What are the differential diagnoses for a patient presenting with vomiting, fever, right upper quadrant abdominal pain, and icteric sclerae?

Differential Diagnoses for Vomiting, Fever, RUQ Pain, and Icteric Sclerae

The most critical differentials to consider are acute cholecystitis (including acalculous cholecystitis), acute cholangitis, and hepatic abscess, with typhoid fever being an important infectious consideration in travelers. 1, 2, 3

Primary Hepatobiliary Differentials

Acute Cholecystitis

• Most common cause of this clinical presentation, characterized by gallbladder inflammation with Murphy's sign (pain on inspiration during RUQ palpation), fever, and leukocytosis. 1, 2
• Jaundice occurs in approximately 10-15% of cases when there is associated choledocholithiasis or Mirizzi syndrome. 3
• Acalculous cholecystitis should be considered, particularly in critically ill patients or those with recent surgery, though it can occur in otherwise healthy individuals with typhoid fever. 1, 4

Acute Cholangitis (Ascending Cholangitis)

• Presents with Charcot's triad (fever, RUQ pain, jaundice) or Reynolds pentad (adding altered mental status and hypotension). 3
• Results from biliary obstruction with bacterial infection, most commonly from choledocholithiasis. 3
• Requires urgent recognition as it can rapidly progress to sepsis and requires emergent biliary decompression. 3

Choledocholithiasis with Biliary Obstruction

• Common bile duct stones causing mechanical obstruction manifest with jaundice, elevated alkaline phosphatase and bilirubin (cholestatic pattern). 3
• May present with or without cholangitis depending on whether bacterial superinfection has occurred. 3

Hepatic Parenchymal Causes

Hepatic Abscess (Pyogenic or Amebic)

• Pyogenic liver abscess presents with fever, RUQ pain, and may cause jaundice through mass effect or biliary compression. 1
• Amebic liver abscess should be considered in patients with travel history to endemic areas (Africa, Asia, Latin America), presenting with high fever, RUQ pain, and icteric sclerae. 5
• Can rarely rupture transdiaphragmatically causing hepatobronchial fistula with productive cough. 5

Acute Hepatitis (Viral, Drug-Induced, or Autoimmune)

• Presents with jaundice, elevated transaminases (hepatocellular pattern), nausea, vomiting, and RUQ discomfort. 3
• Fever is more common with viral hepatitis (particularly hepatitis A) than drug-induced hepatitis. 3

Critical Infectious Consideration

Typhoid Fever with Hepatobiliary Involvement

• Salmonella typhi can cause acute liver failure, acalculous cholecystitis, and cholestatic hepatitis in returning travelers, presenting with high-grade fever, abdominal pain, vomiting, and jaundice. 6, 4
• CT findings may show mesenteric and porta-hepatis lymphadenopathy, terminal ileum thickening, and liver abnormalities. 6
• Blood cultures are diagnostic, and treatment requires IV ceftriaxone or meropenem for multidrug-resistant strains. 6
• This diagnosis is critical to recognize due to rapid progression to life-threatening liver failure. 6

Less Common but Important Differentials

Lemmel's Syndrome

• Juxtapapillary duodenal diverticulum causing biliary obstruction and cholangitis without choledocholithiasis. 7
• Presents with RUQ pain, fever, jaundice, and elevated liver enzymes. 7
• Diagnosed by upper endoscopy and MRCP showing diverticulum with upstream biliary ectasia. 7

Cholecystoenteric Fistula

• Rare complication of chronic cholecystitis causing persistent RUQ pain, fever, and gastrointestinal symptoms. 8
• May be asymptomatic for extended periods before presenting acutely. 8

Key Clinical Pitfalls to Avoid

• Do not dismiss acalculous cholecystitis in non-critically ill patients, as typhoid fever can cause this in otherwise healthy individuals. 4
• Always obtain travel history, as typhoid fever and amebic liver abscess are life-threatening diagnoses that require specific antimicrobial therapy. 6, 5
• Jaundice in acute cholecystitis suggests either choledocholithiasis or severe inflammation causing biliary compression—both require advanced imaging beyond ultrasound. 3
• The combination of fever, RUQ pain, and jaundice (Charcot's triad) should trigger immediate evaluation for acute cholangitis, which is a surgical emergency. 3