Version May 2024
INTRODUCTION — Appendicitis is common and is seen in up to 1 in 10 individuals over a lifetime. Most cases present between the ages of 10 and 30 years. There is a slight male predominance among patients presenting before age 30 (male:female ratio approximately 3:2). (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Epidemiology'.)
This topic reviews the diagnostic evaluation of suspected appendicitis in nonpregnant adults, incorporating the clinical evaluation, laboratory tests, and imaging examinations. Diagnosis of appendicitis in children and pregnant women is discussed separately, as are the pathogenesis, clinical manifestations, differential diagnosis, and management. (See "Acute appendicitis in children: Clinical manifestations and diagnosis" and "Acute appendicitis in pregnancy" and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis" and "Management of acute appendicitis in adults".)
GENERAL APPROACH — The evaluation of patients with suspected appendicitis is driven by the goal of identifying all patients presenting with acute appendicitis as early in their clinical course as possible while minimizing the nontherapeutic laparoscopy/laparotomy rate. Missed diagnosis of appendicitis, especially when perforated, can result in severely adverse patient outcomes, while nontherapeutic operations incur surgical morbidity without treating the underlying condition.
Worldwide there are over 80 diagnostic tools for appendicitis, most relying on a clinician with access to laboratory values. The accuracy was high across the diagnostic tools [1].
As an example, the Alvarado score (table 1) uses data from the history, physical examination, and laboratory testing to describe the clinical likelihood of acute appendicitis. Those with a low Alvarado score are triaged for evaluation of alternative diagnoses. In patients with a higher Alvarado score, imaging and surgical laparoscopic exploration are used to improve the specificity of evaluation and to minimize the likelihood of a negative laparotomy (algorithm 1).
The evaluation for appendicitis in nonpregnant adults can be particularly challenging in several populations, including:
●Women of reproductive age
●Older and frail patients (eg, immunosuppressed, multiple comorbidities)
In women of reproductive age, gynecologic pathologies (eg, pelvic inflammatory disease, adnexal torsion) can mimic appendicitis clinically. Older and frail patients can present with nonclassical or nonspecific clinical features.
Negative appendectomy rate (nontherapeutic operative rate) — The negative appendectomy rate (NAR), also referred to as the nontherapeutic operative rate, for presumed appendicitis is defined as the proportion of all vermiform appendix specimens submitted without pathologic evidence of acute inflammation and is considered a quality metric in the treatment of appendicitis. Historically, the acceptable NAR has varied depending upon patient age and sex and availability of imaging. In young, healthy males with right lower quadrant pain, an NAR less than 10 percent has been considered acceptable, while a rate that approaches 20 percent was often seen in women of reproductive age in whom other pelvic processes can confound the evaluation [2,3]. Observed NARs have decreased in the past decade, which is likely attributable, in part, to the increased utilization of imaging [4].
Studies show that the addition of computed tomography (CT) or ultrasound to the clinical evaluation of suspected appendicitis is associated with a reduction in NAR without an associated increase in perforation rate [5-10]. In a retrospective study of 19,327 patients at 55 hospitals in Washington state over six years, the odds of negative appendectomy for patients not imaged were 3.7 times higher than those who received imaging (95% CI 3.0-4.4) [10]. The benefit of imaging was independent of age, sex, and white blood cell (WBC) count. Appendiceal perforation was the same between patients who were and were not imaged (18.8 versus 15.6 percent).
Adult women are more than twice as likely as men to have a nontherapeutic appendectomy for suspected acute appendicitis [5,11-14]. Imaging with CT can decrease the NAR in this population. A single-center retrospective review of 1425 consecutive patients found that adult women evaluated with a preoperative CT had a significantly lower NAR compared with those who did not undergo CT (21 versus 8 percent) [5].
Perforation — A proportion of appendicitis results in perforation, which can lead to life-threatening complications if left untreated, including intra-abdominal infection, sepsis, intraperitoneal abscesses, and, rarely, death [15]. A few hours of delay between patient presentation with symptoms and treatment does not appear to be associated with an increased risk of perforation.
