Firas Rinawi

School Attendance in Children With Functional Abdominal Pain and Inflammatory Bowel Diseases.

Objective: Inflammatory bowel disease (IBD) and functional abdominal pain (FAP) are associated with debilitating symptoms and frequent medical visits that may disrupt school functioning. The aim of this study was to assess school-related quality of life and school absenteeism in children with IBD, compared with FAP and healthy controls. Methods: School absenteeism and participation in school and after-school activities data were obtained for 43 children with Crohn disease (CD), 31 children with ulcerative colitis (UC), 42 children with FAP, and 30 age-matched healthy controls for the 2013–2014 school year. We used a semistructured questionnaire for both children and parents. For diminishing recall bias, absenteeism data were cross-matched with the patients school annual report cards. Results: Children with FAP, CD, and UC missed significantly more school days than age-matched healthy controls (17.6 [8.75–30], 24 [14–30], and 21 [12–25] vs 5.1 [3.75–6.25], respectively, P < 0.001). Compared with children with FAP, absenteeism because of medical appointments and hospitalization was significantly greater in children with CD and UC (8.8 [4–14] and 7.1 [3–10] vs 4.4 [2–6.25], P = 0.001). Participation of children with FAP and IBD in various school and after-school activities was significantly reduced compared with healthy controls. There was no difference in school attendance and functioning between children with IBD and FAP. Conclusions: FAP has a significant impact on school attendance and functioning similar to IBD. These findings show that significant psychosocial and academic difficulties are faced not only by children with chronic diseases like IBD but also by children with FAP.

Ustekinumab for Resistant Pediatric Crohn Disease.

C rohn disease (CD) is a chronic inflammatory bowel disease that, in the pediatric age group, tends to present with a more severe form than in adults and frequently takes a complicated course (1). Biological treatment is a therapeutic option in patients with CD who either do not respond to immunomodulators or present with extensive and penetrating disease. Biological therapies may also be used to reduce symptoms when immunomodulators are unsuitable or ineffective and to promote growth in stunted children (2). Anti– tumor necrosis factor-a (TNF-a) agents, infliximab and adalimumab, are the only biological agents approved for pediatric CD. Oneyear and 5-year response rates to infliximab in pediatric patients are approximately 89% and 50%, respectively (3). The difference between shortand long-term responses is attributed to the emergence of anti-TNF antibodies, among other factors, leading to a loss of response (4). Therapeutic options for pediatric patients with CD who fail anti-TNF treatment are scarce. Biological agents targeted against cytokines and integrins other than TNF have been studied with apparent efficacy in adult patients with CD (5). Ustekinumab is a human monoclonal antibody that targets the p40 subunit of both interleukin 12 (IL-12) and IL-23 and inhibits their activity. IL-12 and IL-23 have a key role in the differentiation and proliferation of TH1 and TH17 cell subsets. Indeed, ustekinumab is approved for psoriasis in adult patients (6), whereas pediatric data are limited to a single published case report (7). In CD, a recent randomized controlled trial (5) has demonstrated that ustekinumab is effective in achieving remission in patients with moderate-to-severe CD. Data regarding efficacy of ustekinumab in pediatric CD are lacking.

Small bowel villous atrophy: celiac disease and beyond

ABSTRACT Introduction: Small bowel villous atrophy can represent a diagnostic challenge for gastroenterologists and pathologists. In Western countries small bowel atrophy and mild non-atrophic alterations are frequently caused by celiac disease. However, other pathology can mimic celiac disease microscopically, widening the differential diagnosis. The several novelties on this topic and the introduction of the device-assisted enteroscopy in the diagnostic flowchart make an update of the literature necessary. Areas covered: In this review, a description of the different clinical scenarios when facing with small bowel mucosal damage, particularly small bowel atrophy, is described. The published literature on this subject has been summarized and reviewed. Expert commentary: When an intestinal mucosal alteration is histologically demonstrated, the pathology report forms part of a more complex workup including serological data, clinical presentation and clinical history. A multidisciplinary team, including pathologists and enteroscopy-devoted endoscopists, is frequently required to manage patients with small bowel alterations, especially in cases of severe malabsorption syndrome.

