What are the presentation, diagnostic work‑up, and treatment options for Takayasu arteritis?

Takayasu Arteritis: Presentation, Diagnosis, and Treatment

Clinical Presentation

Takayasu arteritis typically presents in a biphasic pattern: an initial acute inflammatory phase with constitutional symptoms followed by a chronic vascular phase characterized by ischemic manifestations from arterial stenosis or occlusion. 1, 2

Acute/Early Phase

• Constitutional symptoms include fever, weight loss, fatigue, night sweats, and malaise 1, 2
• Vascular pain such as carotidynia may occur 3
• This phase may be subtle or entirely absent in some patients 4

Chronic/Vascular Phase

• Diminished or absent peripheral pulses are the most common physical finding 1, 2
• Audible bruits over the subclavian arteries, carotid arteries, or abdominal aorta 1, 2
• Blood pressure discrepancy >10 mmHg between arms is a key diagnostic clue 1, 2
• Lower extremity claudication (calf pain with walking that improves with rest) occurs particularly with abdominal aortic involvement 1
• Hypertension, most commonly from renal artery stenosis 2, 4
• Limb claudication affecting upper or lower extremities 2, 3
• Catastrophic presentations can include stroke, seizures, syncope, myocardial infarction, or vision loss 2, 5, 4

Demographics and Epidemiology

• Predominantly affects women younger than 40 years with a female-to-male ratio of approximately 10:1 2, 3
• More common in Asian populations, though increasingly recognized in Europe and North America 4, 6
• Median age at onset is 25 years 4

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Diagnostic Work-Up

Initial Clinical Assessment

At every clinical encounter, measure blood pressure in all four extremities and perform a comprehensive vascular examination for bruits and pulse deficits. 1, 2, 5

• Assess for constitutional symptoms (fever, weight loss, fatigue) 2, 5
• Document any new vascular symptoms (claudication, hypertension, neurological changes) 2, 5
• Perform four-extremity blood pressure measurements to detect discrepancies 1, 2, 5
• Auscultate for bruits over carotid, subclavian, and abdominal vessels 1, 2
• Palpate all accessible pulses (radial, brachial, femoral, dorsalis pedis, posterior tibial) 1, 2

Laboratory Testing

• Measure inflammatory markers (ESR and CRP) alongside clinical assessment 1, 2, 5
• Critical caveat: Inflammatory markers are elevated in only ~50% of active cases and should never be used in isolation to assess disease activity 1, 2, 5

Imaging Studies

Non-invasive vascular imaging (MRA, CTA, or FDG-PET) combined with clinical assessment is the cornerstone of diagnosis and monitoring. 1, 2

First-Line Imaging Modalities

• CT angiography (CTA) is most commonly used for initial diagnosis (58.8% of cases) due to high spatial resolution and rapid acquisition 2
• MR angiography (MRA) is preferred for longitudinal monitoring (62.3% of follow-up examinations) because it avoids radiation and better assesses vessel wall inflammation 2
• FDG-PET/CT can document arterial involvement and assess disease activity through supraphysiologic FDG uptake in inflamed vessel walls 1, 2

Imaging Findings Indicating Active Disease

• Vascular wall edema 1
• Contrast enhancement of vessel walls 1
• Increased wall thickness 1
• Supraphysiologic FDG uptake on PET 1, 2

Imaging Findings Indicating Chronic Damage

• Arterial stenosis (occurs in 53% of patients) 2, 4
• Occlusion of vessels 2, 3
• Aneurysm formation (23-32% of patients) 2, 4
• Arterial dilation 3, 7

Role of Conventional Angiography

• Reserve catheter angiography for determining central blood pressures, surgical planning, or when non-invasive modalities are inadequate 1
• Pitfall to avoid: Catheter angiography only shows luminal changes and misses vessel wall inflammation, making it inferior for disease activity assessment 1

Imaging Schedule

• During active or early disease: Repeat non-invasive imaging every 3-6 months 1, 2
• During established quiescent disease: Extend intervals but maintain lifelong surveillance 1, 2

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Treatment

Initial Medical Management

Immediately initiate high-dose oral glucocorticoids (prednisone 40-60 mg daily or 1 mg/kg/day, maximum 80 mg) combined with a non-glucocorticoid immunosuppressive agent at the time of diagnosis. 1, 2, 5

• Start treatment as soon as clinical suspicion is high, even before confirmatory imaging, to prevent catastrophic outcomes 2, 5
• Glucocorticoid monotherapy is reserved only for mild disease or diagnostic uncertainty because combination therapy markedly reduces long-term steroid toxicity 1, 2, 5
• IV pulse methylprednisolone (500-1,000 mg/day for 3-5 days) is reserved exclusively for life- or organ-threatening presentations (stroke with ongoing deterioration, vision loss, cardiac ischemia, critical limb ischemia) 1, 5

First-Line Steroid-Sparing Agents

Methotrexate (20-25 mg weekly) is the preferred first-line steroid-sparing agent, particularly in children, due to superior tolerability. 1, 2, 5

