Dermatology MCQ - Viral Infections - Hepatitis C

A 55-year-old woman presents with fatigue, palpable purpura on her lower extremities, and bilateral arthralgias. She reports a history of intravenous drug use 20 years ago. Physical examination reveals livedo reticularis and several ulcerations near the ankles. Laboratory studies show elevated rheumatoid factor, decreased complement levels (C4), and cryoglobulins positive for IgM and IgG. A skin biopsy of a purpuric lesion demonstrates leukocytoclastic vasculitis. Which of the following is the most likely underlying infection associated with this presentation?

A) Hepatitis A virus
B) Hepatitis B virus
C) Hepatitis C virus
D) HIV
E) Syphilis

Correct Answer: C) Hepatitis C virus

Explanation

This presentation is classic for cryoglobulinemic vasculitis secondary to chronic hepatitis C virus (HCV) infection.

Key Clinical Features of HCV-Associated Cryoglobulinemia:

• Triad (Meltzer's Triad): Palpable purpura, arthralgia, and weakness (often with fatigue).

• Cutaneous Findings:

  • Palpable purpura (most common sign), typically on lower extremities.

  • Livedo reticularis (net-like pattern of purplish discoloration).

  • Ulcerations (especially near ankles in severe cases).

• Systemic Involvement: Can cause glomerulonephritis, peripheral neuropathy, and arthralgias.

• Laboratory Findings:

  • Positive cryoglobulins (type II or III; here, mixed IgM-IgG).

  • Elevated rheumatoid factor (IgM RF).

  • Low complement levels (especially C4).

  • Positive HCV antibody and RNA.

Pathogenesis:

• HCV infection stimulates B-cells to produce mixed cryoglobulins (immune complexes that precipitate in cold temperatures).

• These complexes deposit in small vessels, activating complement and causing leukocytoclastic vasculitis (neutrophilic infiltration, fibrinoid necrosis).

Why Not the Other Options?

• (A) Hepatitis A virus: Causes acute hepatitis but not chronic infection or cryoglobulinemia.

• (B) Hepatitis B virus: Can cause polyarteritis nodosa (medium-vessel vasculitis) but is less commonly associated with cryoglobulinemia than HCV.

• (D) HIV: Associated with various skin manifestations (e.g., eosinophilic folliculitis, Kaposi sarcoma) but not typically cryoglobulinemic vasculitis.

• (E) Syphilis: Can cause a variety of rashes (e.g., maculopapular, condylomata lata) but not cryoglobulinemia or leukocytoclastic vasculitis.

Management:

• Direct-acting antivirals (DAAs): Treat the underlying HCV (e.g., sofosbuvir/velpatasvir). This often leads to resolution of cryoglobulinemia.

• Immunosuppression: For severe vasculitis (e.g., corticosteroids, rituximab for B-cell depletion).

• Plasma exchange: For life-threatening cases.

Prognosis:
Excellent with HCV eradication. However, advanced vasculitis (e.g., renal failure) may not fully reverse.

Note: HCV is also associated with:

• Porphyria cutanea tarda (blisters, fragility on sun-exposed skin).

• Lichen planus (violaceous, pruritic papules).

• Necrolytic acral erythema (rare, psoriasiform plaques on feet).