Pediatric Takayasu Arteritis Treatment & Management

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 Takayasu arteritis rarely require bypass surgery or 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. 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 Takayasu arteritis 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.

Monitor medications and adverse effects in patients with Takayasu arteritis. In addition, monitor acute phase reactants as a limited measure of disease activity.

Perform regular imaging of affected vasculature, as well as surveillance imaging for new lesions. Treatment may be monitored with MRI and/or MRA or CT scanning. Mural thickening is observed to decrease with corticosteroid treatment.

Recognizing that Takayasu arteritis may progress in the absence of clinical findings is important. Patients with normal erythrocyte sedimentation rates who are undergoing graft placement have been found to have active aortitis in the resected segment. Periodic imaging may identify an active disease by the appearance of new areas of stenosis, despite normal erythrocyte sedimentation rate and the absence of clinical features. The presence of active disease requires treatment with corticosteroids; however, current markers of disease activity are inadequate to identify all patients with disease flare.

Serial MRI may reveal vessel wall edema, but whether this measures actual inflammation is unclear. Structural changes visible on imaging demonstrate disease progression, but reliable indicators of vessel inflammation prior to structural damage have yet to be identified.

Medical evaluation and treatment of patients with Takayasu arteritis can be performed on an outpatient basis unless the patient is acutely ill. The 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.

Following the acute phase, patients with fibrotic changes require surgical treatment of symptomatic stenotic or occlusive disease.

Activity

Patient activity is generally self limiting, based on cardiac status

Consultations

Consult with the following specialists as needed:

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

Daily high-dose corticosteroid administration is the mainstay of initial therapy. The authors have used prednisone at 1-2 mg/kg/day 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. However, 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 (IV) cyclophosphamide have been used in individuals with glucocorticoid-resistant Takayasu arteritis. 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.^[13]

Historically, cyclosporine has also been used, as it is less toxic than an alkylating agent. However, cyclosporine is often associated with decreased renal function and increased blood pressure, which may aggravate the damage to the heart and great vessels; it is used less frequently.

Mycophenolate mofetil may be useful to treat individuals with glucocorticoid-resistant disease.^{[14, 15]} Case reports suggest disease control and steroid sparing.

TNF inhibitors offer treatment for patients with relapses or refractory disease. Infliximab has been used in children with Takayasu arteritis.^[16] A small open-label 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 10 of 15 patients who were steroid dependent.^{[17, 18, 19]} Escalating doses may be needed to maintain control.^[17]

The role of TNF inhibition in treating initial disease or relapses has 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.

New reports demonstrate the use of rituximab, monoclonal anti-CD20 antibody, for disease control and steroid sparing in patients with Takayasu arteritis. Treatment regimens have been the 4-week lymphoma protocol (375 mg/m² weekly for 4 wk) or the 2-week fixed-dose rheumatoid arthritis protocol (1000 mg repeated once 14 d later).

Similarly, case reports of tocilizumab (monoclonal anti–IL-6 receptor antibody) have described remission induction in Takayasu arteritis resistant to other treatments. IL-6 levels are elevated in Takayasu patients and correspond with disease activity, making this an attractive target for therapy.^[20]

Anecdotal reports of matrix metalloproteinase inhibition using minocycline suggest that this may be a useful adjunctive therapy, which may also allow lower doses of corticosteroids and, thus, reduced toxicity. This does not replace immunosuppressive therapy with steroids and other treatments.