Can normal inflammatory markers rule out acute appendicitis? The reliability of biochemical investigations in diagnosis

Abstract

Background: Acute appendicitis is a common general surgical condition where diagnosis is predominantly clinical, with the aid of adjunct investigations. This study reviews the relationship between normal and elevated biochemical inflammatory markers, duration of symptoms and proven appendicitis. Methods: A multicentre prospective observational study was performed across 27 centres and included a total of 949 patients with clinical suspicion of appendicitis, who had both white cell count (WCC) and C-reactive protein (CRP) recorded and underwent appendicectomy. Results: A total of 90.4% of patients with raised WCC and CRP had appendicitis with a positive predictive value (PPV) of 0.9 and negative predictive value (NPV) of 0.4. Sensitivity and specificity of elevated WCC (sensitivity 66.5%, specificity 66.0%) and elevated CRP (sensitivity 77.3%, specificity 52.0%) lie within ranges identified by previous studies. A total of 39.8% of patients with normal CRP and WCC had appendicitis. Sensitivity and PPV for patients with elevated inflammatory markers were high until 48 h of symptoms (sensitivity 94%, PPV 0.87). NPV was elevated after 24 h (NPV 0.65 in patients with 24-48 h of symptoms, and 0.61 after 48 h), whilst those with symptoms less than 24 h had a lower NPV of 0.52. Conclusion: Whilst elevated inflammatory markers are a helpful aid in the diagnosis of appendicitis, they should not be relied on by themselves. Nor can normal inflammatory markers be used to exclude appendicitis, even in those with prolonged duration of symptoms. The diagnosis of appendicitis should be guided by a combination of clinical judgement with the assistance of inflammatory markers.

The Use of Inflammatory Markers to Rule Out Acute Appendicitis in Pediatrics

“…The inflammatory markers in diagnosing acute appendicitis have a wide variety in sensitivity and specificity. A study conducted by JJY Kim shows that WBC has lower sensitivity than CRP [ 6 ], which goes with our finding. Many other studies show the opposite, with WBC having higher sensitivity and specificity [ 7 - 9 ].…”

Best evidence topic: Can acute appendicitis manifest with normal inflammatory markers?

“… NO matching between duration of symptoms and level of inflammatory markers Jason J. Y. Kim. et al [ 4 ] (2019), ANZ Journal of Surgery Australia Multicentre, prospective, observational study (Level III) 949 patients in 27 centres underwent appendectomy for suspected AA between June and October 2016 Age: adult + paediatrics 749 had histology proven AA patients with normal inflammatory markers in relation to symptoms: Group A – normal WCC/CRP <24 HR (n = 33) Group B – normal WCC/CRP 24-48HR (n = 51) Group C normal WCC/CRP > 48HR (n = 44) Percentage of patients with normal WCC + CRP among those who have histology proven AA A: 48.5% B: 35.3% C: 38.6% Over all 39.8% patients with normal WCC + CRP have histology proven AA Highest false negative result reported in literature Risk of selection bias: only including patients who have undergone Appendicectomy Variable inflammatory marker concentration cut-off values used in previous studies, can make conclusions difficult Lack of blinding of recruiting doctors. PG Vaughan-Shaw.…”

“…The conclusion was: no WCC count or CRP level can safely and sufficiently confirm or exclude the suspected diagnosis of acute appendicitis in patients who present with abdominal pain of 5 days or less in duration. Jason J. Y. Kim et al [ 4 ] recently published a multicentre prospective observational study in 2019 to evaluate the relationship between normal IM, duration of symptoms, and proven appendicitis. Of interest was the finding that a total of 38.9 of patients with normal CRP and WCC had appendicitis.…”

The Role of Neutrophil-Lymphocyte-Ratio (NLR) and Platelet-Lymphocyte-Ratio (PLR) as a Biomarker for Distinguishing Between Complicated and Uncomplicated Appendicitis

“…However, it is worth noting as, with all these markers, the timing of the test can significantly alter its sensitivity and specificity. Tests done within hours of the onset of symptoms can be normal only to rise in the hours and days ahead [ 20 ]. Given the inherent variability in the timing of presentation to secondary care with respect to their onset of symptoms, it is important to interpret these tests in the context of the presentation.…”