Selected Summary

Abstract

Summary: This is a retrospective unblinded study evaluating the use of serology (IBD First Step and Confirmatory System; Prometheus Laboratory, San Diego, CA) vs anemia and/or elevated erythrocyte sedimentation rate (ESR) as a screening tool in patients presenting to a single-center pediatric gastroenterology office for symptoms that were suspicious for inflammatory bowel disease (IBD) such as abdominal pain, weight loss, hematochezia, arthralgias, and diarrhea. Two hundred twenty-seven charts were reviewed for patients seen during a 2-year period (September 2002–September 2004), and 210 had adequate information for inclusion. Forty of these 210 patients were ultimately diagnosed with IBD based on clinical, endoscopic, radiological, and pathological interpretations by the gastroenterologist, which resulted in a prevalence of 19% in this population. Twenty-four were diagnosed with Crohn disease, 15 with ulcerative colitis, and 1 with indeterminate colitis. In patients with proven IBD, anemia or elevated ESR was present in 33 (83%) and both were present in 19 (48%) of patients. The First Step IBD serological testing was positive in 29 (73%), with confirmatory markers positive in 24 (60%). Of the 170 patients without the diagnosis of IBD, 134 had a complete blood count and ESR during the evaluation. Only 5 patients (4%) had both anemia and elevated ESR and 35 (26%) had either anemia or elevated ESR. First Step testing was performed in 170 patients without IBD and was positive in 48 (28%), with confirmatory testing positive in 19 (11%). Therefore, the sensitivity of anemia or an elevated ESR was 83% and specificity was 74% with a positive predictive value (PPV) of 94%. The sensitivity was less for patients who had both anemia and elevated ESR, at 48%, with a higher specificity of 96% with a PPV of 86%. The First Step had a sensitivity of 73% and specificity of 72% with a PPV of only 38%. Adding the confirmatory markers (anti–Saccharomyces cerevisiae antibodies, anti–neutrophil cytoplasmic antibodies, or Escherichia coli outer membrane porin C) resulted in a sensitivity of 60%, specificity of 88%, and a PPV of 56%. On further evaluation, presenting symptoms were fairly similar between the IBD and the non-IBD group (abdominal pain in 100% of IBD and 90% in non-IBD; diarrhea in 80% of IBD and 52% of non-IBD) with the exception of rectal bleeding occurring in 70% of the IBD group and only 24% of the non-IBD group. If a patient had more than one symptom, they were more likely to have IBD (abdominal pain and rectal bleeding in 73% of IBD group and 21% of non-IBD; abdominal pain, rectal bleeding, and diarrhea in 65% of IBD and 12% of those without). Comment: The use of serological markers for the identification and classification of patients with IBD has led to some heated debates about their utility, especially in children. This debate has further expanded with the new Prometheus IBD Serology 7. The aim of this study was to evaluate the use of serology vs more routine laboratory evaluation (complete blood count and ESR) as screening tools in a population of patients referred for symptoms associated with IBD. A screening test should be easy to use and cost effective. An ideal screening test should have high enough sensitivity to lead to a low false-negative rate, and a high enough specificity to prevent too many false-positive tests. The negative predictive value (NPV) should be high so that patients with disease are not missed. Previous studies evaluating the sensitivity and specificity of serological testing for predicting IBD have been in populations with high prevalence of the disease (37%–78%) (1–7). This study attempts to address the utility of serological testing in a group of patients with a lower prevalence of IBD. The sensitivity and specificity of a test should not be influenced by the prevalence of the disease in the population, but may be influenced by the population being studied (eg, patients with known disease vs a screening population or adult patients vs pediatric patients). Clinicians, including primary care providers, have been using serological testing as a screening tool in patients presenting with various complaints; however, the PPV and NPV of a test is influenced by the prevalence of the disease, and this had not been previously evaluated in a lower prevalence (ie, screening) group. Reasons to use the test include assisting in the decision to refer to a specialist and, as advocated by Prometheus, “to assess the need for scoping.” (8) Additionally, clinicians may use these tests in patients with known IBD with the goal of differentiating between Crohn disease and ulcerative colitis, especially when surgery is being considered in cases of indeterminate IBD. Prometheus states that the First Step has a sensitivity rate >94% and a specificity rate >90% (8); however, it is unclear in what population this was determined (eg, adults with known IBD) and it is unclear how this applies to the pediatric patient presenting with symptoms suggestive of IBD. This study shows a similar specificity, but the sensitivity was found to be only 60% for anti–S cerevisiae antibodies, anti-neutrophil cytoplasmic antibodies, or E coli outer membrane porin C, and 73% for the First Step. Conversely, the presence of anemia or an elevated ESR was 83% sensitive, which suggests that these tests are less likely to produce a false-negative test than the IBD serological testing. The likelihood ratio for the presence of anemia or elevated ESR as a screening test for IBD is 3.2. The likelihood ratio for a positive serological test (ie, First Step) is 2.6. This suggests that a patient with anemia or elevated ESR is slightly more likely to have IBD than a patient who has a positive serological test result. The likelihood ratio for a patient without anemia or elevated ESR (ie, negative testing) is 0.002 but is 0.375 for those with a negative serological test. Therefore, absence of anemia or elevated ESR is better at ruling out IBD than a negative First Step serological test result. Drawbacks to this study include the retrospective design and the fact that the clinicians were aware of the results of the laboratory results, which may have influenced their clinical decision about diagnosis. However, further testing was undertaken to confirm the diagnosis of IBD. In addition, because these patients were followed up over time, it is implicit that patients without IBD did not develop IBD in that time period. Patients, families, and clinicians alike would like to have a simple, straightforward test that is highly sensitive and specific to determine if a disease is present. Unlike celiac disease, which has highly sensitive and specific serological tests, no such test exists for patients with IBD. It does not appear that the much more expensive serological testing adds much to the clinical diagnosis of patients presenting to the pediatric gastroenterologist with symptoms suggestive of IBD; however, it may be used as a screening (ie, not diagnostic) test given its high NPV. If used in screening, a number of false-positive tests are likely to be found given the lower PPV. Given the findings in this study, the use of serological testing should not be used for diagnosis, but may be useful on a more selective basis. Further studies exploring the role of serological screening for IBD in a primary care setting are needed to evaluate its role in a nonselected population. The clinical diagnosis (combination of history, physical, routine laboratory tests, endoscopy, radiology, and pathology) of IBD was used as the gold standard for comparison in this study and it appears that it remains as such.