C-Reactive Protein and Serum Lactate Dehydrogenase as Diagnostic Parameters in Acute Appendicitis

Introduction

Appendicitis is the most common disease requiring urgent or emergent surgical intervention. It is estimated that as much as 6% to 7% of the general population develop appendicitis during their lifetime, with the incidence peaking in the second decade of life.^1,2

Diagnosis of appendicitis could be accurately made with a combination of history, physical examination and laboratory studies, as per a clinician’s experience.^1,2

Despite the increased use of ultrasonography, computed tomography scanning and laparoscopy, the rate of misdiagnosis of appendicitis has remained constant (15.3%), as has the rate of appendicular perforation.² In an age accustomed to early and accurate preoperative diagnosis, acute appendicitis remains an enigmatic challenge and a reminder of the art of surgical diagnosis.³ However, till date there is no confirmatory laboratory marker for the pre-operative diagnosis of acute appendicitis and/ or appendicular perforation. Moreover, those that are done are neither clear nor conclusive.⁴

Elevated serum C-reactive protein (CRP) level will help in the early and accurate diagnosis of acute appendicitis and in predicting its serious complications like perforation.4 C-reactive protein (CRP) together with other acute phase proteins increase in response to tissue injury.^2,4

Another important marker which has not been studied much in the literature is the serum lactate dehydrogenase (LDH). Raised lactate level is an early sign of tissue hypoxia and it has been shown to be a marker for mesenteric ischemia as well and also increases in acute intestinal conditions like appendicitis. Lactate levels have been more specific than C-reactive protein or leukocyte count in acute abdomen.^5-7 However, the role of serum LDH levels in case of acute appendicitis and perforated appendix remains controversial with some studies showing a positive correlation between the two and others showing a negative correlation.^5,8

Hence, this study was done to determine the values of C-reactive protein and serum lactate dehydrogenase in clinically diagnosed acute appendicitis and to correlate it with severity of appendicitis. Materials and Methods The present cross-sectional study was done in the Department of Surgery from December 2019 to June 2021. All the patients in the age range of 12 years to 50 years with a diagnosis of acute appendicitis posted for surgery were included in the study.

Exclusion criteria

• Patients not willing to participate in the study • Patients younger than 12 years and older than 50 years

• Patients who were managed conservatively

• Patients with signs and symptoms of liver disease, pancreatic diseases, chronic alcoholism

• Females taking oral contraceptive pills, or pregnant and lactating women

Patients with acute appendicitis attending the OPD were included and written informed consent was taken. Demographic data such as age, gender, residence, occupation, history of present illness were noted. The diagnosis of acute appendicitis was made based on clinical signs and symptoms. Patients were subjected to routine investigations such as CBC, RBS, blood grouping, CRP levels and serum LDH levels, USG of abdomen and pelvis.

Statistical analysis

Results on continuous measurements are presented as mean ± SD (Min-Max) and results on categorical measurements are presented as absolute number and percentage. The statistical software IBM SPSS 24.0.(IBM, Armonk, NY, USA) was used for the analysis of data.

Results

One hundred and ten patients with acute appendicitis attending the OPD of Department of Surgery were randomly selected for the study. In the present study, age distribution was from 11 years to 50 years, and majority patients were in the age range of 11– 20 years constituting 61.82% of the sample (68/110), followed by 21-30 years constituting 26.36% (29/110) and least were in the age range of 41-50 years constituting 2.72% (03/110), while 9.1% (10/110) were aged between 31-40 years. Mean age (years ± SD) was 23.87 ± 6.79 years. In our study, males constituted 63.6% (70/110) and females constituted 36.3% (40/110) with a M:F ratio of 1.7:1.

Clinical diagnosis of early acute appendicitis was predominant, noted in 59% (65/110) patients, while next common was acute suppurative appendicitis constituting 29% patients (Table 1). 77% (85) patients presented within 24 hours of clinical symptoms and 22% (25) presented within 48 hours of clinical symptoms.

In the present study, clinical symptoms like pain in right iliac fossa, vomiting, fever were noted among the cases of appendicitis (Figure 1). In our study, McBurney’s tenderness was commonly seen followed by guarding/ rigidity in patients with appendicitis (Table 2).

In early acute appendicitis, 59% patients showed serum CRP levels of about 3-40 mg/dL, of which two were normal on histopathology. In acute suppurative appendicitis, 29% patients showed serum CRP levels of about 40-100 mg/dL and in gangrenous appendicitis & perforated appendicitis, serum CRP levels were about 100-150 mg/dL (Table 3).

