The management of pruritus in palliative care

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Pruritus commonly accompanies advanced diseases and as such, may negatively influence quality of life for many patients in palliative care.1 Itch is conveyed by the tiny fraction of thin C-fibres with specialised nerve endings.2

These nerve endings respond to histamine and several other factors released from the mast cells.3 Electrical impulses are conveyed to the spinal cord, where they usually undergo extensive modification by, among others, endogenous opioids and descending serotonergic pathways. Human beings are pain oriented, so pain impulses gain priority in the spinal cord and usually suppress the itch stimuli.

Only some itch symptoms originate in the periphery through interaction with histaminergic neurons (pruritoceptive itch).4 One example could be acute urticaria. This is also the reason why antihistamines are not very helpful in most of the itchy conditions in palliative care and their widespread use is based more on tradition than on evidence.

Most of the itch symptoms in palliative care are either the result of modifications in the spinal cord and brain functions by different neurotransmitters (neurogenic itch) or direct damage to the neural pathways (neuropathic itch).

A subset of the neurogenic itch, originating mainly in the higher centres, is called psychogenic itch.4 This latter category is thought to be secondary to psychiatric disorders, such as delusions and parasitosis.5 Drugs may influence neural itch pathways, giving rise to drug-induced itch other than acute histamine release related itch.

In most types of non-pruritoceptive itch, there is nothing to be seen on the skin (referred to as pruritus sine materia) unless it has been damaged by frequent scratching.

Dry skin
In palliative care, the itch most often encountered is that due to dry skin. In most cases it is not a specific entity. However, it may complicate the condition that was previously called senile pruritus. This generalised condition is poorly understood and is related to age-dependent changes in skin biology.6

No specific treatment is known for the condition. However, prevention of skin dehydration and moisturising with cream is the mainstay of therapy.

Pruritus of cholestasis
Another common condition is pruritus of cholestasis. It is now believed that not only the accumulation of bile acids, but also the synthesis of endogenous opioids is the most prevalent mechanism of itch.7 Hence the most effective drugs are opioid antagonists8,9 and probably partial opioid agonists (see Box 1).10-13 Pruritus of cholestasis may also respond to SSRIs.14,15

Paraneoplastic pruritus
Paraneoplastic pruritus is a very rare complication of many malignant tumours.16 It is a poorly understood immunological reaction to the presence of a tumour. It may occur several months before a diagnosis of malignancy as itchy dermatosis. The dermatosis may disappear with effective causal treatment of the malignancy and reappear on its recurrence. This type of pruritus usually responds well to centrally acting SSRIs14,17,18 and the evidence for this is accumulating.

Itch and haematological disorders
Some haematological disorders, such as lymphomas and polycythaemia rubra vera, are frequently complicated by severe itch. Although itch in polycythaemia rubra vera responds well to SSRIs19,20 and aspirin,4 and some itch in lymphomas responds to steroids, there are few specific treatments for these conditions. Symptomatic treatment should be accompanied by cytoreductive treatments until the patient's death.

Neuropathic itch
Neuropathic itch may be caused by many different factors (see box 2). Disruption of neuronal integrity at any level can cause itch. Compression or damage to a peripheral nerve may result in itch localised in the discrete area served by that nerve. An example of this is brachioradial pruritus.

Similarly, damage to the nerve root may result in itch in a dermatomal distribution.5 This type of itch is often seen when metastases of malignant tumours occur in the spinal cord. Damage to the spinal cord and brain may give a distinct distribution of itch. This often responds to drugs that decrease nerve excitability, such as carbamazepine, gabapentin and pregabalin.21,22 However, some forms of neuropathic itch may be very resistant to such therapy.

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