Current Approach to the Diagnosis and Emergency Department Management of Appendicitis in Children

CME REVIEW ARTICLE

Susan C. Lipsett, MD and Richard G. Bachur, MD

of negative appendectomies.2 More recently, the negative appen- Abstract: Concerns about radiation exposure have led to a decrease in the dectomy rate in children approaches 4%, with higher rates in use of computed tomography in suspected appendicitis, with increased re- young children and female adolescents.3 liance on ultrasound. Children with suspected appendicitis should be risk Because of increasing recent concerns about radiation stratified using a combination of clinical signs and symptoms, white blood exposure in children, the rate of CTusage in the evaluation of ap- cell count, and ultrasound in order to guide further evaluation and manage- pendicitis has decreased significantly with a balancing increase ment. Magnetic resonance imaging is a promising imaging modality in ultrasound utilization. Reassuringly, this trend appears to have but remains costly. Ongoing research is evaluating the role of nonoper- had no adverse effect on the rate of ED revisits, appendiceal perfo- ative management in children with confirmed appendicitis. ration, or negative appendectomy rate.4 Recent progress in the Key Words: abdominal pain, appendicitis, clinical decision rule, evaluation of suspected appendicitis has focused on strategies diagnostic testing, surgery that integrate clinical scores, the white blood cell (WBC) count, – and ultrasound findings to risk-stratify children and facilitate (Pediatr Emer Care 2017;33: 198 205) management decisions.

TARGET AUDIENCE EPIDEMIOLOGY This CME activity is intended for physicians who care for The incidence of acute appendicitis in the United States is 11 children with acute abdominal pain, including general pediatri- per 10,000 people per year, with a lifetime risk of appendicitis cians, emergency physicians, and surgeons. between 5% and 10%.5 Appendicitis is most common in children 10 to 19 years of age and has a slight male predominance.5 It LEARNING OBJECTIVES is also slightly more common in the summer months.5 Risk fac- After completion of this article, the reader should be able to: tors for perforation include longer duration of symptoms and younger age.6–8 1. Describe trends in diagnostic imaging for children with suspected appendicitis. DIFFERENTIAL DIAGNOSIS 2. Integrate clinical presentation, laboratory studies, and ultra- The differential diagnosis of a child presenting with suspected sound findings to assess a child’s risk of appendicitis and guide appendicitis is broad and is summarized in Figure 1. Special con- further workup. sideration should be given to the female adolescent, who is at risk 3. Provide appropriate initial management for children with con- of ectopic pregnancy and ovarian pathology, and to the very firmed appendicitis in the emergency department. young child, who is at increased risk of perforation.

cute appendicitis remains a diagnostic challenge for pediatric HISTORY AND PHYSICAL EXAMINATION A acute care clinicians. In this article, we review the historical The first symptom of appendicitis in a child is usually a com- perspective and epidemiology of acute appendicitis in children. plaint of periumbilical or generalized abdominal pain. Classically, We will then outline a basic framework for the diagnostic ap- but not always, over the course of hours, the pain worsens and mi- proach to children with suspected appendicitis, which integrates grates toward the right lower quadrant (RLQ). Low-grade fever, clinical findings, laboratory studies, and imaging modalities. anorexia, nausea, and vomiting may be present, but the abdominal pain generally precedes these symptoms. The child may complain HISTORICAL PERSPECTIVE of pain with walking. The location of pain in appendicitis may Appendicitis was first described in 1886, with prompt surgi- vary, depending on the length and position of the appendix. Thus, cal management recommended as definitive treatment.1 Until the clinicians should not eliminate appendicitis from consideration in late 20th century, diagnosis was purely based on history and phys- children presenting with pain in the right upper quadrant, flank, ical examination, with an acceptable negative appendectomy rate groin, or suprapubic region. Similarly, the duration of the symp- of 20% to 25%.2 The increase in utilization of computed tomogra- toms will affect the intensity of the symptoms and signs, making phy (CT) over the last 2 decades led to a steady decrease in the rate the diagnosis quite difficult in the early stages. The physical examination should begin with a general as- sessment of the appearance and activity level of the child. An ac- Staff Physician (Lipsett) and Chief (Bachur), Division of Emergency Medicine, tive child who is walking easily around the room is less likely to Boston Children’s Hospital, Boston, MA. have appendicitis than the child who is laying quietly in bed resis- The authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no tant to movement. Key components of the examination include financial relationships with, or financial interest in, any commercial careful examination of the lung fields to evaluate for pneumonia organizations pertaining to this educational activity. and a genitourinary examination especially in males (testicular Reprints: Susan C. Lipsett, MD, Division of Emergency Medicine, Boston torsion, hernia) and amenorrheic pubescent girls (hematocolpos). Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (e‐mail: [email protected]). In sexually active girls, a bimanual examination may be indicated Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. to assess for cervical motion tenderness and adnexal tenderness or ISSN: 0749-5161 fullness. The abdominal examination should focus on the location

