Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral ...     

Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease

There is currently no gold standard test for the diagnosis of inflammatory bowel disease(IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis(UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Noninvasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use.     

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.     

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases(IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis.These idiopathic diseases have environmental, genetic,immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type(Th) 1 and Th2 immune responses,other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin,microRNAs, and serum proinflammatory cytokines.An efficient strategy for IBD therapy is represented by the combination of IL-17 A and IL-17 F in acute IL-17 A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17 F knockout, DSS-induced colitis have been observed.Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused reviewin order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.     

Frequency and associated factors of hair loss among patients with inflammatory bowel disease

AIM: To identify the frequency of hair loss among patients with inflammatory bowel disease(IBD) and associated clinical and disease related factors.METHODS: We performed a cross sectional study in a tertiary referral adult IBD clinic.Self-reported history and characteristics of hair loss as well as clinical and demographic information were collected.Data were analyzed using univariate and multivariate analyses.RESULTS: Two hundred and ten consecutive IBD patients were recruited; one hundred and fifty patients met predefined inclusion and exclusion criteria.Thirtythree percent of patients reported a history of hair loss.Age,gender,IBD type and disease duration were not associated with hair loss.Hair loss was reported less frequently among patients with use of mesalamine(54% vs 73%,P = 0.03) and antitumor necrosis factor medications(anti-TNF)(14% vs 40%,P = 0.001).In multivariate analyses adjusting for gender,IBD type and duration of disease,these associations with mesalamine and anti-TNF remained significant [(adjusted values for mesalamine(OR = 0.43,95%CI: 0.19-0.86) and anti-TNFs(OR = 0.28,95%CI: 0.08-0.98)].CONCLUSION: Hair loss is common among patients with IBD.Mesalamine and anti-TNF medications were associated with lower odds of hair loss.Further studies are required to assess the mechanism of hair loss among patients with IBD.     

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.     

A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases： A pilot study

AIM:To investigate the effect of a new oral preparation,highly concentrated in fish cartilage,in a group of inflammatory bowel diseases(IBD)patients with chronic iron deficient anemia.METHODS:In an open label pilot study,we supple-mented a group of 25 patients(11 with Crohn's disease and 14 with ulcerative colitis)in stable clinical conditions and chronic anemia with a food supplement which does not contain iron but contains a standardized fraction of fish cartilage glycosaminoglycans and a mixture of antioxidants(Captafer Medestea,Turin,Italy).Patients received 500 mg,twice a day during meals,for at least 4 mo.Patients were suggested to maintain their alimentary habit.At time 0 and after 2 and 4 mo,emocrome,sideremia and ferritin were examined.Paired data were analyzed with Student's t test.RESULTS:Three patients relapsed during the study(2 in the 3rd mo,1 in the 4th mo),two patients were lost to follow up and two patients dropped out(1 for orticaria,1 for gastric burning).Of the remaining 18 patients,levels of serum iron started to rapidly increase within the 2nd mo of treatment,P < 0.05),whereas serum ferritin and hemoglobin needed a longer period to significantly improve their serum levels(mo 4)P < 0.05.The product was safe,easy to administer and well tolerated by patients.CONCLUSION:These data suggest a potential new treatment for IBD patients with iron deficiency chronic anemia and warrant further larger controlled studies.     

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by     

Quality of care delivered to hospitalized inflammatory bowel disease patients

Hospitalized patients with inflammatory bowel disease(IBD)are at high risk for morbidity,mortality,and health care utilization costs.While the literature on trends in hospitalization rates for this disease is conflicting,there does appear to be significant variation in the delivery of care to this complex group,which may be a marker of suboptimal quality of care.There is a need for improvement in identifying patients at risk for hospitalization in an effort to reduce admissions.Moreover,appropriate screening for a number of hospital acquired complications such as venous thromboembolism and Clostridium difficile infection is suboptimal.This review discusses areas of inpatient care for IBD patients that are in need of improvement and outlines a number of potential quality improvement initiatives such as payfor-performance models,quality improvement frameworks,and healthcare information technology.     

Minimally invasive approaches for the treatment of inflammatory bowel disease

Despite significant improvements in medical management of inflammatory bowel disease, many of these patients still require surgery at some point in the course of their disease. Their young age and poor general conditions, worsened by the aggressive medical treatments, make minimally invasive approaches particularly enticing to this patient population. However, the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting, currently mostly pursued in high-volume referral centers, despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery. The largest body of evidence currently available for terminal ileal Crohn’s disease shows improved short term outcomes after laparoscopic surgery, with prolonged operative times. For Crohn’s colitis, high quality evidence supporting laparoscopic surgery is lacking. Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis. A consensus about patients’ selection and the need for staging has not been reached yet. Despite the lack of conclusive evidence, a wave of enthusiasm is pushing towards less invasive strategies, to further minimize surgical trauma, with single incision laparoscopic surgery being the most realistic future development.     

