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TOPIC OUTLINE

SUMMARY & RECOMMENDATIONS INTRODUCTION ANATOMY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Clinical manifestations - History - Physical examination Laboratory findings Imaging studies - Computed tomography findings - Ultrasound findings - Plain radiograph findings - Magnetic resonance imaging DIAGNOSIS Diagnostic scoring systems DIAGNOSTIC EVALUATION Imaging - Computed tomography Standard CT scan with contrast Appendiceal CT Unenhanced CT - Ultrasonography - Imaging costs Laboratory tests Exploratory laparotomy/laparoscopy DIFFERENTIAL DIAGNOSIS Perforated appendix Cecal diverticulitis Meckel's diverticulitis Acute ileitis Crohn's disease Gynecologic and obstetrical conditions - Tubo-ovarian abscess - Pelvic inflammatory disease - Ruptured ovarian cyst - Mittelschmerz - Ovarian and fallopian tube torsion

- Endometriosis - Ovarian hyperstimulation syndrome - Ectopic pregnancy - Acute endometritis Urologic conditions - Renal colic - Testicular torsion - Epididymitis - Torsion of the appendix testis or appendix epididymis TREATMENT INFORMATION FOR PATIENTS SUMMARY AND RECOMMENDATIONS ACKNOWLEDGMENT REFERENCES

GRAPHICSView All
DIAGNOSTIC IMAGES CT scan normal appendix CT scan image of acute appendicitis Normal appendix by ultrasound imaging Acute appendicitis ultrasound Appendicolith on abdominal films MR image appendicitis in pregnancy CT scan equivocal appendicitis Ultrasound equivocal appendicitis Appendicitis ultrasound FIGURES Appendiceal anatomy Blood supply to the colon and rectum PICTURES Normal appendix US Tuboovarian abscess Ruptured ovarian cyst CT rupt corpus luteum cyst Torsion with salvageable ovary Torsion of fallopian tube Torsion with nonviable ovary Peritoneal endometriosis

RELATED TOPICS
Acute appendicitis in adults: Management

Acute appendicitis in children: Clinical manifestations and diagnosis Acute appendicitis in children: Diagnostic imaging Acute appendicitis in children: Management Acute appendicitis in pregnancy Acute management of nephrolithiasis in children Approach to abdominal pain and the acute abdomen in pregnant and postpartum women Cancer of the appendix and pseudomyxoma peritonei Causes of scrotal pain in children and adolescents Classification and treatment of ovarian hyperstimulation syndrome Clinical features and diagnosis of pelvic inflammatory disease Clinical manifestations and diagnosis of Yersinia infections Clinical manifestations and diagnosis of colonic diverticular disease Clinical manifestations, diagnosis and prognosis of Crohn's disease in adults Clinical manifestations, diagnosis, and management of ectopic pregnancy Diagnosis and acute management of suspected nephrolithiasis in adults Differential diagnosis of abdominal pain in adults Endometritis unrelated to pregnancy Epidemiology, clinical manifestations, and diagnosis of tuboovarian abscess Evaluation and management of ruptured ovarian cyst Evaluation of the acute scrotum in adults History and physical examination in adults with abdominal pain Ovarian and fallopian tube torsion Pathogenesis, clinical features, and diagnosis of endometriosis Patient information: Appendicitis in adults (The Basics) Physiology of the normal menstrual cycle Postpartum endometritis Principles of computed tomography of the chest Treatment of acute diverticulitis Acute appendicitis in adults: Clinical manifestations and diagnosis UpToDate

Official reprint from UpToDate www.uptodate.com 2012 UpToDate Print | Back Acute appendicitis in adults: Clinical manifestations and diagnosis

Authors Carrie E Black, MD Ronald F Martin, MD Section Editors Martin Weiser, MD Ron M Walls, MD, FRCPC, FAAEM Deputy Editor Rosemary B Duda, MD, MPH, FACS Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2012. | This topic last updated: Sep 13, 2012. INTRODUCTION Appendicitis, an inflammation of the vestigal vermiform appendix, is one of the most common causes of the acute abdomen and one of the most frequent indications for an emergent abdominal surgical procedure worldwide [1,2]. The clinical manifestations and diagnosis of appendicitis in adults will be reviewed here. The management of appendicitis in adults and appendicitis in pregnancy and children are discussed separately. (See "Acute appendicitis in adults: Management" and "Acute appendicitis in pregnancy" and "Acute appendicitis in children: Clinical manifestations and diagnosis".) ANATOMY The vermiform appendix is located at the base of the cecum, near the ileocecal valve where the taenia coli converge on the cecum (figure 1) [3,4]. The appendix is a true diverticulum of the cecum. In contrast to acquired diverticular disease, which consists of a protuberance of a subset of the enteric wall layers, the appendiceal wall contains all of the layers of the colonic wall: mucosa, submucosa, muscularis (longitudinal and circular), and the serosal covering [5]. The appendiceal orifice opens into the cecum. Its blood supply, the appendiceal artery, is a terminal branch of the ileocolic artery, which traverses the length of the mesoappendix and terminates at the tip of the organ (figure 2) [4]. The attachment of the appendix to the base of the cecum is constant. However, the tip may migrate to the retrocecal, subcecal, preileal, postileal, and pelvic positions. These normal anatomic variations can complicate the diagnosis as the site of pain and findings on the clinical examination will reflect the anatomic position of the appendix. The presence of B and T lymphoid cells in the mucosa and submucosa of the lamina propria make the appendix histologically distinct from the cecum [5]. These cells create a lymphoid pulp that aids immunologic function by increasing lymphoid products such as IgA and operating as part of the gut-associated lymphoid tissue system [3]. Lymphoid hyperplasia can cause obstruction of the appendix and lead to appendicitis. The lymphoid tissue undergoes atrophy with age [6]. EPIDEMIOLOGY Appendicitis occurs most frequently in the second and third decades of life. The incidence is approximately 233/100,000 population and is highest in the 10 to 19 year-old age group [7] . It is also higher among men (male to female ratio of 1.4:1), who have a lifetime incidence of 8.6 percent compared to 6.7 percent for women [7].

