eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Takayasu Arteritis: Treatment & Medication

Author: Christine Hom, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Rheumatology, New York Medical College
Contributor Information and Disclosures

Updated: Oct 31, 2008

Treatment

Medical Care

Medical evaluation and treatment in patients with Takayasu arteritis (TA) can be performed on an outpatient basis unless the patient is acutely ill. Goals of medical therapy are to control active inflammation and to normalize clinical and laboratory parameters while preventing further vascular damage.

  • Daily high-dose corticosteroid administration is the mainstay of initial therapy. The authors have used prednisone at 1-2 mg/kg/d for 4-6 weeks.
    • Maintain high-dose treatment until all evidence of active disease has resolved.
    • Then taper prednisone dosage over a month to decrease morbidity from corticosteroid treatment; although 60% of patients respond to this treatment, 40% relapse on steroid taper.
  • Patients not responding to corticosteroids or who relapse during corticosteroid taper require an additional agent.
    • Symptoms of patients who relapse on corticosteroid taper may be controlled with weekly infusions of methylprednisolone (30 mg/kg, not to exceed 1 g/wk).
    • However, extensive use of these infusions is associated with significant steroid-induced toxicity if continued for any significant period.
  • Regimens including weekly methotrexate or daily or monthly intravenous cyclophosphamide have been used in individuals with glucocorticoid-resistant TA. Low-dose weekly methotrexate also has been used as a steroid-sparing agent for patients not tolerating corticosteroid taper. Ozen et al used daily oral cyclophosphamide, which was well tolerated in a small series of children.2
  • Cyclosporine may be an alternative therapy offering lower ovarian toxicity than cyclophosphamide. However, cyclosporine is often associated with decreased renal function and increased blood pressure, which may aggravate the damage to the heart and great vessels and is less frequently used.
  • Mycophenolate mofetil may be useful to treat individuals with glucocorticoid-resistant disease.3 Case reports suggest disease control and steroid sparing.
  • A small series (15 patients) showed that tumor necrosis factor (TNF) inhibition using etanercept or infliximab was successful in inducing clinical remission and permitting corticosteroid taper in patients who are steroid dependent.4 The role of TNF inhibition in treating initial disease or relapses is yet to be established, but use of these agents and immunosuppressants, such as mycophenolate, anticipate regimens in which disease is controlled while minimizing morbidity from steroid and cytotoxic treatments.
  • Anecdotal reports of matrix metalloproteinase inhibition using minocycline propose that this may be a useful adjunctive therapy, which may also allow lower doses of corticosteroids and thus reduced toxicity.

Surgical Care

Following the acute phase, patients with fibrotic changes require surgical treatment of symptomatic stenotic or occlusive disease. This can be achieved by percutaneous angioplasty or stenting or, in severe cases, by resection and placement of a manmade graft. Children with TA rarely require bypass surgery of carotid stenting.

Percutaneous balloon angioplasty of the aorta is reported to normalize systolic and diastolic blood pressures within 24 hours, with improvement of exercise tolerance and restoration of peripheral pulses. A high incidence of restenosis (£ 78%) is observed in adults. Both renovascular hypertension and congestive failure due to increased afterload are improved. Improvement has been sustained for as long as 3-5 years.

Endovascular stenting is used in patients with severe stenoses, hypertension, or ischemia during the fibrotic phase of the disease. Multiple stents have been used in children to relieve long-segment renal artery stenosis and attendant renovascular hypertension. Children with TA who have received stents have lowered arterial blood pressures and decreased requirement for antihypertensives. Immunosuppressant-eluting stents could potentially deliver local treatment at sites of inflammation.

Consultations

  • Pediatric rheumatologist
  • Ophthalmologist
  • Pediatric cardiologist
  • Vascular surgeon
  • Interventional radiologist

Activity

Patient activity is generally self-limiting, based on cardiac status.

Medication

The mainstay of initial therapy is daily high-dose corticosteroid administration. Maintain high-dose treatment for several weeks until all evidence of active disease has resolved. Among patients receiving this treatment, 60% respond; however, 40% relapse on steroid taper.

Patients who do not respond to corticosteroids or who relapse during corticosteroid taper require a second agent. Regimens including weekly methotrexate and daily cyclophosphamide have been used in individuals with glucocorticoid-resistant Takayasu arteritis (TA). Low-dose weekly methotrexate has also been used as a steroid-sparing agent for patients not tolerating corticosteroid taper. Cyclosporine may be an alternative therapy offering lower ovarian toxicity than cyclophosphamide. Reports indicate mycophenolate mofetil may help treat glucocorticoid-resistant disease. Leflunomide has been used in glucocorticoid-resistant and methotrexate-resistant disease.5 Tumor necrosis factor (TNF) inhibition with etanercept or infliximab has also been used in relapsing disease or glucocorticoid-dependent disease.

