Inflammatory bowel diseases (IBD) are among the leading cause of financial burden, morbidity and employee absenteeism in developed countries because of their chronic remitting and relapsing courses. IBD is estimated to affect the Canadian economy to the tune of 100 million dollars per year. The data regarding exact prevalence in Asian countries, including Saudi Arabia, is still incomplete as there is underreporting and lack of proper registry of the diagnosed cases. The prevalence of inflammatory bowel disease (Ulcerative colitis, Crohn’s disease) has increased over the last decade in Saudi Arabia due to increased IBD awareness among population, as more patients seek medical help and also due to unknown reasons. There is a need of proper registration of IBD patients and establishment of Crohn’s & colitis foundation of Saudi Arabia (CCFSA) as in other parts of the world. The Crohn’s & colitis foundation of Saudi Arabia will be a forum which will co ordinate IBD treatment and research in the country in addition to health education among IBD population.
Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology and considered traditionally as a disease of the western world. Recently, rising trends have been observed in countries previously known to have a low prevalence and incidence. The aim of this study is to collect epidemiological data on IBD outpatients and to add data from the Kingdom of Saudi Arabia (KSA) to the available IBD literature.
Patients and Methods:
The medical records of 693 Saudi patients with IBD over a period of 17 years, between 1993 and 2009, were reviewed. The demographic and clinical data and methods of diagnosis were retrieved.
The total number of patients in this cohort was 693. It constituted 238 (34.3%) ulcerative colitis (UC) and 455 (65.7%) Crohn's disease (CD) patients. UC was steady throughout the years, whereas only 1.2 CD patients were diagnosed per year in the first 11 years, and 73.7 per year in the last six years. The median age of UC patients was 34 years, ranging from 10 to 80 years with a peak between 21 and 40 years and in CD it was 27 years, ranging from 11 to 73 years with a peak between 11 and 30 years. There was a male preponderance of 1.5:1 and 2:1, respectively. The rest of the data is discussed in this study.
IBD is no longer a rare disease in KSA. UC is in a steady state, whereas CD is increasing significantly and far outnumbering UC.
Crohn's disease; rising trend; Saudi Arabia; ulcerative colitis
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 fibrinolytic 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.
Crohn’s disease; Factor V Leiden; Genetics; Thrombosis; Ulcerative colitis
In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher compared to normal population. The TE is a common extraintestinal complication of IBD, squarely associated with the IBD activity. The application of anticoagulant and thrombolytic therapy in severe IBD is an unresolved issue. Herein we report the first case in literature of an active IBD patient with an upper limb acute arterial occlusion and successful catheter-directed thrombolysis (CDT). A 46-year-old male patient is reported who had Crohn’s disease for 10 years. His right hand suddenly became cold and painful. Angiography proved acute occlusion of the brachial and radial artery. Vascular surgery intervention was not applicable. Endoscopy showed extended, severe inflammation of the colon. Despite the severe endoscopic findings, frequent bloody stools and moderate anaemia, CDT with recombinant tissue plasminogen activator was performed. The control angiography proved improvement, the radial artery pulse appeared. No bleeding complication was observed. This case supports that CDT-after careful estimation of the bleeding risk-can be effective and safe in patients with severe or life-threatening TE and active IBD.
Inflammatory bowel disease; Crohn’s disease; Thromboembolism; Catheter-directed thrombolysis; Gastrointestinal haemorrhage
The association between spondyloarthropathy and inflammatory bowel disease (IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies. Most studies indicate that as many as 10%-15% of cases of IBD are complicated by ankylosing spondylitis (AS) or other forms of spondylarthritis (SpA). Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronicity of articular complications. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonoscopy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time. The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among first- and second-degree relatives of affected AS or IBD patients and finally, the increased cross-risk ratios between AS and IBD, strongly suggest a shared genetic background. So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS. Although functional studies are still needed to better understand its pathogenic role, great effort is being spent therapeutically targeting this pathway that may prove effective for both disorders.
Inflammatory bowel disease; Ulcerative colitis; Crohn’s disease; Ankylosing spondlitis; Sacroiliitis; Spondyloarthropathy
Arthritis is the most common extraintestinal manifestation of inflammatory bowel disease (IBD) and can have a significant impact on morbidity and quality of life. IBD-associated arthropathy is considered a subtype of seronegative spondyloarthropathy, with axial, peripheral, or a combination of both joint manifestations. Peripheral arthritis is generally non-erosive and the oligoarticular variant particularly may correlate with intestinal disease activity. Axial arthritis may include inflammatory back pain, sacroiliitis, or ankylosing spondylitis, and is less likely to correlate with gastrointestinal symptoms. While there have been advances in identifying predisposing genetic factors and in elucidating pathophysiology of inflammatory bowel disease, the mechanisms surrounding the development of arthritis in IBD remain unclear. Treatment of inflammatory bowel disease is not always sufficient for control of arthritis. While treatment with biologic agents is promising, there remains a great need for larger, randomized studies to address optimal therapy of IBD associated arthropathy.
Inflammatory bowel disease; IBD; Arthritis; Ulcerative colitis; Crohn’s disease; Extraintestinal manifestations; DMARDS; Biologics
The prevalence of inflammatory bowel diseases (IBDs) is set to stabilize in Western Europe and North America, as opposed to its increasing trend in developing countries in Asia. The epidemiology of IBDs in areas where the incidence and prevalence are relatively low provides an opportunity for researchers to determine the unknown aspects of them. In this review article, the PubMed and MEDLINE databases were searched from 1970 to 2012 and the epidemiological aspects assessed in Iranian articles were compared with identical subjects in other Asian countries. During this period, there were 21 documented articles on IBD epidemiology in Iran and 52 in Asia. According to the present review, CTLA-gene polymorphism and male/female ratio in ulcerative colitis (UC), incidence of extra-intestinal manifestations, extent of intestinal involvement, and family history in both UC and Crohn’s disease (CD) seemed to be different between Asia and Iran. In contrast, the incidence of primary sclerosing cholangitis in IBD patients and association between NO2/CARD15 mutation and CD as C3435-T allele and UC were nearly the same. The rate of IBD has increased significantly in Iran, as has that of other Asian countries during the last decade. A thorough, well-designed, population-based, multi-regional epidemiologic study seems mandatory due to the substantial demographic and characteristic variability in IBD patients in our region.
Inflammatory bowel disease; Epidemiology; Prevalence; Iran
Inflammatory bowel disease (IBD) is considered as a dysregulated immune mediated disease. Pericarditis in IBD is a very rare disease both as an extra-intestinal manifestation of IBD and an adverse reaction of therapeutic drug for IBD such as mesalazine or sulfasalazine. A 26-year-old IBD male patient who had been taking mesalazine regularly for about 1 month was referred to our hospital because of fever, chest discomfort, and abnormal electrocardiographic findings. The patients was diagnosed as acute myopericarditis, and recovered after cessation of mesalazine using steroid and aspirin. When mesalazine was re-medicated some days after discharge, he suffered from myopericarditis again. Subsequently, myopericarditis was resolved just after cessation of mesalazine again. These findings suggest that the development of myopericarditis is caused by mesalazine.
Myopericarditis; Mesalazine; Inflammatory bowel disease
The majority of patients with inflammatory bowel disease (IBD) achieve good control of the inflammatory activity using available therapies. When remission is achieved and quality of life recovered, a considerable proportion of IBD patients express their desire to travel abroad, be it for business, academic or leisure purposes. Their physicians should help and encourage them whenever possible. However, preventive measures are warranted to minimize the risk, since IBD patients are exposed to the same infections affecting the general population, plus opportunistic infections (OI) related to the immunosuppression. There are a large number of potential OI that might affect patients with IBD. The true prevalence of these infections is unknown, and can vary from country to country. Therefore, reactivation or de novo acquisition of infections such as tuberculosis, malaria, and viral hepatitis will be much more frequent in endemic areas. Therefore, physicians should be aware of these aspects when planning specific preventive measures for patients traveling to a particular country. This includes good control of environmental exposure, chemoprophylaxis when indicated, and the use of a specific vaccination program to prevent endemic infections. In addition, it should be noted that, though the risk of acquiring an infectious disease is probably greater for IBD patients traveling from a developed to a developing country, the inverse situation can also occur; it depends on the previous acquired immunity of the host against infections in any particular environment.
Inflammatory bowel disease; Vaccination; Opportunistic infections
Clostridium difficile (C. difficile) infection (CDI) is the leading identifiable cause of antibiotic-associated diarrhea. While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe, superimposed CDI in patients with inflammatory bowel disease (IBD) has drawn considerable attention in the gastrointestinal community. The majority of IBD patients appear to contract CDI as outpatients. C. difficile affects disease course of IBD in several ways, including triggering disease flares, sustaining activity, and in some cases, acting as an “innocent” bystander. Despite its wide spectrum of presentations, CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients. IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch. Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial. It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone. The use of biologic agents does not appear to increase the risk of acquisition of CDI. For CDI in the setting of underlying IBD, vancomycin appears to be more efficacious than metronidazole. Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.
