Articles On Inflammatory Bowel Disease & Colon Cancer

Intra-abdominal venous and arterial thromboembolism in inflammatory bowel disease. [Review] [102 refs] Di Fabio F. Obrand D. Satin R. Gordon PH. Diseases of the Colon & Rectum. 52(2):336-42, 2009. Venous and arterial thromboembolism constitutes a significant cause of morbidity and mortality in patients with inflammatory bowel disease. The most common thrombotic manifestations are lower extremity deep vein thromboses with or without pulmonary embolism. Occasionally, thromboembolic events occur in the main abdominal vessels, such as the portal and superior mesenteric veins, vena cava and hepatic vein, aorta, splanchnic and iliac arteries, or in the limb arteries. The decision-making process for the treatment of these uncommon thromboembolic complications in inflammatory bowel disease may be very challenging for several reasons: 1) no standardized therapies are available; 2) the decision of starting anticoagulant therapy implies the potential risk of intestinal bleeding; 3) thromboembolic events may recur and be life-threatening if inadequately treated. The literature was searched by using MEDLINE, Embase, and the Cochrane library database. Studies published between 1970 and 2007 were reviewed. We discuss the medical and surgical therapeutic options that should be considered to optimize the outcome and reduce the risk of complications in abdominal thromboembolisms associated with inflammatory bowel disease.

Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects. [Review] [54 refs] Papa A. Scaldaferri F. Danese S. Guglielmo S. Roberto I. Bonizzi M. Mocci G. Felice C. Ricci C. Andrisani G. Fedeli G. Gasbarrini G. Gasbarrini A. Digestive Diseases. 26(2):149-55, 2008. 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. 2008 S. Karger AG, Basel.

Inflammatory bowel disease: thinking outside of the intestines (Part 2). [Review] [42 refs] Ricker JM. Harrison SA. Journal of the Mississippi State Medical Association. 49(12):365-9, 2008. Inflammatory bowel disease (IBD) can present itself in many different ways. Although it mainly affects the gastrointestinal tract, it can manifest itself practically anywhere else within the body. These extraintestinal manifestations (EMs) can occur both during active disease and when the disease is quiescent, and in some cases can precede the diagnosis of IBD. It is imperative for physicians to recognize the EMs of IBD since some of them can cause significant morbidity and mortality if left untreated. This article will review the EMs of IBD which involve the hematologic, cardiovascular, pulmonary, neurologic and urinary systems.

Venous thromboembolism with inflammatory bowel disease. [Review] [28 refs] Freeman HJ. World Journal of Gastroenterology. 14(7):991-3, 2008. Venous thrombosis and thromboembolism appear to be increased in patients with inflammatory bowel disease. Although several acquired and genetic risk factors are known, about half that develop a thromboembolic event have no identifiable risk factor. Control of the inflammatory process is thought to be the key factor in risk reduction for thrombotic events. Prophylactic use of anticoagulants is not universally recommended, but possible use should be reviewed in an individual patient after evaluation of the risks, such as hemorrhage, compared to potential benefits. Particular consideration should be given if there has been a prior thrombotic event, if hospitalization will require surgery, or if an underlying coagulation disorder is present.

Inflammatory bowel disease: thinking outside of the intestines (Part 1). [Review] [63 refs] Ricker JM. Harrison SA. Journal of the Mississippi State Medical Association. 49(12):359-64, 2008. Inflammatory bowel disease (IBD) can present itself in many different ways. Although it mainly affects the gastrointestinal tract, it can manifest itself practically anywhere else within the body. These extraintestinal manifestations (EMs) can occur both during active disease and when the disease is quiescent, and in some cases can precede the diagnosis of IBD. It is imperative for physicians to recognize the EMs of IBD since some of them can cause significant morbidity and mortality if left untreated. This article will review the EMs of IBD which involve the hepatobiliary, mucocutaneous, musculoskeletal and ophthalmologic systems.

Colon cancer surveillance in inflammatory bowel disease patients: current and emerging practices. [Review] [63 refs] Velayos F. Expert review of gastroenterology & hepatology. 2(6):817-25, 2008. Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). The cumulative probability of developing this malignancy is significantly higher than in the general population, making IBD the third highest risk condition for CRC. Since CRC is such a concerning complication, it should be no surprise that patients and physicians want to know what the most important risk factors are for its development, as well as potential strategies for reducing these risks. This article reviews the current practice and emerging technologies for detecting and preventing colon cancer in patients with IBD.

