What is the differential diagnosis and initial management approach for a patient presenting with right upper quadrant (RUQ) pain?

Differential Diagnosis for Right Upper Quadrant Pain

Ultrasound is the mandatory first-line imaging study for all patients presenting with RUQ pain, and the differential diagnosis must be systematically organized by organ system, with biliary disease being most common but accounting for only two-thirds of cases. 1, 2

Biliary and Gallbladder Causes (Most Common)

• Acute cholecystitis presents with gallbladder inflammation, typically with gallstones, fever, leukocytosis, and positive Murphy's sign (pain with inspiration during RUQ palpation) 3, 2
• Biliary colic manifests as episodic severe pain from gallstones causing transient cystic duct obstruction, characteristically radiating to the right shoulder or back 1, 2
• Choledocholithiasis involves common bile duct stones causing obstruction with elevated liver enzymes (particularly alkaline phosphatase and bilirubin) 2
• Acute cholangitis requires the triad of jaundice, fever/chills, and RUQ pain, plus laboratory evidence of biliary stasis and imaging showing biliary dilatation 4

Hepatic Causes

• Hepatitis (viral, alcoholic, or drug-induced) presents with elevated transaminases and may show hepatomegaly on examination 3
• Hepatic abscess can be pyogenic or amebic, requiring urgent recognition as rupture is life-threatening 2
• Hepatic tumor or malignancy may present with RUQ pain and requires cross-sectional imaging for characterization 5

Pancreatic Causes

• Acute pancreatitis presents with elevated amylase and lipase, often with epigastric pain radiating to the back 1, 3

Renal Causes

• Nephrolithiasis in the right kidney can mimic biliary colic but typically shows flank tenderness and hematuria 5
• Pyelonephritis presents with fever, costovertebral angle tenderness, and pyuria 5

Gastrointestinal Causes

• Peptic ulcer disease or gastritis may cause RUQ pain, particularly if involving the duodenal bulb 5
• Hepatic flexure colitis or bowel obstruction can present with RUQ pain 5

Pulmonary Causes

• Right lower lobe pneumonia or pleurisy can refer pain to the RUQ and should be considered with respiratory symptoms 5
• Pulmonary embolism is a critical "can't miss" diagnosis requiring urgent recognition 2

Cardiovascular Causes

• Mesenteric ischemia is life-threatening and presents with pain out of proportion to examination findings 2
• Myocardial infarction (particularly inferior wall) can present atypically as RUQ pain 6

Gynecologic Causes (Women of Reproductive Age)

• Ectopic pregnancy is life-threatening and mandates pregnancy testing before any imaging in all women of reproductive age 1, 3, 2
• Ovarian torsion or ruptured ovarian cyst can cause referred RUQ pain 6

Musculoskeletal Causes

• Rib fracture or costochondritis presents with reproducible chest wall tenderness 6
• Abdominal wall strain shows pain with tensing of abdominal muscles 6

Critical "Can't Miss" Diagnoses

These require immediate recognition and intervention:

• Ruptured ectopic pregnancy 2
• Ruptured hepatic abscess or tumor 2
• Mesenteric ischemia 2
• Pulmonary embolism 2
• Perforated gallbladder with peritonitis 4

Common Pitfalls to Avoid

• Never skip ultrasound and proceed directly to CT, as ultrasound provides rapid, cost-effective diagnosis without radiation exposure and has 96% accuracy for gallstones 1, 3
• Do not order CT without IV contrast for suspected cholecystitis, as critical findings like gallbladder wall enhancement and adjacent liver parenchymal hyperemia cannot be detected without contrast 4, 1
• CT has only 75% sensitivity for gallstones, so negative CT does not exclude cholelithiasis 4, 1
• Always obtain a pregnancy test in women of reproductive age before imaging to avoid missing ectopic pregnancy 1, 3
• Recognize that critically ill patients commonly have gallbladder abnormalities on ultrasound without true acute cholecystitis (acalculous cholecystitis) 4