Aortitis

Aortitis is inflammation of the aortic wall. It is non-infectious or infectious, and it leads to stenosis, occlusion, aneurysm, dissection or aortic regurgitation.

Non-infectious causes are Takayasu arteritis, giant cell arteritis, IgG4-related disease, Behçet disease, spondyloarthropathy (ankylosing spondylitis), rheumatoid arthritis, relapsing polychondritis, Cogan syndrome, sarcoidosis, systemic lupus erythematosus and ANCA-associated vasculitis.

Infectious causes are syphilis, tuberculosis, Salmonella, Staphylococcus aureus and fungi.

Isolated (idiopathic) aortitis is found in 2 to 10% of resected ascending aortic aneurysms.

Takayasu arteritis affects about 1 to 3 in every million each year, 80 to 90% of patients are women, onset is usually under 40 years, and it is more common in Asia, Africa and Latin America. Giant cell arteritis affects people over 50 years, and large vessel involvement is found in up to half on imaging.

Pathophysiology. Granulomatous or lymphoplasmacytic inflammation spreads from the adventitia and vasa vasorum into the media and intima. Destruction of elastic fibres causes dilatation and aneurysm. Fibrosis and intimal proliferation cause stenosis and occlusion.

• Constitutional: fever, weight loss, night sweats, fatigue.
• Pain in the chest, back or abdomen. Limb claudication, absent or reduced pulses, bruits, and a difference in systolic pressure of over 10 mm Hg between the arms.
• Hypertension from renal artery stenosis or aortic narrowing. Aortic regurgitation and heart failure.
• Giant cell arteritis: headache, scalp tenderness, jaw claudication, visual loss, polymyalgia rheumatica.
• Syphilitic, tuberculous or bacterial disease: constitutional illness with features of the infection.

Red flags.

• Visual symptoms, or sudden vision loss (giant cell arteritis, an emergency)
• Sudden severe chest or back pain (dissection, rupture)
• Stroke, limb ischaemia or severe hypertension
• Aneurysm over 50 mm, or rapid growth
• Fever with positive blood cultures or tuberculosis risk

• Inflammatory markers. ESR, CRP, full blood count (anaemia, thrombocytosis). A normal CRP does not exclude Takayasu arteritis.
• Immunology. ANA, ANCA, rheumatoid factor, complement, serum IgG4 and subclasses, HLA-B27.
• Infection screen. Treponemal and non-treponemal syphilis serology, tuberculosis tests (interferon gamma release assay, Xpert MTB/RIF Ultra), blood cultures (3 sets), HIV and hepatitis B and C.
• Imaging. CT or MR angiography: circumferential wall thickening (over 2 to 3 mm), mural enhancement, and the extent of stenosis or aneurysm. FDG PET-CT for activity. Ultrasound of the carotid and temporal arteries (halo and macaroni signs). Echocardiography for the valve and root.
• Tissue. Temporal artery biopsy (giant cell arteritis), biopsy of resected aorta, and tissue culture when infection is possible.
• Features supporting Takayasu arteritis: onset under 40 years, limb claudication, reduced brachial pulse, systolic pressure difference of over 10 mm Hg between arms, bruit over the subclavian arteries or aorta, and angiographic narrowing of the aorta or its main branches.

Differential diagnosis.

• Infectious aortitis (syphilis, tuberculosis, Salmonella) and mycotic aneurysm
• Atherosclerosis with penetrating ulcer
• Fibromuscular dysplasia and mid-aortic syndrome
• Periaortitis and retroperitoneal fibrosis
• Erdheim-Chester disease and aortic lymphoma
• Marfan, Loeys-Dietz and vascular Ehlers-Danlos syndromes
• Coarctation and hypertensive aortopathy

Control inflammation first. Screen for tuberculosis, hepatitis B and Strongyloides before prolonged steroids or biological drugs. Surgery is deferred until the disease is quiet unless life threatening.

Giant cell arteritis.

