Appendicitis Workup

Patients with appendicitis may not have the reported classic clinical picture 37-45% of the time, especially when the appendix is located in an unusual place (see Anatomy). In such cases, imaging studies may be important but not always available. However, patients with appendicitis usually have accessory signs that may be helpful for diagnosis (see Physical Examination). For example, the obturator sign is present when the internal rotation of the thigh elicits pain (ie, pelvic appendicitis), and the psoas sign is present when the extension of the right thigh elicits pain (ie, retroperitoneal or retrocecal appendicitis).

Laboratory tests are not specific for appendicitis, but they may be helpful to confirm diagnosis in patients with an atypical presentation.For example, liver and pancreatic function tests (eg, transaminases, bilirubin, alkaline phosphatase, serum lipase, amylase) may be helpful to determine the diagnosis in patients with an unclear presentation. For women of childbearing age, the level of urinary beta–human chorionic gonadotropin (beta-hCG) is useful in differentiating appendicitis from early ectopic pregnancy.

Studies consistently show that 80-85% of adults with appendicitis have a white blood cell (WBC) count greater than 10,500 cells/µL. Neutrophilia greater than 75% occurs in 78% of patients. Less than 4% of patients with appendicitis have a WBC count less than 10,500 cells/µL and neutrophilia less than 75%.

Dueholm et al further delineated the relationship between the WBC count and the likelihood of appendicitis by calculating likelihood ratios for defined intervals of the WBC count. ^[23]

Table 2. WBC Count and Likelihood of Appendicitis (Open Table in a new window)

Complete blood cell (CBC) tests are inexpensive, rapid, and widely available; however, the findings are nonspecific. In infants and elderly patients, a WBC count is especially unreliable because these patients may not mount a normal response to infection. In pregnant women, the physiologic leukocytosis renders the CBC count useless for the diagnosis of appendicitis.

C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in response to infection or inflammation and rapidly increases within the first 12 hours. CRP has been reported to be useful in the diagnosis of appendicitis; however, it lacks specificity and cannot be used to distinguish between sites of infection.

CRP levels of greater than 1 mg/dL are commonly reported in patients with appendicitis, but very high levels of CRP in patients with appendicitis indicate gangrenous evolution of the disease, especially if it is associated with leukocytosis and neutrophilia. However, CRP normalization occurs 12 hours after onset of symptoms. Several prospective studies 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. ^{[3, 4, 5]} Thimsen et al noted that a normal CRP level after 12 hours of symptoms was 100% predictive of benign, self-limited illness. ^[3]

CRP sensitivity

Multiple studies have examined the sensitivity of CRP level alone for the diagnosis of appendicitis in patients selected to undergo appendectomy. Gurleyik et al noted a CRP sensitivity of 96.6% in 87 of 90 patients with histologically proven disease. ^[24] Similarly, Shakhetrah found a CRP sensitivity of 95.5% in 85 of 89 patients with histologically proven appendicitis. ^[25] Asfar et al reported a CRP sensitivity of 93.6% in 78 patients undergoing appendectomy, ^[26] and Erkasap et al found a CRP sensitivity of 96% in a group of 102 adult patients with right lower quadrant (RLQ) pain, 55 of whom proceeded to appendectomy. ^[27]

Sensitivity of WBC count and CRP level in combination

Investigators have also studied the ability of combinations of white blood cell (WBC) count and CRP to reliably rule out the diagnosis of appendicitis. Gronroos and Gronroos found that the WBC count or CRP level was abnormal in all 200 patients with appendicitis in their cohort of 300 patients operated for suspected appendicitis. ^[28] Ortega-Deballon et al found that a normal WBC count and CRP level had a negative predictive value of 92.3% for the presence of appendicitis in prospectively studied patients referred to a surgeon for RLQ pain. ^[29]

Some studies have examined the sensitivity of a combined WBC count and CRP level in the subpopulation of patients older than 60 years. Gronroos studied 83 patients older than 60 years who underwent appendectomy (73 found to have appendicitis) and found that no patient with appendicitis had both a normal WBC count and CRP level. ^[30] Yang et al retrospectively studied 77 patients older than 60 years with histologically proven appendicitis and found that only 2 had a normal "triple screen" (see below). ^[31]

Several studies also examined the accuracy of the WBC count and CRP level in the subpopulation of pediatric patients with suspected appendicitis. Gronroos evaluated 100 children with pathology-proven appendicitis and found that both the WBC count and CRP level were normal in 7 of 100 patients. ^[32] Stefanutti et al prospectively studied more than 100 children undergoing surgery for suspected appendicitis and found that either the WBC count or CRP level was elevated in 98% of those with pathology-proven appendicitis. ^[33]

Triple screen of WBC count, CRP level, and neutrophilia

Mohammed et al prospectively studied 216 children admitted for suspected appendicitis and found a triple screen sensitivity of 86% and a negative predictive value of 81. ^[34] However, Yang et al found that only 6 of 740 patients with appendicitis had a WBC count less than 10,500 cells/μ L AND neutrophilia that was less than 75%, AND a normal CRP level, yielding a sensitivity of 99.2% for the "triple screen." ^[35]

Urinalysis

Urinalysis may be useful in differentiating appendicitis from urinary tract conditions. Mild pyuria may occur in patients with appendicitis because of the relationship of the appendix with the right ureter. Severe pyuria is a more common finding in urinary tract infections (UTIs). Proteinuria and hematuria suggest genitourinary diseases or hemocoagulative disorders.

