medigraphic.com
Órgano Oficial del Colegio Mexicano de Alergia, Asma e Inmunología Pediátrica y de la Asociación Latinoamericana de Pediatría

2025, Number 2-3

<< Back Next >>

Alerg Asma Inmunol Pediatr 2025; 34 (2-3)

Eosinophils, neutrophil-lymphocyte ratio and other biomarkers in complicated acute appendicitis. A case-control study

Bucio-Cornejo, Dalia Patricia1,2; Medina Vera, Isabel3; Espinosa-Padilla, Sara Elva4,5; Contreras-Verduzco, Francisco Alberto6; Arce-Estrada, Gabriel Emmanuel1,4,7

Language: Portugu?s
References: 51
Page: 49-59
PDF size: 558.26 Kb.


ABSTRACT

Introduction: the diagnostic approach to acute appendicitis involves patient history, physical examination, imaging studies and laboratory tests, as blood count. Objectives: the aim of this study was to investigate the association between complicated (perforated) cases of acute appendicitis in children and blood count biomarkers. Material and methods: a case-control study was conducted at a secondary hospital in Mexico City, comparing patients with uncomplicated acute appendicitis (control group) to those with complicated acute appendicitis and varying stages of severity (case group). The study used clinical records of patients under 18 years old who were diagnosed with acute appendicitis and had blood counts before surgery. The study covered the period from 2019 to 2023. Results: 278 medical records were included, of which 53.6% were from men. The mean age was 9.9 ± 4 years. 73.7% of the cases presented complicated acute appendicitis. Leukocyte and neutrophil counts, as well as neutrophil/lymphocyte and neutrophil/platelet ratios were higher in the complicated appendicitis group. Lymphopenia was more frequent in younger children. In the multivariate analysis, ≥ 55 eosinophils/mm3 (OR = 2.2, 95%CI 1.2-4, p = 0.005) and the value of ≥ 3.18 in the neutrophil/lymphocyte ratio (OR = 4.4, 95%CI 2.2-8.5, p < 0.001) were associated with complicated appendicitis. Conclusion: complete blood count is a useful tool for identifying cases of complicated acute appendicitis in children. This study proposes a cut-off point for eosinophils and other blood biomarkers to identify complicated cases of acute appendicitis.



ABBREVIATIONS:

  • AA = acute appendicitis
  • MLR = monocyte/lymphocyte ratio
  • NLR = neutrophil/lymphocyte ratio
  • PLR = platelet/lymphocyte ratio



INTRODUCTION

Acute appendicitis (AA) is defined as the inflammation of the vermiform appendix and it represents approximately 1% of pediatric emergency visits for abdominal pain.1 It typically results from obstruction of the appendiceal lumen, leading to increased mucus production, bacterial overgrowth, and elevated intraluminal pressure, which can cause necrosis and a high risk of perforation.2 The condition most commonly presents between the ages of 10 and 19 years, while it is relatively rare in infants and preschoolers.3 Nevertheless, the risk of perforation is higher in patients under 10 years of age, with an estimated incidence ranging from 23 to 73% in those older than 1 year and approaching 100% in younger children.4

During the 2015 World Society of Emergency Surgery Congress, a panel of experts convened to evaluate the severity of appendicitis and develop a four-stage classification system:5

Stage 1: hyperemic appendix.

Stage 2: appendix with mucosal erosions, suppuration, and fibrinopurulent exudates.

Stage 3: gangrenous appendix with wall necrosis.

Stage 4: perforated appendix.

Another simpler classification is based on perforation data:6

Uncomplicated acute appendicitis: no data of perforation (hyperemic and congestive appendix).

Complicated acute appendicitis: perforated, with or without localized abscess, with or without peritonitis (phlegmonous, gangrenous and perforated appendix).

The diagnostic approach to AA involves a combination of patient history, physical examination, laboratory tests, and imaging studies. These data are integrated into various diagnostic scales, though none of them offers definitive diagnostic certainty.7 Among the most recognized scales are the Alvarado scale, the Pediatric Appendicitis Score, and the Lintula scale, with the latter two specifically designed for the pediatric population. These scales assess factors such as sex, pain characteristics, accompanying symptoms, and fever to guide clinical diagnosis and inform treatment decisions.

