Journal Information
Vol. 33. Issue. 1.January 2013
Pages 1-154
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Adverse reaction to intravenous iron: hypersensitivity or secondary side effect?
Reacción adversa por la administración intravenosa de hierro: ¿hipersensibilidad o efecto secundario?
Ana E. Sirvent-Pedreñoa, Ricardo Enríquez-Ascarzaa, M. Dolores Redondo-Pachóna, Isabel Millán-del Vallea, César González-Martineza, Francisco Amorós-Amorósa
a Servicio de Nefrología, Hospital General Universitario de Elche, Elche, Alicante,
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To the Editor:

 The replacement of iron is necessary in patients on haemodialysis due to the chronic blood loss that occurs when this technique is employed.1 The intravenous administration of iron is not, however, free from adverse effects. Amongst these, we distinguish certain predictable reactions (an undesired consequence of the pharmacological actions of iron, such as side effects) from unpredictable reactions (in subjects with sensitivity of the immune system or susceptible to reactions such as hypersensitive and anaphylactoid reactions).2 The latter are less common and more serious, and may require suspension of the drug. We describe the case of an adverse reaction to the intravenous administration of iron that manifested as a burning sensation of the tongue, an inadequately defined sensation of peribuccal hyperaesthesia and generalised pruritus.

The patient is a 42-year-old woman who began a haemodialysis programme by right jugular tunnelled catheter following bilateral nephrectomy due to hypernephroma. In the postoperative period, the patient required a transfusion of 2 units of packed red blood cells. Ten days later a test showed: haemoglobin: 9.6g/dl, haematocrit 28.4, mean corpuscular volume: 87.1fl; iron: 56µg/dl, ferritin 233ng/ml; transferrin saturation index: 18%; folic acid: 22ng/ml vitamin B12: 921pg/ml; C-reactive protein: <5mg/l; Kt/V: 1.7. She was treated with omeprazole, vitamin B complex, folic acid and 30µg of darbepoetin weekly. 100mg of iron sucrose (Venofer®) was administered intravenously an hour after haemodialysis. 15 minutes after starting infusion, the patient complained of generalised pruritus, a burning sensation of the tongue and peribuccal hyperaesthesia. Physical examination: blood pressure 100/60mmHg, heart and lung auscultation normal, no lesions of the skin. Iron administration was discontinued and the symptoms gradually disappeared. In the following attempt, the patient was premedicated with dexchlorpheniramine and paracetamol. The reaction was identical and also it occurred with ferric carboxymaltose (Ferinject®). The Allergology Service was consulted: the patch test was negative for both iron preparations; the episode was compatible with the side effect. Clinical manifestations reappeared in a weaker form with the successive administrations of iron without major implications.

The rate of adverse effects associated with the administration of various preparations of intravenous iron (high and low molecular weight iron dextran, ferrous gluconate, iron sucrose) is approximately 38 per million.3 The pruritus associated with ferric carboxymaltose is described as isolated and infrequent (1/100-1000 of patients);4 it seems to be present upon the first administrations and subsequently dissapears.5 The symptoms described by the patient as a burning sensation of the tongue and peribuccal hyperaesthesia, although subject to subjective assessments, did not correspond to the neurological disorders commonly described as paraesthesia or taste disorders4. The clinical profile that our patient presented seemed to signal an anaphylactoid reaction which was not confirmed. Generally speaking, reactions secondary to intravenous iron have been attributed to rapid infusion with an oversaturation of transferrin and the release of free iron, which is responsible for toxicity and vasomotor reactions.6 This limited the total dose of iron administered and the rate of infusion in older formulations. Although ferric carboxymaltose is in this sense better tolerated, there are few studies comparing it to the rest of the formulacions.7 Furthermore, the potential development of severe, even fatal adverse effects remains a source of concern. Many of these reactions have been associated with high molecular weight iron dextran preparations and seem to have an immunological base1,7. However, controlled clinical trials for different intravenous iron preparations are limited by design to detect rare adverse effects as they are conducted in a small number of patients over short follow-up periods.1,2

Given the manifestation of infrequent side effects, it is vitally important that the intensity and seriousness of the reaction be established since this may require the permanent suspension of the drug, with the resulting limitation of the therapeutic arsenal available.


Conflicts of interest

The authors declare that they have no conflicts of interest related to the contents of this article.







Nefrología (English Edition)

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