Pruritus

GENERAL PRINCIPLES

The pathophysiology is debated and may be due to the accumulation of bile acid compounds or endogenous opioid agonists.

DIAGNOSIS

Patients with cholestasis can develop itching with either a normal or elevated bilirubin level.

TREATMENT

Medications

FIRST LINE

Pruritus is best treated with cholestyramine, a basic anion exchange resin. It binds bile acids and other anionic compounds in the intestine and inhibits their absorption. The dose is 4 g mixed with water before and after the morning meal, with additional doses before lunch and dinner, up to a maximum of 16 g/d. Administer cholestyramine apart from other medicines or vitamins as cholestyramine will impair absorption. Colestipol, a similar resin, is also available.

SECOND LINE

• Antihistamines (hydroxyzine, diphenhydramine, or doxepin, 25 mg PO at bedtime) and petrolatum may provide relief from pruritus.

• Rifampin (150-600 mg/d) and naltrexone (25-50 mg/d) are reserved for intractable pruritus. Long­term therapy with rifampin is associated with minor, transient elevations in serum aminotransferase levels in 10%-20% of patients—abnormalities that usually do not require dose adjustment or discontinuation. In rare instances, it can induce severe DILI.

• Ondansetron (Zofran) has demonstrated short-term efficacy in treating pruritus associated with cholestasis since it involves the serotonin system.

• Switching to sertraline (75-100 mg/d) or phenobarbital (90 mg QHS) can be tried if other measures fail.

• Some studies have demonstrated relief of pruritus with phototherapy or plasmapheresis, but clinical experience has been mixed.