Challenges in Managing Takayasu Arteritis

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Presentation given during the 10th Annual Convention of the Philippine Society of Vascular Medicine.

Published in: Health & Medicine

Challenges in Managing Takayasu Arteritis

  1. 1. Challenges in ManagingTAKAYASU ARTERITISSIDNEY ERWIN T. MANAHAN, MD, FPCP, FPRA Internal Medicine - Rheumatology
  2. 2. Scenarios• Among patients in “clinical remission” and on stable medical therapy, what do we do if there is disease progression?• Among patients with fixed stenosis not amenable to medical treatment, when do we send for intervention?
  3. 3. Early Onset Granulomatous Arteritis Cryoglobulinemic Vasculitis (CV) IgA Vasculitis (IgAV) Urticarial Vasculitis (HUV) Polyarteritis Nodosa (PAN) Kawasaki Disease (KD) Microscopic Polyangiitis (MPA) Granulomatosis with Polyangiitis (GPA) Eosinophilic Granulomatosis with Polyangiitis (EGPA) TAKAYASU ARTERITIS (TAK) Giant Cell Arteritis (GCA) Behcet’s Disease (BD) Cogan’s Syndrome (CS)
  4. 4. Disease Course SYSTEMIC VASCULAR BURNOUT (Pre-vasculitic)DISEASE ACTIVITY Inflammatory Features Vascular Insufficiency Constitutional (stenosis, Remission Symptoms aneurysms) TIME COURSE
  5. 5. Diagnosing Takayasu Arteritis 1990 ACR 1996 Sharma Modified• Age <40years • Left midsubclavian artery lesion• Limb claudication • Right midsubclavian artery• Decreased brachial pulse lesion• SBP difference >10mmHg • Characteristic s/sx for >1 month• Bruit over the subclavian or aorta • ESR >20mm/Hr• Arteriogram abnormality • Carotid artery tenderness • Hypertension • Aortic regurgitation or Annuloaortic ectasia • Pulmonary artery lesion • Left mid CCA lesion • Distal inominate artery lesion • Descending thoracic aorta lesion • Abdominal aorta lesion • Coronary Artery lesion
  6. 6. Biomarkers in Diagnosis Ishihara T, et al. Circulation J 2012: doi: 10.1253/circj.CJ-12-0131
  7. 7. TAK Disease Course • Control Inflammation • Relieve symptoms • Limit extent of vessel involvementDISEASE ACTIVITY 80% 20% • Monitor disease activity • Corrective vascular interventions TIME COURSE Ma J, et al. J Vasc Surg 2010; 51: 700-6. Subramanyan R, et al. Circulation 1989, 80: 429-37
  8. 8. Biomarkers of Activity Useful in Monitoring Not Useful• ESR • Fibrinogen, Haptoglobin• CRP (>2050ng/ml) • CRP• Serum Amyloid A (SAA) • -Acid glycoprotein• C4 Binding Protein (C4BP) • Serum Amyloid P• Pentraxin3 (PTX3) • C4a, C3c• Matrix Metalloproteinase-9 • Transthyretin (MMP-9) • 1-microglobin • MMP-2, MMP-3 Ishihara T, et al. Circulation J 2012: doi: 10.1253/circj.CJ-12-0131. Ma J, et al. J Vasc Surg 2010; 51: 700-6.
  9. 9. Biomarkers of ActivityBiomarker Active TA Inactive TA Controls P-valueESR 39.1 + 24.8 15.2 + 9.6 11.3 + 5.1 <0.05Elevated ESR (%) 83 28 0SAA 95.9 (51.9) 49.2 (82) 23.9 (50.1) <0.005C4BP 88.5 (72.6) 61.7 (57.7) 32.6 (32.1) <0.005CRP 6.65 (18.1) 2.3 (5.75) 2.28 (1.58) 0.116C4a 13.3 (13.6) 14.9 (10.4) 16 (23.9) 0.784C3c 689.8 + 263 780.8 + 231 793 + 225 0.513Values listed as Mean + SD or Median (Interquartile range) Ma J, et al. J Vasc Surg 2010; 51: 700-6.
