What are the potential causes of symptoms suggestive of chronic cholecystitis in a middle-aged to elderly female with no gallstones noted on Right Upper Quadrant (RUQ) ultrasound?

Causes of RUQ Symptoms Without Gallstones on Ultrasound

When ultrasound shows no gallstones but symptoms suggest biliary disease, the primary considerations are acalculous cholecystitis (acute or chronic), functional gallbladder disorder, sphincter of Oddi dysfunction, and non-biliary causes that mimic cholecystitis.

Acalculous Cholecystitis

Acute Acalculous Cholecystitis (AAC)

• AAC occurs in critically ill patients with atherosclerotic heart disease, recent trauma, burns, surgery, or hemodynamic instability 1
• The presentation is often insidious with unexplained fever, leukocytosis, hyperamylasemia, or abnormal aminotransferases, and patients frequently lack right upper quadrant tenderness 1
• In elderly bedridden patients, AAC carries high risk of gangrene or perforation and requires early imaging detection 2
• Ultrasound findings meeting Tokyo Guidelines criteria (two major criteria OR one major plus two minor criteria) predict worse prognosis with higher complication rates (27.9% vs 0%), longer symptom duration (8 vs 4 days), and prolonged antibiotic therapy (13 vs 5 days) 2

Chronic Acalculous Cholecystitis

• Patients with typical biliary colic (chronic or recurrent postprandial RUQ pain) without gallstones on ultrasound may have chronic acalculous cholecystitis 3
• Laparoscopic cholecystectomy provides symptom relief in approximately 78% of patients with this presentation 3
• CCK-stimulated hepatobiliary scintigraphy (HIDA scan with CCK) has poor predictive value for surgical outcomes, with positive predictive value of 0.78 and negative predictive value of only 0.20 3, 4
• Reduced gallbladder ejection fraction (<35%) does not reliably predict either histologic chronic cholecystitis or clinical outcome after cholecystectomy 4

Diagnostic Algorithm When Ultrasound is Negative

Initial Imaging Interpretation

• The diagnosis of chronic cholecystitis is difficult on anatomic imaging, as the gallbladder may appear contracted or distended with pericholecystic fluid usually absent 5
• A normal gallbladder wall appearance makes acute gallbladder pathology very unlikely 5
• The sonographic Murphy sign has relatively low specificity and is unreliable after pain medication administration 5, 6

Next-Step Imaging

• Cholescintigraphy (HIDA scan) is the recommended next step when ultrasound is negative or equivocal and clinical suspicion remains high, with sensitivity of 96-97% and specificity of 90% for acute cholecystitis 6, 7
• MRI with MRCP provides comprehensive biliary evaluation with sensitivity of 50-91% for acute cholecystitis and can distinguish acute from chronic cholecystitis based on T2 signal characteristics 6, 7
• CT with IV contrast is appropriate when complications are suspected, detecting emphysematous cholecystitis, perforation, hemorrhage, and gangrenous changes 6, 7

Sphincter of Oddi Dysfunction

• Among patients who undergo cholecystectomy for presumed acalculous cholecystitis but have persistent RUQ pain postoperatively, sphincter of Oddi dysfunction should be considered 3
• Seven of 50 patients (14%) with persistent pain after cholecystectomy had abnormal sphincter of Oddi manometry and improved after endoscopic sphincterotomy 3
• This suggests sphincter of Oddi dysfunction may be the primary cause in some patients presenting with biliary-type pain without gallstones 3

Clinical Pitfalls and Caveats

Elderly and Critically Ill Populations

• Ultrasound usefulness is significantly limited in critically ill patients, where gallbladder abnormalities are common even without acute cholecystitis 5, 6
• In elderly patients, atypical pain or no pain occurs in 12% and 5% respectively, and Murphy's sign is positive in only 43.3% 5
• Fever >38°C occurs in only 6.4-10% of elderly patients with acute cholecystitis 5

Diagnostic Accuracy Limitations

• No single investigation has sufficient diagnostic power to establish or exclude acute cholecystitis without further testing, even in elderly patients 5
• Combining clinical symptoms, signs, and laboratory tests provides better diagnostic accuracy than any single test 5
• The absence of gallstones does not exclude biliary pathology, as acalculous disease accounts for a significant proportion of cholecystitis cases 3, 2, 1