested by the development of a local or systemic allergic reaction when a minimum amount of bovine, porcine or human insulin is administered. More often there are local reactions with the appearance of edema, itching, soreness at the injection site, less often – systemic manifestations of insulin allergy in the form of urticaria, angioedema, anaphylactic reaction. Diagnostics includes the study of an allergic history, laboratory tests (histamine levels, specific immunoglobulins, etc.). Treatment: antihistamines, insulin change, desensitization.
Insulin allergy is an increased reaction of the immune system to repeated parenteral administration of insulin preparations. In most cases, an allergic reaction is local and manifests itself in the form of itching, compaction, soreness at the injection site. Systemic reactions are rare, characterized by skin manifestations (urticaria, Quincke’s edema), anaphylaxis. Insulin allergy is observed in 5-30% of diabetic patients, decreasing with the transition to modern purified drugs (DNA-recombinant human insulin) and strict adherence to the technology of drug administration.
In the treatment of diabetes mellitus, various insulin preparations (bovine, pig, human) are used, differing in the degree of purification and the content of protein or non-protein impurities. Basically, allergic reactions occur to insulin itself, much less often – to protamine, zinc and other substances contained in the drug.
The smallest number of allergic reactions is observed when using various types of human insulin, the largest – when injecting animal insulins. The most immunogenic is bovine insulin, the difference between which and human is most pronounced (two other amino acid residues of the A-chain and one of the B–chain). Pig insulin has less allergenicity (the difference is only in one amino acid residue of the B-chain). The number of cases of insulin allergy has significantly decreased after the introduction of highly purified insulins into clinical practice (the proinsulin content is less than 10 mcg/g).
The development of local reactions may be associated with improper administration of drugs (intradermally, with a thick needle and the associated excessive traumatization of the skin, incorrect choice of injection site, strongly cooled drug, etc.).
Hypersensitivity to the administered drugs is formed with the participation of antibodies of various classes. Early local allergic reactions and anaphylaxis are usually caused by immunoglobulins E. The occurrence of local reactions 5-8 hours after the administration of insulin preparations and the development of insulin resistance are associated with IgG. An allergy to insulin that develops 12-24 hours after administration of the drug usually indicates an allergic reaction of a delayed type (to insulin itself or to zinc present in the drug).
Symptoms of insulin allergy
Insulin allergy is more often manifested by the development of mild local hypersensitivity reactions, which may occur 0.5-1 hour after administration of the drug and quickly disappear (early reactions), or 4-8 hours (sometimes 12-24 hours) after injection – delayed, late reactions, clinical manifestations of which may persist for several days.
The main symptoms of a local allergic reaction are redness, swelling and itching at the injection site. Itching can be local, moderate, sometimes it becomes unbearable and can spread to neighboring areas of the skin. In some cases, traces of scratching are noted on the skin. Sometimes a seal may appear at the site of insulin injection, towering over the skin (papule) and persisting for 2-3 days.
In rare cases, prolonged administration of insulin preparations to the same area of the body can lead to the development of local allergic complications like the Arthus phenomenon. At the same time, itching, painful compaction at the injection site may appear 3-5-10 days after the start of insulin administration. If injections continue to be made in the same area, an infiltrate is formed, which gradually increases, becomes sharply painful and can be suppurated with the formation of an abscess and purulent fistulas, an increase in body temperature and a violation of the general condition of the patient.
Insulin allergy with the development of systemic, generalized reactions occurs in 0.2% of patients with diabetes mellitus, while more often clinical symptoms are limited to the appearance of urticaria (hyperemia, itchy blisters at the injection site), even less often – the development of angioedema Quincke or anaphylactic shock. Systemic reactions are usually associated with the resumption of insulin therapy after a long break.
The diagnosis of insulin allergy is based on a thorough study of the data of the allergological history (the specific relationship between the administration of insulin preparations and the appearance of hypersensitivity symptoms), the characteristic clinical picture, the data of the patient’s examination by an allergist-immunologist, endocrinologist, dermatologist and other specialists.
Standard clinical studies are conducted to assess the general condition of the body and the level of compensation for diabetes mellitus, the level of general and specific immunoglobulins is determined, as well as other studies used in practical allergology to exclude allergic reactions of other etiology.
In specialized institutions, skin allergy tests can be carried out with the introduction of microdoses of various types of insulin. With an intradermal test, an insulin solution is injected at a dose of 0.02 ml (dilution of 0.004 units / ml), the skin reaction is evaluated after an hour by the severity of hyperemia and the size of the papule that has appeared.
Insulin allergy should be differentiated from other allergic diseases, pseudoallergic reactions, viral infections, skin diseases, itching in renal failure and lymphoproliferative diseases, neoplasms.
Treatment of insulin allergy
With mild local hyperreactions, which quickly (within a few minutes, a maximum of an hour) pass on their own, additional therapeutic measures are not required. If the changes persist for a long time, become more pronounced after each injection of insulin, it is necessary to prescribe antihistamines, and insulin injections are recommended to be done in different parts of the body in fractional doses. If the insulin allergy persists, it is necessary to use pork or human insulin, which lacks zinc. A complete transition to the introduction of purified human insulin will be optimal.
With the development of systemic reactions (urticaria, Quincke’s edema, anaphylaxis), it is necessary to provide emergency care with the introduction of adrenaline, glucocorticosteroids, antihistamines, maintaining the function of blood circulation and respiration. Complete cancellation of insulin therapy in these situations is impractical, it is possible to temporarily reduce the amount of injected insulin by 3-4 times and gradually increase the dose to the average therapeutic dose within 2-3 days.
If insulin therapy has been discontinued for 2-3 days or more, it is necessary to check the sensitivity to a particular drug by conducting skin tests and determining the type of insulin that causes allergic reactions to the least extent. After that, desensitization (ASIT) is necessary with the introduction of the minimum first dose of insulin and a gradual increase in dosages. Such a therapeutic approach is possible only in the conditions of a specialized endocrinological or allergological hospital.
Sometimes, with the ineffectiveness of desensitization, the need for insulin therapy and the presence of signs of anaphylaxis, purified human insulin is administered together with glucocorticosteroid hormones (hydrocortisone) in one syringe in small doses intramuscularly.
Prognosis and prevention
When replacing the insulin preparation with a less purified one, the signs of allergy disappear. In rare cases, severe systemic allergic reactions are possible. Prevention consists in the correct selection of insulin preparations and their timely replacement in case of allergic reactions. To do this, patients should be aware of the manifestations of insulin allergy and ways to stop undesirable effects.