Chapter 93 Appendicitis is a common condition requiring emergency surgery. About 7% of people will develop appendicitis sometime during their lifetime. Most cases occur in adolescents and young adults, with the incidence in men being slightly higher than in women.1,2 Although the diagnosis is clinically clear in classic presentations, it still remains elusive in atypical presentations; after missed myocardial infarction and fractures, missed appendicitis represents the largest number of malpractice claims for practicing emergency physicians.3 The earliest evidence of appendicitis is suggested by the presence of right lower quadrant adhesions in an Egyptian mummy from the Byzantine era. In 1492, Leonardo da Vinci drew pictures of the colon and the appendix and called the structure an “orecchio,” which literally means ear. Claudius Amyand removed the first appendix incidentally in 1735 during the repair of a scrotal hernia in an 11-year-old boy. The appendix had perforated, and a cutaneous fecal-draining fistula had developed.4 The half-hour operation was done without anesthesia, and the boy fully recovered. In the early 1800s during the Lewis and Clark expedition, the only trip mortality was Charles Floyd, who was rumored to have died from a ruptured appendix.5 In 1880 in Europe, Lawson Tait performed the first successful planned appendectomy by removing a gangrenous appendix from a 17-year-old woman. Six years later Reginald Fitz, a pathologist, coined the term “appendicitis” when he read his classic paper at the first meeting of the Association of American Physicians. Fitz correctly described many of the pathophysiologic changes associated with appendicitis and advocated early surgery. Three years later, Charles McBurney described a point “determined by the pressure of one finger” between “one and a half and two inches from the anterior spinous process” which, when palpated, was associated with the greatest discomfort in patients with acute appendicitis (McBurney’s point). The general acceptance that appendicitis is a surgical disease did not occur until several decades later. Early surgical intervention became popular in the early 1900s around the time that King Edward VII perforated his appendix and was operated on days before his coronation.6 The appendix is a hollow, muscular, closed-ended tube arising from the posterior medial surface of the cecum, about 3 cm below the ileocecal valve. Its average length is approximately 10 cm, and its normal capacity is 0.1 to 0.3 mL. The role of the appendix in human physiology is unclear, but some recent studies on biofilms suggest that the appendix may act as a repository for commensal bacteria that inoculate the large bowel and protect it from pathogens.7 Innervation of the appendix is derived from sympathetic and vagus nerves from the superior mesenteric plexus. Afferent fibers that conduct visceral pain from the appendix accompany the sympathetic nerves and enter the spinal cord at the level of the 10th thoracic segment. This causes referred pain to the umbilical area. The majority of patients develop appendicitis because of an acute obstruction of the appendiceal lumen. This is often from an appendicolith, but obstruction can also be caused by a calculi, a tumor, a parasite, or enlarged lymph nodes. Of historical note, one of the more common causes of acute appendicitis from foreign objects in the early 19th century was ingested lead shells buried in quail meat.8 A recent case study describes lumen obstruction from a swallowed tongue stud.9 After acute obstruction, intraluminal pressures rise and mucosal secretions are unable to drain. The resulting distention stimulates visceral afferent pathways and is perceived as a dull, poorly localized pain. Abdominal cramping may occur as a result of hyperperistalsis. Next, ulceration and ischemia develop as the intraluminal pressure exceeds the venous pressure, and bacteria and polymorphonuclear cells begin to invade the appendiceal wall. The appendix may appear grossly normal at this time with evidence of pathology apparent only on microscopic examination. With time, the appendix becomes swollen and begins to irritate surrounding structures, including the peritoneal wall. The pain then becomes more localized to the right lower quadrant. If swelling does not abate, hypoxia leads to necrosis and perforation through the appendiceal serosal layer. This can lead to abscess formation or diffuse peritonitis. The time required for the appendix to perforate is highly variable and controversial; some experts believe that unless a virulent organism or genetic predisposition exists, many cases will spontaneously resolve. In most cases, perforation occurs within 24 to 36 hours. Elders may be more prone to earlier perforation owing to anatomic changes in the appendix associated with aging, such as a narrowed appendiceal