Iron III isomaltose induced hypersensitivity reaction

Abstract

Iron isomaltose is considered as safe form of iron with no test dose recommended. Here, we are describing the case of a patient who experienced allergic reaction with this formulation of iron. A 35-year-old South Asian woman experienced allergic reaction, she had mild wheeze on examination of chest. She was given intranasal oxygen at 2 L/min. She was given intravenous acetaminophen 1 g for pain relief, 45.4 mg intravenous chlorphenaramine and intravenous 100 mg hydrocortisone. Within half an hour, all her symptoms improved and her hypoxia resolved. Her chest wheezing also disappeared. Iron isomaltose, although relatively safe, can cause allergic reaction. Intravenous iron can cause allergic reaction therefore it should be administered at the facility where trained staff is present so that necessary treatment can be given in case of hypersensitivity reaction.

Background

Isomaltoside 1000 Monofer, is chemically modified isomaltose-oligosaccharides which have a mean molecular weight of 1000 Da and consist predominantly of 3–5 glucose units. The carbohydrate isomaltoside 1000 is a linear and unbranched structure with theoretically low immunological potential. Hence, a test dose is not necessary.^1–4 Iron isomaltoside 1000 contains strongly bound iron within the iron–isomaltoside formulation, a moiety where iron is in matrix which enables a controlled slow release of bioavailable iron to the iron-binding proteins with potentially reducing risk of free iron toxicity.⁴

Isomaltose 1000 Monofer, with the dose limit of up to 1800 has shown favourable in terms of safety profile and no adverse events usually.^{1 2 5} This is associated with its linear first order kinetics.⁶

Case presentation

A 35-year-old South Asian woman was admitted with complaints of shortness of breath on minimal exertion with no orthopnoea or paroxysmal nocturnal dyspnoea and no history of cough or chest pain. Patient history revealed that she was a vegetarian, since 5 years not having any history of menorrhagia or bleeding from any other site. She was pale on general physical examination but systemic examination was unremarkable. In laboratory workup, complete blood count showed haemoglobin of 59 g/L (normal range: in men 140 g/L and in women 150 g/L)⁷ and mean corpuscular volume of 57.4 fL/red cell in adult (normal range: for mean corpuscular volume are 87±7 fL)^{8 9} which found to be quiet low and peripheral film showed small-sized red blood cells compared with normal with increase central pallor suggestive of iron deficiency anaemia. It was decided to give her intravenous iron isomaltose. Based on her weight, she was injected 1200 mg diluted in 500 mL normal saline.¹⁰ Patient was awake, alert and haemodynamically stable before start of infusion. Post 15 min of initiation and 20 mL of infusion injected, she started complaining of severe backache, joint pain in all small joints and shortness of breath. On pain scale, she described it to be 8/10. The drug infusion was immediately stopped. Her vitals were assessed. She had a heart rate of 82/min, blood pressure of 125/74 mm Hg, temperature of 36.8°C and respiratory rate of 18/min. While oxygen saturation was slightly reduced at 90% on room air.

Investigations

Her baseline haemoglobin value was 59 g/L with haematocrit value of 23.3%. Iron studies were performed with results as follows: iron 10 µg/dL, total iron binding capacity 460 µg/dL, transferrin saturation 2.17% and ferritin 4.6 ng/mL. Her blood urea nitrogen 10 mg/dL and creatinine was 0.8 mg/dL. Haemoglobin electrophoresis was done. It did not reveal any haemoglobin disorders. Vitamin B₁₂ was 245 pg/mL.

Her symptoms suggested allergic reaction then after this reaction renal function remained normal with creatinine of 0.9 mg/dL. Total bilirubin was also within normal limits.

Treatment

Patient had mild wheeze on examination of chest, intranasal oxygen at 2 L/min was given along with intravenous acetaminophen 1 g for pain relief. 45.4 mg intravenous chlorphenaramine and intravenous 100 mg hydrocortisone were also injected as per the protocol for allergic reactions.¹¹ Within half an hour, all the symptoms improved and hypoxia resolved, chest wheezing also disappeared.

Outcome and follow-up

Patient remained clinically stable after this episode till discharge. One pint of packed red blood cells were transfused the next day. She was then prescribed oral iron polymatose 200 mg two times per day for 1 month. After 3 months of oral iron therapy, her iron profile and haemoglobin level improved. Later on oesophagogastroduodenoscopy was also done to evaluate for other causes of iron deficiency anaemia such as esophagitis, celiac disease and gastric ulcer but that was normal.

Discussion

Iron deficiency is one of the common nutritional deficiencies worldwide. In Pakistan, iron deficiency anaemia is common and women of childbearing age due to various factors such as malnutrition, low socioeconomic status, menstruation but most common is pregnancy.^11–15 Normally menstruating, pregnant and women of childbearing age with anaemia are prescribed iron oral supplements which may result in in-sufficient replenishment of iron in body.¹¹ Thus, intravenous forms are readily used in patient with severely low haemoglobin to replenish iron when oral therapy is inadequate^{16 17} intravenous iron formulations at its equivalent dosages are used to rapidly increase iron stores in iron-depleted patients.¹⁸ The availability of different formulations of iron over a period of time has led to decreased incidence of hypersensitivity reactions.¹⁹ In a study, iron isomaltose has been compared with ferric carboxymaltose and the later one proved to have less chances of reactions but this case report is also unique as iron III isomaltose hypersensitivity reaction has also never been reported in Asian ethnicity of age group similar to this patient. There were complaints of backache, small joints pain which has not been observed in previous hypersensitivity reactions. Test dose of iron isomaltose is not recommended.^{1 4 20} The potential for acute hypersensitivity reaction cause by intravenous iron is rare (<1/250 000 administrations) but due to potential of causing a reaction it should be done in a controlled facility with staff trained to manage promptly,^{11 21} it should to be treated in timely manner to decrease mortality.^{21 22}

Learning points.

• Iron isomaltose, although relatively safe but can cause allergic reaction.

• In case of allergic reaction, severity of reaction should be recognised and treatment should be given immediately and accordingly.^{21 22}

• Intravenous iron should be administered in settings where trained staff should be present to anticipate and provide appropriate pharmacological interventions.²¹