Hepatitis c skin changes

Hepatitis C is an acute or chronic infection (> 6 months) caused by the hepatitis C virus (HCV), a hepatotropic RNA virus of which 6 gene types (1-6) are known. The infection leaves no lasting immunity. Extrahepatic involvement is multiform and polyetiologic. They involve the lymphatic-immunologic system, thyroid, kidney, skeletal system, and skin. Skin lesions are detected in 20-40% of patients with acute or chronic HCV infection.

Skin changes that occur as a result of HCV infection can be categorized as follows.

• Early phase of the viral infection:
  • icterus (25%)
  • Nonspecific exanthema (rare)
  • Necrolytic acral erythema (possibly in combination with zinc deficiency)
  • Pruritus
• Chronic phase of the viral infection (> 6 months)
  • Nonspecific exanthema in childhood: Gianotti-Crosti syndrome
  • HCV-induced autoimmunological diseases with consecutive dermatological manifestations (about 20% of patients with chronic hepatitis C have positive ANA and anti-LMK1 = liver kidney microsome-Ak against cytochrome P 450 - typical for autoimmune hepatitis); 50% of patients have a positive RF.
    • Essential mixed cryoglobulinemia: type II: mono- and polyclonal mixed cryoglobulinemia with monoclonal IgM rheumatoid factor and polyclonal IgG (monoclonal IgG or IgA rheumatoid factors in the precipitate are rarer): this type accounts for about 60% of cases of cryoglobulinemia.
    • Urticarial vasculitis
    • Cold urticaria
    • Sjögren's syndrome (13.4% of patients with Sjögren's syndrome have chronic hepatitis C)
    • Lichen planus (?)
    • Oral lichen planus (in a larger Chinese study no close correlation could be proven) see belowLichen ruber mucosae.
    • Erythema induratum (nodular vasculitis)
    • Erythema elevatum diutinum (described as a double infection with HIV)
    • Purpura Schönlein in the context of hepatitis C induced membranous glomerulonephritis
    • Non-IgA vasculitis
    • Pyoderma gangraenosum
    • Antiphospholipid antibody syndrome
    • Necrolytic acral erythema
  • HCV-induced autoimmunologic diseases without immediate (but secondary possible) dermatologic symptoms:
    • Rheumatoid arthritis
    • Idiopathic thrombocytopenia (purpura).
    • Membranous glomerulonephritis (leukocytoclastic vasculitis)
    • Chronic lymphocytic thyroiditis - Hashimoto's thyroiditis (vitiligo, alopecia areata)
    • HCV-induced insulin resistance with consecutive (insulin-resistant) diabetes mellitus (15% of infected persons)
    • Positive ANA (20% of those infected with HCV)
  • Further secondary skin and systemic changes as a result of persistent HCV infection (chronic hepatitis > 6 months):
    • Increased risk of non-Hodgkin's lymphoma
    • Activated psoriasis
    • Pityriasis rubra pilaris (especially the circumscribed type 4 of pityriasis rubra pilaris)
    • REM syndrome
    • Increased coproporphyrin excretion in urine (in larger studies up to 40% of HCV-infected persons even in early phases of HCV infection; the connection has not yet been clarified). No clinical signs of photosensitivity.
    • Secondary skin changes due to developing or manifest liver cirrhosis with the typical liver skin signs (not listed here):
      • Pruritus (especially with cholestatic hepatitis C)
      • Aquagenic pruritus
      • Porphyria cutanea tarda
      • Hidradenitis neutrophilic eccrine
• Secondary skin changes due to antiviral therapy
  • Erythema multiforme
  • DRESS

About 3% of the world population is chronically infected with HCV. The prevalence in Germany is 0.3% of the population, in Mediterranean countries 2-3%, in some African countries up to 22%. Risk groups are i.v. drug addicts (85% are HCV positive), non-sterile piercings, HIV and/or HBV infected persons.

Acute HC infections are asymptomatic in 75% of cases and symptomatic (icteric) in 25%. Symptomatic HCV infections heal spontaneously in half of the cases. Asymptomatic infections generally lead to a chronic course. 20% of patients with asymptomatic infection develop cirrhosis of the liver. There is an increased rate of liver cell carcinoma. HIV/HCV double infections often progress rapidly and are more often cholestatic.

1. Brito-Zerón P et al. (2015) How hepatitis C virus modifies the immunological profile of Sjögren syndrome: analysis of 783 patients. Arthritis Res Ther 17:250.
2. Crowson AN et al (2003) The dermatopathologic manifestations of hepatitis C infection: a clinical, histological, and molecular assessment of 35 cases. Hum Pathol 34: 573-579

3. Inamadar AC et al (2020) Necrolytic acral erythema: current insights. Clin Cosmet Investig Dermatol 13:275-281.

4. Ito A et al (2003) Purpura with cold urticaria in a patient with hepatitis C virus infection-associated mixed cryoglobulinemia type III: successful treatment with interferon-beta. J Dermatol 30: 321-325
5. Halawani MR (2014)Dermatological manifestations of hepatitis C virus infection in Saudi Arabia. Saudi Med J 35:531-537.
6. Kim H (2003) Erythema elevatum diutinum in an HIV-positive patient.
   J Drugs Dermatol 2:411-412.
7. Miyagawa S et al (1990) Acral granulomatous dermatosis. Br J Dermatol 122: 709-713.
8. Pinto-Almeida T et al (2013) Cutaneous lesions and finger clubbing uncovering hypocomplementemic urticarial vasculitis and hepatitis C with mixed cryoglobulinemia. An Bras Dermatol 88:973-976.
9. Reyes-Avilés E et al (2015) Presence of Rheumatoid Factor during Chronic HCV Infection Is Associated with Expansion of Mature Activated Memory B-Cells that Are Hypo-Responsive to B-Cell Receptor Stimulation and Persist during the Early Stage of IFN Free Therapy. PLoS One 10:e0144629.
10. Song J et al. (2016) Lack of evidence of hepatitis in patients with oral lichen planus in China: A case control study. Med Oral Patol Oral Cir Bucal 21:e161-e168.
11. Taborelli M et al. (2016) Hepatitis B and C viruses and risk of non-Hodgkin lymphoma: a case-control study in Italy. Infect Agent Cancer 11:27.
12. Younossi Z et al. (2016) Extrahepatic Manifestations of Hepatitis C: A Meta-analysis of Prevalence, Quality of Life, and Economic Burden. Gastroenterology 150:1599-1608.
13. Ural I et al (2002) Nodular vasculitis associated with chronic hepatitis C. J Eur Acad Dermatol Venereol 16: 298-289.
14. Vogeser M et al (1999) Urinary porphyrin excretion in hepatitis C infection. Clin Chem Lab Med 37:799-804.