Biomarker Panel Rules Out Acute Appendicitis in Low-Risk Kids

August 15, 2013

By Will Boggs, MD

NEW YORK (Reuters Health) Aug 15 - A new biomarker panel may help rule out appendicitis in some children with abdominal pain, an observational study suggests.

"The panel is most useful for those patients with low to moderate or moderately high risk, and is intended to identify those pediatric patients with abdominal pain whose risk of acute appendicitis is low enough that imaging may be deferred in favor of clinical follow-up," Dr. David S. Huckins from Newton-Wellesley Hospital in Newton, Massachusetts told Reuters Health in an email.

Appendicitis is the most common reason for urgent/emergent surgery in the pediatric age group, with more than 75,000 pediatric cases yearly in the U.S.

As many as 50% of children, however, may not have the typical signs and symptoms seen in adults with appendicitis.

Dr. Huckins and colleagues evaluated the diagnostic accuracy of individual plasma biomarkers and combinations of such markers for ruling out acute appendicitis in pediatric patients with abdominal pain whose differential diagnoses included appendicitis.

After an in-depth post hoc analysis of markers and complete blood count values done in conjunction with the study, the researchers arrived at an algorithm that included white blood count (WBC), C-reactive protein (CRP) level, and myeloid-related protein 8/14 complex (MRP 8/14) level.

The overall prevalence of appendicitis among the 503 patients was 28.6% (36% in male patients and 22% in female patients), according to a report online July 29th in the American Journal of Emergency Medicine.

Calculated scores in individual patients ranged from greater than 3 to less than 10 and yielded a negative cutoff of 4. With this cutoff, the biomarker panel gave 96.5% sensitivity, 96.9% negative predictive value, and 0.08 negative likelihood ratio. The specificity was only 43.2%, however.

In patients whose WBC and CRP were normal, the algorithm still provided sensitivity for acute appendicitis of 97.2%, with negative predictive value of 96.8%. Specificity declined to 33.7%, and there were 34 fewer true negatives and one less false negative.

Sensitivity and negative predictive value were somewhat lower for patients with symptoms not exceeding 24 hours (94.4% and 95.1%, respectively) than for patients with symptoms lasting for more than 24 hours (100% and 100%, respectively).

Sixty (32.4%) of 185 CT scans performed were on patients with negative biomarker panel results.

"If these patients were followed clinically rather than referred for immediate CT imaging, this could have potentially reduced CT utilization at initial presentation and the associated risks of radiation exposure by one-third," the researchers say.

"Patients with classic signs and symptoms of acute appendicitis that are considered high risk are not patients for whom this panel should be used," Dr. Huckins said. "The prevalence of true appendicitis in these very high risk patients is too high such that the negative predictive value of the test would be insufficient (negative predictive value diminishes as prevalence rises)."

In high-risk patients, he added, imaging to confirm the diagnosis of appendicitis - or performance of appendectomy -- should not be deferred based on any normal blood test, including this biomarker panel.

"This panel is not approved by the FDA for use in the United States, but is approved for use in the European Union," Dr. Huckins said. "There is an ongoing validation study of this biomarker panel enrolling more than 2,000 patients at more than 20 academic, community, and children's hospitals across the U.S, with results expected near the end of this year or early next year."

Dr. Huckins and four of the other five authors have financial relationships with Venaxis, Inc., which funded the study.


Am J Emerg Med 2013.


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