Case study: It is a typical morning in outpatient clinic. Today you are seeing a long-time patient named Deloris. She is a 46-year-old woman with a history of multiple autoimmune diseases that she manages with a combination of diet, exercise, meditation, and medication. When you enter the exam room, she greets you warmly. Deloris states that her symptoms of scleroderma, Raynaud’s disease, and rheumatoid arthritis have been stable for the past six months. However, she developed severe itching three months ago and nothing seems to make it go away. What do you ask Deloris?
You ask her about the onset of her symptoms, any associated events (such as insect bites or encounters with poison ivy), and treatments that she has tried. She tells you that her itching began three months ago, in the middle of winter. She does not recall any insect bites and was not spending much time outdoors because there was snow on the ground. Deloris denies any exposure to new detergents, perfumes, medications, or foods. She has not had any fevers or rashes, although she has been scratching her skin a fair bit due to the pruritus. She has had an increase in fatigue, which she chalks up to her autoimmune diseases. Deloris has never smoked and she follows a healthy, primarily vegetarian, diet. She tried to treat her symptoms with anti-histamines, but the medications did not alleviate her itching. On physical exam, you notice some deformities of her fingers due to her rheumatoid arthritis and some excoriated areas on her hands and forearms. Otherwise, she is afebrile, her vital signs are stable, heart rate is regular, lungs are clear to auscultation, and her abdomen is soft and non-tender. She does not have any rashes or jaundice. What do you do next?
You are perplexed. Although pruritus falls into the category of annoying but not fatal symptoms, you are also concerned about Deloris’s propensity for developing autoimmune diseases. You ask Deloris if she ever brought up her itching with her rheumatologist. She says no, but then adds that she does have a recent set of lab values in the system since she saw her rheumatologist just last week. When you pull up her labs, you see that Deloris has new elevations in alkaline phosphatase. You begin to wonder if her pruritus is an early sign of liver damage.
You tell Deloris that you want to think through the question of her itching a bit more, and you will call her later this week. After clinic, you decide to call Deloris’s rheumatologist. You tell her that Deloris has had pruritus and note the elevation in alkaline phosphatase. Her rheumatologist immediately agrees with you that this could be a sign of autoimmune diseases involving the liver. Her rheumatologist orders some additional labs based on your conversation, including anti-mitochondrial antibody levels. A week later, she sends you a note: Deloris had elevated anti-mitochondrial antibodies (AMA), suggestive of primary biliary cholangitis (formerly primary biliary cirrhosis).
Primary biliary cholangitis (PBC) is an autoimmune disease involving cholestasis that produces intrahepatic scarring of small bile ducts. As the disease progresses, the scarring may lead to periportal inflammation, fibrosis, possibly cirrhosis and liver failure. Most patients present with symptoms of pruritus and fatigue. AMA and elevated alkaline phosphatase levels are strongly suggestive of the disease. However, liver biopsy is sometimes necessary for staging. How do you treat PBC?
The mainstay for PBC has been treatment with ursodeoxycholic acid (UDCA) and symptomatic management. However, targeted therapies are currently being developed to treat this disease. In the meantime, patients should be advised to avoid alcohol and cigarette smoking. For patients who have not been vaccinated, vaccines for Hepatitis A and B are also recommended. If the disease progresses to liver failure, some patients may require liver transplantation. When you call Deloris back, she has already heard about her diagnosis from her rheumatologist and has scheduled an appointment with a hepatologist for further management.
For more information:
Carey EJ, Ali AH, Lindor KD. Primary Biliary Cirrhosis. The Lancet 2015; 386:1565-75.
National Organization for Rare Disorders (2016). Primary Biliary Cholangitis.
Dr. V. Silverstein
Published on 6/5/18