Chromoendoscopy Is More Effective Than Standard Colonoscopy in Detecting Dysplasia During Long-term Surveillance of Patients With Colitis.

BACKGROUND & AIMS: Patients with colitis have an increased risk of colorectal cancer, compared with persons without colitis. Many studies have shown chromoendoscopy (CE) to be superior to standard methods of detecting dysplasia in patients with colitis at index examination. We performed a prospective, longitudinal study to compare standard colonoscopy vs CE in detecting dysplasia in patients with inflammatory bowel diseases in a surveillance program. METHODS: We analyzed data from 68 patients (44 men, 24 women) diagnosed with ulcerative colitis (n = 55) or Crohn's disease (n = 13) at Mount Sinai Medical Center from September 2005 through October 2011. The patients were followed from June 2006 through October 2011 (median, 27.8 months); each patient was analyzed by random biopsy, targeted white light examination (WLE), and CE. Specimens were reviewed by a single blinded pathologist. The 3 methods were compared by using the generalized estimating equations method, and the odds ratios (ORs) for detection of dysplasia were calculated (primary outcome). Time to colectomy was analyzed by using the Cox model. RESULTS: In the 208 examinations conducted, 44 dysplastic lesions were identified in 24 patients; 6 were detected by random biopsy, 11 by WLE, and 27 by CE. Ten patients were referred for colectomy, and no carcinomas were found. At any time during the study period, CE (OR, 5.4; 95% confidence interval [CI], 2.9-9.9) and targeted WLE (OR, 2.3; 95% CI, 1.0-5.3) were more likely than random biopsy analysis to detect dysplasia. CE was superior to WLE (OR, 2.4; 95% CI, 1.4-4.0). Patients identified as positive for dysplasia were more likely to need colectomy (hazard ratio, 12.1; 95% CI, 3.2-46.2). CONCLUSIONS: In a prospective study of 68 patients with inflammatory bowel diseases, CE was superior to random biopsy or WLE analyses in detecting dysplasia in patients with colitis during an almost 28-month period. A negative result from CE examination was the best indicator of a dysplasia-free outcome, whereas a positive result was associated with earlier referral for colectomy.

6-Mercaptopurine/Azathioprine remains an important contributor in managing Crohn's disease.

Two large studies concluded that AZA started early after diagnosis of Crohn's disease have no late maintenance value. This is contrary to previous studies on 6MP for Crohn's disease and could lead to negating the value of two of the few drugs that have been proven successful. We here outline the many reasons why 6MP remains a valuable drug in the treatment of Crohn's disease.

The effect of intravenous cyclosporine on rates of colonic surgery in hospitalized patients with severe Crohn's colitis.

BACKGROUND: The role of intravenous (IV) cyclosporine in severe Crohn's colitis (CC) is poorly studied. AIM: Our primary aim was to determine the in-hospital colonic resection rate in patients with severe CC who received IV cyclosporine, and the potential predictors of resection among these patients. METHODS: An inpatient pharmacy query of all patients who received IV cyclosporine at Mount Sinai Medical Center for 12.5 years after January 1, 1996 was reviewed. Patients with CC or indeterminate colitis favoring Crohn's were included and their medical records were reviewed. Subsequent need for colonic surgery was assessed. A Kaplan-Meier plot with log-rank testing was performed to determine the rate of colonic surgery avoidance. Forward stepwise logistic regression was performed to determine independent predictors of surgery. RESULTS: Forty-eight patients met our inclusion criteria. Prior thiopurine and anti-tumor necrosis factor (anti-TNF) use was 85% and 69%, respectively. The median follow-up time was 12 months (range, 1 to 60 mo). 12.5% of patients required colonic resection during their admission for IV cyclosporine. Anti-TNF use in the 4 weeks preceding IV cyclosporine was the only predictor of surgery in this setting (P=0.05). The cumulative colonic surgery avoidance rate was 72±13% at 6 months and 59±15% at 12 months. CONCLUSIONS: The use of IV cyclosporine resulted in a low rate of in-hospitalization colonic surgery among CC patients with severe disease, the majority of whom previously failed anti-TNFs and thiopurines.

