Increased risk for demyelinating diseases in patients with inflammatory bowel disease

BACKGROUND & AIMS: Reports of multiple sclerosis (MS), demyelination, and optic neuritis (ON) associated with anti-tumor necrosis factor alpha therapy resulted in warnings on prescribing instructions for infliximab, etanercept, and adalimumab. However, the underlying relationship between IBD and these neurologic conditions has not been established. METHODS: We performed a retrospective cohort study and a retrospective cross-sectional study using 1988 to 1997 data from the General Practice Research Database. A total of 7988 Crohn's disease and 12,185 ulcerative colitis patients were matched for age, sex, and primary care practice to 80,666 randomly selected controls. In the cohort study, incident cases of MS, demyelination, and/or ON (MS/D/ON) had to occur at least 1 year after registration with the physician and after the diagnosis of IBD. In the cross-sectional study, the diagnosis of MS/D/ON could either precede or follow the IBD diagnosis. RESULTS: In the cohort study, the incidence of MS/D/ON was higher in patients with Crohn's disease and ulcerative colitis compared with their matched controls, reaching statistical significance for ulcerative colitis (ulcerative colitis incidence rate ratio [IRR], 2.63; 95% confidence interval, 1.29-5.15; Crohn's disease IRR, 2.12; 95% confidence interval, .94-4.50). In the cross-sectional study, MS/D/ON was more prevalent in patients with Crohn's disease and ulcerative colitis compared with their matched controls (Crohn's disease odds ratio, 1.54; 95% confidence interval, 1.03-2.32; ulcerative colitis odds ratio, 1.75; 95% confidence interval, 1.28-2.39). CONCLUSIONS: Demyelinating diseases occur more commonly among patients with IBD than among non-IBD patients. Future studies should clarify whether treatment with tumor necrosis factor alpha blockers results in further increased incidence of MS/D/ON among IBD patients.     

Increased risk of bacterial endocarditis in inflammatory bowel disease.

PURPOSE: The purpose of this retrospective as well as prospective case-control study was to analyze a possible overrepresentation of inflammatory bowel diseases among patients with native valve endocarditis as well as the factors that predispose patients with inflammatory bowel disease to infective endocarditis. PATIENTS AND METHODS: Among 213 consecutive patients treated for proven native valve endocarditis, six (2.8%) had inflammatory bowel diseases (three with ulcerative colitis and three with Crohn's disease). Three patients with inflammatory bowel disease were from the retrospective group, and three were from the prospective group. The prevalence of inflammatory bowel diseases has been determined to be 0.0641% in the Düsseldorf area. RESULTS: On the basis of these data, a 44-fold overrepresentation of inflammatory bowel diseases among the 213 patients with endocarditis was calculated with a statistical significance of p much less than 0.001. CONCLUSIONS: Inflammatory bowel disease may be considered an independent risk factor for bacterial endocarditis. Reasons may be more frequent bacteremias as a result of the higher incidence of diagnostic and therapeutic interventions, as well as increased permeability of the damaged mucosa for bacteria and the therapeutic immunosuppression in patients with active inflammatory bowel disease. Prophylaxis for bacterial endocarditis should be carefully considered before expected bacteremias in patients with highly active inflammatory bowel disease even in the absence of cardiac factors predisposing to bacterial endocarditis.     

Increased risk of preterm birth among non- smoking, non- alcohol drinking women with maternal periodontitis

The aim of this case-control study was to examine the association between periodontitis and preterm birth among non-smoking, non-alcohol drinking women. The cases were 130 women who delivered a live singleton newborn before 37 weeks gestation. A random sample of 260 women who delivered a normal child on the same day as the cases were selected as controls. Periodontal examinations were performed during 24-hour period postpartum at bedside. Other related information was collected by structured questionnaire and medical records. Multiple logistic regression analysis was performed controlling for age, ethnicity, place of residence, education, occupation, income, pre-pregnancy body mass index (BMI), weight gain, antenatal care (ANC), parity, systematic infections, genitourinary infections, antibiotics used, and history of periodontal treatment. Periodontitis (defined as presence of at least 4 teeth having > or = 1 site with a probing depth (PD) > or = 4 mm, clinical attachment loss (CAL) > or = 3 mm and bleeding on probing (BOP) after 10 seconds at the same site) was diagnosed in 33.9% of cases and 10.4% of controls. Periodontitis was significantly associated with preterm birth (adjusted OR = 4.47, 95%Cl= 2.43, 8.20). These findings suggest that periodontitis may increase the risk of preterm delivery even among women who do not smoke or drink.     