198 www.pec-online.com Pediatric Emergency Care • Volume 33, Number 3, March 2017

FIGURE 1. Differential diagnosis of children with suspected appendicitis. of maximal tenderness, with the RLQ being most suggestive of ap- appendicitis exhibited features such as RLQ tenderness, percus- pendicitis; many clinicians refer to the point of maximal tender- sive tenderness, and guarding.9 ness relative to McBurney point, the position one third of the distance medially along a line drawn from the anterior superior il- LABORATORY EVALUATION iac spine to the umbilicus. Examination of the abdomen should also attempt to identify signs of peritonitis such as rebound tender- A complete blood count with differential should be obtained ness, guarding, and referred pain to the RLQ from palpation of the for all children in whom appendicitis is suspected, as the WBC count and absolute neutrophil count (ANC) have been shown to left lower abdomen (Rovsing sign). Unwillingness to jump or 10–12 cough is also suggestive of peritoneal irritation. Bowel sounds will be useful in predicting risk of appendicitis. be hypoactive in advanced appendicitis. Right-lateral-wall tender- Other laboratory tests, although not generally useful in ness on rectal examination can also be suggestive of appendicitis, predicting risk of appendicitis, may help to exclude alternate eti- but rectal examinations have become less routine in young chil- ologies. A urine pregnancy test should be obtained for all dren. Less specific findings in patients with an inflamed retrocecal postpubertal females. A normal urinalysis rules out new-onset di- appendix include an obturator sign (pain with internal rotation of abetes and decreases the likelihood of urinary tract infection or the right hip) and psoas sign (pain with extension of the hip or flex- nephrolithiasis. It is important to remember that many children “ ” ion of the hip against resistance). with appendicitis will have sympathetic, or sterile, pyuria with Table 1 summarizes the frequency of specific signs and a few WBCs in the urine due to ureteral or bladder irritation. If symptoms in children with suspected appendicitis. It should be the abdominal pain is more prominent in the right upper quadrant noted that many children present with atypical features; for exam- or if there is persistent vomiting, transaminases, serum bilirubin, ple, in the cited study, 40% of children with confirmed appendici- and lipase may be indicated to evaluate for hepatobiliary pathology tis did not have anorexia, 30% did not have maximal tenderness in or pancreatitis. Serum electrolytes should be obtained in ill- the RLQ, and 20% had pain duration of more than 48 hours. Al- appearing or very dehydrated patients. C-reactive protein, although possibly associated with increased risk of perforation and most 20% of children with confirmed appendicitis had report of 13–15 diarrhea. In addition, a substantial number of children without complicated clinical course, does not discriminate appendicitis from other causes of abdominal pain.

