What is the likely diagnosis and next steps for a 32-year-old female patient with a 3-day history of sharp right upper quadrant (RUQ) pain, worsened by inhalation, eating, and sleeping on the affected side, who has a history of taking Liveraide (Silymarin) for 2 months, has a body mass index (BMI) of 34.9, and presents with tenderness on direct and indirect palpation of the RUQ and a positive Murphy's sign, despite no relief from Paracetamol (acetaminophen)?

Likely Diagnosis and Next Steps

The most likely diagnosis is acute cholecystitis, and the immediate next step is to obtain a right upper quadrant ultrasound to confirm the diagnosis and assess for gallstones, gallbladder wall thickening, pericholecystic fluid, and other inflammatory findings. 1, 2

Clinical Reasoning for Acute Cholecystitis

This patient's presentation strongly suggests acute cholecystitis based on several key features:

• Positive Murphy's sign on physical examination is the most specific clinical finding, with a positive likelihood ratio of 2.8, though it has relatively low specificity 1
• Right upper quadrant pain that is continuous, sharp, and aggravated by inhalation and eating is characteristic of gallbladder inflammation 1, 2
• RUQ tenderness on both direct and indirect palpation supports biliary pathology 1
• Obesity (BMI 34.9) is a significant risk factor for gallstone disease, which underlies 95% of acute cholecystitis cases 1
• Progressive worsening over 3 days despite analgesics suggests ongoing inflammation rather than simple biliary colic 2

The lack of documented fever or elevated white blood cell count does not exclude acute cholecystitis, as no single clinical or laboratory finding has sufficient diagnostic power to establish or exclude the diagnosis 1

Immediate Diagnostic Workup

First-Line Imaging: Right Upper Quadrant Ultrasound

Ultrasound is the mandatory first-line imaging test and should be performed immediately 1, 2, 3:

• Sensitivity of 88% and specificity of 80% for acute cholecystitis 1
• 96% accuracy for detecting gallstones 1, 4
• Look for the following ultrasound findings 1, 5, 2:
  • Gallstones or sludge
  • Gallbladder wall thickening (>3mm)
  • Pericholecystic fluid
  • Gallbladder distension
  • Sonographic Murphy's sign (focal tenderness when probe compresses the gallbladder)
  • Stones impacted in the gallbladder neck or cystic duct

At least 2 ultrasound findings are required to establish the diagnosis of acute cholecystitis 5

Laboratory Tests to Order Concurrently

• Complete blood count (white blood cell count, neutrophil count) 1
• C-reactive protein (elevated in acute inflammation) 1
• Liver function tests including ALT, AST, alkaline phosphatase, and total/direct bilirubin to assess for common bile duct stones 1

If Ultrasound is Equivocal or Negative

Second-Line Imaging Options

If clinical suspicion remains high despite equivocal ultrasound findings:

Hepatobiliary scintigraphy (HIDA scan) is the preferred next test 1, 5:

• Sensitivity of 97% and specificity of 90% for acute cholecystitis 1, 5
• Non-visualization of the gallbladder indicates cystic duct obstruction and confirms acute cholecystitis 1

Alternative imaging if HIDA is unavailable 1, 5:

• CT abdomen with IV contrast can identify complications (gangrene, perforation, hemorrhage, emphysematous cholecystitis) and adjacent liver parenchymal hyperemia 1, 5
• MRI with MRCP and IV gadolinium provides comprehensive evaluation with 85-100% sensitivity for cholelithiasis/choledocholithiasis and can distinguish acute from chronic cholecystitis based on T2 signal characteristics 1, 5

Management Algorithm

If Acute Cholecystitis is Confirmed

Early laparoscopic cholecystectomy within 7-10 days of symptom onset is the definitive treatment 2:

• Reduces complications and hospital stay 5
• Single-shot antibiotic prophylaxis if surgery performed early 2

Antibiotic therapy should be initiated 2:

• Amoxicillin/clavulanate, eravacycline, or tigecycline for 2-4 days if source control is adequate 2
• For critically ill patients: piperacillin/tazobactam or eravacycline 2

Immediate surgical consultation is warranted given the acute presentation with symptomatic gallstones 5

If Biliary Colic Without Acute Inflammation

If ultrasound shows gallstones but lacks inflammatory findings (no wall thickening, no pericholecystic fluid, negative sonographic Murphy sign), the diagnosis is biliary colic 5:

• Represents episodic pain from transient cystic duct obstruction 5
• Still warrants elective cholecystectomy to prevent future episodes and complications 5

Common Pitfalls to Avoid

• Do not rely on absence of fever or leukocytosis to exclude acute cholecystitis, as these may be absent in early presentations 1, 5
• Negative sonographic Murphy's sign is unreliable if the patient received pain medication prior to imaging 1
• Early acute cholecystitis may not show wall thickening on initial ultrasound 5
• Do not skip ultrasound and proceed directly to CT, as ultrasound provides superior evaluation of gallstones and is the guideline-recommended first test 1, 3, 6

Alternative Diagnoses to Consider

While acute cholecystitis is most likely, ultrasound will also evaluate for 1, 7:

• Hepatic pathology (abscess, mass)
• Pancreatic inflammation
• Renal pathology (pyelonephritis, nephrolithiasis)
• Peptic ulcer disease
• Ascending cholangitis