Desensitization in patients with hypersensitivity to iron. Report of two cases.

Elizabeth Garcia, Edgardo Chapman, Leidy Alvarez and Monica Duarte Leal Drixie

Contact email: eligarcia.gomez@gmail.com

Summary

Introduction

Iron deficiency anemia is a type of anemia characterized by hyposideremia, whose

most frequent origin is related to blood losses of gynecological or gastrointestinal

origin, the intake of non-steroidal analgesics or absorption and nutritional

disorders. Its treatment includes handling it with iron substitution intravenously.

Presentation of cases

Patients of 20 and 46 years of age diagnosed with secondary iron deficiency

anemia hipermenorreas with a history of failed treatment with oral iron, who

presented a reaction of the anaphylactic type while they receive iron parenteral

sucrose, to whom the desensitization protocol applied for patients with

hypersensitivity to iron was successful.

Discussion

Iron deficiency anemia is a disease that can significantly compromise the quality of

life of the sufferer. The desensitization protocol for patients with hypersensitivity to

iron is a safe and effective treatment option for patients for whom management is

required with intravenous iron with a history of allergy to the medicine.

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Conclusion

This case report shows the usefulness of carrying out the desensitization protocol

for patients with hypersensitivity to iron.

Keywords: Iron deficiency anemia - Hypersensitivity - Intravenous Iron - allergy

INTRODUCTION

Iron deficiency anemia is one of the entities of great interest worldwide, due to the

great relationship that it has with nutritional deficiencies and the compromise to the

quality of life that can be generated by its symptoms.

In a WHO study conducted between 1992- 2005 it was estimated that the

worldwide prevalence of anemia was 24.8%, corresponding to 50% of cases of iron

deficiency anemia. Recently Kassebaum and colleagues published a meta -

analysis reviewing the burden of anemia worldwide between 1990 and 2010, which

recorded that more than 30% of the population has anemia continuing as the main

root cause of iron deficiency1.

At present iron treatment is standardized and is considered an effective and safe

therapeutic measure, however, they have identified cases of allergic reactions after

its administration in all its forms.

It is known that 25% of all adverse reactions correspond to iron hypersensitivity

reactions and that although rare, they can be fatal. The incidence rate and relative

risk of occurrence of allergic reactions to intravenous iron have not been

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determined, because of their rarity, but it is estimated that 1 in every 5 million

doses of intravenous iron applied, have allergic reactions, with a mortality in the US

of 3 deaths per year 2–4

The parenteral iron therapy would be indicated in patients with intolerance or

breach of the oral iron therapy, partial response or absent from the oral iron

therapy, malabsorption of the bowel (inflammatory bowel disease, previous

gastrointestinal surgery), peptic ulcer, active bleeding, postoperative deprivation of

oral diet, perioperative anemia, functional iron deficiency, treatment with

erythropoiesis stimulating agents and specific types of anemia: anemia in

nephrology patients, anemia associated with neoplasia or chemotherapy, anemia

during pregnancy and the postpartum period 5.

Currently we do not have standardized desensitization protocol for this drug, this

review shows two cases of patients with reactions to the intravenous presentation

of iron, whom performed the desensitization of intravenous iron according to

protocol illustrated in another case report already described 4,6,7

DESCRIPTION OF THE CASE

Case 1:

A 20 years old patient, who consulted for hypermenorrhea, diagnosed with

secondary iron deficiency anemia. Treated by the hematology and gynecology, for

one year with hormonal treatment and oral iron, achieving the control of the

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hypermenorrhea but with a persistent iron deficiency and a gastrointestinal

intolerance to the drug (gastritis, constipation). Treatment with parenteral iron

sucrose was ordered after presenting 10 minutes of administration anaphylactic

type reaction: abdominal pain, urticarial, angioedema and dysphonia skin lesions.

Case 2:

A 46-year-old patient diagnosed with secondary iron deficiency anemia to uterine

fibroids hypermenorrhea associated with poor gastrointestinal absorption disorders

and vitamin B12 deficiency, who received treatment with oral iron for about 2 years

without a hematologic response. So a treatment begun with intravenous iron

sucrose, presenting after 5 minutes: urticarial, angioedema, back pain and

dyspnea.

Table 1. Paraclinical for income.

Case HB HTO VCM HCM CHCM Ferritin Iron

1 12.9 39 90.7 30.1 33.2 6.4 70
2 9.8 32 74.5 22.7 30.5 5.5 50
* HB: hemoglobin, HTO: hematocrit, MCV: MCV, MCH: mean corpuscular

hemoglobin, MCHC: hemoglobin, TIBC Total iron binding capacity.

In both cases the persistence of anemia associated with compromise to the quality

of life given by: intense fatigue, weakness, dizziness, he must use parenteral Iron

so a Protocol of desensitization iron sucrose was performed.

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PROTOCOL

The desensitization protocol starts with a hospitalization 48 hours before the start

of the procedure to provide systemic steroids, antihistamines and anti-leukotrienes

(Table 2). The patient is hospitalized in the intensive care unit with continuous

monitoring. An hour before starting the procedure, an intravenous dosage of 80 mg

of methylprednisolone and 25 mg of hydroxyzine are supplied. 10 doses of iron

sucrose are administered with progressive advancements the in concentration, a

dose every 15 minutes. The procedure starts with an intravenous iron sucrose

supply of 0.1 mg to complete a cumulative dose of 100 mg (Table 3).

