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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 4  |  Page : 1262-1266

Diagnostic markers in acute appendicitis


1 Department of General Surgery, Menoufia University, Menoufia, Egypt
2 Department of General Surgery, Bolak El-Dakror, General Hospital, Giza, Egypt

Date of Submission28-Nov-2018
Date of Decision02-Jan-2019
Date of Acceptance08-Jan-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Abdelrahman H Meselhy
Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_375_18

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  Abstract 


Objective
The objective of the study was to determine the value of white cell count (WBC), C-reactive protein (CRP), and bilirubin as diagnostic markers in acute appendicitis.
Background
Appendicitis is a frequent reason for hospital admissions. Elevated CRP, white blood cell count, and serum bilirubin have been suggested as individual markers for appendicitis and appendicular perforation.
Patients and methods
This prospective observational study was conducted on patients admitted with clinical suspicion of acute appendicitis at Menoufia University and Bolak El-Dakror Hospitals in the 6 months period starting from June 2017 involving 150 patients.
Results
A total of 150 patients were operated under suspicion of appendicitis. From these, 65.3% of patients had simple appendicitis, 18.7% had normal appendix, and 16% of patients had complicated appendicitis. Complicated appendicitis was accompanied with higher WBC level with significant correlation (P = 0.03); complicated and simple ones were accompanied with a higher level of total bilirubin than normal appendix with significant differences (P < 0.001). Complicated appendicitis and simple appendicitis were accompanied with higher CRP positivity than in normal appendix with significant differences (P < 0.001).
Conclusion
Combining blood markers was useful in predicting appendicitis and perforated appendicitis, in addition to CRP and WBC, and blood levels of bilirubin.

Keywords: appendicitis, bilirubin, C-reactive protein, white cell count


How to cite this article:
Elgamal AS, Omran W, Meselhy AH. Diagnostic markers in acute appendicitis. Menoufia Med J 2019;32:1262-6

How to cite this URL:
Elgamal AS, Omran W, Meselhy AH. Diagnostic markers in acute appendicitis. Menoufia Med J [serial online] 2019 [cited 2020 Jun 6];32:1262-6. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1262/274267




  Introduction Top


Appendicitis is one of the most common causes of abdominal pain requiring emergency surgery. Different clinical signs and symptoms always mimic the diagnosis of acute appendicitis (AA) with the number of causes leading to pain in right iliac fossa, especially in women [1]. Accurate diagnosis can be aided by additional tests. A delay in diagnosis can lead to appendicular perforation with increased morbidity, and an appendectomy as soon as the condition is suspected, may increase the number of unnecessary appendectomies [1]. Diagnosis of AA is based on history, symptoms, and physical examination backed by elevated erythrocyte sedimentation rate, white blood cell count (WBC), and C-reactive protein (CRP). A number of clinical and laboratory-based scoring systems such as the Alvarado score, Tzanakis score, etc., have been devised to assist the diagnosis. Atypical histories require imaging with ultrasound and/or computed tomography scanning [2]. In practice, the diagnosis of AA is supported by the presence of elevated inflammatory markers, that is, white cell count and CRP. However, some studies have shown that neither of these markers is diagnostic nor specific for AA. Recently, serum bilirubin has been found to play a useful role in the diagnosis of AA [3]. The aim of this study was to determine the value of WBC, CRP, and bilirubin as diagnostic markers of AA.


  Patients and Methods Top


This prospective observational study was conducted on patients admitted with clinical suspicion of AA at Menoufia University and Bolak El-dakror Hospitals in the 6-onth period starting from June 2017 involving 150 patients. The study was approved by the ethical Committee of faculty of medicine Menoufia university and the patient gave an informed consent.

Inclusion criteria

All cases of right iliac fossa pain diagnosed clinically as AA and had undergone appendectomy (open or lap).

Exclusion criteria

  1. Patients with past history of jaundice and other causes of hyperbilirubinemia (hemolytic disease, positive hepatitis viruses, cholelithiasis, acquired or congenital biliary disease, and cancer of the hepatobiliary system)
  2. Patients with other causes of elevation in WBC and CRP
  3. Chronic alcoholism (intake of alcohol of >40 g/day for men and >20 g/day for women for 10 years)
  4. Patients known to be on treatment for any collagen vascular disease
  5. The appendectomy was performed as part of another procedure.


