Q:

9/13/2012
I have read some literature suggesting that adverse reactions to iv iron preparations are primarily non Ige mediated and are possibly anaphylactoid in nature.

I was wondering if there is any role in pre medicating patients with steroids plus or minus antihistamines with prior history of immediate adverse reactions to IV iron preparations as opposed desensitizing patients to these preparations.

A:

Thank you for your inquiry.

As you can see from the abstracts copied below, the mechanism(s) of production of reactions to iron is/are unknown. There have been very few studies of the mechanism(s) involved in these reactions. However, as you mentioned, the weight of evidence suggests that they are not IgE-mediated.

It is not unexpected therefore that they, like non-IgE-mediated reactions to radiocontrast material, might be prevented by a pretreatment regimen of antihistamines and corticosteroids. This has been done successfully on a few occasions. I have copied the references for you (some with complete abstracts) below.

There is also, as you can see, one reference where “desensitization” has been accomplished successfully as well.

Thank you again for your inquiry and we hope this response is helpful to you.

Ann Allergy. 1994 Mar;72(3):224-8.
Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis.
Novey HS, Pahl M, Haydik I, Vaziri ND.
Source
Department of Medicine, University of California, Irvine.
Abstract
Systemic reactions resembling anaphylaxis have occurred after intravenous (IV) iron-dextran administration, a treatment modality that has acquired increased acceptance following the use of erythropoietin for the anemia of patients with chronic renal diseases. Three such patients sustained anaphylactoid reactions immediately after receiving IV test doses of iron-dextran which were their only known exposures. In an effort to determine the mechanism of their reactions, we applied tests for (1) basophil degranulation by iron-dextran, basophil histamine release; (2) a type I anaphylactic reaction, specific IgE antibodies; and (3) an immune complex activation, specific IgG antibodies against iron-dextran. Six other patients with renal diseases served as controls, three of whom had tolerated IV iron-dextran, and three without known exposure. One patient only had any test abnormalities. Her initial positive basophil histamine release and specific IgG antibodies reversed and declined respectively at a 4-month follow-up study. She had developed anaphylaxis, and her studies had been performed at a time after anaphylaxis earlier than the other two. The mechanisms of iron-dextran anaphylaxis may be multiple and not be detectable several months after the incident. Prospective studies will probably be required for a predictive test to be developed.

J Investig Allergol Clin Immunol. 2008;18(4):305-8.
Anaphylaxis to oral iron salts. desensitization protocol for tolerance induction.
de Barrio M, Fuentes V, Tornero P, Sánchez I, Zubeldia J, Herrero T.
Source
Allergy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Abstract
Allergies to iron salts are seldom reported. We studied a patient with iron-deficiency anemia who had suffered anaphylactic reactions caused by oral iron salts. An allergy study was performed using single-blind, placebo-controlled oral challenge and skin tests with various iron salts as well as excipients in commercial formulations. Oral challenges were positive for 2 of the commercial formulations of iron salts. Intradermal tests with ferrous sulphate and ferrous lactate also showed positive results. All of the cutaneous tests using the excipients were negative. A desensitization protocol was designed which enabled us to readminister ferrous sulphate, although antihistamines were necessary to guarantee good tolerance to iron salts. We report a patient with allergy to iron salts, positive skin tests, and positive controlled challenge. We highlight the desensitization protocol designed to complete the therapeutic management of the anemia.

Minerva Pediatr. 2006 Dec;58(6):571-4.
Successful desensitization of a case with desferrioxamine hypersensitivity.
Gülen F, Demir E, Tanaç R, Aydinok Y, Gulen H, Yenigün A, Can D.
Source
Division of Allergy , Department of Pediatrics, Faculty of Medicine, Ege University, Izmir, Turkey.
Abstract
Thalassaemia major is a severe chronic hemolytic disease, resulted with iron overload mainly due to regular blood transfusions. Iron overload may lead to serious organ toxicity and even fatal complications, if no iron excretion is achieved by a chelating agent. First introduced in 1976 as s.c. treatment for thalassaemia major, desferrioxamine (DFO) has substantially improved the life expectancy in the disease. While DFO can cause local allergic reactions including redness, itching, pain and lumps, on rare occasion anaphylactic reactions can occur. The mechanism of anaphylaxis like reactions is not well understood. In this case report, we presented a 10 years-old girl with thalassaemia major who had to stop DFO therapy after appearing of systemic allergic reactions with hypotension, tachycardia, pruritus and urticaria against this drug. Serum IgE level was normal, specific IgE and skin prick tests were negative. Intradermal test was resulted with positive reaction to DFO. The patient was hospitalized and desensitization protocol was initiated with rapid s.c. infusions per 15 min. The protocol was stopped at the 17th cycle because of local reaction reappeared. After that, DFO was further diluted and was restarted with lower dosage and longer infusion period. Then, DFO dosage was increased and the dilutions and infusion times were decreased gradually. By this desensitization programme, the patient would continue to use DFO chelation safely for 10 months.

South Med J. 1994 Oct;87(10):1010-2.
Safe administration of iron dextran to a patient who reacted to the test dose.
Monaghan MS, Glasco G, St John G, Bradsher RW, Olsen KM.
Source
Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205.
Abstract
Parenteral iron therapy is infrequently required but generally well tolerated. We present a case in which intravenous iron dextran was successfully given to a patient who had an anaphylactoid reaction to the test dose. After pretreatment with methylprednisolone, diphenhydramine, ephedrine, and dextran 1, 2 g of iron dextran were safely given over several days; pretreatment was administered only on day 1. In the rare cases in which an anaphylactic agent must be given to a patient with a history of a life-threatening reaction to the agent, pretreatment along with slow escalation of dose may allow safe administration of the offending drug.

Successful Prevention of an Anaphylactoid Reaction to Iron Dextran
Leonard C. Altman, MD; and Penny E. Petersen, MD:
Ann Intern Med. 15 August 1988;109(4):346-347

Ann Allergy Asthma Immunol. 2000 Feb;84(2):262-3.
Successful administration of iron dextran in a patient who experienced a life threatening reaction to intravenous iron dextran.
Hickman MA, Bernstein IL, Palascak JE.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology