What is the first-line treatment for itching due to cholestasis (intrahepatic cholestasis of pregnancy) in pregnancy?

Management of Itching in Intrahepatic Cholestasis of Pregnancy

Ursodeoxycholic acid (UDCA) at 10-15 mg/kg/day is the first-line treatment for itching due to intrahepatic cholestasis of pregnancy. 1, 2

Diagnosis and Assessment

• ICP is diagnosed based on otherwise unexplained pruritus and elevated serum bile acid concentrations (≥11 μmol/L) 1
• Laboratory testing should include serum bile acids, ALT, AST, bilirubin, and γGT to confirm diagnosis and rule out other causes 2
• Higher bile acid levels (≥40 μmol/L) are associated with increased risks for adverse perinatal outcomes 1
• If initial bile acid levels are normal but pruritus persists, testing should be repeated as bile acid elevation may lag behind symptom onset 2

First-Line Treatment

• UDCA at 10-15 mg/kg/day (typically 300 mg 2-3 times daily or 500 mg twice daily) should be initiated promptly upon diagnosis 1
• Clinical improvement in pruritus usually occurs within 1-2 weeks, while biochemical improvement typically takes 3-4 weeks 1, 3
• UDCA is effective in relieving pruritus and improving laboratory abnormalities in 67-80% of ICP patients 1, 4
• If pruritus is not adequately relieved, the dose can be titrated up to a maximum of 21-25 mg/kg/day 1
• Even low doses of UDCA (300-450 mg/day; 4-6 mg/kg/day) have been shown to improve biochemical markers and clinical symptoms in almost 90% of ICP patients 5

Second-Line Treatments for Refractory Pruritus

• For patients who cannot take UDCA or have continued symptoms on maximum dosage, consider the following options:
  • Rifampicin (300-600 mg daily) can be combined with UDCA for refractory cases 1
  • Anion exchange resins such as cholestyramine (4-8 g/day) or colestipol (5-10 g/day), given at least 4 hours after UDCA 1
  • S-adenosyl-methionine may improve pruritus, although it is less effective than UDCA but may have an additive effect when combined 1, 6
  • Antihistamines such as diphenhydramine or hydroxyzine have limited benefit but may help with sleep 1

Supportive Measures

• General recommendations include:
  • Using emollients to prevent dryness of skin 1
  • Avoiding hot baths or showers that can worsen pruritus 1
  • Using cooling gels (e.g., menthol gels) for affected skin areas 1
  • Keeping nails shortened to minimize skin damage from scratching 1
• Topical antipruritics (e.g., menthol creams and calamine lotion) are of limited use as itching is typically widespread 1
• In severe cases of unbearable pruritus, plasmapheresis may provide transient relief 1, 7

Important Considerations

• UDCA and cholestyramine administration should be separated by at least 4 hours 1
• Vitamin K deficiency may be exacerbated by cholestasis and the use of anion exchange resins or rifampicin; replacement should be given in women with steatorrhea or confirmed vitamin K deficiency 1
• Monitor coagulation tests (e.g., INR) in women treated with these drugs 1
• Neonates of women treated with rifampicin should receive vitamin K 1
• UDCA treatment should be discontinued at delivery 2
• If symptoms or abnormal liver tests persist for 4-6 weeks after delivery, further investigation for underlying chronic liver diseases is warranted 7, 2

Efficacy and Safety

• UDCA is well tolerated, with only negligible skin reactions (0.5%) and mild diarrhea (4.7%) reported 4
• While UDCA clearly improves maternal symptoms, a large randomized trial (n=605) did not find significant differences in the composite perinatal outcome compared to placebo 8
• Despite this, UDCA remains the first-line treatment due to its established efficacy in relieving maternal pruritus and improving biochemical parameters 1, 3