eMedicine Specialties > Rheumatology > Vasculitis
Takayasu Arteritis: Treatment & Medication
Updated: Feb 14, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Therapeutic intervention includes corticosteroids with or without cytotoxic agents.
- Corticosteroids are the mainstay of therapy for active Takayasu arteritis, and some patients may require additional cytotoxic agents to achieve remission and discontinue steroid treatment.
- Corticosteroids are started at 1 mg/kg/d PO or divided bid/qid and tapered over weeks to months as symptoms subside. Long-term low-dose corticosteroid therapy may be required.
- Osteoporosis prevention when patients are started on corticosteroids should be seriously considered.
- Cytotoxic agents are used for patients with steroid resistance or relapsing Takayasu arteritis. These agents are usually continued for one year after remission and are then tapered to discontinuation. Agents and doses are as follows:
- Azathioprine 1-2 mg/kg/d PO
- Methotrexate 7.5-25 mg/wk PO or IM
- Cyclophosphamide 2 mg/kg/d PO (should be reserved for patients with the most severe and refractory disease states)
- Cyclosporin A also has been used in steroid-resistant patients at initial doses of 5 mg/kg/d and then 2-3 mg/kg/d for maintenance.
- Mycophenolate mofetil (2 g/d PO) has been used in patients with Takayasu arteritis resistant to steroids and other immunosuppressant drugs.
- In an uncontrolled series of 15 patients, adjunctive treatment with anti–tumor necrosis factor (TNF) agents was effective in patients with active, relapsing Takayasu arteritis despite treatment with steroids and multiple other immunosuppressive agents.2 The initial dose of etanercept was 25 mg twice weekly (7 patients), and infliximab (11 patients [3 were switched from etanercept to infliximab]) was given at 3 mg/kg initially and at 2 weeks, 6 weeks, and every 8 weeks thereafter. In 9 of the 14 responders, an increase in the anti-TNF dosage was required to sustain remission. These preliminary results suggest that anti-TNF therapy may be a useful adjunct to corticosteroids in the treatment of patients with Takayasu arteritis and require further studies. A larger randomized controlled study of anti-TNF therapy for Takayasu arteritis is planned.
- Strict management of traditional cardiovascular risk factors such as dyslipidemia, hypertension, and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease. Additionally, low-dose aspirin may have a therapeutic effect in large vessel vasculitis.
Surgical Care
- Critical stenotic lesions should be treated by angioplasty or surgical revascularization during periods of remission.
- Indications for surgical repair or angioplasty are as follows:
- Renovascular stenosis causing hypertension
- Coronary artery stenosis leading to myocardial ischemia
- Extremity claudication induced by routine activity
- Cerebral ischemia and/or critical stenosis of 3 or more cerebral vessels
- Aortic regurgitation
- Thoracic or abdominal aneurysms larger than 5 cm in diameter
- Severe coarctation of the aorta
- Percutaneous transluminal coronary angioplasty is followed by restenosis at the angioplasty site within 1-2 years in a substantial number of patients.
- Bypass graft procedures have the best long-term patency rate.
Consultations
- Rheumatologist
- Cardiologist
- Vascular surgeon
- Imaging/interventional radiologist
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Immunosuppressive agents
These agents inhibit key factors that mediate immune reactions.
Prednisone (Deltasone, Orasone, Meticorten)
Corticosteroid, first-line therapy; immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity and CD4 counts.
Adult
1 mg/kg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric
0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
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, viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, fungal or tubercular skin infections, GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, and infections may occur with glucocorticoid use; osteoporosis screening and prevention measures should be instituted when corticosteroid therapy is begun
Cyclophosphamide (Cytoxan, Neosar)
May be added to steroid if minimal response to steroid or if on steroid for prolonged period of time. Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
2 mg/kg PO qd
Pediatric
Not established
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects of cyclophosphamide; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life of cyclophosphamide while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity of cyclophosphamide; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause sterility; regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; may cause bladder cancer
Azathioprine (Imuran)
May be added if no response to steroid or if on steroid for long period of time. Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.
