Clinical Features and Diagnosis of Acute Appendicitis: Symptoms, Signs, and Imaging, Resúmenes de Medicina

¡Descarga Clinical Features and Diagnosis of Acute Appendicitis: Symptoms, Signs, and Imaging y más Resúmenes en PDF de Medicina solo en Docsity! Acute appendicitis in adults: Clinical manifestations and differential diagnosis Author: Ronald F Martin, MD Section Editor: Martin Weiser, MD Deputy Editor: Wenliang Chen, MD, PhD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2017. | This topic last updated: Jul 12, 2017. INTRODUCTION — Appendicitis, an inflammation of the vestigial 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 "Management of acute appendicitis in adults" 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 with 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. 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 [28,31,32]). ●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 [31]). 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 [33]. 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 [34-36]. The sensitivity and specificity of an elevated white blood cell (WBC) count in acute appendicitis is 80 percent and 55 percent respectively. Acute appendicitis is unlikely when the WBC count is normal, except in the very early course of the illness [36,37]. In comparison, mean WBC counts are higher in patients with a gangrenous (necrotic) or perforated appendix [38]: ●Acute − 14,500±7300 cells/microL ●Gangrenous − 17,100±3900 cells/microL ●Perforated − 17,900±2100 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 exams — The choice of imaging examination for the diagnosis of acute appendicitis is discussed in detail separately. (See "Acute appendicitis in adults: Diagnostic evaluation", section on 'Imaging'.) 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). 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 acute abdominal pain in pregnant and postpartum women" and "Acute appendicitis in pregnancy".) DIFFERENTIAL DIAGNOSIS — A variety of inflammatory and infectious conditions in the right lower quadrant can mimic the signs and symptoms of acute appendicitis. (See "Causes 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 for 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 103.0°F (39.4°C), 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 exams' above and "Acute appendicitis in adults: Diagnostic evaluation".) 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 acute diverticulitis in adults" and "Acute colonic diverticulitis: Medical management", 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 [48,49]. 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. (See "Meckel's diverticulum", section on 'Clinical presentations'.) 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 Crohn's 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 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 1). (See "Epidemiology, clinical manifestations, and diagnosis of tubo-ovarian abscess", section on 'Clinical presentation'.) Pelvic inflammatory disease — Lower abdominal pain is the cardinal presenting symptom in women with pelvic inflammatory disease (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 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 broad-based 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 acute scrotal pain 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 the 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 acute scrotal pain in adults".) 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 Müllerian 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 acute scrotal pain 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 "Management of acute appendicitis in adults".) 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 5 th to 6 th 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 10 th to 12 th 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 education: 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 differential diagnosis of right lower quadrant abdominal pain includes inflammatory disease processes (eg, Crohn's disease, ruptured cyst), infectious diseases (eg, acute ileitis, tubo-ovarian abscess), and obstetrical conditions (eg, ectopic pregnancy). (See 'Differential diagnosis' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Williams GR. Presidential Address: a history of appendicitis. With anecdotes illustrating its importance. Ann Surg 1983; 197:495. 2. Fitz RH. Perforating inflammation of the vermiform appendix with special reference to its early diagnosis and treatment. Am J Med Sci 1886; 92:321. 3. Jaffe BM, Berger DH. The appendix. In: Schwartz's Principles of Surgery, 8th ed, Schwartz SI, Brunicardi CF (Eds), McGraw-Hill Companies, New York 2005. 4. Buschard K, Kjaeldgaard A. Investigation and analysis of the position, fixation, length and embryology of the vermiform appendix. Acta Chir Scand 1973; 139:293. 5. Mulholland MW, Lillemoe KD, Doherty GM, et al.. Greenfield's Surgery: Scientific Principles and Practice, 4th ed, Lippincott Williams & Wilkins, Philadelphia 2005. 6. Kumar V, Abbas AK, Fausto N. Robbins & Cotran Pathologic Basis of Disease, 7th ed, Saunders Elsevier, Philadelphia 2007. 7. Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990; 132:910. 8. Birnbaum BA, Wilson SR. Appendicitis at the millennium. Radiology 2000; 215:337. 9. Burkitt DP. The aetiology of appendicitis. Br J Surg 1971; 58:695. 10. Butler C. Surgical pathology of acute appendicitis. Hum Pathol 1981; 12:870. 11. Miranda R, Johnston AD, O'Leary JP. Incidental appendectomy: frequency of pathologic abnormalities. Am Surg 1980; 46:355. 12. Arnbjörnsson E, Bengmark S. Obstruction of the appendix lumen in relation to pathogenesis of acute appendicitis. Acta Chir Scand 1983; 149:789. 13. Nitecki S, Karmeli R, Sarr MG. Appendiceal calculi and fecaliths as indications for appendectomy. Surg Gynecol Obstet 1990; 171:185. 14. Jones BA, Demetriades D, Segal I, Burkitt DP. The prevalence of appendiceal fecaliths in patients with and without appendicitis. A comparative study from Canada and South Africa. Ann Surg 1985; 202:80. 15. Lau WY, Teoh-Chan CH, Fan ST, et al. The bacteriology and septic complication of patients with appendicitis. Ann Surg 1984; 200:576. 16. Bennion RS, Baron EJ, Thompson JE Jr, et al. The bacteriology of gangrenous and perforated appendicitis--revisited. Ann Surg 1990; 211:165. 17. Temple CL, Huchcroft SA, Temple WJ. The natural history of appendicitis in adults. A prospective study. Ann Surg 1995; 221:278. 18. Lee SL, Walsh AJ, Ho HS. Computed tomography and ultrasonography do not improve and may delay the diagnosis and treatment of acute appendicitis. Arch Surg 2001; 136:556. 19. Rao PM, Rhea JT, Novelline RA, et al. Helical CT technique for the diagnosis of appendicitis: prospective evaluation of a focused appendix CT examination. Radiology 1997; 202:139. 20. Chung CH, Ng CP, Lai KK. Delays by patients, emergency physicians, and surgeons in the management of acute appendicitis: retrospective study. Hong Kong Med J 2000; 6:254. 21. Guidry SP, Poole GV. The anatomy of appendicitis. Am Surg 1994; 60:68. 22. Takada T, Nishiwaki H, Yamamoto Y, et al. The Role of Digital Rectal Examination for Diagnosis of Acute Appendicitis: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0136996. 23. McBurney, C. Experience with early operative interference in cases of disease of the vermiform appendix. NY Med J 1889; 50:676. 24. Golledge J, Toms AP, Franklin IJ, et al. Assessment of peritonism in appendicitis. Ann R Coll Surg Engl 1996; 78:11. 25. Andersson RE, Hugander AP, Ghazi SH, et al. Diagnostic value of disease history, clinical presentation, and inflammatory parameters of appendicitis. World J Surg 1999; 23:133. 26. Lane R, Grabham J. A useful sign for the diagnosis of peritoneal irritation in the right iliac fossa. Ann R Coll Surg Engl 1997; 79:128. 27. Rovsing, NT. Indirektes Hervorrufen des typischen Schmerzes an McBurney's Punkt. Ein Beitrag zur diagnostik der Appendicitis und Typhlitis. Zentralblatt für Chirurgie, Leipzig, 1907; 34:1257. 28. Izbicki JR, Knoefel WT, Wilker DK, et al. Accurate diagnosis of acute appendicitis: a retrospective and prospective analysis of 686 patients. Eur J Surg 1992; 158:227. 29. Alshehri MY, Ibrahim A, Abuaisha N, et al. Value of rebound tenderness in acute appendicitis. East Afr Med J 1995; 72:504. 30. Jahn H, Mathiesen FK, Neckelmann K, et al. Comparison of clinical judgment and diagnostic ultrasonography in the diagnosis of acute appendicitis: experience with a score- aided diagnosis. Eur J Surg 1997; 163:433. 31. Berry J Jr, Malt RA. Appendicitis near its centenary. Ann Surg 1984; 200:567. Acute appendicitis in adults: Diagnostic evaluation Authors: Ronald F Martin, MD Stella K Kang, MD, MS Section Editor: Martin Weiser, MD Deputy Editors: Wenliang Chen, MD, PhD Susanna I Lee, MD, PhD Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2017. | This topic last updated: Jun 01, 2017. 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 exams. 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. The Alvarado score (table 1) uses data from the history, physical exam, 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 those 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 ●Elderly and frail (eg, immunosuppressed, multiple comorbidities) In women of reproductive age, gynecologic pathologies (eg, pelvic inflammatory disease, adnexal torsion) can mimic appendicitis clinically. Elderly 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 gender 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 [1,2]. Observed NAR have decreased in the past decade, which is likely attributable, in part, to the increased utilization of imaging [3]. 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 [4-9]. 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) [9]. 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 [4,10-13]. 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) [4]. 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 [14]. 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 [15], but rates as high as 80 percent have been reported in specific high-risk populations [16]. Retrospective review of 9048 adults with acute appendicitis found the factors associated with increased risk of perforation to be [17]: ●Male gender (risk ratio [RR] 1.24, 95% CI 1.08-1.43) ●Increasing age (RR 1.04, 95% CI 1.08-1.43) ●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 [17]. INITIAL EVALUATION Clinical evaluation — The diagnostic accuracy of the clinical evaluation for acute appendicitis depends on the experience of the examining physician [18-23]. 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 [24,25]. 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 the elderly and frail, 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) [26]. Some limited evidence also suggests that repeated laboratory evaluation (WBC, CRP) may boost the sensitivity in detecting appendicitis, especially in patients who present early [27]. 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 10 9 /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) [28]. intravenous contrast improves the exam 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 [43]. 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 [44-46]: ●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) 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 the elderly and in women of reproductive age was similar to that seen in the entire cohort, although specificity demonstrated wider confidence intervals [26]. Nonvisualization of the appendix (nondiagnostic result) occurs in 10 to 20 percent of exams and decreases but does not eliminate the likelihood of a positive diagnosis of appendicitis [47-49]. 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 exam 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 exams are high, with 50 to 85 percent of normal appendices not visualized [50,51]. Finally, graded compression of the appendix, integral to the ultrasound exam, can cause significant patient discomfort in patients with appendicitis. Imaging features of acute appendicitis on ultrasound include [52-54]: ●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) [55,56]. 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) [57]: ●Pregnant women (see "Acute appendicitis in children: Clinical manifestations and diagnosis") ●Older children who can cooperate with the exam (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 exam. 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 meta-analysis of seven studies on the MRI diagnosis of appendicitis reported a sensitivity of 95 percent (95% CI 88 to 98 percent) and a specificity of 92 percent (95% CI 87 to 95 percent) [58]. The rate of nondiagnostic exams is higher than that reported with CT but lower than that with ultrasound, with 20 to 40 percent of normal appendices not visualized [59]. Similar to CT, MRI allows for detection of alternative diagnoses should the patient not have appendicitis. However, the exam 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 elderly and those with significant pain. Common relative contraindications include cardiac pacemakers and implanted metallic surgical hardware. (See "Principles of magnetic resonance imaging" and "Principles of magnetic resonance imaging", section on 'Precautions'.) 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 exam 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 either negative, nondiagnostic, or unavailable. In such patients, appendicitis can only be diagnosed intraoperatively or pathologically. (See "Management of acute appendicitis in adults", section on 'Laparotomy versus laparoscopy'.) [26,34] 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'.) 32. Enochsson L, Gudbjartsson T, Hellberg A, et al. The Fenyö-Lindberg scoring system for appendicitis increases positive predictive value in fertile women--a prospective study in 455 patients randomized to either laparoscopic or open appendectomy. Surg Endosc 2004; 18:1509. 33. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986; 15:557. 34. Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study. Ann R Coll Surg Engl 1994; 76:418. 35. Ohle R, O'Reilly F, O'Brien KK, et al. The Alvarado score for predicting acute appendicitis: a systematic review. BMC Med 2011; 9:139. 36. Ebell MH, Shinholser J. What are the most clinically useful cutoffs for the Alvarado and Pediatric Appendicitis Scores? A systematic review. Ann Emerg Med 2014; 64:365. 37. Tan WJ, Acharyya S, Goh YC, et al. Prospective comparison of the Alvarado score and CT scan in the evaluation of suspected appendicitis: a proposed algorithm to guide CT use. J Am Coll Surg 2015; 220:218. 38. Smith MP, Katz DS, Lalani T, et al. ACR Appropriateness Criteria® Right Lower Quadrant Pain--Suspected Appendicitis. Ultrasound Q 2015; 31:85. 39. Yun SJ, Ryu CW, Choi NY, et al. Comparison of Low- and Standard-Dose CT for the Diagnosis of Acute Appendicitis: A Meta-Analysis. AJR Am J Roentgenol 2017; :W1. 40. American College of Radiology (ACR) Committee on Drugs and Contrast Media. ACR manual on contrast media, version 10.1, 2015. Available at: http://www.acr.org/~/media/37D84428BF1D4E1B9A3A2918DA9E27A3.pdf (Accessed on August 17, 2016). 41. Dearing DD, Recabaren JA, Alexander M. Can computed tomography scan be performed effectively in the diagnosis of acute appendicitis without the added morbidity of rectal contrast? Am Surg 2008; 74:917. 42. Hershko DD, Awad N, Fischer D, et al. Focused helical CT using rectal contrast material only as the preferred technique for the diagnosis of suspected acute appendicitis: a prospective, randomized, controlled study comparing three different techniques. Dis Colon Rectum 2007; 50:1223. 43. Pickhardt PJ, Lawrence EM, Pooler BD, Bruce RJ. Diagnostic performance of multidetector computed tomography for suspected acute appendicitis. Ann Intern Med 2011; 154:789. 44. Rao PM, Rhea JT, Novelline RA. Sensitivity and specificity of the individual CT signs of appendicitis: experience with 200 helical appendiceal CT examinations. J Comput Assist Tomogr 1997; 21:686. 45. Whitley S, Sookur P, McLean A, Power N. The appendix on CT. Clin Radiol 2009; 64:190. 46. Choi D, Park H, Lee YR, et al. The most useful findings for diagnosing acute appendicitis on contrast-enhanced helical CT. Acta Radiol 2003; 44:574. 47. Benjaminov O, Atri M, Hamilton P, Rappaport D. Frequency of visualization and thickness of normal appendix at nonenhanced helical CT. Radiology 2002; 225:400. 48. Nikolaidis P, Hwang CM, Miller FH, Papanicolaou N. The nonvisualized appendix: incidence of acute appendicitis when secondary inflammatory changes are absent. AJR Am J Roentgenol 2004; 183:889. 49. Johnson PT, Horton KM, Kawamoto S, et al. MDCT for suspected appendicitis: effect of reconstruction section thickness on diagnostic accuracy, rate of appendiceal visualization, and reader confidence using axial images. AJR Am J Roentgenol 2009; 192:893. 50. Yabunaka K, Katsuda T, Sanada S, Fukutomi T. Sonographic appearance of the normal appendix in adults. J Ultrasound Med 2007; 26:37. 51. Williams R, Shaw J. Ultrasound scanning in the diagnosis of acute appendicitis in pregnancy. Emerg Med J 2007; 24:359. 