Inflammatory diseases of the aorta

The term aortitis encompasses inflammatory changes to the aortic wall from varying etiologies that are associated with certain specific histopathological lesions. The inflammatory response may be limited to the aortic wall or accompanied by changes directly adjacent to the vessel (e. g. retroperitoneal fibrosis) or other vessels (e. g. giant cell arteritis). A distinction is made between infectious and non-infectious aortitis. Takayasu arteritis and giant cell arteritis are the most common causes of non-infectious aortitis [6, 7]; however, an association has been shown between other rheumatological diseases and inflammatory changes to the aortic wall, e. g. rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granulomatosis and Behçet’s disease (Tab. 1, [2]). It is essential to differentiate between non-infectious causes of aortitis and the much rarer infectious causes, as treatment approaches differ greatly. Numerous bacteria have been described as causative agents in infectious inflammation, the most common being Salmonella, Staphylococci and Pneumococci [4, 16]. More rarely, aortic wall infections may be caused by mycobacteria that infiltrate the aortic wall from infected lung tissue, lymph nodes or via milia [22]; however, fungi and viruses have also been described as causative agents in aortitis [8, 20]. Part 2 of this continuing medical education (CME) article provides a detailed description of infectious aortitis.

Takayasu arteritis (synonyms: pulseless disease, occlusive thromboaortopathy and Martorell syndrome) is a chronic inflammatory arteritis primarily affecting the large vessels, in particular the aorta and its branches. Although case reports date back as far as 1830 it was not until 1905 that the characteristic fundal lesions were published by Takayasu, a professor of ophthalmology at the Kanazawa University in Japan as ischemic neuropathy of the optic nerve with annular arteriovenous neo-anastomosis. The disease is rare, with 5000 cases reported throughout Japan between 1990 and 2000, while a US study put the incidence at 2.6 cases per 1,000,000 inhabitants per year. The incidence in European countries is unknown. The majority of cases are still seen in East Asia where young females are almost exclusively affected [5]. A phase of asymptomatic disease generally precedes clinically apparent symptoms and findings. Disease onset is generally seen in the second or third decade of life, whereby the interval between symptom onset and diagnosis may be protracted (range 2–11 years [17]). Nonspecific symptoms include fever, nocturnal sweating, malaise, weight loss, joint and muscle pain as well as mild anemia. As vascular lesions progress, stenosis and occlusion occur with resultant ischemia to end organs [7]. Changes in the aortic region affect the abdominal section in particular and need to be differentiated from other causes of atypical coarctation of the aorta (e.g. mid-aortic syndrome) (Tab. 2). The aortic arch and its branches are affected almost equally. Characteristic features include weakened or absent peripheral pulse (pulseless disease), vascular bruits, renal hypertension due to renal artery stenosis, retinopathy, aortic valve insufficiency due to dilation of the valve ring and subsequent dilated cardiomyopathy and myocardial ischemia due to coronary ostial stenosis. Syncope, epileptic seizures and amaurosis fugax may occur as a result of ischemic or hypertensive cerebral damage. Carotidynia and erythema nodosum are rare clinical findings that may be linked to Takayasu arteritis.

In view of the frequently observed manifestation of decreased perfusion of internal organs or extremities, (duplex) ultrasound plays an important role in the basic diagnostic work-up and can provide valuable early information about the correct diagnosis by differentiating between stenotic morphology and arteriosclerotic lesions (Fig. 1); nevertheless, modern ultrasound methods are not yet able to replace cross-sectional diagnostic imaging. Tab. 3 lists the specific diagnostic criteria defined by the American College of Rheumatology (ACR). Computed tomography (CT) angiography enables visualization of the characteristic pattern of involvement of the aorta and its branches, while at the same time permitting an assessment of the extent of inflammatory changes to the vessel walls (Fig. 2). Digital subtraction angiography (DSA) should only be used in the case of specific questions or for interventional purposes. Although vascular imaging by means of contrast-enhanced magnetic resonance imaging (MRI) is possible, assessing the vessel wall and neighboring structures may be limited due to lower spatial resolution depending on the acquisition technique used ([28], Figs. 3 and 4). Positron emission tomography-computed tomography (PET-CT) plays an increasingly important role in the assessment of inflammatory activity ([14], Fig. 5).

