Inflammatory Biomarkers and Their Combinations for Early Identification of Complicated Appendicitis: A Prospective Observational Diagnostic Accuracy Study and Receiver Operating Characteristic Analysis.

Johnson Sona; Varsha Jose; Varughese Padinjattadathu George

doi:10.51168/6rp7md28

Authors

Sona Johnson Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India
Varsha Jose Associate Professor, Department of Pathology, Al-Azhar Medical College, Thodupuzha, Idukki, Kerala, India.
Varughese Padinjattadathu George Assistant Professor, Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India.

DOI:

https://doi.org/10.51168/6rp7md28

Keywords:

Acute appendicitis, Complicated appendicitis, C-reactive protein, Total leukocyte count, Neutrophil percentage, Lymphocyte percentage, Diagnostic accuracy, ROC analysis, Inflammatory biomarkers

Abstract

Background:

Distinguishing uncomplicated from complicated appendicitis is clinically important because delayed recognition of complicated disease may increase morbidity. This study evaluated the diagnostic performance of routine inflammatory biomarkers and selected combinations for identifying complicated appendicitis.

Methods:

A prospective observational diagnostic accuracy study was conducted at a tertiary care hospital in Idukki district, Kerala, India, during a one-year study period from January 2025 to December 2025. Patients undergoing appendicectomy for clinically suspected acute appendicitis were evaluated. Complicated appendicitis was defined as perforation, gangrene, or acute peritonitis. Preoperative total leukocyte count (TLC), neutrophil percentage, lymphocyte percentage, and C-reactive protein (CRP) were analyzed. Group comparisons, binary diagnostic accuracy measures, and receiver operating characteristic (ROC) analysis were performed.

Results:

Among 191 patients, 74 (38.7%) had complicated appendicitis, and 117 (61.3%) had uncomplicated appendicitis. Complicated appendicitis was associated with older age and longer symptom duration. TLC, neutrophil percentage, and CRP were higher, whereas lymphocyte percentage was lower, in complicated cases (all p<0.001). In binary analysis, CRP and lymphocyte percentage <13% each had 64.8% sensitivity; CRP had the highest specificity (65.1%) and accuracy (65.0%) among individual markers. Combined markers increased specificity, reaching 86.7% for CRP plus neutrophil percentage plus TLC, but sensitivity decreased to 31.5%. ROC analysis showed the greatest discrimination for CRP (AUC 0.842, 95% CI 0.781–0.898), followed by TLC (AUC 0.706, 95% CI 0.626–0.780) and neutrophil percentage (AUC 0.674, 95% CI 0.595–0.750).

Conclusion:

CRP demonstrated the strongest discriminatory performance, while combined markers improved specificity at the cost of sensitivity. Routine inflammatory biomarkers may support clinical risk stratification but should not be used alone to screen for complicated appendicitis.

Recommendations

CRP, TLC, neutrophil percentage, and lymphocyte percentage may be considered adjunctive investigations alongside clinical assessment for early risk stratification of complicated appendicitis.

Author Biographies

Sona Johnson, Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India

is an MBBS graduate affiliated with the Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India. She is involved in clinical pathology services, medical education, and academic activities. Her academic interests include diagnostic pathology and clinical research.
Varsha Jose, Associate Professor, Department of Pathology, Al-Azhar Medical College, Thodupuzha, Idukki, Kerala, India.

is an MBBS, MD graduate and Associate Professor in the Department of Pathology, Al-Azhar Medical College, Thodupuzha, Idukki, Kerala, India. She is involved in undergraduate and postgraduate medical education, diagnostic pathology services, and academic research. Her professional interests include surgical pathology, diagnostic pathology, and clinical research.
Varughese Padinjattadathu George, Assistant Professor, Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India.

is an MBBS, MD graduate and Assistant Professor in the Department of Pathology, Malankara Orthodox Syrian Church Medical College (MOSC Medical College), Kolenchery, Kerala, India. He is involved in medical teaching, diagnostic pathology services, and academic activities. His professional interests include diagnostic pathology and clinical research.

References

1. Gorter RR, Eker HH, Gorter-Stam MAW, Abis GSA, Acharya A, Ankersmit M, et al. Diagnosis and management of acute appendicitis: EAES consensus development conference 2015. Surg Endosc. 2016;30(11):4668–4690. doi:10.1007/s00464-016-5245-7.

2. Di Saverio S, Podda M, De Simone B, Ceresoli M, Augustin G, Gori A, et al. Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines. World J Emerg Surg. 2020;15:27. doi:10.1186/s13017-020-00306-3.