PATHOGENESIS The natural history of appendicitis is similar to that of other inflammatory processes involving hollow visceral organs. Initial inflammation of the appendiceal wall is followed by localized ischemia, perforation, and the development of a contained abscess or generalized peritonitis. Appendiceal obstruction has been proposed as the primary cause of appendicitis [3,8-11]. Obstruction is frequently implicated but not always identified. A study of patients with appendicitis showed that there was elevated intraluminal pressure in only one-third of the patients with nonperforated appendicitis [12]. Appendiceal obstruction may be caused by fecaliths (hard fecal masses), calculi, lymphoid hyperplasia, infectious processes, and benign or malignant tumors. However, some patients with a fecalith have a histologically normal appendix and the majority of patients with appendicitis do not have a fecalith [13,14]. When obstruction of the appendix is the cause of appendicitis, the obstruction leads to an increase in luminal and intramural pressure, resulting in thrombosis and occlusion of the small vessels in the appendiceal wall, and stasis of lymphatic flow. As the appendix becomes engorged, the visceral afferent nerve fibers entering the spinal cord at T8-T10 are stimulated, leading to vague central or periumbilical abdominal pain [8]. Well-localized pain occurs later in the course when inflammation involves the adjacent parietal peritoneum. The mechanism of luminal obstruction varies depending upon the patient's age. In the young, lymphoid follicular hyperplasia due to infection is thought to be the main cause. In older patients, luminal obstruction is more likely to be caused by fibrosis, fecaliths, or neoplasia (carcinoid, adenocarcinoma, or mucocele). In endemic areas, parasites can cause obstruction in any age group. (See "Cancer of the appendix and pseudomyxoma peritonei".) Once obstructed, the lumen becomes filled with mucus and distends, increasing luminal and intramural pressure. This results in thrombosis and occlusion of the small vessels, and stasis of lymphatic flow. As lymphatic and vascular compromise progress, the wall of the appendix becomes ischemic and then necrotic. Bacterial overgrowth occurs within the diseased appendix. Aerobic organisms predominate early in the course, while mixed infection is more common in late appendicitis [15]. Common organisms involved in gangrenous and perforated appendicitis include Escherichia coli, Peptostreptococcus, Bacteroides fragilis, and Pseudomonas species [16]. Intraluminal bacteria subsequently invade the appendiceal wall and further propagate a neutrophilic exudate. The influx of neutrophils causes a fibropurulent reaction on the serosal surface, irritating the surrounding parietal peritoneum [6]. This results in stimulation of somatic nerves, causing pain at the site of peritoneal irritation [5]. During the first 24 hours after symptoms develop, approximately 90 percent of patients develop inflammation and perhaps necrosis of the appendix, but not perforation. The type of luminal obstruction may be a predictor of perforation of an acutely inflamed appendix. Fecaliths were six times more common than true calculi in the appendix, but calculi were more often associated with perforated appendicitis or periappendiceal abscess (45 percent) than were fecaliths (19 percent). This is presumably due to the rigidity of true calculi as compared with the softer, more crushable fecaliths [13]. Once significant inflammation and necrosis occur, the appendix is at risk of perforation, which leads to localized abscess formation or diffuse peritonitis. The time course to perforation is variable. One study showed that 20 percent of patients developed perforation less than 24 hours after the onset of symptoms [17]. Sixty-five percent of patients in whom the appendix perforated had symptoms for longer than 48 hours.

CLINICAL FEATURES Clinical manifestations History Abdominal pain is the most common symptom, and is reported in nearly all confirmed cases of appendicitis [18,19]. The clinical presentation of acute appendicitis is described as a constellation of the following classic symptoms: Right lower quadrant (right anterior iliac fossa) abdominal pain Anorexia Nausea and vomiting In the classic presentation, the patient describes the onset of abdominal pain as the first symptom. The pain is typically periumbilical in nature with subsequent migration to the right lower quadrant as the inflammation progresses [18]. Although considered a classic symptom, migratory pain occurs only in 50 to 60 percent of patients with appendicitis [8,20]. Nausea and vomiting, if they occur, usually follow the onset of pain. Feverrelated symptoms generally occur later in the course of illness. In many patients, initial features are atypical or nonspecific, and can include: Indigestion Flatulence Bowel irregularity Diarrhea Generalized malaise Because the early symptoms of appendicitis are often subtle, patients and clinicians may minimize their importance. The symptoms of appendicitis vary depending upon the location of the tip of the appendix (figure 1) (see 'Anatomy' above). For example, an inflamed anterior appendix produces marked, localized pain in the right lower quadrant, while a retrocecal appendix may cause a dull abdominal ache [21]. The location of the pain may also be atypical in patients who have the tip of the appendix located in the pelvis, which can cause tenderness below McBurney's point. Such patients may complain of urinary frequency and dysuria or rectal symptoms, such as tenesmus and diarrhea. Physical examination The early signs of appendicitis are often subtle. Low-grade fever reaching 101.0F (38.3C) may be present. The physical examination may be unrevealing in the very early stages of appendicitis since the visceral organs are not innervated with somatic pain fibers. However, as the inflammation progresses, involvement of the overlying parietal peritoneum causes localized tenderness in the right lower quadrant and can be detected on the abdominal examination. Rectal examination, although often advocated, has not been shown to provide additional diagnostic information in cases of appendicitis. In women, right adnexal area tenderness may be present on pelvic examination, and differentiating between tenderness of pelvic origin versus that of appendicitis may be challenging. High-grade fever (>101.0F/38.3C) occurs as inflammation progresses. (See "Differential diagnosis of abdominal pain in adults".) Patients with a retrocecal appendix may not exhibit marked localized tenderness in the right lower quadrant since the appendix does not come into contact with the anterior parietal peritoneum (figure 1) [21]. The rectal and/or

