Objectives: Appendicitis can be a diagnostic dilemma in children. Current misdiagnosis rates in children can range as high as 57%. Accurate diagnosis of appendicitis is based upon a variety of clinical scoring systems, traditional lab biomarkers, radiological imaging studies and surgical consultations. Traditional biomarkers provide varied degrees of accuracy and predictability based on duration of symptoms, and cut-off value used. Investigators have researched several novel biomarkers, which may aid in increasing the diagnostic accuracy of traditional biomarkers with the goal of reducing CT utilization and subsequent radiation exposure risks. Calprotectin, a biomarker associated with intestinal mucosa inflammation maybe useful. What is the utility of calprotectin in the diagnosis of acute appendicitis in children with abdominal pain?
Methods: An exhaustive search was conducted through the use of Medline/Ovid, Web of Science, CINAHL, Evidence Based Medicine Review Multifile, and Google Scholar using the keywords: calprotectin, myeloid related protein(MRP 8/14), S100 proteins and appendicitis. Relevant articles were assessed for quality using GRADE. A search on the NHI clinical trials site revealed one ongoing trial related to the use of calprotectin as part of a combination biomarker panel evaluating the panels’ diagnostic accuracy in ruling out acute appendicitis in children with abdominal pain.
Results: Two studies met inclusion criteria and were included in this systematic review. A prospective, blind comparison, to a gold standard study with 503 participants that demonstrated a 3-marker panel of WBC, CRP, and calprotectin showed high sensitivity, high negative predictive value (NPV), and low negative likelihood ratios for acute appendicitis. In comparison, a combination of WBC less than 10k/ul and normal CRP had similar sensitivity and negative likelihood ratios, but reduced specificity and 14% more patients identified as false positive for acute appendicitis. A second prospective, blind comparison to a gold standard, pilot study with 176 participants demonstrated that while normal calprotectin levels showed high sensitivity and high NPV; specificity was low at negative threshold, and a normal WBC count performed better overall.
Conclusion: Calprotectin in combination with traditional inflammatory biomarkers WBC and CRP offers some benefit in the reduction of false positive test results in children with abdominal pain at sufficient low risk for appendicitis; further diagnostic radiological testing may be avoided.
Key Words: Children, appendicitis, calprotectin, MRP 8/14, S100 proteins, human
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