Appendicitis

Aka: Appendicitis, Acute Appendicitis

1. Epidemiology
   1. U.S. Appendectomy rates: 300,000 per year (70,000 of the cases are in children)
      1. Of those appendixes removed for suspected Appendicitis, 10% are normal
   2. Age Distribution
      1. Preschool age Incidence: 1.1 to 3.6 per 10,000
      2. Ages 5 to 9 years old: 6.8 to 18.8 per 10,000
      3. Peak age: 10 to 19 years old
   3. Lifetime Incidence
      1. Women: 6.7%
      2. Men: 8.6%
   4. Incidence Pregnancy
      1. Antepartum: 6.3 per 10,000 pregnancies
         1. Up to 1 in 1000 are taken to surgery for possible Appendicitis in pregnancy
      2. Postpartum: 9.9 per 10,000 postpartum patients
2. Pathophysiology
   1. Appendix is long, thin Diverticulum
      1. Arises from inferior cecum
   2. Appendicitis course
      1. Luminal obstruction
      2. Increased mucous production
      3. Visceral inflammation and Mucosal Ulceration (associated with vague pain onset at 12 hours)
      4. Bacterial Infection and overgrowth
      5. Serosal inflammation and peritoneal inflammation with localized pain (McBurney's Point)
      6. Increased wall tension, followed by necrosis and perforation
   3. Appendix Perforation
      1. Perforation Course
         1. Pus spills into peritoneal cavity
         2. Results in peritonitis
         3. Abscess forms
      2. Perforation at time of surgery increases with age
         1. Young patients: 20%
         2. Elderly: 70%
3. Risk Factors
   1. Decreased Dietary Fiber (high Dietary Fiber protective)
   2. Ingestion of refined Carbohydrates
   3. Infection
      1. Viral epidemic
      2. Amebiasis outbreak
      3. Bacterial Gastroenteritis
4. Precautions
   1. Extremes of age yield atypical presentations
      1. McBurney's Point pain occurs in only 33% of children
      2. Children <3 years old are often only diagnosed after appendix rupture
      3. Newborns may present only irritable or lethargic, and diagnosis is often delayed until after rupture (80%)
         1. Neonatal Appendicitis is also associated with a higher mortality rate
      4. Elderly often have atypical findings and delayed diagnosis
   2. Pregnant patients present with atypical Appendicitis symptoms
      1. Right Upper Quadrant Abdominal Pain in 20% of patients
      2. Rectal Pain in 45% of cases
      3. Swadron, Schmitz, Bridwell, Carius in Herbert (2019) EM:Rap 19(3): 12-4
   3. Consider genitourinary causes with referred pain
      1. Consider referred pain from Scrotum (e.g. Testicular Torsion, incarcerated Inguinal Hernia)
      2. Consider Ectopic Pregnancy, Ovarian Torsion and Pelvic Inflammatory Disease in women
   4. Initial missed Appendicitis diagnosis approaches 50% (especially at extremes of age)
      1. Initial misdiagnosis approaches 100% in under age 2 years
      2. Missed Appendicitis is often complicated by appendix perforation
      3. Gastroenteritis is the most common initial misdiagnosis, when Appendicitis is missed
         1. Exercise caution in applying the Gastroenteritis diagnosis in Abdominal Pain presentations
         2. Most common Appendicitis presenting symptoms in age <3 years are fever, Vomiting, Diarrhea
   5. Observation protocol in a stable patient when diagnosis is unclear
      1. Outpatient with return for recheck in 12 hours for responsible patients (and parents of pediatric patients)
      2. Hospital observation is recommended when follow-up cannot be assured
      3. Perforation is rare (2%) in first 36 hours of symptoms, and serial exams over this time is reasonable
   6. Imaging
      1. Ultrasound lean pediatric patients first if sonographers and radiologists are experienced with Appendix Ultrasound
