Primary Sclerosing Cholangitis - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Primary sclerosing cholangitis is a complex disorder that was first mentioned and described in medical literature in 1867. Primary sclerosing cholangitis is a rapidly evolving disease that may be associated with other conditions. The characteristic features of the disease are the abnormal formation of fibrous tissue in the bile ducts, inflammation, and enlargement of the bile ducts.

Both the intrahepatic and extrahepatic bile ducts are affected by primary sclerosing cholangitis. Symptoms of primary sclerosing cholangitis include itching, fatigue, and jaundice (yellowing mucous membrane discoloration, skin, and skin whites of the eyes). Affected persons may also suffer from nausea or abdominal pain and pass dark urine and light-colored stools. The treatment for primary sclerosing cholangitis is not specified, however, treatment of appearing symptoms helps to slow the progression of the disease.

What Are the Causes of Primary Sclerosing Cholangitis?

Primary sclerosing cholangitis is a multifactorial disorder that is caused by a combination of several factors such as environmental, genetic, and immunologic.

• Researchers state that primary sclerosing cholangitis results from a triggering factor that is not specific and causes an abnormal immune response that leads to an autoimmune reaction. The body’s immune system attacks its bile duct cells, leading to primary sclerosing cholangitis. In most cases, the triggering factors are toxic agents or any infection.

• Genetics has an important role in the onset of primary sclerosing cholangitis as the incidence of the disease is very high among first-degree relatives such as parents, children, and siblings. Researchers have stated that there are 16 genetic regions that can be expected to be associated with primary sclerosing cholangitis. Genetic predisposition means that a person carries genes for the disease which gets triggered due to an external environmental factor.

• Several theories explain the pathogenesis of primary sclerosing cholangitis including leaky gut syndrome in individuals with primary sclerosing cholangitis along with inflammatory bowel disease or the toxic bile theory. But these theories can not explain the cause of all the cases of primary sclerosing cholangitis. Thus, more research and studies must be carried out to know the exact cause of primary sclerosing cholangitis.

Which Population Is Mostly Affected by Primary Sclerosing Cholangitis?

Though primary sclerosing cholangitis is a rare disease, it affects males twice as often as females. The age spectrum is not specific as it can affect any age group. Gradually primary sclerosing cholangitis is becoming one of the main reasons behind liver transplant cases in the United States of America.

What Are the Symptoms of Primary Sclerosing Cholangitis?

Primary sclerosing cholangitis leads to episodes of interrupted or obstructed bile flow from the liver, known as cholestasis. This obstruction occurs due to thickening, inflammation, and formation of abnormal fibrous tissues within the bile ducts. Initially, the patient may be asymptomatic or show only mild symptoms which progress gradually.

Some of the common symptoms of primary sclerosing cholangitis are:

• Abdominal discomfort and pain, especially in the upper right side of the abdomen.

• Fatigue or tiredness.

• Pruritus: Uncomfortable and irritating sensation, creating an urge to scratch the skin.

• Obstructive Jaundice: Blockage of bile flow from the liver leads to absorption of bile into the bloodstream. This results in yellowishness of the skin, mucous membrane, and sclera of the eyes.

• Passing of dark-colored urine and light-colored stools.

• Nausea: Feeling of uneasiness and vomiting.

• Hepatomegaly: Abnormal enlargement of the liver.

• Splenomegaly: Abnormal enlargement of the spleen.

• Sudden weight loss.

• Deficiency of fat-soluble vitamins including A, D, E, and K.

• Hepatic Osteodystrophy: A metabolic bone disease that develops due to chronic liver disease.

• The affected patients may also suffer from osteoporosis, in which the bone density and calcium deposition in bones are reduced. Osteoporosis leads to repeated fractures.

• Episodes of fever, chills, and night sweating due to bacterial cholangitis.

• Scarring and destruction of liver tissues due to bile accumulation.

• Portal Hypertension: Increased blood pressure in the vessels of the liver.

• Ascites: Ascites is defined as the accumulation of fluid in the abdomen.

• Increased chances of development of cholangiocarcinoma. Approximately 8-15 % of affected individuals with primary sclerosing cholangitis develop cholangiocarcinoma.

• Ulcerative colitis and inflammatory bowel disease in almost 60% to 70% of cases of primary sclerosing cholangitis.

Some of the Autoimmune Diseases Associated With Primary Sclerosing Cholangitis Are:

• Celiac Disease: It is also known as gluten-sensitive enteropathy. It is an immune response to eating gluten.

• Sjorgen’s Syndrome: Immune disorder is characterized by the common symptoms of dry mouth and eyes.

• Peyronie’s Disease: Non-cancerous condition resulting from fibrous scar tissue developed on the penis and causes painful and curved erections.

• Psoriasis: A skin disease that commonly causes itchy, scaly, and red patches on elbows, knees, scalp, and trunk. It is a chronic disease with no cure.

• Wegener’s Granulomatosis: It is an uncommon disorder that leads to inflammation of the blood vessels in which the throat, sinuses, lungs, kidneys, and nose.

• Pyoderma Gangrenosum: It is a rare condition characterized by large, painful ulcers that develop on the skin and legs.

How to Diagnose Primary Sclerosing Cholangitis?

The most important step in diagnosing primary sclerosing cholangitis is a medical history and clinical examination. After this, there are a few tests that help to confirm the diagnosis.

These are:

• Liver Functional Test: It is performed to evaluate the concentration and levels of liver enzymes. Elevation of liver enzymes such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase indicate chances of liver disease but specifically primary sclerosing cholangitis.

• Magnetic Resonance Cholangiopancreatography: It is a non-invasive test used to evaluate the extrahepatic and intrahepatic bile ducts.

• Endoscopic Retrograde Cholangiopancreatography: This imaging technique also helps to diagnose primary sclerosing cholangitis. An endoscope (a thin flexible tube) is inserted into the mouth and down through the esophagus, stomach, and bile ducts. A contrast dye is taken to investigate and evaluate the function and health of bile ducts.

• Liver Biopsy: A sample of tissue is taken surgically for a microscopic examination to evaluate the progress of primary sclerosing cholangitis and the state of the liver.

• In some cases, a colonoscopy is recommended to evaluate the function and health of the bowels due to the association of primary sclerosing cholangitis with inflammatory bowel disease and colon cancer.

What Is the Treatment for Primary Sclerosing Cholangitis?

There is no specific treatment for primary sclerosing cholangitis, however, treating the associated symptoms can slow the progress of the disease.

• Narrowed or blocked bile ducts can be treated with medical procedures, such as percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography.

• Itchy skin is cured by skin creams and lotions containing Menthol, camphor, Pramoxine, or Capsaicin. In some cases, antihistamines such as Fexofenadine can also be used.

• Supplements for fat-soluble vitamin deficiency and calcium deficiency in bones.

• Antibiotics such as Penicillin are advised for bile duct infections.

• In cirrhosis or liver failure cases, transplantation is the only treatment choice.

Conclusion:

Primary sclerosing cholangitis is a complex disorder with no specific causative factor. It affects both intrahepatic and extrahepatic bile ducts. The episodic obstruction of bile due to the disease leads to symptoms such as inflammation, abdominal pain, scarring, and cirrhosis of the liver. The treatment for primary sclerosing cholangitis depends on the treatment of associated symptoms.