Authors: Cristina M. Zeretzke-Bien, MD, FAAP, FAAEM, FACEP (Pediatric EM Attending Physician, University of Florida in Gainesville) and Carolyn Holland, MD, MEd, FACEP (EM/PEM Attending Physician, University of Florida in Gainesville) // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital, @EMHighAK)

Clinical Cases

Case 1: Bill is a 22-year-old (yo) male who presents to the emergency department (ED) with a six-hour history of periumbilical abdominal pain that gradually migrated to the right lower quadrant (RLQ). His pain is also associated with vomiting and fever. The patient’s exam shows normal testicles but focal RLQ tenderness with rebound is present. Is this appendicitis?? What is next step in the evaluation/treatment??

Case 2: Kevin is a 5 yo male who presents to the ED with a fever and non-specific, generalized lower abdominal pain. On this day, he had one episode of emesis and associated anorexia. Relevant history includes strenuous exercise the day prior. Is this appendicitis?? What is next step in the evaluation/treatment??

Case 3: Elizabeth is a 65 yo female presents to the ED complaining of a 12-hour history of “sour stomach”, suprapubic pain, and dysuria. The patient says that her symptoms feel similar to previous urinary tract infections (UTIs) so she took some left over antibiotics this morning with minimal relief. She denies fever. Physical exam reveals normal vital signs (VS) and a soft abdomen with no guarding and only mild tenderness over the suprapubic area. The patient’s urinalysis (UA) shows 10 white blood cells (WBCs), 5 red blood cells (RBCs), and no nitrates, bacteria or squamous epithelial cells. Is this appendicitis?? What is next step in the evaluation/treatment??

Introduction/Background

The lifetime risk of appendicitis is 7-8% for all patients. Close to 70% of all cases of appendicitis occur in patients less than 30 years of age with incidence peaks of 10-14 yo males and 15-19 yo females. (Cole MA, 2011) (Bhangu A, 2015) In pregnant females, appendicitis is the most common abdominal emergency not related to pregnancy and it is most commonly seen in the 2nd trimester. (Cole MA, 2011) Due to the complex nature of symptoms and typically uncommon presentations, may unfortunately be missed at the time of initial evaluation. This leads to missed appendicitis being the leading source of malpractice suits against emergency medicine physicians in adult patients with abdominal pain. It is also the 2nd leading source of malpractice suits against emergency physicians for children aged 6 to 17 years of age. (Vissers RJ, 2010) (Cole MA, 2011)

Making the Diagnosis

There is no individual sign or symptom that can reliably exclude appendicitis in any patient. (Vissers RJ, 2010) The three most valuable historical clues include RLQ pain, migration of pain from the periumbilical region to the RLQ, and pain occurring prior to vomiting. Symptoms helpful in excluding appendicitis include previous histories of similar pain and the absence of RLQ pain. (Cole MA, 2011) Of note, the classic presentation of a young adult with mid-epigastric pain that migrates to the RLQ over 12-24 hrs is present in as few as 6% of patients with acute appendicitis. The incidence of correctly diagnosing appendicitis in men is between 78-92% of the time and in women only 58-92% of the time. (Cole MA, 2011). In adolescent females, it has often been said that the only test needed is a urine pregnancy test (serum or urine B-human chorionic gonadotropin), as appendicitis is a clinical diagnosis. WBC count and C reactive protein (CRP) have limited utility in the workup of appendicitis, although CRP has been shown to be helpful in detecting perforation or abscess formation. WBC count and CRP are also both components of some common scoring algorithms. (Rothrock SG G. S., 1992)

There are three commonly used scoring systems to evaluate for appendicitis. These can be helpful to risk stratify patients who have signs and symptoms concerning for appendicitis. These three scores include the Alvarado Score (AS), the Pediatric Appendicitis Score (PAS), and the Appendicitis Inflammatory Response Score (AIRS). The Alvarado score is also known as “MANTRELS”, which stands for migration of pain, anorexia, nausea/vomiting, tenderness in the RLQ, rebound tenderness, elevated temperature, and leukocytosis with a left shift. Although both the Alvarado and the PAS scoring systems provide some useful clinical information, both systems have overall poor diagnostic utility when used as sole methods for determining the need for surgery in cases of children with suspected appendicitis” (Cole MA, 2011). While the Appendicitis Inflammatory Response Score has demonstrated better performance than the Alvarado Score, all scoring systems are, alone, inadequate for determining the need for surgical intervention. They are however, good for risk stratifying the need for imaging studies. (Andersson M, 2008)