Long-term treatment with infliximab in inflammatory bowel disease: safety and tolerability issues. [Review] [83 refs] Caviglia R. Boskoski I. Cicala M. Expert Opinion on Drug Safety. 7(5):617-32, 2008. Crohn's disease and ulcerative colitis represent the most common forms of inflammatory bowel disease (IBD), clinical conditions affecting the small and/or large bowel. It is well known that IBD is an immune-mediated condition and that TNF-alpha plays a pivotal role in the pathogenesis of the disease. TNF-alpha has been scrupulously studied as a target for therapeutic intervention in this setting. A number of biologic compounds have been developed, including the European Medicine Agency (EMEA)-approved agents, infliximab and adalimumab. Although their efficacy in induction and maintenance of remission has been established by several clinical trials, many issues regarding safety remain to be elucidated. In fact, anti-TNF treatment may be associated with a number of rare, but serious, adverse events, including infusion reactions, infections, lymphomas and other malignancies. A black-box warning has to be taken into consideration when looking at potential serious infections such as tuberculosis. Active infections, demyelinating disorders and severe heart failure are contraindications for anti-TNF treatment. This review focuses on drug toxicity and adverse events related to infliximab treatment in IBD.

Role of cytokines in inflammatory bowel disease. [Review] [100 refs] Sanchez-Munoz F. Dominguez-Lopez A. Yamamoto-Furusho JK. World Journal of Gastroenterology. 14(27):4280-8, 2008. Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), represents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal macrophages play an important role in the mucosal immune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major contributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cytokine therapies have been developed and tested for the treatment of IBD patients.

Long-term prognosis in patients with psoriasis. [Review] [85 refs] Gulliver W. British Journal of Dermatology. 159 Suppl 2:2-9, 2008. Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated with substantial comorbidity. Traditional comorbid conditions include psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel disease. Increasingly, an association with metabolic dysfunction, including obesity and the metabolic syndrome, and cardiovascular disease, with consequent effects on morbidity and mortality, has been recognized in psoriasis. The underlying inflammatory mechanisms of both psoriasis and psoriasis-associated comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For effective management of psoriasis and related comorbidities, an integrated approach targeting both cutaneous and systemic inflammation may be beneficial, and strategies to improve overall management of the patient should be encouraged to reduce the disease burden. This paper discusses the emerging role of biological agents in this approach, and offers an appreciation of the role of existing anti-psoriasis and adjunctive therapies.

Skin manifestations of inflammatory bowel disease. [Review] [97 refs] Timani S. Mutasim DF. Clinics in Dermatology. 26(3):265-73, 2008. Ulcerative colitis (UC) is an inflammatory disorder of the colon that is associated with several extraintestinal manifestations in multiple organs. Several mucous membrane and skin disorders occur in patients with UC. These disorders are not unique to UC and often occur secondary to other causes or in the absence of an apparent cause. One or more such disorders may occur together in association with UC. Mucous membrane and skin disorders may antedate, occur with, or postdate the onset of UC. The dermatologist plays an important role in suspecting the diagnosis of UC that presents with associated mucous membrane or skin disorders. This review covers the clinical presentation, differential diagnosis, workup, and management of selected mucocutaneous manifestations in UC.

The human gut microbiome: implications for future health care. [Review] [50 refs] Kinross JM. von Roon AC. Holmes E. Darzi A. Nicholson JK. Current Gastroenterology Reports. 10(4):396-403, 2008. In their intestine, humans possess an "extended genome" of millions of microbial genes-the microbiome. Because this complex symbiosis influences host metabolism, physiology, and gene expression, it has been proposed that humans are complex biologic "superorganisms." Advances in microbiologic analysis and systems biology are now beginning to implicate the gut microbiome in the etiology of localized intestinal diseases such as the irritable bowel syndrome, inflammatory bowel disease, and colon cancer. These approaches also suggest possible links between the gut and previously unassociated systemic conditions such as type 2 diabetes and obesity. The elucidation of the intestinal microbiome is therefore likely to underpin future disease prevention strategies, personalized health care regimens, and the development of novel therapeutic interventions. This review summarizes the research that is defining our understanding of the intestinal microbiome and highlights future areas of research in gastroenterology and human health in which the intestinal microbiome will play a significant role.

