RheumatologyTier 2Disease (DEADMAN)

Vasculitis - Takayasu arteritis

Description

Granulomatous large-vessel vasculitis of the aorta and its major branches
*"Pulseless disease"* - stenosis and occlusion dominate, with aneurysms in a minority
Panarteritis -> intimal proliferation, medial destruction, adventitial fibrosis -> long, smooth, tapered stenoses

Takayasu vs giant cell arteritis - the same lesion, different demographics

	Takayasu	GCA
Age	<40 (usually <50)	>50 (usually >70)
Sex	F:M ~9:1	F:M ~3:1
Ancestry	Asian, Indian, Latin American, Turkish	Northern European
Vessels	Aorta and primary branches, pulmonary arteries	Temporal and cranial arteries, aorta, subclavian/axillary
Dominant lesion	Stenosis and occlusion	Stenosis; aortic aneurysm
Blindness	Rare	The defining risk
Renal artery	Involved -> renovascular hypertension	Spared

*Age is effectively the discriminator* - large-vessel vasculitis under 40 is Takayasu

Numano angiographic types

I - aortic arch branches only
IIa - ascending aorta, arch, arch branches; IIb - + thoracic descending aorta
III - thoracic descending + abdominal aorta + renal arteries
IV - abdominal aorta and/or renal arteries only
V - combined (the commonest)
+P if pulmonary artery involved; +C if coronary

Epidemiology

Rare - ~1-3/million/yr in Western populations, much higher in Japan, India, Korea, Mexico, Turkey
F:M ~9:1
Onset typically 15-40 years; >90% before age 50
Diagnostic delay is long - median 2-3 years (non-specific constitutional phase)

Aetiopathogenesis

Granulomatous panarteritis with giant cells at the media-adventitia junction
Vasa vasorum inflammation -> adventitial thickening ("double ring" sign)
Th1 (IFN-gamma) and Th17 (IL-17) responses; IL-6 drives the systemic features
- *Primarily IL-6-mediated - the reason tocilizumab works and TNF inhibitors work less well*
Late fibrosis -> fixed, burnt-out stenoses that no longer respond to immunosuppression
*HLA-B52:01** - the strongest genetic association (particularly in Japanese populations)
Associations with IBD, sarcoidosis, ankylosing spondylitis suggest shared innate immune pathways

Diagnosis

Two clinical phases

Phase 1 - systemic/"pre-pulseless"
- Fever, malaise, weight loss, night sweats, arthralgia, myalgia
- Carotidynia, erythema nodosum, pyoderma gangrenosum
- Frequently misdiagnosed as infection or another CTD for years
Phase 2 - occlusive/"pulseless"
- Limb claudication (arm > leg), absent or diminished pulses
- Blood pressure difference between arms >10-20 mmHg
- Bruits - carotid, subclavian, abdominal
- Renovascular hypertension (renal artery stenosis)
- Aortic regurgitation (root dilatation)
- Visual disturbance, dizziness, syncope, stroke (carotid/vertebral involvement)
- Angina from coronary ostial disease
*The two phases overlap and inflammation can continue silently during the occlusive phase*

2022 ACR/EULAR classification criteria

Absolute requirements: age <=60 at diagnosis, AND imaging evidence of large-vessel vasculitis
Then weighted items: female sex (+1), angina/ischaemic cardiac pain, arm/leg claudication, vascular bruit, reduced upper-limb pulse, reduced carotid pulse, BP difference between arms >=20 mmHg, and imaging items (number of arterial territories, symmetrical paired involvement, abdominal aorta + renal or mesenteric involvement)
Score >=5 classifies Takayasu arteritis

Examination - the four-limb assessment

Blood pressure in BOTH arms and both legs
- If the subclavian arteries are stenosed, cuff BP UNDERESTIMATES central pressure - "normal" readings can conceal severe hypertension. Use the least-affected limb and central measurement if needed
All pulses including carotid, radial, brachial, femoral, dorsalis pedis
Auscultate for bruits - carotid, supraclavicular, abdominal, renal
Aortic regurgitation murmur
Fundoscopy - hypertensive and ischaemic retinopathy

Laboratory

inc ESR and CRP - but normal in up to 50% during active disease; they underestimate arterial-wall inflammation
Normocytic anaemia, thrombocytosis, hypoalbuminaemia
ANCA, ANA and rheumatoid factor negative
Exclude TB (IGRA/Mantoux) - tuberculous aortitis mimics Takayasu, and treatment requires immunosuppression
Exclude syphilis, IgG4-related aortitis, infective (mycotic) aneurysm, fibromuscular dysplasia, atherosclerosis

