A 30-year-old woman is referred for evaluation of a 1-year history of intermittent, debilitating, postprandial right upper quadrant pain associated with nausea and occasional vomiting. The pain can last from 30 minutes to 2 hours, often radiates to the upper back between the shoulder blades, and is not associated with bowel movements or exercise. The patient denies a history of weight loss, fever, chills, change in urine or stool color, or jaundice. She denies significant alcohol use. Trials of antacids, proton pump inhibitors, and antispasmodics have not been helpful. At times the pain has been severe enough to interrupt her daily activities. The patient recently presented to her local emergency department during an episode of pain. Blood work drawn in the emergency department included alanine aminotransferase 23 U/L (normal, 0–45 U/L), aspartate aminotransferase 29 U/L (normal, 15–41 U/L), alkaline phosphatase 86 U/L (normal, 25–125 U/L), bilirubin 0.6 mg/dL (normal, 0–1 mg/dL), amylase 101 U/L (normal, 25–161 U/L), and lipase 162 U/L (normal, 40–240 U/L). The patient reports that liver chemistries and amylase and lipase levels have been persistently normal during previous episodes of abdominal pain. A right upper quadrant ultrasound reveals a normal-appearing gallbladder without gallbladder wall thickening or gallstones. The intrahepatic and extrahepatic bile ducts are not dilated. The liver and limited views of the pancreas are also unremarkable. The patient underwent an esophagogastroduodenoscopy (EGD) 1 month ago that was normal.
What is the most likely cause for this patient's symptoms? What is the next step in the diagnostic evaluation of this patient?
The Problem
The right upper quadrant pain in this patient is suggestive of biliary origin. However, this pain syndrome accompanied by a normal gallbladder ultrasound and normal liver function tests suggests subtle acalculous gallbladder disease. When such patients are encountered, other causes for right upper quadrant pain need to be considered and reasonably excluded. These include peptic ulcer disease, choledocholithiasis and microlithiasis, pancreatobiliary neoplasia, irritable bowel syndrome, and musculoskeletal pain. Type III sphincter of Oddi dysfunction (SOD) is also in the differential diagnosis, but because of the risks of endoscopic retrograde cholangiopancreatography (ERCP), gallbladder evaluation is usually undertaken first. Peptic ulcer disease can be diagnosed with EGD. Although ultrasound and magnetic resonance cholangiopancreatography (MRCP) have relatively high sensitivity rates for the detection of common bile duct stones, small stones and microlithiasis might be missed. Endoscopic ultrasound and microscopic bile examination for microlithiasis might be useful in a subset of these patients.
The pathophysiology of acalculous gallbladder pain is not well-understood. Theories that have been proposed include those that implicate gallbladder outlet obstruction, those that point to a primary disorder of gallbladder motility, and those that implicate visceral hypersensitivity. Lack of coordination between gallbladder contraction and contractions of the sphincter of Oddi or relative cystic duct narrowing might cause functional gallbladder obstruction. Abnormal gallbladder motility might occur because of entrapment of supersaturated cholesterol crystals in the gallbladder wall, impaired response to cholecystokinin (CCK), or intrinsic defects in the gallbladder musculature. Visceral hypersensitivity might play a role in acalculous biliary pain (biliary dyskinesia) analogous to that in other functional disorders of the gastrointestinal tract.
The most prominent symptom of biliary dyskinesia is right upper quadrant pain. The characteristics of this pain have been defined in the Rome III diagnostic criteria for functional gallbladder disorders ( Table 1 ). Characteristic biliary pain is intermittent, often radiates to the right shoulder or back, is frequently associated with nausea and vomiting, and might be postprandial. Consensus criteria outlined in Rome III define this pain as not being associated with posture, exercise, or bowel movements. Jaundice and fever are usually not present. Physical examination is usually unremarkable except for mild right upper quadrant tenderness. Other Rome III requisite criteria for the diagnosis of acalculous gallbladder disease include an intact gallbladder and normal liver chemistries, amylase, and lipase.
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