Clinical Course Of Crohn's Disease Research Articles

Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn'sdisease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD:IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. The clinical course of CD is milder for those who have previously undergone appendectomy.

Clinical course of new-onset Crohn's disease in children and adolescents in dependency of age, initial location, initial severity level and therapy over the period 2000-2014 based on the Saxon Pediatric IBD-Registry in Germany.

In Saxony, the incidence of Crohn's disease (CD) in children and adolescents increased significantly from 3.3 per 100,000 person-years in 2000 to 5.1 in 2014. The aim of this study was to describe the initial characteristics and the clinical course of CD in children and adolescents and to identify drug treatment options associated with an advantage for a mild course or remission. Clinical data were collected from patients who suffered from inflammatory bowel disease (IBD) and were recruited in the Saxon Pediatric IBD-Registry. All children newly diagnosed with CD in this registry in Saxony between 2000 and 2014 were included in this registry study. Characteristics such as age, disease location and extra-intestinal manifestations at diagnosis were accessed. The severity level of the disease at diagnosis as well as at follow-up were analysed by PCDAI index. Patients were divided into 3 groups according to length of follow-up: 1-3 years, 4-6 years and 7-9 years after diagnosis. A logistic regression model was conducted to examine which baseline parameters are associated with disease progression. There were 338 children and adolescents with CD included in this registry study. At diagnosis, the median age of patients was 12.0 (0.7-14.9), 61.5% (n = 208) of the patients were male. The most common disease location observed in pediatric CD patients was the L3 (55%, n = 176). Patients aged 10-14 years were significantly more likely to present an L2 than patients aged 0-4 years (80.3%, n = 53 vs. 19.7%, n = 13, p = 0.01). During the follow-up, data from 71.3% (n = 241) othe patients were available. Disease activity measured by PCDAI decreased in 47.7% (n = 115) of the patients, 40.7% (n = 98) of the patients were stable and increased in 11.6% (n = 28) of the patients. Patients with intermediate/severe disease at onset were more likely to have an active disease at the end of follow up, too (p = 0.00). Logistic regression analysis of the initial characteristics showed that the age at diagnosis, gender, initial location and initial extra-intestinal manifestation are not associated with the progression of the disease (p>0.05). Furthermore, drug treatment options could be identified from our data, which are associated with benefits for a milder course or remission. From 2000 to 2014, the health status of most pediatric patients with CD had improved or remained stable. Initial characteristics including age at diagnosis, initial localization and initial extra-intestinal manifestation are not associated with the progression of the disease, only the initial activity by PCDAI.

Fucosyltransferase 2 Mutations Are Associated With a Favorable Clinical Course in Crohn's Disease.

Fucosyltransferase 2 (FUT2) participates in intestinal antigen secretion and bacterial adherence. FUT2 homozygous nonsense mutations (FUT2M) and subsequent nonsecretor status is associated with Crohn's disease (CD). The common null allele is rs601338. We assessed the relationship between FUT2M and disease course. In consecutive adult CD outpatients, clinical, biochemical, and genetic data were collected at baseline visits. Patients were longitudinally followed over 5 years. The primary outcome analyzed the relationship between FUT2M and rates of CD patients in persistent steroid-free clinical remission requiring neither surgery, biologics, nor immunomodulators. Sixty-two CD patients were recruited. FUT2M homozygotes (rs601338 or any mutation in linkage disequilibrium) were detected in 27% of CD (17/62). Patients with rs601338 mutations had higher rates of the primary outcome (homozygous: 46.6%, heterozygous: 28.0%, wild-type: 5.3%, P=0.02). Similar findings existed for CD patients with homozygous mutations in any single-nucleotide polymorphism for FUT2 (homozygous: 41.2%, heterozygous: 25.9%, wild-type: 5.6%, P=0.04). On multivariable analysis, rs601338 mutation was associated with the primary outcome (odds ratio=3.4, 95% confidence interval: 1.3-8.7, P=0.01), while other parameters were not. Mutation of rs601338 was associated with lower rates of penetrating disease (homozygous: 13.3%, heterozygous: 28.0%, wild-type: 52.6%, P=0.05) and particularly in high-risk patients (homozygous: 0%, heterozygous: 37.5%, wild-type: 83.3%, P=0.01). FUT2 mutation status is associated with a favorable clinical course in CD. Further confirmatory studies are needed.

