Appendicitis

Epidemiology

Approximately 80,000 US children <18 years of age develop appendicitis each year. Appendicitis can affect children of all ages, including infants younger than 1 year of age. However, the peak incidence is among those 12–18 years old. There is a slight male predominance, with an 8.7% lifetime risk for boys compared with 6.7% for girls. The incidence increases from 1–2 cases per 10,000 children <4 years of age to 25 cases per 10,000 children ages 10–19 years.

There may be a modest seasonal peak in acute appendicitis during summer months, with a higher incidence of perforation in fall and winter. The reason for this is unknown, but some have suggested this pattern may reflect problems with access to care in colder months. Factors that may increase the risk of appendicitis include a low-fiber intake and family history. Approximately one-third of patients with proven appendicitis have a family history of appendicitis, compared with 14% of children with right lower quadrant pain from other causes.

The incidence of perforation decreases with increasing age, from 70% to 95% among 1- to 4-year-old children to 10%–20% among adolescents. ^, Perforation rates are highest among minority and economically disadvantaged children. ^,

Appendicitis that has advanced to perforation is associated with more severe clinical illness, higher morbidity rates, and longer hospital stays. An elapsed time of more than 36 hours from first reported symptoms to the time of surgery correlates with an increased rate of perforation. ^{, ,} Major factors contributing to a delay in surgical intervention are lack of access to care and diagnostic uncertainty. ^, The diagnosis of appendicitis in younger children can be particularly difficult due to the challenges of recognizing the signs and symptoms in nonverbal children.

Pathogenesis

The precipitating event leading to appendicitis typically is occlusion of the lumen of the appendix between the cecal base and the tip. Occlusion can result from a foreign body such as an appendicolith, inflamed mucosa due to an infectious process, or hyperplasia of intramural lymphoid tissue. ^,

Overgrowth and translocation of bowel flora lead to an acute inflammatory infiltrate in the appendiceal wall. Progressive inflammation of the luminal wall increases intraluminal pressure. When full-thickness inflammation occurs, localized peritonitis ensues. If untreated, necrosis and frank gangrene of the appendiceal wall follow. Perforation of the appendix can then lead to expanding peritonitis and the development of an inflammatory phlegmon (i.e., intra-abdominal abscess) or generalized peritonitis. Systemic manifestations of sepsis can ensue.

Etiology

The organisms involved in the infiltration of the bowel wall in appendicitis are commonly found as flora within the lumen of the bowel, namely enteric gram-negative rods such as Escherichia coli , and anaerobic flora such as Bacteroides and Peptostreptococcus species. Studies investigating whether a predominance of certain types of flora is associated with acute appendicitis have found that Fusobacteria species are found in greater abundance in surgical appendectomy specimens, with a coincident reduction in Bacteroides species. Whether this imbalance is a cause or consequence of acute appendicitis has yet to be determined.

Appendicitis also can be caused by myriad other bacterial, viral, or parasitic pathogens either via isolated infection of the appendix, or as a part of more widespread infection of the gastrointestinal system. Yersinia enterocolitica and Yersinia pseudotuberculosis are both associated with granulomatous appendicitis as well as mesenteric lymphadenitis with inflammation of the terminal ileum, also known as pseudoappendicitis. ^, Gastrointestinal actinomycosis can manifest as chronic, granulomatous appendicitis. In Actinomyces appendicitis, chronic inflammation and associated sinus tract and abscess formation may contribute to the formation of a palpable mass surrounding the appendix that can masquerade as an abdominal neoplasm. ^, Onset is most often insidious in nature over the course of weeks to months but has also been associated with a more acute onset indistinguishable from classical acute appendicitis.

Parasites frequently are recovered from the lumen of post-operative appendiceal specimens, including Enterobius vermicularis and Entamoeba histolytica . However, their association with appendicitis is unclear. For example, E. vermicularis is isolated from removed appendices in 1%–4% of cases, but samples containing E. vermicularis do not always demonstrate surrounding inflammation, and it is unclear if this organism is actually capable of inducing mucosal injury in the appendix. ^, E. histolytica appendicitis with associated trophozoite infiltration of the appendiceal wall on pathology has been reported, although this diagnosis can be difficult to distinguish clinically from amoebic dysentery given their similar presentations. ^{, ,}

Adenovirus has been described as a cause of appendicitis, with intranuclear inclusions demonstrated on postoperative specimens . Most often, cases of adenoviral appendicitis are discovered in the setting of lymphoid hyperplasia and intussusception in infants. Cytomegalovirus (CMV) appendicitis occurs in immunocompromised patients, particularly in patients with acquired immunodeficiency syndrome (AIDS) or in patients receiving immunosuppression following solid-organ transplant. Measles virus has also been associated with appendicitis, although it is posited that rather than directly infecting the appendix, measles virus’ association with appendicitis occurs as a secondary effect of obstruction of the appendiceal lumen from surrounding lymphoid hyperplasia.

Clinical Manifestations and Differential Diagnosis

Classically, symptoms of appendicitis are periumbilical pain that migrates to the right lower quadrant, followed by nausea, occasional vomiting, and low-grade fever. The clinical presentation varies greatly, depending on the sequence of pathophysiologic events, location of the appendix in the abdomen, age of the patient, and host response to infection.

In toddlers <2 years, the most common presenting symptoms are vomiting, abdominal pain, fever, abdominal distention, diarrhea, irritability, right hip pain, and limp. In children between the ages of 2 and 5 years, abdominal pain often precedes vomiting and usually is associated with fever and anorexia. Tenesmus, which can be perceived as diarrhea, is common in infants and toddlers and can lead to misdiagnosis. School-age children describe abdominal pain that is constant and worse with movement or coughing. Nausea, vomiting, anorexia, tenesmus, and dysuria also can occur in this age group.

Two retrospective studies of children ^, and one prospective study of children and adults determined the sensitivities and specificities of symptoms. They are, respectively: vomiting, 43% and 64%; fever, 75% and 78%; anorexia, 64% and 43%; and migration of pain, 41% and 54%. In older children, the most sensitive symptom (80%) is increased pain with coughing and movement, but the specificity (52%) is low.

Physical findings also vary by age. In toddlers younger than 2 years of age, nonspecific signs such as fever and diffuse abdominal tenderness are most common. Preschool children 2–5 years of age demonstrate right lower quadrant tenderness, fever, and involuntary guarding. School-age children are more likely to have localized right lower quadrant tenderness or diffuse guarding and rebound tenderness in cases of perforated appendicitis. Two studies ^, found rebound tenderness in children to have low diagnostic accuracy (43%), with a sensitivity of 50% and specificity of 60% for appendicitis. Signs commonly equated with appendicitis such as Rovsing sign, obturator sign, and psoas sign have not been studied in detail for frequency and precision in children ( Table 65.1 ).

Other inflammatory conditions, most commonly gastroenteritis, can produce signs and symptoms similar to those of appendicitis ( Box 65.1 ). In girls, ovarian pathology such as ruptured ovarian cyst and ovarian torsion can cause right lower quadrant pain and peritoneal irritation. In neutropenic patients, differentiating appendicitis from neutropenic enterocolitis can be difficult, and imaging studies often are necessary.