Evaluation of 22 genetic variants with Crohn's disease risk in the Ashkenazi Jewish population: a case-control study.

BACKGROUND: Crohn's disease (CD) has the highest prevalence among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Caucasian populations (NJ). We evaluated a set of well-established CD-susceptibility variants to determine if they can explain the increased CD risk in the AJ population. METHODS: We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status. We generated genetic scores based on the risk allele count alone and the risk allele count weighed by the effect size, and evaluated their predictive value. RESULTS: Three NOD2 SNPs, two IL23R SNPs, and one SNP each at IRGM and PTGER4 were independently associated with CD risk. Carriage of 7 or more copies of these risk alleles or the weighted genetic risk score of 7 or greater correctly classified 92% (allelic count score) and 83% (weighted score) of the controls; however, only 29% and 47% of the cases were identified as having the disease, respectively. This cutoff was associated with a >4-fold increased disease risk (p < 10e-16). CONCLUSIONS: CD-associated genetic risks were similar to those reported in NJ population and are unlikely to explain the excess prevalence of the disease in AJ individuals. These results support the existence of novel, yet unidentified, genetic variants unique to this population. Understanding of ethnic and racial differences in disease susceptibility may help unravel the pathogenesis of CD leading to new personalized diagnostic and therapeutic approaches.

Practice patterns in the use of anti-tumor necrosis factor alpha agents in the management of Crohn's disease: a US national practice survey comparing experts and non-experts.

BACKGROUND: The US Food and Drug Administration currently approves three types of anti-tumor necrosis factor α (anti-TNFα) therapy for treatment of moderate to severe Crohn's disease. There are no guidelines to clarify which of the drugs may be better suited to individual clinical scenarios. AIMS: We gathered national data on the prescribing pattern, comfort levels, and algorithms gastroenterologists use for management of their biologic-requiring Crohn's disease patients. METHODS: An internet survey was mailed to members of the American Gastroenterology Association. Responses were separated into "non-expert" and "expert" physician groups on the basis of whether a practice consisted of >50% of patients with inflammatory bowel disease. We compared experts with non-experts with regard to the use of the three anti-TNF agents, attitudes regarding their relative efficacy, and their experience with adverse events. RESULTS: Of 3,990 eligible gastroenterologists, 473 replied in full (11.9%). Sixty (12.6%) respondents met the criterion for IBD expert physician. Experts were comfortable using both immunomodulators and anti-TNFα therapy. Community physicians were equally comfortable prescribing 6-mercaptopurine, azathioprine, infliximab, and adalimumab, but less comfortable than experts with methotrexate (56 vs. 86%, P<0.05) and certolizumab (68 vs. 89%, P<0.05). Expert physicians were much more likely to have encountered adverse reactions to anti-TNFα therapy. CONCLUSIONS: Our results suggest that experts are more comfortable using a broader array of medical therapy than non-expert physicians. Although both groups had similar concerns regarding side-effects of anti-TNFα therapy, expert physicians were much more likely to have managed a broad range of complications in their patient population.

Cyclosporine is safe and effective in patients with severe ulcerative colitis.

BACKGROUND: Cyclosporine (CSA) is effective in the short-term for severe, steroid refractory ulcerative colitis; but its use has been limited by concerns about safety and colectomy-sparing rates. The aim of this study was to assess the long-term colectomy-sparing effects and safety of CSA in patients hospitalized for ulcerative colitis. METHODS: Review of the patients who underwent intravenous CSA for ulcerative colitis between 1989 and 2003. RESULTS: A total of 71 patients with severe ulcerative colitis were treated with IV CSA. The median length of follow-up was 1.5 years (mean=3 y) (range 1 mo to 14 y) (IQR 0.6 to 4.6). Eighty-five percent (60/71) of patients responded to IV CSA and were discharged on oral CSA. Of these 60 patients, 26 were transitioned from CSA to 6MP. Of the 26 patients who were transitioned from CSA to 6MP, only 1 patient (4%) ultimately required colectomy; whereas colectomy was carried out in 76% (26/34) of the patients who were not transitioned from CSA to 6MP. Only concomitant 6MP therapy was associated with a reduced risk of colectomy (OR 0.01, 95% CI 0.001, 0.09, P<0.0001) on long-term follow-up in this group. Cumulative colectomy rates for the entire cohort were 39% (28/71) at 1 year, 42% (30/71) at 2 years, and 46% (33/71) at 5 years. Side effects were noted in two-thirds of the patients, the majority of which were mild. CONCLUSION: CSA is an effective therapy for severe ulcerative colitis. Long-term efficacy is improved with transition to 6MP. Adverse events with CSA are frequent, but most are mild.

