Iron Deficiency In Inflammatory Bowel Disease Research Articles

Iron Deficiency Anemia in Inflammatory Bowel Diseases-A Narrative Review.

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. IBD has been associated with numerous symptoms and complications, with the most common being iron deficiency anemia (IDA). Iron deficiency in IBD is caused by inadequate intake, malabsorption (including duodenal involvement and surgical removal), and chronic blood loss by mucosal ulcerations. Therefore, an appropriate diet should be enforced. Iron deficiency and iron supplementation have been associated with alterations to gut microbiota. IBD-associated anemia, in particular iron deficiency anemia, is associated with a significant decrease in quality of life and with clinical symptoms such as chronic fatigue, headaches and dizziness, reduced exercise tolerance, pale skin, nails, conjunctiva, and fainting. However, despite these numerous adverse symptoms, IDA remains undertreated. The European Crohn’s and Colitis Organisation (ECCO) guidelines state that patients should be monitored for anemia. Adequate treatment, whether oral or intravenous, should be implemented while taking into consideration C-reactive protein values (CRP), hemoglobin levels, and therapeutic response. It should be stressed that every case of anemia in IBD patients should be treated. Intravenous iron formulations, which are more superior compared to the oral form, should be used. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

P309 Ferritin or transferrin saturation vs. soluble transferrin receptor for iron deficiency diagnosis in inflammatory bowel disease

Abstract Background Iron deficiency is common in inflammatory bowel disease (IBD) and can negatively affect the quality of life even in the absence of anaemia. Diagnosis of iron deficiency is based on ferritin and transferrin saturation (TfS) in routine practice, yet guideline thresholds are not evidence-based. Serum levels of soluble transferrin receptor (sTfR) are the best non-invasive test as it is not influenced by inflammation, but the test is costly with low availability. Thus, the aim of this study was to evaluate for the first time the accuracy of ferritin and/or TfS for diagnosing iron deficiency in IBD and identify the optimal thresholds of these parameters using sTfR as the gold standard. Methods Serum samples were collected from IBD patients (n = 2,072) receiving a biologic in routine practice. Diagnostic accuracy was assessed using receiver operating characteristic curves for ferritin and TfS levels separately or combined. Results No ferritin or TfS threshold had good diagnostic performance in CD patients. In UC patients with CRP <10 mg/l, optimal iron deficiency diagnostic performances were observed with ferritin and TfS thresholds of 65 µg/l and 16%, respectively. For UC patients with CRP >10 mg/l, the thresholds with the best diagnostic performance were 80 µg/l for ferritin and 11% for TfS. There was no added value for combined ferritin and TfS. Conclusion In conclusion, we found that ferritin and TfS are reliable parameters for iron deficiency diagnosis only in UC patients, at thresholds different from current guidelines. In CD patients, sTfR should be used given the poor diagnostic performance of ferritin and TfS.

Curcumin induces mild anemia in a DSS-induced colitis mouse model maintained on an iron-sufficient diet.

Anemia is frequently encountered in patients with inflammatory bowel disease (IBD), decreasing the quality of life and significantly worsening the prognosis of the disease. The pathogenesis of anemia in IBD is multifactorial and results mainly from intestinal blood loss in inflamed mucosa and impaired dietary iron absorption. Multiple studies have proposed the use of the polyphenolic compound curcumin to counteract IBD pathogenesis since it has significant preventive and therapeutic properties as an anti-inflammatory agent and very low toxicity, even at high dosages. However, curcumin has been shown to possess properties consistent with those of an iron-chelator, such as the ability to modulate proteins of iron metabolism and decrease spleen and liver iron content. Thus, this property may further contribute to the development and severity of anemia of inflammation and iron deficiency in IBD. Herein, we evaluate the effects of curcumin on systemic iron balance in the dextran sodium sulfate (DSS) model of colitis in C57Bl/6 and BALB/c mouse strains that were fed an iron-sufficient diet. In these conditions, curcumin supplementation caused mild anemia, lowered iron stores, worsened colitis and significantly decreased overall survival, independent of the mouse strain. These findings suggest that curcumin usage as an anti-inflammatory supplement should be accompanied by monitoring of erythroid parameters to avoid exacerbation of iron deficiency anemia in IBD.

Review article: treating-to-target for inflammatory bowel disease-associated anaemia.

Iron deficiency has a high prevalence in inflammatory bowel disease (IBD) patients, with negative impact on quality of life and work capacity. To propose an innovative approach based on early intervention, treating to target and tight monitoring in the management of iron deficiency in IBD patients. We conducted a literature review on PubMed and Medline using pre-defined keywords and terms to identify relevant studies on iron deficiency in IBD. Many physicians are focused on treating anaemia; however, anaemia is one of the consequences of iron deficiency. Hence, our therapeutic goal for these patients should evolve towards prevention of anaemia by screening and treating iron deficiency. Early diagnosis of iron deficiency is based on a combination of ferritin concentration and transferrin saturation. We consider that normalisation of these biomarkers reflects iron stores replenishment and should be considered as a major therapeutic goal. Treating iron deficiency regardless of the presence of anaemia seems to improve quality of life in several chronic conditions and should be considered as an innovative approach in IBD although strong evidence is still lacking. Tight monitoring is required to allow early detection of iron deficiency recurrence and to consider prompt additional iron supplementation. We propose to extrapolate a three-step strategy (early detection and intervention, treating-to-target and tight monitoring) to the management of iron deficiency in IBD patients. Universally applied, this proactive approach is expected to result in better outcomes in IBD patients.

