Thank you for your recent inquiry.
You are correct. The history is certainly not typical for an allergic reaction to insulin. Such reactions are of course pruritic, but are accompanied almost universally by urticaria. In addition, the symptoms almost always occur within one hour of the administration of insulin. It would be highly unusual for a reaction to persist as long as it has in your patient and not progress to urticaria. It would also be very unusual for an insulin induced response to occur so late after the administration of the drug.
We have no definitive knowledge about cross reaction between Lantus, Levemir, and NPH insulin, but normally, when a patient is allergic to the insulin molecule, they will have allergy to any form of insulin. On occasion, patients may be sensitive to non-insulin components in certain preparations (e.g., protamine) rather than the insulin molecule itself. In those instances, other forms of course can be substituted.
There is no large amount of data, to my knowledge, looking at cross reactivity between glargine insulin and other forms. However, there is one case of a 1-year-old with systemic allergy to insulin who reacted to numerous preparations, but was able to take glargine insulin without difficulty (1).
I am copying below previously posted inquiries along with our responses regarding two other questions we have received about insulin allergy in the last couple of years. I am sending these because of the bibliography contained therein in case you wish to read further about the topic.
However, the strategies for testing described in these postings would not, in my opinion, be necessary for your patient. If you obtained a negative skin test to a prick preparation (1 to 10 dilution), and an intradermal (1 to 100 dilution) of glargine insulin, you could most certainly rule out an allergy to this product. UNFORTUNATELY, A POSITIVE SKIN TEST TO EITHER OF THESE DILUTIONS WOULD NOT NECESSARILY INDICATE THE PRESENCE OF ALLERGY TO THIS PRODUCT. At least 40% of patients taking insulin preparations without adverse event will have a positive skin test to the preparation used. It simply indicates exposure. However, a negative skin test would give you a great deal of help in this regard.
In summary, the history you described is not consistent with insulin allergy to the best of my knowledge. There are no definitive data regarding cross reactivity between glargine and other insulin preparations. Patients reactive to the insulin molecule usually react to any preparation of insulin. However, there are exceptions to this rule as noted in the reference cited below (1).
Finally, a negative skin test as described would essentially rule out immediate hypersensitivity reaction to glargine insulin. Unfortunately, a positive skin test would give you no helpful information as to glargine insulin being the culprit.
Thank you again for your inquiry and we hope this response is helpful to you.
Reference:
1. Diabetes Care, April 2005; Volume 28, Number 4, pages 983-984.
8/26/2008
Q
What is the best testing method for diagnosing insulin allergy; specifically what dilution what you use for the id's and how strong of a dilution would you pursue if the initial weak dilutions are negative?
Also, for the desensitization, would you pre-medicate the patient with antihistamines and/or Singulair and what is the current protocol which is most recommended.
I could not find a recent reference which dealt with these specific issues; your assistance is greatly appreciated
A
Probably the reason you have not found a recent reference dealing with insulin allergy is because this problem has diminished in frequency since the institution of humanized and purified insulin preparations. However, the testing and desensitization protocol has remained essentially unchanged since some of the very earliest reports (1).
A more recent reference with a detailed description of the insulin desensitization schedule is found in Immunology and Allergy Clinics, November 1998. This was a volume on drug hypersensitivity edited by Dr. Steven Tilles. The chapter on Page 809, by Dr. Leslie Grammer, has a description of a typical desensitization protocol. The initial dose for desensitization should be selected by epicutaneous testing. Epicutaneous testing should be carried out with tenfold dilutions. One way to proceed would be to make such tenfold dilutions from an initial concentration of one unit per ml.
One could arbitrarily begin intradermal skin testing with a concentration of 0.0000001 units per ml using the tenfold dilutions made with saline. One likes to begin with a concentration that produces a negative test. Then intradermal tests continue with successive tenfold greater concentrations until the skin test becomes positive. One usually begins the desensitization process with the most concentrated dilution giving a negative skin test on intradermal testing. Then one would proceed using the schedule on Page 811 as a guide, as noted above.
Usually pretreatment with antihistamines and/or Singulair is not indicated.
As noted in the reference cited above, the desensitization process is ideally carried out over several days, and precautions should be in place for hypoglycemic reactions.
Another more recent reference which would be very helpful to you that discusses the desensitization process and testing can be found the textbook, "Patterson's Allergic Disease," edition 6,2002 edited by Grammer and Greenberger. A detailed section on insulin allergy, it's diagnosis and management appears on pages 360-2
11/11/2009
Q
Systemic reactions due to insulin, evaluation and treatment.
A
Thank you for your recent inquiry.
You will find a concise and yet complete discussion of systemic allergic reactions to insulin with the details of management on Pages 304 and 305 of Patterson's Allergic Diseases: Principles and Practice, 7th edition, edited by Drs. Leslie Grammer and Paul Greenberger. It is published by Lippincott Williams and Wilkins.
Also, a recent article in Allergy (see abstract copied below) is an excellent resource in this regard as well.
This response will also be posted on the Academy website.
Thank you again for your inquiry and we hope this response is helpful to you.
Abstract:
Allergy. 2008 Feb;63(2):148-55.
Insulin allergy: clinical manifestations and management strategies.
Heinzerling L, Raile K, Rochlitz H, Zuberbier T, Worm M.
Department of Dermatology and Allergy, Charité Universitätsmedizin, Berlin, Germany.
Insulin allergy in patients with diabetes mellitus on insulin treatment is a rare condition. It is suspected upon noticing immediate symptoms following insulin injections. The immediate vital implications for the patient call for prompt diagnosis and management of insulin allergy. We review current knowledge and procedures based on four diabetic patients who presented in our clinic. Insulin allergy was suspected as they showed immediate symptoms after insulin injection (urticaria, rash, angioedema, hypotension, dyspnea). A detailed allergologic work-up was performed and adequate therapy was initiated. In three of the four patients, a specific immunotherapy was started whereas in one patient a switch to oral antidiabetics was possible and consequently initiated. By standard prick testing and measurement of specific IgE antibodies, a type 1 IgE-mediated allergy was confirmed. After initiation of insulin immunotherapy, the symptoms completely resolved in two out three of patients and significantly improved in the third patient. The fourth patient was successfully switched to oral antidiabetics. Insulin allergy is a rare but severe condition that calls for immediate allergological work-up. It can be managed well in close cooperation between the diabetologist and the allergologist. Specific immunotherapy is efficient and should be considered.
Sincerely,
Phil Lieberman, M.D
KEY WORDS: insulin allergy,drug reaction, pruritus