#37

Pruritus

  • Charles F von Gunten MD
  • Frank Ferris MD

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Background

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 pruritis 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

  • Dermatological (dryness, wetness, irritation, eczema, psoriasis)
  • Metabolic (hepatic failure, renal failure, hypothyroidism)
  • Hematologic (iron deficiency, polycythemia, thrombocytosis, leukemia, lymphoma)
  • Drugs (opioids, aspirin, drug reactions)
  • Infectious (scabies, lice, candida)
  • Allergy (urticaria, contact dermatitis, drug reactions)
  • Psychogenic

Management    Management of pruritus involves eliminating the cause when possible. Symptomatic strategies include:

  • Moisturizers:  Dryness (xerosis) is very common and may exacerbate other causes. The mainstay of treatment is skin hydration.  Note: Most OTC preparations only have small amounts of moisturizer—they are mostly water. Serious dryness requires emollients and moisturizers (such as petroleum jelly) that patients find oily or greasy. Nevertheless, they may applied after bathing, over damp skin, with a superficial covering.
  • 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 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 may be helpful in the presence of skin inflammation. These 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 a paraneoplastic process, opioids or cholestasis.  Also mirtazapine has 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.  There are smaller studies suggest oral naloxone may have less favorable results.  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 (e.g. Aveeno).  More recent pharmacological treatments include cholestyramine for cholestatic pruritis; 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.

References

  1. Fleisher A, Michaels JR. Pruritus. Berger A, Portenoy RK, Weissman DE, eds. In: Principles & Practice of Supportive Oncology. Philadelphia PA: Lippincott-Raven Publishers; 1998: pp245-250.
  2. Krajnik M, Zylicz Z. Understanding pruritis in systemic disease. J Pain Symp Manage. 2001; 21:151-168.
  3. Wilde MI, Markham A.  Ondansetron: a review of its pharmacology and preliminary clinical findings in novel applications. Drugs. 1996; 52:773-794.
  4. Zylicz Z, Smits C, Chem D, Krajnik M.  Paroxetive for pruritis in advanced cancer. J Pain Symptom Manage. 1998; 16:121-124.
  5. Davis MP, Frandsen JL, et al.  Mirtazipine for pruritus.  J Pain Symptom Manage 2003; 25: 288-91.
  6. Wolfhagen FH, Sternieri E, et al.  Oral naltrexone treatment for cholestatic pruritus: a double blind, placebo-controlled study.  Gastroenterology 1997;113: 1264-69.
  7. Miller JL, Hagemann TM.  Use of pure opioid antagonists of opioid induced pruritus.  American Journal of Health-System Pharmacy 2011; 68: 1419-1425.

Version History:  This Fast Fact was originally edited by David E Weissman MD.  2nd Edition published August 2005; 3rd Edition May 2015. Current version re-copy-edited March 2009; then again May 2015.