52. Birnbaum BA, Wilson SR. Appendicitis at the millennium. Radiology 2000; 215:337. 53. Kessler N, Cyteval C, Gallix B, et al. Appendicitis: evaluation of sensitivity, specificity, and predictive values of US, Doppler US, and laboratory findings. Radiology 2004; 230:472. 54. Jeffrey RB Jr, Laing FC, Townsend RR. Acute appendicitis: sonographic criteria based on 250 cases. Radiology 1988; 167:327. 55. Keyzer C, Zalcman M, De Maertelaer V, et al. Comparison of US and unenhanced multi- detector row CT in patients suspected of having acute appendicitis. Radiology 2005; 236:527. 56. Kaewlai R, Lertlumsakulsub W, Srichareon P. Body mass index, pain score and Alvarado score are useful predictors of appendix visualization at ultrasound in adults. Ultrasound Med Biol 2015; 41:1605. 57. Rosen MP, Ding A, Blake MA, et al. ACR Appropriateness Criteria® right lower quadrant pain--suspected appendicitis. J Am Coll Radiol 2011; 8:749. 58. Barger RL Jr, Nandalur KR. Diagnostic performance of magnetic resonance imaging in the detection of appendicitis in adults: a meta-analysis. Acad Radiol 2010; 17:1211. 59. Nikolaidis P, Hammond N, Marko J, et al. Incidence of visualization of the normal appendix on different MRI sequences. Emerg Radiol 2006; 12:223. Acute appendicitis in children: Clinical manifestations and diagnosis Author: David E Wesson, MD Section Editor: Jonathan I Singer, MD Deputy Editor: James F Wiley, II, MD, MPH Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2017. | This topic last updated: May 03, 2017. INTRODUCTION — This topic will discuss the epidemiology, clinical features, and evaluation of children with suspected appendicitis. Detailed discussions of diagnostic imaging and treatment for pediatric appendicitis are found elsewhere. (See "Acute appendicitis in children: Diagnostic imaging" and "Acute appendicitis in children: Management".) ANATOMY — The appendix arises from the cecum, which is located in the right lower quadrant of the abdomen in the majority of children. It may lie in the upper abdomen or on the left side in children with congenital abnormalities of intestinal position (eg, uncorrected malrotation), situs inversus totalis, and after repair of diaphragmatic hernia, gastroschisis, and omphalocele [1]. Some anatomic features of the appendix may play a role in the incidence and presentation of appendicitis throughout childhood. These include the following [2]: ●In the first year of life, the appendix is funnel-shaped, perhaps making it less likely to become obstructed. ●Lymphoid follicles are interspersed in the colonic epithelium that lines the appendix and may obstruct it. These follicles reach their maximal size during adolescence, the age group in which the peak incidence of appendicitis occurs. The Rovsing, obturator, and iliopsoas signs may be difficult to elicit in young children. In addition, as with adults, their accuracy has not been well defined [2,33]. The absence of the classic signs of appendicitis should not cause the clinician to exclude the diagnosis of appendicitis [27]. However, when present in children 3 to 12 years of age, these signs have high specificity for acute appendicitis (86 to 98 percent, depending upon age). Although this classic pattern of clinical findings does occur in school-age children and adolescents, it is less common overall in pediatric patients with appendicitis than in adults. (See 'School-age (5 to 12 years)' below and 'Adolescent' below and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Clinical manifestations'.) In infants and young children, this pattern may not occur at all, perhaps because of differences in the pathophysiology of the disease and in the child's ability to relate information regarding signs and symptoms. (See 'Neonates (0 to 30 days)' below and 'Young children (<5 years)' below.) Furthermore, among children, the absence of classic clinical features of appendicitis (such as fever, anorexia, migration of pain to the right lower quadrant [RLQ], and rebound tenderness) are neither sensitive nor specific for excluding appendicitis, especially in younger patients [2]. This was demonstrated in a prospective series describing children evaluated in an emergency department for suspected appendicitis in whom the following features were noted among the patients with appendicitis [34]: ●Lack of migration of pain to RLQ in 50 percent ●Absence of anorexia in 40 percent ●No rebound tenderness in 52 percent Thus, diagnosing appendicitis among children is frequently challenging because typical symptoms and signs are often not present, specific findings of appendicitis are difficult to elicit in this patient population, and clinical findings frequently overlap with other conditions. (See 'Differential diagnosis' below.) Clinical features by age Neonates (0 to 30 days) — Appendicitis in neonates is rare [24]. The low frequency of appendicitis in these patients is attributed to anatomic differences in the appendix (more funnel-shaped than tubular), soft diet, infrequent diarrheal illnesses, and recumbent positioning [35]. Mortality from neonatal appendicitis approaches 28 percent and reflects the difficulty in establishing the diagnosis prior to advanced disease with bowel perforation and sepsis [36]. Case reports indicate that abdominal distension, vomiting, and decreased feeding are the most commonly reported findings in neonates with appendicitis [24]. Temperature instability and septic shock may also develop. The frequency of clinical features in these patients as illustrated by a case review of 33 neonates is as follows [24]: ●Abdominal distension – 75 percent ●Vomiting – 42 percent ●Decreased oral intake – 40 percent ●Abdominal tenderness – 38 percent ●Sepsis – 38 percent ●Temperature instability – 33 percent ●Lethargy or irritability – 24 percent ●Abdominal wall cellulitis – 24 percent ●Respiratory distress – 15 percent ●Abdominal mass – 12 percent ●Hematochezia (possibly representing necrotizing enterocolitis of the appendix) – 10 percent Thus, findings of neonatal appendicitis are nonspecific and overlap with other more common neonatal surgical diseases, especially volvulus and necrotizing enterocolitis. (See "Clinical features and diagnosis of necrotizing enterocolitis in newborns", section on 'Clinical presentation' and "Intestinal malrotation in children", section on 'Clinical presentation'.) Young children (<5 years) — Appendicitis is uncommon in infants and pre-school children. Fever and diffuse abdominal tenderness with rebound or guarding are the predominant physical findings although irritability, grunting respirations, difficulty with or refusal to ambulate, and right hip complaints may also be present. Localized right lower quadrant tenderness occurs in less than 50 percent of patients. The high frequency of rebound or diffuse tenderness and guarding reflects the high prevalence of perforation and peritonitis in this age group. Typical findings on history are nonspecific such as fever, vomiting, and abdominal pain, all of which can also occur with other surgical diagnoses, such as intussusception. Diarrhea is also relatively common making appendicitis difficult to differentiate from acute gastroenteritis, a much more common condition in these patients [25,26,28]. (See 'Differential diagnosis' below.) Based upon observational studies, the relative frequency and variability of clinical findings in infants and children younger than five years is as follows [25,26,28]: ●Abdominal pain – 72 to 94 percent ●Fever – 62 to 90 percent ●Vomiting – 80 to 83 percent ●Anorexia – 42 to 74 percent ●Rebound tenderness – 81 percent ●Guarding – 62 to 72 percent ●Diffuse tenderness – 56 percent ●Localized tenderness – 38 percent ●Abdominal distension – 35 percent ●Diarrhea (frequent, low volume, with or without mucus) – 32 to 46 percent School-age (5 to 12 years) — Appendicitis is more frequent in this age group when compared to younger children. Abdominal pain and vomiting are commonly present in school-age children; although the typical migration of periumbilical pain to the right lower quadrant may not occur. On physical examination, right lower quadrant tenderness is noted in the majority of patients. Involuntary guarding and rebound tenderness indicate perforation. Other prominent symptoms include fever, anorexia, and pain with movement [37]. Diarrhea, constipation, and dysuria (abdominal pain with voiding not urethral pain which is typical of a urinary tract infection [UTI]) are less frequent, but occur enough to potentially confuse the diagnosis. The relative frequency of these findings is illustrated in an observational study of 379 children 3 to 12 years (84 children under five years of age) [27]: ●Anorexia – 75 percent ●Vomiting – 66 percent ●Fever – 47 percent ●Diarrhea – 16 percent ●Nausea – 79 percent ●Maximum abdominal tenderness in the right lower quadrant – 82 percent ●Difficulty walking – 82 percent ●Pain with percussion, hopping, or coughing – 79 percent Adolescent — The clinical features of appendicitis in this age group are similar to those in adults and often include the classic findings of fever, anorexia, periumbilical abdominal pain that migrates to the right lower quadrant, and vomiting. Involuntary guarding and rebound tenderness are present more often with perforation. The onset of pain typically occurs before vomiting, and is a sensitive indicator of appendicitis. (See 'Clinical manifestations' above and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Clinical manifestations'.) Information regarding menstrual history and sexual activity can be helpful in distinguishing gynecologic disorders from appendicitis in postmenarchal girls. Common conditions include mittelschmerz, ovarian cysts, ectopic pregnancy, or pelvic inflammatory disease. (See 'Other nonsurgical diagnoses' below.) Abdominal examination Approach and analgesia — Despite its limitations, a careful abdominal examination is key to the diagnosis of pediatric appendicitis. A reliable examination requires that the child be quiet and cooperative. To accomplish this, the clinician needs to gain the trust of the child which often requires significant patience. It is also helpful to spend time taking the history, sitting down if possible, and to examine the abdomen before more invasive portions of the examination, such as looking in the ears or pharynx [2]. Similarly, the child can be initially examined in the position in which he or she is most comfortable, such as a caretaker's lap, prior to a standard evaluation. In some patients, the degree of pain makes physical examination of the abdomen challenging. We recommend that children with suspected appendicitis receive analgesia single-center, prospective observational study of 185 children presenting to the emergency department with abdominal pain (prevalence of appendicitis 48 percent), a PCT <0.1 ng/mL and CP <0.5 ng/mL (expressed as a negative commercial fluoroimmunoassay result), when combined with ANC <7500 was able to identify children without appendicitis with 100 percent sensitivity (95% CI 96 to 100 percent) and a negative predictive value of 100 percent (95% CI 90 to 100 percent) [43]. However, further study in larger and more diverse populations is needed before PCT and CP can be routinely recommended in the laboratory evaluation of pediatric appendicitis. Laboratory tests should not be used in isolation to make or exclude the diagnosis of appendicitis. However, in some children, a combination of characteristic clinical findings and elevations in WBC, ANC, or CRP is sufficient to diagnose appendicitis [44]. Based upon observational studies, up to 50 percent of children with appendicitis can undergo surgery using clinical and laboratory findings and avoid diagnostic imaging [45-47]. Negative appendectomy rates of 5 to 6 percent have been reported with this approach. Similarly, normal values for WBC or ANC in children undergoing evaluation for appendicitis have been used to predict a low risk of appendicitis as a component of validated clinical scoring systems [48-51]. (See 'Clinical scoring systems' below.) Elevations in the peripheral white blood cell count (WBC), absolute neutrophil count (ANC), and C-reactive protein (CRP) levels have been noted in children with appendicitis. However, these findings are variable and nonspecific as indicated by the following evidence: ●WBC and ANC – Either the WBC or the ANC is elevated in up to 96 percent of children with appendicitis [22]. This finding, however, is nonspecific because many other diseases that mimic appendicitis (eg, streptococcal pharyngitis, pneumonia, pelvic inflammatory disease, or gastroenteritis) also cause such elevations [2,37,52,53]. Thus, the ability of these tests to discriminate appendicitis from other causes is limited. As an example, in an observational study of 280 children (age 3 to 18 years) evaluated for appendicitis who had symptoms less than 24 hours, a WBC >14,600/mm 3 and an ANC >11,000/mm 3 had sensitivities of 68 and 69 percent, respectively and specificities of 96 and 75 percent, respectively [54]. In another observational report describing 772 children (1 to 19 years of age) with nontraumatic abdominal pain who were evaluated in an emergency department, those patients with either increased WBC (greater than upper limit of normal for age) or elevated neutrophil count (>80 percent mature or immature neutrophils), had an overall sensitivity of 79 percent and specificity of 80 percent [55]. By contrast, in children undergoing appendectomy, a normal WBC or ANC prior to surgery is associated with a negative appendectomy. As an example, in a retrospective observational study of 847 children who underwent appendectomy, a WBC <9000/microliter or <8000/microliter prior to surgery had sensitivities of 92 and 95 percent, respectively for a normal appendix [56]. ●C-reactive protein – Elevation of CRP (>0.6 to 1 mg/dL [6 to 10 mg/L]) has been reported in children with appendicitis, but sensitivities and specificities range widely (sensitivity 58 to 93 percent, specificity 28 to 82 percent) [2,37,54]. CRP appears to be less sensitive in patients who have had symptoms for less than 24 hours but more sensitive than WBC for patients with symptoms for 24 to 48 hours [54,57]. Small observational studies also suggest that an elevated CRP may be more helpful in identifying both a gangrenous appendix (>1 mg/dL [10 mg/L] in 83 percent of patients) and appendiceal perforation (sensitivity and specificity for perforation 76 and 82 percent, respectively at a CRP >5 mg/dL [50 mg/L]) [57,58]. When both CRP and WBC are elevated, specificity for appendicitis is approximately 90 percent, although sensitivity remains low at approximately 40 percent [59]. ●Procalcitonin – In one prospective study of 209 children (1 to 18 years of age), semiquantitative procalcitonin levels (PCT) were higher in patients with definitive appendicitis than in those without definitive appendicitis [59]. However, either WBC or CRP was better able to identify patients with appendicitis than PCT. Thus, PCT should not be routinely used to diagnose appendicitis in children. Among patients with appendicitis, elevation in PCT does suggest perforation. As an example, among 111 children with appendicitis a PCT level >0.18 ng/mL identified children with peritonitis with a sensitivity of 97 percent, specificity 80 percent, and a positive predictive value of 72 percent [60]. A urinalysis is usually performed in children with suspected appendicitis to identify alternative conditions such as a UTI or nephrolithiasis. However, between 7 and 25 percent of patients with appendicitis may have pyuria [23], although bacteria are not typically present in a clean-catch specimen. Less commonly, hematuria may also occur due to appendiceal irritation of the ureter or bladder [61,62]. Thus, the presence of pyuria or hematuria on urinalysis should not be used as the sole information to exclude the diagnosis of appendicitis. EVALUATION AND DIAGNOSIS Clinical suspicion — The diagnosis of appendicitis is made clinically and should be considered in all children with a history of abdominal pain and abdominal tenderness on physical examination. The diagnosis may be straightforward when the classic findings associated with appendicitis are present. However, the variations in presentation by age in children can pose a significant challenge. (See 'Clinical manifestations' above and 'Clinical features by age' above.) In some children with abdominal pain a clear alternative diagnosis is present (eg, streptococcal pharyngitis, pneumonia, pelvic inflammatory disease). These patients should receive specific treatment for the underlying condition rather than undergoing a diagnostic evaluation for appendicitis. (See 'Differential diagnosis' below.) For patients without a clear etiology for their abdominal pain in whom appendicitis is suspected, we suggest a diagnostic approach guided by the clinical impression of risk (low, moderate, or high) derived from history, physical examination, and selected laboratory studies as follows (algorithm 1): ●Low risk – These patients have few signs or symptoms of appendicitis (eg, afebrile, no history of vomiting or anorexia, minimal