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Circulation. Author manuscript; available in PMC 2009 October 9.
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Circulation. 2008 June 10; 117(23): 3039–3051. doi:10.1161/CIRCULATIONAHA.107.760686.

Aortitis

Heather L. Gornik, M.D., M.H.S. and

Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western
Reserve University Medical Director, Non-Invasive Vascular Laboratory Department of
Cardiovascular Medicine The Cleveland Clinic Foundation 9500 Euclid Avenue/Desk S60
Cleveland, Ohio 44120 (216) 445-3689 gornikh@[Link]
Mark A. Creager, M.D.*
Professor of Medicine, Harvard Medical School Simon C. Fireman Scholar in Cardiovascular
Medicine Director, Vascular Center Brigham and Women's Hospital 75 Francis Street Boston,
Massachusetts 02115 (617) 732-5267 mcreager@[Link]
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Keywords
Aortitis; vasculitis; giant cell arteritis; Takayasu arteritis; aortic aneurysm

Aortitis is the all-encompassing term ascribed to inflammation of the aorta. The most common
causes of aortitis are the large vessel vasculitides, giant cell arteritis (GCA) and Takayasu
arteritis, although it is also associated with several other rheumatologic diseases. Infectious
aortitis is a rare but potentially life-threatening disorder. In some cases, aortitis is an incidental
finding at the time of histopathologic examination following surgery for aortic aneurysm. As
the clinical presentation of aortitis is highly variable, the cardiovascular clinician must have a
high index of suspicion to establish an accurate diagnosis of this disorder in a timely fashion.
In this manuscript, we review the pathophysiology, epidemiology, diagnostic approach, and
management of aortitis.

Pathophysiology and Classification

Aortitis is the pathologic term for inflammation of the aortic wall. The classification of aortitis
broadly includes underlying rheumatologic and infectious diseases, along with isolated aortitis
(Table 1). The most common rheumatologic causes of aortitis are the large vessel vasculitides,
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giant cell arteritis (GCA) and Takayasu arteritis, although aortitis is also associated with
systemic lupus erythematosus, rheumatoid arthritis, the HLA-B27 associated
spondyloarthropathies, ANCA-associated vasculitides, Behç;et's disease, Cogan's syndrome,
and sarcoidosis. Infectious etiologies include tuberculosis, syphilis, salmonella and other
bacteria. Aortitis also may occur in isolation (i.e. there is no associated rheumatologic or
infectious disease) or accompany idiopathic retroperitoneal fibrosis or an inflamed abdominal
aortic aneurysm.

Infectious Aortitis
While the majority of cases of aortitis are non-infectious in nature, the possibility of an
infectious cause must always be considered, as treatment strategies for infectious and non-
infectious aortitis diverge widely. A number of organisms have been associated with infectious

* To whom correspondence should be addressed.

Conflicts of Interest None
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aortitis, most commonly Salmonella and Staphylococcal species, along with Streptococcus
pneumonia.1, 2 In most cases of bacterial aortitis, a segment of the aortic wall with pre-existing
pathology, such as an atherosclerotic plaque or aneurysm sac, is seeded by bacteria via the vasa
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vasorum.1, 2 Tuberculous aortitis, an uncommon problem in the developed world, may occur
as a result of direct seeding of the thoracic aorta from adjacent infected tissues, such as infected
lymph nodes or lung lesions, or by military spread.2 Syphilitic or luetic aortitis, now
exceedingly rare, typically involves the ascending aorta and is associated with thoracic aortic
aneurysm. The classic histopathologic finding is “tree-barking” of the aortic intima.2 There is
a chronic inflammatory infiltrate of the medial and adventitial vasa vasorum, which ultimately
leads to medial necrosis and a wrinkled appearance of the intima.2 Small microgummas may
be visualized within the media, and Treponema pallidum organisms may rarely be identified
with specialized staining (Warthin-Starry).2

Non-infectious Aortitis
The most common causes of aortitis are the large-vessel vasculitides GCA and Takayasu
arteritis. Although the epidemiological and clinical features of these two disorders are distinct
(see Clinical Presentation), there may be significant overlap in histopathologic findings (Figure
1). Both GCA and Takayasu arteritis are associated with an inflammatory cellular infiltrate of
the aortic media, adventitia, and vasa vasorum that contains a predominance of lymphocytes,
macrophages, and multinucleated giant cells.2, 3 Over time, there is scarring of the aortic media
and destruction of the elastic lamina.2, 3 Tree-barking may be seen in both of these disorders,
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not only in syphilis-associated aortitis.4 Granuloma formation and multinucleated giant cells
may be seen in both GCA and Takayasu arteritis.2, 3 There are a few pathologic features that
may be used to distinguish Takayasu arteritis and GCA. Takayasu arteritis is more commonly
associated with extensive intimal and adventitial fibrosis or scarring with resultant luminal
narrowing.2, 4, 5 Aortic wall thickness is generally greater among patients with Takayasu
aortitis than giant cell aortitis.2, 5 Giant cell arteritis is more commonly associated with
extensive medial inflammation and necrosis and the formation of aortic aenurysms.2, 5 Giant
cell arteritis is also characterized by focal arterial inflammation and “skip-lesions” are
common, a finding which can lead to false negative findings on temporal artery biopsy.3

