Cryoglobulinaemic Vasculitis
Rheumatology | Small-vessel Vasculitis | Vasculitides
Overview
Takayasu arteritis is a rare, chronic large-vessel vasculitis primarily affecting the aorta and its major branches, leading to stenosis, occlusion, or aneurysm formation. It most commonly affects young women (<40 years), particularly of Asian descent. The global incidence is estimated at 1–2 per million per year, with a female predominance (F:M ~9:1). It is also called “pulseless disease” due to the hallmark feature of absent peripheral pulses in late-stage disease.
Takayasu arteritis is named after Mikito Takayasu, a professor of ophthalmology at Kanazawa University in Japan, who, in 1905, presented a case of a 21-year-old woman with wreath-like retinal vascular anastomoses at the Annual Meeting of the Japanese Ophthalmology Society.
Definition
Stenosis: Narrowing of a vessel, reducing blood flow.
Bruits: Audible vascular turbulence over narrowed vessels, a hallmark in TA.
Anatomy and Physiology
- The aorta and its major branches (subclavian, carotid, renal arteries) are the primary vessels involved.
- These are elastic arteries, accommodating high-pressure blood flow.
Remember
Subclavian and carotid artery involvement often explains neurological and upper limb symptoms in TA.
Aetiology and Risk Factors
Aetiology
- Unknown; likely autoimmune-mediated granulomatous inflammation.
- Possible links to infectious triggers (e.g., Mycobacterium tuberculosis).
- Genetic associations (e.g., HLA-B52) reported in some populations.
Risk Factors
- Female sex
- Age <40 years
- Asian or Latin American ethnicity
- Family history (rare)
Pathophysiology
TAK is a panarteritis, but the initial site of inflammation is around the vasa vasorum and at the medio-adventitial junction. Large and medium-sized arteries are considered immune-privileged sites. Vascular dendritic cells, located near the vasa vasorum, function as gatekeepers by restricting lymphocyte entry and dampening local immune-inflammatory responses.
- Immune tolerance is disrupted when intrinsically abnormal dendritic cells (DCs) become activated by unknown stimuli. Abnormal DCs activate immune response towards large arteries.
- Immune activation targets large arteries → granulomatous inflammation of vessel wall.
- Inflammatory infiltrate damages elastic lamina and media → intimal hyperplasia and fibrosis.
- Leads to:
- Stenosis or occlusion of affected arteries
- Aneurysm formation in weakened segments
- Ischemia in affected organ systems (e.g., brain, limbs, kidneys)
- Chronic phase dominated by fibrotic vessel wall thickening.
Think
The phase of inflammation (active vs fibrotic) impacts treatment and imaging findings.
Clinical Manifestations
Takayasu arteritis most commonly presents in young women under 40–50 years of age, particularly of Asian descent. Early Takayasu arteritis often goes undiagnosed because clinical features are nonspecific, but progression is associated with obstructive or aneurysmal lesions.
In addition to constitutional manifestation symptoms are related to the severity of specific arterial involvement.
| Phase | Description |
| Systemic (Pre-pulseless) phase | Non-specific inflammatory symptoms, mimicking infection or autoimmune disease |
| Occlusive (Vascular) phase | Ischemic symptoms due to progressive arterial stenosis or occlusion |
| Artery Involved | Clinical Manifestations |
| Subclavian artery | Upper limb claudication, asymmetric BP, subclavian steal syndrome |
| Carotid artery | Amaurosis fugax/Takayasu retinopathy (ophthalmic artery) TIA/stroke, carotidynia, cervical bruit |
| Vertebral artery | Posterior circulation TIA, vertigo, ataxia |
| Aortic arch/thoracic aorta | Pulse deficits, aortic regurgitation, thoracic bruit |
| Abdominal aorta | Mesenteric ischemia (intestinal angina), lower limb claudication, bruit |
| Renal arteries | Renovascular hypertension, hypertensive encephalopathy, CKD |
| Coronary arteries | Angina, myocardial infarction |
| Pulmonary arteries | Pulmonary hypertension, dyspnea, hemoptysis |
Think
Suspect Takayasu in young female with unexplained hypertension, arm claudication, or pulse deficits.
