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Chapter 20: Cholestatic Pruritus

Manuel P. Pereira; Sonja Ständer

CHOLESTATIC PRURITUS

Therapeutic Approach

Patients with hepatobiliary diseases with and without cholestasis experience frequently excruciating pruritus. Acquired (eg, primary biliary cholangitis and primary sclerosing cholangitis) and congenital diseases (such as Alagille syndrome) as well as intrahepatic cholestasis of pregnancy are commonly associated with pruritus, but other hepatic disorders may also lead to pruritus. Pruritus begins on normal appearing skin usually on the palms and soles, but may affect the whole body in the course of the disease. Excoriations, lichenification of the skin, and pruriginous lesions may develop due to scratching. Therapeutically, several pharmacological and procedural options are currently available; however, high-quality clinical trials are still scarce. The European Association for the Study of the Liver (EASL) recommends cholestyramine as first-line treatment for cholestatic itch, followed by rifampicin as a second-line option. Oral or intravenous opiate antagonists (naltrexone, naloxone) are regarded as third-line agents, while sertraline constitutes a further therapy option. See Table 20-1.

Table 20-1Cholestatic Pruritus Treatment Table
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Table 20-1 Cholestatic Pruritus Treatment Table
MEDICATION NAME THERAPY USED IN MECHANISM OF ACTION DOSING ADVERSE EFFECTS SUGGESTED MONITORING LEVEL OF EVIDENCE (REFERENCE)
Systemic Therapy
Cholestyramine PBC, PSC, Intra- and extrahepatic cholestasis Bile acid sequestrant 4-16 g/d Constipation, abdominal pain, diarrhea, gastrointestinal hemorrhage Lipid profile IB1,2
Rifampicin PBC, PSC Pregnane X receptor agonist 300-600 mg/d, 10 mg/kg Hepatotoxicity, hemolysis, nephrotoxicity, abdominal pain, nausea, vomiting, diarrhea CBC, liver function tests, serum creatinine, coagulation tests IA3–7
Naltrexone Chronic liver diesase (PBC, PSC, hepatitis, cirrhosis, choledocholithiasis, hepatic and pancretic tumors μ-opioid receptor antagonist 50 mg/d Hepatotoxicity, opioid withdrawal syndrome, abdominal pain, diarrhea, nausea and vomiting, dizziness, headache Liver function tests, signs of opioid withdrawal syndrome, depression/suicidality IB8–10
Naloxone Chronic liver disease (including PBC, PSC, hepatitis C, granulomatous hepatitis, cirrhosis, benign recurrent intrahepatic cholestasis, Alagille syndrome, drug-induced cholestasis, cholestasis after billiary tract surgery μ-opioid receptor antagonist 0.4 mg bolus followed by 0.2 μg/kg body weight per minute i.v., up to 2 consecutive 24-h infusions Hypertension, hypotension, tachycardia, dyspnea, hypoxia, respiratory depression, agitation, irritability, pain, confusion, dizziness, opioid withdrawal syndrome Vital signs, level of consciousness, signs of opioid withdrawal syndrome, use with caution in patients with cardiovascular disease or seizures IB11–13
Nalfurafine (only approved in Japan) PBC, hepatitis, cirrhosis, vanishing bile duct syndrome κ-opioid receptor agonist 2.5-5.0 μg p.os. daily Insomnia, constipation, opioid withdrawal syndrome Assess signs of opioid withdrawal syndrome IB14,15
Nalmefene PBC, hepatitis C, hepatic sarcoidosis μ-opioid receptor antagonist and partial κ-opioid receptor agonist Up to 20 mg twice a day p.os. Drowsiness, nausea, arrhythmia, hypotension, hypertension, opioid withdrawal syndrome Assess signs of opioid withdrawal syndrome IB16
Sertraline PBC, PSC, hepatitis C, postnecrotic cirrhosis Selective serotonin reuptake inhibitor 75-100 mg/d Dizziness, insomnia, fatigue, diarrhea, nausea CBC, liver function tests, renal retention parameters, serum sodium, signs of serotonin syndrome or alteration of the mental status IB6,17...

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