Scoring Systems for diagnosis of appendicitis

AS (Ohle R, 2011) Migration of Pain – 1Anorexia – 1 Nausea – 1 Tenderness in RLQ – 2 Rebound pain – 1 Elevated temperature – 1 Leukocytosis – 2 Left shift – 1 *Score 1-4 (low risk), 5-6 (mod risk), 7-10 (high risk) AIS (Scott AJ, 2015) Vomiting – 1R iliac fossa pain – 1 Rebound tenderness or guarding Light– 1 Moderate – 2 Strong – 3 Temp >38.5C 1 WBC 10-14.9 – 1 >=15 – 2 Proportion of PMNs 70-84% – 1 >=85% – 2 CRP 10-49 – 1 >=50 – 2 Score 0-4 (low risk), 5-8 (intermediate risk), 9-12 (high risk) PAS (Bhatt M, 2009) Migration of pain – 1Anorexia – 1 Nausea/vomiting – 1 Fever >38C – 1 Cough/percussion/hopping tenderness – 2 WBC >10K – 1 Neutrophilia >7500 cells/mm3 – 1 *Score 0-4 (low risk), 5-7 (moderate risk), >= 8 (high risk)

Patients with AS scores less than 3 are at very low risk for appendicitis or significant alternative pathologies and are thus, not likely to benefit from a computed tomography (CT) scan. (Jones RP, 2015). Patients with moderate risk of appendicitis based on scoring algorithms may benefit from imaging studies. In general, plain films are not useful in detecting appendicitis, although a visible calcified appendicolith may be present in approximately 10% of patients with uncomplicated appendicitis. (Rothrock SG G. S., 1992) While plain abdominal x-rays can quickly rule out other causes of abdominal pain such as obstruction or perforation, providers need to remember that perforated appendicitis can be a primary cause of an obstruction (Cole MA, 2011).

Ultrasound (US) is the first choice for imaging in children as children are typically thinner and have less abdominal fat. In addition, US provides the benefit of minimal radiation as compared to the CT scan (Bhangu A, 2015). US has been found to be nearly 90% sensitive and more than 95% specific for diagnosing appendicitis in children. Positive findings include an appendiceal diameter greater 6mm or a “target” sign with five concentric layers. Perforated appendicitis cases make US less accurate. CT is a more accurate test for diagnosing appendicitis as it has greater sensitivity than US. However, CT raises other issues such as radiation exposure and increased cost. (Garcia Pena BM, 1999) While magnetic resonance imaging (MRI) gets rid of risk of radiation exposure, it has no better accuracy than US in looking for perforated appendicitis. In adolescent and adult patients, CT has a sensitivity of 92+% in detecting appendicitis. (Bhangu A, 2015)

Practice Guidelines for evaluation of RLQ pain and treatment of appendicitis in ED Patients [adapted from Emergency Medicine Practice (Cole MA, 2011)]

American College of Radiology Appropriateness Criteria – RLQ Pain – Suspected Appendicitis (Smith MP, 2013) In suspected appendicitis, CT with intravenous (IV) contrast [oral (PO) or per-rectum (PR) may not be needed based on institutional preference] is the examination of choice in all patients EXCEPT:· Pregnant women – US first followed by MRI if needed · Children – US first, followed by CT with IV contrast (PO/PR may not be needed based on institutional preference) if needed · If CT is necessary in children, consider a limited RLQ CT American College of Emergency Physicians Clinical Policy (Howell JM, 2010) In patients with suspicion for appendicitis· History and physical exam (H&P) to risk stratify · Abdominal CT without IV/PO contrast is acceptable, although IV/PO contrast may increase sensitivity · In pediatric patients, US should be used to diagnose but not exclude appendicitis Surgical Infection Society and the Infections Diseases Society of America – (Solomkin JS, 2010) · CT is the diagnostic test of choice to identify intra-abdominal infection (such as appendicitis) for adults not undergoing immediate laparotomy.

In children, the age of presentation also causes some issues in early diagnosis and treatment. Infants and small children under the age of 2 have anatomical differences such as less lymphoid tissue and a funnel-shaped appendix which is more difficult to obstruct. Because of the difficulty in diagnosis due to atypical presentations, it is often initially diagnosed at autopsy. In fact, mortality from acute appendicitis exceeds 80% in this population. Irritability, fussiness, lethargy, and hypotension are often warning signs to consider in the neonate. (Rothrock SG P. J., 2000) (Lin Y, 2003) (Bundy DG, 2007) Toddlers and preschool age children may have symptoms such as vomiting, abdominal pain, fever, and diarrhea with the presentation, but the focal pain in the RLQ does not usually present until later in childhood.

