What are the differential diagnoses to consider in a patient with suspected gallstones?

Differential Diagnosis for Gallstones

When a patient presents with suspected gallstones, the key differential diagnoses include acute cholecystitis, chronic cholecystitis, choledocholithiasis (common bile duct stones), biliary colic, Mirizzi syndrome, acute cholangitis, gallstone pancreatitis, and non-biliary causes such as peptic ulcer disease, hepatitis, pancreatitis from other causes, right lower lobe pneumonia, and intestinal disorders. 1

Biliary-Related Differential Diagnoses

Acute vs. Chronic Cholecystitis

• Acute cholecystitis presents with right upper quadrant pain, fever, elevated white blood cell count, positive Murphy sign (focal tenderness over the gallbladder), gallbladder wall thickening >3mm, pericholecystic fluid, and sonographic Murphy sign on ultrasound 1, 2
• Chronic cholecystitis is difficult to diagnose on imaging, typically shows a contracted or distended gallbladder with stones (present in 95% of cases), thickened fibrotic gallbladder wall, but lacks pericholecystic inflammatory changes and adjacent liver hyperemia seen in acute disease 1
• Cholescintigraphy (HIDA scan) has 97% sensitivity and 90% specificity for acute cholecystitis when ultrasound is equivocal 1, 3

Choledocholithiasis (Common Bile Duct Stones)

• Clinical presentation includes epigastric or right upper quadrant pain, especially when associated with jaundice and/or fever 1
• Ultrasound shows dilated common bile duct (>6mm) with sensitivity of 73% and specificity of 91%, though normal results don't exclude disease 1, 3
• Risk stratification is critical: patients with high likelihood (CBD stone on ultrasound, cholangitis features, or triad of pain/duct dilatation/jaundice) should proceed directly to ERCP or surgical extraction 1
• Intermediate probability patients (CBD dilatation with normal LFTs OR abnormal LFTs with normal caliber ducts) require MRCP or EUS, which have 85-100% sensitivity and 90% specificity 1, 3
• Active stone extraction reduces unfavorable outcomes from 25.3% to 12.7% compared to conservative management 1

Mirizzi Syndrome

• A rare complication (<1% of gallstone patients) characterized by extrinsic compression of the common hepatic duct by an impacted stone in the cystic duct or gallbladder infundibulum 4
• Ultrasound shows shrunken gallbladder with impacted stone(s), dilated intrahepatic and common hepatic ducts, but normal-sized distal common bile duct 4
• Requires open cholecystectomy as definitive treatment 4

Acute Cholangitis

• Presents with Charcot's triad: fever, jaundice, and right upper quadrant pain, caused by bacterial infection of obstructed bile ducts 1
• Represents a medical emergency requiring urgent biliary decompression 1

Gallstone Pancreatitis

• Gallstones migrating to the CBD cause up to 50% of acute pancreatitis cases 1
• Patients with acute pancreatitis and evidence of ongoing bile duct obstruction/cholangitis require ERCP with biliary sphincterotomy within 24-72 hours 5

Non-Biliary Differential Diagnoses

Gastrointestinal Causes

• Peptic ulcer disease or gastritis: pain during meals, acid reflux, nausea; confirmed via gastroscopy 1
• Stenosis or anastomoses: similar to marginal ulcer with dysphagia; confirmed via gastroscopy or barium swallow 1
• Internal herniation: colicky pain, sensation of fullness after meals, sometimes ileus and vomiting but no vegetative symptoms; confirmed via CT or diagnostic laparoscopy 1

Hepatic Causes

• Hepatitis or severe hepatic injury: can elevate CA 19-9 and present with right upper quadrant pain 1
• Liver mass with capsular involvement: requires CT or MRI for diagnosis 1

Other Abdominal Causes

• Pancreatic inflammation from non-gallstone causes 1
• Intestinal disorders and referred pain from elsewhere in abdomen or pelvis 1
• Right lower lobe pneumonia: can cause referred right upper quadrant pain 1

Key Diagnostic Pitfalls to Avoid

• Sonographic Murphy sign has relatively low specificity for acute cholecystitis and is unreliable if patient received pain medication prior to imaging 1
• Normal ultrasound and liver function tests do not exclude biliary disease if clinical suspicion remains high 1
• CA 19-9 elevation (>100 U/ml has 75% sensitivity, 80% specificity in PSC patients) can occur in obstructive jaundice without malignancy, but persistently raised levels after biliary decompression suggest malignancy 1
• In critically ill patients, gallbladder abnormalities are common in the absence of acute cholecystitis, limiting ultrasound usefulness 1
• Dyspeptic symptoms (indigestion, belching, bloating, heartburn, food intolerance) are common in persons with gallstones but are probably unrelated to the stones themselves and frequently persist after surgery 6, 7

Algorithmic Approach

1. Initial evaluation: Right upper quadrant ultrasound (96% accuracy for gallstones) and comprehensive liver function tests 1, 3, 2
2. If acute cholecystitis suspected but ultrasound equivocal: Proceed to HIDA scan 1, 3, 2
3. If CBD dilatation or elevated alkaline phosphatase/bilirubin: Proceed to MRCP or EUS for intermediate probability, or directly to ERCP for high probability 1, 3
4. If imaging negative but symptoms persist: Consider non-biliary causes and CT abdomen with IV contrast to evaluate alternative diagnoses 1