Environmental factors associated with Crohn’s disease in India

Background  

The frequency of diagnosis of Crohn’s disease (CD) in India is increasing. This case-control study was designed to detect associations of environmental and dietary factors with the diagnosis of CD.     

Risk factors associated with postoperative recurrence and repeat surgery in Japanese patients with Crohn’s disease

Purpose

To avoid frequent surgery in patients with Crohn’s disease, it is important to identify the risk factors for postoperative recurrence or repeat surgery. However, there have so far been few studies on this topic from Asian countries. In addition, the recent development of anti-tumor necrosis factor (TNF) therapy may have changed the risk factors. We aimed to identify the factors associated with postoperative recurrence and repeat surgery.

Methods

The postoperative courses of 168 patients were reviewed. We analyzed the cumulative postoperative recurrence and repeat surgery rates and identified the factors affecting these rates.

Results

Postoperative recurrence was observed in 70 patients, and the 1-, 3-, and 5-year cumulative recurrence rates were 17.1, 40.1, and 54.9%, respectively. The recurrence rate was significantly higher in patients with anal lesions and lower in patients newly treated with anti-TNF agents following surgery. In a multivariate analysis, the new introduction of anti-TNF agents was identified as an independent suppressor (hazard ratio 0.50, 95% confidence interval 0.28–0.88). Twenty-four patients underwent repeat surgery, and the 1-, 3-, and 5-year cumulative repeat surgery rates were 4.6, 11.2, and 18.7%, respectively. The surgery rate was significantly higher in patients with penetrating-type disease. In a multivariate analysis, penetrating-type disease (6.98, 2.37–23.35), anal lesions (4.40, 1.14–30.53), and first-time surgery (5.28, 1.17–17.93) were identified as independent risk factors.

Conclusions

Anti-TNF agents have the potential to prevent postoperative recurrence. The new introduction, dose escalation, or switching of anti-TNF agents is recommended in patients with some risk factors.

     

Is early limited surgery associated with a more benign disease course in Crohn’s disease?

AIM:To analyze the difference in disease course and need for surgery in patients with Crohn’s disease(CD).METHODS:Data of 506 patients with incident CD were analyzed(age at diagnosis:31.5±13.8 years).Both hospital and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database,which includes incident CD patients diagnosed between January 1,1977 and December 31,2008.Follow-up data were collected until December 31,2009.All patients included had at least 1year of follow-up available.Patients with indeterminate colitis at diagnosis were excluded from the analysis.RESULTS:Overall,73 patients(14.4%)required resective surgery within 1 year of diagnosis.Steroid exposure and need for biological therapy were lower in patients with early limited surgery(P<0.001 and P=0.09).In addition,surgery rates during follow-up in patients with and without early surgery differed significantly after matching on propensity scores(P<0.001,HR=0.23).The need for reoperation was also lower in patients with early limited resective surgery(P=0.038,HR=0.42)in a Kaplan-Meier and multivariate Cox regression(P=0.04)analysis.However,this advantage was not observed after matching on propensity scores(PLogrank=0.656,PBreslow=0.498).CONCLUSION:Long-term surgery rates and overall exposure to steroids and biological agents were lower in patients with early limited resective surgery,but reoperation rates did not differ.     

Clinical course and longterm prognosis of Japanese patients with Crohn’s disease: predictive factors,rates of operation,and mortality

Background The purpose of this study was to clarify the long-term course of Crohns disease (CD) and predictors of its prognosis in Japan.Methods This was a historical cohort study of 276 patients with CD who had been diagnosed between 1965 and 1998. The clinical course was evaluated by the course of the CD score (CCDS) according to the required treatments. The predictive factors were examined by stepwise regression test. The cumulative rates of operation and survival were calculated by the Kaplan-Meier method.Results Patients with colitis-type CD had significantly lower annual and cumulative operation rates than those with other types, and showed significantly better progress, estimated by the CCDS, than patients with ileocolitis type. Reliable predictors for the 2- to 5-year clinical course after starting treatment were the CCDS, the presence of laparotomy during the initial year, and onset at age 30 years or more. The predictors for the 6- to 10-year clinical course were the duration of symptoms at diagnosis and onset at age 16 years or less. The predictors for the 11- to 15-year clinical course were the CCDS, the maximum International Organization of the Study of Inflammatory Bowel Disease (IOIBD) assessment score during the first year after starting treatment, and the effectiveness of the initial treatment. Relative survival rates at 5, 10, 15, and 20 years after the onset were 98.9%, 98.1%, 97.7%, and 94.9%, respectively.Conclusions CD patients with colitis type showed a better clinical course and had significantly different clinical features compared with the patients with ileitis and ileocolitis type. Prediction of the longterm course of CD is possible by using clinical factors during the first year after starting treatment. The relative survival rates in Japanese patients with CD are not different from those seen in Western countries.     

Perianal disease is associated with psychiatric co-morbidity in Crohn’s disease in remission

Background and aim

Crohn’s disease is a life-long inflammatory disease which can impair quality of life, in particular in patients with psychiatric co-morbidities such as depression and anxiety. The aim of this prospective cohort study was to assess the prevalence of depression and anxiety and related risk factors in patients with quiescent Crohn’s disease.

Methods

A consecutive series of adult patients with confirmed diagnosis of Crohn’s disease, in clinical remission, were included and investigated during ambulatory visits using a standard questionnaire assessing demographic and clinical features of the disease. Within 1 month after the ambulatory visit, all patients were interviewed by phone to assess the presence of psychiatric disorders using standardized questionnaires. The questionnaire assessed the development of psychiatric disorders after the diagnosis of Crohn’s disease, the use of antidepressant or antianxiety therapy and current anxiety or depression by means of the Hospital Anxiety and Depression Scale.

Results

One hundred and ninety-five patients were included. Seventy-two (36.9 %) patients showed anxiety and/or depression symptoms, 46 (23.6 %) patients showed anxiety symptoms, 6 (3.1 %) patients showed depression symptoms and 20 (10.3 %) patients showed both symptoms. Forty-eight of these patients (58 %) were without any antidepressive or antianxiety treatment. Anxiety with or without depression was significantly correlated with female sex (p?=?0.017), history of perianal disease (p?=?0.003) and perianal surgery (p?=?0.042).

Conclusion

Anxiety is a frequent, often untreated, condition in patient affected by Crohn’s disease in clinical remission. Female sex, history of perianal disease and perianal surgery are major risk factors for anxiety.     

Clinical features and oncological outcomes of intestinal cancers associated with ulcerative colitis and Crohn’s disease

Journal of Gastroenterology - Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between...     

Early surgery in Crohn’s disease patients with entero-urinary fistulas: does it change the prognosis?

Background Entero-urinary fistulas (EUF) are observed in only 2–8% of Crohn’s disease (CD) patients. Aim To compare the outcome of patients with EUF, after surgical treatment, with those with non-penetrating and non-stenosing, penetrating, and stenosing phenotypes (B1, B2, and B3 phenotypes). Methods Case-control study of 21 CD patients with EUF submitted to surgical treatment. Each patient with EUF was compared with six patients, two of each group: B1, B2, and B3 phenotypes. They were randomly selected from inflammatory bowel disease database and had the same extent of disease, smoking status, perianal disease, and age at diagnosis. Results One hundred and forty-seven patients were included (n?=?21 EUF; n?=?42 of each group B1, B2, and B3). Comparing B3 group with EUF, the former was more steroid-dependent and resistant (54.8% versus 19.0%, p?=?0.037) and needed anti-TNF therapy more frequently (59.5% versus 23.8%, p?=?0.004). Moreover, B3 patients had a poorer response to anti-TNF therapy without remission free of steroid therapy in comparison with EUF patients (45.2% versus 95.2%, p?p?=?0.956) and steroid-dependence or resistance (p?=?0.141). Surgery rate after index surgery was inferior in EUF in comparison with B2 and B3 groups. Hospital admission rate of patients with EUF was also lower than the B3 group. Conclusion Early surgery seems to be a good choice for patients with EUF as their response to surgery appears not to differ from B2 patients and had a better prognosis than phenotype B3 patients.     

Clinical prognostic factors for disabling Crohn’s disease: A systematic review and meta-analysis

AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn’s disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict the prognosis of different outcomes of CD was undertaken. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigat-ing the above mentioned factors in adult patients with CD. Studies were eligible for inclusion if they describe prognostic factors in CD, with inclusion and exclusion criteria defined as follows. Studies with adult patients and CD, written in English and studying association between clinical factors and at least one prognosis out-come were included. Meta-analysis of effects was un-dertaken for the disabling disease outcome, using odds ratio (OR) to assess the effect of the different factors in the outcome. The statistical method used was Mantel-Haenszel for fixed effects. The 16-item quality assess-ment tool (QATSDD) was used to assess the quality of the studies (range: 0-42). RESULTS: Of the 913 papers initially selected, sixty studies were reviewed and three were included in the systematic review and meta-analysis. The global QA-TSDD scores of papers were 18, 21 and 22. Of a total of 1961 patients enrolled, 1332 (78%) were classified with disabling disease five years after diagnosis. In two studies, age at diagnosis was a factor associated with disabling disease five years after diagnosis. Individu-als under 40 years old had a higher risk of developing disabling disease. In two studies, patients who were treated with corticosteroids on the first flare developed disabling disease five years after diagnosis. Further, perianal disease was found to be relevant in all of the studies at two and five years after diagnosis. Finally, one study showed localization as a factor associated with disabling disease five years after diagnosis, with L3 being a higher risk factor. This meta-analysis showed a significantly higher risk of developing disabling dis-ease at five year     

Hyperhomocysteinemia in patients with Crohn’s disease

Background

Thromboembolic complications have been reported in patients with Crohn’s disease. Among the contributing factors, hyperhomocysteinemia has been described, although controversial data exist. The aim of our study was to assess the incidence of hyperhomocysteinemia in a nonselected group of patients with Crohn’s disease and to determine whether it might represent a risk marker for thrombosis in such patients.

Methods

Fifty consecutive patients were recruited, and clinical and laboratory variables were compared between those without and those with hyperhomocysteinemia. In the latter, gene mutations in N5-N10-methyltetrahydrofolate reductase were searched for, and clinical and laboratory variables were related to hyperhomocysteinemia. The presence/absence of thrombotic episodes in both groups was determined.

Results

Both groups had similar clinically active disease, with higher C-reactive protein values found in those with hyperhomocysteinemia. Hyperhomocysteinemia was found in 46 % of patients. Of these, 74 % had moderate, 13 % intermediate, and 13 % severe increase in serum homocysteine levels. No relationship was found between homocysteine levels, and age, vitamin B12 levels, folic acid levels, Crohn’s Disease Activity Index score, and CRP values. Gene mutations were found in 5 (22 %) patients, 2 homozygotes and 3 heterozygotes. None of the patients with or without hyperhomocysteinemia had episodes of venous or arterial thrombosis, or stroke.

Conclusions

Hyperhomocysteinemia is frequent in patients with Crohn’s disease, and it could be a cofactor for the pathogenesis of thrombotic episodes.     

Risk factors for vitamin D deficiency in patients with Crohn’s disease

Background Although the pathogenesis of osteopenia in Crohns disease is not established, vitamin D deficiency is thought to be an important risk factor. However, little is known about the prevalence of vitamin D deficiency in patients with Crohns disease in Japan. This study aimed to clarify the prevalence of vitamin D deficiency in patients with Crohns disease in Japan and to examine the possible causes of the deficiency.Methods We investigated serum 25-hydroxyvitamin D (25-OHD) levels, various laboratory parameters, and patient histories in 33 outpatients (25 men, 8 women; median age, 37 years; range, 26–57 years) and 15 age- and sex-matched healthy controls (8 men, 7 women; median age, 37 years; range, 24–57 years) and assessed risk factors for vitamin D deficiency.Results Although patients with Crohns disease did not have significantly lower serum concentrations of 25-OHD than controls, 9 of 33 patients (27.3%) were considered vitamin D deficient (serum 25-OHD level 10ng/ml) compared with only 1 of 15 (6.7%) controls. Serum 25-OHD levels were significantly related to disease duration (r = 0.46, P = 0.003), Crohns Disease Activity Index (CDAI) score (r = 0.44, P = 0.005), International Organization for the Study of Inflammatory Bowel Disease score (r = 0.30, P < 0.05), and serum values of ferritin (r = 0.34, P = 0.03), C-reactive protein (r = 0.34, P = 0.03), total cholesterol (r = 0.31, P = 0.04), and intact parathyroid hormone (r = 0.23, P < 0.05). A logistic regression analysis was performed to investigate the ability of variables to predict low or normal 25-OHD values. Results showed that disease duration (P = 0.03) and CDAI score (P = 0.04) could predict the occurrence of vitamin D deficiency (r ² = 0.472, P = 0.0004).Conclusions Vitamin D deficiency exists in patients with Crohns disease in Japan. 25-OHD levels should be assessed in patients who have had Crohns disease for a long time (>15 years) and who have been in the active stage of the disease for long periods.     