pelvic examination is more likely to elicit positive signs than the abdominal examination. Tenderness may be more prominent on pelvic examination, and may be mistaken for adnexal tenderness. Several findings on physical examination have been described to facilitate diagnosis, but these findings pre-dated definitive imaging for appendicitis, and the wide variation in their sensitivity and specificity suggests that they be used with caution to broaden, or narrow, a differential diagnosis. There are no physical findings, taken alone, or in concert, that definitively confirm a diagnosis of appendicitis. Commonly described physical signs include: McBurney's point tenderness is described as maximal tenderness at 1.5 to 2 inches from the anterior superior iliac spine (ASIS) on a straight line from the ASIS to the umbilicus [22]. (Sensitivity 50 to 94 percent; specificity 75 to 86 percent [23-25]). Rovsing's sign refers to pain in the right lower quadrant with palpation of the left lower quadrant. This sign is also called indirect tenderness and is indicative of right-sided local peritoneal irritation [26]. (Sensitivity 22 to 68 percent; specificity 58 to 96 percent [24,27-29]). The psoas sign is associated with a retrocecal appendix. This is manifested by right lower quadrant pain with passive right hip extension. The inflamed appendix may lie against the right psoas muscle, causing the patient to shorten the muscle by drawing up the right knee. Passive extension of the iliopsoas muscle with hip extension causes right lower quadrant pain. (Sensitivity 13 to 42 percent; specificity 79 to 97 percent [27,30,31]). The obturator sign is associated with a pelvic appendix. This test is based on the principle that the inflamed appendix may lay against the right obturator internus muscle. When the clinician flexes the patient's right hip and knee followed by internal rotation of the right hip, this elicits right lower quadrant pain, (Sensitivity 8 percent; specificity 94 percent [30]). The sensitivity is low enough that experienced clinicians no longer perform this assessment. Laboratory findings A mild leukocytosis (white blood cell count >10,000 cells/microL) is present in most patients with acute appendicitis [32]. Approximately 80 percent of patients have a leukocytosis and a left shift (increase in total WBC count, bands [immature neutrophils], and neutrophils) in the differential [33-35]. The sensitivity and specificity of an elevated WBC in acute appendicitis is 80 percent and 55 percent respectively. Acute appendicitis is unlikely when the white blood cell (WBC) count is normal, except in the very early course of the illness [35-37]. In comparison, mean WBC counts are higher in patients with a gangrenous (necrotic) or perforated appendix [38]: Acute 14,500 7,300 cells/microL Gangrenous 17,100 3,900 cells/microL Perforated 17,900 2,100 cells/microL (see 'Perforated appendix' below) 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 a specificity of 86 percent [39]. This compares favorably with a sensitivity and specificity of an elevated WBC of 80 percent and 55 percent respectively. Imaging studies Computed tomography findings The following findings suggest acute appendicitis on standard abdominal

computed tomography (CT) scanning with contrast including (image 1 and image 2) [40-42]: Enlarged appendiceal diameter >6 mm with an occluded lumen Appendiceal wall thickening (>2 mm) Periappendiceal fat stranding Appendiceal wall enhancement Appendicolith (seen in approximately 25 percent of patients) Ultrasound findings The most accurate ultrasound finding for acute appendicitis is an appendiceal diameter of >6 mm (image 3 and image 4) [8,43,44]. Plain radiograph findings Plain radiographs are usually not helpful for establishing the diagnosis of appendicitis (image 5). However, the following radiographic findings have been associated with acute appendicitis: Right lower quadrant appendicolith Localized right lower quadrant ileus Loss of the psoas shadow Free air (occasionally) Deformity of cecal outline Right lower quadrant soft tissue density Magnetic resonance imaging Magnetic resonance imaging (MRI) can assist with the evaluation of acute abdominal and pelvic pain during pregnancy (image 6) [45,46]. A normal appendix is visualized as a tubular structure less than or equal to 6 mm in diameter and filled with air and/or oral contrast material [47]. An enlarged fluid-filled appendix (>7 mm in diameter) is considered an abnormal finding, while an appendix with a diameter of 6 to 7 mm is considered an inconclusive finding [47]. (See "Approach to abdominal pain and the acute abdomen in pregnant and postpartum women" and "Acute appendicitis in pregnancy".) DIAGNOSIS The diagnosis of acute appendicitis is generally made from the history and clinical examination; the diagnosis is supported by the laboratory and/or imaging findings. The patient presenting with acute abdominal pain should undergo a thorough physical examination, including a digital rectal examination. Women should undergo a pelvic examination. (See "History and physical examination in adults with abdominal pain".) An experienced examiner can make the correct diagnosis of appendicitis without imaging [48]. Several studies have found the diagnostic accuracy of clinical evaluation alone to be 75 to 90 percent [18,30,49]. The diagnostic accuracy of the clinical examination may depend on the experience of the examining clinician [50-55]. Patients in whom appendicitis is considered to be extremely likely after assessment by an experienced clinician should proceed directly to appendectomy without further radiologic testing. (See "Acute appendicitis in adults: Management".) The diagnosis of acute appendicitis can be difficult and a delay can result in perforation rates as high as 80 percent [56,57]. The challenging clinical settings include [58]: Children less than 3 years of age. (See "Acute appendicitis in children: Clinical manifestations and diagnosis".) Adults older than age 60 years. (See "Acute appendicitis in adults: Management", section on 'Elderly patients'.)

