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.     

Pancreatic disorders in inflammatory bowel disease

An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been rec-orded in patients with inflammatory bowel disease(IBD) compared to the general population.Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced,in some cases pancreatitis were defined as idiopathic,suggesting a direct pancreatic damage in IBD.Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn's disease and ulcerative colitis.This review will discuss the most common pancreatic diseases seen in patients with IBD.     

Patterns of airway involvement in inflammatory bowel diseases

Extraintestinal manifestations occur commonly in inflammatory bowel diseases(IBD). Pulmonary manifestations(PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and highresolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheo-bronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency.     

From the surface to the single cell: Novel endoscopic approaches in inflammatory bowel disease

Inflammatory bowel diseases(IBD) comprise the two major entities Crohn's disease and ulcerative colitis and endoscopic imaging of the gastrointestinal tract has always been an integral and central part in the management of IBD patients. Within the recent years,mucosal healing emerged as a key treatment goal in IBD that substantially decides about the clinical outcome of IBD patients,thereby demanding for a precise,timely and detailed endoscopic assessment of the mucosal inflammation associated with IBD. Further,molecular imaging has tremendously expanded the clinical utility and applications of modern endoscopy,now encompassing not only diagnosis,surveillance,and treatment but also the prediction of individual therapy response. Within this review we describe novel endoscopic approaches and advanced endoscopic imaging methods for the diagnosis,treatment and surveillance of IBD patients. We begin by providing an overview over novel and advanced imaging techniques such as magnification endoscopy and dye-based and dye-less chromoendoscopy,endomicroscopy and endocytoscopy. We then describe how these techniques can be utilized for the precise and ultrastructural assessment of mucosal inflammation and dysplasia development associated with IBD and outline how they have enabled the endoscopist to gain insight onto the cellular level in real-time. Finally,we provide an outlook on how molecular imaging has rapidly evolved in the recent past and can be used to make individual predictions about the therapeutic response towards biological treatment.     

Non-pulmonary allergic diseases and inflammatory bowel disease: A qualitative review

While the etiological underpinnings of inflammatory bowel disease(IBD) are highly complex, it has been not-ed that both clinical and pathophysiological similarities exist between IBD and both asthma and non-pulmonary allergic phenomena. In this review, several key points on common biomarkers, pathophysiology, clinical manifesta-tions and nutritional and probiotic interventions for both IBD and non-pulmonary allergic diseases are discussed.Histamine and mast cell activity show common behav-iors in both IBD and in certain allergic disorders. IgE also represents a key immunoglobulin involved in both IBD and in certain allergic pathologies, though these links require further study. Probiotics remain a critically important intervention for both IBD subtypes as well as multiple allergic phenomena. Linked clinical phenomena, especially sinonasal disease and IBD, are discussed. In addition, nutritional interventions remain an underuti-lized and promising therapy for modification of both al-lergic disorders and IBD. Recommending new mothers breastfeed their infants, and increasing the duration of breastfeeding may also help prevent both IBD and al-lergic diseases, but requires more investigation. While much remains to be discovered, it is clear that non-pulmonary allergic phenomena are connected to IBD in a myriad number of ways and that the discovery of com-mon immunological pathways may usher in an era of vastly improved treatments for patients.     

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.     

HLA-Cw基因多态性与炎症性肠病的关系

目的 探讨人类白细胞抗原(HLA) -Cw等位基因与炎症性肠病(IBD)的相关性,以期发现IBD的易感基因。方法 采用序列特异性引物聚合酶链反应(PCR-SSP)方法,对100例溃疡性结肠炎(UC)、73例克罗恩病(CD)和106例健康对照进行HLA-Cw基因分型。结果 UC患者组HLA-Cw* 07基因表型频率为0.430,明显高于健康对照组(0.226),P=0.002;CD患者组HLA-Cw* 12基因表型频率为0.356,明显高于健康对照组(0.123),P=0.000。结论 HLA-Cw* 07基因可能与UC易感性密切相关;HLA-Cw*12基因可能与CD易感性密切相关。     

Crucial steps in the natural history of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, progressive and disabling disorders. Over the last few decades, new therapeutic approaches have been introduced which have led not only to a reduction in the mortality rate but also offered the possibility of a favorable modification in the natural history of IBD. The identification of clinical, genetic and serological prognostic factors has permitted a better stratification of the disease, thus allowing the opportunity to indicate the most appropriate therapy. Early treatment with immunosuppressive drugs and biologics has offered the opportunity to change, at least in the short term, the course of the disease by reducing, in a subset of patients with IBD, hospitalization and the need for surgery. In this review, the crucial steps in the natural history of both UC and CD will be discussed, as well as the factors that may change their clinical course. The methodological requirements for high quality studies on the course and prognosis of IBD, the true impact of environmental and dietary factors on the clinical course of IBD, the clinical, serological and genetic predictors of the IBD course (in particular, which of these are relevant and appropriate for use in clinical practice), the impact of the various forms of medical treatment on the IBD complication rate, the role of surgery for IBD in the biologic era, the true magnitude of risk of colorectal cancer associated with IBD, as well as the mortality rate related to IBD will be stressed; all topics that are extensively discussed in separate reviews included in this issue of World Journal of Gastroenterology.     