Clinical characteristics and outcome of fistulizing Crohn's disease: One single‐center experience in Taiwan

Crohn's disease (CD) is characterized by chronic and/or relapsing immune activation and inflammation within the gastrointestinal tract. Approximately 35% of patients with CD are complicated by fistulae. However, little is known about the incidence and natural history of fistulizing CD in Asia, especially enterocutaneous fistulae (ECF). In this study, we aimed to investigate the clinical course and outcomes of patients with fistulizing CD. We performed a retrospective analysis using the database of Chang Gung Memorial Hospital to analysis the clinical characteristics, clinical course of CD, gender, age, medical and surgical treatment, complications, and long‐term outcomes. From January 1989 to November 2016, 97 patients were enrolled (73 males and 24 females) with a median age at diagnosis of CD of 32 years (average 36.28 ± 15.84 years). All of the patients were classified by Montreal classification. Montreal classifications A2 (age 16‐40 years; n = 56, 57.7%), L3 (ileocolonic type; n = 47, 48.5%), and B1 (nonstricturing and nonpenetrating type; n = 43, 44.3%) were the most common phenotypes. ECF occurred in five patients (5.1%), enterovaginal fistula in three patients (3.1%), and enterovesical fistula in two patients (2.0%). The duration of CD before the onset of ECF was 3.9 years, enterovaginal fistula was 2.5 years, and enterovesical fistula was 5 years, and most of the patients complicated with a fistula required surgical treatment.

Clinical Variables as Predictors of First Relapse in Pediatric Crohn's Disease.

IntroductionCrohn's disease (CD) is an immune-mediated inflammatory bowel disease (IBD) that can affect any portion of the gastrointestinal tract from the mouth to the anus. The clinical course of CD is characterized by periods of symptomatic relapse and remission. Clinical variables may identify a subset of patients with CD at risk for relapse. Identifying these patients, and early stratification-based treatment would be of utmost clinical importance in optimizing the management and is likely to improve long-term disease outcome. In pediatric-onset IBD there is a paucity of data for predicting clinical behavior and results are conflicting. With this background, we hypothesized that routinely measured clinical variables at the time of diagnosis would predict relapse in patients with CD, and sought to investigate the clinical predictors of relapse present at the time of diagnosis in our patient population. We further compared differences in clinical variables and laboratory values for patients who relapsed early, compared with those who relapsed late.MethodsWe conducted a retrospective chart review of patients diagnosed with CD by clinical, radiological, endoscopic and histological criteria at St. John Providence Children’s Hospital pediatric GI clinic between 01/2006 and 12/2014. Patients were followed until they had their first relapse or for three years from diagnosis, whichever was earlier. Variables studied included demographic factors (age, gender, race, BMI, BMI percentiles and family history of IBD), presenting symptoms (blood in stools, nocturnal stools, fever, and extra-intestinal manifestations), phenotypic characteristics (using Montreal classification), and laboratory data [white blood cell (WBC) count, hemoglobin, hematocrit, platelet count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)].ResultsTwenty-nine patients were included in the study. One was lost to follow up, and 28 were included in the analyses. The relapse rate was 50% at three years, and 32% patients relapsed within one year of diagnosis. Low BMI percentile at diagnosis (41.5 ± 28.8 vs. 18.0 ± 20.3; p-value 0.03) was a predictor of relapse. Comparing early relapse to those who relapsed late, there were no statistically significant differences between the two groups.ConclusionsLow BMI percentile at presentation was associated with increased risk of relapse, suggesting that routinely measured clinical variables may have role in predicting first relapse in this patient population. There was no significant difference in the variable comparing patients who relapsed early vs. those who relapsed late. Future prospective studies with larger sample sizes need to be done to predict relapse.

Postoperative course of Crohn disease according to timing of bowel resection: Results from the CONNECT Study.

Previous studies have demonstrated that early surgery in Crohn disease (CD) can result in a better clinical course than late surgery. The aim of this study was to compare the clinical course of CD following bowel resection performed at the time of diagnosis (early surgery) and during the course of the disease (late surgery).We reviewed medical records from a hospital-based cohort database that includes Korean CD patients diagnosed before 2009. Patients who underwent bowel resection were included. Age, sex, disease phenotype, time of surgery, medication history including use of corticosteroids, immunomodulators, and biologics, and further surgical history were assessed.In all, 243 CD patients who had undergone bowel resection were included, and 120 patients underwent surgery at the time of diagnosis, while 123 underwent surgery after diagnosis (median 105 months, range 2–277). The use of biologics was significantly higher in the late surgery group than in the early surgery group (P = .020). The use of immunomodulators and reoperation rates did not differ between the groups. Early surgery was associated with less use of biologics (Kaplan–Meier curve analysis P = .015). Multivariate analysis indicated that early surgery and old age at surgery were independent variables associated with less use of biologics.CD patients who underwent bowel resection at the time of diagnosis have a more favorable disease course, represented by less use of biologics. Early surgery might be a treatment option in a subset of CD patients.