School age children finally start to present with more reliable exams, but again symptoms very. Pain with jumping or coughing in this age group is present in 93% and is included in the PAS (Samuel, 2002). School age children also tend to present with fever after 24 hours, focal RLQ pain, and vomiting. Family history may also become relevant in this age group as first degree relatives who have had appendicitis increases the risk 3-10 fold. (Gauderer MWL, 2001)

Adolescents present with a more reliable H&P and often have clinical features that are similar to those seen in adults. They also have behaviors that put them at risk for other pathologies that may mimic appendicitis. Unprotected sexual activity can place adolescent patients at risk for infections such as epididymitis in males, and pelvic inflammatory disease/tubo-ovarian abscess in females. In females of reproductive age, initial testing should include a pregnancy test, a pelvic exam, and possibly ultrasound imaging. On pelvic exam, cervical motion tenderness can be found in up to 28% of female patients with appendicitis. (Bhangu A, 2015) (Cole MA, 2011) . A pregnancy test is also recommended to evaluate for possible ectopic pregnancy. Ultrasound imaging, preferably transvaginal, is suggested to evaluate for ovarian or fallopian tube pathology. Male patients must undergo a full genitourinary exam to fully evaluate for hernias or testicular pathology.

Diagnostic Pitfalls

Common findings in cases where the diagnosis of appendicitis was missed include lack of distress, no rebound or guarding, discharge diagnosis of gastroenteritis, and/or lack of timely follow up (Vissers RJ, 2010).

Inflammation and obstruction of the appendix may be limited to the distal portion of the appendix and this is called “tip appendicitis”. Tip appendicitis is often missed on CT scans, causing false negative CT reads (Cole MA, 2011). Thus, if your index of suspicion is high, even in the setting of a negative CT read, surgical consultation and admission for observation is warranted.

Do not forget about other portions of the physical exam to evaluate alternative causes of RLQ pain. This includes lung auscultation of the lower lung fields to evaluate for pneumonia, a testicle exam in males to evaluate for torsion or epididymitis, and a pelvic exam in females to look for PID or ovarian/fallopian tube pathology (Cole MA, 2011).

Evidence of inflammation in a patient’s urine may be misleading and should not be relied upon to exclude appendicitis (Cole MA, 2011).

Geriatric patients with appendicitis are rare. However, be mindful that older patients may exhibit subtle clinical findings (Vissers RJ, 2010).

Diagnostic pearls

Heme positive diarrhea is more likely due to an entero-invasive infection (ie – salmonella, shigella, etc) than appendicitis (Cole MA, 2011).

A UA with >30 RBC or >20 WBC is more consistent with a UTI than ureteral inflammation from an inflamed appendix (Cole MA, 2011).

Management

Major aspects of treating appendicitis in the ED include pain control, IV fluids, antibiotics, and definitive treatment with surgical consultation (Cole MA, 2011) .

Supportive Care

Providing appropriate pain medication does not interfere with the diagnostic accuracy of appendicitis (Green R, 2005). Volume replacement, as well as keeping the patient NPO (nil per os), are important elements to implement early in the course of treatment for all patients, regardless of age. If fever exists, it is important to provide antipyretics with acetaminophen IV or PR.

Antibiotics

Antibiotics with aerobic and anaerobic actions to cover normal gut flora should be used (Bhangu A, 2015). A 2000 study by Rodriquiz et al demonstrated that antibiotic therapy in pediatric patients with ticarcillin/clavulanate plus gentamicin was associated with fewer infections and faster recovery than the traditional therapy of ampicillin with clindamycin and gentamicin. (Rodriquiz JC, 2000)

Surgical Infection Society and the Infections Diseases Society of America – (Solomkin JS, 2010) · Antibiotics should be initiated once a patient receives the diagnosis of an intra-abdominal infection or once an infection is considered likely. Patients with septic shock should be given immediate antibiotic therapy. For patients without shock, antibiotics should be given as per protocol in the ED.· Recommended antibiotics in pediatric patients include a carbapenem (imipenem, meropenem, or ertapenem), a β-lactam/β-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole. · Recommended antibiotics in adult patients: for mild-to-moderate community-acquired infection, ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin are preferable to regimens with substantial anti-Pseudomonal activity

Definitive therapy

In uncomplicated appendicitis, antibiotic therapy is effective whether given pre or post-operatively. Based on this, it is not unreasonable to make decisions regarding antibiotic therapy with the admitting surgeon. Definitive therapy is an appendectomy. Surgeons may utilize the CRP level to triage appendicitis cases to the operating room. CRP greater than 99 mg/L is present in 90% of cases of complicated appendicitis. Patients with normal CRP levels can have surgery safely postponed up to 12 hours (Sammalkorpi HE, 2015).

