Pediatric Takayasu Arteritis Treatment & Management

  • Author: Christine Hom, MD; Chief Editor: Lawrence K Jung, MD   more...
 
Updated: Dec 6, 2011
 

Surgical Therapy

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.

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Monitoring

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.

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Approach Considerations

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
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Pharmacologic Therapy

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.

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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.

Chief Editor

Lawrence K Jung, MD  Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

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.

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. de Pablo P, Garcia-Torres R, Uribe N, et al. Kidney involvement in Takayasu arteritis. Clin Exp Rheumatol. Jan-Feb 2007;25(1 Suppl 44):S10-4. [Medline].

  2. Ozen S, Ruperto N, Dillon MJ, et al. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. Jul 2006;65(7):936-41. [Medline].

  3. Mwipatayi BP, Jeffery PC, Beningfield SJ, et al. Takayasu arteritis: clinical features and management: report of 272 cases. ANZ J Surg. Mar 2005;75(3):110-7. [Medline].

  4. Hoyer BF, Mumtaz IM, Loddenkemper K, et al. Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab. Ann Rheum Dis. Jan 2012;71(1):75-9. [Medline].

  5. Gedalia A, Cuchacovich R. Systemic vasculitis in childhood. Curr Rheumatol Rep. Dec 2009;11(6):402-9. [Medline].

  6. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. Mar 2007;56(3):1000-9. [Medline].

  7. Miller JH, Gunarta H, Stanley P. Gallium scintigraphic demonstration of arteritis in Takayasu disease. Clin Nucl Med. Nov 1996;21(11):882-3. [Medline].

  8. [Guideline] Pickering TG, Hall JE, Appel LJ, et al. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. Feb 8 2005;111(5):697-716. [Medline].

  9. Chung JW, Kim HC, Choi YH, Kim SJ, Lee W, Park JH. Patterns of aortic involvement in Takayasu arteritis and its clinical implications: evaluation with spiral computed tomography angiography. J Vasc Surg. May 2007;45(5):906-14. [Medline].

  10. Kissin EY, Merkel PA. Diagnostic imaging in Takayasu arteritis. Curr Opin Rheumatol. Jan 2004;16(1):31-7. [Medline].

  11. de Leeuw K, Bijl M, Jager PL. Additional value of positron emission tomography in diagnosis and follow-up of patients with large vessel vasculitides. Clin Exp Rheumatol. 2004;22(6 Suppl 36):S21-6. [Medline].

  12. 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].

  13. Ozen S, Duzova A, Bakkaloglu A, et al. Takayasu arteritis in children: preliminary experience with cyclophosphamide induction and corticosteroids followed by methotrexate. J Pediatr. Jan 2007;150(1):72-6. [Medline].

  14. Daina E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the treatment of Takayasu arteritis: report of three cases. Ann Intern Med. Mar 2 1999;130(5):422-6. [Medline].

  15. Shinjo SK, Pereira RM, Tizziani VA, Radu AS, Levy-Neto M. Mycophenolate mofetil reduces disease activity and steroid dosage in Takayasu arteritis. Clin Rheumatol. Nov 2007;26(11):1871-5. [Medline].

  16. Buonuomo PS, Bracaglia C, Campana A, et al. Infliximab therapy in pediatric Takayasu's arteritis: report of two cases. Rheumatol Int. Oct 23 2009;[Medline].

  17. Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. Jul 2004;50(7):2296-304. [Medline].

  18. Karageorgaki ZT, Mavragani CP, Papathanasiou MA, Skopouli FN. Infliximab in Takayasu arteritis: a safe alternative?. Clin Rheumatol. Jun 2007;26(6):984-7. [Medline].

  19. Tanaka F, Kawakami A, Iwanaga N, et al. Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and methotrexate. Intern Med. 2006;45(5):313-6. [Medline].

  20. Seitz M, Reichenbach S, Bonel HM, Adler S, Wermelinger F, Villiger PM. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series. Swiss Med Wkly. Jan 17 2011;141:w13156. [Medline].

  21. Haberhauer G, Kittl EM, Dunky A, Feyertag J, Bauer K. Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis. Clin Exp Rheumatol. Jul-Aug 2001;19(4):477-8. [Medline].

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Aortogram of a 15-year-old adolescent girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery.
MRI of thorax of 15-year-old adolescent girl with Takayasu arteritis. Note aneurysms of descending aorta.
Coronal MRI of abdomen of 15-year-old adolescent girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys.
 
 
 
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