Vascular complications associated with inflammatory bowel disease

Thromboembolic episode is a well known extraintestinal manifestation of inflammatory bowel disease, but it is a clinical rare complication. Histological and hematological studies suggest that a hypercoagulable state is involved in the pathogenesis of inflammatory bowel disease. However, the exact mechanism of hypercoagulability is still unknown. During the acute recurrences there is an increase of factor VIII, fibrinogen, platelet, factor V and decrease of antithrombin III. Hematologic disorders seem markedly correlated with the activity of the disease. We report on two patients with Inflammatory bowel disease and hypercoagulable state. We review the literature and discuss about the pathogenic mechanisms of such complication.     

Pulmonary complications in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Between 1996 and 1998 we investigated the occurrence of lung disorders in 82 patients with inflammatory bowel disease (30 patients with ulcerative colitis and 52 patients with Crohn's disease) and a control group of 60 subjects. The aim of our study was to determine the occurrence of pulmonary complications in patients with inflammatory bowel disease, to investigate whether ulcerative colitis or Crohn's disease are connected with a typical lung function disorder, with the inflammatory activity of the disease or if they depend on the presence of other extraintestinal manifestations. METHODOLOGY: We investigated the occurrence of lung disorders in terms of the following parameters: clinical pulmonary symptoms, chest radiography and pulmonary function tests (body plethysmography, pneumotachography, lung transfer capacity for carbon monoxide, and blood gas analysis). RESULTS: Lung function abnormalities were significantly more frequent in patients with inflammatory bowel disease as compared to controls (p<0.001). There was no apparent correlation between these abnormalities and either bowel disease activity or drug administration (sulphasalazine, mesalazine). CONCLUSIONS: Despite the lack of radiological abnormalities, we identified a high incidence of pulmonary function abnormalities (suspicious of interstitial lung disorder) in patients with inflammatory bowel disease; 56.7% of patients with ulcerative colitis and 57.7% of patients with Crohn's disease had reduced lung transfer factor.     

Therapy insight: Osteoporosis in inflammatory bowel disease--advances and retreats

There is a discrepancy between the high rates of reduced bone mineral density (BMD) reported in patients with inflammatory bowel disease (IBD) and the relatively low fracture rates observed in population-based studies. When fractures occur, they are most common among the elderly IBD population. It has become clear that BMD is but one of several important factors to be considered when assessing fracture risk. Ideally, BMD should be assessed selectively, as opposed to assessing this measure in all IBD patients simply because they carry an IBD diagnosis. Preventing bone loss should begin with an attempt to limit corticosteroid-induced bone loss. This can be done by using the minimum effective prednisolone dose, substituting budesonide when appropriate, administering other steroid-sparing immunomodulators, or by prescribing additional agents that enhance bone health. The administration of calcium and vitamin D appears to maintain or enhance bone mass. Bisphosphonates are of unclear additional benefit to the majority of patients who are at low fracture risk. Although more data are required to understand the best strategy to prevent fractures, a greater appreciation of the role of selective BMD testing and the utility of simple therapeutic strategies (such as calcium and vitamin D supplements) is emerging.     

Vascular development in inflammatory bowel disease

There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn's disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.     

Perioperative complications in inflammatory bowel disease

Almost 50% of patients with inflammatory bowel disease (IBD) will undergo surgery for their disease at some stage of its clinical course. Complications seen following surgery may occur early or late in the postoperative period. Patient factors, including active inflammatory disease, malnutrition, and use of immunosuppressant medications, make these patients a challenging surgical group and at increased risk for surgical complications. The purpose of this review is to characterize the complications that are commonly seen following surgery in patients with IBD and to discuss the surgical and patient factors that may influence their development.     

Therapy with stem cells in inflammatory bowel disease

Inflammatory bowel disease(IBD) affects a part of the young population and has a strong impact upon quality of life. The underlying etiology is not known, and the existing treatments are not curative. Furthermore, a significant percentage of patients are refractory to therapy. In recent years there have been great advances in our knowledge of stem cells and their therapeutic applications. In this context, autologous hematopoietic stem cell transplantation(HSCT) has been used in application to severe refractory Crohn’s disease(CD), with encouraging results. Allogenic HSCT would correct the genetic defects of the immune system, but is currently not accepted for the treatment of IBD because of its considerable risks. Mesenchymal stem cells(MSCs) have immune regulatory and regenerative properties, and low immunogenicity(both autologous and allogenic MSCs). Based on these properties, MSCs have been used via the systemic route in IBD with promising results, though it is still too soon to draw firm conclusions. Their local administration in perianal CD is the field where most progress has been made in recent years, with encouraging results. The next few years will be decisive for defining the role of such therapy in the management of IBD.     

