type 2 (mixed) cryoglobulinemia
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Introduction
Disease characterized by recurrent episodes of purpura, arthralgias, weakness & multiorgan involvement. Similar to type 3 (mixed) cryoglobulinemia.
Etiology
- frequently associated with:
- chronic infection
- hepatitis B
- hepatitis C (> 80-90%)
- HIV1[3]
- autoimmune disorders
- lymphoproliferative disorders
- essential or idiopathic cryoglobulinemia is generally due to hepatitis C[3]
Pathology
- deposition of immune complexes
- polyclonal immunoglobulins + monoclonal IgM or IgA[3]
- generally IgM kappa with anti-immunoglobulin specificity (rheumatoid factor)
- rheumatoid factor is monoclonal*
- other components:
- hepatitis C antigen
- other infectious agents
- cellular & nuclear antigens
- complement
- present in smaller quantities than type 1 globulins (50-500 mg/dL)
- cryoglobulins disappear when infection resolves
- non-systemic, small vessel vasculitis
- occurs secondary to immune complex deposition & complement fixation on surface of endothelial cells
- histopathology of vascular structures similar to leukocytoclastic vasculitis
* Distinguishes type 2 from type 3
Clinical manifestations
- recurrent symptoms
- common
- local & systemic small vessel vasculitis
- arthralgias & arthritis (15-20%)
- peripheral neuropathy 5%
- Raynaud's phenomenon 40%
- acrocyanosis[3]
- less common manifestations
- focal segmental sclerosing glomerulonephritis
- membranoproliferative glomerulonephritis
- hepatomegaly
- pulmonary manifestations (uncommon)
- serositis: pleurisy, pericarditis
- thyroiditis
Laboratory
- blood collection & specimen processing
- blood collected in pre-warmed tubes
- kept at 37 degrees during clotting to keep cryoglobulins from precipitating with clot
- serum separated from clot at 37 degrees
- incubation at 4 degrees C for 72 hours
- cryoglobulins in serum/plasma
- trace amounts of cryoglobulins may be found in normal individuals
- serum protein electrophoresis & immunofixation elecrophoresis
- serum complement levels (C1q-C4, CH50) are generally decreased
- erythrocyte sedimentation rate is generally increased
- rheumatoid factor is generally positive (monoclonal IgM)
- hepatitis serology
- frequently positive for hepatitis C
- may be positive for hepatitis B
- biopsy of vascular structures
Complications
- glomerulonephritis secondary to deposition of immune complexes (most common)
- focal segmental glomerulonephritis
- membranoproliferative glomerulonephritis[3][5]
- hepatosplenomegaly
- hepatic cirrhosis
- pneumonitis
- pulmonary hemorrhage
- serositis
- thyroiditis
- lymphoproliferative disorder
Management
- therapy directed at underlying disease
- ledipasvir & sofosbuvir for treatment of hepatitis C[3]
- idiopathic or essential cryoglobulinemia
More general terms
Additional terms
References
- ↑ Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 527
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 610, 784, 849
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018.
- ↑ Brahn E, Scoville CD Biochemical markers of disease activity. Baillieres Clin Rheumatol 1988 2:153 PMID: https://www.ncbi.nlm.nih.gov/pubmed/2458192
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17185147
- ↑ Dammacco F, Sansonno D. Therapy for hepatitis C virus-related cryoglobulinemic vasculitis. N Engl J Med. 2013 Sep 12;369(11):1035-45. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24024840