Women in the second and third trimesters of pregnancy, due to the displacement of the appendix by the uterus and the resulting changes in the physical examination. (See "Acute appendicitis in pregnancy".) No single feature or combination of features is a highly accurate predictor of acute appendicitis, although prediction rules based upon combinations of features may have some clinical utility [3,18,19,40,59-61]. Diagnostic scoring systems Several scoring systems have been proposed to standardize the correlation of clinical and laboratory variables. The Alvarado score is the most widely used diagnostic aid for the diagnosis of appendicitis and has been modified slightly since it was introduced [62,63]. The modified Alvarado scale assigns a score to each of the following diagnostic criteria: Migratory right iliac fossa pain (1 point) Anorexia (1 point) Nausea/vomiting (1 point) Tenderness in the right iliac fossa (2 points) Rebound tenderness in the right iliac fossa (1 point) Fever >37.5C (1 point) Leukocytosis (2 points) A low Alvarado score (<5) has more diagnostic utility to rule out appendicitis than a high score (7) does to rule in the diagnosis. In a systematic review of 42 retrospective and prospective studies that included over 8300 patients with suspected acute appendicitis and/or right iliac fossa pain, overall 99 percent of patients with acute appendicitis had a score of 5 [64]. However, a high score (7) alone had poor diagnostic predictive utility as the overall sensitivity was 82 percent and the specificity was 81 percent. The Alvarado score was most accurate in men but over-predicted the probability of acute appendicitis in women in all risk groups. A management guide based upon total points includes: A patient with a score of 0 to 3 could be considered to have a low risk of appendicitis and would be discharged with advice to return if there was no improvement in symptoms, subject to social circumstances. A patient with a score of 4 to 6 would be admitted for observation and re-examination. If the score remains the same after 12 hours, operative intervention is recommended. A male patient with a score of 7 to 9 would proceed to appendectomy. A female patient who is not pregnant with a score of 7 to 9 would undergo diagnostic laparoscopy, then appendectomy if indicated by the intraoperative findings. The surgical management of appendicitis during pregnancy is discussed separately. (See "Acute appendicitis in pregnancy".) Because of the diagnostic challenges of diagnosing acute appendicitis in women, some authors have advocated diagnostic laparoscopy to minimize the high false-negative rate in women regardless of score [63], while others have suggested using CT scans to help with the diagnosis of patients with an equivocal clinical presentation and a score between 4 to 6 [65]. (See 'Imaging' below.) Several other scoring systems have been described as well, but none are typically in common use [66-68]. A systematic review of several published scoring systems showed a diagnostic sensitivity of 53 to 99 percent and specificity of 30 to 99 percent [69]. As a general rule, the addition of these decision aids to clinical judgment has

the potential to improve specificity and lead to lower false-positive rates in diagnosis of acute appendicitis, but decision aids cannot definitively determine or exclude the possibility of appendicitis [69]. DIAGNOSTIC EVALUATION Imaging Imaging modalities such as computed tomography (CT) and ultrasonography (US) are increasingly used to support the clinical diagnosis of acute appendicitis. Although some studies suggest that the increased use of imaging has decreased the nontherapeutic appendectomy rate (NAR) for acute appendicitis [70,71], many surgeons will and should proceed with surgical exploration, in the absence of imaging, if there is strong clinical support for appendicitis. (See 'Clinical manifestations' above.) Based upon prospective trials and retrospective data, imaging studies do not improve the overall diagnostic accuracy for acute appendicitis (image 7 and image 8); the diagnostic accuracy of an experienced surgeon is comparable to CT scan imaging in the assessment of patients with an equivocal presentation of acute appendicitis [18,49,51]. However, in a retrospective review, the CT scan changed the treatment plan in 58 percent of patients [72]. Differences in studies may, in part, be due to the experience of the surgeons and the populations being evaluated. Although diagnostic imaging is unnecessary when the clinical diagnosis of appendicitis is certain, imaging should be performed when the diagnosis of appendicitis is suspected but unclear. Diagnostic imaging may be useful in children, elder adults, or women of childbearing age with an unclear presentation. Similarly, patients with comorbidities such as diabetes, obesity, and immunocompromise may have a higher occurrence of atypical presentation of acute appendicitis. These populations are more likely to present with unclear symptoms such as vague abdominal pain. (See "Acute appendicitis in children: Diagnostic imaging" and "Acute appendicitis in adults: Management", section on 'Special considerations' and "Acute appendicitis in pregnancy", section on 'Diagnosis'.) Computed tomography Based upon retrospective reviews, adult women are more than twice as likely as men to have a nontherapeutic appendectomy for acute appendicitis [71,73-76], and therefore women may benefit from a preoperative CT scan if the diagnosis is uncertain (image 1 and image 2). A retrospective review of 1425 consecutive patients undergoing an appendectomy found that adult women evaluated with a preoperative CT scan had a significantly lower nontherapeutic appendectomy rate (NAR) compared with adult women without a preoperative diagnostic CT scan (21 versus 8 percent) [71]. There was no reduction in NAR for men or children. Preoperative CT protocols for imaging include: Standard abdominal-pelvic CT with IV and oral contrast Focused appendiceal CT with rectal contrast Non-contrast CT In most clinical settings, if there is sufficient diagnostic concern and uncertainty to warrant a CT scan to diagnose appendicitis, a full abdominal-pelvic CT with IV and oral contrast should be performed or a decision should be made to proceed to the operating room for abdominal exploration by laparotomy or laparoscopy. Standard CT scan with contrast A commonly used protocol involves a standard abdominal and pelvic CT scan (16-MDCT or higher) with intravenous and oral contrast. (See "Principles of computed tomography of the chest".)