Extraintestinal manifestations of inflammatory bowel disease. [Review] [35 refs] Ardizzone S. Puttini PS. Cassinotti A. Porro GB. Digestive & Liver Disease. 40 Suppl 2:S253-9, 2008. Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations (EIMs) that may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. As many as 36% of patients with IBD have at least one EIM. Some are more common related to active colitis (joint, skin, ocular, and oral manifestations). Others are especially seen with small bowel dysfunction (cholelithiasis, nephrolithiasis, and obstructive uropathy), and some are nonspecific disorders (osteoporosis, hepatobiliary disease, and amyloidosis). Patients with perianal Crohn's disease are at higher risk for developing EIMs than other IBD patients. Also the presence of one EIM appears to confer a higher likelihood of developing other manifestations than would be expected by chance alone. The identified pathogenetic autoimmune mechanisms include genetic susceptibility antigenic display of autoantigen, aberrant self-recognition, and immunopathogenetic autoantibodies against organ-specific cellular antigen(s) shared by colon and extra-colonic organs. Microbes may play an important role, probably by molecular mimicry. Early recognition of these extraintestinal manifestations should help guide therapy that will reduce overall morbidity in affected patients. This paper reviews the diagnosis, therapy and management of the more common EIMs.

Thrombosis and inflammatory bowel disease-the role of genetic risk factors. [Review] [56 refs] Tsiolakidou G. Koutroubakis IE. World Journal of Gastroenterology. 14(28):4440-4, 2008. Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Recent data suggest thromboembolism as a disease-specific extraintestinal manifestation of IBD, which is developed as the result of multiple interactions between acquired and genetic risk factors. There is evidence indicating an imbalance of procoagulant, anticoagulant and fibrinolitic factors predisposing in thrombosis in patients with IBD. The genetic factors that have been suggested to interfere in the thrombotic manifestations of IBD include factor V Leiden, factor II (prothrombin, G20210A), methylenetetrahydrofolate reductase gene mutation (MTHFR, 6777T), plasminogen activator inhibitor type 1 (PAI-1) gene mutation and factor XIII (val34leu). In this article we review the current data and future prospects on the role of genetic risk factors in the development of thromboembolism in IBD.

Gut, inflammation and osteoporosis: basic and clinical concepts. [Review] [123 refs] Tilg H. Moschen AR. Kaser A. Pines A. Dotan I. Gut. 57(5):684-94, 2008. Chronic inflammatory disorders such as inflammatory bowel diseases (IBD) affect bone metabolism and are frequently associated with the presence of osteoporosis. Bone loss is regulated by various mediators of the immune system such as the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, or interferon-gamma. TNF-alpha, a master cytokine in human IBD, causes bone erosions in experimental models and these effects are exerted by osteoclasts. Other TNF-related cytokines such as receptor activator of nuclear factor kappa B (RANK), its ligand, RANKL, and osteoprotegerin are important mediators in inflammatory processes in the gut and are critically involved in the pathophysiology of bone loss. The awareness and early diagnosis of osteoporosis in states of chronic inflammation, together with applied therapies such as bisphosphonates, may be beneficial in inflammation-associated osteoporosis. Although several mechanisms may contribute to osteoporosis in patients with IBD and coeliac disease, inflammation as an important factor has so far been neglected. As key inflammatory mediators in IBD such as TNF-alpha are involved in the disease process both in gut and bone, we hypothesise that neutralisation of TNF-alpha could prove an efficient strategy in the treatment of inflammation-related osteoporosis in the future.

A 2008 panorama on osteoporosis and inflammatory bowel disease. [Review] [46 refs] Sapone N. Pellicano R. Simondi D. Sguazzini C. Reggiani S. Terzi E. Rizzetto M. Astegiano M. Minerva Medica. 99(1):65-71, 2008. The availability of osteodensitometry has contributed significantly to increase the awareness of inflammatory bowel disease (IBD)-associated bone disease. Reported osteoporosis prevalence in patients with IBD range from 2% to 30%. The fractures risk varies between studies, influenced by demographic, clinical and genetic factors. The main pathogenetic factors involved are malabsorption, treatment with glucocorticoids, inflammation (increased cytokine production) and hypogonadism. A screening should be considered for all patients with small bowel Crohn's disease and especially for those with extensive disease, multiple resections, and malnutrition. Supplementation with both calcium and vitamin D is frequently the first step taken, but is insufficient to inhibit bone loss in many patients requiring use of glucocorticoids. Among available therapies, only biphosphonates are effective for treatment of glucocorticoid-induced osteoporosis.

