Acute Appendicitis and Peritonitis

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Harrison's Principles of Internal Medicine, 19e
356: Acute Appendicitis and Peritonitis
Danny O. Jacobs
ACUTE APPENDICITIS
INCIDENCE AND EPIDEMIOLOGY
Appendicitis occurs more frequently in Westernized societies. Although its incidence is decreasing for uncertain reasons, acute appendicitis remains
the most common emergency general surgical disease affecting the abdomen, with a rate of approximately 100 per 100,000 personyears in Europe
and the Americas or about 11 cases per 10,000 people annually. Approximately 9% of men and 7% of women will experience an episode during their
lifetime. Appendicitis occurs most commonly in 10 to 19yearolds, although the average age at diagnosis appears to be gradually increasing, as is the
frequency of the disease in African Americans, Asians, and Native Americans. Overall, 70% of patients are less than 30 years old and most are men; the
maletofemale ratio is 1.4:1.
One of the more common complications and most important causes of excess morbidity and mortality is perforation, whether it is contained and
localized or unconstrained within the peritoneal cavity. In contrast to the trend observed for appendicitis and appendectomy, the incidence of
perforated appendicitis (~20 cases per 100,000 personyears) is increasing. The explanation for this phenomenon is unknown. Approximately 20% of
all patients have evidence of perforation at presentation, but the percentage risk is much higher in patients under 5 or over 65 years of age.
PATHOGENESIS OF APPENDICITIS AND APPENDICEAL PERFORATION
Appendicitis was first described in 1886 by Reginald Fitz. Its etiology is still not completely understood. Fecaliths, incompletely digested food residue,
lymphoid hyperplasia, intraluminal scarring, tumors, bacteria, viruses, and inflammatory bowel disease have all been associated with inflammation of
the appendix and appendicitis.
Although not proven, obstruction of the appendiceal lumen is believed to be an important step in the development of appendicitis. In some cases,
obstruction leads to bacterial overgrowth and luminal distension, with an increase in intraluminal pressure that can inhibit the flow of lymph and
blood in some cases. Then, vascular thrombosis and ischemic necrosis with perforation of the distal appendix may occur. Any perforation that occurs
near the base of the appendix should raise concerns about another disease process. Most patients who will perforate do so before they are evaluated
by surgeons.
Appendiceal fecaliths (or appendicoliths) are found in approximately 50% of patients with gangrenous appendicitis who perforate but are rarely
identified in those who have simple disease. As mentioned earlier, the incidence of perforated, but not simple, appendicitis is increasing. The rate of
perforated and nonperforated appendicitis is correlated in men but not in women. Together these observations suggest that the underlying
pathophysiologic processes are different and that simple appendicitis does not always progress to perforation. Furthermore, some cases of simple
acute appendicitis may resolve spontaneously or with antibiotic therapy, and recurrent disease is remotely possible. The relative frequency of these
events is unknown.
When perforation occurs, the resultant leak may be contained by the omentum or other surrounding tissues to form an abscess. Free perforation
normally causes severe peritonitis. These patients may also develop infective suppurative thrombosis of the portal vein and its tributaries along with
intrahepatic abscesses. The prognosis of the very unfortunate patients who develop this dreaded complication is very poor.
CLINICAL MANIFESTATIONS
More refined approaches to diagnosis, supportive care, and surgical intervention are likely responsible for the remarkable decrease in the risk of
mortality from simple appendicitis to currently less than 1%. Nevertheless, it is still important to identify patients who might have appendicitis as early
as possible to minimize their risk of developing complications. Patients who have had symptoms for more than 48 h are more likely to perforate.
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356: Acute Appendicitis and Peritonitis, Danny O. Jacobs Page 1 / 8
Appendicitis should be included in the differential diagnosis of abdominal pain for every patient in any age group unless it is certain that the organ has
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been previously removed (Table 3561).
intrahepatic abscesses. The prognosis of the very unfortunate patients who develop this dreaded complication is very poor.
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CLINICAL MANIFESTATIONS
More refined approaches to diagnosis, supportive care, and surgical intervention are likely responsible for the remarkable decrease in the risk of
mortality from simple appendicitis to currently less than 1%. Nevertheless, it is still important to identify patients who might have appendicitis as early
as possible to minimize their risk of developing complications. Patients who have had symptoms for more than 48 h are more likely to perforate.