A complete blood count is one of the most valuable and commonly requested laboratory tests in emergency settings. This readily accessible, low-cost test provides detailed information on the composition and quantity of blood cells, including erythrocytes, leukocytes, and platelets. This test helps clinicians to identify and evaluate a range of pathologies affecting various organs and systems.8

An ideal marker for diagnosing and assessing the severity of AA should be straightforward, provide rapid results, and offer high accuracy, sensitivity, and specificity, all while being cost-effective. Consequently, routinely performed blood tests are highly valuable indicators. Commonly used assessments include absolute leukocyte count; levels of neutrophils, lymphocytes, monocytes, and platelets, as well as, neutrophil/lymphocyte ratio (NLR); monocyte/lymphocyte ratio (MLR) and platelet/lymphocyte ratio (PLR).4

The aim of this study was to investigate the association between complicated cases of acute appendicitis in children and blood count biomarkers.



MATERIAL AND METHODS

A case-control study was conducted at a secondary hospital in Mexico City to compare patients with uncomplicated acute appendicitis (control group) to those with complicated acute appendicitis of varying severity (case group). The study used convenience sampling, focusing on clinical records of patients under 18 years old diagnosed with acute appendicitis and who had pre-surgical blood counts from 2019 to 2023. Exclusion criteria included records with underlying pathologies affecting leukocyte levels, incomplete information, prior antibiotic treatment before diagnosis or blood counts, and concurrent infections at the time of diagnosis. Additionally, patients without a blood count or staging report for acute appendicitis were eliminated from the study. The study was conducted without funding. It received approval from the Ethics Committee of the institution (approval number 302-010-02-24) and was conducted in accordance with the declaration of Helsinki.

For the statistical analysis, we employed two classifications AA and examined differences between groups:

  • 1. Complicated and uncomplicated cases.
  • 2. Severity stages based on histopathological findings of the appendix (hyperemic, phlegmonous, gangrenous and perforated).

Sex and age were included in the statistical analysis as both confounding and non-confounding variables. Continuous variables were expressed as median (percentile 25-75th) and dichotomous variables as frequencies and percentages. Kolmogorov-Smirnov test was applied to assess the normality of the variables. To compare quantitative variables, Mann-Whitney U statistical analysis and Kruskal-Wallis for independent samples tests were used, when comparing proportions, the χ2 or Fisher's exact tests were used. Receiver operating characteristic (ROC) curves were generated and the area under the curve and 95% confidence intervals (CI) were calculated. Cut-off points for the variables were determined using the Youden index (Y = sensitivity + specificity-1), taking the value closest to 1. The variables analyzed were dichotomized according to the evaluated cut-off points. The χ2 test was applied, and the odds ratio (OR) and 95%CI were calculated. Significant variables identified in the bivariate analysis were subsequently examined using a multivariate analysis. Two methods were used: first, the input method and then the backward stepwise method (WALD). Significance level used was p < 0.05. The analyses were performed using the Statistical Package for Social Sciences (SPSS) version 25.0.



RESULTS

Five hundred and six clinical records of patients diagnosed with AA were identified and of these, 225 that did not meet the inclusion criteria were excluded and three were eliminated; the rest (n = 278) were included in the study of which, 53.6% were men and the mean age was 9.9 ± 4 years.

Table 1 summarizes the differences between the complicated and uncomplicated acute appendicitis groups as well as between severity groups according to the pathology report.

It was observed that those cases that presented lymphopenia were younger (9 [5.4-12.3 years]) compared to those that did not present it (11 [8.5-14.1 years]), p = 0.0003 (Figure 1).

Table 2 shows the analysis of the cut-off points found for each variable in the context of complicated AA and the multivariate and retrograde multivariate analysis. In both, the variables eosinophils and NLR were associated with complicated AA.



DISCUSSION

The aim of our study was to describe the relationship between the severity of AA in pediatric population (using the classification by macroscopic findings, based on pathology reports, and the classification based on the presence or absence of perforation), with the levels of leukocytes, neutrophils, lymphocytes, eosinophils, platelets and with the quotients derived from these.

Age and sex were not considered confounding variables because their distributions were similar between the groups with complicated and uncomplicated appendicitis, as well as among the four groups classified by macroscopic findings. These two variables were included in the modeling of the multivariate analysis showing that they were not significant for association with complicated appendicitis.