Imaging

Modality	Role
Catheter angiography	Gold standard for luminal anatomy - beading, long smooth tapered stenoses, occlusions, aneurysms. Invasive; shows lumen only, not wall
MRA	First-line non-invasive. Shows wall thickening and oedema in EARLY disease before luminal change. Poor resolution of distal arteries
CTA	Excellent luminal and wall detail; calcification. Radiation burden matters in young women with repeated imaging
FDG-PET/CT	More sensitive than MRI in early disease and useful for monitoring activity. Steroids suppress uptake - image before or early in treatment
Ultrasound	Carotid/subclavian wall thickening; helps distinguish arteritis from atherosclerosis; operator-dependent

Baseline whole-aorta imaging in everyone, then serial imaging - clinical assessment and inflammatory markers alone miss progression
Echocardiogram - aortic root, aortic regurgitation, LV function

Management

Axis: disease phase - suppress active inflammation, then revascularise fixed lesions once quiescent. The two must not be reversed.

A. Induction

Prednis(ol)one 0.5-1 mg/kg/day, tapered over months
- Pulse methylprednisolone for critical ischaemia
*Add a steroid-sparing agent at the outset - relapse on steroid monotherapy is the rule (>50%)*
- Methotrexate, azathioprine, mycophenolate or leflunomide

B. Refractory or relapsing disease

Tocilizumab (anti-IL-6R) - the disease is primarily IL-6-driven
- *Abolishes CRP and ESR - relapse must then be judged on imaging and symptoms*
TNF inhibitors (infliximab, adalimumab) - effective in some series but less effective than in other vasculitides
Rituximab - limited evidence, used in refractory disease
JAK inhibitors - emerging

C. Vascular management

Antiplatelet (low-dose aspirin) in all with arterial stenosis
Aggressive blood pressure control
- ACE inhibitor/ARB for renovascular hypertension - with caution and monitoring if bilateral renal artery stenosis
- Measure BP in the least-affected limb and cross-check centrally
Statin, smoking cessation, cardiovascular risk factor management

D. Revascularisation

*Only for critical, symptomatic, FIXED lesions and only during remission*
- Operating on an actively inflamed vessel causes restenosis, anastomotic aneurysm and graft failure
Indications: critical limb or organ ischaemia, cerebrovascular symptoms with severe carotid/vertebral stenosis, renovascular hypertension refractory to medical therapy, severe coarctation, severe aortic regurgitation, expanding aneurysm
Bypass grafting outperforms angioplasty/stenting for durability in Takayasu (restenosis rates after endovascular treatment are high)
Continue immunosuppression through the perioperative period

E. Monitoring

Clinical: symptoms, pulses, BP in all four limbs, bruits, new murmurs
ESR/CRP (unreliable, and uninterpretable on tocilizumab)
Serial MRA or PET at 6-12 month intervals - progression can be entirely silent
ITAS2010 / Kerr criteria for activity assessment
Bone protection, vaccination, cardiovascular risk assessment
Pregnancy: possible with quiescent disease; risk of hypertension, pre-eclampsia and aortic dissection - manage in a high-risk unit

Associations

*HLA-B52:01**
Inflammatory bowel disease (Crohn > UC)
Ankylosing spondylitis and other spondyloarthropathies
Sarcoidosis
Erythema nodosum, pyoderma gangrenosum
Tuberculosis - epidemiological association and a critical differential
Renovascular hypertension; aortic regurgitation
Pulmonary artery involvement (~50% on imaging) -> pulmonary hypertension
Coronary ostial stenosis -> angina and MI in young women

Natural history & complications

Chronic and relapsing - relapse in >50%, often clinically silent
Vascular damage accrues even with normal inflammatory markers - the reason for serial imaging
10-yr survival ~80-90%; ~20% follow a monophasic course requiring no long-term therapy
Late deaths from stroke, myocardial infarction, heart failure, aortic rupture and renal failure

Poor prognostic markers

Severe aortic regurgitation
Retinopathy
Severe hypertension
Aneurysm formation
Progressive disease course
Presence of two or more of these markedly reduces survival

Complications

Stroke and TIA; visual loss
Renovascular hypertension and CKD
Aortic regurgitation and heart failure
Myocardial infarction from coronary ostial disease
Aortic aneurysm, dissection and rupture
Limb claudication and critical ischaemia
Pulmonary hypertension
Restenosis and graft failure after revascularisation performed during active disease
Glucocorticoid toxicity in young women - osteoporosis, growth impairment, diabetes, cataract

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