eMedicine Specialties > Rheumatology > Vasculitis
Cryoglobulinemia: Treatment & Medication
Updated: Jul 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The goal of therapy is to treat underlying conditions, as well as to limit the precipitant cryoglobulin and the resultant inflammatory effects. Thus, HCV testing is required. HCV-antibody or HCV-RNA testing may be diagnostic. If HCV test results are negative and clinical suspicion remains high, these tests may be performed on the cryoprecipitate. Asymptomatic cryoglobulinemia does not require treatment. Some authors recommend intervening as little as possible except when faced with severe deterioration of renal or neurologic function. Secondary cryoglobulinemia is best managed with treatment of the underlying malignancy or associated disease. Otherwise, cryoglobulinemia is treated simply with suppression of the immune response. A paucity of controlled studies evaluating the relative efficacy of various therapies limits the use of existing data.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used in patients with arthralgia and fatigue.
- Immunosuppressive medications (eg, corticosteroid therapy and/or cyclophosphamide or azathioprine) are indicated upon evidence of organ involvement such as vasculitis, renal disease, progressive neurologic findings, or disabling skin manifestations.
- Plasmapheresis is indicated for severe or life-threatening complications related to in vivo cryoprecipitation or serum hyperviscosity. Concomitant use of high-dose corticosteroids and cytotoxic agents is recommended for reduction of immunoglobulin production. Some authors recommend using concomitant cytotoxic medications or corticosteroids to reduce a rebound phenomenon that may develop after plasmapheresis.
- Pegylated interferon alfa (IFN-alfa) combined with ribavirin has demonstrated efficacy in patients with cryoglobulinemia associated with hepatitis C, and efficacy in patients with chronic myelogenous leukemias and low-grade lymphomas has been reported. The details of therapy and the recommended approach vary based on the clinical setting, and expert opinion should be sought.
- Case reports have detailed the remission of hepatitis B–related cryoglobulinemic vasculitis with entecavir therapy.38
- Small and uncontrolled studies suggest the anti-CD20 chimeric monoclonal antibody rituximab is effective in controlling disease manifestations such as vasculitis, peripheral neuropathy, arthralgias, low-grade B-cell lymphomas, renal disease, and fever.39,40 Rituximab therapy has been used predominately in HCV-related mixed cryoglobulinemia refractory to or unsuitable for corticosteroids and antiviral (IFN-alfa) therapy. Rituximab therapy is reportedly well tolerated in this patient population; however, treatment results in increased titers of HCV-RNA of undetermined significance. The National Institutes of Health has launched a large trial of rituximab in the treatment of mixed cryoglobulinemia.
Consultations
- Rheumatologist or clinical immunologist
- Nephrologist upon evidence of renal disease (ie, hypertension, abnormal findings on urinalysis)
- Hematologist upon evidence of underlying hematological disease or for plasmapheresis
- Gastroenterologist or hepatologist for patients with underlying hepatitis
Medication
The overall aim of therapy is treatment of any underlying condition and general suppression of the immune response. Mild anti-inflammatory medications (eg, NSAIDs) are effective in mild cases, and corticosteroid therapy is reserved for the more severe or refractory cases. Patients who require potent immunosuppression or other more aggressive therapies for severe disease should be treated by a specialist. Cyclophosphamide may be used as a steroid-sparing agent or administered concomitantly in severe cases of vasculitis, particularly in patients with renal disease. Azathioprine is commonly used as a steroid-sparing agent, and chlorambucil has also been used for severe vasculitis.
Nonsteroidal anti-inflammatory drugs
NSAIDs such as ibuprofen, naproxen, and indomethacin have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. NSAIDs may have additional mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions. NSAIDs are used to reduce the resultant inflammatory response of cryoglobulin precipitation.Ibuprofen (Advil, Motrin, Excedrin IB, Ibuprin)
NSAIDs are the DOC in patients with mild symptoms of arthralgia or fatigue. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult
600-800 mg PO tid/qid
Pediatric
30-40 mg/kg/d PO divided tid/qid
Coadministration with aspirin increases the risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, angiotensin II receptor blockers, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; coadministration with ACE inhibitors, angiotensin II receptor blockers, and potassium-sparing diuretics may result in hyperkalemia; may increase PT when combined with anticoagulants or aggravate bleeding tendency because of the antiplatelet effect of NSAIDs; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; history of GI bleeding or perforation; renal insufficiency; anticoagulation; coagulopathy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Most common toxicities include gastrointestinal manifestations such as nausea, abdominal pain, peptic ulcer disease, and renal insufficiency; may cause increased blood pressure in patients with hypertension due to blunting of effects of antihypertensive medications; patients with congestive heart failure may have exacerbations due to fluid and sodium retention; caution in coagulation abnormalities or during anticoagulant therapy
Corticosteroids
These medications are used to reduce the resultant immune response from cryoglobulin precipitation, particularly in patients with more severe symptoms or some evidence of organ damage.
