Shedding light on the itch of cholestasis

Abstract

The psychological burden and considerable morbidity associated with intractable pruritus is not to be underestimated. This is compounded by a relative lack of understanding of the mechanisms of generalized pruritus and a scarcity of robust approaches to management. I was thus delighted to read the fascinating article by Hussain et al. in the current issue of the BJD in which a detailed literature review was undertaken to probe our understanding of generalized pruritus induced by cholestasis in the context of primary biliary cholangitis. A thorough evaluation of treatment approaches was also performed, with a focus on phototherapy. This review informs the authors’ objectives of undertaking a definitive, prospective study of the use of ultraviolet B (UVB) phototherapy for cholestatic pruritus, which in parallel will also test mechanistic hypotheses. Certainly, management of cholestatic pruritus is a challenge and is usually based on medical approaches, such as with cholestyramine, rifampicin and naltrexone, prior to consideration of biliary drainage procedures and even liver transplantation. The role of UVB phototherapy must be considered given preliminary evidence to support its use, its wide availability and good safety profile. Thus, raising awareness of this treatment option is essential. The authors discuss likely mechanisms for the action of UVB phototherapy in cholestatic pruritus and these include the increase in urinary excretion of bile salts, altered bile salt structure and reduced synthesis mediated by vitamin D. The authors also discuss the potential pathogenic roles of autotaxins, lysophosphatidic acid, proteases and tryptases and the effects of UVB on these parameters. Furthermore, altered expression of receptors may also be implicated, in particular those expressed on sensory neurons. Hussain and colleagues have set the scene for their definitive prospective study of phototherapy for cholestatic jaundice by undertaking two online surveys, one of dermatologists and the other of patients with cholestatic pruritus. It is clear from these online surveys that there is wide variation in opinion with respect to how phototherapy is used for patients with both cholestatic and uraemic pruritus, how much benefit there is for patients and in the regimes used. Surprisingly, few patients with cholestatic pruritus had received phototherapy and while only the minority of those treated found it to be effective, there was considerable variation in the number of sessions used. With respect to patients, 80% of survey respondents would be happy to try phototherapy for their symptoms of itch. According to the limited published studies, mainly of case series showing efficacy of UVB phototherapy for cholestatic pruritus, fairly lengthy treatment courses may be required. In the current review, the authors very eloquently set the scene for a prospective study, which will address efficacy of UVB phototherapy for cholestatic pruritus and investigate possible mechanisms. This is also anticipated to open up avenues for exploring other possible treatment targets. We will await the outcomes of this study with interest and in the meantime raise awareness of this easily available, safe and often effective treatment for this debilitating condition.