Impact of vitamin D on the hospitalization rate of Crohn's disease patients seen at a tertiary care center

AIMTo study the association between vitamin D level and hospitalization rate in Crohn’s disease (CD) patients.METHODSWe designed a retrospective cohort study using adult patients (> 19 years) with CD followed for at least one year at our inflammatory bowel disease center. Vitamin D levels were divided into: low mean vitamin D level (< 30 ng/mL) vs appropriate mean vitamin D level (30-100 ng/mL). Generalized Poisson Regression Models (GPR) for Rate Data were used to estimate partially adjusted and fully adjusted incidence rate ratios (IRR) of hospitalization among CD patients. We also examined IRRs for vitamin D level as a continuous variable.RESULTSOf the 880 CD patients, 196 patients with vitamin D level during the observation period were included. Partially adjusted model demonstrated that CD patients with a low mean vitamin D level were almost twice more likely to be admitted (IRR = 1.76, 95%CI: 1.38-2.24) compared to those with an appropriate vitamin D level. The fully adjusted model confirmed this association (IRR = 1.44, 95%CI: 1.11-1.87). Partially adjusted model with vitamin D level as a continuous variable demonstrated, higher mean vitamin D level was associated with a 3% lower likelihood of admission with every unit (ng/mL) rise in mean vitamin D level (IRR = 0.97, 95%CI: 0.96-0.98). The fully adjusted model confirmed this association (IRR = 0.98, 95%CI: 0.97-0.99).CONCLUSIONNormal or adequate vitamin D stores may be protective in the clinical course of CD. However, this role needs to be further characterized and understood.

Association study between OCTN1 functional haplotypes and Crohn's disease in a Korean population.

Crohn's disease (CD) is a chronic inflammatory bowel disease with multifactorial causes including environmental and genetic factors. Several studies have demonstrated that the organic cation/carnitine transporter 1 (OCTN1) non-synonymous variant L503F is associated with susceptibility to CD. However, it was reported that L503F is absent in Asian populations. Previously, we identified and functionally characterized genetic variants of the OCTN1 promoter region in Koreans. In that study, four variants demonstrated significant changes in promoter activity. In the present study, we determined whether four functional variants of the OCTN1 promoter play a role in the susceptibility to or clinical course of CD in Koreans. To examine it, the frequencies of the four variants of the OCTN1 promoter were determined by genotyping using DNA samples from 194 patients with CD and 287 healthy controls. Then, associations between genetic variants and the susceptibility to CD or clinical course of CD were evaluated. We found that susceptibility to CD was not associated with OCTN1 functional promoter variants or haplotypes showing altered promoter activities in in vitro assays. However, OCTN1 functional promoter haplotypes showing decreased promoter activities were significantly associated with a penetrating behavior in CD patients (HR=2.428, p=0.009). Our results suggest that the OCTN1 functional promoter haplotypes can influence the CD phenotype, although these might not be associated with susceptibility to this disease.

Influence of a Positive Family History on the Clinical Course of Inflammatory Bowel Disease.

Previous studies on the difference in phenotypes and disease course between familial and sporadic inflammatory bowel disease (IBD) have been controversial, although family history is considered to increase the risk of developing IBD. The influence of family history on phenotype and disease course of IBD was analysed in 2805 Korean patients with Crohn's disease (CD) and 3266 with ulcerative colitis (UC). Familial IBD was defined as the existence of one or more first-, second- and/or third-degree relatives affected with CD or UC. A positive family history of IBD was noted in 191 patients with CD (6.8%) and 212 patients with UC (6.5%). In the patients with CD, the probability of anti-TNF use was higher in the familial cases than in the sporadic cases (56.3 vs 43.4%, respectively, at 10 years, p = 0.019). When analysed after excluding patients who had undergone intestinal resection within 1 year of diagnosis, the cumulative probability of intestinal resection was higher in the familial cases than in the sporadic cases (55.0 vs 32.2%, respectively, at 10 years; p = 0.007). In multivariate analysis, family history was an independent risk factor for the time to first intestinal resection in patients with CD (hazard ratio: 1.61, 95% confidence interval: 1.13-2.29; p = 0.009). In patients with UC, younger age at diagnosis and more females were observed in the familial cases (p < 0.001). The present study suggests the possibility of a more aggressive clinical course of CD in familial compared with sporadic cases.

