What is the differential diagnosis and initial work‑up for isolated right upper quadrant pain in a patient with no other symptoms?

Differential Diagnosis for Isolated Right Upper Quadrant Pain

Ultrasound is the mandatory first-line imaging study for any patient presenting with isolated right upper quadrant pain, rated 9/9 by the American College of Radiology. 1

Biliary and Gallbladder Causes (Most Common)

Biliary disease accounts for approximately two-thirds of RUQ pain cases, making it the leading diagnostic consideration: 1

• Acute cholecystitis presents with gallbladder inflammation, often accompanied by gallstones, fever, and positive Murphy's sign on examination 1
• Biliary colic manifests as episodic severe pain from transient cystic duct obstruction by gallstones, typically radiating to the right shoulder or back 1
• Choledocholithiasis involves common bile duct stones causing obstruction with elevated liver enzymes 1
• Acute cholangitis requires the classic triad of jaundice, fever/chills, and RUQ pain, plus laboratory evidence of biliary stasis and imaging showing biliary dilatation 1

Hepatic Causes

• Hepatitis (viral, alcoholic, or drug-induced) can present with isolated RUQ pain 2, 3
• Hepatic abscess may cause RUQ pain and requires urgent recognition 1, 2
• Hepatic tumor or mass (benign or malignant) should be considered 2

Pancreatic Causes

• Pancreatitis can manifest with RUQ pain, though epigastric pain is more typical 2
• Pancreatic head mass may cause biliary obstruction and RUQ pain 4

Renal and Urologic Causes

• Nephrolithiasis (right kidney stones) can present as isolated RUQ pain 2, 3
• Pyelonephritis of the right kidney may cause RUQ pain without classic flank pain 2
• Renal abscess is a rare but important consideration 2

Gastrointestinal Causes

• Peptic ulcer disease (duodenal ulcer) can manifest as RUQ pain 2, 5
• Right-sided colonic pathology (hepatic flexure diverticulitis, colitis) may present with RUQ pain 2
• Periampullary duodenal diverticulum (Lemmel syndrome) can cause biliary obstruction and RUQ pain 4

Pulmonary and Thoracic Causes

• Pneumonia (right lower lobe) frequently causes referred RUQ pain 2, 5
• Pulmonary embolism is a critical "can't miss" diagnosis that may present with RUQ pain 1
• Pleural effusion or empyema can manifest as RUQ pain 6, 2

Musculoskeletal and Referred Pain

• Rib fracture or costochondritis may mimic intra-abdominal pathology 5
• Spinal pathology (discitis, paraspinal abscess) can cause referred RUQ pain, as demonstrated in case reports 6
• Abdominal wall muscle strain should be considered when pain is reproducible on palpation 5

Critical "Can't Miss" Diagnoses

These life-threatening conditions must be actively excluded: 1

• Ruptured ectopic pregnancy (obtain pregnancy test before imaging in all reproductive-age women) 1
• Ruptured hepatic abscess or tumor 1
• Mesenteric ischemia 1
• Pulmonary embolism 1
• Perforated gallbladder with peritonitis 1

Initial Diagnostic Work-Up

Laboratory Testing

Order the following initial laboratory studies:

• Complete blood count to assess for leukocytosis suggesting infection or inflammation 5
• Comprehensive metabolic panel including liver function tests (AST, ALT, alkaline phosphatase, bilirubin) to evaluate hepatobiliary pathology 5
• Lipase to assess for pancreatitis 5
• Urinalysis to evaluate for urinary tract infection or nephrolithiasis 5
• Pregnancy test (quantitative β-hCG) in all reproductive-age women before imaging 1

Imaging Strategy

Ultrasound is the definitive first-line imaging modality, rated 9/9 (usually appropriate) by the American College of Radiology: 1, 3

• Ultrasound provides 96% accuracy for gallstones and evaluates multiple organ systems rapidly without radiation exposure 1
• Ultrasound should assess for gallstones, gallbladder wall thickening (>3mm), pericholecystic fluid, bile duct dilatation, sonographic Murphy's sign, and hepatic abnormalities 1
• Ultrasound identifies alternative diagnoses beyond biliary disease in over one-third of cases initially suspected to be cholecystitis 2

Escalate to CT abdomen/pelvis with IV contrast when: 1

• Ultrasound findings are nondiagnostic or equivocal 1
• Patient presentation is atypical for standard biliary disease 1
• Patient is critically ill and requires comprehensive evaluation 1
• Complications are suspected (perforation, abscess, gangrenous cholecystitis) 1

Consider MRI with MRCP when: 1

• Biliary pathology is suspected but ultrasound is equivocal, with 85-100% sensitivity for cholelithiasis/choledocholithiasis 1
• Patient is pregnant and additional imaging beyond ultrasound is needed 1

Critical Pitfalls to Avoid

• Never rely on CT as first-line imaging for suspected biliary disease: CT has only 75% sensitivity for gallstones, so negative CT does not exclude cholelithiasis 1
• Never order CT without IV contrast for suspected cholecystitis: Critical findings like gallbladder wall enhancement and adjacent liver parenchymal hyperemia cannot be detected without contrast 1
• Do not assume normal inflammatory markers exclude serious pathology: Fever is absent in approximately 50% of acute cholecystitis cases 1
• Recognize that critically ill patients commonly have gallbladder abnormalities on ultrasound without true acute cholecystitis (acalculous cholecystitis) 1
• After multiple negative hepatobiliary investigations, broaden the differential to include referred pain from thoracic or spinal sources 6

Urgent Referral Indications

Refer immediately to the emergency department or acute surgical service if: 1

• Fever with leukocytosis suggesting acute cholecystitis or cholangitis 1
• Signs of peritonitis (guarding, rigidity, rebound tenderness) 1
• Hemodynamic instability 1
• Suspected perforation or abscess formation 1