Table 2. Treatment prior to the procedure

Drug name Presentation Dose

administered
Prednisone 50 mg tablets 50 mg orally

every 24 hours
Cetirizine 10 mg tablets 10 mg orally

every 12 hours
Montelukast 10 mg tablets 10 mg orally

every 12 hours

Table 3. Desensitization protocol for parenteral iron

Number of Mg delivered Amount, ml Time, min

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 dosages
DOSE 1 0.1 mg 0.1 15
DOSE 2 0.2 mg 0.2 15
DOSE 3 0.5 mg 0.5 15
DOSE 4 1 mg 1 15
DOSE 5 2 mg 2 15
DOSE 6 5 mg 5 15
DOSE 7 10 mg 10 15
DOSE 8 20 mg 20 15
DOSE 9 50 mg 50 15
DOSE 10 100 mg 100 30

In both cases the procedure is completed without complications. It is prescribed

cetirizine 10 mg orally every 12 hours and montelukast 10 mg orally every 12 hours

to continue daily for the rest of the hospitalization and proceeds to continue the

administration of iron daily in equal doses to complete the estimated deficit for the

patient.

In both cases the supply of 1400 mg intravenous iron sucrose in total was required

to meet their requirements. The daily supply of 200 mg intravenous of this drug the

first of 20 mg intravenous in 30 minutes was performed in the hospital in two

doses, and no reaction after 180 mg remaining were applied in 4 hours.

In neither cases secondary allergic reactions occurred. However it should be made

it clear in the medical history that in case of having symptoms that suggest a

hypersensitivity reaction in any instance of the procedure, the drug would be

stopped and the treatment described in (Table 4) will start. and once the reaction

is exceeded they should continue with the previously tolerated dose.

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Table 4. Treatment recommendations by clinical symptoms

Symptom Treatment.
Urticarial and / or Metilprednisolona

angioedema 80 mg IV* +

hydroxyzine 25 mg

Iv
Anaphylaxis* Adrenalin 1/1000,

0.3 mg IM *
* IV: Intravenous, IM: intramuscular, anaphylaxis: defined by urticaria and / or

angioedema + cough, dyspnea, abdominal pain, hypotension, hypo perfusion,

commitment of consciousness.

Table 5. Indications for daily administration of iron

DOSE 1 DOSE 2
20 mg IV in 15 Apply 180 mg after

minutes 30 minutes with no

reaction to previous

dose

DISCUSSION

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The reactions after the administration of intravenous iron can be divided into acute

(immediately after start of infusion), delayed (from one hour to one day after the
3,4,7
infusion), or late (days after administration)

Factors have been identified that are associated with an increased risk of a

hypersensitivity reaction to the drug and its degree of severity such as: history of

previous reaction to intravenous iron, the rapid pace of infusion, severe heart or

respiratory disease, mastocytosis, old age, beta-blockers or ACE inhibitor, severe

asthma or eczema8.

Today it is already known that there is a greater susceptibility to allergic reactions

with intravenous iron with the presentation orally, that because the medicine goes

directly into the blood fluid and does not pass by way of hepcidin - ferroportin to

intestinal level protects against iron overload and regulates the metabolism of
2,9
elemental iron making is slowly released during erythropoiesis

Hypersensitivity reactions can be recognized based on the symptoms and signs of

the patient and can range from mild itching, flushing, hot flashes, hypertension,

back pain or joint pain, mild cough, chest tightness, mild dyspnea, tachycardia and

hypotension in the presence of severe anaphylaxis. The initial reaction can worsen
10
quickly generating a high risk of mortality .

There are two cases of patients with anaphylactic reactions to iron parenteral

sucrose, in which the events occurred after the first contact with the drug, with a

reaction of the anaphylactic type, and where the drug is essential to treat the

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disease, before the evidence of no response to oral treatment, which is required to

implement a desensitization protocol achieving the expected response.

Patients were informed that the drug desensitization induces a transient,

immunological tolerance to a maximum of 48 hours after the last dose is given.

Clarifying that if there is a need to use the drug past this time, the procedure must

be done again.

CONCLUSION

These case reports reflect the utility of using the desensitization protocol in patients

with hypersensitivity to iron, when it has not been possible by other treatments to

recover the hemoglobin level and the mean corpuscular volume and to replenish

iron deposits.

STATEMENTS

Acknowledgements: none.

Conflict of interest: The authors of this publication declare no conflict of interest.

Availability of data and materials: there are no digital record of the medical

records of the patients as part of the case reports.

Contribution of the authors: all authors were involved in the care of the patients,

making and the editing of the document.

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Consent for publication: This case report does not have any confidential

information of patients, images or videos. An informed consent was filled out with

each patient for this publication.

Ethical considerations and authorization of publication: A document validated

by the institutional ethics committee of Santa Fe de Bogota Foundation, which was

the location of the cases reported.

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