Takayasu Arteritis

• Granulomatous, medium and large vessels, young females

Description

Takayasu arteritis (TA), also known as pulseless disease, is a chronic, progressive, and idiopathic granulomatous vasculitis of the medium and large vessels, primarily affecting the aorta and its main branches. It is characterised by granulomatous inflammation, intimal thickening, and vascular stenosis leading to diminished or absent pulses, hence the name “pulseless disease.”

Pathogenesis

The exact cause of TA remains unknown; however, it is widely accepted to be autoimmune in nature. The disease process involves an initial inflammation of the vessel wall leading to granuloma formation and subsequent fibrosis. The resultant vascular stenosis, occlusion, and aneurysm formation are primarily responsible for the clinical manifestations.

Epidemiology, Risk Factors & Associations

• TA predominantly affects females in their second and third decades of life, with a female-to-male ratio of approximately 8:1.
• More common in Asia, particularly in Japan.
• HLA genotypes (HLA-B*52) linked to disease susceptibility.
• Some viral triggers have been suggested, none have been definitively proven.

Clinical Features

TA presents in two phases:

• Pre-pulseless or systemic phase – Characterised by non-specific symptoms such as fever, weight loss, fatigue, and arthralgia
• Pulseless phase – Associated with vascular insufficiency due to vascular stenosis or occlusion. Features may include weak or absent pulses (most commonly in the upper limbs), blood pressure discrepancies, claudication, dizziness, visual disturbances, and aortic regurgitation.

Complications

Untreated or severe TA can lead to significant morbidity and mortality. Complications include:

• Hypertension (due to renal artery stenosis, poor prognostic factor)
• Congestive heart failure (most common cause of death)
• Stroke
• Visual loss
• Aortic aneurysm, dissection, and aortic valve regurgitation.

Subtypes

There are no recognised subtypes of Takayasu arteritis.

Pathological Features

Morphology

• Involves all three layers of the arterial wall (panarteritis), with intimal thickening, medial destruction, and adventitial fibrosis.

Histopathology

• Early-stage – Granulomatous inflammation with lymphocytes, histiocytes, multinucleated giant cells, and occasionally plasma cells.
• Late-stage disease – Characterised by intimal fibrosis and scarring, leading to luminal narrowing and occlusion.

Biochemistry

• Systemic inflammation – Elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Genetics

There is a recognised association with HLA-B52. No specific causative gene has been identified to date.

Radiological Features

General Features

• Stenosis or occlusion of the large vessels, primarily the descending thoracic and abdominal aorta and its major branches with left subclavian artery most commonly affected.
• Aneurysm formation, vessel wall thickening, or calcification.
• Pulmonary arteries are affected in half of cases.

CTA

• Vessel wall thickening, luminal narrowing or dilation, occlusion, or aneurysm formation.
• Quantify the extent of calcification within the vessel wall.

MRI

• Wall thickening: T1 hypointense compared to surrounding tissues.
• Vessel wall inflammation – Abnormal Gd enhancement of the vessel wall due to increased vascular permeability. Oedema: Seen on T2-weighted sequences with fat saturation.

FDG-PET

• Increased uptake at sites of active inflammation
• Useful for assessing disease activity in the early stages, prior to structural changes.

Grading and Staging

Hata classification is a commonly used system to classify the angiographic findings of Takayasu arteritis. It categorises the disease into five types based on the vessels involved:

• Type I: Involvement of the branches from the aortic arch.
• Type IIa: Involvement of the ascending aorta, aortic arch and its branches, possibly extending to the descending thoracic aorta.
• Type IIb: Similar to Type IIa but extends to include the abdominal aorta.
• Type III: Involves the descending thoracic aorta, abdominal aorta, and/or renal arteries.
• Type IV: Involves only the abdominal aorta and/or renal arteries.
• Type V: A combination of Type IIb and Type IV (i.e., it involves the ascending aorta, aortic arch and its branches, the thoracic descending aorta, the abdominal aorta, and the renal arteries).

Differential Diagnosis

The differential diagnosis of TA includes other causes of large vessel vasculitis:

• Giant Cell Arteritis (GCA) – Also affects medium- to large-vessels. Typically affects individuals aged over 50, often presents with cranial symptoms such as jaw claudication and temporal headache and primarily involves the cranial vessels.
• Moyamoya disease – Progressive vasculopathy leading to stenosis of main intracranial arteries. Characteristic angiographic features include arterial stenosis or occlusion of the Circle of Willis, with development of collateral vasculature producing a cloud of smoke enhancement pattern.

Management

• TA is usually managed by a multidisciplinary team including rheumatologists and vascular specialists.
• Initial treatment involves high-dose glucocorticoids to control inflammation, followed by immunosuppressive agents such as methotrexate, azathioprine, or cyclophosphamide to maintain remission.
• For disease refractory to these measures, biological agents like TNF-alpha inhibitors or IL-6 inhibitors can be used.
• Vascular interventions such as angioplasty, stenting, or bypass grafting may be necessary for severe stenosis or occlusion.
• Regular monitoring with clinical assessment and imaging (MRA or CTA) is crucial for disease management.