A number of findings suggest acute appendicitis on standard abdominal CT scanning [40-42]: Enlarged appendiceal diameter >6 mm with an occluded lumen Appendiceal wall thickening (>2 mm) Periappendiceal fat stranding Appendiceal wall enhancement Appendicolith (seen in approximately 25 percent of patients) The sensitivity and specificity of CT with IV and oral contrast for acute appendicitis is in the range of 91 to 98 and 75 to 93 percent, respectively [18,49,60,72,77-79]. Air in the appendix or a contrast-filled lumen in a normal appearing appendix virtually excludes the diagnosis. However, a nonvisualized appendix does not rule out appendicitis. This is particularly important to remember in patients who have had symptoms for a short duration, since only minimal inflammatory changes may be present in the right lower quadrant. An advantage of a complete abdominal CT scan is that it permits visualization of the entire abdomen. An alternative diagnosis is found in up to 15 percent of patients [72]. Furthermore, a CT scan can assist in the treatment plan for patients with a palpable abdominal mass, such as those in whom an appendiceal phlegmon or abscess may have developed. These features are more likely in patients who present after having prolonged symptoms (four to five days). (See "Acute appendicitis in adults: Management".) A drawback of the standard CT protocol is that it takes up to two hours to administer oral contrast. In addition, a CT scan involves radiation exposure and intravenous contrast, with the potential for contrast-induced renal nephropathy. Cost and availability are also considerations, particularly in resource-poor settings. Appendiceal CT A focused appendiceal CT scan can be performed with rectal contrast alone and thin cuts through the right iliac fossa. Because full oral contrast is not given, the scan can be performed within 15 minutes. Rectal contrast provides good visualization of the pericecal region without the need to wait for oral contrast to reach the right lower quadrant, which may be an unpleasant procedure for the patient. In a report using a limited appendiceal CT scan with rectal contrast, the sensitivity of the most common findings for acute appendicitis were as follows [40]: Right lower abdominal quadrant fat stranding (100 percent sensitivity) Focal cecal thickening (69 percent specificity) Adenopathy (63 percent sensitivity) One study reported that a focal appendiceal CT had 98 percent accuracy and sensitivity with rectal contrast along a limited area (15 cm) of the pelvis centered 3 cm superior to the cecal tip [19,80]. The relevance of focal appendiceal imaging is questionable outside of large medical centers, as this technique requires personnel to administer rectal contrast and a radiologist on site for the verification of positioning. In addition, an appendiceal CT scan only evaluates the appendix, and the images may be unrevealing in the presence of other abdominal pathology. Unenhanced CT The administration of contrast for imaging adds time, expense, and risk of an allergic reaction. A number of studies have suggested that adequate imaging can be obtained without contrast. In various reports, unenhanced CT had a sensitivity of 88 to 96 percent, specificity of 91 to 98 percent, and diagnostic

accuracy of 94 to 97 percent for appendicitis, with the added advantage of total exam time of 5 to 15 minutes [51,81,82]. Test characteristics may depend at least in part upon the patient's body habitus [18]. Some radiologists maintain that if the BMI exceeds 25 that the CT is less accurate and therefore oral contrast is necessary. An important limitation of unenhanced CT is the diminished ability to diagnose other abdominal pathology, potentially diminishing the role of the examination in patients in whom there is diagnostic uncertainty (eg, elder patients, women, atypical presentation). Unenhanced CT may be of some value in patients who have renal failure or clinical instability. However, for most patients where there is sufficient diagnostic uncertainty to warrant a CT scan for appendicitis, a full abdominalpelvic CT with IV and oral contrast should be performed or a decision should be made to proceed to the operating room for abdominal exploration. Ultrasonography Ultrasound (US) is reliable to confirm the clinical diagnosis of acute appendicitis, but is not reliable to exclude the diagnosis (picture 1 and image 9) [83]. Accuracy is diminished in obese patients. At least eight sonographic internal inflammatory changes of the appendix have been described [8,43,44]. The most accurate ultrasound finding for acute appendicitis is an appendiceal diameter of >6 mm with a sensitivity, specificity, negative predictive value and positive predictive value of 98 percent [43,44]. In various reports, the sensitivity and specificity by US in the diagnosis of appendicitis ranged from 35 to 98 percent and 71 to 98 percent, respectively [18,51,71,74]. Advantages of US compared with CT imaging include: Results obtained more efficiently No radiation exposure No use of intravenous or intestinal contrast agents Disadvantages of US compared with CT imaging include: Less diagnostic accuracy Less likely to reveal an accurate alternative diagnosis Accuracy is operator dependent Technical challenges: Patients with a large body habitus and/or a large amount of overlying bowel gas Imaging costs The use of preoperative imaging studies in the diagnosis of acute appendicitis has increased with time, from 32 percent (1995 through 1999) to 95 percent (2001 through 2008), at one representative academic institution [71]. The increase in the use of CT scanning for the diagnosis of appendicitis has been largely justified by the assumption that it decreases the rates of perforated appendicitis as well as nontherapeutic appendectomies [84,85]. In two studies that performed cost analysis, one showed that the cost of a nontherapeutic appendectomy was 16 times more expensive than a focused appendiceal CT scan, while another reported that an appendectomy was 22 times more expensive than nonenhanced CT scanning, implying cost savings if a reduction in nontherapeutic appendectomy rates could be achieved [82,86]. However, in one retrospective review, most patients undergoing negative appendectomy had a preoperative CT scan, and more than 50 percent of those patients had CT interpretations that were positive for, or could not exclude, acute

