|Year : 2011 | Volume
| Issue : 1 | Page : 6-11
Evaluation of the modified Alvarado score incorporating the C-reactive protein in the patients with suspected acute appendicitis
Sheikh Muzamil Shafi1, Misbah Afsheen Malah2, Hilal Razvi Malah3, Farooq Ahmed Reshi2
1 Department of Surgery, Sheri Kashmir Institute of Medical Sciences, Srinagar, India
2 Department of Surgery, SMHS Hospital, Srinagar, Jammu and Kashmir, India
3 Department of Medicine, Sheri Kashmir Institute of Medical Sciences, Srinagar, India
|Date of Web Publication||24-Aug-2011|
Sheikh Muzamil Shafi
Lal Bazar, Srinagar, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background : Acute appendicitis is perhaps the most common surgically correctable cause of acute abdominal pain and its diagnosis remains difficult in many instances. Some of the signs and symptoms can be subtle to both the clinician and the patient and may not be present in all the instances. Arriving at the correct diagnosis is essential; however a delay in diagnosis may allow progression to perforation and significantly increase the morbidity and mortality.
Materials and Methods : This study was a prospective study and comprised 200 patients admitted with suspected acute appendicitis. The patients were selected unbiased from all age groups of either sex and were evaluated on the basis of predetermined proforma. Subsequent to hospital admission, the preoperative modified Alvarado score (MAS) was determined and C-reactive protein levels (CRP) were estimated. The results of the MAS and preoperative CRP levels were compared with the histopathology of the removed appendix.
Results : Among all the patients studied, 12, 52, and 136 patients had preoperative MAS of <5, 5-6, and 7-9 respectively. One hundred sixty six patients had CRP level raised. A total of 158 patients were histopathologically positive for apendicitis. The sensitivity and specificity of MAS in patients with a score of 5-6 were 58% and 13.5% respectively. In patients with a score of 7-9, MAS had sensitivity and specificity of 93% and 50% respectively. We found 93% sensitivity and 85% specificity of CRP for the diagnosis of acute appendicitis. When combined with CRP, the sensitivity and specificity of MAS in patients with score of 7-9 were raised to 98% and 54% respectively. Moreover, the sensitivity of MAS in patients with a score of 5-6 was raised significantly from 58% to 93%.
Conclusion : We concluded that MAS in combination with the CRP levels is very helpful in the diagnosis of acute appendicitis especially in patients with modified a Alvarado scores in the middle range, who are categorized as "equivocal" for appendicitis by the Alvarado score.
Keywords: Appendicitis, C-reactive protein, modified Alvarado score
|How to cite this article:|
Shafi SM, Malah MA, Malah HR, Reshi FA. Evaluation of the modified Alvarado score incorporating the C-reactive protein in the patients with suspected acute appendicitis. Ann Nigerian Med 2011;5:6-11
|How to cite this URL:|
Shafi SM, Malah MA, Malah HR, Reshi FA. Evaluation of the modified Alvarado score incorporating the C-reactive protein in the patients with suspected acute appendicitis. Ann Nigerian Med [serial online] 2011 [cited 2019 Jul 17];5:6-11. Available from: http://www.anmjournal.com/text.asp?2011/5/1/6/84220
| Introduction|| |
The appendix is a structure without apparent function, yet it has been a frequent cause of morbidity and mortality. Methods of treating diseases of appendix have been developed primarily within the last 80 years, but knowledge of the disease goes back much further into the past. 
Appendicitis may occur for several reasons, such as an infection of the appendix, but the most important is the obstruction of the appendiceal lumen due to lymphoid hyperplasia, insipisated stools, etc., leading to bacterial overgrowth. The continued mucus secretion causes distention of the lumen leading to lymphatic and then venous obstruction, ensuing acute inflammatory response and ultimately to acute appendicitis, gangrene and perforation of the appendix. 
Among young male patients, the negative appendectomy rate is relatively low (5-22%), while for women of child-bearing age, the figure may be as high as 30-50%. In young children, the diagnosis may be wrong in 30-46% of the patients. The difficulty in diagnosing acute appendicitis in old age is reflected by the high incidence of perforation, 60-90% in many reports, rather than by a high rate of negative appendectomy. 