Pulmonary manifestations of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease(IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered inthe case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.     

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride(PLC) in colonic inflammatory bowel disease.METHODS:Patients suffering from mild to moderate ulcerative colitis(UC) or Crohn's disease(CD) colitis,with disease activity index(DAI) between 3 and 10 and under stable therapy with oral aminosalicylates,mercaptopurine or azathioprine,for at least 8 wk prior to baseline assessments,were considered suitable for enrollment.Fourteen patients were enrolled to assume PLC 2 g/d(two active tablets twice daily) orally.Clinical-endoscopic and histological activity were assessed by DAI and histological index(HI),respectively,following a colonoscopy performed immediately before and after 4 wk treatment.Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2.Histological response was defined as an improvement of HI of at least 1 point.We used median values for the analysis.Differences pre-and post-treatment were analyzed by Wilcoxon signed rank test.RESULTS:All patients enrolled completed the study.One patient,despite medical advice,took deflazacort 5 d before follow-up colonoscopy examination.No side effects were reported by patients during the trial.After treatment,71%(SE 12%) of patients achieved clinical response,while 64%(SE 13%) obtained remission.Separating UC from CD patients,we observed a clinical response in 60%(SE 16%) and 100%,respectively.Furthermore 60%(SE 16%) of UC patients and 75%(SE 25%) of CD patients were in clinical remission after therapy.The median DAI was 7 [interquartile range(IQR):4-8] before treatment and decreased to 2(IQR:1-3)(P 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5(IQR:4-9) before treatment to 2(IQR:1-3) after treatment(P 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7(IQR:5.5-7.5) before therapy to 1.5(IQR:0.5-2.5) after therapy,differences observed were not significant(P = 0.06).Seventy-nine percent(SE 11%) of patients showed improvement of HI of at least 1 point,while only one CD and two UC patients showed HI stability;none showed HI worsening.Median HI decreased from 1(IQR:1-2),to 0.5(IQR:0-1) at the endoscopic control in the whole population(P 0.01),while it changed from 1(IQR:1-2) to 0.5(IQR:0-1) in UC patients(P 0.01) and from 1.5(IQR:1-2) to 0.5(IQR:0-1) in CD patients(P = not significant).The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients.No side effects were reported during treatment or at 4 wk follow-up visit.CONCLUSION:PLC improves endoscopic and histological activity of mild to moderate UC.Further studies are required to evaluate PLC efficacy in colonic CD patients.     

Role of wireless capsule endoscopy in inflammatory bowel disease

Capsule endoscopy (CE) offers state-of-the-art imaging of the small bowel. In Crohn's disease its clinical role is still uncertain. This report analyses the usefulness of CE in patients with suspected Cronh's disease, in patients with established Crohn's disease (when assessing severity, occult gastrointestinal bleeding and/or as a guide to therapy), in patients with inflammatory bowel disease unclassified (IBDU), and in individuals with ulcerative colitis. The first item in this group is the most important although there is no strong evidence to establish the position of CE in the diagnostic workup. In patients with established Crohn's disease, recently developed activity scores are promising tools for an accurate assessment of severity. As a guide to therapy, CE should be focused on patients with unexplained symptoms when other investigations are inconclusive. In postoperative Crohn's Disease, international consensus recommended considering CE only if ileocolonoscopy is contraindicated or unsuccessful. In the case of IBDU, studies have shown a significant proportion of patients reclassified with Crohn's disease. In this setting, CE could have a role determining small bowel involvement. The role of CE in ulcerative colitis is limited. Some authors advocate CE before colectomy for refractory cases in order to exclude Crohn's disease. In summary, CE offers a new horizon in inflammatory bowel disease, and a better knowledge of mucosal abnormalities that could offer a paradigm shift: changing from symptom-based disease activity estimation to direct mucosal healing monitoring. Nevertheless, randomized controlled studies are still needed to provide stronger evidence in this setting.     

Vaccines and recommendations for their use in inflammatory bowel disease

The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocom-promised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine.     