The perforation rate in hospital admissions for acute appendicitis in the United States from 2001 to 2010 was 30 percent [16], but rates as high as 80 percent have been reported in specific high-risk populations [17]. Retrospective review of 9048 adults with acute appendicitis found the factors associated with increased risk of perforation to be [18]:
●Male sex (risk ratio [RR] 1.24, 95% CI 1.08-1.43)
●Increasing age (RR 1.04, 95% CI 1.03-1.04)
●Three or more comorbid illnesses (RR 2.8, 95% CI 1.36-3.49)
●Lack of medical insurance coverage (RR 1.43, 95% CI 1.24-1.66)
In this study, the mean time from presentation to operation (8.6 hours) was not associated with risk of perforation [18].
INITIAL EVALUATION
Clinical evaluation — The diagnostic accuracy of the clinical evaluation for acute appendicitis depends on the experience of the examining clinician [19-24]. The patient presenting with acute abdominal pain should undergo a thorough physical examination, including a digital rectal examination. Women should undergo a pelvic examination. Women of reproductive age should be queried regarding the possibility of pregnancy.
Clinical symptoms and signs suggestive of appendicitis include a history of central abdominal pain migrating to the right lower quadrant, anorexia, fever, and nausea/vomiting. On examination, right lower quadrant tenderness, along with classical signs of peritoneal irritation (eg, rebound tenderness, guarding, rigidity, referred pain), may be present. Other signs (eg, the psoas or obturator signs) may help the clinician localize the inflamed appendix [25,26]. This is discussed in more detail separately. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Clinical manifestations'.)
Importantly, a high index of suspicion for the diagnosis of appendicitis should be maintained when evaluating older and frail patients, who can present with nonclassical symptoms (eg, generalized abdominal pain, lack of leukocytosis).
Laboratory tests — The laboratory evaluation of patients with suspected appendicitis should include:
●White blood cell (WBC) count with differential
●Serum C-reactive protein (CRP)
●Serum pregnancy test in women of childbearing age
The diagnostic performance of the first two studies is moderate individually, but sensitivity improves substantially in combination (table 2) [27]. Some limited evidence also suggests that repeated laboratory evaluation (WBC, CRP) may boost the sensitivity in detecting appendicitis, especially in patients who present early [28]. However, no WBC count or CRP level can safely and sufficiently confirm or exclude the suspected diagnosis of acute appendicitis. As an example, one retrospective multicenter study of 1024 adults with suspected appendicitis reported that with a disease prevalence of 57 percent (580 diagnosed with appendicitis), an abnormal cutoff value of WBC >10 x 109/L or CRP >10 mg/L yielded a positive predictive value (PPV) of 61.5 (95% CI 58.4-64.7) and a negative predictive value (NPV) of 88.1 (95% CI 81.8-94.4) [29].
Others have investigated the utility of neutrophil-to-lymphocyte ratio (NLR). A meta-analysis of 17 observational studies involving close to 9000 patients of all ages (some pregnant) found that NLR, at a cutoff value of 4.7, predicted appendicitis with a sensitivity of 89 percent and specificity of 91 percent (area under curve [AUC] 0.96). NLR at a cutoff value of 8.8, on the other hand, predicted complicated appendicitis with a sensitivity of 77 percent and specificity of 100 percent (AUC 0.91) [30].
Although mild elevations in serum bilirubin (total bilirubin >1.0 mg/dL) have been noted to be a marker for appendiceal perforation with a sensitivity of 70 percent and specificity of 86 percent [31], the test is not discriminatory and is generally not helpful in the evaluation of patients suspected of acute appendicitis.
Alvarado score calculation — The Alvarado score can be used to identify patients with a very low likelihood of acute appendicitis so as to triage them to evaluation for other causes of abdominal pain. Patients with a high Alvarado score should be further evaluated with imaging prior to treatment.
