What is the definition, diagnosis, and management of appendicitis, including signs and symptoms, laboratory findings, imaging, differential diagnosis, and medical and surgical treatment options?

Appendicitis: Comprehensive Clinical Overview

Definition

Appendicitis is inflammation of the vermiform appendix, classified as uncomplicated (simple inflammation without perforation) or complicated (perforation, abscess, gangrene, or peritonitis), affecting approximately 96.5-100 per 100,000 adults annually. 1

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Signs and Symptoms

Classic Presentation

• Periumbilical pain migrating to the right lower quadrant is the hallmark symptom, with sensitivity of 80% and specificity of 90%. 2
• Anorexia, nausea, and intermittent vomiting typically accompany the pain, with this triad present in approximately 90% of confirmed cases. 1
• Low-grade fever develops as inflammation progresses. 1

Critical Physical Examination Findings

• Right lower quadrant tenderness with guarding and rebound tenderness are the most reliable physical findings. 3, 4
• Positive psoas sign significantly increases likelihood of appendicitis. 5
• The presence of fever combined with migratory pain to the right lower quadrant substantially increases diagnostic probability. 5

Important Diagnostic Pitfalls

• Vomiting occurring BEFORE pain onset makes appendicitis unlikely and should prompt consideration of alternative diagnoses. 5
• Absence of classic pain migration, right lower quadrant pain, guarding, or fever substantially decreases the likelihood of appendicitis. 5
• Children under 5 years frequently present atypically and have higher perforation rates due to delayed diagnosis—maintain high clinical suspicion despite atypical presentations. 3
• Women of childbearing age have more variable presentations than men, necessitating imaging in all female patients. 4

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Laboratory Findings

Diagnostic Laboratory Tests

• Complete blood count with differential showing WBC >10,000/mm³ combined with C-reactive protein ≥8 mg/L has a positive likelihood ratio of 23.32. 3
• Elevated white blood cell count with left shift supports the diagnosis but is nonspecific. 6

Clinical Scoring Systems

• The Alvarado score stratifies patients into low, intermediate, or high-risk categories (score 7-10 indicates high risk), guiding imaging and surgical decisions. 2
• The Pediatric Appendicitis Score aids risk stratification in children but should not be used alone for diagnosis. 3

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Imaging

Imaging Algorithm

For Adults:

• CT abdomen/pelvis with IV contrast is the gold standard for non-pregnant adults, with sensitivity of 94-100% and specificity of 93-95%. 2
• Young males under 40 years with classic presentation may proceed directly to surgery without imaging. 2
• All female patients should undergo diagnostic imaging regardless of clinical presentation. 4

For Pregnant Patients:

• First trimester patients should undergo ultrasound or MRI to avoid ionizing radiation. 4
• Timely surgical intervention is critical in pregnant patients to decrease complications including preterm labor. 6

For Pediatric Patients:

• Ultrasound is the recommended first-line imaging modality for all children, with sensitivity of 76% and specificity of 95%. 3
• Point-of-care ultrasound performed by emergency physicians or surgeons shows higher accuracy (sensitivity 91%, specificity 97%). 3
• If ultrasound is non-diagnostic and clinical suspicion remains high, CT with IV contrast or MRI should be used. 3

High-Risk CT Findings

• Appendiceal diameter ≥7 mm indicates appendicitis. 1
• Appendicolith (fecal conglomeration in appendiceal lumen), mass effect, or appendiceal diameter >13 mm are associated with approximately 40% failure rate of antibiotic-first approach and mandate surgical management in fit patients. 1

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Differential Diagnosis

Must-Exclude Conditions

• Ectopic pregnancy in all women of childbearing age
• Ovarian torsion or ruptured ovarian cyst
• Pelvic inflammatory disease
• Diverticulitis (typically older patients, left-sided pain)
• Mesenteric adenitis (more common in children)
• Gastroenteritis (vomiting typically precedes pain)
• Urinary tract infection or nephrolithiasis
• Inflammatory bowel disease
• Meckel's diverticulitis

Key Differentiating Features

• Gastroenteritis: vomiting before pain onset excludes appendicitis. 5
• Urinary pathology: urinalysis with pyuria and bacteriuria. 2
• Gynecologic pathology: requires imaging in all female patients. 4

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Medical Management

Antibiotic Therapy

Immediate Antibiotic Administration:

• Broad-spectrum IV antibiotics must be administered immediately once appendicitis is diagnosed or strongly suspected, before surgical intervention. 3, 4

Antibiotic Regimens for Uncomplicated Appendicitis:

• Piperacillin-tazobactam monotherapy (3.375 g IV every 6 hours). 1
• Combination therapy: cephalosporins or fluoroquinolones with metronidazole. 1
• Ertapenem 1 g IV once daily for 5-14 days (FDA-approved for complicated intra-abdominal infections including appendicitis). 7
• Aminoglycoside-based regimens, carbapenem monotherapy, or beta-lactam/beta-lactamase inhibitor combinations. 3

For Severe Beta-Lactam Allergies:

