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ORIGINAL ARTICLE Table of Contents   
Year : 2011  |  Volume : 8  |  Issue : 3  |  Page : 309-312
Appendicitis in paediatric age group: Correlation between preoperative inflammatory markers and postoperative histological diagnosis


1 Department of Surgery, Specialist Registrar in General Surgery, Aintree University Hospital, Liverpool, United Kingdom
2 Department of Surgery, Associate Specialist in General Surgery, Prince Charles Hospital, Merthyr Tydfil, United Kingdom
3 Department of Surgery, CT2 doctor in General Surgery, Pilgrim Hospital, Boston, Lincolnshire, United Kingdom
4 Department of Surgery, Consultant General Surgeon and Lead Paediatric Surgeon, Prince Charles Hospital, Merthyr Tydfil, United Kingdom

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Date of Web Publication11-Jan-2012
 

   Abstract 

Introduction: Clinical diagnosis of appendicitis can be challenging, particularly in the paediatric age group. There is an increased risk of perforation in paediatrics; therefore, a need for sensitive and specific diagnostic tool is mandatory. Aim: The aim of this study is to evaluate the role of preoperative inflammatory markers in supporting the clinical diagnosis of appendicitis in the paediatric age group. Materials and Methods: Retrospective study of 268 emergency paediatric appendicectomies performed in a District General Hospital in Wales, over a period of seven years (2002-2009). The data collected from hospital database include preoperative inflammatory markers, C-reactive protein (CRP) and white blood cells count (WBCC) and post-operative histology. Statistical analysis was performed using Fisher's exact test. Results: The median age group in the study was 12 (2-16). 141 (53%) patients were <12 years, while 127 (47%) patients were 12-16 years old. Male : female ratio = 1 : 1 (134 each). Inflammatory markers were not done for 94 patients (35%). CRP was done for 149 cases (55.6%), while WBCC was done for 172 cases (64%). Both markers were done together for 147 cases (54.8%). Histology was positive (inflamed / gangrenous appendix) in 202 cases (75.4%). Eight cases were associated with Enterobious vermicularis infestation and one patient had carcinoid tumour. The sensitivity and specificity of CRP were 82% and 60%, respectively, with positive predictive value (PPV) of 87% (P<0.0001), while those of WBCC were 80% and 59%, respectively, with PPV of 88% (P<0.0001). The sensitivity and specificity of both markers together were 80% and 70%, respectively, with PPV= 81% (P = 3.11E-8). 94 patients (35%) had an appendicectomy operation based on clinical diagnosis alone without preoperative inflammatory markers having been tested. In 28 cases (30%) out of these, postoperative histology revealed normal appendix (P = 0.18). Conclusion: CRP and WBCC are simple tests that can provide a significant role supporting the clinical diagnosis of acute appendicitis in the paediatric age group.

Keywords: Appendicitis, C-reactive protein, inflammatory markers, paediatrics, white blood cell count

How to cite this article:
Mekhail P, Naguib N, Yanni F, Izzidien A. Appendicitis in paediatric age group: Correlation between preoperative inflammatory markers and postoperative histological diagnosis. Afr J Paediatr Surg 2011;8:309-12

How to cite this URL:
Mekhail P, Naguib N, Yanni F, Izzidien A. Appendicitis in paediatric age group: Correlation between preoperative inflammatory markers and postoperative histological diagnosis. Afr J Paediatr Surg [serial online] 2011 [cited 2019 Nov 21];8:309-12. Available from: http://www.afrjpaedsurg.org/text.asp?2011/8/3/309/91676

   Introduction Top


Diagnosis of acute appendicitis is challenging - particularly in the paediatric age group- even in the hands of experienced surgeons. [1] In 1990, Addiss et al. mentioned that acute appendicitis represents the most common abdominal emergency in the USA. [2] Acute appendicitis can be atypically presented in children with non-specific abdominal symptoms. In addition, there is increased incidence of perforation within the paediatric age group "20-50%"., [3],[4],[5] Hence, finding cheap, quick and reliable investigatory tool is mandatory. The role of CT scan in diagnosing acute appendicitis is controversial, particularly in paediatrics. Some studies showed minimal improvement in the accuracy of the diagnosis of appendicitis using the CT scan. [6] Different studies showed sensitivity of 87% (higher diagnostic accuracy), and decreased negative laparotomy from 14.7 to 4.1 using the CT scan. [7],[8] However, CT in this age group carries significant increase in lifetime radiation risk. [9]