While several scoring systems have been proposed to standardize the clinical and laboratory assessment for acute appendicitis [32-34], the modified Alvarado score is the most widely used [35,36].
The modified Alvarado scale assigns a score to each of the following diagnostic criteria (table 1):
●Migratory right lower quadrant pain (1 point)
●Anorexia (1 point)
●Nausea or vomiting (1 point)
●Tenderness in the right lower quadrant (2 points)
●Rebound tenderness in the right lower quadrant (1 point)
●Fever >37.5°C (>99.5°F) (1 point)
●Leukocytosis of WBC count >10 x 109/L (2 points)
The score is obtained by summing the components. Higher values indicate higher probability of appendicitis. The maximum total score is 9. The original Alvarado score included left shift as an additional factor, resulting in a total score of 10 [35].
Scores of <4 and <5 have both been assessed as a cutoff for low risk of acute appendicitis in the literature and have resulted in an overall similarly low likelihood of acute appendicitis with either cutoff score [37,38]. For the purposes of triage, the score of <4 is selected for its potential to rule out appendicitis with greater certainty, given reported variability in the prevalence of acute appendicitis in patients with a score of 4 [37-39]. Initial triage in the diagnostic workup of appendicitis using Alvarado score is as follows (algorithm 1):
●Patients with a score of 0 to 3 are unlikely to have appendicitis and should be evaluated for other possible diagnoses. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Differential diagnosis' and "Causes of abdominal pain in adults", section on 'Lower abdominal pain syndromes'.)
●Patients with a score of ≥4 should be evaluated further for appendicitis. Surgical evaluation and imaging, if readily available, should be pursued.
A low Alvarado score (<4) has more diagnostic utility to "rule out" appendicitis than a high score (≥7) does to "rule in" the diagnosis [27]. The accuracy of the score in women of reproductive age is equivalent to that in all adults [27]. In a systematic review of 42 retrospective and prospective studies that included over 8300 patients with suspected acute appendicitis and/or right lower quadrant pain, overall, 99 percent of patients with acute appendicitis had a score of >4 [37]. In contrast, a high score (≥7) alone had poor diagnostic utility as the overall specificity was 81 percent.
IMAGING
Selection of modality — Imaging is used mainly to increase the specificity of the diagnostic evaluation for appendicitis and to decrease the negative appendectomy rate. Computed tomography (CT) is the preferred modality, with ultrasound and magnetic resonance imaging (MRI) reserved for radiosensitive populations such as pregnant women and children. CT demonstrates the highest diagnostic accuracy and lowest rates of nondiagnostic examinations (ie, nonvisualization of the appendix). However, as expedited workup is a priority in suspected appendicitis, the choice of imaging is subject to the availability of the scanner technology and radiologist expertise (table 3) [40]. In a contemporary worldwide observational study of over 4000 patients suspected of acute appendicitis, 21.2 percent underwent abdominal CT, 43.3 percent underwent abdominal ultrasound (US), 6.7 percent underwent both CT and US, and 28.8 percent did not undergo any radiological investigation [41].
Computed tomography — Abdominopelvic CT is recommended as the preferred test in the imaging evaluation of suspected appendicitis in adults (image 1 and image 2) [40]. If available, low-radiation-dose image acquisition protocols should be used as they do not compromise diagnostic accuracy [42-45]. Intravenous contrast is recommended, although CT without contrast is an acceptable alternative when intravenous contrast is contraindicated. The use of oral or rectal contrast varies greatly among individual practices due to the tradeoffs that exist in diagnostic expediency, diagnostic confidence, and patient tolerability of the examination (see below).
CT demonstrates higher diagnostic accuracy than ultrasound or MRI (table 2). Other advantages of CT include less variability in diagnostic performance than ultrasound or MRI. CT demonstrates the lowest rates of nondiagnostic tests as the normal appendix is visualized in almost all cases (table 3). When compared with MRI, CT scanners and radiologist expertise are more readily available, and the examination is better tolerated by most patients. As CT imaging usually includes the abdomen and pelvis, the examination evaluates for other pathologies should the patient prove to not have appendicitis. The disadvantages of CT are patient exposure to ionizing radiation and iodinated contrast.