Appendicitis should be included in the differential diagnosis of abdominal pain for every patient in any age group unless it is certain that the organ has
been previously removed (Table 3561).
TABLE 3561
Some Conditions That Mimic Appendicitis
Crohn’s disease Meckel’s diverticulitis
Cholecystitis or other gallbladder disease Mittelschmerz
Diverticulitis Mesenteric adenitis
Ectopic pregnancy Omental torsion
Endometriosis Pancreatitis
Gastroenteritis or colitis Lower lobe pneumonia
Gastric or duodenal ulceration Pelvic inflammatory disease
Hepatitis Ruptured ovarian cyst or other cystic disease of the ovaries
Kidney disease, including nephrolithiasis Smallbowel obstruction
Liver abscess Urinary tract infection
The appendix’s anatomical location, which varies, directly influences how the patient presents for care. Where the appendix can be “found” ranges
from local differences in how the appendiceal body and tip lie relative to its attachment to the cecum (Figs. 3561 and 3562), to where the appendix
is actually situated in the peritoneal cavity—for example, from its typical location in the right lower quadrant, to the pelvis, right flank, right upper
quadrant (as may be observed during pregnancy), or even the left side of the abdomen for patients with malrotation or who have severely redundant
colons.
FIGURE 3561
Regional anatomical variations of the appendix.
FIGURE 3562
Locations of the appendix and cecum.
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FIGURE 3562
Locations of the appendix and cecum.
Because the differential diagnosis of appendicitis is so extensive, deciding if a patient has appendicitis can be difficult (Table 3562). Soliciting an
appropriate history requires detecting symptoms that might suggest alternative diagnoses. Patients with appendicitis may not have any abdominal
discomfort early in the disease process. Furthermore, many patients may not present with the classically described history or physical findings.
TABLE 3562
Relative Frequency of Common Presenting Symptoms
Symptoms Frequency
Abdominal pain >95%
Anorexia >70%
Constipation 4–16%
Diarrhea 4–16%
Fever 10–20%
Migration of pain to right lower quadrant 50–60%
Nausea >65%
Vomiting 50–75%
What is the classic history? Nonspecific complaints occur first. Patients may notice changes in bowel habits or malaise and vague, perhaps intermittent,
crampy, abdominal pain in the epigastric or periumbilical region. The pain subsequently migrates to the right lower quadrant over 12–24 h, where it is
sharper and can be definitively localized as transmural inflammation when the appendix irritates the parietal peritoneum. Parietal peritoneal irritation
may be associated with local muscle rigidity and stiffness. Patients with appendicitis will most often observe that their nausea, if present, followed the
development of abdominal pain, which can help distinguish them from patients with gastroenteritis, for example, where nausea occurs first. Emesis, if
present, also occurs after the onset of pain and is typically mild and scant. Thus, timing of the onset of symptoms and the characteristics of the
patient’s pain and any associated findings must be rigorously assessed. Anorexia is so common that the diagnosis of appendicitis should be
questioned in its absence.
Arriving at the correct diagnosis is even more challenging when the appendix is not located in the right lower quadrant, in women of childbearing age,
and in the very young or elderly. Because the differential diagnosis of appendicitis is so broad, often the key question to answer expeditiously is
whether the patient has appendicitis or some other condition that requires immediate operative intervention. A major concern is that the likelihood of
a delay in diagnosis is greater if the appendix is unusually positioned. All patients should undergo a rectal examination. An inflamed appendix located
may be associated with local muscle rigidity and stiffness. Patients with appendicitis will most often observe that their nausea, if present, followed the
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development of abdominal pain, which can help distinguish them from patients with gastroenteritis, for example, where nausea occurs first. Emesis, if
present, also occurs after the onset of pain and is typically mild and scant. Thus, timing of the onset of symptoms and the characteristics of the
patient’s pain and any associated findings must be rigorously assessed. Anorexia is so common that the diagnosis of appendicitis should be
questioned in its absence.
