eMedicine Specialties > Emergency Medicine > Gastrointestinal

Appendicitis, Acute: Differential Diagnoses & Workup

Author: Sandy Craig, MD, Adjunct Associate Professor, Department of Emergency Medicine, University of North Carolina at Chapel Hill, Carolinas Medical Center
Contributor Information and Disclosures

Updated: Jun 1, 2009

Differential Diagnoses

Other Problems to Be Considered

Appendiceal stump appendicitis
Typhilitis
Epiploic appendagitis
Psoas abscess
Yersiniosis

Workup

Laboratory Studies

Complete blood cell count

Studies consistently show that 80-85% of adults with appendicitis have a WBC count greater than 10,500 cells/mm³. Neutrophilia greater than 75% occurs in 78% of patients. Fewer than 4% of patients with appendicitis have a WBC count less than 10,500 cells/mm³ and neutrophilia less than 75%.

Dueholm et al, in 1989, further delineated the relationship between WBC count and the likelihood of appendicitis by calculating likelihood ratios for defined intervals of the WBC count.³

 Table 1. WBC Count and Likelihood of Appendicitis

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*CI, confidence interval.

CBC tests are inexpensive, rapid, and widely available; however, the findings are nonspecific.

The literature is inconsistent with regard to WBC counts in children and elderly patients with appendicitis.

C-reactive protein test

C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to infection or inflammation. A rapid assay is widely available.

Several prospective studies (Thimsen 1989, Albu 1994, de Carvalho 2003) have shown that, in adults who have had symptoms for longer than 24 hours, a normal CRP level has a negative predictive value of 97-100% for appendicitis.^4,5

In a 1989 study of 70 patients, Thimsen et al noted that a normal CRP level after 12 hours of symptoms was 100% predictive of benign, self-limited illness.⁴

Multiple studies have examined the sensitivity of CRP alone for the diagnosis of appendicitis in patients selected to undergo appendectomy.

• Gurleyik et al, in 1995, found that 87 of 90 patients with histologically proven appendicitis had an elevated CRP, a sensitivity of 96.6%.⁶
• Shakhetrah, in 2000, found that 85 of 89 patients with histologically proven appendicitis had an elevated CRP, a sensitivity of 95.5%.⁷
• Asfar et al, in 2000, completed a prospective double blind study of 78 patients undergoing appendectomy and found that CRP had a sensitivity of 93.6%.⁸
• Erkasap et al, in 2000, prospectively studied the more relevant group of 102 adult patients with RLQ pain, 55 of whom proceeded to appendectomy. In this group, the sensitivity of CRP was 96%.⁹

Investigators have also studied the ability of combinations of WBC and CRP to reliably rule out the diagnosis of appendicitis.

• Gronroos, in 1999, studied 300 patients operated for suspected appendicitis (200 positive, 100 negative) and found that WBC or CRP was abnormal in all 200 patients with appendicitis.¹⁰
• Ortega-Deballon et al, in 2008, prospectively studied patients referred to a surgeon for RLQ pain and found that normal WBC and CRP had a negative predictive value of 92.3% for the presence of appendicitis.¹¹
• Yang, in 2006, retrospectively studied 897 patients who underwent appendectomy (740 with appendicitis, 157 without) and found that only 6 of 740 patients with appendicitis had WBC <10,500 cells/mm³ AND neutrophilia >75%, AND a normal CRP. This yields a sensitivity of 99.2% for the "triple screen".¹²

Some studies have examined the sensitivity of combined WBC and CRP in the subpopulation of patients older than 60 years.

• Gronroos, in 1999, studied 83 patients older than 60 years who underwent appendectomy (73 found to have appendicitis) and found that no patient with appendicitis had both normal WBC and CRP.¹³
• Yang et al, in 2005, retrospectively studied 77 patients older than 60 years with histologically proven appendicitis and found that only 2 had a normal "triple screen."¹⁴

Several studies have examined the accuracy of CRP and WBC in the subpopulation of pediatric patients with suspected appendicitis.

• Gronroos, in 2001, studied 100 children with pathology-proven appendicitis and found that both WBC and CRP were normal in 7 of the 100 patients.¹⁵
• Mohammed, in 2004, prospectively studied 216 children admitted for suspected appendicitis and found triple screen sensitivity and negative predictive value of 86% and 81%, respectively.¹⁶
• Stefanutti et al, in 2007, prospectively studied more than 100 children undergoing surgery for suspected appendicitis and found that either WBC or CRP was elevated in 98% of those with pathology-proven appendicitis (CI, 95.3-100%).¹⁷

CRP is nonspecific and does not distinguish between various types of infection or inflammation.

