Appendicitis

Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. The diagnosis can frequently be established clinically, but imaging is used in uncertain cases. Computed tomography (CT) scan provides the highest diagnostic accuracy. Perforation occurs in 13%–20% of cases and can present as localized (abscess/phlegmon) or free perforation with generalized peritonitis. The standard treatment is appendectomy, but localized perforations are frequently managed non-operatively with antibiotics.

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Overview

Definition

Appendicitis is the inflammation of the vermiform appendix.

Epidemiology

  • Lifetime risk: approximately 8%
  • 6% of the population gets appendicitis.
  • Peak incidence: 10–19 years of age
  • Males > females
  • The most common acute surgical problem in the pediatric population

Etiology

  • Obstruction of appendiceal orifice (implicated, but not often proven)
  • Cause of obstruction varies with age.
    • Children and young adults: lymphoid follicular hyperplasia secondary to infection
    • Older adults:
      • Fecaliths
      • Calculi
      • Fibrosis
      • Tumors (benign or malignant)
    • Rare: parasites (usually in endemic areas)

Pathophysiology and Clinical Presentation

Pathophysiology

  • Obstruction of appendiceal orifice is the 1st step (presumed).
  • Mucus accumulation and luminal distention:
    • Bacterial overgrowth (mixed; aerobes and anaerobes):
      • Escherichia coli 
      • Peptostreptococcus
      • Pseudomonas
      • Bacteroides fragilis
    • Increase in transmural pressure → thrombosis and occlusion of small vessels
    • Ischemia and necrosis (gangrene)
    • Eventual perforation

Time course

Early:

  • Usually first 24 hours
  • Distention of the appendix stimulates T8–10 afferent nerves.
  • Vague periumbilical pain develops.

Late:

  • Usually after 24 hours
  • Invasion of appendiceal wall by bacteria + ischemia
  • Propagation of neutrophilic exudate → fibropurulent reaction involving serosal surface
  • Peritoneal irritation → localized pain and tenderness

Perforation:

  • Affects 13%–20% of cases
  • In 65% of cases, symptoms last longer than 48 hours.
  • In 20% of cases, symptoms last less than 24 hours.
  • More likely with calculus as the obstructing culprit:
    • Walled-off perforation: abscess formation
    • Free perforation: generalized peritonitis

Acute appendicitis

Image: “Acute Appendicitis” by Ed Uthman. License: CC BY 2.0

Clinical presentation

Classic:

  • Periumbilical pain that later migrates to the right lower quadrant (RLQ)
  • Anorexia
  • Nausea/vomiting
  • Fever

Atypical:

  • Indigestion
  • Diarrhea
  • Generalized malaise

Anatomic factors:

  • Anterior appendix (most common): pronounced localized RLQ pain
  • Retrocecal: dull abdominal pain
  • Pelvic: dysuria, diarrhea, tenesmus (from bladder and rectal irritation)

Diagnosis

History

  • Duration of symptoms: typically 24–48 hours
  • Abdominal pain:
    • Sudden onset 
    • Constant, becoming progressively worse
    • Exacerbated by movement
  • Anorexia, nausea, diarrhea/constipation may or may not be present.
  • Symptoms may be vague/atypical in the elderly.
  • Adults (eliminate other causes):
    • History of inflammatory bowel disease
    • History of colorectal cancer/previous colonoscopy
    • Reproductive/sexually transmitted diseases in women (rule out pelvic inflammatory disease (PID), ectopic pregnancy)
  • Children:
    • Most common in 5–12-year-olds
    • Very rare in neonates
    • Rule out viral illness:
      • History of concurrent or preceding respiratory symptoms
      • History of sick contacts with similar symptoms

Physical exam

General:

  • Low-grade fever (up to 38.3°C (101°F))
  • High fever may indicate late appendicitis/necrosis/perforation.
  • Desire to lie still, with difficulty ambulating (common in children)
  • Signs of dehydration if prolonged vomiting/anorexia:
    • Tachycardia
    • Orthostatic hypotension
    • Decreased urinary output

Abdominal exam:

  • RLQ tenderness
  • Localized rebound tenderness (peritoneal irritation)
  • Signs:
    • McBurney’s point tenderness: maximal tenderness at 3.8–5.0 cm (1.5–2 in) from anterior iliac spine on a straight line to the umbilicus 
    • Rovsing’s sign: pain in the RLQ with palpation of the left lower quadrant
    • Psoas sign: RLQ pain with passive hip extension (characteristic of retrocecal appendix)
    • Obturator sign: RLQ pain with internal hip rotation with a flexed knee (pelvic appendix)
  • Generalized peritonitis suggests perforation.

Rectal exam:

  • Not helpful for establishing appendicitis diagnosis
  • May be helpful if an alternative diagnosis is suspected

Pelvic exam:

  • May be needed in a female if PID is suspected
  • Appendicitis (especially pelvic) may also produce tenderness on pelvic exam.

