Skin manifestations of liver disease

Overview

Skin signs of liver disease arise through four mechanisms: bilirubin accumulation, oestrogen excess, portal hypertension, and synthetic failure (clotting factors, albumin).

Sign	Mechanism	Key associations
Jaundice	Bilirubin deposition; sclerae yellow first; visible in sclerae at ~35-50 micromol/L	Hepatocellular disease (mixed bilirubin); cholestasis (conjugated - dark urine)
Spider naevi	↑Oestrogens (impaired hepatic metabolism) → arteriovenous dilatation; SVC territory; >5 abnormal	Cirrhosis; also normal in pregnancy
Palmar erythema	Oestrogen excess → palmar vasodilation; thenar/hypothenar, sparing central palm	Cirrhosis, pregnancy, thyrotoxicosis, RA
Leukonychia / Terry's nails	Hypoalbuminaemia → nail bed oedema → opacity; proximal 2/3 white, distal 1/3 pink	Cirrhosis, heart failure, T2DM
Caput medusae	Portal hypertension → blood through para-umbilical portosystemic anastomoses; flow away from umbilicus	Portal hypertension (distinguishes from IVC obstruction: flow upward throughout)
Pruritus	Cholestasis → pruritogen accumulation (bile salts, endogenous opioids, lysophosphatidic acid)	PBC, intrahepatic cholestasis of pregnancy
Xanthelasma / xanthomata	Cholestasis → impaired biliary cholesterol excretion → hyperlipidaemia → lipid skin deposition	PBC
Bruising / purpura	↓Clotting factor synthesis (factor VII first to fall); thrombocytopaenia from hypersplenism	Advanced cirrhosis / hepatic failure
Peripheral oedema	↓Albumin → ↓oncotic pressure + portal hypertension + secondary hyperaldosteronism	Cirrhosis, hepatic failure
Dupuytren's contracture	Palmar fascia fibrosis; ring and little fingers; mechanism unclear - abnormal fibroblast activity	Alcohol-related liver disease
Hyperpigmentation	PBC: bile salt deposition stimulates melanocytes; haemochromatosis: iron + melanin deposition ('bronze diabetes')	PBC, haemochromatosis
Lichen planus	Violaceous flat-topped polygonal papules; molecular mimicry between viral and keratinocyte antigens	Hepatitis C (also hepatitis B)
Gynaecomastia / hair loss	Oestrogen excess → feminisation; more prominent with alcohol (also suppresses testosterone directly)	Alcohol-related cirrhosis

💡

Spider naevi and palmar erythema can be normal in pregnancy. When found together in a non-pregnant adult, particularly with other signs, they strongly warrant liver function testing.

Investigations

🥇 First-line

•LFTs (bilirubin, ALT, AST, ALP, GGT, albumin) - ↓albumin and ↑bilirubin = synthetic failure; ↑ALP/GGT = cholestasis

•Clotting screen (PT/INR) - prolonged PT = impaired clotting factor synthesis; used in Child-Pugh and MELD scoring

•FBC - thrombocytopaenia suggests hypersplenism; hepatitis B and C serology; abdominal ultrasound (portal vein >13 mm suggests portal hypertension)

🥈 Second-line

•Antimitochondrial antibody (AMA) - positive in >95% of PBC; serum ferritin and transferrin saturation (haemochromatosis); liver biopsy for histological confirmation

Management

•Treat underlying disease: abstinence (alcohol); tenofovir / entecavir (hepatitis B); sofosbuvir/velpatasvir (hepatitis C); ursodeoxycholic acid (PBC); venesection (haemochromatosis)

•Cholestatic pruritus - first-line: cholestyramine (bile acid sequestrant) before and after breakfast

•Cholestatic pruritus - second-line: rifampicin (hepatic enzyme inducer; monitor LFTs - hepatotoxic); naltrexone (opioid antagonist)

•Cholestatic pruritus - third-line: sertraline, plasmapheresis, nasobiliary drainage, or liver transplantation in refractory cases

•Oedema/ascites: sodium restriction; spironolactone (first choice - aldosterone antagonist); add furosemide if needed

•Coagulopathy: phytomenadione (vitamin K) IV or oral if cholestasis contributing; FFP for acute bleeding; platelet transfusion if thrombocytopaenic bleeding

⚠️

Rifampicin is hepatotoxic - it is second-line for cholestatic pruritus, not first-line. LFTs must be monitored and the drug stopped if transaminases rise significantly.

Disease-specific patterns

•Alcoholic cirrhosis - spider naevi, palmar erythema, leukonychia, Dupuytren's contracture, caput medusae, gynaecomastia, loss of body hair, bruising, oedema

•Primary biliary cholangitis (PBC) - severe pruritus (often presenting symptom), xanthelasma, xanthomata, hyperpigmentation, jaundice (late)

•Haemochromatosis - bronze hyperpigmentation, loss of body hair, signs of cirrhosis if advanced

•Hepatitis C - lichen planus, porphyria cutanea tarda (photosensitive blistering on dorsum of hands), palpable purpura (mixed cryoglobulinaemia)

•Wilson's disease - Kayser-Fleischer rings (copper in Descemet's membrane), jaundice