Takayasu Arteritis

Introduction And Epidemiology

Chronic inflammatory large vessel vasculitis predominantly targeting aorta and major branches.
Previously termed pulseless disease or non-specific aortoarteritis.
Represents third most common childhood vasculitis.
Demonstrates highest prevalence in Asian populations.
Pediatric cases account for approximately 5% of all patients.
Mean diagnosis age spans 8 to 13 years.
Female-to-male ratio approaches 3:1 to 4:1 in pediatric cohorts.
Southeast Asian and African populations exhibit primarily aneurysmal complications, whereas occlusive disease predominates in Western nations.

Exact etiology remains unidentified.
Exhibits strong association with active tuberculosis infection.
Associated with specific human leukocyte antigen-B alleles.
Driven by cellular immunity involving T-cells with restricted receptor repertoire.
Features elevated serum levels of interleukin-1, interleukin-6, and tumor necrosis factor-alpha.
Presence of anti-endothelial cell antibodies assists ongoing inflammation and expression of adhesion molecules.

Characterized as granulomatous panarteritis.
Initial inflammation targets vasa vasorum and medio-adventitial junction.
Mononuclear cell infiltration includes CD4, CD8 lymphocytes, plasma cells, and macrophages.
Giant cell granulomatous reaction induces laminar necrosis.
Fragmentation of elastic fibers triggers elasticophagia.
Follows triphasic progression.
- Phase I constitutes systemic, pre-pulseless period featuring low-grade fever, malaise, anorexia, and weight loss.
- Phase II constitutes vasculitic stage featuring angiodynia or vessel tenderness.
- Phase III constitutes late, fibrotic, occlusive burnt-out phase leading to pulseless extremities.
Healed phase exhibits pan-layer fibrosis and intimal neovascularization.

Type I involves aortic arch branches.
Type IIa involves ascending aorta, aortic arch, and branches.
Type IIb involves ascending aorta, arch, branches, and descending thoracic aorta.
Type III involves descending thoracic aorta, abdominal aorta, and renal arteries.
Type IV involves abdominal aorta and renal arteries.
Type V combines Type IIb and Type IV features.
Coronary or pulmonary artery involvement designated via C(+) or P(+) modifiers.

Diagnosis frequently delayed secondary to nonspecific early constitutional symptoms.
Supradiaphragmatic disease produces central nervous system stroke, transient ischemic attacks, and cardiac symptoms.
Infradiaphragmatic disease produces severe hypertension and abdominal bruits.
Vascular features include claudication, diminished pulses, asymmetric blood pressure, and vascular bruits.
Cardiovascular features include high-renin renovascular hypertension, myocarditis, and heart failure.
Valvular involvement causes aortic regurgitation secondary to thickened, retracted leaflets.
Neurological features encompass headache, stroke, and encephalopathy.
Cutaneous nodules, ulcers, and retinopathy remain uncommon in pediatric populations.

EULAR/PRINTO/PRES criteria remain standard for pediatric classification.
- Mandatory criterion requires angiographic abnormalities of aorta or main branches.
- Requires one of the following additional features.
  - Decreased peripheral artery pulses or extremity claudication.
  - Blood pressure difference exceeding 10 mm Hg between limbs.
  - Bruits over aorta or major branches.
  - Hypertension exceeding childhood normative data.
Elevated erythrocyte sedimentation rate or C-reactive protein.
Ishikawa diagnostic criteria utilize age under 40, left and right mid-subclavian artery involvement as major criteria.

Erythrocyte sedimentation rate frequently elevated but serves as poor marker during remission.
C-reactive protein accurately correlates with thrombotic risk.
Novel biomarkers include tissue plasminogen activator, E-selectin, and anti-monocyte antibodies.
Pentraxin-3 provides superior sensitivity and specificity for monitoring disease activity during corticosteroid treatment.
Chest radiograph demonstrates increased mediastinal widening and bare aorta lacking collaterals.
Echocardiography detects dilated chambers, non-pulsatile descending aorta flow, and valvular defects.
Computed tomographic angiography reveals precise wall thickness and concentric luminal changes.
Magnetic resonance angiography facilitates vessel wall inflammation assessment without radiation.
18F PET CT accurately detects active metabolic inflammation.
Conventional angiography remains gold standard, revealing smooth-walled, tapered narrowing, aneurysms, and prominent collaterals.
Subclavian and thoracoabdominal artery involvement highly prevalent in children.

Infectious aortitis requires exclusion.
Tuberculosis affects descending thoracic and abdominal aorta, causing erosion and aneurysms.
Takayasu arteritis causes stenosis and predominantly involves aorta and major branches.
Autoimmune etiologies include systemic lupus erythematosus and sarcoidosis.
Inflammatory vasculopathies encompass Kawasaki disease, polyarteritis nodosa, and granulomatosis with polyangiitis.
Noninflammatory vasculopathies include congenital aortic coarctation, Marfan syndrome, and Ehlers-Danlos syndrome.
Giant cell arteritis excluded due to extreme rarity in childhood populations.

Demands early diagnosis and prompt multimodal immunosuppression.
Corticosteroid induction utilizes daily high-dose oral prednisone or intravenous methylprednisolone pulse therapy.
Methotrexate and azathioprine serve as primary maintenance and steroid-sparing agents.
Cyclophosphamide, cyclosporine, and mycophenolate mofetil indicated for severe, refractory, or rapidly progressive disease.
Biological therapies including tumor necrosis factor inhibitors (etanercept, infliximab) combat glucocorticoid-dependency.
Interleukin-6 blockade via tocilizumab demonstrates promising efficacy for refractory cases.
Low-dose aspirin prophylaxis mitigates inherent prothrombotic state.
Aggressive antihypertensive pharmacotherapy prevents ongoing renovascular damage.

Indicated for limb-threatening ischemia, severe renovascular hypertension, or progressive heart failure.
Percutaneous balloon angioplasty with stenting achieves 90% success in renal artery dilation.
Restenosis risk approaches 20-25%.
Procedural complications include intimal flap dissection and catastrophic aortic rupture.
Surgical resection and manmade graft replacement reserved for severe, occlusive disease unamenable to angioplasty.
Aortic valve replacement required for severe regurgitation.

Childhood disease carries higher mortality rate approaching 35% comparable to adult populations.
Five-year survival rate in adults reaches 94%.
Morbidity driven by progressive end-organ ischemia.
Complications include stroke, myocardial infarction, progressive renal failure, and mesenteric ischemia.
Poor prognostic indicators encompass severe refractory hypertension, retinopathy, poor functional capacity, and cardiac involvement.
Chronic endothelial insult significantly accelerates premature atherosclerosis risk.
Mandatory long-term surveillance incorporates advanced non-invasive imaging to detect asymptomatic progressive stenosis.