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 1 change in the skin or body and eliciting vigorous scratching”.

 Mild to moderate pruritus is a common problem which increases with age in the general 2 population.

 Pruritus in the absence of skin disease may have a systemic cause. Diagnosis of a systemic 1 cause is made by the history, clinical examination and use of appropriate investigations.

 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 Skin diseases associated with Systemic diseases associated pruritus with pruritus Often limited in extent Asteatosis (dry skin) Biliary and hepatic disease

This is a diagnosis of Dermatitis / eczema Haematological disorders e.g. exclusion lymphoma Dermatitis herpetiformis Folliculitis Infectious diseases e.g. HIV Iron deficiency Lichen planus Malignancy Pruritus ani and vulvae

Psoriasis Medications e.g.opioids Scabies Neurological diseases Urticaria 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 1 mediated itch is associated with the sedative effect of the drug.

1  Low sedative H1 antihistamines are indicated in histamine-mediated itch. 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) 5 in certain types of pruritus.

34.2 GUIDELINES  Skin disorders should be diagnosed and treated appropriately. 2 [Level 4]  It is important to exclude drugs as a cause of pruritus. 2 [Level 4]

 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 [Level 4]

Table 34.2 Management of pruritus 1 [Level 4]

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 [Level 4]

 Failure of one treatment should lead to the selection of an alternative anti-pruritic agent appropriate to the cause. 2 [Level 4]

Table 34.3 General measures used in the management of pruritus 1 [Level 4]

Avoid alcohol / spicy foods Tepid showers

Avoid vigorous scratching Use an emollient as soap substitute and a moisturiser

Keep nails short Ultraviolet phototherapy. e.g. uraemia / AIDS / malignant skin infiltrations

Table 34.4 Topical agents used in the management of pruritus 1, 6 [Level 4]

Topical agent Dose Comments Emollient e.g. Use as required Soap substitute and moisturiser. Oilatum® Lauromacrogols Use as required. Available as Balneum® Plus. Specific anti-pruritic

- bath oil agent useful for dry itchy skin or dermatoses.

- cream Menthol Add to aqueous cream Acts as skin cooling agent. to make a 1-2% compound.

Apply several times daily. Corticosteroids Apply sparingly. Useful in dermatitis / eczema. Short term use (topical) recommended. Doxepin cream 5% Apply bd-qds. May cause transient stinging and drowsiness. Limit to small localized areas of dermatitis. Local anaesthetics Apply as required (see Benzocaine may cause contact dermatitis.

- Lidocaine comments). Absorption is variable. There is a risk of cardiac arrhythmias if high absorption. Restrict use to small - Benzocaine local areas of pruritus for a short period. Capsaicin cream 0.025% or 0.075% May cause burning on initial use. Settles after a few applied three times days. Useful for pruritus secondary to uraemia. daily. Also useful for neuropathic pain.

Table 34.5 Systemic drugs used in the management of pruritus

Class of Name of Indications for use Dose (oral Comments drug drug unless otherwise stated)

H1 receptor Non sedative Histamine induced itch Consult BNF for Non-sedating drugs can be used 1 antagonist Levocetirizine individual doses during daytime. ( Level 4) Desloratidine Fexofenadine Sedative Chlorpheniramine Hydroxyzine Promethazine Trimeprazine / Alimemazine

H2 receptor Ranitidine Urticaria / Hodgkins 300mg daily in Enhances effect of H1 receptor 1 antagonist lymphoma / divided doses antagonists in urticaria. [Level 4] Polycythaemia Rubra Vera

Combined H1 Doxepin Chronic urticaria not 10mg-75mg od Beware drug interactions. and H2 responding to H1 receptor antihistamines 1, antagonists 2

[Level 4]

5HT3 Ondansetron Itch secondary to spinal 4mg-8mg No clinical trials but likely to be class 8, antagonists opioids intravenously daily. effect. 9, 10 [Level 1] Can be given orally. 8, 11 SSRI* Paroxetine Unknown cause. 5mg-10mg od Anti-pruritic effect wears off after 4- [Level 3] Paraneoplastic itch 6 weeks. Some evidence for higher doses e.g.30mg. 1 NaSSA** Mirtazapine Malignant homeostasis / 7.5mg-30mg od Sedative at low doses. [Level 4] Lymphoma / Uraemia Anion- Colestyramine Cholestatic disorders 4g bd or tds Not effective if complete biliary tract exchange obstruction. resins 1, 12 [Level 3] 13 Rifamycin Rifampicin Intrahepatic cholestasis Starting dose 75mg May cause bloating, constipation. [Level 1] od. Maximum dose Beware drug interactions. 150mg bd Immuno- Thalidomide Uraemia Seek specialist Avoid in fertile women. modulator 14 advice before use [Level 1] 2 Androgens Danazol Cholestasis 200mg od No clinical reports to support use as [Level 4] Maximum dose yet. Beware liver toxicity. 200mg tds Corticosteroi Prednisolone Hodgkins lymphoma 30mg-60mg od 1 ds [Level 4] Dexamethasone 4mg-8mg od

* 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 morphine- induced 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- HT3 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