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Pediatric Takayasu Arteritis Treatment & Management

  • Author: Christine Hom, MD; Chief Editor: Lawrence K Jung, MD  more...
 
Updated: Nov 03, 2015
 

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 standard initial therapy.

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

Patient activity is generally self limiting, based on cardiac status. Most children participate uneventfully in school and play activities.

Consult with the following specialists as needed:

  • Pediatric rheumatologist
  • Ophthalmologist
  • Pediatric cardiologist
  • Vascular surgeon
  • Interventional radiologist
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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. In an adult series of 15 supraaortic stenosis treated with endovascular stenting and 24 lesions treated with carotid bypass surgery, 53% reoccluded in the stent group and 12.5% in the surgical group.[23]

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. For superficial lesions, ultrasound may be an effective way to monitor disease without radiation exposure. FDG-PET, with its coregistered CT, has significant radiation exposure but can image the thoracic aorta.

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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.[24]

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, up to 90% respond; however, two thirds progress or relapse on steroid taper.

Patients who do not respond to glucocorticoids or who relapse during corticosteroid taper require a second agent. For patients with ongoing inflammatory disease or those dependent on moderate doses of prednisone, many immunosuppressant and anticytokine regimens have been tried. Methotrexate, infliximab, etanercept, cyclosporine, cyclophosphamide, and mycophenolate mofetil have all had some steroid-sparing effect. These medications can allow disease control and weaning from steroids. Other patients remain steroid dependent but are able to taper the steroid dose. Small numbers of patients are resistant to multiple treatments and continue to have active disease.

Mycophenolate mofetil may be useful to treat individuals with glucocorticoid-resistant disease.[25, 26] Case reports suggest disease control and steroid sparing. In a series of 21 patients,[27] the average sedimentation rate fell from 68 to 43 mm/h (P =.003) and the average prednisone dose from 36 to 19 mg/d. Cases of patients discontinuing prednisone and having no progression of disease for several months are reported.

Leflunomide has been used in glucocorticoid-resistant and methotrexate-resistant disease.[28] Tumor necrosis factor (TNF) inhibition with etanercept or infliximab has also been used in relapsing disease or glucocorticoid-dependent disease. 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; it is used less frequently.

TNF inhibitors offer treatment for patients with relapses or refractory disease. Infliximab has been used in children with Takayasu arteritis.[29, 30, 31] In patients treated with TNF inhibitors, renewed disease activity has been seen on withdrawal. Patients with disease despite treatment may benefit from a change to a different TNF inhibitor, or escalating the dose, in the case of infliximab.  A retrospective case series by Stern et al found that infliximab was equivalent to cyclophosphamide with fewer adverse effects, making infliximab an alternative therapeutic option.[32]  

Response to TNF inhibitors in a small series has ranged from 74-90%; patients continuing treatment have been reported with stable disease for 24-36 months. These are patients previously with active disease, with relapse, or with progression on treatment.[33] In a series of 15 patients,[29] 14 were able to taper steroids and 10 were able to wean off steroids entirely while on infliximab. One patient did not respond. Withdrawal of the TNF inhibitor was briskly followed by relapse, suggesting that control of active disease is possible, but treatment is needed to maintain control.

The presence of antiendothelial antibodies and plasmablast expansion in patients with active Takayasu arteritis suggest a role for B-cell–based therapies. Reports using rituximab, monoclonal anti-CD20 antibody for disease control and steroid sparing in patients with Takayasu arteritis show promise.[8] 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). Patients were able to taper prednisone and had no new disease manifestations. Peripheral plasmablasts decreased in number, rising again with signs of relapse.

Similarly, case reports of tocilizumab (monoclonal anti–IL-6 receptor antibody) have described remission induction in Takayasu arteritis resistant to other treatments.[9, 10] IL-6 levels are elevated in Takayasu patients and correspond with disease activity, making this an attractive target for therapy.[34]

IL-6 blockade reduces production of Th17 cells, indirectly reducing levels of TNF-aα and IL-6. Treated patients showed lower C-reactive protein levels and reversal of some ischemic changes (pulses improved). FDG-PET scans showed decreased FDG uptake in the great vessels. After 6 monthly infusions, patients were transitioned to weekly methotrexate as maintenance.[9]

A 3-year-old girl was treated with tocilizumab[35] and stenosis of the brachiocephalic artery demonstrated increased flow along with normal inflammatory markers. This child continued for over 2 years on tocilizumab and mycophenolate mofetil.