TABLE 1. Frequency of Signs and Symptoms in Children With CLINICAL SCORES Suspected Appendicitis9 Although history, physical examination, and laboratory findings are helpful in the evaluation of a patient with suspected appen- Finding Appendicitis, % No Appendicitis, % dicitis, no single finding sufficiently predicts a child’s risk. Thus, several clinical scores have been developed that combine historical Anorexia 59.6 47.4 and examination factors with WBC count to better risk stratify in- Nausea and/or vomiting 71.1 55.7 dividuals with suspected appendicitis.11,16,17 Migration of pain 50.2 27.5 The Kharbanda low-risk rule for appendicitis states that pa- Gradual onset of pain 55.3 55.4 tients with an ANC of less than 6.75 Â 103/μL and either no max- Pain duration of <48 h 82.2 74.1 imal tenderness in the RLQ or maximal tenderness in the RLQ but Absence of diarrhea 82.9 78.4 no pain with walking, jumping, or coughing have a low risk of ap- 11 Guarding 63.6 42.3 pendicitis. With a sensitivity of 98%, the rule was very effective Percussive tenderness 69.3 39.0 in identifying children who were unlikely to have appendicitis and Decreased bowel sounds 36.3 14.3 in whom imaging may be deferred while observing the patient for improvement or progression. RLQ tenderness 67.8 53.4 The original Alvarado score (also known by the mnemonic Rovsing sign 31.9 15.9 MANTRELS) was intended to direct adult patients to surgery,16 Rebound pain 48.5 24.7 but does not have sufficient performance in children to determine Temperature ≥38°C 17.3 19.7 the need for operative care.18,19 Similarly, Samuel17 proposed the Adapted from Becker et al.9 Pediatric Appendicitis Score (PAS) to identify high-risk patients in need of surgery (Table 2). Subsequent studies indicated that

TABLE 2. Calculation of the PAS and Alvarado Score16,17

Finding PA S A lvar ad o RLQ tenderness to palpation 22 RLQ pain with hopping, coughing, or percussion (PAS) or rebound tenderness (Alvarado) 2 1 Anorexia 11 Nausea and/or vomiting 11 Migration of pain to RLQ 11 Fever ≥38°C (PAS) or >37.3°C (Alvarado) 1 1 WBCs ≥10,000/μL 12 ≥75% neutrophils (PAS) or left shift (Alvarado) 1 1 Adapted from Alvarado16 and from Samuel.17 the PAS cannot be used for that purpose,18,19 but can be used for without an appendicolith or localized free fluid (Fig. 2). While the risk stratification to guide further evaluation. overall sensitivity has been cited at 88%, with a specificity of 94%,22 Thus, the current preferred approach to suspected appendici- ultrasound is operator dependent, and sensitivity is as low as 35% tis is to use clinical scores or decision algorithms to risk stratify pain institutions where ultrasound is used infrequently in the evalua- tients into those who may require further observation (low risk), tion of suspected appendicitis.23 Sensitivity of ultrasound is highly those who would benefit from additional data through advanced dependent on the ability to visualize the appendix. When the ap- imaging (medium risk), and those who need more urgent surgi- pendix is visualized and able to be characterized as normal or abnor- cal consultation for advanced or possibly complicated appendi- mal, the sensitivity of ultrasound is close to 98%.23 Unfortunately, citis (high risk). Two recent publications have combined the ultrasound fails to visualize the appendix in nearly 50% of cases.23 clinical score with the results of ultrasound to further refine A nonvisualized appendix is more common in patients with high decision making.20,21 body mass index.24 In an ultrasound with a nonvisualized appendix, the presence of secondary signs, such as focal phlegmon, hyperechoic pericecal fat, or a moderate to large amount of free IMAGING fluid should be considered highly suggestive of appendicitis.25 The most common imaging modalities in the emergency de- One recent retrospective study found that a nonvisualized appen- partment evaluation of suspected appendicitis are CT and ultra- dix without secondary signs in a patient with WBC of less than sound. Computed tomography has superior test characteristics, 7.5 Â 103/mL had a negative predictive value of 98.9%.26 Impor- but ultrasound is more commonly used as a first-line modality tantly, the sensitivity and negative predictive value of ultrasound to limit radiation exposure in children. Plain films of the abdo- improve with duration of abdominal pain.27 men are not routinely indicated without concerns for obstruc- Computed tomography has a sensitivity of 94% and a specific- tion or alternative diagnoses; occasionally, the plain film can ity of 95% for the diagnosis of appendicitis in children (Fig. 3).22 If reveal appendicoliths, urolithiasis, or significant constipation. CT is performed, intravenous contrast alone is generally adequate.28 On ultrasound, an inflamed appendix will generally appear as Enteral contrast could be considered if there is concurrent concern an enlarged, hyperemic, noncompressible tubular structure with or for bowel obstruction, abscess, or inflammatory bowel disease. Some institutions have developed reduced-dose CT scan protocols specifically for the diagnosis of appendicitis, which can further help limit radiation exposure in children.29,30 Because of the aforementioned limitations of ultrasound and appropriate concerns about radiation exposure with CT, there has been increasing interest in the use of magnetic resonance imaging (MRI) in the diagnosis of appendicitis (Fig. 4). Magnetic resonance imaging appears to have excellent test characteristics31 but is limited by availability and cost and is not yet widely used as a routine diagnostic modality.

