Cholangitis – Causes, Symptoms, Diagnosis, Treatment

Cholangitis is a serious life-threatening situation affecting the hepatobiliary system. It is an autoimmune disorder that leads to the gradual destruction of intrahepatic bile ducts resulting in periportal inflammation, cholestasis. Cholangitis can be categorized as primary sclerosing (PSC), secondary (acute) cholangitis, and a recently characterized form, known as IgG4-associated cholangitis (IAC). Roles of genetic and acquired factors have been noted in the development of various forms of cholangitis. PSC commonly follows a chronic and progressive course that may terminate in hepatobiliary neoplasms. In particular, PSC commonly has been associated with inflammatory bowel disease. Bacterial infections are known as the most common cause for AC.

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct (cholangitis), usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.^[1][2]

Types of Cholangitis

Cholangitis is an inflammation of the bile ducts. Types of cholangitis include the following:

• Acute cholangitis or ascending cholangitis
• Primary sclerosing cholangitis (PSC)
• Secondary sclerosing cholangitis (SSC)
• Recurrent pyogenic cholangitis (RPC)

Established subtypes of PSC are[rx]:

• Classic – Affects small and large bile ducts
• Small-duct – Affects only small bile ducts
• Associated with autoimmune hepatitis – Affects small and large bile ducts

Causes of Cholangitis

Intrinsic or Extrinsic Compressive Causes (Either Benign or Malignant)

• Cholangiocarcinoma
• Mirizzi syndrome
• Compressive lymphadenopathy
• Portal hypertensive biliopathy
• Diffuse intrahepatic malignancy
• Postoperative strictures
• Chronic pancreatitis

Infectious Causes

• AIDS cholangiopathy (e.g., Cryptosporidium parvum, cytomegalovirus)
• Recurrent pyogenic cholangitis (also known as oriental cholangio-hepatitis)
• Helminthic infection (e.g., Clonorchis, Opisthorchis, Ascaris)

Ischemic Causes

• Posttransplant non-anastomotic strictures
• Postintraarterial chemotherapy
• Postradiation therapy

Immunologic Causes

• IgG4-associated cholangiopathy
• Eosinophilic cholangitis
• Mast cell cholangiopathy
• Histiocytosis X
• Systemic vasculitis
• Hepatic allograft rejection
• Primary biliary cholangitis

Congenital and/or Idiopathic Causes

• Choledochal cysts (e.g., Caroli disease)
• Progressive familial intrahepatic cholestasis [rx]

Other, less common causes of cholangitis include:

• A tumor
• Blood clots
• A narrowing of a duct that may happen after surgery
• Swollen pancreas
• A parasite infection
• A backflow of bacteria from your small intestine
• A blood infection (bacteremia)
• A test done to check your liver or gallbladder (such as a test where a thin tube or endoscope is put into your body)

Symptoms of Cholangitis

Each person’s symptoms may vary, and may be non-specific or severe, including:

• A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).^[rx]
• Pain in the upper right part of your belly (abdomen)
• Fever
• Chills
• Yellowing of the skin and eyes (jaundice)
• Nausea and vomiting
• Clay-colored stools
• Dark urine
• Low blood pressure
• Lethargy
• Changes in alertness

If you have chronic cholangitis for a long time, you may have

• pain in the upper right side
• night sweats
• swollen feet and ankles
• darkening of the skin (hyperpigmentation)
• muscle pain
• bone or joint pain
• bloating (fluid in the stomach area)
• fat deposits (xanthomas) in the skin around the eyes and eyelids
• fat deposits in the elbows, knees, palms, and soles of the feet
• diarrhea or greasy bowel movements
• clay-colored bowel movements
• weight loss
• mood changes and memory problems

If you have acute cholangitis, you may also have other symptoms. These include sudden symptoms like

• high fever for more than 24 hours trusted Source
• chills
• nausea
• vomiting
• back pain
• pain below the shoulder blades
• dull pain or cramps in the upper right side
• sharp or dull pain in the middle of the stomach
• low blood pressure
• confusion
• yellowing of the skin and eyes (jaundice)

Your doctor may find signs of cholangitis in other parts of the body. These include