Urinalysis

One study of 500 patients with acute appendicitis revealed that approximately one third reported urinary symptoms, most commonly dysuria or right flank pain. One in 7 patients had pyuria greater than 10 WBC per high power field, and 1 in 6 patients had greater than 3 RBC per high power field. Thus, the diagnosis of appendicitis should not be dismissed due to the presence of urologic symptoms or abnormal urinalysis.¹⁸

Imaging Studies

• Computed tomography
  • Abdominal CT has become the most important imaging study in the evaluation of patients with atypical presentations of appendicitis. Studies have found a decrease in negative laparotomy rate and appendiceal perforation rate when pelvic CT was used in selected patients with suspected appendicitis.^19,20,21,22
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    CT scan reveals an enlarged appendix with thickened walls, which do not fill with colonic contrast agent, lying adjacent to the right psoas muscle.

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    CT scan reveals an enlarged appendix with thickened walls, which do not fill with colonic contrast agent, lying adjacent to the right psoas muscle.

  • Note that one study of asymptomatic volunteers undergoing pelvic CT found that 42% had an "abnormal" appendiceal diameter of greater than 6 mm and 78% of appendices did not fill after oral contrast. Thus, findings on CT must be correlated with the clinical scenario.²³
  • Advantages of CT scanning include its superior sensitivity and accuracy compared with those of other imaging techniques, ready availability, noninvasiveness, and potential to reveal alternative diagnoses. Disadvantages include radiation exposure, potential for anaphylactic reaction if intravenous contrast agent is used, lengthy acquisition time if oral contrast is used, and patient discomfort if rectal contrast is used.
  • Initial studies evaluated sequential (nonhelical) CT in the diagnosis of appendicitis. In 1993, Malone evaluated nonenhanced, sequential CT in 211 patients and reported a sensitivity of 87% and a specificity of 97%.²⁴ The addition of intravenous and oral contrast agent increased sensitivity to 96-98%. Thus, sequential CT with oral and intravenous contrast enhancement is highly accurate but time consuming and expensive; it is best used for equivocal presentations when helical CT is not available.
  • In 1997, Lane et al evaluated helical CT without contrast enhancement and found a sensitivity of 90% and specificity of 97%.²⁵ More recent studies of noncontrast helical CT in adults with suspected appendicitis showed a sensitivity of 91-96% and a specificity of 92-100%.^{26,27,28,29,30}  
  • In a 2004 study of pediatric patients, Kaiser et al found that nonenhanced CT was 66% sensitive.³¹ Sensitivity increased to 90% with the use of intravenous contrast material. In a 2005 study of 112 pediatric patients, Hoecker and Bilman found that unenhanced CT achieved a sensitivity of 87.5%, specificity of 98.7%, positive predictive value of 91.3%, and negative predictive value of 90.8%.³²
  • In 1997, Rao et al found that focused (lower abdominal and upper pelvic) helical CT with 3% Gastrografin instilled into the colon (without intravenous contrast agent) had a superior sensitivity of 98% and specificity of 98%.³³ Focused helical scanning without intravenous contrast agent eliminates the risk of anaphylaxis and reduces the cost to about $230. Acquisition time is less than 15 minutes. Radiation exposure is less than that of a standard obstruction series. Alternative diagnoses are revealed in up to 62% of patients and include diverticulitis, nephrolithiasis, adnexal pathology, RLQ tumor, small-bowel hernias, and ischemia.
  • The literature suggests that limited helical CT with rectal contrast enhancement is a highly accurate, time-efficient, cost-effective way to evaluate adults with equivocal presentations for appendicitis. Two studies of focused helical CT with rectal contrast in children suggest a sensitivity of 95-97%. This is an excellent diagnostic approach in patients with equivocal presentations who are poor candidates for intravenous contrast.
  • One recent retrospective study of 173 adults found that helical CT with intravenous contrast only has a sensitivity of 100%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 100%.³⁴ An earlier study of 78 patients with appendicitis found sensitivity of 91.9%, specificity of 87.5%, and accuracy of 91%.³⁵ In a 2005 retrospective review of 23 published reports, Anderson et al found that CT without oral contrast was at least as accurate as CT with oral contrast, achieving sensitivity of 95%, specificity of 97%, positive predictive value of 97%, and negative predictive value of 96%.³⁶ Elimination of oral contrast reduces emergency department length of stay and delay to operative intervention.
  • Continued improvements in helical CT technology may allow nonenhanced helical CT to be the imaging test of choice for adults with suspected appendicitis. Additional studies are needed to identify subgroups that derive the most benefit from diagnostic imaging.
• Ultrasonography
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    Sagittal graded compression transabdominal sonogram shows an acutely inflamed appendix. The tubular structure is noncompressible, lacks peristalsis, and measures greater than 6 mm in diameter. A thin rim of periappendiceal fluid is present.

