Normal inflammatory markers and acute appendicitis: a national multicentre prospective cohort analysis
Authors: de Jonge J. , Scheijmans J. C. G. , van Rossem C. C. , van Geloven A. A. W. , Boermeester M. A. , Bemelman W. A. ,   on behalf of the Snapshot Appendicitis Collaborative Study group, Van Acker G. J. , Akkermans B. , Akkersdijk G. J. , Algie G. D. , Allema J. H. , Andeweg C. S. , Appeldoorn N. , van Baal J. G. , den Bakker C. M. , Bartels S. A. , van den Berg C. , Boekestijn B. , den Boer F. C. , Boerma D. , van den Boom A. L. , Boute M. C. , Bouwense S. A. , Bransen J. , van Brussel F. A. , Busch O. R. , de Castro S. M. , Cense H. A. , Croese C. , van Dalen T. , Dawson I. , van Dessel E. , Dettmers R. , Dhar N. , Dohmen F. Y. , van Dongen K. W. , van Duijvendijk P. , Dulfer R. R. , Dwars B. J. , Eerenberg J. P. , van der Elst M. , van den Ende E. , Fassaert L. M. , Fikkers J. T. , Foppen J. W. , Furnee E. J. , Garssen F. P. , Gerhards M. F. , van Goor H. , de Graaf J. S. , Graat L. J. , Groot J. , van der Ham A. C. , Hamming J. F. , Hamminga J. T. , van der Harst E. , Heemskerk J. , Heijne A. , Heikens J. T. , Heineman E. , Hertogs R. , van Heurn E. , van den Hil L. C. , Hooftwijk A. G. , Hulsker C. C. , Hunen D. R. , Ibelings M. S. , Klaase J. M. , Klicks R. , Knaapen L. , Kortekaas R. T. , Kruyt F. , Kwant S. , Lases S. S. , Lettinga T. , Loupatty A. , Matthijsen R. A. , Minnee R. C. , Mirck B. , Mitalas L. , Moes D. , Moorman A. M. , Nieuwenhuijs V. B. , Nieuwenhuijzen G. A. P. , Nijk P. D. , Omloo J. M. , Ottenhof A. G. , Palamba H. W. , van der Peet D. L. , Pereboom I. T. , Plaisier P. W. , van der Ploeg A. P. , Raber M. H. , Reijen M. M. , Rijna H. , Rosman C. , Roumen R. M. , Scmitz R. F. , van der Velden A. P. Schouten , Scheurs W. H. , Sigterman T. A. , Smeets H. J. , Sonnevled D. J. , Sosef M. N. , Spoor S. F. , Stassen L. P. , van Steensel L. , Stortelder E. , Straatman J. , van Susante H. J. , Suykerbuyk de Hoog D. E. , Terwisscha van Scheltinga C. , Toorenvliet B. R. , Verbeek P. C. , Verseveld M. , Volders J. H. , Vriens M. R. , Vriens P. W. , Vrouenraets B. C. , van de Wall B. J. , Wegdam J. A. , Westerduin E. , Wever J. J. , Wijfels N. A. , Wijnhoven B. P. , Winkel T. A. , Zeillemaker A. M. van der Zee D. C. , Zietse C. 
Published: April 2021

Abstract
Purpose
For the diagnosis of acute appendicitis, the combination of clinical and laboratory variables achieves high diagnostic accuracy. Nevertheless, appendicitis can present with normal laboratory tests of inflammation. The aim of this study was to investigate the incidence of normal inflammatory markers in patients operated for acute appendicitis.

Methods
This is an analysis of data from a prospective, multicentre SNAPSHOT cohort study of patients with suspected acute appendicitis. Only patients with histopathologically proven acute appendicitis were included. Adult patients with acute appendicitis and normal preoperative inflammatory markers were explored further in terms of abdominal complaints, preoperative imaging results and intraoperative assessment of the degree of inflammation and compared to those with elevated inflammatory markers.

Results
Between June and July 2014, 1303 adult patients with histopathologically proven acute appendicitis were included. In only 23 of 1303 patients (1.8%) with proven appendicitis, both preoperative white blood cell count and C-reactive protein levels were normal. Migration of pain was reported less frequently in patients with normal inflammatory markers compared to those with elevated inflammatory marker levels (17.4% versus 43.0%, p = 0.01). Characteristics like fever, duration of symptoms and localized peritonitis were comparable. Only 4 patients with normal inflammatory markers (0.3% overall) had complicated appendicitis at histopathological evaluation.

Conclusion
Combined normal WBC and CRP levels are seen in about 2 per 100 patients with confirmed acute appendicitis and can, although rarely, be found in patients with complicated appendicitis.