Answer is D (Strongly Positive Rheumatoid factor): Type I Cryoglobulinemia (simple cryoglobulinemia) is typically associated with Monoclonal IgM paraprotenemia producing a Hyperviscosity type syndrome. Type I Cryoglobulins rarely have Rheumatoid Factor Activity and do not activate complement in vitro (hence complement levels are usually normal). `Monoclonal Cryoglobulins (Type I) rarely exhibit Rheumatoid Factor activity and do not interfere with complement mediated function in vitro' -- 'Cryoglobulins and Cryoglobulinemia' from Clinical Reviews in Allergy and Immunology: Vol 16, Number 3 (1998) page 249-264 `Type I Cryoglobulins do not activate the complement cascade and are therefore associated with normal complement levels' Mixed Cryoglobulinemias (Type II/Type III) are associated with Strongly Positive Rheumatoid Factors and Reduced Complement levels. Hypocomplementemia occurs in 90% of patients with mixed cryoglobulinemias. Rheumatoid factor is positive in 80-100% ofpatients with mixed cryoglobulinemia Cryoglobulinemia Cryoglobulins are immunoglobulins that precipitate as serum is cooled below core body temperature (below 37deg C) and re-dissolve on re-warming. Cryoglobulinemia is characterized by the presence of cryoglobulins in the serum. Cryoglobulinemia is most commonly classified into three types in accordance with the Brouet Classification based on the components of the cryoprecipitate. Type I (Simple Cryoglobulinemia) and Type II, Type III (Mixed cryoglobulinemia) Feature Type I Type II Type III (Simple Cryoglobulinemia) (Mixed Cryoglobulinemia) (Mixed Cryoglobulinemia) Cryoglobulin Single Monoclonal Mixed Monoclonal' Mixed Polyclonal Molecular composition Monoclonal IgM or Monoclonal IgG Monoclonal IgM* (>IgG*) Polyclonal IgG Polyclonal IgM and Polyclonal IgG Composed entirely of Monoclonal Immunoglobulins, usually IgM or IgG Composed of Monoclonal Immunoglobulins usually IgM along with Polyclonal Composed of polyclonal immunoglobulin of more than once isotype such as polyclonal IgM and polyclonal IgG Immunoglobulin usually IgG Rheumatoid Factor Activity Rheumatoid factor activity is absent (rarely present) - Rheumatoid Factor activity is strongly positive Rheumatoid factor activity is positive Monoclonal IgM in Type I Syndrome does not have Rheumatoid Factor Activity Monoclonal IgM in Type II Syndrome has Rheumatoid Factor activity against IgG ' Polyclonal IgM has Rheumatoid factor activity Complement Activation in Vitro Do not activate the complement cascade Activate the complement cascade Activate the complement cascade Complement levels normal Complement levels reduced Complement levels reduced. Predominant clinical manifestation Primarily related to Hyperviscosity and consequent thrombosis Primarily related to vasculitis due to immune complex formation and activation of complement * Acrocyanosis * Retinal Hemorrhages * Raynaud's phenomenon with digital ulceration * Livido reticularis * Aerial reticularis * Aerial Thrombosis * Cutaneous vasculitis * Renal Glomerulonephritis * Neuropathy (Vasculitis) * Abdominal pain (mesenteric vasculitis) * Ahralgia & myalgia Mitzer's Triad: Purpura + Ahralgia + Weakness Associations Lymphoproliferative Diseases * Chronic hepatitis C * Autoimmune disease * Sjogren's syndrome * CLL * NHL Autoimmune Diseases * Multiple Myeloma * `Waldenstroms Macroglobulinemia' * Monoclonal Gammopathy * Systemic Lupus Erythematous * Rheumatoid Ahritis * Inflammatory Bowel Disease * Biliary Cirrhosis Chronic Infections * Viral (EBV, CMV, HIV, Hepatitis E) * Bacterial (Leprosy, Spirochetal, SBE) * Fungal * Parasitic