Emergency Medicine

Appendicitis

For this illness that still demands clinical diagnosis almost 75 years after it was first described, do you know the classic pattern of pain and other symptoms? How does presentation vary with the position of the appendix? What is the best diagnostic imaging method? Who is at risk for perforation? When does laparoscopic appendectomy make sense? These and other questions are addressed.

By Marc S. Itskowitz, MD, and Sandra M. Jones, MD

Acute appendicitis is the most common surgical emergency. There are approximately 250,000 cases of appendicitis per year in the United States, and approximately 7% of persons in Western countries have appendicitis at some time during their lives. The peak incidence is in the second and third decades, with 80% of cases occurring in persons younger than 45 years of age. Appendicitis is 1.3 to 1.6 times more common in males than in females. Incidence reflects a slight familial tendency but little or no seasonal effect. Although cases of appendicitis increased in the first part of the 20th century, there has been a significant decline since the 1930s.

What are the anatomical and functional characteristics of the appendix?

The appendix is attached to the cecum and lies in the right lower quadrant in most patients. Within the right lower quadrant, the appendix can lie medial, lateral, anterior, or posterior to the cecum. The appendix is behind bowel or mesentery or in the pelvis in about 15% of patients. Notable exceptions include patients with intestinal malrotation, in which the cecum and appendix are in the left upper quadrant, and in pregnancy, in which the gravid uterus pushes the cecum and appendix into the right upper quadrant.

The average adult appendix is 9 to 10 cm in length with a diameter of 0.5 to 1 cm. Its blood supply, the appendiceal artery, is a terminal branch of the ileocolic artery, which traverses the length of the appendix. The function of the human appendix is unknown, but the abundance of organized lymphoid tissue within it suggests an immunologic role. Contrary to earlier reports, appendectomy does not increase the risk of colonic malignancy, regardless of the age at which appendectomy is performed.

What is the pathogenesis of appendicitis?

Appendicitis likely develops primarily from lumenal obstruction with subsequent bacterial infection. Fecaliths obstruct the lumen in approximately 35% of acutely inflamed appendices. Other less common lesions include calculi, tumors, parasites, or foreign bodies. In young patients, lymphoid follicular hyperplasia secondary to viral or bacterial infection is thought to be the main culprit in appendiceal obstruction. In older patients, luminal obstruction by neoplasia also occurs. Rarely, barium can occlude the lumen and precipitate appendicitis.

When the appendiceal lumen becomes obstructed, the mucosa continues to secrete fluid until the intraluminal pressure exceeds 60 cm of water. The appendix becomes hypoxic, leading to mucosal ulceration and bacterial invasion. Infection causes more swelling and more ischemia because of small intramural vessel thrombosis. Gangrene and perforation typically occur in 24 to 36 hours, but the timing is highly variable.

At least one-third of inflamed appendices have no obstructing lesion in the lumen, and the pathogenesis of appendicitis in these patients is unknown. Infections by viruses, parasites, or bacteria may initiate appendicitis. Temporospatial clustering of appendicitis cases in one study suggests an infectious trigger. Stimulation of the rich immune system in the appendix by an unidentified luminal antigen could play a role. Chemically induced appendicitis has also been suggested. Blunt or colonoscopic trauma may also precipitate inflammation. Postoperative appendicitis may be related to trauma or fecal stasis.

The decline of appendicitis cases in the United States since the 1930s has led some to suggest that dietary fiber or household hygiene is important in the pathogenesis of appendicitis. According to the "fiber hypothesis," fecaliths develop more readily in people who consume a diet deficient in fiber, because their stools are more tenacious. Societies with high fiber intake (Asia, India, Africa) have less than one-tenth the incidence of appendicitis compared with locations where fiber intake is lower (Europe, North America). A high-fiber diet speeds stool transit times, reduces fecal viscosity, and inhibits fecalith formation.

The "hygiene hypothesis" suggests that decreases in the incidence of appendicitis were caused by improvements in hygiene that made intestinal infections less common.

A genetic predisposition for appendicitis exists. A history of appendicitis in a first-degree relative is associated with a 3.5- to 10-fold relative risk for developing this disorder. The strongest familial associations have been noted when children develop appendicitis at unusually young ages.

What are the clinical manifestations of appendicitis?

The classic sequence of symptoms is dull epigastric or periumbilical abdominal pain followed by anorexia, nausea, vomiting, right lower quadrant pain, and fever. The initial pain is usually not severe and reaches peak intensity in about four hours. After the initial pain subsides, it reappears in the right lower quadrant as a progressively severe ache exacerbated by movement. Patients usually seek medical attention 12 to 48 hours after the pain begins, but delays of up to several days may occur.

