Pruritus

Top tips:

  1. Treat pruritis if it is impairing quality of life or sleep.
  2. Identify additional contributing factors (i.e. extrahepatic biliary obstruction, non-liver causes).
  3. Monitor with validated itch scores.
  4. Non-pharmacological management should be attempted in all patients.
  5. If localized, consider additional topical therapies.
  6. If generalized, systemic treatment may be beneficial.

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Step 1: Assess and treat possible contributing factors

Confirm the diagnosis of cholestatic pruritis

Liver causes:
  • Consider the etiology of cholestasis with referral made to relevant specialties as required (e.g. Gastroenterology for extrahepatic biliary obstruction, Hepatology for primary biliary cholangitis).
  • Cirrhosis related cholestasis can also cause pruritus.
  • Characteristics of cholestasis associated pruritus: the intensity does not correlate with the severity of underlying liver disease; it has diurnal variation – worse itch in the late evening ; scratching often has little effect on the itch.
Non-liver causes:
  • Dermatological: xerosis, drug hypersensitivities, allergies, infestations, contact dermatitis
  • Systemic: drug induced, uremia, hypercalcemia, hematologic malignancies- more common in Hodgkin’s lymphoma, multiple myeloma, polycythemia vera

 

Step 2: Consider Non-Pharmacological Management

Non-pharmacological measures should be attempted in all patients prior to considering pharmacological therapy.

Good skin care and moisturizers are considered first line treatment.
Some general principles to follow:
  • Baths are better than showers (daily in lukewarm water for at least 15 minutes)
  • Avoid harsh soaps, body washes, bubble baths, etc. Try gentle, lightweight cleansers (eg. Cerave, Cetaphil- both glycerin based), and only apply to limited areas such as the axilla and the groin
  • Post bath: pat dry and moisturize skin within two minutes of getting out. Skin will still be damp. Ideally use hypoallergenic moisturizers with ceramides (eg. Cerave) that are free from fragrance and additives. Do not use the moisturizers on areas of broken skin.
  • Topical baby oil up to three times a week has shown positive effects on itching, sleep and overall quality of life.
Other skin care strategies include the following:
  • Keep skin cool by wearing light and cool clothing.
  • Avoid scratching – keep fingernails short, encourage massaging rather than scratching, wear gloves at night
  • Maintain a humid home environment, especially in the winter

See: Itch Patient Handout (in Development)

Step 3: If pruritis persists AND is LOCALIZED , can consider topical pharmacological treatment
Over-the-counter creams
  • Benadryl cream, Calamine lotion, Aveeno lotion with oatmeal
Pramoxine
  • Gold Bond Medicated Anti-Itch products (OTC) – contain pramoxine, dimethicone, menthol
  • Pramox HC (hydrocortisone 1%/pramoxine 1%) – apply two times a day for 4 weeks
Capsaicin 0.025% cream
  • Can be applied 2-4 times a day to affected areas
  • It may initially cause a burning sensation to the area
Menthol, Camphor and Phenol
(Must be compounded by pharmacy)

  • Separate products that can be added to most creams, typically in the range of 0.3-1.0%
  • All three may be added together, commonly with a 0.3% concentration for each, applied 1-2 times daily
Step 4: If pruritis persists despite topical therapies OR if pruritis is GENERALIZED,
consider systemic therapies

Note - Antihistamines have not been systematically evaluated in cirrhosis.

They may have a non-specific anti-pruritic effect and can be useful adjunctive therapy for some patients. Given their sedating properties they should be administered at nighttime if used. They can worsen hepatic encephalopathy.

If used, hydroxyzine is used more commonly than Benadryl – start low and titrate to effect.

Medication: Recommended Dose Additional information

Cholestyramine

4g PO before and after breakfast with additional doses at lunch and dinner PRN
Max: 16 mg/day

First line

  • Unpleasant taste - mix with fruit juice
  • Affects medication absorption - take meds 1 hr before or 4-6 hours after use
  • Adverse effects: anorexia, constipation, diarrhoea, abdominal discomfort, bloating

The subsequent therapies should ONLY be initiated with liver specialist guidance. They can be associated with serious side effects. Consultation should also address whether the patient may be a candidate for liver transplantation.