Arriving at the correct diagnosis is even more challenging when the appendix is not located in the right lower quadrant, in women of childbearing age,
and in the very young or elderly. Because the differential diagnosis of appendicitis is so broad, often the key question to answer expeditiously is
whether the patient has appendicitis or some other condition that requires immediate operative intervention. A major concern is that the likelihood of
a delay in diagnosis is greater if the appendix is unusually positioned. All patients should undergo a rectal examination. An inflamed appendix located
behind the cecum or below the pelvic brim may prompt very little tenderness of the anterior abdominal wall.
Patients with pelvic appendicitis are more likely to present with dysuria, urinary frequency, diarrhea, or tenesmus. They may only experience pain in
the suprapubic region on palpation or on rectal or pelvic examination. A pelvic examination in women is mandatory to rule out conditions affecting
urogynecologic organs that can cause abdominal pain and mimic appendicitis such as pelvic inflammatory disease, ectopic pregnancy, and ovarian
torsion. The relative frequencies of some presenting signs are displayed in Table 3563.
TABLE 3563
Relative Frequency of Some Presenting Signs
Signs Frequency (%)
Abdominal tenderness >95%
Right lower quadrant tenderness >90%
Rebound tenderness 30–70%
Rectal tenderness 30–40%
Cervical motion tenderness 30%
Rigidity ~10%
Psoas sign 3–5%
Obturator sign 5–10%
Rovsing’s sign 5%
Palpable mass <5%
Patients with simple appendicitis normally only appear mildly ill with a pulse and temperature that are usually only slightly above normal. The provider
should be concerned about other disease processes beside appendicitis or the presence of complications such as perforation, phlegmon, or abscess
formation if the temperature is >38.3°C (~101°F) and if there are rigors.
Patients with appendicitis will be found to lie quite still to avoid peritoneal irritation caused by movement, and some will report discomfort caused by a
bumpy car ride on the way to the hospital or clinic, coughing, sneezing, or other actions that replicate a Valsalva maneuver. The entire abdomen should
be examined systematically starting in an area where the patient does not report discomfort if possible. Classically, maximal tenderness is identified in
the right lower quadrant at or near McBurney’s point, which is located approximately onethird of the way along a line originating at the anterior iliac
spine and running to the umbilicus. Gentle pressure in the left lower quadrant may elicit pain in the right lower quadrant if the appendix is located
there. This is Rovsing’s sign (Table 3564). Evidence of parietal peritoneal irritation is often best elicited by gentle abdominal percussion, jiggling the
patient’s gurney or bed, or mildly bumping the feet.
TABLE 3564
Classic Signs of Appendicitis in Patients with Abdominal Pain
Maneuver Findings
Rovsing’s sign Palpating in the left lower quadrant causes pain in the right lower quadrant
the right lower quadrant at or near McBurney’s point, which is located approximately onethird of the way along a line originating at the anterior iliac
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spine and running to the umbilicus. Gentle pressure in the left lower quadrant may elicit pain in the right lower quadrant if the appendix is located
there. This is Rovsing’s sign (Table 3564). Evidence of parietal peritoneal irritation is often best elicited by gentle abdominal percussion, jiggling the
patient’s gurney or bed, or mildly bumping the feet.
TABLE 3564
Classic Signs of Appendicitis in Patients with Abdominal Pain
Maneuver Findings
Rovsing’s sign Palpating in the left lower quadrant causes pain in the right lower quadrant
Obturator sign Internal rotation of the hip causes pain, suggesting the possibility of an inflamed appendix located in the pelvis
Iliopsoas sign Extending the right hip causes pain along posterolateral back and hip, suggesting retrocecal appendicitis
Atypical presentation and pain patterns are common, especially in the very old or the very young. Diagnosing appendicitis in children can be especially
challenging because they tend to respond so dramatically to stimulation and obtaining an accurate history may be difficult. In addition, it is important
to remember that the smaller omentum found in children may be less likely to wall off an appendiceal perforation. Observing the child in a quiet
surrounding may be helpful.
Signs and symptoms of appendicitis can be subtle in the elderly who may not react as vigorously to appendicitis as younger people. Pain, if noticed,
may be minimal and have originated in the right lower quadrant or, otherwise, where the appendix is located. It may never have been noticed to be
intermittent, or there may only be significant discomfort with deep palpation. Nausea, anorexia, and emesis may be the predominant complaints. The
rare patient may even present with signs and symptoms of distal bowel obstruction secondary to appendiceal inflammation and phlegmon or abscess
formation.