The estimated effective radiation dose of abdominopelvic CT is 8 to 10 mSv with the standard dose and 2 to 4 mSv with low-dose techniques [42]. To put these numbers into context, the effective dose from annual background radiation is 3.1 mSv and from plain abdominal radiography is 0.7 mSv. A Korean population study reported an association between CT scan for appendicitis and a higher risk of hematologic malignancies (incidence rate ratio [IRR] 1.26, 95% CI 1.09-1.45; eg, leukemia [IRR 1.40, 98.75% CI 1.04-1.87]), especially in children, but not of overall cancer (IRR 1.04, 95% CI 0.99-1.09) [46]. Although provocative, these results should be cautiously interpreted because the study design did not control for confounding factors, it is not clear if the focus on hematologic malignancies was determined a priori, the absolute differences between the two groups are small and may not be clinically relevant, some patients may have undergone more than one CT scan, and, finally, this study did not specify whether the standard or low-dose technique was used. (See "Radiation-related risks of imaging".)
Intravenous contrast administration is recommended in CT examinations performed for the diagnosis of appendicitis. Relative contraindications to contrast administration are [47]:
●Renal insufficiency (estimated glomerular filtration rate [eGFR] <30 mL/minute per 1.73 m2)
●History of hypersensitivity reaction to iodinated contrast
Noncontrast CT is an acceptable alternative if intravenous contrast is contraindicated. While reasonably high diagnostic accuracy is seen with noncontrast CT [48,49], intravenous contrast improves the examination value in other ways. In patients with appendiceal perforation where CT is used not only for diagnosis but also for treatment planning, contrast improves the delineation of the phlegmon or abscess. In one study, an alternative diagnosis was made in 42 percent (893 out of 2122) of patients without appendicitis, and the pathologic diagnosis was better characterized with intravenous contrast administration [50].
The use of oral or rectal contrast varies greatly among individual practices. The advantage of enteral contrast is that it distends the bowel, improving appendix visualization. Oral contrast administration delays scanning by one to two hours. Rectal contrast avoids this delay but is not well tolerated.
The imaging features of acute appendicitis on abdominopelvic CT are [51-53]:
●Enlarged appendiceal double-wall thickness (>6 mm)
●Appendiceal wall thickening (>2 mm)
●Periappendiceal fat stranding
●Appendiceal wall enhancement
●Appendicolith (seen in a minority of patients)
Diagnosing appendicitis based on a single criterion is not advised. As an example, while appendiceal diameter is larger in patients with appendicitis, more than 20 percent of patients without appendicitis have an appendiceal diameter >7 mm [54].
A meta-analysis of 72 studies on the ability of CT to diagnose appendicitis in adults reported a sensitivity of 95 percent (95% CI 95 to 97 percent) and a specificity of 96 percent (95% CI 93 to 97 percent). On subgroup analysis, diagnostic performance in older adults and in women of reproductive age was similar to that seen in the entire cohort, although specificity demonstrated wider confidence intervals [27]. CT performed with low-radiation-dose techniques demonstrates comparable diagnostic performance to standard-dose CT [55]. Nonvisualization of the appendix (nondiagnostic result) occurs in 10 to 20 percent of examination and decreases but does not eliminate the likelihood of a positive diagnosis of appendicitis [56-58].
A 2019 Cochrane review of 64 studies found that CT had a summary sensitivity of 95 percent (95% CI 93 to 96 percent) and a summary specificity of 94 percent (95% CI 92 to 95 percent) when diagnosing appendicitis in adults [44]. In subgroup analysis, summary sensitivity was higher for CT with intravenous contrast, rectal contrast, and intravenous and oral contrast, but not oral contrast alone, compared with CT without contrast. Summary specificity did not improve with contrast enhancement. Compared with standard-dose CT, low-dose CT did not differ in performance.
