Laboratory Studies
Complete blood count with manual differential
The white blood cell (WBC) count is often mildly elevated, and a left shift is present. In children, it is helpful to obtain a manual differential. When an extremely elevated WBC count is present, either the patient has a perforated appendix or another process (eg, a viral illness) is responsible.
In both pediatric and adult patients, the WBC count is not always elevated. Thus, an increased percentage of bands on manual cellular differential may be just as reliable. Because an accurate history and physical is often more difficult to obtain, a persistently elevated percentage of bands may be the only objective finding of appendicitis in pediatric patients.
C-reactive protein
The C-reactive protein (CRP) level is often elevated in patients with acute appendicitis. However, an exact cutoff point that can accurately discriminate between acute appendicitis and other pathology has not been determined. [15]
Bilirubin
A study by Pogorelić et al suggested that hyperbilirubinemia could be useful as an indicator of perforated appendicitis in children. [16]
Urinalysis
Although not mandatory, urinalysis is often done to rule out urinary tract infections; however, pyuria (WBCs in the urine) is commonly observed in appendicitis because the inflammatory process may lie adjacent to the right ureter.
Urine pregnancy test
Females of reproductive age with abdominal pain should undergo urine testing to rule out pregnancy.
Electrolyte and renal panel
This test is not required but may be useful to help guide electrolyte resuscitation prior to appendectomy.
Additional biomarkers
The biomarkers calprotectin (CP) and serum amyloid A (SAA) are also elevated in patients with acute appendicitis. As with CRP, exact cutoff points to assist in the diagnosis of acute appendicitis have not been determined. [17] Procalcitonin has not been shown to be helpful in diagnosing acute appendicitis, but it may have value in identifying perforated appendicitis. [15] Plasma pentraxin-3 may have diagnostic value in the setting of acute appendicitis. [18]
Imaging Studies
In patients with classic appendicitis, no imaging studies are needed. This statement was confirmed by a retrospective study determining predictive values for appendicitis (Alvarado score) on the basis of history and physical findings. A prospective comparison of the accuracy of the Alvarado score with ultrasonographic (US) findings was similar. [19]
In the workup of atypical appendicitis, additional imaging studies may be required. [20] Controversy exists as to the most accurate, rapid, and cost-effective method of diagnosing atypical appendicitis while avoiding delays that may increase morbidity.
Plain abdominal radiography
For the most part, abdominal roentgenograms are not helpful in making the diagnosis of appendicitis. Roughly 85% of patients have normal radiographic findings, and 10% have nonspecific findings. [21] The two most common nonspecific findings associated with appendicitis are ileus and small-bowel obstruction. A more specific abnormality is a fecalith in the right lower quadrant (RLQ), but this is observed in only 4-5% of radiographs.
Other findings may include loss of the psoas shadow and deformity of the cecal outline. Rarely, free air under the diaphragm may also be present in patients with perforated appendicitis.
Abdominal/pelvic ultrasonography
US is an ideal noninvasive means of visualizing the abdominal cavity. [22, 23, 24] It is inexpensive and portable, and it can be rapidly performed with little or no patient preparation. Most important, it poses no ionizing radiation risk to the patient; therefore, it is particularly safe to use in children and pregnant women. On the other hand, US is operator-dependent, which means that it requires some experience and expertise to produce consistent quality results.
The wall elements of the appendix have a typical "target" appearance and can be visualized by using graded US compressive technique with a high-resolution transducer, occasionally supplemented with color Doppler.
Appendicitis is suspected when the study demonstrates wall thickening (>6 mm), luminal distention, and lack of compressibility. In addition, US is useful in detecting free intraperitoneal fluid and fluid collections consistent with abscess formation.
Prospective studies showed excellent results, with an average sensitivity of 86% and a specificity of 94% under the conditions of well-controlled clinical trials (and, therefore, experienced examiners). [25] In addition, many reported studies included patients with classic appendicitis instead of patients with equivocal clinical histories and physical findings.