The pathogenesis of both GCA and Takayasu arteritis is unknown. Both are felt to be antigen-
driven cell mediated autoimmune processes, although the specific antigenic stimuli have not
been identified.3 Both GCA and Takayasu arteritis have been associated with specific HLA-
linked antigens and a resultant genetic predisposition. Giant cell arteritis has been associated
with HLA-DR4, while Takayasu arteritis has been associated with HLA-BW52, -DR2, and -
MB1 in Japanese patients and possibly with HLA-DR4 in non-Asian patients.3, 6-8 HLA-DR1
has a negative association with the development of Takayasu arteritis in Caucasians and may
be protective.8
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In addition to GCA and Takayasu arteritis, other rheumatologic disorders including rheumatoid
arthritis, systemic lupus erythematous, Wegener's granulomatosis, Behçet's disease,
polyarteritis nodosum, and microscopic polyangiitis may lead to aortitis.2, 5, 9-13 In the case
of rheumatoid-associated aortitis, rheumatoid nodules are in the aortic wall in up to 50% of
pathologic specimens.2 In addition to these disorders, aortitis has been reported in the HLA
B-27 associated seronegative spondyloarthropathies Reiter's syndrome and ankylosing
spondylitis.14, 15 There are case reports of aortitis associated with sarcoidosis.16 Cogan
syndrome is an usual disorder characterized by episodes of interstitial keratitis and
vestibuloauditory dysfunction (i.e., eye and ear symptoms), in which aortitis occurs in up to
10% of cases.17

Aortitis also occurs in association with idiopathic retroperitoneal fibrosis (Ormond's disease),
inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis, a group

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of clinical disorders now categorized as chronic periaortitis.18-22 These disorders are unique
in that inflammation, while symptomatic, is limited to the aorta and peri-aortic tissues, rather
than a manifestation of a widespread vasculitis. Similarly in a significant percentage of cases,
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the diagnosis of aortitis is an incidental histopathologic finding, since there is no rheumatologic

disorder, infection, or symptoms attributable directly to the aortitis.5, 23 Such cases of
idiopathic isolated aortitis are typically localized to the ascending thoracic aorta and occur in
association with ascending aortic aneurysm. Patchy necrosis of the aortic media is the primary
histologic finding, along with an inflammatory cellular infiltrate, which may include
multinucleated giant cells.5

Epidemiology
The epidemiology of aortitis as a distinct clinical entity is poorly characterized. One survey-
based study of 1,290 hospitals in Japan determined a crude incidence of 0.01 cases of aortitis
per 100,000 children per year.24 While comparable data on the incidence of aortitis in Western
populations or adults are not available, the epidemiology of the large-vessel vasculitides GCA
and Takayasu arteritis, the most common causes of aortitis, have been studied in some depth.

Giant cell arteritis is a disorder in persons of advanced age and is more common among
Caucasian women.25 In the Olmsted County, Minnesota population, the average age and sex-
adjusted incidence of GCA among individuals aged 50 years or older during a fifty year period
was 18.8/100,000 per year.25 The overall incidence of GCA increased substantially during the
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fifty year follow-up period of the study, perhaps due to advances in diagnostic modalities. In
this cohort, the incidence of GCA was more than two-fold higher among women than men
(24.4 vs. 10.3 per 100,000 per year, respectively) and the mean age at the time of diagnosis
was 75 years.25 The long-term survival of patients with GCA did not significantly differ from
age-matched control patients without GCA. Not surprisingly, a similar incidence of GCA as
reported in Olmsted County has been reported in Scandinavian countries.26, 27 The reported
incidence of GCA is lower in other racial groups, including Southern Europeans, Israelis, and
Hispanic Americans.28-31 There is little published data regarding the epidemiology of GCA
in non-Western countries, although one Japanese study reported a very low prevalence of
1.5/100,000 individuals aged 50 years or older.32

The epidemiology of Takayasu arteritis is not as well characterized as that of GCA. In general,
Takayasu arteritis is a disorder of young women, and is rare relative to GCA.27 Data from
Olmstead County, Minnesota, based upon a very small number of cases, estimated an incidence
of 2.6 per 1 million residents per year, which is higher than that reported in any other
epidemiologic series.27, 33 An incidence of 0.4-1 case per 1 million residents per year has been
reported in Germany.27, 34 Although originally described by the Japanese ophthalmologist Dr.
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Mikoto Takayasu, there is no data to support an increased incidence of this disorder in Japan.
27, 35

There are circumstances in which the prevalence of aortitis is substantially higher than in that
of the general population. In a Cleveland Clinic case series of 1,204 consecutive pathologic
specimens taken from patients who underwent aortic surgery over twenty years, the prevalence
of aortitis on surgical pathology specimens was 4.3%.23 Most of the surgeries were performed
for aortic aneurysmal disease. In nearly 70% of patients with evidence of aortitis, there was no
underlying systemic disease, and the vascular inflammation was a truly incidental finding in
the majority of these cases of isolated idiopathic aortitis.23

Clinical Presentation
The clinical presentation of aortitis varies across a spectrum of symptoms and clinical signs,
ranging from back or abdominal pain with fever to acute severe aortic insufficiency to an

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incidentally-identified large thoracic aortic aneurysm (Table 2). Acute aortic syndromes,
including aortic dissection and rupture can occur in persons with aortitis.9, 36, 37 Inflammation-
associated thrombus formation in the aortic lumen with peripheral embolization has also been
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reported.38, 39 The underlying cause of the aortitis and its concomitant manifestations
determine the presenting symptoms. The location of aortic inflammation (e.g., ascending
thoracic versus abdominal aorta) and the presence of coexisting arteritis in other blood vessels
also determine clinical presentation. Due to the varied presentation of aortitis, and the often
non-specific nature of its symptoms and signs, the index of suspicion of the evaluating clinician
must be high to establish an accurate diagnosis in a timely fashion.

