Pruritus or itching is a symptom of liver diseases that can be particularly troublesome. Pruritus is associated with cholestatic liver diseases, i. e. diseases in which there is a decrease in biliary excretion either because of intrinsic liver disease or biliary obstruction. Diseases that often present with pruritus are primary biliary cirrhosis, sclerosing cholangitis, pancreatic cancer with obstruction of the bile duct and intrahepatic cholestasis of pregnancy. Itching is often manifested most strongly in the palms and soles of the feet, however, it may be widespread and so intense that it interferes with daily activites and sleeping.
Pathogenesis of pruritus associated with cholestasis is not known with precision. One theory is related to increased bile salts that would pruritogenic skin. Another theory attributes itching to elevated levels of endogenous opioids found in patients with cholestasis. Symptomatic improvement observed when using opioid antagonists confirms its role in the pathogenesis of pruritus. More recently it has been described that lysophosphatidic acid, a phospholipid produced by the enzyme autotaxin, seems to be the specific substance that causes this symptom.
Often the treatment of underlying liver disease alleviates this annoying symptom. When there is obstruction of the extra-hepatic bile duct, itching may be an indication for an internal or external biliary drainage.
- Good lubrication of the skin with moisturizers.
- Avoiding hot water baths. Warm water can relieve symptoms.
- Avoiding excessive friction when drying after bathing.
- Application of menthol powder.
- Medications such as antihistamines and sedatives (phenobarbital).
The use of resins that adsorb bile salts, such as cholestyramine and colestipol, is one of the most frequently used for the treatment of pruritus associated with cholestasis. Cholestyramine dose ranges from 4 to 16 g per day. Occasionally it is poorly tolerated and can cause constipation. It is important to remember that cholestyramine is a resin that sequesters other medicines, including ursodeoxycholic acid, so it should be taken 4 hours before any other medication.
Although ursodeoxycholic acid has a very defined role in the management of chronic cholestatic diseases and reduces circulating levels of bile salts, its effect on the control of itching is marginal. In our experience, it has limited effectivity in pruritus.
Rifampicin is a potent inducer of cytochrome P-450 microsomal enzyme system responsible for metabolizing bile salts. It may be useful for the management of pruritus when used in doses of 300 to 600 mg/d. Rifampicin can be hepatotoxic. It is important to remember that their use can lead to significant changes in the metabolism of other drugs.
Opioid antagonists such as naltrexone are oral medications that have been incorporated in the management of pruritus associated with cholestasis. Other antagonists such as naloxone are only for intravenous use. Nalmefene, a new more powerful drug, may be of some benefit. It is important that treatment with these drugs are controlled by physicians experienced in its use, since they can precipitate an opioid withdrawal syndrome with intensification of chronic pain in some patients.
When the previous therapies have failed, occasionally other therapies whose effectiveness is based on anecdotal cases or small series, such as ultraviolet light or MARS may be used. In our experience, the use of liver albumin dialysis (MARS) can have dramatic effect on intractable pruritus, although its effect is not persistent in time.
Intractable pruritus is a generally accepted indications for liver transplantation.