When comparing age group percentages with the severity strata of appendicitis, we observed that younger patients were generally more affected by the most severe forms. In fact, the only patient in the infant group was classified in the most severe category of acute appendicitis. This case had to be eliminated for statistical analysis purposes because there was only one. It is important to note that the greater severity observed in the younger age groups may be associated with the higher incidence of lymphopenia that we observed in these children. In contrast, the teenager group had a higher percentage of patients in the less severe categories of acute appendicitis. Our results are like those reported in a study that included the Mexican pediatric population, in which it was observed that preschoolers with complicated AA had lower levels of lymphocytes when compared to patients with uncomplicated AA of the same age. However, this difference was not observed in the group of schoolchildren, nor in the group of teenagers.9

Prabhudas, et al. reported that younger children experience immunological adaptations after exposure to new antigens, which are essential for developing immunological memory. During this adaptation period, fluctuations in lymphocyte counts are common and can lead to transient lymphopenia. Since the immune system in younger children is still developing, they are more prone to secondary lymphopenia.10 This increased susceptibility is attributed to a combination of factors, including infection susceptibility, immune system immaturity, prenatal and neonatal influences, postnatal immunological adaptation, and genetic factors, as discussed by Gervassi and Horton.11 So, lymphopenia has previously been associated with complicated AA in children,12,13 with the development of intra-abdominal abscesses after appendectomy in children with complicated appendicitis and with AA in adults.14,15

The results of our study are consistent with recent reports,16,17 showing that leukocyte and neutrophil counts were higher in the more severe AA groups, using both four-stage5 and perforation data6 classifications.

The systemic inflammatory response can cause neutrophilia and lymphopenia, resulting in increased NLR and PLR. Both are indicators of inflammation in AA. Regarding NLR, Delgado-Miguel, Miguel-Ferrero, et al., reported elevated levels in complicated AA cases,16,18 as was observed in our study, in which NLR was also higher in the complicated AA group.

Other research has shown the usefulness of NPR in distinguishing between complicated and uncomplicated cases of AA.19,20 In our study, it was observed that this index was also higher in the complicated AA group, with a difference close to the threshold of statistical significance.

Complicated AA was associated with a more intense inflammatory response and elevated NPR, which can lead to complications such as perforation and abscess formation.17,19

In our study, NPR was observed to be significantly higher in patients with complicated AA compared to those with uncomplicated appendicitis. This finding is consistent with the available literature, which suggests that an elevated NPR may be an indicator of an intense systemic inflammatory response, reinforcing the notion that NPR is a useful and reliable biomarker to differentiate between complicated and uncomplicated AA cases, since the increase in neutrophil and platelet counts is indicative of a severe acute inflammatory process.

In reference to the cut-off points of the variables studied that turned out to be significant in the association with complicated AA cases, there are several investigations that are shown in Table 3, where the cases of our study (Hospital Pediátrico Coyoacán) have also been included.

It is possible that patients with pain in the right iliac fossa and without clear histological criteria for AA are in an early phase of the disease. At this stage, the classic neutrophil infiltration necessary for a histological diagnosis of AA has not yet occurred.45 In contrast, in cases of lymphoid hyperplasia of the appendix, commonly observed in pediatric age and typically associated with inflammatory conditions such as viral gastroenteritis and mesenteric adenitis, an increase in eosinophils has been observed in the wall of the appendix. This increase, although higher in cases of reactive lymphoid hyperplasia, has also been seen in AA.46 These histological findings suggest that AA may be, at least in part, due to a reaction with type I hypersensitivity characteristics. Other findings supporting this idea include eosinophil infiltration, mast cell degranulation, germinal center edema, perivascular histiocytic proliferation and muscle edema, all of which are common in the appendicular tissue of AA cases.47

It has also been observed that in cases of AA with elevated eosinophil levels in the appendix wall, this increase correlates with the severity of inflammation in the organ.48 Similarly, an elevation of the TH2 cytokine profile (IL-4, IL-5 and IL-9) has been demonstrated in the appendiceal lavage fluid, as well as elevated levels of immunoglobulin E in the appendiceal samples from cases of phlegmonous appendicitis.49 Among these cytokines, IL-5 acts as a chemotactic factor that guides eosinophils to the target organ, which may be the appendix. Once in the tissue, eosinophils release several proteins such as eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin, which have potent inflammatory properties that destroy cells.50