Anorexia, nausea, or vomiting usually follows the onset of abdominal pain. A low-grade fever is typical; high fever or rigors suggest a complication or a different diagnosis. Diarrhea occurs in a few patients, and men occasionally report testicular pain.

Atypical appendicitis presentations are common and may occur because of the position of the appendix, the age of the patient, or coexisting conditions such as pregnancy. For example, in retrocecal and retroileal appendicitis, the inflamed appendix is shielded from the anterior abdominal wall by the overlying cecum and ileum. The pain, therefore, seems less intense. The classic shift of pain from the epigastrium to the right lower quadrant may not occur. Urinary frequency may result from direct irritation of the ureter. Muscular rigidity is absent and abdominal tenderness is minimal in these cases of retrocecal and retroileal appendicitis.

In pelvic appendicitis, the inflamed appendix is located in the pelvic region. Pain is often localized to the left lower abdomen. The absence of abdominal tenderness can be deceiving, but tenderness is usually elicited on pelvic examination. The urge to urinate and defecate is prominent, and dysuria and diarrhea may occur.

Appendicitis in infants can be a diagnostic dilemma and the diagnosis is often delayed. Infants cannot report pain, and lethargy, irritability, and anorexia may be the only or earliest symptoms noted by parents. Likewise, the diagnosis of appendicitis in the elderly is often delayed. Even with advanced inflammation, pain is often minimal and fever absent. Appendicitis in the third trimester of pregnancy is also difficult to diagnose. Patients often seek obstetric explanations for their signs and symptoms. Maximal abdominal tenderness may be adjacent to the umbilicus or in the right subcostal area because of cecal displacement by the gravid uterus.

What diagnostic tests are useful in appendicitis?

Appendicitis remains a clinical diagnosis. The three signs and symptoms that are most predictive of acute appendicitis are pain in the right lower quadrant, abdominal rigidity, and migration of pain from the periumbilical region to the right lower quadrant. A reliable historical feature is the characteristic sequence of symptoms, which is periumbilical abdominal pain followed by anorexia, nausea, fever, and right lower quadrant pain. The diagnosis of appendicitis should be reconsidered in patients in whom nausea and emesis are the first signs of illness.

The most valuable physical examination finding is localized tenderness. McBurney's point is located two inches from the anterior superior iliac spine on a line drawn from this process through the umbilicus. However, the site of maximal tenderness may be some distance away from McBurney's point. Rebound tenderness, which suggests peritoneal inflammation, is also referred to the right lower quadrant. Local hyperesthesia of the skin and muscular rigidity may be present.

Several signs of muscle inflammation may also be present. The psoas sign is elicited by asking the patient to raise a straightened right leg against resistance by the examiner; alternatively, the patient lies on the left side and the examiner gently hyperextends the straightened right leg to stretch the psoas major muscle. The obturator sign is sought by passive internal rotation of the right leg with the patient supine and the right hip and knee flexed. Pain in the right lower quadrant with palpation in the left lower quadrant (Rovsing's sign) is associated with a pelvic appendix.

Elevated white blood cell counts are common in acute appendicitis, with the average leukocyte count ranging from 10,000 to 16,000 cells/mm³. Significant peripheral lymphocytopenia is also common. Although leukocytosis is common, 30% of patients with acute appendicitis have a normal white blood cell count. Small numbers of erythrocytes and leukocytes are found in the urine in about half of patients with appendicitis. However, urinary erythrocyte counts exceeding 30 cells per high-power field or leukocyte counts exceeding 20 cells per high-power field suggest a urinary tract disorder.

Pelvic cultures may be useful in sexually active, menstruating women. A beta-human chorionic gonadotropin level is mandatory to rule out pregnancy.

Diagnostic imaging should be performed in patients suspected of having appendicitis in whom the diagnosis is unclear. The best radiologic test is a computed tomography (CT) scan. An abdominal CT scan for acute appendicitis has a sensitivity of 95% and a specificity of 90%. Air in the appendix or a contrast-filled lumen in a normal-appearing appendix virtually excludes the diagnosis. However, a nonvisualized appendix does not rule out appendicitis. A benefit of a complete abdominal CT scan is that it permits visualization of the entire abdomen, and an alternative diagnosis is found in up to 15% of patients. Alternative diagnoses include, but are not limited to, colitis, diverticulitis, small-bowel obstruction, inflammatory bowel disease, adnexal cysts, acute cholecystitis, and acute pancreatitis.

