Center for Pediatric Inflammatory Bowel Disease

Clinical Studies: Diagnostics

Diagnostic testing for Clostridium difficile in pediatric inflammatory bowel disease should include both toxin A and toxin B

J.E. Markowitz, R.N. Baldassano, P. Mamula, G.W. Telega, H.R. Drott, M. Morris and D.A. Piccoli

Background:

Clostridium difficle is an important cause of symptomatic diarrhea in the pediatric population. In patients with inflammatory bowel disease (IBD), the symptoms associated with C. difficile may be confused with the symptoms of a disease flare. Kader et al (Gastroenterol 1998; 115: 1329-34) demonstrated the inadequacy of single toxin assays in the pediatric IBD population.

Aims

To evaluate the efficacy of single toxin assays in the pediatric IBD population and to assess whether the toxins identified remained consistent on repeated measurements. Subjects in our IBD database who had fecal C. difficile testing performed at The Children's Hospital of Philadelphia from January 1996 to August 1999 were studied. We retrospectively analyzed the relative frequencies of positive assays for C. difficle toxin A alone, toxin B alone and toxins A and B together. Positive specimens from the same patient submitted within 14 days of each other were counted only once.

Results

4437 total specimens were submitted during this time period. Seven hundred specimens were submitted from 273 patients with IBD. One hundred eleven specimens from 81 patients were positive for at least one C. difficle toxin. In this study, 29.7% of IBD patients who had fecal C. difficile testing had at least one positive assay. Thirty-nine specimens were positive for toxin A alone, forty-seven were positive for toxin B alone and twenty-five were positive for toxins A and B. Toxin A assay alone had a false negative rate of 42.3%, while toxin B assay alone had a false negative rate of 35.1%. Twenty-three patients tested positive for the same toxins on subsequent analysis.

Conclusions

Single toxin assays for C. difficile are not adequate for initial or follow-up diagnosis of C. difficile infection. The toxin isolated in the first positive specimen was not predictive of the toxin found in subsequent positive specimens. In patients with IBD, false-negative assays for C. difficile could result in inappropriate and potentially harmful treatments. Submitted-AGA abstracts. May 2000

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Small Bowel Radiography is Inadequate for the Diagnosis or Exclusion of Pediatric Inflammatory Bowel Disease

Robert N. Baldassano, MD, John Tung, MD, Eduardo Ruchelli, MD, Soroosh Mahboubi, MD, Aimee E. Christian, PhD and Eric S. Maller, MD

Objective

The aims of our study were: 1.) To determine whether a small bowel follow through (BaFT) was a valuable test for the primary care provider to obtain during the initial evaluation of a child with symptoms consistent with Crohn's disease (CD). 2.) To determine the sensitivity and specificity of the BaFT when compared to the "gold standard" of colonoscopy and ileal biopsies in the diagnosis of small bowel (terminal ileal) CD in the pediatric population.

Study Design

We retrospectively analyzed the records of 164 patients who had colonoscopy with ileal biopsies at the Children's Hospital of Philadelphia between 1994 and 1996. BaFT, in addition to colonoscopy was done in 84 of the 164 patients. Blinded from the clinical diagnoses, a radiologist and pathologist analyzed the radiographs and biopsies, respectively. Chi-square analysis was done to determine association between the two analytical methods.

Results

Of the 84 patients whose small bowel radiographs and TI biopsies were reviewed, 36 (43%) had CD, 11 (13%) had ulcerative colitis (UC), 5 (6%) had indeterminant colitis (IND) and 32 (38%) were normal. Using BaFT as a screening test for the diagnosis of TI CD resulted in a sensitivity of 45% (17/37) and a specificity of 96% (45/47). The positive predictive value was calculated to be 90% (17/19), whereas the negative predictive value was calculated to be 70% (45/65).

Conclusions

The child who presents with signs and symptoms of CD should undergo a colonoscopy and ileoscopy in order to make the diagnosis. A BaFT is important in the evaluation of CD, but a negative or normal study should not be used alone to rule out CD in a child with symptoms suggestive of CD.

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Evaluation of cytokine levels from the intestinal mucosa to be used to identify ulcerative colitis in pediatric patients

K. Brown, J. Kriss, M. Mascarenhas, D. Piccoli, E. Rand, C. Liacouras, E. Maller, R. Verma, A. Mulberg, D. Broussard, B. Haber, R. Baldassano

This study was sponsored by the Edmunds Family Fund for the Study of Pediatric Ulcerative Colitis

Ulcerative colitis (UC) is a chronic, relapsing disorder of unknown immunoregulatory dysfunction. Most studies of IBD pathogenesis to data involve adults with long-standing disease on immunomodulatory therapies. However, because the disease usually begins in the second decade of life, these studies may not help our understanding of the pathogenesis of new or early mucosal lesions.

An assessment of the intestinal cytokine profile of newly diagnosed pediatric patients with UC was undertaken as an initial step in understanding the mechanisms of immunodysregulation. Intestinal biopsy and colonic specimens from children with UC were cultured for 24-hours in media and cytokine profiles (i.e. INF-(, IL-2, IL-4, IL-6, IL-13) from culture supernatants were evaluated by enzyme-linked immunosorbent assay (ELISA). The presence of IL-6(>750 pg/mL) predicted histology consistent with UC. Levels of IL-6 closely paralleled histologic disease severity: mild (2100 pg/mL), moderate (12,000 pg/mL) or severe (42,000 pg/mL). The other cytokines evaluated were less sensitive and specific for IBD.

This study outlines graded production of the proinflammatory cytokine IL-6 in the intestinal lamina propria of children with UC. IL-6 production may be a marker of a predominant THELPER2 cells responses or implicate macrophages as important antigen-presenting cells in generating the early mucosal lesions in pediatric IBD patients.

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