Hydradenitis suppurativa and inflammatory bowel disease: An unusual,but existing association

Inflammatory bowel disease (IBD) could be associated with several extra-intestinal manifestations (EIMs) involving musculoskeletal, hepatopancreatobiliary, ocular, renal, and pulmonary systems, as well as the skin. In the last years, hidradenitis suppurativa (HS) is acquiring an increasing interest. IBD, especially Crohn’s disease (CD), is among the most reported associated diseases in HS patients. The aim of this paper is to give a brief overview of data showing a possible epidemiologic and pathogenetic association between IBD and HS. We performed a pooled-data analysis of four studies and pooled prevalence of HS in IBD patients was 12.8%, with a 95%CI of 11.7%-13.9%. HS was present in 17.3% of subjects with CD (95%CI: 15.5%-19.1%) and in 8.5% of UC patients (95%CI: 7.0%-9.9%). Some items, especially altered immune imbalance, are generally involved in IBD pathogenesis as well as invoked by HS. Smoking is one of the most relevant risk factors for both disorders, representing a predictor of their severity, despite, actually, there being a lack of studies analyzing a possible shared pathway. A role for inheritance in HS and CD pathogenesis has been supposed. Despite a genetic susceptibility having been demonstrated for both diseases, further studies are needed to investigate a genetic mutual route. Although the pathogenesis of IBD and HS is generally linked to alterations of the immune response, recent findings suggest a role for intestinal and skin microbiota, respectively. In detail, the frequent finding of Staphylococcus aureus and coagulase-negative staphylococci on HS cutaneous lesions suggests a bacterial involvement in disease pathogenesis. Moreover, microflora varies in the different cutaneous regions of the body and, consequently, two different profiles of HS patients have been identified on these bases. On the other hand, it is well-known that intestinal microbiota may be considered as “the explosive mixture” at the origin of IBD despite the exact relationship having not been completely clarified yet. A better comprehension of the role that some bacterial species play in the IBD pathogenesis may be essential to develop appropriate management strategies in the near future. A final point is represented by some similarities in the therapeutic management of HS and IBD, since they may be controlled by immunomodulatory drugs. In conclusion, an unregulated inflammation may cause the lesions typical of both HS and IBD, particularly when they coexist. However, this is still a largely unexplored field.     

Clinical management of inflammatory bowel disease in the organ recipient

There was estimated a higher incidence of de novo inflammatory bowel disease(IBD)after solid organ transplantation than in the general population.The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy.IBD course after liver transplantation(LT)is variable,but about one third of patients may worsen,needing an increase in medical therapy or a colectomy.Active IBD at the time of LT,discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimusbased immunosuppression may be associated with an unfavorable outcome of IBD after LT.Anti-tumor necrosis factor alpha(TNFα)therapy for refractory IBD may be an effective and safe therapeutic option after LT.The little experience of the use of biological therapy in transplanted patients,with concomitant anti-rejection therapy,suggests there be a higher more careful surveillance regarding the risk of infectious diseases,autoimmune diseases,and neoplasms.An increased risk of colorectal cancer(CRC)is present also after LT in IBD patients with primary sclerosing cholangitis(PSC).Anannual program of endoscopic surveillance with serial biopsies for CRC is recommended.A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention,but it is used infrequently in the majority of LT centers.About 30%of patients develop multiple IBD recurrence and 20%of patients require a colectomy after renal transplantation.Like in the liver transplantation,anti-TNFαtherapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation.A large number of patients are needed to confirm the preliminary observations.Regarding the higher clinical complexity of this subgroup of IBD patients,a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.     

Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn’s disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.     