Laboratory studies

  • Complete blood count (CBC): leukocytosis with a left shift
  • Inflammatory markers: ↑ erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
  • Chemistry may show dehydration pattern: low K (potassium), low Na (sodium), metabolic alkalosis
  • Urinalysis: may show mild pyuria due to proximity of the right ureter
  • Pregnancy test: Perform on all females of reproductive age.

Alvarado score

  • A numerical scale for predicting the likelihood of appendicitis based on clinical and laboratory findings
  • Facilitates decision making
  • Mnemonic: MANTRELS
Table: Alvarado score
SymptomsMigratory pain in the right iliac fossa1
Anorexia1
Nausea and vomiting1
SignsTenderness in the right iliac fossa2
Rebound tenderness1
Elevated temperature1
Laboratory findingsLeukocytosis2
Shift to left1
Total10
Interpretation:
  • 0–4: Appendicitis is less likely.
  • 5–6: Appendicitis is possible; imaging evaluation needed
  • 7–8: Appendicitis is probable → surgical consultation
  • 9–10: Appendicitis is highly likely → surgical consultation

Imaging

Imaging is not required for diagnosis if the Alvarado score is very low (< 3) or high (> 7).

  • Computed tomography (CT) scan:
    • Highest diagnostic accuracy
    • Should be performed with intravenous contrast unless contraindicated (renal failure, allergy)
    • Findings of appendicitis:
      • Appendiceal diameter > 6 mm (0.24 in) with occluded lumen
      • Appendiceal wall thickening  > 2 mm (0.08 in)
      • Appendiceal wall enhancement
      • Periappendiceal fat stranding
      • Appendicolith (in about 25% of cases)
  • Ultrasound (US):
    • Lower diagnostic accuracy than CT
    • Operator dependent
    • Preferred test in children and pregnant women as it avoids radiation
    • Signs of appendicitis:
      • Non-compressible appendix
      • Appendix diameter > 6 cm (2.4 in)
      • Focal pain with pressure from US probe
      • Increased echogenicity of surrounding fat
      • Fluid in RLQ
      • “Target sign”:
        • Hypoechoic (fluid-filled lumen)
        • Hyperechoic (mucosa/submucosa)
        • Hypoechoic (muscularis layer)
  • Magnetic resonance imaging (MRI):
    • Inferior to CT scan
    • An alternative when CT is contraindicated

Management

Initial management

  • Intravenous resuscitation (hydrate and replace electrolytes)
  • NPO (nothing by mouth)
  • Analgesia, nausea control
  • Intravenous antibiotics:
    • Cefoxitin
    • Cefazolin + metronidazole
    • Clindamycin + ciprofloxacin/aztreonam

Non-perforated appendicitis

Non-operative management:

  • Growing evidence that appendicitis can be managed with antibiotics alone
  • 90% will initially respond to antibiotics.
  • Recurrence rate of 20%–30% in the first year

Appendectomy:

  • Laparoscopic:
    • Lower rate of wound infections
    • Less pain on postoperative day 1
    • Shorter hospital stay
  • Open:
    • Lower rate of intraabdominal infections
    • Shorter operative time

Laparoscopic appendectomy

Image: “Appendix-Entfernung” by Life-of-hannes.de. License: Public Domain

Perforated appendicitis

Initial non-operative management:

  • Preferred approach as immediate surgery has high risk of complications:
    • More extensive surgery (ileocecectomy) may be required
    • Risk of postoperative abscess, fistula
  • Indicated for contained perforation:
    • Cecal phlegmon or abscess > 3 cm (1.18 in) on CT scan
    • Stable patient without diffuse peritonitis
  • Intravenous antibiotics: broad-spectrum enteric coverage
  • Intravenous fluids and bowel rest
  • Radiologically guided drainage of an abscess
  • Successful (patient is discharged home with 7–10-day course of oral antibiotics):
    • ↓ Pain
    • ↓ Fever
    • ↓ Leukocytosis
  • Unsuccessful: rescue appendectomy during the same admission

Interval appendectomy:

  • Generally recommended 6–8 weeks after successful nonoperative management 
  • If not performed:
    • Up to 30% risk of recurrence during the 1st year
    • 10%–29% risk of neoplasm in perforated appendix 
  • Colonoscopy should also be considered for patients > 40.

