Faculty Bibliography

The role of vitamin D has long been discussed in many chronic diseases, and its significance in inflammatory bowel disease has recently gained attention. This article reviews vitamin D homeostasis, the involvement of vitamin D in the pathophysiology of inflammatory bowel disease, and vitamin D deficiency as a result of inflammatory bowel disease. In addition, this article explores the possibility of age, specifically in the elderly population, as a risk factor for developing vitamin D deficiency in patients with inflammatory bowel disease.

Small bowel adenocarcinoma is a rare but well-known complication of Crohn's disease. The diagnosis of small bowel adenocarcinoma remains difficult since its presentation is highly variable and mimics active or obstructive Crohn's disease. The diagnosis is often delayed and typically detected only at surgery in an advanced stage with a poor prognosis. We report a case of metastatic ileal adenocarcinoma in a patient with Crohn's disease with prolonged survival. Our case describes serial promising treatment options of these advanced malignancies and raises a possible role for checkpoint immunotherapy.

PURPOSE OF REVIEW/OBJECTIVE:Early- and late-onset of inflammatory bowel disease (IBD) may perhaps be etiologically distinct and potentially attributed to genetics, environmental or microbial factors. We review disease factors and clinical characteristics, as well as unique management and treatment strategies to consider when caring for the "baby" or "baby boomer" with IBD. RECENT FINDINGS/RESULTS:Around 25% of cases of initial diagnosis of IBD is made before the age of 18 years old, and another 15-20% made after the age of 60. Crohn's disease (CD) typically presents as ileocolonic and stricturing or penetrating phenotype among early-onset, whereas among late-onset, it is mainly colonic and inflammatory. Pediatric ulcerative colitis (UC) is mostly pan-colonic versus primarily left-sided among the elderly. Treatment goal for both age groups is primarily symptom control, with growth and development also considered among pediatric patients. Due to alterations in pharmacokinetics, careful monitoring and reduced dose should be considered. A multidisciplinary care team is necessary to ensure better clinical outcomes. Onset of disease at either spectrum of age requires careful management and treatment, with both unique disease- and age-appropriate factors carefully considered.

Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10-8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.

OPINION STATEMENT: Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is becoming more prevalent with the elderly being the fastest growing group. Parallel to this, there is an increasing interest in the use of complementary and alternative medicine (CAM). Nearly half of patients with IBD have used CAM at one time. The elderly patients, however, are burdened by comorbid conditions, polypharmacy, and altered functional status. With increasing use of complementary and alternative medicine in our elderly patients with IBD, it is vital for the provider to provide counsel on drug-herb potential interactions. CAM includes herbal products, diet, dietary supplements, acupuncture, and prayer. In this paper, we will review common CAM, specifically herbs, that are used in patients with IBD including the herb background, suggested use, evidence in IBD, and most importantly, potential interactions with IBD medications used in elderly patients. Most important evidence-based adverse events and drug-herb interactions are summarized. The herbs discussed include Triticum aestivum (wheat grass), Andrographis paniculata (chiretta), Boswellia serrata, tormentil, bilberry, curcumin (turmeric), Plantago ovata (blond psyllium), Oenothera biennis (evening primrose oil), germinated barley foodstuff, an herbal preparation of myrrh, chamomile and coffee extract, chios mastic gum, wormwood (absinthe, thujone), Cannabis sativa (marijuana, THC), tripterygium wilfordii (thunder god vine), Ulmus rubra (slippery elm bark), trigonella foenugraecum (fenugreek), Dioscorea mexicana (wild yam), Harpagophytum procumbens (devil's claw), ginger, cinnamon, licorice, and peppermint.

OPINION STATEMENT: As new and effective novel therapies in inflammatory bowel disease (IBD) become available, patients are living longer with advancing age and are at increased risk for malignancy. The management of IBD and malignancy involves multiple combinations of chemotherapy agents and IBD drugs, with the potential for interactions between these therapies. Interactions may either potentiate the effectiveness of drug class or exacerbate their common side effects. In this review article, we present a guide on studied interactions between IBD therapies and chemotherapy agents, specifically those of colorectal cancer, breast cancer, non-Hodgkin's lymphoma, and melanoma. The pharmacology and pharmocokinetics of each IBD drug will be discussed. Then, the IBD drug and chemotherapy interactions are summarized in table format. This guide will provide a quick reference to guide clinicians with this challenging management of two disease processes.

Background Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn's disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. Methods We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn's Disease Activity Index [CDAI] score of >/=100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). Results The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P