The usual picture of appendicitis is often not classical, leaving in many cases a diagnostic problem. In patients with questionable findings, the aggressive surgical approach has been "when in doubt, take it out," and the price paid was the frequent removal of normal appendices. The negative laparotomy was associated with definite morbidity but the mortality rate was minimal compared to the lethal potential of appendiceal perforation and peritonitis. 
To increase the diagnostic accuracy and to decrease the negative appendectomy rate, a variety of different approaches have been described, including the development of predictive scoring systems,  computer-aided diagnosis,  performance of diagnostic laparoscopy, , ultrasonography,  computed tomography,  and magnetic resonance imaging.  The broad application of these studies in the preoperative diagnosis of appendicitis, however, remains controversial. 
Diagnostic scoring systems have been developed in an attempt to improve the diagnostic accuracy of acute appendicitis. The most prominent of those scores is that developed by Alvarado. In his original paper, Alvarado recommended an operation for all patients with a score of 7 or more and observation for patients with scores of 5 or 6.  Subsequent prospective studies have suggested that the Alvarado score alone is inadequate as a diagnostic test. ,
The classic Alvarado score included left shift of neutrophil maturation (given a score of 1) yielding a total score of 10 but Kalan et al., omitted this parameter which is not routinely available in many laboratories, and produced a modified score. The modified Alvarado score has been widely accepted after it was successfully tested in different studies. 
An elevated level of C-reactive protein (CRP), an acute phase protein, is one of many downstream indicators of inflammation. In most, though not all diseases, the circulating value of CRP reflects ongoing inflammation and/or tissue damage much more accurately than do other laboratory parameters of the acute-phase response. The CRP concentration is thus a very useful but a nonspecific biochemical marker of inflammation, measurement of which contributes importantly to (a) screening for organic disease, (b) monitoring of the response to treatment of inflammation and infection, and (c) detection of intercurrent infection in immunocompromised individuals. 
The aim of this study was to determine the sensitivity and specificity of MAS separately and in combination with the CRP, to ensure preoperative diagnostic accuracy of appendicitis in patients with suspected acute appendicitis.
| Materials and Methods|| |
This study was a prospective study and comprised 200 patients admitted in various surgical wards of our hospital. The patients were selected unbiased from all age groups of either sex and were evaluated on the basis of predetermined proforma.
Subsequent to hospital admission, preoperative MAS was determined and CRP was estimated. CRP of up to 10 μg/ml was considered upper limit of normal standard. Decision to operate was not affected by the preoperative modified Alvarado score or CRP levels.
Determination of the modified Alvarado score (MAS): MAS is based on three symptoms, three signs and one laboratory investigation, as shown in the [Table 1].
The estimated score was not revealed to the operating surgeon preoperatively, but postoperatively the calculated score of each patient was compared with the operative findings and the histopathology report.
Estimation of C-reactive protein (CRP):A rapid latex agglutination slide test was the standard for the qualitative and semi quantitative in vitro determination of CRP in the sample. It is based on the latex agglutination test. It was a qualitative test with the detection limit of approximately 6 mg/l.
For qualitative determination, the latex reagent was mixed thoroughly with the serum. Marked agglutination indicated a CRP concentration of more than 6 mg/l. A smooth homogenous milky suspension indicated a CRP concentration of less than 6 mg/l.
For semiquantitative determinations serum dilutions were prepared with the diluent provided with the kit according to the [Table 2].
Each dilution was tested according to qualitative procedure described above until no further agglutination was observed. The CRP concentration was then estimated from the last dilution with visible agglutination:
CRP (mg/l) = Highest dilution with a positive reaction
X reagent sensitivity (6 mg/l)
Normal levels can be up to 6 mg/l in healthy adults. There are no significant differences in mean CRP values between adult males and nonpregnant females. ,
| Results|| |
The study was conducted on 200 selected patients of all age groups and either sex with the age range of 4-65 years. The mean age of the patient was 23.30 years. There were 118 males and 82 females [Table 3].
The difference in age (years) with regard to sex was statistically nonsignificant (P= 0.092).
The preoperative modified Alvarado score of all the patients included in the study was determined. On the basis of this scoring, there were 12 patients with score of <5, 52 with a score of 5-6, and 136 with a score of 7-9.