Systemic complications of inflammatory bowel disease

Radiologic assessment of the sacroiliac joints should be part of every inflammatory bowel disease patient's workup; ankylosing spondylitis is 10 to 20 times more common in ulcerative colitis patients than in normal persons. Iritis, which occurs in 10 to 20% of ulcerative colitis patients, often precedes bowel symptoms. It may be necessary to use long-term, low-dose steroid therapy to control frequently recurring iritis.     

Extraintestinal complications of inflammatory bowel disease

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.     

炎症性肠病肝胆并发症的研究进展

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD),是一种免疫介导的慢性特发性胃肠道炎症性疾病,常伴随有肠外表现(extrainte stinal manifestations,EIMs),且涉及多个器官.肝胆系统病变是IBD常见的肠外表现,包括原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)、非酒精性脂肪肝、胆石症、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)、小胆管性PSC、IgG4相关性胆管炎(IgG4-associated cholangitis,IAC)、肉芽肿性肝炎、淀粉样变性、自身免疫性肝炎(autoimmune hepatitis,AIH)、PSC/AIH重叠综合征和门静脉血栓形成等.本综述从IBD相关的肝胆并发症方面简述了该领域的研究进展,以期能为认识IBD相关肝病的发病机制和临床治疗提供新的启示.     

Preventing infective complications in inflammatory bowel disease

Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis,which comprise the inflammatory bowel diseases(IBD).This is due to the increasing use of immunosuppressives and in particular the biological agents,which are being used earlier in the course of disease,and for longer durations,as these therapies result in better clinical outcomes for patients.This,however,has the potential to increase the risk of opportunistic and serious infections in these patients,most of which are preventable.Much like the risk for potential malignancy resulting from the use of these therapies long-term,a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection.This outcome is achieved by the physician’s tailored use of justified therapies,and the patients’education and actions to minimize infection risk.The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.     

Genetic risk factors in patients with inflammatory bowel disease and vascular complications: case-control study

BACKGROUND: Inherited risk factors have been suggested to play an important role in the pathogenesis of vascular complications of inflammatory bowel disease (IBD). The aim of the present study was to investigate the role of mutations associated with cardiovascular disease in IBD patients with or without vascular complications compared with thrombotic and healthy controls (HC). METHODS: Twelve polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of 30 IBD patients with vascular complications (IBD-VC) compared with 60 IBD patients without vascular complications, 30 thrombotic controls (TC), and 54 healthy controls, using a commercially available kit. RESULTS: No significant differences between IBD-VC and TC concerning the carriage of these mutations were found. The frequencies of the factor V (FV) 506 RQ (Leiden) genotype and the 506Q allele were significantly higher in these groups than in HC (P < 0.05) but not IBD controls (P > 0.05). The allele frequency of the mutant 4G allele of the plasminogen activator inhibitor (PAI) polymorphism, similar in the IBD-VC and TC groups, was significantly higher in these groups compared with the IBD group (P = 0.03) and the HC (P = 0.001). It is noteworthy that there was a trend of association of FV R506Q polymorphism with venous thrombosis and PAI-1 gene polymorphism with arterial thrombosis. CONCLUSIONS: Our results suggest that the investigated gene polymorphisms do not differ in patients with IBD-VC and TC. FV R506Q and PAI-1 gene polymorphisms might be associated with the increased risk of development of vascular complications in IBD.     

Vascular endothelial growth factor in inflammatory bowel disease

BACKGROUND AND AIMS: Angiogenesis is an important component of tissue regeneration. As Inflammatory bowel disease (IBD) involves inflammation, ulceration, and regeneration of the intestinal mucosa, angiogenesis may be an integral part of IBD pathology. This study investigated the role of vascular endothelial growth factor in IBD. PATIENTS AND METHODS: The VEGF plasma (pVEGF) and serum (sVEGF) levels were assessed in patients with ulcerative colitis (UC; n=50) or Crohn's disease (CD; n=44) and in healthy controls (n=23). The immunohistochemical expression of VEGF was also assessed in surgical material from 11 patients with active IBD. RESULTS. Overall the sVEGF levels ranged from 30-899 pg/ml (median 200 pg/ml) and were significantly higher than the pVEGF levels (range 20-80 pg/ml, median 30 pg/ml). pVEGF levels were significantly lower in patients with active and quiescent CD than in healthy controls. Despite the lower pVEGF levels noted also for patients with UC, the difference was not significant. sVEGF levels were also reduced in patients with IBD, but the difference was not significant. No association of pEGF/sVEGF with beta-thromboglobulin and platelet factor 4 levels (markers of platelet activation) was noted. On immunohistochemistry VEGF was not expressed in the inflammatory component (lymphocytes and macrophages), the fibroblasts, or the muscular layer of the intestinal wall. The intestinal epithelium was negative in CD, while a cytoplasmic reactivity was noted in UC and normal controls. CONCLUSION. As VEGF is a vascular and epithelial cell survival factor, the defective VEGF response ability, confirmed here for patients with CD, may be a key element in the pathology of the disease. The pathology of UC, however, seems not to be VEGF dependent.     

