Pruritus cholestatic L29.9

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Cholestatic itching; cholestatic pruritus; Cholestatic Pruritus; Pruritus in cholestasis

Definition
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Pruritus caused by various hepatobiliary disorders. Pruritus is an early symptom of cholestasis and thus a common complication of acquired or congenital liver disease.

Etiopathogenesis
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In a larger study, 60% of pruritus patients suffered from either viral hepatitis (40%), mainly hepatitis C, or biliary tract disease (primary or secondary sclerosing cholangitis). Recent underestimates indicate an increased concentration of lysophosphatidic acid (LPA) in the serum of patients with cholestatic pruritus. LPA acts via LPA receptors.

This is caused by an increased activity of the membrane ectoenzyme autotaxin (ATX). Autotaxin catalyzes the formation of LPA from lysphosphatidylcholine. Autotaxin activity correlates with the severity of itching. Autotaxin inhibitors will be of particular interest for this form of itching.

In addition to autotaxin and its cleavage product lysophosphatidic acid, endogenous opioids play a role, since a reduced hepatobiliary excretion probably leads to an accumulation of these substances. This could play a role in the action of u-opioid receptor antagonists (e.g. naltrexone) (Ständer S 2018).

Manifestation
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It is not uncommon (about 25%) for years of pre-existing pruritus to occur even before the hepatic disease was diagnosed.

Clinical features
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It is not uncommon for cholestatic pruritus to begin as a localized itching on the soles of the feet or palms of the hands or in other places (arms and legs). In the course of time, generalized pruritus often develops. Genitoanal pruritus is rather rare.

The itching is perceived as "pure" itching only in a smaller proportion of patients; more frequent are mixed sensations such as burning or pricking. Triggers are tight-fitting clothing, sweating or stress. Aquagenic triggering (showering, bathing) is rare. Mostly the itching occurs during the whole day; about 25% of the patients notice an increase or even the exclusive occurrence in the evening or at night.

Internal therapy
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Therapy primarily depends on the treatment of the underlying diseases (DD: intrahepatic (K71.0) and extrahepatic cholestasis (K83.1)).

Cholestyramine (anion expander): Results are interpreted very differently.

Alternative: ursodeoxycholic acid (UDCA: 10-15mg(kgkgkg/day); even with this medication only little success is to be expected.

Alternative: it is accepted that gabapentin should be used as an initial antipruritic therapy (Cave: efficacy is only expected after 8 weeks).

Alternative: Opioid receptor antagonists (naltrexone, naloxone)

Alternative: controversial is the use of systemic antihistamines (the influence of histamine is controversial in the CP)

Alternatively, in case of resistance to therapy: phototherapy, plasmapheresis, albumin dialysis, nasobiliary drainage.

Literature
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  1. Hegade VS et al (2016) The safety and efficacy of nasobiliary drainage in the treatment of refractory cholestatic pruritus: a multicentre European study. Aliment Pharmacol Ther 43: 294-302.
  2. Hegade VS et al (2019) Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus. Liver Int 39:967-975.

  3. Huesmann M et al (2013) Cholestatic pruritus: a retrospective analysis of clinical characteristics and treatment response. JDDG 11: 158-169
  4. Kremer AE et al (2015) Pathogenesis and Management of Pruritus in PBC and PSC. Dig Dis 33 Suppl 2:164-175.
  5. Stand S (2018) Pruritus, Prurigo. In: Braun-Falco`s Dermatology, Venerology Allergology G. Plewig et al (Hrsg) Springer Verlag S 587
  6. Stull C et al (2016) Advances in therapeutic strategies for the treatment of pruritus. Expert Opinion Pharmacother 17: 671-687.


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Last updated on: 29.10.2020