Acute acalculous cholecystitis is uncommon in children and is usually caused by infection. Pathogens include streptococci (groups A and B), gram-negative organisms, particularly Salmonella and Leptospira interrogans. Parasitic infestation with ascaris or Giardia lamblia may be found. Calculous cholecystitis rarely follows abdominal trauma or burn injury or is associated with a systemic vasculitis, such as periarteritis nodosa.
Clinical features include RUQ or epigastric pain, nausea, vomiting, fever, and jaundice. RUQ guarding and tenderness are present. Ultrasonography discloses an enlarged, thick-walled gallbladder, without calculi. Serum alkaline phosphatase (ALP) activity and direct-reacting bilirubin levels are elevated. Leukocytosis is usual.
Patients can recover with treatment of systemic and biliary infection. Because the gallbladder can become gangrenous, daily ultrasonography is useful in monitoring gallbladder distention and wall thickness. Cholecystectomy is required in patients who fail to improve with conservative management. Cholecystostomy drainage is an alternative approach in a critically ill patient.
Cholelithiasis is relatively rare in otherwise healthy children, occurring more commonly in patients with various predisposing disorders (Table 358-2). In children, >70% of gallstones are the pigment type, 15-20% are cholesterol stones, and the remainder are composed of a mixture of cholesterol, organic matrix, and calcium bilirubinate. Black pigment gallstones, composed mostly of calcium bilirubinate and glycoprotein matrix, are a common complication of chronic hemolytic anemias. Brown pigment stones form mostly in infants as a result of biliary tract infection. Unconjugated bilirubin is the predominant component, formed by the high β-glucuronidase activity of infected bile. Cholesterol gallstones are composed purely of cholesterol or contain >50% cholesterol along with a mucin glycoprotein matrix and calcium bilirubinate. Calcium carbonate stones have also been described in children.
Patients with hemolytic disease (including sickle cell anemia, the thalassemias, and red blood cell enzymopathies) and Wilson disease are at increased risk for black pigment cholelithiasis. In sickle cell disease, pigment gallstones can develop before age 4 yr and have been reported in 17-33% of patients aged 2-18 yr. Genetic variation in the promoter of uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (the [TA]7/[TA]7 and [TA]7/[TA]8 genotypes) underlies Gilbert syndrome, a chronic form of unconjugated hyperbilirubinemia, and is a risk factor for pigment gallstone formation in sickle cell disease.
Cirrhosis and chronic cholestasis also increase the risk for pigment gallstones. Sick premature infants might also have gallstones; their treatment is often complicated by such factors as bowel resection, necrotizing enterocolitis, prolonged parenteral nutrition without enteral feeding, cholestasis, frequent blood transfusions, and use of diuretics. Cholelithiasis in premature infants is often asymptomatic and might resolve spontaneously. Brown pigment stones are found in infants with obstructive jaundice and infected intra- and extrahepatic bile ducts. These stones are usually radiolucent owing to a lower content of calcium phosphate and carbonate and a higher amount of cholesterol than in black pigment stones.
Cholesterol cholelithiasis in children most often affects obese adolescent girls. Cholesterol gallstones are also found in children with disturbances of the enterohepatic circulation of bile acids, including patients with ileal disease and bile acid malabsorption, such as those with ileal resection, ileal Crohn disease, and cystic fibrosis. Pigment stones can also occur in these patients.
Cholesterol gallstone formation seems to result from an excess of cholesterol in relation to the cholesterol-carrying capacity of micelles in bile. Supersaturation of bile with cholesterol, leading to crystal and stone formation, could result from decreased bile acid or from an increased cholesterol concentration in bile. Other initiating factors that may be important in stone formation include gallbladder stasis or the presence in bile of abnormal mucoproteins or bile pigments that can serve as a nidus for cholesterol crystallization.
Prolonged use of high-dose ceftriaxone, a 3rd-generation cephalosporin, has been associated with the formation of calcium-ceftriaxone salt precipitates (biliary pseudolithiasis) in the gallbladder. Biliary sludge or cholelithiasis can be detected in >40% of children treated with ceftriaxone for ≥10 days. In rare cases, children become jaundiced and develop abdominal pain; precipitates usually resolve spontaneously within several months after discontinuation of the drug.
Acute or chronic cholecystitis is often associated with gallstones. The acute form may be precipitated by impaction of a stone in the cystic duct. Proliferation of bacteria within the obstructed gallbladder lumen can contribute to the process and lead to biliary sepsis. Chronic calculous cholecystitis is more common. It can develop insidiously or follow several attacks of acute cholecystitis. The gallbladder epithelium commonly becomes ulcerated and scarred.
The most important clinical feature of cholelithiasis is recurrent abdominal pain, which is often colicky and localized to the RUQ. An older child might have intolerance for fatty foods. Acute cholecystitis may be the 1st manifestation, with fever, pain in the RUQ, and often a palpable mass. Jaundice occurs more commonly in children than adults. Pain can radiate to an area just below the right scapula. A plain roentgenogram of the abdomen can reveal opaque calculi, but radiolucent (cholesterol) stones are not visualized. Accordingly, ultrasonography is the method of choice for detecting gallstones. Hepatobiliary scintography is a valuable adjunct in that failure to visualize the gallbladder provides evidence of cholecystitis.
Cholecystectomy is curative. Laparoscopic cholecystectomy is routinely performed in symptomatic infants and children with cholelithiasis. Common bile duct stones are unusual in children, occurring in 2-6% of cases with cholelithiasis, often in association with obstructive jaundice and pancreatitis. Operative cholangiography should be done at the time of surgery, however, to detect unsuspected common duct calculi. Endoscopic retrograde cholangiography with extraction of common duct stones is an option before laparoscopic cholecystectomy in older children and adolescents.
Asymptomatic patients with cholelithiasis pose a more difficult management problem. Studies in adults indicate a lag time of more than a decade between initial formation of a gallstone and development of symptoms. Spontaneous resolution of cholelithiasis has been reported in infants and children. If surgery is deferred for any patient, however, parents should be counseled about signs and symptoms consistent with cholecystitis or obstruction of the common bile duct by a gallstone. In patients with chronic hemolysis or ileal disease, cholecystectomy can be carried out at the same time as another surgical procedure. Because laparoscopic surgery can safely be performed in children with sickle cell disease, elective cholecystectomy is being done more commonly at the time of gallstone diagnosis, before symptoms or complications develop. In cases associated with liver disease, severe obesity, or cystic fibrosis, the surgical risk of cholecystectomy may be substantial so that the risks and benefits of the operation need to be carefully considered.