  10. 10. The IDEAL Imaging Modality in TAK• Facilitate early diagnosis• Provide assessment of disease extent• Provide assessment of inflammatory activity• Demonstrate response to treatment• Distinguish vs. atherosclerotic plaques Mason J. Nature Rev Rheum 2010.
  11. 11. Performance of Imaging Modalities CT/ MR High Resolution 18F-FDG PET Angiography Ultrasound ScanEarly diagnosis   Disease extent   Disease activity   Evaluate response   Differentiate vs.   atherosclerosis Monitor every No SINGLE modality 6 MONTHS for evidence of provides all the progressive vascular disease information required. Modalities may have distinct or complementary roles in care. Mason J. Nature Rev Rheum 2010.
  12. 12. Determining TAK ActivityNational Institutes of Health (NIH) Criteria• Systemic Features• Elevated ESR or CRP• Symptoms of Vascular Ischemia• Typical Angiographic Features New onset OR Worsening of any two of the above criteria reflects disease activity. Kerr GS, et al. Ann Int Med 1994.
  13. 13. Determining TAK Activity REMISSION SUSTAINED REMISSION• Absence of symptoms • Remission criteria for AT• Normal inflammatory LEAST 6 months markers • Steroid dose <10mg/day• No new imaging findings
  14. 14. Controlling Disease Activity Prednisone DMARDs BIOLOGICS Japan Guidelines MTX • Starting dose: 20-30 mg/d AZA Infliximab* • Maximum dose: 60 mg/d CsA Etanercept* CYC American College of Rheumatology Tocilizumab • Max starting dose: 60 mg/d MMF* Open-label trials JCS Joint Working Group. Circ J 2011; 75: 474-503. Mukhtyar C, et al. Ann Rheum Dis 2008; doi: 10.1136/ard.2008.088351. Johnston SL, et al. J Clin Path 2002; 55: 481-486
  15. 15. Medical Management of TAKPrednisone 0.5 – 1 mkd Difficult to taper Is diseaseMTX 7.5 – 25mg/wkAZA 2 mkd INACTIVE?CsA 3 mkd (Can taper steroids)CYC PO 50-100 mg/d(IV 300-750 mg/m2 /mo) IneffectiveMMF 1.5 – 3 mg/d IneffectiveInfliximab 5mg/kg/dose IneffectiveEtanercept 25 mg 2/wk Tocilizumab 8 mg/kg/mo JCS Joint Working Group. Circ J 2011; 75: 474-503. Johnston SL, et al. J Clin Path 2002; 55: 481-486
  16. 16. TAK SurgeryBest done during Inactive Phase• Prevent restenosis, anastomotic failure, thrombosis, hemorrhage and infectionIf Urgent surgery during Active Phase• ESR <30mm/hr• CRP <1mg/dl JCS Joint Working Group. Circ J 2011; 75: 474-503. Johnston SL, et al. J Clin Path 2002; 55: 481-486
  17. 17. Indications for TAK Surgery• Aortic root dilation >50mm on CT• Aortic coarctation• Aortic valve regurgitation >75% EF• Dilatation of branches of aorta >30mm• Symptomatic cerebral ischemia• Critical stenosis of >3 cerebral vessels• Cardiac ischemia w/ confirmed CAD• Renal artery lesions – esp those with HF, unstable angina, renovascular HPN, decreased renal function JCS Joint Working Group. Circ J 2011; 75: 474-503. Johnston SL, et al. J Clin Path 2002; 55: 481-486
  18. 18. Summary• Reviewed the course of Takayasu Arteritis• Discussed definitions of disease activity and remission – Role of biomarkers – Role of imaging studies• Presented the medical management of Takayasu Arteritis• Enumerated indications for surgical intervention

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