Clostridium difficile; Inflammatory bowel disease; Antibiotics; Colectomy
BACKGROUND—Inflammatory bowel disease (IBD) is associated with an increased incidence of thromboembolic disease. Hyperhomocysteinaemia (hyper-tHcy), a condition associated with the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR), is linked with an increased incidence of thromboembolic disease. Hyper-tHcy has been reported in patients with IBD.
AIMS—To assess the prevalence of the C677T MTHFR genotype and the contribution of this genotype to hyper-tHcy in patients with IBD.
METHODS—Patients with established IBD (n=174) and healthy controls (n=273) were studied. DNA samples were genotyped for the MTHFR (C677T) mutation. Subjects were categorised as homozygous for the thermolabile variant (TT), heterozygous for wild type and variant (CT), or homozygous for the wild type (CC).
RESULTS—Plasma homocysteine concentrations were significantly higher in patients with IBD than in healthy controls. A total of 17.5% of ulcerative colitis and 16.8% of Crohn's disease patients were homozygous for the C677T variant compared with 7.3% of controls. Homozygosity (TT) for the variant was associated with higher plasma tHcy levels in patients with IBD and in healthy controls. When all subjects who were TT for the variant were excluded, median plasma tHcy was still significantly higher in IBD than controls. Plasma vitamin B12 levels were lower in patients with IBD irrespective of MTHFR genotype.
CONCLUSIONS—There is an association between the thermolabile MTHFR C677T variant and IBD. This accounts in part for the raised plasma tHcy found in patients with IBD and may contribute to the increased incidence of thromboembolic complications. All patients with IBD should receive low dose folic acid and vitamin B12 therapy to protect against the thromboembolic complications of raised tHcy.
Keywords: methylenetetrahydrofolate reductase; C677T variant; inflammatory bowel disease
Enterocutaneous fistulas (ECF) are debilitating and usually result following complex abdominal surgery. While there is an association with inflammatory bowel disease (IBD), a large number of fistulas occur after surgery not related to IBD. The consequences of ECF include short bowel syndrome and the need for long term parenteral nutrition.
ECF can heal spontaneously and in the case of IBD can be cured by medical therapy in some instances. Those that do not resolve spontaneously have to be cured by surgery which is complex and associated with a high morbidity. It is not considered traditional treatment to use the same medical therapy as in IBD to cure ECF caused by other conditions.
A small case series has reported three patients with persistent ECF not related to IBD to have healed following use of Infliximab which is the treatment commonly used for ECF caused by IBD. Infliximab acts by inhibiting the activity of the inflammatory cytokine TNF- alpha. It is not known if this cytokine is present in ECF tissue in the absence of IBD.
The aim of this study is to demonstrate the presence of inflammatory markers in tissue surrounding non-IBD ECF and in particular to quantify the presence of the cytokine TNF- alpha. We hypothesise that TNF - alpha levels are raised in non-IBD ECF.
Tissue and serum from ECF of IBD and non-IBD patients will be prospectively collected at St. Mark's Hospital Intestinal Failure Unit. The control group will consist of patients undergoing colonoscopy for bowel cancer screening, with normal findings. Biopsies of the terminal ileum will be obtained from this group during colonoscopy. The fistula tract and serum cytokine profiles of interleukins (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, TNF- alpha, IFN-y, MCP-1, EGF and VEGF will be assessed.
This study aims to assess the presence or absence of TNF- alpha expression in the ECF tissue in non-IBD origin. If our hypothesis is correct we would then be able to study the use of the TNF- alpha inhibitor Infliximab as a therapeutic option in the treatment of non-IBD ECF. Secondary aims include assessing the spectrum of inflammatory cytokines and markers present in tissue and serum of non-IBD ECF when compared with IBD ECF and normal controls.
This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-α blocking agents should be considered as first-line therapy.
Inflammatory bowel disease; Spondylitis; Rheumatic diseases
Background. It is unusual for the antineutrophil cytoplasmic antibody with cytoplasmic pattern (cANCA) to present in patients with inflammatory bowel disease (IBD) without vasculitis. The purpose of this study was to describe the occurrence and characteristics of pediatrics IBD with cANCA. Methods. A retrospective review of pediatric IBD associated with cANCA serology in patients from King Abdulaziz University Hospital, Saudi Arabia, between September 2002 and February 2012.
