Skin staining following intravenous iron infusion

Abstract

This report describes the case of a 36-year-old woman, gravida 3, para 2, at 11 weeks' gestation, who received a ferric carboxymaltose infusion for iron deficiency anaemia after medical management of a miscarriage. The following morning, light brown skin staining was noted at the infusion site, and the staining was present 2 months later at follow-up. Skin staining following intravenous iron infusion is a rare but important side effect. The skin staining is potentially permanent but may fade in time. Such an adverse effect may have cosmetic consequences for the patient.

Background

Iron deficiency anaemia (IDA) is a common health problem, especially during pregnancy, affecting up to 57% of pregnant women in low-income countries and approximately 24% in high-income countries.¹ It is well known that IDA is associated with significant morbidity for mother and infant. Preterm labour and low birth weight are common sequelae, potentially affecting neonatal health,^{2 3} while women may be more susceptible to peripartum and postpartum haemorrhage, requiring blood transfusion.⁴ Considering these adverse health outcomes, it is important not only to identify the cause of IDA but also to treat the underlying condition. Ferric carboxymaltose is an intravenous iron supplement useful for rapid correction of IDA or to relieve symptoms associated with this condition. Systematic and narrative reviews indicate intravenous iron not only is safe for pregnant women in the second and third trimesters but also replenishes iron stores at a quicker rate, with fewer adverse effects, in comparison with oral iron.^5–7

Although rare, intravenous iron infusions can cause skin staining.⁸ A number of cases have been identified.^9–11 To the best of our knowledge, no cases of skin staining within the obstetric population have been reported in the literature. Such an adverse effect may be aesthetically undesirable in this patient cohort and may cause distress. Healthcare professionals who fail to inform patients of the risk of skin staining may be faced with patient complaints and legal prosecution. This report describes the case of a woman who developed brown skin staining after receiving ferric carboxymaltose for IDA postmiscarriage.

Case presentation

The patient was a 36-year-old woman, gravida 3, para 2, at 11 weeks' gestation, who presented to the maternity emergency unit with vaginal bleeding, abdominal pain, and associated nausea and vomiting. A total of three admissions due to hyperemesis within the past month were recorded. All episodes were managed conservatively. Previous pregnancies were uneventful, with one previous caesarean section and a subsequent vaginal birth. No relevant medical or surgical history was noted other than taking fluoxetine 40 mg for depression. There was no history of smoking, alcohol or drug abuse and no known drug allergies.

On examination, there were signs of dehydration. Abdominal examination revealed a soft and non-tender abdomen. Sterile speculum and vaginal examination revealed a normal cervix with a closed cervical os. There was no cervical tenderness elicited and full blood count was unremarkable. Urine was positive for ketones, consistent with dehydration. Subsequent ultrasound demonstrated a missed miscarriage. After discussion of the appropriate management options, medical management consisted of mifepristone 200 mg followed by misoprostol 400 mg 36 hours later. After 3 days, the products of conception were passed, and repeat ultrasound at this time showed an incomplete miscarriage.

The haemoglobin level decreased from 124 g/L on admission to 94 g/L following miscarriage. Given the acute blood loss, it was decided to commence an intravenous iron infusion to increase iron levels. Prior to starting the infusion, consent was sought by the midwife, risk of skin staining was explained and the discussion was documented in the clinical notes. The intravenous cannula was flushed first with 10 mL of 0.9% sodium chloride. After flushing the intravenous cannula to ensure it was working, 1000 mg of ferric carboxymaltose was dissolved in 250 mL of 0.9% sodium chloride and was administered over 15 min as per protocol. No adverse reactions were noted at this time. The following morning, painless light brown skin staining (2.5×5.2 cm) was noted at the site of the infusion in the right antecubital fossa (figure 1). The clinicians explained that this was an unfortunate side effect and that the staining may be permanent or may fade in time.

Figure 1.

Template of skin staining in the right antecubital fossa.

Outcome and follow-up

At follow-up 1 week later, ultrasound demonstrated an incomplete miscarriage. The skin staining was still evident and appeared unchanged. The haemoglobin level had increased to 110 g/L, despite persistent complaints of vaginal bleeding. A further haemoglobin level repeated 1 week later was normal at 124 g/L and ultrasound at this time showed a complete miscarriage. No change in skin staining was observed 2 months later at outpatient follow-up.

Discussion

Skin staining due to extravasation of iron into subcutaneous tissue is a rare but important side effect of intravenous iron infusions. Infusion site extravasation or skin discolouration occurs at a rate of approximately 1.6%.⁸ In this case, the skin staining remained unchanged 2 months later. It is unclear whether the pigmentation will be permanent or if it will fade in time. Laser treatment may lighten skin staining but does not completely clear it.¹² Case reports noted that such skin pigmentation may appear hours or days after the infusion but may also persist for up to 1 year.^9–11 Hermitte-Gandoliere et al ¹³ identified 51 cases of skin staining due to intravenous iron infusions over a 6-year period. Women aged 20–49 years were most commonly affected, with skin staining persisting for 1 and 6 months in 37.2% and 17.6% of cases, respectively. Based on the available evidence, presentation and timing of symptoms are often variable, with some reporting symptoms during the infusion and others having a delayed reaction. In all cases examined, women were affected, possibly due to menstruation and physiological demands of pregnancy resulting in an increased requirement for intravenous iron.

Since existing evidence indicates that intravenous iron is effective and safe to treat IDA in pregnancy,^5–7 it is likely that it will be prescribed increasingly for obstetric patients. Given the negative effects of IDA for both mother and infant, as well as the risk of potentially permanent skin staining, intravenous iron infusions should be commenced where clinical benefit outweighs risk of adverse events. It is imperative that a set protocol is established prior to starting such infusions. Patients should be informed of the risk of long-lasting skin staining before administering the infusion. As in the case presented, this discussion should be documented. Further steps should include inspecting the cannula site before and during the infusion, as well as flushing the cannula site with saline before and after the infusion.^{14 15} Although iron leakage is non-harmful, skin staining may be unsightly for some patients. To avoid such adverse consequences, staff performing such infusions should follow a set protocol, understand the risks of the procedure and monitor for potential side effects.^{14 15}

Learning points.

• Skin staining after intravenous iron infusion is a rare but important side effect and may have cosmetic repercussions for patients.

• Skin staining may be permanent or may fade in time.

• Given the safety and efficacy of ferric carboxymaltose in pregnancy and post partum, it is likely this medication will be prescribed more frequently for this patient cohort.

• Prior to commencing such infusions, patients should be informed of the risk of skin staining. The discussion should be documented, and a set protocol should be followed to minimise the risk of skin staining.