Extraintestinal Manifestations Of Inflammatory Bowel Disease Research Articles

Comparing Disease Characteristics between African-American and Caucasian Inflammatory Bowel Disease Patients

Purpose: The incidence of inflammatory bowel disease (IBD) in non-caucasian minority groups, including African-Americans (AA), appears to be increasing but there is limited understanding of phenotypic differences and outcomes by race. Here we describe the disease characteristics of self-identified AA patients at the University of Chicago and compare them to the disease characteristics of caucasian patients.Figure: No Caption available.Methods: This was a retrospective review of the IBD registry at the University of Chicago, which captures all outpatients seen in the outpatient clinics. Data regarding self-identified race, IBD type, location, extent, surgery, family, and smoking history, medications, extraintestinal manifestations (EIMs), cancer and dysplasia history, and involvement in clinical trials were abstracted from the database. The data were then divided by race and compared via univariate chi-square analysis with a significance level of p< 0.10. Results: For Crohn's disease (CD) patients, 797 caucasians and 86 AA were identified. For ulcerative colitis (UC) patients, 345 caucasians and 19 AA were identified. Among CD patients, AA had significantly higher rates of joint symptoms (31.2% v. 20.1%, p=0.015) and pyoderma gangrenosum (3.5% v. 1.1%, p=0.073). AA CD patients had a significantly lower rate of ileal involvement (45.4% v. 60.4%, p=0.007), but no difference in rates of upper gastrointestinal, jejunal, colonic, or perianal disease. Among UC patients, AA had significantly higher rates of EIMs overall (42.1% v. 20.8%, p=0.029), joint symptoms (26.3% v. 12.1%, p=0.072), and pyoderma gangrenosum (5.3% v. 0.6%, p=0.028). There was no significant difference in disease extent. We also found no significant differences in medication usage, clinical trial enrollment, prevalence of dysplasia or cancer, surgical, family, or smoking histories between AA and caucasian patients for either disease. Conclusion: We describe one of the largest cohorts of AA IBD patients, and found several significant differences between these patients and caucasian IBD patients. In this study population, IBD EIMs are more common in AA patients compared to caucasians in both UC and CD. In addition, no racial disparities were detected in treatments or clinical trial enrollment. These findings can help clinicians understand their patients' disease better upon presentation and suggest genetic traits linked to racial phenotype underlying this difference in disease phenotype.Table: Disease location and extent

Sudden Hearing Loss: Could it be Inflammatory Bowel Disease?

Purpose: Cogan's syndrome (CS) is a rare autoimmune disorder characterized by ocular and vestibuloauditory symptoms. We describe a patient initially diagnosed with CS and was later found to have Crohn's disease (CD). Case: A 36-year-old woman with no medical history initially developed acute eye pain and photophobia. After evaluation by ophthalmology, she was treated for iritis with a topical steroid. A week later, she developed unilateral hearing loss. Rheumatology workup revealed negative antinuclear antibody, antinuclear cytoplasmic antibody, rheumatoid factor, hepatitis serologies and HLA-B27. Erythrocyte sedimentation rate and C-reactive protein were normal. Chest x-ray was negative for lymphadenopathy or other lesions. She was diagnosed with CS and refused Methotrexate due to potential side effects. A month later she developed panuveitis despite topical steroid therapy. Adalimumab was given, but she had an injection site reaction which caused her to stop the medication. She then presented to GI clinic with an 8 lb weight loss and new-onset intermittent, lower abdominal pain. She denied nausea, vomiting, diarrhea, constipation, or rectal bleeding. Colonoscopy was performed, which revealed a normal colon but multiple ulcers in the terminal ileum. Pathology showed chronic active ileitis consistent with Crohn's disease. MR enterography revealed mild wall thickening and enhancement involving a 3 cm segment of terminal ileum. The patient was diagnosed with CD five months after her initial symptoms began. Discussion: Less than 250 case reports of CS have been described. The syndrome is defined in two forms: “typical” or “atypical.” Typical CS is characterized by nonsyphilitic interstitial keratitis affecting one or both eyes. A majority of patients develop symptoms in the eye or ear alone, but rapidly involve both within three months. Atypical CS includes other inflammatory complications such as eye involvement other than interstitial keratitis. In contrast to typical CS, there is often a delay of more than two years between ocular and audiovestibular manifestations. Previous case series show an association with inflammatory bowel disease. In this population, CS symptoms often precede inflammatory bowel disease (IBD) diagnosis. On the other hand, auditory impairment is a rare extraintestinal manifestation of IBD. We use this case to stress the importance of evaluating for IBD in a patient with auditory and visual complaints.