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    Sagittal graded compression transabdominal sonogram shows an acutely inflamed appendix. The tubular structure is noncompressible, lacks peristalsis, and measures greater than 6 mm in diameter. A thin rim of periappendiceal fluid is present.

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    Transverse graded compression transabdominal sonogram of an acutely inflamed appendix. Note the targetlike appearance due to thickened wall and surrounding loculated fluid collection.

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    Transverse graded compression transabdominal sonogram of an acutely inflamed appendix. Note the targetlike appearance due to thickened wall and surrounding loculated fluid collection.

  • In 1986, Puylaert described a graded compression technique for evaluating the appendix with transabdominal sonography.³⁷ A 5-MHz transducer is used. Gentle but firm pressure is applied on the RLQ to displace intervening bowel gas and to decrease the distance between the transducer and the appendix, improving image quality. An outer diameter of greater than 6 mm, noncompressibility, lack of peristalsis, or periappendiceal fluid collection characterizes an inflamed appendix. The normal appendix is not visualized in most cases. A posterolateral approach is suggested to evaluate the retrocecal area. Scattered case reports endorse transvaginal sonography in women with low pelvic tenderness if the appendix is not visualized on transabdominal scans.
  • Numerous studies have documented a sensitivity of 85-90% and a specificity of 92-96%. Five studies of graded compression ultrasonography in children showed overall sensitivities of 85-95% and specificities ranging from 47-96%. One study found sensitivity of 35% and specificity of 98% in pediatric patients with perforated appendicitis. The cost is approximately $225.
  • Advantages of sonography include its noninvasiveness, short acquisition time, lack of radiation exposure, and potential for diagnosis of other causes of abdominal pain, particularly in the subset of women of childbearing age. Many authorities believe that ultrasonography should be the initial imaging test in pregnant women and in pediatric patients because radiation exposure is particularly undesirable in these groups.
  • One new study suggests that ultrasonography should be incorporated as a first-line imaging modality for the diagnosis of acute appendicitis in adults.³⁸
    • In this study, 151 patients with suspected appendicitis underwent the designed protocol. Graded-compression ultrasonography was performed first. Patients with positive results on graded-compression ultrasonography underwent surgery. Those with inconclusive or negative results underwent contrast-enhanced multidetector CT. Patients with positive findings on CT also underwent surgery. Patients with negative CT findings were admitted for observation. Positive ultrasonography was confirmed at surgery in 71 of 79 patients, and positive CT was confirmed in 21 patients. Thirty-nine patients with normal CT results recovered and did not require surgery. The sensitivity and specificity of this protocol was 100% and 86%, respectively. 
    • Poortman et al concluded that this diagnostic pathway using primary graded-compression ultrasonography and complementary multidetector CT yields a high diagnostic accuracy for acute appendicitis without adverse events from delay in treatment. Although ultrasonography is less accurate than CT, it can be used as a primary imaging modality and avoids the disadvantages of CT. Observation is safe for patients with negative findings on ultrasonography or CT.
  • The principal disadvantage is that ultrasonography is operator dependent. Because nonvisualization is interpreted as a noninflamed appendix, technical expertise and commitment to a thorough examination are essential in obtaining maximum sensitivity.
  • If graded compression sonogram of the RLQ is positive for appendicitis, appendectomy should be performed. If negative, this finding is not sufficiently sensitive to rule out the possibility of appendicitis. Consideration should be given to further observation and focused helical CT with rectal contrast enhancement.
  • Tzanakis and others proposed a clinical scoring system that assigns 6 points if appendiceal ultrasonogram is positive, 4 points for RLQ tenderness, 3 points for rebound tenderness, and 2 points for WBC count greater than 12,000. In their prospective study of 303 adults using a total score cut-off of 8 points or greater, they found sensitivity, specificity, and accuracy of 95.4%, 97.4%, and 96.5%, respectively.³⁹ These findings should be confirmed by additional studies before routine clinical use.
• Abdominal radiography
  • The kidneys-ureters-bladder (KUB) view is typically used. Visualization of an appendicolith in a patient with symptoms consistent with appendicitis is highly suggestive of appendicitis, but this occurs in fewer than 10% of cases.
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    Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in the right lower quadrant. An appendicolith is seen in fewer than 10% of patients with appendicitis, but, when present, it is essentially pathognomonic.

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    Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in the right lower quadrant. An appendicolith is seen in fewer than 10% of patients with appendicitis, but, when present, it is essentially pathognomonic.

