What are the differential diagnoses for a 60-year-old female patient with a history of acute cholecystitis, cholelithiasis, hypertension, dyslipidemia, and asthma, presenting with recurrent right upper quadrant (RUQ) pain, tenderness in the RUQ and epigastric area, and a positive Murphy's sign?

Differential Diagnoses for Recurrent RUQ Pain with Positive Murphy's Sign

The three most likely differential diagnoses for this 60-year-old female with recurrent RUQ pain, positive Murphy's sign, and known cholelithiasis are: (1) acute cholecystitis, (2) chronic cholecystitis with recurrent biliary colic, and (3) choledocholithiasis with biliary obstruction.

1. Acute Cholecystitis (Most Likely)

This patient's presentation strongly suggests acute cholecystitis requiring immediate ultrasound confirmation and early laparoscopic cholecystectomy within 7-10 days. 1, 2

Supporting Clinical Features:

• Positive Murphy's sign is the most specific clinical finding for acute cholecystitis, with a positive likelihood ratio of 2.8 1
• Recurrent RUQ pain with tenderness on deep palpation of the RUQ and epigastric area 1
• Known history of cholelithiasis (gallstones underlie 95% of acute cholecystitis cases) 1
• Previous episode of acute cholecystitis 3 months prior requiring antibiotics 3

Key Diagnostic Considerations:

• The absence of fever and normal vital signs does not exclude acute cholecystitis, as no single clinical or laboratory finding has sufficient diagnostic power to establish or exclude the diagnosis 1
• Ultrasound must be performed immediately as the mandatory first-line imaging test, with 81% sensitivity and 83% specificity 3
• At least 2 ultrasound findings are required to establish the diagnosis: gallstones/sludge, gallbladder wall thickening (>3mm), pericholecystic fluid, gallbladder distension, sonographic Murphy's sign, or stones impacted in the cystic duct 1, 4
• If ultrasound is equivocal, hepatobiliary scintigraphy (HIDA scan) is the gold standard next test with 97% sensitivity and 90% specificity 1, 4

2. Chronic Cholecystitis with Recurrent Biliary Colic

This represents symptomatic cholelithiasis causing episodic severe pain from transient cystic duct obstruction. 4, 5

Supporting Clinical Features:

• Recurrent episodes of RUQ pain separated by pain-free intervals (3 months between episodes, then 1 month) 5
• Known cholelithiasis with previous hospitalization 5
• Pulsating RUQ pain characteristic of biliary colic 5
• No vomiting or fever during the most recent episode 4

Diagnostic Distinction:

• Chronic cholecystitis is difficult to diagnose on anatomic imaging; the gallbladder may appear contracted or distended, and pericholecystic fluid is usually absent 6
• The absence of inflammatory ultrasound findings (wall thickening, pericholecystic fluid) with negative sonographic Murphy sign would favor biliary colic over acute inflammation 4
• Approximately 35% of patients with untreated gallstones develop complications or recurrent symptoms requiring cholecystectomy 5

3. Choledocholithiasis (Common Bile Duct Stones)

Common bile duct stones occur in 3-10% of patients undergoing cholecystectomy and can cause RUQ pain with or without jaundice. 5

Supporting Clinical Features:

• Known cholelithiasis increases risk for CBD stone migration 5
• RUQ and epigastric pain pattern consistent with biliary obstruction 5
• Age 60 years (gallstone prevalence increases with age, affecting 20% of adults over 40) 5

Critical Diagnostic Steps:

• Absence of jaundice on physical examination (white sclerae noted) makes this less likely but does not exclude it 6
• Ultrasound can detect CBD dilation, though sensitivity for CBD stones is lower than for gallbladder stones 5
• If clinical suspicion remains high, MRCP or intraoperative laparoscopic ultrasonography can detect CBD stones 5
• Endoscopic retrograde cholangiopancreatography (ERCP) may be required if choledocholithiasis is confirmed 5, 7

Immediate Management Algorithm

Given the acute presentation with positive Murphy's sign and symptomatic gallstones, the following stepwise approach is warranted:

1. Obtain immediate RUQ ultrasound to confirm diagnosis and assess for complications 6
2. Initiate antibiotic therapy (amoxicillin/clavulanate, eravacycline, or tigecycline for 2-4 days if source control is adequate) 1, 2
3. Obtain immediate surgical consultation for early laparoscopic cholecystectomy within 7-10 days, which reduces complications (11.8% vs 34.4% for delayed surgery), shortens hospital stay (5.4 vs 10.0 days), and lowers costs 3, 1, 2
4. If ultrasound is equivocal, proceed to HIDA scan or consider CT abdomen with IV contrast to identify complications including gangrene, perforation, or adjacent liver parenchymal hyperemia 4

Important Clinical Pitfalls:

• Do not delay imaging or surgical consultation based on absence of fever or leukocytosis 1
• The sonographic Murphy sign has relatively low specificity and may be absent if pain medication was administered prior to imaging 6, 2
• In patients over 65 years, laparoscopic cholecystectomy is associated with lower 2-year mortality (15.2%) compared with nonoperative management (29.3%) 3