APPROACH TO THE CHILD WITH A NONDIAGNOSTIC ULTRASOUND The most challenging scenario is a patient who has moderate suspicion of appendicitis, but has a nondiagnostic ultrasound. Management of such a patient depends on risk tolerance of the clinical team and patient/family, the ability to have close outpatient follow-up, and the availability of advanced imaging modalities. A child who is overall well appearing, has improving symptoms or signs and a normal WBC count and differential, and can reliably return if symptoms worsen may be discharged home with careful counseling after an oral fluid challenge. Patients with more FIGURE 2. Ultrasound, tip appendicitis. Case courtesy of Dr Maulik severe clinical symptoms, worsening symptoms or signs, or an el- S. Patel, Radiopaedia.org, rID: 13043. evated WBC count may be considered for CT scan, MRI scan, or

FIGURE 3. Computed tomography, acute appendicitis with appendicolith and surrounding fat edema. A, Axial view. B, Coronal view. Case courtesy of Dr David Cuete, Radiopaedia.org, rID: 27049. inpatient admission with serial abdominal examinations. Because visualize necessary structures, pain control is best offered prior patients with a high pretest probability of appendicitis and an to ultrasound. equivocal or even negative ultrasound still have significant risk Once appendicitis is confirmed, antibiotics should be given to of appendicitis,20 these patients should be considered for advanced all patients. While one prospective cohort study did not show a imaging such as CT or MRI. Serial ultrasounds have also been benefit of preoperative antibiotics in children with appendicitis, used successfully in patients with initially equivocal ultrasounds this study was limited by small numbers.35 The American Pediatric and persistent clinical concern for appendicitis.24 A basic ap- Surgical Association recommends that all children with appendici- proach to risk stratification and management is outlined tis receive preoperative broad-spectrum antibiotics.36 Vital signs in Figure 5. should be obtained frequently to monitor for evolving sepsis. Sur- gical consultation should be obtained, with transfer to an appropriate facility when necessary. EARLY MANAGEMENT CONSIDERATIONS All children with suspected appendicitis should not be allowed to eat or drink. In the hemodynamically unstable or ill- ADDITIONAL MANAGEMENT CONSIDERATIONS appearing patient, fluid resuscitation, empiric broad-spectrum antibiotics, and emergency surgical consultation are crucial. Urgent Versus Emergent Operative Care For less critical patients, intravenous analgesics and antiemetics When surgical management is indicated, operative care should be offered. It has been shown that use of opioids does not should proceed in an urgent, but not necessarily emergent, manner. – mask features important for diagnosis of appendicitis32 34; thus, While overall duration of symptoms does predict perforation, re- early pain management is encouraged. As ultrasound requires cent studies have shown that taking a reasonable amount of time graded compression in the RLQ to displace bowel gas and to perform an appropriate examination and to conduct serial examinations does not increase the risk of histopathologic perforation or postoperative wound infections.37,38 Given the routine use of preoperative antibiotics39 and current surgical techniques, early perfo- rations have excellent outcomes.36

Operative Versus Nonoperative Management Children with perforated appendicitis may be admitted for intravenous antibiotics pending percutaneous and per-rectum drain- age procedures and/or delayed appendectomy. While the majority of children with nonperforated appendicitis undergo urgent appendectomy, a growing body of research suggests that select children with uncomplicated appendicitis may be adequately treated nonoperatively with antibiotics.40–46 Ratesofsubse- quent appendectomy were 20% to 40% in studies with 1-year follow-up,43,44,46 and the presence of an appendicolith has been shown to lead to an unacceptably high rate of relapse.40 Are- FIGURE 4. Axial T2-weighted MRI demonstrating a dilated cent study suggested that involvement of the patient and/or fam- fluid-filled appendix (arrow) with periappendiceal fat stranding ily in the decision for operative or nonoperative management is and 2 appendicoliths (dark signal within the appendix lumen). Case a reasonable option that could lead to decreased morbidity and courtesy of Radiologypics.com. cost.47 Opportunities exist for future research to identify those