Results. Out of 131 patients with IBD screened for cANCAs, cANCA was positive in 7 (5.3%) patients of whom 4 had ulcerative colitis and 3 had Crohn's disease. The median age was 8.8 years (2–14.8 years). Six (86%) were males. Of the 7 patients, 5 (71%) were Saudi Arabians and 2 were of Indian ethnicity. The most common symptoms were diarrhea, abdominal pain, weight loss, and rectal bleeding. None had family history or clinical features suggestive of vasculitis involving renal and respiratory systems.
No difference in the disease location or severity was observed between cANCA positive and cANCA negative patients apart from male preponderance in cANCA positive patients. Conclusion. The occurrence of cANCA in pediatric IBD is rare. Apart from male preponderance, there were no peculiar characteristics for the cANCA positive patients.
Thromboembolic disease has been recognized as a complication of inflammatory bowel disease (IBD). The relative contributions of inherited or acquired thrombophilia and the inflammatory response to the mechanism of this tendency are unclear. Thrombotic events are more common in active disease although significant numbers also occur spontaneously. The aim of this study was to investigate common thrombophilic markers in patients with active IBD.
Twenty-six patients with IBD who had active disease, and 40 sex- and age-matched non-IBD patients were recruited into the study. For all the subjects, complete blood counts, C-reactive protein levels, erythrocyte sedimentation rate, International normalized ratio, activated partial thromboplastin time, and levels of lupus anticoagulant, anticardiolipin antibodies (ACA IgG), proteins C and S, antithrombin-III (AT-III), and factor V were measured.
The International normalized ratio, activated partial thromboplastin time, and levels of proteins C and S were comparable between the two groups. However, antithrombin-III levels were significantly lower in the IBD group as compared with that in the healthy control group (P < 0.001). ACA IgG was detected in one patient in the IBD group. Factor V Leiden mutation was present in 3.8% of the patients in the IBD group, whereas the prevalence was 2.5% in the control group. Significantly elevated platelet counts were observed in patients with active Crohn's disease compared with that in the control group (P < 0.001), but they were not significantly increased in active ulcerative colitis (P = 0.231).
The present study failed to establish a strong association between the common thrombophilic markers and the active clinical course of IBD, with the exception of high platelet counts and lower levels of AT-III in the IBD group as compared with those in the control group. All other parameters of thrombophilia were comparable between the two groups.
Active state; inflammatory bowel disease; thrombophilic markers
Metabolic bone disease is common in patients with inflammatory bowel disease (IBD). Our aim was to determine the frequency of bone loss among Saudi patients with IBD and possible contributing risk factors.
Settings and Design:
We retrospectively reviewed Saudi patients with IBD, between 18 and 70 years of age, who had bone mass density (BMD) determined by dual-energy X-ray absorptiometry scanning at one of three hospitals in the Kingdom of Saudi Arabia from 2001 to 2008.
Patients and Methods:
Case notes and BMDs results were carefully reviewed for demographic and clinical data. Low bone mass, osteopenia, and osteoporosis were defined according to the WHO guidelines.
Statistical Analysis Used:
Predictive factors for BMD were analyzed using group comparisons and stepwise regression analyses.
Ninety-five patients were included; 46% had Crohn's disease (CD) and 54% had ulcerative colitis (UC). The average age was 30.9±11.6 years. Using T-scores, the frequency of osteopenia was 44.2%, and the frequency of osteoporosis was 30.5% at both lumbar spine and proximal femur. Only 25.3% of patients exhibited a BMD within the normal range. Our results revealed a positive correlation between the Z-score in both the lumbar spine and the proximal femur and body mass index (BMI) (P=0.042 and P=0.018, respectively). On regression analysis BMI, age, and calcium supplementation were found to be the most important independent predictors of BMD.
Saudi patients with IBD are at an increased risk of low BMD and the frequency of decreased BMD in Saudi patients with CD and UC were similar. BMI and age were the most important independent predictors of low BMD.
Bone mineral density; inflammatory bowel disease; osteopenia; osteoporosis; Saudi
Extraintestinal manifestations (EIMs) in pediatric patients with inflammatory bowel disease (IBD) are poorly characterized. We examined the prevalence of EIMs at diagnosis, subsequent incidence, and risk factors for EIMs.
