Treatment of pruritus of cholestasis
cholestasis is a devastating symptom which impairs quality of life to
such an extent that patients can be driven to suicide. Typically,
pruritus of cholestasis manifests itself initially without any visible
skin manifestations and exacerbates at night. The resulting scratching
can lead to excoriations and in chronic forms to marked thickening of
the cutis and subcutis.
The etiology is still unclear; it stands to reason, however, that some
cholephile is involved. The main contenders remain bile acids and
endorphins (1). Treatment should follow a step-wise approach described
and referenced below. There are three particular conditions where an
alternative algorithm should be employed:
- Cholestasis due to deficiency in BSEP/MDR3 (BRIC). This should be thought off when hepatic
alkaline phosphatase is markedly elevated and g-glutamyl transpeptidase
normal. This usually does not respond to cholestyramine.
- Intrahepatic cholestasis of pregnancy (ICP); in this situation, UDCA should be started
immediately. Cholestyramine has no effect.
- Pruritus in hepatitis C (Pruritus
in hepatitis C). This is probably a multifactorial symptom which
can be quite difficult to treat.
Treatment of pruritus usually starts with pharmacological treatments
but in some instances moderately invasive procedures are required. If
the pruritus is due to ductopenia such as in end-stage primary biliary
cirrhosis or primary sclerosing cholangitis, liver transplantation
might have to be considered. The different treatment modalities are
listed with increasing side effects / invasiveness. In most instances,
going through the list pruritus should be alleviated at level 3 to 4.
- Cholestyramine / Colestipol.
These are organic anion binding resins. Cholestyramine will
successfully treat pruritus in 90 % of the cases (exceptions see
above). It should be taken an hour ahead of breakfeast and one to two
hour ahead of other medication and at bed-time - again separated by at
least two hours from any other medication. Its taste is disagreeable;
therefore, I recommend to swirl it up in half a glass of an opaque
fluid (milk or orange juice), down it rapidly and flush with a glass of
water. Usual dosage: 2 x 4 - 8 g/d.
- Enzyme inducers.
Rifampicin induces canalicular transporters and detoxifying enzymes via
the pregnane X receptor. A meta-analysis on a very limited number of
patients has proclaimed it to be effective in 77 % of patients and to
be safe (2). However, cases of hepatotoxicity have been described and
adequate monitoring is required (3). It has supplanted phenobarbital
since it is more effective and better accepted by patients. Usual
dosage is 10 mg/kg. I start with 600 mg. An effect can be seen after
about 5 days - if after 10 days pruritus persists, alternatives should
- Opiate antagonists. Their
effects can be quite impressive but at the expense of an opioid
withdrawal syndrome which can be very disturbing to the unprepared
patient. A thoughtful editorial (4) references my approach: I
hospitalize the patient and start naloxone at 0.002 mg/kg/h. If
tolerated, the infusion rate is increased at 6 - 12 h intervals up to
0.2 mg/kg/h. If effective,
the patient is switched to oral naltrexone
12.5 mg b.i.d. and naltrexone is increased as needed up to 250 mg/d (in
most cases 2 x 50 mg will suffice).
- Other pharmacological agents:
H3-antagonists such as ondansetrone, SSRI such as sertraline and
THC-agonists have been reported to be effective in small case series.
No controlled studies are available. A trial of such agents may be
justified before stepping up to more invasive procedures as described
- Ursodeoxycholic acid: Is
clearly effective in ICP (see above) but in other conditions its
effects are moderate at best. Since it takes a long time to exert its
effect I usually do not employ it as a first line drug - again with the
exception of ICP.
- Plasmapheresis / Anion
absorption techniques: A variety of techniques including
plasmapheresis alone, combined with anion absorption or hemodialysis
techniques with anion absorption such as MARS or PROMETHEUS have been
used successfully in case report and small series. No controlled
studies are available.
- Endoscopic / surgical biliary
diversion: Surgical internal or external biliary diversion is an
accepted treatment for PFIC. Nasogastric biliary drainage can alleviate
severe pruritus (5).
- Liver transplantation
should be considered in patients with diseases known to progress when
all measures fail even if liver function is good.