Giant Cell Arteritis

The classic clinical presentation of GCA is headache, temporal artery abnormalities on physical
examination, and elevated markers of inflammation in an older adult. Specific criteria have
been established for the diagnosis of GCA by the American College of Rheumatology (Table
3), with the presence of three or more of five diagnostic criteria conferring a sensitivity of 94%
and a specificity of 91% for the diagnosis.40 In addition to the classic headache and finding of
temporal artery thickening, common manifestations of GCA include polymyalgia rheumatica,
scalp tenderness, jaw claudication (due to involvement of the branches of the external carotid
artery), visual field changes (due to involvement of the ophthalmic, posterior ciliary, or retinal
arteries), and mono or polyneuropathy.41 Giant cell arteritis less commonly presents with arm
or leg claudication because of arterial occlusive disease that involves the aortic branch vessels
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and large peripheral arteries, particularly the subclavian and axillary arteries.41 In these cases,
the classic radiologic finding is long-segment, tapering lesions in the axillary and subclavian
arteries and significant wall thickening. Femoropopliteal or tibioperoneal involvement with
similar radiographic findings also occurs.42 This may cause intermittent claudication. Coronary
GCA, manifest as tapering lesions in the coronary arteries and myocardial infarction, also has
been reported (Figure 2).43 The frequency of aortic involvement in GCA is not known. It is
suggested that all patients with temporal GCA who present with symptoms suggestive of
extracranial vascular involvement undergo an imaging study to evaluate the aorta and large
vessels.41

There is an association between a history of GCA and the development of aortic aneurysm,
particularly thoracic aortic aneurysm, as a manifestation of extracranial involvement.36, 37 In
the Olmsted County cohort, patients treated for GCA had a 17-fold increase in the incidence
of thoracic aortic aneurysm compared to age and gender-matched controls.37 While 18% of
patients with GCA and aortic aneurysm were diagnosed with thoracic aortic aneurysm at the
time of diagnosis in this population, the majority developed aneurysm during follow-up, a
median of 5.8 years after the initial diagnosis. More than half of the patients with GCA-
associated thoracic aneurysm died of acute aortic dissection. In this cohort, GCA was also
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associated with a more than two-fold (relative risk 2.4) increased risk of developing abdominal
aortic aneurysm, a median of 2.5 years after initial presentation with GCA.37 Risk factors for
the development of aortic and large-vessel complications in GCA have been identified,
including the presence of a murmur of aortic insufficiency at diagnosis, concomitant
hyperlipidemia, and coronary artery disease.36 Presentation with classic cranial symptoms and
signs of temporal arteritis (i.e., headache, scalp tenderness, abnormal temporal artery
pulsations, higher erythrocyte sedimentation rate) was a negative predictor of an aortic
complication36. Evidence of GCA has also been identified on histopathologic specimens of
patients undergoing thoracic aortic aneurysm repair, including those not known to have aortic
involvement5, 23. In some of these cases there was a known history of temporal arteritis, in
others suggestive symptoms, and in some, this is a truly isolated finding (idiopathic isolated
aortitis).

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Takayasu arteritis
In contrast to GCA, Takayasu arteritis is a much rarer disorder with a predilection for young
women. The average age at diagnosis is 25-30 years, and anywhere from 75-97% of patients
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are female.44-46 As is the case for GCA, specific diagnostic criteria for Takayasu arteritis have
been established47 (Table 4). The presence of three or more of five criteria has a sensitivity of
91% and a specificity of 98% for this diagnosis.47

The most common presentation of Takayasu arteritis includes symptoms due to arterial
occlusive disease of the aorta, aortic arch, and large vessels. Other common names for Takayasu
arteritis, including pulseless disease and aortic-arch syndrome, reflect its clinical presentation.
Nearly all patients with Takayasu arteritis either present initially or ultimately develop large
vessel manifestations of the disease, including hypertension due to supra-renal aortic or renal
artery occlusive disease, pulse deficits and/or vascular bruits, and upper and/or lower extremity
claudication.44, 45 A comprehensive vascular examination, including measurement of blood
pressure in both arms and palpitation and auscultation of pulses in all major vascular regions
is a critical component of the clinical evaluation of all patients with suspected Takayasu
arteritis. In addition, we recommend measurement of blood pressure in all four extremities for
such patients.

Aortic involvement in Takayasu arteritis is very common, with angiographic abnormalities

demonstrated on aortography in nearly all patients.44-46 The abdominal aorta is the most
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common site of involvement (Figure 3, followed by the descending thoracic aorta and aortic
arch)44-46. At the time of aortography, stenotic lesions in the aorta are most frequently detected,
although aortic aneurysm is also common and has been reported in up to 45% of patients in
published case series.44-46, 48, 49 Case series have also reported rapid aortic aneurysm
expansion, aortic rupture, and the development of aortic aneurysm at the site of anastomoses
of prior reconstructive surgery among patients with Takayasu arteritis.48-50 Branch vessel
disease is highly prevalent in Takayasu arteritis, with the subclavian, innominate, renal,
common carotid, vertebral, and mesenteric arteries most often involved.44, 45

While presentation with symptoms or signs related to aortic or arterial occlusive disease is
most common, other symptoms may be present at the time of diagnosis. Some patients with
Takayasu arteritis may present with neck pain due to carotid arterial inflammation.44, 46
Constitutional symptoms, neurologic symptoms, and musculoskeletal symptoms are less
common.44 Nearly 40% of patients with Takayasu arteritis develop cardiac abnormalities,
including acute myocardial infarction, angina pectoris, and acute aortic insufficiency.44 In
these cases, the cardiac pathology is directly related to the aortic inflammation, including aortic
insufficiency as a result of aortic root dilatation, and coronary ostial stenoses due to aortitis
(Figure 4).44, 51 Takayasu arteritis may also involve the pulmonary arteries and present with
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symptoms mimicking pulmonary embolism or with isolated pulmonary hypertension.52 The

prevalence of angiographically proven pulmonary artery involvement among patients with
Takayasu arteritis is poorly characterized, with values ranging from 14.3% to 70% percent in
published series.53-56 Stenotic or occlusive lesions are the most common abnormalities noted
in the pulmonary arteries, although aneurysmal dilatation has also been described.45

Aortitis in Association with Other Rheumatologic Disorders

Aortitis should be suspected among patients presenting with evidence of systemic
inflammatory disorders or vasculitis with any clinical features suggestive of aortic involvement
(Table 2). Acute aortic insufficiency, evidence of arterial occlusive disease involving the
extremities or renal or visceral vessels, unexplained aortic dissection, or a new finding of an
aortic aneurysm in a patient without risk factors should raise the possibility of aortitis. In some
cases, the combination of aortic findings with other pathognomonic clinical features may point

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to a particular entity. For example, Behçet's disease may present with aortic aneurysm or acute
insufficiency in association with uveitis and oral and/or genital ulceration.11 A patient with
longstanding ankylosing spondylitis who develops aortic insufficiency should be suspected of
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having aortic valvulitis or ascending thoracic aneurysm.15 A young adult patient presenting
with vertigo and acute ocular symptom (e.g., interstitial keratitis, iritis, subconjunctival or
conjunctive hemorrhage), possibly with fever (Cogan syndrome) should undergo careful
cardiac examination and echocardiography to rule out the presence of acute aortic
insufficiency.17

Idiopathic Isolated Aortitis

Patients with the isolated aortitis variants, such as chronic periaortitis of the abdominal aorta
or idiopathic isolated aortitis of the thoracic aorta, may present with symptoms related to aortic
inflammation or may be diagnosed incidentally on the basis of surgical pathology from an
aortic procedure. Patients with inflammatory abdominal aortic aneurysms, perianeurysmal
aortitis, or Ormond's disease may present with constitutional symptoms, back or abdominal
pain, and elevated inflammatory markers.18-20 Inflammatory abdominal aortic aneurysm
accounts for 3-10% of all abdominal aortic aneurysms. This entity is more strongly associated
with tobacco smoking, younger age at presentation, and family history of aortic aneurysm.18,
22 Idiopathic isolated abdominal periaortitis has also been reported in the absence of aortic
aneurysm or retroperitoneal fibrosis.57 Acute renal failure due to ureteral obstruction has been
reported in patients with retroperitoneal fibrosis.20 In rare cases, claudication due to arterial
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occlusive disease also occurs.58 In the case of idiopathic isolated aortitis of the thoracic aorta,
the inflammation and aortitis is sub-clinical in nature and usually diagnosed incidentally at the
time of histopathology review following thoracic aortic aneurysm surgery.23

Infectious Aortitis
The diagnosis of infectious aortitis is difficult to establish. This disorder generally presents in
older individuals with preexisting aortic pathology, such as abdominal aortic aneurysm or
atherosclerosis of the abdominal aorta.1 Common presenting symptoms are back or abdominal
pain. Bacteremia may or may not be present.1 Aortitis should also be suspected among older
patients with atherosclerosis and sepsis with bacteremia from a typical organism, such as
Salmonella species.1, 59, 60 In such cases, immediate cross- sectional aortic imaging (CTA or
MRA) should be performed to exclude the possibility of infectious aortitis. Establishing the
diagnosis of infectious aortitis or mycotic aortic aneurysm early on is critical, as this condition
is associated with a high rate of rupture and subsequent mortality if left untreated.1, 59-62 The
diagnosis of tuberculous aortitis is very difficult to establish, as this disorder is exceedingly
rare and can mimic Takayasu arteritis.63 Delay in diagnosis may occur, and patients may be
treated with immunosuppressive therapy before the diagnosis of tuberculosis is made. As such,
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the possibility of tuberculous aortitis should be considered among patients with aortitis or
atypical aortic aneurysms who have a history of pulmonary or extrapulmonary tuberculosis or
chronic immunosupression or who present with a suspicious finding such as a cavitary lung
lesion, pleural effusion, or lymphadenitis.63 In such cases, a definitive diagnosis should be
pursued before glucocorticoids are given.

Diagnostic Testing
When the diagnosis of aortitis is suspected on the basis of clinical presentation, expedient
imaging of the entire aorta with an appropriate modality is critical to establish the diagnosis.
Modern imaging tools for the aorta include computed tomography angiography (CT), magnetic
resonance angiography (MRA), and ultrasonography. Positron emission tomography (PET)
scanning has emerged for targeted imaging of vascular inflammation, and may be particularly
useful when combined with traditional cross sectional imaging modalities.

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Angiography
Though once the gold-standard for diagnosing aortitis, particularly aortitis due to Takayasu
arteritis, technological advances in non-invasive cross sectional imaging techniques have
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generally led to the replacement of conventional aortography with CTA or MRA. In addition
to their non-invasive nature, CTA and MRA have the additional advantage of imaging the
components of the aortic wall and periaortic structures, rather than the lumen only, as is the
case of conventional angiography. Invasive aortography is generally reserved for cases in
which diagnosis of an acute aortic syndrome is uncertain, despite non-invasive imaging, or for
performance of catheter-based revascularization procedures in select patients.

Non-Invasive Angiographic Imaging (CTA and MRA)

Computed tomography, generally with the administration of iodinated contrast (CTA), is
widely available in most medical centers and also allows for the rapid exclusion of aortic
pathologies which may mimic acute aortitis, including aortic dissection, intramural hematoma,
and penetrating atherosclerotic ulcer. In addition, CTA allows for accurate assessment of
stenotic lesions of the aorta or large arteries, most common in Takayasu arteritis, as well as the
presence and extent of aortic aneurysm or thrombus. Computed tomography in the setting of
acute aortitis may demonstrate thickening of the aortic wall and peri-aortic inflammation,
although milder degrees of inflammation or wall edema may not be apparent.64 It is considered
less sensitive than other modalities for evaluation of the degree of inflammation in the aortic
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wall.64 Computed tomography is of use in the long-term follow-up of patients with treated
aortitis, particularly for monitoring progression of thoracic aortic aneurysm. Unlike MRA,
computed tomography can also be used to assess the extent of aortic and arterial calcification,
a complication of long-standing, “burnt out” aortitis (Figure 5).65 Aside from concerns
regarding decreased sensitivity for assessment of disease activity in aortitis, the primary
limitation of CTA is the requisite radiation exposure and need for iodinated contrast for optimal
vascular imaging.

Magnetic resonance angiography, generally with gadolinium contrast enhancement, continues

to is emerging as a non-invasive imaging modality of choice for aortitis, particularly aortitis
associated with GCA and Takayasu arteritis.64 Magnetic resonance imaging may be used to
image the entire aorta without radiation exposure or iodinated contrast, and it provides excellent
resolution of the aortic wall. Areas of active aortitis may appear as vessel wall edema,
enhancement, or wall thickening on MRA66 (Figure 6). Specific MRI imaging protocols have
been developed to enhance characterization of the blood vessel wall in the setting of arteritis,
including the so-called “edema weighted” technique.67 Similar to CTA, MRA can detect aortic
aneurysm and areas of aortic or arterial stenosis, the large-vessel complications of aortic wall
inflammation. Improvement of vessel wall edema with immunosuppressive therapy has been
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demonstrated in patients with Takayasu arteritis and patients with GCA undergoing
immunosuppressive therapy and followed with serial imaging studies.68, 69 One study in a
larger cohort of patients with Takayasu arteritis found that MRI assessment of vessel wall
edema did not fully correlate with clinical disease activity.66 These investigators have
hypothesized that the finding of vessel wall edema may not be due to active inflammation,
rather tissue remodeling after inflammation has resolved.66 While the role of MRA for
prospective assessment of disease activity in aortitis remains controversial, it is clearly an
invaluable non-invasive tool for the diagnosis of aortitis, as well as associated aneurysm
formation or arterial stenosis.

Recently, the use of 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET),

either alone or in combination with contrast-enhanced CTA or MRA, has emerged as a potential
tool for initial diagnosis and for assessment of disease activity of aortitis due to either GCA or
Takayasu arteritis.69-72 Recent imaging series have reported a sensitivity of 60-92% and a

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specificity of 88-100% of 18F-FDG PET for diagnosis of active inflammation in arteritis, but
these studies have been limited by small sample size, heterogeneous patient population, and
inconsistent choice of a reference standard.70, 72, 73 Hybrid imaging with 18F-FDG PET and
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either CTA or MRA allows for more precise anatomic localization of disease activity, with
increased uptake of 18F-FDG felt to be a surrogate marker of increased activity of inflammatory
cells. The presence of wall thickening, arterial stenosis, luminal thrombus, and aneurysm
cannot be assessed by PET alone; CTA and MRA are complementary to PET for complete
evaluation of the patient with aortitis (Figure 7). The role of 18F-FDG PET in the diagnosis
and follow-up of patients with aortitis will ultimately need to be established with larger clinical
studies.

Ultrasound
Though generally not utilized as a primary diagnostic modality for aortitis, abdominal
ultrasound or transthoracic or transesophageal echocardiography may demonstrate
circumferential thickening of the aortic wall. Abdominal ultrasonography is useful for the
diagnosis of abdominal aortic aneurysm occurring as a complication of aortitis, on in
association with chronic periaortitis or inflammatory aneurysm. In addition, echocardiography
plays a key role in assessment of the aortic root and aortic valve in the setting of aortitis of the
ascending thoracic aorta associated with aortic insufficiency and aneurysm formation.74-76

Recently, peripheral vascular ultrasound has also been used in the diagnosis and surveillance
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of both GCA and Takayasu arteritis. The presence of a hypoechoic (i.e., dark) halo around the
vessel lumen on color duplex ultrasound of the temporal arteries (“halo sign”) is associated
with active inflammation on temporal artery biopsy.77-79 In addition, the absence of a temporal
artery “halo sign” has a negative predictive value of 92-96% for temporal arteritis on biopsy.
77, 78 Reduction and complete resolution of the periluminal “halo” may occur in response to
glucocorticoid therapy.77 A recent study identified abnormalities of the abdominal aorta on
duplex ultrasound, including aortic wall thickening, small aneurysms, and the “halo sign”
among a majority of patients with biopsy-proven GCA.80 Takayasu arteritis may present with
extensive, concentric arterial wall thickening on color duplex ultrasound of involved arterial
segments, reflective of vessel wall inflammation (Figure 8).79, 81, 82 The thickening is generally
brighter than the “halo sign” of GCA and has been named the “macaroni sign”.79, 81 Marked
thickening of the intimal-medial complex may be seen in the subclavian and common carotid
arteries, in particular, and is often bilateral.81, 83-85 Duplex ultrasound may also identify areas
of arterial stenosis or occlusion in the setting of both GCA and Takayasu arteritis. Thickness
of the carotid intimal-medial complex has shown early promise as a quantifiable marker of
disease activity among patients with Takayasu arteritis, and may have potential as a marker of
therapeutic response among patients receiving immunosuppressive therapy.86, 87
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Laboratory Testing
While the diagnosis of aortitis is generally made on the basis of clinical presentation and aortic
imaging, key laboratory tests are helpful. The initial evaluation of a patient with suspected
aortitis should include markers of inflammation, namely erythrocyte sedimentation rate (ESR)
and c-reactive protein (CRP), a complete blood count, assessment of kidney and liver function,
and blood cultures to exclude the unlikely but critical diagnosis of infectious aortitis. Additional
laboratory testing should be based upon the clinical assessment of the patient and the
differential diagnosis of the underlying cause. A rheumatologic panel, including anti-nuclear
antibodies, anti-neutrophil cytoplasmic antibodies, and rheumatoid factor may be helpful in
the appropriate clinical setting. Skin testing for tuberculosis and serologic testing for syphilis
should be reserved for those rare cases in which the clinical suspicion of these very unlikely
disorders is high. In cases of aortitis associated with retroperitoneal fibrosis, secondary causes

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such as lymphoma should be considered, and a biopsy should be obtained if there is clinical
suspicion of malignancy on the basis of clinical presentation and imaging studies.
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While ESR and CRP are typically markedly elevated in cases of aortitis due to GCA and other
systemic vasculitides, these inflammatory markers may be unreliable for prediction of disease
activity among patients with Takayasu arteritis.44, 88, 89 Accordingly, the American College
of Rheumatology diagnostic criteria for GCA includes elevated ESR, while the criteria for
Takayasu arteritis do not include elevated markers of inflammation.40, 47 Recent clinical
investigation has focused on the identification of novel and more sensitive laboratory markers
for disease activity among patients with Takayasu arteritis, with IL-6, IL-18, and certain matrix
metalloproteinases showing promise in small studies.88, 90, 91

Management
Once the diagnosis of aortitis has been established, the approach to management depends upon
the underlying cause. The goals of therapy include both the immediate treatment of aortic
inflammation, or infection in rare cases, and surveillance and management of aortic and arterial
complications.

Infectious Aortitis
The uncommon case of infectious aortitis requires rapid diagnosis, antibiotic therapy, and
NIH-PA Author Manuscript

consultation with a vascular surgeon. The initial treatment of suspected infectious aortitis is
intravenous antibiotics with broad antimicrobial coverage of the most likely pathologic
organisms, particularly Staphylococcal species and gram negative rods.1 Antibiotics should be
initiated as soon as the diagnosis of infectious aortitis is suspected, and while awaiting
microbiologic data. The antibiotic regimen can then be tailored, based upon the results of
culture and sensitivity data. Due to case series reporting a very high mortality rate among
patients with gram-negative infectious aortitis treated with medical therapy alone, a
combination strategy of intensive antibiotic therapy and surgical debridement, with aneurysm
repair if necessary, is generally recommended, although no clinical trials have explored the
optimal management of such patients.1, 60-62, 92-94 There are small case series, each with no
more than a few cases, of combined medical and endovascular management of mycotic
aneurysm.95-98 Despite aggressive therapy, mortality associated with infectious aortitis
remains high in reported series, largely due to a high rate of aortic rupture.1, 59, 61, 62, 93, 94
While no clinical studies have established the optimal duration of antibiotic therapy for aortitis,
a treatment course of at least 6 to 12 weeks following surgical debridement and clearance of
blood cultures is generally recommended, with a longer course reserved for patients with
immunosuppressive disorders.1
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Aortitis Associated with Large Vessel Vasculitis

Immunosuppressive therapy is the primary treatment of non-infectious aortitis due to large-
vessel vasculitis, and patients are ideally managed by a multi-disciplinary team that includes
a rheumatologist and medical and surgical cardiovascular specialists. Once the diagnosis of
non-infectious aortitis due to GCA or Takayasu arteritis has been established, oral
glucocorticoid therapy should be initiated. In general, an initial starting dose of 40-60
milligrams prednisone daily (for GCA) or 1 milligram/kilogram prednisone daily (for Takayasu
arteritis) is prescribed, although the optimal starting dose of steroid therapy for patients with
aortitis has not been established.41, 44, 99 The prednisone dose is gradually tapered over time
with close monitoring of symptoms, vascular signs, inflammatory markers, and imaging
studies. Most patients with arteritis are treated with steroids over a period of months, or even
years, in attempt to achieve complete remission.44, 100

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Despite glucocorticoid therapy, the relapse rate for both GCA and Takayasu arteritis is high,
up to 50% or greater.44, 100-102 In addition to recurrent symptoms, re-elevation of inflammatory
markers may be a helpful sign of relapsed disease, particularly among patients with GCA.41,
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88 Due to decreased sensitivity of inflammatory markers for monitoring disease activity in

Takayasu arteritis, the diagnosis of relapse is more difficult.88 The NIH criteria for disease
activity in Takayasu arteritis define active disease as new or worsening of two or more of the
following: systemic symptoms attributable to arteritis, elevated ESR, vascular symptoms or
examination findings, or typical angiographic abnormalities.44 The role of edema-weighted
MRI, 18F-FDG PET, vascular ultrasound, and novel inflammatory biomarkers (e.g., IL-6) in
the diagnosis of relapse in Takayasu arteritis are areas of ongoing investigation.

Due to the need for long-term therapy and the potential for steroid-related adverse effects,
medications to prevent osteoporosis, gastric ulceration, and Pneumocystis (carinii) jiroveci
pneumonia should be prescribed, as indicated, for patients with aortitis requiring long-term
glucocorticoid therapy.103 Patients should also be carefully monitored for the development of
steroid-induced diabetes mellitus or hypertension, secondary infections, and cataracts,
common complication of long-term glucocorticoid therapy.100, 104 Patients with visual
symptoms related to GCA are generally admitted to the hospital for intravenous glucocorticoid
therapy, followed by oral therapy, although the likelihood of permanent visual deficits remains
high, even among those aggressively treated.105, 106 Patients with severe symptoms related to
aortitis, such as acute aortic insufficiency or coronary artery involvement, should similarly be
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treated in hospital with initial intravenous therapy.

Several studies have investigated potential steroid-sparing regimens for both GCA and
Takayasu arteritis, because of the potential need for long-term immunosuppressive therapy.
Daily administration of prednisone (45 mg daily) was found to be superior to every other day
treatment (90mg) in the management of GCA.107 Recently, a small randomized trial compared
standard oral prednisone therapy to initial induction therapy with intravenous
methylprednisolone (15mg/kg) followed by oral therapy among patients with GCA.108 At 78
weeks of follow-up, patients randomized to initial intravenous induction therapy had a lower
oral steroid requirement and were less likely to relapse, although there was no significant
difference in adverse clinical events between the two groups.108 Three randomized clinical
trials have investigated the potential benefit of the addition of methotrexate to standard oral
steroid therapy for the initial treatment of GCA with conflicting findings, and such combination
therapy is not generally recommended.109-111 A recent small trial of the anti-tumor necrosis
factor agent, infliximab, for the maintenance of remission in patients with GCA found no
benefit.112 Adjunctive, steroid-sparing therapy has also been investigated in the management
of Takayasu arteritis, particularly among patients with difficult to treat or relapsing disease.
99, 113 In small studies, methotrexate, azathioprine, mycophenolate mofetil, and infliximab
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have shown promise.114-117 These agents are an option for use in steroid-refractory patients,
although data from large randomized clinical trials are needed to determine their optimal role.