  • The consensus in the literature is that plain radiographs are insensitive, nonspecific, and not cost-effective.
• Barium enema study
  • A single-contrast study can be performed on an unprepared bowel. Absent or incomplete filling of the appendix coupled with pressure effect or spasm in the cecum suggests appendicitis. The cost is approximately $420.
  • Multiple studies have found that the sensitivity of a barium enema study is in the range of 80-100%. However, as many as 16% of studies in adults (22-39% in children) were technically unsuitable for interpretation and excluded from data analysis.
  • Advantages of barium enema study are its wide availability, use of simple equipment, and potential for diagnosis of other diseases (eg, Crohn disease, colon cancer, ischemic colitis) that may mimic appendicitis.
  • Disadvantages include its high incidence of nondiagnostic results, radiation exposure, insufficient sensitivity, and invasiveness. These disadvantages make barium enema study a poor screening examination for use by emergency departments.
  • Barium enema study has essentially no role in the diagnosis of acute appendicitis in the era of ultrasonography and CT.
• Radionuclide scanning
  • Whole blood is withdrawn for radionuclide scanning. Neutrophils and macrophages are labeled with technetium-99m albumin and administered intravenously. Images of the abdomen and pelvis are obtained serially over 4 hours. Localized uptake of tracer in the RLQ suggests appendiceal inflammation.
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    Technetium-99m radionuclide scan of the abdomen shows focal uptake of labeled WBCs in the right lower quadrant consistent with acute appendicitis.

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    Technetium-99m radionuclide scan of the abdomen shows focal uptake of labeled WBCs in the right lower quadrant consistent with acute appendicitis.

  • Four early studies in adults with suspected appendicitis showed a sensitivity of 80-90% and specificity of 92-100%.^40,41,42,43 Two studies of newer labeling techniques achieved sensitivities of 98% for the presence of appendicitis.^44,45
  • Although future studies may confirm sensitivity as high as 98%, the acquisition time of 5 hours and the lack of availability are disadvantages to its use as a high-sensitivity ED screening test for appendicitis.
• Magnetic resonance imaging
  • MRI plays a relatively limited role in the evaluation because of high cost, long scan times, and limited availability, though the lack of ionizing radiation makes it an attractive modality in pregnant patients.
  • A single retrospective study assessed the accuracy of MRI in 51 pregnant patients with suspected appendicitis in whom ultrasonography was nondiagnostic. Sensitivity, specificity, positive and negative predictive values, and accuracy for MRI was 100%, 93.6%, 91.4%, 100%, and 94.0%, respectively.⁴⁶
  • Cobben et al showed that MRI is far superior to transabdominal ultrasonography in evaluating pregnant patients with suspected appendicitis.⁴⁷
  • When evaluating pregnant patients with suspected appendicitis, graded compression ultrasound should be the imaging test of choice. If ultrasonography demonstrates an inflamed appendix, the patient should undergo appendectomy. If graded compression ultrasonography is nondiagnostic, the patient should undergo MRI of the abdomen and pelvis.

Other Tests

Clinical diagnostic scores

Several investigators have created diagnostic scoring systems in which a finite number of clinical variables is elicited from the patient and each is given a numerical value. The sum of these values is used to predict the likelihood of acute appendicitis.

The best known of these is the MANTRELS score, which tabulates migration of pain, anorexia, nausea and/or vomiting, tenderness in the RLQ, rebound tenderness, elevated temperature, leukocytosis, and shift to the left (Table 2).

Table 2. MANTRELS Score

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Source.—Alvarado, 1986.⁴⁸

Clinical scoring systems are attractive because of their simplicity; however, none has been shown prospectively to improve on the clinician's judgment in the subset of patients evaluated in the ED for abdominal pain suggestive of appendicitis. The MANTRELS score, in fact, was based on a population of patients hospitalized for suspected appendicitis, which differs markedly from the population seen in the ED.

McKay et al reviewed 150 emergency department patients who underwent abdominopelvic CT to rule out appendicitis. In that series, patients with a MANTRELS score of 3 or lower had a 3.6% incidence of appendicitis, patients with scores of 4-6 had a 32% incidence of appendicitis, and patients with scores of 7-10 had a 78% incidence of appendicitis. These investigators suggested that patients with an Alvarado score of 0-3 could be discharged without imaging, that those with scores of 7 or above receive surgical consultation, and those with scores of 4-6 undergo computed tomography.⁴⁹

Schneider et al, in 2007, studied 588 patients aged 3-21 years and found that a MANTRELS score of 7 or greater had a positive predictive value of 65% and a negative predictive value of 85%. They concluded that the MANTRELS score was not sufficiently accurate to be used as the sole method for determining the need for appendectomy in the pediatric population.⁵⁰

Computer-aided diagnosis

A retrospective database of clinical features of patients with appendicitis and other causes of abdominal pain is entered into a computer. It is then used in prospectively assessing the risk of appendicitis.

Computer-aided diagnosis can achieve a sensitivity greater than 90% while reducing rates of perforation and negative laparotomy by as much as 50%.

The principle disadvantages are that each institution must generate its own database to reflect characteristics of its local population. Specialized equipment and significant initiation time are required.

Computer-aided diagnosis is not widely available in US EDs.

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