Immunosuppressive agents

These agents are used to suppress inflammation, thus delaying progression of thrombosis, stenosis, and aneurysm.


Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.

Adult

1-2 mg/kg/d PO qd or divided bid

Pediatric

Not to exceed 1-2 mg/kg/d PO qd or divided bid

Induction of cytochrome P450 enzymes decreases vaccine effectiveness; phenytoin and rifampin decrease corticosteroid effectiveness

Documented hypersensitivity; serious infections; systemic fungal infections; varicella; GI bleeding or ulceration

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in patients with hypertension, congestive heart failure, or diabetes


Methotrexate (MTX, Rheumatrex, Folex PFS)

Inhibits tetrahydrofolate reductase and has potent anti-inflammatory effects possibly mediated through adenosine receptors. 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

10-20 mg/wk PO/IM/SC

Pediatric

5-15 mg/m2/wk PO/IM/SC

NSAIDs may cause increased or prolonged levels of MTX; MTX may decrease clearance of theophylline; penicillins may decrease renal excretion of MTX; broad-spectrum PO antibiotics may decrease MTX bioavailability; large doses of folate may decrease MTX's efficacy; additional folate antagonists (eg, TMP/SMX) may have additive myelosuppression

Documented hypersensitivity; hepatic or renal impairment; bone marrow suppression

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Photosensitivity; bone marrow suppression; hepatotoxicity; pulmonary fibrosis; teratogenicity; oncogenic potential


Cyclophosphamide (Cytoxan, Neosar)

Alkylating agent, believed to be cytotoxic to dividing cells by cross-linking cellular DNA. Processed in liver to active metabolites; byproducts (eg, acrolein) accumulate in bladder and cause cystitis.

Adult

1-2.5 mg/kg/d PO or 500 mg to 1 g/m2 BSA IV every mo

Pediatric

Administer as in adults

Allopurinol; chloramphenicol; digoxin; hydrochlorothiazide; live vaccines; pentostatin; rotavirus vaccine; succinylcholine; tamoxifen

Documented hypersensitivity; severely depressed bone marrow function; with PO dosing, severe hemorrhagic cystitis is 15%, but with IV hydration with MESNA, hemorrhagic cystitis occurs rarely if ever

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increased risk of infections; alopecia; hemorrhagic cystitis; teratogenicity; oncogenic potential; male and female infertility; cardiomyopathies


Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft vs host disease for a variety of organs. Doses used in autoimmune diseases are generally lower than those used in transplant patients. Initiate at lowest dose possible, then taper to lowest effective dose as soon as possible. Attempt discontinuing cyclosporine to determine if therapy can stop.

Adult

1-3 mg/kg/d PO initially; may increase gradually to 5 mg/kg/d PO as needed to control symptoms; maintain at lowest effective dose

Pediatric

Administer as in adults

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease cyclosporine concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase cyclosporine toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis since it 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

Evaluate renal and liver functions often by measuring BUN, serum creatinine, and serum bilirubin levels and liver enzymes; may increase risk of infection and lymphoma; reserve IV use only for those who cannot take PO

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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Further Reading

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Keywords

Takayasu arteritis, TA, Takayasu's arteritis, Takayasu disease, Takayasu's disease, Takayasu syndrome, Takayasu's syndrome, pulseless disease, nonspecific aortoarteritis, reverse coarctation, aortic arch syndrome, aortitis syndrome, vascular insufficiency, myocarditis, aortic regurgitation, thrombosis, hypertension, aortic root dilation, mesenteric ischemia, carotidynia, granulomatous vasculitis, tuberculosis, stroke, cardiac failure, ventricular fibrillation, erythema nodosum–like lesions, pyoderma gangrenosum, leukocytoclastic vasculitis, panniculitis, syncope

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Contributor Information and Disclosures

Author

Christine Hom, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Rheumatology, New York Medical College
Christine Hom, MD is a member of the following medical societies: American College of Rheumatology, American Medical Association, and Arthritis Foundation
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Thomas JA Lehman, MD, FAAP, FACR, Clinical Professor of Pediatrics, Department of Pediatrics, Division of Pediatric Rheumatology, Weill-Cornell University; Chief, Hospital for Special Surgery
Thomas JA Lehman, MD, FAAP, FACR is a member of the following medical societies: PM American Allergy Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting; Pfizer Honoraria Consulting

Chief Editor

Barry L Myones, MD, Associate Professor, Departments of Pediatrics and Immunology, Pediatric Rheumatology Section, Baylor College of Medicine; Director of Research, Pediatric Rheumatology Center, Texas Children's Hospital
Barry L Myones, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American College of Rheumatology, American Heart Association, American Society for Microbiology, Clinical Immunology Society, and Texas Medical Association
Disclosure: Nothing to disclose.

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