Clinical features of interleukin 10 receptor gene mutations in children with very early-onset inflammatory bowel disease.

In the present study, we studied a cohort of patients with very early onset inflammatory bowel disease (IBD) to determine the frequency of mutations in the interleukin 10 (IL10) receptor genes as a cause of early-onset IBD. Sanger sequencing was performed to determine the presence of IL10 and/or IL10 receptor mutations in 17 patients with a diagnosis of very early onset IBD (disease onset <2 years of age in 15 patients, between 3 and 4 years in the other 2). Mutation screening was performed including all of the coding regions of the IL10, IL10RA, and IL10RB genes. We then compared the follow-up findings of the patients with IL10 receptor mutations in terms of demographic, clinical, laboratory, and treatment response properties with those of patients diagnosed as having very early onset IBD with no mutation. We identified 3 patients bearing mutations in the IL10 or IL10 receptor genes, including 1 mutation in IL10RB that has been described recently (c.G477A, p.Trp159*) and 2 novel mutations affecting the IL10RA gene (c.T192G, p.Tyr64 and c.T133G, p.Trp45Gly). Collectively, these mutations thus provided genetic etiology for 17.6% of the cohort under investigation. The presence of a family history of IBD and the clinical course of Crohn disease differed between patients with mutations in the IL-10 pathway and those without such mutations. Although perianal fistulas were found in all of the patients with IL10 receptor mutations, they were found in only 14.3% of those without such mutations. The lower values of weight-for-age and height-for-age z scores, necessity for more intensive therapy, achievement of longer periods until remission, and frequent relapses in the patients bearing mutations in the IL10 receptor genes all underlined the severity of the disease and its relatively poor response to treatment. In spite of the small number of patients with mutations affecting the IL-10 signaling pathway in our study, in all of the patients with IL10 receptor mutations, the disease onset occurs at an early age, the prognosis is poor, and the response to treatment is insufficient.

Mild clinical behaviour of Crohn disease in elderly patients in a Latin American country: A case-control study.

Crohn disease is characterized by fluctuating clinical behaviour, which is influenced by various factors. There are no data from Latin America that evaluate the clinical behaviour of Crohn disease in elderly patients. To evaluate the clinical course of elderly onset Crohn disease compared with younger onset in the Mexican population. The present analysis was a case-control study that included 132 patients with a histopathological diagnosis of Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a tertiary care centre. Statistical analysis was performed using SPSS version 17 (IBM Corporation, USA) and descriptive statistics, χ2 and Fisher's exact test for categorical variables and Student's t test for numerical variables. Univariate and multivariate analysis were performed to identify associated risk factors and OR was calculated. A total of 132 patients (73 men and 59 women) were divided into two groups according to age at diagnosis: 27 cases (>60 years of age) and 105 controls (≤60 years of age). Factors influencing the clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI 1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02); mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001); response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR 4.96 [95% CI 1.70 to 14.48]; P=0.002). Elderly patients with Crohn disease had a mild clinical course characterized by the lack of escalation to immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term remission.