diffuse abdominal tenderness with a soft abdomen on palpation, or no right lower quadrant tenderness). If obtained, white blood cell count (WBC), absolute neutrophil count (ANC), and C-reactive protein (CRP) are typically normal. Alternatively, patients can be determined to be low risk by a Pediatric Appendicitis Score (PAS) ≤2 (table 1) or according to the refined Low-Risk Appendicitis Rule (ANC <6750/mm 3 AND either maximal abdominal tenderness not in the right lower quadrant (RLQ) or RLQ tenderness but no abdominal pain with walking, jumping, or coughing) [48-51]. (See 'Clinical scoring systems' below.) •Further evaluation – Children with a clear alternative diagnosis should undergo specific treatment for the identified condition and no further evaluation for appendicitis is indicated. Patients without an obvious alternative diagnosis may still have appendicitis, especially if signs or symptoms are of a short duration (<24 hours). For example, up to 2 percent of patients categorized as low risk by the PAS and up to 7 percent of patients identified as low risk by the refined Low-Risk Appendicitis Rule ultimately have appendicitis [48-51]. However, the risk of appendicitis in these patients is low enough to make close follow-up the most appropriate approach. Children without RLQ pain or tenderness may be discharged home with clear instructions to the caregivers to return if pain increases or becomes localized to the RLQ. The clinician should ensure that the caregivers are reliable and understand that a specific diagnosis for their child’s abdominal pain has not been made and appendicitis is still possible. Patients with RLQ pain or tenderness should undergo assured reevaluation within 12 to 24 hours. Some clinicians may choose to admit children with RLQ tenderness to the hospital for serial examination. ●Moderate risk – Children with a moderate risk for appendicitis have some signs or symptoms of appendicitis (eg, low-grade fever, vomiting or anorexia, right lower quadrant tenderness, or abdominal pain with walking, jumping, or coughing). The WBC, ANC, or CRP can be normal or elevated. Alternatively, a PAS of 3 to 6 (table 1) suggests an intermediate risk of appendicitis that ranges from 8 to 48 percent. Patients who are not low risk by the refined Low- Risk Appendicitis Rule (ANC >6750/mm 3 OR RLQ tenderness with pain on walking, jumping, or coughing) have an estimated risk of appendicitis between 12 and approximately 50 percent. (See 'Clinical scoring systems' below.) •Further evaluation – The best approach for these patients is not clear and depends upon local resources. Options include surgical consultation, diagnostic imaging, hospital admission with serial abdominal examinations by a surgeon with pediatric expertise, or a combination of these approaches. ●High risk – Children at high risk for appendicitis have classic findings of appendicitis, especially recent onset (one to two days) of abdominal pain that over time has migrated from the periumbilical region to the RLQ followed by low-grade fever, vomiting, and anorexia and associated with RLQ tenderness on physical examination. WBC, ANC, and/orCRP are typically elevated. A PAS score ≥7 (table 1) indicates a high risk of appendicitis (50 to 60 percent). (See 'Clinical scoring systems' below.) •Further evaluation – These children warrant prompt evaluation by a surgeon with pediatric expertise prior to urgent imaging to determine the need for appendicitis varies widely. This variation may be due, in part, to differences in inclusion and exclusion criteria in the studies discussed above. ●A PAS of 3 to 6 or 7 is indeterminate for appendicitis and the best approach is not clear. Options include surgical consultation, diagnostic imaging, serial abdominal examinations while being observed in the hospital, or a combination of these approaches depending upon local resources ●In isolation, the PAS may be inadequate to stratify risk among children with abdominal pain, especially among patients with a high prevalence of appendicitis. Clinical pathways that utilize the PAS have the potential to achieve acceptable diagnostic accuracy and low utilization of computed tomography (CT). As an example, in a prospective observational study of 196 children with abdominal pain who were evaluated using a clinical pathway based upon the PAS to determine discharge (PAS ≤3), emergency ultrasonography (PAS 4 to 7), or surgery consult (PAS 8 to 10) in a children’s hospital emergency department, the sensitivity and specificity of the pathway for appendicitis was 92 and 95 percent, respectively [72]. Perforated appendicitis occurred in 15 percent of patients and the negative appendectomy rate among the 68 children undergoing operation was 4.4 percent. CT of the abdomen was performed in 7 percent of patients. No child with a PAS ≤3 had appendicitis. Refined Low-Risk Appendicitis Score — The Refined Low-Risk Appendicitis Score consists of the following low-risk items [51]: ●Absence of maximal tenderness in the right lower quadrant (RLQ) OR RLQ tenderness without pain on walking, jumping, or coughing ●Absolute neutrophil count less than 6750/mm 3 In a prospective cohort of 2625 children evaluated at multiple centers, these criteria had a sensitivity of 98 percent, specificity of 24 percent, and negative predictive value of 95 percent in identifying children without appendicitis [51]. Alvarado score — The Alvarado score (also called the MANTRELS score) is a 10-point score derived from eight components: ●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) ●Elevated temperature >37.5°C (1 point) ●Leukocytosis (2 points) ●Shift of the white blood cell count (1 point) The Alvarado score does not have adequate accuracy for the diagnosis of appendicitis in children. In a systematic review of the diagnostic accuracy of the Alvarado score which included 1075 children, a score of ≥5 for admission and ≥7 for surgery had pooled sensitivities of 99 percent and 76 percent among pediatric patients, respectively [73]. However, the Alvarado score had a significant tendency to exaggerate the probability of appendicitis in intermediate (score 5 or 6) and high (score 7 to 10) risk children. Furthermore, analysis suggested that the diagnostic accuracy of the score was inconsistent in children. In a separate systematic review of six prospective studies (1589 patients), no Alvarado score had an acceptable performance for ruling in appendicitis [69]. For example, using a score of ≥9 for the performance of surgery in children with a 40 percent pretest probability of appendicitis would have resulted in a 19 percent frequency of negative appendectomy [70]. On the other hand, this review also found that an Alvarado score <5 in children with a pretest probability for appendicitis up to 40 percent reduced the likelihood of appendicitis to <3 percent and which for some clinicians would permit the safe discharge of such patients to home observation. However, this risk of appendicitis is still greater than what is found for a Pediatric Appendicitis Score of 2 to 3. (See 'Pediatric appendicitis score'above.) The use of the Alvarado score for the diagnosis and management of appendicitis in adults is discussed separately. (See "Acute appendicitis in adults: Diagnostic evaluation", section on 'Alvarado score calculation'.) Imaging — For children who do not have a typical presentation for appendicitis or in whom appendicitis cannot be excluded clinically, imaging can be helpful to establish or exclude the diagnosis. Ultrasonography (US) and computed tomography (CT), separately or in combination, are the modalities used most frequently; although evidence suggests that magnetic resonance imaging instead of CT can provide similar diagnostic accuracy in a timely manner without radiation exposure. (See "Acute appendicitis in children: Diagnostic imaging", section on 'Imaging approach'.) We suggest the following approach to the use of imaging studies for children with suspected appendicitis (see 'Clinical suspicion' above and "Acute appendicitis in children: Diagnostic imaging", section on 'Imaging decision'): ●Children with a typical clinical presentation for acute appendicitis are likely to have appendicitis. For these patients at high risk for appendicitis, we suggest clinicians consult a surgeon with pediatric experience prior to obtaining urgent imaging studies. ●Children who have a low risk for appendicitis based upon the clinical examination and, when indicated, laboratory studies may be managed without imaging at the initial evaluation. These patients warrant clear instructions regarding signs of appendicitis that should prompt reevaluation, or, if right lower quadrant pain or tenderness is present, assured reevaluation within 12 to 24 hours. ●Children with atypical or equivocal clinical findings of appendicitis suggesting a moderate likelihood for appendicitis warrant diagnostic imaging. The Pediatric Appendicitis Score (PAS) or the Refined Low-Risk Appendicitis Score may be useful in establishing the level of risk in children with appendicitis. (See 'Pediatric appendicitis score' above and 'Refined Low-Risk Appendicitis Score' above.) Chronic or recurrent appendicitis — Chronic appendicitis refers to the pathologic finding of chronic inflammation or fibrosis of the appendix found in a subset of patients undergoing appendectomy. Chronic appendicitis is a rare finding in children. These patients are clinically characterized by prolonged (>7 days) right lower quadrant pain that may be intermittent and a normal white blood cell count. Most patients have resolution of pain with appendectomy. Crohn's disease is a consideration in patients who have persistent pain after surgery. (See "Management of acute appendicitis in adults", section on 'Chronic appendicitis'.) Recurrent appendicitis can occur but is also rare in children; such cases may be caused by a retained foreign body (eg, fecalith) in the lumen of the appendix. Stump appendicitis is a form of recurrent appendicitis that is related to incomplete appendectomy that leaves an excessively long stump after open or laparoscopic surgery. (See "Acute appendicitis in children: Management", section on 'Late'.) DIFFERENTIAL DIAGNOSIS — Appendicitis often presents with characteristic clinical features that make the evaluation and diagnosis straightforward. However, many diseases can mimic acute appendicitis in children (table 2). (See "Causes of acute abdominal pain in children and adolescents".) Emergent surgical diagnoses — Although conditions other than appendicitis may also require operative management, the urgency and surgical approach may vary depending upon the diagnosis. ●Bowel obstruction – Bowel obstruction must always be considered in the child who has had abdominal surgery and presents with vomiting and abdominal pain. Vomiting may be bilious. In addition, plain films of the abdomen often show distended loops of bowel with air-fluid levels or pneumoperitoneum. ●Intestinal malrotation – Although most children with malrotation present in infancy with abdominal distension and bilious vomiting, a small percentage are diagnosed outside of infancy with abdominal pain and a variety of nonspecific clinical findings. Patients with volvulus often have pain out of proportion to physical examination findings. In patients with signs of obstruction, plain abdominal radiographs should be performed to exclude signs of perforation. The diagnosis of malrotation is confirmed by a limited upper gastrointestinal series or computed tomography of the abdomen with intravenous contrast. Prompt surgical intervention is required in patients with volvulus. (See "Intestinal malrotation in children", section on 'Diagnosis'.) ●Intussusception – Intussusception describes invagination of a part of the intestine into itself. Patients typically have an abrupt onset of intermittent episodic abdominal pain with vomiting, blood in the stool, and less commonly, lethargy or a palpable sausage-shaped abdominal mass in the right upper quadrant. In the hands of an experienced ultrasonographer, the sensitivity and specificity of ultrasound for establishing the diagnosis of intussusception approach 100 percent. The diagnosis can also be made with a contrast enema (air or barium), which may reduce the intussusceptum, thereby avoiding an operation. (See "Intussusception in children", section on 'Diagnosis'.) ●Ovarian torsion – Although ovarian torsion does not occur commonly in children, the presentation is nonspecific and easily confused with appendicitis. Features include acute onset of moderate to severe abdominal pain, vomiting, and an adnexal mass. The character of the pain may be sharp, stabbing, colicky, or crampy, and may radiate to ●Mittelschmerz – This ovulatory event causes recurrent midcycle pain in females with regular ovulatory cycles. This pain is 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. The onset of pain midcycle and a history of recurrence help to differentiate mittelschmerz from appendicitis. (See "Evaluation of acute pelvic pain in the adolescent female", section on 'Mittelschmerz'.) ●Pneumonia – An infiltrate in the lower lobes of the lungs may irritate the diaphragm and cause abdominal pain that can mimic findings of appendicitis in children. Cough, fever, tachypnea, rales on auscultation, and/or decreased oxygen saturation help to distinguish pneumonia from appendicitis. In many children, pneumonia can be diagnosed based upon clinical findings alone. The presence of infiltrates on chest radiograph, which may be subtle on presentation, confirms the diagnosis of pneumonia in children with compatible clinical findings. However, pneumonia can be difficult to identify when respiratory signs and symptoms are subtle [79]. Because of the overlap in clinical presentation, some children may warrant chest radiographs and abdominal imaging. (See "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Clinical presentation' and "Fever without a source in children 3 to 36 months of age", section on 'Pneumonia' and "Community-acquired pneumonia in children: Clinical features and diagnosis", section on 'Diagnosis'.) ●Urinary tract infection – Urinary tract infections (UTI) may cause abdominal pain and vomiting, particularly in young children. Although white blood cells may also be seen on urinalysis in patients with appendicitis, children with UTIs will generally have bacteria on microscopic examination and a dipstick positive for leukocyte esterase and/or nitrites. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Rapidly available tests'.) ●Streptococcal pharyngitis – Young children with streptococcal pharyngitis may have vomiting and abdominal pain in addition to a sore throat. Suggestive clinical findings include sore throat, tender anterior cervical nodes, and exudative pharyngitis. Rapid antigen detection can quickly diagnose group A streptococcal disease in most cases. (See "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis", section on 'Diagnosis'.) ●Gastroenteritis – Gastroenteritis occurs commonly in children younger than two years. In resource-rich countries, a viral etiology is most common, and the presence and quantity of diarrhea can be variable. Diarrhea may also occur in children with appendicitis, especially patients younger than five years of age. In most instances, children with gastroenteritis have diffuse abdominal tenderness without guarding or rebound. The diagnosis of gastroenteritis should be made cautiously in children with abdominal pain and vomiting who do not have diarrhea. In one retrospective review of cases of missed appendicitis, 42 percent of children were initially diagnosed with gastroenteritis [23]. (See "Acute viral gastroenteritis in children in resource-rich countries: Clinical features and diagnosis", section on 'Clinical presentation'.) Yersinia enterocolitica gastroenteritis can cause focal abdominal pain that is clinically indistinguishable from appendicitis. (See "Clinical manifestations and diagnosis of Yersinia infections", section on 'Pseudoappendicitis'.) ●Mesenteric lymphadenitis – Children with abdominal pain who undergo ultrasound demonstrate mesenteric lymphadenitis in 9 to 32 percent of cases [80,81]. This radiologic finding is a nonspecific indicator of infection, inflammation, and rarely, malignancy. Etiologies of mesenteric lymphadenitis include viral and bacterial gastroenteritis, inflammatory bowel disease, and lymphoma. (See "Causes of acute abdominal pain in children and adolescents", section on 'Gastrointestinal'.) 