A positive CT result indicates that treatment for appendicitis should be initiated, whereas a negative result indicates that a normal appendix has been visualized and appendicitis is highly unlikely as the diagnosis. A nondiagnostic result does not rule out appendicitis, and continued evaluation is warranted (algorithm 1).
Ultrasound — An abdominal ultrasound focused on the right lower quadrant is the preferred imaging examination in children and pregnant women and is recommended over CT in these populations. In other populations, ultrasound represents an alternative to CT if the latter is not readily available (eg, within three hours) (image 3 and image 4). (See "Acute appendicitis in children: Clinical manifestations and diagnosis" and "Acute appendicitis in pregnancy".)
Advantages of ultrasound include the lack of ionizing radiation and intravenous contrast. Unlike CT or MRI, ultrasound can be performed at the bedside (table 3). However, an important disadvantage is that ultrasound demonstrates lower diagnostic accuracy than CT or MRI (table 2). The test performance is highly variable and depends on patient-specific (eg, body habitus, discomfort and alertness, appendix location relative to overlying bowel) and operator-specific (eg, experience) variables. Rates of indeterminate examinations are high, with 50 to 85 percent of normal appendices not visualized [59,60]. Finally, graded compression of the appendix, integral to the ultrasound examination, can cause significant patient discomfort in patients with appendicitis.
Imaging features of acute appendicitis on ultrasound include [61-63]:
●Noncompressible appendix with double-wall thickness diameter of >6 mm
●Focal pain over appendix with compression
●Appendicolith
●Increased echogenicity of inflamed periappendiceal fat
●Fluid in the right lower quadrant
A meta-analysis of 38 studies on the ability of ultrasound to diagnose appendicitis reported a sensitivity of 85 percent (95% CI 79 to 90 percent) and a specificity of 90 percent (95% CI 93 to 95 percent) [64,65].
A positive ultrasound result indicates that treatment for appendicitis should be initiated, whereas a negative result indicates that a normal appendix has been visualized and appendicitis is highly unlikely as the diagnosis. Importantly, a nondiagnostic result does not rule out appendicitis, and continued evaluation is warranted (algorithm 1).
Magnetic resonance imaging — MRI of the abdomen should be used in the imaging evaluation of suspected appendicitis in (image 5 and image 6) [40]:
●Pregnant women (see "Acute appendicitis in children: Clinical manifestations and diagnosis")
●Older children who can cooperate with the examination (see "Acute appendicitis in children: Clinical manifestations and diagnosis")
MRI is recommended over CT in these populations as minimizing ionizing radiation exposure is a priority. If readily available, MRI may also be substituted for CT in young women (age <30 years) in whom gynecologic diagnoses remain in the differential diagnosis after the initial clinical evaluation and examination. However, lesser overall experience with MRI evaluation for acute appendicitis contributes to greater variability in its test performance characteristics compared with CT.
An advantage of MRI over CT is that it does not expose the patient to ionizing radiation or intravenous iodinated contrast (table 3). Intravenous contrast can be administered to improve accuracy if images without contrast prove nondiagnostic. Diagnostic accuracy is comparable to CT and is better than ultrasound (table 2). A Cochrane review of 58 studies on the MRI diagnosis of appendicitis reported a summary sensitivity of 0.95 percent (95% CI 0.94-0.97) and a summary specificity of 0.96 (95% CI 0.95-0.97). Sensitivity and specificity remained high on subgroup analysis for pregnant women (sensitivity 0.96 [95% CI 0.88-0.99]; specificity 0.97 [95% CI 0.95-0.98]); children (sensitivity 0.96 [95% CI 0.95-0.97]; specificity 0.96 [95% CI 0.92-0.98]); and adults (sensitivity 0.96 [95% CI 0.93-0.97]; specificity 0.93 [95% CI 0.80-0.98]), regardless of different scanning techniques and protocols [66].