Chromoendoscopy-targeted biopsies are superior to standard colonoscopic surveillance for detecting dysplasia in inflammatory bowel disease patients: a prospective endoscopic trial.

OBJECTIVES: Patients with extensive, longstanding chronic ulcerative or Crohn's colitis face greater risks of developing colorectal cancer. Current standard surveillance relies on detecting dysplasia using random sampling at colonoscopy but may fail to detect dysplasia in many patients. Dye spraying techniques have been reported to aid in detecting otherwise subtle mucosal abnormalities in the setting of colitis. We prospectively compared dye-spray technique using methylene blue to standard colonoscopic surveillance in detecting dysplasia. METHODS: One hundred fifteen patients were referred to the Chromoendoscopy Study Group and prospectively screened for the study. One hundred two (64 M, 38 F) (79 UC 23 CC) patients meeting the inclusion criteria were enrolled. Following a standard bowel preparation, each patient was examined using standard office endoscopic equipment by three methods: (a) standard surveillance colonoscopy with four random biopsies every 10 cm (for a total of at least 32 samples); (b) a targeted biopsy protocol; and finally (c) methylene blue (0.01%) dye spray was segmentally applied throughout the colon and any pit-pattern abnormality or lesion rendered visible by the dye spray was targeted and biopsied. Each patient had a single examination, which included two passes of the colonoscope. Specimens were reviewed in a blinded fashion by a single gastrointestinal pathologist. The three methods were then compared with each patient serving as his or her own control. RESULTS: Targeted biopsies with dye spray revealed significantly more dysplasia (16 patients with low grade and 1 patient with high grade) than random biopsies (3 patients with low-grade dysplasia) (P= 0.001) and more than targeted nondye spray (8 patients with low-grade and 1 patient with high-grade dysplasia) (P= 0.057). Targeted biopsies with and without dye spray detected dysplasia in 20 patients compared with 3 using Method (a) (P= 0.0002, two-tailed exact McNemar's Test). There were no adverse events. CONCLUSIONS: Colonoscopic surveillance of chronic colitis patients using methylene blue dye-spray targeted biopsies results in improved dysplasia yield compared to conventional random and targeted biopsy methods. Accordingly, this technique warrants incorporation into clinical practice in this setting and consideration as a standard of care for these patients. The value of multiple random biopsies as a surveillance technique should be revisited.

Cyclosporine and infliximab as rescue therapy for each other in patients with steroid-refractory ulcerative colitis.

BACKGROUND & AIMS: In patients with severe corticosteroid-refractory ulcerative colitis, cyclosporine or infliximab may be added in an effort to induce remission. If the patient then fails either of these drugs, it is unknown whether success can be achieved by using the other agent. The aim of this study was to assess outcomes of using cyclosporine after failure of infliximab, and vice versa. METHODS: We retrospectively reviewed the charts of 19 patients with corticosteroid-refractory ulcerative colitis who received either infliximab after failed cyclosporine or cyclosporine after failed infliximab. Acute salvage therapy was defined as having received the alternate drug within 4 weeks of discontinuing the first agent. RESULTS: Ten patients received infliximab after failing cyclosporine; 9 patients received cyclosporine after failing infliximab. Four patients (40%) in the infliximab-salvage group achieved remission, as did 3 (33%) in the cyclosporine-salvage group. Remission lasted a mean of 10.4 months (range, 4.4-17.03 mo) and 28.5 months (range, 5.0-41.5 mo), respectively. Severe adverse events included one patient who developed sepsis and died after receiving infliximab salvage. One patient who received cyclosporine salvage developed herpetic esophagitis, and another patient who received cyclosporine salvage developed pancreatitis and bacteremia. CONCLUSIONS: In patients with severe corticosteroid-refractory ulcerative colitis who fail treatment with either cyclosporine or infliximab, remission rates using acute salvage therapy by crossing over to the other drug occur in approximately one third of patients and have limited duration. Serious adverse events occurred in 16%, including 1 death, suggesting that the risks of acute salvage therapy may outweigh the benefits.