A limitation of abdominal CT scanning is that it takes up to two hours to perform the test after a patient receives the standard oral preparation. In addition, a normal appendix is visualized in only 75% of patients. An appendiceal CT scan can be performed with rectal contrast alone and thin cuts through the right iliac fossa. Because oral contrast is not given, the scan can be performed within 15 minutes, and exposes the patient to only one-third the radiation of standard abdominal CT. Results of an appendiceal CT scan are 93% to 98% accurate in confirming or ruling out appendicitis. The routine use of appendiceal CT in emergency department patients improves patient care both by averting unnecessary appendectomies and by expediting delivery of the necessary medical or surgical treatment.

Computed tomography scans may be less accurate in diagnosing appendicitis in younger children compared with adults. A relative lack of body fat makes it difficult to identify fat streaking and visually separate an inflamed appendix from surrounding tissue or bowel.

Abdominal radiography has a low sensitivity and specificity for the diagnosis of acute appendicitis. Plain radiographs are abnormal in about 55% of patients with early acute appendicitis and are usually not helpful for establishing the diagnosis. Multiple nonspecific abnormalities may be seen, including a right lower quadrant appendicolith, localized right lower quadrant ileus, loss of the psoas shadow, deformity of the cecal outline, and right lower quadrant soft tissue densities. Plain radiographs are not useful for establishing the diagnosis of acute appendicitis and have no role in the diagnostic workup, unless an alternative diagnosis is being considered that might show up on plain film.

Ultrasonography is used to diagnose acute appendicitis, especially in children and pregnant women. It can be very useful for defining pelvic pathology in women. Limitations of ultrasonography are that it is operator-dependent and may be nondiagnostic in those with a large body habitus or a large amount of bowel gas. Although appendicitis may be ruled out if the appearance of the appendix is normal on ultrasonography, a normal appendix is seen in less than 5% of patients. Failure to see the appendix, whether it is diseased or normal, limits the usefulness of this imaging modality for the diagnosis of acute appendicitis. The overall sensitivity of ultrasonography varies between 75% and 90%; specificity ranges from 86% to 100%.

Is there a role for diagnostic laparoscopy in suspected appendicitis?

Laparoscopy is the only diagnostic procedure other than formal laparotomy that allows direct visualization of the appendix. The entire appendix must be seen before the operator can conclude it is normal (free of disease). Feasibility of laparoscopy in obese patients and those with previous abdominal operations depends greatly on the surgeon's experience with the procedure. Diagnostic laparoscopy is most useful for female patients, since a gynecologic cause of symptoms is identified in approximately 10% to 20% of women with suspicion of appendicitis. However, laparoscopy is an invasive procedure with approximately a 5% complication rate, usually associated with the use of general anesthesia.

Between 6% and 30% of patients with a preoperative diagnosis of acute appendicitis do not have appendicitis at laparotomy. This is more common in young women than in any other group. Another acute surgical disease is found instead of appendicitis in 4% to 13% of patients who undergo surgery. Negative exploration occurs in 20% of operations for suspected appendicitis; gastroenteritis and gynecologic disorders are two of the common alternative diagnoses in these cases.

What is the treatment for appendicitis?

Appendectomy is the only acceptable treatment for acute appendicitis. Although appendicitis occasionally resolves without surgery, a policy of nonoperative treatment is hazardous because delay risks perforation. Patients who present within 24 to 72 hours after symptom onset can usually be treated with immediate appendectomy.

In contrast, patients who present with a longer duration of symptoms and have findings localized to the right lower quadrant are presumed to have appendiceal abscesses and should be treated initially with antibiotics, intravenous fluids, and bowel rest. Immediate surgery in these patients is associated with increased morbidity, often requires extensive dissection, and has the additional risks of spreading a localized infection throughout the peritoneal cavity and injuring adjacent structures. Percutaneous CT-guided drainage of the abscess, with appropriate antibiotic coverage, allows the majority of abscesses to resolve. Most patients have a follow-up CT scan when their drain output is minimal and no longer purulent. Antibiotics are continued for 14 days or for one week after documented resolution of the abscess. Elective appendectomy is performed six to ten weeks later to prevent recurrent appendicitis, which occurs in up to 20% of patients. Older patients should also have a colonoscopy or barium enema to rule out cecal pathology.

Appendectomy can be performed through a traditional open procedure or laparoscopically. The operative approach depends on the confidence in the diagnosis, history of prior surgery, and the patient's age, gender, and body habitus. For example, a conventional appendectomy is recommended for a thin, adolescent man with a classic presentation for acute appendicitis. On the other hand, for an obese, premenopausal female with equivocal symptoms, a laparoscopic approach is recommended. Laparoscopy is preferred when the diagnosis of appendicitis is in doubt, especially in premenopausal females and in the obese. A number of published studies have compared open versus laparoscopic surgery for appendicitis. The weight of the evidence suggests that in adults, although operative costs are higher with laparoscopy, overall costs to society are lower because pain is reduced and patients can return to work sooner.

The procedure begins with a diagnostic laparoscopy and continues with appendectomy if appropriate. The success rates are high, and complications are infrequent. Compared with open appendectomy, laparoscopic appendectomy requires less postoperative analgesia, a shorter hospital stay, and a shorter period of disability. Surgical wound infections are also less frequent. Laparoscopy may offer an advantage to patients in whom the diagnosis is uncertain since it permits inspection of other abdominal organs. This benefit is greater for women, who have higher negative appendectomy rates, and in whom laparoscopy often reveals other pathology.

Evidence supports the use of systemic antibiotics to prevent wound infection in appendicitis. In patients with acute nonperforated appendicitis, antibiotic coverage for surgical wound prophylaxis is adequate and postoperative antibiotics are unnecessary. In those with perforated appendicitis, the antibiotic regimen should cover enteric gram-negative rods and anaerobes. A second- or third-generation cephalosporin or a fluoroquinolone plus metronidazole is adequate for most patients. Antibiotics should be continued for seven to ten days.

What are the pathologic findings in appendicitis?

Acute appendicitis is classified as simple, gangrenous, or perforated on the basis of the operative findings and histologic appearance. Focal or extensive necrosis characterizes gangrenous appendicitis, and microscopic perforation is often present. Perforated appendicitis refers to the gross disruption or even dissolution of the appendix.

Microscopically, a cellular infiltrate of lymphocytes and plasma cells is found in early stages. An inflammatory exudate of polymorphonuclear leukocytes involves all layers of the wall and the lumen as the disease progresses. Infectious agents, tumors, and foreign bodies may also be seen. Bacterial overgrowth commonly occurs within the diseased appendix. Aerobic organisms predominate early, while mixed infections are more common in late appendicitis. Common organisms involved in gangrenous and perforated appendicitis include Escherichia coli, Klebsiella, Peptostreptococcus, Bacteroides fragilis, and Pseudomonas species.

Granulomatous appendicitis occurs in a small percentage of patients, most of whom do not develop subsequent signs of inflammatory bowel disease. Uncommonly, appendicitis can be caused by a carcinoid tumor that obstructs the appendiceal lumen.

What are the complications of appendicitis?

Complications of appendicitis include wound infection, perforation, peritonitis, abscess formation, urinary tract disorders, and pylephlebitis.

The overall perforation frequency is 10% to 30%. Perforation within 12 hours of pain onset is unusual, but the risk of this complication rises significantly after 48 hours. Sixty-five percent of patients with perforated appendicitis have been symptomatic longer than 48 hours. Perforation rates are highest in children and the elderly, due to delays in presentation and diagnosis. Perforation occurs in 90% of children younger than two years of age and in 35% of all children. In the elderly, a combination of delayed and atypical presentations, confounding medical conditions, and a decreased index of suspicion contribute to higher rates of perforation. Between 40% and 75% of patients older than 60 years of age have a perforated appendix by the time of the operation.

Perforation is recognized preoperatively in 70% of patients. Suggestive clinical features include symptom duration of more than 36 hours, fever higher than 38.58 C, toxic appearance, diffuse abdominal tenderness, abdominal mass, and marked leukocytosis. Appendiceal perforation leads to multiple complications, including peritonitis, abscess formation, wound infection, urinary retention, and small bowel obstruction. Other intra-abdominal abscesses may develop after perforation, most commonly in the pelvis.

Pylephlebitis is septic thrombophlebitis of the portal venous system. This rare complication of appendiceal perforation is characterized by high fever, rigors, jaundice, and abnormal liver function tests.

What is the mortality rate for appendicitis?

When appendicitis was first described in 1886, the mortality rate for patients with perforated appendicitis approached 30%. This has declined to less than 1% since the introduction of broad-spectrum antibiotics, advanced surgical techniques, safer anesthesia, and improved postoperative care. There is a direct correlation between the perforation rate and the morbidity and mortality of appendicitis in nearly all published reports.