What are the causes of non‑infectious aortitis?

Non-Infectious Aortitis Causes

Non-infectious aortitis results from autoimmune large-vessel vasculitides (primarily giant cell arteritis and Takayasu arteritis), systemic inflammatory diseases, or presents as clinically isolated disease without systemic features.

Primary Large-Vessel Vasculitides

The most common causes of non-infectious aortitis are the primary large-vessel vasculitides 1, 2:

• Giant cell arteritis (GCA) – the leading cause in patients over age 50, particularly affecting women of European descent, with both temporal arteritis and disseminated forms causing granulomatous inflammation with giant cells in the aortic wall 1, 3
• Takayasu arteritis – predominantly affects younger patients (typically under 40 years), causing inflammatory infiltrate, smooth muscle and fibroblast necrosis, and progressive fibrosis within the aortic wall 1, 4

These conditions destroy the medial layers through inflammatory infiltrate and severely affect the vasa vasorum, decreasing blood supply to the media and leading to wall weakening, aneurysm formation, and potential rupture 1.

Systemic Inflammatory and Autoimmune Diseases

Multiple systemic conditions can manifest with aortic involvement 1:

• Behçet's disease – a vasculitis affecting large and medium-sized vessels that can involve the aorta 1
• Rheumatoid arthritis-associated aortitis – can lead to aortic wall inflammation, though secondary typical aortic dissections are unusual; the diseased aorta may rupture 1
• IgG4-related disease – an increasingly recognized cause that may initially present as clinically isolated aortitis 3
• Ankylosing spondylitis – up to 80% of patients develop aortic root or valve disease, and nearly 50% exhibit aortic valve regurgitation 5
• Inflammatory abdominal aortic aneurysm – etiology unknown, probably representing an immune response to lipids infiltrating the aortic wall 1
• Aortitis in relation to retroperitoneal fibrosis (Ormond's disease) 1
• Sjögren's syndrome, sarcoidosis, ulcerative colitis, and psoriatic arthritis – all documented as causes in clinical series 6
• Granulomatosis with polyangiitis – may initially present as clinically isolated aortitis before systemic features emerge 3

Clinically Isolated Aortitis (CIA)

Clinically isolated aortitis represents 66% of histopathologically proven aortitis cases at the time of surgery and is defined as aortitis identified pathologically or radiologically without clinical evidence of systemic vasculitis 3, 7:

• CIA most commonly occurs in women of European descent over age 50, mirroring the demographics of GCA 3
• Two distinct histological patterns emerge: (1) necrotizing aortitis with giant cells (53/71 cases in one series), which is more likely idiopathic and linked to medial degeneration, and (2) diffuse band-like aortitis (16/71 cases), which carries increased risk of systemic inflammatory disease 8
• 15% of patients initially classified as CIA develop features of systemic disease during follow-up, most often GCA, emphasizing the need for long-term surveillance 7
• CIA-GPI (granulomatous pattern of inflammation) is pathologically indistinguishable from aortitis due to GCA, and many cases may represent extracranial GCA 3

Critical Clinical Pitfall

Do not assume CIA is a benign, self-limited condition: 45% of CIA patients develop new radiographic vascular lesions, 40% require additional vascular surgery, and 12% die during follow-up 7. Serial imaging surveillance is mandatory even when patients remain asymptomatic 7.

Medial Degeneration Association

Prominent medial degeneration was present in 23/71 cases of non-infectious aortitis, all in the necrotizing aortitis with giant cells category, suggesting a possible etiological relationship between chronic inflammation and degenerative changes 8.

Diagnostic Considerations

Atypical polymyalgia rheumatica (PMR) features are present in 72% of aortitis cases, along with diffuse lower limb pain (50%), constitutional symptoms (37%), inflammatory low back pain (28%), and fever (22%) 6. These should be considered "red flags" prompting aortic imaging, particularly when acute phase reactants are elevated 6.

The median interval from symptom onset to diagnosis is 21 months, reflecting the non-specific nature of presenting symptoms and the need for high clinical suspicion 6.