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type 3 (mixed) cryoglobulinemia

Disease characterized by recurrent episodes of purpura, arthralgias, weakness & multiorgan involvement. Similar to type 2 (mixed) cryoglobulinemia. Etiology: 1) frequently associated with: a) chronic infection b) hepatitis B c) hepatitis C (> 90%), MKSAP17 does not mention hepatitis C [1] d) autoimmune disorders 1] systemic lupus erythematosus 2] vasculitis e) lymphoproliferative disorders 2) essential or idiopathic cryoglobulinemia is generally due to hepatitis B or C Epidemiology: - accounts for 50% of cases of cryoglobulinemia Pathology: 1) deposition of immune complexes a) generally polycloncal IgM with anti-immunoglobulin specificity (rheumatoid factor) b) polyclonal rheumatoid factor* c) other components: 1] hepatitis C antigen 2] other infectious agents 3] cellular & nuclear antigens 4] complement 2) present in smaller quantities than type 1 globulins (50-500 mg/dL) 3) cryoglobulins disappear when infection resolves 4) non-systemic, small vessel vasculitis - occurs secondary to immune complex deposition & complement fixation on surface of endothelial cells 2) histopathology of vascular structures similar to leukocytoclastic vasculitis * Distinguishes type 3 from type 2 Clinical manifestations: 1) recurrent symptoms 2) common a) local & systemic small vessel vasculitis - palpable purpura 70% - urticaria 10% - cutaneous ulceration 4% b) arthralgias & arthritis 58% c) peripheral neuropathy 25% d) Raynaud's phenomenon 60% 3) less common manifestations a) focal segmental sclerosing glomerulonephritis b) hepatomegaly c) pulmonary manifestations (uncommon) - diffuse pulmonary vasculitis - alveolar hemorrhage - bronchiolitis obliterans (BOOP) - bronchiectasis - pneumonitis - pulmonary hemorrhage d) serositis: pleurisy, pericarditis e) thyroiditis Laboratory: 1) blood collection & specimen processing a) blood collected in pre-warmed tubes b) kept at 37 degrees during clotting to keep cryoglobulins from precipitating with clot c) serum separated from clot at 37 degrees d) incubation at 4 degrees C for 72 hours 2) cryoglobulins in serum/plasma - trace amounts of cryoglobulins may be found in normal individuals 3) serum protein electrophoresis & immunofixation electrophoresis - polyclonal IgG, polyclonal IgM rheumatoid factor 4) complement levels (C1q-C4, CH50) are generally decreased 5) erythrocyte sedimentation rate is generally increased 6) rheumatoid factor is generally positive (polyclonal IgM) [1] 7) hepatitis serology: a) frequently positive for hepatitis C b) may be positive for hepatitis B 8) biopsy of vascular structures Complications: 1) glomerulonephritis secondary to deposition of immune complexes (most common) a) focal segmental glomerulonephritis b) membranoproliferative glomerulonephritis [1,3] 2) hepatosplenomegaly 3) hepatic cirrhosis 4) pneumonitis 5) pulmonary hemorrhage 6) serositis a) pleurisy b) pericarditis 7) thyroiditis 8) lymphoproliferative disorder Management: 1) therapy directed at underlying disease 2) idiopathic or essential cryoglobulinemia a) prednisone b) other immunosuppressive agents

Related

cryoglobulin

General

cryoglobulinemia (cryoglobulinemic vasculitis)

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015
  2. Brahn E, Scoville CD Biochemical markers of disease activity. Baillieres Clin Rheumatol 1988 2:153 PMID: 2458192
  3. Roccatello D, Fornasieri A, Giachino O et al Multicenter study on hepatitis C virus-related cryoglobulinemic glomerulonephritis. Am J Kidney Dis. 2007 Jan;49(1):69-82. PMID: 17185147