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 5 th to 6 th 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 10 th to 12 th 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 education: Appendicitis in adults (The Basics)" and "Patient education: Appendicitis in children (The Basics)") SUMMARY AND RECOMMENDATIONS ●The classic presentation of appendicitis includes the following historical and physical examination findings (see 'Clinical manifestations' above): •Anorexia •Periumbilical pain (early) •Migration of pain to the right lower quadrant (often within 24 hours of onset of symptoms) •Pain with movement: walking or shifting position in bed or on stretcher •Vomiting (typically occurring after the onset of pain) •Fever (commonly occurring 24 to 48 hours after onset of symptoms) •Right lower quadrant tenderness •Signs of localized or generalized peritoneal irritation ●Although this classic pattern of clinical findings does occur in school-age children and adolescents, it is less common overall in pediatric patients with appendicitis than in adults and may not occur at all in children younger than five years of age. (See 'Clinical features by age' above.) ●Despite its limitations, a reliable abdominal examination is key to demonstrating the physical findings of appendicitis and requires that the child be quiet and cooperative. We recommend that children with suspected appendicitis receive analgesia commensurate with the degree of pain, including intravenous opioid medications (Grade 1B). (See 'Approach and analgesia' above and 'Physical findings' above.) ●Although limited in their ability to differentiate appendicitis from other causes of abdominal pain, the following laboratory tests are typically obtained in children undergoing evaluation for appendicitis (see 'Laboratory testing' above): •White blood cell count (WBC) •Differential with calculation of the absolute neutrophil count (ANC) •C-reactive protein (CRP) •Urinalysis •Urine pregnancy test in postmenarchal females ●We suggest a diagnostic approach guided by the clinical impression of risk (low, moderate, or high) derived from history, physical examination, and selected laboratory studies to determine next steps in evaluation and treatment of children with possible pediatric appendicitis (algorithm 1). Validated clinical scoring systems have been developed to assist in this process. (See 'Clinical suspicion' above and 'Clinical scoring systems' above.) ●We suggest the following approach to the use of imaging studies for children with suspected appendicitis (see 'Clinical suspicion' above and "Acute appendicitis in children: Diagnostic imaging", section on 'Imaging decision'): •Children with a typical clinical presentation for acute appendicitis are likely to have appendicitis. For these patients at high risk for appendicitis, we suggest clinicians consult a surgeon with pediatric experience prior to obtaining urgent imaging studies. •Children who have a low risk for appendicitis based upon the clinical examination and, when indicated, laboratory studies may be managed without imaging at the initial evaluation. These patients warrant clear instructions regarding signs of appendicitis that should prompt reevaluation, or, if right lower quadrant pain or tenderness is present, assured reevaluation within 12 to 24 hours. •Children with atypical or equivocal clinical findings of appendicitis suggesting a moderate likelihood for appendicitis warrant diagnostic imaging. Ultrasonography is the recommended initial imaging test. ●Children with a clear alternative diagnosis should undergo specific treatment for the identified condition and no further evaluation for appendicitis is indicated. (See 'Differential diagnosis' above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Akbulut S, Ulku A, Senol A, et al. Left-sided appendicitis: review of 95 published cases and a case report. World J Gastroenterol 2010; 16:5598. 2. Bundy DG, Byerley JS, Liles EA, et al. Does this child have appendicitis? JAMA 2007; 298:438. 3. Rabah R. Pathology of the appendix in children: an institutional experience and review of the literature. Pediatr Radiol 2007; 37:15. 4. Bennion RS, Baron EJ, Thompson JE Jr, et al. The bacteriology of gangrenous and perforated appendicitis--revisited. Ann Surg 1990; 211:165. 5. Lamps LW. Infectious causes of appendicitis. Infect Dis Clin North Am 2010; 24:995. 50. Bhatt M, Joseph L, Ducharme FM, et al. Prospective validation of the pediatric appendicitis score in a Canadian pediatric emergency department. Acad Emerg Med 2009; 16:591. 51. Kharbanda AB, Dudley NC, Bajaj L, et al. Validation and refinement of a prediction rule to identify children at low risk for acute appendicitis. Arch Pediatr Adolesc Med 2012; 166:738. 52. Sack U, Biereder B, Elouahidi T, et al. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children. BMC Surg 2006; 6:15. 53. Williams R, Mackway-Jones K. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. White cell count and diagnosing appendicitis in children. Emerg Med J 2002; 19:428. 54. Kharbanda AB, Cosme Y, Liu K, et al. Discriminative accuracy of novel and traditional biomarkers in children with suspected appendicitis adjusted for duration of abdominal pain. Acad Emerg Med 2011; 18:567. 55. Wang LT, Prentiss KA, Simon JZ, et al. The use of white blood cell count and left shift in the diagnosis of appendicitis in children. Pediatr Emerg Care 2007; 23:69. 56. Bates MF, Khander A, Steigman SA, et al. Use of white blood cell count and negative appendectomy rate. Pediatrics 2014; 133:e39. 57. Peltola H, Ahlqvist J, Rapola J, et al. C-reactive protein compared with white blood cell count and erythrocyte sedimentation rate in the diagnosis of acute appendicitis in children. Acta Chir Scand 1986; 152:55. 58. Chung JL, Kong MS, Lin SL, et al. Diagnostic value of C-reactive protein in children with perforated appendicitis. Eur J Pediatr 1996; 155:529. 59. Kwan KY, Nager AL. Diagnosing pediatric appendicitis: usefulness of laboratory markers. Am J Emerg Med 2010; 28:1009. 60. Gavela T, Cabeza B, Serrano A, Casado-Flores J. C-reactive protein and procalcitonin are predictors of the severity of acute appendicitis in children. Pediatr Emerg Care 2012; 28:416. 61. Paajanen H, Somppi E. Early childhood appendicitis is still a difficult diagnosis. Acta Paediatr 1996; 85:459. 62. Heitz C, Singer JI. Recurrent abdominal pain and hematuria. Pediatr Emerg Care 2011; 27:663. 63. England RJ, Crabbe DC. Delayed diagnosis of appendicitis in children treated with antibiotics. Pediatr Surg Int 2006; 22:541. 64. Samuel M. Pediatric appendicitis score. J Pediatr Surg 2002; 37:877. 65. Kharbanda AB, Taylor GA, Fishman SJ, Bachur RG. A clinical decision rule to identify children at low risk for appendicitis. Pediatrics 2005; 116:709. 66. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986; 15:557. 67. Pogorelić Z, Rak S, Mrklić I, Jurić I. Prospective validation of Alvarado score and Pediatric Appendicitis Score for the diagnosis of acute appendicitis in children. Pediatr Emerg Care 2015; 31:164. 68. Kharbanda AB, Stevenson MD, Macias CG, et al. Interrater reliability of clinical findings in children with possible appendicitis. Pediatrics 2012; 129:695. 69. Ebell MH, Shinholser J. What are the most clinically useful cutoffs for the Alvarado and Pediatric Appendicitis Scores? A systematic review. Ann Emerg Med 2014; 64:365. 70. Kharbanda AB. Appendicitis: do clinical scores matter? Ann Emerg Med 2014; 64:373. 71. Zúñiga RV, Arribas JL, Montes SP, et al. Application of Pediatric Appendicitis Score on the emergency department of a secondary level hospital. Pediatr Emerg Care 2012; 28:489. 72. Saucier A, Huang EY, Emeremni CA, Pershad J. Prospective evaluation of a clinical pathway for suspected appendicitis. Pediatrics 2014; 133:e88. 73. Ohle R, O'Reilly F, O'Brien KK, et al. The Alvarado score for predicting acute appendicitis: a systematic review. BMC Med 2011; 9:139. 74. Vázquez BJ, Thomas R, Pfluke J, et al. Clinical presentation and treatment considerations in children with acute omental torsion: a retrospective review. Am Surg 2010; 76:385. 75. Mavridis G, Livaditi E, Baltogiannis N, et al. Primary omental torsion in children: ten-year experience. Pediatr Surg Int 2007; 23:879. 76. Dann PH, Amodio JB, Rivera R, Fefferman NR. Primary bacterial peritonitis in otherwise healthy children: imaging findings. Pediatr Radiol 2005; 35:198. 77. Antal P, Gauderer M, Koshy M, Berman B. Is the incidence of appendicitis reduced in patients with sickle cell disease? Pediatrics 1998; 101:E7. 78. Al-Nazer MA, Al-Saeed HH, Al-Salem AH. Acute appendicitis in patients with sickle cell disease. Saudi Med J 2003; 24:974. 79. Pezone I, Iezzi ML, Leone S. Retrocardiac pneumonia mimicking acute abdomen: a diagnostic challenge. Pediatr Emerg Care 2012; 28:1230. 80. Hernandez JA, Swischuk LE, Angel CA, et al. Imaging of acute appendicitis: US as the primary imaging modality. Pediatr Radiol 2005; 35:392. 81. Schulte B, Beyer D, Kaiser C, et al. Ultrasonography in suspected acute appendicitis in childhood-report of 1285 cases. Eur J Ultrasound 1998; 8:177. Acute appendicitis in pregnancy Authors: Andrei Rebarber, MD Brian P Jacob, MD Section Editors: Charles J Lockwood, MD, MHCM Deborah Levine, MD Martin Weiser, MD Deputy Editor: Kristen Eckler, MD, FACOG Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2017. | This topic last updated: Feb 17, 2017. INTRODUCTION — Acute appendicitis is the most common general surgical problem encountered during pregnancy [1]. The diagnosis is particularly challenging during pregnancy because of the relatively high prevalence of abdominal/gastrointestinal discomfort, anatomic changes related to the enlarged uterus, and the physiologic leukocytosis of pregnancy. Appendiceal rupture occurs more frequently in pregnant women, especially in the third trimester, possibly because these challenges and reluctance to operate on pregnant women delay diagnosis and treatment [2,3]. INCIDENCE — Acute appendicitis is suspected in 1/600 to 1/1000 pregnancies and confirmed in 1/800 to 1/1500 pregnancies [4-7]. In a case control study of 53,000 women undergoing appendectomy, pregnant women were less likely to have appendicitis than age- matched, nonpregnant women [8]. The incidence of appendicitis was slightly higher in the second trimester than in the first and third trimesters or postpartum. In addition, cohort study of over 350,000 pregnancies reported that the rate of acute appendicitis was 35 percent lower during the antepartum period than the time outside of pregnancy. This study reported the lowest rates of appendicitis during the third trimester [9]. For women aged 15 to 34 years, there was no increased risk in postpartum appendicitis compared with the time outside of pregnancy. In contrast, an 84 percent increased risk of postpartum appendicitis was reported for women older than 35 years. CLINICAL FEATURES Patient presentation — In the "classic" presentation, the patient describes the onset of abdominal pain as the first symptom. The pain is periumbilical initially and then migrates to the right lower quadrant as the inflammatory process progresses [10-12]. Anorexia, The diagnosis of acute appendicitis in a laboring patient requires a high index of suspicion, is especially difficult, and may not be possible. Labor can be associated with pain that may be lateralized, fever if chorioamnionitis is present, leukocytosis, and vomiting. Persistence or progression of these symptoms after delivery should prompt physical examination and imaging studies to evaluate for appendicitis. Imaging Ultrasonography — The initial modality of choice for diagnostic imaging of the appendix in pregnancy is graded compression ultrasonography [34]. The clinical diagnosis of suspected appendicitis is supported by identification of a noncompressible blind-ended tubular structure in the right lower quadrant with a maximal diameter greater than 6 mm (image 1A-B) [35,36]. The diagnosis should not be excluded if the appendix appears normal, unless sonographic findings suggest a likely alternative diagnosis (eg, ovarian torsion, nephrolithiasis). Test performance appears to be lower in pregnant women than nonpregnant individuals because the gravid uterus can interfere with visualizing the appendix and performing graded compression, particularly in the third trimester, leading to inconclusive ultrasound findings [37-39]. Several studies reported nonvisualization of the appendix in a large percentage of pregnant women with suspected appendicitis [40-44]. However, in one review of studies of the value of ultrasound in diagnosing appendicitis in pregnancy, sensitivity ranged from 67 to 100 percent and specificity ranged from 83 to 96 percent, compared to general population in whom sensitivity and specificity were 86 and 96 percent, respectively [45]. We believe that the wide variation in the reported diagnostic performance of graded compression ultrasonography for appendicitis during pregnancy is due to multiple factors such as gestational age, maternal body mass index (BMI), and importantly, the training and experience of the sonologist or radiologist. (See "Diagnostic imaging procedures during pregnancy" and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis".) Magnetic resonance imaging — For pregnant women whose ultrasound examination is inconclusive for appendicitis, magnetic resonance imaging (MRI) is the preferred next test as it avoids the ionizing radiation of computed tomography and appears to be cost-effective (image 2) [34,46,47]. When MRI is performed in pregnant women, gadolinium is not routinely administered because of theoretical fetal safety concerns, but may be used if essential [48]. (See "Diagnostic imaging procedures during pregnancy", section on 'Magnetic resonance imaging'.) MRI has a high sensitivity and specificity for diagnosing appendicitis during pregnancy. A meta-analysis of 12 studies that included 933 pregnant women who underwent MRI evaluation for suspected acute appendicitis reported a sensitivity of 94 percent (95% CI 87 to 98 percent) and specificity of 97 percent (95% CI 96 to 98 percent) [49]. The largest study of pregnant women suspected of having acute appendicitis (over 700 women), which was not included in the above meta-analysis, reported 61 women had surgically confirmed disease out of 66 women with suggestive MRI findings (ie, appendiceal dilation, appendicolith, free fluid, and fat stranding) [50]. Based on this detection rate, the study reported the following pooled data for MRI assessment of appendicitis in pregnant women: ●Positive predictive value 92.4 percent (95% CI 83.2-97.5) ●Negative predictive value 99.7 percent (95% CI 98.9-99.9) ●Sensitivity 96.8 percent (95% CI 89-99.6) ●Specificity 99.2 percent (95% CI 98.2-99.8) ●Accuracy 99.0 percent (95% CI 98.0-99.6) Of the five women with false-positive MRI studies, pathologic evaluation identified one ovarian torsion, one appendicolith with mild lymphoid hyperplasia, one fibrous obliteration of the appendiceal lumen without changes of acute appendicitis, and two normal appendices. Compared with ultrasound, additional benefits of MRI include potential identification of peri-appendiceal findings when the appendix is not visualized and recognition of other causes of abdominal pain. In the study of over 700 women above, of 207 women whose appendix was not visible on MRI, three were surgically diagnosed with appendicitis; two women had positive secondary MRI findings (ie, right lower quadrant fluid and pericecal stranding) for appendicitis and one woman had a negative MRI [50]. Of 643 pregnant women whose MRI studies were negative for appendicitis, 72 women had alternate MRI findings that could have accounted for their acute pain. If there is a prolonged wait time for MRI evaluation, the risk of potential appendiceal rupture is balanced against the potential benefits of the study, such as identifying a different cause of pain or avoiding surgery. If MRI if not readily available, then computed tomography (CT) scan can be performed if the diagnosis is unclear. If either imaging modality is not available quickly or if the patient declines CT because of the radiation exposure, surgery should not be delayed in pregnant women with findings suggestive of appendicitis despite inconclusive ultrasound results. Computed tomography — CT is generally widely available. The main findings of appendicitis on CT are right lower quadrant inflammation, an enlarged nonfilling tubular structure, and/or an appendicolith (image 3). The initial experience with helical computed tomography for the diagnosis of appendicitis in pregnancy appears promising, but data are limited to small case series [51]. Modifications to the CT protocol can limit estimated fetal radiation exposure to less than 3 mGy, well below doses known to potentially cause adverse fetal effects (30 mGy for risk of carcinogenesis, 50 mGy for deterministic effects [52,53]), and do not limit diagnostic performance [51,54]. Standard abdominal CT scanning with an oral contrast preparation and intravenous contrast or a specialized appendiceal CT scanning protocol can also be used, but are associated with higher fetal radiation exposure (20 to 40 mGy [53,55]). The relative advantages and disadvantages of the two protocols and what constitutes a positive study are described separately. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Imaging exams'.) We perform CT when clinical findings and ultrasound examination are inconclusive and MRI is not available, given the proven diagnostic value of CT in nonpregnant individuals: overall sensitivity 94 percent (95% CI 91-95), specificity 95 percent (95% CI 93-96), positive likelihood ratio 13.3 (95% CI 9.9-17.9), and negative likelihood ratio 0.09 (95% CI 0.07-0.12) [56]. Data from studies in pregnant women are more limited. A meta-analysis of three retrospective studies in pregnant women reported the sensitivity and specificity of CT in cases of normal/uncertain ultrasonography were: sensitivity 85.7 percent (95% CI 63.7-96) and specificity 97.4 percent (95% CI 86.2-99.9) [57]. These studies included 2 to 49 patients with appendicitis. In one of the studies, the negative laparotomy rates among patients who underwent (1) clinical examination alone, (2) clinical evaluation and ultrasound examination, and (3) clinical evaluation and ultrasound examination followed by CT were 54 percent (7/13), 36 percent (20/55), and 8 percent (1/13), respectively [38]. The ultrasound studies were interpreted as either diagnostic of appendicitis or as normal/inconclusive, thus the authors did not determine whether CT was useful after a normal versus an inconclusive ultrasound study. (See "Diagnostic imaging procedures during pregnancy", section on 'Effects of ionizing radiation on the fetus' and "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Imaging exams'.) DIFFERENTIAL DIAGNOSIS — The differential diagnosis of suspected acute appendicitis includes disorders typically considered in nonpregnant individuals (see "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Differential diagnosis'). In addition, pregnancy-related causes of lower abdominal pain, fever, leukocytosis, nausea/vomiting, and changes in bowel function, need to be considered: ●The possibility of ectopic pregnancy should be excluded in any woman with a positive pregnancy test and right lower quadrant pain. (See "Ectopic pregnancy: Clinical manifestations and diagnosis".) ●Indigestion, bowel irregularity, nausea/vomiting, and malaise are common symptoms of both appendicitis and normal early pregnancy. In appendicitis, nausea and vomiting, if they occur, follow the onset of pain, whereas nausea and vomiting of pregnancy are not associated with pain. (See "Clinical manifestations and diagnosis of early pregnancy".) ●Round ligament syndrome is a common cause of mild right lower quadrant pain in early pregnancy, but is not associated with other symptoms and is not progressive. (See "Clinical manifestations and diagnosis of early pregnancy".) ●Pyelonephritis is more common in pregnant women than in nonpregnant women. Pregnant women with right-sided pain, fever, leukocytosis, and pyuria may be treated for pyelonephritis without further investigation, in which case the actual diagnosis of appendicitis may be delayed. ●In the second half of pregnancy, preeclampsia and HELLP syndrome can be associated with nausea/vomiting and abdominal pain, but in contrast to appendicitis, the pain is usually in the right upper quadrant or epigastrium, hypertension is usually present, and fever and leukocytosis are atypical. (See "Preeclampsia: Clinical features and diagnosis"and "HELLP syndrome".) SURGICAL APPROACH — When the diagnosis is relatively certain, both open and a laparoscopic appendectomy are considered. No randomized trials have been performed to suggest that one technique is better than another, and the choice of technique should be based on the surgeon’s experience level. The intraoperative management of pregnant women undergoing non-obstetric surgery and monitoring of the fetus are reviewed separately. (See "Management of the pregnant patient undergoing nonobstetric surgery".) Open appendectomy — When performing an open appendectomy in a pregnant woman, a transverse incision is made at McBurney's point or, more commonly, over the point of maximal tenderness [14,15]. When the diagnosis is less certain, we suggest a lower midline vertical incision since it permits adequate exposure of the abdomen for diagnosis and treatment of surgical conditions that mimic appendicitis. A vertical incision can also be used for a cesarean delivery, if subsequently required for the usual obstetric indications. It is prudent to minimize traction on the uterus and uterine manipulation, although an association between these maneuvers and preterm birth is unproven. Laparoscopic appendectomy — Case reports, case series and small cohort studies on the use of laparoscopic appendectomy in pregnancy suggest that laparoscopy can be performed successfully during all trimesters and with few complications [4,64-75]. The decision to proceed with a laparoscopic approach should take into consideration the skill and experience of the surgeon, as well as clinical factors such as the size of the gravid uterus. Suggestions for modification of laparoscopic technique during pregnancy include slight left lateral positioning of the patient during the second half of pregnancy, avoiding the use of any cervical instruments, use of open entry techniques or placement of trocars under direct visualization, and limiting intraabdominal pressure to less than 12 mmHg [76]. The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines recommend insufflation pressures of 10 to 15 mm Hg and that the port position should be adapted for fundal height [77]. (See "Laparoscopic surgery in pregnancy".) However, concern has been raised that laparoscopic appendectomy may be associated with higher rates of preterm delivery and fetal loss [78-80]. In a 2012 meta-analysis of 11 studies that included 3415 women, the risk of fetal loss was greater for laparoscopic versus open appendectomy in pregnant women [79]. In the largest of the included studies, the rates of fetal loss in the laparoscopic and open groups were 7 percent and 3 percent, respectively. Limitations of the studies in this meta-analysis include retrospective design and lack of adjustment for confounders such as patient age, duration or pregnancy, complications of appendicitis, surgeon skill, and clinical setting. A subsequent 2014 systematic review that included many of the above studies stated that while low-grade evidence suggested that laparoscopic appendectomy during pregnancy may be associated with higher rates of fetal loss, the evidence was not strong enough to determine the preferred modality of appendectomy during pregnancy [80]. In our practice, we find the use of laparoscopy safe, especially when patients are appropriately monitored and no overt signs of preterm labor exist. Laparoscopy affords optimal visualization and recovery when performed by experienced surgeons. We use slightly lower intraabdominal pressures of 10 to 12 mmHg (which provides excellent visualization), an open entry technique, and directly visualized trocar insertion. LONG-TERM OUTCOME — The long-term prognosis for women who undergo appendectomy during pregnancy is generally good, but data are limited to observational series. It appears that preexisting morbidities, and not the surgery itself, are the greater risk factors for postoperative adverse obstetric events. In a national cohort study of nearly 20,000 women who underwent either appendectomy or cholecystectomy during pregnancy, risk factors most strongly associated with an adverse obstetric outcome included cervical incompetence, preterm labor during the current pregnancy (but prior to surgery), vaginitis or vulvovaginitis, and sepsis [81]. Other factors that had a more moderate impact on risk included non-white race/ethnicity, Medicaid insurance, drug abuse or dependence, multiple gestation, and open surgery (ie, laparotomy). Of the approximately 5 percent of women with adverse obstetric outcome at all stages of pregnancy, children had normal development at 13 to 17 months of age [82]. SUMMARY AND RECOMMENDATIONS ●Acute appendicitis is the most common general surgical problem encountered during pregnancy. (See 'Introduction' above.) ●The clinical manifestations of appendicitis in pregnancy are similar to those in nonpregnant individuals; however, the following points should be noted: •Right lower quadrant pain is the most common symptom and occurs within a few centimeters of McBurney's point in most pregnant women, regardless of the stage of pregnancy. In late pregnancy, pain may be the right mid or upper quadrant. Rebound tenderness and guarding are less prominent in pregnant women, especially in the third trimester. (See 'Patient presentation' above.) •Mild leukocytosis can be a normal finding in pregnant women: the total leukocyte count may be as high as 16,900 cell/microL in the third trimester and 29,000 cells/microLduring labor, so leukocytosis may or may not be a sign of appendicitis. (See 'Laboratory' above.) ●The clinical diagnosis should be strongly suspected in pregnant women with classic findings: abdominal pain that migrates to the right lower quadrant, right lower quadrant tenderness, nausea/vomiting, fever, and leukocytosis with left shift. (See 'Diagnosis' above.) With a nonclassical presentation, which often happens in late pregnancy, imaging is indicated. The primary goal of imaging is to reduce delays in surgical intervention due to diagnostic uncertainty. A secondary goal is to reduce, but not eliminate, the negative appendectomy rate. ●Imaging: •We suggest graded compression ultrasonography in pregnant patients suspected of having appendicitis. Appendicitis is diagnosed if a noncompressible blind ended tubular structure is visualized in the right lower quadrant with a maximal diameter greater than 6 mm. (See 'Ultrasonography' above.) •If clinical findings and ultrasound are inconclusive, or in centers where experience with sonographic examination of the appendix is limited, we suggest magnetic resonance imaging (MRI), where available, because it avoids fetal exposure to ionizing radiation and performs well in diagnosis of lower abdominal/pelvic disorders. (See 'Magnetic resonance imaging' above.) •We suggest computed tomography (CT) when MRI is not available, given its proven value in nonpregnant individuals. (See 'Computed tomography' above.) ●The decision to proceed to laparotomy should be based upon the clinical findings, diagnostic imaging results, and clinical judgment. Delaying intervention for more than 24 hours increases the risk of perforation. (See 'Management and short-term outcome' above.) ●When the diagnosis is relatively certain, we suggest performing appendectomy through a transverse incision over the point of maximal tenderness (Grade 2C). When the diagnosis is less certain, we suggest a lower midline vertical incision (Grade 2C). (See 'Surgical approach' above.) ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge William Barth, Jr, MD, and Joel Goldberg, MD, FACS, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Tamir IL, Bongard FS, Klein SR. Acute appendicitis in the pregnant patient. Am J Surg 1990; 160:571. 2. Bickell NA, Aufses AH Jr, Rojas M, Bodian C. How time affects the risk of rupture in appendicitis. J Am Coll Surg 2006; 202:401. 3. Weingold AB. Appendicitis in pregnancy. Clin Obstet Gynecol 1983; 26:801. 4. Andersen B, Nielsen TF. Appendicitis in pregnancy: diagnosis, management and complications. Acta Obstet Gynecol Scand 1999; 78:758. 5. Mourad J, Elliott JP, Erickson L, Lisboa L. Appendicitis in pregnancy: new information that contradicts long-held clinical beliefs. Am J Obstet Gynecol 2000; 182:1027. 6. Mazze RI, Källén B. Appendectomy during pregnancy: a Swedish registry study of 778 cases. Obstet Gynecol 1991; 77:835. 7. Abbasi N, Patenaude V, Abenhaim HA. Management and outcomes of acute appendicitis in pregnancy-population-based study of over 7000 cases. BJOG 2014; 121:1509. 8. Andersson RE, Lambe M. Incidence of appendicitis during pregnancy. Int J Epidemiol 2001; 30:1281. 9. Zingone F, Sultan AA, Humes DJ, West J. Risk of acute appendicitis in and around pregnancy: a population-based cohort study from England. Ann Surg 2015; 261:332. 10. Lee SL, Walsh AJ, Ho HS. Computed tomography and ultrasonography do not improve and may delay the diagnosis and treatment of acute appendicitis. Arch Surg 2001; 136:556. 11. Birnbaum BA, Wilson SR. Appendicitis at the millennium. Radiology 2000; 215:337. 12. Chung CH, Ng CP, Lai KK. Delays by patients, emergency physicians, and surgeons in the management of acute appendicitis: retrospective study. Hong Kong Med J 2000; 6:254. 13. Richards C, Daya S. Diagnosis of acute appendicitis in pregnancy. Can J Surg 1989; 32:358. 57. Basaran A, Basaran M. Diagnosis of acute appendicitis during pregnancy: a systematic review. Obstet Gynecol Surv 2009; 64:481. 58. Young BC, Hamar BD, Levine D, Roqué H. Medical management of ruptured appendicitis in pregnancy. Obstet Gynecol 2009; 114:453. 59. Silvestri MT, Pettker CM, Brousseau EC, et al. Morbidity of appendectomy and cholecystectomy in pregnant and nonpregnant women. Obstet Gynecol 2011; 118:1261. 60. Babaknia A, Parsa H, Woodruff JD. Appendicitis during pregnancy. Obstet Gynecol 1977; 50:40. 61. McGory ML, Zingmond DS, Tillou A, et al. Negative appendectomy in pregnant women is associated with a substantial risk of fetal loss. J Am Coll Surg 2007; 205:534. 62. Ito K, Ito H, Whang EE, Tavakkolizadeh A. Appendectomy in pregnancy: evaluation of the risks of a negative appendectomy. Am J Surg 2012; 203:145. 63. Vasireddy A, Atkinson S, Shennan A, Bewley S. Management of appendicitis. Surgical management remains best option during pregnancy. BMJ 2012; 344:29. 64. Curet MJ, Allen D, Josloff RK, et al. Laparoscopy during pregnancy. Arch Surg 1996; 131:546. 65. Gurbuz AT, Peetz ME. The acute abdomen in the pregnant patient. Is there a role for laparoscopy? Surg Endosc 1997; 11:98. 66. Affleck DG, Handrahan DL, Egger MJ, Price RR. The laparoscopic management of appendicitis and cholelithiasis during pregnancy. Am J Surg 1999; 178:523. 67. Wu JM, Chen KH, Lin HF, et al. Laparoscopic appendectomy in pregnancy. J Laparoendosc Adv Surg Tech A 2005; 15:447. 68. Donkervoort SC, Boerma D. Suspicion of acute appendicitis in the third trimester of pregnancy: pros and cons of a laparoscopic procedure. JSLS 2011; 15:379. 69. Holzer T, Pellegrinelli G, Morel P, Toso C. Appendectomy during the third trimester of pregnancy in a 27-year old patient: case report of a "near miss" complication. Patient Saf Surg 2011; 5:11. 70. Machado NO, Grant CS. Laparoscopic appendicectomy in all trimesters of pregnancy. JSLS 2009; 13:384. 71. Lemieux P, Rheaume P, Levesque I, et al. Laparoscopic appendectomy in pregnant patients: a review of 45 cases. Surg Endosc 2009; 23:1701. 72. Sadot E, Telem DA, Arora M, et al. Laparoscopy: a safe approach to appendicitis during pregnancy. Surg Endosc 2010; 24:383. 73. Hannan MJ, Hoque MM, Begum LN. Laparoscopic appendectomy in pregnant women: experience in Chittagong, Bangladesh. World J Surg 2012; 36:767. 74. Kirshtein B, Perry ZH, Avinoach E, et al. Safety of laparoscopic appendectomy during pregnancy. World J Surg 2009; 33:475. 75. Jeong JS, Ryu DH, Yun HY, et al. Laparoscopic appendectomy is a safe and beneficial procedure in pregnant women. Surg Laparosc Endosc Percutan Tech 2011; 21:24. 76. Al-Fozan H, Tulandi T. Safety and risks of laparoscopy in pregnancy. Curr Opin Obstet Gynecol 2002; 14:375. 77. Guidelines Committee of the Society of American Gastrointestinal and Endoscopic Surgeons, Yumi H. Guidelines for diagnosis, treatment, and use of laparoscopy for surgical problems during pregnancy: this statement was reviewed and approved by the Board of Governors of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), September 2007. It was prepared by the SAGES Guidelines Committee. Surg Endosc 2008; 22:849. 78. Walsh CA, Tang T, Walsh SR. Laparoscopic versus open appendicectomy in pregnancy: a systematic review. Int J Surg 2008; 6:339. 79. Wilasrusmee C, Sukrat B, McEvoy M, et al. Systematic review and meta-analysis of safety of laparoscopic versus open appendicectomy for suspected appendicitis in pregnancy. Br J Surg 2012; 99:1470. 80. Walker HG, Al Samaraee A, Mills SJ, Kalbassi MR. Laparoscopic appendicectomy in pregnancy: a systematic review of the published evidence. Int J Surg 2014; 12:1235. 81. Sachs A, Guglielminotti J, Miller R, et al. Risk Factors and Risk Stratification for Adverse Obstetrical Outcomes After Appendectomy or Cholecystectomy During Pregnancy. JAMA Surg 2017. 82. Choi JJ, Mustafa R, Lynn ET, Divino CM. Appendectomy during pregnancy: follow-up of progeny. J Am Coll Surg 2011; 213:627. Causes of abdominal pain in adults Authors: Robert M Penner, BSc, MD, FRCPC, MSc Mary B Fishman, MD Sumit R Majumdar, MD, MPH Section Editors: Andrew D Auerbach, MD, MPH Mark D Aronson, MD Deputy Editor: Daniel J Sullivan, MD, MPH Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2017. | This topic last updated: Feb 22, 2016. INTRODUCTION — The evaluation of abdominal pain requires an understanding of the possible mechanisms responsible for pain, a broad differential of common causes, and recognition of typical patterns and clinical presentations. This topic reviews the etiologies of abdominal pain in adults. The emergent and non-urgent evaluation of abdominal pain of adults discussed elsewhere. (See "Evaluation of the adult with abdominal pain in the emergency department" and "Evaluation of the adult with abdominal pain".) Abdominal pain in pregnant and postpartum women and patients with HIV is discussed elsewhere. (See "Approach to acute abdominal pain in pregnant and postpartum women"and "Evaluation of abdominal pain in the HIV-infected patient".) PATHOPHYSIOLOGY OF ABDOMINAL PAIN ●Neurologic basis for abdominal pain – Pain receptors in the abdomen respond to mechanical and chemical stimuli. Stretch is the principal mechanical stimulus involved in visceral nociception, although distention, contraction, traction, compression, and torsion are also perceived [1]. Visceral receptors responsible for these sensations are located on serosal surfaces, within the mesentery, and within the walls of hollow viscera. Visceral mucosal receptors respond primarily to chemical stimuli, while other visceral nociceptors respond to chemical or mechanical stimuli. The events responsible for the perception of abdominal pain are not completely understood, but depend upon the type of stimulus and the interpretation of visceral nociceptive inputs in the central nervous system (CNS). As an example, the gastric mucosa is insensitive to pressure or chemical stimuli. However, in the presence of inflammation, these same stimuli can cause pain [2]. The threshold for perceiving pain liver disease. Patients may be asymptomatic or have abdominal pain, dyspepsia, or gastrointestinal bleeding. (See "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Clinical manifestations' and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management", section on 'Clinical manifestations'.) Epigastric pain — Pancreatic and gastric etiologies often cause epigastric pain (table 2). ●Acute myocardial infarction – Epigastric pain can be the presenting symptom of an acute myocardial infarction. Patients may have associated shortness of breath or exertional symptoms. (See "Angina pectoris: Chest pain caused by myocardial ischemia", section on 'History'.) ●Pancreatitis – Both acute and chronic pancreatitis are associated with abdominal pain that often radiates to the back. Most patients with acute pancreatitis have acute onset of persistent, severe epigastric pain. The pain is steady and may be in the mid- epigastrium, right upper quadrant, diffuse, or, infrequently, confined to the left side. (See "Clinical manifestations and diagnosis of acute pancreatitis", section on 'Clinical features'.) The two primary clinical manifestations of chronic pancreatitis are epigastric pain and pancreatic insufficiency. The pain is typically epigastric, is occasionally associated with nausea and vomiting, and may be partially relieved by sitting upright or leaning forward. (See "Clinical manifestations and diagnosis of chronic pancreatitis in adults", section on 'Clinical manifestations'.) ●Peptic ulcer disease – Upper abdominal pain or discomfort is the most prominent symptom in patients with peptic ulcers. Patients most often have epigastric pain, but occasionally the discomfort localizes to one side. (See "Peptic ulcer disease: Clinical manifestations and diagnosis", section on 'Clinical manifestations'.) ●Gastroesophageal reflux disease (GERD) – Most patients with GERD complain of heartburn, regurgitation, and dysphagia. However, some patients may also complain of epigastric and/or chest pain. (See "Clinical manifestations and diagnosis of gastroesophageal reflux in adults", section on 'Clinical features'.) ●Gastritis/gastropathy – Gastritis refers to inflammation in the lining of the stomach. Gastritis is predominantly an inflammatory process, while the term gastropathy denotes a gastric mucosal disorder with minimal to no inflammation. Acute gastropathy often presents with abdominal discomfort/pain, heartburn, nausea, vomiting, and hematemesis. Gastropathy may be caused by a variety of etiologies including alcohol and non-steroid anti-inflammatory medications. (See "Acute hemorrhagic erosive gastropathy and chronic chemical gastropathy", section on 'Acute hemorrhagic erosive gastropathy' and "NSAIDs (including aspirin): Pathogenesis of gastroduodenal toxicity", section on 'Gastric damage'.) ●Functional dyspepsia – Functional dyspepsia is defined as the presence of one or more of the following symptoms: postprandial fullness, early satiation, and epigastric pain or burning, with no evidence of structural disease (including at upper endoscopy) to explain the symptoms. (See "Functional dyspepsia in adults".) ●Gastroparesis – Patients with gastroparesis can present with nausea, vomiting, abdominal pain, early satiety, postprandial fullness, bloating, and, in severe cases, weight loss. The most common causes are idiopathic, diabetic, or postsurgical (figure 2). (See "Gastroparesis: Etiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.) Left upper quadrant pain — Left upper quadrant pain is often related to the spleen (table 3). ●Splenomegaly – Splenomegaly can cause left upper quadrant pain or discomfort, referred pain to the left shoulder, and/or early satiety. Splenomegaly has multiple causes (table 5). (See "Approach to the adult with splenomegaly and other splenic disorders", section on 'Symptoms' and "Approach to the adult with splenomegaly and other splenic disorders", section on 'Causes of splenomegaly'.) ●Splenic infarction – Patients with splenic infarction classically present with severe left upper quadrant pain, though atypical presentations are common. Splenic infarction is associated with a variety of underlying conditions (eg, hypercoagulable state, embolic disease from atrial fibrillation, conditions associated with splenomegaly). (See "Approach to the adult with splenomegaly and other splenic disorders", section on 'Splenic infarction'.) ●Splenic abscess – Splenic abscesses are uncommon and typically are associated with fever and tenderness in the left upper quadrant. They may also be associated with splenic infarction. (See "Approach to the adult with splenomegaly and other splenic disorders", section on 'Splenic abscess'.) ●Splenic rupture – Splenic rupture is most often associated with trauma. The patient may complain of left upper abdominal, left chest wall, or left shoulder pain (ie, Kehr's sign). Kehr's sign is pain referred to the left shoulder that worsens with inspiration and is due to irritation of the phrenic nerve from blood adjacent to the left hemidiaphragm. (See "Approach to the adult with splenomegaly and other splenic disorders", section on 'Splenic rupture' and "Management of splenic injury in the adult trauma patient", section on 'History and physical examination'.) LOWER ABDOMINAL PAIN SYNDROMES — Lower abdominal pain syndromes (table 6) often cause pain in either or both lower quadrants. Women may have lower abdominal pain from disorders of the internal female reproductive organs (table 7). (See 'Women' below.) Lower abdominal pain syndromes that are generally localized to one side include (table 6): ●Acute appendicitis – Acute appendicitis typically presents with periumbilical pain initially that radiates to the right lower quadrant. It is associated with anorexia, nausea, and vomiting. However, occasionally patients present with epigastric or generalized abdominal pain. The pain localizes to the right lower quadrant when the appendiceal inflammation begins to involve the peritoneal surface. (See "Acute appendicitis in adults: Clinical manifestations and differential diagnosis", section on 'Clinical manifestations'.) ●Diverticulitis – The clinical presentation of diverticulitis depends upon the severity of the underlying inflammatory process and whether or not complications are present. Left lower quadrant pain is the most common complaint in Western countries, occurring in 70 percent of patients. Right-sided diverticulitis is more common in Asian patients. The pain is usually constant and is often present for several days prior to presentation. Patients may also have nausea and vomiting. (See "Clinical manifestations and diagnosis of acute diverticulitis in adults", section on 'Clinical manifestations'.) Abdominal pain from some genitourinary etiologies may be localized to either side (table 6): ●Kidney stones – Kidney stones usually cause symptoms when the stone passes from the renal pelvis into the ureter. Pain is the most common symptom and varies from a mild to severe. Patients may have flank pain, back pain, or abdominal pain. (See "Diagnosis and acute management of suspected nephrolithiasis in adults", section on 'Clinical manifestations'.) ●Pyelonephritis – Patients with pyelonephritis may or may not have symptoms of cystitis (dysuria, frequency, urgency, and/or hematuria). These patients also have fever, chills, flank pain, and costovertebral angle tenderness. (See "Acute uncomplicated cystitis and pyelonephritis in women", section on 'Clinical manifestations' and "Acute uncomplicated cystitis and pyelonephritis in men", section on 'Clinical manifestations'.) Other etiologies of lower abdominal pain may not always be localized to one side (table 6): ●Cystitis – Patients with cystitis may complain of suprapubic pain as well as dysuria, frequency, urgency, and/or hematuria. (See "Acute uncomplicated cystitis and pyelonephritis in women", section on 'Clinical manifestations' and "Acute uncomplicated cystitis and pyelonephritis in men", section on 'Clinical manifestations'.) ●Acute urinary retention – Patients with bladder outlet obstruction leading to acute urinary retention present with the inability to pass urine. They may have associated lower abdominal and/or suprapubic pain or discomfort. (See "Acute urinary retention", section on 'Clinical presentation'.) ●Infectious colitis – Patients with infectious colitis generally have diarrhea as the predominant symptom but may also have associated abdominal pain, which may be severe. Patients with clostridium difficile infection can present with an acute abdomen and peritoneal signs in the setting of perforation and fulminant colitis (table 8). (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "Approach to the adult with acute diarrhea in resource-rich settings", section on 'Stool cultures'.) DIFFUSE ABDOMINAL PAIN SYNDROMES — Abdominal pain syndromes may have diffuse, non-specific abdominal or variable presentations of pain (table 9). ●Ketoacidosis – Patients with ketoacidosis (eg, from diabetes or alcohol) may have diffuse abdominal pain as well as nausea and vomiting. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Abdominal pain in DKA' and "Fasting ketosis and alcoholic ketoacidosis", section on 'Clinical presentation'.) ●Adrenal insufficiency – Patients with adrenal insufficiency may have diffuse abdominal pain as well as nausea and vomiting. Patients with adrenal crisis may present with shock and hypotension. Patients with chronic adrenal deficiency may also complain of malaise, fatigue, anorexia, and weight loss. (See "Clinical manifestations of adrenal insufficiency in adults", section on 'Autoimmune primary adrenal insufficiency' and "Clinical manifestations of adrenal insufficiency in adults", section on 'Gastrointestinal complaints'.) ●Foodborne disease – A foodborne disease will typically manifest as a mixture of nausea, vomiting, fever, abdominal pain, and diarrhea. Toxin-mediated illnesses can occur within hours of ingestion, but bacterial colitis generally requires 24 to 48 hours to develop. Certain foods may be linked to particular pathogens (table 15). (See "Differential diagnosis of microbial foodborne disease", section on 'Clinical manifestations'.) ●Irritable bowel syndrome (IBS) – Patients with IBS can present with a wide array of symptoms which include both gastrointestinal and extraintestinal complaints. However, the symptom complex of chronic abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Clinical manifestations'.) ●Constipation – Constipation may be associated with abdominal pain. Diseases associated with constipation include neurologic and metabolic disorders, obstructing lesions of the gastrointestinal tract, including colorectal cancer, endocrine disorders such as diabetes mellitus, and psychiatric disorders such as anorexia nervosa (table 16). Constipation may also be due to a side effect of drugs (table 17). (See "Etiology and evaluation of chronic constipation in adults".) ●Diverticulosis – Uncomplicated diverticulosis is often asymptomatic and an incidental finding on colonoscopy or sigmoidoscopy. However, these patients may have symptoms of abdominal pain and constipation. (See "Colonic diverticulosis and diverticular disease: Epidemiology, risk factors, and pathogenesis", section on 'Symptomatic uncomplicated diverticular disease'.) ●Lactose intolerance – Symptoms of lactose intolerance include abdominal pain, bloating, flatulence, and diarrhea. The abdominal pain may be cramping in nature and is often localized to the periumbilical area or lower quadrants. (See "Lactose intolerance: Clinical manifestations, diagnosis, and management", section on 'Clinical features'.) LESS COMMON CAUSES — Less common causes of abdominal pain include (table 18): ●Abdominal aortic aneurysm (AAA) – Most patients with AAA have no symptoms. When patients with a nonruptured AAA do have symptoms, abdominal, back, or flank pain is the most common clinical manifestation. Classically, ruptured AAA is associated with severe pain, hypotension, and a pulsatile abdominal mass, but patients may have variable presentations. (See "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Asymptomatic AAA' and "Clinical features and diagnosis of abdominal aortic aneurysm", section on 'Symptomatic (nonruptured) AAA'.) ●Abdominal compartment syndrome – Abdominal compartment syndrome generally occurs in patients who are critically ill. Patients have a tensely distended abdomen. (See "Abdominal compartment syndrome in adults".) ●Abdominal migraine – Recurrent abdominal pain may occur in patients with abdominal migraine [9]. These patients usually also suffer from typical migraine headaches, although occasional patients present with gastrointestinal symptoms only [10]. Abdominal migraines have also been linked to cyclic vomiting syndrome. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults" and "Cyclic vomiting syndrome", section on 'CVS and migraines'.) ●Acute intermittent porphyria (AIP) – AIP is a rare cause of abdominal pain. The presentation of AIP is highly variable and patients have nonspecific symptoms. Abdominal pain is the most common and often earliest symptom. (See "Pathogenesis, clinical manifestations, and diagnosis of acute intermittent porphyria", section on 'Acute attacks'.) ●Angioedema – Angioedema with abdominal pain may be caused by hereditary angioedema (HAE) or related to ACE inhibitor therapy. It can present with recurrent episodes of abdominal pain, accompanied by nausea, vomiting, colicky pain, and diarrhea. (See "Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis" and "ACE inhibitor-induced angioedema", section on 'Intestine'.) ●Celiac artery compression syndrome – Celiac artery compression syndrome (also referred to as celiac axis syndrome, median arcuate ligament syndrome, and Dunbar syndrome) is defined as chronic, recurrent abdominal pain related to compression of the celiac artery by the median arcuate ligament. (See "Celiac artery compression syndrome".) ●Chronic abdominal wall pain – Chronic abdominal wall pain usually refers to anterior cutaneous nerve entrapment syndrome. Pain associated with nerve entrapment is characteristically maximal in an area <2 cm in diameter. (See "Anterior cutaneous nerve entrapment syndrome", section on 'Clinical features'.) ●Colonic pseudo-obstruction – Pseudo-obstruction is characterized by signs and symptoms of a mechanical obstruction of the small or large bowel in the absence of a mechanical cause. The main clinical feature is abdominal distention, but patients may have associated abdominal pain, nausea, and vomiting. Acute colonic pseudo- obstruction is also known as Ogilvie's syndrome. (See "Acute colonic pseudo- obstruction (Ogilvie's syndrome)", section on 'Clinical manifestations' and "Chronic intestinal pseudo-obstruction", section on 'Clinical manifestations'.) ●Eosinophilic gastroenteritis – Eosinophilic gastroenteritis belongs to a group of diseases that includes eosinophilic esophagitis, gastritis, enteritis, and colitis. Symptoms depend on what part of the gastrointestinal tract is affected. (See "Eosinophilic gastroenteritis".) ●Epiploic appendagitis – Epiploic appendagitis (also known as appendicitis epiploica, hemorrhagic epiploitis, epiplopericolitis, or appendagitis) is a benign and self-limited condition of the epiploic appendages. Patients with epiploic appendagitis most commonly present with acute or subacute onset of lower abdominal pain. The pain is on the left side in 60 to 80 percent of patients, but has also been reported in the right lower quadrant. (See "Epiploic appendagitis".) ●Familial Mediterranean fever – The typical manifestations of familial Mediterranean fever are recurrent attacks of severe pain (due to serositis at one or more sites) and fever, lasting one to three days and then resolving spontaneously. Most patients have abdominal pain. In between attacks, patients feel entirely well. (See "Clinical manifestations and diagnosis of familial Mediterranean fever".) ●Helminthic infections – Patients with helminthic infections can manifest with gastrointestinal symptoms, including abdominal pain. The clinical manifestations for specific helminth infections are discussed in the appropriate topics. ●Herpes zoster – Herpes zoster neuropathic pain may precede the development of skin lesions. Depending on the dermatome involved, this pain can be confused with other etiologies, such cholecystitis or renal colic. (See "Clinical manifestations of varicella-zoster virus infection: Herpes zoster", section on 'Clinical manifestations'.) ●Hypercalcemia – Hypercalcemia can cause abdominal pain, either directly or as an etiology for pancreatitis or constipation. (See "Clinical manifestations of hypercalcemia", section on 'Gastrointestinal abnormalities'.) ●Hypothyroidism – Hypothyroidism can occasionally cause abdominal pain in the setting of constipation and ileus. (See "Clinical manifestations of hypothyroidism", section on 'Gastrointestinal disorders'.) ●Lead poisoning – Abdominal pain is associated with acute lead poisoning. (See "Adult occupational lead poisoning", section on 'Clinical manifestations'.) ●Meckel's diverticulum – Meckel's diverticulum is usually clinically silent and can be found incidentally, or can present with a variety of clinical manifestations including gastrointestinal bleeding or other acute abdominal complaints. Acute abdominal pain related to Meckel's diverticulum can be the result of diverticular inflammation, similar to acute appendicitis, related to bowel obstruction, or perforation of the Meckel's or adjacent bowel. (See "Meckel's diverticulum", section on 'Clinical presentations' and "Meckel's diverticulum", section on 'Acute abdominal pain'.) ●Narcotic bowel syndrome – The most common side effect of opioids is constipation, but some patients may have associated abdominal pain. (See "Cancer pain management with opioids: Prevention and management of side effects", section on 'Bowel issues'.) ●Pseudoappendicitis – Acute yersiniosis or campylobacter infection can mimic appendicitis presenting with right lower abdominal pain, fever, vomiting, leukocytosis, ●Leiomyomas (fibroids) – Leiomyomas may cause pelvic pressure or pain. These symptoms may be related to bulk or infrequently fibroids can cause acute pain from degeneration (eg, carneous or red degeneration) or torsion of a pedunculated tumor. Pain may be associated with a low grade fever, uterine tenderness on palpation, elevated white blood cell count, or peritoneal signs. ●Ovarian hyperstimulation – Ovarian hyperstimulation syndrome can cause abdominal discomfort from enlarged ovaries in women undergoing fertility treatment (table 19). (See "Pathogenesis, clinical manifestations, and diagnosis of ovarian hyperstimulation syndrome", section on 'Clinical manifestations'.) ●Ovarian cancer – Women with ovarian cancer may present with bloating or abdominal or pelvic pain. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Pelvic and abdominal symptoms'.) Postoperative patients — A variety of postoperative complications can cause abdominal pain: ●Postoperative ileus (see "Postoperative ileus", section on 'Clinical features') ●Surgical site infections (see "Complications of abdominal surgical incisions", section on 'Surgical site infection') ●Hematoma/seroma formation and nerve injury (see "Complications of abdominal surgical incisions", section on 'Hematoma and seroma' and "Complications of abdominal surgical incisions", section on 'Nerve injury') Sickle cell — Severe intermittent crises of abdominal pain can occur with sickle cell anemia, particularly after an acute precipitant, such as dehydration. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Acute painful episodes'.) Patients with sickle cell may also have right upper quadrant pain in the setting of hepatic involvement. The liver can be affected by a number of complications due to the disease itself and its treatment. (See "Hepatic manifestations of sickle cell disease", section on 'Disorders associated with the sickling process' and "Hepatic manifestations of sickle cell disease", section on 'Disorders related to coexisting conditions'.) HIV — Etiologies of abdominal pain in patients with human immunodeficiency virus (HIV) can be related to opportunistic infections (eg, cytomegalovirus, mycobacterium avium complex) in the setting of severe immunodeficiency, or may be due to other more common etiologies seen in the general population (eg, appendicitis, diverticulitis) (table 20). (See "Evaluation of abdominal pain in the HIV-infected patient".) 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 5 th to 6 th 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 10 th to 12 th 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 topic (see "Patient education: Acute abdomen (belly pain) (The Basics)") ●Beyond the Basics topics (see "Patient education: Upset stomach (functional dyspepsia) in adults (Beyond the Basics)" and "Patient education: Chronic pelvic pain in women (Beyond the Basics)") SUMMARY ●Pain receptors in the abdomen respond to mechanical and chemical stimuli. The type and density of visceral afferent nerves makes the localization of visceral pain imprecise. Pain originating in the viscera may also be perceived as originating from a site distant from the affected organ (referred pain) (figure 1). (See 'Pathophysiology of abdominal pain' above.) ●Upper abdominal pain typically has characteristic locations: right upper quadrant pain (table 1), epigastric pain (table 2), or left upper quadrant pain (table 3). (See 'Upper abdominal pain syndromes' above.) ●Lower abdominal pain syndromes (table 6) often cause pain in either or both lower quadrants. Women may have lower abdominal pain from disorders of the internal female reproductive organs (table 7). (See 'Lower abdominal pain syndromes' above.) ●Abdominal pain syndromes may have diffuse or non-specific pain (table 9). (See 'Diffuse abdominal pain syndromes' above.) ●There are many other less common causes of abdominal pain (table 18). (See 'Less common causes' above.) ●Certain etiologies are specific to special population of patients (women (table 7), postoperative patients, sickle cell patients, and HIV patients). (See 'Special populations'above.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Ray BS, Neill CL. Abdominal Visceral Sensation in Man. Ann Surg 1947; 126:709. 2. Bentley FH. Observations on Visceral Pain : (1) Visceral Tenderness. Ann Surg 1948; 128:881. 3. CHAPMAN WP, HERRERA R, JONES CM. A comparison of pain produced experimentally in lower esophagus, common bile duct, and upper small intestine with pain experienced by patients with diseases of biliary tract and pancreas. Surg Gynecol Obstet 1949; 89:573. 4. Brown FR. The Problem of Abdominal Pain. Br Med J 1942; 1:543. 5. Bloomfield AL, Polland WS. EXPERIMENTAL REFERRED PAIN FROM THE GASTRO-INTESTINAL TRACT. PART II. STOMACH, DUODENUM AND COLON. J Clin Invest 1931; 10:453. 6. DWORKEN HJ, BIEL FJ, MACHELLA TE. Supradiaphragmatic reference of pain from the colon. Gastroenterology 1952; 22:222. 7. Ryle JA. Visceral pain and referred pain. Lancet 1926; 1:895. 8. Saik RP, Greenburg AG, Farris JM, Peskin GW. Spectrum of cholangitis. Am J Surg 1975; 130:143. 9. Roberts JE, deShazo RD. Abdominal migraine, another cause of abdominal pain in adults. Am J Med 2012; 125:1135. 10. d'Onofrio F, Cologno D, Buzzi MG, et al. Adult abdominal migraine: a new syndrome or sporadic feature of migraine headache? A case report. Eur J Neurol 2006; 13:85. 11. Gayer G, Hertz M, Strauss S, Zissin R. Congenital anomalies of the spleen. Semin Ultrasound CT MR 2006; 27:358. ●Patients in the antibiotic-first group had favorable clinical outcomes (including reduction in white-cell count [15], avoidance of peritonitis [4], and general symptom reduction [14,16,17]). ●As compared with the appendectomy group, patients in the antibiotic-first group had lower or similar pain scores [4,14,15], required fewer doses of narcotics [15], and had a quicker return to work [14,15]. ●As compared with the appendectomy group, the rate of perforation was not higher in the antibiotic-first group. ●After initial treatment success, 10 to 37 percent of the patients in the antibiotic-first group eventually required appendectomy for recurrent appendicitis or symptoms of abdominal pain (mean time to appendectomy, 4.2 to 7 months [4,15,16]). A separate, observational study showed an overall recurrence rate of 13.8 percent in 159 patients treated initially with antibiotics then followed for two years [24]. However, serious questions remain regarding the efficacy of using antibiotics as the primary treatment for appendicitis. As examples: ●Does antibiotic treatment increase hospital utilization, and therefore cost, both during the initial phase of treatment and for recurrences? ●Does the success in avoiding immediate surgery justify the fear and burden of potential recurrence or missed appendiceal neoplasm (especially in older adults)? ●Although high-risk patients (eg, older adults, immunocompromised, patients with medical comorbidities) could potentially benefit the most from nonsurgical treatment of appendicitis, they were excluded from all trials cited above. Thus, the efficacy of the antibiotic-first approach to management of appendicitis in this group of patients remains unknown. (See 'Special considerations' below.) Large multicenter randomized trials in the US are needed before the antibiotic-first approach could be considered comparable to appendectomy. Thus, we reiterate that the antibiotic-first approach should only be offered to selected patients (eg, poor surgical candidates, patients who refuse surgery) after a careful explanation of the risks. In general, appendectomy is still considered the standard of care in the treatment of acute uncomplicated appendicitis [25]. SURGICAL OUTCOMES Laparotomy versus laparoscopy — An appendectomy is performed by the conventional open laparotomy approach or by laparoscopy. The laparoscopic approach is used to perform an estimated 58 percent of all appendectomies in the United States [26-29]. The operative approach in patients with a suspected appendicitis depends upon the confidence in the diagnosis, history of prior surgery, the patient's age, gender, and body habitus, and the skills of the surgeon. Randomized trials and prospective and retrospective observational studies evaluating laparoscopic and open techniques have been performed to assess outcomes [28-31]. The pertinent findings include: ●A trend analysis of prospectively collected data on 7446 patients undergoing a laparoscopic appendectomy found that complication rates have significantly decreased over a decade of observation [29]. For procedures performed at the end of the study period compared with procedures performed at the beginning, there were significant reductions in the following outcomes: •Conversion from a laparoscopic to an open procedure (2.2 to 1.2 percent) •Intraoperative complications (3.1 to 0.7 percent) •Surgical postoperative complications (6.1 to 1.9 percent) •General postoperative complications (4.9 to 1.5 percent) •Rate of reoperation (3.4 to 0.7 percent) •Duration of hospital stay (4.9 to 3.5 days) ●A meta-analysis of 56 randomized trials and 11 studies compared the outcomes of approximately 6000 adults and children with suspected acute appendicitis undergoing either laparoscopic appendectomy or conventional open laparotomy [30]. There were both significantly better and worse outcomes for the laparoscopic approach compared with the conventional open laparotomy. There were no significant differences for adult outcomes compared with children. The significantly better outcomes with the laparoscopic approach included: •A lower rate of wound infections (odds ratio [OR] 0.43, 95% CI 0.34-0.54) •Less pain on postoperative day 1 by the VAS pain score (8 mm, CI 5-11 mm) •Shorter duration of hospital stay (1.1 days, CI 0.7-1.5 days) •Shorter duration for return of bowel function (no data provided) The significantly worse outcomes for the laparoscopic approach included: •A higher rate of an intra-abdominal abscess (OR 1.77, CI 1.14-2.76) •A longer operative time (10 minutes, CI 6-15 minutes) •Higher operative and in-hospital costs ●Outcome data on 235,473 patients with suspected acute appendicitis undergoing a laparoscopic or open appendectomy between 2000 and 2005 were obtained from the US Nationwide Inpatient Sample [27]. The frequency of laparoscopic appendectomies increased from 32 to 58 percent over the study time period. The proportion of patients with uncomplicated appendicitis was significantly higher in the laparoscopic group (76 versus 69 percent). •Patients undergoing a laparoscopic appendectomy for uncomplicated (eg, nonperforated, no abscess) acute appendicitis were significantly more likely to have a shorter mean hospital stay (1.5 versus 1.8 days), higher rates of intraoperative complications (OR 2.61, CI 2.23-3.05), and higher costs (22 percent) compared with patients treated by an open appendectomy. •For patients with complicated appendicitis, defined as an appendiceal perforation or abscess, laparoscopic approach was significantly associated with a shorter mean hospital stay (3.5 versus 4.2 days), higher rates of intraoperative complications (OR 1.61, CI 1.33-1.94), and higher hospital costs (9 percent) compared to patients undergoing an open appendectomy for complicated appendicitis. Although laparoscopic appendectomy has gained widespread acceptance, these data show that there are benefits and limitations to the laparoscopic approach. As a result, the choice of laparoscopic or open appendectomy is best decided by the surgeon based on personal experience, institutional capabilities, severity of disease, body habitus, and other factors. There are clinical settings when laparoscopy may be the preferred approach. These include: ●An uncertain diagnosis – The laparoscopic approach provides an advantage in patients in whom the diagnosis is uncertain since it permits inspection of other abdominal organs. This benefit may be greater for women of childbearing age, who traditionally have had higher negative appendectomy rates, and in whom laparoscopy may reveal other causes of pelvic pathology [32-35]. In a study of 181 women who underwent laparoscopy for suspected acute appendicitis, 86 (48 percent) were diagnosed with a gynecologic disorder as the etiology of the symptoms [35]. ●Obese patients – Laparoscopic appendectomy is useful in the overweight or obese patient, since exposure of the right lower quadrant during open appendectomy may require larger, morbidity-prone incisions [36-38]. In a retrospective review of 13,330 obese patients undergoing a primary appendectomy for confirmed appendicitis, the laparoscopic approach (n = 10,409 patients) was associated with a 57 percent reduction in overall morbidity compared with an open appendectomy (5.23 versus 13.49 percent, odds ratio [OR] 0.43, 95% CI 0.36-0.52) [38]. In addition, the mortality rate was also significantly lower for the patients undergoing a laparoscopic appendectomy (0.11 versus 0.58 percent, OR 0.47, 0.32-0.65). ●Elderly patients – Elderly patients may benefit significantly from a laparoscopic approach, as hospital stay is shorter and discharge rates to home are higher in this population than with an open appendectomy. In a retrospective review based upon outcome data from the North Carolina Hospital Association Patient Data System on 29,244 appendectomies performed in adults, 2,722 were performed in elderly patients (defined as age >65 years) [39]. Among the elderly patients, laparoscopic appendectomy had the following benefits compared with elderly patients undergoing an open appendectomy: •For uncomplicated appendicitis, laparoscopic appendectomy was associated with the following significant benefits: shorter length of hospital stay (4.6 versus 7.3 days), higher rate of discharge to home rather than a step-down facility (91 versus 79 percent), fewer complications (13 versus 22 percent), and lower mortality rate (0.4 versus 2.1 percent). •For a perforated appendix, laparoscopic appendectomy was associated with the following significant benefits: shorter length of hospital stay (6.8 versus 9.0 days), higher rate of discharge to home (87 versus 71 percent), and equivalent mortality rates (0.37 versus 0.15 percent). The appendix or mesoappendix can be gently grasped with a Babcock clamp and retracted anteriorly. The appendiceal artery is identified and divided between hemostatic clips, using an ultrasonic scalpel, a laparoscopic gastrointestinal anastomosis (GIA) stapler or other vessel ligation device. The appendix is cleared to its attachment with the cecum, and the appendiceal base is divided using a laparoscopic gastrointestinal anastomosis stapler (GIA) stapler, taking care not to leave a significant stump [51]. It is sometimes necessary to include part of the cecum within the stapler to ensure that the staples are placed in healthy, uninfected tissue. The appendix is then removed through the umbilical port, using a specimen bag to avoid the risk of wound infection. The operative field is inspected for hemostasis and irrigated with saline if needed and then the fascial defect and skin incisions are closed. OPEN APPENDECTOMY Incision — The patient should be reexamined after the induction of general anesthesia, as this allows deep palpation of the abdomen. If a mass representing the inflamed appendix can be palpated, the incision can be located over the mass. If no appendiceal mass is detected, the incision