lumen, thinner mucosal lining, decreased lymphoid tissue, and atherosclerosis.10 No direct cause of obstruction is noted in approximately one third of cases; it is surmised that in these cases inflammation is caused by viral, bacterial, or parasitic infection with subsequent mucosal ulceration or lymphoid hyperplasia.2 Appendicitis is classically described as starting with the vague onset of dull periumbilical pain and continuing with the development of anorexia, nausea, and vomiting. The pain then migrates to the right lower quadrant, and a low-grade fever may develop. In most instances the patient has not previously experienced similar pain.2 Unfortunately, the presentation may be highly variable. If the appendix is retrocecal or retroiliac, the pain may be blunted by the presence of overlying bowel. If the appendix is elongated, the pain may be referred to the flank, pelvis, or right upper quadrant. Other, less typical symptoms seen with appendicitis are increased urinary frequency and the desire to defecate.2 The most common finding on physical examination is localized abdominal tenderness, usually in the right lower quadrant. Tenderness is often noted over McBurney’s point, an area approximately 2 cm from the anterior superior iliac spine on an imaginary line drawn from that anatomic landmark to the umbilicus. However, because only 35% of patients have the base of their appendix within 5 cm of this point, the pain of appendicitis can be localized in other areas of the abdomen.11 Other physical examination findings include guarding and rigidity. Guarding is usually voluntary, and the patient can often be persuaded to relax. Rigidity is involuntary and implies more significant underlying pathology.2 Both of these findings reflect the tensing of the abdominal wall musculature to protect the underlying bowel. Rebound tenderness, indicative of peritoneal inflammation, is a late finding in patients with appendicitis and usually occurs only after the appendix is significantly inflamed or ruptured. Rebound tenderness can be elicited by gradually pressing over the area of tenderness for 5 to 10 seconds and then quickly withdrawing the hand to just above the skin level. A positive response occurs when the patient reports increased pain as the hand is removed. Patients with rebound tenderness are very uncomfortable with this maneuver, and it should not be repeated unnecessarily.11 Evidence of peritoneal irritation can also be elicited by abdominal wall percussion or by having the patient cough, resulting in pain referred to the right lower quadrant. Isolated rectal tenderness may rarely be the only site of localized pain in patients with a low-lying or retrocecal appendix. In general, however, rectal tenderness has a very limited diagnostic value, especially if concurrent right lower quadrant pain and tenderness are present.12,13 Although a single rectal examination may provide other important information, such as the discovery of a rectal mass or occult blood, multiple examinations are not justified. Although any of the aforementioned signs may be present in patients with acute appendicitis, a review of 10 studies that evaluated 13 signs and symptoms of adult appendicitis identified certain findings that have a high positive likelihood ratio of identifying patients with appendicitis. These were migration of pain from the periumbilical area to the right lower quadrant, right lower quadrant tenderness, and abdominal wall rigidity.2 Conversely, the presence of pain for more than 48 hours, a history of previous episodes of similar pain, the lack of migration and right lower quadrant pain, and the lack of worsening pain with movement or cough make appendicitis less likely.2,13 A similar review of children with appendicitis concluded that fever and rebound tenderness are the most common findings.14 Vital signs are often normal, particularly early in the course. A low-grade fever is present in 15% of all patients with appendicitis, and in 40% of patients if perforation has occurred.15 Young children with acute appendicitis usually are diagnosed after perforation has occurred. This may be because many common childhood illnesses are associated with nausea, anorexia, and vomiting, and young children may have difficulty communicating their discomfort.16 Anatomically, children have a thinner appendiceal wall and a less developed omentum, which may predispose them to perforation and diffuse peritonitis. The diagnosis of acute appendicitis in women of childbearing age is especially challenging. Before the advent of imaging, as many as 45% of women with symptoms suggestive of appendicitis had a normal appendix at surgery, and as many as one third of women with true appendicitis were initially misdiagnosed. Gynecologic disease can easily masquerade as appendicitis owing to the proximity of the right ovary, the fallopian