Adult
1-2 mg/kg PO qd in single or divided doses
Pediatric
Administer as in adults
Toxicity increases with allopurinol, and dose must be reduced; 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
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur
Methotrexate (Folex PFS, Rheumatrex)
May be added if steroid not effective or if on steroid for prolonged period of time. Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.
Adult
7.5-25 mg/wk PO/IM
Pediatric
Not established
Oral aminoglycosides may decrease absorption and blood levels of concurrent oral MTX; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity of MTX; folic acid or its derivatives contained in some vitamins may decrease response to MTX
Coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase MTX plasma levels; may decrease phenytoin serum levels
Probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity of MTX; may increase plasma levels of thiopurines
Documented hypersensitivity, alcoholism, hepatic insufficiency, documented immunodeficiency syndromes, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Monitor CBCs monthly and liver and renal function every 1-3 mo during therapy (monitor more frequently during initial dosing, dose adjustments, or with risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems
Discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs including salicylates has not been tested)
Cyclosporine (Sandimmune, Neoral, Gengraf)
May be added if steroid ineffective or on steroid for prolonged period of time. Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions. For children and adults, base dosing on ideal body weight.
Adult
3 mg/kg/d PO qd or divided bid; if creatinine clearance increases by >30%, dosage must be lowered
Pediatric
Administer as in adults
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; concomitantly with PUVA or UVB radiation in psoriasis (may increase risk of cancer)
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
May cause hypertension and paresthesias; evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO; may cause gout
Infliximab (Remicade)
May be added if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-a and inhibits its binding to TNF-a receptor. Reduces infiltration of inflammatory cells and TNF-a production in inflamed areas.
Adult
3 mg/kg IV (in combination with methotrexate or other immunosuppressants); follow by additional 3 mg/kg IV at 2 and 6 wk after first dose; repeat q8wk thereafter; can be increased to 10 mg/kg IV q4-8wk
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
May adversely affect normal immune responses and allow development of superinfections (more cases of lymphoma were observed in TNF-a –blockers compared with controls); may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections
Etanercept (Enbrel)
May be added if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Soluble p75 TNF receptor fusion protein (sTNFR-Ig). Inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses.
Adult
25 mg SC 2 times/wk with or without concomitant administration of MTX
Can be increased to 50 mg SC 2 times/wk
Pediatric
Not established
None reported
Documented hypersensitivity; sepsis; concurrent live vaccination
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Serious infections may develop and the therapy should be discontinued if they occur; possible adverse effects include injection site pain, redness and swelling at injection site, and headaches; rare cases of lupuslike symptoms and heart failure have been reported (discontinue treatment if symptoms develop)
Mycophenolate (CellCept, Myfortic)
May be added if steroids and other immunosuppressant drugs are ineffective in achieving or maintaining remission. Inhibits purine synthesis and proliferation of human lymphocytes. Promising published case report of 3 patients with resistant disease treated with mycophenolate mofetil. Reduced toxicity makes this regimen an attractive alternative.
Adult
1 g PO bid
Pediatric
Not established
In combination with either acyclovir or ganciclovir may result in higher levels for both interacting drugs due to competition for renal tubular excretion; aluminum or magnesium present in some antacids and cholestyramine-containing products may decrease absorption, reducing levels (do not administer together); probenecid may increase levels of mycophenolate; salicylates and azathioprine may increase toxicity; may decrease levonorgestrel AUC; may decrease live virus vaccine immune response; may increase free fraction levels of theophylline when administered in combination with theophylline
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Increases risk for infection (monitor blood count); severe renal impairment (CrCl <25 mL/min) may have increased adverse effects due to increase free MPA; caution in patients with active peptic ulcer disease; incidence of malignancies and lymphoma is consistent with that reported for other immunosuppressants (0.9%); commonly causes constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis; rare reports include interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus; do not chew, crush, or cut Myfortic tab
More on Takayasu Arteritis |
| Overview: Takayasu Arteritis |
| Differential Diagnoses & Workup: Takayasu Arteritis |
 Treatment & Medication: Takayasu Arteritis |
| Follow-up: Takayasu Arteritis |
| Multimedia: Takayasu Arteritis |
| References |
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References
Yagi K, Kobayashi J, Yasue S, et al. Four unrelated cases with Takayasu arteritis and CD36 deficiency: possible link between these disorders. J Intern Med. Jun 2004;255(6):688-9. [Medline].
