Infectious Diseases

Appendicitis

Are you sure your patient has appendicitis? What should you expect to find?

  • The typical presentation for appendicitis is in a young patient (10-50 years of age - peak incidence second and third decades), who presents with 12-36 hours of vague abdominal pain, initially localized in the periumbilical area, and then becomes more severe and localizes to the right lower quadrant.

  • This pain may be accompanied by anorexia, nausea, or vomiting. In appendicitis, the order of presenting symptoms is fairly consistent, starting with anorexia, followed by pain, which may be followed by nausea and/or vomiting.

  • On examination, the patient is generally laying still on the examination table because of exacerbation of pain with movement, mildly tachycardic, and with tenderness to light and deep palpation in the right lower quadrant.

  • This typical presentation may differ based on timing of presentation, in patients at the extremes of age, and in conditions, such as pregnancy or immunosuppression.

How did the patient develop appendicitis? What was the primary source from which the infection spread?

  • Appendicitis is most commonly caused by appendiceal luminal obstruction that can result from fecalith, lymphoid hyperplasia, neoplasm, or parasites. This leads to an increase in intraluminal pressure and, eventually, to mucosal ischemia, gangrene, and perforation.

Which individuals are of greater risk of developing appendicitis?

  • There are no specific conditions that predispose a person to developing appendicitis.

  • Appendicitis can occur in any age group, but the incidence is highest in persons10-20 years of age.

Beware: there are other diseases that can mimic appendicitis:

  • There are many conditions that can mimic appendicitis. It is important to recognize other etiologies that can cause acute abdominal pain and need early surgical intervention. These diagnoses most often include perforated ulcers of the stomach or bowel, perforated colon cancer, diverticulitis of the colon, biliary tract disease, and Meckel's diverticulum. In females, ectopic pregnancy, pelvic inflammatory disease, and large or ruptured ovarian cysts should be included in the differential diagnosis.

  • Other conditions may cause similar acute or more chronic abdominal pain and may not need acute/emergent surgical intervention. Examples of these conditions include gastroenteritis, urinary tract infections and stones, pancreatitis, and neoplasms. A common cause of non-surgical pain in children is mesenteric adenitis. In females, ectopic pregnancy, pelvic inflammatory disease, and large or ruptured ovarian cysts should be included in the differential diagnosis.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

  • Appendicitis will generally cause an elevation in peripheral WBC along with a left shift (neutrophilia +/- bandemia). However, many patients with very early appendicitis have a normal WBC count.

  • A urinalysis should be performed to rule out urinary tract disease as a cause of abdominal pain, keeping in mind that appendicitis may cause mild pyuria or bacteruria. Urine ketones are also common in acute appendicitis.

  • Chemistries should be ordered to look for any electrolyte abnormalities or signs of dehydration.

  • Pre-operative labs, such as coagulation factors, should be ordered when indicated.

  • All women of child-bearing age should have a pregnancy test performed both for pre-operative evaluation and to rule out ectopic pregnancy.

Results that confirm the diagnosis

  • There are no laboratory tests that will confirm a diagnosis of appendicitis.

  • In most cases, the right history, coupled with lab results, are enough to confirm the clinical diagnosis of appendicitis and to support treatment.

  • The only test able to confirm acute appendicitis is the histopathologic evaluation of the appendiceal specimen.

What imaging studies will be helpful in making or excluding the diagnosis of appendicitis?

  • When the history and physical exam are consistent with acute appendicitis in a patient in whom suspicion for other diagnoses is low, no imaging studies are needed and the patient should be taken to surgery.

  • CT scan of the abdomen (estimated cost US $2,000) can help confirm or rule out appendicitis when the clinical diagnosis is somewhat unclear. The sensitivity of CT for acute appendicitis is 87-98% (2-13% false-negative results - normal CT despite acute appendicitis present), and its specificity is 83-97% (3-17% false-positive results - CT indicating appendicitis when not present).

  • Traditionally CT scans for appendicitis have been performed with IV and oral +/- rectal contrast. Recent studies have challenged this, finding that eliminating oral contrast may not change the accuracy of diagnosis.

  • CT scan is also useful in delineating acute simple appendicitis with isolated inflammation from complicated appendicitis which includes inflammation and rupture of the appendix accompanied by an inflammatory mass (phlegmon) and/or an intra-abdominal abscess. In addition, CT scan will often identify any extra-appendiceal pathology, such as intra-abdominal mass, and disease processes such as ovarian cysts or inflammatory bowel disease.