Prevalence of Stroke and Transient Ischemic Attack in the Setting of Inflammatory Bowel Disease: A Retrospective Review (P07.001)

Objective: To assess the prevalence of stroke and Transient Ischemic Attack in the setting of Inflammatory Bowel Disease. Background Ischemic stroke in patients with Inflammatory Bowel Disease (IBD), Crohn9s Disease (CD) and Ulcerative Colitis (UC), is a well-recognized phenomenon but its prevalence is unknown. The association between the type of IBD, disease severity, and stroke risk is also not well known. Design/Methods: We performed a retrospective review of 10,134 patients with IBD in a Cleveland Clinic database, by cross-matching ICD-9-CM diagnosis codes for stroke and transient ischemic attack (TIA) with those for IBD. We analyzed this data using a multivariable logistic regression method. Results: A total of 103 patients had IBD plus either stroke or TIA yielding a prevalence of 1.02 per 100 patients. We also analyzed the association of traditional vascular risk factors and stroke in the setting of IBD as well as IBD-related factors and stroke. Traditional vascular risk factors significantly increased stroke risk. Although not statistically significant, patients with extra-intestinal manifestations of IBD had a higher risk of stroke (OR 2.9) as did those with CD compared with UC (OR 1.3). Severity of disease, based on the number of IBD-related surgeries, did not correlate with stroke risk. We found no link between any particular medical therapy and stroke risk, but patients receiving statins had significantly fewer IBD-related surgeries than those not receiving statins (OR 2.07). The prevalence of stroke or TIA in our IBD population was lower than previously reported. Conclusions: Further studies are needed to clarify the association between IBD and stroke, to elucidate the risk factors, and to investigate the potential disease-modifying effect of statins in these patients. Disclosure: Dr. Dangayach has nothing to disclose. Dr. Fong has nothing to disclose. Dr. Katzan has received personal compensation for activities with Genentech Inc as a speaker. Dr. Rose has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Shen has nothing to disclose. Dr. DeGeorgia has received personal compensation for activities with Osram Medical Incorporated as a consultant.

Recurrent Mesalazine-Induced Myopericarditis in a Patient with Ulcerative Colitis

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.

Cardiovascular disease in Crohnʼs and Ulcerative Colitis: An echocardiographic evaluation