Prednisone (Sterapred)
DOC in patients with evidence of acute vasculitis.
Adult
1 mg/kg/d PO in divided doses; up to 120 mg/d has been reported
Pediatric
2-3 mg/kg/d PO
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in severe bacterial, viral, or fungal infection; active peptic ulcer disease; diabetes mellitus; toxicities include weight gain, dyspepsia, mood changes, infection, peptic ulcer disease, hypertension, diabetes mellitus, osteoporosis, avascular necrosis, cataracts, glaucoma, myopathy, and skin changes; growth retardation in children; abrupt discontinuation may result in adrenal crisis
Immunosuppressive agents
These are commonly used as steroid-sparing agents.
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, interfering with growth of normal and neoplastic cells.
Adult
1-5 mg/kg/d PO
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; infection; severely depressed bone marrow function; severe cytopenias
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Toxicities include nausea and vomiting, leukopenia, thrombocytopenia, anemia, infection, alopecia, hemorrhagic cystitis, infertility, teratogenicity, and increased risk of infection; monitor CBC count and UA at regular intervals
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
2-3 mg/kg/d PO single or divided dose
1 mg/kg/d initial; increase depending on clinical and hematologic response and toxicity
Pediatric
Administer as in adults
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity; low levels of serum thiopurine methyltransferase (TPMT); active infection (relative); severe cytopenias (relative)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Nausea and vomiting; hematologic toxicities may occur; check TPMT level prior to initiation of therapy; pancreatitis rarely occurs; monitor CBC count and LFTs at regular intervals; may also monitor 6-thioguanine (6-TG) and 6-methyl mercaptopurine (6-MMP) levels
Chlorambucil (Leukeran)
Alkylates and cross-links strands of DNA, inhibiting DNA replication and RNA transcription.
Adult
0.1-0.2 mg/kg/d PO
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; previous resistance to medication; active infection (relative)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in history of seizure disorders or in patients diagnosed with bone marrow suppression; gastrointestinal effects, dermatitis or erythema multiforme, cystitis, pulmonary fibrosis, hepatotoxicity, infertility, teratogenic effects, peripheral neuropathy, and secondary malignancy may occur; monitor CBC count and LFTs at regular intervals
Interferons
These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. IFN-alfa is generally administered subcutaneously.
Interferon alfa-2b (Intron A)
Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. Has antiviral activity in HCV infection.
Adult
Not recommended without consultation
Pediatric
Not established
Potential risk of renal failure when administered concurrently with interleukin-2; theophylline may increase IFN-alfa toxicity by reducing clearance; cimetidine may increase antitumor effects of IFN-alfa; zidovudine and vinblastine may increase toxicity of IFN-alfa
Documented hypersensitivity; patients who have anaphylactic sensitivity to mouse IgG, egg protein, or neomycin; autoimmune disease (relative)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Fatigue; headache; arthralgias; myalgias; fever; nausea; autoimmunity; depression and suicidal ideation may be adverse effects of treatment; infrequently, severe or fatal GI hemorrhage is reported in association with IFN-a therapy; prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if a response occurs, continue treatment until no further improvement is observed; whether continued treatment after that time is beneficial is not known
Peginterferon alfa-2a (Pegasys)
Used in combination with ribavirin to treat patient with chronic HCV infection who have compensated liver disease and have not received IFN-alfa previously. Consists of interferon alfa-2a attached to a 40-kD branched PEG molecule. Predominantly metabolized by the liver.
Adult
180 mcg SC qwk
Pediatric
Not established
Theophylline may increase toxicity by reducing clearance; cimetidine may increase the antitumor effects; zidovudine and vinblastine may increase toxicity
Documented hypersensitivity; decompensated liver disease; significant preexisting psychiatric disease; ongoing or recent alcohol use; platelet count <70,000/µL
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Insomnia; mental dysfunction (eg, mood dysfunction, depression, psychosis, aggressive behavior, hallucinations, violent behavior, suicidal ideation, suicide attempt, suicide, homicidal ideation [rare]), even without previous history of psychiatric illness; flulike symptoms; rash and pruritus; anorexia; neutropenia; thrombocytopenia; thyroid dysfunction; retinal abnormalities
Peginterferon alfa-2b (PEG-Intron)
Escherichia coli recombinant product. Used to treat chronic HCV infection in patients not previously treated with INF-alfa who have compensated liver disease. Exerts cellular activities by binding to specific membrane receptors on cell surface, which, in turn, may suppress cell proliferation and may enhance phagocytic activity of macrophages. May also increase cytotoxicity of lymphocytes for target cells and inhibit virus replication in virus-infected cells.
Adult
Inject SC qwk for 1 y using weight-based dosing as follows:
37-45 kg: 40 mcg (0.4 mL of 100 mcg/mL)
46-56 kg: 50 mcg (0.5 mL of 100 mcg/mL)
57-72 kg: 64 mcg (0.4 mL of 160 mcg/mL)
73-88 kg: 80 mcg (0.5 mL of 160 mcg/mL)
89-106 kg: 96 mcg (0.4 mL of 240 mcg/mL)
107-136 kg: 120 mcg (0.5 mL of 240 mcg/mL)
137-160 kg: 150 mcg (0.5 mL of 300 mcg/mL)
Pediatric
Not established
Concurrent administration with interleukin 2 may increase nephrotoxicity; theophylline, zidovudine, and vinblastine may increase toxicity; cimetidine may increase antitumor effects
Documented hypersensitivity; autoimmune hepatitis; pancreatitis; colitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Insomnia; mental dysfunction (eg, mood dysfunction, depression, psychosis, aggressive behavior, hallucinations, violent behavior, suicidal ideation, suicide attempt, suicide, homicidal ideation [rare]), even without previous history of psychiatric illness; flulike symptoms; rash and pruritus; anorexia; neutropenia; thrombocytopenia; thyroid dysfunction; retinal abnormalities
Antiviral agents
Nucleoside analogs are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit herpes simplex virus (HSV) polymerase with 30-50 times the potency of human alpha-DNA polymerase.
Ribavirin (Virazole)
Antiviral nucleoside analogs. Chemical name is 1-beta-D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, has little effect on the course of HCV infection. When used with IFN, significantly augments rate of sustained virologic response.
Adult
10.6 mg/kg/d PO or divided bid
Pediatric
Not established
Decreases zidovudine effects
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Closely monitor patients with COPD and asthma for deterioration of respiratory function
Antiviral Agent, Oral
This agent inhibits the viral reverse transcriptase enzyme, which limits viral replication.
Entecavir (Baraclude)
Guanosine nucleoside analogue with activity against HBV polymerase. Competes with natural substrate deoxyguanosine triphosphate to inhibit HBV polymerase activity (ie, reverse transcriptase). Less effective for lamivudine-refractory HBV infection. Indicated for treatment of chronic hepatitis B infection. Available as tab and oral solution (0.05 mg/mL; 0.5 mg = 10 mL).
Adult
Treatment for nucleoside naive: 0.5 mg PO qd 2 h ac or 2 h pc
CrCl 30-49 mL/min: 0.25 mg PO qd or 0.5 mg q48h
CrCl 10-29 mL/min: 0.15 mg PO qd or 0.5 mg q72h
CrCl <10 mL/min: 0.05 mg PO qd or 0.5 mg qwk
Receiving lamivudine or lamivudine resistance: 1 mg PO qd 2 h ac or 2 h pc
CrCl 30-49 mL/min: 0.5 mg PO qd or 1 mg q48h
CrCl 10-29 mL/min: 0.3 mg PO qd or 1 mg q72h
CrCl <10 mL/min: 0.1 mg PO qd or 1 mg qwk
Pediatric
<16 years: Not established
>16 years: Administer as in adults
Not a substrate, inhibitor, or inducer of cytochrome P450; coadministration with drugs that reduce renal function (eg, aminoglycosides, cidofovir, cyclosporine) or that compete for active tubular secretion (eg, probenecid, salicylates) may increase serum concentration of either entecavir or coadministered drug
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Reduce dose with renal impairment; if on hemodialysis, administer afterwards; common adverse effects include headache, tiredness, dizziness, and nausea; may elevate liver enzyme levels; may cause lactic acidosis; severe acute exacerbations of hepatitis B may occur in patients who discontinue antihepatitis B therapy
Antineoplastic agents
These agents inhibit cell growth and proliferation.