Data for 1649 patients from the PediIBD Consortium Registry, diagnosed with IBD before 18 years of age [1007(61%) with Crohn’s disease, 471(29%) with ulcerative colitis, and 171(10%) with indeterminate colitis], were analyzed using logistic regression, Kaplan-Meier, log rank tests and Cox models.
EIMs were reported prior to IBD diagnosis in 97 of 1649 patients (6%). Older children at diagnosis had higher rates compared with younger children, and arthritis (26%) and aphthous stomatitis (21%) were most common. Among the 1552 patients without EIM at diagnosis, 290 developed at least one EIM. Kaplan-Meier estimates of cumulative incidence were 9% at 1 year, 19% at 5 years, and 29% at 15 years after diagnosis. Incidence did not differ by IBD type (p=0.20), age at diagnosis (p=0.22), or race/ethnicity (p=0.24). Arthritis (17%) and osteopenia/osteoporosis (15%) were the most common EIMs after IBD diagnosis.
In our large cohort of pediatric IBD patients, 6% had at least one EIM before diagnosis of IBD. At least one EIM will develop in 29% within 15 years of diagnosis. Incidence of EIMs both before and after diagnosis of IBD differs by type of EIM and may be slightly higher in girls, but is independent of the type of IBD, age at diagnosis, and race/ethnicity.
children; adolescents; ulcerative colitis; Crohn’s disease; arthritis; sclerosing cholangitis
Low bone mineral density is an established, frequent, but often neglected complication in patients with inflammatory bowel disease (IBD). Data regarding the diagnosis, therapy and follow-up of low bone mass in IBD has been partially extrapolated from postmenopausal osteoporosis; however, the pathophysiology of bone loss is altered in young patients with IBD. Fracture, a disabling complication, is the most important clinical outcome of low bone mass. Estimation of fracture risk in IBD is difficult. Numerous risk factors have to be considered, and these factors should be weighed properly to help in the identification of the appropriate patients for screening. In this editorial, the authors aim to highlight the most important clinical aspects of the epidemiology, prevention, diagnosis and treatment of IBD-related bone loss.
Inflammatory bowel disease; Crohn’s disease; Osteoporosis; Osteopenia; Prevention
Inflammatory bowel disease (IBD) describes chronic inflammatory disease of the intestines and has a variable course; Crohn's disease and ulcerative colitis comprise the two main forms of the condition. Although IBD occurs worldwide, its epidemiologic and clinical characteristics vary depending upon the geographic location and the ethnicity of the population. Identifying the characteristic features of IBD in populations living in different geographical locations and with different ethnicities may provide significant clues about its etiology and pathophysiology, which in turn may be helpful in the development of more appropriate treatment strategies for IBD for these different populations. Therefore, it is important for each country and region to evaluate critically the epidemiology, genomics, and clinical characteristics of IBD among its own population. We have performed a critical review of the recent data in Korea, and describe herein the current epidemiologic and genotypic status, as well as the clinical manifestations and therapeutic responses of IBD that are unique to Korean patients.
Inflammatory bowel diseases; Crohn's disease; Ulcerative colitis; Korea
The immunosuppressant azathioprine (AZA) is widely used in the treatment of inflammatory bowel disease (IBD) for both inducing and maintaining remission. However, the adverse effects of AZA can often necessitate a dose reduction or discontinuation. Bone marrow suppression is one of the most serious complications with AZA treatment. On the other hand, some reports have suggested that neutropenia during AZA therapy reduced the relapse rates of IBD patients, and there have been some cases where eradication of the sensitized leukocytes by leukapheresis or bone marrow transplantation improved the IBD, which may explain the relevant role of neutropenia in controlling disease activity. This report describes the case of a 22-year-old male patient who had Crohn's colitis and complicated perianal fistulas that required immunosuppression; he achieved endoscopically determined remission and showed accelerated mucosal healing as well as clinical remission following the AZA-induced pancytopenia.
Crohn's disease; Improvement; Pancytopenia
The inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. UC results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for CD in twins, and a much less robust phenotypic concordance for UC, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage, and genome-wide association analyses. Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in CD and UC. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this research topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed.
inflammatory bowel disease; chronic intestinal inflammation; colitis-associated colon cancer; Crohn’s disease; ulcerative colitis
Despite recent advancements in the understanding of the pathogenesis of inflammatory bowel disease (IBD) and the development of therapeutic agents to treat it, the complications of IBD are significant contributors to morbidity, decreased quality of life and economic burden in terms of hospitalizations, resource use and time away from work. To date, biological agents, such as infliximab – a tumour necrosis factor-alpha monoclonal antibody – have proven to be the most effective therapeutic agents; however, little research investigating how clinicians use biologicals in clinical practice has been conducted. This study aimed to describe the clinical practice patterns of infliximab use among Canadian physicians for the treatment of medically refractory IBD and, furthermore, investigated several factors possibly influencing these patterns.
Little is known about physician perceptions of and practices in using infliximab – a biological agent that was approved in Canada for the treatment of Crohn’s disease in 2001, and for ulcerative colitis in 2006.
To describe Canadian gastroenterologists’ use and perceptions of infliximab in the treatment of refractory inflammatory bowel disease (IBD), and to identify factors that may influence a gastroenterologist’s decision to initiate infliximab therapy.
A postal questionnaire was distributed to all practicing clinicians captured in the 2007 membership of the Canadian Association of Gastroenterology. Each physician was contacted up to a maximum of three times.
Of 466 questionnaires mailed out, responses were received from 336 (72%), with 292 respondents (63%) returning fully completed surveys. For 80% of respondents, IBD patients comprised less than 30% of their clinical practice. Most prescribed infliximab at an initial dose of 5 mg/kg (97%), prescribed loading doses at 0, 2 and 6 weeks (88%), premedicated with corticosteroids (74%), administered maintenance infusions at eight-week intervals (89%), co-administered immunosuppressive agents (81%) and continued infliximab ‘indefinitely’ as long as it was effective and well tolerated (76%). Most gastroenterologists (>70%) identified lack of drug insurance coverage and provincial funding criteria as important barriers to prescribing infliximab.
Most Canadian gastroenterologists exhibited similar practice patterns with respect to the use of infliximab for induction and maintenance therapy of IBD. Common barriers to the initiation of infliximab therapy were identified.
Inflammatory bowel diseases; Infliximab; Treatment
The incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD), are rising in western countries. The modern hygienic lifestyle is probably at the root of a disease where, in genetically susceptible hosts, the intestinal commensal flora triggers dysregulated immune and inflammatory responses. Current therapies ranging from anti-inflammatory drugs to immunosuppressive regimens, remain inadequate. Advances in our understanding of the cell populations involved in the pathogenetic processes and recent findings on the regenerative, trophic and immunoregulatory potential of stem cells open new paths in IBD therapy. Hematopoietic and mesenchymal stem cells are catalyzing the attention of IBD investigators. This review highlights the pivotal findings for stem cell-based approaches to IBD therapy and collects the encouraging results coming in from clinical trials.
Inflammatory bowel disease; Stem cells; Hematopoietic stem cell; Mesenchymal stem cells; Cell therapy
Too often anemia is considered a rare or unimportant manifestation in inflammatory bowel disease (IBD). However, over the last 10 years a number of studies have been conducted and the most relevant conclusions obtained are: (1) anemia is quite common in IBD; (2) although in many cases anemia parallels the clinical activity of the disease, many patients in remission have anemia, and iron, vitamin B12 and/or folic acid deficiency; (3) anemia, and also iron deficiency without anemia, have important consequences in the clinical status and quality of life of the patient; (4) oral iron can lead to gastrointestinal intolerance and failure of treatment; (5) intravenous iron is an effective and safe way to treat iron deficiency; (6) erythropoietin is needed in a significant number of cases to achieve normal hemoglobin levels. Thus, the clinician caring for IBD patients should have a comprehensive knowledge of anemia, and apply recently published guidelines in clinical practice.
Anemia; Inflammatory bowel diseases; Ferritin; Iron
The incidence of Clostridium difficile infection (CDI)
has significantly increased in the last decade in the United States
adding to the health care burden of the country. Patients with
inflammatory bowel disease (IBD) have a higher prevalence of CDI and
worse outcomes. In the past, the traditional risk factors for CDI were
exposure to antibiotics and hospitalizations in elderly people. Today,
it is not uncommon to diagnose CDI in a pregnant women or young adult
who has no risk factors. C. difficile can be detected
at the initial presentation of IBD, during a relapse or in
asymptomatic carriers. It is important to keep a high index of
suspicion for CDI in IBD patients and initiate prompt treatment to
minimize complications. We summarize here the changing epidemiology,
pathogenesis, risk factors, clinical features, and treatment of CDI in