Screening and surveillance colonoscopy in chronic Crohn's colitis: results of a surveillance program spanning 25 years.

BACKGROUND & AIMS: Since 1980, we have followed 259 patients with chronic Crohn's colitis in a prospective colonoscopic surveillance program. Our initial results through August 1998 showed a 22% chance of developing definite dysplasia or cancer by the fourth surveillance examination. We now update the results of all examinations since September 1998 until April 2005. METHODS: All patients had at least 7 years of Crohn's colitis affecting at least one third of the colon. Patients were recalled every 1 to 2 years or sooner if dysplasia was found. Pathology was classified as normal, dysplasia (indefinite, low-grade [LGD], or high-grade [HGD]), or carcinoma. Lesions were classified as flat, polyp, or mass. RESULTS: A total of 1424 examinations were performed on 259 patients. Ninety percent had extensive colitis. The median age at diagnosis was 22 years (range, 2-61 y), and the median disease duration was 18 years (range, 7-49 y). On screening examination, definite dysplasia or cancer was found in 18 patients (7%). Thirteen had LGD, 2 had HGD, and 3 had cancer. On surveillance examinations, a first finding of definite dysplasia or cancer was found in an additional 30 patients (14%). Twenty-two had LGD, 4 had HGD, and 4 had cancer. The cumulative risk of detecting an initial finding of any definite dysplasia or cancer after a negative screening colonoscopy was 25% by the 10th surveillance examination. The cumulative risk of detecting an initial finding of flat HGD or cancer after a negative screening colonoscopy was 7% by the ninth surveillance examination. CONCLUSIONS: Periodic surveillance colonoscopy should be part of the routine management of chronic extensive Crohn's colitis.

Relapses of inflammatory bowel disease during pregnancy: in-hospital management and birth outcomes.

BACKGROUND: There are few studies that describe the medical treatment and colitis response rates among patients with a severe relapse of inflammatory bowel disease (IBD) during pregnancy, and few studies of the effect of such a relapse on birth outcomes in these patients. OBJECTIVES: To describe the treatment and response rates of severe colitis in pregnancy, and to assess the effects of a severe relapse of colitis during pregnancy on birth outcomes. METHODS: We performed a case control study of pregnant patients with IBD hospitalized for a disease relapse at two large treatment centers between 1989 and 2001. Details of management of disease relapse and maternal and fetal outcomes were recorded. RESULTS: Eighteen patients (11 ulcerative colitis, 6 Crohn's disease, 1 indeterminate colitis), mean age 28.6 yr (range 19-38) formed the study group; 41 age-matched pregnant IBD patients without disease relapse formed the control group. Study patients were hospitalized at a mean of 15.9-wk gestation (range 8-35) for a mean of 10.4 days (range 3-31). All 18 patients received IV hydrocortisone (mean dose 199 mg/day) and 7 patients (39%) either continued taking or were commenced on immunomodulators: IV cyclosporine (5 patients) and azathioprine/6-MP (3 patients). Fifteen patients (83%) had a clinical response to these medical treatments, 3 patients required colectomy. There were significant differences between study and control groups in gestation period (35.0 wk vs 38.7 wk, respectively, P= 0.0001) and birth weight (2,001 g vs 3,018 g, respectively, P < 0.0001). CONCLUSIONS: Treatment with IV hydrocortisone and IV cyclosporine appears effective at inducing remission of colitis but their use must continue to be confined to severely ill patients being treated at specialized centers. Severe relapses of colitis during pregnancy increase the risk of preterm birth and low birth weight.

Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial.

BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score

Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease.

