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Cryoglobulinemia Clinical Presentation

  • Author: Adam M Tritsch, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jun 15, 2016
 

History

Specific clinical manifestations associated with type I cryoglobulinemia are related to hyperviscosity and thrombosis, as would be expected given the usual high concentrations of immunoglobulins and limited interference with complement function. These manifestations include the following:

  • Acrocyanosis
  • Retinal hemorrhage
  • Severe Raynaud phenomenon with digital ulceration
  • Livedo reticularis
  • Purpura
  • Arterial thrombosis

Specific clinical manifestations associated with types II and III cryoglobulinemia include the following:

  • Joint involvement (usually, arthralgias in the proximal interphalangeal [PIP] joints, metacarpophalangeal [MCP] joints, knees, and ankles)
  • Fatigue
  • Myalgias
  • Renal immune-complex disease
  • Cutaneous vasculitis
  • Peripheral neuropathy

Meltzer triad (ie, purpura, arthralgia, and weakness) was first described in 1966 by Meltzer and Franklin in cases of essential mixed cryoglobulinemia. This triad is generally seen with types II and III cryoglobulinemia and is seen in up to 25-30% of patients.[25, 26]

Cutaneous manifestations

These manifestations are nearly always present in cryoglobulinemia. Observed lesions have a predilection for dependent areas (particularly the lower extremities) and include erythematous macules and purpuric papules (90-95%), as well as ulcerations (10-25%).[19, 26, 18, 27]

Lesions in nondependent areas are more common in type I cryoglobulinemia (head and mucosa), as are livedo reticularis, Raynaud phenomenon, and ulcerations. Nailfold capillary abnormalities are common and include dilatation, altered orientation, capillary shortening, and neoangiogenesis.[28] See the image below.

Rash on lower extremities typical of cutaneous sma Rash on lower extremities typical of cutaneous small-vessel vasculitis due to cryoglobulinemia secondary to hepatitis C infection.

Musculoskeletal manifestations

Symptoms such as arthralgias and myalgias are rare in type I cryoglobulinemia and are common in types II and III disease. Frank arthritis and myositis are rare. Arthralgias commonly affect the proximal interphalangeal and metacarpophalangeal joints of the hands, knees, and ankles. Musculoskeletal symptoms are described in more than 70% of persons with cryoglobulinemia.[29, 30, 26]

Renal manifestations

Renal disease may occur secondary to thrombosis (type I cryoglobulinemia) or immune complex deposition (types II and III). The incidence of renal disease varies from 5-60%. Histologically, membranoproliferative glomerulonephritis is almost always the lesion in mixed cryoglobulinemia. Clinically, isolated proteinuria and hematuria are more common than nephrotic syndrome, nephritic syndrome, or acute renal failure. Renal involvement is one of the most serious complications of cryoglobulinemia and typically manifests early in the course of the disease (within 3-5 y of diagnosis). Failure to treat may result in renal failure.[19, 31, 32]

Pulmonary manifestations

A reduction in forced expiratory flow rates and the presence of interstitial infiltrates revealed by chest radiographs are common in mixed cryoglobulinemia. Approximately 40-50% of patients are symptomatic with dyspnea, cough, or pleuritic pain. Severe pulmonary disease is rare.[33, 34, 35, 36]

Neuropathy

Neuropathy is common in types II and III disease (as determined with electromyographic and nerve conduction studies), affecting 70-80% of patients. Symptomatic disease was once reported as less common (5-40%); however, more recently, subjective symptoms have been reported up to 91% of patients. Sensory fibers are more commonly affected than motor fibers, with pure motor neuropathy in approximately 5% of patients.[37, 26, 38, 39]

Other manifestations

Patients with cryoglobulinemia may also present with the following:

  • Abdominal pain has been reported in 2-22% of patients; vasculitis of the small mesenteric vessels that leads to acute abdomen has been reported
  • Sicca symptoms have been reported in 4-20% of patients [26, 33]
  • Acrocyanosis has been reported in up to 9% of patients
  • Arterial thrombosis has been reported in 1% of patients
  • A high incidence of new cases of thyroid autoimmunity and dysfunction hase been found in patients (particularly women) with hepatitis C–associated mixed cryoglobulinemia. [40]
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Physical

Skin manifestations include the following:

  • Ischemic necrosis (40% in type I, 0-20% in mixed types)
  • Palpable purpura (15% in type I, 80% in mixed types)
  • Livedoid vasculitis (1% in type I, 14% in type III)
  • Cold-induced urticaria (15% in type I, 10% in type III)
  • Hyperkeratotic spicules in areas exposed to cold
  • Scarring of tip of nose, pinnae, fingertips, and toes
  • Acrocyanosis
  • Nailfold capillary abnormalities