appendicitis [71]. Several studies have failed to demonstrate a significant reduction in the overall institutional rates for nontherapeutic appendectomies despite the increased use of CT scan over time [60,72,73,75,77,87-89]. Results of studies that included analysis of perforated appendicitis are mixed. One study showed an observed rate of appendiceal perforation of 9 percent in patients who underwent routine CT imaging compared with 25 percent in patients in whom CT scanning was not used [75]. Other studies have demonstrated a fairly constant rate of perforated appendix over time despite the increased use of CT scan [71,73,89]. Cost analysis for studies such as these is complicated by the value of CT scanning in patients in whom therapeutic appendectomy was performed; as a result, the cost savings depend upon an absolute rate reduction for nontherapeutic appendectomies [72,90]. Additionally, cost calculations depend upon local institutional variables and surgeon variables; selected institutional observations may not be applicable to all practices. Laboratory tests Laboratory tests serve a supportive role in the diagnosis of appendicitis. No single laboratory test or combination of tests is an absolute marker for appendicitis [43,87]. A complete blood count (CBC) with a differential should be obtained, but cannot be used to confirm or exclude the diagnosis of appendicitis. A mild leukocytosis and a left shift (increase in total white blood cell count, bands [immature neutrophils], and neutrophils) can be present in acute appendicitis as well as other acute etiologies of abdominal pain. A pregnancy test should be performed for all women of childbearing age. 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 a specificity of 86 percent [39], the test is not discriminatory and generally not helpful in the evaluation of patients suspected of acute appendicitis. Exploratory laparotomy/laparoscopy The acceptable nontherapeutic appendectomy rate (NAR) varies depending upon the age and sex of the patient. For example, in young healthy males with right lower quadrant pain, the negative appendectomy rate (NAR) should be less than 10 percent, while a rate that approaches 20 percent is reasonable in young women in whom other pelvic processes can make accurate diagnosis more difficult (eg, pelvic inflammatory diseases, tubo-ovarian abscess) [81,91]. No significant difference in NAR was noted in comparing laparoscopic and open appendectomy [71]. A low NAR has been achieved in some centers that use close in-hospital observation [92]. DIFFERENTIAL DIAGNOSIS A variety of inflammatory and infectious conditions in the right lower quadrant can mimic the signs and symptoms of acute appendicitis. (See "Differential diagnosis of abdominal pain in adults".) Perforated appendix During the first 24 hours after the onset of abdominal pain and associated symptoms, approximately 90 percent of patients develop inflammation and perhaps necrosis of the appendix, but not perforation. Once significant inflammation and necrosis occur, the appendix is at risk of perforation, which leads to localized abscess formation or diffuse peritonitis. The time course to perforation is variable. One study showed that 20 percent of patients developed perforation less than 24 hours after the onset of symptoms [17]. Sixty-five percent of patients in whom the appendix perforated had symptoms for longer than 48 hours.

A perforated appendix must be considered in a patient whose temperature exceeds 103.0F (39.4C), the WBC count is greater than 15,000 cells/microL, and imaging studies reveal a fluid collection in the right lower quadrant. (See 'Pathogenesis' above and 'Laboratory findings' above and 'Imaging' above.) Cecal diverticulitis Cecal diverticulitis usually occurs in young adults and presents with signs and symptoms that can be virtually identical to those of acute appendicitis. Right-sided diverticulitis occurs in only 1.5 percent of patients in Western countries, but is more common in Asian populations (accounting for as many as 75 percent of cases of diverticulitis). Patients with right-sided diverticulitis tend to be younger than those with left-sided disease and often are misdiagnosed with acute appendicitis. Computed tomographic (CT) scanning of the abdomen with IV and oral contrast is the diagnostic test of choice in patients suspected of having acute diverticulitis. (See "Clinical manifestations and diagnosis of colonic diverticular disease" and "Treatment of acute diverticulitis", section on 'Right-sided (cecal) diverticulitis'.) Meckel's diverticulitis Meckel's diverticulitis presents in a fashion similar to acute appendicitis. A Meckel's diverticulum is a congenital remnant of the omphalomesenteric duct and is located on the small intestine two feet from the ileocecal valve [93,94]. Meckel's diverticulitis should be included in the differential diagnosis as the small bowel may migrate into the right lower quadrant and mimic the symptoms of appendicitis. If an inflamed appendix is not found on abdominal exploration for acute appendicitis, the surgeon should search for an inflamed Meckel's diverticulum. Acute ileitis Acute ileitis, due most commonly to an acute self-limited bacterial infection (Yersinia, Campylobacter, Salmonella, and others), should be considered when acute diarrhea is a prominent symptom. Other clinical manifestations of acute yersiniosis include abdominal pain, fever, nausea and/or vomiting. Yersiniosis cannot be readily distinguished clinically from other causes of acute diarrhea that present with these symptoms. However, localization of abdominal pain to the right lower quadrant along with acute diarrhea may be a diagnostic clue for yersiniosis. (See "Clinical manifestations and diagnosis of Yersinia infections", section on 'Acute yersiniosis'.) Acute yersiniosis presenting with right lower abdominal pain, fever, vomiting, leukocytosis, and understated diarrhea may be confused with acute appendicitis. At surgery, findings include visible inflammation around the appendix and terminal ileum and inflammation of the mesenteric lymph nodes; the appendix itself is generally normal. Yersinia can be cultured from the appendix and involved lymph nodes. (See "Clinical manifestations and diagnosis of Yersinia infections", section on 'Pseudoappendicitis'.) Crohn's disease Crohn's disease can present with symptoms similar to appendicitis, particularly when localized to the distal ileum. Fatigue, prolonged diarrhea with abdominal pain, weight loss, and fever, with or without gross bleeding, are the hallmarks of Crohn's disease. An acute exacerbation of Crohns disease can mimic acute appendicitis and may be indistinguishable by clinical evaluation and imaging. Crohn's disease should be suspected in patients who have persistent pain after surgery, especially if the appendix is histologically normal. (See "Clinical manifestations, diagnosis and prognosis of Crohn's disease in adults".) Gynecologic and obstetrical conditions The following gynecologic diseases may present with symptoms and/or clinical findings that are included in the differential of acute appendicitis: Tubo-ovarian abscess A tubo-ovarian abscess (TOA) is an inflammatory mass involving the fallopian tube, ovary, and, occasionally, other adjacent pelvic organs (eg, bowel, bladder). These abscesses are found most

