Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management

Miguel A Montoro-Huguet, Santos Santolaria-Piedrafita, Pablo Cañamares-Orbis, José Antonio García-Erce, Miguel A Montoro-Huguet, Santos Santolaria-Piedrafita, Pablo Cañamares-Orbis, José Antonio García-Erce

Abstract

Iron is an essential nutrient to life and is required for erythropoiesis, oxidative, metabolism, and enzymatic activities. It is a cofactor for mitochondrial respiratory chain enzymes, the citric acid cycle, and DNA synthesis, and it promotes the growth of immune system cells. Thus, iron deficiency (ID) leads to deleterious effects on the overall health of individuals, causing significant morbidity. Iron deficiency anemia (IDA) is the most recognized type of anemia in patients with celiac disease (CD) and may be present in over half of patients at the time of diagnosis. Folate and vitamin B12 malabsorption, nutritional deficiencies, inflammation, blood loss, development of refractory CD, and concomitant Heliobacter pylori infection are other causes of anemia in such patients. The decision to replenish iron stores and the route of administration (oral or intravenous) are controversial due, in part, to questions surrounding the optimal formulation and route of administration. This paper provides an algorithm based on the severity of symptoms; its impact on the health-related quality of life (HRQL); the tolerance and efficiency of oral iron; and other factors that predict a poor response to oral iron, such as the severity of histological damage, poor adherence to GFD, and blood loss due to mucosal lesions.

Keywords: celiac disease; gluten-free diet; iron deficiency; iron deficiency anemia; iron intravenous; iron oral; malabsorption; micronutrient deficiencies; patient-blood management (PBM).

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagnosis of iron deficiency.
Figure 2
Figure 2
Prevalence of CD in patients with IDA in different setting. (1) OR of 12.5 (95% CI 1.74–90) (compared to the prevalence of CD controls); (2) Diagnosis celiac desease based on serology results without duodenal biopsy.
Figure 3
Figure 3
In CD there is a component of systemic inflammation which in some cases may also contribute to the pathogenesis of anaemia. This contribution is less than that due to malabsorption. The figure illustrates some mechanisms involved in the pathogenesis of anemia of chronic disease.
Figure 4
Figure 4
Factors influencing the development of anemia in CD. The main and most frequent cause of anemia in CD is malabsorption. The figure illustrates other components that may contribute to its pathogenesis to a lesser extent. CD “celiac disease”; GFD: “gluten free diet”; IBD: “inflammatory bowel disease”.
Figure 5
Figure 5
A proposed algorithm for iron replacement in patients with CD and IDA or ID. GFD: gluten-free diet; GIPs: gluten-immunogenic peptides in urine or feces samples; HRQL: health-related quality of life. # In the presence of mild symptoms, consider not giving oral iron and wait for resolution of lesions after GFD. ‡ Some causes of non-response to oral iron replacement include poor adherence to the GFD (consider the presence of GIPs in urine or stool samples as an indicator of poor adherence), slow histological response to the GFD (“slow responders”), refractory celiac, and blood loss due to mucosal lesions (Crohn’s disease, jejunoileitis, and malignancy). (*: Consider transfusion of red blood cells.; ** See Tables 5 and 6).
Figure 6
Figure 6
Dosage of intravenous iron according to hemoglobin (Hb) levels (g/dL) (adults). * Dosage may vary depending on the patient’s clinical condition and the physician’s clinical judgment. Hb: haemoglobin; h: hours; kg: kilograms of patient weight.

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