Inflammatory bowel disease (IBD) is a systemic affliction. Several case reports have linked pericardial tamponade and pericarditis to IBD and some suggest that cardiovascular disease (CVD) may be one of the extraintestinal manifestations of IBD. Little attention has been paid toward the study of CVD in IBD patients from an echocardiographic perspective. The aim of our study is to survey for such abnormalities in both Crohn's and Ulcerative Colitis as well as being among the first to report such findings in a predominantly black population, an often underreported IBD group. We conducted a retrospective cohort study, from January 2000 to December 2010, approved by our hospital's institutional review board. IBD patients (both inpatients and those seen in clinic) were collected by ICD-9 code and were analyzed for whether or not an echocardiogram was conducted, its indication and findings, demographics and IBD history. Patients under 18 were excluded. If a patient had more than one echocardiogram performed, only the first study was included in our analysis. Forty out of 294 IBD patients had an echocardiogram performed. Thirtysix patients were black (28 being Afro-Caribbean). Twenty-two patients were women. Fifteen patients had Crohn's. Twenty-two patients had exposure to steroids. Seven patients had exposure to immunomodulators. Thirteen patients had exposure to tobacco. Mean age and duration of IBD at time of echocardiogram was 51.5 and 9.3 years, respectively. Twenty patients had extraintestinal manifestations. See Table 1 and 2 for indications and echocardiogram findings. When it was observed that patients with rheumatoid arthritis had a high incidence of heart failure, further investigation led to findings of a lower left ventricular mass and increased end diastolic volume. In an Italian study from 2007, 69% of Crohn's patients had morphologic alterations. Our study affirms the importance of cardiac echo in the evaluation of autoimmune disease, such as IBD. While no large-sized effusions or severe valvulopathies were appreciated, it is well established that other imaging modalities such as cardiac MRI or cardiac PET-CT have better performance in detecting early cardiovascular abnormalities. Perhaps more significant findings could have been observed if the above were used. Given our small sample size, adjusting for cardiac risk factors (e.g. diabetes, family history) was not done but could be remedied with larger scale investigations. Despite our patient population's homogeneity being one of the study's strengths, it is also means results will lack generalizability. Finally, whether the 86% of our IBD patients who did not receive an echo need to have CVD screening is of debate.

Assessing Response and Loss of Response to Biological Therapies in IBD

The advent of biological therapies for inflammatory bowel disease (IBD) began in 1998 with the approval of infliximab for the treatment of refractory (to conventional agents) Crohn's disease (CD). Since then, the indications for anti-tumor necrosis factor-α (anti-TNFα) therapy have increased to include induction and maintenance of clinical responses and remissions for luminal and fistulizing CD, the treatment of children with CD, and the treatment of adults with ulcerative colitis. Additional utilities of biological therapies have included demonstrable mucosal healing, improvement in quality of life, reduction in surgeries and hospitalizations, and the treatment of extraintestinal manifestations of IBD including central and peripheral arthritis and pyoderma gangrenosum. Natalizumab has also been approved for the treatment of refractory Crohn's in patients who have failed conventional agents and anti-TNFα therapies. Unfortunately, despite the overall effectiveness of biological agents in a spectrum of indications for IBD, a significant proportion of patients do not respond or lose response over time. In this review, we intend to appraise the latest evolution in treatment strategies in IBD and to suggest an evidence-based approach and risk stratification while coping with cases of non-responders or loss of response to biological therapies. We conducted a literature search of English publications listed in the electronic databases of MEDLINE (source PUBMED) and constructed an analytical review based on definitions of response and loss of response, considering potential responsible mechanisms, clinical assessment tools, and finally recommending a practical approach for its prevention and management. Favorable clinical outcome appears to be the consequence of sustained therapeutic drug levels, and the current literature supports a practice of dose adjustments. When immunogenicity develops to a single biological agent, response can be regained by introduction of an alternative biological agent of the same or different class. Efficacy is reduced with second-line agents either within or across classes compared with naive patients. In the absence of direct measurement of drug levels and anti-drug antibodies, clinical judgment is necessary to assess the mechanisms of loss of response, and more empiric decision making may be necessary to determine the choice of second-line biological agents. Optimal treatment strategies are still controversial. It is essential to recognize the spectrum of mechanisms affecting response and loss of response to form a logical and efficient management algorithm, and, perhaps, it is time to incorporate the measurement of trough levels and anti-drug antibodies in the strategy of such an assessment. Prospective controlled trials are direly needed to investigate the optimal tailored management in individual patients who lose response.

Inflammatory bowel disease in the Hubei Province of China.