Vaccinations in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease (IBD) frequently requires administration of immunosuppressive therapies, which increases susceptibility to a number of infectious pathogens. However, many infections can be prevented by correct and appropriate utilization of vaccinations. While several guidelines have been published on vaccination schedules in patients with IBD, vaccination rates remain suboptimal and even lower than those in the general population. This is due to many factors including poor awareness of the importance of vaccines by gastroenterologists and general practitioners as well as potential prejudices of patients regarding the safety and benefits of vaccines. With the aim of increasing awareness about the key role of immunization in the management of patients with IBD, the present review examines the existing literature relating to the main vaccinations and their application in these patients. We also summarize current evidence in order to provide clinicians with an easy source of reference for the principal recommendations for prevention of infectious diseases in patients with IBD. In addition, the recommendations about traveling for IBD patients are briefly explored. Lastly, since it is important for gastroenterologists to be aware of recommendations on vaccination, we recommend implementing educational programs to ensure compliance with current guidelines.     

Arterial thromboembolic complications of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease are legion and are demonstrated in one-third of those afflicted. In general, they do not mandate surgery. Three patients with active pancolonic ulcerative colitis developed arterial thromboembolic complications prior to surgical treatment. Thromboembolic complications are not fully understood, as is evidenced by the paucity of information in the literature, and only sporadic cases of arterial thromboemboli are found. These have been described primarily in the postsurgical patient. To ascertain whether others have encountered similar cases, a survey form was distributed to members of The American Society of Colon and Rectal Surgeons, yielding an additional 54 patients with thromboembolic complications. Approximately two-thirds were deep venous thromboses and/or pulmonary emboli. Ten patients had cerebrovascular accidents, and eight had arterial emboli. Eleven patients, over 21 percent, suffered multiple events. There were four resultant mortalities. An arterial thromboembolic event in a patient with ulcerative colitis is usually associated with pancolonic disease, has a poor long-term prognosis, and is an indication for colectomy.     

Communicating with patients with inflammatory bowel disease

Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are chronic illnesses that affect hundreds of thousands of Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain, gastrointestinal bleeding, malabsorption, and weight loss requiring continuous medical and surgical attention. Despite recent advances in therapy, IBD follows a course of exacerbations and remissions with approximately 25-50% of patients relapsing annually. Hence, these diseases are readily encountered in primary care and gastroenterology clinics. Though medical and surgical treatment options have improved significantly, little has been written about the psychosocial aspects of IBD. Currently, there is a paucity of data concerning effective communication methods enabling physicians to develop stronger rapport with patients suffering from IBD, the care of whom requires a multidisciplinary approach involving primary care physicians, gastroenterologists, and colorectal surgeons. Because IBD has a high morbidity, it is worthwhile to further investigate those social factors that will improve patients' quality of life. In this paper, we summarize some of the common problems that emerge when taking care of patients with IBD and provide initial guidelines based on the world literature regarding the management and education of patients with IBD. Both primary care physicians and specialists (gastroenterologists, colorectal surgeons) need to be aware of the questions and concerns of IBD patients and to be capable of dispensing the information in a clear and concise manner. Using the case scenario format, we review the most common aspects of communication for health care professionals taking care of IBD patients and suggest ways to establish and maintain long-term doctor-patient relationships. The two most significant interventions that dramatically improve quality of life and patient-physician relationships are proper patient education and appropriate treatment of concurrent depression and anxiety. We hope that our review will form a framework by which different members of the medical team learn their roles in the complex management decisions affecting IBD patients.     

Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects

Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD), are chronic inflammatory conditions, characterized by a microvascular and also macrovascular involvement. Chronically inflamed intestinal microvessels of IBD patients have demonstrated significant alterations in their physiology and function compared with vessels from healthy and uninvolved IBD intestine. Recently, some studies have revealed that the poor mucosal healing, refractory inflammatory ulcerations and damage in the IBD intestine could depend on microvascular dysfunction, resulting in diminished vasodilatory capacity and tissue hypoperfusion in the IBD gut. Furthermore, several data show that the activation of intestinal endothelium plays a critical role in the pathogenesis and/or in perpetuating and amplifying the inflammatory process in IBD and, consequently, it is now emerging as a potential use of anticoagulant or coagulation-related drugs in treating IBD. IBD is also associated with an increased risk of macrovascular venous and arterial thrombosis. Thrombotic events occur prevalently as deep vein thrombosis and pulmonary embolism. They happen at an earlier age than in non-IBD patients. Prothrombotic risk factors in IBD patients could be distinguished as acquired, such as active inflammation, immobility, surgery, steroid therapy, and use of central venous catheters, and inherited. Furthermore, it has been found that IBD, per se, is an independent risk factor for thrombosis. The prevention of thromboembolic events in IBD patients includes the elimination of removable risk factors and, if thrombosis occurs, a pharmacological therapy similar to that used for thromboembolic events occurring in the general population.