• Visual symptoms: methylprednisolone 500 to 1,000 mg intravenously once daily for 3 days, then prednisolone 1 mg/kg orally once daily (maximum 60 mg).
• Otherwise prednisolone 40 to 60 mg orally once daily (maximum 60 mg), tapered by 5 to 10 mg every 2 weeks to 20 mg, then by 1 to 2.5 mg every 2 to 4 weeks, over 12 to 18 months or longer. Calcium, vitamin D, gastric protection, bone protection, and monitoring of glucose and blood pressure.
• Steroid sparing: tocilizumab 162 mg subcutaneously once weekly (every 2 weeks with a response), or methotrexate 15 to 25 mg orally once weekly with folic acid 5 mg once weekly on a different day. Avoid methotrexate in pregnancy and at eGFR under 30 mL/min/1.73 m2. Monitor full blood count and liver enzymes.

Takayasu arteritis.

• Prednisolone 0.5 to 1 mg/kg orally once daily (maximum 60 mg) for 4 weeks, then taper by 5 to 10 mg every 1 to 2 weeks to 15 to 20 mg, then slowly, with a steroid sparing agent from the start.
• Methotrexate 15 to 25 mg orally once weekly with folic acid 5 mg once weekly, or azathioprine 1 mg/kg orally once daily increased to a maximum of 2 mg/kg daily (check TPMT or NUDT15 first, full blood count weekly for 4 weeks then monthly, and reduce to a quarter of the dose with allopurinol), or mycophenolate mofetil 1 g orally twice daily (maximum 3 g daily, contraindicated in pregnancy, full blood count monthly).
• Relapse or refractory disease: tocilizumab 8 mg/kg intravenously every 4 weeks (maximum 800 mg) or 162 mg subcutaneously once weekly, or infliximab 5 mg/kg intravenously at weeks 0, 2 and 6, then every 6 to 8 weeks, with tuberculosis excluded. Cyclophosphamide 15 mg/kg intravenously every 2 weeks for 3 doses, then every 3 weeks (reduce at creatinine clearance under 30 mL/min), with mesna, for severe disease.
• Relapse occurs in about half of patients.

IgG4-related aortitis. Prednisolone 0.6 mg/kg orally once daily (usually 30 to 40 mg) for 2 to 4 weeks, then taper over 3 to 6 months. Rituximab 375 mg/m2 intravenously weekly for 4 weeks for relapse or steroid sparing.

Behçet disease, spondyloarthropathy and others. Treat the underlying disease with rheumatology: prednisolone with azathioprine and cyclophosphamide or infliximab for Behçet arterial disease, and non-steroidal drugs with a TNF inhibitor for spondyloarthropathy.

Infectious aortitis. Treat the organism with prolonged antibiotics and surgery for aneurysm, abscess or rupture. Syphilitic aortitis is treated with penicillin.

Vascular care.

• Blood pressure under 130/80 mm Hg. Check pressure in the arm with the higher reading, or the leg. Ramipril 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, and 5 mg daily at creatinine clearance under 30 mL/min) unless renal artery stenosis is bilateral. Check potassium and creatinine 1 to 2 weeks after each change. Amlodipine 5 mg once daily, increased to 10 mg (maximum 10 mg daily).
• Aspirin 75 to 100 mg orally once daily for ischaemic events, and atorvastatin 40 mg once daily with liver enzymes at baseline and 3 months.
• Revascularisation or aneurysm repair when inflammation is quiet (normal ESR and CRP for at least 3 to 6 months), by symptoms, with bypass preferred to stenting for most stenoses. Aneurysm repair at 50 to 55 mm or more, and aortic valve and root surgery for severe regurgitation.

Special groups.

• Pregnancy: plan when disease has been quiet for at least 6 months. Prednisolone and azathioprine are compatible, and aspirin 75 to 100 mg daily is used. Stop methotrexate, mycophenolate, cyclophosphamide and ACE inhibitors before conception. Control blood pressure with labetalol, modified release nifedipine or methyldopa.
• Region: in sub-Saharan Africa tuberculous and HIV-related aortitis is common, so exclude infection before immunosuppression.

Monitoring. Symptoms, ESR and CRP every 4 to 8 weeks during induction, then every 3 months. Imaging (MR angiography, CT or PET-CT) every 6 to 12 months, because progression can occur with normal markers. Blood pressure at each visit. Full blood count and liver enzymes on methotrexate, azathioprine and mycophenolate, neutrophils and liver enzymes on tocilizumab, and glucose and blood pressure on steroids.

Referral and escalation. Refer to rheumatology and a vascular or aortic team. Emergency for visual loss, suspected dissection or stroke.