      2. CT Abdomen should be obtained if indicated and other modalities are non-diagnostic (despite radiation risk)
         1. Risk of missed appendix outweighs risk of radiation exposure when clinical suspicion dictates
      3. Consider MRI Abdomen in children and pregnant patients
   7. Documentation
      1. Clearly document history, examination, patient stability and decision making
         1. Explain abnormal findings (including labs)
      2. More likely alternative diagnoses should be explained and fit classic diagnostic criteria
         1. Gastroenteritis should primarily be Vomiting and Diarrhea without focal tenderness
         2. Exercise caution in diagnosing Constipation as cause of focal Abdominal Pain
      3. Discharge Instructions should reflect an unclear diagnosis (as opposed to Constipation)
         1. Include precautions for return
         2. Encourage re-evaluation within 24-36 hours if symptoms persist
   8. References
      1. Claudius and Kassinove in Herbert (2012) EM:RAP 12(10): 2-3
      2. Weinstock in Herbert (2018) EM:Rap 18(7): 5-7
5. History
   1. Present illness
      1. Abdominal Pain onset and distribution
      2. Fever
      3. Recent food intake including Anorexia
      4. Nausea or Vomiting
      5. Constipation
      6. Diarrhea
      7. Genitourinary symptoms (e.g. Dysuria, frequency, Hematuria, Vaginal Discharge)
      8. Last Menstrual Period and risk of pregnancy
   2. Past history
      1. Recent Abdominal Trauma
      2. Abdominal Surgeries
      3. Gynecologic History including menstrual history
      4. Sexual History including Sexually Transmitted Infection, Contraception
6. Symptoms
   1. Anorexia (low predictive value)
      1. Positive Likelihood Ratio: 1.3 (adults and children)
      2. Negative Likelihood Ratio: 0.64 (LR- 0.58 in children)
      3. Test Sensitivity: 68 to 84% (children)
      4. Test Specificity: 64 to 66% (children)
   2. Nausea
      1. Positive Likelihood Ratio: 0.69 to 1.2
      2. Negative Likelihood Ratio: 0.7 to 0.84
      3. Test Sensitivity: 58-68%
      4. Test Specificity: 40%
   3. Vomiting
      1. Positive Likelihood Ratio: 0.92 (LR+ 1.3 children)
      2. Negative Likelihood Ratio: 1.1 (LR- 0.65 in children)
      3. Test Sensitivity: 50%
      4. Test Specificity: 45-69%
   4. Abdominal Pain (occurs in virtually all cases)
      1. Predictive value of findings
         1. Right lower quadrant pain (Most important history finding)
            1. Positive Likelihood Ratio: 7.3 to 8.5 (LR+ 1.4 in children)
            2. Negative Likelihood Ratio: <0.28
            3. Test Sensitivity: 81-96%
            4. Test Specificity: 53%
         2. Pain occurs before Vomiting
            1. Positive Likelihood Ratio: 2.8
            2. Test Sensitivity: 100%
            3. Test Specificity: 64%
         3. Pain migration from Periumbilical Pain to Right Lower Quadrant Abdominal Pain
            1. Likelihood Ratio: 3.2 to 3.6 (LR+ 1.8 in children)
            2. Negative Likelihood Ratio: 0.50 (LR- 0.7 in children)
            3. Test Sensitivity: 46% (children)
            4. Test Specificity: 90% (children)
      2. Course of pain (Classic): Occurs in 50% of cases
         1. Initial: Crampy Periumbilical Pain for 12-24 hours
         2. Later: Steady, sharp RLQ Abdominal Pain
         3. Provocative: Cough or Movement
7. Signs
   1. Typical Presentation
      1. Low grade fever (38.3 - 39.4 C)
         1. Positive Likelihood Ratio: 1.9 (LR+1.2 in children)
         2. Negative Likelihood Ratio: 0.58 (LR- 0.9 in children)
         3. Test Sensitivity: 67-75%
         4. Test Specificity: 69-78%
         5. Often absent in elderly
      2. Abdominal rigidity