Methods

Full clinical history and examination were done.

Laboratory investigations including:

  1. WBC total and differential: WBC greater than 10 500 cells/μl: 80–85% of adults with appendicitis.
  2. CRP: CRP levels greater than 1 mg/dl are common in patients with appendicitis


  3. In adults who have had symptoms for longer than 24 h, a normal CRP level has a negative predictive value (NPV) of 97–100% for appendicitis

  4. Total serum bilirubin level: when bilirubin is raised, the likelihood of appendicitis was greater than 1.


Operative findings recorded: noncomplicated (inflamed, gangrenous without perforation), complicated (perforation, abscess, peritonitis), and normal.

Statistical analyses

Data were analyzed using the Statistical Package for the Social Sciences (SPSS; SPSS Inc., Chicago, Illinois, USA). Continuous variables were expressed as mean and standard deviation or range and median. Sensitivities, specificities, positive predictive value, and NPV of white cell count, CRP, and bilirubin were calculated separately or in combination for all patients. One-way analysis of variance test was used to analyze the difference between means of variables among patients' groups. Results were considered statistically significant when the P value is of less than or equal to 0.05.


  Results Top


A total of 150 patients with a mean age of studied patients of 22.6 years with male predominance (53.3%) [Table 1]; the mean duration of pain was 2.2 days; mean WBCs level was 13.01; total bilirubin 0.94; and CRP was positive in 34.7%; 65.3% of patients had simple appendicitis; 18.7% had normal appendix; and 16% of patients had complicated appendicitis. There was insignificant correlation between age and type of appendicitis and there was insignificant correlation between sex and type of appendicitis.
Table 1: Demographic data of the studied patients regarding to age, sex and pathologically finding

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We found that complicated appendicitis was accompanied with higher WBC level with significant correlation (P = 0.03) [Table 2] and [Figure 1]; complicated appendicitis was accompanied with prolonged pain duration with significant correlation (P < 0.001); complicated appendicitis and simple appendicitis were accompanied with higher CRP positivity than in normal appendix with significant differences (P < 0.001) [Table 2] and [Figure 2]; elevated bilirubin level was higher only in complicated appendicitis than normal and simple appendicitis with significant differences (P < 0.001); total bilirubin level had 29.5% sensitivity, 89.3% specificity and an accuracy of 40.67% in diagnosing appendicitis [Table 3].
Table 2: Comparison between the three studied groups according white blood cells and C-reactive protein findings

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Figure 1: Comparison between the three studied groups according white blood cells.

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Figure 2: Comparison between the three studied groups according C-reactive protein findings.

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Table 3: Sensitivity, specificity, and accuracy of bilirubin in detect the normal and abnormal appendicitis in relation to pathological findings as a gold standard method

