TAKAYASU ARTERITIS

SIDNEY ERWIN T. MANAHAN, MD, FPCP, FPRA

Internal Medicine - Rheumatology

Challenges in Managing

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?

Early Onset Granulomatous Arteritis

TAKAYASU ARTERITIS (TAK)

Giant Cell Arteritis (GCA)

Polyarteritis Nodosa (PAN)

Kawasaki Disease (KD)

Cryoglobulinemic Vasculitis (CV)

IgA Vasculitis (IgAV)

Urticarial Vasculitis (HUV)

Microscopic Polyangiitis (MPA)

Granulomatosis with Polyangiitis (GPA)

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Behcet’s Disease (BD)

Cogan’s Syndrome (CS)

Disease Course

TIME COURSE

DIS

EA

SE A

CT

IVIT

Y

SYSTEMIC

(Pre-vasculitic)

VASCULAR BURNOUT

Constitutional

Symptoms

Inflammatory

Features

Vascular

Insufficiency

(stenosis,

aneurysms) Remission

Diagnosing Takayasu Arteritis

1990 ACR

• Age <40years

• Limb claudication

• Decreased brachial pulse

• SBP difference >10mmHg

• Bruit over the subclavian or aorta

• Arteriogram abnormality

1996 Sharma Modified

• Left midsubclavian artery lesion

• Right midsubclavian artery

lesion

• Characteristic s/sx for >1 month

• ESR >20mm/Hr

• 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

Biomarkers in Diagnosis

Ishihara T, et al. Circulation J 2012: doi: 10.1253/circj.CJ-12-0131

TAK Disease Course

TIME COURSE

DIS

EA

SE A

CTIV

ITY

• Control Inflammation

• Relieve symptoms

• Limit extent of vessel involvement

• Monitor disease activity

• Corrective vascular interventions

20%

80%

Ma J, et al. J Vasc Surg 2010; 51: 700-6. Subramanyan R, et al. Circulation 1989, 80: 429-37

Biomarkers of Activity

Useful in Monitoring

• ESR

• CRP (>2050ng/ml)

• Serum Amyloid A (SAA)

• C4 Binding Protein (C4BP)

• Pentraxin3 (PTX3)

• Matrix Metalloproteinase-9

(MMP-9)

Not Useful

• Fibrinogen, Haptoglobin

• CRP

• -Acid glycoprotein

• Serum Amyloid P

• C4a, C3c

• Transthyretin

• 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.

Biomarkers of Activity

Biomarker Active TA Inactive TA Controls P-value

ESR 39.1 + 24.8 15.2 + 9.6 11.3 + 5.1 <0.05

Elevated ESR (%) 83 28 0

SAA 95.9 (51.9) 49.2 (82) 23.9 (50.1) <0.005

C4BP 88.5 (72.6) 61.7 (57.7) 32.6 (32.1) <0.005

CRP 6.65 (18.1) 2.3 (5.75) 2.28 (1.58) 0.116

C4a 13.3 (13.6) 14.9 (10.4) 16 (23.9) 0.784

C3c 689.8 + 263 780.8 + 231 793 + 225 0.513

Values listed as Mean + SD or Median (Interquartile range)

Ma J, et al. J Vasc Surg 2010; 51: 700-6.

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.

Performance of Imaging Modalities

CT/ MR

Angiography

High Resolution

Ultrasound

18F-FDG PET

Scan

Early diagnosis

Disease extent

Disease activity

Evaluate response

Differentiate vs.

atherosclerosis

Mason J. Nature Rev Rheum 2010.

Monitor every

6 MONTHS

for evidence of

progressive

vascular disease

No SINGLE modality provides all the

information required. Modalities may have distinct or

complementary roles in care.

Determining TAK Activity

National 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.

Determining TAK Activity

REMISSION

• Absence of symptoms

• Normal inflammatory

markers

• No new imaging findings

SUSTAINED REMISSION

• Remission criteria for AT

LEAST 6 months

• Steroid dose <10mg/day

Controlling Disease Activity

Prednisone

Japan Guidelines

• Starting dose: 20-30 mg/d

• Maximum dose: 60 mg/d

American College of Rheumatology

• Max starting dose: 60 mg/d

DMARDs

MTX

AZA

CsA

CYC

MMF

BIOLOGICS

Infliximab*

Etanercept*

Tocilizumab

* 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

Prednisone 0.5 – 1 mkd

Is disease

INACTIVE?

(Can taper steroids)

MTX 7.5 – 25mg/wk

AZA 2 mkd

CsA 3 mkd

CYC PO 50-100 mg/d

(IV 300-750 mg/m2 /mo)

MMF 1.5 – 3 mg/d

Infliximab 5mg/kg/dose

Etanercept 25 mg 2/wk

Ineffective

Ineffective

Difficult to taper

Tocilizumab 8 mg/kg/mo

Ineffective

Medical Management of TAK

JCS Joint Working Group. Circ J 2011; 75: 474-503. Johnston SL, et al. J Clin Path 2002; 55: 481-486

TAK Surgery

Best done during Inactive Phase

• Prevent restenosis, anastomotic failure, thrombosis,

hemorrhage and infection

If 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

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

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