Although our study observed higher median blood eosinophil levels in complicated acute appendicitis cases compared to uncomplicated cases, this difference was not statistically significant. However, eosinophil count emerged as one of the two significant variables in both multivariate analyses with its cut-off point showing a significant association with complicated AA cases. So, we conducted an exhaustive literature review to contrast our results, but we found no evidence that established a cut-off point for blood eosinophil levels to associate with AA and complicated AA cases. Existing evidence only supports a cut-off point for eosinophils in the appendix wall in adults.51 Therefore, although limited to the pediatric population, our study is the first to propose a cut-off point for blood eosinophil levels to identify complicated AA cases.

Establishing a cut-off point for blood eosinophil levels could enhance our understanding of the pathophysiology of complicated AA in children. In such cases, damage to the appendix epithelium might stimulate the proliferation and release of eosinophils into the bloodstream. These eosinophils could then accumulate in the tissue, where they produce mediators that may exacerbate tissue damage,50 potentially contributing to the development of complicated AA.

This study has several limitations, including the selection bias inherent to its retrospective design at a single institution. In addition, the irregular availability of reagents and equipment in the laboratory prevented the inclusion of variables such as monocytes, basophils, and other inflammatory biomarkers such as C-reactive protein and procalcitonin. Although the usefulness of these biomarkers in identifying complicated cases of AA has been previously demonstrated16 many of the records reviewed lacked these reports, so it was decided not to include them in the study so as not to compromise the sample size. We also did not exclude parasitic infections in patients presenting with eosinophilia. But despite its limitations, this study highlights the importance of considering eosinophils as a potentially useful biomarker to differentiate between complicated and uncomplicated appendicitis, suggesting their inclusion in future prospective studies to improve the diagnosis and management of this condition.



CONCLUSIONS

  • 1. A blood count is a useful tool for identifying cases of complicated acute appendicitis in children.
  • 2. Patients with complicated AA showed higher leukocyte and neutrophil values, as well as elevated NLR and NPR.
  • 3. Lymphopenia was more frequent in younger patients with AA.
  • 4. This study proposes cutoff points to identify complicated AA in pediatric patients for the following variables: leukocytes, neutrophils, eosinophils, NLR, PLR, and NPR.
  • 5. The most reliable markers to associate with complicated AA are blood eosinophil levels and NLR.
  • 6. This study is pioneering in that it proposes a cutoff point based on blood eosinophil levels to identify complicated cases of AA in both children and adults.
  • 7. These parameters should be included in prospective studies to take on a predictive character.


REFERENCES

  1. Caperell K, Pitetti R, Cross KP. Race and acute abdominal pain in a pediatric emergency department. Pediatrics. 2013; 131 (6): 1098-1106. doi: 10.1542/peds.2012-3672.

  2. Mandeville K, Monuteaux M, Pottker T, Bulloch B. Effects of timing to diagnosis and appendectomy in pediatric appendicitis. Pediatr Emerg Care. 2015; 31 (11): 753-758. doi: 10.1097/PEC.0000000000000596.

  3. Wickramasinghe DP, Xavier C, Samarasekera DN. The worldwide epidemiology of acute appendicitis: an analysis of the global health data exchange dataset. World J Surg. 2021; 45 (7): 1999-2008. doi: 10.1007/s00268-021-06077-5.

  4. Ha SC, Tsai YH, Koh CC, Hong SG, Chen Y, Yao CL. Blood biomarkers to distinguish complicated and uncomplicated appendicitis in pediatric patients. J Formos Med Assoc. 2024; 123 (10): 1093-1098. doi: 10.1016/j.jfma.2024.01.023.

  5. Gomes CA, Sartelli M, Di Saverio S, Ansaloni L, Catena F, Coccolini F et al. Acute appendicitis: proposal of a new comprehensive grading system based on clinical, imaging and laparoscopic findings. World J Emerg Surg. 2015; 10: 60. doi: 10.1186/s13017-015-0053-2.

  6. Sallinen V, Akl EA, You JJ, Agarwal A, Shoucair S, Vandvik PO et al. Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg. 2016; 103 (6): 656-667. doi: 10.1002/bjs.10147.

  7. 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 (1): 27. doi: 10.1186/s13017-020-00306-3.