BACKGROUND: Intravenous cyclosporine (i.v. CsA) is an effective therapy for patients with inflammatory bowel disease (IBD). However, data regarding its adverse events in these patients are limited. METHODS: A retrospective chart review of the initial 111 consecutive patients with IBD treated with i.v. CsA followed by a predetermined duration of oral therapy. RESULTS: One hundred eleven patients (64 UC, 47 CD; mean age 33 yr, range 16-68) received i.v. CsA at 4 mg/kg/day, then oral CsA at 8 mg/kg/day, with dose adjustment based on serum creatinine. The mean treatment duration was 9.3 months (range 1 wk to 34 months). Major adverse events occurred in 17 (15.3%) patients. Nephrotoxicity (serum creatinine > or = 1.4 mg/dL [123 micromol/L] or a rise by at least 33% over baseline not responding to dose adjustment) sufficiently severe to warrant discontinuation of therapy occurred in 6 (5.4%) patients. Serious infection occurred in 7 (6.3%) patients, seizures in 4 (3.6%) patients, anaphylaxis in 1 (0.9%) patient, and death in 2 (1.8%) patients. Minor adverse events (transient effects with complete resolution either spontaneously or with dose adjustment) comprised: paresthesias (51%), hypomagnesemia (42%), hypertension (39%), hypertrichosis (27%), headache (23%), minor nephrotoxicity (defined as above but with restoration of normal serum creatinine with dose adjustment; 19% of patients), abnormal liver function tests (19%), minor infections (15%), hyperkalemia (13%), and gingival swelling (4%). CONCLUSIONS: In our initial experience, limited duration CsA therapy was frequently associated with adverse events although the majority of these were minor and responded to dose adjustment. Although not all severe adverse events can be clearly attributed to CsA use alone, its high incidence suggests that vigorous monitoring by experienced clinicians at tertiary care centers may be required.

Pouch-ouch.

PURPOSE OF REVIEW: For patients who require colectomy, the ileal pouch anal anastomosis operation has alleviated the need for permanent ileostomy and has improved associated self-esteem issues. The most common complication of this surgery, however, is pouchitis. This review highlights the most recent research in the pathophysiology, risk factors, diagnosis and management of pouchitis, and pouch surveillance for neoplasia in patients who had ulcerative colitis. RECENT FINDINGS: Markers of inflammation, including fecal lactoferrin and mucosal cytokines, have been reported as useful in differentiating between irritable pouch syndrome and pouchitis. Numerous risk factors for the development of pouchitis have been identified. They include the presence of perinuclear antinuclear cytoplasmic antibodies, steroid use prior to colectomy, dysplasia as the indication for colectomy, the presence of extraintestinal manifestations, and an elevated platelet count. Therapy for acute pouchitis remains a short course of antibiotics. For chronic pouchitis, studies found success with rifaximin, tinidazole, and oral budesonide. Cancer in the residual rectal mucosa, in the ileal mucosa, and in pouch polyps occurs frequently enough to warrant surveillance. SUMMARY: Risk factors for the development of pouchitis should be discussed with patients. Less invasive diagnostic strategies have been proposed and antibiotics are still the mainstay of therapy.

Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial.

BACKGROUND & AIMS: A randomized placebo-controlled trial evaluated the efficacy of natalizumab induction therapy in patients with Crohn's disease. METHODS: Patients (N = 509) with moderately to severely active Crohn's disease and active inflammation characterized by elevated C-reactive protein concentrations were randomized (1:1) to receive natalizumab 300 mg or placebo intravenously at Weeks 0, 4, and 8. The primary end point was induction of response (> or =70-point decrease from baseline in the Crohn's Disease Activity Index score at Week 8 sustained through Week 12). Additional efficacy end points included the proportion of patients with sustained remission (Crohn's Disease Activity Index score <150 points) and response or remission over time. RESULTS: Response at Week 8 sustained through Week 12 occurred in 48% of natalizumab-treated patients and 32% of patients receiving placebo (P < .001). Sustained remission occurred in 26% of natalizumab-treated patients and 16% of patients receiving placebo (P = .002). Week 4 response rates were 51% for natalizumab and 37% for placebo (P = .001). Responses remained significantly higher at subsequent assessments (P < .001) in natalizumab-treated patients. Natalizumab-treated patients also had significantly higher remission rates at Weeks 4, 8, and 12 (P < or = .009). The frequency and types of adverse events were similar between treatment groups. CONCLUSIONS: Natalizumab induced response and remission at Week 8 that was sustained through Week 12. Response and remission rates for natalizumab were superior to those for placebo at Weeks 4, 8, and 12, demonstrating the early and sustained efficacy of natalizumab as induction therapy in patients with elevated C-reactive protein and active Crohn's disease. Natalizumab was well tolerated in this study.