Joint expedition: linking gut inflammation to arthritis. [Review] [85 refs] Jacques P. Elewaut D. Mucosal immunology. 1(5):364-71, 2008. The tight connection between intestinal inflammation and arthritis in spondyloarthritis (SpA) has been studied extensively. Subclinical gut inflammation, which can be considered as a model for early Crohn's disease, was shown to be strongly associated with joint inflammation. Several early mucosal abnormalities were uncovered even in the absence of histological signs of inflammation, providing clues into the pathogenesis of SpA. Nevertheless, many questions remain unanswered. In this review, we highlight recent progress on this intimate relationship between gut and joint inflammation. Emerging evidence exists favoring a role for genes beyond human leukocyte antigen B27 in the genetic predisposition of SpA and intestinal inflammation. Furthermore, the role of these predisposing genes in modulating host-pathogen interaction at mucosal surfaces and the subsequent link between gut and joint inflammation are of utmost importance in understanding the pathogenesis of SpA.

Extraintestinal manifestations of inflammatory bowel disease. [Review] [35 refs] Ardizzone S. Puttini PS. Cassinotti A. Porro GB. Digestive & Liver Disease. 40 Suppl 2:S253-9, 2008. Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations (EIMs) that may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. As many as 36% of patients with IBD have at least one EIM. Some are more common related to active colitis (joint, skin, ocular, and oral manifestations). Others are especially seen with small bowel dysfunction (cholelithiasis, nephrolithiasis, and obstructive uropathy), and some are nonspecific disorders (osteoporosis, hepatobiliary disease, and amyloidosis). Patients with perianal Crohn's disease are at higher risk for developing EIMs than other IBD patients. Also the presence of one EIM appears to confer a higher likelihood of developing other manifestations than would be expected by chance alone. The identified pathogenetic autoimmune mechanisms include genetic susceptibility antigenic display of autoantigen, aberrant self-recognition, and immunopathogenetic autoantibodies against organ-specific cellular antigen(s) shared by colon and extra-colonic organs. Microbes may play an important role, probably by molecular mimicry. Early recognition of these extraintestinal manifestations should help guide therapy that will reduce overall morbidity in affected patients. This paper reviews the diagnosis, therapy and management of the more common EIMs.

Vascular and cellular stress in inflammatory bowel disease: revisiting the role of homocysteine. [Review] [97 refs] Peyrin-Biroulet L. Rodriguez-Gueant RM. Chamaillard M. Desreumaux P. Xia B. Bronowicki JP. Bigard MA. Gueant JL. American Journal of Gastroenterology. 102(5):1108-15, 2007. Moderate hyperhomocysteinemia is a complex trait commonly associated with inflammatory bowel disease (IBD). Nutritional deficiencies and genetic determinants have been identified as risk factors for moderate hyperhomocysteinemia, such as folate and vitamin B(12) deprivation and polymorphisms in the 5,10 methylenetetrahydrofolate reductase (MTHFR) encoding gene, respectively. Homocysteine has a crucial role in cellular stress, epigenetic events, inflammatory processes, and host-microbial interactions. Hyperhomocysteinemia might therefore influence the clinical history of IBD, including disease severity, susceptibility to particular enteric infections, and the risk for the development of colorectal cancer. In contrast, homocysteine metabolism does not seem to contribute to the greater risk of thrombosis in IBD subjects. Herein, we review the evidence linking homocysteine metabolism to the pathophysiology of IBD. Furthermore, we discuss the relevance of screening and treating folate and vitamin B(12) deficiencies in IBD subjects. Given the peculiar frequency of such deficiencies in IBD, normalizing vitamin levels should be an integral part of the management of these patients, especially those with active disease, history of intestinal resection, and/or treated with methotrexate.

Clinical studies with curcumin. [Review] [21 refs] Hsu CH. Cheng AL. Advances in Experimental Medicine & Biology. 595:471-80, 2007. Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects. In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea. The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin following oral application. Nevertheless, the pharmacologically active concentration of curcumin could be achieved in colorectal tissue in patients taking curcumin orally and might also be achievable in tissues such as skin and oral mucosa, which are directly exposed to the drugs applied locally or topically. The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers. Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.

Basic and clinical aspects of osteoporosis in inflammatory bowel disease. [Review] [131 refs] Rodriguez-Bores L. Barahona-Garrido J. Yamamoto-Furusho JK. World Journal of Gastroenterology. 13(46):6156-65, 2007. Low bone mineral density and the increased risk of fracture in gastrointestinal diseases have a multifactorial pathogenesis. Inflammatory bowel disease (IBD) has been associated with an increased risk of osteoporosis and osteopenia and epidemiologic studies have reported an increased prevalence of low bone mass in patients with IBD. Certainly, genetics play an important role, along with other factors such as systemic inflammation, malnutrition, hypogonadism, glucocorticoid therapy in IBD and other lifestyle factors. At a molecular level the proinflammatory cytokines that contribute to the intestinal immune response in IBD are known to enhance bone resorption. There are genes influencing osteoblast function and it is likely that LRP5 may be involved in the skeletal development. Also the identification of vitamin D receptors (VDRs) and some of its polymorphisms have led to consider the possible relationships between them and some autoimmune diseases and may be involved in the pathogenesis through the exertion of its immunomodulatory effects during inflammation. Trying to explain the physiopathology we have found that there is increasing evidence for the integration between systemic inflammation and bone loss likely mediated via receptor for activated nuclear factor kappa-B (RANK), RANK-ligand, and osteoprotegerin, proteins that can affect both osteoclastogenesis and T-cell activation. Although glucocorticoids can reduce mucosal and systemic inflammation, they have intrinsic qualities that negatively impact on bone mass. It is still controversial if all IBD patients should be screened, especially in patients with preexisting risk factors for bone disease. Available methods to measure BMD include single energy x-ray absorptiometry, DXA, quantitative computed tomography (QCT), radiographic absorptiometry, and ultrasound. DXA is the establish method to determine BMD, and routinely is measured in the hip and the lumbar spine. There are several treatments options that have proven their effectiveness, while new emergent therapies such as calcitonin and teriparatide among others remain to be assessed.

Therapy insight: how the gut talks to the joints--inflammatory bowel disease and the spondyloarthropathies. [Review] [58 refs] Meier C. Plevy S. Nature Clinical Practice Rheumatology. 3(11):667-74, 2007. Axial and peripheral arthritis can occur in up to 30% of patients with inflammatory bowel disease. Likewise, the presence of gut inflammation in primary spondyloarthropathies is underappreciated, with subclinical gut inflammation documented in up to two-thirds of patients with this group of inflammatory disorders. Common genetic and immunologic mechanisms underlie the coincidence of inflammation in the joints and the intestine. New research highlights the critical role of innate and adaptive immune responses directed against components of the enteric microbial flora in driving gut and articular inflammation. Indeed, elucidation of genetic and serological immune markers will define clinically important subgroups of patients with these heterogeneous diseases. The treatment of inflammatory articular manifestations of inflammatory bowel disease is similar to the treatment of primary spondyloarthropathies. A notable exception is the use of NSAIDs, which can precipitate flares of inflammatory bowel disease and should be used with caution. Agents that target tumor necrosis factor have been a major advance in the treatment of both gut and joint inflammation in inflammatory bowel disease.

Neurologic manifestations of ulcerative colitis. [Review] [120 refs] Scheid R. Teich N. European Journal of Neurology. 14(5):483-93, 2007. Ulcerative colitis (UC) has traditionally been considered to be an inflammatory disease limited to the colonic mucosa. However, since it has been shown that UC is frequently accompanied by various extraintestinal disorders, there is increasing evidence that UC may also manifest in the nervous system. The following review focuses particularly on these possible manifestations of UC, both in the peripheral (PNS), and in the central nervous system (CNS). A systematic literature search according to the MEDLINE database was performed for this purpose. Although a reliable differentiation may clinically not always be possible, three major pathogenic entities can be differentiated: (i) cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii) systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and cerebral demyelination. With the exception of thromboembolism and sensorineural hearing loss, evidence for a causal relationship relies merely on single case reports or retrospective case series. Considering the CNS-manifestations, similarities between UC-associated disorders of the white matter and acute disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures, unspecified encephalopathies and confusional states are most likely epiphenomena that have to be regarded symptomatic rather than as own entities. A prospective study on the neurologic aspects of UC would be very welcome.