Incidence of Bowel Surgery and Associated Risk Factors in Pediatric-Onset Crohn's Disease.

Background:Data describing the incidence and the risk factors for surgical interventions in pediatric Crohns disease (CD) is inconsistent. Our aim was to describe the rates of intestinal surgery and to identify associated risk factors in a large cohort of children with CD. Methods:Medical charts of 482 children with CD from the Schneider Pediatric Inflammatory Bowel Disease cohort who were diagnosed between 1981 and 2013 were carefully reviewed retrospectively. Results:Of 482 patients, 143 (29.7%) underwent intestinal surgery with a median follow-up time of 8.6 years (range, 1–30.5). Kaplan–Meier survival estimates of the cumulative probability of CD-related intestinal surgery were 14.2% at 5 years and 24.5% at 10 years from diagnosis. Of these, 14% needed more than one operation. Multivariate Cox models showed that isolated ileal disease (hazard ratio [HR] 2.39, P = 0.008), complicated behavior (penetrating or stricturing) (HR 2.44, P < 0.001) and higher severity indices, at diagnosis, including Harvey–Bradshaw (HR 1.06, P = 0.009) and short Pediatric Crohns Disease Activity Index (HR 1.02, P = 0.001) were associated with increased risk for intestinal surgery. Age, gender, family history of CD, early introduction of immunomodulators, treatment with anti–tumor necrosis factor &agr;, or diagnosis before the year 2000 did not affect the risk of bowel surgery. Conclusions:Ileal location, complicated behavior, and higher disease activity indices at diagnosis are independent risk factors for bowel surgery, whereas anti–tumor necrosis factor &agr; treatment and diagnosis during the “biological era” are not associated with diminished long-term surgical risk.

The Characteristics and Long-term Outcomes of Pediatric Crohnʼs Disease Patients with Perianal Disease

Background: Data on the outcomes of children with perianal Crohns disease are limited. We aimed to assess phenotypic features at diagnosis and long-term disease-specific outcomes of this phenotype. Methods: The medical records of 296 pediatric onset patients with Crohns disease, diagnosed from 2001 to 2015, were reviewed retrospectively. Baseline characteristics included age, sex, severity indices, laboratory data, endoscopic findings, and anthropometric measurements. Main outcome measures included time to first flare, hospitalization, surgery, and biological therapy. Results: Of the 296 included patients (median age 14.2 years), 70 (24%) had nonfistulizing perianal findings, whereas only 40 (13%) had fistulizing perianal disease at diagnosis. Perianal involvement was associated with female sex (P = 0.01), whereas fistulizing perianal disease resulted in a greater use of immunomodulators (P = 0.01). Time to hospitalization was shorter for both nonfistulizing and fistulizing perianal disease (hazard ratio [HR] 1.66 and 1.34, respectively, P = 0.027) and time to biological therapy (HR 2.1 and 1.7, respectively, P = 0.002). There were no differences in time to first flare or surgery. During a median follow-up of 8.5 years, additional 26 patients (10%) developed fistulizing perianal disease after a median time of 3.5 years. The presence of nonfistulizing disease at diagnosis was a significant risk factor for the development of fistulizing perianal disease (HR 3.4, P = 0.002). At the end of follow-up, complicated disease was more common in patients with any perianal involvement (P = 0.01). Conclusions: Pediatric patients with Crohns disease with both nonfistulizing and fistulizing disease have worse clinical outcomes. Nonfistulizing disease is a risk factor for the development of fistulizing disease over time.

Risk of Colectomy in Patients with pediatric-onset Ulcerative Colitis.

