What is the pathophysiology and treatment of acute appendicitis?

Pathophysiology and Treatment of Acute Appendicitis

Pathophysiology

Acute appendicitis results from luminal obstruction leading to bacterial overgrowth, increased intraluminal pressure, venous congestion, ischemia, and potential perforation, though growing evidence suggests not all cases progress inevitably to perforation and spontaneous resolution may occur. 1

• The traditional understanding is that appendiceal obstruction (by fecaliths, lymphoid hyperplasia, or other causes) initiates a cascade of inflammation, bacterial proliferation, and progressive tissue damage 1
• However, current evidence challenges the notion that perforation is the inevitable endpoint, with data suggesting many cases may resolve spontaneously without intervention 1, 2
• Perforation rates vary from 16-40%, with higher frequencies in younger patients (40-57%) and those over 50 years (55-70%) 1
• Mortality risk is <0.1% for uncomplicated appendicitis, 0.6% for gangrenous appendicitis, and approximately 5% for perforated appendicitis 1

Clinical Presentation and Diagnosis

Diagnosis requires synthesis of clinical findings, laboratory markers, and imaging, with CT being the most reliable modality for confirming uncomplicated versus complicated disease. 1, 3

• Classic presentation includes periumbilical pain migrating to the right lower quadrant, anorexia, nausea/vomiting, and low-grade fever, achieving approximately 90% diagnostic accuracy when all present 3
• Laboratory findings may be atypical, particularly in immunocompromised patients who may lack leukocytosis but typically have elevated C-reactive protein 1
• CT imaging identifies critical prognostic features including appendiceal diameter ≥7 mm, presence of appendicoliths, and signs of perforation 3

Treatment Approach

Surgical Management (First-Line for Most Patients)

Laparoscopic appendectomy within 24 hours of diagnosis remains the gold standard treatment, offering superior outcomes with lower complication rates compared to open surgery. 1, 4

• Laparoscopic appendectomy should be performed within 24 hours of admission to minimize complications and is associated with less pain, lower surgical site infection rates (8.7% vs 11.1% for open), shorter hospital stays, and earlier return to work 1, 4
• Conventional three-port laparoscopic technique is preferred over single-incision approaches due to shorter operative times and less postoperative pain 4
• For stump closure, endoloops/suture ligation or polymeric clips are recommended 4
• The normal-appearing appendix should be removed during surgery when no other pathology is found in symptomatic patients, as macroscopic judgment of early appendicitis is often inaccurate 4

Antibiotic Management

A single preoperative dose of broad-spectrum antibiotics covering gastrointestinal bacteria is mandatory for all patients undergoing appendectomy. 4

• Piperacillin-tazobactam is FDA-approved for complicated appendicitis (with rupture or abscess) caused by beta-lactamase producing E. coli or Bacteroides fragilis group organisms 5
• Alternative regimens include combination therapy with cephalosporins or fluoroquinolones plus metronidazole 3
• For uncomplicated appendicitis, postoperative antibiotics are not recommended 4
• In complicated appendicitis with adequate source control, antibiotics should not be continued beyond 3-5 days postoperatively 4

Non-Operative Management (Selected Cases Only)

Antibiotic therapy alone may be considered for uncomplicated appendicitis without appendicolith on CT, but approximately 30% will require appendectomy within one year, limiting its application. 1, 4, 3

• Success rates are approximately 70% initially, but one-third require subsequent surgery within the first year 3, 6
• CT findings that predict antibiotic failure include: appendicoliths, mass effect, and appendiceal diameter >13 mm (≈40% failure rate) 3
• Antibiotics may reduce wound infections compared to surgery (RR 0.25) but increase negative appendectomy rates if delayed surgery becomes necessary (RR 3.16) 6
• This approach requires CT-confirmed diagnosis of uncomplicated appendicitis and is contraindicated in patients with high-risk imaging features 1, 3

Complicated Appendicitis with Abscess/Phlegmon

Early appendectomy demonstrates superior outcomes compared to initial non-operative management in complicated appendicitis, with lower rates of bowel resection (3.3% vs 17.1%). 4

• Patients with large appendiceal abscess or phlegmon may undergo percutaneous drainage and antibiotic management followed by interval appendectomy 7
• Interval appendectomy is not routinely recommended after non-operative management in young adults (<40 years) and children, but should be performed for those with recurrent symptoms 4

Special Populations

Immunocompromised and Transplant Patients

Transplanted patients with acute appendicitis should undergo appendectomy as soon as possible, usually within 24 hours from diagnosis, as they have high rates of complicated appendicitis despite atypical laboratory findings. 1

• These patients may show normal or low white blood cell counts (median 7,500 vs 12,500 cells/mm³ in non-transplanted) but elevated CRP 1
• Laparoscopic appendectomy should be preferred whenever feasible 1
• Perforation rate is 8.2% with complication rates around 25% post-operatively 1

Patients ≥40 Years Old

Both colonoscopy and interval full-dose contrast-enhanced CT scan are recommended for follow-up in patients ≥40 years with complicated appendicitis due to higher incidence of appendicular neoplasms (3-17%). 4, 8

• Routine histopathological examination of all appendectomy specimens is mandatory to avoid missing unexpected malignancy 4
• The incidence of malignancy in the antibiotic-treated group is approximately 0.3%, though follow-up data are limited 6

Pregnant and Immunosuppressed Patients

These populations should undergo timely surgical intervention to decrease the risk of complications rather than attempting non-operative management. 7

Common Pitfalls to Avoid

• Delaying appendectomy beyond 24 hours from admission increases risk of adverse outcomes 4
• Failure to perform routine histopathological examination may miss unexpected findings including malignancy 4
• Attempting antibiotic-only treatment in patients with appendicoliths, mass effect, or appendiceal diameter >13 mm on CT leads to high failure rates 3
• Failure to follow up patients ≥40 years old who have higher risk of underlying malignancy 4, 8
• Assuming normal laboratory values exclude appendicitis in immunocompromised patients who may lack typical leukocytosis 1
• Abdominal drains should not be routinely placed following appendectomy for complicated appendicitis 4