tube, and the uterus to the appendix.17,18 Findings that may be more suggestive of abdominal pain of gynecologic origin are included in Table 93-1. Of note, although cervical motion tenderness is more common in patients with pelvic inflammatory disease, up to a quarter of women with appendicitis may also exhibit it.19 Because obtaining an accurate diagnosis of appendicitis is especially challenging in women, ancillary imaging should strongly be considered. Table 93-1 Pregnant women have an overall risk of developing appendicitis similar to the general population.20 Of the three trimesters, appendicitis appears to occur slightly more often in the second trimester for unknown reasons. The diagnosis of appendicitis during pregnancy can be difficult, as early symptoms of appendicitis such as nausea and vomiting occur frequently in a normal pregnancy. Laboratory values are even less helpful, as leukocytosis is common during pregnancy. The accuracy of the physical examination may also be compromised, as enlargement of the uterus may alter the location of the appendix to the right flank or right upper quadrant. However, one study of pregnant patients with appendicitis found that most women still had presenting symptoms of right lower quadrant pain and tenderness, even when it occurred late in pregnancy.21 Although maternal death from appendicitis is extremely rare, fetal abortion occurs in about 5 to 15% of simple appendicitis cases and up to 37% of complicated cases.22 Because the morbidity is high, extra caution should be taken with pregnant women with abdominal pain. Elders are three times more likely to have a perforated appendix at surgery compared with the general population. There appear to be multiple causes for this, including anatomic age-related changes of the appendix, delay in seeking medical care, atypical presentations, and minimally elevated laboratory values.9 The complication rate after the removal of a normal appendix or an acutely inflamed appendix is roughly 3% and increases approximately three to four times if perforation occurs.14 The most common complication is infection. Localized wound infection occurs in about 2 to 7%, and deep intra-abdominal abscess occurs in 0.8 to 2%, with the higher percentages representing cases in which perforation has occurred.23 Other complications include a prolonged ileus, small bowel obstruction, pneumonia, and urinary retention and infection. In young women, perforation may cause obstruction of the fallopian tubes, leading to infertility, though recent studies suggest this is not as prevalent as once believed.24,25 Pregnant patients with appendicitis have an increased risk of premature labor (15-45%) and fetal death. The mortality of uncomplicated appendicitis in otherwise healthy individuals is less than 0.1% but increases to about 3 to 4% with perforation in patients with comorbidities or advanced age. Although reported perforation rates vary significantly from study to study, the overall average is 20 to 30%. This increases greatly at the extremes of age. Elders have perforation rates as high as 60%, and children younger than 3 years can have perforation rates as high as 80 to 90%.9,15 The identification of factors that may increase a patient’s risk for perforation is evolving. The traditional belief has been that the natural course of appendicitis is inflammation that, if surgery is delayed, ultimately progresses to necrosis and perforation. Many experts now feel that in most patients the natural course of appendicitis is spontaneous resolution without perforation.26 This view is supported by general autopsy reports from the presurgical era, in which up to one third of corpses had evidence of periappendiceal scarring, and by studies that report successful resolution of early appendicitis with nonoperative management.27 It is hypothesized that a subset of the population is genetically predisposed to perforation owing to an early aggressive and exaggerated inflammatory response.28 The evidence for this is the relatively consistent population perforation rate even with the advent of increased imaging and earlier diagnoses. Most cases of perforation occur before medical evaluation, and hospital delays in operative management rarely appear to increase perforation rates.29 C-reactive protein (CRP) is an acute-phase reactant synthesized by hepatocytes in response to an acute injury or inflammation. It has a slower rate of rise than the WBC count and a shorter half-life. A meta-analysis suggests that the overall sensitivity of CRP is approximately 62% and specificity 66%, thereby limiting its usefulness as a stand-alone diagnostic tool in patients with appendicitis.30 Several studies, however, have examined the diagnostic utility of combining the CRP and WBC count. Although most patients with complicated (perforated) appendicitis will have elevations of