Such good results reported in prospective clinical trials were not often duplicated in routine clinical conditions. In fact, US has proved no more accurate than clinical evaluation by a surgeon, and low sensitivity and high false-negative rates have been reported. [21, 26, 27]
In a study that included 275 pediatric patients, Prada Arias et al assessed the diagnostic accuracy of US for differentiating appendicitis (n = 132) from nonspecific acute abdominal pain (n = 143). [28] US had a sensitivity of 94.7% and a specificity of 87.4% for differentiating appendicitis, with a 12.6% false-positive rate and a 5.3% false-negative rate. There was a 17.4% false-negative rate in the perforated group, as well as a 6.3% false-negative rate in the high-risk group and a 12.2 false-positive rate in the low-risk group.
US is most useful for excluding other diagnoses. In women, pelvic pathology, such as pelvic inflammatory disease, ruptured graafian follicle, twisted ovarian cyst or tumor, endometriosis, and ruptured ectopic pregnancy can be readily detected by means of US.
US is of limited value when the appendix is not visualized. A negative ultrasound study without visualization of the appendix has a 10% risk of appendicitis. For inconclusive findings, the risk of appendicitis may be as high as 68%. [29]
Tang et al proposed a predictive model for complicated pediatric appendicitis in which US of the appendix was combined with measurement of laboratory inflammatory indicators, including WBC count, neutrophil percentage, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), CRP, and procalcitonin. [30] They found that CRP, NLR, the presence of an appendicolith, and peripheral retina echo enhancement were independent risk factors for complicated appendicitis in children.
Computed tomography with contrast
Findings on computed tomography (CT) become more prominent with enhanced disease. [23] Specific findings include an edematous and thick-walled appendix, inflammatory streaking of surrounding fat, and the presence of an appendicolith. Abscess formation, a small amount of free air in the RLQ, and a pericecal phlegmon suggest a perforated appendix.
In most clinical trials, CT has appeared superior to US for evaluating the acute abdomen. Because it has been shown to yield precise information, it has increasingly become a screening tool for acute appendicitis in the emergency department. In well-conducted clinical trials, CT has shown excellent sensitivity and specificity (87-100% and 91-97%, respectively). [31, 32, 33]
As with US, however, the good results reported in prospective clinical trials were rarely duplicated in routine clinical conditions. In one study, the use of CT in patients with acute appendicitis rose from 25% to 68% over a 5-year period, yet the rate of negative appendectomy remained largely unchanged, suggesting that the information obtained from imaging studies may not have much influence on the clinical decision-making process. [34]
One of the potential clinical dilemmas involves the failure of CT to identify a normal appendix. The accuracy of CT for identifying a normal appendix is in the range of 44-51% in asymptomatic patients. [35, 36] It is probably unsafe to assume that nonvisualization of the appendix excludes the diagnosis of acute appendicitis unless there is a collaborating history or physical findings. In a patient who has no evidence of inflammation in the ileocecal region and whose appendix is not visualized, there is still a chance that acute appendicitis is present.
In cases of suspected acute appendicitis where CT findings are equivocal, the use of clinical scoring systems may be diagnostically helpful. [37, 38] Such systems include the Alvarado, Eskelinen, appendicitis inflammatory response, Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA), and adult appendicitis score (AAS) systems.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) has been shown to assist in the evaluation of acute appendicitis. A dilated appendix (>7.5 mm [39] ) has been shown to be abnormal. MRI may be more helpful in diagnosing abdominal pain in pregnant women. [40]
Technetium-labeled white blood cell scan
Despite a reported sensitivity of 98% and specificity of 95%, the time required for performing the scan and its lack of around-the-clock availability make this a less-than-ideal diagnostic test for appendicitis. [41]
Barium contrast studies
Historically, a single-contrast barium enema was used to diagnose patients with atypical signs and symptoms. The goal was to assess the patency of the appendiceal lumen. In addition, the colonic wall could be examined for extrinsic mass effects caused by appendicitis. Although this remains a simple, inexpensive, and safe study, it has been largely supplanted by US and CT and is rarely used today.
Procedures
With the exception of an open surgical exploration, the only diagnostic procedure for acute appendicitis is diagnostic laparoscopy.
Histologic Findings
A small percentage of normal-appearing appendices have focal appendicitis on microscopic examination. In addition, early appendicitis may be encountered in the form of increased interleukin (IL)-2 and tumor necrosis factor (TNF)-α secretion, which cannot be detected on gross examination. Approximately 1% of patients have appendicitis from carcinoid or adenocarcinoma. [21]