White blood cells count (WBCC) and C-reactive protein (CRP) are two inflammatory markers that usually rise with variable inflammatory conditions including appendicitis; therefore, they can be used to support the clinical diagnosis of acute appendicitis but with low specificity and positive predictive value (PPV). [10],[11] Many studies performed on adults showed higher rates of normal appendices in the presence of positive signs and symptoms if WBCC and CRP are within normal limits. [12],[13],[14],[15] Therefore, Gronroos et al. suggested that we can potentially avoid 25% of negative appendicectomies by measuring WBCC and CRP levels in patients with clinically suspected appendicitis. [12]

The aim of this study is to evaluate the role of preoperative inflammatory markers in supporting the clinical diagnosis of appendicitis in paediatrics.


   Materials and Methods Top


A retrospective study of all emergency appendicectomies was performed in paediatric age group in a District General Hospital in Wales over a period of seven years (2002-2009). All elective or interval appendicectomies were excluded from the study. Data was retrieved from theatre system database, operative notes and patient data enquiry computer system "AVALON" The data collected included preoperative inflammatory markers: CRP and (WBCC), intra-operative findings and post-operative histology. Histological results were categorically divided into two groups:

  1. Positive appendicitis group including inflamed, gangrenous and perforated appendix.
  2. Negative appendicitis group including normal appendix, follicular hyperplasia and non-inflamed appendix with Enterobious vermicularis infestation.


Results of the inflammatory markers were interpreted qualitatively as either normal or elevated.

The study population were divided into two age groups: children younger than 12 years old and teenagers between 12 and 16 years.

Statistical analysis was performed using Fisher's exact test.


   Results Top


Two hundred and sixty eight paediatric patients had emergency appendicectomy performed between 2002 and 2009. The median age was 12 (2-16), 53% (141 patients) were children <12 years and 47% (127 patients) were teenagers between 12 and 16 years of age. Male : female ratio was 1 : 1 (134 patients each). Thirty five percent (94 patients) had their operation based on the clinical diagnosis without preoperative inflammatory markers. Approximately 55.6% (149 patients) had preoperative CRP. Sixty four percent (172 patients) had preoperative WBCC done while in 54.8% (147 patients) both markers were performed together.

With regard to histology, 202 patients (75.4%) had positive appendicitis (inflamed, gangrenous or perforated appendix). Sixty five patients (24.3%) had normal appendix and one patient had carcinoid tumour [Table 1].
Table 1: Breakdown of cases

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3% patients had E. vermicularis (EV) infestation (three associated with inflamed appendix).

The sensitivity and specificity of CRP alone were 82% and 60%, respectively, with a PPV of 87% (P<0.0001). The sensitivity and specificity of WBCC alone were 80% and 59%, respectively, with a PPV of 88% (P<0.0001). Assessing both inflammatory markers together was statistically significant with a sensitivity and specificity of 80% and 70%, respectively, PPV = 81% (P= 3.11E-8).

Statistical significance of WBCC and CRP analysis according to gender and according to age group is demonstrated in [Table 2] and [Table 3].
Table 2: Statistical signifi cance of CRP+WBCC combined, according to gender

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Table 3: Statistical signifi cance of CRP and WBCC combined, according to age group

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Combined CRP and WBCC analysis is statistically more significant among the teenage group (>12 years old) - with sensitivity and specificity of 92% and 100%, respectively, PPV of 100% - compared to the younger children (<12 years old).

There was no significant statistical difference within both genders.

Among the group of patients who had appendicectomy based on the clinical diagnosis without analysis of inflammatory markers (94 patients), 28 patients (30%) had normal appendix (negative histology),

P = 0.18. This ratio was smaller in the groups who had preoperative WBCC, CRP or both being 11.6% (P = 0.0004), 12.8% (P = 0.0014) and 10.9% (P = 0.0003), respectively. [Table 4] shows Breakdown of data according to age, gender and inflammatory markers.
Table 4: Breakdown of data according to age, gender and infl ammatory markers

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Although the incidence of perforation was higher in children <12 years than in teens (14.9% vs. 8.7%), it was not statistically significant (P = 0.13).