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.     

Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine

BACKGROUND: Inflammatory bowel disease (IBD) is commonly treated with immunomodulators such as azathioprine and 6-mercaptopurine (6-MP). Studies examining lymphoma risk in IBD patients treated with these medications have been underpowered and have yielded conflicting conclusions. AIMS: The purpose of this meta-analysis was to provide a more precise estimate of the relative risk of lymphoma among IBD patients treated with azathioprine or 6-MP. METHODS: Studies were included if they were English language, full article, cohort studies specifically designed to evaluate cancer as an adverse outcome of treatment with azathioprine or 6-MP. Pooled standardised incidence ratios were calculated to estimate the relative risk of lymphoma associated with therapy. Heterogeneity was assessed using Poisson regression. Sensitivity analyses examined the influence of individual studies on risk estimate and heterogeneity statistics. RESULTS: Six studies were identified that met our inclusion criteria. When the data were combined across all studies, the pooled relative risk was 4.18 (95% confidence interval 2.07-7.51; 11 observed cases, 2.63 expected). Sensitivity analysis showed that exclusion of any one study had a relatively small effect on the pooled relative risk estimate (range 3.49-5.21) but excluding either the study with the highest or lowest estimated relative risk eliminated the statistically significant heterogeneity. CONCLUSIONS: Our data suggest an approximate fourfold increased risk of lymphoma in IBD patients treated with azathioprine/6-MP. The increased risk of lymphoma could be a result of the medications, the severity of the underlying disease, or a combination of the two.     

Increased risk of early colorectal neoplasms after hepatic transplant in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is associated with an increase in colon and rectal carcinoma. Immunosuppression after transplantation increases the incidence of certain types of tumors. PURPOSE: We reviewed the postoperative course of IBD patients who had undergone hepatic transplantation for primary sclerosing cholangitis to see whether there was an increase in the rate of colorectal neoplasms. METHODS: The charts of 44 patients from two institutions who had undergone a hepatic transplant for primary sclerosing cholangitis were reviewed. Of these 44 patients, 33 had IBD (32 chronic ulcerative colitis, 1 Crohn's). Of these 33 patients, 2 had previously undergone total colectomy/proctectomy and 4 died in the perioperative period. The remaining 27 patients had all undergone colonoscopic evaluation just prior to transplant. Postoperatively all patients were given prednisone, cyclosporine, and azathioprine. Minimum follow-up was 12 months; mean follow-up was 39 months. RESULTS: Three of the 27 patients (11.1 percent) developed early colorectal neoplasms (2 cancers, 1 large villous adenoma with severe dysplasia) at 9, 12, and 13 months post-transplant. All three patients were successfully treated with a total colectomy/proctectomy or resection of any remaining colon. These 3 patients had a mean 19-year history of IBD (range, 9–27 years), while the 24 patients without tumors had a mean 18-year history of IBD (range, 6–39 years). CONCLUSION: There is a subset of transplant patients with primary sclerosing cholangitis and IBD who rapidly develop colorectal neoplasms. Frequent surveillance is recommended for IBD patients in the post-transplant period.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

Increased risk of atrial fibrillation in patients with inflammatory bowel disease: A nationwide population-based study

BACKGROUND Inflammatory bowel disease (IBD), a chronic inflammatory disease of the gastrointestinal tract, could play a role in the pathophysiology of atrial fibrillation (AF). AIM To investigate the association between IBD and AF development. METHODS We performed a population-based cohort study using records in the Korean National Health Insurance Services database between 2010 and 2014. A total of 37696 patients with IBD (12349 with Crohn’s disease and 25397 with ulcerative colitis) were identified. The incidence rate of newly diagnosed AF in patients with IBD was compared with that in a 3 times larger cohort of 113088 age- and sex-matched controls without IBD. RESULTS During 4.9 ± 1.3 years of follow-up, 1120 patients newly diagnosed with AF (348 in the IBD group and 772 in controls) were identified. After adjustments using multivariable Cox proportional hazards, patients with IBD were at a 36%[95% confidence interval (CI) 20%-54%] higher risk of AF than controls. The association between IBD and the development of AF was stronger in younger than in older patients. Patients without cardiovascular risk factors showed a higher risk of AF primarily. Additionally, patients receiving immun-omodulators [Hazard ration (HR) 1.46, 95%CI 1.31-1.89], systemic corticosteroids (HR 1.37, 95%CI 1.10-1.71), or biologics agents (HR 2.38, 95%CI 1.51-3.75) were at higher risk of AF than patients without them. CONCLUSION IBD significantly increased the risk of AF, and the impact of IBD on developing AF was in patients with moderate to severe disease.     

