Dermatology MCQ - Inflammatory Dermatoses - Environmental factors in urticarial vasculitis

A 52-year-old woman presents with a 2-month history of painful urticarial plaques that individual lesions last for over 48 hours and resolve with residual hyperpigmentation. A skin biopsy confirms leukocytoclastic vasculitis. As part of the workup for an underlying cause, which of the following environmental or exogenous factors is most strongly and classically associated with this condition?

A. Chronic sun exposure
B. Infection with Hepatitis C virus
C. A diet high in histamine-rich foods
D. Exposure to nickel
E. Physical pressure on the skin

Correct Answer: B. Infection with Hepatitis C virus

Answer & Explanation

Explanation:

Urticarial vasculitis (UV) is often a manifestation of an underlying systemic process, frequently driven by the deposition of immune complexes. Among the options provided, chronic infection with Hepatitis C virus (HCV) is one of the most well-established and strong associations.

• Pathophysiological Link: HCV infection can lead to the production of cryoglobulins (mixed cryoglobulinemia, Type II and III). These circulating immune complexes deposit in small vessels, activate complement, and initiate a neutrophilic inflammatory response, resulting in the histologic picture of leukocytoclastic vasculitis, which can present clinically as urticarial vasculitis.

The other options are incorrect or represent triggers for other conditions:

• A. Chronic sun exposure: While UV radiation can provoke several photodermatoses (e.g., polymorphic light eruption, solar urticaria) and is implicated in the pathogenesis of lupus, it is not a classic, primary environmental trigger for urticarial vasculitis.

• C. A diet high in histamine-rich foods: This can be a trigger for histamine-mediated urticaria and angioedema, but it does not cause the immune-complex mediated vessel damage characteristic of urticarial vasculitis.

• D. Exposure to nickel: This is a classic cause of allergic contact dermatitis, a type IV delayed hypersensitivity reaction. It does not cause a small-vessel vasculitis.

• E. Physical pressure on the skin: This is the trigger for pressure urticaria, a form of chronic inducible urticaria. While the lesions can be painful and long-lasting, they are not due to vasculitis on histology and do not typically show the leukocytoclasia, fibrinoid necrosis, or post-inflammatory hyperpigmentation of UV.

Key Associations for Underlying Causes of Urticarial Vasculitis

• Pathophysiology Recap: UV is an immune complex-mediated small-vessel vasculitis. The inciting factor is often an antigen that leads to persistent immune complex formation.

• Major Associated Conditions/Triggers (the "ESSPI" mnemonic is useful):

  • Exogenous antigens: Drugs (e.g., penicillin, NSAIDs), Infections (Hepatitis B/C, streptococcus, EBV, parvovirus B19).

  • Serum sickness and Serum sickness-like reactions.

  • Systemic autoimmune diseases: SLE (the most common autoimmune association), Sjögren's syndrome, rheumatoid arthritis.

  • Paraproteinemias / Idiopathic: Cryoglobulinemia (strongly linked to HCV), IgA vasculitis, Schnitzler syndrome (UV + monoclonal IgM gammopathy), and idiopathic (no cause found in up to 50%).

• Prognosis: Highly dependent on the underlying cause. Idiopathic UV limited to the skin often has a chronic but relatively benign course. UV associated with systemic disease (like SLE or HCV) carries the prognosis of the underlying condition.

• Management:

  1. Investigate: A thorough workup for the triggers listed above is mandatory (e.g., CBC, ESR, urinalysis, complement levels C3/C4, C1q, ANA, RF, cryoglobulins, hepatitis serology, SPEP/UPEP).

  2. Treat the Cause: The cornerstone of management is addressing the underlying trigger (e.g., antiviral therapy for HCV, immunosuppression for SLE, discontinuing an offending drug).

  3. Symptomatic Control: For skin-limited disease, treatments may include antihistamines, colchicine, dapsone, or hydroxychloroquine. More severe or systemic cases often require systemic corticosteroids and steroid-sparing agents like azathioprine or mycophenolate mofetil.