on 18-Feb-2021 (Thu)

The epidemiology of aortitis as a distinct entity is poorly studied. Vasculitis has a worldwide distribution, with the greatest prevalence among Asians. In a nationwide Japanese survey conducted among children in 1290 hospitals, a crude incidence of 0.01 per 100,000 per year was reported [1]. In the United States and European populations, the incidence is 1-3 new cases per million per year. In a cohort of 1204 surgical aortic specimens described by Rojo-Leyva et al., 168 (14%) had inflammation and 52 (4.3%) were classified as having idiopathic aortitis [2]. Among 383 individuals with thoracic aortic aneurysms, 12% had idiopathic aortitis [2]

IA usually affects patients with atherosclerotic and/or aneurysmal disease and/or infective endocarditis [15]. Except for cases secondary to endocarditis, IA is more frequent in the elderly and in men, probably because of higher rates of aortic plaques and/or aneurysms favoring secondary infection [16,17]. In a retrospective study of patients entering the Mayo Clinic between 1976 and 1999 [18], only 29 cases of operated IA are reported, with two thirds affecting the abdominal aorta

Exceptional in western countries, cases of aortitis due to Mycobacterium tuberculosis can be observed in developing countries. It affects the abdominal aorta in two thirds of cases and it can be the sole manifestation of tuberculosis in one third of cases [19]

Physical examination may reveal abnormal heart sounds, sounds over the major arteries, or pulse abnormalities. Although there are no specific blood tests, unexpectedly high values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should be considered suspicious. Diagnosis is usually suspected by echocardiography as the first-line imaging technique and should be confirmed with other imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), and positron emission tomography (PET) which can reveal inflammation, vessel wall changes (typically wall edema) and lumen changes (including aneurysmal dilatation and stenosis or occlusions) (Figure 2)

Inflammation of the aorta can cause aortic dilatation. This can occur in up to 45% of GCA cases. When the proximal aorta is involved, symptoms and signs of aortic valve regurgitation can be present. Also, it can cause fibrous thickening and ostial stenosis of major aortic branches, as in the “pulseless” phase of TKA, resulting in reduced or absent peripheral pulses, low arm blood pressure, or in contrast with hypertension due to renal artery stenosis. Depending on other involved vessels, ocular disturbances, neurological deficits, claudication, and other manifestations of vascular impairment may accompany this disorder (Table 2) [4,20-23].

Other non-specific clinical manifestations include pain, fever, weight loss, and general status alteration, which may mimic other entities. It is not uncommon to diagnose unexpectedly NIA in patients assessed for unexplained fever or chest, abdominal, or back pain, or in those with rash or arthralgia suggestive of collagen vascular disorders.

IA is associated with various bacterial and viral pathogens, which may also affect other organs with a panoply of clinical manifestations. Exposure history, high-risk behavior, immunosuppression, and recent surgical instrumentation are important to orient the diagnosis

No specific laboratory tests exist for the diagnosis of aortitis. CRP and ESR are increased in most patients with vasculitis. However, they are frequently increased in other disorders that are usually considered in the differential diagnosis of these patients, notably rheumatic disorders and malignancies. Thus, their diagnostic usefulness is quite limited, serving mainly as tools for monitoring disease activity during therapy. Normal ESR does not exclude aortitis (e.g., in case of GCA)

Smooth muscle myosin is predominantly found in the aortic medial layer, and preliminary testing showed that it is elevated in patients with injury of the aortic wall [24]. However, it lacks specificity, making its clinical use for aortitis suboptimal.

In case of IA, microbiology is of paramount importance to identify the etiology. Blood cultures are positive in 50% to 85% of the patients and microorganisms can be isolated from the excised aortic tissue in up to 76% of patients [25]

Pentraxin-3 (PTX-3) is a new promising potential biomarker for IA. It belongs to the pentraxin family like CRP and is selectively produced by vascular endothelial cells, macrophages and neutrophils [24,26]. A study comparing the usefulness of CRP and PTX3 showed that PTX3 is more specific for arterial inflammation than CRP (CRP: sensitivity 65.2%, specificity 94.4%; PTX3: sensitivity 82.6%, specificity 77.8%). Furthermore, PTX3 levels showed no correlation with prednisolone dose used for the treatment of TKA, suggesting that this biomarker reflects pathogenic activity of the disease regardless of therapeutic steroid use [26]

The thoracic and abdominal aorta and the peripheral aortic branches are easily accessible to vascular ultrasound, which may demonstrate mural thickening, aortic aneurysms, or a perivascular hypoechoic halo reflecting wall edema. After pharmacological treatment, often wall edema decreases and echocardiography may be used to follow closely the clinical evolution providing evidence of therapeutic efficacy and revealing increased wall echogenicity secondary to fibrosis [29]. Furthermore, color Doppler allows functional evaluation of stenotic segments, which may guide management (Figures 3 and 4).

Echocardiography plays a key role in the assessment of the aortic root and aortic valve in the setting of aortitis of the ascending thoracic aorta associated with aortic valve sclerosis [30-32]. Regardless of the extent of aortitis, the presence of aortic valve insufficiency and aneurysmal change of aortic root are mandatory [33,34].

Compared to MRI or PET, CT is more precise for the assessment of aortic wall thickness and regularity, aortic diameter, aortic branches, intramural hematoma, mural calcifications, and inflammatory periaortic soft tissue changes. It readily identifies complications of IA and allows detection of mycotic aneurysms that are particularly at high risk of fatal rupture if left untreated

The drawbacks of CT and CTA are inferior characterization of wall changes especially in early phases, the use of ionizing radiation and iodinated contrast media

Although spatial resolution is inferior to CT and CTA, MRI has superior soft tissue characterization and can detect the earliest signs of inflammation in the vessel wall as well as the luminal changes of the mature phase.

PET is sensitive for early aortitis and may be useful for monitoring response to treatment: persistent 18 F-FDG uptake in the arterial wall at follow-up despite adequate therapy was reported to have a predictive value for vascular remodeling and aneurysmal dilatation [41].

If the infectious agent is unknown, antibiotic therapy should cover all common pathogens known to cause aortitis, including staphylococcal species and Gram-negative organisms [47]. Gram-negative pathogens are reported to show an aggressive course of infection including aortic rupture [48,49]. In addition to standard antibiotic agents, new substances like tigecycline are effective and can be applied in cases of allergies to cephalosporins or multiresistant pathogens [50]

Antibiotic treatment should be monitored by regular measurement of white blood cell count and CRP, and should be continued after the acute phase for 6 to 12 weeks to prevent disease relapse [47,51]. In cases of foreign material in close relation to the infected area, for example coated stent grafts, a sustained antibiotic therapy for one year or even lifelong may be considered [52-54]

Lesions at high risk of rupture, for example intramural hematoma or infections with Gram-negative germs, may be treated aggressively with early surgical or catheter-based interventions [51,52,59-61]. Successful treatment of aortovenous fistulas with covered stents and arterial occluders is reported in selected patients [53]. In addition, a stepwise approach with “bridging” an iliac-enteric fistula or a ruptured mycotic aneurysm with a coated stent-graft before elective surgical repair is also described [62,63]

In intermediate risk patients, watchful waiting is recommended

Conservative therapy without surgical intervention can be applied to low-risk lesions showing intact aortic wall without aneurysm formation. However, these patients should be reassessed after one year and beyond to exclude delayed aneurysm formation