         1. Positive Likelihood Ratio: 3.8
         2. Negative Likelihood Ratio: 0.82
      3. Involuntary abdominal guarding
         1. Positive Likelihood Ratio: 1.8 (LR+ 2.1 in children)
         2. Negative Likelihood Ratio: <0.54 (LR- 0.47 in children)
         3. Test Sensitivity: 21-74%
         4. Test Specificity: 57-84%
      4. Rebound Abdominal Tenderness (RLQ Abdominal Pain when LLQ pressure is released)
         1. Positive Likelihood Ratio: 2.03 to 6.3 (LR+ 2.2 in children)
         2. Negative Likelihood Ratio: <0.86
         3. Test Sensitivity: 26-63%
         4. Test Specificity: 69%
      5. Point tenderness in right lower quadrant (RLQ)
         1. See McBurney's Point
      6. RLQ tenderness on pelvic exam or rectal exam
      7. Decreased or absent bowel sounds
         1. Positive Likelihood Ratio (children): 3.1
         2. Negative Likelihood Ratio (children): 0.69
   2. Perforated Appendix
      1. Accentuated pain
      2. Vomiting
      3. Higher fever and Leukocytosis
      4. Tender RLQ mass
         1. Suggests Appendiceal abscess
         2. Also seen with Phlegmon (Cecum inflammation)
   3. Extrapelvic Appendix
      1. Right back Muscle inflammed (tender below 12th rib)
      2. Psoas and Illiopsoas inflammation
         1. Patient keeps right thigh flexed or rigid extension
         2. Iliopsoas Test (Psoas Sign)
            1. Positive Likelihood Ratio: 2.4 (LR+ 3.2 in children)
            2. Negative Likelihood Ratio: 0.90 (LR- 0.7 in children)
            3. Test Sensitivity: 16%
            4. Test Specificity: 95%
      3. Right Ureter Inflammation (Dysuria or Pyuria)
   4. Intrapelvic Appendix
      1. Diffuse Suprapubic Pain
      2. No abdominal Muscle rigidity
      3. Bladder irritation (Dysuria)
      4. Rectum irritation (tenesmus)
      5. Obturator internus inflammation
         1. Obturator Test
      6. Palpable tender mass on rectal exam
   5. Additional exam signs
      1. Rovsing's Sign
         1. Right Lower Quadrant Abdominal Pain occurs on palpation of the left lower quadrant
         2. Positive Likelihood Ratio (children): 3.5
         3. Negative Likelihood Ratio (children): 0.72
      2. Psoas Sign (see above)
         1. Patient in the left lateral decubitus position
         2. Right lower quadrant pain with hyperextension of the the right hip
      3. Obturator Sign (Obturator Test)
         1. Right lower quadrant pain on internal rotation of the flexed right thigh
         2. Positive Likelihood Ratio (children): 3.5
         3. Negative Likelihood Ratio (children): 0.73
      4. Dunphy's Sign
         1. Increased pain with cough
      5. Pain provoked by hopping, percussion or coughing
         1. Positive Likelihood Ratio (children): 1.6
         2. Negative Likelihood Ratio (children): 0.52
         3. Test Sensitivity: 72% (children)
         4. Test Specificity: 91% (children)
8. Labs
   1. Precautions
      1. No lab marker has sufficient Test Sensitivity to exclude Appendicitis
      2. Al-Abed (2014) Am J Surg S0002-9610(14): 00360-2 [PubMed]
   2. Complete Blood Count: Neutrophilic Leukocytosis
      1. Poor predictive value (poor sensitivity and Specificity)
         1. Leukocytes normal in 20-25% of Appendicitis cases
      2. High Negative Predictive Value
         1. In children, Likelihood Ratio with WBC <10,000 is 0.22
      3. Leukocytosis with Neutrophilia
         1. Test Sensitivity: 94%
         2. Test Specificity: 80%
      4. Interpretation
         1. Leukocytes range: 10,000 to 20,000 (in 75% of Appendicitis cases)
         2. Leukocytosis over 15,000 compels evaluation
         3. Higher Leukocytosis suggests appendix perforation
