Extraintestinal Manifestations Of Inflammatory Bowel Disease Research Articles

New choices, new challenges: Anti-TNF versus anti-integrin molecule therapy in IBD.

The arrival of vedolizumab for the treatment of inflammatory bowel disease (IBD) provides a welcome opportunity to apply a novel mechanism of action to many patients who warrant biologic treatment. Whilst, in the past two decades, anti-tumor necrosis factor (TNF) therapies (locally infliximab and adalimumab) have revolutionized the management of IBD, it is increasingly clear that a significant proportion of patients are either primary non-responders, have secondary loss of response, are intolerant, or have had serious adverse reactions (including infusion-related, paradoxical immune-inflammatory reactions, cardiac failure, demyelinating, and/or infective complications) to these agents.1, 2 In addition, there are an increasing number of patients with IBD who are at higher risk of anti-TNF exposure given the pleiotropic role of the cytokine TNF in both regulatory and pathological processes in humans, which remain only superficially understood. These risks include those relatively immunosuppressed, those with prior skin, solid and lymphatic malignancies, and other comorbidities. Hence, the challenge for the clinician is positioning vedolizimub in the treatment algorithm for IBD. There are limited data to definitively support vedolizumab as a first-line biologic in place of anti-TNF therapies or for when and how to introduce vedolizumab as a second-line biologic post anti-TNF. It is unclear whether head-to-head trials of anti-integrin and anti-TNF therapies will occur, but it would be imprudent to compare the registration trials of these agents given the multiple confounders of patient selection, prior treatment exposure (non-response), study duration, and variation in endpoints measured between studies. Multiple Bayesian network meta-analyses have attempted to address the issue of comparing these agents, but results are conflicting,3 as the only trials available for meta-analysis are the GEMINI registration trials, which lack long-term data on vedolizumab.4 Nevertheless, it is interesting that as in Fig. 1, in Crohn's disease (CD) for example, clinical remission rates at 1 year (approximately) are virtually identical in the registration trials of infliximab, adalimumab, and vedolizumab. Hence, if one assumes similar efficacy between the classes, the most obvious factor favoring vedolizumab over anti-TNF therapies is its apparent excellent tolerability and safety demonstrated in the GEMINI studies,4 along with recent real-world data.5 Given its gut-specific effect on the α4β7 integrin subunits, systemic complications are theoretically rare. In the Cochrane review by Bickston et al., the placebo group had a slight higher proportion of one or more adverse effects compared with the vedolizumab group (90% vs 89%),6 and according to a meta-analyses, vedolizumab was found to have fewer treatment withdrawals in the GEMINI trials than reported in landmark studies of other drugs such as azathioprine, methotrexate, and infliximab in CD.7 It follows that there are a number of patient subgroups where safety and tolerability are paramount, even if at a small cost of efficacy (or lack of evidence thereof), and thus, vedolizumab should be considered as a first-line option. This includes the elderly patient with IBD, where at least one study showed that anti-TNF use in a rather sick, elderly group culminated in 11% having serious infections, 3% developing malignancies, and 10% dying within the follow-up period.8 Patients with pediatric-onset IBD, consigned to long-term immunosuppression, and at higher risk of potentially fatal systemic complications such as T-cell lymphomas, might also be considered for vedolizumab first line. Additionally those with a history of solid organ or skin (e.g. melanoma) malignancy may also be candidates for a gut-specific therapy like vedolizumab given the uncertain impact of anti-TNF therapies on cancer recurrence and survival.9 A targeted agent like vedolizumab in a patient with no systemic or extra-intestinal manifestations of IBD and in settings of limited yet highly symptomatic disease such as those perhaps with ulcerative proctitis, segmental colitis, or limited ileal CD could also be considered. Yet, there are no robust data to support these assumptions currently. Conversely, the use of anti-TNF therapies as first line compared with vedolizumab is supported by data in many patient subgroups, including perianal fistulizing disease, extra-intestinal manifestations, mitigation of postoperative recurrence in CD and acute severe colitis. Quality, sensible use of these expensive agents would, for instance, in the setting of loss of response to a first anti-TNF agent, first attempt to regain response to this agent (e.g. with dose intensification) before moving to the alternative anti-TNF agent and only then if this fails switch out of class to vedolizumab (and vice versa). However, one must also be mindful of the ‘law of diminishing returns’ in that for every new trial of treatment, it generally holds that a lower potential response rate can be expected.10 In conclusion, the IBD clinician not only can celebrate the availability of vedolizumab, but also ponder the added complexity this choice provides day-to-day clinical decision-making. Perhaps, the most important factor influencing the use of vedolizumab is the comparative importance of safety versus efficacy for the individual patient.

