Pruritus secondary to primary biliary cholangitis: a review of the pathophysiology and management with phototherapy

Abstract

Summary Background Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disorder characterized by destruction of liver bile ducts leading to intrahepatic cholestasis. It causes intractable pruritus for which ultraviolet (UV)B phototherapy is an experimental treatment when alternative therapies fail. The pathophysiology of cholestatic itch and the mechanism of action of narrowband UVB in this condition remains poorly understood. Objectives To summarize the current literature and propose testable hypotheses for the mechanism of action of phototherapy in attenuating itch. Methods A focused PubMed search for articles relating to the pathogenesis of itch in cholestatic disease was performed. A total of 3855 articles were screened and 50 were found suitable for literature review. Evidence from this literature review was combined with author expertise in the area. Results Formulated hypotheses focus on the role of bile salts, autotaxin and specific receptors including G‐protein‐coupled bile acid receptor, Gpbar1 (also known as TGR5) and the nuclear transcription factor farnesoid X receptor. Conclusions Several testable mechanisms through which phototherapy may exert its effects are discussed in this review. The next steps are to carry out an objective assessment of the efficacy of phototherapy in cholestatic pruritus, gain further knowledge on the underlying pathways, and subsequently trial its use against current licensed therapies. Such studies could lead to increased mechanistic understanding, identification of novel therapeutic targets and the potential to refine phototherapy protocols, leading to improved control of itch and quality of life in patients with PBC. What's already known about this topic? Primary biliary cholangitis (PBC) is frequently associated with intractable pruritus for which current treatment options are often unsuccessful. Phototherapy is used as an experimental treatment for PBC‐associated pruritus when alternative better‐studied treatments fail. What does this study add? This study reviews the current literature on the pathophysiology and management of cholestatic pruritus, an area which remains poorly understood. We propose testable hypotheses of the mechanisms behind the attenuation of cholestatic pruritus with phototherapy.

Evaluation of G-Protein-Coupled Bile Acid Receptor 1 (TGR5) Levels in Intrahepatic Cholestasis of Pregnancy

“…The role of various factors including bile acids, opioids, steroids, and lysophosphatidic acid has been discussed, but none of them was considered as the key mediator [23]. It has been reported that elevated bile acid concentration in circulation and in the tissues during cholestasis causes itching by activating TGR5 [24][25][26].…”

The pharmacology of itch

“…The BJD champions evidence-based dermatology. A review article included in this virtual issue considers the problem of severe, treatmentresistant pruritus associated with primary biliary cholangitis, in which destruction of liver bile ducts leads to intrahepatic cholestasis (Hussain, Samuel, Hegade, Jones, & Reynolds, 2019). Our understanding of its pathophysiology is summarized by the review, including specific receptors such as the G-protein-coupled bile acid receptor GPBAR1 and the nuclear transcription factor farnesoid X receptor.…”

Shedding light on the itch of cholestasis

“…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.…”