eMedicine Specialties > Cardiology > Peripheral Vascular Disease

Aortitis: Treatment & Medication

Author: Masato Okada, MD, FACP, FACR, FAAAAI, Consulting Staff, Section of Allergy and Rheumatology, Department of Medicine, St Luke's International Hospital, Tokyo
Coauthor(s): Justin D Pearlman, MD, PhD, ME, MA, Director of Dartmouth Advanced Imaging Center, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center
Contributor Information and Disclosures

Updated: Mar 25, 2008

Treatment

Medical Care

Extremely careful attention to accurate and thorough diagnosis is crucial. If vasculitis stems from infection, eradicating the infection prior to initiating immune suppression therapy is generally vital. The primary goals of therapy are to (1) stop progression of inflammatory disease, (2) treat complications, and (3) monitor for reactivation.

• The mainstay of therapy for arteritis is corticosteroids; however, a substantial percentage of patients require additional immunosuppressive agents such as cyclophosphamide, methotrexate, or mycophenolate mofetil.
  • Daily prednisone in doses of 1 mg/kg, not to exceed 60 mg/d, should be given for 1-3 months to patients with active arteritis. When the symptoms and laboratory test results related to the inflammatory process improve, the prednisone should be tapered slowly over several months. The maximum reduction should be 10% of the daily amount per week. Long-term low-dose prednisone therapy may be necessary to prevent progression of arterial stenoses.
  • As many as 75% of patients respond favorably to this regimen, but the remaining patients and patients whose disease relapses with the tapering must receive immunosuppressants.
  • Weekly doses of methotrexate are thought to be less toxic than daily doses of cyclophosphamide. In a study by Hoffman et al¹⁰ of 16 patients whose disease was resistant to corticosteroid therapy, weekly methotrexate (mean dose 17.1 mg; range 10-25 mg) produced remissions in 81%. Relapse occurred in 44% when the corticosteroids were tapered to or near discontinuation; reinstitution of corticosteroids led to remission, and 3 of 7 patients in this group successfully stopped glucocorticoid therapy.
  • A promising case report of 3 patients with resistant disease who were treated with mycophenolate mofetil (1 g PO bid) has been published¹¹ , and the lower toxicity of mycophenolate mofetil makes this regimen an attractive alternative.
  • Anti-tumor necrosis factor agents (anti-TNFs), etanercept and infliximab, were administered to patients with active and relapsing Takayasu arteritis despite glucocorticoid therapy. Only 1 out of 15 patients did not respond and 10 patients achieved sustained remission.¹² Larger and randomized controlled studies are necessary to determine the role of anti-TNFs in the management of aortitis.
  • Aortic involvement in temporal arteritis (giant cell arteritis) is not uncommon. Nuenninghoff at al¹³ reported that 46 out of 168 patients (27%) had large-artery complication. Eighteen percent of the patients had aortic aneurysm and/or aortic dissection, and 13% developed large-artery stenosis. Low-dose aspirin in addition to glucocorticoid is accepted as a standard in the initial treatment of giant cell arteritis because of the benefit in reducing the rate of visual loss and cerebrovascular accidents. Long-term, low-dose aspirin has not been shown to have any effect in aortic complication.
  • Matsuyama et al¹⁴ administered minocycline, 100 mg bid, for 3 months to 11 patients who had active Takayasu arteritis despite prednisolone therapy. Nine out of 11 patients were considered to be in remission at the end of the study.
• No reliable method of determining the activity of arteritis is established, and no single test should be relied upon. As mentioned above, FDG-PET and MMP-3 and MMP-9 might provide additional information to monitor the activity of aortitis.
  • According to vascular specimens obtained at the time of bypass surgery and sequential angiographic studies, active vasculitis is present in approximately 50% of patients who lack symptoms of active inflammation or have a normal ESR.
  • To prevent progression of vascular lesions and to reduce the necessity of surgical procedures in the later stage, careful monitoring of disease activity with sequential imaging studies and more prolonged immunosuppressive treatments may be necessary.
• As the prognosis of patients with arteritis improves, prevention of atherosclerotic disorders becomes more important. Treatment of hypertension and congestive heart failure should be instituted if these complications occur, and serum cholesterol levels and homocysteine levels should be monitored, especially if the patients require long-term corticosteroid therapy.