LABORATORY TESTING
Laboratory testing does not identify patients with appendicitis but can help the clinician work through the differential diagnosis. The white blood cell
count is only mildly to moderately elevated in approximately 70% of patients with simple appendicitis (with a leukocytosis of 10,000–18,000 cells/μL). A
“left shift” toward immature polymorphonuclear leukocytes is present in >95% of cases. A sickle cell preparation may be prudent to obtain in those of
African, Spanish, Mediterranean, or Indian ancestry. Serum amylase and lipase levels should be measured.
Urinalysis is indicated to help exclude genitourinary conditions that may mimic acute appendicitis, but a few red or white blood cells may be present as
a nonspecific finding. However, an inflamed appendix that abuts the ureter or bladder may cause sterile pyuria or hematuria. Every woman of
childbearing age should have a pregnancy test. Cervical cultures are indicated if pelvic inflammatory disease is suspected. Anemia and guaiacpositive
stools should raise concern about the presence of other diseases or complications such as cancer.
IMAGING
Plain films of the abdomen are rarely helpful and so are not routinely obtained unless the clinician is worried about other conditions such as intestinal
obstruction, perforated viscus, or ureterolithiasis. Less than 5% of patients will present with an opaque fecalith in the right lower quadrant. The
presence of a fecalith is not diagnostic of appendicitis, although its presence in an appropriate location where the patient complains of pain is
suggestive.
The effectiveness of ultrasonography as a tool to diagnosis appendicitis is highly operator dependent. Even in very skilled hands, the appendix may not
be visualized. Its overall sensitivity is 0.86, with a specificity of 0.81. Ultrasonography, especially intravaginal techniques, appears to be most useful for
identifying pelvic pathology in women. Ultrasonographic findings suggesting the presence of appendicitis include wall thickening, an increased
appendiceal diameter, and the presence of free fluid.
The sensitivity and specificity of computed tomography (CT) are 0.94 and 0.95, respectively. Thus, CT imaging, given its high negative predictive value,
may be helpful if the diagnosis is in doubt, although studies performed early in the course of disease may not have any typical radiographic findings.
Suggestive findings on CT examination include dilatation >6 mm with wall thickening, a lumen that does not fill with enteric contrast, and fatty tissue
stranding or air surrounding the appendix, which suggests inflammation (Figs. 3563 and 3564). The presence of luminal air or contrast is not
consistent with a diagnosis of appendicitis. Furthermore, nonvisualization of the appendix is a nonspecific finding that should not be used to rule out
the presence of appendiceal or periappendiceal inflammation.
FIGURE 3563
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The sensitivity and specificity of computed tomography (CT) are 0.94 and 0.95, respectively. Thus, CT imaging, given its high negative predictive value,
may be helpful if the diagnosis is in doubt, although studies performed early in the course of disease may not have any typical radiographic findings.
Suggestive findings on CT examination include dilatation >6 mm with wall thickening, a lumen that does not fill with enteric contrast, and fatty tissue
stranding or air surrounding the appendix, which suggests inflammation (Figs. 3563 and 3564). The presence of luminal air or contrast is not
consistent with a diagnosis of appendicitis. Furthermore, nonvisualization of the appendix is a nonspecific finding that should not be used to rule out
the presence of appendiceal or periappendiceal inflammation.
FIGURE 3563
Computed tomography with oral and intravenous contrast of acute appendicitis. There is thickening of the wall of the appendix and
periappendiceal stranding (arrow).
FIGURE 3564
Appendiceal fecalith (arrow).
SPECIAL PATIENT POPULATIONS
Appendicitis in the most common extrauterine general surgical emergency observed during pregnancy. Early symptoms of appendicitis such as nausea
and anorexia may be overlooked. Diagnosing appendicitis in pregnant patients may be especially difficult because as the uterus enlarges the appendix
may be pushed higher along the right flank even to the right upper quadrant or because the gravid uterus may obscure typical physical findings.
Ultrasonography may facilitate early diagnosis. A high index of suspicion is required because of the effects of unrecognized and untreated appendicitis
on the fetus. For example, the fetal mortality rate is four times greater (from 5 to 20%) in patients with perforation.
