Introduction: Acute abdominal pain is a common complaint in emergency departments, with acute appendicitis being one of the leading causes. Diagnosis based on clinical signs and symptoms, the diagnostic approach has evolved to include inflammatory markers such as leukocyte count, neutrophil count, and CRP. AIM: To determine the usefulness of Lymphocyte to C Reactive Protein Ratio in predicting the differentiation between Acute Appendicitis and Perforated Appendicitis. Methodology: This study is a prospective observational study. The sample size is calculated at a 95% confidence level with an α error of 0.05, based on the sensitivity of the lymphocyte-to-C-reactive protein ratio (LCR) for diagnosing acute appendicitis, which is 79.4% according to the reference seed article. Result: Our study found that acute appendicitis was more common than perforated appendicitis, with significant differences in inflammatory markers (LCR, NLR, and CRP) between the groups, while the Alvarado score showed no statistical significance. Conclusion: Inflammatory markers like LCR, NLR, and CRP are significant in diagnosing and predicting complications of acute and perforated appendicitis.
Acute abdominal pain is a common complaint in emergency departments, with acute appendicitis being one of the leading causes1. Traditionally diagnosed based on clinical signs and symptoms, the diagnostic approach has evolved to include inflammatory markers such as leukocyte count, neutrophil count, and CRP. If left untreated, appendicitis can rupture, leading to severe complications. In resource-limited settings like India, accurate diagnosis remains a challenge.”The appendix is a blind muscular tube with mucosal, submucosal, muscular, and serosal layers2. Acute appendicitis is the most common cause of non-traumatic emergency abdominal surgery, with a lifetime risk of 7–8% . While its global incidence is 100 per 100,000, rates are higher in developing countries. Ultrasound (USG) and computed tomography (CT) are commonly used to differentiate between acute and perforated appendicitis, but they require specialized equipment and experienced radiologists, which may not be readily available in peripheral hospitals3,4. Therefore, highly accurate inflammatory markers should be examined to predict the risk of perforation.The lymphocyte-to-C-reactive protein ratio (LCR) is a newly used biomarker for assessing systemic inflammation in perforated appendicitis, with an LCR ≤0.172 indicating a higher risk of perforation. C-reactive protein (CRP) is a non-specific inflammatory marker commonly used in diagnosing acute abdominal conditions. Produced by the liver, its normal blood level is under 10 mg/L but can rise significantly within 8–12 hours of infection or injury5,6,7. Controlled by interleukin-6, CRP can increase up to 1,000 times in response to inflammation. Elevated CRP levels are seen in infections, autoimmune disorders, inflammatory arthritis, neoplasia, and aging . The ALVARADO score is both simple to remember and to use, being based on three symptoms, three signs & two laboratory values. The score indicated ≥ 6 indicates high probability of acute appendicitis8. It can be helpful for safe and accurate decision making in patients with acute appendicitis9. It can also help sort patients into different groups for monitoring and observation10,11.
AIM
To determine the usefulness of Lymphocyte to C Reactive Protein Ratio in predicting the differentiation between Acute Appendicitis and Perforated Appendicitis.
This study is a prospective observational study. The sample size is calculated at a 95% confidence level with an α error of 0.05, based on the sensitivity of the lymphocyte-to-C-reactive protein ratio (LCR) for diagnosing acute appendicitis, which is 79.4% according to the reference seed article. The required sample size is 252 patients, with an additional 10% added for non-response, bringing the total to 277, which is further rounded off to 280 patients for this study. The inclusion criteria include patients aged 12 to 50 years diagnosed with appendicitis based on clinical examination (Alvarado Score) and ultrasonography findings. Exclusion criteria include patients with appendicular mass, appendicular malignancy, and those managed conservatively for acute appendicitis or who underwent a negative appendectomy. Children under 12 and adults over 50 are excluded due to less effective CRP responses. Additionally, patients with a history of jaundice, signs of liver disease, chronic alcoholism, or other acute inflammatory conditions are excluded, as CRP is produced exclusively in the liver and increases in response to inflammation. Patients unwilling to participate in the study are also excluded.
STATISTICAL ANALYSIS
Categorical variables were presented as numbers and percentages, while descriptive statistics summarized demographic data through means, standard deviations, and proportions. Differences in LCR between acute and perforated appendicitis were analyzed using t-tests for normal data and Mann-Whitney U tests for non-normal data. ROC curve analysis determined the optimal LCR cut-off value, assessing sensitivity, specificity, and AUC to evaluate its diagnostic accuracy. Data was entered into Excel and analyzed using SPSS version 21.0, with statistical significance set at P < 0.05.
Table 1: Distribution of cases according to age group
Age Group |
Acute Appendicitis |
Perforated Appendicitis |
Total |
||
|
N |
% |
N |
% |
N |
12-21 |
113 |
88.98 |
14 |
11.02 |
127 |
22-31 |
73 |
93.59 |
5 |
6.41 |
78 |
32-41 |
39 |
86.67 |
6 |
13.33 |
45 |
42-51 |
23 |
76.67 |
7 |
23.33 |
30 |
Total |
248 |
88.57 |
32 |
11.43 |
280 |
Table 1 shows that acute appendicitis is more common than perforated appendicitis across all age groups, with the highest AA cases in the 22-31 age group (93.59%) and the highest PA cases in the 42-51 age group (23.33%), indicating an increased risk of perforation with age due to delayed medical care.
