Primary sclerosing cholangitis (PSC) is characterized by inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts, leading to dilation of preserved segments. Irregular biliary strictures and dilations cause the characteristic “beading” of the intrahepatic and extrahepatic biliary tree seen by MRI. Inflammatory bowel disease (Chapter 15), most commonly ulcerative colitis, coexists in approximately 70% of individuals with PSC. Conversely, the prevalence of PSC in individuals with ulcerative colitis is about 4%. Like inflammatory bowel disease, PSC tends to occur in the third through fifth decades of life and has a 2:1 male predominance (see
Table 16.5 http://ebooksmedicine.net
Fig. 16.28 Imagingstudiesofapatientwithprimarysclerosingcholangitis.
(A)Magneticresonancecholangiographyofthebileductsshowsfocaldilationinsomeducts(bright, broad areas) andstricturingofothers(thinning or absence). (B)EndoscopicretrogradecholangiographyofthesamepatientshowsnearlyidenticalfeaturesasinA. (Courtesy of Dr. M. Edwyn Harrison, MD, Mayo Clinic, Scottsdale, Arizona.)
Several features of PSC suggest immunologically mediated injury to bile ducts. T cells in the periductal stroma, the presence of autoantibodies, an association with HLA-B8 and other MHC alleles, and clinical linkage to ulcerative colitis all support an underlying, immunologic process. First-degree relatives of patients with PSC are at increased risk for developing the disease, suggesting that genetic factors also contribute.
In one model, it is proposed that T cells activated in the damaged mucosa of patients with ulcerative colitis migrate to the liver, where they recognize a cross-reacting bile duct antigen and initiate an autoimmune assault on bile ducts. Autoantibody profiles in PSC are not as characteristic as in PBC, but atypical perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) that recognize a nuclear envelope protein are found in up to 80% of patients. The pathogenic relationship of pANCA to PSC is unknown.
MORPHOLOGYMorphologicchangesdifferbetweenlargeducts(intrahepaticandextrahepatic)andsmallerintrahepaticducts.Large duct inflammation resemblesthatseeninulcerativecolitis,takingtheformofneutrophilsinfiltratingintotheepitheliumsuperimposedonachronicinflammatorybackground.Inflamedareasdevelopstricturesasscarringnarrowsthelumen.Thesmaller ducts, however,oftenhavelittleinflammationandshowastrikingcircumferential,“onion skin” fibrosis aroundanatrophicductlumen(
Fig.16.29 ),whicheventuallyisobliterated,leavinga“tombstone”scar.Becausethelikelihoodofsamplingsmall-ductlesionsonarandomneedlebiopsyissmall,diagnosisdependsonradiologicimagingoftheextrahepaticandlargeintrahepaticducts.Asthediseaseprogresses,theliverbecomesmarkedlycholestatic,culminatingincirrhosis.Biliaryintraepithelialneoplasiaoftenappearinthesettingofchronicinflammationandcholangiocarcinomadevelopsinupto7%ofpatients,usuallywithafataloutcome.