Pruritus in palliative care

Chronic renal failure

Pruritus secondary to chronic renal failure presents in nondialysis and dialysis patients alike. It can be generalized or localized and paroxysmal or continuous. There are multiple possible causal factors and current treatments to target these factors. For example, most uremic patients have dry skin, in which case emollients are suggested and can be combined with all treatments.^5,7 Ultraviolet B light therapy can be helpful, although the exact mechanism of action remains unknown. Antihistamines are not usually helpful in pruritus secondary to chronic renal failure, so histamine is unlikely to be a contributing factor.^5,7–9 Paroxetine and mirtazapine can be tried, as serotonin regulation is likely involved.^10,11 Cholestyramine might help with increased concentrations of bile acids seen in uremic patients. Opioid antagonists have been used for the purported opioid receptor imbalance.⁷

Cholestasis

Cholestasis is commonly associated with pruritus, but the pathogenesis is still unclear. There is no correlation between the level of bile acids and the degree of pruritus, which explains why lowering the level of bile acids with cholestyramine is often ineffective. Another postulated mechanism is altered central opioidergic transmission; for that reason, opioid antagonists are used.^8,9 Other possibilities include increased serotonin release, for which paroxetine, mirtazapine, or ondansetron can be prescribed. Again, histamine might be involved but to a lesser extent, as antihistamines are generally ineffective. Ultraviolet B light therapy is also an option.^{5,8,9,12–15}

Opioid-induced itch

Opioid-induced itch is more common with spinal opioids than with systemic opioids. The exact mechanism of opioid-induced pruritus is unknown; however, it is thought to be centrally mediated by μ-opioid receptors and inhibited by κ-opioid receptors. Opioids might also activate serotonin pathways, which explains why ondansetron (a 5-HT₃ receptor antagonist) relieves itch secondary to spinal morphine.^5,16,17

Solid tumours

Solid tumours can be associated with paraneoplastic pruritus, which in fact might be the presenting symptom that precedes the diagnosis by months or years. The pathophysiology is not well understood, but appears to involve an immunologic reaction to tumour-specific antigens. Antihistamines are ineffective. The itch can be generalized or tumour specific: scrotal itch in prostate cancer, perianal itch in colorectal cancer, or vulvar itch in cervical cancer. Solid tumours can also cause pruritus via biliary obstruction (eg, in pancreatic cancer); in such cases, decompression through stenting can be very effective.^5,6,8,9,16

Hematologic disorders

Pruritus associated with hematologic disorders, such as lymphoma and polycythemia vera, is more common than pruritus associated with solid tumours. Pruritus is present in approximately 30% of patients with Hodgkin disease and might precede the diagnosis by up to 5 years. In polycythemia vera, 30% to 50% of patients have itching after contact with water. Although these patients have increased histamine levels, H₁ receptor antagonists are ineffective.^5,6,8,9,17

Nonpharmacologic treatments

Ultraviolet B light therapy is thought to act by decreasing the number of mast cells and free nerve endings in the skin. It is often done 3 times a week; although it is most useful in pruritus secondary to uremia, it can also help with cholestasis and malignant skin infiltrations.^5,19 This regimen, however, is impractical for palliative patients toward end of life.

Another nonpharmacologic approach to pruritus, specific to cholestasis, is the placement of a stent to decompress biliary obstruction. Such obstructions are commonly observed in pancreatic cancer patients. This procedure might negate the need for any pharmacologic treatment, thus eliminating potential adverse side effects of certain drugs.

Pharmacologic treatments

Previously, H₁ receptor antagonists were the drug of choice for any type of pruritus. In fact, they are helpful only in cases in which histamine release occurs in the skin. This is, unfortunately, neither the only nor the biggest cause of pruritus seen in palliative care. In the past they might have appeared to work ubiquitously, perhaps owing to first-generation sedating effects.

Paroxetine is a serotonin reuptake inhibitor; because serotonin might have a role in pruritus secondary to malignant disease, as well as cholestasis, uremia, and opioids, it is therefore reasonable to try the drug in palliative patients with pruritus secondary to any of these illnesses. Patients can start with small doses, such as 5 to 10 mg nightly, which will cause fewer side effects than higher doses. Effects can usually be observed within 24 to 48 hours.^5,11,19,20

Mirtazapine is an antidepressant with 5-HT₂, 5-HT₃, and H₁ receptor antagonist properties. As with paroxetine, it can be used for uremic, cholestatic, and malignant pruritus. Treatment usually begins with a 15-mg dose nightly, but a lower dose of 7.5 mg to begin is also effective. Mirtazapine has few side effects.^10,19,20

Ondansetron, a 5-HT₃ receptor antagonist, can be used for pruritus associated with opioids, cholestasis, and uremia. It is fairly expensive though and can cause constipation, with which palliative patients are often afflicted.^5,14,20

Naltrexone and naloxone have previously been used to treat uremia, cholestasis, and opioid-induced pruritus, as μ-opioid receptor agonists are central mediators of pruritus.^5,20–22 However, these drugs are often inappropriate in the palliative population. Palliative patients might be using opioids for the management of pain or dyspnea, and opioid antagonists could reverse analgesia or lead to withdrawal symptoms. For opioid-induced pruritus secondary to systemic opioids, the initial strategy is to rotate to a different opioid. Spinal opioids are often given with bupivacaine, which decreases itch as well.

Treatment options are summarized in Table 1.^{2,5–11,14,16–18,20–22}

You advise Mrs P. to discontinue the antihistamines, as they are not likely helping with her itch. You review the general principles of dry skin care and recommend emollients, bathing less often, etc. You also prescribe a small dose of paroxetine (5 mg each night at bedtime). Within 48 hours, her pruritus has improved dramatically.