Immunocompromised patients may present with only mild tenderness and may have many other disease processes in their differential diagnosis,
including atypical infections from mycobacteria, Cytomegalovirus, or other fungi. Enterocolitis is a concern and may be present in patients who
present with abdominal pain, fever, and neutropenia due to chemotherapy. CT imaging may be very helpful, although it is important not to be overly
cautious and delay operative intervention for those patients who are believed to have appendicitis.
TREATMENT
356: Acute Appendicitis and Peritonitis, Danny O. Jacobs
TREATMENT Acute Appendicitis Page 6 / 8
In the absence of contraindications, a patient who has a strongly suggestive medical history and physical examination with supportive laboratory
findings should undergo appendectomy urgently. In this instance, imaging studies are not required. In patients in whom the evaluation is suggestive
including atypical infections from mycobacteria, Cytomegalovirus, or other fungi. Enterocolitis is a concern and may be present in patients who
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present with abdominal pain, fever, and neutropenia due to chemotherapy. CT imaging may be very helpful, although it is important not to be overly
cautious and delay operative intervention for those patients who are believed to have appendicitis.
TREATMENT
TREATMENT Acute Appendicitis
In the absence of contraindications, a patient who has a strongly suggestive medical history and physical examination with supportive laboratory
findings should undergo appendectomy urgently. In this instance, imaging studies are not required. In patients in whom the evaluation is suggestive
but not convincing, imaging and further study are appropriate. Pelvic ultrasonography is indicated in women of childbearing age. Thereafter, CT
may accurately indicate the presence of appendicitis or other intraabdominal processes that warrant intervention. Whenever the diagnosis is
uncertain, it is prudent to observe the patient and repeat the abdominal examination over 6–8 h. Any evidence of progression is an indication for
operation. Narcotics can be given to patients with severe discomfort, especially if the first abdominal examination is completed before drugs are
administered.
All patients should be fully prepared for surgery and have any fluid and electrolyte abnormalities corrected. Either laparoscopic or open
appendectomy is a satisfactory choice for patients with uncomplicated appendicitis. Management of those who present with a mass representing a
phlegmon or abscess can be more difficult. Such patients are best served by treatment with broadspectrum antibiotics, drainage if there is an
abscess >3 cm in diameter, and parenteral fluids and bowel rest if they appear to respond to conservative management. The appendix can then be
more safely removed 6–12 weeks later when inflammation has diminished.
Laparoscopic appendectomy now accounts for approximately 60% of all appendectomies. Laparoscopic appendectomy is associated with less
postoperative pain and, possibly, a shorter length of stay and faster return to normal activity. Patients who undergo laparoscopic appendectomy
also appear to have fewer wound infections, although the risk of intraabdominal abscess formation may be higher. A laparoscopic approach may
also be useful when the exact diagnosis is uncertain, yet direct visualization and exploration of the abdomen are needed. A laparoscopic approach
may also facilitate exposure in those who are very obese. A thorough examination of the abdomen is indicated if the appendix appears normal at
operation, which can be expected to occur in up to 15–20% of cases.
Absent complications, most patients can be discharged within 24–40 h of operation. The most common postoperative complications are fever and
leukocytosis. Continuation of these findings beyond 5 days should raise concern for the presence of an intraabdominal abscess. The mortality rate
for uncomplicated, nonperforated appendicitis is 0.1–0.5%, which approximates the overall risk of general anesthesia. The mortality rate for
perforated appendicitis or other complicated disease is much higher, ranging from 3% overall to a high as 15% in the elderly.
ACUTE PERITONITIS
Acute peritonitis, or inflammation of the visceral and parietal peritoneum, is most often but not always infectious in origin, resulting from perforation
of a hollow viscus. This is called secondary peritonitis, as opposed to primary or spontaneous peritonitis, when a specific intraabdominal source
cannot be identified. In either instance, the inflammation can be localized or diffuse.