Increased aggregation response of platelets in patients with inflammatory bowel disease

Background Platelets play an important role in hemostatic and inflammatory responses. To evaluate any potential enhancement of platelet activity in patients with inflammatory bowel disease (IBD), we measured the platelet aggregation responses to various stimuli. Methods Twenty-two healthy controls, 24 patients with ulcerative colitis (UC) and 25 patients with Crohn's Disease (CD) were studied. The aggregation responses induced by three agonists (epinephrine, collagen, and ADP) were measured by an 8-channel aggregometer. The platelet-derived microparticles (PDMP) levels were measured by an enzyme-linked immunosorbent assay. Results Twenty-one out of the 22 healthy controls did not respond to epinephrine (0.1 μg/ml), collagen (0.2 μg/ml), or ADP (1.0 μM). Eight out of the 12 active UC patients were sensitive to all agonists, and 4 patients showed increased sensitivity to epinephrine/collagen or epinephrine/ADP. Three out of the 12 inactive UC patients were normal, but 9 of these patients showed increased sensitivity, mainly to epinephrine. Ten out of the 12 active CD patients were sensitive to all agonists, and 2 active CD patients were sensitive to epinephrine/collagen or epinephrine/ADP. Eight out of the 13 inactive CD patients were sensitive to two or all agonists. Even after remission, almost all of the UC and CD patients showed some increased sensitivity to the agonists. The platelet number and the plasma PDMP levels were significantly higher in the active IBD patients than in the control group. Conclusions Platelet aggregation responses are enhanced in IBD, even in inactive-phase patients. This increased sensitivity of the platelets may play an important role in the pathophysiology of IBD.     

Increased serum levels of eotaxin in patients with inflammatory bowel disease

BACKGROUND: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and phagocytic cells, are potent and selective chemoattractants for eosinophils and basophils. The eosinophil is a potent inflammatory cell thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study we investigated the serum concentrations of eotaxin and eotaxin-2 in patients with Crohn disease and ulcerative colitis. METHODS: Thirty-one patients with Crohn disease, 35 patients with ulcerative colitis and 41 control patients were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase sandwich enzyme-linked immunosorbent assays. RESULTS: Significantly increased serum eotaxin levels were observed in both patients with Crohn disease (289.4+/-591.5 pg/ml) and ulcerative colitis (207.0+/-243.4 pg/ml) when compared with controls (138.0+/-107.8 pg/ml) (P < 0.01). Moreover, patients with active Crohn disease and ulcerative colitis showed significantly higher serum eotaxin levels than patients with quiescent disease (434.0+/-776.8 pg/ml versus 113.8+/-65.4 pg/ml in Crohn disease and 295.7+/-337.1 versus 121.2+/-91.9 pg/ml in ulcerative colitis, P < 0.05). In contrast, there was no significant difference in eotaxin-2 serum levels among patients with Crohn disease (863.5+/-448.2 pg/ml), ulcerative colitis (1028.3+/-431.4 pg/ml) and controls (981.4+/-539.4 pg/ml). CONCLUSIONS: Eotaxin is significantly increased in serum of patients with active Crohn disease and ulcerative colitis, suggesting that this cytokine may play a role in the pathogenesis of IBD.     

