Q:

Referred patient with chronic renal failure, asthma, hypertention, IDDM who was placed on procrit. After 1st injection, developed nasal congestion. After 2nd injection, asthma symptoms & localized hives. Suggestions on evaluation?

A:

Thank you for your recent inquiry.

Unfortunately I do not have any definitive suggestions for you. The literature is very sparse in this area, and although anaphylactic reactions have been noted to epoetin-alpha, I could find no case reports describing these events, no skin test protocols, and the only reported desensitization I could find was not a protocol designed for an IgE-mediated event, but rather for a case of acute exanthematic pustulosis.

Nonetheless, I have sent you this reference in case there was a decision to try and readminister an erythropoietic agent.

However, there is one other possible strategy that may be of benefit to you. If such an agent needs to be administered, you have other options. Erythropoietin agents do differ structurally, and these differences may well have effects on their immunologic cross-reactivity. I have copied below the chemical descriptions of Aranesp compared to Procrit, and as you can see, there are distinct differences which have resulted in differences in molecular weight.

In addition, I have copied below an abstract of an article which discusses these differences. Thus, you may consider administering an alternative erythropoietic agent such as Aranesp. You might also consider diluting both drugs and skin testing to both prior to any attempt to do so, and if you do decide to do so, I would perform a graded challenge perhaps starting with a 1:100,000 dilution of the agent that is going to be administered.

Except for these comments, I have no other suggestions for you, and I am sorry that none of these are truly definitive in nature.

Nonetheless, thank you again for your inquiry.

Reference:
Desensitization of epoetin-α in a confirmed case of acute exanthematic pustulosis Allergy
F. J. Ruano, ALLERGY Volume 64, Issue 12, pages 1797-1798, December 2009

Chemical Descriptions of Aranesp and Procrit:

Aranesp is an erythropoiesis stimulating protein, closely related to erythropoietin, that is produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Aranesp is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains (Egrie 2001). The 2 additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone. The additional carbohydrate chains increase the approximate molecular weight of the glycoprotein from 30,000 to 37,000 daltons. Aranesp is formulated as a sterile, colorless, preservative- free protein solution for intravenous (IV) or subcutaneous (SC) administration.

PROCRIT (epoetin alfa) is a 165-amino acid erythropoiesis-stimulating glycoprotein manufactured by recombinant DNA technology. It has a molecular weight of approximately 30,400 daltons and is produced by mammalian cells into which the human erythropoietin gene has been introduced. The product contains the identical amino acid sequence of isolated natural erythropoietin.

Abstract:
Curr Med Res Opin. 2003;19(5):430-2. Epoetins: differences and their relevance to immunogenicity. Haselbeck A.
Source
Roche Diagnostics GmbH, D-82372 Penzberg, Germany. anton.haselbeck@roche.com
Abstract
Recombinant human erythropoietin (epoetin) is a highly active molecule and as such is used at very low therapeutic concentrations that require stabilisation. Commercially available epoetins differ in the stabilisers used in their formulations, which result in variations between epoetin preparations in storage and handling requirements. The stability and solubility of the epoetins are also affected by differences in the carbohydrate moieties that exist between them. However, it is the difference in stabilising agents that is thought to be the major cause of the upsurge in pure red cell aplasia (PRCA) cases observed predominantly with one epoetin alfa formulation, Eprex (Johnson & Johnson). In 1998 the European formulation of Eprex was changed with the replacement of human serum albumin (HSA), by polysorbate 80 and glycine. This formulation change coincided with an increased incidence of PRCA. In contrast, the incidence of PRCA has remained low with other HSA-containing epoetin alfa products and with epoetin beta. Therefore, it appears that the change in Eprex formulation has resulted in reduced protein stability and increased immunogenicity.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology