Aortitis

Health / By

Aortitis – 5 Interesting Facts

  1. Aortitis refers to inflammation of the aorta related to noninfectious or infectious etiologies.(1,2,3,4)
  2. Giant cell arteritis and Takayasu arteritis are the most common etiologies of noninfectious aortitis.
  3. Gram-positive cocci, particularly Staphylococcus, Enterococcus, and Streptococcus pneumoniae, are the most common causes of infectious aortitis.
  4. Inflammation may be limited to the thoracic or abdominal aorta or spread along the entire length and extend to its major branches.(1)
  5. Diagnosis of the underlying etiology is important to guide management.(1,4)

Classifications

  • Aortitis may be classified as infectious or noninfectious.(1)
  • Noninfectious aortitis is classified based on location and the extent of inflammation.(1)
    • Type I: limited to the aortic arch and its branches
    • Type IIa: confined to the ascending aorta, and the aortic arch and its branches
    • Type IIb: features of type IIa plus involvement of the thoracic descending aorta
    • Type III: involves the thoracic descending aorta, abdominal aorta, and/or renal arteries
    • Type IV: involves the abdominal aorta and/or renal arteries
    • Type V: features of types IIb and IV

Incidence and Prevalence

  • The incidence and prevalence may be underestimated since many patients are asymptomatic.(1)
  • Reported annual incidence:(1)
    • 1-3 cases per 1,000,000 persons in the United States and European populations
    • 0.01 cases per 100,000 children in Japan
  • Aortitis reported to be present in 168 (14%) of 1,204 aortic surgical specimens collected between 1977 and 1997 in a tertiary medical center in the United States (Arthritis Rheum 2000 Apr;43(4):901).
  • Aortitis identified in 47 (6.9%) of 684 surgical aortic specimens in a single Canadian medical center between 2003 and 2013.
    • 40 patients (5.8%) had noninfectious aortitis
      • Idiopathic aortitis in 32 patients
      • Giant cell arteritis in 5 patients
      • Takayasu arteritis in 1 patient
      • Isolated polymyalgia rheumatica in 1 patient
      • Rheumatoid arteritis in 1 patient
    • 7 patients (1%) had infectious aortitis
    • Reference – CMAJ Open 2017 Jun 19;5(2):E483full-text
  • Prevalence of aortitis of 6.1% among 610 adults in Denmark who had pathological exam after resection of the ascending aorta (Arthritis Res Ther 2011 Jun 15;13(3):R87full-text, commentary can be found in Arthritis Res Ther 2011 Jul 22;13(4):119full-text).
  • Aortitis reported to be present by computed tomography (CT) angiography in 26 (65%) of 40 patients with newly-diagnosed, biopsy-proven giant cell arteritis (Ann Rheum Dis 2012 Jul;71(7):1170).
  • While infectious aortitis used to be the most prevalent type, noninfectious aortitis has become predominant.(1)

Risk Factors

Noninfectious Aortitis

  • history of connective tissue disease, diabetes, advanced age, and aortic valve pathology associated with increased risk of aortitis
    •  based on cross-sectional study
    •  610 adults had sample of tissue submitted for pathology after resection of the ascending aorta between January 1997 and March 2009 in Denmark
    • 37 adults (6.1%) had aortitis
      •  10 adults had conditions associated with aortitis or aortic aneurysms (temporal arteritis, Crohn disease, rheumatoid arthritis, systemic lupus erythematosus, infectious aortitis, Marfan syndrome)
      •  27 adults had idiopathic aortitis
    • factors associated with aortitis included
      •  history of connective tissue disease (adjusted odds ratio [OR] 4.7, 95% CI 1.6-13.6)
      •  diabetes (adjusted OR 5.2, 95% CI 0.9-29.7)
      •  age > 67 years (OR 2.5, 95% CI 0.8-7.6)
      •  aortic valve pathology (OR 2.3, 95% CI 1.1-4.9)
    • Reference – Arthritis Res Ther 2011 Jun 15;13(3):R87full-text
  • female gender and active smoking associated with idiopathic aortitis
    •  based on case-control study
    •  50 adults who had surgical resection for ascending aortic aneurysm and idiopathic aortitis were matched with 100 adults who had ascending aortic aneurysm repair for noninflammatory ascending aortic aneurysm
    • factors associated with increased risk of idiopathic aortitis
      •  female gender (odds ratio [OR] 2.41, 95% CI 1.2-4.85)
      •  active smoking (OR 3.37, 95% CI 1.12-10.08)
    • Reference – Arthritis Res Ther 2009;11(1):R29full-text

Infectious Aortitis

  • Risk factors for infectious aortitis include:
    • Atherosclerotic and/or aneurysmal disease
    • Aortic trauma
    • Presence of indwelling central venous catheter
    • Infective endocarditis
    • Congenital aortic anomalies, such as coarctation and patent ductus arteriosus
    • Conditions causing impaired immunity, including
      • Cancer
      • Diabetes mellitus
      • Alcoholism
      • Immunosuppressive therapies
    • References – (3), Clin Cardiol 2009 Sep;32(9):488full-text

Causes of Aortitis

Causes of Noninfectious Aortitis

  • Giant cell arteritis and Takayasu arteritis are most the common etiologies of noninfectious aortitis.(1,2)
  • Other large vessel vasculitides that may cause noninfectious aortitis include:(4)
    • Human leukocyte antigen B27 (HLA-B27)-associated spondyloarthropathies, such as:
      • Ankylosing spondylitis
      • Reactive arthritis
    • Immunoglobulin G4 (IgG4)-related aortitis
  • Variable vessel vasculitides that may cause noninfectious aortitis include:(4)
    • Behcet syndrome
    • Cogan syndrome
    • Relapsing polychondritis
    • Rheumatoid arthritis (RA)
    • Systemic lupus erythematosus (SLE)
    • Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, such as:
      • Granulomatosis with polyangiitis
      • Polyarteritis nodosa
    • Sarcoidosis
  • Other causes of noninfectious aortitis include:(1,4)
    • Chronic periaortitis, which may be caused by:
      • Isolated idiopathic (thoracic or abdominal) aortitis
      • Inflammatory abdominal aortic aneurysm
      • Idiopathic retroperitoneal fibrosis
      • Perianeurysmal retroperitoneal fibrosis
    • Neoplastic disease
    • Radiation
    • Trauma
    • Drugs, such as ergot alkaloids, dopaminergic drugs, and methysergide
    • Postimplantation syndrome following endovascular treatment of aortic aneurysms
  • Underlying conditions in 32 patients with noninfectious aortitis in Spain between 2010 and 2013
    • Giant cell arteritis in 13 patients
    • Isolated polymyalgia rheumatica (PMR) in 11 patients
    • Sjogren disease in 2 patients
    • Takayasu arteritis, sarcoidosis, ulcerative colitis, and psoriatic arthritis in 1 patient each
    • Large vessel vasculitis that also involved the aorta in 2 patients
    • Reference – Clin Exp Rheumatol 2015 Mar-Apr;33(2 Suppl 89):S-19

Causes of Infectious Aortitis

  • Bacterial causes of infectious aortitis include:(1,3)
    • Gram-positive cocci, particularly Staphylococcus, Enterococcus, and Streptococcus pneumoniae (detected in about 60% of cases of infectious aortitis)
    • Salmonella spp.
    • Treponema pallidum
    • Mycobacterium tuberculosis
    • Campylobacter fetus
    • Listeria monocytogenes
    • Pasteurella multocida
    • Brucella melitensis
    • Haemophilus influenzae
    • Clostridium septicum
    • Burkholderia pseudomallei
    • Nocardia asteroides
    • Coxiella burnetii
  • Fungal causes of infectious aortitis include:(1,4)
    • Candida
    • Aspergillus
    • Cryptococcus
    • Paracoccidioidomycosis
  • Viral causes associated with infectious aortitis include:(4)
    • Hepatitis B
    • Hepatitis C
    • HIV

Pathogenesis

Noninfectious Aortitis

  • Rheumatologic diseases are usually the underlying causes of noninfectious aortitis, most commonly giant cell arteritis or Takayasu arteritis.(2)
    • Pathogenesis of giant cell arteritis:
      • Dendritic cells in vessel wall become activated and recruit T cells and monocytes to vessel wall
      • Macrophages coalesce and form multinucleated giant cells
      • Giant cells secrete metalloproteinases and reactive oxygen species, compromising structural integrity of the vessel
      • Additionally, intimal proliferation leads to reduced blood flow resulting in partial or complete ischemia
    • Pathogenesis of Takayasu arteritis:
      • Via vaso vasorum, the intima, media, and adventitia are affected by inflammatory infiltrate consisting of natural killer cells, CD4- and CD8-positive T cells, gamma delta T cells, macrophages, and neutrophils
      • Intimal hyperplasia, fibrosis, and thickening of arterial wall results in progressive loss to diameter of arterial lumen
      • Stenosis and occlusion may result with subsequent symptoms and complications

Infectious Aortitis

  • Infection can occur when the aortic intima barrier is damaged by:
    • Infection of an existing intimal injury or atherosclerotic plaque (most common)
    • Septic embolization of the vasa vasorum and lymphogenic spread (typically seen in bacterial endocarditis)
    • Pathogen invasion from neighboring contiguous infection focus extending to the aorta wall (rare)
    • Bacterial contamination of the vascular wall at the time of trauma (for example, during a penetrating injury)
    • Reference – Clin Cardiol 2009 Sep;32(9):488full-text

General Evaluation

Clinical Presentation

  • Clinical presentation varies based on etiology, location of inflammation, and the presence of arteritis in other blood vessels.(1)
  • Patients with aortitis may present with wide spectrum of nonspecific symptoms and clinical signs including:(1,4)
    • Back or abdominal pain
    • Fever
    • Rash or arthralgia suggesting collagen vascular disorder
    • Ocular disturbances
    • Neurologic deficits
    • Claudication
    • Signs and symptoms of aortic regurgitation
    • Elevated inflammatory markers
  • Patients may also be asymptomatic with aortitis diagnosed incidentally.(1,3)
  • Findings in patients with specific underlying causes:(2,3,4)
    • Patient with infectious aortitis may present with nonspecific findings related to the primary infection
    • Patients with giant cell arteritis are typically ≥ 65 years old and may present with:
      • Headache
      • Swelling of temporal artery
      • Scalp tenderness
      • Polymyalgia rheumatica
      • Jaw claudication
      • Visual disturbances
    • Patients with Takayasu arteritis are typically < 40 years old and may present with:
      • Weight loss
      • Fatigue
      • Weakened or absent brachial artery pulse
      • Vascular bruits
      • Extremity claudication (subclavian or iliac arteries)
      • Blood pressure difference > 10 mm Hg between arms
      • Renal hypertension
      • Aortic valve insufficiency
      • Ostial coronary stenoses leading to angina
      • Involvement of pulmonary vasculature
      • Syncope, epileptic seizures, or amaurosis fugax due to cerebral damage

History

Chief Concern

  • Symptoms of aortitis are often nonspecific and include:(1)
    • Chest, back, or abdominal pain
    • Fever
    • Weight loss

Past Medical History

  • Ask about a history of rheumatologic conditions associated with aortitis, most commonly giant cell arteritis or Takayasu arteritis.(1,2)
  • Ask about history of risk factors for infectious aortitis, including:
    • Atherosclerotic and/or aneurysmal disease
    • Aortic trauma
    • Infective endocarditis
    • Congenital aortic anomalies, such as coarctation and patent ductus arteriosus
    • Conditions causing impaired immunity, including:
      • Cancer
      • Diabetes mellitus
      • Alcoholism
      • Immunosuppressive therapies
    • Reference – Clin Cardiol 2009 Sep;32(9):488full-text

Physical

General Physical

  • Check for fever.(1)
  • Check for bruits over the major arteries including the subclavian artery and carotid artery.(1)

Skin

  • Check for rash, which may be associated with collagen vascular disorders.(4)

HEENT

  • Palpate the temporal arteries; swelling, tenderness, or pulse attenuation may suggest giant cell arteritis.(1,2)
  • Check for any ocular symptoms; impaired vision may suggest arteritic optic nerve neuropathy seen in giant cell arteritis.(1,2)

Cardiac

  • Check for any abnormal heart sounds due to aortic or mitral valve regurgitation.(1)

Extremities

  • Check for limb claudication.(1,2)
  • Check for a reduced or absent peripheral pulse.(1,2)
  • Check blood pressure in both arms, as a difference between left and right arms > 10 mmHg suggests vascular obstruction.(2)

Diagnostic Testing

Testing Overview

  • Appropriate blood tests include:
    • Complete blood count with differential
    • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
    • Rheumatologic inflammatory labs
    • Assessment of liver and kidney function
  • Perform blood cultures if an infectious etiology is suspected.
  • Multiple imaging modalities may be useful in the evaluation of patients with suspected or known aortitis.(1,4)
    • Goal of imaging is to:
      • Identify and localize acute and chronic changes to the aortic wall
      • Assess structural luminal changes
    • Useful imaging techniques include:
      • Computed tomography (CT)
      • Magnetic resonance imaging (MRI)
      • Positron imaging tomography (PET)
      • Echocardiography and vascular ultrasound
  • Consider a temporal artery biopsy if giant cell arteritis is suspected; see Giant Cell Arteritis (GCA) for additional information.

Blood Tests

  • Appropriate blood tests in the evaluation of aortitis include:
    • Complete blood count with differential; leukocytosis and neutrophilia reported to be present in 65%-83% of patients with infectious aortitis.
    • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
      • Elevated in most patients, although normal values do not rule out aortitis
      • Not specific for diagnosis
    • Rheumatologic tests including:
      • Antinuclear antibodies (ANA), and if positive, consider other ANA subtypes
      • Antineutrophil cytoplasmic antibodies (ANCA)
      • Rheumatoid factor (RF) and anti-CCP antibodies
    • Kidney function tests
    • Liver tests
    • Total IgG and IgG4 (if IgG4-related disease suspected)
    • Human leukocyte antigen (HLA) typing, such as HLA-B27 (if spondyloarthropathy is suspected)
    • References – (1,2), Clin Cardiol 2009 Sep;32(9):488full-text, Prim Care 2018 Jun;45(2):237
  • Perform blood culture and subsequent Gram staining to identify the infectious pathogen.(1,3)
    • Take ≥ 3 sets of aerobic and anaerobic blood cultures at 6 to 8 hour intervals before starting antimicrobial therapy.
    • In patients with severe disease, 2 blood cultures taken at 1-hour intervals may be appropriate and allow earlier initiation of antibiotics.
    • Blood cultures are reported positive in 50%-85% of patients with infectious aortitis.
    • Negative blood culture does not rule out infectious aortitis.
    • Broad-spectrum polymerase chain reaction (PCR) may help to identify a pathogen in certain cases.
  • If tertiary syphilis is suspected as a possible etiology, obtain a rapid plasma reagin (RPR) test and/or Venereal Disease Research Laboratory (VDRL) test; see Tertiary Syphilis for additional information.
  • If tuberculous is suspected, obtain an interferon gamma release assay or a tuberculin skin test; see Pulmonary Tuberculosis for additional information.

Imaging Studies

Computed Tomography (CT) and Computed Tomography Angiography (CTA)
  • CT and CTA provide good spatial resolution, are widely available, and are noninvasive.(1,4)
    • Scan time is generally < 1 minute.
    • Maximum intensity projection, multiplanar reformatting, and volume rendering are used in conjunction with standard sequential axial views for three dimensional (3D) reconstruction.
  • CT is useful for the assessment of:(4)
    • Aortic wall thickness and regularity
    • Aortic diameter
    • Aortic branches
    • Intramural hematoma
    • Mural calcifications
    • Changes in inflammatory periaortic soft tissue
    • Identifying complications of infectious aortitis, including mycotic aneurysm
  • CTA allows for:(4)
    • Visualization of ectasia, dilatation, stenosis, occlusion, and thrombosis
    • Identification of complications, such as:
      • Saccular aneurysm
      • Pseudoaneurysm
      • Thrombosis
    • Guidance of revascularization when needed
  • Drawbacks include:(1)
    • Limited utility in early phases
    • Requirement of ionizing radiation and iodinated contrast
Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA)
  • MRI is useful for the assessment of the vascular wall and lumen with multiplanar and 3D reformation imaging.(1,4)
  • Compared to computed tomography, MRI is associated with:(1,4)
    • Inferior spatial resolution
    • Improved soft tissue characterization
    • Better detection of early signs of inflammation, while also detecting luminal changes in mature phase
    • Longer scan times (> 45 minutes)
    • Option to perform cardiac sequences to identify endocardial, myocardial, and pericardial complications
  • MRA:(4)
    • MRA provides luminal information comparable to computed tomography angiography, including vessel stenosis, dilation, and thrombosis.
    • It may overestimate the degree of branch point stenosis.
    • MRA is associated with poor performance in the distal branches and suboptimal calcium visualization.
  • MRI does not require ionizing radiation and is the preferred methodology in young patients for follow-up.(4)
  • MRI may be associated with artifacts and safety concerns in patients with implanted cardiac devices.(4)
Positron Emission Tomography (PET) and PET-Computed Tomography (PET-CT)
  • PET is a useful imaging modality for assessing active inflammation.(1,3,4)
    • An accumulation of fluorodeoxyglucose ([18F]FDG) signals the presence of inflammatory infiltrates.
    • Large vessel uptake is graded on a 4-point scale:
      • None (grade 0)
      • Lower than liver uptake (grade 1)
      • Similar to liver uptake (grade 2)
      • Higher than liver uptake (grade 3)
    • Uptake is considered significant when aortic signal is grade ≥ 2.
    • PET is sensitive for early aortitis since inflammatory cell infiltration likely to occur prior to development of edema
    • PET is associated with lower spatial resolution and limited morphologic assessment, but sensitivity and specificity can be improved when computed tomography arthrography (CTA) or magnetic resonance arthrography (MRA) are combined with PET.
    • In patients with infectious aortitis, PET may show increased uptake in only 1 aortic segment, with additional extravasal activity focus representing an infection focus.
  • 18-FDG-PET or 18-FDG-PET/CT may help detect large vessel vasculitis in patients with giant cell arteritis or Takayasu arteritis (level 2 [mid-level] evidence)
    •  based on systematic review of diagnostic case-control studies
    • systematic review of 8 studies evaluating 18-FDG-PET and/or 18-FDG-PET/CT in 400 patients (170 patients with large vessel vasculitis and 230 controls)
      •  5 studies evaluated patients with giant cell arteritis and Takayasu arteritis and 3 studies evaluated patients with only giant cell arteritis
      •  5 studies used 18-FDG-PET and 3 studies used 18-FDG-PET/CT
      •  5 studies used semiquantitative PET interpretation and 3 studies used quantitative interpretation
    •  reference standard was diagnosis of large vessel vasculitis based on American College of Rheumatology (ACR) diagnostic criteria
    • pooled diagnostic performance of 18-FDG-PET or 18-FDG-PET/CT for large vessel vasculitis in analysis of all studies
      •  sensitivity 75.9% (95% CI 68%-82.1%)
      •  specificity 93% (95% CI 88.9%-96%), results limited by significant heterogeneity
      •  positive likelihood ratio 7.3 (95% CI 3.7-14.2)
      •  negative likelihood ratio 0.3 (95% CI 0.2-0.4)
    • Reference – Z Rheumatol 2016 Nov;75(9):924
  • PET appears to have high sensitivity and specificity for diagnosing large vessel vasculitis in patients with giant cell arteritis but may only have moderate sensitivity and specificity in patients with Takayasu arteritis (level 2 [mid-level] evidence)
    •  based on systematic review of diagnostic studies without diagnostic uncertainty
    • systematic review of 21 diagnostic studies evaluating PET or PET/CT in 413 patients with large vessel vasculitis and 299 controls
      •  8 studies evaluated patients with giant cell arteritis, 8 studies evaluated patients with Takayasu arteritis, and 5 studies evaluated patients with either condition
      •  control group included patients with cancer, infection, rheumatoid arthritis, small vessel vasculitis, or undefined conditions
      •  5 studies evaluated PET/CT and 12 studies evaluated PET alone
      •  38% of patients were under corticosteroid and/or immunosuppressive treatment
    • reference standard for
      •  giant cell arteritis was ACR diagnostic criteria and/or positive temporal artery biopsy
      •  Takayasu arteritis was ACR diagnostic criteria and/or Ishikawa modified Sharma criteria
    •  FDG-PET showed FDG vascular uptake in 70% of patients with large vessel vasculitis and 7% of controls (p < 0.05)
    • pooled performance of PET in diagnosing large vessel vasculitis in giant cell arteritis in analysis of 4 studies with 57 patients and 176 controls
      •  sensitivity 90% (95% CI 79%-96%)
      •  specificity 98% (95% CI 94%-99%)
      •  positive likelihood ratio 28.7 (95% CI 11.5-71.6)
      •  negative likelihood ratio 0.15 (95% CI 0.07-0.29)
    • pooled performance of PET or PET/CT in diagnosing large vessel vasculitis in Takayasu arteritis in analysis of 7 studies with 191 patients and 46 controls
      •  sensitivity 87% (95% CI 78%-93%)
      •  specificity 73% (95% CI 63%-81%), results limited by significant heterogeneity
      •  positive likelihood ratio 4.2 (95% CI 1.5-12)
      •  negative likelihood ratio 0.2 (95% CI 0.1-0.5)
    • Reference – Medicine (Baltimore) 2015 Apr;94(14):e622full-text
  • 18-F-FDG PET-CT may be useful for detecting giant cell arteritis in adults with clinical suspicion and negative unilateral temporal artery biopsy (level 2 [mid-level] evidence)
    •  based on retrospective diagnostic cohort study without blinding
    • 127 adults (mean age 77 years, 69% female) with clinical suspicion of giant cell arteritis and negative unilateral temporal artery biopsy were assessed with 18-F-FDG PET-CT
      • all patients were evaluated initially for new-onset headache, girdle syndrome, and severe/isolated persistent constitutional syndrome with raised acute phase reactants
      • prior to 2020, the protocol used delayed 18-F-FDG PET-CT imaging 60 minutes after IV radiotracer administration; after 2020, the protocol was amended to imaging 90 minutes after IV radiotracer administration due to evidence of increased sensitivity
    • reference standard was clinical confirmation after at least 1 year of follow-up
    • clinical diagnosis was based on age ≥ 50 years at onset, presence of clinical symptoms, elevated acute phase reactants, evidence of large vessel vasculitis on 18-F-FDG PET-CT, clinical response to glucocorticoid therapy, and no change in diagnosis for at least 1 year
    • 73 adults were diagnosed with giant cell arteritis upon clinical review of medical records
    • for detection of giant cell arteritis, 18-F-FDG PET-CT had
      • sensitivity of 83.5% (95% CI 73%-91.2%)
      • specificity of 85.1% (95% CI 72.8%-93.3%)
      • positive predictive value of 88.3% (95% CI 79.9%-93.5%)
      • negative predictive value of 79.3% (95% CI 69.3%-86.7%)
    • Reference – Arthritis Res Ther 2024 Jan 4;26(1):13full-text
Echocardiography and Vascular Ultrasound
  • Echocardiography and vascular ultrasound are widely available and do not require ionizing radiation.(1,4)
  • Echocardiography and vascular ultrasound may identify:(1,4)
    • Aortic and branch vessel thickening
    • Mural edema, which appears as echolucent “halo” reflecting wall edema
    • Aortic aneurysm
    • Aortic root dilation
    • Aortic valve insufficiency
    • Secondary myocardial dysfunction
  • Doppler assessment provides a functional evaluation of stenotic segments.(1,4)
  • High-resolution transthoracic echocardiography (TTE) may identify complications, including:(4)
    • Aortic dissection
    • Intramural hematoma
    • Penetrating ulcer
  • Transesophageal echocardiography (TEE) may be particularly useful for diagnosing infectious aortitis.(4)
    • TEE often identifies atherosclerotic nidus.
    • Other findings may include:
      • Aortic mural thickening with fusiform aneurysms
      • Saccular aneurysms
      • Ulceration with pseudoaneurysm and thrombus
    • Abscess cavities may appear as 1 or more focal echolucencies.
    • TEE is the modality of choice to rule out infective endocarditis.
  • 3D TTE and TEE technology are useful for identifying complications and for surgical planning.(4)
  • Vascular ultrasound is useful for imaging the thoracic aorta, abdominal aorta, and peripheral aortic branches.(4)
    • Giant cell arteritis is diagnosed by a “halo” sign in the temporal arteries.
    • Takayasu arteritis is indicated by the “macaroni” sign, consisting of extensive concentric thickening of the aorta and/or branch vessels, with brighter echogenicity.
    • Idiopathic aortitis may show mural thickening with echolucent periaortic mass.
  • Drawbacks include:(4)
    • An inability to image through bone and air (prohibiting a comprehensive evaluation of the thoracic aorta)
    • Operator dependence
    • Fibrosis, false lumen, and hematoma can all appear echolucent, leading to difficult tissue characterization.

Histopathologic Findings

  • Aortitis initial diagnosis algorithm – Adapted from In Vivo 2021;35(1):41, Rheumatology 2020;59(3):487, Rheum Dis 2018;77(5):636,Vascul Pharmacol 2016;80:1. Last reviewed 2022.Copyright ©2022 EBSCO Information Services.
  • Histopathology after aneurysm repair may lead to incidental diagnosis.(4)
  • Inflammatory patterns in aortitis and periaortitis include:
    • Granulomatous/giant cell pattern:
      • It is the most common inflammatory pattern.
      • Granulomatous/giant cell pattern is composed of clusters of epithelioid macrophages with or without giant cells or compact/well-formed granulomas.
      • The presence or absence of compact/well-formed granulomas may indicate the underlying condition.
        • They are typically absent in patients with giant cell arteritis, granulomatosis with polyangiitis, or eosinophilic granulomatosis with polyangiitis.
        • They may be present in patients with rheumatoid arthritis or Takayasu arteritis.
        • Compact/well-formed granulomas are usually present in patients with sarcoidosis, mycobacterial infection, or fungal infection.
      • Aortic involvement in giant cell arteritis (GCA) is associated with less adventitial scarring and predilection for the inner half of the media compared to Takayasu arteritis.
    • Lymphoplasmacytic pattern:
      • Lymphoplasmacytic pattern is composed of lymphocytes and plasma cells without a granulomatous component.
      • It is much less common than a granulomatous/giant cell pattern.
      • Etiologies to consider include IgG4-related disease, systemic lupus erythematous, ankylosing spondylitis, and syphilitic aortitis.
    • Mixed inflammatory pattern:
      • Mixed inflammatory pattern is composed of most or all inflammatory cells without a granulomatous component.
      • It is relatively uncommon.
      • It is associated with aortitis in Cogan syndrome, Behcet syndrome, and relapsing polychondritis.
    • Suppurative pattern:
      • Suppurative pattern is defined by marked neutrophilic infiltrates with extensive necrosis and cell debris.
      • It is associated with bacterial infections or fungal infections.
      • A focal granulomatous reaction may be present.
      • Fibrosis and lymphoplasmacytic infiltrates may be present in chronic stages.
      • Plasma cells may show a focally high expression of IgG4 in patients with chronic active infections from gram-positive bacteria (the presence of a coexisting suppurative pattern and bacteria allows differentiation from IgG4-related aortitis).
    • Reference – Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology Consensus statement on surgical pathology of the aorta (Cardiovasc Pathol 2015 Sep-Oct;24(5):267)

Evaluation of Common Underlying Conditions

Evaluation of Giant Cell Arteritis

  • There is no universally accepted diagnostic criteria.
  • American College of Rheumatology (ACR) provisional classification criteria requires ≥ 3 of the following:
    • Age > 50 years
    • Localized headache that was not preexisting
    • Temporal artery abnormalities (tenderness or reduced pulsation)
    • Elevated erythrocyte sedimentation rate ≥ 50 mm/hour
    • Abnormal arterial biopsy (evidence of vasculitis with mostly mononuclear cell infiltration or granulomatous inflammation or evidence of giant cells)
  • Initiate glucocorticoids as soon as a clinical diagnosis is strongly suspected; do not wait to confirm the diagnosis with biopsy or imaging.
  • Temporal artery biopsy can confirm diagnosis.
  • Diagnose patients with a positive clinical presentation and response to glucocorticoids, even if a negative temporal artery biopsy results.

Evaluation of Takayasu Arteritis

  • Consider in patients < 40 years old with certain clinical findings, such as:
    • Absent or weak peripheral pulses and/or arterial bruits (most common presenting signs)
    • Carotidynia or Fay syndrome, characterized by unilateral tenderness in the neck in the region of carotid bifurcation (occurs in 10%-30% of patients at presentation)
    • Arterial bruit
    • Angina
    • Limb claudication
    • > 10 mmHg discrepancy in blood pressure between upper limbs
  • Diagnosis is generally confirmed by angiography or imaging with magnetic resonance angiography (MRA) or positron emission tomography (PET).
  • Classification criteria have been used for Takayasu arteritis, including:
    • American College of Rheumatology (ACR) classification criteria and Chapel Hill Consensus Conference nomenclature
    • European Alliance of Associations for Rheumatology/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria for diagnosis of childhood Takayasu arteritis
    • National Institute of Health (NIH) criteria for disease activity for Takayasu arteritis

Management

Management Overview

  • Treatment decisions should involve a multidisciplinary team consisting of:(1)
    • Vascular or cardiothoracic surgeons
    • Cardiologists
    • Internal medicine/rheumatology specialists
    • Infectious disease specialists
  • Surgical or endovascular intervention
    • Consider immediately if there is any evidence of:
      • Aortic aneurysm
      • Vascular ulcer
      • Vascular fistula
      • Vessel occlusion
    • To optimize outcomes and avoid complications, surgical procedures should be performed:
      • During disease remission in patients with vasculitis
      • After control of the underlying infection in patients with infectious aortitis
  • Initiate glucocorticoid treatment if clinical diagnosis suggests noninfectious aortitis.
    • Choice of regimen varies based on the underlying rheumatologic condition and disease activity.
      • For patients with giant cell arteritis, standard initial regimen is prednisone 60 mg/day orally.
      • For patients with Takayasu arteritis, standard initial regimen is prednisone 1 mg/kg body weight/day orally (maximum dose of 60 mg/day).
    • Consider the use of adjunctive immunosuppressive therapy to improve disease control and allow glucocorticoid tapering.
  • Initiate antimicrobial therapy if infectious aortitis is suspected.
    • Broad-spectrum empiric antibiotic therapy should cover common pathogens known to cause aortitis, including staphylococcal species and gram-negative bacteria.
    • Targeted therapy is based on the isolated pathogen and antibiotic sensitivity pattern.
    • Duration is based on the need for surgical excision, clinical and laboratory factors, and imaging findings.
  • Continue closely monitoring for vascular complications including:(1)
    • Septic emboli
    • Acute limb ischemia
    • Stroke
    • Aortic dissection/rupture

Medications

Medications for Noninfectious Aortitis

  • Glucocorticoids are first-line treatment for noninfectious aortitis.(1,2)
    • Choice of regimen varies based on the underlying rheumatologic condition and disease activity.
      • For patients with giant cell arteritis, standard initial regimen is prednisone 60 mg/day orally.
      • For patients with Takayasu arteritis, standard initial regimen is prednisone 1 mg/kg body weight/day orally (maximum dose of 60 mg/day).
    • Consider bone protection and gastrointestinal protection to reduce complications of glucocorticoid treatment.
    • Follow-up includes monitoring of symptoms and inflammatory markers, as well as potential complications from long-term glucocorticoid use.
    • Gradual tapering of glucocorticoids is required to reduce adverse events.
  • Immunosuppressive therapy may be used as an adjunctive therapy.(1,2)
    • Immunosuppressive therapy can be used to improve disease control and allow steroid tapering.
    • Consider use in patients with:
      • Glucocorticoid-resistant disease
      • Relapse during steroid tapering
      • Side effects of glucocorticoid treatment
      • Recurrent relapse
    • Adjunctive therapy options include:
      • Methotrexate
      • Azathioprine
      • Cyclophosphamide
      • Mycophenolate mofetil
      • Tumor necrosis factor (TNF) inhibitors (for example, infliximab or adalimumab)
      • Interleukin-6 (IL-6) inhibitors (for example, tocilizumab)
      • Rituximab
      • Leflunomide

Medications for Infectious Aortitis

  • If infectious aortitis is suspected, initiate IV antibiotic therapy.
    • Collect blood cultures before the first dose of antibiotics.
    • Broad-spectrum empiric antibiotic therapy should cover common pathogens known to cause aortitis, including staphylococcal species and gram-negative bacteria.
    • Adjust antibiotics regimen once the pathogen and its antibiotic sensitivity are known.
    • Duration of antibiotic therapy is based on the need for surgical excision, clinical and laboratory factors, and imaging findings.
      • Antibiotics may be given for:
        • 2-4 weeks before surgery to improve surgical conditions
        • 6-12 weeks after surgical excision and blood culture clearance
      • Consider a longer course in patients with immunocompromise or if inflammatory markers do not return to normal.
      • For difficult-to-treat microorganisms, life-long oral antibiotics may be needed.
    • References – (1,3), Clin Cardiol 2009 Sep;32(9):488full-text
  • Antimicrobial therapy for specific pathogens:
    • For streptococcal infection, see Infective Endocarditis
    • For staphylococcal infections, see:
      • Staphylococcus aureus
      • Staphylococcus aureus Bacteremia
      • Methicillin-resistant Staphylococcus aureus (MRSA)
      • Infective Endocarditis
    • For nontyphoidal Salmonella spp. Infection, see Nontyphoidal Salmonellosis
    • For syphilitic aortitis, see Tertiary Syphilis
    • For mycobacterial aortitis, see Pulmonary Tuberculosis and Disseminated Tuberculosis

Surgery and Procedures

  • Open surgery or endovascular therapy can be considered depending on the underlying etiology and symptom severity.(1,3)
    • Surgical repair typically consists of replacement of the diseased segment.
    • There is limited evidence on the long-term success of endovascular procedures.
  • To optimize outcomes and avoid complications, surgical procedures should be performed:(1)
    • During disease remission in patients with vasculitis
    • After control of underlying infection in patients with infectious aortitis
  • Consider immediate surgical intervention in patients with:(1)
    • Aortic aneurysms
    • Vascular ulcers
    • Vascular fistula
    • Vessel occlusion
  • Surgery in patients with noninfectious aortitis:(2)
    • Surgery is guided by the principles of treatment of arteriosclerosis.
    • Some clinicians recommended performing procedures during disease remission.
    • Restenosis rate reported to be higher after angioplasty with or without stents compared to surgery.
    • There is limited data on the use of drug-eluting stents or balloons.
  • Surgery in patients with infectious aortitis:
    • Surgical options should be carefully considered based on the risk of rupture.
      • The risk is typically higher in infectious aortitis than noninfectious aortitis, with intramural hematoma or infection with gram-negative bacteria associated with especially high risk of rupture.
      • Low-risk lesions without aneurysm formation and with an intact aortic wall may be treated with antibiotics alone, although patients should be closely monitored.
    • If possible, antibiotics may be given for 2-4 weeks before surgery to reduce the risk of mortality and morbidity.
    • Reported procedures include in situ or ex situ reconstruction using autologous vein grafts, allografts, or alloplastic materials.
      • There is limited evidence to compare methods.
      • Samples should be sent for microbiologic testing.
    • In patients with secondary aortitis, distant focus of infection may also require removal.
    • In patients in an acute hemorrhage phase, a 2-step approach of endovascular placement of a stent followed by surgical repair after patient stabilization is reported to be successful.
    • Systemic antibiotics should be continued at least 6-12 weeks after surgical debridement
    • Local antibiotics, such as gentamycin sponges or rifampicin-soaked grafts, may also be used.
    • References – (1,3), Clin Cardiol 2009 Sep;32(9):488full-text

Cause-Specific Management

Giant Cell Arteritis (Including Temporal Arteritis)

  • Glucocorticoids are first-line treatment for GCA and should be initiated as soon a clinical diagnosis of GCA is made or is suspected, particularly in those with acute visual disturbance.
    • Use high-dose glucocorticoids (40-60 mg/day prednisone-equivalent) for induction of remission in patients with active GCA.
    • In patients with acute or intermittent visual loss, consider methylprednisolone 0.25-1 g IV for up to 3 days.
    • Once symptoms of active GCA have resolved and symptoms of ocular manifestations are stable, glucocorticoid dose should be tapered, to a target dose of 15-20 mg/day within 2-3 months, and ≤ 5 mg/day after 1 year.
  • Immunosuppressants, such as tocilizumab and methotrexate, may also be considered as adjunctive therapy in patients with increased risk of glucocorticoid-related adverse effects or complications, or in those with refractory disease.
    • Tocilizumab dose is 162 mg/week subcutaneously.
    • Methotrexate may be considered as an alternative.
    • Immunosuppressants can also be tapered on an individual basis once the patient is no longer taking glucocorticoids and is in sustained remission.
  • Management of relapsing disease typically involves reinstituting or increasing dose of glucocorticoids, as well as use of adjunctive therapy, depending on severity of relapse.
    • For major relapse, reinstitute or escalate dose of glucocorticoid therapy.
    • For minor relapses, increase glucocorticoid dose to at least last effective dose.
    • Consider initiating or modifying adjunctive therapy, especially if symptoms of cranial ischemia are present or after recurrent disease relapses.
  • Follow up and monitor disease activity regularly based on symptoms, clinical findings, and erythrocyte sedimentation rate/C-reactive protein levels.

Takayasu Arteritis

  • The approach to management consists of induction of remission using high-dose glucocorticoids, often in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs); for refractory or relapsing disease despite conventional DMARD therapy, tocilizumab or tumor necrosis factor (TNF)-inhibitors may be used.
  • For the induction of remission:
    • Immediate initiation of high-dose glucocorticoid therapy is recommended (EULAR Grade D, Level 5) and addition of immunosuppressants to treatment regimen should be considered.
      • Start most patients on 40-60 mg/day of a prednisone-equivalent.
      • Taper the dose once the disease is controlled; aim for a target dose of:
        • 15-20 mg/day within 2-3 months
        • ≤ 10 mg/day after 1 year
      • Glucocorticoids are reported to be effective for the treatment of Takayasu arteritis, but disease relapse is common and immunosuppressant/glucocorticoid-sparing agents may be required to maintain remission (level 3 [lacking direct] evidence)
      • European Alliance of Associations for Rheumatology (EULAR) recommends giving nonbiologic DMARDs in combination with glucocorticoids to all patients (EULAR Grade C, Level 4).
    • Prevention of adverse effects of therapy:
      • All patients treated with glucocorticoid medications should receive bone protection to prevent glucocorticoid-induced osteoporosis.
      • In patients on glucocorticoid or other immunosuppressant therapies (such as methotrexate, azathioprine, or cyclophosphamide):
        • Consider pneumococcal and influenza vaccines in season
        • Screen for tuberculosis
      • Consider pneumocystis pneumonia prophylaxis for any patient on ≥ 20 mg/day of prednisone for > 1 month and any patient treated with immunosuppressive regimens.
  • For the treatment of refractory disease despite conventional DMARD therapy, EULAR recommends considering the use of tocilizumab or TNF-inhibitors (EULAR Grade C, Level 4).
  • For the treatment of relapse:
    • For minor relapses, increase glucocorticoid dose to at least the last effective dose (EULAR Grade A, Level 1b)
    • For major relapse (either with signs or symptoms of ischemia or progressive vascular inflammation), reinstitution or dose escalation of glucocorticoid therapy is recommended in the same manner as if new onset of disease (EULAR Grade C, Level 2b)
    • EULAR also recommends considering the use of tocilizumab or TNF-inhibitors in patients with an inadequate response to conventional DMARD therapy (EULAR Grade C, Level 4)
  • Antiplatelet agents may be considered on an individual basis in special situations, but they are not routinely recommended (EULAR Grade C, Level 4)
  • Reconstructive vascular surgery is often required.
    • Elective endovascular interventions or reconstructive surgery should be performed during stable remission (EULAR Grade C, Level 4).
    • Arterial vessel dissection or critical vascular ischemia should be referred urgently to a vascular team (EULAR Grade C, Level 4).
    • A high rate of restenosis is reported with both vascular bypass and angioplasty.

Follow-Up

  • Monitor patients for their response to therapy and the development of complications; follow-up methods include:(1)
    • Measurement of inflammatory markers
    • Use of imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), echocardiography, or positron emission tomography (PET)

Complications

  • Complications of aortitis include:(1)
    • Aortic aneurysms (including abdominal aortic aneurysm and thoracic aortic aneurysm)
    • Aortic dissection
    • Aortic valve insufficiency from aortic root dilatation
    • Vascular occlusion
    • Vascular fistulas
    • Vascular ulcers
    • Hematomas
    • Thrombosis
    • Acute limb ischemia
    • Septic emboli in patients with infectious aortitis

Prognosis

Noninfectious Aortitis

  • The prognosis varies based on underlying cause and disease severity.(3)
  • Depending on the underlying etiology, some patients may need long-term glucocorticoid or immunosuppressive therapy.(1)
  • Relapse is common.(1)
  • Prognosis in patients with giant cell arteritis:
    • aortic manifestations associated with increased mortality in patients with giant cell arteritis
      •  based on cohort study
      •  204 patients diagnosed with giant cell arteritis between 1950 and 2004 were followed for median 8.8 years
      • cumulative incidence of large vessel manifestations at 10 years 24.9%
        •  incidence of any large vessel event 5 per 100 person-years within first year of diagnosis
        •  incidence of aortic aneurysm/dissection remained stable within 5 years of diagnosis, but increased 5 years after diagnosis
      • mortality
        • compared to general population
          •  giant cell arteritis associated with no significant difference in mortality (standardized mortality ratio [SMR] 1, 95% CI 0.9-1.2)
          •  giant cell arteritis with aortic manifestation associated with increased mortality (SMR 5.1, 95% CI 3.4-7.4)
        • among patients with giant cell arteritis
          • factors associated in increased mortality include
            •  large vessel manifestations (hazard ratio [HR] 2.4, 95% CI 1.6-3.6)
            •  aortic aneurysm/dissection (HR 3.4, 95% CI 2.2 to 5.4)
          •  large artery stenosis not associated with increased mortality (HR 1.5, 95% CI 0.9-2.5)
      • Reference – Ann Rheum Dis 2013 Dec 1;72(12):1989full-text
    • aortitis at onset of giant cell arteritis associated with increased risk of vascular events, higher steroid requirement, and multiple relapses
      •  based on retrospective cohort study
      •  22 adults with biopsy-proven giant cell arteritis were followed for mean of 7.8 years
      •  10 adults had aortitis at time of diagnosis based on aortic helical computed tomography (CT) scans
      •  cardiovascular risk profile, clinical presentation, and inflammatory markers similar between patients with aortitis and patients without aortitis
      • comparing patients with aortitis vs. without aortitis
        •  mortality 70% vs. 42% (not significant)
        •  vascular mortality 50% vs. 0% (p = 0.02)
        •  mean number of vascular events 1.33 vs. 0.25 (p = 0.009)
        •  stroke in 40% vs. 0% (p = 0.03)
        •  relapse in 60% vs. 27% (not significant)
        •  multiple relapses in 50% vs. 0% (p = 0.012)
        •  discontinuation of steroids at last follow-up in 20% vs. 66% (p = 0.04)
      • Reference – J Rheumatol 2012 Nov;39(11):2157
  • type V disease (extensive involvement of the aorta) associated with increased risk of disease activation in patients with clinically inactive Takayasu arteritis
    •  based on retrospective cohort study
    • 59 patients (mean age 42 years, 85% women) with inactive Takayasu arteritis were followed for median 58 months
      •  30 patients (50.8%) were classified as type V (involvement of ascending aorta, aortic arch, aortic arch branches, descending thoracic aorta, abdominal aorta, and/or renal arteries)
      •  no patients had medical therapy at time of diagnosis
    •  during follow-up, 13 patients (22%) had disease activation
    • comparing disease activation group vs. stable group
      •  baseline renovascular hypertension in 38.5% vs. 8.7% (p = 0.019)
      •  baseline type V disease in 92.3% vs. 39.1% (p = 0.008)
    •  type V disease associated with increased risk of disease activation in multivariate analysis (odds ratio 10.97, 95% CI 1.14-105.18)
    • Reference – J Rheumatol 2015 Mar;42(3):489
  • isolated aortitis associated with increased risk of aneurysm compared to aortitis associated with giant cell arteritis
    •  based on retrospective cohort study
    • 117 patients with noninfectious aortitis were followed for median 34 months
      •  73 had giant cell arteritis-related aortitis
      •  44 had isolated aortitis defined as aortitis associated with inflammatory syndrome without any other criteria for giant cell arteritis and no diagnosis for other causes of aortitis
    • comparing patients with isolated aortitis vs. patients with giant cell arteritis-related aortitis
      •  aortic aneurysm at diagnosis in 38.6% vs. 20.5% (p = 0.03)
      •  aortic aneurysm at diagnosis or during follow-up in 50% vs. 26% (p = 0.008)
      •  aortic surgery at diagnosis or during follow-up in 36.4% vs. 13.7% (p = 0.004)
    • compared to giant cell arteritis-related aortitis
      •  isolated aortitis in patients < 60 years old associated with significantly decreased aortic aneurysm-free survival (p = 0.003)
      •  isolated aortitis in patients ≥ 60 years old associated with similar aortic aneurysm-free survival
    • Reference – Autoimmun Rev 2016 Jun;15(6):571

Infectious Aortitis

  • Infectious aortitis is fatal if left untreated.(3)
  • Reported survival by treatment modality:
    • 60%-100% in patients who have a combination of medical and surgical treatment.
      • 75%-100% in patients treated before development of aneurysm
      • 62% in patients who develop aneurysm
      • 65% in patients with rupture of aneurysm
    • As low as 10% in patients treated with medication alone
    • Reference – Clin Cardiol 2009 Sep;32(9):488full-text
  • Factors reported to be associated with poor prognosis include:
    • Advanced age
    • A delay in diagnosis
    • Gram-negative bacterial infection
    • Immunosuppression
    • Infection foci in the thoracic aorta
    • Medical treatment without surgical intervention
    • The presence of complications such as rupture, embolization, or septic shock
    • Reference – Clin Cardiol 2009 Sep;32(9):488full-text

Guidelines and Resources

Guidelines

International Guidelines

  • Society of Cardiovascular Pathology and Association for European Cardiovascular Pathology Consensus statement on surgical pathology of aorta: inflammatory diseases can be found in Cardiovasc Pathol 2015 Sep-Oct;24(5):267.

United States Guidelines

  • American College of Radiology (ACR) Appropriateness Criteria for nontraumatic aortic disease can be found in ACR 2020 PDF.

European Guidelines

Review Articles

Patient Information

References

  1. Bossone E, Pluchinotta FR, Andreas M, et al. Aortitis. Vascul Pharmacol. 2016 May;80:1-10.
  2. Töpel I, Zorger N, Steinbauer M. Inflammatory diseases of the aorta: Part 1: Non-infectious aortitis. Gefasschirurgie. 2016;21(Suppl 2):80-86full-text.
  3. Töpel I, Zorger N, Steinbauer M. Inflammatory diseases of the aorta: Part 2: Infectious aortitis. Gefasschirurgie. 2016;21(Suppl 2):87-93full-text.
  4. Hartlage GR, Palios J, Barron BJ, et al. Multimodality imaging of aortitis. JACC Cardiovasc Imaging. 2014 Jun;7(6):605-19.

Related Posts

Related Posts:

15585

Sign up to receive the trending updates and tons of Health Tips

Join SeekhealthZ and never miss the latest health information

15856