• anemia of chronic disease
• epidemiology
• iron deficiency anemia

• None

• Anemia of chronic disease
• Childhood
• Inflammatory bowel disease
• Iron-deficiency anemia
• Pediatrics

• Humans
• Child
• Anemia/etiology
• Anemia/diagnosis
• Anemia/therapy
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Italy
• Gastroenterology/standards
• Societies, Medical

• Child
• Humans
• Adolescent
• Delayed Diagnosis
• Inflammatory Bowel Diseases/diagnosis
• Colitis, Ulcerative/diagnosis
• Crohn Disease/diagnosis
• Referral and Consultation

• Humans
• Quality of Life
• Retrospective Studies
• Inflammatory Bowel Diseases/complications
• Crohn Disease/complications
• Crohn Disease/diagnosis
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Anemia/diagnosis
• Anemia/epidemiology
• Anemia/etiology

• Crohn's disease
• anemia
• children
• iron suppletion
• ulcerative colitis

• Crohn’s disease
• Diagnostic delay
• Inflammatory bowel disease
• Pediatric
• Ulcerative colitis

• anemia
• iron deficiency
• pathway
• pediatric inflammatory bowel disease

• FUT2
• fucosylation
• inflammatory bowel disease
• intestinal barrier
• l-fucose

• Animals
• Colitis/chemically induced
• Colitis/metabolism
• Colitis/pathology
• Colitis/prevention & control
• Dextran Sulfate/toxicity
• Epithelial Cells/drug effects
• Fucose/pharmacology
• Fucosyltransferases/physiology
• Inflammation/etiology
• Inflammation/metabolism
• Inflammation/pathology
• Inflammation/prevention & control
• Intestinal Mucosa/drug effects
• Intestinal Mucosa/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Protective Agents/pharmacology
• Galactoside 2-alpha-L-fucosyltransferase

• Crohn’s disease
• children
• dietary management
• nutrition

• Child
• Crohn Disease/diet therapy
• Diet
• Dietary Supplements
• Dysbiosis
• Enteral Nutrition
• Gastrointestinal Microbiome
• Gastrointestinal Tract
• Humans
• Inflammatory Bowel Diseases
• Nutrition Assessment
• Nutritional Status
• Nutritive Value
• Remission Induction

• Adolescent
• Anemia, Iron-Deficiency/drug therapy
• Child
• Child, Preschool
• Ferric Compounds/adverse effects
• Gastroenterology
• Humans
• Infusions, Intravenous
• Male
• Maltose/analogs & derivatives
• Retrospective Studies

• Anemia, Iron-Deficiency/epidemiology
• Anemia, Iron-Deficiency/etiology
• Brazil/epidemiology
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/epidemiology
• Prevalence
• Quality of Life
• Referral and Consultation
• Retrospective Studies
• Risk Factors

• Anemia of chronic disease
• Childhood
• Inflammatory bowel disease
• Iron-deficiency anemia
• Pediatrics

• Anemia
• Crohn’s disease
• Inflammatory bowel disease
• Ulcerative colitis

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn's disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

Malnutrition is observed more frequently in patients with inflammatory bowel disease (IBD) than in the general population and associated with adverse clinical outcomes. This study aimed to review the current knowledge regarding the efficacy of dietary and nutritional intervention in IBD patients. Exclusive enteral nutrition might be inferior to corticosteroid treatment in adults with active Crohn’s disease (CD) but might even be superior considering the adverse effects of corticosteroid treatment in children. Total parenteral nutrition has no advantage over enteral nutrition, which is considered a more physiologic modality in organ function. Current guidelines do not yet recommend ω3-polyunsaturated fatty acid supplementation for the prevention and maintenance of remission in IBD patients. Dietary fiber supplementation could be effective in the relief of symptoms and maintenance of remission in ulcerative colitis (UC). Although vitamin D may be favorable to clinical course of IBD and bone density. Probiotic supplementation has proven to be effective in preventing and treating pouchitis for UC but is less effective in treating CD. Nutritional interventions not only correct nutritional deficiencies but also improve symptoms and clinical courses of the disease. Hence, nutritional approaches need to be developed to significantly evaluate the effectiveness of dietary interventions used to treat IBD.