Case-control study of factors that trigger inflammatory bowel disease flares

AIM:To explore the association between inflammatory bowel diseases(IBD)flares and potential triggers.METHODS:Patients evaluated for an acute flare of IBD by a gastroenterologist at the Dallas VA Medical Center were invited to participate,as were a control group of patients with IBD in remission.Patients were systematically queried about nonsteroidal anti-inflammatory drug use,antibiotic use,stressful life events,cigarette smoking,medication adherence,infections,and travel in the preceding 3 mo.Disease activity scores were calculated for each patient at the time of enrollment and each patient’s chart was reviewed.Multivariate regression analysis was performed.RESULTS:A total of 134 patients with IBD(63 with Crohn’s disease,70 with ulcerative colitis,and 1 with indeterminate colitis)were enrolled;66 patients had flares of their IBD and 68 were controls with IBD in remission(for Crohn’s patients,average Crohn’s disease activity index was 350 for flares vs 69 in the controls;for UC patients,Mayo score was 7.6 for flares vs 1 for controls in those with full Mayo available and 5.4p for flares vs 0.1p for controls in those with partial Mayo score).Only medication non-adherence was significantly more frequent in the flare group than in the control group(48.5%vs 29.4%,P=0.03)and remained significant on multivariate analysis(OR=2.86,95%CI:1.33-6.18).On multivariate regression analysis,immunomodulator use was found to be associated with significantly lower rates of flare(OR=0.40,95%CI:0.19-0.86).CONCLUSION:In a study of potential triggers for IBD flares,medication non-adherence was significantly associated with flares.These findings are incentive to improve medication adherence.     

Trefoil factors in inflammatory bowel disease

Inflammatory bowel disease(IBD),which comprises ulcerative colitis and Crohn’s disease,is characterized by inflammation of the gastrointestinal tract.The trefoil factors 1,2,and 3(TFF1-3)are a family of peptides that play important roles in the protection and repair of epithelial surfaces,including the gastrointestinal tract.TFFs may be involved in IBD pathogenesis and are a potential treatment option.In the present review,we describe the TFF family and their potential role in IBD by summarizing the current knowledge of their expression,possible function and pharmacological role in IBD.     

Colorectal cancer in inflammatory bowel disease: What is the real magnitude of the risk?

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in IBD. IBD-associated CRC (IBD-CRC) affects patients at a younger age than sporadic CRC. The prognosis for sporadic CRC and IBD-CRC is similar, with a 5-year survival of approximately 50%. Identifying at risk patients and implementing appropriate surveillance for these patients is central to managing the CRC risk in IBD. The increased risk of colorectal cancer in association with IBD is thought to be due to genetic and acquired factors. The link between inflammation and cancer is well recognised but the molecular biology, immune pathobiology and genetics of IBD-CRC are areas of much ongoing research. This review examines the literature relating to IBD-CRC, focusing on the incidence of IBD-CRC and examining potential risk factors including age at diagnosis, gender, duration and extent of colitis, severity of inflammation, family history of sporadic CRC and co-existent primary sclerosing cholangitis (PSC). Confirmed risk factors for IBD-CRC are duration, severity and extent of colitis, the presence of co-existent PSC and a family history of CRC. There is insufficient evidence currently to support an increased frequency of surveillance for patients diagnosed with IBD at a younger age. Evidence-based guidelines advise surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis, with the interval for further surveillance guided by risk factors (extent of disease, family history of CRC, post-inflammatory polyps, concomitant PSC, personal history of colonic dysplasia, colonic strictures). There is a move away from using random colonic biopsies towards targeted biopsies aimed at abnormal areas identified by newer colonoscopic techniques (narrow band imaging, chromoendoscopy, confocal microendoscopy).     

Cytomegalovirus in inflammatory bowel disease: A systematic review

AIM: To identify definitions of cytomegalovirus(CMV) infection and intestinal disease, in inflammatory bowel disease(IBD), to determine the prevalence associated with these definitions.METHODS: We conducted a systematic review and interrogated Pub Med, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both Me SH-terms and free searches were performed. We included all types of English-language(clinical) trials concerning diagnostics and prevalence of CMV in IBD.RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia.CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials.     

Has the risk of colorectal cancer in inflammatory bowel disease decreased?

The association between inflammatory bowel disease(IBD)and colorectal cancer(CRC)has been acknowledged for almost a century and is assumedly promoted by a chronic inflammation-driven carcinogenic process in the intestine in combination with a genetic predisposition.The magnitude of the risk of CRC in IBD remains a continuing subject of debate.The early,high risk estimates for CRC in IBD were most likely overestimated due to selected patient populations originating from tertiary referral centers with a disproportional high percentage of patients with severe disease.Later population-based studies calculating risk estimates from a broad spectrum of IBD patients have found the risk to be significantly lower.At present,there is evidence that IBD patients with longstanding and extensive disease with uncontrolled inflammation are those at increased risk.Additional,other recognized risk factors include early age at onset,family history of CRC,and concomitant primary sclerosing cholangitis.A significant amount of effort is put into identifying potential preventive factors of CRC in IBD,including surveillance programs and chemopreventive agents but the individual effect of these remains uncertain.Interestingly,recent studies have reported a decline in risk of CRC over time.Surveillance programs and the new treatment strategies,particular biological treatment might be part of the reason for the observed decline in risk of CRC in IBD over time but future studies will have investigate this assumption.