LDH levels in early acute appendicitis patients [49 (44.55%)] were 190-300 u/L, in acute suppurative appendicitis patients [17 (15.45%)] were 190-300 U/L, and in gangrenous appendicitis patients [9 (8.18%)] were >300 U/L (Table 4).

On histopathological examination, acute appendicitis was reported in 88.1% (97/110) cases, gangrenous appendicitis in 9.0% (10/110) cases and acute appendicitis with perforation in 2.7% (03/110) cases.

In the present study, we found the sensitivity and specificity of C-reactive protein with negative and positive predictive values of 50% and 99.07% as 99.07% and 50% respectively (Table 5 & 6).

In the present study, we found the sensitivity and specificity of serum LDH with negative and positive predictive values of 80% and 98.18% as 98.04% and 100% respectively (Table 7 & 8).

Discussion

In the present study, age distribution of patients was between 12 to 52 years. Majority of cases were noted between 12 – 22 years constituting 61.82% of the sample, followed by 23-32 years constituting 26.3%. Mean age (years ± SD) was 23.87 ± 6.79 years. In a study conducted by Shekfi Xharra et al.,⁹ the age range was from 5 to 59 years with the mean (SD) age being 19.7 years (±10.5), whereas 83.5% of patients were below 30 years of age. Yogesh Kukreja et al.,¹⁰ observed the common age group as 20 – 29 years followed by younger than 20 years. In our study, majority were males constituting 63.6% and females constituted 36.3% with a M:F ratio of 1.7:1.Yogesh Kukreja et al., ¹⁰ in thier study reported male predominance with 70% males and 30% females.

We observed the sensitivity and specificity of C-reactive protein with negative and positive predictive values of 50% and 99.07% as 99.07% and 50%. Essam F et al¹¹ observed a group of patients with normal appendix and reported the mean CRP level as 10.6 mg/L and the median level as 10.6 mg/L. The patients with histopathologically proven appendicitis were divided into two groups- a group that included patients without complicated appendicitis and a group that included patients with complicated appendicitis depending on the intraoperative notes. The means CRP in the first group was 40 mg/L and the median was 20 mg/L, whereas in the group of complicated appendicitis, the mean CRP was 9 mg/L. In the study conducted by Ghimire et al., ¹² strong positive C-reactive protein i.e >85 mg/ dL was seen in 38.88% of patients. Among them, most were histopathological gangrenous type. In their study, the relation of CRP level with the severity of acute appendicitis was found to be positive. Yogesh Kukreja et al¹⁰ in the meta-analysis of 22 published articles concluded that CRP is a test of medium accuracy in diagnosing acute appendicitis. The CRP levels increased if symptoms were present for more than 12 hours and were also found to increase with an advancing stage of the appendiceal inflammation found at operation and the length of preoperative phase of illness.

Gimire et al¹² noted the sensitivity and specificity of C-reactive protein as 84.31% and 66.66% respectively. Similar findings of sensitivity of 53-88% and specificity of 46-82% was noted in a meta-analysis by Chung JL et al. ¹³ In the study by Lamture Y R et al.,¹⁴ sensitivity and specificity of C-reactive protein was reported as 81.28% and 92.86% with negative and positive predictive values of 26.26% and 99.37% respectively.

Essam et al¹¹ reported the specificity and sensitivity of CRP as a diagnostic test for acute appendicitis to be 86.6 and 93.3% respectively. Other studies also showed significant association between C-reactive protein and appendicitis.^15-19

We found the sensitivity and specificity of serum LDH with negative and positive predictive values of 80% and 98.18% as 98.04% and 100% respectively. Few other studies^5,7,8,10,18 also reported the association of serum LDH and appendicitis to be significant.

In our study, on histopathological examination, acute appendicitis was reported in 88.1% cases, gangrenous appendicitis in 9.0% cases and acute appendicitis with perforation in 2.7% cases. Choudhary Suresh Kumar et al.,¹⁵ observed that 64 (54.33%), 12 (10.00%) and 44 (36.67%) cases out of 146 cases examined were diagnosed with acute, gangrenous and perforated appendicitis respectively on the basis of histopathological examination.¹⁵

In the present study, we found a significant association of C-reactive protein and/or serum LDH in the diagnosis of appendicitis. We also found higher levels in severe and complicated appendicitis.

Conclusion

CRP and LDH can lead to precise prediction of severity of acute appendicitis for the treatment. Raised CRP has more sensitivity for complications in acute appendicitis than specificity. If clinical symptoms and image examinations indicate that a person has appendicitis, a person with high CRP and LDH should undergo surgery immediately.

Conflict of Interest

Nil

Financial support

Nil

Local Ethics Committee- approval was granted for this study