Environmental influences on inflammatory bowel disease manifestations. Lessons from epidemiology

Environmental factors play an important role in the disease manifestation, course and prognosis of inflammatory bowel disease. Observations on temporal trends and geographical distribution point at risk factors associated with a Western lifestyle. A large number of studies have been performed on various factors such as diet, smoking, and several infectious agents. Childhood exposures modifying immune responses in later life form a particularly interesting field. However, so far, only smoking in Crohn's disease, and smoking cessation in ulcerative colitis can be considered established as risk factors for the manifestation of the disease. Smoking is also associated with a poor prognosis in Crohn's disease. A strong negative association of appendectomy with ulcerative colitis has been very consistent across many studies; however, the implications of this finding are still obscure.     

Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders

Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system’s ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD.     

Novel therapies for inflammatory bowel disease.

Looking back at successes and failures in newer approaches to treating IBD, it is tempting--although still difficult--to draw conclusions about pathogenesis. When a therapy proves effective, do clinicians truly know how it works? Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than preclinical models suggest, can failures in effectiveness from delivery or dosing be differentiated? The disappointing results of clinical trials with IL-10--so at odds with the prediction of benefit from animal models--bring into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is judged. The variability of response even to the most narrowly targeted agents suggests that these diseases are far more heterogeneous in humans than in their murine counterparts. Clinicians are only just beginning to recognize subclinical markers of response, and it may soon be possible to predict response on the basis of genetic composition. For the moment, however, the field of pharmacogenetics is embryonic. Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. Only through considered evaluation of clinical evidence may clinicians determine which therapies should remain novelties and which should become an accepted part of the armamentarium.     

Medical therapy for inflammatory bowel disease.

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.     

Ankylosing spondylitis and inflammatory bowel disease. I. Prevalence of inflammatory bowel disease in patients suffering from ankylosing spondylitis.

To establish the prevalence of inflammatory bowel disease in ankylosing spondylitis (AS), 79 AS patients underwent detailed medical screening, including sigmoidoscopic and roentgenological examination, 48 had gastrointestinal symptoms and the others did not. In 3 patients a diagnosis of Crohn's disease was made which was previously established. In all other patients inflammatory bowel disease could be excluded. The prevalence of inflammatory bowel disease in this series of patients with AS therefore was 3.8%.     

Surgery for inflammatory bowel disease

Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease （IBD）, there are still clear indications for operative management of IBD and its complications. We present an overview of indications, procedures, considerations, and controversies in the surgical therapy of IBD.     

炎症性肠病结肠镜检查的评价

随着结肠镜对炎症性肠病镜下和活检病理形态改变的认识不断加深 ,它的使用价值也不断提高。Ｆｒ櫣ｈｍｏｒｇｅｎ总结过去 10年经验 ,发现对溃疡性结肠炎确诊率达 93.9% ,对克罗恩病达 77.3%。因此 ,近年来有倾向 ,结肠镜应列为诊断炎症性肠病的常规检查。结合我院过去 2 0年中炎症性肠病所见的形态改变 ,对其使用价值进行讨论。　　炎症性肠病在结肠镜下的形态 ,首先表现为分布方式和累及部位不同。溃疡性结肠炎呈连续性分布 ,并且疾病初期往往先累及直肠 ,逐渐向近端结肠蔓延 ,严重者累及整个结肠 ,仅有极少数倒灌性肠炎者可达回肠末端近…     

Biologic therapies for chronic inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) make up the so-called chronic inflammatory bowel disease (IBD). Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin a4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors.Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab), T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.     

Use of prebiotics for inflammatory bowel disease.

The relevance of diet in both the pathogenesis and the therapy of inflammatory bowel disease is an evolving science. Disturbance of intestinal microflora (dysbiosis) is putatively a key element in the environmental component causing inflammatory bowel disease. Prebiotics are among the dietary components used in an attempt to counteract dysbiosis. Such predominantly carbohydrate dietary components exert effects on the luminal environment by physicochemical changes through pH alteration, by production of short chain fatty acids and by selectively promoting putatively 'health-beneficial' bacteria. The present review elaborates on some of the background rationale and mechanisms on the use of prebiotics. Additionally, published animal and human trials are discussed.     

Salicylates for inflammatory bowel disease

Targeted delivery of 5-aminosalicylic acid to the small intestine and colon by controlled-release or azo-bonded compounds potentially offers treatment for ileal Crohn's disease as well as ulcerative colitis. The pharmacokinetics of sulphasalazine and aminosalicylate derivatives have been discussed and potential modes of action reviewed. These include actions on epithelial cell-surface receptors, cellular events and barrier function. Evidence for an influence of salicylates on circulating and tissue inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic peptides, eicosanoids, cytokines and reactive oxygen metabolites. The precise mechanism remains unknown, but a pluripotential mode of action is an advantage when influencing the network of events that constitutes chronic inflammation. Controlled clinical trials of salicylates in ulcerative colitis and Crohn's disease have been reviewed. Their main role remains as maintenance therapy for ulcerative colitis, but relatively high doses of controlled-release preparations benefit patients with ileal Crohn's disease, following resection, or those who have recently relapsed. Finally, issues of clinical relevance have been addressed, including the choice of salicylate and safety, indications for initiating therapy, dose and duration of treatment, role in managing refractory colitis and future developments.     

Self-management for people with inflammatory bowel disease.

In North America and the United Kingdom, we are in the age of self-management. Many patients with chronic diseases are ready to participate in the therapeutic decision-making process, and join their physicians in a co-management model. It is particularly useful to consider this concept at a time when physician shortages and waiting times are on the front page every day, with no immediate prospect of relief. Conditions such as diabetes, asthma, chronic obstructive pulmonary disease, recurrent urinary tract infections and others lend themselves to this paradigm of medical care for the informed patient. The present paper reviews some of the literature on self-management for the patient with inflammatory bowel disease (IBD), and provides a framework for the use of self-management in the IBD population, with emphasis on the concept of a patient passport, and the use of e-mail, supported by an e-mail contract, as proposed by the Canadian Medical Protective Association. Examples of specific management strategies are provided for several different IBD scenarios. Eliminating the need for some office visits has clear environmental and economical benefits. Potential negative consequences of this form of patient care are also discussed.     

Fibromyalgia in inflammatory bowel disease.

OBJECTIVE: Studies of the rheumatological complications of inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) have focused on peripheral arthritis and spondylitis, and less is known about soft tissue rheumatism, specifically the fibromyalgia syndrome (FM). Our aim was to estimate the prevalence of FM and assess pain thresholds in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Seventy-two patients with UC and 41 with CD attending consecutively at the Gastroenterology Outpatient Clinic were assessed for the presence of FM and tenderness thresholds. FM was diagnosed according to the American College of Rheumatology 1990 criteria. Tenderness was measured by manual palpation and with a dolorimeter. One hundred twenty healthy subjects served as controls. RESULTS: FM was documented in 30 of 113 patients with IBD (30%), specifically in 49% of patients with CD and 19% with UC (p = 0.001); in controls the rate was 0%. Subjects with CD exhibited more tenderness and reported more frequent and more severe FM associated symptoms than subjects with UC. Patients with CD had a higher tender point count, 11.3 (+/- 6.5), than those with UC, 6.4 (+/- 5.7) (p = 0.001); in healthy controls, the count was 0.1 (+/- 0.5). Tenderness thresholds (kg) were lower in CD 2.9 (+/- 1.7) than UC 3.9 (+/- 2.0) (p = 0.005) and controls 5.8 (+/- 0.9). CONCLUSION: FM is common in IBD, particularly Crohn's disease. The lower pain threshold in Crohn's disease may suggest a disease-specific effect. Recognizing FM in patients with IBD will prevent misdiagnosis and ensure correct treatment.     

Hyposplenism in inflammatory bowel disease.

Splenic function was assessed in 35 patients with ulcerative colitis and 20 patients with Crohn's disease. Hyposplenism was diagnosed if there were Howell-Jolly bodies in the peripheral blood film or if there was prolongation of clearance from the peripheral blood of injected 51-Cr-labelled heat-damaged red blood cells. Thirteen of the patients with ulcerative colitis had hyposplenism as compared with only one patient with Crohn's disease. Conversely, heat-damaged red cell clearance values faster than the normal range were found in six out of the 20 patients with Crohn's disease. Four patients with hyposplenism and ulcerative colitis developed life-threatening septicaemia in the early postcolectomy period, two of these being further complicated by disseminated intravascular coagulation.