• Colitis, ulcerative
• Crohn disease
• Inflammatory bowel disease
• Nutrition

• inflammatory bowel disease
• paediatric gastroenterology

• NHS Research Scotland
• Catherine McEwan Foundation

Upper gastrointestinal tract predominant Crohn's Disease (CD) remains an elusive clinical entity, manifesting limited or vague symptomatology, eluding clinical suspicion, and delaying subsequent diagnostic evaluation. As a result, it has not been widely described and there is a lack of clear recommendations for diagnosis or management. Standard IBD evaluation including serologic testing, imaging, and endoscopy may initially not be fruitful. Furthermore, endoscopic evaluation may be grossly normal in patients without long standing-disease. We describe an 18-year-old male who presented with only unexplained, persistent iron-deficiency anemia. Extensive outpatient testing including multiple endoscopic evaluations with standard biopsies was unfruitful. Ultimately, a positive fecal calprotectin prompted enteroscopy with endoscopic mucosal resection (EMR) in an effort to obtain a larger, deeper tissue specimen. Grossly cobblestoned mucosa along with histopathology revealing focal crypt abscesses, chronic inflammation in the lamina propria, and superficial foveolar epithelial regenerative changes were consistent with CD. This patient's case illustrates the need for a high degree of suspicion for CD in patients with unexplained or persistent iron deficiency anemias. Persistent investigation yielded an elevation in fecal calprotectin suggesting underlying gastrointestinal inflammation and prompted advanced endoscopic evaluation with EMR. Waxing and waning tissue findings are characteristic of CD and pose a unique challenge in patients with upper gastrointestinal predominant pathology. As such, diligent workup including laboratory evaluation, imaging, and serial endoscopy is critical to establish pathology and dictate subsequent management in IBD, especially upper gastrointestinal tract predominant CD.

• Anemia
• Crohn disease
• Iron-deficiency
• Screening
• Ulcerative colitis

• Ferric carboxymaltose (FCM)
• inflammatory bowel disease (IBD)
• iron deficiency (ID)
• pediatric

• inflammatory bowel disease
• telephone
• crohn’s disease
• ulcerative colitis
• cost
• healthcare utilization

• Crohn's disease
• Exclusive enteral nutrition
• Nutrition
• Paediatric

• ferric carboxymaltose
• intravenous iron
• iron deficiency anaemia
• iron sucrose
• paediatric

To determine the prevalence of anemia and its association with disease severity in children and adolescents with IBD.

CEDATA-GPGE is a registry for pediatric patients with IBD in Germany and Austria from 90 specialized centers. As markers of disease severity, analysis included patient self-assessment on a Likert scale (1–5; 1 = very good) and physicians' general assessment (0 = no activity to 4 = severe disease) and the disease indices. Anemia was defined as hemoglobin concentration below the 3rd percentile.

Prevalence of anemia was 65.2% in CD and 60.2% in UC. Anemic CD and UC patients showed significantly worse self-assessment than patients without anemia (average ± standard deviation; CD: 3.0 ± 0.9 versus 2.5 ± 0.9, p < 0.0001; UC: 2.9 ± 0.9 versus 2.3 ± 0.9, p < 0.0001). Accordingly, physicians' general assessment (PGA) was significantly worse in anemic than in nonanemic patients in CD (p < 0.0001) and UC (p < 0.0001). PCDAI in anemic CD, p < 0.0001, and PUCAI in anemic UC patients, p < 0.0001, were significantly higher than in nonanemic patients. 40.0% of anemic CD and 47.8% of anemic UC patients received iron during follow-up.

Almost 2/3 of pediatric IBD patients are anemic. Patients' self-assessment and disease severity as determined by PGA and activity indices are worse in anemic patients. Contrastingly, only a minority received iron therapy.

