Pruritus can affect patients with primary biliary cholangitis (PBC) regardless of cholestasis or stage of disease1,2

In clinical trials, a visual analog scale (VAS) is sometimes used to assess pruritus severity.

  • Patients may assess itch intensity with a VAS
    • The patient indicates the intensity of pruritus on a line, with extremes from 0: no pruritus at all to 10: the worst pruritus you can imagine3
  • 19% of patients present with pruritus at diagnosis of PBC4
  • Over the course of the disease, up to 80% of patients may experience pruritus5,6
    • According to one study, 45% of patients with pruritus were not on any pruritus treatments.7
  • The impact of pruritus should not be underestimated
    • Severe treatment-refractory pruritus in and of itself is an approved indication for liver transplant, even when liver disease is not advanced8,9
    • Severe pruritus has been linked to depression and patient suicide9
  • Lifestyle interventions may include10
    • Keeping fingernails short and filed to alleviate the effects of scratching
    • Consulting a dermatologist for skin disorders linked with scratching

General recommendations for treating chronic pruritus11

Avoid
  • Increasing dryness of skin (excessive washing and bathing)
  • Contact with irritants
  • Very hot and spicy food
  • Excitement, strain, negative stress
Apply
  • Mild nonalkaline soaps
  • Lukewarm water
  • Soft clothing permeable to air
  • Skin moisturizer
  • Topical agents with symptomatic relief (eg, containing tannin, camphor, menthol, etc)
  • Wet, cool, or moist wraps
Try
  • Relaxation techniques
  • Training to stop the cycle of itch, scratch, itch

Severity of pruritus can fluctuate within a single day or over longer periods of time.8

  • Pruritus may present anywhere on the body9
  • Per published treatment guidelines, over-the-counter topical treatments may not always prove efficacious8
  • Case report evidence advocates invasive physical approaches in resistant pruritus cases, such as extracorporeal albumin dialysis, plasmapheresis, and bile duct drainage1,12-15

For some patients, several therapeutic options may provide relief from pruritus.

  • Ursodeoxycholic acid (UDCA) has variable effect on the severity of pruritus8,16
  • Guidelines for managing pruritus are available through the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL)1,8,9

Guideline-recommended pruritus treatment options8,9

FIRST-LINE BILE ACID SEQUESTRANTS

These should be used as initial therapy for patients with PBC who have pruritus.

  • Cholestyramine: 4 g up to 4 times daily, given 2-4 hours before or after UDCA
  • Colestipol, colesevelam
The following agents may be used for pruritus that is refractory to bile acid sequestrants:
SECOND-LINE
  • Rifampicin: 150-300 mg twice daily
THIRD-LINE ORAL OPIOID ANTAGONISTS

  • Naltrexone: 50 mg daily or 12.5 mg daily increasing by 12.5 mg every 3-7 days (up to 50 mg), until pruritus is ameliorated
  • Nalmefene, intravenus naloxone
FOURTH-LINE SELECTIVE SEROTONIN REUPTAKE INHIBITORS

  • Sertraline: 75-100 mg daily

As with all medications, the risk/benefit profile should be considered prior to use.


Discuss pruritus with your patients and how treatment options can help to minimize its effect on quality of life.

  • Additional guidance is provided in the following papers:
    • Hohenester S, Oude-Elferink RPJ, Beuers U. Primary biliary cirrhosis. Semin Immunopathol. 2009;31(3):283-307. doi:10.1007/s00281-009-0164-5.
    • Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2009;50(1):291-308. doi:10.1002/hep.22906. (AASLD guidelines)
    • Weisshaar E, Szepietowski JC, Darsow U, et al. European guideline on chronic pruritus. Acta Derm Venereol. 2012;92(5):563-581. doi:10.2340/00015555-1400.

References:  1. Hohenester S, Oude-Elferink RPJ, Beuers U. Primary biliary cirrhosis. Semin Immunopathol. 2009;31(3):283-307. doi:10.1007/s00281-009-0164-5.  2. Talwalkar JA, Souto E, Jorgensen RA, Lindor KD. Natural history of pruritus in primary biliary cirrhosis. Clin Gastroenterol Hepatol. 2003;1(4):297-302. doi:10.1016/S1542-3565(03)00134-4.  3. Wolfhagen FHJ, Sternieri E, Hop WCJ, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997;113(4):1264-1269. doi:10.1053/gast.1997.v113.pm9322521.  4. Prince M, Chetwynd A, Newman W, Metcalf JV, James OFW. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow-up for up to 28 years. Gastroenterology. 2002;123(4):1044-1051. doi:10.1053/gast.2002.36027.  5. Bergasa NV, Mehlman JK, Jones EA. Pruritus and fatigue in primary biliary cirrhosis. Baillières Clin Gastroenterol. 2000;14(4):643-655. doi:10.1053/bega.2000.0109.  6. Kremer AE, Bolier R, van Dijk R, Elferink RPJO, Beuers U. Advances in pathogenesis and management of pruritus in cholestasis. Dig Dis. 2014;32(5):637-645. doi:10.1159/000360518.  7. Hegade VS, Mells GF on behalf of UK-PBC Consortium, Beuers U, et al. Patient experience of pruritus in the UK-PBC research cohort. Poster presented at: The International Liver Congress; May 23-24, 2014; Milan, Italy.  8. European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267. doi:10.1016/j.jhep.2009.04.009.  9. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2009;50(1):291-308. doi:10.1002/hep.22906. (AASLD guidelines)  10. Michalak A, Hanc M, Fatyga A, Skublewska A, Prystupa A, Mosiewicz J. Pruritus in liver disease—pathenogenisis and treatment. J Pre-Clin Clin Res. 2011;5(2):47-49.  11. Weisshaar E, Szepietowski JC, Darsow U, et al. European guideline on chronic pruritus. Acta Derm Venereol. 2012;92(5):563-581. doi:10.2340/00015555-1400.  12. Parés A, Cisneros L, Salmerón JM, et al. Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2004;99(6):1105-1110. doi:10.1111/j.1572-0241.2004.30204.x.  13. Pusl T, Denk GU, Parhofer KG, Beuers U. Plasma separation and anion adsorption transiently relieve intractable pruritus in primary biliary cirrhosis. J Hepatol. 2006;45(6):887-891. doi:10.1016/j.jhep.2006.08.008.  14. Alallam A, Barth D, Heathcote EJ. Role of plasmapheresis in the treatment of severe pruritus in pregnant patients with primary biliary cirrhosis: case reports. Can J Gastroenterol. 2008;22(5):505-507.  15. Beuers U, Gerken G, Pusl T. Biliary drainage transiently relieves intractable pruritus in primary biliary cirrhosis [letter]. Hepatology. 2006;44(1):280-281. doi:10.1002/hep.21271.  16. Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian multicenter double-blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994;19(5):1149-1156. doi:10.1002/hep.1840190512.