Iron deficiency anemia in inflammatory bowel disease

Anemia is a common extraintestinal manifestation of inflammatory bowel disease(IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia(IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used labora-tory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and con-venient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD.     

Treatment of iron deficiency anemia in pediatric inflammatory bowel disease

Opinion statement Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B₁₂ and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.     

Anaemia and iron deficiency in children with inflammatory bowel disease

Background and aimsAnaemia and iron deficiency are common in children with Inflammatory Bowel Disease (IBD) however it is not known if the prevalence of anaemia and iron deficiency alters following diagnosis.MethodsLaboratory results from diagnosis, and at follow up one and two years later were recorded retrospectively in children with IBD recruited from a tertiary centre. Anaemia was defined using WHO standards and iron deficiency defined using published guidelines.Results46 children (16 girls) with Crohn's disease and 34 children (18 girls) with UC were studied. 75% of children with IBD were anaemic at diagnosis, 30% were anaemic at follow up two years later. 90% of children with Crohn's and 95% of children with Ulcerative Colitis (UC) were iron deficient at diagnosis. At follow up two years later 70% of children with Crohn's and 65% of children with UC were iron deficient.ConclusionsPersistent anaemia and iron deficiency are common in childhood IBD, prevalence alters with duration of time from diagnosis.     

Iron replacement therapy in inflammatory bowel disease patients with iron deficiency anemia: A systematic review and meta-analysis

Background and aimsIron deficiency anemia (IDA) is a common problem in patients with Inflammatory Bowel Disease (IBD) and has a significant negative impact on quality of life. The aim was to compare the clinical efficacy of intravenous (IV) versus oral (PO) iron replacement in adult IBD with iron deficiency anemia (IDA).MethodsA systematic search for randomized controlled trials comparing the efficacy of IV versus PO iron therapy in the treatment of IDA in adult IBD patients. The primary outcome was the mean change in the hemoglobin at the end of study and secondary outcomes include mean change in ferritin, clinical disease activity index, quality of life score and the adverse reaction rate.ResultsThe search strategy identified 757 articles while only three industry-funded articles met the inclusion criteria for systematic review and meta-analysis. The total sample size was 333 patients with 203 patients receiving IV therapy. IV route was associated with a 6.8 g/L higher mean hemoglobin increment and 110 μg/L higher mean ferritin increment. The IBD activity index and Quality of Life scores were comparable between the two treatment groups. More adverse events were reported in the oral treatment group with the odds for discontinuation being 6.2 (CI 2.2, 17.1).ConclusionsIntravenous iron treatment is better tolerated and more effective than oral iron treatment in improving ferritin. The higher hemoglobin gain with the IV route was small and of uncertain clinical significance. The combined sample size of the included studies was small and further clinical trials are required.     

Secretory immunoglobulin deficiency in a family with inflammatory bowel disease.

A family with 4 of 10 first-degree relatives affected with inflammatory bowel disease (IBD) was studied to determine whether any distinct immunological abnormalities occur in the affected members, as compared with unaffected members of the family, normal controls, and other unrelated patients with IBD. Red cell blood type and HL-A phenotypes did not distinguish between healthy and affected members, although HL-A2, 32, B27, and B12 were the predominant haplotypes in members with IBD. There was no significant difference between the two groups in the lymphocyte subpopulation counts of T cells, B cells, and cells carrying Fc or complement receptors. The in vitro mitogen response, however, to phytohemagglutinin and pokeweed mitogen were depressed in the affected members. Serum IgA and C3 levels were significantly elevated in members with IBD compared to healthy subjects with values of 232 +/- 69 (mean +/- SD) versus 148 +/- 29 mg per dl for IgA (P less than 0.05) and 173 +/- 32 versus 115 +/- 22 mg per dl for C3 (P less than 0.025), respectively. Plasma and, to a lesser extent, peripheral lymphocytes from 2 affected members who were tested were cytotoxic to allogeneic colonic epithelial cells. Salivary IgA was normal in the affected family members and unrelated patients with IBD. However, the free secretory component of salivary IgA was absent or markedly depressed in family members, as well as in unrelated patients with ulcerative colitis. This deficiency of the secretory immune system appears to characterize more frequently ulcerative colitis than Crohn's disease and may compromise mucosal host defenses in IBD.     

Prevalence and factors associated with vitamin C deficiency in inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn’s disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.AIMTo determine proportions and factors associated with vitamin C deficiency in CD and UC patients.METHODSIn this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.RESULTSOf 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1% vs 16.9%, P < 0.001) and fecal calprotectin (50.0% vs 20.0%, P = 0.009) had significantly higher proportions of deficiency compared to those without. Penetrating disease (P = 0.03), obesity (P = 0.02) and current biologic use (P = 0.006) were also associated with deficiency on univariate analysis. On multivariate analysis, the objective inflammatory marker utilized for analysis (elevated CRP) was the only factor associated with deficiency (odds ratio = 3.1, 95% confidence interval: 1.5-6.6, P = 0.003). There was no difference in the presence of clinical symptoms of scurvy in those with vitamin C deficiency and those without.CONCLUSIONVitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.     