Surgical Care

According to the experience at the Cleveland Clinic Foundation, vascular interventions for Takayasu arteritis resulted in a high failure rate: eleven out of 31 bypass grafts, 3 of 7 percutaneous transluminal angioplasty, and 5 of 7 stents restenosed or occluded.¹⁵

• Angioplasty or bypass grafts or stents may be necessary once arterial stenosis has occurred.
• Surgical repair or angioplasty are necessary in cases described as follows:
  • Significant hypertension resulting from renovascular stenosis
  • Myocardial ischemia secondary to coronary artery involvement
  • Disabling extremity claudication unresponsive to medical treatment
  • Cerebral ischemia
  • Aortic root dilatation leading to significant aortic regurgitation
  • Thoracic or abdominal aortic aneurysms larger than 5 cm in diameter
• Stenoses or occlusions affecting lengthy portions of an artery may make angioplastic dilation of an involved segment technically difficult. In addition, the heavily scarred arteries in patients with Takayasu arteritis sometimes are not managed as easily by angioplasty as cases of atherosclerosis. Bypass grafting can abolish the possibility of restenosis resulting from continued inflammation in a treated segment.

Consultations

• Infectious disease - To eliminate possibility of Neisseria, Rickettsia, spirochete, fungal, or viral (herpes, hepatis B, hepatitis C) causes
• Rheumatology - To investigate the many immunologic diseases that may result in vasculitis, including Henoch-Schönlein purpura, SLE, rheumatoid arthritis, cryoglobulinemia, serum sickness, Wegener granulomatosis, polyangiitis, Churg-Strauss syndrome, Goodpasture syndrome, and Kawasaki disease
• Cardiology - To evaluate aortic insufficiency, congestive heart failure, ischemia, and stenoses, for consideration of valve replacement, aneurysm repair, angioplasty, or stent placement
• Cardiovascular surgery - To evaluate carotid stenosis, aortic dilation, arterial bypasses, and/or perform diagnostic biopsy

Activity

Activity may be limited by claudication (ie, ischemic pain from limb use) or by aortic insufficiency and congestive heart failure.

Medication

No reliable method exists for determining the activity of arteritis. According to vascular specimens obtained at the time of bypass surgery and sequential angiographic studies, active vasculitis is present in approximately 50% of patients who lack symptoms of active inflammation or have a normal ESR. To prevent progression of vascular lesions and to reduce the necessity of surgical procedures in the later stage, careful monitoring of disease activity with sequential imaging studies and more prolonged immunosuppressive treatments may be necessary.

As the prognosis of patients with Takayasu arteritis improves, prevention of atherosclerotic disorders becomes more important. Treatment of hypertension and congestive heart failure should be instituted if these complications occur, and serum cholesterol and homocysteine levels should be monitored, especially if the patients require long-term corticosteroid therapy.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Sterapred)

Mainstay of therapy. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Daily doses should be given to patients with active Takayasu arteritis. As many as 75% of patients respond favorably to this regimen, but remaining patients, and patients who relapse with tapering, must receive immunosuppressants. Maximum reduction should be 10% of daily amount per week. Long-term low-dose therapy may be necessary to prevent progression of arterial stenoses. Complications include aseptic necrosis of hip, corticosteroid dependence, and ulcers.

Immunosuppressants

A substantial percentage of patients with aortitis or other forms of vasculitis require additional immunosuppressive agents (eg, cyclophosphamide, methotrexate, mycophenolate mofetil).

Methotrexate (Folex PFS, Rheumatrex)

Unknown mechanism of action in treatment of inflammatory reactions. May affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).
Weekly doses thought to be less toxic than daily doses of cyclophosphamide. In one study of 16 patients whose disease was resistant to corticosteroid therapy, weekly methotrexate (mean dose 17.1 mg; range 10-25 mg) produced remissions in 81%. Relapse occurred in 44% when corticosteroids were tapered to or near discontinuation. Reinstitution of corticosteroids led to remission, and 3 of 7 patients in this group successfully stopped glucocorticoid therapy.

Mycophenolate (CellCept)

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.

Cyclophosphamide (Cytoxan)

Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Anti-tumor necrosis factor agents

These agents are disease modifying drugs.

Etanercept (Enbrel)

Soluble p75 TNF receptor fusion protein (sTNFR-Ig). Inhibits TNF binding to cell surface receptors, which, in turn, decreases inflammatory and immune responses.

Infliximab (Remicade)

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. Used with methotrexate in patients who have had inadequate response to methotrexate monotherapy.

Antibiotics

Empiric antimicrobial therapy should cover all likely pathogens in the context of the clinical setting.

Minocycline (Dynacin, Minocin)

Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma.

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