Pruritus cholestatic L29.9

Pregnancy cholestasis:

• Generalized pruritus with inconspicuous skin during pregnancy, especially on palms and soles, disappears after delivery.
• Laboratory: GPT and bilirubin are often elevated; an increase in serum bile acid concentration > 10 µmol/l (take fasting values!) is conclusive.
• With bile acids > 40 µmol/l, there is an increased rate of premature births and stillbirths as well as increased perinatal mortality; the fetal prognosis correlates with the severity of the clinical picture
• Therapy: ursodeoxycholic acid 12.5-20 mg/kg bw/d, daily dose about 1g (4 tbls), leads to reduction of pruritus and fetal risks; close monitoring, early initiation if necessary.
• There is a risk of recurrence in subsequent pregnancy as well as when taking oral contraceptives

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

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).

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

It is not uncommon for cholestatic pruritus to begin as localized itching on the soles of the feet or palms of the hands or other sites (arms and legs). Over time, frequent development of generalized pruritus. Genitoanal pruritus is uncommon.

The pruritus is experienced as "pure" itching in only a smaller proportion of patients; mixed sensations such as burning or stinging are more common. Triggers include tight-fitting clothing, sweating, or stress. Rare is aquagenic triggering (showering, bathing). In most cases, itching occurs throughout the day; about 25% of patients notice an intensification or even the exclusive occurrence in the evening or at night.

A special form of cholestatic pruritus is pruritus in pregnancy cholestasis.

Therapy is primarily based on treatment of underlying disease (DD: intrahepatic (K71.0) and extrahepatic cholestasis (K83.1)).

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

Alternative: ursodeoxycholic acid (UDCA: 10-15mg per kg bw/day); even with this medication, little success can be expected.

Alternative: it is accepted that gabapentin should be used as initial antipruritic therapy (Cave: efficacy can only be 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).

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

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, Venereology Allergology G. Plewig et al (eds) Springer Verlag p 587.
6. Stull C et al (2016) Advances in therapeutic strategies for the treatment of pruritus. Expert Opin Pharmacother 17: 671-687.