Extra-Gastrointestinal Manifestations of Inflammatory Bowel Disease May Be Less Common Than Previously Reported.

Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra-intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published. We have conducted a study of these manifestations using electronic primary care records. We have identified extra-intestinal manifestations in IBD and non-IBD patients and derived odds ratios (ORs) using conditional logistic regression. A total of 56,097 IBD patients (32.5% Crohn's disease, 48.3% ulcerative colitis (UC) and 19.2% not classified) were matched to 280,382 non-IBD controls. We found records of pyoderma gangrenosum (OR=29.24), erythema nodosum (OR=5.95), primary sclerosing cholangitis (OR=188.25), uveitis (OR=2.81), ankylosing spondylitis (OR=7.07), sacroiliitis (OR=2.79) and non-rheumatoid inflammatory arthritides (OR=2.66) to be associated with IBD. One or more of these was recorded in 8.1% of IBD patients and 2.3% of controls. Non-specific arthritides were present in many more patients, affecting 30% of IBD patients and 23.8% of controls overall. We also found weaker associations with a number of conditions not generally considered to be extra-intestinal manifestations including psoriasis, ischemic heart disease, multiple sclerosis and hay fever. Although "classical" extra-intestinal manifestations are strongly associated with IBD, most IBD patients remain unaffected. Arthropathies, perceived to be the commonest extra-intestinal manifestation, are not strongly associated with IBD, and the proportion of arthropathies attributable to IBD is likely to be small.

Hearing Loss in Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) has many characteristics of autoimmune diseases. Sensorineural hearing loss has been reported in many autoimmune diseases. Little is known about hearing loss in patients with IBD. A prospective blinded comparative study was conducted over a 3-year period. IBD patients and controls underwent a complete otorhinolaryngeal examination and eudiometry test. Altogether 105 participants (76 patients and 29 controls) took part in this study. Mean age was 36, 51% were males, and 40% of the patients were presently hospitalized due to IBD exacerbation. Audiometric examination revealed that any hearing loss (mild to severe) was found in 29 (38%) of the IBD population, compared to 4 (14%) of the control group (p=0.02). Extraintestinal manifestation (EIM) was present in 33/76 (43%) of IBD patients. Any hearing loss and moderate to severe hearing loss were found in 17/33 (52%) and 7/33 (21%) in the EIM-positive group compared to 12/43 (28%) and 4/43 (9%) in the EIM-negative group (p=0.036 and p=0.14, respectively). Out of patients over the age of 40 with other EIMs, all 11/11 (100%) of patients had any hearing loss compared to 8/12 (66%) of patients over the age of 40 without other EIMs, p=0.035. Hearing loss may be another EIM of IBD. It is found in 38% of IBD patients and in up to 52% of patients with other EIMs and increases over the age of 40. Early hearing evaluation should be recommended to these high-risk IBD patients.

Cerebral Sinus Thrombosis: A Rare but Fatal Complication of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an idiopathic autoimmune disease. Extra intestinal manifestation of IBD has been reported to be 25 to 35%. There is a well-known risk of thrombosis in patients with IBD. It rarely involves cerebral vasculature in the form of arterial stroke or venous sinus thrombosis. This case is about 35 yrs old male who was a known case of ulcerative colitis for the last 10 years. He presented with history of severe thunderclap headache for the last few hours along with vomiting. He also had three episodes of seizure, generalized tonic clonic in nature. The examination does not show any focal asymmetry except mild drowsiness. His CT brain showed Focal cortical and subcortical area in the left posterior parietal region displaying multiple foci of hyper density with perifocal edema. CT venogram showed an intraluminal filling defect in the superior sagittal sinus suggestive of venous sinus thrombosis. Conclusion: Cerebral venous sinus thrombosis are considered as one of the rare but fatal complication of inflammatory bowel disease. It must be considered in all those with inflammatory bowel disease wherein absence of any other vascular risk factor patient presents with acute severe headache and focal or diffuse neurological symptoms including seizure

Inflammatory bowel disease imaging: Current practice and future directions.

