What are the diagnostic criteria for Primary Sclerosing Cholangitis (PSC)?

Diagnostic Criteria for Primary Sclerosing Cholangitis

The diagnosis of PSC requires three essential components: cholestatic liver biochemistry (elevated alkaline phosphatase), characteristic cholangiographic findings showing multifocal bile duct strictures and segmental dilatations on MRCP, and exclusion of secondary causes of sclerosing cholangitis. 1, 2

Core Diagnostic Requirements

1. Cholestatic Biochemical Profile

• Elevated serum alkaline phosphatase is the most common and characteristic biochemical abnormality, though a normal alkaline phosphatase does not exclude PSC 1
• Serum aminotransferases are typically elevated 2-3 times the upper limit of normal, but can be normal 1
• Serum bilirubin is usually normal at diagnosis in the majority of patients 1
• Gamma-glutamyl transferase elevation accompanies the alkaline phosphatase rise 2

2. Characteristic Cholangiographic Features

• MRCP is the principal imaging modality for diagnosis, with sensitivity of 86% and specificity of 94% 1, 2
• The hallmark finding is multifocal strictures with segmental dilatations creating a "beading" appearance of bile ducts 1
• ERCP should be reserved only for patients requiring tissue acquisition (cytological brushings) or therapeutic intervention, not for initial diagnosis 1
• MRCP may be less sensitive than ERCP in detecting early PSC changes and has reduced specificity in cirrhotic patients 1

3. Exclusion of Secondary Sclerosing Cholangitis

Mandatory exclusion of secondary causes is required before confirming PSC diagnosis 1, 2. Secondary causes include:

• Choledocholithiasis 1
• Surgical biliary trauma 1
• Intra-arterial chemotherapy 1
• Recurrent pancreatitis 1
• IgG4-associated cholangitis 1
• AIDS cholangiopathy, ischemic cholangitis, and other conditions 1

Additional Diagnostic Testing

Serological Evaluation

• Measure serum IgG4 levels in all patients to exclude IgG4-associated sclerosing cholangitis, which is steroid-responsive and has different management 1, 2
• Obtain ANA, AMA, smooth muscle antibodies, and HIV antibodies to identify alternative diagnoses or overlap syndromes 1
• Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) is positive in 33-88% of PSC patients but is non-specific and not diagnostically useful 1
• IgG levels are modestly elevated (1.5 times upper limit of normal) in approximately 60% of patients 1

Role of Liver Biopsy

• Liver biopsy is NOT routinely recommended when cholangiography shows typical PSC findings 1, 2
• Biopsy should be considered when: 1, 2
  • Cholangiography is normal (to diagnose small duct PSC)
  • Clinical suspicion of IgG4-associated sclerosing cholangitis exists
  • Overlap syndromes with autoimmune hepatitis are suspected
  • Aminotransferases are disproportionately elevated
• The classic histological finding is concentric "onion-skin" periductal fibrosis, but this is often absent on small biopsy specimens 1

Assessment for Inflammatory Bowel Disease

• Perform colonoscopy with colonic biopsies in all PSC patients, as 60-80% have concomitant inflammatory bowel disease, most commonly ulcerative colitis 1, 2

Small Duct PSC Variant

• Patients with clinical, biochemical, and histological features compatible with PSC but normal cholangiography are classified as small duct PSC 1
• This diagnosis requires liver biopsy for confirmation 1

Common Diagnostic Pitfalls

Distinguishing PSC from IgG4-Associated Sclerosing Cholangitis

• Long biliary strictures with prestenotic dilatations and low common bile duct strictures suggest IgG4-SC 1
• Beading, peripheral duct pruning, and pseudodiverticula point toward PSC 1
• Cholangiography alone cannot distinguish between these conditions—serum IgG4 measurement is essential 1

Clinical Presentation Considerations

• Many patients are asymptomatic at diagnosis, with PSC discovered incidentally during evaluation of persistently elevated alkaline phosphatase 1
• When symptomatic, patients present with right upper quadrant discomfort, fatigue, pruritus, and weight loss 1
• Episodes of cholangitis (fever and chills) are uncommon at presentation unless prior biliary surgery or instrumentation has occurred 1