Elsevier

Seminars in Hematology

Volume 46, Issue 4, October 2009, Pages 339-350
Seminars in Hematology

Pathogenesis and Management of Iron Deficiency Anemia: Emerging Role of Celiac Disease, Helicobacter pylori, and Autoimmune Gastritis

https://doi.org/10.1053/j.seminhematol.2009.06.002Get rights and content

The causes of iron deficiency vary significantly during different stages of life, and according to gender and socioeconomic circumstances. Although dietary iron is important, iron deficiency anemia (IDA) is mostly attributed to blood loss and may be the presenting clinical feature of occult bleeding from the gastrointestinal (GI) tract heralding underlying malignancy. Conventional GI diagnostic workup fails to establish the cause of iron deficiency in about one third of patients. However, abnormal iron absorption caused by hereditary iron-refractory iron deficiency anemia (IRIDA) or acquired disease is increasingly recognized as an important cause of unexplained iron deficiency. The recent availability of convenient, non-invasive screening methods to identify celiac disease, autoimmune atrophic gastritis and Helicobacter pylori infection has greatly facilitated the recognition of patients with these entities. Cure of previously refractory IDA by H pylori eradication provides strong evidence supporting a cause-and-effect relation. The intriguing recent observations of H pylori antibodies directed against epitopes on gastric mucosal cells in atrophic gastritis imply an autoimmune mechanism triggered by H pylori and directed against gastric parietal cells by means of antigenic mimicry. Improved understanding of the role of abnormal iron absorption in IDA has important implications for current concepts related to the pathogenesis and management of IDA.

Section snippets

Causes of Iron Deficiency

Although recent evidence suggests that the iron status of developed populations is improving and the incidence of IDA is declining, the worldwide prevalence of iron deficiency continues to be a significant problem. Populations residing in developing countries are especially vulnerable. Even within developed countries, certain population subgroups are at increased risk for developing iron deficiency due to increased physiological requirements. These include infants, growing children, adolescents

Gastrointestinal Blood Loss

Blood loss is the most common cause of iron deficiency in adults, and the various causes are described in detail in standard textbooks. When physiologic causes of iron deficiency are unlikely, it is mandatory to exclude pathological causes of iron deficiency, in particular GI blood loss. Ingestion of aspirin and nonsteroidal anti-inflammatory drugs should not be overlooked as a cause, because even low doses of aspirin taken to prevent the complications of atherosclerosis may cause significant

Decreased Iron Absorption

In recent years, there has been an increasing awareness of subtle, non-bleeding GI conditions that may result in abnormal iron absorption leading to IDA in the absence of GI symptoms. Thus, the importance of celiac disease as a possible cause of IDA refractory to oral iron treatment, without other apparent manifestations of malabsorption syndrome,24 is increasingly recognized. In addition, Helicobacter pylori has been implicated in several recent studies as a cause of IDA refractory to oral

Therapy of Iron Deficiency Anemia

The most desirable treatment of iron deficiency is cure of the underlying disease. This is of critical importance when the cause of anemia is malignant or non-malignant bleeding diseases of the gastrointestinal tract, in celiac disease responsive to gluten-free diet, or in H pylori gastritis where H pylori eradication will often result in the cure of anemia even without the addition of iron therapy. However, in the vast majority of cases and particularly in women with excessive menstrual blood

Conclusions

Iron deficiency is the consequence of an imbalance between increased requirements, limited supply, or abnormal blood loss. In adults, anemia is traditionally attributed to blood loss and, importantly, iron deficiency may on occasion be heralding an underlying malignancy associated with occult GI bleeding. Consequently, a GI diagnostic workup is mandatory in adult males and in postmenopausal females. However, GI studies fail to establish the cause of iron deficiency in about one third of

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