Diet and Nutrition in Inflammatory Bowel Disease: A Review of the Literature.

Diet is thought to contribute to the development of inflammatory bowel disease (IBD) and may act as a mediator of inflammation in patients with IBD. Patients commonly associate their diet with symptoms and inquire about dietary modifications to manage their IBD. Without clinical guidelines and well-established nutritional data, healthcare providers managing patients with IBD may find it difficult to provide recommendations. Strong evidence for enteral nutrition, particularly in the pediatric population, has been established in Crohn's disease (CD) as a therapeutic option. Enteral nutrition may also serve as an adjunct to an exclusion diet. Recent studies such as the randomized trial comparing the Specific Carbohydrate Diet to a Mediterranean Diet in CD patients provide additional insights in forming dietary plans. A low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in quiescent IBD and an anti-inflammatory diet have also been explored as adjunctive therapies. In this review, we discuss the latest evidence for the role of diet in IBD both as a therapeutic modality and as an opportunity to provide patient-centered care.

Adverse Events and Compliance Among Inflammatory Bowel Disease Patients Treated With Home- vs Office-Based Biologic Infusions.

BACKGROUND: Biologic medications are a common therapy for those with inflammatory bowel disease (IBD). There are limited data on the outcomes of home-based biologic infusions for patients with IBD. The aim of this study was to compare the safety and efficacy of biologic infusions for IBD patients who receive either home- or office-based administration. METHODS: Patients receiving infliximab or vedolizumab were analyzed retrospectively over a period of 152 weeks. Survival free of major adverse events including delayed infusion reaction, steroid initiation, drug discontinuation, or IBD-related emergency department visits, admission, and surgery were compared using a Kaplan-Meier curve. Individual adverse events, infusion-.related quality measures, and markers of patient adherence were analyzed. RESULTS: Adverse event-free survival was greater among those receiving home-based infusion (n = 154) compared with office-based infusion (n = 133). The office infusion cohort had higher rates of delayed infusion reactions (4 vs 0), IBD-related surgery (6 vs 0), and drug discontinuation (44 vs 35); this was a sicker cohort of patients compared with those in the home infusion group. Home infusion patients were less likely to receive correct weight-based dosing for infliximab (71.7% vs 89.3%), obtain labs for drug monitoring (53.2% vs 71.4%), and adhere to routine clinic visits (37.9% vs 58.1%). CONCLUSIONS: The home-based infusion of biologics for IBD appears safe with lower rates of major adverse events compared with office-based infusions. However, those receiving home infusion were less likely to receive correct weight-based dosing for infliximab and were poorly adherent to routine follow-up.

There are higher rates of adverse events among inflammatory bowel disease patients infused with biologics in the office rather than at home. The quality of care delivered and patient adherence to follow-up is reduced among those receiving home infusions.

Hormone Replacement Therapy Is Associated with Disease Activity Improvement among Post-Menopausal Women with Inflammatory Bowel Disease.

(1) Background: There are limited data available to guide clinical decision-making regarding the effects of hormone replacement therapy (HRT) in post-menopausal women with inflammatory bowel disease (IBD). In this study, we sought to characterize a population of post-menopausal women with IBD and to determine the effects of HRT on their disease activity. (2) Methods: A multicenter, retrospective, case-control cohort study of post-menopausal women with IBD was conducted. The physician global assessment (PGA) score was used to quantify disease activity. To control for the effects of menopause, IBD patients who had not undergone HRT were used as controls. (3) Results: There was a significant reduction in the frequency of PGA scores ≥2 post HRT treatment (p < 0.01). HRT treatment was associated with a 5.6× increase in the odds of post-HRT PGA score improvement compared to controls (OR 5.6; 95% CL 1.6, 19.7) in our univariate logistic regression analysis. (4) Conclusion: Post-menopausal IBD women who underwent HRT therapy showed an improvement in their disease symptoms following HRT compared to post-menopausal women without HRT therapy, who showed no change.

Sarcopenia Is More Prevalent Among Inflammatory Bowel Disease Patients Undergoing Surgery and Predicts Progression to Surgery Among Medically Treated Patients.