either or both laboratory values, most authorities have concentrated on the negative predictive value of a normal WBC count and CRP in ruling out appendicitis. Two meta-analyses assessing use of the combined values in adults found that patients with a WBC count below 10,000/mm3 and a CRP below 6 to 12 mg/L were unlikely to have appendicitis (negative likelihood ratio of 0.09), whereas those with a WBC count above 10,000/mm3 and a CRP above 8 mg/L were likely to have appendicitis (positive likelihood ratio of 23.32).31,32 Unfortunately, this test combination appears less helpful in pediatric patients, with one study showing that 7% of patients with acute uncomplicated appendicitis have a normal WBC count and CRP.32 In infection, CRP doubles every 8 hours and peaks at 36 to 50 hours; there is therefore growing interest in tracking a repeat CRP in patients with examination findings equivocal for appendicitis. A recent pediatric study showed that children with appendicitis had a 6-hour CRP increase of at least 4.8 mg/L.33 Several scoring systems have been developed that assign numerical values to different aspects of the history, physical examination, and laboratory test results in patients with right lower quadrant pain in an attempt to assist risk stratification in clinical decision-making. The modified Alvarado score uses a 9-point scoring system as follows: migratory right lower quadrant pain, 1 point; anorexia, 1 point; nausea or vomiting, 1 point; temperature above 37.5° C, 1 point; right lower quadrant tenderness, 2 points; rebound tenderness, 1 point; and leukocytosis, 2 points. A score below 4 is considered low risk, 4 to 6 represents moderate risk, and more than 6 represents high risk. Unfortunately, these scoring systems have yielded inconsistent results when used by themselves to determine the need for operative intervention and were particularly inaccurate when applied to female patients and patients at the extremes of age.2,34 Recent renewed interest in these scales has occurred, however, to determine if they can be used to stratify a patient’s need for advanced imaging. Whereas a low modified Alvarado score (<4) does not reliably exclude acute appendicitis, high scores (>6) may identify patients who would benefit from surgical consultation without imaging studies.35,36 Plain radiographs are not useful in diagnosing appendicitis owing to very low sensitivity and specificity. They are not recommended in the evaluation of appendicitis unless there is a significant concern for bowel obstruction, free air, or pneumonia.37 Barium enemas have a sensitivity of about 80 to 90% for detection of appendicitis, and the diagnosis is essentially ruled out if the entire appendix is filled with contrast.35 Unfortunately, a normal appendiceal lumen is often not visualized with this technique. Barium enemas are most helpful when other colon pathology is high in the differential diagnosis. The use of nuclear imaging with tagged WBCs has been well studied as a diagnostic tool for acute appendicitis.36,38 The reported sensitivities of nuclear scans depend on the tag used and range from 88 to 98%. The overall usefulness of these scans is limited owing to poor specificity; any process causing inflammatory changes in the lower abdomen can lead to a false-positive scan. Graded compression ultrasound (US) has been prospectively shown to improve the clinical accuracy of the diagnosis of acute appendicitis.39 The reported sensitivity and specificity of US for acute appendicitis in most studies are 75 to 90% and 85 to 95%, respectively.40 There have been some recent advances in US techniques. One group reports an astonishing 98% visualization rate (compared with the often cited 2-45%) with the addition of simple repositioning maneuvers.41 Similarly, small studies using contrast-enhanced Doppler or harmonic waves (which allow for better resolution) show promise of higher sensitivities with lower radiation exposure.42–44
Acute Appendicitis
Perspective
Historical Perspective
Principles of Disease: Pathophysiology
Clinical Features
Physical Examination
Special Considerations
Women
More suggestive of appendicitis
Migration of pain and tenderness localized to the right lower quadrant, anorexia, normal or minimally abnormal pelvic examination findings (i.e., isolated right adnexal tenderness)
More suggestive of pelvic inflammatory disease
Several days of symptoms, history of pelvic inflammatory disease, hunger, diffuse lower abdominal pain, bilateral adnexal tenderness, cervical motion tenderness, vaginal discharge
Pregnant Women
Elder Patients
Complications
Diagnostic Strategies
Leucocyte Count and C-Reactive Protein
Diagnostic Scores
Imaging Studies
Barium Enemas
Nuclear Medicine Scans
Ultrasonography
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Acute Appendicitis
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