Pulmonary manifestations include the following:

  • Dyspnea
  • Cough
  • Pleurisy
  • Pleural effusions
  • Bronchiectasis

Gastrointestinal manifestations include the following:

  • Abdominal pain (2-22%)
  • Hemorrhage
  • Hepatomegaly or signs of cirrhosis (ie, palmar erythema, abdominal wall collateral vessels, spider angiomata)
  • Splenomegaly

Renal manifestations include the following:

  • Membranoproliferative glomerulonephritis described in all types (more common in type II)
  • Intraluminal cryoglobulin deposition
  • Hypertension
  • Nephrotic-range proteinuria with resultant edema

Joint manifestations include the following:

  • Arthralgias (5% of type I, 20-58% of mixed)
  • Frank arthritis and progressive joint deformity (distinctly rare)

Nervous system manifestations include the following:

  • Sensorimotor neuropathy
  • Visual disturbances
  • CNS involvement (rare, although pseudotumor cerebri and cerebral vascular events have been described)

Fever is another manifestation.

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Causes

Disease associations vary with the type of cryoglobulinemia, as follows:

  • Type I is observed in lymphoproliferative disorders (eg, multiple myeloma, Waldenström macroglobulinemia).
  • Types II and III are observed in chronic inflammatory diseases such as chronic liver disease, infections (chronic HCV infection), and coexistent connective-tissue diseases (SLE, Sjögren syndrome). Mixed cryoglobulinemia is rarely associated with lymphoproliferative disorders.

Infections associated with cryoglobulinemia include the following:

  • Viral - Hepatitis A, B, and C (see Differentials); HIV; Epstein-Barr virus (EBV); cytomegalovirus (CMV); adenovirus; chikungunya
  • Bacterial - Endocarditis, streptococcal infections, syphilis, Lyme disease, leprosy, Q fever, brucellosis
  • Fungal -Coccidioidomycosis
  • Parasitic -Malaria, toxoplasmosis, others

Other disorders associated with cryoglobulinemia include the following:

  • Autoimmune diseases - SLE, rheumatoid arthritis, Sjögren syndrome
  • Vasculitis -Polyarteritis nodosa (especially hepatitis B–associated), Henoch-Schönlein purpura
  • Lymphoproliferative disorders - Waldenström macroglobulinemia, multiple myeloma, lymphoma, leukemia (eg, chronic lymphocytic leukemia, hairy cell leukemia)
  • Renal diseases -Proliferative glomerulonephritis
  • Liver diseases - Hepatitis A, B, and C (30-98% of patients with HCV infection have cryoglobulins, especially type II); cirrhosis

Cryoglobulinemia may occur as a familial or idiopathic disorder. Finally, cases have been reported following vaccination (eg, with pneumococcal vaccine).

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Contributor Information and Disclosures
Author

Adam M Tritsch, MD Resident Physician, Department of Internal Medicine, Eisenhower Army Medical Center, Fort Gordon, Georgia

Adam M Tritsch, MD is a member of the following medical societies: American College of Physicians

Disclosure: Partner received stocks from Amgen for none.

Coauthor(s)

Colin C Edgerton, MD Clinical Assistant Professor, Department of Medicine, Medical College of Georgia; Clinical Assistant Professor, Department of Medicine, Uniformed Services University

Colin C Edgerton, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Genentech; Pfizer; Mallinckrodt.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Acknowledgements

Craig Ainsworth, MD Chief of Medical Residents, Department of Internal Medicine, Eisenhower Army Medical Center

Craig Ainsworth, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Robert John Oglesby, MD Chief of Rheumatology Service, Department of Medicine, Walter Reed Army Medical Center; Associate Professor of Medicine, Uniformed Services University of the Health Sciences

Robert John Oglesby, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and Arthritis Foundation

Disclosure: Nothing to disclose.

Timothy M Straight, MD Instructor, Department of Medicine, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

References
  1. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. 2011 Aug 23. [Medline].

  2. Trendelenburg M, Schifferli JA. Cryoglobulins are not essential. Ann Rheum Dis. 1998 Jan. 57(1):3-5. [Medline].

  3. Néel A, Perrin F, Decaux O, Dejoie T, Tessoulin B, Halliez M, et al. Long-term outcome of monoclonal (type 1) cryoglobulinemia. Am J Hematol. 2014 Feb. 89(2):156-61. [Medline].

  4. Terrier B, Karras A, Kahn JE, Le Guenno G, Marie I, Benarous L, et al. The spectrum of type I cryoglobulinemia vasculitis: new insights based on 64 cases. Medicine (Baltimore). 2013 Mar. 92(2):61-8. [Medline].