Free protein S deficiency in patients with chronic inflammatory bowel disease.

Free protein S, protein C, and C4b-binding protein (C4b-BP) were measured in randomly selected outpatients: 22 with Crohn's disease (CD) and 16 with ulcerative colitis (UC). Active disease was recorded in 10 patients with CD and 4 with UC. Fourteen patients (63.6%) with CD and 4 (25%) with UC had free protein S values below the normal range, with mean values of 62% and 78% of that found in healthy control subjects (p < 0.01). The C4b-BP level was 127% in patients with CD as compared with 89% in both healthy subjects and UC patients (p < 0.01). The protein C levels were similar in the three groups. The present results add to the factors already known favouring thromboembolic complications in inflammatory bowel disease and which might play a major role both for the pathogenesis and for the increased tendency to venous thromboembolism in these diseases.     

Functional bowel disorders in inflammatory bowel disease

Patients with IBD in remission often have ongoing gastrointestinal symptoms that are related to active inflammation. It is now apparent that functional gastrointestinal disorders may overlap with IBD and increase morbidity and diminish the quality of life of patients. Recognition and treatment of functional symptoms that may be the result of IBD are crucial in the appropriate medical management of these patients.     

Small bowel length in inflammatory bowel disease

Small intestinal length has a particular significance in patients with inflammatory bowel disease (IBD). A determination of intestinal length by a standardised and simple technique is of interest for surgical decision making in primary and recurrent disease and in the evaluation and management of postoperative malabsorption. The aim of the present investigation was to analyse intestinal length in patients with IBD and define a standard method for this measurement. Material and methods: Two consecutive series of patients, Crohn's disease (n = 279) and ulcerative colitis (n = 315) and a control group (n = 77) underwent standardised intra-operative small intestinal length measurement. Results: Small intestinal length correlated to weight and height and was less in women than in men (P < 0.001) in both IBD groups and the controls. The small bowel in patients with Crohn's disease was significantly shorter than in patients with ulcerative colitis and in controls, P < 0.001. Also in Ulcerative Colitis small bowel length was significantly less than in controls, P < 0.001. In CD patients there was no difference in bowel length with regards to the anatomical extent of the disease. Original small bowel length in patients with CD and one or two bowel resections (n = 67) was not different from that in patients with three or more resections (n = 88). Conclusion: Small bowel length correlated to weight, height and sex. Patients with CD had a significantly shorter small intestine at first laparotomy, compared with U.C. patients and controls. In CD-patients there was no difference between the anatomical subgroups.

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Résumé. La longueur de l'intestin grêle a une signification tout à fait particulière chez les patients atteints de maladie inflammatoire de l'intestin (IBD). Une détermination de la longueur de l'intestin au moyen d'une technique standardisée et simple est utile lors d'une prise de décision chirurgicale chez des patients atteints de manière primaire ou récurrente de la maladie et dans l'évaluation et le management des troubles d'absorption postopératoire. Le but de la présente étude est d'analyser la longueur de l'intestin chez des patients atteints d'IBD et de définir une méthode standard de mesure. Materiel et methode: Deux séries consécutives de patients atteints de maladie de Crohn (n = 279) et de colite ulcéreuse (n = 315) ainsi qu'un groupe-contr?le (n = 77) ont fait l'objet d'une mesure standardisée per-opératoire de la longueur de l'intestin. Resultats: La longueur de l'intestin est corrélée au poids et à la taille et est plus petite chez les femmes que chez les hommes (P < 0,001) dans les deux groupes de maladie inflammatoire et dans le groupe-contr?le. L'intestin grêle des patients atteints de maladie de Crohn est significativement plus court que celui des patients atteints de colite ulcéreuse et que celui du groupe-contr?le (P < 0,001). De même que l'intestin grêle des patients atteints de colite ulcéreuse est significativement plus court que celui des groupes-contr?le (P < 0,001). Chez des patients atteints de maladie de Crohn, il n'y a pas de différence dans la longueur de l'intestin en relation avec l'étendue de la maladie anatomique. La longuer initiale de l'intestin chez les patients atteints de maladie de Crohn ayant fait l'objet d'une ou de deux résections segmentaires (n = 67) n'est pas significativement différente de celle mesurée chez les patients faisant l'objet de 3 ou plus résections (n = 88). Conclusion: La longueur de l'intestin grêle est corrélée au poids, à la taille et au sexe. Les patients porteurs d'une maladie de Crohn ont un intestin grêle significativement plus court à la première laparotomie que ceux atteints de colite ulcéreuse ou que les sujets-contr?le. Chez les patients porteurs de maladie de Crohn, il n'y a pas de différence significative entre les différents sous-groupes anatomiques.

