From an UpToDate article entitled "Nutrient Deficiencies in Inflammatory Bowel Diseases":
Iron — Literature reviews suggest that 35 to 90 percent of adults with IBD are iron deficient [31]. Iron deficiency is probably the primary cause of the anemia that affects 16 percent of outpatients and up to 70 percent of inpatients [1,31]. Iron deficiency has a significant negative impact on quality of life and can lead to developmental and cognitive abnormalities in children and adolescents [32]. A study in adults with IBD and anemia demonstrated that oral iron supplementation increased hemoglobin concentration and improved quality of life without changing disease activity [33].
Other causes of anemia — Iron deficiency in IBD is usually caused by chronic blood loss. The resulting anemia is compounded by suppression of erythropoietin production and alteration of iron metabolism caused by proinflammatory cytokines, reactive oxygen metabolites, and nitric oxide, a condition called the anemia of chronic inflammation (anemia of chronic disease) [34]. Other potential contributors to anemia in patients with IBD include vitamin B12 deficiency, folic acid deficiency, or drug-induced anemia (eg, in patients treated with sulfasalazine or thiopurines). (See "Anemia of chronic disease (anemia of chronic inflammation)".)
Assessment — Assessment of iron deficiency in patients with IBD is complicated by the fact that ferritin is an acute phase reactant. Because serum ferritin levels increase in the setting of inflammation, patients with active IBD or acute infection may have a "falsely" normal ferritin concentration. Thus, patients with anemia and active IBD may be iron deficient regardless of the serum ferritin levels. Some have suggested that for patients with active inflammatory disease, serum ferritin levels below 100 mcg/L should be considered abnormal [31]. In addition, serum ferritin may be falsely normal in a patient with hypoalbuminemia.
Supplementation — There are two main issues related to iron supplementation in patients with IBD:
■Oral iron supplementation can potentially worsen symptoms and/or IBD activity. The available data suggest that many patients (approximately 75 percent) tolerate oral supplementation without worsening of disease activity, but some develop gastrointestinal side effects, a subset of which may be attributable to worsening IBD disease activity [33,35-37]. There are no established predictors of tolerance.
■Iron might increase oxidative stress and thereby contribute to carcinogenesis in IBD by augmenting oxidative damage and epithelial proliferation due to inflammation [38-44]. This is a theoretical concern, mainly from animal models. Whether these observations are clinically important in humans with IBD is unclear.
There are two general options to replete iron stores in patients with IBD: oral and parenteral (intramuscular, intravenous) supplementation. Oral formulations are much more convenient and less expensive and have, thus, generally been preferred as a first-line option. Indications for parenteral supplementation in adults include severe anemia (hemoglobin less than 10 grams per dL), intolerance, or inappropriate response to oral iron (a response is considered appropriate if the hemoglobin concentration increases by at least 2 g/dL or reaches normal within four weeks of treatment), severe intestinal disease activity, concomitant therapy with an erythropoietic agent, or patient preference [45]. The dosing and administration are discussed separately. (See "Treatment of anemia due to iron deficiency" and "Iron requirements and iron deficiency in adolescents".)
Tolerance to oral iron therapy varies substantially among patients with IBD. Those with mild intolerance (eg, mild nausea, bloating, diarrhea, upper gastrointestinal complaints) thought to be due to the iron may still be able to take oral iron supplements by taking smaller doses. Several oral formulations are available, some of which may be better tolerated than others. However, differences in tolerability may in part be due to variations in their iron content (with better tolerability in preparations containing less iron). Thus, whether one or another formulation has an optimal efficacy/safety profile is unclear since there have been no direct comparisons in patients with IBD. (See "Treatment of anemia due to iron deficiency", section on 'Side effects'.)
Among the parenteral formulations, intravenous iron sucrose has been most extensively studied in IBD and appears to be well-tolerated, effective, and safer than iron dextran [35,36,46,47]. A multicenter randomized, controlled trial showed that intravenous iron sucrose treatment is superior to oral iron in correcting hemoglobin and iron stores in IBD patients [48]. The main disadvantages of intravenous iron sucrose are its relatively higher cost, the need for parenteral administration, and the possibility of allergic reactions. Another disadvantage of intravenous iron sucrose is the dose limitation of 200 mg iron per infusion because anemic patients with IBD frequently have an iron deficit of 1000 mg or more. Thus, multiple infusions of iron sucrose are required. Ferric carboxymaltose (FCM) is an intravenous iron preparation that can be administered in single doses of up to 1000 mg iron within 15 minutes. Fixed dose FCM has been demonstrated to have better efficacy and compliance than individually calculated iron sucrose doses in patients with IBD and iron deficiency anemia [49]. (See "Treatment of anemia due to iron deficiency", section on 'Ferric carboxymaltose'.)
Although the available data are limited, we suggest the following approach to iron supplementation in patients with IBD and evidence of iron deficiency:
■In patients with mild to moderate IBD disease activity who have no known sensitivity to oral iron, we suggest supplementation with oral iron. Specific suggestions for initial treatment are presented elsewhere. (See "Treatment of anemia due to iron deficiency", section on 'Choice of preparation' and "Treatment of anemia due to iron deficiency", section on 'Expected response'.)
■In patients with severe IBD disease activity, we suggest intravenous FCM to avoid worsening gastrointestinal symptoms, since these patients are already particularly fragile. Other indications for parenteral iron supplementation in adults include severe anemia (hemoglobin less than 10 grams per dL), intolerance, or inappropriate response to oral iron (a response is considered appropriate if the hemoglobin concentration increases by at least 2 g/dL or reaches normal within four weeks of treatment), concomitant therapy with an erythropoietic agent, or patient preference. Intravenous ferric gluconate complex may be an acceptable alternative in centers where iron sucrose is unavailable, although its efficacy and safety in IBD have not been evaluated directly. Specific suggestions for the choice of agent and calculation of the dose of iron are presented elsewhere. Blood transfusion is generally reserved for patients with severe anemia or hemodynamic instability. (See "Treatment of anemia due to iron deficiency", section on 'Parenteral iron therapy' and "Treatment of anemia due to iron deficiency", section on 'Blood transfusion'.)
■Children and adolescents with iron deficiency anemia are managed similarly to adults, although the clinical indications for instituting parenteral treatment or transfusion vary. (See "Iron requirements and iron deficiency in adolescents" and "Indications for red blood cell transfusion in infants and children" and "Iron deficiency in infants and young children: Treatment", section on 'Oral iron therapy'.)
■Options for patients who have previously been intolerant to oral iron therapy include parenteral iron preparations, a trial with an alternative oral agent, or a gradual increase in the dose of iron (which can be accomplished by using a liquid formulation of iron sulfate). Administration with food may improve tolerability, albeit while also reducing absorption. (See "Treatment of anemia due to iron deficiency", section on 'General principles' and "Treatment of anemia due to iron deficiency", section on 'Side effects'.)
■Failure of the anemia to respond to treatment with oral or parenteral iron may indicate either an erroneous diagnosis of iron deficiency or the presence of a component of the anemia of chronic disease (anemia of chronic inflammation). In such cases, addition of erythropoietin to the treatment program may result in improvement of the anemia [50,51]. (See "Anemia of chronic disease (anemia of chronic inflammation)".)