• Fatigue
• Itchy skin
• Dry eyes and mouth
• Pain in the upper right abdomen
• Swelling of the spleen
• Bone, muscle or joint (musculoskeletal) pain
• Swollen feet and ankles (edema)
• Buildup of fluid in the abdomen due to liver failure (ascites)
• Fatty deposits (xanthomas) on the skin around the eyes, eyelids or in the creases of the palms, soles, elbows or knees
• Yellowing of the skin and eyes (jaundice)
• Darkening of the skin that’s not related to sun exposure (hyperpigmentation)
• Weak and brittle bones (osteoporosis), which can lead to fractures
• High cholesterol
• Diarrhea, which may include greasy stools (steatorrhea)
• Underactive thyroid (hypothyroidism)
• Weight loss

Diagnosis of Cholangitis

• Complete blood count (CBC) – This test measures your white blood cell count. You may have a high white blood cell count if you have an infection.
• Liver function tests – A group of special blood tests that can tell if your liver is working properly.
• Blood cultures – Tests to see if you have a blood infection.
• Laboratory tests – In most patients, liver biochemical tests usually show elevation of the serum alkaline phosphatase. The serum aminotransferases are generally less than 300 international unit/L. The serum albumin concentration may be low in patients with active inflammatory bowel disease, although in early-stage PSC is often normal.[rx] Elevation of serum immunoglobulin G4 (IgG4), which is a marker of autoimmune pancreatitis, has been reported in patients with PSC.[rx][rx][rx]
• Cholangiography – It is helpful for the evaluation of affected biliary radicles greater than 100 micro millimeters. Various options such as Endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiopancreatography (MRCP), or percutaneous transhepatic cholangiography (PTC) are available to obtain cholangiograms. However, being noninvasive and accurate makes MRCP as the preferred test of choice to distinguish SDPSC from LDPSC.[rx][rx][rx][rx] Small duct primary sclerosing cholangitis involves biliary calibers less than 100 micro millimeters, which lead to normal cholangiogram.[rx] However, cumulative follow-up data by Bjornsson et al. reported that nineteen (22.9%) of SDPSC progress to large duct PSC after a median of 7.4 years.[rx]
• Liver biopsy – The most specific histologic finding in SDPSC is the “onion skin” pattern, which describes as fibrous obliteration and concentric replacement of connective tissue in small bile ducts.[rx] Although, this classic finding histology alone is not enough for making a diagnosis of SDPSC.[rx]
• Liver ultrasound – Ultrasound findings are commonly used to rule out a secondary cause of chronic cholestasis, such as pancreatic disease and gallbladder abnormalities.[rx]
• Ultrasound (also called sonography). This test creates images of your internal organs on a computer screen using high-frequency sound waves. It is used to see organs in your bellies such as the liver, spleen, and gallbladder. It also checks blood flow through different vessels. It can be done outside the body (external). Or it may be done inside the body (internal). If internal, it is called an endoscopic ultrasound (EUS).
• CT scan – A CT scan may be done with a dye that is swallowed or injected through an IV. This will show the abdomen and pelvis including the bile drainage area. It can help determine why there is a blockage.
• Magnetic resonance cholangiopancreatography (MRCP) – This test is used to look for any problems in your abdomen. It can show if there are gallstones in your bile duct. The test is done from outside your body. It does not involve putting a tube (endoscope) into your body. It uses a magnetic field and radio frequency to make detailed pictures.
• ERCP (endoscopic retrograde cholangiopancreatography) – This is used to find and treat problems in your liver, gallbladder, bile ducts, and pancreas. It uses X-ray and a long flexible tube with a light and camera at one end (an endoscope). The tube is put into your mouth and throat. It goes down your food pipe (esophagus), through your stomach, and into the first part of your small intestine (the duodenum). A dye is put into your bile ducts through the tube. The dye lets the bile ducts be seen clearly on X-rays. If required, this procedure can also help open up your bile ducts.
• Percutaneous transhepatic cholangiography (PTC) – A needle is put through your skin and into your liver. Dye is put into your bile duct so that it can be seen clearly on X-rays. This procedure can also be used to open up the bile ducts if your physicians are unable to do it internally with an ERCP.