• Azathioprine (2 mg/kg/day) is an acceptable alternative when methotrexate is contraindicated or not tolerated 1, 2, 5
• TNF inhibitors may be used as initial adjunctive therapy when rapid disease control is needed or conventional agents are contraindicated 2

Glucocorticoid Tapering Strategy

• Taper to 15-20 mg daily within 2-3 months once remission is achieved 5
• Aim for ≤10 mg daily within 1 year 5
• After achieving remission for 6-12 months, taper off glucocorticoids completely rather than maintaining long-term low-dose therapy 1, 2, 5
• Continue non-glucocorticoid immunosuppressive agents during and after the glucocorticoid taper 1, 2, 5

Management of Refractory Disease

For patients failing glucocorticoids plus conventional immunosuppressants (methotrexate or azathioprine), add a TNF inhibitor (infliximab or adalimumab) as the next therapeutic step. 1, 2, 5

• TNF inhibitors have broader clinical experience and observational data demonstrating higher remission rates and fewer relapses 1, 2
• Tocilizumab is reserved for cases where TNF inhibitors are contraindicated, ineffective, or not tolerated 1, 2

Adjunctive Antiplatelet Therapy

• Add aspirin (75-150 mg daily) or another antiplatelet agent for patients with active disease and critical cranial or vertebrobasilar involvement 2, 5
• Caution: Bleeding risk is increased; exercise particular care after surgical procedures or in patients with high bleeding propensity 2

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Surgical and Interventional Management

Timing of Revascularization

Elective revascularization procedures (bypass grafting, angioplasty, stenting) must be postponed until disease is quiescent; operating during active inflammation is associated with markedly worse outcomes including higher restenosis rates and procedural complications. 1, 2, 5

Indications for Urgent Intervention

• Life- or organ-threatening ischemia (progressive stroke, critical limb ischemia, severe cardiac ischemia) 1, 5
• Renovascular hypertension refractory to optimized medical therapy and immunosuppression 1
• Progressive worsening of renal function despite medical therapy 1

Perioperative Management

• If surgery cannot be delayed, administer high-dose glucocorticoids in the periprocedural period 1, 2, 5
• All surgical decisions require collaborative planning between vascular surgeon and rheumatologist to ensure accurate disease activity assessment, optimal timing, and appropriate perioperative immunosuppression 1, 5

Outcomes and Expectations

• Many patients develop collateral vessels that bypass stenotic segments, potentially eliminating the need for revascularization 1
• Restenosis is common even after successful procedures 4
• Observational data consistently show superior outcomes when surgery is performed during disease quiescence 1, 2, 5

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Long-Term Monitoring

Lifelong clinical surveillance is mandatory for all patients with Takayasu arteritis, even those in apparent remission, because vascular remodeling can progress when disease appears clinically quiescent. 1, 2, 5

At Every Clinical Visit

• Measure blood pressure in all four extremities 1, 2, 5
• Perform vascular examination for new bruits or pulse deficits 1, 2, 5
• Assess for constitutional symptoms (fever, weight loss, fatigue) 2, 5
• Assess for vascular symptoms (claudication, hypertension, neurological changes) 2, 5
• Measure inflammatory markers (ESR, CRP) but do not rely on them solely 1, 2, 5

Imaging Surveillance

• Repeat non-invasive imaging every 3-6 months during active or early disease 1, 2
• Extend intervals for established quiescent disease but maintain lifelong surveillance 1, 2
• New arterial stenosis or vessel wall thickening in new territories warrants escalation of immunosuppressive therapy, even if clinically asymptomatic 1

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Common Pitfalls and How to Avoid Them

Pitfall 1: Relying Solely on Inflammatory Markers

• Problem: ESR and CRP are normal in approximately 50% of active cases 1, 2, 5
• Solution: Combine laboratory markers with clinical examination and imaging; never use inflammatory markers in isolation to assess disease activity 1, 2, 5

Pitfall 2: Performing Elective Surgery During Active Inflammation

• Problem: Active inflammation is linked to significantly worse surgical outcomes, higher restenosis rates, and procedural complications 1, 2, 5
• Solution: Defer all elective revascularization until disease quiescence is documented by clinical assessment and imaging 1, 2, 5

Pitfall 3: Using Glucocorticoid Monotherapy as First-Line Treatment

• Problem: Glucocorticoid monotherapy leads to substantially higher long-term steroid toxicity without improving outcomes 1, 2, 5
• Solution: Initiate combined glucocorticoid-sparing immunosuppression at diagnosis; reserve monotherapy only for mild disease or diagnostic uncertainty 1, 2, 5

Pitfall 4: Discontinuing Monitoring in Clinical Remission

• Problem: Vascular changes and disease progression occur even when patients appear clinically quiescent 1, 2
• Solution: Maintain lifelong clinical and imaging surveillance for all patients, regardless of apparent remission status 1, 2, 5

Pitfall 5: Delaying Treatment While Awaiting Confirmatory Testing

• Problem: Delay can lead to catastrophic outcomes including stroke, myocardial infarction, or irreversible organ damage 2, 5
• Solution: Start high-dose glucocorticoids immediately when clinical suspicion is high, even before imaging confirmation 2, 5