• Ciprofloxacin plus metronidazole. 3

For Complicated Appendicitis:

• Carbapenem therapy: Meropenem 1 g every 8 hours, Doripenem 500 mg every 8 hours, or Imipenem/Cilastatin 1 g every 8 hours. 8
• Carbapenem-sparing regimen: Ceftolozane/Tazobactam 1.5 g every 8 hours plus Metronidazole 500 mg every 6 hours. 8
• Add Vancomycin (25-30 mg/kg loading dose, then 15-20 mg/kg every 8 hours) or Teicoplanin for gram-positive coverage. 8

Antibiotic-First Approach for Uncomplicated Appendicitis

Patient Selection Criteria:

• Approximately 70% of patients with uncomplicated appendicitis can be successfully treated with antibiotics alone, avoiding surgery. 1
• However, 30.7% of antibiotic-treated patients require appendectomy within one year, meaning two-thirds avoid surgery. 9
• Antibiotic treatment may result in 76 more unsuccessful treatments per 1000 people compared to surgery. 9

Contraindications to Antibiotic-First Approach:

• Presence of appendicolith on CT (40% failure rate). 1
• Appendiceal diameter >13 mm (40% failure rate). 1
• Mass effect on imaging. 1
• Pregnant patients (require timely surgical intervention). 6
• Immunocompromised patients (require timely surgical intervention). 6, 4

Clinical Monitoring:

• Patients must show sustained improvement in clinical symptoms and signs within 24 hours while receiving antimicrobial therapy. 8
• Hospital or emergency department observation is necessary to evaluate symptom evolution for patients with negative imaging but persistent clinical suspicion. 4

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Surgical Management

Timing of Surgery

For Uncomplicated Appendicitis:

• Appendectomy should be performed as soon as reasonably feasible once diagnosis is established. 3
• Surgery within 8 hours is recommended for uncomplicated cases. 3
• Delaying surgery up to 10-16 hours to accommodate surgeon preference or hospital efficiency does not significantly increase morbidity or mortality. 10

For Complicated Appendicitis:

• Surgery should be performed within 24 hours. 3
• Patients with perforated appendicitis require urgent intervention to provide adequate source control. 8

Surgical Approach

Laparoscopic vs. Open:

• Laparoscopic appendectomy is the preferred approach and remains the most common treatment, though both laparoscopic and open approaches are acceptable based on surgeon expertise. 3, 1
• Both approaches are viable with similar outcomes. 8

Intraoperative Considerations:

• Routine intra-operative irrigation does not prevent intra-abdominal abscess formation and may be avoided. 8

Management of Periappendiceal Abscess

For Well-Circumscribed Abscess:

• Patients with a well-circumscribed periappendiceal abscess can be managed with percutaneous image-guided drainage plus antibiotics, with efficacy rates of 70-90% and lower complication rates than immediate surgery. 8, 3
• Approximately 80% of patients successfully treated with percutaneous drainage do not require subsequent appendectomy. 3
• Appendectomy is generally deferred in such patients. 8

For Periappendiceal Phlegmon:

• Selected patients presenting several days after symptom onset with a periappendiceal phlegmon or small abscess not amenable to percutaneous drainage may delay or avoid source control procedures with antimicrobial therapy alone. 8

Interval Appendectomy:

• After successful non-operative management of complicated appendicitis with abscess, interval appendectomy may not be necessary in 80% of cases. 3
• Interval appendectomy should always be performed for patients with recurrent symptoms. 8

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Special Populations

Pregnant Patients

• Require timely surgical intervention to decrease complications including preterm labor and low birth weight. 6, 4
• Use ultrasound or MRI for diagnosis in first trimester. 4

Immunocompromised Patients

• Should undergo timely surgical intervention due to higher risk of complications. 4

Pediatric Patients

• Children under 5 years have higher perforation rates—maintain high suspicion despite atypical presentations. 3
• For complicated appendicitis, surgery should be performed within 24 hours. 3

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Complications and Outcomes

Surgical Complications

• Antibiotics may reduce wound infections (RR 0.25) compared to surgery. 9
• Mortality for uncomplicated appendicitis is 0.1-0.5%; for complicated appendicitis, 1-5%. 2
• Negative appendectomy rate is 10-20% when proceeding directly to surgery without imaging. 2
• Antibiotics probably increase negative appendectomy rates (RR 3.16) when surgery is eventually required. 9

Antibiotic Treatment Complications

• Uncertain difference in Clostridium difficile diarrhea rates. 9
• Uncertain difference in intra-abdominal abscess or collection rates. 9

Malignancy Risk

• Routine histopathology should be obtained after appendectomy to identify unexpected findings, including rare malignancies (0.3% incidence in antibiotic-treated patients). 3

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Follow-Up Considerations

• If a patient is discharged after negative imaging, 24-hour follow-up must be ensured due to measurable false-negative rates. 3, 4
• Hospitals should establish standardized clinical pathways involving surgeons, emergency physicians, radiologists, and other specialists to ensure comprehensive management from presentation through discharge. 4