A 52-year-old woman is evaluated for a 6-month history of progressive fatigue and generalized pruritus. She has had no significant prior medical conditions or surgery and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Her sister has Sjögren syndrome. Physical examination shows skin excoriations and mild hepatomegaly. Laboratory results are as follows. The pathogenesis of this patient's disease process most closely resembles that of which of the following conditions?

Question

A 52-year-old woman is evaluated for a 6-month history of progressive fatigue and generalized pruritus.  She has had no significant prior medical conditions or surgery and takes no medications.  The patient does not use tobacco, alcohol, or illicit drugs.  Her sister has Sjögren syndrome.  Physical examination shows skin excoriations and mild hepatomegaly.  Laboratory results are as follows.  The pathogenesis of this patient's disease process most closely resembles that of which of the following conditions?

Quizplus · Accepted Answer

11ec160b_3ae6_8582_9249_ab0fbe6ad349_MD0001_00 Primary biliary cholangitis (PBC, formerly primary biliary cirrhosis) is a chronic autoimmune liver disease characterized by destruction of small and midsized intrahepatic bile ducts with resulting cholestasis. It is most common in middle-aged women and is frequently associated with other autoimmune disorders (eg, Sjögren syndrome, rheumatoid arthritis). Clinical features include fatigue, itching, and hepatomegaly. Serum alkaline phosphatase is elevated, and antimitochondrial antibody titers are positive in most cases. Biopsy findings in PBC typically show patchy lymphocytic inflammation, leading to granulomatous destruction of intrahepatic bile ducts (ie, florid duct lesion), with necrosis and micronodular regeneration of periportal tissues. Of the diseases listed, only graft versus host disease (GVHD) causes similar immune-mediated destruction of intrahepatic bile ducts. GVHD occurs in immunocompromised patients following transplant of allogeneic bone marrow or other lymphocyte-rich tissues (eg, nonirradiated blood). Donor T-cells migrate into host tissues, where they recognize host major histocompatibility complex antigens as foreign. Liver involvement is often heralded by a rise in alkaline phosphatase and characterized histologically by lymphocytic infiltration and destruction of small intrahepatic bile ducts, highlighting the immunologic etiology of both diseases. (Choice A) Serious acetaminophen overdose causes direct hepatocellular toxicity resulting in liver failure with centrilobular necrosis that can extend to include entire lobules. (Choice B) Alcohol-induced hepatitis (due to toxicity from chronic ethanol ingestion) is characterized by hepatocellular swelling and necrosis, steatosis, Mallory bodies, neutrophilic infiltration, and fibrosis. (Choice C) Budd-Chiari syndrome is due to occlusion of the hepatic veins with a resulting increase in intrahepatic pressure. Gross findings include hepatomegaly with a tense capsule and reddish-purple parenchyma. Typical microscopic findings include severe centrilobular congestion and necrosis. (Choice E) Hemochromatosis is due to abnormal iron absorption and results in deposition of hemosiderin in the liver. Biopsy is characterized by visible iron within hepatocytes. (Choice F) Reye syndrome occurs in children with underlying inborn errors in metabolism; acute viral illness (often with concomitant aspirin use) promotes mitochondrial injury and subsequent alterations in metabolism that result in encephalopathy and hepatic dysfunction. Biopsy demonstrates panlobular microvesicular steatosis. Educational objective: Primary biliary cholangitis is a chronic autoimmune liver disease characterized by lymphocytic infiltrates and destruction of small and midsized intrahepatic bile ducts. Similar findings are seen in hepatic graft versus host disease, highlighting the immunologic etiology of both disorders. __________ References: Aspects of the pathophysiology of primary biliary cirrhosis. (http://www.ncbi.nlm.nih.gov/pubmed/26641487)

A 52-Year-Old Woman Is Evaluated for a 6-Month History of Progressive