Examination findings
- Unequal/absent pulses (usually upper limbs)
- Blood pressure discrepancy between arms (>20 mmHg)
- Bruits over subclavian/carotid/aorta
- Hypertension (due to renal artery involvement)
- Retinopathy (from carotid involvement)
Remember
Always check bilateral BP in young women with claudication or unexplained hypertension.
Diagnosis
| Classification Criteria for Takayasu Arteritis (2022 ACR/EULAR) | ||
| Category | Feature | Points |
| Absolute Requirements | Age ≤ 60 years at time of diagnosis | Required |
| Evidence of vasculitis in the aorta or its branches on imaging | Required | |
| Additional Clinical Criteria | Female sex | +1 |
| Angina or ischemic cardiac pain | +2 | |
| Arm or leg claudication | +2 | |
| Vascular bruit over aorta or major arteries | +2 | |
| Reduced or absent pulse in upper extremity (axillary, brachial, or radial arteries) | +2 | |
| Carotid artery abnormality on imaging | +2 | |
| Systolic blood pressure difference ≥ 20 mm Hg between arms | +1 | |
| Additional Imaging Criteria | One affected arterial territory | +1 |
| Two affected arterial territories | +2 | |
| Three or more affected arterial territories | +3 | |
| Symmetric involvement of paired arteries (e.g., bilateral carotid or renal arteries) | +1 | |
| Abdominal aorta involvement with either renal or mesenteric arteries | +3 | |
| Diagnosis = Total score ≥ 5 | ||
Investigations:
- Inflammatory markers: ↑ ESR, ↑ CRP
- Imaging:
- CT Angiography (CTA) or MR Angiography (MRA): Vessel wall thickening, stenosis, aneurysm
- PET-CT: Active inflammation
- Conventional angiography: Gold standard for vessel lumen but not wall
- Autoimmune panel: Usually negative (ANA, ANCA)
Differential Diagnoses:
| Condition | Differentiators |
| Giant cell arteritis | Age >50, temporal artery involvement |
| Atherosclerosis | Older age, risk factors, calcifications |
| Fibromuscular dysplasia | String-of-beads appearance, no systemic symptoms |
| Coarctation of aorta | Congenital, BP difference in upper vs lower limbs |
Classification
Based on angiographic pattern (Numano classification):
| Type | Involvement |
| I | Aortic arch and branches |
| IIa | Ascending aorta, arch, branches |
| IIb | IIa + thoracic descending aorta |
| III | Thoracic + abdominal aorta |
| IV | Abdominal aorta, renal arteries |
| V | Entire aorta and branches |
Remember
Most patients have Type V, with widespread arterial involvement.
Treatment
| Phase | Treatment |
| Active inflammation | High-dose corticosteroids (prednisolone 1 mg/kg/day) |
| Steroid-sparing | Methotrexate, azathioprine, mycophenolate mofetil |
| Refractory | Biologics (e.g. tocilizumab, TNF inhibitors) |
| Vascular complications | Revascularization (angioplasty or bypass) after controlling inflammation |
Monitoring: ESR/CRP, imaging every 6–12 months.
Think
Treat inflammation aggressively before vascular repair to reduce restenosis.
Complications and Prognosis
Complications
- Hypertension (renal artery stenosis)
- Stroke, TIA
- Aortic regurgitation or aneurysm
- Limb ischemia
- Retinopathy/visual loss
- Treatment-related: Steroid toxicity, infection
Prognosis
- Chronic relapsing course
- 10-year survival >85% with treatment
- Relapse rates 30–50%; require long-term follow-up
Poor Prognostic Factors
- Delayed diagnosis
- Extensive vascular involvement (Type V)
- Severe hypertension
- Cardiac or neurologic complications
References
- Johnston SL et al. Takayasu arteritis: a review. J Clin Pathol. 2002;55(7):481–486.
- Kerr GS et al. Takayasu arteritis. Ann Intern Med. 1994;120(11):919–929.
- Terao C et al. Genetic associations with Takayasu arteritis. Curr Opin Rheumatol. 2015;27(1):1–7.
- Maksimowicz-McKinnon K et al. Clinical features and prognosis of Takayasu arteritis. Arthritis Rheum. 2007;56(3):1000–1009.
- Hellmich B et al. EULAR recommendations for large vessel vasculitis. Ann Rheum Dis. 2020;79(1):19–30.
Discussion