  • Abdominal ultrasound (estimated cost US $400) may be nearly as accurate in young children. However, it requires an experienced operator and uses graded compression to identify a dilated appendix. It can be useful to rule out ovarian pathology in female patients.

  • Diagnosis of appendicitis in pregnancy can be difficult as the need for accurate and timely diagnosis must be weighed against the risk of exposure to ionizing radiation. Ultrasound is fairly accurate in early pregnancy when the appendix can be visualized but is very operator dependent. Many centers are turning to MRI when available as it has been shown to have high sensitivity and specificity for appendicitis in pregnancy.

  • Plain films of the abdomen (estimated cost US $300) may be useful if they reveal an appendicolith or air-fluid levels; however, their utility in helping confirm or rule out appendicitis is minimal.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has appendicitis, what therapies should you initiate immediately?

  • Treatment for simple acute appendicitis has historically been surgical, and an immediate surgical consultation should be made once the diagnosis is reached or strongly suspected.

  • Patients with suspected or confirmed clinical diagnosis of appendicitis should be kept NPO, and crystalloid fluid resuscitation should be initiated. Any electrolyte abnormalities should be corrected.

  • In patients presenting with complicated appendicitis with abscess or phlegmon, surgery is often deferred and the patient is treated acutely with antibiotics alone. A meta-analysis comparing this approach to that of immediate operation found that deferred surgery plus antibiotics is associated with lower rates of complications, similar hospital length of stay, and lower reoperation rates.

  • If surgery is not immediate, broad-spectrum antibiotics should be initiated.

If I am not sure what pathogen is causing the infection what anti-infective should I order?

  • Antibiotics are used for one of two reasons in the treatment of appendicitis: Prophylaxis, in which a dose of the antibiotic selected is given preoperatively, within 1 hour of the incision, to decrease the risk of surgical site infection (including wound infection), or therapeutic, in which antibiotic therapy is continued after surgery to help control an already established infectious process.

  • In early acute appendicitis, only prophylactic antibiotic are needed and there is no need to continue administration after the operation is completed.

  • Therapeutic antibiotics with or without surgery are generally indicated in complicated appendicitis when the appendix has ruptured and/or there is a phlegmon or abscess present.

  • For treatment of patients with complicated appendicitis who undergo surgery and receive post-operative therapeutic antibiotics, it is still recommended to administer a dose of prophylactic antibiotics during the hour prior to incision even if treatment was started earlier. This provides drug levels in the incision at the time of operation to reduce the risk of surgical site infection in previous uninjured and uninfected tissue.

  • Infection in appendicitis is caused by normal colonic flora and is, therefore, polymicrobial. Antibiotics must, therefore, cover this normal flora and should be effective against anaerobic and gram(-) facultative bacteria.

  • Recommended regimens for prophylactic antibiotics for acute appendicitis includes:

    • cefoxitin

    • cefotetan

    • ampicillin/sulbactam

    • cefmetazole

    • piperacillin/tazobactam

    • ertapenem

    • ciprofloxacin or an aminoglycoside + metronidazole or clindamycin

Table I.

lists the most current recommended regimens for treatment of intra-abdominal infections, which are applicable to appendicitis, when therapeutic antibiotics are indicated.
  Mild to moderate infection Dose Severe Infections Dose
Single Drug Regimen ertapenemcefoxitinmoxifloxacintigecyclinticarcillin/clavulanate 1g qd1g q6h400mg qd100mg,then50mgq12h3.1g IV q6h imipemen/cilastatinmeropenemdoripenempiperacillin/tazobactam 1g q8h1g q8h500mg q8h 3.375 q6h
Multidrug Regimen cefazolincefuroximeceftriaxonecefotaximeciprofloxacinlevaquin(above with)metronidazole 1g q6h1g q8h1g qd2g q8h400mg q12h750mg qd500mg q8-12h or 1500mg q24h cefepimeceftazidimeciprofloxacinlevaquin(above with)metronidazole 2g q12h1g q8h400mgq12h750mg qd500mg q8- 12hor 1500mg q 24h

2. Next list other key therapeutic modalities

  • Surgery is the standard of care for acute simple appendicitis.

  • Patients presenting with a more prolonged course can often develop complicated appendicitis in which a secondary periappendiceal abscess or an inflammatory mass (phlegmon) is present. In this scenario, surgical treatment is often deferred.