The appendix removed at surgery was subjected to histopathological examination. The histological diagnosis of acute appendicitis was made only if there was involvement of muscularis of the appendix. In all cases at least two transverse sections from the proximal half and one longitudinal section from the distal half were studied. On the basis of operative findings and histopathology report, patients were postoperatively diagnosed either as positive or negative for appendicitis.
Out of 42 cases negative for appendicitis, 19 had clear-cut other diagnosis. Rest of the patients had final diagnosis of nonspecific abdominal pain [Table 4].
|Table 4: Showing diagnosis other than appendicitis in the selected patients|
Click here to view
Out of 118 male patients, 98 were positive for appendicitis. Similarly out of 82 female patients 60 were positive for appendicitis [Table 5].
Thus, sex distribution of cases with regard to appendicitis was statistically significant (P-value = 0.001).
Distribution of cases in different age groups with respect to histopathology of the removed appendix was as follows in [Table 6].
|Table 6: Different age groups and histopathology of the removed appendix|
Click here to view
Statistically, a nonsignificant difference was observed (P= 0.855) in patients positive for appendicitis with regard to different age groups. Thus, any particular age group was not affected by appendicitis.
Modified Alvarado scoring in patients with positive histopathology for appendicitis was as follows; [Table 7]
|Table 7: Modified Alvarado scoring in patients with positive histopathology|
Click here to view
A statistically highly significant difference was observed (P-value = 0.0001) in MAS with regard to appendicitis. Sensitivity of MAS was maximum (93 %) in patients with a score of 7-9.
The results of CRP and its sensitivity and specificity in our study are shown in the [Table 8].
Statistically, a highly significant difference was observed in patients with raised CRP regarding appendicitis. Maximum sensitivity (93%) was observed in patients with raised CRP.
All the selected patients were subjected to appendectomy during the study period. On the basis of operative findings patients were divided into three groups;
Group A: Uninflamed appendix (42 patients): no apparent abnormality of the appendix, no signs of inflammation, no evidence of inflamed tip of appendix, no periappendicular fluid, no thickness of wall, or any fecolith within the appendix.
Group B: Inflamed but uncomplicated appendix (126 patients): thickened, edematous, grossly inflamed appendix with or without any fecolith, periappendicular fluid, or inflamed omentum.
Group C: Complicated appendix (32 patients): perforated appendix, appendicular lump, or abscess formation.
In group C, 30 patients had a score of 7-9; 2 patients had a score of 6. None of these patients had a score less than 6. All patients in this group had a raised C-reactive protein level.
Among 158 patients out of 200, who proved to be histopathologically positive for appendicitis, 63 had a score of 7-9. Among these patients, 62 had a raised CRP level; only one had a normal level. Fifteen patients had a score of 5-6; 14 of these patients had a raised CRP level, and 1 had a normal level. There was one patient with histopathology positive with a score of less than 5; this patient had a raised level of CRP [Table 9].
|Table 9: Sensitivity and specificity of MAS incorporating CRP in patients with positive histopathology|
Click here to view
Thus, in patients with positive appendicitis with a preoperative score of 7-9, the sensitivity was raised from 93% to 98% when C-reactive protein was also positive. In patients with a score of 5-6, the sensitivity was raised significantly from 58% to 93%.
Correlation of MAS and CRP in patients with negative histopathology was as in the [Table 10].
| Discussion|| |
Incorrectly diagnosing a patient with appendicitis, although not catastrophic, often subjects the patient to unnecessary laparotomy.  Removal of a noninflamed appendix also causes complications. Negative appendectomy is not a trivial problem. Flum and Koepsell assessed its impact in the United States--length of hospital stay, rate of complications, and mortality were all significantly higher in the negative appendectomy group. 
Laboratory studies can be helpful in the diagnosis of appendicitis, but no single test is definitive. A white blood cell count is perhaps the most useful test. Abdominal ultrasonography is a popular imaging modality for acute appendicitis having a sensitivity and specificity of 0.86 and 0.81 respectively. 
Because of the difficulty in diagnosing appendicitis, it is not uncommon for a normal appendix to be found at appendectomy. Sometimes referred to as misdiagnosis, this can occur more than 15% of the time, with considerably higher percentages in infants, the elderly and young women. Negative appendectomy is to be avoided when possible, due to the risk of surgical complications and the cost associated with the unnecessary surgery. 