Objectives: Data describing the incidence and risk factors for colectomy in pediatric ulcerative colitis (UC) is inconsistent. Our aim was to describe the colectomy rate and to identify risk factors associated with colectomy in a large cohort of children with UC with long-term follow-up. Materials and Methods: We performed a retrospective chart review of pediatric UC cases that were diagnosed at Schneider Childrens Medical Center of Israel between 1981 and 2013. Potential predictors for colectomy including age at diagnosis, sex, disease extent, severity indices, and different therapeutic regimens during disease course were assessed. Results: Of 188 patients with pediatric onset UC, 34 (18%) underwent colectomy. Median follow-up was 6.9 years (range, 1–30). Kaplan-Meier survival estimates of the cumulative probability for colectomy were 4% at 1 year and 17% at 10 years from diagnosis. Multivariate Cox models showed that male sex (hazard ratio 4.2, P = 0.001) and severe disease at diagnosis reflected by Pediatric Ulcerative Colitis Activity Index score ≥65 (hazard ratio 8.9, P < 0.001) were associated with increased risk for colectomy. Age, disease extent, ethnicity, family history of inflammatory bowel disease, early introduction of immunomodulators, or treatment with antitumor necrosis factor &agr; agent did not affect the risk of colectomy. Conclusions: Male sex and higher Pediatric Ulcerative Colitis Activity Index score at diagnosis are independent risk factors for colectomy.

Pediatric-Onset Inflammatory Bowel Disease Poses Risk for Low Bone Mineral Density at Early Adulthood

BACKGROUND Inflammatory bowel disease (IBD) is known to pose a risk for low bone mineral density (BMD) in children and adults. We aimed to evaluate the impact of pediatric-onset IBD on BMD in adulthood. METHODS Records of pediatric-IBD patients were retrospectively reviewed for documentation of dual-energy X-ray absorptiometry (DXA) scans in adulthood. BMD was expressed as z-score. RESULTS Sixty one patients were included. Mean (±SD) age at diagnosis was 14.7 (±2.4) years. Mean age at first DXA scan in adulthood was 23.9 years (±4.8). Median BMD z-score was -1.2 SD (IQR, -1.8 to -0.4), significantly lower than expected in normal population (p<0.001). Osteopenia (BMD z-score ≤-1 SD) was noted in 44.3% (n=27), and osteoporosis (BMD z-score ≤-2.5 SD) in 8.2% (n=5). Bone-status showed no correlation with age, disease severity, vitamin D status at diagnosis, IBD subtype or duration of disease. Positive correlation (r=0.306) was identified between low weight z-score at diagnosis and abnormal bone-status in adulthood. Among 36 patients with multiple DXA scans, there was no significant change in BMD during follow-up of 2.4 years. CONCLUSIONS Osteopenia and osteoporosis are frequent in adult IBD patients with pediatric-onset disease and correlates with low weight z-score at diagnosis.

Evolution of disease phenotype in pediatric-onset Crohn's disease after more than 10 years follow up-Cohort study.

BACKGROUND Pediatric-onset Crohns disease (CD) is a heterogeneous disorder which is subjected to progression and complications in a substantial proportion of patients. AIMS We aimed to assess the progression in pediatric-onset CD phenotype on long term follow up. METHODS Medical charts of pediatric onset CD patients with at least 10 years follow-up were analyzed retrospectively. Disease phenotype was determined at diagnosis and during follow up at different time points. Phenotype was determined according to the Paris classification. The impact of possible predictors on phenotype progression was assessed as well as the association between different therapeutic regimens during disease course and phenotype progression. RESULTS Progression of disease location, behavior, and perianal involvement was observed in 20%, 38% and 20% of patients, respectively, after a median follow-up of 16.4 (±4.4) years. Microscopic ileocolonic disease at diagnosis was significant predictors for progression of disease extent. Treatment with anti tumor necrosis factor-ɑ agents and number of flares per years of follow-up were associated with progression of disease extent, behavior and perianal involvement. CONCLUSION Disease extent, behavior and prevalence of perianal disease change significantly over time in pediatric-onset CD. In our cohort, most clinical, laboratory and endoscopic parameters do not serve as predictors for long-term disease progression.

