akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

胆汁うっ滞時のかゆみ

消化器の先生からご相談

 

Up to date で復習、 要点を以下引用します。

 

  • Intrahepatic cholestasis of pregnancy – 100 percent (pruritus is a prerequisite for making the diagnosis)
  • Primary biliary cirrhosis – up to 80 percent by 10 years
  • Primary sclerosing cholangitis – 20 to 40 percent of patients at presentation, increasing as the disease progresses
  • Malignant biliary tract obstruction – 45 percent
  • Chronic viral hepatitis – 20 percent
  • Nonmalignant biliary tract obstruction – 17 percent
  • Cirrhosis – 7 percent

 

基本

  • Primary biliary cirrhosis: Ursodeoxycholic acid
  • Primary sclerosing cholangitis: Endoscopic treatment of dominant strictures
  • Malignant extrahepatic biliary obstruction: Bile duct stenting
  • Drug-induced cholestasis: Discontinuation of the offending medication

 

中等・重症

 

  • We initially treat with a bile acid sequestrant such as cholestyramine (total daily dose of 4 to 16 grams).
  • If the bile acid sequestrant does not provide adequate, relief we switch to rifampin (150 to 300 mg twice daily). 
  • If symptoms persist, we then switch to an opioid antagonist, such as naltrexone (12.5 to 50 mg/day). 
  • Switching to sertraline (75 to 100 mg daily) or phenobarbital 90 mg at bedtime can be tried if other measures fail. Phenobarbital has the disadvantage of causing somnolence during the first few weeks of use.

 

難治性

  • Phenobarbital has been effective in case series. It can be given as 90 mg at bedtime, although it has the disadvantage of causing somnolence during the first few weeks of use.
  • Phototherapy with ultraviolet light (UV-B) has been helpful in case reports. The mechanism is unknown, although hypotheses include an alteration in skin sensitivity to pruritogens or a modification in bile salt turnover by mobilizing skin bile salts. In our experience, phototherapy has been unsuccessful in more than 80 percent of patients with primary biliary cirrhosis who failed to respond to cholestyramine. 
  • Some studies have demonstrated relief of pruritus following plasmapheresis in patients with cholestasis. However, clinical experience has been mixed. This technique is too cumbersome and expensive for routine use but may have a role when all else fails, particularly when a more definitive treatment is anticipated, such as in patients awaiting liver transplantation.
  • Propofol was given to three patients at subhypnotic doses via intravenous infusion. Marked improvement in pruritus was noted without disabling sedation. The proposed mechanism was inhibition of ventral and dorsal spinal nerve roots modulated by endogenous opioid-like ligands.
  • Androgens (such as norethandrolone, methyltestosterone, and stanozolol) increase serum bile acids and worsen jaundice, yet they paradoxically relieve pruritus in some patients with cholestasis . How this occurs is not known, but multiple side effects limit the use of these drugs.
  • Delta-9-tetrahydrocannabinol (Marinol) was helpful in a case series of three patients.
  • The Molecular Adsorbent Recirculating System (a hemofiltration device) has been effective in case series

 

まとめ

Pruritus may develop in patients with cholestasis due to any cause, including primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, biliary obstruction, chronic viral hepatitis, cirrhosis, prolonged drug-induced cholestasis, and inherited cholestasis syndromes. 

 

Pruritus in patients with cholestasis may be generalized or localized (particularly to the palms of the hands and soles of the feet). The intensity of the pruritus is variable and it can wax and wane spontaneously. The severity does not correlate with the severity of the underlying liver disease.

 

A presumptive diagnosis of cholestasis-associated pruritus can be made in a patient with cholestasis who complains of itching. An extensive evaluation is generally not required, provided the cause of the cholestasis is known, though patients should have a skin examination to look for evidence of dermatologic disorders associated with pruritus (eg, atopic dermatitis or contact dermatitis).

 

The treatment of choice for pruritus associated with cholestasis is correction of the underlying hepatobiliary disease, when possible. If the underlying hepatobiliary disease cannot be corrected, treatment is aimed at the pruritus itself. The treatment chosen will depends on the severity of symptoms and the underlying disease:

 

For mild pruritus, we suggest general measures such as warm baths with or without an antihistamine (Grade 2C). 

 

For patients with primary biliary cirrhosis and moderate to severe pruritus, we suggest treatment with a bile acid sequestrant rather than an alternative medication (such as rifampin or an opioid antagonist) (Grade 2B). We also recommend treatment with ursodeoxycholic acid (UDCA) rather than treating with a bile acid sequestrant alone (Grade 1A). UDCA may improve pruritus in these patients and delays the progression to end-stage liver disease, enhances survival, and is well-tolerated. Bile acid sequestrants should be given two to four hours before or after ingestion of UDCA.

 

In women with intrahepatic cholestasis of pregnancy and moderate to severe pruritus, we suggest treatment with UDCA (Grade 2B). UDCA has been studied in women with intrahepatic cholestasis of pregnancy and is well-tolerated and safe. Its use has been associated with relief or pruritus, decreased levels of endogenous bile acids, normalization of alanine aminotransferase levels, and improved fetal outcomes.

 

For patients with moderate to severe pruritus who do not have primary biliary cirrhosis or intrahepatic cholestasis of pregnancy, we suggest treatment with a bile acid sequestrant such as cholestyramine or colestipol (Grade 2B).

 

For patients who do not respond to or do not tolerate a bile acid sequestrant, we suggest the following approach (Grade 2C):

 

-First, we switch to rifampin. (See 'Rifampin' above.)

 

-If symptoms persist, we then switch to an opioid antagonist, such as naltrexone. Opioid antagonists are generally well tolerated with the exception of a self-limited opioid withdrawal-like syndrome that usually resolves spontaneously within two days. Opioid antagonists should not be used in patients receiving opioid-containing medications or in patients with acute hepatitis, liver failure, or severe liver dysfunction.

 

-Switching to sertraline or phenobarbital at bedtime can be tried if other measures fail. Phenobarbital has the disadvantage of causing somnolence during the first few weeks of use.

 

If medical treatments fail and the pruritus is severe, liver transplantation may be the only effective therapy.

 

私は、リファンピシンを胆汁うっ滞時のかゆみに使用する事を知りませんでした。

2006年に Liver Intからメタアナが報告されていました。

 

Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials.  (PMID : 16953834) Liver Int. 2006 Oct;26(8):943-8.

 

なお、結論は、以下の通りです。

This meta-analysis suggests that rifampin is safe and effective for treatment of pruritus due to chronic cholestasis. This analysis also suggests that use of rifampin for short duration is associated with a low risk of hepatotoxicity.