Misdiagnosis (most common) OR Missed Diagnosis

Viral syndrome

Intussusception

UTI

Gastroenteritis

Kidney stones

PID

Ovarian/Testicular Torsion

URI / Pneumonia

Final Clinical Pearls

Clinical presentation depends on age of presentation

Limit radiation when possible and explore imaging techniques such as ultrasound

when possible and explore imaging techniques such as Labs are sometimes necessary

TREAT PAIN! Pain control will not mask the diagnosis .

. Antibiotics in uncomplicated appendicitis can be a shared decision with surgery.

References/Further reading

Andersson M, A. R. (2008). The appendicitis inflammatory response score: a tool for the diagnosis of acute appendicitis that outperforms the Alvarado Score. World Journal of Surgery, 32(8), 1843-49.

Bhangu A, S. K. (2015). Acute appendicitis: modern understanding of pathogenesis. The Lancet, 386, 1278-87.

Bhatt M, J. L. (2009). Prospective validation of the pediatric appendicitis score in a Canadian pediatric emergency department. Academic Emergency medicine, 16(7), 591-6.

Bundy DG, B. J. (2007, July 25). Does this child have appendicitis? Journal of the American Medical Association, 298(4), 438-51.

Cole MA, M. N. (2011). Evidence-based management of suspected appendicitis in the emergency department. Emergency Medicine Practice, 13(10), 1-32. Retrieved from ebmedicine.net

Garcia Pena BM, M. D. (1999). Ultrasonography and liminted computed topography in the diagnosis and management of appendicitis in children. Journal of the American Medical Association, 282, 1041-46.

Gauderer MWL, C. M. (2001). Acute appendicitis in children: the importance of family history. Journal of Pediatric Surgery, 36, 1214-17.

Green R, B. B. (2005). Early analgesia for children with acute abdominal pain. Pediatrics, 116, 978-83.

Howell JM, E. O. (2010). Clinical Policy: Critical issues in the evaluation and management of emergency department patients with suspected appendicitis. Annals of Emergency medicine, 55(1), 71-116.

Jones RP, J. R. (2015). The Alvarado score as a method for reducing the number of CT studies when appendiceal ultrasound fails to visualize the appendix in adults. Gastrointestinal Imaging, 204, 519-26.

Lin Y, L. C. (2003). Appendicitis in infancy. Pediatric Surgery International, 19, 1-3.

Ohle R, O. F. (2011). The Alvarado score for predicting acute appendicitis: a systematic review. BMC Medicine, 9, 139. Retrieved from http://www.biomedcentral.com

Paulson EK, K. M. (2003, January 16). Suspected Appendicitis. New England Journal of Medicine, 348(3), 236-42.

Rodriquiz JC, B. D. (2000). Comparison of two antibiotics regiments in the treatment of perforated appendicitis in pediatric patients. International Journal Clinical Pharmacology and Therapeutics, 38, 492-99.

Rothrock SG, G. S. (1992). Plain abdominal radiography in the detection of major disease in children. Annal of Emergency Medicine, 21, 1423-29.

Rothrock SG, P. J. (2000). Acute appendicitis in children emergency department diagnosis and management. Annals of Emergency Medicine, 36, 39-51.

Rothrock, S. (2008). Appendicitis. In R. S. Baren JM, Pediatric Emergency Medicine (pp. 576-81). Philadephia, PA: Saunders Elsevier.

Sammalkorpi HE, L. A. (2015). High admission C-reactive protein level and longer in-hospital delay to surgery are associated with increased risk of complicated appendicitis. Langerbecks Archives of Surgery, 400, 221-28.

Samuel. (2002). Pediatric appendicitis score. Journal of Pediatric Surgery, 37, 877-81.

Scott AJ, M. S. (2015). Risk stratification by the Appendicitis Inflammatory Response score to guide decision-making in patients with suspected appendicitis. British Journal of Surgery, 102(5), 563-72.

Smith MP, K. D. (2013). Right lower quadrant pain — suspected appendicitis. ACR Appropriateness Criteria. American College of Radiology. Retrieved 2015, from American College of Radiology: https://acsearch.acr.org/list

Solomkin JS, M. J. (2010). Diagnosis and Management of Complicated Intra-abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clinical Infectious Diseases, 52(2), 133-64.

Vissers RJ, L. W. (2010). Pitfalls in appendicitis. Emergency Medicine Clinics of North America, 28, 103-18.

Wesson, D. E. (2015, September 14). Acute appendicitis in children: Management. Retrieved from UpToDate: http://www.uptodate.com/contents/acute-appendicitis-in-children-management