To analyze clinical features and response to treatment in inflammatory bowel disease (IBD) patients from the Hubei Province of China. Clinical data was collected retrospectively from 74 patients with IBD [66 with ulcerative colitis (UC) and 8 with Crohn's disease (CD)] admitted to The Second Hospital, Hubei Medical University from 1986 to 1995. The most common symptoms in IBD patients were abdominal pain, diarrhea, blood and mucus in stool, and constipation. Extraintestinal manifestations of IBD were not common. In these patients, inflammation was predominantly located in the sigmoid and left colon in UC cases, and in the ileum and colon in CD cases. Treatment with sulphasalazine and corticosteroids was effective in 95% of UC cases; However, about 42% of UC patients showed disease recurrence during the follow-up period of 1.11 years. Five out of eight CD patients had part of their intestine removed, whereas three were treated with anti-tuberculosis drugs or the antibiotic metronidazole. Out of four patients we followed up for 1-8 years, one died of severe complications after surgery, two experienced recurrence while in treatment with drugs, and one remained in remission under sulphasalazine treatment after surgery. Five percent of the patients reported a family history of IBD. About 34% of the patients were smokers and 32% of the patients were alcoholic. Epidemiological studies are urgently needed in the Hubei Province of China to assess the role that genetics and environmental factors play in the pathogenesis of inflammatory bowel diseases.

Presentation and outcome of histoplasmosis in pediatric inflammatory bowel disease patients treated with antitumor necrosis factor alpha therapy: A case series

Antitumor necrosis factor alpha (aTNF) therapies are commonly used in the treatment of pediatric inflammatory bowel disease (IBD). However, inhibition of the TNF-alpha pathway predisposes to serious infections, including histoplasmosis, which is the most common invasive fungal infection in individuals on aTNF therapy and carries a high mortality rate when associated with delayed diagnosis. Few data exist on the frequency, presentation, and appropriate treatment of pediatric patients with histoplasmosis on aTNF therapy. Following Institutional Review Board approval, cases were identified then reviewed with their primary gastroenterologist and infectious disease specialists. Herein we describe histoplasmosis in five pediatric patients receiving aTNF therapy for IBD in an endemic area. Histoplasmosis is an important complication of treatment with TNF-alpha neutralizing agents. Children with IBD treated with aTNF therapy who develop the infection may present with minimal pulmonary symptoms. While discontinuation of aTNF therapy is important initially, few data exist to determine when and how aTNF therapy can be reinstituted. Recognition of Histoplasma capsulatum is often delayed due to the overlap of symptoms with some of the extraintestinal manifestations of IBD and other more prevalent infectious complications.

Pleuropericarditis in a Patient with Inflammatory Bowel Disease: A Case Presentation and Review of the Literature

Inflammatory bowel disease (IBD) can affect the lung parenchyma and airways. Rarely it involves the pleural space and pericardium, causing inflammatory exudative pleural and/or pericardial effusions. In this report, we describe a 76-year-old patient with recurrent sterile exudative pleuropericarditis that gradually responded to treatment with steroids, and we review the relevant literature. Thoracic serositis in patients with IBD can cause pleuritis, pericarditis, pleuropericarditis, or myopericarditis. This is a relatively rare presentation of the uncommon and probably underreported and underrecognized pulmonary extraintestinal manifestations of IBD. Pleuropericardial inflammatory disease and effusion can be directly related to IBD, its complications, associated infections, or the medications used to treat it. Serositis directly related to IBD is a diagnosis of exclusion. It is important to evaluate the pleural effusion and rule out other etiologies before making this diagnosis. Pleural or pericardial biopsies are rarely necessary, and probably show nonspecific acute and chronic inflammatory changes. Although the specific pathophysiology of pleuropericardial disease in patients with IBD remains unclear, the response to systemic steroids is usually adequate.

