Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study

Background: The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods: We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results: The study population included 269 children (105 [39%] Crohn\u27s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn\u27s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn\u27s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions: Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, <it>NOD2</it>, <it>IL23R</it>, <it>IRGM</it>, <it>ATG16L1</it>, <it>PTGER4</it>, <it>NKX2-3</it>, <it>IL12B</it>, <it>PTPN2</it>, <it>TNFSF15 </it>and <it>STAT3</it>, 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.</p> <p>Results</p> <p>Three <it>NOD2 </it>SNPs, two <it>IL23R </it>SNPs, and one SNP each at <it>IRGM </it>and <it>PTGER4 </it>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).</p> <p>Conclusions</p> <p>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.</p

CBT for Anxiety and Associated Somatic Complaints in Pediatric Medical Settings: An Open Pilot Study

Objective: To examine the initial feasibility and potential efficacy of a cognitive-behavioral intervention for youth with anxiety disorders and non-medical somatic symptoms. Background: Based on a strong relationship between somatic complaints and anxiety disorders, screening youngsters seeking medical care due to physical symptoms with no organic basis may enhance the recognition of anxiety disorders and facilitate access to appropriate services. Method: Seven boys and girls, ages 8 through 15, with medically unexplained gastrointestinal complaints and anxiety disorders received a 12-session cognitive-behavioral intervention targeting anxiety and physical symptoms. Assessments were conducted at baseline and following treatment. Results: All participants were classified as treatment responders. Three of the seven participants no longer met diagnostic criteria for their principal anxiety disorder. Children\u27s physical discomfort decreased from a moderate to minimal level based on self- and parent-reports. Conclusions: Our modified cognitive-behavioral approach has promise for reducing anxiety and somatic symptoms in children seeking medical care

Pediatric colonic inflammatory myofibroblastic tumor presenting as colo-colonic intussusception: A case report and review of the literature

Inflammatory myofibroblastic tumors (IMTs) are rare tumors of intermediate biologic potential most often reported in children. Histologic characteristics of IMT include spindle cell proliferation with chronic inflammatory cell infiltrate. IMTs can occur anywhere in the body but are most commonly reported in lung, bowel mesentery, and liver. Nonmesenteric alimentary IMTs are exceedingly rare. We present the second case of colonic IMT presenting as colo-colonic intussusception in a child. The patient is a 12-year-old female who presented with vague abdominal pain for three months. Her workup revealed an intraluminal mass in the descending colon on both CT and colonoscopy. Intraoperatively, the mass was seen causing colo-colonic intussusception. Laparoscopic segmental colon resection was performed, and the patient did well postoperatively. Histology and immunohistochemistry of the mass confirmed IMT

Illness-Specific Anxiety: Implications for Functioning and Utilization of Medical Services in Adolescents with Inflammatory Bowel Disease

Purpose. Adolescents with inflammatory bowel disease (IBD) may be at heightened risk for developing anxiety and depression. This cross-sectional pilot study examined the relationship between anxiety and depression and health-related behaviors. Methods. Thirty-six adolescents with diagnosed IBD, ages 12-17, and their parents were recruited from two pediatric gastroenterology medical centers. Results. Clinical levels of anxiety (22%) and depressive symptoms (30%) were reported by patients. Regression analyses revealed that IBD-specific anxiety was significantly associated with greater utilization of medical services and worsened psychosocial functioning. Practice Implications. Results provide preliminary support that IBD-specific anxiety may play an important role in disease management, yet concerns are rarely systematically assessed by health professionals

Integrating Illness Concerns Into Cognitive Behavioral Therapy for Children and Adolescents with Inflammatory Bowel Disease and Co-Occurring Anxiety

Purpose: To examine the feasibility and preliminary benefits of an integrative cognitive behavioral therapy (CBT) with adolescents with inflammatory bowel disease and anxiety. Design and Methods: Nine adolescents participated in a CBT program at their gastroenterologist\u27s office. Structured diagnostic interviews, self-report measures of anxiety and pain, and physician-rated disease severity were collected pretreatment and post-treatment. Results: Postintervention, 88% of adolescents were treatment responders, and 50% no longer met criteria for their principal anxiety disorder. Decreases were demonstrated in anxiety, pain, and disease severity. Practice Implications: Anxiety screening and a mental health referral to professionals familiar with medical management issues is important

Treatment for Comorbid Pediatric Gastrointestinal and Anxiety Disorders: A Pilot Study of a Flexible Health Sensitive Cognitive-Behavioral Therapy Program

Anxiety is a prevalent and impairing psychiatric condition among children and adolescents with inflammatory bowel disease (IBD). Despite the need for effective treatment, no studies have examined the benefit of cognitive-behavioral therapy (CBT) for anxiety disorders among children or adults with IBD. The aim of this paper is twofold: (a) to briefly describe a newly adapted CBT protocol, treatment of anxiety and physical symptoms related to IBD (TAPS + IBD), that concurrently addresses anxiety (including IBD-specific anxiety) and disease management among children and adolescents with IBD in pediatric medical offices; and (b) to present initial pilot data examining the feasibility and potential efficacy of TAPS + IBD compared to nondirective supportive therapy (NDST) among youth with comorbid IBD and anxiety. Twenty-Two youth (59% female; mean age 13.2 ± 2.1) with comorbid IBD and anxiety disorder were randomly assigned to a 13-session TAPS + IBD or NDST program. Following treatment, participants in TAPS + IBD demonstrated higher treatment response rates relative to the NDST control treatment. Compared with NDST, TAPS + IBD was associated with significantly greater reductions in IBD-specific anxiety immediately following treatment and 3 months later. TAPS + IBD shows initial promise for the treatment of anxiety in youth with IBD. The direct integration of behavioral health strategies into medical settings and use of a flexible CBT approach sensitive to acute disease fluctuations appears to be beneficial among youth with comorbid IBD and anxiety

Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect

Background: TNF-α has a major role in the pathogenesis of Crohn\u27s disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD. Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model. Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2\u27s herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis. Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients