Cutaneous cryoglobulinemic vasculitis

Abstract

The Chapel Hill Consensus Conference criteria define cryoglobulinemic vasculitis (CV) as vasculitis, with cryoglobulin immune deposits, affecting small vessels (i.e. capillaries, venules, or arterioles), and associated with cryoglobulins in the serum. Hepatitis C virus (HCV) infection is the underlying etiologic factor in the majority of cases of CV, but it also occurs secondary to other infections (e.g., hepatitis B), connective tissue diseases (e.g., Sjögren's syndrome), and hematolymphoid proliferations (e.g., Waldenström's macroglobulinemia). Purpura, arthralgia, and weakness are the most common presenting signs and symptoms but any organ can be affected (skin, kidney, and nerves most frequently). The extent of involvement and disease severity progress with time in the absence of treatment. Recurrent palpable purpura associated with post-inflammatory hyperpigmenation is the most frequent cutaneous manifestation of CV but others include nodules, leg ulcers, livedo racemosa, and digital gangrene, i.e., signs of muscular-vessel vasculitis. Skin biopsy shows a small-vessel neutrophilic vasculitis equally affecting superficial and deep dermal and subcutis vessels, with neutrophilic muscular-vessel vasculitis in a minority of cases. Thrombosis, in some instances by hyaline/ type I cryoglobulin thrombi, contributes to the ischemic damage. By direct immunofluorescence, abundant IgM, and complement deposits are found in the affected vessels, highlighting the immune-complex mediated pathogenesis. Adverse prognostic factors for HCV-related CV include the presence of ulcers and renal insufficiency. Anti-HCV therapy (interferon-α and ribavirin) with or without rituximab is associated with a favorable clinical response, but relapse is common. In some patients, the persistent CV necessitates the administration of immunosuppressive agents.