   3. C-Reactive Protein (C-RP)
      1. Increases within 6-12 hours
      2. Higher False Positive Rate in obese children
      3. Test Sensitivity for Appendicitis: 76%
         1. Test Sensitivity improves if C-RP remains normal despite >24 hours of symptoms
         2. In some studies, normal C-RP at 24 hours had a nearly 100% Negative Predictive Value
   4. Urinalysis
      1. Sterile pyuria can occur if appendix is adjacent to ureter
      2. Do not exclude Appendicitis based on urine alone unless urine findings are definitive
9. Differential Diagnosis: General
   1. See Abdominal Pain
   2. See Abdominal Pain Causes
   3. See Right Lower Quadrant Abdominal Pain
   4. See Periumbilical Abdominal Pain
   5. Regional ileitis (Crohn's Disease)
   6. Perforated Duodenal Ulcer
   7. Meckel's Diverticulitis
   8. Small Bowel Obstruction
   9. Intussusception
   10. Acute Pancreatitis
   11. Diverticulitis
   12. Gastroenteritis
   13. Constipation
   14. Abdominal Trauma
   15. Ectopic Pregnancy
   16. Endometriosis
   17. Ovarian Torsion
   18. Testicular Torsion
   19. Incarcerated Inguinal Hernia
   20. Pelvic Inflammatory Disease
   21. Urinary Tract Infection or Pyelonephritis
   22. Ureterolithiasis
   23. Diabetic Ketoacidosis
   24. Henoch Schonlein Purpura
   25. Right lower lobe Pneumonia
10. Differential Diagnosis: Identified after Negative Appendectomy
    1. Mesenteric adenitis (23%)
    2. Lymphoid Hyperplasia (10%)
    3. Gastroenteritis (4%)
    4. Ovarian Cyst (3%)
11. Diagnosis
    1. Alvarado Score (MANTRELS Score)
       1. Originally designed for use in adults and later modified for use in all ages
       2. Unreliable - not recommended (misses almost a third of Appendicitis cases)
    2. Pediatric Appendicitis Score
       1. Unreliable alone, but better efficacy when combined with Appendix Ultrasound (see Pediatric Appendicitis Pathway)
    3. Appendicitis Inflammatory Response Score
    4. No further testing if Appendicitis diagnosis is clear
       1. Based on history and examination
    5. Most suggestive findings of Appendicitis
       1. Adults
          1. Right Lower Quadrant Abdominal Pain
          2. Abdominal rigidity
          3. Radiation of Periumbilical Pain to right lower quadrant
       2. Children
          1. Absent or decreased bowel sounds
          2. Positive Psoas Sign
          3. Positive Obturator Sign
          4. Positive rovsing sign
    6. Most suggestive findings of perforation
       1. Symptom duration >2 days
       2. Fever >38 C (100.4 F)
       3. Free fluid on ullrasound
       4. Appendix diameter >9.7 mm
12. Imaging
    1. CT Abdomen with contrast
       1. Preferred in most cases (except children and pregnancy)
       2. See CT Abdomen in Appendicitis
    2. RLQ Abdominal Ultrasound
       1. See Ultrasound in Appendicitis
       2. Preferred in children and pregnancy
       3. Limited utility in obese children and larger teens and adults
       4. Combine with pelvic Ultrasound in female patients (consider Ovarian Torsion evaluation)
       5. If appendix is not visualized, or high clinical suspicion despite negative Ultrasound
          1. Appendicitis probability 4.2% if Non-diagnostic Ultrasound and WBC <9k, <65% PMN
             1. Anandalawar (2015) J Am Coll Surg 220(6): 1010-7 [PubMed]
          2. Perform other imaging or perform close interval serial examinations
          3. In children or pregnancy, consider MRI Abdomen
       6. RLQ Abdominal Ultrasound before Abdominal MRI in children is preferred
          1. Ultrasound first strategy is faster and more cost-effective
          2. Despite RLQ Abdominal Ultrasound being inconclusive in 25% of cases
