What is the appropriate diagnosis and management for a patient with right upper quadrant (RUQ) pain, jaundice, and ultrasound findings suggestive of gallbladder disease, with a history of drug-induced liver injury (DILI) due to Pulmonary Tuberculosis (PTB) treatment with HRZE (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol)?

Diagnosis and Management of RUQ Pain with Jaundice and Gallbladder Findings in a Patient with Drug-Induced Liver Injury

This patient has acute cholecystitis superimposed on drug-induced liver injury from HRZE therapy, requiring urgent surgical consultation for cholecystectomy while managing the underlying DILI. 1

Primary Diagnosis

Acute cholecystitis is the most likely diagnosis based on the clinical presentation of RUQ pain (8/10, crampy, radiating to back), positive Murphy's sign, nausea/vomiting, jaundice, ultrasound findings of gallbladder wall thickening, and a polyp. 1, 2 The presence of jaundice indicates either concurrent cholangitis or severe cholecystitis with biliary obstruction, though the drug-induced liver injury complicates this picture. 1

Key Diagnostic Features Present:

• Positive Murphy's sign - highly suggestive of acute cholecystitis 1, 2
• RUQ tenderness with appropriate localization 1, 2
• Gallbladder wall thickening on ultrasound - consistent with acute inflammation 1
• Jaundice with icteric sclera - suggests either cholangitis component or severe cholecystitis 1
• Recent onset of severe pain with systemic symptoms (nausea/vomiting, initial chills) 1

Critical Distinction: Acute Cholecystitis vs. Acute Cholangitis

The diagnosis of acute cholangitis requires clinical signs (jaundice, fever, chills, RUQ pain), laboratory findings (inflammation markers and biliary stasis), AND imaging findings of biliary dilatation or obstructing etiology. 1 While this patient has jaundice and RUQ pain, the absence of fever since admission and lack of documented biliary ductal dilatation makes cholangitis less likely, though it cannot be completely excluded without reviewing the complete ultrasound report. 1

Immediate Diagnostic Workup Required

Laboratory Assessment Needed:

• Complete blood count to assess for leukocytosis indicating infection 2
• Liver function tests (ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin) to differentiate obstructive vs. hepatocellular jaundice and assess DILI severity 1, 2
• Pancreatic enzymes (amylase, lipase) to exclude pancreatitis 2
• Inflammatory markers (CRP, procalcitonin if available) to assess severity of infection 1

Additional Imaging Strategy:

If the initial ultrasound findings are equivocal or if clinical suspicion for complications persists, obtain CT abdomen with IV contrast as the next imaging modality. 1 This is particularly important in this case because:

• CT with IV contrast can detect complications including perforation, gangrenous cholecystitis, emphysematous changes, hemorrhage, and adjacent liver parenchymal hyperemia that ultrasound may miss 1, 2
• CT has a negative predictive value approaching 90% for acute cholecystitis 1
• CT can better evaluate for alternative diagnoses and assess the extent of disease 1, 3
• Important caveat: CT without IV contrast should NOT be ordered, as critical findings like gallbladder wall enhancement and liver hyperemia cannot be detected without contrast 1, 2

If biliary ductal obstruction or choledocholithiasis is suspected based on laboratory values showing cholestatic pattern, MRCP should be considered to evaluate the biliary tree and identify the level and cause of obstruction. 1

Management Algorithm

Immediate Management (First 24 Hours):

1. NPO status and IV fluid resuscitation 1
2. Broad-spectrum IV antibiotics covering gram-negative organisms and anaerobes (e.g., piperacillin-tazobactam or ceftriaxone plus metronidazole) 1
3. Pain control with appropriate analgesics 2
4. Antiemetics for nausea/vomiting 2
5. Urgent surgical consultation for cholecystectomy planning 1, 3

Definitive Treatment:

Laparoscopic cholecystectomy is the treatment of choice for acute cholecystitis and should be performed urgently (within 72 hours of symptom onset when possible). 3, 4 However, this case requires special consideration:

• The presence of jaundice necessitates careful evaluation for common bile duct obstruction before or during surgery 1
• If cholangitis is confirmed (biliary dilatation on imaging with appropriate clinical picture), ERCP with biliary decompression should be performed before or instead of immediate cholecystectomy 1
• The 0.4 cm gallbladder polyp is an incidental finding that does not change acute management but the gallbladder should still be removed and sent for pathology 1

Management of Concurrent DILI:

HRZE therapy should remain on hold until the acute cholecystitis is resolved and liver function tests are trending toward normalization. 2 After cholecystectomy and clinical improvement:

• Reassess liver function tests 1-2 weeks post-operatively
• Consider reintroduction of anti-TB therapy with a modified regimen, potentially avoiding the most hepatotoxic agents initially or using close monitoring
• Hepatology consultation may be warranted for guidance on safe TB treatment resumption

Critical Pitfalls to Avoid

• Do not attribute all symptoms to DILI alone - this patient has clear evidence of acute gallbladder pathology requiring surgical intervention 3, 4
• Do not delay surgical consultation waiting for liver enzymes to normalize - acute cholecystitis requires urgent surgical management regardless of concurrent DILI 1, 3
• Do not skip CT imaging if complications are suspected - ultrasound has limited sensitivity for detecting complications like perforation or gangrene 1
• Do not order CT without IV contrast - this misses critical diagnostic findings 1, 2
• Do not assume jaundice is solely from DILI - evaluate for biliary obstruction and cholangitis 1
• Do not restart HRZE therapy until acute cholecystitis is resolved and appropriate hepatology input is obtained 2

Prognosis and Follow-up

Early cholecystectomy for acute cholecystitis has excellent outcomes with low morbidity and mortality when performed before complications develop. 3 The concurrent DILI complicates management but should not delay necessary surgical intervention. Post-operative management will require careful coordination between surgery, infectious disease, and hepatology services to safely resume tuberculosis treatment.