Takayasu Arteritis (TA)

Epidemiology

• Predominantly affects young women (female:male ratio up to 9-10:1)
• Median onset age: 25 years; ~25% begin before age 20
• Most prevalent in Japan, China, India, and Southeast Asia (Japan: ~150/million/year vs. 8-25/million in Western Europe/North America)
• HLA associations: HLA-Bw52, Dw12, DR2, and DQw1 in Japanese patients; different associations in Korean and Indian populations
• Non-HLA susceptibility loci identified: SVEP1, CFL2, VPS8, chr13q21
• In Mexican patients, prior exposure to Mycobacterium tuberculosis has been implicated

Pathogenesis

• Panarteritis with infiltration of dendritic cells, T cells (αβ, γδ, and cytotoxic), NK cells, and macrophages
• The majority of lymphocytes are perforin-secreting killer lymphocytes (T cells and NK cells)
• T cell receptors are oligoclonal, suggesting response to a specific but unknown antigen
• Growth factor-driven mesenchymal cell proliferation leads to intimal hyperplasia, fibrosis, and arterial stenosis or occlusion
• Local matrix metalloproteinase synthesis predisposes to aneurysmal dilation
• Chronic inflammation leads to aneurysm formation, stenosis, or thrombosis - more frequently than in GCA

Morphology / Histopathology

• Irregular thickening of the vessel wall with intimal hyperplasia
• Histology ranges from adventitial mononuclear infiltrates and perivascular cuffing of vasa vasorum → to intense mononuclear inflammation in the media → to granulomatous inflammation with giant cells and patchy medial necrosis
• As disease progresses: collagenous scarring with chronic inflammatory infiltrates in all three layers
• Late phase: intimal proliferation with superimposed atherosclerosis, medial necrosis with scarring, adventitial fibrosis
• Aortic root involvement can cause dilation and aortic valve insufficiency

Vascular Distribution

• 90% have stenotic/occlusive lesions; ~25% have aneurysms

• 53% of patients have lesions both above and below the diaphragm
• Lesion types: stenotic (93%), occluded (57%), dilated (16%), aneurysmal (7%)
• Stenotic lesions are ~4x more common than aneurysmal

Clinical Features

Phase 1 - Pre-pulseless (Systemic/Inflammatory Phase)

• Fever, night sweats, malaise, fatigue, weight loss
• Arthralgia/myalgia
• Elevated ESR and CRP

Phase 2 - Pulseless (Occlusive/Vascular Phase)

• Absent or diminished radial/carotid pulses ("pulseless disease")
• Blood pressure discrepancy between arms (>10 mmHg is significant)
• Subclavian or aortic bruit
• Carotidynia (tenderness over carotid arteries, up to 25%)

• Erythema nodosum (most common)
• Pyoderma gangrenosum-like ulcerations (well described in Japan, often precede diagnosis by ~3 years, predominantly upper extremities)
• Livedo reticularis, purpura
• Sweet syndrome (reported association)

ACR Classification Criteria (1990, updated 2022)

1. Onset before age 40 years
2. Limb claudication
3. Decreased brachial artery pulse
4. Unequal arm blood pressure (>10 mmHg)
5. Subclavian or aortic bruit
6. Angiographic evidence of narrowing/occlusion of aorta or its primary branches or large limb arteries

Investigations

• Elevated ESR and CRP (active disease)
• Normochromic normocytic anemia
• Raised platelet count
• No specific serologic marker; ANA/ANCA typically negative

Imaging Examples

Differential Diagnosis

• Giant cell arteritis (GCA) - most difficult to distinguish; primary differentiator is age <50 (TA) vs ≥50 (GCA)
• Cogan's syndrome (keratitis + vestibuloauditory dysfunction)
• Syphilitic aortitis (exclude with FTA-ABS)
• Atherosclerosis
• IgG4-related disease
• Inflammatory bowel disease-associated vasculitis
• Sarcoidosis, radiation-induced arteritis, Behçet's disease
• Congenital coarctation, Marfan's syndrome, Ehlers-Danlos

Treatment

Glucocorticoids (First-line)

• Prednisone 1 mg/kg/day (Andrews' Diseases of the Skin recommends tapering over 8-12 weeks to ≤20 mg/day)
• ~85% of patients present with active disease
• Initial dose continued 4-12 weeks before gradual taper
• ~two-thirds achieve remission, but >half later relapse
• Relapses especially common when prednisone falls below 20 mg/day
• 86% of patients experience glucocorticoid-related adverse events at 10-year follow-up

Steroid-sparing Agents

• Methotrexate: 0.3 mg/kg/week (start ≤15 mg/week, increase to 25 mg/week) - moderately effective; most patients still need 5-10 mg/day prednisone
• Azathioprine: 2 mg/kg/day
• Mycophenolate mofetil: 2000 mg/day
• Cyclosporine, leflunomide

Biologic Therapies (Refractory Disease)

• Anti-TNF agents: Infliximab (5 mg/kg IV), etanercept - effective but rarely curative; relapses common on stopping
• Tocilizumab (IL-6 receptor antagonist): effective in individual patients, but a small RCT (n=18) showed no effect on time-to-relapse vs. placebo; disease progression masked by normalized inflammatory markers has been reported
• Tofacitinib (JAK inhibitor): emerging evidence showing higher complete remission rates at 6 and 12 months vs. methotrexate, lower relapse rates, longer relapse-free survival
• Rituximab: used in refractory cases (also for IgG4-related disease)
• Abatacept, ustekinumab: suggested as potential options

Surgical / Endovascular Interventions

• Percutaneous transluminal angioplasty (PTA) for significant stenoses
• Bypass surgery for critical occlusions
• Aortic valve and root replacement if significant aortic regurgitation
• Important: Ideally perform during disease remission to reduce restenosis risk
• Coronary ostial stenosis may require coronary artery bypass grafting

Prognosis

• 15-year survival: >95% overall (Japan 96.5%; US 94-96%)
• Survival falls to 67% in patients with serious complications or progressive disease
• 74% report compromised daily activities; 23% unable to work
• 10-year survival in Korea: 87%

Recent Evidence (2024-2025)