Optimizing therapy in patients with pancolitis.

Pancolitis affects approximately 20% to 40% of the total ulcerative colitis population and remains a therapeutic challenge for clinicians. Practitioners must focus on pancolitis when evaluating a patient for ulcerative colitis, because pancolitis is associated with more severe and fulminant disease and a higher rate of colorectal cancer and colectomy. It is imperative for clinicians to be knowledgeable in the clinical course, medications, and appropriate manner to induce and maintain clinical remission to prevent serious sequelae of the disease. The purpose of this article is to provide a review of the treatment of pancolitis for general gastroenterologists, because medical management decisions have life-long effects for this subgroup of patients.

Is perianal Crohn's disease associated with intestinal fistulization?

BACKGROUND: When cases of Crohn's disease (CD) are described as "fistulizing," distinctions are often not drawn between perianal and intestinal fistulization. The question, therefore, remains open as to whether or not there is truly an association between perianal fistulization and intraabdominal intestinal fistulization in CD. AIMS: We have sought to determine the association between perianal and intestinal fistulization by analyzing the cases of CD recorded in databases from six international centers. PATIENTS: Six databases provided information on 5491 cases of CD in the United States, France, Italy, and The Netherlands. Of these cases, 1686 had isolated ileal disease and 1655 had Crohn's colitis. METHODS: An association between perianal disease and internal fistulae was sought by calculating relative risks for the chance of internal fistulae among patients with perianal fistulae relative to those without. Statistical significance was calculated by the Mantel-Haenszel procedure, stratifying on the separate centers. All statistical tests and estimates were implemented using SAS for the PC. RESULTS: Among the 1686 cases with isolated ileal disease, the evidence of an association between perianal disease and internal fistulization was not consistent across centers, with relative risks ranging from 0.8 to 2.2. For patients with Crohn's colitis (n = 1655), the association was much stronger and more consistent, with an estimated common relative risk of 3.4, 95% confidence interval (2.6-4.6, p < 0.0001). CONCLUSIONS: We have found a statistically significant association between perianal CD and intestinal fistulization, much stronger and more consistent in cases of Crohn's colitis than in cases limited to the small bowel.

Consensus conference: Colorectal cancer screening and surveillance in inflammatory bowel disease.

The idiopathic inflammatory bowel diseases, ulcerative colitis and Crohn's colitis, are associated with an increased risk for developing colorectal cancer. To reduce colorectal cancer mortality in inflammatory bowel disease, most patients and their physicians choose to follow a program of surveillance colonoscopy in an attempt to detect early neoplastic lesions at a curable stage. Colectomy is typically reserved for patients whose biopsy findings are indicative of heightened cancer risk based on interpretation by pathologists. Despite the absence of prospective controlled clinical trials to formally evaluate the benefits, risks, and costs of this approach, enough circumstantial evidence has accrued to warrant its widespread adoption in practice. Nevertheless, no standardized guidelines have yet been set forth to guide the gastroenterologist in performing surveillance. A panel of international experts was assembled to develop consensus recommendations for the performance of surveillance. The findings are presented herein.

Crohn's is not a 6-week disease: lifelong management of mild to moderate Crohn's disease.

Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targeted toward lifelong management, taking into consideration not only the short-term but also the long-term aspects of the disease. With this in mind, here we review the classifications and natural history of Crohn's disease and discuss possible predictive factors for the disease evolution in a patient. Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease.