PSC -- Approach to Diagnosis - PART 2

[Guest guest]

Changes

in immunologic markers are not unusual. Serum

immunoglobulin levels are frequently elevated, particularly IgG

and IgM. Although serum IgG4

levels are usually within normal limits, approximately 9% of patients can

present with elevated IgG4 (> 140 mg/dL). These patients differ from those with normal serum IgG4

levels in that they have a lower frequency of associated IBD, higher PSC Mayo

risk scores, and shorter time to liver transplantation, possibly representing a

more severe course of disease. The pancreatogram

may be abnormal in these patients, causing confusion with another entity known

as autoimmune sclerosing pancreatitis. Additional studies are needed to better

define diagnostic criteria and to determine whether this subgroup of patients

with PSC and increased IgG4 levels will respond similarly to steroid therapy as

patients with autoimmune sclerosing pancreatitis.

As many

as 97% of patients with PSC have at least one detectable autoantibody; however, the presence of multiple

antibodies does not correlate with disease activity. Anti-smooth

muscle antibodies and antinuclear antibodies are found in up to 75% of patients

with PSC. But when antimitochondrial

antibodies are detected, consideration should be given to primary biliary

cirrhosis as a more likely diagnosis. Cases of

PSC-primary biliary cirrhosis overlap have been described, although exceedingly

rare. Perinuclear antineutrophil cytoplasmic

antibody (p-ANCA) has been described in up to 80% of patients with PSC, as well

as in 30% of their unaffected family members. P-ANCA

in PSC appears to be unrelated to ulcerative colitis, as it may be seen in

patients with PSC without ulcerative colitis. Recent

investigation has shown that antibodies to the baker's yeast Saccharomyces cerevisiae

(ASCA) are found in up to 44% of patients with PSC irrespective of the presence

of IBD, but its significance is yet to be determined.

Gastroenterologists

frequently use serum CA 19-9 as a screening test for cholangiocarcinoma in

patients with PSC. However, this tumor marker is not

specific for cholangiocarcinoma and levels can be elevated in many

circumstances, including both malignant and benign conditions.

Thus, an abnormal serum CA 19-9 level can be found not only in patients

with cholangiocarcinoma, pancreatic cancer, and hepatocellular

carcinoma, but also in those with PSC without cancer, alcoholic liver disease, cholangitis, autoimmune hepatitis, chronic viral hepatitis,

and pancreatitis. We have

previously evaluated the utility of CA 19-9 as a screening tool in patients

with PSC and found that a serum value > 129 U/mL

could adequately differentiate between benign and malignant strictures with a

sensitivity of 78.6% and specificity of 98.5%. These

numbers were in agreement with data reported by other investigators. However, the positive predictive value was only 56.6%, and

almost all cases of cholangiocarcinoma that had an elevated CA 19-9 level were

too advanced to qualify for any curative treatment. These

findings suggest that serum CA 19-9 does not perform well as a screening test. Other

diagnostic modalities are needed to identify patients who could benefit from

early intervention.

ERCP

traditionally had been the gold standard for the diagnosis of PSC. With its significant safety advantages and advances in

quality, magnetic resonance cholangiopancreatography

(MRCP) has challenged this concept. Early cholangiographic changes can include fine or deep

ulcerations of the common bile duct. In a small

subgroup of patients, these changes can affect the cystic duct or gallbladder. As PSC progresses, segmental fibrosis develops within the

bile ducts, with saccular dilatation of the normal

areas between them, leading to the typical " beads-on-a-string "

appearance seen on cholangiography (Figure 1). Although these strictures can be found anywhere on the

biliary tree, the intrahepatic and extrahepatic bile ducts are simultaneously

involved in the vast majority of cases.

Figure 1.

(click image to zoom)

ERCP

from a patient with elevated serum ALP and a history of ulcerative colitis. The right and left intrahepatic branches show multiple

diffuse areas of attenuation, stenosis, and dilatation consistent with PSC.

A

subgroup representing 5% to 10% of all PSC patients will have " small-duct

PSC, " with histologic features and cholestatic liver test findings typical of PSC, yet no cholangiographic changes. Small-duct

PSC may progress into large-duct disease, although the actual proportion of

patients who experience progression is unknown.

The

emergence of MRCP is a noninvasive method of diagnosing PSC. The

typical finding on MRCP is high T2 signal intensity in wedge-shaped areas with

bile duct dilatation (Figure 2 and Video). Multiple

studies have compared the diagnostic accuracy of MRCP to that of ERCP . Most of these studies have shown that the effectiveness of

MRCP, read by experienced radiologists, may approach that of invasive cholangiography. Although MRCP

will never replace ERCP completely, it may eventually become a better

diagnostic option given its obvious safety advantages. Recent

studies have also shown that MRCP may be more cost effective in certain

clinical situations.

Figure 2.

(click image to zoom)

MRCP

from the same patient as in Figure 1, showing areas of narrowing within the intrahepatic

branches.