Thoracic manifestations of inflammatory bowel disease. [Review] [113 refs] Black H. Mendoza M. Murin S. Chest. 131(2):524-32, 2007. BACKGROUND: A growing number of case reports suggest that pulmonary disease occurs in association with inflammatory bowel disease (IBD) more frequently than previously recognized. Screening studies have also identified pulmonary abnormalities in a significant proportion of IBD patients. METHODS: A focused literature review of respiratory abnormalities in IBD patients and 55 English-language case series documenting 171 instances of respiratory pathology in 155 patients with known IBD. RESULTS: Screening studies using respiratory symptoms, high-resolution CT, and pulmonary function testing support a high prevalence of respiratory abnormalities among patients with IBD. Case reports and series document a spectrum of respiratory system involvement that spans from larynx to pleura, with bronchiectasis as the single most common disorder. IBD patients have a threefold risk of venous thromboembolism, and recent investigations have also revealed possible ties between IBD and other diseases involving the respiratory system, including sarcoidosis, asthma, and alpha(1)-antitrypsin deficiency. CONCLUSION: Respiratory symptoms and diagnosed respiratory system disorders are more common among patients with IBD than generally appreciated. The spectrum of respiratory disorders occurring among patients with IBD is very broad. Diseases of the large airways are the most common form of involvement, with bronchiectasis being the most frequently reported form of IBD-associated lung disease.

Toxicity of infliximab in the course of treatment of Crohn's disease. [Review] [97 refs] Bratcher JM. Korelitz BI. Expert Opinion on Drug Safety. 5(1):9-16, 2006. Infliximab is a monoclonal antibody directed against the pro-inflammatory mediator TNF-alpha, which was approved in the US in 1998 for treatment-resistant Crohn's disease. Since that time, the indications have dramatically expanded to include rheumatoid arthritis, ankylosing spondylitis, psoriasis and most recently, active ulcerative colitis. Although the safety profile in the initial studies was quite favourable, subsequent studies have shown that a small percentage of patients reported severe side effects, including pneumonia, tuberculosis, lymphoma, drug-induced lupus and hepatotoxicity. Although these complications are rare, it is important to properly screen patients for predisposing conditions before beginning treatment. Furthermore, concurrent use of other immunosuppresive agents, such as 6-mercaptopurine, may reduce the incidence of less serious side effects, such as arthralgias, myopathies and other antibody-associated diseases. Since its approval, infliximab has revolutionised the treatment of Crohn's disease and has shown benefit in a variety of other inflammatory conditions, but significant toxicities can occur that necessitate thorough screening protocols and periodic clinical evaluation.

Use of herbal preparations in the treatment of oxidant-mediated inflammatory disorders. [Review] [94 refs] Kaplan M. Mutlu EA. Benson M. Fields JZ. Banan A. Keshavarzian A. Complementary Therapies in Medicine. 15(3):207-16, 2007. Complementary and alternative medicine (CAM) use has increased in popularity in recent years and herbal therapy alone is now a billion dollar market. For centuries herbs have been used as food and for medicinal purposes. Various herbs have been identified as possessing anti-inflammatory and antioxidative properties, and they are currently being used to treat inflammatory disorders as well as those caused by reactive oxygen species (ROS). Asthma, Alzheimer's disease, inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and atherogenesis are all disorders where inflammation and ROS are involved in their pathogenesis. This review examines the pathogenesis of the above mentioned ROS-mediated inflammatory disorders, as well as discusses the antioxidant and anti-inflammatory mechanisms of various herbs and the clinical trials where herbs have been used to treat these disorders

Urogenital complications of Crohn's disease. [Review] [36 refs] Kane S. American Journal of Gastroenterology. 101(12 Suppl):S640-3,2006. Urogenital complications in Crohn's disease is a very narrow, specific area for consideration. The most frequent conditions that fall under this rubric include fistulous disease involving the genitourinary tract, nephrolithiasis, intrinsic renal diseases associated with Crohn's disease, and considerations in those who have had surgical procedures that alter normal pelvic anatomy. Fistulas involving the ureters, urinary bladder, and vagina are discussed. Nephrolithiasis is commonly in the form of calcium oxalate and uric acid, and is a well-known complication of Crohn's disease secondary to multiple mechanisms. Intrinsic renal disease is relatively rare and includes interstitial nephritis, amyloidosis, IgA nephropathy, and obstructive uropathy. Women who have undergone ileopouch anal anastomosis procedures are at risk for sexual dysfunction, dyspareunia, and decreased fecundity.

