Relation between infection and autoimmunity in mixed cryoglobulinemia

Mixed cryoglobulinemia (MC) is a systemic vasculitis of small to medium-siz ed vessels due to the vascular deposition of circulating immune-complexes ( CIC) and complement. A leukocytoclastic vasculitis is the histologic hallma rk of cutaneous manifestations of the disease, while a clonal B lymphocyte expansion in blood, bone marrow, liver, and spleen represents the underlyin g pathologic alteration responsible for the production of cryo-CIC and non- cryo CIC with rheumatoid factor activity. A causative role of hepatitis C virus (HCV) infection has been demonstrated in the large majority of MC patients. Hepatitis C virus is both a hepatotr opic and a lymphotropic virus; due to this latter biological peculiarity, H CV may trigger a constellation of autoimmune-lymphoproliferative disorders, Besides MC, other important HCV-related diseases are porphyria cutanea tar da, autoimmune hepatitis, membranoproliferative glomerulonephritis,: and B cell neoplasias. Hepatitis C virus-related MC represents a link between aut oimmune and lymphoproliferative disorders; moreover, MC is an important mod el to study the complex relation between infections and immune system alter ations in humans. During the last years many other autoimmune manifestation s have been correlated with HCV infection; namely, sicca syndrome, chronic polyarthritis, polydermatomyositis, fibromyalgia, autoimmune thyroiditis, l ung fibrosis, and diabetes mellitus. It is often difficult to verify whethe r the above associations are coincidental or a pathogenetic link actually e xists. At least for particular patients' subsets and in some geographic are as, a causative role of HCV seems to be likely. The geographically heteroge neous distribution of HCV-related autoimmune diseases suggests the contribu tion of important environmental and genetic factors in the pathogenesis of such conditions. In clinical practice, patients with recent-onset, atypical rheumatic and autoimmune disorders should be carefully investigated for po ssible HCV infection; this is particularly advisable for correct diagnosis and adequate therapeutic strategy. (C) 2000 Lippincott Williams & Wilkins, Inc.