          3. Imler (2017) Acad Emerg Med 24(5): 569-77 +PMID:28207968 [PubMed]
       7. MRI Abdomen is preferred in pregnancy
          1. RLQ Ultrasound has Test Sensitivity in pregnancy as low as 18% (but a high Test Specificity)
    3. MRI Abdomen without contrast
       1. Consider in children, pregnancy
          1. Eliminates the ionizing radiation risk and IV contrast of CT Abdomen
       2. However, longer study (10 min for fast protocol) and may require sedation in children
       3. Non-contrast MRI is as accurate as with gadolinium contrast in pregnancy
       4. Test Sensitivity and Test Specificity >90% in children
       5. Efficacy in pregnancy
          1. Test Sensitivity: 94% (range 87 to 98%, best efficacy with MR-expert radiologists)
          2. Test Specificity: 97% (range 96 to 98%)
          3. Duke (2016) AJR Am J Roentgenol 206(3): 508-17 [PubMed]
       6. References
          1. Kearl (2016) Acad Emerg Med 23(2): 179-85 [PubMed]
13. Management: Surgical Management
    1. Supportive Perioperative Care
       1. Intravenous Fluids
       2. Oral or parenteral Analgesics
          1. Acetaminophen
          2. NSAIDs (e.g. Ibuprofen or Toradol)
          3. Opioids (e.g. Dilaudid, Morphine)
    2. Acute Suppurative Appendicitis
       1. Appendectomy
          1. Laparoscopic appendectomy is preferred over open appendectomy
             1. Lower postoperative complications (e.g. Wound Infection), recovery time
             2. Dai (2017) Gastroenterol J 5(4): 542-53 [PubMed]
       2. Bacterial coverage
          1. Typical: Aerobic and anaerobic Gram Negative Rods (e.g. e coli, Klebsiella), Bacteroides
          2. Uncommon: Enterococcus, Pseudomonas aeruginosa
          3. Rare: Actinomyces, Candida
       3. Antibiotic options prior to surgery (continued if perforation found at surgery)
          1. Metronidazole 500 mg IV q8 hours AND choose one of following
             1. Ceftriaxone 75 mg/kg IV up to 2 g IV q24 hours OR
             2. Ciprofloxacin 400 mg IV q12 hours OR
             3. Levofloxacin 750 mg IV q24 hours
             4. Moxifloxacin 400 mg IV q24 hours OR
          2. Carbapenem single agent management (choose one)
             1. Imipenem 500-1000 mg IV q6 hours OR
             2. Doripenem 500 mg IV q8 hours
             3. Ertapenem
          3. Other antibiotic options
             1. Piperacillin/Tazobactam (Zosyn)
       4. Avoid antibiotics with growing resistance to gram-negative Anaerobes
          1. Cefotetan or Cefoxitin
          2. Ampicillin-sulbactam (Unasyn) and Clindamycin
    3. Appendicitis with Abscess
       1. Initial antibiotics as in perforated Appendicitis
          1. Continue antibiotics until no fever or Leukocytosis
       2. Percutaneous drainage
          1. Drain left in place
          2. Remove drain when cathetergram normal
       3. Appendectomy follows drainage
    4. Perforated Appendicitis (esp. with peritonitis or Septic Shock)
       1. Initial antibiotics
          1. Piperacillin-Tazobactam (Zosyn) 3.375 to 4.5 g IV q6-8 hours
          2. Carbapenem single agent management (choose one)
             1. Moxifloxacin 400 mg IV q24 hours OR
             2. Imipenem 500-1000 mg IV q6 hours OR
             3. Doripenem 500 mg IV q8 hours
          3. Metronidazole 500 mg IV q8 hours AND choose one of following
             1. Ciprofloxacin 400 mg IV q12 hours OR
             2. Ceftolozone-Tazobactam 1.5 g IV q8 hours OR
             3. Ceftazidime-Avibactam 2.5 g IV q8 hours OR
             4. Aztreonam 1 g IV q8 hours
             5. Ampicillin 2 g IV q6 hours AND Aminoglycoside (Gentamycin OR Tobramycin)
       2. Appendectomy and perforated or gangrenous appendix