Arterial structure and function in inflammatory bowel disease

Inflammatory bowel disease(IBD) is the result of a combination of environmental,genetic and immunologic factors that trigger an uncontrolled immune response within the intestine,which results in inflammation among genetically predisposed individuals. Several studies have reported that the prevalence of classic cardiovascular risk factors is lower among subjects with IBD than in the general population,including obesity,dyslipidaemia,diabetes and hypertension. Therefore,given the risk profile of IBD subjects,the expected cardiovascular morbidity and mortality should be lower in these patients than in the general population. However,this is not the case because the standardized mortality ratio is not reduced and the risk of coronary heart disease is increased in patients with IBD. It is reasonable to hypothesize that other factors not considered in the classical stratification of cardiovascular risk may be involved in these subjects. Therefore,IBD may be a useful model with which to evaluate the effects of chronic low-grade inflammation in the development of cardiovascular diseases. Arterial stiffness is both a marker of subclinical target organ damage and a cardiovascular risk factor. In diseases characterized by chronic systemic inflammation,there is evidence that the inflammation affects arterial properties and induces both endothelial dysfunction and arterial stiffening. It has been reported that decreasing inflammation viaanti tumor necrosis factor alpha therapy decreases arterial stiffness and restores endothelial function in patients with chronic inflammatory disorders. Consistent with these results,several recent studies have been conducted to determine whether arterial properties are altered among patients with IBD. In this review,we discuss the evidence pertaining to arterial structure and function and present the available data regarding arterial stiffness and endothelial function in patients with IBD.     

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence,diagnosis and treatment

Inflammatory bowel diseases(IBD), Crohn`s disease and ulcerative colitis, are chronic conditions associated with high morbidity and healthcare costs. The natural history of IBD is variable and marked by alternating periods of flare and remission. Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing, a great proportion of IBD patients remain symptomatic despite effective control of inflammation. These symptoms may include but not limited to abdominal pain, dyspepsia, diarrhea, urgency, fecal incontinence, constipation or bloating. In this setting, commonly there is an overlap with gastrointestinal(GI) motility and absorptive disorders. Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment. Therefore, in this review we describe the prevalence,diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.     

Helicobacter pylori infection and inflammatory bowel disease: Is there a link?

Helicobacter pylori(H.pylori)infection is one of the most widely spread infectious diseases in humans.It can cause chronic gastritis,peptic ulcer disease and gastric malignancies and has been associated with extra-gastric disorders.H.pylori elicit a chronic systemic inflammatory response which,under certain conditions,may trigger autoimmune reactions and may be implicated in the pathogenesis of autoimmune diseases.Although the pathogenesis of inflammatory bowel disease(IBD)is unknown,it is thought to result from complex interactions between environmental factors and microbiota in the gut of individuals who are genetically susceptible.Several bacterial and viral agents have been implicated in the aetiology of IBD.In theory,H.pylori infection could be involved in the pathogenesis of IBD by inducing alterations in gastric and/or intestinal permeability or by causing immunological derangements resulting in absorption of antigenic material and autoimmunity via various immunological pathways.Similar mechanisms may also be responsible for the co-existence of IBD with other autoimmune diseases and/or extra-intestinal manifestations.However,the epidemiological data fail to support this association.Infact,various studies indicate that the prevalence of H.pylori infection is low in patients with IBD,suggesting a protective role for this infection in the development of IBD.In this report,we aim to shed light on proposed mechanisms and confounding factors underlying the potential link between H.pylori infection and IBD.     

News in brief

There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of, inflammatory bowel disease (IBD). Unfortunately, owing to methodological difficulties inherent in undertaking appropriately targeted and blinded trials, there are limited high-quality data regarding the effects on IBD of interventions aimed to ameliorate stress and mood disorders. Nevertheless, patients want psychological intervention as well as conventional medical strategies. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there are no strong data as of yet to indicate that stress management has a beneficial effect on the activity or course of IBD. As yet, which, when and how interventions targeted at psychological stress and mood disturbances should be offered to individual patients with IBD is not clear.     

伴有肛周疾病的炎症性肠病患者肛门功能及生活质量分析

目的分析肛周疾病对炎症性肠病（IBD）患者肛门直肠功能和生活质量的影响。 方法回顾性分析2018年6月至2020年6月淮安市第二人民医院收治的伴有肛门不适的53例IBD患者（IBD组）。其中CD43例，UC10例。包括肛瘘35例，大便失禁15例，肛门纤维化8例。选择同期来淮安市第二人民医院体检的健康人20名作为健康对照组。通过肛门直肠测压对IBD患者和健康对照组受试者肛门功能进行评估并进行比较。采用炎症性肠病患者生活质量量表（IBDQ）评分对IBD患者生活质量进行评估。 结果IBD患者与健康对照组最大肛门静息压、最大挤压压、直肠容量感觉阈值、最大耐受容量、肛管抑制反射阳性水平差异均无统计学意义（P均>0.05）。大便失禁的IBD患者最大肛门静息压、IBDQ评分均低于非大便失禁的IBD患者，且差异均有统计学意义（P<0.05）。CD与UC患者IBDQ评分差异无统计学意义（P>0.05）；大便失禁IBD患者IBDQ评分低于非大便失禁IBD患者，且差异有统计学意义（P<0.05）。 结论合并肛周疾病的IBD患者肛门直肠功能受损，大便失禁的患者生活质量差。     

