What is the differential diagnosis and management for a middle-aged woman with a history of gallstones presenting with right upper quadrant pain that is not exacerbated by palpation?

Right Upper Quadrant Pain Without Tenderness on Palpation

Initial Diagnostic Approach

In a middle-aged woman with known gallstones presenting with RUQ pain that is not exacerbated by palpation, ultrasound remains the mandatory first imaging study, but the absence of a positive Murphy sign significantly reduces the likelihood of acute cholecystitis and should prompt consideration of chronic cholecystitis, biliary dyskinesia, choledocholithiasis, or non-biliary causes. 1

Key Clinical Distinction

• The absence of tenderness on palpation (negative Murphy sign) has relatively low specificity for excluding acute cholecystitis, but when combined with lack of fever and normal white blood cell count, shifts the differential toward chronic or functional biliary disorders rather than acute inflammatory processes 1
• The sonographic Murphy sign—focal tenderness when the ultrasound probe directly compresses the gallbladder—has low specificity and becomes unreliable if the patient received pain medication prior to imaging 1, 2

Differential Diagnosis Priority

Most Likely Diagnoses in This Context:

Chronic Cholecystitis:

• Associated with gallstones in 95% of cases and results from recurrent episodes of acute inflammation 1
• Presents with recurrent postprandial RUQ pain without acute inflammatory signs 2
• Difficult to diagnose on imaging; gallbladder may appear contracted or distended with wall thickening but typically lacks pericholecystic fluid 1
• On MRI, chronic inflammation shows low T2 signal intensity in the gallbladder wall (versus high signal in acute cholecystitis due to edema) 1, 2

Biliary Dyskinesia:

• Causes typical biliary colic without gallstones or with stones present 2
• Diagnosed by cholecystokinin-augmented cholescintigraphy showing gallbladder ejection fraction <35% 2
• The American College of Radiology rates this as acceptable practice under current guidelines 1

Choledocholithiasis:

• Stones in the common bile duct can cause intermittent RUQ pain without peritoneal signs 2
• May present with elevated liver function tests, particularly GGT and alkaline phosphatase 2

Recommended Diagnostic Algorithm

Step 1: Right Upper Quadrant Ultrasound (9/9 Rating - Usually Appropriate)

• Order comprehensive RUQ ultrasound evaluating for gallstones (96% accuracy), gallbladder wall thickening, bile duct dilatation, and hepatic abnormalities 1, 2
• Specifically assess for common bile duct diameter; normal caliber has 95-96% negative predictive value for choledocholithiasis 3
• Document presence or absence of sonographic Murphy sign, though recognize its limitations 1

Step 2: Laboratory Studies

• Obtain liver function tests including GGT, alkaline phosphatase, AST/ALT, total and direct bilirubin, and complete blood count 2
• GGT elevates earlier and persists longer than alkaline phosphatase in cholestatic disorders, helping confirm hepatobiliary origin 2
• Elevated cholestatic enzymes suggest bile duct pathology requiring further evaluation 2

Step 3: If Ultrasound Shows Gallstones But No Acute Cholecystitis

Consider cholecystokinin-augmented cholescintigraphy (HIDA scan with CCK):

• Calculate gallbladder ejection fraction; <35% supports diagnosis of chronic gallbladder disease or biliary dyskinesia 2
• This test is particularly useful for patients with typical biliary-type pain but negative ultrasound for acute inflammation 1, 2
• May be less useful in patients with atypical symptoms 1

Step 4: If Ultrasound Shows Bile Duct Dilatation or Elevated LFTs

Proceed directly to MRCP:

• MRCP has 85-100% sensitivity and 90% specificity for detecting choledocholithiasis 1, 2, 3
• Superior to ultrasound for visualizing gallbladder neck, cystic duct, and common bile duct stones 1, 2
• Can identify partial biliary obstruction, biliary strictures, and sphincter of Oddi dysfunction causing intermittent symptoms 2
• The American College of Radiology recommends MRCP over CT for suspected biliary sources of RUQ pain 1

Step 5: If Ultrasound and Initial Workup Are Negative or Equivocal

Order CT abdomen with IV contrast:

• CT is not first-line for biliary disease but becomes appropriate when ultrasound is negative and alternative diagnoses must be excluded 1
• CT can identify peptic ulcer disease, pancreatitis, hepatic masses, renal pathology, and other non-biliary causes of RUQ pain 1, 4
• CT has only ~75% sensitivity for gallstones and should not replace ultrasound as initial imaging 1, 2

Critical Clinical Pitfalls to Avoid

Do not skip ultrasound and proceed directly to CT:

• Ultrasound is superior for gallbladder pathology, avoids radiation exposure, and is more cost-effective 1, 2
• CT misses up to 25% of gallstones, particularly non-calcified cholesterol stones 1, 2

Do not order HIDA scan as the primary test if elevated LFTs are present:

• Elevated LFTs indicate biliary obstruction requiring anatomic visualization of bile ducts, which HIDA scan does not provide 3
• MRCP is the appropriate test for elevated LFTs with RUQ pain 3

Do not assume negative Murphy sign excludes all biliary disease:

• Chronic cholecystitis, biliary dyskinesia, and choledocholithiasis can all present with RUQ pain without peritoneal signs 1, 2

Do not proceed to ERCP without non-invasive imaging confirmation:

• ERCP is therapeutic, not diagnostic, and carries risks of pancreatitis and perforation 3
• Always confirm biliary obstruction with ultrasound and/or MRCP before ERCP 3

Management Considerations Based on Findings

If chronic cholecystitis or biliary dyskinesia with low ejection fraction:

• Laparoscopic cholecystectomy is the treatment of choice for symptomatic patients 5
• Ursodeoxycholic acid (8-10 mg/kg/day in divided doses) can be considered for patients who are poor surgical candidates, though stone recurrence occurs in 30-50% within 2-5 years 6, 5

If choledocholithiasis confirmed:

• ERCP with stone extraction is indicated 5
• Cholecystectomy should follow if gallbladder stones are also present 5

If all biliary imaging is negative:

• Consider non-biliary causes including peptic ulcer disease, hepatic pathology, pancreatic disease, renal pathology, or referred pain from thoracic sources 1, 7, 4