In our study, all the patients were operated and decision to operate was not prejudiced by the preoperative modified Alvarado scoring or the level of CRP. On the basis of operative findings, patients were separated into uninflamed appendix, inflamed but uncomplicated appendix, and complicated appendix: groups A--C respectively.
On the basis of MAS, Gyomber D and Luck, grouped the patients as "unlikely" (score <5), "possible" (score 5-6) and "probable" appendicitis (score 7-9). Comparing histological findings to the modified Alvarado score, positive appendicitis was found in 38%, 73%, and 93% of the "unlikely," "possible," and "probable" groups respectively.  Similar results were found in our study.
Out of 42 patients with negative appendix, 12 had a raised value of CRP and 30 patients had CRP levels within normal range. In studies conducted by Asfar and Safar,  13 out of 14 negative laparotomies had a CRP levels within the normal range.
In our study, CRP levels of all patients with complicated appendix were significantly raised preoperatively. Similar results were found in a study conducted by Gurleyik E, and Unalmişer S. In their study, the mean serum CRP value was 5 (0-12.6) mg/l in patients with normal appendix, 33.8 (5-85.1) mg/l in patients with nonperforated appendicitis, and 128.5 (79.2-230) mg/l in patients with perforated appendixes.  Eryilmaz R found in his study that although CRP increases with inflammation, it increases markedly after the occurrence of complication. 
Sensitivity and specificity of CRP in our study was 93.00%, and 85.00% respectively. The positive predictive value was 92.77%. Gurleyik and Unalmişer in their study calculated the sensitivity, specificity, and accuracy of serum CRP measurements as 93.5, 80, and 91%, respectively. 
In our study 30 of 42 patients with negative appendectomy had CRP levels within the normal range. If preoperative serum levels of CRP were to be believed, 30 negative laparotomies would have been avoided. In this study the negative exploration rate was 21%. In studies conducted by Erickson et al., negative appendectomy rate would have been fallen from 24% to 16% if preoperative serum values of CRP would have been followed. 
The sensitivity and specificity of MAS was raised when CRP levels were combined. In patients with a score of 7-9, the sensitivity was raised from 93% to 98% and specificity from 50% to 54%. In patients with a score of 5-6, the sensitivity was raised significantly from 58% to 93% and specificity from 13.5% to 23.5%.
In a previous study, Chan, et al. found that the Alvarado score was most accurate only at the two extremes of the score.  Our study also found it to be most accurate at the extreme of the scores. When CRP was also incorporated, we found that the sensitivity of the middle score (5-6) rose significantly from 58% to 93%.
| Conclusion|| |
Our study concluded that diagnostic accuracy of acute appendicitis on the basis of clinical examination was less than 80%. MAS was sensitive, but with a relatively low specificity and alone does not contribute to the diagnosis of acute appendicitis in patients with equivocal clinical findings. CRP levels were found to be highly sensitive and specific for the diagnosis of acute appendicitis. The sensitivity and specificity was increased when CRP levels were combined with MAS. All the cases with complicated appendicitis were found to have high MAS with raised levels of CRP, reflecting increased accuracy of the combination in diagnosing acute appendicitis. When CRP levels were within the normal limits and the scores were low, acute appendicitis was unlikely. We found MAS to be most accurate at the extreme of the scores. When CRP was also incorporated in the patients with the middle score of 5-6 (equivocal for appendicitis), the sensitivity rose significantly from 58% to 93%.
Our study showed that in patients with high MAS and raised CRP levels, the probability of acute appendicitis was significantly increased with improved sensitivity and specificity. We believe that both MAS and CRP levels should be estimated in all patients who come to hospital with complaints of pain in the right iliac fossa. These are not costly to the patient, are noninvasive, and do not require any sophisticated equipments or technical expertise. Moreover, the results of these parameters can be obtained within no time making a surgeon to establish diagnosis immediately and thereby avoiding unwanted explorations and preventing complications (perforation, abscess).
