Neera Gupta

Presentation and Disease Course in Early- Compared to Later-Onset Pediatric Crohn’s Disease

BACKGROUND:The relationship between the age at diagnosis and disease course is poorly defined in children with Crohns disease (CD). We examined the presentation and course of disease in patients 0–5 compared to 6–17 yr of age at diagnosis.METHODS:We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient.RESULTS:In total, 98 patients (9.9%) were of 0–5 yr of age at diagnosis. The mean follow-up time was 5.6 ± 5.0 yr in the younger group and 3.3 ± 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0–5 yr of age group (P < 0.001). The 6–17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0–5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6–17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6–17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6–17 yr of age patients.CONCLUSIONS:The 6–17 yr of age patients with CD appear to have a more complicated disease course compared to 0–5 yr of age children. The 0–5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.

Gender Differences in Presentation and Course of Disease in Pediatric Patients With Crohn Disease

OBJECTIVE. The objective of this study was to determine gender differences in pediatric patients with Crohn disease. METHODS. We conducted a retrospective cohort study of 989 consecutive pediatric patients (566 boys, 423 girls) who had Crohn disease (aged 0 to 17 years at diagnosis) by using the Pediatric IBD Consortium Registry. Uniform data were analyzed to compare the presentation and course of disease according to gender. RESULTS. Median follow-up time was 2.8 years. Mean ± SD age at diagnosis of inflammatory bowel disease (11.5 ± 3.8 years) did not differ by gender. Compared with boys, girls had a higher prevalence of mouth sores at symptom onset and a higher prevalence of hypoalbuminemia at the time of diagnosis. Location of disease did not differ by gender. A higher proportion of girls had abnormal anti–outer membrane porin of Escherichia coli levels compared with boys. Girls were at increased risk for erythema nodosum/pyoderma gangrenosum and decreased risk for growth failure compared with boys. CONCLUSIONS. Girls appear to have an overall more severe course of disease; however, boys are at increased risk for developing growth failure. Disease course and the impact of disease severity on growth according to gender in pediatric Crohn disease require prospective study.

Postoperative Outcome of Colectomy for Pediatric Patients With Ulcerative Colitis

Background: Few studies have reported on the surgical outcomes of colectomy in pediatric patients with ulcerative colitis (UC). Patients and Methods: We conducted a retrospective chart review of all pediatric patients diagnosed with UC who underwent colectomy at UCSF between 1980 and 2005 to identify early (within 30 days) and later complications of surgery. Results: Complete medical records were available for 31 patients [12.4 ± 3.3 (range 6–19) years] with UC who underwent colectomy at UCSF Childrens Hospital. Total colectomy with ileal pouch anal anastomosis (IPAA) was performed in 21 of the 31 patients (12 without diverting ileostomy). Five of the 31 patients had an initial colectomy with IPAA and J-pouch performed later; 4 had an initial subtotal colectomy for urgent indications. Only one of 31 had IPAA with S-pouch. The median number of early postoperative complications was 1.0; 4 required additional surgery to treat complications. The most common early complications were small intestinal obstruction in 6 (19%) and wound infection in 4 (13%). Preoperative medications included corticosteroids in 25 (81%), 6-mercaptopurine/azathioprine in 10 (32%), and 5-aminosalicylates in 19 (61%). Medication exposure was not related to postoperative complications. Late complications included pouchitis in 12 (39%), anastomotic, anal, or rectal strictures in 5 (16%), and fistulas in 5 (16%); 1 (3%) was subsequently diagnosed as having Crohn disease. Conclusions: Postcolectomy morbidity is common among pediatric patients with UC. Preoperative medications were not associated with postoperative complications. Investigations to determine preoperative factors affecting surgical outcomes and long-term satisfaction following this surgery in a large pediatric cohort are needed.

