Cholestatic pruritus is a severe itching sensation that arises from underlying liver conditions. It is not a skin condition itself, meaning the itching occurs without a visible rash or primary skin lesions. Instead, this intense itch results from the body’s impaired ability to properly excrete bile, leading to a buildup of certain substances that irritate nerve endings.
Understanding Cholestasis
Cholestasis refers to any condition where the flow of bile from the liver is reduced or completely blocked. Bile, a digestive fluid produced by the liver, plays a role in breaking down fats in the small intestine and eliminating waste products from the body. When bile flow is impaired, these substances, including conjugated bilirubin and bile salts, reflux back into the bloodstream and accumulate in various tissues.
This impairment can originate either within the liver (intrahepatic cholestasis) or outside the liver (extrahepatic cholestasis). Intrahepatic causes involve diseases that damage liver cells or small bile ducts within the liver, such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Certain medications, viral hepatitis, or even pregnancy can also lead to intrahepatic cholestasis.
Extrahepatic cholestasis results from physical blockages in the larger bile ducts outside the liver. Common culprits include gallstones, tumors, or strictures that narrow the bile ducts.
The Itch of Cholestasis
The pruritus associated with cholestasis is characterized by its intense and generalized nature, though it commonly affects the palms of the hands and soles of the feet. Many individuals report that the itching worsens at night, disrupting sleep patterns. Psychological stress, heat, and contact with certain fabrics like wool can also exacerbate the sensation.
The precise mechanisms behind cholestatic pruritus are still being investigated, but several theories exist. One theory suggests that accumulated bile acids in the skin irritate nerve endings, causing the itch. While bile acid levels are elevated in cholestasis, itch severity does not always correlate directly with their concentration, suggesting other factors are involved. Other proposed pruritogens include lysophosphatidic acid (LPA), which activates itch-sensing neurons, and imbalances in the body’s opioid system. An increase in endogenous opioids has been observed, and opioid receptor antagonists can reduce itching.
Diagnosing Cholestatic Pruritus
Diagnosing cholestatic pruritus involves identifying both severe itching and underlying cholestasis. A doctor begins with a thorough medical history and physical examination, looking for signs such as jaundice (yellowing of the skin and eyes) and excoriations from scratching. Blood tests are standard, checking for elevated levels of liver enzymes like alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), and bilirubin and bile acid levels.
Imaging tests are employed to determine the cause of cholestasis. An abdominal ultrasound can visualize the bile ducts and identify potential blockages like gallstones. Magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) can be used for more detailed imaging of the bile ducts to pinpoint abnormalities. Sometimes, a liver biopsy is performed to assess liver damage and confirm the underlying cause.
Managing the Itch
Managing cholestatic pruritus involves a multi-pronged approach, starting with general measures to soothe the skin. Keeping the skin well-moisturized and avoiding hot baths can provide relief. Specific medications are used to address the itch. Bile acid sequestrants, such as cholestyramine, are a first-line treatment. These resins work by binding to bile acids in the intestine, preventing their reabsorption and promoting their excretion, reducing their accumulation.
If bile acid sequestrants are not effective, other medications are considered. Rifampicin, a pregnane X receptor agonist, can reduce pruritic mediators and modulate bile acid metabolism. Opioid antagonists like naltrexone are also used, particularly if opioid system imbalances contribute to the itching.
Sertraline, an antidepressant, can reduce itch intensity in some patients. For severe cases that do not respond to conventional medical therapies, ultraviolet B (UVB) light therapy is considered to reduce pruritus. Ultimately, addressing the underlying cause of cholestasis is important for long-term relief from itching.