Risk of Extra-Intestinal Cancer in Inflammatory Bowel Disease: Meta-Analysis of Population-Based Cohort Studies

Extra-intestinal manifestations of inflammatory bowel disease (IBD) are relatively common, whereas the risk of extra-intestinal cancer (EIC) remains uncertain. The aim of this study was to obtain a reliable estimate of the risk of EIC in Crohn's disease (CD) and ulcerative colitis (UC) by performing a meta-analysis of population-based cohort studies. A systematic literature review was performed using MEDLINE (1966-2009) and abstracts from recent international conferences. Eight population-based cohort studies comprising a total of 17,052 patients with IBD were available. Standardized incidence ratios (SIRs) of EICs were pooled in a meta-analysis approach using STATA software. Overall, IBD patients were not at increased risk of EIC (SIR, 1.10; 95% confidence interval (CI) 0.96-1.27). However, site-specific analyses revealed that CD patients had an increased risk of cancer of the upper gastrointestinal tract (SIR 2.87, 95% CI 1.66-4.96), lung (SIR 1.82, 95% CI 1.18-2.81), urinary bladder (SIR 2.03, 95% CI 1.14-3.63), and skin (SIR 2.35, 95% CI 1.43-3.86). Patients with UC had a significantly increased risk of liver-biliary cancer (SIR 2.58, 95% CI 1.58-4.22) and leukemia (SIR 2.00, 95% CI 1.31-3.06) but a decreased risk of pulmonary cancer (SIR 0.39, 95% CI 0.20-0.74). Although the overall risk of EIC was not significantly increased among patients with IBD, the risk of individual cancer types differed from that of the background population as well as between CD and UC patients. These findings may primarily be explained by smoking habits, extra-intestinal manifestations of IBD, and involvement of the upper gastrointestinal tract in CD.

Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease

Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated.

Musculoskeletal manifestations of inflammatory bowel disease

Extraintestinal manifestations develop in ≈25% of patients with inflammatory bowel disease (IBD). Musculoskeletal symptoms are the most common extraintestinal manifestations of IBD, often associated with colonic involvement, and present as either articular (arthritis) or periarticular inflammation including enthesitis, myositis, or soft tissue rheumatism (fibromyalgia). Musculoskeletal manifestations can precede or be synchronous with the development of bowel disease or develop following the diagnosis of IBD. Their clinical course often correlates with IBD activity but it can also be independent of the activity of bowel disease. Controlling intestinal inflammation remains the cornerstone therapeutic approach for the musculoskeletal manifestations of IBD.

P081 - Pancreatic insufficiency in inflammatory bowel disease. Assessment by fecal elastase-1

Clinically significant disease of the pancreas in association with inflammatory bowel disease (IBD) is unusual but reported. IBD patients have a risk of developing pancreatitis as well as pancreatic insufficiency (PI). Pancreatic elastase-1 is a human and pancreas specific enzyme that is not degraded during intestinal transport and correlates with exocrine pancreatic function test. The aim of this study was to evaluate the relationship between inflammatory bowel disease and pancreatic insufficiency as an extraintestinal manifestation of IBD.

Do HLA antigens predict the occurrence of extraintestinal manifestations of IBD?