Rituximab (Rituxan)
Genetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.
Immunomodulates response against malignant cells.
Adult
60-75 mg/m2 IV as a single dose; repeat q21d
Alternatively, 20-30 mg/m2/d for 2-3 d; repeat in 4 wk
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypotension, bronchospasm, and angioedema may occur; discontinue treatment if life-threatening cardiac arrhythmias occur
More on Cryoglobulinemia |
| Overview: Cryoglobulinemia |
| Differential Diagnoses & Workup: Cryoglobulinemia |
Treatment & Medication: Cryoglobulinemia |
| Follow-up: Cryoglobulinemia |
| Multimedia: Cryoglobulinemia |
| References |
| « Previous Page | Next Page » |
References
Trendelenburg M, Schifferli JA. Cryoglobulins are not essential. Ann Rheum Dis. Jan 1998;57(1):3-5. [Medline].
Uki J, Young CA, Suzuki T. A 22S cryomacroglobulin with antibody-like activity. I. Physico-chemical characterization and modification of its cryoproperties. Immunochemistry. Nov 1974;11(11):729-40. [Medline].
Wang AC, Wells JV, Fudenberg HH. Chemical analyses of cryoglobulins. Immunochemistry. Jul 1974;11(7):341-5. [Medline].
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].
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. Jan 1975;12(1):29-37. [Medline].
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. Oct 15 2002;169(8):4644-50. [Medline].
Abel G, Zhang QX, Agnello V. Hepatitis C virus infection in type II mixed cryoglobulinemia. Arthritis Rheum. Oct 1993;36(10):1341-9. [Medline].
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. May 1998;185(1):86-90. [Medline].
Sansonno D, Dammacco F. Hepatitis C virus, cryoglobulinaemia, and vasculitis: immune complex relations. Lancet Infect Dis. Apr 2005;5(4):227-36. [Medline].
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). Jun 2006;45(6):685-93. [Medline].
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. May 1997;25(5):1237-44. [Medline].
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. Feb 1995;21(2):305-12. [Medline].
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. Oct 1995;131(10):1119-23. [Medline].
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. Aug 1980;69(2):287-308. [Medline].
Brouet JC, Clauvel JP, Danon F, Klein M, Seligmann M. Biologic and clinical significance of cryoglobulins. A report of 86 cases. Am J Med. Nov 1974;57(5):775-88. [Medline].
Beddhu S, Bastacky S, Johnson JP. The clinical and morphologic spectrum of renal cryoglobulinemia. Medicine (Baltimore). Sep 2002;81(5):398-409. [Medline].
Bryce AH, Kyle RA, Dispenzieri A, Gertz MA. Natural history and therapy of 66 patients with mixed cryoglobulinemia. Am J Hematol. Jul 2006;81(7):511-8. [Medline].
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].
La Civita L, Zignego AL, Monti M, Longombardo G, Pasero G, Ferri C. Mixed cryoglobulinemia as a possible preneoplastic disorder. Arthritis Rheum. Dec 1995;38(12):1859-60. [Medline].
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. Oct 23 2006;166(19):2101-8. [Medline].
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. Feb 1995;88(2):115-26. [Medline].
Cohen SJ, Pittelkow MR, Su WP. Cutaneous manifestations of cryoglobulinemia: clinical and histopathologic study of seventy-two patients. J Am Acad Dermatol. Jul 1991;25(1 Pt 1):21-7. [Medline].
Rossi D, Mansouri M, Baldovino S, Gennaro M, Naretto C, Alpa M, et al. Nail fold videocapillaroscopy in mixed cryoglobulinaemia. Nephrol Dial Transplant. Sep 2004;19(9):2245-9. [Medline].
Ramos-Casals M, Trejo O, García-Carrasco M, Cervera R, Font J. Mixed cryoglobulinemia: new concepts. Lupus. 2000;9(2):83-91. [Medline].
Weinberger A, Berliner S, Pinkhas J. Articular manifestations of essential cryoglobulinemia. Semin Arthritis Rheum. Feb 1981;10(3):224-9. [Medline].
Levo Y, Gorevic PD, Kassab HJ, Zucker-Franklin D, Franklin EC. Association between hepatitis B virus and essential mixed cryoglobulinemia. N Engl J Med. Jun 30 1977;296(26):1501-4. [Medline].
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. Feb 1995;47(2):618-23. [Medline].