  8. El Brihi J, Pathak S. Normal and abnormal complete blood count with differential. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.

  9. Ortiz-Ley JD, Rodríguez-Zepeda ADR, Paque-Bautista C, González AP, Cano-Rodríguez MT, Cortés-Salim P et al. Índices inflamatorios predictores de apendicitis aguda complicada en niños. Rev Med Inst Mex Seguro Soc. 2023; 61 (Suppl 2): S161-S170.

  10. PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O et al. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011; 12 (3): 189-194. doi: 10.1038/ni0311-189.

  11. Gervassi AL, Horton H. Is infant immunity actively suppressed or immature? Virology (Auckl). 2014; 2014 (5): 1-9. doi: 10.4137/VRT.S12248.

  12. Sahin C, Güler EM, Karaman Ayyildiz HN, Akis Yildiz Z, Arpacik M, Ilce Z. The role of IL-6, thiol-disulfide homeostasis, and inflammatory biomarkers in the prediction of acute appendicitis in children: a controlled study. Pediatr Surg Int. 2023; 39 (1): 75. doi: 10.1007/s00383-023-05366-5.

  13. Zvizdic Z, Jonuzi A, Glamoclija U, Vranic S. The predictive value of plasma sodium and other laboratory parameters in determining complicating appendicitis in children. Med Princ Pract. 2024; 33 (4): 347-354. doi: 10.1159/000538778.

  14. Lodwick DL, Cooper JN, Kenney B, Deans KJ, Minneci PC, Thakkar RK. Lymphocyte depression as a predictor of postoperative intraabdominal abscess after appendectomy in children. J Pediatr Surg. 2017; 52 (1): 93-97. doi: 10.1016/j.jpedsurg.2016.10.028.

  15. Chávez Sánchez W. Leucocitosis asociada a grado de severidad y linfopenia asociada a apendicitis gangrenosa en pacientes con diagnóstico de apendicitis aguda en el servicio de cirugía del Hospital Vitarte durante el período enero – julio 2015 [Tesis]. Universidad Ricardo Palma; 2016. Disponible en: https://repositorio.urp.edu.pe/handle/20.500.14138/498.

  16. Delgado-Miguel C, Muñoz-Serrano A, San Basilio M, Miguel-Ferrero M, de Ceano-Vivas M, Martínez L. The role of the neutrophil-to-lymphocyte ratio in avoiding negative appendectomies. An Pediatr (Engl Ed). 2023; 98 (1): 12-18. doi: 10.1016/j.anpede.2022.08.005.

  17. Telafarli MA, Yeni M. The diagnostic value of the systemic immune-inflammatory index in acute appendicitis cases in the emergency department. Langenbecks Arch Surg. 2023; 408 (1): 136. doi: 10.1007/s00423-023-02871-y.

  18. Delgado-Miguel C, Miguel-Ferrero M, García A, Delgado B, Camps J, Martínez L. Neutrophil-to-lymphocyte ratio as a predictor of postoperative complications and readmissions after appendectomy in children. Updates Surg. 2023; 75 (8): 2273-2278. doi: 10.1007/s13304-023-01639-9.

  19. Moreno-Alfonso JC, Molina Caballero A, Yárnoz Irazábal MC, Pérez Martínez A. Blood cell indices as predictors of complicated appendicitis: a diagnostic study. J Pediatr Surg Open. 2023; 4: 100072. doi: 10.1016/j.yjpso.2023.100072.

  20. Sener K, Cakir A, Kilavuz H, Altug E, Güven R. Diagnostic value of systemic immune inflammation index in acute appendicitis. Rev Assoc Med Bras (1992). 2023; 69 (2): 291-296. doi: 10.1590/1806-9282.20221003.

  21. Al-Gaithy ZK. Clinical value of total white blood cells and neutrophil counts in patients with suspected appendicitis: retrospective study. World J Emerg Surg. 2012; 7 (1): 32. doi: 10.1186/1749-7922-7-32.

  22. McGowan DR, Sims HM, Zia K, Uheba M, Shaikh IA. The value of biochemical markers in predicting a perforation in acute appendicitis. ANZ J Surg. 2013; 83 (1-2): 79-83. doi: 10.1111/ans.12032.