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Accepted: 11 March 1997     

Joint disease in inflammatory bowel disease

The joint disorders taxonomically included in the group of seronegative spondyloarthropathies under the generic name of enteropathic arthropathy represent the most frequent extra-intestinal manifestation of inflammatory bowel disease (IBD), affecting 33% of patients. Their frequency is similar to that of ulcerative colitis and Crohn's disease. Enteropathic arthropathy consists of two main joint alterations, peripheral and axial arthritis, as well as a variable group of other peri-articular disorders. Type 1, or pauciarticular, peripheral arthritis generally coincides with IBD exacerbations, while type 2, or polyarticular, peripheral arthritis follows an independent course from IBD. Axial involvement precedes and follows an independent course from IBD and can behave as ankylosing spondylitis or asymptomatic sacroiliitis. The treatment of these rheumatologic disorders is based on the application of general measures and the use of nonsteroidal anti-inflammatory agents; intraarticular corticosteroid administration may eventually become necessary. Sulphasalazine and/or infliximab, which are indicated when the previously mentioned measures fail, can be used to treat both the articular and intestinal diseases simultaneously.     

Hepatobiliary disease in inflammatory bowel disease

Many hepatobiliary diseases are seen in IBD. PSC is the most common, occurring in 7.5% of patients with UC. The cause of PSC is not well understood, but PSC seems to be associated with genetic susceptibility, sharing some immunologic abnormalities with UC. A characteristic cholangiogram in a patient with abnormal liver function tests usually establishes the diagnosis. Liver biopsy is not essential but can help make the diagnosis of small duct PSC in patients with a normal cholangiogram. There are no medications that treat PSC effectively. Endoscopic dilation of dominant strictures reduces the frequency of cholangitis and may improve survival. OLT remains the only proven treatment of advanced PSC. Cholangiocarcinoma is a feared complication of PSC that is difficult to diagnose. Cholelithiasis, PBC, portal vein thrombosis, and hepatic abscess are hepatobiliary disorders that occur less frequently in IBD patients.     

Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

Objectives: Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron.

Materials and methods: A retrospective cohort study was designed involving children with inflammatory bowel disease followed in that unit between January 2001 and April 2016. Laboratory results were collected at the moment of diagnosis, after one-year follow-up and prior each IV iron administration performed during the study period. Anemia was defined according to World Health Organization criteria and the iron deficiency was defined using recent guidelines.

Results: Were studied 69 patients 71% had CD and 29% UC. 50.7% were female. Mean patient age at diagnosis was 13.3 years (range 1--17 years). Prevalence of ID and IDA at diagnosis was 76.8% and 43.5%, respectively. After one year follow-up, those values decreased to 68.1% (p?=?.182) and 21.7% (p?=?.002), respectively. Hemoglobin significantly increased (p?<?.001). Intravenous iron was administered to 92.8% of patients. No adverse reactions were reported.

Conclusions: Intravenous iron is the first line in the treatment of Iron deficiency anemia in Inflammatory Bowel disease and it is safe and effective. Persistent anemia and iron deficiency are common.     

Cholelithiasis in inflammatory bowel disease

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.     

Chromoendoscopy in inflammatory bowel disease

Chromoendoscopy with methylene blue or indigo carmine significantly increases the diagnostic yield of finding intraepithelial neoplasia in patients with longstanding colitis. The number needed to treat is 14 for panchromoendoscopy to identify 1 additional patient with dysplasia. Chromoendoscopy can greatly facilitate the identification of flat lesions harboring intraepithelial neoplasia. Chromoendoscopy can guide biopsies and clearly reduces the amount of biopsies that are needed per patient. Magnifying endoscopy or CLE are additional techniques, which can be used in conjunction with chromoendoscopy to further reduce the amount of biopsies and to further increase the diagnostic yield. Chromoendoscopy is an established clinical procedure and recommended by many gastroenterological societies for surveillance of patients with longstanding ulcerative colitis. Thus, intravital staining should be an essential part of the diagnostic armamentarium of every colonoscopist.     

MicroRNAs in inflammatory bowel disease

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene and protein expression. miRNAs are critical to a normal immune response and have altered expression in multiple immune-mediated disorders. This emerging role of miRNAs in the pathogenesis of multiple disease states has led to investigations into miRNA expression profiles in inflammatory bowel disease (IBD). The discovery of miRNAs in IBD is likely to contribute to our understanding of IBD pathogenesis and lead to clinical advances in IBD. This review focuses on miRNA expression in inflammation, autoimmune disorders, and inflammation-associated cancer, as well as their function in the biology and management of IBD.     

Cyclosporine in inflammatory bowel disease

For the past decade, the use of oral and intravenous cyclospo rine has been examined for patients with inflammatory bowe disease who have demonstrated resistance to steroid treatment. Updated and new results from a number of studies offer short-term and long-term data on cyclosporine and its effectiveness in achieving and maintaining remission from disease. Short-term and long-term toxicity associated with cyclosporine is reviewed here, as well as quality of life among patients who have been treated successfully. Also discussed are practice patterns among clinicians using cyclosporine in its varied formulations and the appropriate settings for its use