Extraintestinal manifestations are commonly seen in (up to 40%) in patients with either ulcerative colitis (UC) or Crohn’s disease (CD). Many of them are associated with active disease (recurrent mouth ulcers, erythema nodosum, uveitis, Type 1, or reactive large joint arthropathy). Others pursue a clinical course independent of the intestinal disease (sacroiliitis, ankylosing spondylitis, Type 2 or small joint arthropathy, primary sclerosing cholangitis). Pyoderma gangrenosum usually occurs with active intestinal disease but can occasionally occur when the intestinal inflammation is largely in remission. For CD, both groups of these extraintestinal manifestations occur in patients with colonic involvement, and rarely occur when only small intestinal disease is present. Data on the HLA associations are limited both in terms of numbers of studies and numbers of patients studied. However, a particularly strong association has been found between the Class II allele DRB1*0103, and Type 1 arthropathy.1 Of patients with either UC or CD who develop the acute, large joint arthropathy in association with active disease, 38% of them carry this allele, compared with about 8% of UC patients as a whole, and only 2% of the healthy population. It is interesting to note that patients who develop a reactive arthropathy following infection (Salmonella, Campylobacter, Reiter’s syndrome) also have a high carriage rate of this allele. This allele is also associated with the risk of having recurrent mouth ulcers or uveitis, although less strongly compared with Type 1 arthropathy. Uveitis and recurrent mouth ulcers are also associated with HLA B27. Erythema nodosum has a particularly strong association with a polymorphism in the promoter region of the TNF gene (-1031C).2 There are further HLA associations with some of those extraintestinal manifestations that are independent of inflammatory bowel disease (IBD) activity. Ankylosing spondylitis (AS) occurs in 1%–2% of patients with IBD and differs from sporadic AS in having no gender association (compared with a marked male predominance in sporadic AS) and in having a weaker association with HLA B27 (60% compared with 90% in sporadic AS). Nevertheless, the association is highly significant. Patients with sacroiliitis only have a 22% risk of having HLA B27, a percentage that is little different from the normal control population. Patients with Type II arthropathy, a seronegative, symmetrical small joint disease, have a strong association with HLA B44. Data concerning primary sclerosing cholangitis (PSC) are conflicting. Most studies find an association with HLA DR3. In the largest study the haplotype HLA DRB1*0301, DQB1*0201 (the classical autoimmune haplotype) was found in 25% of patients with PSC and colitis, 16% of patients with pancolitis only, and 10% of controls (Cullen S, Chapmann RG, Jewell DP. Submitted). These data clearly indicate that individuals possessing certain HLA alleles are at risk of developing extraintestinal manifestations, should they have the misfortune of developing IBD. In contrast, they are unlikely to occur in patients with IBD who do not possess these alleles. Furthermore, these associations can explain why these manifestations often overlap in a single individual. The outstanding questions concern the mechanisms of pathogenesis. Since the HLA region on the short arm of chromosome 6 is a very gene-dense region, it cannot be assumed that the allelic associations that have been identified are the relevant genes as opposed to having identified an allele which is in linkage disequilibrium with a more relevant polymorphism in a neighboring gene. Until this problem has been overcome, functional studies to explore pathogenic mechanisms cannot sensibly begin.

Pulmonary manifestation of inflammatory bowel disease in pregnancy

Inflammatory bowel disease (IBD) is a systemic disease that can present with pulmonary manifestations. IBD may be exacerbated during pregnancy. We describe the first reported case of pulmonary manifestation of ulcerative colitis (UC), an IBD, with necrobiotic nodules, in a pregnant patient. A 27-year-old woman with a history of UC, 25 weeks pregnant, presented to our hospital with bilateral pulmonary nodules. After serologic and radiologic evaluation, she underwent biopsy by video assisted thoracic surgery and a tissue diagnosis was made. This case illustrates the need to consider extra intestinal manifestations of IBD, the need to establish diagnosis by biopsy, and the consideration of appropriate therapeutics in the pregnant patient.

Pulmonary Nodules as an Extra-Intestinal Manifestation of Inflammatory Bowel Disease: A Case Series and Review of the Literature

Inflammatory bowel disease (IBD) exhibits a wide spectrum of pulmonary manifestations [1]. Pulmonary nodules, however, are an uncommon extra-intestinal manifestation (EIM) of IBD with only a few cases documented in the literature (Table 1). A review of the case reports reveal that the pulmonary nodules linked to IBD exhibit a variety of histological patterns. The pulmonary nodules and respiratory symptoms relating to the lung pathology respond favorably to systemic or oral corticosteroid therapy and all patients show resolution or substantial improvement of pulmonary nodules on follow-up radiographs (Table 1). We present a case series of three patients who presented with pulmonary nodules as an EIM of IBD. The English-language literature is reviewed and we will highlight the clinical as well as histological importance of pulmonary nodules in IBD.

Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine‐induced pancreatitis

Pancreatitis is a potentially severe condition. Patients with inflammatory bowel disease (IBD) seem to be at increased risk for acute pancreatitis. To describe the incidence, main causes and possible predictive factors of acute pancreatitis in inflammatory bowel disease. Information was retrospectively extracted from the clinical records of patients followed in the IBD Units of nine hospitals in Madrid (n = 5073). A total of 82 acute pancreatitis episodes were diagnosed (cumulative incidence, 1.6%); 98% of them were mild. Recurrent acute pancreatitis developed in 13% of patients. Most cases of acute pancreatitis (63.4%) were attributed to drug exposure [azathioprine/mercaptopurine (AZA/MP) n = 46, mesalazine (mesalamine) n = 6]; 20.7% were idiopathic, and 12.2% were biliary. Incidence of acute pancreatitis in patients treated with AZA/MP was 3.1%. In patients with acute pancreatitis, female gender (OR 3.4 95% CI: 1.3-9.3; P = 0.012) and Crohn's disease (CD) (OR 5.8 95% CI: 1.6-20.6; P = 0.007) were risk factors for AZA/MP-associated acute pancreatitis, the latter also when analysed only in patients treated with AZA/MP (n = 1477) (OR 5.2 95% CI: 1.8-14; P = 0.002). The incidence of acute pancreatitis in our IBD patients (1.6%) is similar to that previously described. Drugs, mainly AZA/MP, are the leading cause. AZA-induced acute pancreatitis is always mild. Patients with CD are at a higher risk for AZA/MP-associated acute pancreatitis. The frequency of idiopathic acute pancreatitis is higher than expected, suggesting that part of these cases could be extraintestinal manifestations of IBD.

Auto-evaluation. Infection a Helicobacter Pylori

Extraintestinal manifestations (EIMs) are commonly seen in patients with inflammatory bowel disease (IBD); management of EIMs is difficult and increases the primary disease burden. Recently, tofacitinib (TOF) was reported to be a promising option for treatment of EIMs. We aimed to review published articles and report experience to date.The PubMed, Cochrane Library, and Web of Science databases were searched to identify eligible studies. The inclusion criteria were as follows: confirmed diagnosis of IBD; definitive EIMs; treatment with TOF; human study and published in English. The Newcastle–Ottawa Scale score and Cochrane Collaboration’s tool for assessing risk of bias were used to determine the quality of the selected studies.Twenty-three studies met the inclusion criteria and were included. For nonrandomized studies, 16 were low quality, 5 were moderate quality, and 1 was high quality. For the one randomized controlled trial, the overall bias risk was low. The most concerning EIMs were dermatological manifestations, rheumatologic manifestations, and others, such as primary sclerosing cholangitis, autoimmune hepatitis, uveitis, and Takayasu arteritis. After administering doses of 5–20 mg/d TOF, the included studies reported varying degrees of clinical remission for both the primary disease and EIMs, except for musculoskeletal EIMs.TOF might benefit EIMs in IBD, especially ulcerative colitis, and elevated dosages and longer treatment times may increase its effectiveness. Manifestation-specific results and large prospective studies are highly warranted.

Thrombosis and inflammatory bowel disease-the role of genetic risk factors

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.

American Gastroenterological Association Consensus Development Conference on the Use of Biologics in the Treatment of Inflammatory Bowel Disease, June 21–23, 2006

The American Gastroenterological Association (AGA) convened a panel of gastroenterologists expert in the area of inflammatory bowel disease (IBD) that developed this consensus statement based on expert presentations of current scientific knowledge about IBD and through subsequent group discussion. This statement reflects the panel's assessment of medical knowledge available when written. Thus, readers should view this statement in the context of data that will accumulate after its creation. The opinions, conclusions, and recommendations expressed in this report are those of the consensus panel members and may or may not reflect the official opinion of the American Gastroenterological Association Institute. The conference upon which this report is based was funded through an unrestricted educational grant from Abbott Laboratories. Abbott Laboratories representatives did not attend the conference, nor did they participate in any way in the development of this report.