Rifampicin

150mg PO daily (titration q 2 weekly to 150-300 mg twice daily if non-response)
Max: 300mg PO BID

Second line

  • Check for drug interactions before use
  • Avoid if bilirubin >2.5 mg/dL (43 umol/L)
  • Take on empty stomach - 1 hour prior to meals or 2 hours after meals.
  • Adverse effects: nausea, anorexia, hemolytic anemia, thrombocytopenia, renal impairment, hepatotoxicity

    Monitor CBC and LFTs q2 weeks for first 2 months and monthly thereafter

Naltrexone

12.5mg PO daily (titrate by 12.5mg every 3-7 days)
Max: 50mg/day

Third line

Do not use with acute hepatitis, abnormal liver enzymes or decompensated cirrhosis

Adverse effects: opiate withdrawal-like reactions, reduced threshold to pain, chance of developing hepatitis

Serially monitor liver enzymes and LFTs given the risk of hepatotoxicity

Sertraline

37.5-50mg PO daily
Max: 50mg PO daily

Fourth line (Limited evidence for use)

AVOID in decompensated cirrhosis since it is metabolized by liver

AVOID in patients taking monoamine oxidase inhibitors (MOA) in previous 14 days

Adverse effects: bleed risk, QT prolongation

Serially monitor liver enzymes and LFTs given the risk of hepatotoxicity.

Alternative salvage therapies
(at certain specialty centres only)
  1. Ultraviolet B phototherapy
  2. Plasmapheresis
  3. Albumin dialysis using molecular adsorbent recirculating system
Fifth line (Limited Evidence for use)

Liver transplantation candidacy should be considered if pruritis is
severe and uncontrolled.


This section was adapted from content using the following evidence based resources in combination with expert consensus. The presented information is not intended to replace the independent medical or professional judgment of physicians or other health care providers in the context of individual clinical circumstances to determine a patient’s care.

Authors (Alphabetical): Amanda Brisebois, Sarah Burton-Macleod, Ingrid DeKock , Martin Labrie, Noush Mirhosseini, Mino Mitri, Kinjal Patel, Aynharan Sinnarajah, Puneeta Tandon

Thank you to pharmacists Omer Ghutmy and Meghan Mior for their help with reviewing these pages. 

Helpful Links:
  1. Goals of care: https://www.albertahealthservices.ca/frm-103547.pdf
  2. CKM Itchiness Patient Handout: https://www.ckmcare.com/Resources/Details/135
References:
  1. Davison SN on behalf of the Kidney Supportive Care Research Group. Conservative Kidney Management Pathway; Available from: https//:www.CKMcare.com.
  2. Bhalerao A, Mannu GS. Management of pruritus in chronic liver disease. Dermatol Res Pract. 2015;2015:295891. doi: 10.1155/2015/295891. Epub 2015 Mar 10. PMID: 25861254; PMCID: PMC4377431.
  3. Bunchorntavakul C, Reddy KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. 2012 May;16(2):331-46. doi: 10.1016/j.cld.2012.03.010. PMID: 22541702.
  4. Düll MM, Kremer AE. Treatment of Pruritus Secondary to Liver Disease. Curr Gastroenterol Rep. 2019 Jul 31;21(9):48. doi: 10.1007/s11894-019-0713-6. PMID: 31367993.
  5. European Association for the Study of the Liver. Electronic address: [email protected]; European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol. 2017 Jul;67(1):145-172. doi: 10.1016/j.jhep.2017.03.022. Epub 2017 Apr 18. PMID: 28427765.
  6. Siemens W, Xander C, Meerpohl JJ, Buroh S, Antes G, Schwarzer G, Becker G. Pharmacological interventions for pruritus in adult palliative care patients. Cochrane Database Syst Rev. 2016 Nov 16;11(11):CD008320. doi: 10.1002/14651858.CD008320.pub3. PMID: 27849111; PMCID: PMC6734122.

We gratefully acknowledge the Physician Learning Program for their design assistance.


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