  23. Shimizu T, Ishizuka M, Kubota K. A lower neutrophil to lymphocyte ratio is closely associated with catarrhal appendicitis versus severe appendicitis. Surg Today. 2016; 46 (1): 84-89. doi: 10.1007/s00595-015-1125-3.

  24. Beecher SM, Hogan J, O'Leary DP, McLaughlin R. An appraisal of inflammatory markers in distinguishing acute uncomplicated and complicated appendicitis. Dig Surg. 2016; 33 (3): 177-181. doi: 10.1159/000444101.

  25. Aydin OU, Soylu L, Dandin O, Uysal Aydin E, Karademir S. Laboratory in complicated appendicitis prediction and predictive value of monitoring. Bratisl Lek Listy. 2016; 117 (12): 697-701. doi: 10.4149/BLL_2016_132.

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

  27. Shin DH, Cho YS, Kim YS, Ahn HC, Oh YT, Park SO et al. Delta neutrophil index: A reliable marker to differentiate perforated appendicitis from non-perforated appendicitis in the elderly. J Clin Lab Anal. 2018; 32 (1): e22177. doi: 10.1002/jcla.22177.

  28. 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.

  29. Prasetya D, Rochadi, Gunadi. Accuracy of neutrophil lymphocyte ratio for diagnosis of acute appendicitis in children: A diagnostic study. Ann Med Surg (Lond). 2019; 48: 35-38. doi: 10.1016/j.amsu.2019.10.013.

  30. Vargas-Rodríguez LJ, Barrera Jerez JF, Ávila Ávila KA, Rodríguez Mongui DA, Muñoz Espinosa BR. Marcadores de severidad de la apendicitis aguda: estudio de prueba diagnóstica. Rev Colomb Gastroenterol [Internet]. 2022; 37 (1): 3-9. Disponible en: https://revistagastrocol.com/index.php/rcg/article/view/538

  31. Patmano M, Cetin DA, Gümüs T. Laboratory markers used in the prediction of perforation in acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2022; 28 (7): 960-966. doi: 10.14744/tjtes.2021.83364.

  32. Mekrugsakit N, Tullavardhana T. The value of complete blood count parameters in predicting complicated acute appendicitis; a prognostic accuracy study. Arch Acad Emerg Med. 2023; 11 (1): e42. doi: 10.22037/aaem.v11i1.2020.

  33. Ishizuka M, Shimizu T, Kubota K. Neutrophil-to-lymphocyte ratio has a close association with gangrenous appendicitis in patients undergoing appendectomy. Int Surg. 2012; 97 (4): 299-304. doi: 10.9738/CC161.1.

  34. Kahramanca S, Ozgehan G, Seker D, Gökce EI, Seker G, Tunc G et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2014; 20: 19-22.

  35. Kelly ME, Khan A, Riaz M, Bolger JC, Bennani F, Khan W et al. The utility of neutrophil-to-lymphocyte ratio as a severity predictor of acute appendicitis, length of hospital stay and postoperative complication rates. Dig Surg. 2015; 32 (6): 459-63. doi: 10.1159/000440818.

  36. Yardimci S, Ugurlu MU, Coskun M, Attaallah W, Yegen SC. Neutrophil-lymphocyte ratio and mean platelet volume can be a predictor for severity of acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2016; 22 (2): 163-168. doi: 10.5505/tjtes.2015.89346.

  37. Sevinc MM, Kinaci E, Cakar E, Bayrak S, Ozakay A, Aren A et al. Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg. 2016; 22 (2): 155-162. doi: 10.5505/tjtes.2016.54388.

  38. Khan A, Riaz M, Kelly ME, Khan W, Waldron R, Barry K et al. Prospective validation of neutrophil-to-lymphocyte ratio as a diagnostic and management adjunct in acute appendicitis. Ir J Med Sci. 2018; 187 (2): 379-384. doi: 10.1007/s11845-017-1667-z.

  39. Hajibandeh S, Hajibandeh S, Hobbs N, Mansour M. Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis. Am J Surg. 2020; 219 (1): 154-163. doi: 10.1016/j.amjsurg.2019.04.018.

  40. Begic-Kapetanovic S, Avdagic N, Zaciragic A, Hasic S, Babic N et al. Could the neutrophil-to-lymphocyte ratio serve as a marker in the diagnosis and prediction of acute appendicitis complications in children? Arch Med Sci. 2019; 17 (6): 1672-1678. doi: 10.5114/aoms.2019.87697.