  • Specifically, in perforated appendicitis with a large abscess, current treatment consists of drainage of the abscess (ideally by a percutaneous approach by interventional radiology or by surgical means when necessary). This approach may avoid morbidity from a more extensive operation, which may require bowel resection and/or need for stoma formation. These patients are treated with therapeutic antibiotics.

  • In patients presenting with an inflammatory mass or phlegmon, many surgeons choose to treat with antibiotics and avoid emergent appendectomy for similar reasons.

  • In all of the mentioned situations, if the patient develops generalized peritonitis or the abdominal exam fails to improve in 24-48 hours, surgery may be necessary

Controversial or evolving therapies:

  • In the above cases when appendectomy was avoided in the acute setting, the standard of care used to be interval appendectomy after the acute inflammation had resolved (at least 4-6 weeks later). More recent studies have shown that the risk of recurrent appendicitis in these patients may not be greater than that in the general public (7% lifetime risk) and that surgery can probably be safely avoided unless symptoms recur. Others had previously reported recurrence rates of up to 30%; hence, the previous standard of interval appendectomy. Further studies are still needed to help inform any decision in this regard. If an observant strategy is used, further studies must be completed to rule out neoplastic disease, especially in patients > 40 years of age (i.e., colonoscopy +/- repeat CT scan).

  • In the past, the standard of care for acute appendicitis was immediate appendectomy to avoid disease progression that could result from postponing the surgery overnight. The rationale was that, by avoiding any possible disease progression in those few hours, one would minimize the risk of perforation and, therefore, prevent complications, such as wound infection, need for long term antibiotics, prolonged hospital stay, and intra-abdominal abscess (all more commonly seen with perforated appendicitis). Newer studies have challenged this recommendation, especially in children, by showing that the perforation rate and subsequent complication rate does not appear to increase if the patient is started on antibiotics and the surgery is delayed overnight, provided the initial presentation is not consistent with peritonitis. However, other retrospective studies in the adult population oppose this view and have found a higher perforation rate as the time between symptom onset and surgery increases. More studies, particularly randomized prospective trials, need to be done to clarify these issues and help identify a specific population in which this practice may be safe.

    Several recent studies have evaluated the role of using antibiotics alone (without appendectomy) for the treatment of acute appendicitis. Studies on this topic have had varied results.

    A small single center study that carefully selected patients with presumed appendicitis and no systemic signs of inflammation found that treatment with antibiotics by mouth alone led to a low failure rate of 12% at 7 days and low recurrence rates after 6 months with a 2 year follow-up.

    A Cochrane review done in 2011 found that patients treated with antibiotics alone were less likely to be cured within 2 weeks without major complications. A more recent study, which examined a California statewide database, found low rates of treatment failure and recurrence.

    A recent multicenter randomized clinical trial done in Finland showed that antibiotic treatment was inferior to surgical treatment, although most patients did not require surgery within 1 year and those who did go on to surgery did not suffer major complications.

  • Given these conflicting results, no definitive recommendation can be made for the use of antibiotics alone to treat appendicitis and further well-conducted randomized trials are needed to determine when and in which populations this treatment may be safe. When discussing treatment options with patients, it seems reasonable to include antibiotic treatment alone as an option, with the caveat that approximately 25% of patients may require surgery within 1 year.

What should you tell the family about the patient's prognosis?

  • In general, prognosis after an episode of acute appendicitis is very good.

  • Common complications after appendectomy include wound infection, intra-abdominal abscess, and leakage from the appendiceal stump.

  • Complications are more likely to occur with more advanced stages of disease (ruptured appendicitis < abscess present < peritonitis).

  • Complications are also more likely at age extremes or in those who are immunocompromised (partially driven by more advanced stage of disease at presentation).

  • Complications with antibiotic treatment alone include recurrence of appendicitis and antibiotic-associated complications such as diarrhea and Clostridium difficile infection.

Add what-if scenarios here:

  • If the surgeon's expertise and conditions allow, laparoscopic appendectomy is usually preferred over open surgery given the lower rate of wound infection and hernia. However, if adequate exposure cannot be obtained laparoscopically, the operation should be immediately converted to an open approach.

  • During surgery, if the appendix is severely inflamed and this extends to the cecum, a more extensive resection, such as ileo-cecectomy or right hemicolectomy, may need to be performed to allow for safe anastomosis.

  • If a mass is palpated or pre-operative imaging was highly suggestive of malignancy, a more formal cancer surgery should be performed (again, usually a right hemicolectomy).

