Definitions

• Cryoglobulins: a group of immunoglobulins (IgM, IgG, IgA) that precipitate in vitro at cold (< 37°C).
• Cryoglobulinemia: a condition characterized by elevated serum cryoglobulin concentration
• Cryoglobulinemic vasculitis: a vasculitis caused by the deposition of temperature-dependent IgG and IgM immunoglobulins/immune complexes (i.e., cryoglobulins), with subsequent inflammation of surrounding tissue

Etiology

Strongly associated with Hepatitis C virus (HCV) (most common). Other causes: B-cell lymphoproliferative disorders (esp. Type I), other autoimmune diseases (e.g., SLE, RA), other infections.

Clinical features

• Meltzer's Triad: Palpable purpura (lower extremities), arthralgias, weakness/myalgias.
• Peripheral neuropathy (sensory > motor), renal involvement (glomerulonephritis, often MPGN), Raynaud phenomenon.
• Fatigue, fever, hepatosplenomegaly.

Diagnostics

• Serology
  • Cryoglobulinemia (type II and/or III; rarely type I)
  • Rheumatoid factor: elevated in almost 100% of cases
  • ↓ C4 (90% of cases)
  • Hepatitis C diagnostics
• Urinalysis: microhematuria, proteinuria, erythrocyte casts