Table 2: Gender-wise distribution of cases in study subjects
SEX |
STUDY SUBJECTS |
|
|||
|
Acute appendicitis |
Perforated appendicitis |
TOTAL |
||
|
N |
% |
N |
% |
|
Male |
139 |
86.34 |
22 |
13.66 |
161 |
Female |
109 |
91.60 |
10 |
8.40 |
119 |
Total |
248 |
88.57 |
32 |
11.43 |
280 |
p-value |
0.127 |
In total, 248 participants had acute appendicitis (88.57%), while 32 had perforated appendicitis (11.43%). This distribution shows that both males and females are predominantly diagnosed with acute appendicitis, with a smaller percentage having perforated appendicitis. This table also shows that males have higher chances of perforation.
Table 3: Distribution of cases in acute and perforated appendicitis
STUDY SUBJECTS |
NO OF CASES |
|
|
N |
% |
Acute appendicitis |
248 |
88.57 |
Perforated appendicitis |
32 |
11.43 |
TOTAL |
280 |
100.00 |
The table 3 represents distribution of cases among 280 subjects in which most participants 248(88.57%) have acute appendicitis, while 32 (11.43%) have perforated appendicitis.
Table 4: Distribution of cases according to clinical history
History |
Number |
Percentage% |
Abdominal Pain |
280 |
100.0 |
Fever |
196 |
70.0 |
Vomiting |
225 |
80.4 |
Nausea |
240 |
86.0 |
Anorexia |
196 |
70.0 |
The table 4 represents the symptoms of a group of patients. All 280 patients had abdominal pain. More than half, 196(70.0%) patients, also had a fever. A large number, 225(80.4%) patients, experienced vomiting, and 240(86.0%) patients reported feeling nauseous. Finally, 196(70.0%) patients said they had a loss of appetite.
Table 5: Distribution of cases according to HsCRP
HsCRP(mg/dl) |
Number |
Percentage% |
<3 |
31 |
11.07 |
4-5 |
137 |
48.93 |
6-7 |
61 |
21.79 |
8-9 |
29 |
10.36 |
10-12 |
22 |
7.86 |
Grand Total |
280 |
100 |
In present study, out of total 280 patients, 11.07% were patients having HsCRP level (<3 mg/dl). 48.93% patients having HsCRP level between 4-5mg/dl. 21.79% patients having HsCRP level between 6-7 mg/dl. 10.36% patients having HsCRP level between 8-9 mg/dl.7.86% patients having HsCRP level between 1012 mg/dl.
Table 6: ROC analysis results and sensitivity, specificity, ppv, npv values of lcr and nlr value perforation prediction
Values |
LCR |
NLR |
AUC |
0.1(1-1) |
0.812(0.720-0.905) |
Cut off |
0.172 |
8.8 |
P-value |
<0.001 |
<0.001 |
Sensitivity |
93.75 |
84.37 |
Specificity |
94.14 |
91.67 |
Negative predictive value |
99.02 |
82.48 |
Positive predictive value |
99.6 |
95.83 |
Table 6 shows the ROC analysis of LCR and NLR, both significant for differentiating perforation (p < 0.001), with an LCR cut-off of 0.172 (93.75% sensitivity, 94.14% specificity) and an NLR cut-off of 8.8 (84.37% sensitivity, 91.67% specificity).
Table 7: Comparison Between CRP and LCR in perforated and acute appendicitis
Variables |
Perforated Appendicitis |
Acute Appendicitis |
p-value |
CRP |
|
|
|
Mean ± Std |
9.44 ± 1.95 |
5.11±1.66 |
<0.001 |
Median |
10.00 |
5.00 |
|
Range(min-max) |
5-12 |
2-11 |
|
LCR |
|
|
<0.001 |
Mean ± Std |
0.141 ± 0.021 |
0.474±0.207 |
|
Median |
0.145 |
0.441 |
|
Range(min-max) |
0.100-0.172 |
0.180-1.55 |
|
Table 7 represents the ROC analysis of LCR (lymphocyte-to-C-reactive protein ratio) and NLR (neutrophil-to-lymphocyte ratio) in which the LCR and NLR parameters were found significant in the differentiation of perforation with p value <0.001. The cut-off point for the LCR value was found as 0.172. For this cut-off point, the sensitivity value was 93.75%, and the specificity was 94.14%. The cut-off point for the NLR value was found 8.8. For this cut-off point the sensitivity and specificity was 84.37% and 91.67% respectively.