How do you contract appendicitis and how frequent is this disease?

  • Appendicitis is the most common surgical emergency. The lifetime risk of developing appendicitis is approximately 7%, and this has not changed over the past few decades.

  • The male:female ratio of appendicitis is slightly skewed with a male predominance of 1.3:1. There is a peak incidence of appendicitis between 10 and 20 years of age.

  • Perforated appendicitis, typically occurring with delayed presentation, is seen more commonly in the very young and vey old.

  • There is no reported seasonal variance in the incidence of appendicitis.

  • The infection in appendicitis is caused by normal colonic flora in an abnormal location, the peritoneal cavity. It is, therefore, polymicrobial in nature.

  • Appendicitis is not a zoonotic disease.

What pathogens are responsible for this disease?

  • The infection in appendicitis is always polymicrobial. Intraoperative cultures usually show gram-negative organisms and anaerobes.

  • Most commonly identified specific organisms include Bacteroides fragilis and Escherichia coli.

  • Tuberculous appendicitis does occur but is very rare. Diagnosis is usually only made after careful histologic review of the pathology.

  • Although parasitic infections have been postulated as a possible cause of appendiceal obstruction and, therefore, appendicitis, most studies have failed to show a definite cause-effect relationship between intestinal parasites and appendicitis.

How do these pathogens cause appendicitis?

  • Endoluminal obstruction is usually the cause of appendicitis, and fecaliths are found in 40% of cases of acute appendicitis, 65% of cases in which the appendix has become gangrenous, and 90% of cases in which there is definite appendiceal rupture.

  • Obstruction leads to an increase in intraluminal pressure, which, in turn, leads to venous congestion and mucosal ischemia. This allows for translocation of normal colonic bacteria into the peritoneal cavity. Eventually, there is arterial compromise that may lead to gangrene, full thickness wall perforation and free release of colonic contents and bacteria into the peritoneal cavity.

  • If left untreated, this may result in abscess formation and/or inflammation of surrounding organs.

What other clinical manifestations may help me to diagnose and manage appendicitis?

  • Appendicitis occurring at extremes of age can vary in presentation. Very young children may have non-specific symptoms, such as anorexia or refusal to walk/play as normal, and elderly patients may develop symptoms late during the course of appendicitis.

  • Also, the location of the appendix can influence the presenting symptoms. Normally, the appendix is an intraperitoneal organ located behind the cecum (retrocecal, intraperitoneal). In this position, pain is in the classical right lower quadrant location. However, if the inflamed appendix is in the pelvis, patients may complain of lower abdominal pain. Likewise, if the appendix is retroperitoneal, it may cause flank or back pain. If the appendix is displaced superiorly by the gravid uterus in pregnancy, pain may be localized to the right upper quadrant.

  • If the inflamed appendix irritates the bladder or rectum, there may be dysuria or diarrhea as the presenting complaint.

  • McBurney described the location of maximal tenderness in patients with appendicitis as "from 11/2 to 2" inside of the right anterior superior spinous process of the ileus, on a line drawn to the umbilicus." The finding of localized tenderness at this point is highly suggestive of appendicitis and is still used today.

  • There are many variations to this presentation.

  • Patients at the extremes of age may have non-specific mild diffuse abdominal tenderness.

  • Immunosuppressed patients may also have very non-specific and non-impressive exams due to the lack of inflammatory response.

  • The appendix may be in an unusual location; for example, it may be retroperitoneal or pelvic in origin, leading to tenderness in the flank or low in the pelvis, or it may be displaced by a gravid uterus in the case of pregnancy, and tenderness will be high in the abdomen.

  • Other physical exam findings that may be present include "Rovsing's sign" or pain in the right lower quadrant on palpation in the left lower quadrant, the "psoas sign" or pain in the right lower quadrant with flexion of the right hip against resistance, and the "obturator sign" or pain in the right lower quadrant with flexion of the right knee and internal rotation at the hip.

  • In more advanced cases, when the appendix has perforated or there is abscess formation, physical exam may reveal generalized peritonitis, which may include rebound tenderness, involuntary guarding, or rigidity. These patients generally appear systemically ill.

  • Rectal exam may reveal tenderness in those in whom the appendix or an abscess lies near the rectum.

  • A pelvic exam should be performed in all women of childbearing age who present with lower abdominal pain, as tenderness on palpation of the cervix may suggest pelvic inflammatory disease or the exam may reveal ovarian pathology.