BACKGROUND: Sarcopenia is common in inflammatory bowel disease (IBD); however, estimates of its prevalence and impact on clinical outcomes are variable. This study sought to compare the prevalence of sarcopenia in IBD patients starting new biologics vs patients undergoing IBD surgeries, and its association with common clinical predictors of nutritional status, adverse events, and clinical outcomes. METHODS: This was a multicenter retrospective cohort study of IBD patients who had a computed tomography (CT) scan within 6 months prior to new biologic initiation (medical cohort) or IBD surgery (surgery cohort). The lowest sex-specific quartile of the total psoas area index at the L3 level defined sarcopenia. Prevalence and predictors of sarcopenia, performance of common clinical nutritional markers, and association with adverse events and clinical outcomes at 1 year were determined. RESULTS: A total of 156 patients were included (48% medical cohort, 52% surgery cohort). Sarcopenia was more common in the surgery cohort (32% vs 16%; P < .02). In the medical cohort, sarcopenia predicted need for surgery at 1 year (odds ratio, 4.75; 95% confidence interval, 1.10-20.57; P = .04). Low albumin and body mass index (BMI) were associated with the presence of sarcopenia; however, 24% of sarcopenic patients had both normal BMI and albumin. CONCLUSIONS: Sarcopenia is more prevalent among IBD patients undergoing surgery and predicts the need for surgery in patients starting new biologic therapy. Low albumin and BMI were similar between cohorts, suggesting a unique role for sarcopenia as a relevant clinical marker of lean muscle mass depletion for surgically and medically treated IBD patients.

Sarcopenia is more common in inflammatory bowel disease surgery patients compared with medical patients, and predicts need for surgery in medical patients. Differences in skeletal muscle measurements compared with albumin and body mass index suggest that sarcopenia may be challenging to detect in routine clinical settings.

Novel and Emerging Therapies for Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and to also improve the safety profile and tolerability of these medications. In this review we will discuss novel treatment target agents including selective janus kinase (JAK) inhibitors, anti-interleukin (IL) (IL-12/IL-23), leukocyte trafficking/migrating inhibitors (such as sphingosine-1-phosphate receptor modulator) and other small molecules currently in development.

Therapeutic Drug Monitoring for Current and Investigational Inflammatory Bowel Disease Treatments.

This article reviews therapeutic drug monitoring (TDM) use for current inflammatory bowel disease (IBD) treatments. IBD comprises Crohn's disease and ulcerative colitis-chronic gastrointestinal inflammatory disorders. Treatment options for moderate to severe IBD include thiopurines; methotrexate; biologic agents targeting tumor necrosis factor, α4ß7 integrin or interleukins 12 and 23; and Janus kinase inhibitors. TDM is recommended to guide treatment decisions for some of these agents. Published literature concerning TDM for IBD treatments was reviewed. S.D.L., R.S., and E.V.L. drew on their clinical experiences. Polymorphisms resulting in altered enzymatic activity inactivating thiopurine metabolites can lead to myelotoxicity and hepatotoxicity. Increased elimination of biologic agents can result from immunogenicity or higher disease activity, leading to low drug concentration and consequent nonresponse or loss of response. TDM may aid treatment and dose decisions for individual patients, based on monitoring metabolite levels for thiopurines, or serum drug trough concentration and antidrug antibody levels for biologic agents. Challenges remain around TDM implementation in IBD, including the lack of uniform assay methods and guidance for interpreting results. The Janus kinase inhibitor tofacitinib is not impacted by enzyme polymorphisms or disease activity, and is not expected to stimulate the formation of neutralizing antidrug antibodies. TDM is associated with implementation challenges, despite the recommendation of its use for guiding many IBD treatments. Newer small molecules with less susceptibility to patient variability factors may fulfill the unmet need of treatment options that do not require TDM, although further study is required to confirm this.

Mimics of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) may present with nonspecific symptoms and diagnostic findings. Therefore, many diseases may mimic the clinical symptoms, endoscopic findings, and histologic features of IBD. In this paper, we will review mimics of IBD, dividing the diseases that can imitate IBD into noninfectious and infectious causes. For each disease state, we will discuss the clinical symptoms and endoscopic and histologic features. Finally, we will discuss how to distinguish these distinct disorders from IBD.

Outcomes of Endoscopic Therapy for Luminal Strictures in Crohn's Disease.

Backgrounds: We sought to describe the outcomes of endoscopic therapy of luminal strictures in patients with Crohn's disease (CD) at a large tertiary referral center. Methods: All patients who had undergone endoscopic dilation of CD strictures between January 1, 1990 and November 30, 2013 were identified. Demographics, disease characteristics including medication use and history of surgeries, details of endoscopic procedures, and long-term outcomes were analyzed. A successful procedure was defined as ability of the endoscope to pass through the stricture after dilation or effacement of the dilating balloon under fluoroscopy. Kaplan-Meier and Cox proportional hazards analysis were used. Results: For this study 286 index procedures for CD-related stricture dilation were performed in 273 patients (53.8% women) with median age of 45.9 years (range, 14.9-92.2). The most common stricture locations were ileocolonic anastomosis (36.4%) and colon (13.9%). One hundred fourteen (41.8%) patients had a second dilation. The cumulative probability of need for a second dilation following the index procedure was 33.6% at 1 year (95% CI, 25.9%-38.7%), 53.9% at 3 years (45.9%-61.2%), and 60.2% at 5 years (51.4%-67.5%). Six adverse events occurred after the first procedure: 4 perforations, 1 patient with bleeding, and 1 patient with abdominal pain requiring hospitalization. A total of 82 (30%) patients required surgery for their stricture. Conclusions: In a large cohort, endoscopic stricture dilation in CD was safe and effective. About 33% of patients required a second dilation at 1 year after the initial dilation; younger age and smaller inner diameter of the index stricture predicted need for a second dilation. 10.1093/ibd/izy049_video1izy049.video15794820307001.