Extraintestinal manifestations and complications in inflammatory bowel diseases. [Review] [137 refs] Rothfuss KS. Stange EF. Herrlinger KR. World Journal of Gastroenterology. 12(30):4819-31, 2006. Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.

Therapy insight: Vascular complications in patients with inflammatory bowel disease. [Review] [55 refs] Koutroubakis IE. Nature Clinical Practice Gastroenterology & Hepatology. 2(6):266-72, 2005. Inflammatory bowel disease (IBD) is associated with an increased risk of vascular complications. The most important of these complications are arterial and venous thromboembolism, which represent a significant cause of morbidity and mortality in IBD patients. Recent data suggest that thromboembolism is a disease-specific extraintestinal manifestation of IBD. The most common thrombotic manifestations in IBD are deep vein thrombosis of the leg and pulmonary emboli. It has been suggested that disease activity and the extent of colonic localization are correlated with the risk of developing thromboembolism. The occurrence of thrombosis in patients with IBD is partially attributed to the existing hypercoagulable state in IBD. Both coagulation and fibrinolysis are activated in patients with IBD; this is especially true for those with active disease. The most common risk factors for thrombophilia in IBD patients with venous thromboembolism are Leiden mutation in the gene encoding factor V, hyperhomocysteinemia, and antiphospholipid antibodies. The main genetic defects that have been established as risk factors for venous thrombosis are rather uncommon in IBD, but when present increase the risk of thromboembolism. Screening for coagulation defects seems justified only in IBD patients with a history of thrombosis or a family history of venous thromboembolic events. Antithrombotic treatment of IBD patients with venous thromboembolism is similar to that of thrombotic non-IBD patients.

Boswellic acids in chronic inflammatory diseases. [Review] [69 refs] Ammon HP. Planta Medica. 72(12):1100-16, 2006. Oleogum resins from BOSWELLIA species are used in traditional medicine in India and African countries for the treatment of a variety of diseases. Animal experiments showed anti-inflammatory activity of the extract. The mechanism of this action is due to some boswellic acids. It is different from that of NSAID and is related to components of the immune system. The most evident action is the inhibition of 5-lipoxygenase. However, other factors such as cytokines (interleukins and TNF-alpha) and the complement system are also candidates. Moreover, leukocyte elastase and oxygen radicals are targets. Clinical studies, so far with pilot character, suggest efficacy in some autoimmune diseases including rheumatoid arthritis, Crohn's disease, ulcerative colitis and bronchial asthma. Side effects are not severe when compared to modern drugs used for the treatment of these diseases.

Prevention and treatment of osteoporosis in inflammatory bowel disease.[see comment]. [Review] [179 refs] Lichtenstein GR. Sands BE. Pazianas M. Inflammatory Bowel Diseases. 12(8):797-813, 2006. The following are guidelines for evaluation and consideration for treatment of patients with inflammatory bone disease (IBD) after bone mineral density (BMD) measurements. The Crohn's & Colitis Foundation of America (CCFA) has indicated that its recommendations are intended to serve as reference points for clinical decision-making, not as rigid standards, limits, or rules. They should not be interpreted as quality standards.