The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease (IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques (computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities.

Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease.

Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.

Incidencia a los 2 años de nuevas enfermedades inflamatorias mediadas por inmunidad en la cohorte de pacientes con enfermedad inflamatoria intestinal del estudio AQUILES

ObjectiveTo describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study. Materials and methodsOver a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists). ResultsA total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). ConclusionsIn patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD.

Clinical Features and Differential Diagnosis of Ulcerative Colitis and Crohn Disease

Inflammatory bowel disease (IBD) is composed of two major subtypes, ulcerative colitis (UC) and Crohn disease (CD). These chronic disorders, characterized by inflammation of the gastrointestinal tract, demonstrate a variety of clinical features, including intestinal and extraintestinal manifestations during periods of relapse and remission over many years. This review examines the clinical features of IBD, including the extraintestinal manifestations and diagnosis. Figures include examples of images conducted via computed tomography (CT), magnetic resonance imaging, and position emission tomography (PET)/CT. Tables list the location frequencies of UC and CD at the time of diagnosis, extraintestinal manifestations of IBD, differential diagnosis of UC and CD, and clinical utility of fecal calprotectin in the evaluation and management of IBD. This review contains 4 highly rendered figures, 5 tables, and 48 references.

Extraintestinal Manifestations of Inflammatory Bowel Disease

The extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) can be classified as the following: (a) true EIMs due to reactive IBD affecting organ systems, (b) complications secondary to IBD activity, (c) non–IBD-specific autoimmune disease which occurs in increased frequency in individuals with IBD. Overlap is frequent between EIMs and extraintestinal complications, and it is increasingly evident that multiple organ systems may be involved. This review covers EIMs through their epidemiology, etiology/genetics/pathogenesis, prognosis, complications, and treatment. Also detailed are the organ systems involved with reactive IBD, including musculoskeletal, pulmonary, dermatological, ophthalmic, and hepatobiliary manifestations. Figures show the classification, etiology, and pathogenesis of EIMs of IBD, musculoskeletal and pulmonary manifestations of IBD, metastatic Crohn disease of the intergluteal cleft, pyoderma gangrenosum, oral apthous ulcers, Sweet syndrome, leucocytoclastic vasculitis, anti-tumor necrosis factor–induced psoriasis, uveitis, episcleritis, and primary sclerosing cholangitis. Tables list the modified New York criteria for ankylosing spondylitis, pulmonary manifestations of IBD and IBD-related treatment, diagnostic techniques in lung disorders associated with IBD, dermatologic manifestations of IBD based on classifications, specific cutaneous manifestations or granulomatous cutaneous lesions with the same histological features as the underlying bowel disease, reactive cutaneous manifestation of IBD with immunological mechanisms triggered by common antigens shared by gut bacteria and skin, cutaneous disorders or dermatosis associated with IBD, secondary cutaneous manifestations due to complications of IBD and adverse effects of IBD treatment, treatment of dermatological manifestations of IBD, diagnosis of ophthalmological manifestations of IBD, and other hepatobiliary manifestations of IBD. This review contains 13 highly rendered figures, 12 tables, and 79 references.

