Aurelio Lorenzo

Emigration to western industrialized countries: A risk factor for developing inflammatory bowel disease

BACKGROUND A higher incidence of inflammatory bowel disease (IBD) in industrialized areas has been previously reported, but the effect of emigrating to western industrialized countries for a period of time and returning to the country of origin is unknown. Aim of the study was to evaluate the effect of emigrating to another country and returning to the place of origin on the risk of IBD. METHODS A prospective case-control study was performed. Inclusion criteria were all patients >18 years diagnosed with Crohns disease (CD) or ulcerative colitis (UC) in the last 10 years. Healthy, unrelated controls, matched by sex, age and smoking habits, with no family history of IBD were included. All patients and controls were interviewed and emigration was defined as living for at least one year in another country. RESULTS 242 consecutive patients with IBD (105 CD and 137 UC) and 242 controls were included. Patients who had previously emigrated developed more frequently IBD than controls (OR 1.93, 95%CI 1.19-3.15, p<0.01). Patients who emigrated to European countries developed more frequently IBD than controls (OR 1.91, 95%CI 1.07-3.47, p=0.02), but not those who had emigrated to Latin America (OR 1.48, 95%CI 0.67-3.27, p=0.32). Emigration plays a significant role in the development of UC (OR 2.24, 95%CI:1.29-3.88, p<0.01), but not in CD (OR 1.56, 95%IC:0.83-2.92, p=0.15). CONCLUSIONS People who emigrate to westernised countries have a higher risk for developing IBD, especially UC. Environmental factors related with industrialization seem to play an important role in the pathogenesis of these diseases.

Psychological impact of Crohn's disease on patients in remission: anxiety and depression risks

BACKGROUND the role of anxiety and depression in CD patients in remission has been poorly investigated. OBJECTIVE the aim of the study was to evaluate the frequency of anxiety and depression symptoms in CD patients in remission, and potential factors influencing the development of these symptoms. METHODS CD patients older than 18 years in remission for at least 6 months before study entry were included. CD remission was defined as a Crohn s Disease Activity Index (CDAI) < 150 points together with C-reactive protein < 5 mg/L. A demographic questionnaire was filled in, and all patients were clinically classified. The therapy maintaining remission was also recorded. A Hospital Anxiety and Depression scale (HAD) was administered to all patients. Results are shown as OR and 95% CI, and analyzed by logistic regression. RESULTS 92 consecutive patients were included (48 male, mean age 37 years, range from 18 to 71 years). One patient failed to correctly fill in the questionnaire. Anxiety and depression symptoms were present in 36 (39%) and 22 (24%) patients, respectively. Infliximab therapy was the only factor associated with anxiety (OR = 3.11; 95% CI: 1.03-9.43; p < 0.05). In contrast, the presence of depressive symptoms is less frequent in patients under infliximab therapy (OR = 0.16; 95% CI: 0.02-0.97; p < 0.05). CONCLUSIONS despite clinical remission, an important number of CD patients present with anxiety or depressive symptoms. Infliximab therapy in CD patients is associated to more anxiety but fewer depressive symptoms. CD patients in remission would probably benefit from psychological support.

CARD15 Mutations in Patients With Crohn's Disease in a Homogeneous Spanish Population

OBJECTIVES:Three mutations in CARD15 have been repeatedly shown to be involved in Crohns disease susceptibility, mainly in Caucasian individuals. However, those findings were not replicated in all populations studied so far. In this work, we studied the role of CARD15 mutations in a relatively homogeneous population from the Northwest of Spain, Galicia.METHODS:One hundred and sixty-five patients with Crohns disease and a similar number of healthy controls were recruited from a single center in Galicia. All individuals were genotyped for the three main Crohns disease associated CARD15 variants (R702W, G908R, and 1007fs). Association analyses were performed to study the influence of those mutations on Crohns disease overall and on clinical subphenotypes.RESULTS:The allele frequencies of CARD15 variants were lower in this population than in most of the European populations studied so far. G908R and 1007fs were significantly associated with overall susceptibility to Crohns disease. However, these associations were lost after stratification to clinical subgroups, probably due to the small number of cases in these subgroups. Significant associations were found between G908R and 1007fs and the behavior of Crohns disease, but they were due to the influence of years of disease on the behavior of the disease rather than being the result of a direct effect of these mutations on disease behavior.CONCLUSIONS:The CARD15 variants G908R and 1007fs, but not R702W, are associated with susceptibility to Crohns disease in Galicia. Interestingly, the frequency of these mutations appears to be lower than in other Caucasian populations studied so far.

Ulcerative colitis in northern Portugal and Galicia in Spain

Background: Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. Methods: A cross‐sectional study was conducted during a 15‐month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. Results: A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846–4.058; OR 5.799, 95% CI: 3.433–9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641–15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. Conclusions: In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease. (Inflamm Bowel Dis 2010)

Complementary and alternative medicine in inflammatory bowel disease patients: frequency and risk factors.

BACKGROUND The use of complementary and alternative medicine in inflammatory bowel disease patients is progressively increased. AIM To evaluate the use of complementary and alternative medicine in inflammatory bowel disease patients and to know potential risk factors for their use. The subjective response of these therapies and the impact on treatment adherence were also evaluated. METHODS Prospective, descriptive and transversal study. Inflammatory bowel disease patients were classified according to demographic and clinical characteristics. A questionnaire about the use of complementary and alternative medicine was collected. RESULTS 705 patients were included. 126 patients (23%) had used complementary and alternative medicine. The most commonly used was herbal remedies (n=61), homoeopathy (n=36), acupuncture (n=31), kefir (n=31) and aloe vera (n=25). Factors associated with its use were extraintestinal manifestations (OR 1.69, CI 95% 1.11-2.57) and long-term evolution of the disease (OR 2.08, CI 95% 1.44-2.99). Most patients (74%) had the subjective feeling that use of complementary and alternative medicine had not improved their condition, 11 had adverse events related to its use and 11% of patients discontinued their conventional drugs. CONCLUSIONS Use of complementary and alternative medicine in inflammatory bowel disease patients is frequent, especially in those with extraintestinal manifestations and long-term evolution. The use of these therapies was not perceived as a benefit for patients.