Incidence of stricturing and penetrating complications of Crohn's disease diagnosed in pediatric patients

Background: The development of disease complications is poorly characterized in pediatric patients with Crohns disease (CD). Methods: We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age 0–17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry. Results: Mean age at diagnosis was 11.5 ± 3.8 (standard deviation) years. Median follow‐up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications). Conclusions: Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patients risk for the development of complicated disease and to determine optimal treatment regimens. (Inflamm Bowel Dis 2009;)

Sex Differences in Statural Growth Impairment in Crohn’s Disease: Role of IGF-1

Background: Growth impairment in Crohns disease (CD) is more common in males than females for unknown reasons. Since insulin‐like growth factor‐1 (IGF‐1) is important for statural growth, we hypothesized that IGF‐1 levels are lower in males with CD. Methods: Sex differences in hormone Z‐scores based on chronological age (CA‐Z) and bone age (BA‐Z) were examined in a cross‐sectional study of 82 CD patients <21 years of age (43% female). Results: IGF‐1 CA‐Z and BA‐Z‐scores were 0.50 units (P = 0.04) and 1.24 units (P = 0.003) lower in males. Mean bone age (12.2 years) was lower than chronological age (13.1 years) (P < 0.0001). Erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and albumin did not differ by sex (P ≥ 0.08), but were associated with IGF‐1 CA‐Z and BA‐Z‐scores (P ≤ 0.02). Insulin‐like growth factor binding protein‐3 (IGFBP‐3) CA‐Z and BA‐Z‐scores were 0.71 units (P = 0.004) and 1.26 units (P < 0.001) lower in males. Inflammatory markers were correlated with sex hormone CA‐Z and BA‐Z and pituitary hormone BA‐Z‐scores in males (P ≤ 0.03), but not females (P ≥ 0.25). IGF‐1 BA‐Z‐scores were positively associated with height BA‐Z‐scores (P = 0.03). Mean height BA‐Z‐scores were lower in males (P = 0.03). Conclusions: Lower IGF‐1 levels in males may explain sex differences in growth impairment in CD. Inflammation appears to more adversely affect hormone levels and statural growth in males. Prospective longitudinal studies are needed to further clarify the role of IGF‐1 in sex differences in statural growth impairment in pediatric CD. (Inflamm Bowel Dis 2011;)

Growth Hormone Treatment for Growth Failure in Pediatric Patients with Crohn's Disease

OBJECTIVE To investigate the effect of human growth hormone (GH) injections on growth velocity in growth-impaired children with Crohns disease (CD). STUDY DESIGN Ten children and adolescents (mean age, 12.6 +/- 4.5 years; 6 males) with CD and poor height growth were treated with open-label recombinant GH, 0.043 mg/kg/day administered via subcutaneous injection, for 1 year. Patients were retrospectively matched with untreated patients (3 comparisons per case) by race, age, sex, and baseline height. Primary endpoint was height velocity; secondary endpoints were disease activity, body composition, and bone density determined by dual-energy x-ray absorptiometry scan. RESULTS Mean height velocity increased by 5.33 +/- 3.40 (mean +/- standard deviation) cm/year in the GH-treated patients during the year of GH treatment, compared with 0.96 +/- 3.52 cm/year in the comparison group (P = .03). Height z-score increased by 0.76 +/- 0.38 in the treated group, compared with 0.16 +/- 0.40 in the comparison group (P < .01), and weight z-score increased by 0.81 +/- 0.89 in the treated group, compared with 0.00 +/- 0.57 in the comparison group (P < .01). Bone density revealed an increase of 0.31 +/- 0.33 in the lumbar spine z-score (P = .03 vs baseline). CONCLUSIONS GH treatment increases height velocity and may enhance bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is needed to evaluate the ultimate impact of GH treatment.