PGI25 - Comparing Short Form – 6 Dimension (SF-6D) Derived Utilities and Euroqol Questionnaire – 5 Dimensions (EQ-5D) Mapped Utilities Among Patients with Iron Deficiency in Inflammatory Bowel Disease (ID-IBD) Treated with Ferric Maltol (FM) Vs Placebo

PGI25 - Comparing Short Form – 6 Dimension (SF-6D) Derived Utilities and Euroqol Questionnaire – 5 Dimensions (EQ-5D) Mapped Utilities Among Patients with Iron Deficiency in Inflammatory Bowel Disease (ID-IBD) Treated with Ferric Maltol (FM) Vs Placebo

Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review.

Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients.The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD.Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004.A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics.In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron.

Iron-deficiency anaemia in an outpatient inflammatory bowel disease cohort

Iron deficiency is found frequently in patients with inflammatory bowel disease (IBD) and can have a significant effect on their quality of life. The causes of iron deficiency are gastrointestinal blood loss, poor oral intake of iron, malabsorption, and inflammation. Previous studies have highlighted the correlation between higher iron stores and quality of life as well as the under diagnosis and treatment of iron deficiency in IBD by medical professionals. This article analyses the diagnosis and treatment of iron deficiency in the authors' local IBD cohort. The authors compared their findings to guidance developed by the British Society of Gastroenterology (BSG) and reviewed similar studies, comparing management options that use different iron preparations.

Anemia in inflammatory bowel disease: A neglected issue with relevant effects

Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

Editorial: Intravenous Iron for the Treatment of Iron Deficiency in IBD: the Pendulum Is Swinging

Intravenous (IV) iron therapy has been a major asset in the management of refractory iron-deficiency anemia in inflammatory bowel disease (IBD) and other diseases. However, the cost-effectiveness of parenteral substitution as the first-line treatment of this condition in IBD has been questioned. A study published by Reinisch et al. in this issue of the journal fails to show non-inferiority of iron isomaltose 1,000, a novel high-dose IV preparation, compared to oral iron sulfate.

Intravenous iron in inflammatory bowel diseases

Anemia and iron deficiency are the most common extraintestinal complications of inflammatory bowel diseases (IBDs) and are often undertreated. We review the evidence on intravenous (i.v.) iron overcoming the limitations of oral iron in IBD. Recent reports demonstrate that i.v. iron is at least as effective, quicker, and better tolerated than oral iron. Moreover, experimental data confirm that oral and parenteral iron have divergent effects on intestinal mucosa: oral iron severely increasing inflammation. Observational and randomized studies prove that i.v. iron is not only effective but also well tolerated with no negative influence in the activity of IBD. A new formulation, iron carboxymaltose, which permits higher individual doses, has been shown more effective and less costly than standard iron sucrose. Another formulation, iron isomaltoside, shows promising in in-vitro and small clinical studies, but data from large trials are not available yet. Oral iron is not an ideal option for treating anemia and iron deficiency in IBD. i.v. iron should be preferred at least in five scenarios: intolerance to oral iron, severe anemia, failure of oral therapy, need for a quick recovery, and use of erythropoietin. Direct evidence in IBD patients not only confirms the effectiveness of i.v. iron, but also demonstrates that new, more convenient preparations probably will become the standard in the near future.

A Shift From Oral to Intravenous Iron Supplementation Therapy Is Observed Over Time in a Large Swiss Cohort of Patients With Inflammatory Bowel Disease

In 2007, leading international experts in the field of inflammatory bowel disease (IBD) recommended intravenous (IV) iron supplements over oral (PO) ones because of superior effectiveness and better tolerance. We aimed to determine the percentage of patients with IBD undergoing iron therapy and to assess the dynamics of iron prescription habits (IV versus PO). We analyzed anonymized data on patients with Crohn's disease and ulcerative colitis extracted from the Helsana database. Helsana is a Swiss health insurance company providing coverage for 18% of the Swiss population (1.2 million individuals). In total, 629 patients with Crohn's disease (61% female) and 398 patients with ulcerative colitis (57% female) were identified; mean observation time was 31.8 months for Crohn's disease and 31.0 months for ulcerative colitis patients. Of all patients with IBD, 27.1% were prescribed iron (21.1% in males; 31.1% in females). Patients treated with steroids, immunomodulators, and/or anti-tumor necrosis factor drugs were more frequently treated with iron supplements when compared with those not treated with any medications (35.0% versus 20.9%, odds ratio, 1.94; P < 0.001). The frequency of IV iron prescriptions increased significantly from 2006 to 2009 for both genders (males: from 2.6% to 10.1%, odds ratio = 3.84, P < 0.001; females: from 5.3% to 12.1%, odds ratio = 2.26, P = 0.002), whereas the percentage of PO iron prescriptions did not change. Twenty-seven percent of patients with IBD were treated with iron supplements. Iron supplements administered IV were prescribed more frequently over time. These prescription habits are consistent with the implementation of guidelines on the management of iron deficiency in IBD.