One study of 500 patients with acute appendicitis revealed that approximately one third reported urinary symptoms, most commonly dysuria or right flank pain. ^[36] One in 7 patients had pyuria greater than 10 WBCs per high power field (hpf), and 1 in 6 patients had greater than 3 red blood cells (RBCs) per hpf. Thus, the diagnosis of appendicitis should not be dismissed due to the presence of urologic symptoms or abnormal urinalysis. ^[36]

Urinary 5-hydroxyindoleacetic acid

According to a report by Bolandparvaz et al, measurement of the urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels could be an early marker of appendicitis. ^[6]  The rationale of such measurement is related to the large amount of serotonin-secreting cells in the appendix. The investigators noted that U-5-HIAA levels increased significantly in acute appendicitis, decreasing when the inflammation shifted to necrosis of the appendix. ^[6]  Therefore, such decrease could be an early warning sign of perforation of the appendix.

Computed tomography (CT) scanning with oral contrast medium or rectal Gastrografin enema has become the most important imaging study in the evaluation of patients with atypical presentations of appendicitis. Intravenous contrast is usually not necessary.

Studies have found a decrease in negative laparotomy rate and appendiceal perforation rate when pelvic CT imaging was used in selected patients with suspected appendicitis. ^{[37, 38, 39, 40]} An enlarged appendix is shown in the CT below.

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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The use of CT has dramatically increased since the introduction of multidetector CT (MDCT) scanners. A large, single center study found that MDCT has a high rate of sensitivity and specificity (98.5% and 98%, respectively) for diagnosing acute appendicitis. ^[41]

In adults with appendicitis, the diagnostic performance of CT scans with intravenous contrast alone is comparable to that of scans with both intravenous and oral contrast, and patients who receive CT scans with intravenous contrast alone are discharged more quickly from the emergency department. ^[42]

CT scanning may also be used to detect atypically located acute appendicitis, including inguinal or femoral canal, subhepatic, retrocecal, intraperitoneal abdominal midline as well as left side in situs inversus or intestinal malrotation patients. ^[43] In this setting, patients may have an atypical presentation that causes a misleading or confusing diagnosis.

Concerns have grown over the possible adverse effects on patients from exposure to radiation from CT scanning. Low-dose abdominal CT allows for a 78% reduction in radiation exposure compared to traditional abdominopelvic CT and may be preferable for diagnosing children and young adults in whom exposure to CT radiation is of particular concern. ^[7] Ultrasonography may offer a safer alternative as a primary diagnostic tool for appendicitis, with CT scanning used in those cases in which ultrasonograms are negative or inconclusive.

An algorithm for screening pediatric patients (≤18 y) with suspected appendicitis appears to reduce the use of CT scanning without affecting diagnostic accuracy. ^{[44, 45]}  This tool also has implications for reducing the levels of radiation exposure and the cost of using this imaging modality. The algorithm includes pediatric surgery consultation without imaging studies in patients with an unequivocal history; for those with an equivocal history, physical examination, and ultrasonographic findings, the algorithm includes consultation and physical examination before obtaining CT studies. ^[45]

Investigators analyzed data from 331 pediatric patients with suspected appendicitis 2 years before (41%; n = 136) and 3 years after (59%; n = 195) implementation of the new algorithm and found a significant decrease in the use of CT scanning from 39% to 18%, respectively. ^{[44, 45]}  Moreover, although the negative appendectomy rate rose from 9% pre-implementation of the algorithm to 11% post-implementation, this increase was not significant and there was no association between negative appendectomy and CT scan utilization. ^{[44, 45]}

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Because of concerns about patient exposure to radiation during computed tomography (CT) scans, ultrasonography has been suggested as a safer primary diagnostic modality for appendicitis, with CT scanning used secondarily when ultrasonograms are negative or inconclusive. ^{[46, 47, 48]}

A healthy appendix usually cannot be viewed with ultrasonography. When appendicitis occurs, the ultrasonogram typically demonstrates a noncompressible tubular structure of 7-9 mm in diameter (see the images below).