FIGURE 5. Basic approach to risk stratification and workup of children with suspected appendicitis. who are likely to succeed with medical management alone ver- 5. Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis sus those who may benefit from early operative intervention. and appendectomy in the United States. Am J Epidemiol. 1990;132: 910–925. FUTURE DIAGNOSTIC STRATEGIES 6. Bonadio W, Peloquin P, Brazg J, et al. Appendicitis in preschool aged children: regression analysis of factors associated with perforation outcome. The optimal diagnostic approach to patients with suspected J Pediatr Surg. 2015;50:1569–1573. appendicitis is an active area of research. Refined management strategies will likely include electronic medical record–based de- 7. Narsule CK, Kahle EJ, Kim DS, et al. Effect of delay in presentation on rate of perforation in children with appendicitis. Am J Emerg Med. 2011;29: cision support with age-adjusted and gender-adjusted risk strati- – fication. Improvements in ultrasound technology and scanning 890 893. techniques, as well as more standardized reporting, will aid clini- 8. Nelson DS, Bateman B, Bolte RG. Appendiceal perforation in children cians in risk stratification. Use of point-of-care ultrasound may diagnosed in a pediatric emergency department. Pediatr Emerg Care.2000; help streamline care for children with suspected appendici- 16:233–237. tis.48 Finally, while the WBC and ANC have been the main 9. Becker T, Kharbanda A, Bachur R. Atypical clinical features of pediatric laboratory values used in the diagnosis of appendicitis in chil- appendicitis. Acad Emerg Med. 2007;14:124–129. dren, other biomarkers from both the serum and urine, identi- 10. Anandalwar SP, Callahan MJ, Bachur RG, et al. Use of white blood cell fied through studies of the pathophysiology of the disease, are count and polymorphonuclear leukocyte differential to improve the 49–55 being investigated. predictive value of ultrasound for suspected appendicitis in children. JAm Coll Surg. 2015;220:1010–1017. REFERENCES 11. Kharbanda AB, Dudley NC, Bajaj L, et al. Validation and refinement of a 1. Keyzer C. Historical Background, Anatomy and Function, Etiology and prediction rule to identify children at low risk for acute appendicitis. Arch – Epidemiology. In: Keyzer C, Gevenois PA, eds. Imaging of Acute Pediatr Adolesc Med. 2012;166:738 744. Appendicitis in Adults and Children. 1st ed. Berlin, Germany: 12. Wang LT, Prentiss KA, Simon JZ, et al. The use of white blood cell count Springer-Verlag; 2012:3–9. and left shift in the diagnosis of appendicitis in children. Pediatr Emerg – 2. Keyzer C, Gevenois PA. Coursey Cea. Impact of imaging on negative Care.2007;23:69 76. appendectomy rate. In: Imaging of Acute Appendicitis in Adults and 13. Gavela T, Cabeza B, Serrano A, et al. C-reactive protein and procalcitonin Children. 1st ed. Berlin, Germany: Springer-Verlag; 2012:221–232. are predictors of the severity of acute appendicitis in children. Pediatr – 3. Bachur RG, Hennelly K, Callahan MJ, et al. Diagnostic imaging and Emerg Care. 2012;28:416 419. negative appendectomy rates in children: effects of age and gender. 14. Panagiotopoulou IG, Parashar D, Lin R, et al. The diagnostic value of white Pediatrics. 2012;129:877–884. cell count, C-reactive protein and bilirubin in acute appendicitis and its – 4. Bachur RG, Levy JA, Callahan MJ, et al. Effect of reduction in the use of complications. Ann R Coll Surg Engl. 2013;95:215 221. computed tomography on clinical outcomes of appendicitis. JAMA Pediatr. 15. Sammalkorpi HE, Leppäniemi A, Mentula P. High admission 2015;169:755–760. C-reactive protein level and longer in-hospital delay to surgery are

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