Patients with inflammatory bowel disease are at risk for vaccine-preventable illnesses

BACKGROUND: Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive therapies, potentially increasing their risk of developing an infection. Empiric data suggest that vaccines are underutilized in immunocompromised patients, despite published guidelines recommending their use. We aimed to assess exposure risk and immunization status among patients receiving care in an IBD specialty clinic. METHODS: Patients completed a self-administered, pretested, structured questionnaire during a routine visit for the management of IBD. Survey questions related to medical and immunization histories, and exposures to known risk factors for influenza, pneumococcus, viral hepatitis, and varicella. Additionally, in a subgroup of patients who agreed to donate a sample of blood, immune status to hepatitis A (HAV), hepatitis B (HBV), and varicella was determined. RESULTS: Two hundred four patients were asked to participate in the study; 169 completed surveys and comprised the study population. Mean age was 35 yr (range 13-75 yr). One hundred forty-six respondents (86%) reported current or prior use of immunosuppressive medications. Only 45% of respondents recalled tetanus immunization within the past 10 yr, 41 (28%) reported regularly receiving flu shots, and 13 (9%) reported having received pneumococcal vaccine. The most common reasons for nonimmunization with influenza included lack of awareness (49%) and concern for side effects (18%). Responses indicated that 75 (44%) patients were at risk for HBV but only 47 (28%) had been vaccinated against the infection; of patients with previous HBV vaccination, only three of nine (33%) had measurable antibodies against hepatitis B surface antigen. CONCLUSIONS: Immunization against selected vaccine-preventable illnesses was uncommon in patients with IBD, despite the presence of significant risk factors. Efforts to improve immunization status among patients with IBD and other chronic, immune-mediated conditions are needed.     

Abnormalities of uterine cervix in women with inflammatory bowel disease

INTRODUCTION Cervical cancer is responsible for almost 4000 deaths annually in the United States[1]. Due in large part to mass screening protocols with papanicolaou (Pap) smears, mortality from cervical cancer has declined by over 70% in the past 50 years…     

Diet and risk of inflammatory bowel disease

BackgroundA better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses.AimTo review current knowledge on dietary risk factors for inflammatory bowel disease.MethodsThe PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease.ResultsEstablished non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case–control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate).ConclusionsA diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects.     

Voluntary childlessness is increased in women with inflammatory bowel disease

BACKGROUND: The women's health aspect of inflammatory bowel disease (IBD) is a newer area of study; childbearing issues have received little attention despite the fact that IBD affects women predominantly during their childbearing years. The aim of this study was to better understand patients' considerations about pregnancy-related issues and to examine trends in childbearing so that physicians are able to better tailor their advice to IBD-specific concerns. METHODS: Data were gathered from specific questions in 3147 surveys mailed anonymously to all members of the Crohn's and Colitis Foundation of America (CCFA) Illinois Carol Fisher chapter. The subjects were provided a pre-addressed, pre-stamped return envelope and were instructed to return their completed surveys with no identifying information. Subjects were from the Illinois community. Females IBD patients were 15-44 of age and were members of the CCFA Illinois Carol Fisher chapter. RESULTS: In this study, 169 females age 15-44 years with IBD, 110 with Crohn's disease (CD) and 59 with ulcerative colitis (UC), were identified. Most subjects were white. IBD patients had a higher rate of voluntary childlessness (CD 18%, UC 14%) than the 6.2% seen in the general population (P = 0.001 for CD, P = 0.08 for UC). Women with UC had a lower rate of temporary childlessness (CD 28%, UC 13.6%) than the general population (33%) (P = NS and P < 0.0001 for UC).The rates of nonvoluntary childlessness in IBD were similar to the general population. Women with IBD also had fewer children than their state and national counterparts. The state of the patients' IBD, including those who had gone through a previous pregnancy with IBD, did not alter their resolve to have children. The educational level of our subjects was higher than the nationwide and statewide levels; 76% of the subjects used contraception before diagnosis of IBD, and 82% used it after diagnosis. The most common choices were oral contraception, barrier methods, and abstinence. This study was unable to compare the lifetime rates of complications of pregnancy with population-based controls because such data were unavailable. Furthermore, their findings in this study may not be generalized to all ethnic groups because our population was mostly white. CONCLUSIONS: Women with IBD had a higher rate of voluntary childlessness and fewer children than the general population. These observations are likely attributable to a higher educational achievement and to racial background of the patients rather than to IBD-related reasons. Although contraception use in patients with IBD was lower that in the general population, use was higher after the diagnosis of IBD than before the diagnosis. Contraceptive choices and adoption rates were similar to the general population. Women with CD were more affected by miscarriages after diagnosis with IBD than those with UC.