Snapshot A 40-year-old gentleman presents with bilateral lower extremity swelling and rash. He complains of general fatigue and weight loss in the past few months. He has a past medical history of untreated hepatitis C. On physical exam, he has a purpuric rash bilaterally on his lower extremities and upper extremities and acrocyanosis of his fingers. He is found to have proteinuria and hematuria with low serum complement levels. His creatinine is 2.0 mg/dL (baseline was 0.9 mg/dL). He is started on interferon and ribavirin for the untreated hepatitis C. Introduction Hyperviscosity syndrome resulting from cryoglobulins (single or mixed immunoglobulins) in the blood Epidemiology Females:male ratio is 3:1 Mean age 42-52 ETIOLOGY Pathogenesis proteins, mainly immunoglobulins, precipitate at cold temperatures IgM antibody (but different from cold agglutinin disease) deposition often against anti-hepatitis C IgG precipitated clumps can block blood vessels Associated conditions most commonly underlying hepatitis C less commonly hepatitis B endocarditis Sjogren's syndrome multiple myeloma MGUS lymphoproliferative disorder Presentation Symptoms similar to other vasculitidies fever, malaise, weight loss, and myalgias renal disease membranoproliferative glomerulonephritis joint pain peripheral neuropathy dermatologic purpura with or without ulcerations livedo reticularis acrocyanosis retinal hemorrhage no GI symptoms (in contrast to Henoch-Schonlein purpura) STUDIES ↑ ESR ↓ Complement level in particular, C4 Can have + rheumatoid factor Cryoglobulins isolated from serum Tissue biopsy of organ sometimes necessary for diagnosis hyaline thrombi occluding small blood vessels Urine studies most commonly isolated proteinuria and hematuria Differential Diagnosis HSP Cold agglutinin disease Acute glomerulonephritis Other vasculitidies Treatment Treat underlying hepatitis C (interferon and ribavirin) For severe disease pulse prednisone plasmapheresis Complications Renal failure Infection Cardiovascular disease Prognosis Depends on concomitant disease Good if underlying hepatitis C successfully treated Worst in those with renal disease or lymphoproliferative disease