Table 8: Comparison of laboratory blood values and Alvarado score values between acute appendicitis and perforated appendicitis.
|
Acute appendicitis |
Perforated appendicitis |
p-value |
|
mean ± SD |
mean ± SD |
|
Neutrophils |
12.5±2.10 |
14.9±1.75 |
<0.001 |
Lymphocytes |
2.2±0.61 |
1.32±0.32 |
<0.001 |
CRP |
5.1±1.66 |
9.4±1.95 |
<0.001 |
Alvarado score |
8.9±0.93 |
9.3±0.89 |
0.297 |
Table 8 compares neutrophils, lymphocytes, CRP, and Alvarado scores between acute and perforated appendicitis, showing significantly higher neutrophils and CRP, lower lymphocytes in the perforated group (p < 0.001), while Alvarado scores were not significantly different (p = 0.297).
In the present study, from a total of 280 patients, maximum number of patients belongs to the age group of 12-21 years followed by 22-31 years. Minimum patients were in the age group 42-51 years. Our findings were comparable to the finding of Ramu Abhirup H. et al (2021)12 who reported that most of the patients belongs to less than 20 years followed by 20-30 years and least patients were in the age group 40-50 years. Similarly; another study done by Dnyanmote Anuradha et al (2018)13 reported that maximum patients belong to the age group 21-30 years and least patients belong to the age group 51-60 years.
This present study was conducted on 280 patients of appendicitis. Out of which 161 are males making up 57.50% of the group, while 119 are females, accounting for 42.50%. This shows a slightly higher proportion of males compared to females in the study. Our finding was comparable to the finding of Ugurlu Celil et al (2021)13 who reported that study participants consist of 135 females (41.7%) and 197 males (59.3%). There is also higher proportion of males compared to females. Similarly; Ramu Abhirup H. et al (2021)12 also reported that study subjects consist of 57 male and 43 females.
In the current study, among the total 280 cases 248 (88.57%) patients had acute appendicitis and 32(11.43%) patients had perforated appendicitis. Our findings were comparable to the finding of Ugurlu Celil et al (2021)14 who found that perforation was observed in 34(10.2%) and no perforation was observed in 298(89.8%).
In present study, among 280 patients’ abdominal pain was present in 100.00% of the patients, Vomiting was present in 80.4% of the patients, Fever was present in 70.0% of the patients, Nausea was present in 86.00% of the patients and Anorexia was present in 70.00% of the patients. The study done by Ketika et al (2023)15 observed that most common symptom pain abdomen seen in 100% patients followed by vomiting 64.3%. Fever was found in 40% of the patients.
In our study serum HsCRP was elevated in 88% of the total patients this rate corresponds to study done by Kamat V Vijay et al (2019)16 where CRP levels was elevated in 84% of patients with acute appendicitis, also study done by Dnyanmote A et al (2018) [67] where 82.14% of patients had elevated CRP.
In our study we compared the LCR and NLR parameters, which can be taken from serum laboratory tests in both acute appendicitis and perforated appendicitis group. We found that all these parameters were statistically significant. In our findings, we have observed that LCR cut-off value was 0.172 with sensitivity and specificity of 93.75% and 94.14% respectively. We have also observed NLR cutoff value 8.8 with sensitivity and specificity of 84.37% and 91.67% respectively. Our findings were comparable to the Ugurlu Celil et al (2021)14 reported that LCR cut-off was 0.179 with sensitivity and specificity 79.4% and 82.6% respectively. He also reported the NLR cut-off value was 8.65 with sensitivity and specificity of 79.4% and 81.9% respectively.
In present study we compared the CRP and LCR in acute and perforated appendicitis group. The mean value of CRP in perforated appendicitis group was 9.44 ± 1.95(<0.001), while in the acute appendicitis group was 5.11±1.66. The mean value of LCR in perforated appendicitis group was 0.141 ± 0.021 (<0.001), while in the acute appendicitis group was 0.474±0.207. Our findings were comparable to the Ugurlu Celil et al (2021)14 reported that mean value of CRP in perforated appendicitis group was 10.36 ±10.56 (<0.001), while in the acute appendicitis group was 4.74±2.55. The mean value of LCR in perforated appendicitis group was 0.09±0.12 (<0.001), while in the acute appendicitis group was 0.32±0.24.
In our study we observed the comparison of laboratory values Neutrophils, Lymphocytes, C-reactive protein and Alvarado score values of patients in acute appendicitis and perforated appendicitis and we found that among the study groups Neutrophils, Lymphocytes, C-reactive protein values were statistically significantly different (p<0.001) whereas, the Alvarado scores were not statistically significantly different between the groups (p = 0.297). Our findings were comparable to the study done by Ugurlu Celil et al (2021)13 reported that Neutrophils, Lymphocytes, C-reactive protein values were statistically significant whereas, the Alvarado score were not statistically significant between the groups.
Our study found that acute appendicitis was more common than perforated appendicitis, with perforation risk increasing with age. LCR and NLR were significant markers for differentiation, with LCR cut-off at 0.172 (93.75% sensitivity, 94.14% specificity) and NLR cut-off at 8.8 (84.37% sensitivity, 91.67% specificity). CRP and LCR values were significantly different between acute and perforated appendicitis groups, aligning with previous studies. Neutrophils, lymphocytes, and CRP were statistically significant in differentiating the groups, while the Alvarado score was not. Overall, inflammatory markers like LCR and CRP can aid in diagnosing and predicting appendicitis complications.