          1. Appendectomy wound left open
          2. Continue antibiotics for 7 days
          3. If fever, Leukocytosis, or obstipation persist
             1. Obtain CT Abdomen and Pelvis
             2. Abscess present
                1. Percutaneous drainage
                2. Base antibiotics on Gram Stain and culture
             3. No abscess
                1. Consider imipenem 500 mg IV q6 hours
    5. References
       1. (2018) Sanford Guide (accessed 7/1/2018)
       2. Helmer (2002) Am J Surg 183:609 [PubMed]
14. Management: Antibiotic Only Regimen
    1. Contraindications
       1. Appendicolith (25% of cases)
          1. Risk of appendiceal rupture
          2. Response to antibiotics initially 78% (41% go on to appendectomy within 90 days)
       2. Perforation Appendix
       3. Appendix Abscess
    2. Background
       1. CT-confirmed Appendicitis has an 8% False Positive Rate (normal at time of surgery)
    3. Protocols
       1. Adult inpatient/outpatient protocol (73% resolution rate)
          1. Ertapenem 15 mg/kg IV every 12 hours (children) up to 1 g IV q24 hours (adults) for 2-4 days
          2. Then Levaquin 500 mg daily and Metronidazole 500 mg orally tid for 7 days
          3. Salminen (2015) JAMA 313(23): 2340-8 [PubMed]
       2. Outpatient protocols (duration 7-10 days)
          1. Third-Generation Cephalosporin (e.g. Cefdinir) AND Metronidazole OR
          2. Fluoroquinolone AND Metronidazole
       3. Avoid Amoxicillin/Clavulanate (Augmentin) or Ampicillin/Sulbactam (Unasyn)
          1. Growing E. coli Antibiotic Resistance
          2. Original study used Augmentin for 4 days (original study protocol)
             1. Appendectomy needed in only 7-12% of cases at 7-30 days and in 12-30% in the next year
             2. Higher risk of peritonitis (8% versus 2%)
                1. Appendix diameter <10mm might reduce that risk
             3. References
                1. Vons (2011) Lancet 377(9777):1573-9 +PMID:21550483 [PubMed]
    4. Efficacy
       1. Appendicitis without appendicolith (CODA Trial)
          1. Response to antibiotics initially 92% (25% go on to appendectomy within 90 days)
       2. Appendicitis WITH appendicolith (CODA Trial)
          1. Response to antibiotics initially 78% (41% go on to appendectomy within 90 days)
       3. After 7 years, 39% treated with antibiotics only, required later appendectomy
          1. Sippola (2020) JAMA Surg 155(4): 283-9 [PubMed]
       4. Safety
          1. Delaying surgery for antibiotic-only regimen does not appear to increase appendiceal rupture rate
    5. References
       1. Park (2014) Int J Surg 12(9): 897-900 [PubMed]
       2. Talan (2021) N Engl J Med 385:1116-23 [PubMed]
15. Management: Other Regimens
    1. Appendicitis in Pregnancy (1 case per 1500 births)
       1. Site of surgical incision is controversial
       2. Transverse incision at McBurney's Point recommended
       3. Popkin (2002) Am J Surg 183:20-2 [PubMed]
16. Prognosis
    1. Mortality overall
       1. Nonperforated: <1%
       2. Perforated: 5%
    2. Mortality if age over 75 years: 25%
    3. Mortality in pregnancy
       1. Mother: Up to 4%
       2. Fetus: 43%
17. References
    1. Claudius in Majoewsky (2012) EM:RAP-C3 2(3): 2
    2. Mehta (2021) Crit Dec Emerg Med 35(12): 21-9
    3. James (1987) Basic Surgical Practice, Hanley, p.218-23
    4. Benabbas (2017) Acad Emerg Med 24(5): 523-51 [PubMed]
    5. Old (2005) Am Fam Physician 71:71-8 [PubMed]
    6. Paulson (2003) N Engl J Med 348:236-42 [PubMed]
    7. Rothrock (2000) Ann Emerg Med 36:39-51 [PubMed]
    8. Snyder (2018) Am Fam Physician 98(1): 25-33 [PubMed]
    9. Wagner (1996) JAMA 276:1589-94 [PubMed]