The rate of nondiagnostic examinations is higher than that reported with CT but lower than that with ultrasound, with 20 to 40 percent of normal appendices not visualized [67]. Similar to CT, MRI allows for detection of alternative diagnoses should the patient not have appendicitis. However, the examination itself is less well tolerated than ultrasound or CT. The patient is usually required to lie still in a magnet for >10 minutes; this can be very uncomfortable for those who are claustrophobic, very young, or older and those with significant pain. Common relative contraindications include cardiac pacemakers and implanted metallic surgical hardware. (See "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging", section on 'Assessing implants, devices, or foreign bodies for MRI' and "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging".)
Plain radiography — Plain radiography is not recommended in the diagnostic workup of suspected appendicitis, nor do findings on plain radiograph change the level of suspicion for appendicitis. The examination does not visualize the appendix.
SURGICAL EXPLORATION — In a minority of patients, surgical exploration may be warranted if clinical suspicion for appendicitis is high but imaging studies are negative, nondiagnostic, or unavailable. In such patients, appendicitis can only be diagnosed intraoperatively or pathologically.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Appendicitis in adults".)
SUMMARY
●The evaluation of patients with suspected appendicitis is driven by the goal of identifying all patients presenting with acute appendicitis while minimizing the negative appendectomy rate (nontherapeutic operative rate). Missed diagnosis of appendicitis, especially when perforated, can result in severely adverse patient outcomes. (See 'General approach' above.)
●The diagnostic evaluation of children and pregnant women differs from that of nonpregnant adults and is discussed separately. (See "Acute appendicitis in pregnancy" and "Acute appendicitis in children: Clinical manifestations and diagnosis".)
●Clinical symptoms and signs suggestive of appendicitis include a history of central abdominal pain migrating to the right lower quadrant, anorexia, fever, and nausea/vomiting. (See 'Clinical evaluation' above and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis".)
●The initial physical examination of patients with suspected appendicitis should include a digital rectal examination. Women should also undergo a pelvic examination. (See 'Clinical evaluation' above and "Acute appendicitis in children: Clinical manifestations and diagnosis".)
●The laboratory evaluation of suspected appendicitis should include white blood cells (WBC) with differential and serum C-reactive protein (CRP). A serum pregnancy test should be performed for women of childbearing age. (See 'Laboratory tests' above.)
●The Alvarado score can be used to identify patients with a very low likelihood of acute appendicitis so as to triage them to evaluation for other causes of abdominal pain (table 1). (See 'Alvarado score calculation' above.)
•Patients with a score of 0 to 3 are unlikely to have appendicitis and should be evaluated for other possible diagnoses. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Differential diagnosis' and "Causes of abdominal pain in adults", section on 'Lower abdominal pain syndromes'.)
•Patients with a score of ≥4 should be evaluated further for appendicitis. Surgical evaluation and imaging, if readily available, should be pursued.
●For most patients with suspected appendicitis, we recommend abdominopelvic computed tomography (CT) with intravenous contrast. Low-radiation-dose techniques, if available, should be used for image acquisition. If readily available, magnetic resonance imaging (MRI) is acceptable as a substitute for CT in young women (age <30 years) in whom gynecologic diagnoses are still included in the differential diagnosis after the initial clinical evaluation. (See 'Computed tomography' above and 'Magnetic resonance imaging' above.)
●If CT is not readily available (<3 hours), we recommend an abdominal ultrasound. Ultrasound demonstrates lower diagnostic accuracy and higher rates of nondiagnostic examinations than CT or MRI. (See 'Ultrasound' above.)
●In a minority of patients, surgical exploration may be warranted if clinical suspicion for appendicitis is high but imaging studies are negative, nondiagnostic, or unavailable. In such patients, appendicitis can only be diagnosed intraoperatively or pathologically. (See 'Surgical exploration' above.)
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