Low-Dose Naltrexone for Pruritus in Systemic Sclerosis PDF Print E-mail
Thursday, 01 March 2012 16:43
Tracy Frech, Kirsten Novak, Monica P. Revelo, Maureen Murtaugh, Boaz Markewitz, Nathan Hatton, Mary Beth Scholand, Edward Frech, David Markewitz, and Allen D. Sawitzke
Received 31 May 2011; Accepted 14 July 2011


Systemic sclerosis (SSc; scleroderma) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs including the skin, lungs, and gastrointestinal tract (GIT). This chronic disease process results in pain and pruritus, two distinct, but interacting phenomena. Pruritus is most common in the early stages of disease and may subside as the disease progresses. SSc patients that complain of pruritus have more significant skin involvement, more severe finger ulcers, worse respiratory symptoms, and a greater number of GIT complaints. Of interest, pruritus is independently associated with GIT symptoms in SSc. Although pruritus is associated with significant disability, management guidelines for pruritus in SSc do not exist.

Pruritus is also a feature of primary biliary cirrhosis (PBC), which occurs more commonly in SSc than the normal population. There is a known association with PBC and oxidative stress as well as endothelial dysfunction. Pharmaceutical management suggestions for treatment of pruritus in PBC include cholestyramine, rifampin, sertraline, and naloxone. More recently, pilot trials of low-dose naltrexone hydrochloride (LDN), which is a pharmaceutical similar to naloxone, have recently gained increasing recognition for treating chronic pain associated with fibromyalgia, multiple sclerosis, and Crohn’s disease.

Evidence supporting the hypotheses that increased opioid-mediated neurotransmission in the brain is a mechanism of pruritus and that central opioidergic tone is increased in cholestasis provides a rationale for treating the pruritus of cholestasis with opiate antagonists in PBC. Another potential mechanism of action of LDN is through attenuation of the production of proinflammatory cytokines and superoxides potentially mediated by activity of toll-like receptor. Modulation of mitochondrial apoptosis has also been proposed as a mechanism of LDN. In SSc, oxidative stress may be important in disease pathogenesis. Thus, an agent that potentially modulates oxidative stress is attractive as an emerging therapeutic in SSc. Given the putative mechanisms of action of LDN and the roles of these various pathways in SSc, our hypothesis is that LDN may be a reasonable agent to treat pruritus in SSc.

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