Risk of Repeat Surgery for Perianal Crohn Disease

See Article on Page 176-181 Perianal involvement of Crohn disease (CD) is known to be a common complication of CD. Due to the wide variety of anal manifestations of CD, the exact prevalence of perianal Crohn disease (PCD) is not known. However, it is estimated that a majority of patients with CD may undergo surgical treatment for PCD. The most common causes of operative treatment are perianal abscesses and anal fistulas because surgical treatment is mandatory to control acute sepsis. Contrary to fistulas of a cryptoglandular origin, those of CD are different in terms of pathogenesis and clinical course. Due to the unpredictable clinical course and increased risk of recurrence, conservative treatment is generally accepted to be more appropriate for treating patients with PCD. Repeated surgical treatment may deteriorate continence, which results in decreased quality of life for the patient. Therefore, an estimate of the clinical course and a prediction of recurrence after surgical treatment have clinical significance in the treatment of patients with PCD. Despite the clinical importance of PCD, literature concerning the risk factors of repeat surgical treatment for PCD is scarce. A recent retrospective study reported the cumulative risks of reoperation for patients operated on for PCD, as well as the related risk factors [1]. According to the study, the risk of reoperation increases during the disease's course, reaching up to 50% after the first surgical treatment, and risk factors associated with reoperation are a young age at the onset of CD, a history of abdominal surgery for CD, and the type of surgery. Although some controversies may exist, the risk of reoperation most likely increases in proportion to the time. Therefore, early onset of CD may be related with an increased risk of reoperation for PCD. Also, considering that the clinical course of CD with fistulizing PCD seems to be more aggressive, patients with abdominal surgery may have aggressive PCDs. Concerning surgical treatment, conservative treatment is recommended. However, a curative treatment such as a fistulotomy can be done in selected cases [2]. Compared with incision and drainage or seton placement, a fistulotomy or a fistulectomy would reduce the risk of reoperation because of the its radical characteristics. However, the choice of radical treatment should be prudent because of sphincter division, the risk of incontinence, and compromised wound healing. While this study is a clinically significant attempt to investigate factors related with repeat surgery, it lacks data regarding whether and how the usage of a biologic agent influences the clinical course of PCD. Some reports showed the effectiveness of using the anti-tumor necrosis factor (TNF) antibody in fistula healing for Crohn anal fistulas [3,4]. Although anti-TNF therapy seems to be promising, a multidisciplinary approach is mandatory because surgical treatment is essential to control acute sepsis and may be a preliminary procedure to enhance the effect of medical treatment.

Crohn's disease in Korea: past, present, and future.

The epidemiology, genetics, and clinical manifestations of Crohn's disease (CD) vary considerably among geographic areas and ethnic groups. Thus, identifying the characteristics of Korean CD is important for establishing management strategies appropriate for Korean patients. Since the mid-2000s, many studies have investigated the characteristic features of Korean CD. The incidence and prevalence rates of CD have been increasing rapidly in Korea, especially among the younger population. Unlike Western data, Korean CD shows a male predominance and a lower proportion of isolated colonic disease. Perianal lesions are more prevalent than in Western countries. Genome-wide association studies have confirmed that genetic variants in TNFSF15, IL-23R, and IRGM, but not ATG16L1, are associated with CD susceptibility in the Korean population. Studies of the associations between genetic mutations and the clinical course of CD are underway. Although it has been generally accepted that the clinical course of Korean CD is milder than that in Western countries, recent studies have shown a comparable rate of intestinal resection in Korean and Western CD patients. An ongoing nationwide, hospital-based cohort study is anticipated to provide valuable information on the natural history and prognosis of Korean CD in the near future.

Crohn's Disease Clinical Network and Cohort (CONNECT) Study: The First Step Toward Nationwide Multicenter Research of Crohn's Disease in Korea.

Crohn's Disease Clinical Network and Cohort (CONNECT) Study: The First Step Toward Nationwide Multicenter Research of Crohn's Disease in Korea.

Crohn's disease and polymorphism of heat shock protein gene HSP70‐2 in the Chinese population

Crohn's disease (CD) is a multifactorial disorder with a pivotal role of the genetic component. A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in CD. The purpose of this study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD in the Chinese population. One hundred patients with CD and 190 healthy individuals were genotyped for the HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis. The genotype frequency of the PstI polymorphism did not differ between patients and controls. The A allele was higher in CD patients than in controls (61% vs 52%, P = 0.047, odds ratio [OR] = 1.423, 95% confidence interval [CI]: 1.004-2.015). Furthermore, this polymorphism was higher in the penetrating or fistula surgery of CD patients than in controls (63% vs 52%, P = 0.049, OR = 1.530, 95% CI: 1.001-2.337; Table ). But there was no significant difference between the penetrating or fistula surgery patients and no surgery patients (P = 0.673, OR = 0.883, 95% CI: 0.495-1.574). We used multivariate analysis to determine the effects of genotypes on sex, disease behavior, disease location, and so on. No significant difference was observed between these parameters and genotype. This study reported that the allele A of PstI polymorphism was the association between CD and HSP70-2 gene in the Chinese population. It was also association between penetrating or fistula surgery of CD and HSP70-2 gene in the Chinese population.