Evaluation of adalimumab therapy in multidisciplinary strategy for perianal Crohn's disease patients with infliximab failure.

BACKGROUND Infliximab has improved the management of perianal Crohns disease, but intolerance and loss of efficacy can occur. The use of a second antibody can be less effective. OBJECTIVE Our aim was to determine if the use of adalimumab, based on a multidisciplinary strategy, can enhance outcomes for patients with fistulizing disease and infliximab failure. MATERIAL AND METHODS Sixteen patients with perianal disease and infliximab failure were treated with adalimumab. Complex fistulas were assessed using magnetic resonance imaging (MRI). Patients with severe conditions as determined by radiology were examined under anesthesia, and seton placement was performed when appropriate. Setons were removed when external discharge had ceased and there was no radiological evidence of fistula activity. RESULTS Nine patients (56%) underwent MRI. Setons were inserted in seven (43%). The baseline perianal disease activity index (PDAI) decreased after 4 weeks and remained at similar levels 24 and 48 weeks after treatment. The complete response rate was 50% after four weeks and 87.5% of these patients remained in remission after 48 weeks of treatment. CONCLUSIONS For patients with Crohns perianal fistulas and infliximab failure, adalimumab as a multidisciplinary approach to management, using MRI to guide surgical drainage when necessary, results in a favourable response and low recurrence rate.

Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn's disease

BACKGROUND AND AIMS Crohns disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD. METHODS forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated. RESULTS at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution. CONCLUSIONS adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response.

Health related quality of life in patients with Cohn´s disease in remission.

BACKGROUND Crohns disease (CD) affects Health Related Quality of Life (HRQoL) especially in patients with clinical activity but their impact over the disease during periods of remission has not been sufficiently studied. OBJECTIVE To evaluate HRQoL in CD patients in remission and to identify socio-demographic and clinical factors related. METHODS We included patients with CD in remission for at least 6 months, defined as a CDAI < 150 and a CRP < 5 mg/L. Socio-demographic and clinical parameters were recorded. HRQoL was evaluated with Short Form 36 Questionnaire (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results were analyzed using multiple regressions with a confidence interval of 95%. RESULTS Nine two patients (X = 37 +- 11.4 years, 52.2% men) were consecutively included. Two patients failed to fill correctly the questionnaire and were excluded. Scores on the SF-36 were lower than in the general population of similar age and sex. The most affected dimension in the SF-36 was General Health (47.98 +- 19.58) and the IBDQ Systemic Symptoms (5.15 +- 1.27). Age, colonic location and previous surgery was related with worse HRQoL, while higher educational status, more time since diagnosis, steroid-resistance and inflammatory behavior, was associated with better HRQoL. CONCLUSIONS Despite being in remission, CD patients had affected their HRQoL, so we must continue working to achieve improvement in HRQL of these patients during these periods of the disease.

Association of NOD2/CARD15 mutations with previous surgical procedures in Crohn's disease

OBJECTIVE The aim of this study is to assess the importance of NOD2/CARD15 gene mutations as prognostic factors for surgical indications in Crohns disease. PATIENTS AND EXPERIMENTAL DESIGN: A total of 165 Crohn s disease patients were studied, considering previous surgery related to Crohns disease. We analyzed for previous surgery in global procedures as well as separately for the two main surgical indications: ileal resection and fistula treatment. The need for appendectomy was also studied. All patients were genotyped for the three CARD15 mutations, and association studies were developed using Chi-square statistics and Fishers exact test whenever appropriate. RESULTS Carriers of the G908R or 1007fs mutation needed surgery more frequently, both for ileal resection and fistula repair. In contrast, appendectomy was not associated with CARD15 mutations. CONCLUSIONS As previously reported in this population, the R702W mutation does influence parameters of disease or need of surgery. The need for Crohns disease-related surgery is higher in carriers of the G908R or 1007fs CARD15 mutation in the Galician population. Nevertheless, the frequency of these mutations does not allow their use to predict the course of disease.

NOD2, CD14 and TLR4 mutations do not influence response to adalimumab in patients with Crohn's disease: a preliminary report

INTRODUCTION Adalimumab is a recombinant fully-human monoclonal immunoglobulin (IgG1) antibody utilized in the treatment of Crohns disease. Unfortunately no clinical or genetic markers exist to predict response to anti-tumor necrosis factor-alpha (TNF) therapy. The aim of this study was to evaluate the association between selected genes involved in cytokine regulation and response to adalimumab treatment in Crohns disease. METHODS twenty-four patients with Crohns disease either naïve (n = 8) or had lost response or were unable to tolerate the chimeric anti-TNF antibody infliximab (n=16) were enrolled in the study. Patients were genotyped for main polymorphisms in NOD2, CD14 and TLR4 genes. Response to adalimumab treatment was defined as a decrease of Crohns disease activity index of at least 100 points or a closure of at least 50% of fistulas in case of fistulizing Crohns disease. RESULTS overall, 75% of patients did respond to treatment. However, no statistically significant association was found between any of the genotypes and the response to adalimumab. CONCLUSIONS In our small study group no association between the studied polymorphisms and response to adalimumab was apparent. Systematic studies to search for genetic markers of response to anti-TNF therapy are necessary.