ETIOLOGY
Infective organisms may contaminate the peritoneal cavity after spillage from a hollow viscus, because of a penetrating wound of the abdominal wall,
or because of the introduction of a foreign object like a peritoneal dialysis catheter or port that becomes infected. Secondary peritonitis most
commonly results from perforation of the appendix, colonic diverticuli, or the stomach and duodenum. It may also occur as a complication of bowel
infarction or incarceration, cancer, inflammatory bowel disease, and intestinal obstruction or volvulus. Conditions that may cause secondary bacterial
peritonitis and their mechanisms are listed in Table 3565. Over 90% of the cases of primary or spontaneous bacterial peritonitis occur in patients
with ascites or hypoproteinemia (<1 g/L).
Aseptic peritonitis is most commonly caused by the abnormal presence of physiologic fluids like gastric juice, bile, pancreatic enzymes, blood, or urine.
It can also be caused by the effects of normally sterile foreign bodies like surgical sponges or instruments. More rarely, it occurs as a complication of
systemic diseases like lupus erythematosus, porphyria, and familial Mediterranean fever. The chemical irritation caused by stomach acid and activated
pancreatic enzymes is extreme and secondary bacterial infection may occur.
TABLE 3565
Conditions Leading to Secondary Bacterial Peritonitis
Bowel Perforation Perforation or Leakage of Other Organs
Appendicitis trauma (blunt or penetrating) Biliary leakage (e.g., after liver biopsy)
Anastomotic leakage Cholecystitis
Aseptic peritonitis is most commonly caused by the abnormal presence of physiologic fluids like gastric juice, bile, pancreatic enzymes, blood, or urine.
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It can also be caused by the effects of normally sterile foreign bodies like surgical sponges or instruments. More rarely, it occurs as a complication of
systemic diseases like lupus erythematosus, porphyria, and familial Mediterranean fever. The chemical irritation caused by stomach acid and activated
pancreatic enzymes is extreme and secondary bacterial infection may occur.
TABLE 3565
Conditions Leading to Secondary Bacterial Peritonitis
Bowel Perforation Perforation or Leakage of Other Organs
Appendicitis trauma (blunt or penetrating) Biliary leakage (e.g., after liver biopsy)
Anastomotic leakage Cholecystitis
Adhesion Intraperitoneal bleeding
Diverticulitis Pancreatitis
Iatrogenic (including endoscopic perforation) Salpingitis
Ingested foreign body Traumatic or other rupture of urinary bladder
Inflammation Loss of peritoneal integrity
Intussusception Intraperitoneal chemotherapy
Neoplasms Iatrogenic (e.g., postoperative foreign body)
Obstruction Perinephric abscess
Peptic ulcer disease Peritoneal dialysis or other indwelling devices
Strangulated hernia Trauma
Vascular (including ischemia or embolus)
CLINICAL FEATURES
The cardinal signs and symptoms of peritonitis are acute, typically severe, abdominal pain with tenderness and fever. How the patient’s complaints of
pain are manifested depends on their overall physical health and whether the inflammation is diffuse or localized. Elderly and immunosuppressed
patients may not respond as aggressively to the irritation. Diffuse, generalized peritonitis is most often recognized as diffuse abdominal tenderness
with local guarding, rigidity, and other evidence of parietal peritoneal irritation. Physical findings may only be identified in a specific region of the
abdomen if the intraperitoneal inflammatory process is limited or otherwise contained as may occur in patients with uncomplicated appendicitis or
diverticulitis. Bowel sounds are usually absent to hypoactive.
Most patients present with tachycardia and signs of volume depletion with hypotension. Laboratory testing typically reveals a significant leukocytosis,
and patients may be severely acidotic. Radiographic studies may show dilatation of the bowel and associated bowel wall edema. Free air, or other
evidence of leakage, requires attention and could represent a surgical emergency. In stable patients in whom ascites is present, diagnostic
paracentesis is indicated, where the fluid is tested for protein and lactate dehydrogenase and the cell count is measured.
THERAPY AND PROGNOSIS
Whereas mortality rates can be less than 10% for reasonably healthy patients with relatively uncomplicated, localized peritonitis, mortality rates >40%
have been reported for the elderly or immunocompromised. Successful treatment depends on correcting any electrolyte abnormalities, restoration of
fluid volume and stabilization of the cardiovascular system, appropriate antibiotic therapy, and surgical correction of any underlying abnormalities.
Acknowledgment
The wisdom and expertise of Dr. William Silen is gratefully acknowledged in this updated chapter on acute appendicitis and peritonitis.

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