Cryoglobulinemia -: Study of etiologic factors and clinical and immunologic features in 443 patients from a single center

We analyzed the clinical manifestations and immunologic features of 443 consecutive patients (258 women and 185 men; mean age, 56 yr) with cryoglobulinemia from a single center. Infectious diseases were detected in 331 (75%) patients, autoimmune diseases in 94 (24%), hematologic diseases in 33 (7%), and essential cryoglobulinemia in 49 (11%). Hepatitis C virus (HCV) infection was found in 321 (73%) patients, Hepatitis B virus surface antigen in 15 (3%), and human immunodeficiency virus (HIV) antibodies in 29 (7%). Forty (9%) patients had primary Sjögren syndrome, 30 (7%) systemic lupus erythematosus, 7 (2%) polyarteritis nodosa, and 6 (2%) progressive systemic sclerosis. Finally, 16 (4%) patients had non-Hodgkin lymphoma, 3 chronic lymphocytic leukemia, 3 multiple myeloma, and 2 Hodgkin lymphoma. We observed a strong overlap between HCV and some autoimmune (50% in Sjögren syndrome, 67% in polyarteritis nodosa) or hematologic (50% in non-Hodgkin lymphoma) diseases. Clinical manifestations attributable to cryoglobulinemia were present in 206 (47%) patients. The most common manifestations were cutaneous involvement in 112 (25%) patients, renal in 103 (23%), articular involvement in 91 (21%), and peripheral neuropathy in 35 (8%) patients. Other clinical manifestations included weakness in 45 (10%) patients, fever in 21 (5%), and polyadenopathies in 22 (5%). Patients with cryocrits >5% showed symptomatic cryoglobulinemia more frequently than those with cryocrits <5% (65% versus 43%, p = 0.001). Patients with cryocrits >5% showed a higher frequency of cutaneous features (47% versus 21%, p < 0.001), peripheral neuropathy (20% versus 6%, p < 0.001), and renal involvement (42% versus 30%, p = 0.03). Finally, patients with symptomatic cryoglobulinemia showed a higher prevalence of low C4 (56% versus 40%, p = 0.008), rheumatoid factor (69% versus 42%, p < 0.001), and antinuclear antibodies (52% versus 30%, p < 0.001).