Risk factors for osteoporosis in inflammatory bowel disease patients

Inflammatory bowel disease (IBD) patients exhibit higher risk for bone loss than the general population. The chronic inflammation causes a reduction in bone mineral density (BMD), which leads to osteopenia and osteoporosis. This article reviewed each risk factor for osteoporosis in IBD patients. Inflammation is one of the factors that contribute to osteoporosis in IBD patients, and the main system that is involved in bone loss is likely RANK/RANKL/osteoprotegerin. Smoking is a risk factor for bone loss and fractures, and many mechanisms have been proposed to explain this loss. Body composition also interferes in bone metabolism and increasing muscle mass may positively affect BMD. IBD patients frequently use corticosteroids, which stimulates osteoclastogenesis. IBD patients are also associated with vitamin D deficiency, which contributes to bone loss. However, infliximab therapy is associated with improvements in bone metabolism, but it is not clear whether the effects are because of inflammation improvement or infliximab use. Ulcerative colitis patients with proctocolectomy and ileal pouches and Crohn’s disease patients with ostomy are also at risk for bone loss, and these patients should be closely monitored.     

May bacterial or pancreatic proteases play a critical role in inflammatory bowel disease?

In a recent review paper, Carroll and Maharshak discussed a critical role of enteric bacterial proteases in the pathogenesis of inflammatory bowel disease (IBD). I take a great interest in this paper as I also suspected proteases, not from the bacteria, but those originated from the pancreas that failed to be inactivated in the lower gut due to a reduction in gut bacteria, may have played a critical role in the pathogenesis of IBD, which was first published more than a decade ago and discussed again in more detail in a recent paper published in this journal. Antibiotics may result in a big reduction in gut bacteria and bacterial proteases, but multiple studies demonstrated dramatic increased of pancreatic proteases like trypsin and chymotrypsin in the feces of animals or patients treated with antibiotics. Multiple large-scale studies also demonstrated use of antibiotics caused an increase but not decrease in the risk of developing IBD, suggesting impaired inactivation and degradation of pancreatic proteases may have played a more critical role in the pathogenesis of IBD.     

Intestinal microbiota: The explosive mixture at the origin of inflammatory bowel disease?

Inflammatory bowel diseases(IBDs), namely Crohn's disease and ulcerative colitis, are lifelong chronic disorders arising from interactions among genetic, immunological and environmental factors. Although the origin of IBDs is closely linked to immune response alterations, which governs most medical decision-making, recent findings suggest that gut microbiota may be involved in IBD pathogenesis. Epidemiologic evidence and several studies have shown that a dysregulation of gut microbiota(i.e., dysbiosis) may trigger the onset of intestinal disorders such as IBDs. Animal and human investigations focusing on the microbiota-IBD relationship have suggested an altered balance of the intestinal microbial population in the active phase of IBD. Rigorous microbiota typing could, therefore, soon become part of a complete phenotypic analysis of IBD patients. Moreover, individual susceptibility and environmental triggers such as nutrition, medications, age or smoking could modify bacterial strains in the bowel habitat. Pharmacological manipulation of bowel microbiota is somewhat controversial. The employment of antibiotics, probiotics, prebiotics and synbiotics has been widely addressed in theliterature worldwide, with the aim of obtaining positive results in a number of IBD patient settings, and determining the appropriate timing and modality of this intervention. Recently, novel treatments for IBDs, such as fecal microbiota transplantation, when accepted by patients, have shown promising results. Controlled studies are being designed. In the near future, new therapeutic strategies can be expected, with non-pathogenic or modified food organisms that can be genetically modified to exert anti-inflammatory properties.     

Iron, anaemia, and inflammatory bowel diseases

Iron deficiency anaemia is one of the most common disorders in the world. Also, one third of inflammatory bowel disease (IBD) patients suffer from recurrent anaemia. Anaemia has significant impact on the quality of life of affected patients. Chronic fatigue, a frequent IBD symptom itself, is commonly caused by anaemia and may debilitate patients as much as abdominal pain or diarrhoea. Common therapeutic targets are the mechanisms behind anaemia of chronic disease and iron deficiency. It is our experience that virtually all patients with IBD associated anaemia can be successfully treated with a combination of iron sucrose and erythropoietin, which then may positively affect the misled immune response in IBD.