cryoglobulinemiassocierad

Cryoglobulins are immunoglobulins that precipitate at low temperatures. Cryoglobulinemia refers to the clinical syndrome caused by circulating cryoglobulins that activate immune responses and deposit in small- to medium-sized vessels, causing a vasculitis. Cryoglobulins are classified by Brouet into three types: Type I, consisting of a single monoclonal immunoglobulin; Type II, mixed monoclonal and polyclonal immunoglobulins; and Type III, polyclonal immunoglobulins.

Most Type I cryoglobulinemia is associated with hematologic disorders such as monoclonal gammopathy, multiple myeloma, or Waldenström macroglobulinemia. Mixed cryoglobulinemia (Types II and III) is associated with chronic infections, particularly hepatitis C, autoimmune diseases, or B-cell dyscrasia.

Clinical features include palpable purpura, arthralgias, weakness, fatigue; peripheral neuropathy; renal involvement like membranoproliferative glomerulonephritis; Raynaud's phenomenon; and in severe cases, vasculitic organ involvement and life-threatening complications. Laboratory findings: cryoglobulins detected in serum, often with low C4, positive rheumatoid factor, elevated ESR; hepatitis C serology; cryocrit quantification.

Diagnosis requires sample handling: blood kept at 37°C until serum is separated, then cooled to precipitate cryoglobulins for testing. Management focuses on treating the underlying condition (e.g., antiviral therapy for hepatitis C), plus immunosuppression for systemic disease (corticosteroids, rituximab). Plasmapheresis may be used in severe or life-threatening cryoglobulinemia. Avoidance of cold exposure is advised. Prognosis varies with underlying disease and response to antiviral therapy; HCV-associated cryoglobulinemia has improved outcomes with direct-acting antivirals.