Use of Anti-Tumor Necrosis Factors and Anti-Integrins in the Treatment of Crohn's Disease.

In patients with Crohn's disease (CD), anti-tumor necrosis factor (TNF) therapy is efficacious for the induction and maintenance of clinical remission, mucosal healing, reducing rates of surgery and hospitalizations, and improving health-related quality of life. The decision between anti-TNFs and anti-integrins as first-line treatment in CD depends on disease severity, safety concerns, and prescription coverage. Given the existing data on long-term outcomes and safety, anti-TNFs are often preferred to anti-integrins. Additional clinical experience and preferably prospective, head-to-head studies will be important to determine whether vedolizumab should be considered more often for first-line therapy in CD.

The Role of Diet in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Diet may play both a causal and therapeutic role for inflammatory bowel disease (IBD). Physicians caring for patients with IBD are often asked to make dietary recommendations. However, there are no well-established guidelines on the use of diet as a treatment of IBD. In this review, we describe the evidence supporting diet as a potential cause for IBD, patient-perceived symptoms based on diet, current research on various diets as a treatment for IBD, and areas of future research. RECENT FINDINGS: New studies in murine models suggest that dietary emulsifiers may trigger the gut inflammatory cascade. New studies of restriction diets in patients have shown a relationship between dietary intake, symptoms, and bowel inflammation. Until several ongoing clinical trials are completed, a reasonable approach to dietary recommendations for patients with IBD is to propose a well-balanced, healthy (low-fat, low-sugar) diet prepared from fresh ingredients, such as the Mediterranean diet, with exclusions of self-identified foods that worsen or trigger IBD-related symptoms.

Cytomegalovirus and the Seemingly Immunocompetent Host: A Case of a Perforating Gastric Ulcer.

Cytomegalovirus (CMV) infection of the gastrointestinal tract has a variety of presentations. We present a case of gastric perforation, which is a relatively infrequent presentation of CMV infection. If the cause of gastric perforation is not readily apparent, testing for CMV should be considered. If CMV workup is positive, an evaluation for immunocompromise is prudent as CMV infections are more common in immunocompromised individuals.

Incidence and Prevalence of Crohn's Disease and Ulcerative Colitis in Olmsted County, Minnesota From 1970 Through 2010.

BACKGROUND & AIMS: The incidence and prevalence of inflammatory bowel diseases (IBD) continue to increase worldwide. We sought to update incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) in a well-defined United States population, calculating values for Olmsted County, Minnesota through 2010. We also calculated prevalence values. METHODS: The resources of the Rochester Epidemiology Project were used to identify county residents who were diagnosed with IBD (CD or UC), based on previously set criteria. Those with new diagnoses of CD or UC between 1970 and 2010 were identified as incidence cases, and those meeting diagnostic criteria on January 1, 2011, were identified as prevalence cases. Incidence rates were estimated (adjusted for age and sex to the US white population in 2010). Trends in incidence based on age at diagnosis, sex, and year of diagnosis were evaluated by Poisson regression. RESULTS: The incidence cohort included 410 patients with CD (51% female) and 483 individuals with UC (56% male). Median age of diagnosis was 29.5 years for persons with CD (range, 4-93 years) and 34.9 years for UC (range, 1-91 years). From 2000 through 2010, the adjusted annual incidence rate for CD was 10.7 cases per 100,000 person-years (95% confidence interval [CI], 9.1-12.3 person-years) and for UC was 12.2 per 100,000 (95% CI, 10.5-14.0 person-years). On January 1, 2011, there were 380 residents with CD, with an adjusted prevalence of 246.7 cases per 100,000 persons (95% CI, 221.7-271.8 cases per 100,000 persons), and 435 residents with UC, with an adjusted prevalence of 286.3 (95% CI, 259.1-313.5 cases per 100,000 persons). Male sex was significantly associated with a higher incidence rate of UC, and younger age was significantly associated with a higher incidence rate of CD. CONCLUSIONS: Estimated incidence rates for UC and CD in Olmsted County are among the highest in the United States. Extrapolating the adjusted prevalence to the most recent US Census, there could be approximately 1.6 million persons in the United States with IBD.

Ventricular septal defect and bivalvular endocarditis.

