What are the diagnostic approaches and treatment options for primary sclerosing cholangitis (PSC)?

Primary Sclerosing Cholangitis Diagnosis

MRCP should be your first-line imaging modality for diagnosing PSC, with sensitivity of 86% and specificity of 94%, reserving ERCP only for therapeutic intervention or tissue sampling of suspicious strictures. 1

When to Suspect PSC

Suspect PSC in the following clinical scenarios:

• Unexplained cholestatic biochemistry (elevated alkaline phosphatase and γ-glutamyl transpeptidase) occurring in approximately 75% of patients 2
• Any patient with inflammatory bowel disease (IBD), as 60-80% of PSC patients have concurrent IBD 2
• Young to middle-aged males with persistently elevated alkaline phosphatase 2
• Symptomatic presentation including pruritus, fatigue, jaundice, or right upper quadrant pain 2
• Acute cholangitis with Charcot's triad (fever, right upper quadrant pain, jaundice) 2

Diagnostic Imaging Algorithm

Primary Imaging: MRCP

MRCP is the principal imaging modality with diagnostic accuracy comparable to ERCP (sensitivity 80-100%, specificity 89-100%) but without procedural risks. 1

• Look for the characteristic beading appearance caused by multifocal short strictures of bile ducts 1
• MRCP may be less sensitive than ERCP in detecting early PSC changes and has reduced specificity in cirrhotic patients 1
• Contrast-enhanced MRI provides additional information about liver parenchyma, varices, cholangiocarcinoma, and lymphadenopathy 1

When to Use ERCP

Reserve ERCP exclusively for:

• Patients requiring tissue acquisition (cytological brushings) from suspicious strictures 1
• Therapeutic intervention for dominant strictures 1
• Never perform ERCP without expert multidisciplinary assessment first 1

Critical caveat: Patients undergoing ERCP must receive prophylactic antibiotics 1

Role of Liver Biopsy

Liver biopsy is NOT routinely needed for diagnosis but should be reserved for specific scenarios: 1

• Small duct PSC (when MRCP is normal but clinical suspicion remains high)
• Suspected overlap syndromes (PSC-autoimmune hepatitis or IgG4-related sclerosing cholangitis)
• Unclear diagnosis where histopathology would alter management 1

The hallmark histological finding is concentric "onion skin" periductal fibrosis, though this is often absent on small biopsy specimens. 1

Distinguishing PSC from IgG4-Related Sclerosing Cholangitis

Cholangiography alone cannot distinguish these entities. 1 However, certain features favor PSC:

• Beading pattern
• Peripheral duct pruning
• Pseudodiverticula 1

Features more suggestive of IgG4-SC include long biliary strictures with prestenotic dilatations and low common bile duct strictures. 1 Measure serum IgG4 levels and consider liver biopsy when IgG4-SC is suspected, as corticosteroids may be indicated in this variant. 1

Mandatory Screening for Associated Conditions

All patients with newly diagnosed PSC must undergo:

• Colonoscopy with colonic biopsies to identify concurrent IBD 1
• Screening for oesophageal varices if cirrhosis or portal hypertension is present 1

Non-Invasive Risk Stratification

Perform risk stratification using non-invasive assessment including transient elastography, which correlates strongly with histological fibrosis stage and has prognostic significance. 1 Enhanced liver fibrosis testing also correlates with elastography and helps stratify prognosis. 1

All patients require lifelong follow-up given the unpredictable disease course and serious complications. 1

Surveillance for Cholangiocarcinoma

When evaluating for cholangiocarcinoma (CCA) in PSC patients with dominant strictures or clinical deterioration:

• Obtain serum CA 19-9 (though it has low diagnostic accuracy and is NOT recommended for routine surveillance) 1
• Perform contrast-enhanced cross-sectional imaging (MRI or CT) as the initial preferred investigation 1
• CA 19-9 ≥129 U/mL with malignant-appearing stricture raises concern for CCA (but exclude bacterial cholangitis first, which causes false positives) 1
• Mandatory pathological sampling of suspicious strictures during ERCP using brush cytology, FISH analysis, or cholangioscopy 1

Important limitation: Conventional brush cytology has only 18-40% sensitivity despite 100% specificity. 1 FISH analysis for polysomy improves sensitivity to 41% with 98% specificity. 1

Annual ultrasound of the gallbladder should be performed to screen for polyps, with specialist HPB multidisciplinary team review if identified. 1