What are the skin manifestations of liver disease and how are they managed?

Skin Manifestations of Liver Diseases and Their Management

Pruritus is the most common skin manifestation of liver disease, particularly in cholestatic disorders, and should be managed with rifampicin as first-line treatment for hepatic pruritus. 1

Common Cutaneous Manifestations of Liver Disease

Pruritus

• Pruritus is a common symptom in various hepatobiliary disorders, particularly in cholestatic conditions 1
• The skin in hepatic pruritus is often hyperpigmented and excoriated, with hands and feet being the worst-affected areas 1
• Pruritus with fatigue at presentation may indicate more aggressive disease, such as primary biliary cholangitis 1
• There is poor correlation between pruritus and bile acid levels, suggesting other factors are involved 1

Vascular Changes

• Spider angiomas (spider nevi) - small dilated blood vessels radiating from a central arteriole 2, 3
• Palmar erythema - redness of the palms, particularly at the thenar and hypothenar eminences 3, 4
• "Paper money skin" - multiple small blood vessels visible on the upper trunk 4, 5
• Caput medusae - dilated periumbilical veins due to portal hypertension 3, 5

Hormonal Changes

• Gynecomastia - enlargement of male breast tissue due to altered estrogen metabolism 4, 5
• Loss of axillary and pubic hair - related to hormonal imbalances 5

Pigmentary Changes

• Jaundice - yellowing of skin and sclera due to hyperbilirubinemia 3, 4
• Hyperpigmentation - particularly in cholestatic disorders 1, 3

Nail and Hair Changes

• Clubbing, white nails (Terry's nails), watch-glass deformity 5
• Muehrcke's lines - paired white bands across the nails 3, 4
• Brittleness of nails and hair thinning 5

Management of Hepatic Pruritus

First-line Treatment

• Rifampicin is the first-line treatment for hepatic pruritus (start at 150 mg twice daily, can increase to 600 mg twice daily) 1
• Monitor for hepatotoxicity and inform patients about potential discoloration of secretions 1
• Two meta-analyses support rifampicin's effectiveness in reducing hepatic pruritus 1

Second-line Treatment

• Cholestyramine (9 g daily orally) - binds bile salts in the gut lumen, preventing absorption of bile acids 1
• Less evidence supports its use compared to rifampicin, but it has traditionally been used as first-line therapy 1

Third-line Treatment

• Sertraline (75-100 mg daily) - well-tolerated with evidence from a small RCT 1, 6

Fourth-line Treatment

• Naltrexone (50 mg daily) or nalmefene (0.25-1 mg/kg per day intravenously) 1
• Opioid antagonists have more side effects than cholestyramine and rifampicin, which may limit their use 1

Fifth-line Options

• Systemic dronabinol, phenobarbital, propofol, or topical tacrolimus ointment 1
• Newer agents targeting bile acid transport, autotaxin, and lysophosphatidic acid metabolism 1

Treatments to Avoid

• Gabapentin should not be used for hepatic pruritus (ineffective) 1, 6
• Long-term sedative antihistamines should be avoided except in palliative care (risk of dementia) 1

Management of Specific Liver Conditions

Cholestasis of Pregnancy

• Ursodeoxycholic acid (UDCA, 10-20 mg/kg per day) is the first-line treatment 1
• UDCA improves pruritus and liver tests in 67-80% of patients 1
• Dexamethasone is ineffective for pruritus in cholestasis of pregnancy 1

Autoimmune Hepatitis

• Pruritus is not a typical feature of autoimmune hepatitis; its presence may suggest an alternative diagnosis 1
• Hyperpigmentation and pruritus are inconsistent with the diagnosis of autoimmune hepatitis 1

Hepatitis C-Related Skin Manifestations

• Pruritus and other skin disorders can be either extrahepatic manifestations of HCV or side effects of antiviral therapy 1
• Direct-acting antiviral therapy is preferred over interferon-based regimens for HCV patients with skin manifestations 1

Diagnostic Approach

• Liver function tests should be part of the investigation of generalized pruritus without an underlying dermatosis 1
• Consider bile acids and antimitochondrial antibodies in the workup 1
• Any significant hepatic impairment should prompt referral to a hepatology center 1

Clinical Pearls

• Cutaneous manifestations may be the first clue to underlying liver disease 2, 3, 4
• The presence of a constellation of skin signs is more useful in pointing toward an underlying hepatobiliary condition than any single manifestation 3
• In patients with large bile duct obstruction, restoration of biliary drainage often leads to prompt resolution of pruritus 1
• Recognition of skin manifestations of liver disease can lead to earlier diagnosis and improved outcomes 2, 3