Isolated Idiopathic Aortitis

In rare cases, active aortitis on histopathology may be found incidentally in patients with
thoracic or abdominal aneurysm who have undergone surgical repair.4, 5, 23 Such patients may
have no known history of vasculitis and no systemic signs or symptoms to suggest active or
prior disease. The optimal management of such patients is uncertain, and the decision to treat
with a course of glucocorticoid therapy should be considered on a case-by-case basis depending
on the clinical presentation of the patient and the location and extent of inflammation.
Inflammatory markers, such as the ESR or CRP, will be unreliable during recovery from major
aortic surgery, but may be helpful in long-term follow-up. In such patients, imaging of the
entire aorta for evidence of active disease or aneurysm in other vascular beds should be

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 Gornik and Creager Page 11

considered. Patients with isolated idiopathic aortitis require careful follow-up, as small case
series have identified a propensity toward aneurysm formation in other vascular beds over time.
5, 23
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Surgical and Endovascular Therapy

In addition to immunosuppressive therapy, patients with aortitis due to large-vessel vasculitis
must be closely monitored for the development of vascular complications, particularly
evidence of aortic aneurysm or new aortic or arterial occlusive disease. A comprehensive
vascular examination should be performed at each visit. Measurement of bilateral arm and
ankle pressures is useful to assess for arterial occlusive disease, particularly among patients
with Takayasu arteritis. Patients with known thoracic or abdominal aneurysm due to treated
aortitis should be monitored periodically for aneurysm expansion, with indications for surgical
correction the same as for other etiologies.118 All patients with Takayasu arteritis or GCA with
known aortic involvement should undergo periodic imaging for the development of thoracic
or abdominal aortic aneurysm, given the known risk of these complications.36, 37, 48, 49 It is
preferable if inflammation of the aorta can be treated with a course of immunosuppressive
therapy prior to surgery. Ideally, patients should be in clinical remission before elective repair
of an aortitis-related aneurysm. Open aortic reconstructive surgery is generally the standard of
treatment for aortic aneurysms associated with aortitis, although endovascular techniques have
recently been employed with early reported successes.95, 119-121 While endovascular treatment
has the theoretical advantage of avoiding extensive manipulation of inflamed aortic tissue,
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there have been no head-to-head trials of the optimal strategy for management of aortic
aneurysm in patients with aortitis. As endovascular techniques for the treatment of aortic
aneurysm in all anatomic locations evolve, particularly the thoracic aorta, this will undoubtedly
be an area of future investigation.

For patients with severe symptoms from aortic or arterial occlusive disease due to GCA or
Takayasu arteritis, such as secondary hypertension or arm or leg claudication, surgical or
catheter-based revascularization of the aorta or large arteries is a therapeutic option (Figure 3).
As is the case for treatment of aneurysmal disease, elective surgery is ideally deferred until the
patient has achieved a clinical remission with immunosuppressive therapy and inflammation
has been controlled. Secondary hypertension due to severe aortic or renal arterial occlusive
disease from Takayasu arteritis has been treated with balloon angioplasty, although the rate of
restenosis is high.44, 122 The addition of endovascular stenting has improved outcome in these
patients, to some extent, though the restenosis rate remains substantial in recent case series.
123-125 In certain cases, surgical bypass grafting may be associated with more durable long-
term outcome for arterial occlusive disease than endovascular procedures among patients with
Takayasu arteritis.125, 126 Among patients with GCA with severe arm claudication or critical
limb ischemia due to long-segment axillary or subclavian artery stenosis or occlusion,
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treatment generally involves surgical revascularization with upper extremity arterial bypass
grafting from the common carotid artery to the axillary or brachial artery. Large cases series
exploring outcomes in such cases are limited. Endovascular therapy has recently been applied
to select arterial occlusive lesions in patients with GCA with successful results in case series,
however the typical long-segment nature of the occlusive lesions of GCA is associated with a
significant risk of restenosis.127, 128

Acknowledgment
The authors thank Mr. Abizer Sakarwala for research assistance in preparation of this manuscript.

Funding Sources: Dr. Creager receives support as Program Director for a Research Career Development Program in
Vascular Medicine (K12 HL083786) from the National Heart, Lung, and Blood Institute (NHLBI). He is the Simon
C. Fireman Scholar in Cardiovascular Medicine at Brigham and Women's Hospital.

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 Gornik and Creager Page 12

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Figure 1.
Pathologic findings in Takayasu arteritis. Shown are gross (Panel A) and histologic (Panel B)
pathology of the innominate artery of a 27 year-old woman with Takayasu arteritis with arch
vessel involvement. There is extensive intimal thickening with attenuation of the media and
adventitial fibrosis (Panel A). Histology revealed degeneration of the media with a dense
inflammatory infiltrate, including giant cells (arrow). (Image courtesy Dr. Richard N. Mitchell,
Department of Pathology, Brigham and Women's Hospital).
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Figure 2.
Coronary giant cell arteritis. This 75 year-old woman presented with non-ST segment elevation
myocardial infarction and concomitant bilateral arm claudication.43 There is a tapering lesion
in the left anterior descending artery (arrow), typical of GCA. (Reproduced from Jang, et al.
43, with permission of the publisher).
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Figure 3.
Aortic occlusive disease in a patient with Takayasu arteritis and bilateral leg claudication.
Shown are MRA images demonstrating severe, diffuse stenosis of the infrarenal abdominal
aorta and common iliac arteries (Panels A and B). A prominent collateral vessel is noted
(arrow). The patient underwent endovascular revascularization (Panel C, volume rendered
CTA). (Image courtesy Drs. Gary Hoffman and Paul Schoenhagen, Cleveland Clinic
Foundation).
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Figure 4.
Takayasu arteritis involving the coronary ostia. Shown are high-grade ostial stenoses of the
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left main coronary artery (Panel A) and right coronary artery (Panel B). Coronary involvement
in association with Takayasu arteritis is generally ostial in location and due to aortitis at the
aortic root. (Reproduced from Kang, et al.51, with permission of the publisher).
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Figure 5.
Computed tomogram of severe aortic and coronary calcification in a patient with a remote
history of aortitis (“porcelain aorta”). Shown are volume-rendered CT images demonstrating
severe calcification of the thoracic and abdominal aorta (arrowheads), as well as the coronary
arteries (arrows). There is diffuse aneurysmal dilatation of the ascending thoracic aorta. (Image
courtesy Dr. Paul Schoenhagen, Departments of Radiology and Cardiovascular Medicine,
Cleveland Clinic Foundation).