Bombardieri S, Paoletti P, Ferri C, Di Munno O, Fornal E, Giuntini C. Lung involvement in essential mixed cryoglobulinemia. Am J Med. May 1979;66(5):748-56. [Medline].
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. Sep 1989;8(3):331-8. [Medline].
Bertorelli G, Pesci A, Manganelli P, Schettino G, Olivieri D. Subclinical pulmonary involvement in essential mixed cryoglobulinemia assessed by bronchoalveolar lavage. Chest. Nov 1991;100(5):1478-9. [Medline].
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. Jun 2008;31(6):1374-8. [Medline].
Della Rossa A, Tavoni A, Bombardieri S. Cryoglobulinemia. In: Hochberg M, ed. Rheumatology. 3rd ed. Philadelphia: Pa: Mosby; 2003:1697-1703.
Montagnino G. Reappraisal of the clinical expression of mixed cryoglobulinemia. Springer Semin Immunopathol. 1988;10(1):1-19. [Medline].
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. Jun 1992;19(6):889-95. [Medline].
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. Jun 1966;40(6):837-56. [Medline].
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. Oct 2008;103(10):2488-94. [Medline].
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. Jan 2003;119(1):114-22. [Medline].
Enomoto M, Nakanishi T, Ishii M, Tamori A, Kawada N. Entecavir to treat hepatitis B-associated cryoglobulinemic vasculitis. Ann Intern Med. Dec 16 2008;149(12):912-3. [Medline].
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. May 15 2003;101(10):3827-34. [Medline].
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). Jul 2006;45(7):842-6. [Medline].
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. May 1 2004;103(9):3428-30. [Medline].
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].
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. Nov 1989;87(5):519-24. [Medline].
Gemignani F, Pavesi G, Fiocchi A, Manganelli P, Ferraccioli G, Marbini A. Peripheral neuropathy in essential mixed cryoglobulinaemia. J Neurol Neurosurg Psychiatry. Feb 1992;55(2):116-20. [Medline].
Gorevic PD. Connective Tissue Disease Associated with Other Immunologic Disorders. Cryoglobulinemia. In: Koopman WJ, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 13th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1997:1572-8.
Gorevic PD. Cryopathies: Cryoglobulins and Cryofibrinogenemia. In: Samter's Immunologic Disease. 5th ed. Boston, Mass: Little, Brown, and Co; 1995:951-974.
Guillevin L, Pagnoux C. Indications of plasma exchanges for systemic vasculitides. Ther Apher Dial. Apr 2003;7(2):155-60. [Medline].
Koukoulaki M, Abeygunasekara SC, Smith KG, Jayne DR. Remission of refractory hepatitis C-negative cryoglobulinaemic vasculitis after rituximab and infliximab. Nephrol Dial Transplant. Jan 2005;20(1):213-6. [Medline].
Lunel F, Musset L, Cacoub P, Frangeul L, Cresta P, Perrin M, et al. Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage. Gastroenterology. May 1994;106(5):1291-300. [Medline].
Madore F, Lazarus JM, Brady HR. Therapeutic plasma exchange in renal diseases. J Am Soc Nephrol. Mar 1996;7(3):367-86. [Medline].
Meltzer M, Franklin EC. Cryoglobulinemia--a study of twenty-nine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med. Jun 1966;40(6):828-36. [Medline].
Miescher PA, Huang YP, Izui S. Type II cryoglobulinemia. Semin Hematol. Jan 1995;32(1):80-5. [Medline].
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. May 15 2003;101(10):3818-26. [Medline].
Further Reading
Keywords
cryoglobulinemia, cryoproteinemia, cryoglobulins, immunoglobulins, essential cryoglobulinemia, simple cryoglobulinemia, type I cryoglobulinemia, type II cryoglobulinemia, type III cryoglobulinemia, mixed cryoglobulinemia, essential cryoglobulinemia, idiopathic cryoglobulinemia, hepatitis C virus, HCV, secondary cryoglobulinemia, glomerulonephritis, chronic vasculitis, cryoprecipitation, systemic lupus erythematosus, SLE, Sjögren syndrome, Sjögren's syndrome, hyperviscosity, thrombosis, acrocyanosis, retinal hemorrhage, Raynaud phenomenon, Raynaud's phenomenon, livedo reticularis, purpura, arterial thrombosis, multiple myeloma, Waldenström macroglobulinemia, Waldenström's macroglobulinemia, chronic liver disease
Treatment & Medication: Cryoglobulinemia