Hearing Loss in Patients with Inflammatory Bowel Disease

Objectives: Inflammatory bowel disease (IBD) has many characteristics of autoimmune diseases. Sensorineural hearing loss has been reported in many autoimmune diseases. Little is known about hearing loss in patients with IBD. Methods: A prospective blinded comparative study was conducted over a 3-year period. IBD patients and controls underwent a complete otolaryngology examination and audiometry test. Results: A total of 105 participants (76 patients and 29 controls) took part in this study. A total of 59 (77%) had Crohn’s disease (CD) and 17 (23%) had ulcerative colitis (UC). Mean age was 36 years, 51% were males and 40% of the patients were presently hospitalized due to IBD exacerbation. Sixteen of 76 (21%) of the IBD patients complained of hearing loss since first IBD diagnosis and 13% had current hearing disabilities. Audiometric examination revealed that any hearing loss (mild to severe) was found in 23 (30%) of the IBD population, compared with 3 (10%) of the control group ( P &lt; .05). Sensorineural was the hearing deficiency type in 93% of them. Out of 46 patients, whose extraintestinal manifestation (EIM) status was clearly documented, 43% (n = 20) had EIMs. Hearing loss was present in 5 out of 20 (25%) of these patients, compared with 0 out of 23 who did not have EIMs ( P &lt; .01). IBD phenotype, current hospitalization, and disease type were not different between these groups. Conclusions: Sensorineural hearing loss may be another EIM of IBD. It is found in 30% of IBD patients, and in up to 43% of patients with other EIMs. Early hearing evaluation should be recommended to IBD patients who have other EIMs.

Improving Maintenance Medication Adherence in Adult Inflammatory Bowel Disease Patients: A Pilot Study.

Medication nonadherence in inflammatory bowel disease (IBD) may lead to suboptimal control of the disease, decreased quality of life, and poor outcomes. This pilot study evaluated the feasibility, intervention mechanism, and potential effectiveness of a three-month continuous self-improvement (CSI) intervention to enhance medication adherence (MA) in adult nonadherent IBD patients. Adult IBD patients taking a daily or twice-daily dosed maintenance medication were screened electronically for two months to determine baseline MA levels. Nonadherent IBD participants were randomized to the CSI or the attention control (AC) intervention and monitored for three months. The CSI intervention consisted of a data evaluation and system refinement process in which system changes were identified and implemented. The AC group was given educational information regarding IBD disease process, extra-intestinal manifestations of IBD, and medical therapy. Demographic statistics, change scores for within and between-group differences, and effect size estimates were calculated. Nine nonadherent participants (medication adherence score <0.85) were eligible for randomization. The intervention was found feasible and acceptable. Although no statistically significant improvement in MA was found (P=0.14), adherence improved in 3 of 4 of the CSI group and 1 of 2 in the attention control group. The effect size calculation of 1.9 will determine the sample size for future study. The results of this pilot study showed the intervention was feasible and had a positive effect on MA change score and adherence levels. A larger fully powered study is needed to test of the effectiveness of this innovative intervention.

Pulmonary manifestations of inflammatory bowel disease

Extraintestinal manifestations of inflammatory bowel disease (IBD) are a systemic illness that may affect up to half of all patients. Among the extraintestinal manifestations of IBD, those involving the lungs are relatively rare and often overlooked. However, there is a wide array of such manifestations, spanning from airway disease to lung parenchymal disease, thromboembolic disease, pleural disease, enteric-pulmonary fistulas, pulmonary function test abnormalities, and adverse drug reactions. The spectrum of IBD manifestations in the chest is broad, and the manifestations may mimic other diseases. Although infrequent, physicians dealing with IBD must be aware of these conditions, which are sometimes life-threatening, to avoid further health impairment of the patients and to alleviate their symptoms by prompt recognition and treatment. Knowledge of these manifestations in conjunction with pertinent clinical data is essential for establishing the correct diagnosis and treatment. The treatment of IBD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management. Corticosteroids, both systemic and aerosolized, are the mainstay therapeutic approach, while antibiotics must also be administered in the case of infectious and suppurative processes, whose sequelae sometimes require surgical intervention.

Thrombosis in inflammatory bowel disease: Are we tailoring prophylaxis to those most at risk?

Inflammatory bowel disease (IBD) is a disease-specific risk factor for incident and recurrent venous thromboembolism (VTE). The reasons are acquired, multifactorial, and related to prothrombotic aberrations during active disease, although the mechanisms remain incompletely elucidated. VTE represents a potentially life-threatening extraintestinal manifestation of IBD, but the associated morbidity and mortality can be reduced by appropriate use of thromboprophylaxis. Nevertheless, despite international guidelines advocating thromboprophylaxis in hospitalised patients with IBD, practice is highly variable, since 65% of gastroenterologists may not use pharmacological VTE prophylaxis in hospitalised patients with acute severe colitis. Furthermore, there is no guidance on appropriate prophylaxis for ambulatory outpatients with active disease who are at an appreciable risk of VTE. Thus the question: are we tailoring thromboprophylaxis to those patients with IBD who are most at risk?

