Faculty Bibliography

Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16S ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated Escherichia coli in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone. E. coli isolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an adherent-invasive E. coli (AIEC) pathotype. In comparison to non-AIEC E. coli, colonization of germ-free mice with CD-SpA E. coli isolates induced T helper 17 cell (TH17) mucosal immunity, which required the virulence-associated metabolic enzyme propanediol dehydratase (pduC). Modeling the increase in mucosal and systemic TH17 immunity we observed in CD-SpA patients, colonization of interleukin-10-deficient or K/BxN mice with CD-SpA-derived E. coli lead to more severe colitis or inflammatory arthritis, respectively. Collectively, these data reveal the power of IgA-seq to identify immunoreactive resident pathosymbionts that link mucosal and systemic TH17-dependent inflammation and offer microbial and immunophenotype stratification of CD-SpA that may guide medical and biologic therapy.

The United States spends a greater share per gross domestic product on health care than any other developed country in the world. Cost-conscious, high-value care has an important role in the practice of medicine. Inflammatory bowel disease (IBD) affects 1.6 million people in the United States and is responsible for significant health care costs, with estimates as high as $31.6 billion annually, a large portion of which is attributable to the use of biologic therapies. As the number of therapeutic targets for IBD expands, gastroenterologists can anticipate the arrival of novel therapeutic agents on the market, and these may carry significant costs. Vedolizumab, a monoclonal antibody directed against the gut-selective integrin α4β7, is a novel biologic agent approved for the treatment of Crohn's disease and ulcerative colitis. Cost-effectiveness is an area of research that aims to assess the added value (in terms of both cost and utility) of diagnostic or therapeutic interventions. This article reviews the current literature evaluating the cost-effectiveness of vedolizumab for the treatment of IBD.

Cerebral venous thrombosis (CVT) is a rare but devastating complication of inflammatory bowel disease (IBD). Here we describe six IBD patients with cerebral venous thrombosis. The patients presented with hours to days of headache and were found to have venous thrombosis on imaging. Four of the six patients had ulcerative colitis and two had Crohn's disease. All six patients were treated with therapeutic anticoagulation. There were two deaths; one patient became comatose and died despite anticoagulation while the other recovered well from the sinus thrombosis but died after a bowel perforation 3 weeks later. This case series demonstrates the critical need for early recognition of neurological symptoms in patients with IBD during disease flares. It is important to recognize the clinical signs in order to start anticoagulation expeditiously and improve neurological outcomes.

Osteoporosis is a leading cause of morbidity in patients with inflammatory bowel disease (IBD). Bone loss is an early systemic process and occurs even before clinical disease manifests. Bone disease is attributed to vitamin D deficiency, steroid use, and/or systemic inflammation. In this review, we discuss the molecular pathways of bone loss mediated by inflammatory cytokines and other mediators. Further research will hopefully clarify the mechanisms of inflammation-induced bone loss in IBD and guide effective treatment modalities

BACKGROUND: Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. AIM: To assess the effectiveness of a corticosteroid withdrawal method. METHODS: Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29-75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. RESULTS: Median durations for disease and corticosteroid dependency were 21 (range 3-45) and 14 (range 2-45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5-73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). CONCLUSIONS: Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients