GUIDELINES FOR THE MANAGEMENT OF PRURITUS IN PALLIATIVE CARE 34.1 GENERAL PRINCIPLES Pruritus may be defined as: an intense cutaneous discomfort occurring with pathological change in the skin or body and eliciting vigorous scratching. 1 Mild to moderate pruritus is a common problem which increases with age in the general population. 2 Pruritus in the absence of skin disease may have a systemic cause. Diagnosis of a systemic cause is made by the history, clinical examination and use of appropriate investigations. 1 Pruritus is distressing for patients and a challenge for clinicians to manage effectively. It is 1, 2, 3 incompletely understood and is difficult to treat in many circumstances. Pruritus may be primary or secondary. Table 34.1 lists the causes of pruritus. 4 In advanced malignancy, cholestatic jaundice is probably the most frequent cause. Table 34.1 Causes of pruritus 4 Idiopathic Often limited in extent This is a diagnosis of exclusion Skin diseases associated with pruritus Asteatosis (dry skin) Dermatitis / eczema Dermatitis herpetiformis Folliculitis Lichen planus Pruritus ani and vulvae Psoriasis Scabies Urticaria Systemic diseases associated with pruritus Biliary and hepatic disease Haematological disorders e.g. lymphoma Infectious diseases e.g. HIV Iron deficiency Malignancy Medications e.g.opioids Neurological diseases Thyroid disease Uraemia Drugs used to treat pruritus should be selected according to the underlying mechanism causing the pruritus. There is no broad spectrum anti-pruritic agent. Antihistamines are not effective in treating chronic pruritus as histamine is not the causative agent. Any benefit in non-histamine mediated itch is associated with the sedative effect of the drug. 1 Low sedative H 1 antihistamines are indicated in histamine-mediated itch. 1 This includes insect bite reactions, drug rashes, most forms of urticaria and cutaneous mastocytosis.
Iron deficiency, with or without anaemia may cause pruritus. This can respond to iron therapy which should be continued until iron stores are replaced. 2 Serum iron is the most reliable investigation as haemoglobin levels are poor indicators of iron deficiency. Serotonin is thought to produce itch by both peripheral and central mechanisms. The central mechanism is thought to involve the opioid neurotransmitter system. 1 These theories provide the rationale for the use of opioid antagonists or selective serotonin reuptake inhibitors (SSRIs) in certain types of pruritus. 5 34.2 GUIDELINES Skin disorders should be diagnosed and treated appropriately. 2 It is important to exclude drugs as a cause of pruritus. 2 Table 34.2 illustrates a step approach to the management of pruritus. Emollients should be used as a soap substitute and as a moisturiser. Calamine lotion should be avoided as it is extremely drying and can exacerbate pruritus, especially in the elderly or those with dry skin. 1 Table 34.2 Management of pruritus 1 Step 1 Treat underlying cause if possible Step 2 Use general measures (see Table 34.3) Step 3 Consider topical agents (see Table 34.4) Step 4 Consider drug treatments (see Table 34.5) The effectiveness of any treatment should be reviewed on a regular basis. 2 Failure of one treatment should lead to the selection of an alternative anti-pruritic agent appropriate to the cause. 2 Table 34.3 General measures used in the management of pruritus 1 Avoid alcohol / spicy foods Avoid vigorous scratching Keep nails short Tepid showers Use an emollient as soap substitute and a moisturiser Ultraviolet phototherapy. e.g. uraemia / AIDS / malignant skin infiltrations
Table 34.4 Topical agents used in the management of pruritus 1, 6 Topical agent Dose Comments Emollient e.g. Use as required Soap substitute and moisturiser. Oilatum Lauromacrogols - bath oil - cream Menthol Corticosteroids (topical) Use as required. Add to aqueous cream to make a 1-2% compound. Apply several times daily. Apply sparingly. Available as Balneum Plus. Specific anti-pruritic agent useful for dry itchy skin or dermatoses. Acts as skin cooling agent. Useful in dermatitis / eczema. Short term use recommended. Doxepin cream 5% Apply bd-qds. May cause transient stinging and drowsiness. Limit to small localized areas of dermatitis. Local anaesthetics - Lidocaine - Benzocaine Apply as required (see comments). Capsaicin cream 0.025% or 0.075% applied three times daily. Benzocaine may cause contact dermatitis. Absorption is variable. There is a risk of cardiac arrhythmias if high absorption. Restrict use to small local areas of pruritus for a short period. May cause burning on initial use. Settles after a few days. Useful for pruritus secondary to uraemia. Also useful for neuropathic pain.