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Figure 6.
Magnetic resonance angiography in a patient with Takayasu arteritis and active aortitis. Shown
are oblique sagittal (top row) and oblique axial (bottom row) images of the thoracic aorta with
T-2 weighted black blood (left column) and edema-weighted imaging (right column). There
is wall thickening of the descending thoracic aorta (best seen on axial images) with increased
signal consistent with edema and inflammation (arrows). Periaortic inflammation and
lymphadenopathy were also present. (Image courtesy Dr. Paul Schoenhagen, Departments of
Radiology and Cardiovascular Medicine, Cleveland Clinic Foundation).
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Figure 7.
Combination of 18F-FDG PET and computed tomography for assessment of Takayasu arteritis.
Shown are sagittal plane contrast-enhanced computed tomographic (CTA) images of the
thoracic and abdominal aorta (Panel A), 18F-FDG PET – CTA overlay (Panel B), and 18F-FDG
PET alone (Panel C). There are areas of FDG-uptake, consistent with inflammation, visualized
in the descending thoracic and abdominal aorta. (Image courtesy Dr. Paul Schoenhagen,
Departments of Radiology and Cardiovascular Medicine, Cleveland Clinic Foundation).
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Figure 8.
High resolution B-mode ultrasound of the common carotid artery a patient with active
Takayasu arteritis. There is marked, diffuse, concentric thickening of the vessel wall with a
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heterogeneous appearance (arrow). The intimal-medial complex is markedly thickened. This

finding has been termed the “macaroni sign”.81 No atherosclerotic plaque is visualized. Similar
findings were present in the contralateral common carotid artery.
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Table 1
Causes of Aortitis

Inflammatory
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Large-Vessel Vasculitis
Giant cell arteritis (temporal arteritis)
Takayasu arteritis
Rheumatoid arthritis
Systemic lupus erythematosis
HLA-B27 associated spondyloarthropathies
• Ankylosing spondylitis
• Reiter syndrome

Other vasculitides
• ANCA-associated* vasculitides
■ Wegener's arteritis
■ Polyarteritis nodosum
■ Microscopic polyangiitis
• Behçet's disease
• Cogan syndrome
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• Relapsing polychondritis

Sarcoidosis
Isolated Aortitis
Isolated idiopathic (thoracic) aortitis
Chronic periaortitis
• Idiopathic retroperitoneal fibrosis (Ormond's disease)
• Inflammatory abdominal aortic aneurysm
• Perianeurysmal aortitis
• Idiopathic isolated abdominal periaortitis

Infectious
Bacterial
• Salmonella spp.
• Staphylococcus spp.
• Streptococcus pneumoniae
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• Other

Luetic (Syphilis)
Mycobacterial (i.e., M. tuberculosis)
Other

*
ANCA – Anti-neutrophil cytoplasmic antibody

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Table 2
Varied Spectrum of Clinical Presentation of Aortitis

Back or abdominal pain with fever

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Systemic inflammatory syndrome due to vasculitis

Aneurysmal disease
• Thoracic aortic aneurysm
• Abdominal aortic aneurysm

Cardiac abnormalities
• Aortic insufficiency (acute or chronic)
• Stable angina pectoris or acute coronary syndrome due to coronary involvement

Aortic thrombosis with distal embolization

Aortic dissection or rupture (rare)
Upper and/or lower extremity claudication with pulse deficits
Hypertension in a young patient (Takayasu arteritis)
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Table 3
American College of Rheumatology Classification Criteria of Giant Cell
Arteritis40*
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1. Age at disease onset >=50 years

     Development of symptoms or findings beginning at age 50 or older
2. New headache
     New onset of or new type of localized pain in the head
3. Temporal artery abnormality
     Temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries
4. Elevated erythrocyte sedimentation rate
     Erythrocyte sedimentation rate >=50 mm/hour by the Westergren method
5. Abnormal artery biopsy
     Biopsy specimen with artery showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation,
usually with multinucleated giant cells

(Adapted from Hunder, et al. 40 with permission of the publisher.)

*
The presence of three or more criteria is consistent with the diagnosis of giant cell arteritis with a sensitivity of 94% and a specificity of 91%
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Table 4
American College of Rheumatology Classification Criteria of Takayasu
Arteritis47*
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1. Age at disease onset < 40 years

     Development of symptoms or findings related to Takayasu arteritis at age less than 40 years
2. Claudication of extremities
     Development and worsening of fatigue and discomfort in muscles of one or more extremity while in use, especially the upper extremities
3. Decreased brachial artery pulse
     Decreased pulsation of one or both brachial arteries
4. Blood pressure difference >10 mm Hg
     Difference of >10 mm Hg in systolic blood pressure between arms
5. Bruit over subclavian arteries or aorta
     Bruit audible on auscultation over one or both subclavian arteries or abdominal aorta
6. Arteriogram abnormality
     Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities, not
due to arteriosclerosis, fibromuscular dysplasia, or similar causes; changes usually focal or segmental

(Adapted from Arend, et al.47 with permission of the publisher.)

*
The presence of any three or more criteria is consistent with a diagnosis of Takayasu arteritis with a sensitivity of 91% and a specificity of 98%.
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