Clinical factors predictive of Crohn’s disease complications and surgery

Crohn's disease (CD) is a progressive disease that is subdivided into three phenotypes: inflammatory, stricturing and penetrating. At diagnosis, most CD patients have inflammatory disease. However, the natural history of CD is one of progression over time to structural complications of the gastrointestinal tract (strictures and fistulae) requiring hospitalizations and surgeries. There is now evidence that early treatment with immunosuppressants and biologics can halt the development of inflammatory damage/fibrosis because of their potential to induce complete mucosal healing. This change in the natural course of CD, mediated by mucosal healing, is associated with a reduction in the incidence of serious complications (those requiring hospitalization and surgeries). Nevertheless, the clinical course of CD varies considerably from one patient to another, and the exact point at which immunosuppressants and/or biologics should be used has not yet been established. Given the difficulty in predicting which individuals will progress to complications and the fact that these therapeutic agents are associated with certain risks (lymphomas and opportunistic infections), efforts are underway to identify the risk factors that will facilitate the classification of patients into high-risk and low-risk groups at the time of diagnosis and to tailor therapy accordingly. This paper is a review of the currently available evidence on the clinical risk factors predictive of CD complications and surgery.

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

Cytomegalovirus (CMV) infection is common in humans. The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression. The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease (CD) and ulcerative colitis (UC). CMV does not interfere in the clinical course of CD. However, CMV reactivation is frequent in severe or steroid-resistant UC. It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease. Different methods are used to diagnose CMV colitis. Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry, other tests on blood or tissue samples are currently being investigated. Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease; further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa. Specific endoscopic features have not been described in active UC and CMV infection. CMV colitis is usually treated with ganciclovir for several weeks, there are different opinions about whether or not to stop immunosuppressive therapy. Other antiviral drugs may be used. Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

Genetic factors conferring an increased susceptibility to develop Crohn's disease also influence disease phenotype: results from the IBDchip European Project

ObjectiveThrough genome-wide association scans and meta-analyses thereof, over 70 genetic loci (Crohn's disease (CD) single nucleotide polymorphisms (SNPs)) are significantly associated with CD. We aimed to investigate the influence of...

Clinical predictive factors for Crohn's disease complications

Crohn's disease (CD) is a progressive disease that is subdivided in three phenotypes: inflammatory, stricturing, and penetrating. At diagnosis most CD patients have inflammatory disease. However, the natural history of CD evolves over time to structural digestive tract complications (strictures and fistulae) which are associated with hospitalisations and surgeries. Nowadays, there is evidence that early treatment with immunosuppressants and biologics can interrupt the development of inflammation- destruction/fibrosis through its potential to induce complete mucosal healing. The change in CD natural history, mediated by mucosal healing, is associated with a reduction in serious complications (hospitalisations and surgeries). Nevertheless, the clinical course of CD varies considerably between patients and there is still no definition for the timing of immunosuppressants and/or biologics use. This medication is associated to certain risks (lymphomas and opportunistic infections) and the difficulty to predict, on an individual basis, the progression to complications have triggered efforts to identify risk factors that allow at diagnosis to classify patients in high and low risk groups and to tailor therapy. This paper is an updated compilation of evidence of clinical risk factors predictive for CD complications.

Perianal Crohnʼs disease findings other than fistulas in a population-based cohort

The cumulative incidence of and risk factors for perianal Crohn's disease (CD) for findings other than fistulas are unknown. The medical records of 310 incident cases of CD from Olmsted County, Minnesota, diagnosed between 1970 and 2004, were reviewed for evidence of perianal disease findings other than fistulas. Cumulative incidence was estimated using the Kaplan-Meier method, and associations between baseline factors and time to first event were assessed using proportional hazards regression. Four types of lesions were studied: anorectal strictures, deep anal canal ulcers, anal fissures, and perianal skin tags. The 10-year cumulative probability from time of diagnosis was 5.8% (95% confidence interval [CI], 2.6%-8.8%) for anorectal strictures, 6.6% (3.6%-9.6%) for deep anal canal ulcers, 10.5% (6.8%-14.1%) for anal fissures, and 18.7% (13.9%-23.3%) for perianal skin tags. The cumulative probability for any perianal lesion other than fistulas was 21.3% (16.5%-25.8%) at 5 years and 29.2% (23.5%-34.5%) at 10 years. Baseline factors associated with time to first perianal lesion other than fistulas were age (hazard ratio [HR] per 10 years, 0.9; 95% CI, 0.8-0.98; P = 0.026), female gender (HR, 1.7; 95% CI, 1.1-2.7; P = 0.013), and presence of extraintestinal manifestations (HR, 1.7; 95% CI, 1.03-2.8; P = 0.038). Perianal lesions other than fistulas occurred frequently during the clinical course of CD. Female gender and extraintestinal manifestations were associated with increased risks for perianal lesions other than fistulas, while older age at diagnosis was associated with a slightly decreased risk.