Skeletal morbidity in inflammatory bowel disease. [Review] [79 refs] van Hogezand RA. Hamdy NA. Scandinavian Journal of Gastroenterology - Supplement. (243):59-64, 2006. Patients with Crohn's disease are at increased risk of developing disturbances in bone and mineral metabolism because of several factors, including the cytokine-mediated nature of the inflammatory bowel disease, the intestinal malabsorption resulting from disease activity or from extensive intestinal resection and the use of glucucorticoids to control disease activity. Inability to achieve peak bone mass when the disease starts in childhood, malnutrition, immobilization, low BMI, smoking and hypogonadism may also play a contributing role in the pathogenesis of bone loss. The relationship between long-term use of glucocorticoids for any disease indication and increased risk for osteoporosis and fractures is well established. However, the relationship between Crohn's disease and ulcerative colitis and bone loss remains controversial. Depending on the population studied the prevalence of osteoporosis has thus been variably reported to range from 12 to 42% in patients with inflammatory bowel disease (IBD). In IBD most studies demonstrate a negative correlation between bone mineral density (BMD) and glucocorticoid use, but not all authors agree on the relationship between long-term glucocorticoid use and continuing bone loss. Whereas prospective studies do suggest sustained bone loss at both trabecular and cortical sites in long-term glucocorticoid users with inflammatory bowel disease, a decrease in bone mass is also observed in patients with active Crohn's disease not using glucocorticoids, and bone loss is not universally observed in patients with Crohn's disease using orally or rectally administered glucocorticoids. Data on vertebral fractures are scarce and there is no agreement about the risk of non-vertebral fractures in patients with Crohn's disease, although it has been suggested that non-vertebral fracture risk may be increased by up to 60% in patients with IBD. A recent publication reports an increased risk of hip fractures in Crohn's disease related to current and cumulative corticosteroid use and use of opiates, although these fractures could not be related to the severity of osteoporosis. The issue of the magnitude of the problem of osteoporosis has become particularly relevant in Crohn's disease, since the ability of therapeutic interventions to beneficially influence skeletal morbidity has been clearly established in patients with osteoporosis, whether post-menopausal women, men or glucocorticoid users. The main question that arises is whether all patients with Crohn's disease should be treated with bone protective agents on the assumption that they all have the potential to develop osteoporosis or whether the use of these agents should be restricted to patients clearly at risk of osteoporosis and fractures, providing these can be identified. We recommend, based on the available literature and our own experience, that all patients with Crohn's disease should be screened for osteoporosis by means of a bone mineral density measurement in addition to full correction of any potential calcium and vitamin D deficiency, to allow timely therapeutic intervention of the patient at risk while sparing the vast majority unnecessary medical treatment.

Skeletal muscle disorders associated with inflammatory bowel diseases: occurrence of myositis in a patient with ulcerative colitis and Hashimoto's thyroiditis--case report and review of the literature. [Review] [39 refs] Paoluzi OA. Crispino P. Rivera M. Iacopini F. Palladini D. Consolazio A. Paoluzi P. International Journal of Colorectal Disease. 21(5):473-7, 2006. Ulcerative colitis (UC) and Crohn's disease are inflammatory bowel diseases often associated with extra-intestinal manifestations. Of these, neutrophilic dermatoses and arthropathies are the more frequently observed, while the occurrence of striated muscle disorders, namely, myositis, has been very rarely diagnosed in these kinds of patients. The coexistence of immuno-mediated diseases in patients with inflammatory bowel diseases and myositis suggests a common aetiopathogenetic mechanism underlying these conditions. The present report refers to a rare case of a 51-year-old female with UC and Hashimoto's thyroiditis who developed myositis.

Osteoporosis in patients with inflammatory bowel disease: risk factors, prevention, and treatment. [Review] [69 refs] Katz S. Reviews in Gastroenterological Disorders. 6(2):63-71, 2006. Patients with inflammatory bowel disease (IBD) are at increased risk for osteoporotic fracture. Bone density testing and osteoporosis management are recommended for IBD patients at greater risk for fracture (ie, postmenopausal women, men aged . 60 years, and those with low body mass indices, glucocorticoid use, family history of osteoporosis, and malabsorption). Patient management includes modification of osteoporosis risk factors, such as calcium and vitamin D supplementation, hormone deficiency correction, and smoking cessation. When indicated, bisphosphonates, such as risedronate and alendronate, have been shown to increase bone mass and reduce fracture risk in patients with glucocorticoid-induced osteoporosis. Infliximab, an anti-tumor necrosis factor a antibody, increases bone mineral density, but this effect has not as yet translated into reduced fracture risk.

Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications. [Review] [45 refs] Twig G. Zandman-Goddard G. Szyper-Kravitz M. Shoenfeld Y. Annals of the New York Academy of Sciences. 1051:166-73, 2005. Systemic thromboembolism is an extraintestinal manifestation of inflammatory bowel disease (IBD), and an important cause of patient morbidity and mortality. The underlying basis for the hypercoagulable state in IBD is complex, and involves altered activity of all three components that govern hemostasis: platelets, fibrinolysis, and the coagulation cascade. Currently, there are no distinct guidelines for treating or preventing thromboembolic (TE) events in IBD patients compared with the general population. However, the prothrombotic state in IBD stems, at least in part, from several modifiable factors, such as hyperhomocysteinemia and an active inflammatory state. In this review we summarize the mechanisms that favor thrombosis in IBD, and the principles that need to be applied for the primary and secondary prevention of TE in this selected group of patients.