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, 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, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

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

  2. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013 Jan. 65(1):1-11. [Medline].

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

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

  5. 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. 2012 Jan. 71(1):75-9. [Medline].

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

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

  8. Ernst D, Greer M, Stoll M, Meyer-Olson D, Schmidt RE, Witte T. Remission achieved in refractory advanced takayasu arteritis using rituximab. Case Rep Rheumatol. 2012. 2012:406963. [Medline].

  9. Salvarani C, Magnani L, Catanoso MG, et al. Rescue treatment with tocilizumab for Takayasu arteritis resistant to TNF-a blockers. Clin Exp Rheumatol. 2012 Jan-Feb. 30(1 Suppl 70):S90-3. [Medline].

  10. Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012 Nov. 64(11):1720-9. [Medline].

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

  12. [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. 2005 Feb 8. 111(5):697-716. [Medline].

  13. Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010 May. 69(5):798-806. [Medline].

  14. Szugye HS, Zeft AS, Spalding SJ. Takayasu Arteritis in the pediatric population: a contemporary United States-based single center cohort. Pediatr Rheumatol Online J. 2014. 12:21. [Medline].

  15. Dagna L, Salvo F, Tiraboschi M, Bozzolo EP, Franchini S, Doglioni C, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med. 2011 Oct 4. 155(7):425-33. [Medline].

  16. Ishihara T, Haraguchi G, Tezuka D, Kamiishi T, Inagaki H, Isobe M. Diagnosis and assessment of Takayasu arteritis by multiple biomarkers. Circ J. 2013. 77(2):477-83. [Medline].

  17. 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. 2007 May. 45(5):906-14. [Medline].

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

  19. Ginde S, Cava JR, Southern JF, Saudek DE. Delayed contrast-enhanced magnetic resonance imaging in the evaluation of Takayasu arteritis. J Am Coll Cardiol. 2012 Mar 20. 59(12):e23. [Medline].

  20. Jiang L, Li D, Yan F, Dai X, Li Y, Ma L. Evaluation of Takayasu arteritis activity by delayed contrast-enhanced magnetic resonance imaging. Int J Cardiol. 2012 Mar 8. 155(2):262-7. [Medline].

  21. 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].

  22. Schmidt WA, Blockmans D. Use of ultrasonography and positron emission tomography in the diagnosis and assessment of large-vessel vasculitis. Curr Opin Rheumatol. 2005 Jan. 17(1):9-15. [Medline].

  23. Kim YW, Kim DI, Park YJ, Yang SS, Lee GY, Kim DK. Surgical bypass vs endovascular treatment for patients with supra-aortic arterial occlusive disease due to Takayasu arteritis. J Vasc Surg. 2012 Mar. 55(3):693-700. [Medline].

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

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

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

  27. Goel R, Danda D, Mathew J, Edwin N. Mycophenolate mofetil in Takayasu's arteritis. Clin Rheumatol. 2010 Mar. 29(3):329-32. [Medline].

  28. 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. 2001 Jul-Aug. 19(4):477-8. [Medline].

  29. 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. 2004 Jul. 50(7):2296-304. [Medline].

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

  31. 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].

  32. Stern S, Clemente G, Reiff A, Ramos MP, Marzan KA, Terreri MT. Treatment of Pediatric Takayasu arteritis with infliximab and cyclophosphamide: experience from an American-Brazilian cohort study. J Clin Rheumatol. 2014 Jun. 20 (4):183-8. [Medline].

  33. Schmidt J, Kermani TA, Bacani AK, Crowson CS, Matteson EL, Warrington KJ. Tumor necrosis factor inhibitors in patients with Takayasu arteritis: experience from a referral center with long-term followup. Arthritis Care Res (Hoboken). 2012 Jul. 64(7):1079-83. [Medline].

  34. 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. 2011 Jan 17. 141:w13156. [Medline].

  35. Bravo Mancheno B, Perin F, Guez Vazquez Del Rey Mdel M, Garcia Sanchez A, Alcazar Romero PP. Successful tocilizumab treatment in a child with refractory Takayasu arteritis. Pediatrics. 2012 Dec. 130(6):e1720-4. [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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