PTU-060 Phenotypic Characterisation of Inflammatory Bowel Disease in South Asians in the United Kingdom-Insights into a Shifting Landscape

IntroductionThe aetiology of inflammatory bowel disease (IBD) remains elusive. The increasing incidence of IBD in developing countries and immigrant populations appears to outpace what genetic influences alone could instigate. There...

Multidisciplinary Teams as Standard of Care in Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD), ulcerative colitis and Crohn disease have been associated with extraintestinal manifestations. These include arthralgia and arthritis, erythema nodosum, pyoderma gangrenosum, primary sclerosing cholangitis and autoimmune hepatitis, episcleritis and uveitis. Increasingly, other conditions, such as psoriasis and multiple sclerosis, have been described to be associated with IBD. It may be proper to consider IBD to be one of a spectrum of immune-mediated inflammatory diseases (IMIDs) clustered according to genetic predisposition and immunological imbalance. In general, IMIDs affect young people at the peak of their working life and, therefore, are associated with a high societal cost (1). Extraintestinal manifestations are important predictors of morbidity and temporary work disability (1). IBD is managed by gastroenterologists and, when required, by colorectal surgeons, but ideally should be managed in the setting of a multidisciplinary team. In the current issue of the Canadian Journal of Gastroenterology, this is illustrated by the report from Maastricht (The Netherlands) by Stolwijk et al (2) (pages 199–205) demonstrating the high prevalence of self-reported musculoskeletal spondyloarthropathy (SpA) in patients with IBD. However, one-half of these patients never consulted a rheumatologist. The population-based cumulative incidence of SpA in Crohn disease is reported to be 6.7% at 10 years, 13.9% at 20 years and 18.6% at 30 years. However, this may have missed patient-reported musculoskeletal symptoms. Lack of rheumatology referral misses an opportunity for accurate diagnosis, appropriate imaging and management strategies. SpA may follow a disease course separate from the activity of IBD and, therefore, may warrant therapeutic strategies dictated by musculoskeletal disease burden and morbidity. These include consideration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the context of IBD, immunosuppressive drugs and anti-tumour necrosis factor (anti-TNF) agents. SpAs are also a group of overlapping, chronic inflammatory rheumatic diseases; therefore, accurate phenotyping is important for management. Musculoskeletal symptoms may also be a side effect of drug therapy in IBD such as delayed hypersensitivity reactions to anti-TNF agents, thiopurines, nutritional deficiencies and corticosteroid withdrawal. Equally important is to recognize that gastrointestinal symptoms in patients with SpA may be a manifestation of IBD and require investigation by a gastroenterologist. In general, the extraintestinal manifestations of IBD and the associated IMIDs respond to anti-TNF therapy, except primary sclerosing cholangitis. However, the use of etanercept may rarely be associated with development of IBD. Etanercept is ineffective in IBD and, therefore, SpA in the presence of IBD should be treated with the anti-TNF monoclonal antibodies. Other IMIDs, such as psoriasis and drug-induced lupus, may manifest while under treatment with anti-TNF agents. While some of these manifestations may require discontinuation of anti-TNF therapy, others may be managed while continuing anti-TNF therapy (such as methotrexate for psoriasis). Multidisciplinary IMID clinics are, therefore, a very effective organizational structure that can assess the entire disease spectrum in patients with IBD to determine the full burden of disease. Although rheumatologists, dermatologists and gastroenterologists represent key members of such multidisciplinary IMID teams, ophthalmologists and hepatologists also participate (Box 1). Such teams are effective in coordinating trials, learning from one anothers’ management algorithms and ensuring effective management of the entire disease burden (Box 2). In academic centres, this should become the standard of care. Such collaborative teams enhance quality of care and may reduce disease burden and morbidity. BOX 1 Collaborative clinical care teams in inflammatory bowel disease Multiple specialties Mutiple support services Surgeons: colorectal, general Radiologists Rheumatologists Nutritioinsts Dermatologists Nurse practitioners Hepatologists Clinical psychologists Opthalmologists Social workers Primary care View it in a separate window BOX 2 Collaborative models in inflammatory bowel disease (IBD) Research Clincal Educational Clinical trials IBD care teams Patients Traditrional studies Physicians Genetic studies Health care providers Biomarker studies View it in a separate window

Can Early Onset of Disease Be One of the Risk Factors for Low Bone Mineral Density in Patients with Inflammatory Bowel Disease?