commonly in reproductive age women and typically result from upper genital tract infection. Tubo-ovarian abscess is usually a complication of pelvic inflammatory disease. The classic presentation includes acute lower abdominal pain, fever, chills, and vaginal discharge. However, fever is not present in all patients, some patients report only low-grade nocturnal fevers or chills, and not all women present in an acute fashion. Clinical history and CT imaging can help differentiate TOA from acute appendicitis (picture 2). (See "Epidemiology, clinical manifestations, and diagnosis of tuboovarian abscess", section on 'Clinical presentation'.) Pelvic inflammatory disease Lower abdominal pain is the cardinal presenting symptom in women with PID although the character of the pain may be quite subtle. The recent onset of pain that worsens during coitus or with jarring movement may be the only presenting symptom of PID; the onset of pain during or shortly after menses is particularly suggestive. On physical examination, only about one-half of patients with PID have fever. Abdominal examination reveals diffuse tenderness greatest in the lower quadrants, which may or may not be symmetrical. Rebound tenderness and decreased bowel sounds are common. On pelvic examination, the finding of a purulent endocervical discharge and/or acute cervical motion and adnexal tenderness with bimanual examination is strongly suggestive of PID. Clinical history and CT imaging can help differentiate PID from acute appendicitis (See "Clinical features and diagnosis of pelvic inflammatory disease".) Ruptured ovarian cyst Rupture of an ovarian cyst is a common occurrence in women of reproductive age and may be associated with the sudden onset of unilateral lower abdominal pain. The pain often begins during strenuous physical activity, such as exercise or sexual intercourse and may be accompanied by light vaginal bleeding due to a drop in secretion of ovarian hormones and subsequent endometrial sloughing. Blood from the rupture site may seep into the ovary, which can cause pain from stretching of the ovarian cortex, or it may flow into the abdomen, which has an irritant effect on the peritoneum. Serous or mucinous fluid released upon cyst rupture is not very irritating; the patient may remain asymptomatic despite accumulation of a large volume of intraperitoneal fluid. On the other hand, spillage of sebaceous material upon rupture of a dermoid cyst causes a marked granulomatous reaction and chemical peritonitis, which is usually quite painful. The right lower quadrant is most commonly affected, possibly because the rectosigmoid colon protects the left ovary from the effects of abdominal trauma. Rupture of a simple cyst usually results in only mild to moderate tenderness on deep palpation. If the cyst has not completely collapsed, an adnexal mass may be palpable on bimanual examination. At the other end of the spectrum, release of sebaceous material or blood into the abdomen may cause overt peritonitis with rigidity of the abdominal wall and rebound tenderness. Cervical motion tenderness may also be present. Intraabdominal hemorrhage may be associated with Cullen's sign (ie, periumbilical ecchymoses). Clinical history and CT imaging can help differentiate a ruptured ovarian cyst from acute appendicitis (picture 3 and picture 4). (See "Evaluation and management of ruptured ovarian cyst".) Mittelschmerz Mittelschmerz refers to midcycle pain in an ovulatory woman caused by normal follicular enlargement just prior to ovulation or to normal follicular bleeding at ovulation. The pain is typically mild and unilateral; it occurs midway between menstrual periods and lasts for a few hours to a couple of days. Fluid or blood is released from the ruptured egg follicle and can cause irritation of the lining of the abdominal wall. (See "Physiology of the normal menstrual cycle".) Ovarian and fallopian tube torsion Ovarian torsion refers to the twisting of the ovary on its ligamentous supports, often resulting in impedance of its blood supply (picture 5). Isolated fallopian tube torsion is uncommon (picture 6). Expedient diagnosis is important to preserve ovarian function and prevent adverse sequelae.

However, the diagnosis can be challenging because the symptoms are relatively nonspecific. The most common symptom of ovarian torsion is sudden onset lower abdominal pain, often associated with waves of nausea and vomiting. Fever, although an uncommon finding in ovarian torsion, may be a marker of necrosis, particularly in the setting of an increased white blood cell count. Clinical history and CT imaging can help differentiate the diagnosis from acute appendicitis (picture 7). (See "Ovarian and fallopian tube torsion".) Endometriosis Endometriosis is defined as the presence of endometrial glands and stroma at extrauterine sites. These ectopic endometrial implants are usually located in the pelvis, but can occur nearly anywhere in the body (picture 8). Common symptoms of endometriosis include pelvic pain (which is usually chronic and often more severe during menses or at ovulation), dysmenorrhea, deep dyspareunia, cyclical bowel or bladder symptoms, abnormal menstrual bleeding, and infertility. There are often no abnormal findings on physical examination; when findings are present, the most common is tenderness upon palpation of the posterior fornix. Ultrasound is mostly useful for diagnosing ovarian endometriomas; it lacks adequate resolution for visualizing adhesions and superficial peritoneal/ovarian implants, which are more common than endometriomas. (See "Pathogenesis, clinical features, and diagnosis of endometriosis".) Ovarian hyperstimulation syndrome Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction therapy and may be accompanied by or mistaken for cyst rupture. Clinical findings include bloating, nausea, vomiting, diarrhea, lethargy, shortness of breath, and rapid weight gain. Severe ovarian hyperstimulation syndrome is characterized by large ovarian cysts, ascites, and, in some patients, pleural and/or pericardial effusion, electrolyte imbalance (hyponatremia, hyperkalemia), hypovolemia, and hypovolemic shock. Marked hemoconcentration, increased blood viscosity, and thromboembolic phenomena including disseminated intravascular coagulation occur in the most severe cases. (See "Classification and treatment of ovarian hyperstimulation syndrome".) Ectopic pregnancy Ectopic pregnancy has clinical symptoms and sonographic features similar to those of a ruptured ovarian cyst. In women with acute pelvic pain or abnormal vaginal bleeding, a positive pregnancy test strongly suggests the presence of an ectopic pregnancy if an intrauterine pregnancy cannot be visualized sonographically. If an intrauterine pregnancy is visualized, then pelvic pain and intraperitoneal fluid could be due to a ruptured ovarian cyst (eg, corpus luteum cyst, theca lutein cyst) or heterotopic pregnancy. (See "Clinical manifestations, diagnosis, and management of ectopic pregnancy", section on 'Heterotopic pregnancy'.) Acute endometritis Acute endometritis occurs after an obstetrical delivery or, rarely, after an invasive uterine procedure. The diagnosis is largely based upon the presence of fever, gradual onset of uterine tenderness, foul uterine discharge, and leukocytosis in an at-risk setting. (See "Postpartum endometritis" and "Endometritis unrelated to pregnancy".) Urologic conditions Renal colic Pain is the most common symptom and varies from a mild and barely noticeable ache to discomfort that is so intense that it requires parenteral analgesics. The pain typically waxes and wanes in severity, and develops in waves or paroxysms that are related to movement of the stone in the ureter and associated ureteral spasm. Paroxysms of severe pain usually last 20 to 60 minutes. Pain is thought to occur primarily from

