Skin signs of viral hepatitis

What is viral hepatitis?

Viral hepatitis is inflammation of the liver due to infection with viruses from the hepatotrophic family: hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV). Many other viruses can also cause hepatitis; this review will focus on the skin changes associated with infection by the known hepatotrophic viruses.

Hepatitis C virus

 

 

Who gets skin changes related to viral hepatitis?

Viral hepatitis due to hepatotrophic viruses can be divided into acute and chronic forms.

• Acute viral hepatitis
  • HAV, HBV, HCV, HEV
• Chronic viral hepatitis
  • HBV, HCV, HEV

Skin changes are found in up to 17% of HCV-positive patients.

HDV is usually a co-infection in patients with chronic HBV accelerating progression to early liver failure.

HEV is the most common cause of acute viral hepatitis worldwide, although it is often asymptomatic or only mildly symptomatic with jaundice following a prodromal phase. It can progress to chronic infection in immunocompromised patients.

What causes skin changes with viral hepatitis?

Skin changes in acute viral hepatitis can be nonspecific such as the itch secondary to jaundice. Chronic viral hepatitis can cause progressive liver failure and skin changes due to cirrhosis or hepatocellular carcinoma.

Skin changes seen with viral hepatitis can be due to:

• Direct viral infection of skin cells with viral particles detected in keratinocytes and lymphocytes
• Autoimmune origin as HCV is lymphotropic promoting B-cell proliferation and circulating autoantibodies can be detected
• Effects on the liver seen in acute viral hepatitis and subsequent chronic liver disease.

What are the cutaneous features of viral hepatitis?

Skin signs of acute viral hepatitis

• Jaundice and associated pruritus in icteric acute viral hepatitis
• Acute urticaria is commonly associated with viral infections including HAV, HBV, and HCV
• A transient exanthem may precede typical symptoms of acute HAV infection
• Serum-sickness-like reaction — presents as urticaria, fever, headache, and joint pain in 20–30% of patients with acute HBV
• Erythema multiforme
• Erythema nodosum
• Henoch-Schönlein purpura reported with HAV, HBV, HEV.

Jaundice 

Erythema nodosum 

Henoch-Schönlein purpura 

Skin signs of chronic viral hepatitis

At least 20% of patients with chronic hepatitis due to HBV or HCV develop skin changes, only a few of which are diagnostic of viral hepatitis.

Skin conditions associated with both HBV and HCV

• Cryoglobulinaemia types II and III (mixed) — can present with skin signs of cutaneous vasculitis or systemic vasculitis
• Lichen planus
• Skin cancer — cutaneous squamous cell carcinoma
• Dermatomyositis — has been reported in association with HBV or HCV-related hepatocellular carcinoma, and HCV-induced autoimmunity
• Anti-cardiolipin antibodies without thrombocytopenic thrombosis can be associated with both HBV and HCV, and antiphospholipid syndrome with HCV

Skin conditions more often associated with HBV

• Papular acrodermatitis of childhood (Gianotti-Crosti syndrome)

Vasculitis due to cryoglobulinaemia 

Lichen planus 

Gianotti-Crosti syndrome 

Skin conditions more often associated with HCV

• Pruritus affects 15% of patients with chronic HCV
• Mixed cryoglobulinaemia is common in chronic HCV and can proceed to clinical systemic vasculitis with palpable purpura and Raynaud phenomenon
• Immune thrombocytopenic purpura — common autoimmune complication of chronic HCV infection
• Porphyria cutanea tarda — up to 50% of patients have markers of HCV infection
• Necrolytic acral erythema — is pathognomonic for HCV and is predominantly reported in skin of colour
• Oral lichen planus — globally 2% of oral lichen planus patients have HCV and 1% of patients with chronic HCV develop lichen planus
• Sjögren syndrome (secondary SjS/HCV-SjS) — 18% of HCV patients have sicca symptoms (dry mouth and eyes), with positive rheumatoid factor (RF) and ANA but negative anti-Ro/La. Sjögren-like sialadenitis is commonly detected on salivary gland biopsy but may be asymptomatic.
• Other oral conditions — caries, gingivitis
• Low serum zinc in HCV is due to a reduction in copper-zinc superoxide dismutase, and skin signs can include aphthous stomatitis, dermatitis, and hair loss
• Psoriasis, particularly of late onset, may be more common in patients with HCV than in the general population.

Porphyria cutanea tarda 

Erosive oral lichen planus 

Non-specific skin signs of chronic liver failure and cirrhosis

• Jaundice
• Dry skin (xerosis)
• Excoriations and nodular prurigo due to itch
• Bleeding and bruising — ecchymoses, purpura, petechiae, red or purple haemorrhages, bleeding gums can be due to thrombocytopenia and hypersplenism
• Spider telangiectasis
• Palmar erythema
• Nail changes — clubbing, onycholysis, and leukonychia; Terry nails can occur in advanced cirrhosis [see Nail terminology]
• Loss of armpit and pubic hair
• Low serum zinc particularly in patients with cirrhosis and hepatocellular carcinoma
• Bier spots — small irregular hypopigmented macules on the limbs which disappear with pressure
• Caput medusae — dilated veins around the umbilicus, a sign of portal hypertension and liver cirrhosis

Bier spots 

Purpura 

Terry nails