| References|| |
|1.||Maide RH. The evolution of surgery for appendicitis. Surgery 1964;55:741-52. |
|2.||Beauchamp, Evers, Mattox, Sabiston text book of surgery. 17 th ed, vol 2. The Biological Basis of Modern Surgical Practice. Elsevier; 2004. p. 1381-2. |
|3.||Hoffmann J, Rasmussen O. Aids in the diagnosis of appendicitis. Br J Surg 1989;76:774-9. |
|4.||Teicher IR, Landa B, Cohen M, Kabnick LS, Wise L. Scoring system to aid in diagnosis of acute appendicitis. Ann Surg 1983;198:753-9. |
|5.||Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557-64. |
|6.||De Dombal FT, Leaper DJ, Staniland JR, McCann AP, Horrocks JC. Computer aided diagnosis of acute abdominal pain. BMJ 1972;2:913. |
|7.||Olsen JB, Myren CJ, Haahr PE. Randomized study of the value of laparoscopy before appendicectomy. Br J Surg 1993;80:822923. |
|8.||Moberg AC, Ahlberg G, Leijonmarck CE, Montgomery A, Reiertsen O, Rosseland AR, et al. Diagnostic laparoscopy in 1043 patients with suspected appendicitis. Eur J Surg 1998;164:83340. |
|9.||Puylaert JB. Acute appendicitis: US evaluation using graded compression. Radiology 1986;158:35560. |
|10.||Balthazar EJ. Appendicitis: Prospective evaluation with high resolution CT. Radiology 1991;180:214. |
|11.||Incesu L, Coskun A, Selcuk MB, Akan H, Sozubir S, Bernay F. Acute appendicitis: MR imaging and sonographic correlation. Am J Roentgenol 1997;168:66974. |
|12.||Adams DH, Fine C, Brooks DC. High resolution real time ultrasonography: A new tool in the diagnosis of acute appendicitis. Am J Surg 1988;155:93-7. |
|13.||Zinner MJ, Ashley SW. Maingot's Abdominal Operations. 11 th ed. McGraw Hill; 2007. p. 589-608. |
|14.||Ohmann C, Yang Q, Franke C. Diagnostic scores for acute appendicitis. Eur J Surg 1995;161:273-81. |
|15.||Macklin CP, Radcliffe GS, Merei JM, Stringer MD. A prospective evaluation of the modified Alvarado scores for acute appendicitis in children. Ann R Coll Surg Engl 1997;79:2035. |
|16.||Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: A prospective study. Ann R Coll Surg Engl 1994;76:418-9. |
|17.||Al-Hashemy AM, Seleem MI. Appraisal of the modified Alvarado Score for acute appendicits in adults. Saudi Med J 2004;25:1229-31. |
|18.||Pepys MB, Hirschfield GM. C-reactive protein: A critical update. J Clin Invest 2003;111:1805-12. |
|19.||Benjamin IS. Managing acute appendicitis. BMJ 2002;325:505-6. |
|20.||Gyomber D, Luck A, Slater L. Analysis of Modified Alvarado Score in a peripheral hospital: Reducing the negative appendicectomy rate. The Royal Australasian College of Surgeons Annual Scientific Congress: 15-19 th May 2006; Sydney Convention and Exhibition Centre, Darling Harbour, Sydney. |
|21.||Asfar S, Safar H. Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis? J R Coll Surg Edinb 2000;45:21-4. |
|22.||Gurleyik E, Gurleyik G. Accuracy of Serum C-reactive protein measurements in diagnosis of acute appendicitis compared with surgeon's clinical impression. Dis Colon Rectum 1995;38:1270-4. |
|23.||Eryilmaz R, Sahin M, Alimoğlu O, Baş G, Ozkan OV. The value of C-reactive protein and leucocyte count in preventing negative appendectomies. Ulus Travma Derg 2001;7:142-5. |
|24.||Albu E, Miller BM, Choi Y, Lakhanpal S, Murthy RN, Gerst PH. Diagnostic value of C-reactive protein in acute appendicitis. Dis Colon Rectum 1994;37:49-51. |
|25.||Eriksson S, Granstrom L. Laboratory tests in patients with suspected acute appendicitis. Acta Chir Scand 1994;155:117-20. |
|26.||Chan MY, Tan C, Chiu MT, Ng YY. Alvarado score: An admission criterion in patients with right iliac fossa pain. Surgeon 2003;1:39-41. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]