A Simple Blood Test for Appendicitis?
Biomarkers are hot stuff these days. Knowing that the clinical diagnosis of appendicitis, especially in young children, is very inaccurate, any improvement to decrease complications and unnecessary procedures would be welcome. But, we're not there yet.
Source: Benito J, Acedo L, Medrano L, et al. Usefulness of new and traditional serum biomarkers in children with suspected appendicitis. Am J Emerg Med. 2016;34(5):871-876; doi:10.1016/j.ajem.2016.02.011. See AAP Grand Rounds commentary by Dr. Erin Bennett (subscription required).
PICO Question: Among children 2-14 years of age with suspected appendicitis, are there biomarkers that accurately predict the absence of acute appendicitis?
Study type: Diagnosis
Study design: Prospective cohort
This article took me a while to figure out, primarily because the report itself obscured some of the information I was most interested in. However, I think I finally dissected the key items of interest.
This study was carried out at a tertiary academic hospital in Spain, complete with 24/7 pediatric imaging and consultations (ergo results may not apply to community hospitals in the US or elsewhere). Over an approximate 18-month period, the authors accumulated 185 2 - 14 year old children evaluated for appendicitis in their emergency department to look at traditional lab and imaging studies compared to a newer combination test called APPY1, which is a biomarker panel that combines total white blood cell count, C-reactive protein, and calprotectin into 1 yes/no answer. Apparently the details of what constitutes a yes or no answer is proprietary - I couldn't sort that out from the article's description of the test.
The authors reported the APPY1 test had 97.8% sensitivity (CI 92.2 - 99.4), a specificity of 40.6% (31.3 - 50.5), and a negative predictive of value 95.1% (83.9 - 98.7). To assess the clinical utility of those numbers, one needs to step back and decide how such a test could be useful in clinical practice. Clinicians can improve on appendicitis management by eliminating the need for expensive and difficult tests, such as ultrasonography (highly dependent on skill of the person operating the transducer, not easily managed 24/7 in the typical hospital) or abdominal CT scan (radiation exposure, maybe not as accurate as a well-done sonogram), while not missing anyone with appendicitis.
Have you heard of SnNOut? A highly sensitive test (like APPY1) can help rule out a particular diagnosis, but often at the expense of low specificity (also like APPY1). That's not necessarily a bad thing if you could eliminate obtaining a sonogram or CT scan without missing any cases of appendicitis. You'd save a child from unnecessary imaging studies and surgical procedures. So, APPY1 might be useful for this purpose, but a lot more work needs to be done.
The study had a few drawbacks, most of which the authors realized. First, the study used a convenience sample. During the study period, this institution actually had 840 children with suspected appendicitis present for treatment, but study enrollment only occurred when the study investigators were present. So, only about 20% of the target population was enrolled, not very good (plus the authors don't tell us how many were approached for enrollment and refused). That could introduce unexpected bias.
The authors had a good "gold standard" for appendicitis diagnosis of children who underwent appendectomy: the histopathology of the appendix. However, for those children who didn't have appendectomy, the gold standard was review of hospital records for 15 days to see if they came back for care, or telephone follow up. About 10% of these patients were lost to follow up. We don't know if any of those subsequently sought care at another institution for appendicitis, nor do we know anything about outcomes beyond 15 days of the ED visit.
The third drawback is that only 11% of the patients were under 6 years of age, so we have little idea of how this test performs in the patient population most difficult to diagnose by other means.
I said at the top that biomarkers are hot now; in fact, they have been for at least a decade, as advances in molecular medicine guide product development. A couple of web sites are great for those who desire more information. Check the Biomarkers Consortium of the Foundation for the National Institutes of Health website as well as the U.S. Food and Drug Administration's Biomarker Qualification Program.
In spite of the limitations above, this study is a step forward in the use of biomarkers for appendicitis, particularly if APPY1 is inexpensive and easy to perform in the outpatient setting.