  5. Jablonska J, Zabek J, Pawelczyk A, Kubisa N, Fic M, Laskus T, et al. Hepatitis C virus (HCV) infection of peripheral blood mononuclear cells in patients with type II cryoglobulinemia. Hum Immunol. 2013 Dec. 74(12):1559-62. [Medline].

  6. Uki J, Young CA, Suzuki T. A 22S cryomacroglobulin with antibody-like activity. I. Physico-chemical characterization and modification of its cryoproperties. Immunochemistry. 1974 Nov. 11(11):729-40. [Medline].

  7. Wang AC, Wells JV, Fudenberg HH. Chemical analyses of cryoglobulins. Immunochemistry. 1974 Jul. 11(7):341-5. [Medline].

  8. Pastore Y, Lajaunias F, Kuroki A, Moll T, Kikuchi S, Izui S. An experimental model of cryoglobulin-associated vasculitis in mice. Springer Semin Immunopathol. 2001. 23(3):315-29. [Medline].

  9. Saulk PH, Clem W. Studies on the cryoprecipitation of a human IGG3 cryoglobulin: the effects of temperature-induced comformational changes on the primary interaction. Immunochemistry. 1975 Jan. 12(1):29-37. [Medline].

  10. Kikuchi S, Pastore Y, Fossati-Jimack L, Kuroki A, Yoshida H, Fulpius T, et al. A transgenic mouse model of autoimmune glomerulonephritis and necrotizing arteritis associated with cryoglobulinemia. J Immunol. 2002 Oct 15. 169(8):4644-50. [Medline].

  11. Abel G, Zhang QX, Agnello V. Hepatitis C virus infection in type II mixed cryoglobulinemia. Arthritis Rheum. 1993 Oct. 36(10):1341-9. [Medline].

  12. Magalini AR, Facchetti F, Salvi L, Fontana L, Puoti M, Scarpa A. Clonality of B-cells in portal lymphoid infiltrates of HCV-infected livers. J Pathol. 1998 May. 185(1):86-90. [Medline].

  13. Sansonno D, Dammacco F. Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis. 2005 Apr. 5(4):227-36. [Medline].

  14. De Re V, De Vita S, Sansonno D, Gasparotto D, Simula MP, Tucci FA. Type II mixed cryoglobulinaemia as an oligo rather than a mono B-cell disorder: evidence from GeneScan and MALDI-TOF analyses. Rheumatology (Oxford). 2006 Jun. 45(6):685-93. [Medline].

  15. Sansonno D, Gesualdo L, Manno C, Schena FP, Dammacco F. Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus-infected patients with cryoglobulinemic membranoproliferative glomerulonephritis. Hepatology. 1997 May. 25(5):1237-44. [Medline].

  16. Sansonno D, Cornacchiulo V, Iacobelli AR, Di Stefano R, Lospalluti M, Dammacco F. Localization of hepatitis C virus antigens in liver and skin tissues of chronic hepatitis C virus-infected patients with mixed cryoglobulinemia. Hepatology. 1995 Feb. 21(2):305-12. [Medline].

  17. Karlsberg PL, Lee WM, Casey DL, Cockerell CJ, Cruz PD Jr. Cutaneous vasculitis and rheumatoid factor positivity as presenting signs of hepatitis C virus-induced mixed cryoglobulinemia. Arch Dermatol. 1995 Oct. 131(10):1119-23. [Medline].

  18. Gorevic PD, Kassab HJ, Levo Y, Kohn R, Meltzer M, Prose P, et al. Mixed cryoglobulinemia: clinical aspects and long-term follow-up of 40 patients. Am J Med. 1980 Aug. 69(2):287-308. [Medline].

  19. Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. 1974 Nov. 57(5):775-88. [Medline].

  20. Beddhu S, Bastacky S, Johnson JP. The clinical and morphologic spectrum of renal cryoglobulinemia. Medicine (Baltimore). 2002 Sep. 81(5):398-409. [Medline].

  21. Bryce AH, Kyle RA, Dispenzieri A, Gertz MA. Natural history and therapy of 66 patients with mixed cryoglobulinemia. Am J Hematol. 2006 Jul. 81(7):511-8. [Medline].

  22. Invernizzi F, Pioltelli P, Cattaneo R, Gavazzeni V, Borzini P, Monti G, et al. A long-term follow-up study in essential cryoglobulinemia. Acta Haematol. 1979. 61(2):93-9. [Medline].

