What are the differential diagnoses for an adult patient with a history of gallstones or other biliary disease presenting with right upper quadrant pain and potential fever?

Differential Diagnoses for Adult with RUQ Pain, Fever, and History of Biliary Disease

In an adult with known gallstones or biliary disease presenting with right upper quadrant pain and potential fever, you must systematically evaluate for acute cholecystitis, ascending cholangitis, choledocholithiasis, biliary colic, and life-threatening complications including perforation and sepsis. 1

Primary Biliary/Gallbladder Differentials to Elicit

Acute Cholecystitis

• Most likely diagnosis in this clinical context, characterized by cystic duct obstruction from gallstones causing gallbladder inflammation 2, 3
• Elicit: Persistent RUQ pain (not colicky), fever >100.4°F, nausea/vomiting, pain worsening with deep inspiration 4, 5
• Physical exam: Murphy's sign (arrest of inspiration with RUQ palpation) has the highest diagnostic value with positive LR of 15.64 5
• Note that absence of fever does NOT exclude cholecystitis—fever sensitivity ranges only 31-62% 5

Ascending Cholangitis

• Critical "can't miss" diagnosis requiring urgent intervention 1
• Elicit the Charcot triad: jaundice, fever/chills, and RUQ pain 1
• This represents infected bile from common bile duct obstruction, typically with visible jaundice (though jaundice sensitivity is only 11-14%) 5
• Requires immediate blood cultures, antibiotics, and biliary decompression 1

Choledocholithiasis

• Common bile duct stones causing obstruction without infection 1
• Elicit: Episodic RUQ pain, jaundice, elevated bilirubin and alkaline phosphatase 1
• May progress to cholangitis if untreated 6

Biliary Colic (Uncomplicated)

• Transient cystic duct obstruction without inflammation 1
• Elicit: Severe episodic pain lasting 30 minutes to several hours, radiating to right shoulder or back, often postprandial 1
• Key distinction: Pain resolves completely between episodes, no fever, no persistent tenderness 1

Complications of Gallstone Disease to Assess

Gangrenous Cholecystitis/Perforation

• Life-threatening emergency requiring immediate recognition 1, 4
• Elicit: Severe persistent pain, high fever, peritoneal signs (abdominal rigidity, rebound tenderness), hemodynamic instability 4
• Occurs when gallbladder wall necrosis leads to perforation 7

Gallbladder Empyema

• Purulent material within gallbladder 2
• Elicit: More severe systemic signs including high fever, marked leukocytosis, toxic appearance 2

Mirizzi Syndrome

• Gallstone impacted in gallbladder neck causing external compression of common hepatic duct 6
• Elicit: Jaundice with RUQ pain, may progress to cholecystocholedochal fistula 6

Gallstone Ileus

• Small bowel obstruction from gallstone migration through cholecystoenteric fistula 6
• Elicit: Abdominal distension, vomiting, inability to pass gas/stool, history of prior biliary symptoms 6

Alternative Diagnoses That Mimic Biliary Disease

Hepatic Causes

• Hepatic abscess (ruptured or intact): Elicit prolonged fever, rigors, recent bacteremia 1
• Hepatitis: Elicit viral exposure, alcohol use, medication history, diffuse RUQ tenderness 1

Pancreatic Causes

• Acute pancreatitis: Elicit epigastric pain radiating to back, elevated lipase/amylase 7

Gastrointestinal Causes

• Peptic ulcer disease/perforation: Elicit epigastric pain, NSAID use, sudden onset if perforated 7
• Gastroenteritis/colitis: Elicit diarrhea, diffuse abdominal pain 1

Pulmonary Causes

• Right lower lobe pneumonia: Elicit cough, dyspnea, pleuritic chest pain 1
• Pulmonary embolism: Elicit dyspnea, tachycardia, risk factors for thromboembolism 1

Renal Causes

• Pyelonephritis: Elicit costovertebral angle tenderness, urinary symptoms 1
• Nephrolithiasis: Elicit colicky flank pain radiating to groin 1

Gynecologic Causes (in women of reproductive age)

• Ectopic pregnancy: ALWAYS obtain pregnancy test before imaging 1
• Ovarian torsion/hemorrhagic cyst: Elicit sudden onset pain, pelvic examination findings 1
• Pelvic inflammatory disease: Elicit vaginal discharge, cervical motion tenderness 1

Vascular Causes

• Mesenteric ischemia: Elicit pain out of proportion to examination, atrial fibrillation, vascular disease history 1

Critical Clinical Pitfalls

• No single finding rules out cholecystitis: Even negative Murphy's sign (LR- 0.40) and absence of RUQ tenderness (LR- 0.4) cannot exclude the diagnosis 8, 5
• Sonographic Murphy's sign has low specificity and is unreliable if patient received pain medication before imaging 2
• Jaundice is uncommon in uncomplicated cholecystitis—its presence suggests choledocholithiasis or cholangitis 5
• Critically ill patients commonly have gallbladder abnormalities on imaging without true acute cholecystitis (acalculous cholecystitis) 1
• Right upper quadrant pain alone has highly variable diagnostic accuracy (LR+ 0.92-14.02) depending on associated features 5

Immediate Diagnostic Approach

• Ultrasound is mandatory first-line imaging (rated 9/9 appropriateness) with 81% sensitivity and 83% specificity for acute cholecystitis 7, 3
• If ultrasound equivocal and clinical suspicion high, proceed to hepatobiliary scintigraphy (HIDA scan) with 97% sensitivity and 90% specificity 2
• CT with IV contrast if complications suspected (perforation, abscess, gangrene) or alternative diagnoses need evaluation 7, 1
• Laboratory: CBC, comprehensive metabolic panel, lipase to assess for infection, biliary obstruction, and pancreatitis 4, 5