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  Discussion Top


In the present study, we aimed to determine the value of WBC, CRP, and bilirubin as diagnostic markers of AA. In all, 150 patients were involved with a mean age of studied patients of 22.6 years with male predominance (53.3%). In our study, the male was higher than female like in the study off Subramanyam et al. [4] who found the male sex was predominant. On the contrary in the study by Farooqui et al. [5] the female sex was predominant than the male. High rates of negative appendectomy (operation without histological confirmation of appendicitis) have been reported with some groups such as women of reproductive age having rates of up to 26% [6]. This agrees with our study as we found that the female predominance was higher in normal appendicitis after operation. In our study the mean age was 22.6 years. In D'Souza et al. [7] study the mean age was 29.4 years. Those at the extremes of age often present a significant diagnostic challenge as they may present with atypical signs and symptoms. Infants may appear listless while the elderly may present with confusion. A high index of suspicion is therefore required to make the diagnosis in such cases [8]. This disagrees with our result as the age was an insignificant factor in relation to the type of appendicitis. In the present study, we found that 65.3% of patients had simple appendicitis, 18.7% had normal appendix, and 16% of patients had complicated appendicitis. In the study by D'Souza et al. [7] they had simple appendicitis in 89 (63%) cases, and perforated appendicitis in 19 (14%) cases. In the present study, we found that the mean duration of pain was 2.2 days and it was significant to the type of appendicitis as in complicated appendicitis the duration of pain was longer. In the study by Wani et al. [9], the total duration of pain for the involved patients in this study were 100 h. In the present study, we found that the mean WBC level was 13.01, total bilirubin 0.94, and the CRP was positive in 34.7%. In our study, we founded elevation in WBC with significant affection on the type of appendicitis; this agrees with the study by Farooqui et al. [5] as they observed that patients with AA had significantly higher blood levels of WBC (P < 0.001). In our study, we observed elevation in the level of total bilirubin for the involved patients and it was significant to the type of appendicitis as it was elevated in different types of appendicitis, but it was more significant in cases with complicated appendicitis. This agrees with the result by Hong et al. [10] as they observed that the average of serum total bilirubin was 0.849 mg/dl (minimum: 0.050 mg/dl; maximum: 4.310 mg/dl) and it was a significant factor in diagnosing appendicitis. In our study, the CRP was a significant factor in diagnosing appendicitis as it is elevated in different types of appendicitis. In Wani et al. [9] study they observed that CRP was elevated in 35 cases of perforated appendicitis (value >10 mg/dl). Sensitivity and specificity of CRP in predicting perforation were 83 and 74%, respectively. The CRP levels fail to rise in some cases of inflammation though the reason for this was not clear in the literature. It also fails to rise in cases of hepatocellular dysfunction. These might explain the false negative cases [9]. In Farooqui et al. [5] study, the level of CRP was not significantly increased among patients suffering from AA compared with patients suffering from other diseases. An explanation could be that CRP reacts slower compared with, for example, WBC. Thus, in the patient with appendicitis, who normally has a short and acute symptomatic history, the CRP may not react until later. In contrast, the patients with perforated appendicitis may have a more severe disease and a longer duration of inflammation. This may result in the significant elevation of CRP levels for perforated disease; this agrees with our result as the CRP level was elevated in complicated appendicitis than simple appendicitis. In our study, we found that serum total bilirubin was nonreliable in simple appendicitis but it was reliable in complicated appendicitis as it was more specific in diagnosing complicated appendicitis with 58.33% sensitivity, 89.29% specificity, and an accuracy of 75.0%. These results agree with the result by D'Souza and colleagues as they confirmed that there is a high specificity of bilirubin (0.82) for perforated appendicitis; also the meta-analysis by Giordano et al. [11] proved hyperbilirubinemia to be a predictor of appendicular perforation. In the study by Subramanyam, they agree with us and proved that serum bilirubin is a reliable diagnostic marker in AA particularly in gangrenous/perforated appendicitis. Wani et al. [9] demonstrated that bilirubin, CRP, and ultrasound are effective for differentiation of perforated from nonperforated appendicitis. Bilirubin, CRP, and ultrasonography are important preoperative biochemical and sonographer markers of perforation, respectively, in appendicitis. Thus, these three tests collectively help in early prediction of perforation and prevention of complications [9]. Anderson [12] reported that appendicitis is unlikely when all inflammatory variables are normal. Sengupta and colleagues reported an NPV of 100% for TLC and CRP in AA, concluding that patients experiencing lower abdominal pain with normal TLC and CRP are unlikely to have appendicitis. As per Shaw and colleagues both TLC and CRP can be in the normal range as may be because of a lag in changes of inflammatory variables with the time of onset of symptoms [13]. In a study by Tucker et al. [14] the CRP level ranged from 1 to 453 mg/l with a mean of 56.53 ± 86.49 mg/l. The presence of raised CRP was not statistically significant. So, it was observed in the Ambre and colleagues study that CRP was not statistically significant for diagnosing the appendicitis. So, the TLC count was a significant indicator of AA than CRP for predicting the severity of appendicitis [14]. In Ambre and colleagues study, the mean total bilirubin for AA was 1.50. The mean total bilirubin in probable cases of appendicitis was 1.10. The study done by Sand et al. [15] reported a relatively high incidence of hyperbilirubinemia (24.9%) from an analysis of 538 AA patients, of whom 50.7% were verified as having perforated appendicitis. In a study by Noh et al. [16], bilirubin showed the highest specificity in diagnosing complicated cases at 75% compared with WBC (19%) and CRP (35%). Patel et al. [17] have reported a sensitivity of 65.33% for hyperbilirubinemia in acute uncomplicated cases and 92% for complicated appendicitis. In a study done by Khan et al. [18] hyperbilirubinemia in 86.6% of patients of AA bilirubin ranged from 1.2 to 8.4 mg/dl. So, the authors have observed that investigating the level of bilirubin is important for diagnosing appendicular infection. However, when all three values, that is, total count, CRP, and bilirubin is combined, we may safely predict about the severity of appendix infection.