  23. La Civita L, Zignego AL, Monti M, Longombardo G, Pasero G, Ferri C. Mixed cryoglobulinemia as a possible preneoplastic disorder. Arthritis Rheum. 1995 Dec. 38(12):1859-60. [Medline].

  24. Saadoun D, Sellam J, Ghillani-Dalbin P, Crecel R, Piette JC, Cacoub P. Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia. Arch Intern Med. 2006 Oct 23. 166(19):2101-8. [Medline].

  25. Meltzer M, Franklin EC, Elias K, McCluskey RT, Cooper N. Cryoglobulinemia--a clinical and laboratory study. II. Cryoglobulins with rheumatoid factor activity. Am J Med. 1966 Jun. 40(6):837-56. [Medline].

  26. Monti G, Galli M, Invernizzi F, Pioltelli P, Saccardo F, Monteverde A, et al. Cryoglobulinaemias: a multi-centre study of the early clinical and laboratory manifestations of primary and secondary disease. GISC. Italian Group for the Study of Cryoglobulinaemias. QJM. 1995 Feb. 88(2):115-26. [Medline].

  27. Cohen SJ, Pittelkow MR, Su WP. Cutaneous manifestations of cryoglobulinemia: clinical and histopathologic study of seventy-two patients. J Am Acad Dermatol. 1991 Jul. 25(1 Pt 1):21-7. [Medline].

  28. Rossi D, Mansouri M, Baldovino S, Gennaro M, Naretto C, Alpa M, et al. Nail fold videocapillaroscopy in mixed cryoglobulinaemia. Nephrol Dial Transplant. 2004 Sep. 19(9):2245-9. [Medline].

  29. Ramos-Casals M, Trejo O, García-Carrasco M, Cervera R, Font J. Mixed cryoglobulinemia: new concepts. Lupus. 2000. 9(2):83-91. [Medline].

  30. Weinberger A, Berliner S, Pinkhas J. Articular manifestations of essential cryoglobulinemia. Semin Arthritis Rheum. 1981 Feb. 10(3):224-9. [Medline].

  31. Levo Y, Gorevic PD, Kassab HJ, Zucker-Franklin D, Franklin EC. Association between hepatitis B virus and essential mixed cryoglobulinemia. N Engl J Med. 1977 Jun 30. 296(26):1501-4. [Medline].

  32. Tarantino A, Campise M, Banfi G, Confalonieri R, Bucci A, Montoli A, et al. Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis. Kidney Int. 1995 Feb. 47(2):618-23. [Medline].

  33. Bombardieri S, Paoletti P, Ferri C, Di Munno O, Fornal E, Giuntini C. Lung involvement in essential mixed cryoglobulinemia. Am J Med. 1979 May. 66(5):748-56. [Medline].

  34. Viegi G, Fornai E, Ferri C, Di Munno O, Begliomini E, Vitali C, et al. Lung function in essential mixed cryoglobulinemia: a short-term follow-up. Clin Rheumatol. 1989 Sep. 8(3):331-8. [Medline].

  35. Bertorelli G, Pesci A, Manganelli P, Schettino G, Olivieri D. Subclinical pulmonary involvement in essential mixed cryoglobulinemia assessed by bronchoalveolar lavage. Chest. 1991 Nov. 100(5):1478-9. [Medline].

  36. Girard N, Vasiljevic A, Cottin V, Falchero L, Meyronet D, Thivolet-Bejui F, et al. Respiratory failure with diffuse bronchiectases and cryoglobulinaemia. Eur Respir J. 2008 Jun. 31(6):1374-8. [Medline].

  37. Della Rossa A, Tavoni A, Bombardieri S. Cryoglobulinemia. Hochberg M, ed. Rheumatology. 3rd ed. Philadelphia: Pa: Mosby; 2003. 1697-1703.

  38. Montagnino G. Reappraisal of the clinical expression of mixed cryoglobulinemia. Springer Semin Immunopathol. 1988. 10(1):1-19. [Medline].

  39. Ferri C, La Civita L, Cirafisi C, Siciliano G, Longombardo G, Bombardieri S, et al. Peripheral neuropathy in mixed cryoglobulinemia: clinical and electrophysiologic investigations. J Rheumatol. 1992 Jun. 19(6):889-95. [Medline].

  40. Fallahi P, Ferrari SM, Ruffilli I, Elia G, Giuggioli D, Colaci M, et al. Incidence of thyroid disorders in mixed cryoglobulinemia: Results from a longitudinal follow-up. Autoimmun Rev. 2016 Jul. 15 (7):747-51. [Medline].

  41. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Sebastiani M, Ferrari D, et al. High values of CXCL10 serum levels in mixed cryoglobulinemia associated with hepatitis C infection. Am J Gastroenterol. 2008 Oct. 103(10):2488-94. [Medline].