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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In pediatric patients, the American College of Emergency Physicians (ACEP) 2010 clinical policy update recommends using ultrasonography for confirmation, but not exclusion, of acute appendicitis. To definitively exclude acute appendicitis, CT is recommended. ^{[8, 9]}

Ultrasonography followed by magnetic resonance imaging (MRI) appears to be an effective combination for accurately diagnosing appendicitis in children. ^{[49, 50]} In a retrospective study of 662 patients younger than age 18 years presenting to the emergency department with abdominal pain, ultrasonography/MRI was performed in 397 patients and CT scanning was used in 265. In the ultrasonography/MRI group, ultrasound was positive for appendicitis in 19.7% of patients, and MRI identified an additional 62 cases, of which 7 (11.3%) were complicated. In the CT group, 55.4% of patients positive for appendicitis, of which 19.4% were complicated. ^{[49, 50]}

The false-positive rate was similar in the two groups (1.4% in the ultrasonography/MRI group and 2.5% in the CT group), and there were no false-negatives in either group. ^{[49, 50]} No significant differences between groups were observed in mean overall length of hospital stay, time to antibiotic administration, time to appendectomy, or perforation rate. ^{[49, 50]}

Vaginal ultrasonography alone or in combination with transabdominal scan may be useful to determine the diagnosis in women of childbearing age. One study of 22 pregnant women in the first and second trimesters showed that graded compression ultrasonography had a sensitivity of 66% and specificity of 95%. ^[10]

Ultrasonography findings may also aid clinicians in differentiating complicated from uncomplicated appendicitis, which in turn guides the decision making regarding whether to administer antibiotic therapy first or initiate and perform appendectomy. ^[51] In a retrospective, blinded study, the medical records of 119 patients with acute appendicitis were reviewed, of which 32 patients had complicated appendicitis (including gangrenous, with or without perforation). Investigators found that the only significant independent predictor of complicated appendicitis was loss of the normally echogenic submucosal layer, with 100% sensitivity and 92.0% specificity. ^[51]

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The kidneys-ureters-bladder (KUB) radiographic view is typically used to visualize an appendicolith in a patient with symptoms consistent with appendicitis. This finding is highly suggestive of appendicitis, but appendicoliths also occur in fewer than 10% of cases. The consensus in the literature is that plain radiographs are insensitive, nonspecific, and not cost-effective.

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In the past, barium enema examination was used to diagnose appendicitis; in the era of ultrasonography and CT scanning, barium enema study has essentially no role in the diagnosis of acute appendicitis.

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 typical radiologic sign of appendicitis is the "reverse 3," which typically manifests as an indentation of the cecum. However, the appendix cannot be visualized in 50% of healthy individuals; therefore, barium enema lacks reliability.

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Whole blood is withdrawn for radionuclide scanning. Neutrophils and macrophages are labeled with technetium Tc 99m (^99m Tc) albumin and administered intravenously. Then, images of the abdomen and pelvis are obtained serially over 4 hours. Localized uptake of tracer in the RLQ suggests appendiceal inflammation; this is shown in the image below.

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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Traditionally, magnetic resonance imaging (MRI) has played a relatively limited role in the evaluation of appendicitis because of its high cost, long scan times, and limited availability. However, the lack of ionizing radiation makes it an attractive modality in pregnant patients. In fact, Cobben et al showed that MRI is far superior to transabdominal ultrasonography in evaluating pregnant patients with suspected appendicitis. ^[52]  Moreover, the sensitivity and specificity of MRI for appendicitis appears to be similar to those of computed tomography (CT) scanning. ^[53]

Nonetheless, when evaluating pregnant patients with suspected appendicitis, graded compression ultrasonography 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.

When used for evaluating pediatric patients, MRI has a higher sensitivity than ultrasound. In a prospective comparison of ultrasound and MRI in 104 children with suspected appendicitis, researchers found that MRI had a sensitivity of 100% compared to ultrasound which had a sensitivity of 76%. Tolerance of MRI was comparable to that of tolerance for ultrasound. ^[54]

A retrospective study of 662 patients younger that age 18 years who presented to the emergency department with abdominal pain found that ultrasound followed selectively by MRI accurately diagnosed pediatric appendicitis. ^{[49, 50]}

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In the early stages of appendicitis, the appendix grossly appears edematous with dilation of the serosal vessels. Microscopy demonstrates neutrophil infiltrate of the mucosal and muscularis layers extending into the lumen. As time passes, the appendiceal wall grossly appears thickened, the lumen appears dilated, and a serosal exudate (fibrinous or fibrinopurulent) may be observed as granular roughening. At this stage, mucosal necrosis may be observed microscopically.

At the later stages of appendicitis, the appendix grossly shows marked signs of mucosal necrosis extending into the external layers of the appendiceal wall that can become gangrenous. Sometimes, the appendix may be found in a collection of pus. At this stage of appendicitis, microscopy may demonstrate multiple microabscesses of the appendiceal wall and severe necrosis of all layers.