Can Early Onset of Disease Be One of the Risk Factors for Low Bone Mineral Density in Patients with Inflammatory Bowel Disease?

Diagnosis and Therapeutic Management of Extra-Intestinal Manifestations of Inflammatory Bowel Disease

Extra-intestinal manifestations (EIMs) are reported frequently in patients with inflammatory bowel disease (IBD) and may be diagnosed before, concurrently or after the diagnosis of IBD. EIMs in IBD may be classified based on their association with IBD disease activity. The first group has a direct relationship with the activity of the bowel disease and includes pauciarticular arthritis, oral aphthous ulcers, erythema nodosum and episcleritis. The second group of EIMs appears to follow an independent course from the underlying bowel disease activity and include ankylosing spondylitis and uveitis. The third group includes EIMs that may or may not be related to intestinal inflammation, such as pyoderma gangrenosum and probably primary sclerosing cholangitis (PSC). Genetic susceptibility, aberrant self-recognition and immunopathogenic autoantibodies against organ-specific cellular antigens shared by the colon and extra-colonic organs may contribute to the pathogenesis and development of these EIMs. The use of biological agents in the IBD armamentarium has expanded the treatment options for some of the disabling EIMs and these agents form the cornerstone in managing most of the disabling EIMs. PSC is one of the most common hepatobiliary manifestations associated with IBD in which no clear treatment options exist other than endoscopic therapy and liver transplantation. Future research targeting the pathogenesis, early diagnosis and treatment of these EIMs is required.

Golimumab May Induce Exacerbation of Inflammatory Bowel Disease When it Is Used for the Treatment of Ankylosing Spondylitis: A Case Report with a Review of Literature

Purpose: Golimumab is a human IgG monoclonal antibody specific for human tumor necrosis factor alpha (TNF-α). Golimumab has been approved for use in rheumatological conditions; however, its use in inflammatory bowel disease (IBD) is still in clinical trials. We report a case of an exacerbation of ulcerative proctitis after starting on golimumab for ankylosing spondylitis (AS). A 25-year-old male with ulcerative proctitis was treated with topical mesalamine with symptoms resolution for 14 months. In January 2011, the patient started complaining of right hip and lower back pain. An X-ray revealed joint space narrowing and right sacroiliitis. Blood test for HLA B27 was positive. The patient was referred to rheumatologist for further management. He was started on golimumab for the treatment of AS in March 2011. One month later his joint and back pain improved markedly with golimumab treatment. Three months after being on golimumab, he presented with hematochezia associated with watery diarrhea and weight loss. Physical examination was unremarkable except for left lower quadrant tenderness. Colonoscopy revealed active ulcerative proctitis confirmed by biopsy. The dose of topical meselamine was increased to twice a day. The patient's symptoms partially improved after one month, however, some symptoms persisted. Golimumab therapy was stopped and adalimumab was started as treatment for intestinal and extra-intestinal manifestations of IBD. His symptoms improved markedly within a few weeks of golimumab cessation and initiation of adalimumab. Follow-up flexible sigmoidoscopy revealed resolution of proctitis. His proctitis is currently in remission; however, he still has minimal joint discomfort. To our knowledge, this is the fourth reported case in the English literature suggesting worsening of inflammatory bowel disease on golimumab. In conclusion, the use of golimumab for treating ankylosing spondylitis in patients with inflammatory bowel disease may exacerbate their intestinal disease.Table: No Caption available.