  41. Cruz-Vallejo RN, Quispe-Zaga E, Nieto-Gutiérrez W. Neutrophilic-lymphocytes and platelet-lymphocytes ratios as predictors for acute perforated appendicitis in children. Bol Med Hosp Infant Mex. 2021; 78 (6): 557-564. doi: 10.24875/BMHIM.21000057.

  42. Rajalingam VR, Mustafa A, Ayeni A, Mahmood F, Shammout S, Singhal S et al. The role of neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) as a biomarker for distinguishing between complicated and uncomplicated appendicitis. Cureus. 2022; 14 (1): e21446. doi: 10.7759/cureus.21446.

  43. Ayeni A, Mahmood F, Mustafa A, Mcleish B, Kulkarni V, Singhal S et al. Predicting the severity of acute appendicitis in children using neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Cureus. 2022; 14 (8): e28619. doi: 10.7759/cureus.28619.

  44. Yesilalioglu S, Az A, Sogut O, Ergenc H, Demirel I. Systemic inflammatory markers for distinguishing uncomplicated and complicated acute appendicitis in adult patients. North Clin Istanb. 2023; 10 (4): 507-513. doi: 10.14744/nci.2022.79027.

  45. Carvalho N, Carolino E, Coelho H, Cóias A, Trindade M, Vaz J et al. IL-5 serum and appendicular lavage fluid concentrations correlate with eosinophilic infiltration in the appendicular wall supporting a role for a hypersensitivity type I reaction in acute appendicitis. Int J Mol Sci. 2022; 23 (23): 15086. doi: 10.3390/ijms232315086.

  46. Ucar Karabulut K, Erinanc H, Yonar A, Kisinma A, Ucar Y. Correlation of histological diagnosis and laboratory findings in distinguishing acute appendicitis and lymphoid hyperplasia. Ann Surg Treat Res. 2022; 103 (5): 306-311. doi: 10.4174/astr.2022.103.5.306.

  47. Aravindan KP, Vijayaraghavan D, Manipadam MT. Acute eosinophilic appendicitis and the significance of eosinophil - Edema lesion. Indian J Pathol Microbiol. 2010; 53 (2): 258-261. doi: 10.4103/0377-4929.64343.

  48. Acharya A, Markar SR, Ni M, Hanna GB. Biomarkers of acute appendicitis: systematic review and cost-benefit trade-off analysis. Surg Endosc. 2017; 31 (3): 1022-1031. doi: 10.1007/s00464-016-5109-1.

  49. Carvalho N, Barros A, Coelho HO, Moita CF, Neves-Costa A, Pedroso D et al. A Th2 cytokine profile in appendicular lavage fluid suggests allergy as a possible etiology for acute appendicitis. Mediators Inflamm. 2019; 2019: 8146257. doi: 10.1155/2019/8146257.

  50. Gurtner A, Gonzalez-Perez I, Arnold IC. Intestinal eosinophils, homeostasis and response to bacterial intrusion. Semin Immunopathol. 2021; 43 (3): 295-306. doi: 10.1007/s00281-021-00856-x.

  51. Shrestha R, Shrestha A, Tiwari M, Ranabhat S, Maharjan S. Role of eosinophils in acute appendicitis. JNMA J Nepal Med Assoc. 2015; 53 (197): 12-17.



AFFILIATIONS

1 Hospital Pediátrico Coyoacán. Ciudad de México, México.

2 ORCID: 0009-0001-9185-3820

3 Unidad de Metodología de la Investigación, Instituto Nacional de Pediatría. Ciudad de México, México. ORCID: 0000-0003-4027-2329

4 Laboratorio de Inmunodeficiencias Primarias, Instituto Nacional de Pediatría. Ciudad de México, México.

5 ORCID: 0000-0003-4859-3151

6 Servicio de Alergia, Instituto Nacional de Pediatría. Ciudad de México, México. ORCID: 0000-0003-3998-3916

7 ORCID: 0000-0002-3944-3779



CORRESPONDENCE

Dr. Gabriel Emmanuel Arce-Estrada. E-mail: arce.emmanuel@gmail.com




Received: 08/19/2025. Accepted: 11/07/2025.

2020     |     www.medigraphic.com