Safety and Efficacy of Total-Dose Infusion of Low Molecular Weight Iron Dextran for Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease

Intravenous iron has been suggested as a safe and effective treatment of anemia complicating inflammatory bowel disease (IBD). Low molecular weight (LMW) iron dextran has the ability to administer the patient's total iron requirement in a single infusion. The aim of this study was to assess the safety and efficacy of the total dose of LMW iron dextran infusion for the treatment of iron deficiency in IBD. Fifty IBD patients (27 female, 35 Crohn's disease, 15 ulcerative colitis) were included in the study. Mean +/- standard deviation (SD) hemoglobin and ferritin levels before the infusion were 9.88 +/- 1.42 g/dl and 13.9 +/- 10.9 ng/ml, respectively. A 25-mg test dose was followed by infusion of the total dose of LMW iron dextran based on the iron deficit. Several clinical and laboratory parameters were measured before and on week 4 after infusion. Four patients (8%) developed adverse reactions during the test infusion and did not receive the total-dose infusion. Only one patient developed an allergic reaction during the total-dose infusion. In the remaining 45 patients, the mean +/- SD iron dose that was given was 1,075 +/- 269 mg. The mean +/- SD elevation of hematocrit and hemoglobin on week 4 was 4.9 +/- 1.9% and 1.7 +/- 0.8 g/dl, respectively. Hematopoietic response was observed in 23 of 45 patients (51.1%). Total parenteral iron replacement with LMW iron dextran is an easy, safe, and effective alternative method for treating iron deficiency anemia in IBD. Harmless adverse reactions may develop in a minority of patients.

Use of agents stimulating erythropoiesis in digestive diseases

Anemia is the most common complication of inflammatory bowel disease (IBD). Control and inadequate treatment leads to a worse quality of life and increased morbidity and hospitalization. Blood loss, and to a lesser extent, malabsorption of iron are the main causes of iron deficiency in IBD. There is also a variable component of anemia related to chronic inflammation. The anemia of chronic renal failure has been treated for many years with recombinant human erythropoietin (rHuEPO), which significantly improves quality of life and survival. Subsequently, rHuEPO has been used progressively in other conditions that occur with anemia of chronic processes such as cancer, rheumatoid arthritis or IBD, and anemia associated with the treatment of hepatitis C virus. Erythropoietic agents complete the range of available therapeutic options for treatment of anemia associated with IBD, which begins by treating the basis of the inflammatory disease, along with intravenous iron therapy as first choice. In cases of resistance to treatment with iron, combined therapy with erythropoietic agents aims to achieve near-normal levels of hemoglobin/hematocrit (11-12 g/dL). New formulations of intravenous iron (iron carboxymaltose) and the new generation of erythropoietic agents (darbepoetin and continuous erythropoietin receptor activator) will allow better dosing with the same efficacy and safety.

Common Misconceptions in the Diagnosis and Management of Anemia in Inflammatory Bowel Disease

Anemia is the most common systemic complication of inflammatory bowel disease (IBD); so common that it is almost invariably not investigated and rarely treated. Several misconceptions are the reason for these clinical errors, and our goal will be to review them. The most common misconceptions are: anemia is uncommon in IBD; iron deficiency is also uncommon; just by treating the intestinal disease, anemia will be corrected; iron deficiency is the only cause for anemia in IBD; ferritin is an accurate parameter for the diagnosis of iron deficiency in IBD; the impact of anemia on the quality of life of IBD patients is limited; iron supplementation is rarely needed in IBD; high-dose oral iron solves the problem of iron malabsorption in IBD; intravenous (IV) iron is dangerous and of no proven benefit in IBD; IV iron is useful only for severe anemia; and erythropoietin has no role in the treatment of IBD anemia. These misconceptions are not evidence-based. On the contrary, there is enough evidence to support the following statements: (a) anemia is very common in IBD, (b) anemia should be investigated with care because many factors can be responsible, (c) treatment of anemia results in clear improvement in the objective parameters of well-being, especially in the quality of life, (d) IV iron is safe and effective in the treatment of iron deficiency anemia in IBD patients, and (e) erythropoietin is useful in a subset of patients with refractory anemia. Anemia diagnosis and treatment must not be neglected in IBD patients, and several misconceptions should be promptly abandoned.