Determination of bone age in pediatric patients with Crohn's disease should become part of routine care†

Background:Impaired growth and delayed puberty are common in pediatric Crohns disease (CD). Bone age (BA) is important for interpretation of statural growth. Our aims were to 1) determine the distribution of BA-Z scores; 2) identify clinical factors associated with BA-Z scores; and 3) compare anthropometric Z scores based on chronological age (CA) (CA-Z) versus BA-Z in pediatric CD. Methods:CD patients ⩽CA 15 in females and 17 years in males were enrolled in a cross-sectional study. BA was determined with left hand/ wrist x-ray. In all, 49 patients (65% male; 84% Caucasian; mean CA 13 years) examined between January 2007 and July 2009 qualified for the study. Results:Mean BA-Z score was −1.40 ± 1.50 (standard deviation). 41% had BA-Z score < −2.0. Mean BA-Z scores were lower in females (P = 0.02), Caucasians (P = 0.006), Tanner stage 1-3 children (P = 0.004), and patients with colonic disease (P = 0.0006), past corticosteroid exposure (P = 0.01), current azathioprine/6-mercaptopurine treatment (P = 0.003), or lower height (P = 0.006), weight (P < 0.001), or body mass index (BMI) (P = 0.01) CA-Z scores. Mean height, weight, and BMI BA-Z scores were 0.73 units (P < 0.0001), 0.51 units (P < 0.0001), and 0.23 units (P < 0.0001) greater than mean height, weight, and BMI CA-Z scores. Conclusions:Low BA occurs frequently in CD. Determination of BA should become the standard of care in pediatric CD patients, allowing clinically meaningful interpretation of growth in the context of skeletal maturation, leading to improved treatment recommendations, as growth is a dynamic marker of disease status. Prospective longitudinal studies are required to clarify determinants of BA and patterns of BA advancement in CD.

Predictors of proctocolectomy in children with ulcerative colitis.

Objectives: Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database. Methods: Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging. Results: Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 ± 4.4 years in both boys and girls. Average follow-up was 6.8 (±4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio [HR] 2.55, 99% confidence interval [CI] 1.21–5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15–17.04) at time of diagnosis and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25–2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90–9.57) or tacrolimus (HR 3.66, 99% CI 1.60–8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery. Conclusion: Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis.

Inducible ventricular flutter and fibrillation predict for arrhythmia occurrence in coronary artery disease patients presenting with syncope of unknown origin.

Ventricular Fibrillation and Syncope. Introduction: Ventricular fibrillation and ventricular flutter (cycle length ≤230 msec) induced at electrophysiologic studies are thought to be nonspecific findings in patients presenting with syncope of unknown origin. However, there are limited data on the prognosis of these patients in long‐term follow‐up.

Report of the CCFA Pediatric Bone, Growth and Muscle Health Workshop, New York City, November 11-12, 2011, With Updates

Abstract:Growth retardation, delayed puberty, decreased bone mass, altered bone architecture, hypovitaminosis D and skeletal muscle mass deficits are common in children with inflammatory bowel diseases. The Crohn’s and Colitis Foundation of America sponsored a multidisciplinary workshop on the subject of Bone and Skeletal Growth in Pediatric IBD, held in New York City in November 2011. The topic of the workshop was a key recommendation of the Foundations Pediatric Challenges meeting in 2005. The Litwin Foundation provided a generous grant to support this crucial research and workshop through the CCFA. The workshop featured 15 presentations by researchers from the United States, Canada, Switzerland, Germany, and the United Kingdom and a number of posters elucidating diverse aspects of the problem of growth retardation and compromised bone health in pediatric Crohns disease and ulcerative colitis. The workshop comprised original, basic, and clinical research and relevant reviews of underlying genetics, molecular biology, endocrinology, immunology, and bone physiology research. Investigators funded by CCFA and the Litwin Family Foundation are marked by an asterisk after their name in the text. Workshop presentations fell under 3 broad categories: “Mechanisms of Suppression and Growth of Bone Cell Function by Inflammation,” “Impact of IBD on Growth and Bone Health,” and “Approaches to Address Growth Failure and Low Bone Mass in Children with IBD,” summarized herein. We have cited the publications that resulted from this granting mechanism in the appropriate section and references for pertinent updates on each topic.