Immediate appendectomy:

  • Always indicated for unstable patient with generalized peritonitis/free perforation
  • May require more extensive resection (ileocecectomy)
  • Requires washout and drainage of peritoneal cavity
  • Can also be performed for contained perforation with small phlegmon or abscess (< 3 cm (1.18 in))

Prognosis

  • Mortality is low: 0.09%–4%
  • Complications of appendectomy:
    • Wound infection: 3.3%–10.3%
    • Pelvic/abdominal abscess: 9.4%
    • Stump appendicitis: if appendix was not completely removed, leaving more than 0.5 cm (0.2 in) stump

Differential Diagnosis

Gastrointestinal

  • Gastroenteritis: acute self-limited viral illness presenting with abdominal pain, vomiting, and diarrhea. Imaging and labs may be largely normal. Condition is treated supportively with bowel rest and intravenous hydration.
  • Mesenteric lymphadenitis: inflammation of mesenteric lymph nodes associated with acute or chronic abdominal pain. Mesenteric lymphadenitis commonly localizes to RLQ because of a large number of lymph nodes in that area. Computed tomography scan/US will show lymphadenopathy.
  • Epiploic appendagitis: ischemia/infarction of the colonic fatty appendages. Epiploic appendagitis presents with acute or subacute lower abdominal pain. Computed tomography scan can confirm the diagnosis. Usually, this self-limited illness is treated with oral anti-inflammatory medications.
  • Meckel’s diverticulitis: inflammation of Meckel’s diverticulum. The condition may be impossible to clinically distinguish from acute appendicitis as the pain is similar; however, it may be more central or left-sided. Occasionally, there is a history of intermittent lower gastrointestinal bleeding. Computed tomography scan may or may not be diagnostic. Sometimes, diagnosis is made during surgery.
  • Right-sided diverticulitis: inflammation of colonic diverticula. Usually left-sided, but right-sided presentation can also occur, especially in young patients and in Asian populations. Patients present with RLQ pain, fever, and change in bowel habits. Diagnosis is made by CT scan.
  • Terminal ileitis: inflammation of the terminal ileum that can have an antecedent history of abdominal cramping, weight loss, and diarrhea. The ileitis may be non-specific, due to Crohn’s disease or Yersinia infection. Diagnosis is made acutely by CT scan. Colonoscopy (Crohn’s) and serum antibody titers (Yersinia) can help establish the etiology.

Genitourinary

  • Right ureteric colic: obstructive stone in the right ureter that presents as intermittent (colicky) pain of the right flank/groin. Urinalysis will show the presence of red blood cells. Diagnosis is established by non-contrast CT scan.
  • Urinary tract infection: bacterial infection of the urinary tract in the form of cystitis (bladder infection) or right-sided acute pyelonephritis (kidney involvement). Presents with suprapubic pain and dysuria (cystitis) or right costovertebral angle tenderness and fever (pyelonephritis). Diagnosis is made by urinalysis and CT scan.

Gynecologic

  • Right-sided ectopic pregnancy: pregnancy in the right fallopian tube. Presents with right-sided abdominal pain. When ruptured, can present with fever, sepsis, and peritonitis. Usually, there is a history of a missed menstrual period. Findings include a positive pregnancy test and pain with cervical manipulation (pelvic exam). Diagnosis is confirmed with pelvic US.
  • PID: sexually transmitted infection involving internal reproductive organs, usually in a young adult woman. Pelvic inflammatory disease presents with lower abdominal pain (mostly bilateral), fever, and vaginal discharge. Diagnosis is established with pelvic exam and US.
  • Ovarian and fallopian tube torsion: causes acute ischemia of the ovary/fallopian tube. Torsion presents with abdominal pain (RLQ if on the right), fever, and nausea/vomiting. When suspected, a Doppler pelvic US (looking at the blood flow) should be performed. The condition can affect females of both adult and pediatric age.
  • Ruptured ovarian cyst (right): fluid or blood released from the cyst causes peritoneal irritation and acute onset of RLQ abdominal pain. Diagnosis is made by pelvic US.

References

  1. Martin, R.F. (2020). Acute appendicitis in adults: Clinical manifestations and differential diagnosis. Retrieved 11 December 2020, from https://www.uptodate.com/contents/acute-appendicitis-in-adults-clinical-manifestations-and-differential-diagnosis?search=appendicitis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2 
  2. Pisano M., Capponi M.G., Ansaloni L. (2014). Acute Appendicitis: An Open Issue. Current Trends in Diagnostic and Therapeutic Options. Retrieved 11 December 2020, from https://www.sciencedirect.com/topics/medicine-and-dentistry/alvarado-score
  3. Smink D., Soybel D.I. (2020). Management of acute appendicitis in adults. Retrieved 11 December 2020, from https://www.uptodate.com/contents/management-of-acute-appendicitis-in-adults?search=appendicitis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  4. Wesson D.E., Brandt M.L. (2019). Acute appendicitis in children: Clinical manifestations and diagnosis. Retrieved 11 December 2020, from https://www.uptodate.com/contents/acute-appendicitis-in-children-clinical-manifestations-and-diagnosis?search=appendicitis&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3

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