Cryoglobulinemia Summary Cryoglobulins: • Cryoglobulins are Igs in the serum that precipitate in vitro at temperatures below 37°C and redissolve on rewarming. • They can activate the immune system, leading to the deposit of immune complexes in tissues causing endothelial injury and end-organ damage. • They can cause: - Arthralgia - Purpura - Skin ulcers - Glomerulonephritis - Peripheral neuropathy • Cryoglobulins Cause Organ Damage Through 2 Different Pathways: - 1. Vascular Sludging (Hyperviscosity Syndrome, Mainly in Type I Cryoglobulinemia) - 2. Immune-Mediated Mechanisms (Principally Vasculitis, in Mixed Cryoglobulinemia) Meltzer's Triad - Mixed Cryoglobulinemia Syndrome: • Clinical triad of Palpable purpura, Arthralgia, Weakness. • It is generally seen with the mixed cryoglobulinemia syndrome in 80% of patients. Etiology - Mixed Cryoglobulinemia Syndrome • Idiopathic • Infections: HCV infection, HBV infection, HIV infection • Autoimmune diseases: - 10% SLE or RA - 5 to 20% Sjögren's syndrome - type II cryoglobulinemia • Lymphoproliferative disorders. Types: • Type I Cryoglobulins: - Single monoclonal immunoglobulins usually associated with hematological disorders. - (Ischemia, livedo reticularis & skin necrosis, peripheral neuropathy, arthralgia, and arthritis) • Types II and III are Mixed Cryoglobulins: - Composed of monoclonal or polyclonal IgM respectively, having rheumatoid factor activity that bind to polyclonal immunoglobulins. • Type III Often Secondary to Autoimmune Disorders. Labs/Diagnosis: • Cryocrit - Detect the presence of serum cryoglobulins • Elevated serum rheumatoid factor level • Low serum C4 complement level • Immunofixation - Dissolved cryoglobulin • Viral serologies • Biopsies of organs involved. DDX: • ANCA (Antineutrophil cytoplasmic antibody) associated vasculitis - GPA, EGPA, microscopic polyangiitis. • IgA vasculitis (Henoch-Schönlein purpura) • Cutaneous small-vessel vasculitis • Hypersensitivity vasculitis • Vasculitis associated with connective tissue disorder (e.g. systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome) #Cryoglobulinemia #Cryoglobulins #diagnosis #types #classification #rheumatology #vasculitis