Table 34.5 Class of drug H 1 receptor antagonist 1 ( Level 4) H 2 receptor antagonist 1 Combined H 1 and H 2 receptor antagonists 1, 2 5HT 3 antagonists 8, 9, 10 [Level 1] 8, 11 SSRI* [Level 3] NaSSA** 1 Anionexchange 1, 12 resins [Level 3] Rifamycin 13 [Level 1] Immunomodulator 14 [Level 1] Androgens 2 Corticosteroi ds 1 Systemic drugs used in the management of pruritus Name of drug Non sedative Levocetirizine Desloratidine Fexofenadine Sedative Chlorpheniramine Hydroxyzine Promethazine Trimeprazine / Alimemazine Ranitidine Doxepin Ondansetron Paroxetine Indications for use Histamine induced itch Urticaria / Hodgkins lymphoma / Polycythaemia Rubra Vera Chronic urticaria not responding to H 1 antihistamines Itch secondary to spinal opioids Unknown cause. Paraneoplastic itch Dose (oral unless otherwise stated) Consult BNF for individual doses 300mg daily in divided doses 10mg-75mg od 4mg-8mg intravenously daily. Can be given orally. Comments Non-sedating drugs can be used during daytime. Enhances effect of H 1 receptor antagonists in urticaria. Beware drug interactions. No clinical trials but likely to be class effect. 5mg-10mg od Anti-pruritic effect wears off after 4-6 weeks. Some evidence for higher doses e.g.30mg. 7.5mg-30mg od Sedative at low doses. Mirtazapine Malignant homeostasis / Lymphoma / Uraemia Colestyramine Cholestatic disorders 4g bd or tds Not effective if complete biliary tract obstruction. Rifampicin Intrahepatic cholestasis Starting dose 75mg od. Maximum dose 150mg bd Thalidomide Uraemia Seek specialist advice before use Danazol Cholestasis 200mg od Maximum dose 200mg tds Prednisolone Dexamethasone Hodgkins lymphoma 30mg-60mg od 4mg-8mg od May cause bloating, constipation. Beware drug interactions. Avoid in fertile women. No clinical reports to support use as yet. Beware liver toxicity. * Selective serotonin reuptake inhibitor. ** Noradrenergic and specific serotoninergic antidepressant.
34.3 STANDARDS 1. All patients should be asked about the presence of pruritus at assessment and the results documented in the case notes. 7 [Grade D] 2. Reversible causes of pruritus should be treated where appropriate. 7 [Grade D] 3. General and topical measures should always be considered first. 7 [Grade D] 4. The efficacy of any medication used should be reviewed every one / two weeks. 7 [Grade D] 5. Drug treatment should be selected according to the most likely underlying aetiology. 7 [Grade D] 34.4 REFERENCES 1. Twycross R, Greaves MW, Handwerker H, Jones EA, Libretto P, Szepietowski JC et al. Itch: scratching more than the surface. Q J Med 2003; 96: 7-26. 2. Zylicz Z, Twycross R, Jones A (eds). Pruritus in Advanced Disease. Oxford. Oxford University Press. 2004. 3. Thorns A, Edmonds P. The management of pruritus in palliative care patients. Eur J Palliat Care 2000; 7: 9-12. 4. Pittelkow MR, Loprinzi CL. Pruritus and sweating In: Doyle D, Hanks GWC, Cherney NI, Calman K (eds). Oxford Textbook of Palliative Medicine, 3rd edition. Oxford. Oxford University Press. 2003. p.573-586. 5. Jones EA, Zylicz Z. Treatment of pruritus caused by cholestasis with opioid antagonists. Palliat Med 2005; 8(6): 1290-1294. 6. Drake L, Cohen L, Gillies R, Flood JG, Riordan AT, Phillips SB et al. Pharmacokinetics of doxepin in subjects with pruritic atopic dermatitis. J Am Acad Dermatol 1999; 41(2): 209-214. 7. Merseyside and Cheshire Palliative Care Network Audit Group. Meeting on Management of Pruritus in Palliative Care. Expert Consensus. December 2003. 8. Borgeat A, Stirnemann HR. Ondansetron is effective to treat spinal or epidural morphineinduced pruritus. Anesthesiology 1999; 90(2): 432-436. 9. Dimitriou V, Voyagis GS. Opioid-induced pruritus: repeated vs single dose ondansetron administration in preventing pruritus after intrathecal morphine. Br J Anaesth 1999; 83(5): 439-441. 10. Kyriakides K, Hussain SK, Hobbs GJ. Management of opioid-induced pruritus: a role for 5- HT 3 antagonists? (Clinical Trial) Br J Anaesth 1999; 82(3): 439-441. 11. Zylicz Z, Smits C, Krajnik M. Paroxetine for pruritus in advanced cancer. J Pain Sympt Manage 1998; 16(2): 121-124. 12. Connolly CS, Kantor GR, Menduke H. Hepatobiliary pruritus: what are effective treatments? J Am Acad Dermatol 1995; 33(5 Pt 1): 801-805. 13. Price TJ, Patterson WK, Olver IN. Rifampicin as treatment for pruritus in malignant cholestasis. Support Care Cancer 1998; 6(6): 533-535. 14. Silva SRT, Viana PC, Lugon NV, Hoette M, Ruzany F, Lugon JR. Thalidomide for the treatment of uraemic pruritus. A cross over randomized double-blind trial. Nephron 1994; 67(3): 270-273.
15. Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage 2001; 21(2): 151-168. 34.5 CONTRIBUTORS Lead Contributors External Reviewer Dr S Fradsham Specialty Registrar in Palliative Medicine Aintree University Hospitals NHS Foundation Trust Liverpool Dr C Lewis-Jones Consultant in Palliative Medicine/Medical Director St Johns Hospice Wirral and Wirral University Teaching Hospital NHS Foundation Trust Dr CM King Consultant Dermatologist Royal Liverpool and Broadgreen University Hospitals NHS Trust Liverpool Dr G Leng Medical Director Hospice of the Good Shepherd Chester