  42. Nash JW, Ross P Jr, Neil Crowson A, Taylor J, Morales JE, Yunger TM, et al. The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney. Am J Clin Pathol. 2003 Jan. 119(1):114-22. [Medline].

  43. Iannuzzella F, Vaglio A, Garini G. Management of hepatitis C virus-related mixed cryoglobulinemia. Am J Med. 2010 May. 123(5):400-8. [Medline].

  44. Mazzaro C, Monti G, Saccardo F, Zignego AL, Ferri C, De Vita S, et al. Efficacy and safety of peginterferon alfa-2b plus ribavirin for HCV-positive mixed cryoglobulinemia: a multicentre open-label study. Clin Exp Rheumatol. 2011 Dec 7. [Medline].

  45. Enomoto M, Nakanishi T, Ishii M, Tamori A, Kawada N. Entecavir to treat hepatitis B-associated cryoglobulinemic vasculitis. Ann Intern Med. 2008 Dec 16. 149(12):912-3. [Medline].

  46. Zaja F, De Vita S, Mazzaro C, Sacco S, Damiani D, De Marchi G, et al. Efficacy and safety of rituximab in type II mixed cryoglobulinemia. Blood. 2003 May 15. 101(10):3827-34. [Medline].

  47. Quartuccio L, Soardo G, Romano G, Zaja F, Scott CA, De Marchi G, et al. Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids. Rheumatology (Oxford). 2006 Jul. 45(7):842-6. [Medline].

  48. Sansonno D, De Re V, Lauletta G, Tucci FA, Boiocchi M, Dammacco F. Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20. Blood. 2003 May 15. 101(10):3818-26. [Medline].

  49. Sneller MC, Hu Z, Langford CA. A randomized controlled trial of rituximab following failure of antiviral therapy for hepatitis C virus-associated cryoglobulinemic vasculitis. Arthritis Rheum. 2012 Mar. 64(3):835-42. [Medline]. [Full Text].

  50. Roccatello D, Sciascia S, Baldovino S, Rossi D, Alpa M, Naretto C, et al. Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study. Am J Nephrol. 2016. 43 (4):251-60. [Medline].

  51. Mazzaro C, Dal Maso L, Urraro T, Mauro E, Castelnovo L, Casarin P, et al. Hepatitis B virus related cryoglobulinemic vasculitis: A multicentre open label study from the Gruppo Italiano di Studio delle Crioglobulinemie - GISC. Dig Liver Dis. 2016 Apr 2. [Medline].

  52. Boyer O, Saadoun D, Abriol J, Dodille M, Piette JC, Cacoub P, et al. CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood. 2004 May 1. 103(9):3428-30. [Medline].

  53. Ferri C, Moriconi L, Gremignai G, Migliorini P, Paleologo G, Fosella PV, et al. Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange. Nephron. 1986. 43(4):246-53. [Medline].

  54. Ferri C, Pietrogrande M, Cecchetti R, Tavoni A, Cefalo A, Buzzetti G, et al. Low-antigen-content diet in the treatment of patients with mixed cryoglobulinemia. Am J Med. 1989 Nov. 87(5):519-24. [Medline].

  55. Gemignani F, Pavesi G, Fiocchi A, Manganelli P, Ferraccioli G, Marbini A. Peripheral neuropathy in essential mixed cryoglobulinaemia. J Neurol Neurosurg Psychiatry. 1992 Feb. 55(2):116-20. [Medline].

  56. Gorevic PD. Connective Tissue Disease Associated with Other Immunologic Disorders. Cryoglobulinemia. Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 13th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997. 1572-8.

  57. Guillevin L, Pagnoux C. Indications of plasma exchanges for systemic vasculitides. Ther Apher Dial. 2003 Apr. 7(2):155-60. [Medline].

  58. Koukoulaki M, Abeygunasekara SC, Smith KG, Jayne DR. Remission of refractory hepatitis C-negative cryoglobulinaemic vasculitis after rituximab and infliximab. Nephrol Dial Transplant. 2005 Jan. 20(1):213-6. [Medline].

  59. Miescher PA, Huang YP, Izui S. Type II cryoglobulinemia. Semin Hematol. 1995 Jan. 32(1):80-5. [Medline].

 
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Rash on lower extremities typical of cutaneous small-vessel vasculitis due to cryoglobulinemia secondary to hepatitis C infection.
Renal biopsy sample that shows membranoproliferative glomerulonephritis in a patient with hepatitis C–associated cryoglobulinemia (hematoxylin and eosin; magnified X 200).
 
 
 
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