Treatment of Cholangitis

Management

Complications of chronic cholestasis

• Bone disease – Osteoporosis and pathologic fracture is the most common bone disease in cholestatic liver disease such as primary biliary cirrhosis. Hence, it is recommended that the Dexa scan be obtained at the diagnosis of primary biliary cirrhosis. This can be prevented by daily oral vitamin D and calcium supplementation and daily exercise. Estrogen therapy in a postmenopausal patient with primary biliary cirrhosis has shown to prevent loss of bone mass or bone mineral density.
• Fat-soluble vitamin deficiency – Deficiency of fat-soluble vitamins A, D, E, and K are secondary to malabsorption due to decreased amounts of bile salts in the intestinal lumen. Levels of these vitamins should be checked periodically and supplemented accordingly.
• Hyperlipidemia – About 85% of patients with primary biliary cirrhosis have deranged lipid profile. As the disease progress, HDL decreases, and LDL increases. Statins are recommended and have not shown to have a deleterious effect on liver function. In addition, patients with primary biliary cirrhosis and abnormal lipid profile have not shown to have elevated risk for myocardial infarction and strokes.
• Pruritus – The actual cause of pruritus is understood poorly in primary biliary cirrhosis. Nonetheless, various agents have shown to provide symptomatic relief. These are cholestyramine, rifampin UDCA, naltrexone, and antihistamines like diphenhydramine and hydroxyzine.
• Steatorrhea – The cause for steatorrhea in primary biliary cirrhosis is thought to be secondary to a decreased level of bile acid in the small intestine. Patients who have other coexisting autoimmune diseases such as celiac disease and scleroderma, small intestinal bacterial overgrowth (SIBO) can be the cause for steatorrhea as well. It is essential to find out the cause for steatorrhea and treat it accordingly. In patients who do not have sufficient bile acids in the small intestine, the medium-chain triglycerides (TGs) should be substituted for long-chain TGs in the diet, and total fat intake should be reduced. In the case of SIBO, intermittent broad-spectrum antibiotics can be used.
• Liver transplant: Liver transplant is the standard gold treatment for Primary biliary cirrhosis – Patients with primary biliary cirrhosis will develop complications related to cirrhosis (hepatic encephalopathy, recurrent ascites, severe portal hypertensive gastropathy, bleeding, or hemorrhage secondary to gastric or esophageal varices). They will also have disabling symptoms such as fatigue, intractable pruritus, and severely deranged bilirubin level in the absence of liver cancer. These patients should be evaluated for a liver transplant.
• Liver scarring (cirrhosis) – Cirrhosis makes it difficult for your liver to work and may lead to liver failure. It indicates the later stage of primary biliary cholangitis. People with primary biliary cholangitis and cirrhosis have a poor prognosis and higher risk of other complications.
• Increased pressure in the portal vein (portal hypertension) – Blood from your intestine, spleen and pancreas enters your liver through a large blood vessel called the portal vein. When scar tissue from cirrhosis blocks normal blood flow through your liver, blood backs up. This causes increased pressure inside the vein. Also, because blood doesn’t flow normally through your liver, drugs and other toxins aren’t filtered properly from your bloodstream.
• Enlarged spleen (splenomegaly) – Your spleen can become swollen with white blood cells and platelets because your body no longer filters toxins out of the bloodstream as it should.
• Gallstones and bile duct stones – If bile cannot flow through the bile ducts, it may harden into stones, causing pain and infection.
• Enlarged veins (varices) – When blood flow through the portal vein is slowed or blocked, blood may back up into other — usually those in your stomach and esophagus. Increased pressure may cause delicate veins to break open and bleed. Bleeding in the upper stomach or esophagus is a life-threatening emergency that requires immediate medical care.
• Liver cancer – Liver scarring (cirrhosis) increases your risk of liver cancer.
• Weak bones (osteoporosis) – People with primary biliary cholangitis have an increased risk of weak, brittle bones that may break more easily.
• Vitamin deficiencies – A lack of bile affects your digestive system’s ability to absorb fats and the fat-soluble vitamins, A, D, E and K. Because of this, some people with advanced primary biliary may have low levels of these vitamins.
• Decreased mental function (hepatic encephalopathy) – Some people with primary biliary cholangitis with liver failure have personality changes and problems with memory and concentration.
• Increased risk of other disease – Primary biliary cholangitis is associated with metabolic or immune system disorders, including thyroid problems, limited scleroderma (CREST syndrome) and rheumatoid arthritis.

References

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