Long-Term Outcomes After Primary Bowel Resection in Pediatric-Onset Crohn’s Disease

Background There is limited evidence on the long-term outcome of intestinal resection in pediatric-onset Crohns disease (POCD) with no established predictors of adverse outcomes. We aimed to investigate clinical outcomes and predictors for adverse outcome following intestinal resection in POCD. Methods The medical records of patients with POCD who underwent at least 1 intestinal resection between 1990 and 2014 were reviewed retrospectively. Main outcome measures included time to first flare, hospitalization, second intestinal resection, and response to nonprophylactic biologic therapy. Results Overall, 121 patients were included. Median follow-up was 6 years (range 1-23.6). One hundred and seven (88%) patients experienced at least 1 postsurgical exacerbation, 52 (43%) were hospitalized, and 17 (14%) underwent second intestinal resection. Of 91 patients who underwent surgery after the year 2000, 37 (41%) were treated with antitumor necrosis factor ɑ (anti-TNFɑ) (nonprophylactic) following intestinal resection. Time to hospitalization and to second intestinal resection were shorter among patients with extraintestinal manifestations (EIMs) (HR 2.7, P = 0.006 and HR = 3.1, P = 0.03, respectively). Time to initiation of biologic treatment was shorter in patients with granulomas (HR 2.1, P = 0.038), whereas being naïve to anti-TNFɑ treatment before surgery was a protective factor for biologic treatment following surgery (HR 0.3, P = 0.005). Undergoing intestinal resection beyond the year 2000 was associated with shorter time to first flare (HR 1.9, P = 0.019) and hospitalization (HR 2.6, P = 0.028). Conclusion Long-term risk for flares, hospitalization, or biologic treatment is significant in POCD following bowel resection. EIMs increase the risk for hospitalization and second intestinal resection.

Hypergammaglobulinemia is a marker of extraintestinal manifestations in pediatric inflammatory bowel disease

BACKGROUND/AIMS The significance of hypergammaglobulinemia as a phenotypic feature of inflammatory bowel disease is unknown. Thus, we aimed to analyze the magnitude and significance of hypergammaglobulinemia in newly diagnosed pediatric inflammatory bowel disease patients. MATERIALS AND METHODS The medical records of 296 pediatric onset inflammatory bowel disease patients who were evaluated from 2002 to 2015 were retrospectively reviewed. Patients with recorded immunoglobulin G (IgG) levels were categorized as either normal or high IgG levels at diagnosis. Baseline characteristics included age at onset, sex, severity indices, laboratory data, extraintestinal manifestations, endoscopic findings, and anthropometric measurements. RESULTS Of 184 subjects [mean age, 13.2±2.8 years; 105 (60%) males] with recorded IgG levels, 129 (70%) had Crohn disease, 46 (25%) had ulcerative colitis, and 9 (5%) had unclassified inflammatory bowel disease. Overall, 46 patients (25%) had hypergammaglobulinemia, including 30 (23%) with Crohn disease, 14 (30%) with ulcerative colitis, and 2 (22%) with unclassified disease. Hypergammaglobulinemia was associated with the female sex (55% vs. 35%; p=0.03) and extraintestinal manifestations (70% vs. 10%; p<0.0001), including arthritis, skin disorders, and primary sclerosing cholangitis but not with arthralgia. It was also associated with corticosteroid induction (68% vs. 45%; p=0.02) and maintenance with an immunomodulator (61% vs. 21%; p=0.0001) after diagnosis. In ulcerative colitis patients, hypergammaglobulinemia was associated with a high pancolitis prevalence (p=0.002). CONCLUSION Hypergammaglobulinemia is a marker of extraintestinal manifestations in pediatric inflammatory bowel disease and may assist in distinguishing arthritis from arthralgia.