What is the negative likelihood ratio for appendicitis in the absence of leukocytosis (elevated white blood cell count) or an elevated C-Reactive Protein (CRP)?

Negative Likelihood Ratio for Appendicitis with Normal Inflammatory Markers

When both leukocytosis and CRP are absent, the negative likelihood ratio for appendicitis is approximately 0.08-0.25, meaning appendicitis cannot be reliably excluded based on normal laboratory values alone. 1, 2

Key Diagnostic Performance

The negative likelihood ratio (LR-) for normal inflammatory markers is insufficient to rule out appendicitis:

• Normal WBC count alone has a negative likelihood ratio of only 0.25, which does not reliably exclude appendicitis 2
• Combined normal WBC and CRP in elderly patients showed 100% negative predictive value in one series of 83 patients, though this finding requires broader validation 1, 3
• In pediatric populations, the APPY1 test panel demonstrated a negative likelihood ratio of 0.06 with 95.1% negative predictive value, superior to standard inflammatory markers alone 1

Critical Clinical Implications

Do not rule out appendicitis based solely on normal inflammatory markers, as this approach leads to missed diagnoses:

• 39.8% of patients with both normal CRP and WBC had confirmed appendicitis on pathology 4
• Early appendicitis may not yet demonstrate laboratory abnormalities, particularly within the first 24 hours of symptoms 2, 4
• The sensitivity of WBC count is only 66.5% and CRP is 77.3%, meaning substantial numbers of true appendicitis cases have normal values 4

Timing Considerations

The diagnostic performance of inflammatory markers varies significantly with symptom duration:

• Before 24 hours: Negative predictive value is only 0.52, making normal labs particularly unreliable early in disease course 4
• 24-48 hours: Negative predictive value improves to 0.65 4
• After 48 hours: Negative predictive value reaches 0.61, but still insufficient to exclude disease 4

Recommended Diagnostic Approach

Clinical findings must drive risk stratification rather than laboratory values alone 2:

• Use validated clinical scoring systems (AIR score or Alvarado score) that incorporate symptoms, physical examination, AND laboratory values together 1
• Intermediate-risk patients require systematic diagnostic imaging regardless of laboratory values 1, 2
• CT scanning remains appropriate even with normal laboratory values when clinical suspicion exists 2
• The neutrophil percentage >75% is the most sensitive individual marker (82% sensitivity) and should be evaluated in all suspected cases 2

Common Pitfalls to Avoid

Never base operative decisions solely on CRP or WBC count 5:

• The false-negative rate for CRP is approximately 3%, meaning some patients with appendicitis will have completely normal values 6
• Clinical judgment combined with imaging remains superior to laboratory-based decision making 5, 4
• In elderly patients specifically, do not base diagnosis on elevated leukocytes and CRP alone, though normal values in this population may be more reassuring 1, 2