should be centered over McBurney's point, one-third of the distance from the anterior superior iliac spine to the umbilicus. A curvilinear incision in a skin fold allows for an excellent cosmetic result. It is important not to make the incision too medial or too lateral. An incision placed too medial opens onto the anterior rectus sheath, rather than the desired oblique muscles, while an incision placed too lateral may be lateral to the abdominal cavity. Some surgeons prefer a transverse incision, however, because it is easily extended to increased exposure if needed (figure 2). Mobilization and resection — The dissection begins through the subcutaneous tissue to the external oblique fascia, which is sharply incised lateral to the rectus sheath. Using a muscle-splitting technique, the external oblique is bluntly separated in the direction of the muscle fibers; the internal oblique and transversus abdominus muscles are bluntly separated in a similar fashion. The peritoneum is sharply entered, avoiding injury to the underlying intestine. The surgeon can often locate the appendix by sweeping a finger laterally to medially in the right paracolic gutter. Thin adhesions between the appendix and surrounding structures may generally be freed with blunt dissection; occasionally, sharp dissection is required for more dense adhesions. If the appendix cannot be identified through palpation, it can be located by following the teniae coli to its origin at the cecal base. Once identified and freed from adhesions, the appendix is delivered through the incision. The mesoappendix may be grasped with a Babcock clamp, taking care not to tear the appendiceal wall and cause spillage of enteric contents. The appendiceal artery, which runs in the mesoappendix, is divided between hemostats and tied with 3-0 absorbable suture. A non-absorbable purse-string suture is placed in the cecal wall around the appendix. After crushing the appendiceal base with a Kelly clamp, the appendix is doubly tied with 2-0 absorbable suture. The appendix is excised with a scalpel, and the remaining stump is cauterized to prevent a mucocele. The appendiceal stump is typically inverted into the cecum while the purse-string suture is tightened, although the usefulness of this is debatable [52-56].The surgical bed is then irrigated with saline. Closure — The incision is closed in layers with running 2-0 absorbable suture, beginning with the peritoneum, followed by the transversus abdominus, internal oblique, and external oblique. Irrigation is performed at each layer. To improve analgesia and limit postoperative narcotic requirements, the external oblique fascia may be infused with local anesthetic. Scarpa's fascia is closed with interrupted 3-0 absorbable suture, followed by a subcuticular closure or staples for the skin. In nonperforated appendicitis, the skin may be closed primarily with a low likelihood of wound infection. Postoperative management — With both the open and laparoscopic approaches, most patients are discharged within 24 to 48 hours of surgery. Patients may be started on a clear liquid diet post-operatively and advanced to regular diet as tolerated. Antibiotics are not required postoperatively in nonperforated appendicitis. PERFORATED APPENDICITIS — The time course of progression of appendicitis to necrosis and perforation varies among patients. Approximately 20 percent of patients with perforated appendicitis present within 24 hours of the onset of symptoms [57]. Although perforation is a major concern when evaluating a patient with more than 24 hours of symptoms, perforation can develop more rapidly and should always be considered. Patients with perforated appendicitis may appear acutely ill and have significant dehydration and electrolyte abnormalities, particularly if fever and vomiting have been present for a considerable time. The pain usually localizes to the right lower quadrant if the perforation has been walled off by surrounding intra-abdominal structures such as the omentum, or can be diffuse if generalized peritonitis ensues. Other unusual presentations of appendiceal perforation can occur, such as retroperitoneal abscess formation due to perforation of a retrocecal appendix or liver abscess formation due to hematogenous spread of infection through the portal venous system. An enterocutaneous fistula can result from an intraperitoneal abscess that fistulizes to the skin. Appendiceal perforation can result in a small bowel obstruction, manifested by bilious vomiting and obstipation. High fevers and jaundice can be seen with pylephlebitis (septic portal vein thrombosis) and can be confused with cholangitis. The management of appendiceal perforation will depend on the nature of the perforation. A free perforation can cause intraperitoneal dissemination of pus and fecal material. Urgent laparotomy is necessary for free perforation with appendectomy and irrigation and drainage of the peritoneal cavity. These patients are typically quite ill and may be septic. The diagnosis is not always appreciated before exploration and a midline incision is prudent. If the diagnosis of perforated appendicitis is certain, a right lower quadrant incision can be used. For management of a contained perforation, nonoperative treatment is an option. (See 'Staged approach' below.) Treatment should be individualized for each patient, based on the clinical situation and the hospital's capabilities. Incision — Operative technique is similar in appendectomies for perforated or nonperforated appendicitis. In an open appendectomy for perforation, a larger incision may be needed to provide adequate exposure for drainage of abscesses, enteric contents, and purulent material. In some instances, a lower midline incision is preferable to a right lower quadrant incision. In both open and laparoscopic approaches, the goal is to remove any infected material and drain all abscess cavities. Copious irrigation is used to reduce the likelihood of postoperative abscess formation. Once the appendix and infected material have been removed, the muscle layers of the open incision are closed as previously described. Drains — Peritoneal drains are not necessary, as they do not reduce the incidence of wound infection or abscess after appendectomy for perforated appendicitis [58,59]. A systematic review identified five trials examining the use of drains after emergency appendectomy [60]. There were no significant differences between the groups for intraperitoneal abscess or wound infection. The length of hospital stay was significantly longer for the drainage compared with no drainage. Closure — Skin closure techniques include primary closure, loose partial closure, and closure with secondary intention. Because of wound infection rates ranging from 30-50 percent with primary closure of grossly contaminated wounds, many advocate delayed primary or secondary closure [61,62]. However, a cost-utility analysis of contaminated appendectomy wounds showed primary closure to be the most cost-effective method of wound management [63]. Our technique of skin closure is interrupted permanent sutures or staples every 2 cm with loose wound packing in between. Removal of the packing in 48 hours often leaves an excellent cosmetic result with an acceptable incidence of wound infection. If heavy fecal contamination is present, the skin is often left open to close secondarily. Postoperative management — Postoperatively, these patients often have an ileus, and diet should only be advanced as the clinical situation warrants. Patients may be discharged once they tolerate a regular diet, usually in five to seven days. The duration of antibiotic therapy in such patients is discussed elsewhere. (See "Antimicrobial approach to intra-abdominal infections in adults", section on 'Duration of therapy'.) Staged approach — Patients who present 24 to 72 hours after the onset of symptoms usually undergo immediate appendectomy. In contrast, patients who present with a longer duration of symptoms (more than five days) and have findings localized to the right lower quadrant should be treated initially with antibiotics, intravenous fluids, and bowel rest. These patients will often have a palpable mass on physical examination; a computed tomography (CT) scan may reveal a phlegmon or abscess. Fortunately, many of these SPECIAL CONSIDERATIONS Normal appendix — The diagnosis of appendicitis can be uncertain. In some historical studies, more than 15 percent of patients with suspected appendicitis have a normal appendix at laparotomy, with higher percentages in infants, the elderly and young women [82]. However, the use of imaging studies appears to have reduced the negative appendectomy rate to less than 10 percent [2]. If an uninflamed appendix is encountered at appendectomy, it is important to search for other causes of the patient's symptoms, including terminal ileitis, cecal or sigmoid diverticulitis or a perforating colon carcinoma, Meckel's diverticulitis, mesenteric adenitis, or uterine, fallopian, or ovarian pathology in a female. If necessary, the right lower quadrant incision may be extended medially to afford exposure to left-sided pelvic organs. Even if the appendix appears normal, early intramural or serosal inflammatory changes can sometimes be found in subsequent microscopic evaluation [83,84]. Accordingly, the normal appearing appendix should be removed. Moreover, if right lower quadrant pain recurs, appendicitis can be excluded from the differential diagnosis [85-87]. Elderly patients — One in every 2000 adults over age 65 will develop appendicitis annually, making appendicitis an important cause of abdominal pain in this age group. The elderly tend to have a diminished inflammatory response, resulting in a less remarkable history and physical examination [88]. For these reasons, older patients often delay seeking medical care and as a result, they have a considerably higher rate of perforation at the time of presentation [89,90]. These patients may have cardiac, pulmonary, and renal conditions with resulting morbidity and mortality from perforation. In one series, the mortality from perforated appendicitis in patients over age 80 was 21 percent [91]. In addition, diverticulitis and colonic neoplasms are more common in this age group and can mimic appendicitis. Elderly patients can also have a redundant sigmoid colon that can cause right- sided pain from sigmoid disease. Accordingly, prompt CT scanning can improve diagnostic accuracy in this population [92]. Laparoscopic appendectomy can be used successfully in the elderly population and results in shorter hospitalization for older patients with both perforated and nonperforated appendicitis [39,93]. A study of 2722 appendectomies in patients over 65 years of age demonstrated a significantly shorter length of stay (4.6 versus 7.3 days) and a higher rate of discharge to home (91.4 versus 78.9 percent), fewer complications (13.0 versus 22.4 percent), and a lower mortality rate (0.4 versus 2.1 percent) than with open operation [39]. It is notable that this study showed fewer complications with laparoscopic appendectomy than open operation, which differs from other large population based studies [26,27]. Immunocompromised patients — Immunocompromised patients are increasingly common in surgical practice and include organ transplant patients and those receiving immunosuppressive therapy for autoimmune diseases, cancer and AIDS. Although certain causes of abdominal pain are specific to the immunocompromised state, appendicitis remains a concern [94,95]. (See "Surgical issues in HIV infection".) The immunocompromised are susceptible to infection, and their immune response is blunted due to immunosuppressive medication or disease. As a result, they may not exhibit the typical signs and symptoms of appendicitis, and may have only mild tenderness on examination. In addition, laboratory and radiological tests may not show the expected level of inflammation. An expanded differential diagnosis includes but is not limited to opportunistic (mycobacterial) and viral (cytomegalovirus) infections, fungal infections, secondary malignancies (lymphoma and Kaposi's sarcoma), and typhlitis. Because of the broad differential diagnoses, there is often delay in reaching a diagnosis and presentation to surgical evaluation, which can increase the risk of perforation [94,96]. CT is particularly useful in this patient population, as it may not only diagnose appendicitis, but may eliminate or diagnose other potential causes for the patient's symptoms. If appendicitis is strongly suspected, operation should not be delayed, as there is no specific contraindication to operation in immunocompromised patients. Children — Appendicitis in children is discussed in detail separately. (See "Acute appendicitis in children: Diagnostic imaging" and "Acute appendicitis in children: Clinical manifestations and diagnosis" and "Acute appendicitis in children: Management".) Pregnancy — Pregnancy poses unique challenges in the diagnosis of appendicitis. Acute appendicitis in pregnancy is discussed in detail separately. (See "Acute appendicitis in pregnancy".) Appendiceal neoplasms — Neoplasms of the appendix are rare, occurring in less than one percent of appendectomies. Patients may present with symptoms of appendicitis, a palpable mass, intussusception, urologic symptoms, or an incidentally discovered mass on abdominal imaging or at laparotomy for another purpose. It is not uncommon for patients with an appendiceal neoplasm to have acute appendicitis as well [97]. Typically, the diagnosis is not appreciated until laparotomy or pathologic evaluation of the appendectomy specimen. The most common appendiceal tumors include cystic neoplasms, carcinoid tumors, adenocarcinoma, and metastases. Other tumors have been reported but are extremely rare, such as lymphoma, stromal tumors (leiomyoma and leiomyosarcoma), and Kaposi's sarcoma [76]. Primary adenocarcinoma of the appendix — Standard treatment is right hemicolectomy and reoperation is recommended if the diagnosis is made on pathologic evaluation of an appendectomy specimen. This is discussed in detail elsewhere. (See "Cancer of the appendix and pseudomyxoma peritonei".) Cystic neoplasms and pseudomyxoma peritonei — Sometimes referred to as mucoceles, mucinous neoplasms of the appendix include a spectrum of diseases including simple cyst, mucinous cystadenoma, mucinous cystadenocarcinoma, and pseudomyxoma peritonei. If there is any preoperative suspicion of an appendiceal tumor, care must be taken to avoid spillage of mucin-secreting cells throughout the abdomen. These tumors are discussed in detail elsewhere. (See "Cancer of the appendix and pseudomyxoma peritonei".) Carcinoid tumor of the appendix — As noted above, appendicitis can uncommonly be caused by a carcinoid that obstructs the appendiceal lumen. Simple appendectomy is sufficient in most cases of appendiceal carcinoid while right hemicolectomy is indicated if the tumor is >2 cm in diameter or if the adjacent mesenteric nodes are involved. Management of carcinoid tumors is discussed elsewhere in detail. (See "Cancer of the appendix and pseudomyxoma peritonei" and "Clinical characteristics of carcinoid tumors".) Chronic appendicitis — Chronic appendicitis refers to the pathologic finding of chronic inflammation or fibrosis of the appendix found in a subset of patients undergoing appendectomy [98,99]. These patients are clinically characterized by prolonged (>7 days) right lower quadrant pain that may be intermittent and a normal white blood cell count. Most patients have resolution of pain with appendectomy. Chronic appendicitis may be present in 14 to 30 percent of adults undergoing appendectomy [98,99] but is much rarer in children. Recurrent appendicitis can occur but is also rare in children; such cases may be caused by a carcinoid tumor or a retained foreign body (eg, fecalith) in the lumen of the appendix [100]. Stump appendicitis is a form of recurrent appendicitis that is related to incomplete appendectomy that leaves an excessively long stump after open or laparoscopic surgery. (See "Acute appendicitis in children: Management", section on 'Late'.) 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 5 th to 6 th 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 10 th to 12 th 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 education: Appendicitis in adults (The Basics)") SUMMARY AND RECOMMENDATIONS — Surgery remains the gold standard for the treatment of appendicitis. ●The preoperative preparation for appendectomy includes intravenous hydration, correction of electrolyte abnormalities, and perioperative antibiotics. (See 'Preoperative preparation' above.) ●Both open and laparoscopic approaches to appendectomy are appropriate for all patients. Patients treated with a laparoscopic appendectomy have significantly fewer wound infections, less pain, and a shorter duration of hospital stay, but higher rates of readmission, intra-abdominal abscess formation, and higher hospital costs. (See 'Surgical outcomes' above.) ●An appendectomy rather than medical management with antibiotics alone is the gold standard for patients with a history and clinical findings, and radiographic images,