   Discussion Top


Acute appendicitis by definition is characterized by a local inflammatory reaction that will in turn progress to a systemic inflammatory response. Detecting this inflammatory response through an easy, minimally invasive, widely available and cost-effective method is always desirable. [1] Several inflammatory markers have been anticipated to increase diagnostic accuracy in acute appendicitis including serum amyloid A, [16] interleukins and cytokines, [11] phospholipase A [17] and leucocyte elastase. [18]

The clinical diagnosis will remain the corner stone in acute appendicitis; nevertheless, laboratory investigations provide significant complimentary aid in diagnosis. The literature suggests that sensitivity of clinical examination alone in paediatric age group ranges between 54% and 70% compared to 70% and 87% in adults. [19],[20],[21],[22],[23] In our cohort, 30% (28/940) of patients who underwent appendicectomy based solely on clinical diagnosis had histologically normal appendices. WBCC and CRP are the most commonly used inflammatory markers that can represent a selective rise according to the stage of the disease i.e. WBCC increases more at the early process of appendicitis while CRP increases more dramatically in advanced appendicitis. [24]

Leucocytosis is a non-specific reaction induced by many conditions. This is reflected in numerous reports by an acceptable sensitivity (79-93%) but a rather low specificity for appendicitis. This is similar to our finding of lower specificity and higher sensitivity for WBCC. [25]

Despite the decreased specificity of WBCC and CRP in confirming acute appendicitis in children and adults, [7],[9],[10] the combined presence of normal WBCC and CRP in a patient makes the diagnosis of acute appendicitis highly unlikely particularly in adults. [9],[10],[11],[12],[15] In a study conducted by Stefanutti et al. on 100 children, they concluded that WBCC or CRP value alone does not appear to provide any additional information in the diagnosis of acute appendicitis. However, the sensitivity of the combined two tests is extremely high. Normal values of both WBCC and CRP are very unlikely in a pathologically confirmed appendicitis. [1] Our study showed that the increased sensitivity of each inflammatory marker solitarily is comparable to their sensitivity when combined together, while the specificity was significantly higher when both tests were performed together compared to their individual analysis in confirming the diagnosis of acute appendicitis in the paediatric age.

As the leucocyte response is reduced in children below five years of age, it was shown that the WBC count is better than CRP in the correct diagnosis of appendicitis in every age group of children except infants. [26] The number of patients <5 years old in our study was too small (8) to conduct statistical analysis.

Moreover, in a study involving 189 laparotomy for appendicitis, the results showed that measurement of IL-6 or CRP but not WBC had additional diagnostic value on the diagnosis of advanced or perforated appendicitis. [27] Our study, although, did not show significant statistical difference between CRP and WBCC in advanced or perforated appendicitis (P = 0.12).


   Conclusion Top


CRP and WBCC levels can support the clinical diagnosis of acute appendicitis in the paediatric age. We recommend those tests in all paediatric patients with suspected acute appendicitis as this may decrease the incidence of negative appendicectomies.

 
   References Top

1.Stefanutti G, Ghirardo V, Gamba P. Inflammatory markers for acute appendicitis in children: Are they helpful? J Pediatr Surg 2007;42:773-6.  Back to cited text no. 1
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2.Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology ofappendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910-25.   Back to cited text no. 2
[PUBMED]    
3.O'Toole SJ, Karamanoukian HL, Allen JE, Caty MG, O'Toole D, Azizkhan RG, et al. Insurance-related differences in the presentation of pediatric appendicitis. J Pediatr Surg 1996;31:1032-4.  Back to cited text no. 3
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4.Gamal R, Moore TC. Appendicitits in children aged 13 years and younger. Am J Surg 1990;159:589-92.  Back to cited text no. 4
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5.Pearl RH, Hale DA, Molloy M, Schutt DC, Jaques DP. Paediatric appendicectomy. J Pediatr Surg 1995;30:173-8.  Back to cited text no. 5
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6.Flum DR, Morris A, Koepsell T, Dellinger EP. Has misdiagnosis of appendicitis decreased over time? A population-based analysis. JAMA 2001;286:1748-53.   Back to cited text no. 6
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7.Warner BW. Diagnosing appendicitis in children: It comes down to the physical examination. Gastroenterology 2004;127:675-7.  Back to cited text no. 7
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9.Kosloske AM, Love CL, Rohrer JE, Goldthorn JF, Lacey SR. The Diagnosis of Appendicitis in Children: Outcomes of a Strategy Based on Pediatric Surgical Evaluation. Pediatrics 2004;113;29-34.  Back to cited text no. 9
    