  Conclusion Top


Combining blood markers was useful in predicting appendicitis and perforated appendicitis in addition to CRP and WBC and blood levels of bilirubin.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ambre SR, Chavan S. Hyperbilirubinemia as a diagnostic marker for acute appendicitis. Int Surg J 2018; 5:2091–2096.  Back to cited text no. 1
    
2.
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Al-Abed YA, Alobaid N, Myint F. Diagnostic markers in acute appendicitis. Am J Surg 2015; 209:1043–1047.  Back to cited text no. 3
    
4.
Subramanyam VV, Bangla G, Jyothi C. Serum bilirubin reliable diagnostic marker in detecting complicated appendicitis. J Evid Based Med Healthc 2016; 3:66–71.  Back to cited text no. 4
    
5.
Farooqui W, Pommergaard HC, Burcharth J, Eriksen JR. The diagnostic value of a panel of serological markers in acute appendicitis. Scand J Surg 2015; 104:72–78.  Back to cited text no. 5
    
6.
Flum DR, Morris A, Koepsell T, Dellinger EP. Has misdiagnosis of appendicitis decreased over time? A population-based analysis. JAMA 2001; 286:1748–1753.  Back to cited text no. 6
    
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D'Souza N, Karim D, Sunthareswaran R. Bilirubin; a diagnostic marker for appendicitis. Int J Surg 2013; 11:1114–1117.  Back to cited text no. 7
    
8.
Paulson EK, Kalady MF, Pappas TN. Suspected appendicitis. N Engl J Med 2003; 348:236–242.  Back to cited text no. 8
    
9.
Wani MD, Mir SA, Bhat JA, Gul S, Maqbool U, Moheen HA. Hyperbilirubinemia, C-reactive protein and ultrasonography as predictors of appendicular perforation: a prospective study. Saudi Surg J 2014; 2:1–5.  Back to cited text no. 9
    
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Hong YR, Chung CW, Kim JW, Kwon C, Ahn DH, Kwon SW, et al. Hyperbilirubinemia is a significant indicator for the severity of acute appendicitis. Korean Soc Coloproctol 2012; 28:247–252.  Back to cited text no. 10
    
11.
Giordano S, Paakkonen M, Salminen P, Grönroos JM. Elevated serum bilirubin in assessing the likelihood of perforation in acute appendicitis: a diagnostic meta-analysis. Int J Surg 2013; 11:795–800.  Back to cited text no. 11
    
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Anderson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis, Br J Surg 2004; 91:28–37.  Back to cited text no. 12
    
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Vaughan-Shaw PG, Rees JR, Bell E, Hamdan M, Platt T. Normal inflammatory marks in appendicitis: evidence from two independent cohort studied. JRSM Short Rep 2011; 2:43.  Back to cited text no. 13
    
14.
Tucker A, Sloan K, Gartsin I, Verghis R. White cell counts, CRP and appendicitis? Is there a role for preoperative blood tests? A cohort study. J Health Med Informat 2015:6:2.  Back to cited text no. 14
    
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Sand M, Becharz FG, Holland-Letz T, Sand D, Mehnert G, Mann B. Diagnostic value of hyperbilirubinemia as a predictive factor for appendicular perforation in acute appendicitis. Ann J Surg 2009; 198:193–198.  Back to cited text no. 15
    
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Noh H, Chang SJ, Han A. The diagnostic value of preoperative laboratory markers in children with complicated appendicitis. J Korean Surg Soc 2012; 83:237–241.  Back to cited text no. 16
    
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Patel D, Shah NJ, Patel B, Parikh M, Patel D, Dalal C. Evaluation of hyperbilirubinemia as a diagnostic marker for acute appendicitis and its role in the prediction of complicated appendicitis. Int J Res Med 2014; 3:28–33.  Back to cited text no. 17
    
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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