3. Moris D, Paulson EK, Pappas TN. Diagnosis and management of acute appendicitis in adults: A review. JAMA. 2021;326(22):2299–2311. doi:10.1001/jama.2021.20502.

4. Snyder MJ, Guthrie M, Cagle S. Acute appendicitis: Efficient diagnosis and management. Am Fam Physician. 2018;98(1):25–33.

5. Teoule P, Laffolie J, Rolle U, Reissfelder C. Acute appendicitis in childhood and adulthood. Dtsch Arztebl Int. 2020;117(45):764–774. doi:10.3238/arztebl.2020.0764.

6. Golz RA, Flum DR, Sanchez SE, Liu X, Donovan C, Drake FT. Geographic association between incidence of acute appendicitis and socioeconomic status. JAMA Surg. 2020;155(4):330–338. doi:10.1001/jamasurg.2019.6030.

7. Harris J, Fleming CA, Stassen PN, Mullen D, Mohan H, Foley J, et al. Comparison of intra-operative diagnosis with histopathological diagnosis of acute appendicitis in paediatric and adult cohorts: An analysis of over 1000 patients. Ir J Med Sci. 2022;191(4):1809–1813. doi:10.1007/s11845-021-02770-5.

8. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte ratio is associated with perforated appendicitis in elderly patients in the emergency department. Aging Clin Exp Res. 2017;29(3):529–536. doi:10.1007/s40520-016-0584-8.

9. Pehlivanli F, Aydin O. Role of platelet-to-lymphocyte ratio as a biomedical marker for the preoperative diagnosis of acute appendicitis. Surg Infect (Larchmt). 2019;20(8):631–636. doi:10.1089/sur.2019.042.

10. Celik B, Nalcacioglu H, Ozcatal M, Altuner Torun Y. Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg. 2019;25(3):222–228. doi:10.5505/tjtes.2018.06709.

11. Gil-Vargas M, Cruz-Peña I, Saavedra-Pacheco MS. Sensitivity and specificity of the neutrophil-to-lymphocyte ratio in pediatric patients with complicated acute appendicitis. Cir Cir. 2022;90(2):223–228. doi:10.24875/CIRU.20001179.

12. Tekeli A, Caliskan MB, Bahadir GB, Erdemir OK. Evaluation of systemic immune-inflammation index efficacy in predicting complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg. 2023;29(5):566–573. doi:10.14744/tjtes.2022.42472.

13. Zarog M, O’Leary P, Kiernan M, Bolger J, Tibbitts P, Coffey S, et al. Circulating fibrocyte percentage and neutrophil–lymphocyte ratio as biomarkers of uncomplicated and complicated appendicitis: A prospective cohort study. Int J Surg. 2023;109:343–351. doi:10.1097/JS9.0000000000000234.

14. Aydogdu B, Azizoglu M, Arslan S, Aydogdu G, Basuguy E, Salik F, et al. A novel diagnostic scoring system for pediatric appendicitis based on age- and sex-adjusted hematological parameters. Gac Med Mex. 2023;159(2):103–109. doi:10.24875/GMM.M22000753.

15. Sousa J, Hawkins R, Shenoy A, Petroze R, Mustafa M, Taylor J, et al. Enterobius vermicularis–associated appendicitis: A 22-year case series and comprehensive review of the literature. J Pediatr Surg. 2022;57(7):1494–1498. doi:10.1016/j.jpedsurg.2021.09.038.

16. Guana R, Giuliano C, Pollio B, Perin S, Zambaiti E, Cerrina A, et al. Role of coagulation tests in the management of acute appendicitis in children. Minerva Pediatr. 2023;75(3):288–294. doi:10.23736/S2724-5276.23.07200-2.

17. Marzuillo P, Coppola C, Caiazzo R, Macchini G, Di Sessa A, Guarino S, et al. Acute kidney injury in children with acute appendicitis. Children (Basel). 2022;9(5):620. doi:10.3390/children9050620.

18. Haghi AR, Kasraianfard A, Monsef A, Kazemi AS, Rahimi S, Javadi SMR. Diagnostic values of procalcitonin and interleukin-6 in acute appendicitis. Turk J Surg. 2019;35(1):19–22. doi:10.5578/turkjsurg.4113.

19. Cui W, Liu H, Ni H, Qin X, Zhu L. Diagnostic accuracy of procalcitonin for overall and complicated acute appendicitis in children: A meta-analysis. Ital J Pediatr. 2019;45:78. doi:10.1186/s13052-019-0673-3.