10.Gronroos JM. Do normal leukocyte count and C-reactive protein value exclude acute appendicitis in children? Acta Paediatr 2001;90:649- 51.  Back to cited text no. 10
    
11.Dalal I, Somekh E, Bilker-Reich A, Boaz M, Gorenstein A, Serour F. Serum and peritoneal inflammatory mediators in children with suspected acute appendicitis. Arch Surg 2005;140:169-73.  Back to cited text no. 11
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12.Gronroos JM, Gronroos P. Leukocyte count and C-reactive protein in the diagnosis of acute appendicitis. Br J Surg 1999;86:501-4.  Back to cited text no. 12
    
13.Yang HR, Wang YC, Chung PK, Chen WK, Jeng LB, Chen RJ. Laboratory tests in patients with acute appendicitis. ANZ J Surg 2006;76:71-4.  Back to cited text no. 13
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14.Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 2004;91:28-37.  Back to cited text no. 14
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15.Asfar S, Safar H, Khoursheed M, Dashti H, al-Bader A. Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis? J R Coll Surg Edinb 2000;45:21-4.  Back to cited text no. 15
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16.Lycopoulou L, Mamoulakis C, Hantzi E, Demetriadis D, Antypas S, Giannaki M, et al. Serum amyloid A protein levels as a possible aid in the diagnosis of acute appendicitis in children. Clin Chem Lab Med 2005;43:49-53.  Back to cited text no. 16
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17.Gronroos JM, Forsstrom JJ, Irjala K, Nevalainen TJ. Phospholipase A2, C-reactive protein, and white blood cell count in the diagnosis of acute appendicitis. Clin Chem 1994;40:1757-60.  Back to cited text no. 17
    
18.Eriksson S, Granstrom L, Olander B, Pira U. Leukocyte elastase as a marker in the diagnosis of acute appendicitis. Eur J Surg 1995;161:901-5.  Back to cited text no. 18
    
19.Wade DS, Marrow SE, Balsara ZN, Burkhard TK, Goff WB. Accuracy of ultrasound in the diagnosis of acute appendicitis compared with the surgeon's clinical impression. Arch Surg 1993;128:1039-46.  Back to cited text no. 19
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20.Wilson DH, Wilson PD, Walmsley RG, Horrocks JC, De Dombal FT. Diagnosis of acute abdominal pain in the accident and emergency department. Br J Surg 1977;64:250-4.  Back to cited text no. 20
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21.Bergeron E, Richer B, Gharib R, Giard A. Appendicitis is a place for clinical judgement. Am J Surg 1999;177:460-2.  Back to cited text no. 21
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22.Styrud J, Eriksson S, Segelman J, Granström L. Diagnostic accuracy in 2,351 patients undergoing appendicectomy for suspected acute appendicitis: A retrospective study 1986-1993. Dig Surg 1999;16:39-44.  Back to cited text no. 22
    
23.Saidi RF, Ghasemi M. Role of Alvarado score in diagnosis and treatment of suspected acute appendicitis. Am J Emerg Med 2000;18:230-1.  Back to cited text no. 23
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24.Chung JL, Kong MS, Lin SL, Lin TY, Huang CS, Lou CC, et al. Diagnostic value of C-reactive protein in children with perforated appendicitis. Eur J Pediatr 1996;155:529-31.  Back to cited text no. 24
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25.Hallan S, Asberg A, Edna TH. Additional value of biochemical tests in suspected acute appendicitis. Eur J Surg 1997;163:533-8.  Back to cited text no. 25
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26.Paajanen H, Mansikka A, Laato M, Kettunen J, Kostiainen S. Are serum inflammatory markers age dependent in acute appendicitis? J Am Coll Surg 1997;184:303-8.  Back to cited text no. 26
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27.Sack U, Biereder B, Elouahidi T, Bauer K, Keller t, Tröbs RB. Diagnostic Value of Blood Inflammatory Markers for Detection of Acute Appendicitis in Children. BMC Surg 2006;6:15.  Back to cited text no. 27
    

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Correspondence Address:
Peter Mekhail
Specialist Registrar in General Surgery, 2 Maes Yr Efail, Llangennech, Llanelli, SA14 8WD
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0189-6725.91676

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]

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