Hidradenitis suppurativa associated with Crohn’s disease and spondyloarthropathy: response to anti-TNF therapy

An association of hidradenitis suppurativa with Crohns disease is supported by previous repent. We here report a patient with hidradenitis suppurativa who subsequently developed peripheral arthritis, sacroiliitis, and Crohns disease. A significant attenuation of bowel, cutaneous, and joint symptoms was achieved after treatment with monoclonal antibody against tumor necrosis factor (TNF). The pathogenetic aspects according to the literature and response to the various therapeutic measures applied are also presented.     

Decision-making in ileocecal Crohn’s disease management: surgery versus pharmacotherapy

Ileocecal Crohn’s disease (CD) can be treated medically as well as surgically. Both treatment modalities have been improved markedly in the last two decades, making CD more manageable. However, multidisciplinary research, addressing issues such as timing of surgery or medical treatment versus surgery, is scarce. Particularly in limited ileocecal CD, ileocolic resection might be a good alternative to long-term medical therapy. This review discusses the evidence on medical and surgical treatment options for ileocecal CD. It provides an aid in decision-making by discussing a treatment algorithm that can be used until further evidence on treatment is available.     

Clinical updates on perianal fistulas in Crohn’s disease

Introduction: Perianal fistulizing disease is an aggressive and debilitating phenotype of Crohn’s disease (CD), representing a significant therapeutic challenge. New work has led to advancement in epidemiology and long-term outcomes of perianal disease. The range of therapeutic options continues to expand, including new biologic agents, biosimilars, and stem cell therapy.

Areas covered: We discuss updates to all aspects of management of perianal disease, with a focus on the last 3 years of published data. Areas considered include new data on epidemiology and prognostication, medical and surgical therapy, and stem cell therapy.

Expert commentary: The presence of perianal disease at CD diagnosis portends a significantly worse disease course. Patients with perianal disease require close monitoring to identify those who are at risk for worsening disease, suboptimal biologic drug levels, and signs of developing neoplasm. With the impending availability of local mesenchymal stem cell therapy, this becomes increasingly important as this therapy, although extremely promising, is thus far only effective in patients without proctitis.     

Natural history and long-term clinical course of Crohn’s disease

Crohn’s disease is a chronic inflammatory disease process involving different sites in the gastrointestinal tract.Occasionally,so-called metastatic disease occurs in extra-intestinal sites.Granulomatous inflammation may be detected in endoscopic biopsies or resected tissues.Genetic,epigenetic and environmental factors appear to play a role.Multiple susceptibility genes have been described in both familial and non-familial forms while the disease is phenotypically heterogeneous with a female predominance.The disorder occurs over a broad age spectrum,from early childhood to late adulthood.More than 80%are diagnosed before age 40 years usually with terminal ileal and colonic involvement.Pediatric-onset disease is more severe and more extensive,usually with a higher chance of upper gastrointestinal tract disease,compared to adult-onset disease.Long-term studies have shown that the disorder may evolve with time into more complex disease with stricture formation and penetrating disease complications(i.e.,fistula,abscess).Although prolonged remission may occur,discrete periods of symptomatic disease may re-appear over many decades suggesting recurrence or re-activation of this inflammatory process.Eventual development of a cure will likely depend on identification of an etiologic cause and a fundamental understanding of its pathogenesis.Until now,treatment has focused on removing risk factors,particularly cigarette smoking,and improving symptoms.In clinical trials,clinical remission is largely defined as improved numerical and endoscopic indices formucosal healing.Deep remissionis a conceptual,moreextendedgoal that may or may not alter the long-term natural history of the disease in selected patients,albeit at a significant risk for treatment complications,including serious and unusual opportunistic infections.     

Isolated ileitis associated with primary sclerosing cholangitis in three patients with Crohn’s disease

Background Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn’s disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. Aim and methods We report three cases of patients with isolated Crohn’s ileitis associated with PSC and in whom colonic inflammation was never documented. Results Patients were followed up 10–23 years and each patient underwent 6–7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9–10 years. Conclusions Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept that colonic mucosal inflammation is critical for the pathogenesis of PSC in inflammatory bowel disease.     

Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn’s disease

Backgrounds

In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn’s disease, prognosis is related to the severity of mucosal inflammation.

Aim

The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn’s disease.

Methods

A retrospective cohort study was performed in patients newly diagnosed with Crohn’s disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal.

Results

Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5–4.2, p < 0.0001).

Conclusions

In newly diagnosed Crohn’s disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.