• Iron deficiency
• inflammatory bowel disease
• intravenous iron
• iron deficiency anemia
• pediatrics

• iron deficiency
• anemia
• inflammatory bowel disease
• vitamin d
• hepcidin

• Adolescent
• Anemia, Iron-Deficiency/etiology
• Biomarkers/blood
• C-Reactive Protein/analysis
• Child
• Child, Preschool
• Colitis, Ulcerative/blood
• Colitis, Ulcerative/complications
• Crohn Disease/blood
• Crohn Disease/complications
• Cross-Sectional Studies
• Female
• Hemoglobins/analysis
• Hepcidins/blood
• Humans
• Iron/blood
• Linear Models
• Male
• Nutritional Status
• Orosomucoid/analysis
• Vitamin D/analogs & derivatives
• Vitamin D/blood
• Vitamin D Deficiency/etiology

• K24 RR023356 NCRR NIH HHS
• R01 DK087694 NIDDK NIH HHS
• T32 DK007734 NIDDK NIH HHS
• UL1 TR000454 NCATS NIH HHS

• hepcidin
• inflammatory bowel disease
• iron deficiency anaemia

• Anemia
• Crohn’s disease
• Inflammatory bowel disease
• Ulcerative colitis

Divalent metal-ion transporter 1 (DMT1) has been found to play an important role in the iron metabolism and hemogenesis. However, little is known about the potential role of DMT1 in the pathogenesis of anemia from patients with inflammatory bowel disease (IBD). Herein, we investigated expression of DMT1 in the intestinal mucosa by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, and found that DMT1 was significantly decreased in the inflamed mucosa of active IBD patients compared with that in those patients at remission stage and healthy controls. To further study the mechanism, we cultured HCT 116 cell line in vitro. Expression of DMT1 in HCT116 was demonstrated to be markedly decreased under stimulation with TNF for 24 and 48 h, while JNK inhibitor (JNK-IN-7) could significantly reverse the decrease. Interestingly, anti-TNF therapy successfully improved anemia in clinical responsive Crohn’s disease patients, and DMT1 was found to be markedly up-regulated in intestinal mucosa. Taken together, our studies demonstrate that decreased expression of DMT1 in intestinal mucosa leads to compromised absorption and transportation of iron and that blockade of TNF could rescue anemia and promote DMT1 expression in gut mucosa. This work provides a therapeutic approach in the management of anemia in IBD.

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn’s disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using “pediatric inflammatory bowel disease”, “pediatric Crohn’s disease”, “linear growth”, “pubertal growth”, “bone health”, and “vitamin D” as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients’ growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a “top-down” approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients’ nutritional status.

• Bone health
• Enteral nutrition
• Growth
• Height
• Pediatric inflammatory bowel disease
• Pediatric Crohn’s disease
• Linear growth
• Pubertal growth
• Vitamin D
• Weight loss

• Adolescent
• Adolescent Nutritional Physiological Phenomena
• Age Factors
• Biological Products/therapeutic use
• Body Height
• Bone Development
• Child
• Child, Preschool
• Crohn Disease/complications
• Crohn Disease/diagnosis
• Crohn Disease/drug therapy
• Female
• Gastrointestinal Agents/therapeutic use
• Growth Disorders/diagnosis
• Growth Disorders/drug therapy
• Growth Disorders/etiology
• Growth Disorders/physiopathology
• Human Growth Hormone/therapeutic use
• Humans
• Immunosuppressive Agents/therapeutic use
• Male
• Nutrition Assessment
• Nutritional Status
• Puberty, Delayed/etiology
• Puberty, Delayed/physiopathology
• Remission Induction
• Risk Factors
• Treatment Outcome
• Weight Gain
• Young Adult

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.

• Anemia
• Inflammatory bowel disease
• Iron deficiency
• Anemia of chronic disease
• Erythropoietin

• Anemia/complications
• Anemia, Iron-Deficiency/complications
• Cytokines/metabolism
• Dietary Supplements
• Erythropoietin/therapeutic use
• Ferritins/blood
• Folic Acid Deficiency/complications
• Hemolysis
• Hepcidins/blood
• Humans
• Inflammatory Bowel Diseases/complications
• Iron/administration & dosage
• Prognosis
• Quality of Life
• Vitamin B 12 Deficiency/complications