Cryoglobulinemie

Cryoglobulinemia is a medical condition defined by the presence of cryoglobulins in the blood—immunoglobulins that precipitate at temperatures below normal body temperature. These cryoglobulins form immune complexes that can deposit in small and medium-sized vessels, causing a vasculitic syndrome with systemic manifestations.

There are three main types, described in the Brouet classification. Type I consists of monoclonal cryoglobulins and is commonly associated with hematologic malignancies such as multiple myeloma or Waldenström macroglobulinemia. Types II and III are mixed cryoglobulins; type II contains a monoclonal immunoglobulin with rheumatoid factor activity and polyclonal IgG, while type III includes polyclonal IgG and IgM. Types II and III are frequently linked to infections (notably hepatitis C) and autoimmune diseases; type I is more often linked to malignancy.

Pathophysiology involves immune complex–mediated inflammation with deposition in vessels and complement consumption, leading to inflammation and organ dysfunction. Clinically, cryoglobulinemia commonly presents with a triad of palpable purpura, arthralgia or arthritis, and weakness. Renal involvement (often membranoproliferative glomerulonephritis), peripheral neuropathy, and abdominal pain can occur. Low levels of complements, especially C4, are typical.

Diagnosis requires specific handling of blood samples to detect cryoglobulins: samples must be kept warm until separation and then observed for cryoprecipitation on cooling; cryocrit quantification and immunofixation help classify the type. Serology for hepatitis C, RF positivity (more common in type II), and assessment of renal function are common. Imaging and biopsy may be used to evaluate organ involvement.

Treatment targets the underlying cause and disease activity. Hepatitis C antiviral therapy is central for types II and III. In severe or organ-threatening cases, plasmapheresis, corticosteroids, and rituximab may be employed; underlying hematologic diseases in type I are managed accordingly. Prognosis varies with the underlying condition and response to treatment.