A 63-year-old man presented with generalized fatigue, chills, malaise, dyspnea, intermittent fevers, and 50-pound weight loss of 4 months' duration. Blood cultures were positive for pan-sensitive Streptococcus anginosus. Transesophageal echocardiography showed an 11 mm × 3 mm mobile mass attached to the mitral valve, a 16 mm × 16 mm mobile mass attached to the pulmonary valve, and a small membranous ventricular septal defect. The patient received 12 weeks of intravenous (IV) antibiotics with eventual resolution of the masses. Multi-valve endocarditis involving both the left and right chambers is rarely reported without prior history of IV drug use or infective endocarditis. Our case emphasizes the importance of careful assessment for ventricular septal defects or extra-cardiac shunts in individuals who present with simultaneous right and left-sided endocarditis.

Incidence of Spondyloarthropathy in patients with ulcerative colitis: a population-based study.

OBJECTIVE: Spondyloarthritis (SpA) is an important extraintestinal manifestation of inflammatory bowel disease (IBD). We assessed the cumulative incidence and clinical spectrum of SpA in a population-based cohort of patients with ulcerative colitis (UC). METHODS: The medical records of a population-based cohort of residents of Olmsted County, Minnesota, USA, diagnosed with UC from 1970 through 2004 were reviewed. Patients were followed longitudinally until moving from Olmsted County, death, or June 30, 2011. We used the European Spondylarthropathy Study Group, Assessment of Spondyloarthritis International Society (ASAS) criteria, and modified New York criteria to identify patients with SpA. RESULTS: The cohort included 365 patients with UC, of whom 41.9% were women. The median age at diagnosis of UC was 38.6 years (range 1.2-91.4). Forty patients developed SpA based on the ASAS criteria. The cumulative incidence of a diagnosis of SpA after an established diagnosis of UC was 4.8% at 10 years (95% CI 95% CI 2.2%-7.3%), 13.7% at 20 years (95% CI 9.0%-18.1%), and 22.1% at 30 years (95% CI 4.3%-29.1%). CONCLUSION: The cumulative incidence of all forms of SpA increased to about 22% by 30 years from UC diagnosis. This value is slightly greater than what we previously described in a population-based cohort of Crohn disease diagnosed in Olmsted County over the same time period. SpA and its features are associated with UC, and heightened awareness on the part of clinicians is needed for diagnosing and managing them.

Clinical factors associated with development of severe-complicated Clostridium difficile infection.

BACKGROUND & AIMS: Clostridium difficile infection (CDI) can cause life-threatening complications. Severe-complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe-complicated CDI. METHODS: We analyzed data from 1446 inpatient cases of CDI (48.6% female; median age, 62.5 years; range, 0.1-103.7 years) at the Mayo Clinic from June 28, 2007, to June 25, 2010. Patients with severe-complicated CDI (n = 487) were identified as those who required admission to the intensive care unit or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe-complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, Minnesota to assess the association of comorbid conditions with the development of severe-complicated infection in a population-based cohort. The linear combinations of variables identified by using logistic regression models provided scores to predict the risk of developing severe-complicated CDI. RESULTS: In a multivariable model that included all inpatients, increasing age, leukocyte count >15 × 10(9)/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe-complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe-complicated CDI. CONCLUSIONS: Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe-complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes.

Incidence of spondyloarthropathy in patients with Crohn's disease: a population-based study.

OBJECTIVE: Spondyloarthritis (SpA) is an extraintestinal manifestation of inflammatory bowel disease with significant clinical effects, although the frequency is uncertain. We assessed the cumulative incidence and clinical spectrum of SpA in patients with Crohn's disease (CD) in a population-based cohort. METHODS: The medical records of a population-based cohort of Olmsted County, Minnesota, residents diagnosed with CD between 1970 and 2004 were reviewed. Patients were followed longitudinally until migration, death, or December 31, 2010. We used the European Spondylarthropathy Study Group, Assessment of Spondyloarthritis international Society (ASAS) criteria and modified New York criteria to identify patients with SpA. The Kaplan-Meier method was used to estimate the cumulative incidence of SpA following diagnosis of CD. RESULTS: The cohort included 311 patients with CD (49.8% females; median age 29.9 yrs, range 8-89). Thirty-two patients developed SpA based on ASAS criteria. The cumulative incidence of SpA after CD diagnosis was 6.7% (95% CI 2.5%-6.7%) at 10 years, 13.9% (95% CI 8.7%-18.8%) at 20 years, and 18.6% (95% CI 11.0%-25.5%) at 30 years. The 10-year cumulative incidence of ankylosing spondylitis was 0, while both the 20-year and 30-year cumulative incidences were 0.5% (95% CI 0-1.6%). CONCLUSION: We have for the first time defined the actual cumulative incidence of SpA in CD using complete medical record information in a population-based cohort. The cumulative incidence of all forms of SpA increased to approximately 19% by 30 years from diagnosis of CD. Our results emphasize the importance of maintaining a high level of suspicion for SpA when following patients with CD.