Bilateral Hand Necrosis in Undiagnosed Ulcerative Colitis

Purpose: Thromboembolic disease is a common extra-intestinal manifestation of inflammatory bowel disease (IBD) associated with significant morbidity. Here in we present a case of bilateral hand necrosis in a patient with undiagnosed ulcerative colitis. Case: A 63-year-old male presents with severe bilateral hand pain. He had noted darkening and subsequently necrosis of his fingertips which progressed proximally over a two month period. Investigations were non-revealing for vasculitis, cryoglobulinemia, or other rheumatological state. A hypercoagulable workup was non-revealing. Amputation of his left hand was performed and pathology revealed vaso-occlusive disease with diffuse thrombi in superficial and deep small and large vessels without evidence of vasculitis. A DVT of his left lower extremity had been diagnosed 4 months prior to his presentation and he had been on therapeutic anticoagulation with Coumadin®. He reported frequent diarrhea over the preceding five years. He had no family history of IBD. He had never had a colonoscopy. CT of his abdomen and pelvis revealed diffuse colonic wall thickening. An IBD-7 serology was consistent with ulcerative colitis. A colonoscopy revealed pan-ulceration starting in his rectum. Biopsies from colon showed crypt abscesses without evidence of microthrombi. Patient eventually succumbed to hospital acquired pneumonia. Discussion: A variety of host factors may contribute to the hypercoagulability and thromboembolic events associated with IBD. The most common thromboembolic events in IBD result in deep venous thrombosis and pulmonary embolisms. Above we report a unique case of microthrombi to hand vasculature associated with ulcerative colitis. It is known that chronic gut inflammation alters microvascular hemodynamics and cell-signaling. Also a variety of factors including thrombocytosis, high levels of clotting factors V, VIII, fibrinogen, accelerated thromboplastin generation, anti-thrombin III deficiency, decreased protein C and S, elevated anticardiolipin antibodies, and elevated homocystein levels contribute to thromboembolic events. However, such as in the case presented, no single consistent coagulation abnormality is typically identified. The immense morbidity associated with extra-intestinal manifestations of IBD is highlighted in this case.Figure: Patient's right hand.

Phenotypic Characterisation of Inflammatory Bowel Disease in South Asians in the United Kingdom: Insights into a Shifting Landscape

Purpose: The aetiology of inflammatory bowel disease (IBD) remains elusive; a complex interplay of genetic, environmental and immunological influences. The increasing incidence of IBD in developing countries and immigrant populations appears to outpace what genetic influences alone could instigate and may provide valuable insights into aetiology. There is a relative dearth of literature on the phenotypic characteristics of South Asian immigrant populations. The aim of our study was to define the clinical phenotype of IBD in South Asians living in North-West England. Methods: We conducted a retrospective study of 102 patients of South Asian origin attending IBD clinics at our hospital. Clinical data including demographics, disease characteristics (Montreal classification), treatment and blood results were obtained using electronic case records. Results: Of 102 patients reviewed, 54 were male. The median age was 38 years (range 16-80) and mean disease duration was 9.4 years. Seventy-three patients had ulcerative colitis (UC) and 29 had Crohn's disease (CD). Five patients were current or ex smokers (4.9%). Seventeen patients had extra-intestinal manifestations of IBD (16.7%). Of UC patients 35 had pancolitis, 33 left sided disease and 5 had proctitis. Of patients with CD, 3 had ileal disease, 10 colonic disease and 16 had ileocolonic disease. Five CD patients had stricturing disease, 10 had penetrating disease (6 also stricturing) and 14 had non-penetrating, non-stricturing disease. Perianal disease was noted in 3 at diagnosis and 5 subsequently developed it. Eighty patients received steroids, topical steroids (29), 5-ASA (96), topical 5-ASA (30), azathioprine (55), 6-mercaptopurine (4), cyclosporine (2), methotrexate (9), infliximab (20) and adalimumab (9). Fifty-seven patients received at least one immunomodulatory therapy with the median time to use being 12 months (range 0-276 mo). Thirteen patients (7 CD, 3 UC) required surgery (3 total colectomy, 10 subtotal). Mean time to surgery was 4 years (range 0-13 years). Seventeen patients had disease progression leading to Montreal reclassification (median time 60 months; range 1-216 mo). Conclusion: We noted a higher prevalence of UC with a predominance of pancolonic disease and a significant proportion of CD with penetrating or stricturing disease. The majority of patients required immunomodulatory therapy with the median time to use being only 12 months, suggesting a relatively more aggressive disease course. Epidemiologic insights from such populations may provide further clues in defining an aetiological paradigm for IBD and should form an important area of further research. A case control study exploring differences is underway at our institution.