Hoffman GS, Merkel PA, Brasington RD, et al. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. Jul 2004;50(7):2296-304. [Medline].
Andrews J, Al-Nahhas A, Pennell DJ, Hossain MS, Davies KA, Haskard DO. Non-invasive imaging in the diagnosis and management of Takayasu's arteritis. Ann Rheum Dis. Aug 2004;63(8):995-1000. [Medline].
Andrews J, Mason JC. Takayasu's arteritis--recent advances in imaging offer promise. Rheumatology (Oxford). Jan 2007;46(1):6-15. [Medline].
Daina E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the treatment of Takayasu arteritis: report of threecases. Ann Intern Med. Mar 2 1999;130(5):422-6. [Medline].
Joh JH, Kim DK, Park KH, Kim DI. Surgical management of Takayasu's arteritis. J Korean Med Sci. Feb 2006;21(1):20-4. [Medline].
Liang P, Hoffman GS. Advances in the medical and surgical treatment of Takayasu arteritis. Curr Opin Rheumatol. Jan 2005;17(1):16-24. [Medline].
Lie JT. Pathology of isolated nonclassical and catastrophic manifestations of Takayasu arteritis. Int J Cardiol. Oct 1 1998;66 Suppl 1:S11-21. [Medline].
Numano F. Takayasu arteritis, Buerger disease and inflammatory abdominal aortic aneurysms: is there a common pathway in their pathogenesis?. Int J Cardiol. Oct 1 1998;66 Suppl 1:S5-10. [Medline].
Numano F, Kobayashi Y. Takayasu arteritis--beyond pulselessness. Intern Med. Mar 1999;38(3):226-32. [Medline].
Rizzi R, Bruno S, Stellacci C, Dammacco R. Takayasu's arteritis: a cell-mediated large-vessel vasculitis. Int J Clin Lab Res. 1999;29(1):8-13. [Medline].
Schmidt WA, Blockmans D. Use of ultrasonography and positron emission tomography in the diagnosis and assessment of large-vessel vasculitis. Curr Opin Rheumatol. Jan 2005;17(1):9-15. [Medline].
Seo P, Stone JH. Large-vessel vasculitis. Arthritis Rheum. Feb 15 2004;51(1):128-39. [Medline].
Sharma BK, Jain S, Sagar S. Systemic manifestations of Takayasu arteritis: the expanding spectrum. Int J Cardiol. Aug 1996;54 Suppl:S149-54. [Medline].
Tanaka F, Kawakami A, Iwanaga N, Tamai M, Izumi Y, Aratake K. Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med. 2006;45(5):313-6. [Medline].
Yasuda K. Surgical treatment of Takayasu's Arteritis. Intern Med. Nov 1998;37(11):903-4. [Medline].
Further Reading
Keywords
Takayasu arteritis, TA, pulseless disease, Takayasu's disease, Takayasu's arteritis, Takayasu disease, aortic arch syndrome, middle aortic syndrome stenotic lesions, angioplasty, renovascular stenosis, coronary artery stenosis, extremity claudication, cerebral ischemia, critical stenosis, aortic regurgitation, thoracic aneurysm, abdominal aneurysm, percutaneous transluminal coronary angioplasty, PTCA
