Clinical Burden of Anemia in Inflammatory Bowel Disease: Role of Iron Deficiency And Iron Replacement Therapy, Observational Study (RIDART-1)

BACKGROUND

Anemia is the most common extraintestinal manifestation of IBD, occurring in 6 to 74 percent of patients. This wide range in the prevalence of anemia is related to differences in study design, in the criteria used to define anemia and to the increasing awareness of anemia in these patients. According to a recent meta-analysis of European studies involving 2192 IBD patients, the overall prevalence of anemia in Europe was 27%, ulcerative colitis patients being less likely to develop anemia than those with Crohn's disease. Therefore, anemia represents a significant clinical and social burden in IBD management; this is more evident in southern Europe where the prevalence of anemia is close to 40%. Most cases of anemia in IBD are due to iron deficiency (IDA) and to anemia of inflammation (AI). Guidelines concerning the diagnosis and treatment of IDA in IBD have been published by the European Crohn's and Colitis Organisation. According to present guidelines iron supplementation should be started when IDA is present or even in the presence of iron deficiency without anemia. A meta-analysis of iron supplementation studies in IBD-associated IDA found that intravenous iron is more effective and better tolerated than oral iron supplementation, but the sample size of the included studies was small; absolute indications for intravenous iron include severe anemia (haemoglobin <10.0 g/dL) and intolerance or inadequate response to oral iron.

Although the ECCO diagnostic criteria for IDA are simple, and iron supplementation represents a cheap and usually effective treatment, many IBD patients with IDA are not properly treated. The inconsistent adherence, by many physicians, to treatment guidelines for IDA in IBD is often motivated by the belief that mild to moderate degrees of anemia may not have a significant impact on the patient's quality of life or do not represent the main clinical problem of the patient, that oral iron supplementation may adversely affect disease activity, and that parenteral iron administration may cause severe side effects.

RATIONALE

In order to improve the diagnostic and therapeutic work-up of anemia in IBD, it is necessary to precisely define the prevalence and pathogenesis of anemia in the Italian IBD population and gain informations about how anemic patients, particularly those with IDA, are usually managed and followed-up. In addition, since IDA and AI are the most common forms of anemia in IBD, and both mechanisms often concur to the pathogenesis of anemia in the same subject, stringent diagnostic criteria to distinguish the three conditions (IDA, AI and coexistence of IDA and AI) are urgently needed. The differential diagnosis between IDA and AI is often difficult since inflammation modifies serum ferritin and transferrin saturation (TfSat) that become unreliable as indicators of iron status. Recently, serum hepcidin concentration has been identified as a new index of iron status that can be useful to differentiate IDA and AI in IBD. Hepcidin, a peptide produced by the liver in response to increased iron stores, inflammation and reduced erythropoietic activity, is the master regulator of body iron homeostasis and acts by inhibiting iron absorption and iron release from hepatocytes and macrophages to plasma. The potential role of serum hepcidin determination as a diagnostic tool in the differential diagnosis of anemia in IBD and in other inflammatory diseases must be clearly defined. The investigation of these topics is important since a more accurate pathogenetic diagnosis of anemia in IBD, while preventing the useless and potentially harmful treatment of AI with iron supplementation, might allow the identification and appropriate treatment of IDA patients in the presence of inflammation.