urinary obstruction with distention of the renal capsule. (See "Diagnosis and acute management of suspected nephrolithiasis in adults" and "Acute management of nephrolithiasis in children".) Testicular torsion Testicular torsion is a urologic emergency that is more common in neonates and postpubertal boys, although it can occur at any age. Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis. If fixation of the lower pole of the testis to the tunica vaginalis is insufficiently broadbased or absent, the testis may torse (twist) on the spermatic cord, potentially producing ischemia from reduced arterial inflow and venous outflow obstruction. (See "Causes of scrotal pain in children and adolescents", section on 'Testicular torsion' and "Evaluation of the acute scrotum in adults", section on 'Testicular torsion'.) Epididymitis Epididymitis occurs more frequently among late adolescents, but also occurs in younger boys who deny sexual activity and is most common cause of scrotal pain in adults in the outpatient setting. Several factors may predispose postpubertal boys to develop subacute epididymitis, including sexual activity, heavy physical exertion, and direct trauma (eg, bicycle or motorcycle riding). Bacterial epididymitis in prepubertal boys is associated with structural anomalies of the urinary tract. In acute infectious epididymitis, palpation reveals induration and swelling of the involved epididymis with exquisite tenderness. More advanced cases often present with testicular swelling and pain (epididymo-orchitis) with scrotal wall erythema and a reactive hydrocele. (See "Causes of scrotal pain in children and adolescents", section on 'Epididymitis' and "Evaluation of the acute scrotum in adults", section on 'Epididymitis'.) Torsion of the appendix testis or appendix epididymis The appendix testis is a small vestigial structure on the anterosuperior aspect of the testis (an embryologic remnant of the Mllerian duct system). The appendix epididymis is a vestigial remnant of the Wolffian duct that is located at the head of the epididymis. The pedunculated shape of these appendages predisposes them to torsion, which can produce scrotal pain that ranges from mild to severe. Most cases of torsion of the appendix testis occur between the ages of 7 and 14 years, and rarely occur in adults. (See "Causes of scrotal pain in children and adolescents", section on 'Torsion of the appendix testis or appendix epididymis' and "Evaluation of the acute scrotum in adults", section on 'Torsion of the appendix testis'.) TREATMENT The management of acute appendicitis in children and adults is discussed in detail separately. (See "Acute appendicitis in children: Management" and "Acute appendicitis in adults: Management".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Appendicitis in adults (The Basics)"). SUMMARY AND RECOMMENDATIONS Appendicitis is one of the most common causes of the acute

abdomen and one of the most frequent indications for an emergent abdominal surgical procedure worldwide. The tip of the appendix can be found in a retrocecal or pelvic location, as well as medial, lateral, anterior or posterior to the cecum. Anatomic variability can complicate the diagnosis, as clinical presentation will reflect the anatomic position of the appendix. (See 'Anatomy' above.) Appendiceal obstruction plays a role in the pathogenesis of appendicitis, but it is not required for the development of appendicitis. (See 'Pathogenesis' above.) The classic symptoms of appendicitis include right lower quadrant abdominal pain, anorexia, fever, nausea and vomiting. The abdominal pain is initially periumbilical in nature with subsequent migration to the right lower quadrant as the inflammation progresses (see 'Clinical manifestations' above). Patients with appendicitis can also present with atypical or nonspecific symptoms, such as indigestion, flatulence, bowel irregularity, and generalized malaise; and not all patients will have migratory abdominal pain. The constellation of findings from history, physical examination, and laboratory studies will usually lead an experienced examiner to the correct diagnosis of appendicitis without diagnostic imaging (see 'Diagnosis' above). A clinical diagnosis can be more challenging in women, who may benefit from the addition of radiologic imaging when the diagnosis is unclear. Diagnostic imaging should be performed when the diagnosis of appendicitis is suspected but unclear (eg, elderly patients, patients with comorbid illnesses, women of childbearing age). We perform a standard abdominal CT scan with intravenous and oral contrast. (See 'Standard CT scan with contrast' above.) The differential diagnosis of right lower quadrant abdominal pain includes inflammatory disease processes (eg, Crohns disease, ruptured cyst), infectious diseases (eg, acute ileitis, tubo-ovarian abscess), and obstetrical conditions (eg, ectopic pregnancy). (See 'Differential diagnosis' above.) ACKNOWLEDGMENT We are saddened by the untimely death of John Marx, MD, who passed away in July 2012. We wish to acknowledge Dr. Marx's dedication and his many contributions to UpToDate, in particular, his work as editor-in-chief for Emergency Medicine and as a section editor and author for Adult Trauma. Use of UpToDate is subject to the Subscription and License Agreement.

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