Pruritus (itching) is a common and often distressing symptom near the end of life.
The itch sensation may arise from stimulation of the skin itch receptor via unmyelinated C fibers, or itch may arise as a central phenomenon without skin involvement (e.g., opioid-induced pruritus).
Although histamine causes pruritus, many patients with pruritus show no signs of histamine release. Besides histamine, serotonin, prostaglandins, kinins, proteases, and physical stimuli have all been implicated as mediators of pruritus.

Common causes include:
- dermatological (dryness, wetness, irritation, eczema, psoriasis)
- metabolic (hepatic failure, renal failure, hypothyroidism),
- hematologic / oncologic (iron deficiency, polycythemia, thrombocytosis, leukemia, lymphoma)
- drugs (opioids, aspirin, drug reactions)
- infection (scabies, lice, candida)
- allergy (urticaria, contact dermatitis)
- psychogenic

Management of pruritus involves eliminating the cause when possible. Symptomatic strategies include:
- Moisturizers. The mainstay of treatment of dryness is skin hydration; serious dryness requires emollients and moisturizers, such as petroleum jelly.
- Cooling agents. Cooling agents (e.g., calamine and/or menthol in aqueous cream, 0.5%-2%) are mildly antipruritic. They may act as a counterirritant or anesthetic. A more direct way to anesthetize the skin is with the eutectic mixture of local anesthetics lidocaine and prilocaine (EMLA cream).
- Antihistamines. These may be helpful in relieving itch when associated with histamine release. Morphine causes non-immune mediated histamine release from mast cells. Although there is not much supporting research, many report benefits of combining H1 and H2 receptor subtype antihistamines. These may have central effects as well as peripheral antihistaminergic effects. Doxepin (10-30 mg PO at bedtime), a tricyclic antidepressant, is a very potent antihistamine and may help in more refractory cases.
- Topical steroids. These may be helpful in the presence of skin inflammation. They are best applied in ointment rather than cream formulations to alleviate dryness. Systemic steroids have been used in refractory cases.
- Newer generation antidepressants. There are accounts of paroxetine being used successfully to treat pruritus associated with a paraneoplastic process, opioids, or cholestasis. Mirtazapine has also been shown to improve pruritus at low doses of 15 mg/day in small case reports; this is likely due to its known antihistamine effects and its blockage of post-synaptic 5HT2 and 5HT3 receptors.
- Opioid antagonists. Low dose, continuous infusions of IV naloxone has the largest body of data supporting its use in adult and pediatric patients with opioid-induced pruritus. Small studies suggest a potential role for methylnaltrexone in opioid-induced pruritus.
- Other. An old-fashioned but effective remedy is immersion in an oatmeal bath. More recent pharmacological treatments include cholestyramine for cholestatic pruritis; and ondansetron for patients with cholestatic, opioid-induced, or renally-induced pruritus. Since the pain-sensing neurological system seems to be responsible for pruritis, agents like gabapentin have also been reported to be helpful.

Adapted from von Gunten C and Ferris F. Palliative Care Network of Wisconsin. Fast facts and concepts #37. Pruritus. Internet. Accessed on June 21, 2016.