Title : Appendicitis biomarker review
Abstract:
Acute appendicitis is the leading cause of emergency abdominal surgery worldwide, affecting approximately 7% of the population at some stage of life, with perforation rates reaching up to 20% underscoring the importance of accurate and timely diagnosis.
Traditionally, clinicians have used WBC and CRP to support clinical suspicion. However, both have suboptimal accuracy, especially in distinguishing uncomplicated from complicated appendicitis. CRP, a common marker, exhibits a sensitivity of 46– 94% and specificity of 32–84%, with a high negative predictive value that can aid in ruling out severe disease; however, its overall sensitivity and specificity are limited. Similarly, WCC alone shows little predictive value in distinguishing uncomplicated from complicated appendicitis, and elevated levels of WCC and CRP are nonspecific, correlating with various differential diagnoses. Traditional clinical markers such as temperature have also demonstrated limited relevance, especially in children under five, where elevated temperature is not statistically significant between disease severities.
In addition, for certain circumstances we rely on imaging for diagnosis. However, these tools have notable limitations: ultrasound sensitivity is around 71.8% with a specificity of 44.8%, while CT sensitivity ranges from 28% to 95%, and specificity from 71% to 100%. This variability emphasises the need for reliable biomarkers to improve diagnostic accuracy, particularly given that a third of cases present atypically and that older patients often experience more complicated disease courses compounded by co-morbidities.
Ideally we would utilise inexpensive, readily available indices derived from the complete blood count, such as neutrophil-to-lymphocyte ratio (NLR), platelet-tolymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-platelet ratio (NPR), and systemic immune-inflammation index (SII). These ratios reflect different aspects of the systemic inflammatory response and have been evaluated across paediatric, adult, and special populations. They are cost-effective, easily accessible, and reproducible, providing objective measures to improve diagnosis, assess severity, and monitor patients managed conservatively. These biomarkers have the potential to stratify risk effectively, guide management decisions—whether surgical or conservative—and ultimately reduce negative appendectomy rates.
While appendectomy remains the gold standard treatment, accurate diagnosis before surgery continues to challenge clinicians. Misdiagnosis leads either to delayed treatment and perforation or to unnecessary appendectomies, both of which carry morbidity.
This review synthesises current evidence on these novel biomarkers, comparing their diagnostic accuracy, strengths, and limitations, while also highlighting gaps in the literature. The overall aim is to enhance diagnostic precision and patient outcomes in appendicitis management.