What other additional laboratory findings may be ordered?

  • C-reactive protein (CRP) is a marker of inflammation and may be elevated in appendicitis. Taken together, elevated WBC and elevated CRP are very sensitive for appendicitis (although fairly non-specific).

  • Elevation of WBC greater than 18,000 is unusual in acute appendicitis but may be an indication that perforation has occurred.

How can appendicitis be prevented?

  • The only sure prevention for appendicitis is appendectomy.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

Anaya, DA,, Dellinger, EP, McKean, S,. "Antimicrobial prophylaxis in surgery". Principles and practice of hospital medicine. McGraw Hill. 2012.

Ansaloni, L,, Catena, F,, Coccolini, F. "Surgery versus conservative antibiotic treatment in acute appendicitis: a systematic review and meta-analysis of randomized controlled trials.". Dig Surg. vol. 28. 2011. pp. 210-21.

DiSaverio, S,, Sibilio, A,, Giorgini, E. "The NOTA study (none-operative treatment for acute appendicitis.". Ann Surg. vol. 260. 2014. pp. 109-117.

(A prospective cohort study which examined the use of antibiotic treatment alone for suspected appendicitis. The study population consisted of carefully selected patients and the authors found a low rate of treatment failure and recurrence.)

Ditillo, MF,, Dziura, JD,, Rabinovici, R. "Is it safe to delay appendectomy in adults with acute appendicitis?". Ann Surg. vol. 244. 2006. pp. 656-60.

Drake, FT,, Alfonso, R,, Bhargava, P. "Enteral contrast in the computed tomography diagnosis of appendicitis.". Ann Surg. vol. 260. 2014. pp. 311-316.

(This study looked at concordance between CT scan findings and final pathology comparing scans which used enteral contrast and those which did not.)

Drake, FT,, Flum, DR. "Improvement in the diagnosis of appendicitis". Adv Surg. vol. 47. 2013. pp. 299-328.

(A recent review of diagnostic techniques for appendicitis.)

Drake, FT,, Mottey, NE,, Farrokhi, ET. "Time to appendectomy and risk of perforation in acute appendicitis.". JAMA. vol. 149. 2014. pp. 837-844.

(An article which compared time from admission to surgery in patients with simple appendicitis and those who were found to have a perforation.)

Hasday, SJ,, Chhabra, KR,, Dimick, JB. "Antibiotics vs. surgery for acute appendicitis: towards a patient-centered approach.". JAMA. vol. 151. 2016. pp. 107-108.

(Discussion regarding an antibiotic-only approach as an option when discussing treatment of acute appendicitis with patients.)

Liu, K,, Fogg, L. "Use of antibiotics alone for treatment of uncomplicated acute appendicitis: a systematic review and meta-analysis.". Surgery. vol. 150. 2011. pp. 673-83.

McCutcheon, BA,, Chang, DC,, Marcus, LP. "Long-term outcomes of patients with nonsurgically managed uncomplicated appendicitis.". J Am Coll Surg. vol. 218. 2014. pp. 905-913.

(A large, retrospective database review which examined outcomes after antibiotic-only treatment for acute simple appendicitis.)

Salminen, P,, Paajanen, H,, Rautio, T. "Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized trial.". JAMA. vol. 313. 2015. pp. 2340-2348.

(A large, multicenter, randomized trial that compared antibiotic treatment alone to surgical treatment in patients with acute simple appendicitis.)

Similis, C,, Symeonides, P,, Shorthouse, AJ. "A meta-analysis comparing conservative treatment versus appendectomy for complicated appendicitis (abscess or phlegmon).". Surgery. vol. 147. 2010. pp. 818-828.

(A meta-analysis of trials comparing antibiotic treatment to immediate surgery for complicated appendicitis.)

Solomkin, JS,, Mazuski, JE,, Bradley, JS. "Diagnosis and management of complicated intra-abdominal infections in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America.". Surg Infect. vol. 11. 2010. pp. 79-109.

Udgiri, N,, Curras, E,, Kella, VK. "Appendicitis, is it an emergency?". Amer Surg. vol. 77. 2011. pp. 898-901.

Wilms, IMHA,, de Hoog, DENM,, De Visser, DC. "Appendectomy versus antibiotic treatment for acute appendicitis (Review).". Cochrane Database of Sys Rev. vol. 11. 2011.

(A review of articles comparing surgery to antibiotic treatment alone for acute appendicitis.)
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