Cholestatic Pruritus
Overview
Pruritis is an unpleasant sensation of the skin or mucous membranes that promotes the desire to scratch or rub. It is common in patients with kidney and liver disease/cholestasis and can be caused by multiple factors and can be extremely distressing leading to poor sleep, anxiety, and depression.
- Use this calculator to assess the severity of itch
- Even if your patient does not have Kidney Disease consider using ESAS-r-Renal for other concomitant symptoms
- Pruritis can be divided into 4 categories:
- Proprioceptive pruritis – originates in the skin and can be triggered by several chemical mediators, such as histamine, cytokines, opioids, and neuropeptides. Other examples include dermatological disorders (e.g. inflammation, infestation, contact dermatitis, xerosis)
- Neuropathic pruritis – damage along the afferent pathways causing itch, such as post-herpetic pruritus
- Neurogenic pruritis – such as uremic or cholestatic itch, centrally induced and unresponsive to anti-histamines
- Psychogenic pruritis – associated with psychiatric disorders and is the least common category
- CKD associated pruritus is a common and often severe symptom for patients with advanced stage kidney disease
- Cholestasis: the intensity does not correlate with the severity of underlying liver disease; it has diurnal variation - worse itch in the late evening
- Opioid-induced itch: likely centrally mediated
- Solid tumors (paraneoplastic pruritis): may involve an immunologic reaction to tumor specific antigens
- Hematologic disorders: (e.g. lymphoma, polycythemia vera)
- Metabolic disturbances (e.g. iron deficiency)
- Drug Hypersensitivities
- Dry skin conditions
General Principles
- Non-pharmacological management should be attempted in all patients
- Provide patients with the Itchiness Patient Handout
- Encourage good skin care and moisturizers
Soak & Seal
- Baths are better than showers (daily in lukewarm water for at least 15 min)
- Avoid harsh soaps, body washes, bubble baths etc. Try mild, unscented soap or gentle cleansers (e.g. CeraVe, Cetaphil), and only in limited places such as the axilla and groin areas
- Post bath: pat dry and moisturize skin within two minutes of getting out. Skin will still be damp. Ideally, use hypoallergenic moisturizers with ceramides (e.g. 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 personal care tips:
- Avoid scratching
- Keep finger and toe nails short and filed
- Use of cotton gloves at night for those individuals with the strong urge to scratch
- Encourage massaging and gentle pressure rather than scratching
- Keep skin cool by wearing light, loose, cotton clothing
- Use natural fiber bedding
- Maintain a humid home environment, especially in the winter; try using a cool humidifier in bedrooms and in common areas
- Avoid vasodilators such as coffee, alcohol, spices, and hot water
Ultraviolet B light therapy (phototherapy)
- Not much is known about the long-term effects of UVB, but a trial of three times a week for 3 weeks may provide some relief for a period of time. Requires referral to Dermatology
Acupuncture
- Although there is a lack of good evidence about its efficacy, patients may wish to consider this as an alternative or complementary treatment option
General Principles
- The goal of therapy is to balance symptom control with careful protection of physical function and cognition
- Treat the patient's daily pruritus if it is impairing their sleep or quality of life
- If pruritus persists and is localized, can consider topical pharmacological treatment
- If pruritus persists despite topical therapies or if pruritus is generalized, systemic treatment may be beneficial
- Over-the-counter creams: Benadryl cream, Calamine lotion, Aveeno lotion with oatmeal
- Antihistamines are not recommended in the treatment of CKD Associated Pruritus
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
- Do not use in or around the eyes.
- Do not apply to large areas
Capsaicin 0.025% or 0.075% Ointment
- Zostrix 0.025% and Zostrix Hp 0.075%
- Can be applied 2-4 times a day to affected areas
- It may initially cause burning to the area
- Wear gloves while applying
- Wash hand throroughly afterwards
Menthol, Camphor and Phenol are 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
- Must be compounded by pharmacy
Gamma-Linolenic acid (GLA) 2.2% cream
- Apply cream twice daily to identified dry skin
- May not be easily accessible in Alberta
- Antihistamines are not recommended in the treatment of CKD Associated Pruritis.
- Some medications are being used off-label for pruritus
Cholestyramine First-line Agent
- 4 gm, orally, before and after breakfast with additional doses at lunch and dinner as needed
- Maximum dose: 16 grams/day
Rifampin Second-line Agent
10 mg/kg in frail and elderly individuals and a maximum dose of 8 mg/kg in those with impaired hepatic function; consultation with an expert is recommended
Contraindicated in patients with Jaundice associated with reduced bilirubin; patients taking the following medications: atazanavir, darunavir, fosamprenavir, praziquantel, ritonavir/saquinavir, saquinavir, or tipranavir
Use with caution in patients with diabetes mellitus, history of alcoholism, and bleeding disorder (may cause vitamin K-dependent coagulation disorders and bleeding). It may cause Steven-Johnson syndrome, flu-like syndrome, thrombocytopenia, leukopenia, or anemia, pulmonary toxicity, fungal or bacterial infection including C.difficile-associated diarrhea (with prolonged use)
Rifampin 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. 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. Monitor CBC and LFTs every 2 weeks for first 2 months and monthly thereafter. It causes teeth, urine, feces, sweat, saliva, and tears discoloration. Remove contact lenses during therapy as it may cause permanent staining. Monitor for compliance
Naltrexone Third-line Agent
- 12.5mg daily
- To be titrated by 12.5mg every 3-7 days up to 50 mg/day
- Maximum Dose: 50mg/day
Contraindicated in patients with acute hepatitis and abnormal liver enzymes and in patients receiving opioid analgesics
Use with caution in patients with depression, history of suicidal thoughts, bleeding disorders, hepatic and renal impairment, and history of opioid addiction
Contraindicated in patients with decompensated cirrhosis
Use with caution in patients with compensated cirrhosis
- Monitor liver function test. An increase in naltrexone area under the curve of approximately 5-10-fold in patients with compensated and decompensated liver cirrhosis