While it is possible to classify patients based on the pattern of aortic and aortic branch involvement, this does not contribute to assessing the prognosis. The Ishikawa classification [10] is more suitable for this as it takes complications already present at the time of diagnosis into consideration (Tab. 4). There is a correlation between classification and patient prognosis: the greater the number of fulfilled minor criteria, the more severe and complicated the disease course [11, 23].

First described in 1937 by Horton et al. giant cell arteritis is the most common form of non-infectious arteritis [cited in 10]. The aorta itself is affected by inflammatory changes in only a subgroup of patients [3]. Stenotic as well as aneurysmal lesions of the supra-aortic branches are most commonly seen. This disease predominantly affects females aged over 50 years and the prevalence increases with age. The incidence in Europe is put at 15–25 per 100,000 inhabitants per year, making it considerably higher compared to Takayasu arteritis [5]. Patients generally seek medical advice for headaches and impaired vision caused by arteritic optic nerve neuropathy. A history of jaw claudication indicating involvement of the external carotid artery and its branches is pathognomic for this disease. Fever, muscle pain, weight loss, cranial nerve deficits and double vision are rarer manifestations [7, 12]. Temporal swelling along the course of the temporal artery with tenderness on palpation is clinically striking (Fig. 6). The erythrocyte sedimentation rate (ESR) and C‑reactive protein (CRP) level are almost always both elevated. Normocytic normochromic anemia and thrombocytosis are also not uncommon. Involvement of the subclavian artery can cause arm claudication, pain at rest and ultimately lead to gangrene of the fingers and hands.

Early diagnosis is particularly important in view of the prognosis of ophthalmological complications [19]. As with Takayasu arteritis, the ACR has defined specific diagnostic criteria (Tab. 5). A temporal artery biopsy should be performed (prior to initiating therapy) in addition to the clinical and laboratory investigations mentioned previously. A minimum biopsy length of at least 1.5–2 cm is considered necessary due to segmental involvement of the arterial wall. Doppler and duplex ultrasound show characteristic findings (hypoechoic border or “halo”; Fig. 7, [1]); however, depending on the initial ACR score (Tab. 5) a number of studies have shown sensitivity and specificity to be significantly lower compared with temporal artery biopsy (69 and 82 vs. 93 and 91.2 %, respectively [2, 13, 24]). Having said that, a high ACR score and positive bilateral ultrasound findings generally make temporal artery biopsies unnecessary. Cross-sectional imaging methods, such as CT and MRI are well-suited to assessing vessels that cannot be visualized by ultrasound. In the case of low ACR scores and equivocal ESR, CRP and biopsy findings, PET-CT can be used to establish the diagnosis [14].

Aortic involvement has been described in a number of systemic rheumatic diseases; Tab. 1 shows the most important of these [2]. Suspicion of inflammatory aortic lesions should be aroused if patients with signs of an underlying rheumatic disease exhibit clinical indications of acute aortic valve insufficiency, renal or mesenteric artery occlusion, decreased perfusion to the extremities or aortic aneurysms in the absence of typical risk factors for arteriosclerosis. In some cases, however, the manifestation of typical clinical symptoms may point the way to the appropriate diagnosis (e. g. oral or genital ulcerations in AAA are specific for Behçet’s disease). Rational basic laboratory diagnostics can be helpful here from a number of perspectives: etiological classification of symptoms, type and activity of the disease processes and an evaluation of function of and damage to affected organ systems (Tab. 6).

Corticosteroids form the central pillar of treatment in management of non-infectious aortitis; for example, 40–60 mg prednisone for 4 weeks followed by a gradual dose reduction is the standard treatment [18]. In addition to monitoring clinical symptoms the ESR is a good follow-up parameter [18]. Some authors recommend initial treatment with 1,000 mg methyl prednisone daily for 3 days in giant cell arteritis patients with ocular symptoms (see Ness et al. [20] for a detailed schedule). Efficacy varies from study to study and appears to depend on the extent of inflammatory lesions at the time of treatment initiation. It is fair to assume that only one in every two patients will fully respond to steroid treatment; furthermore, steroid-induced adverse effects are seen in up to 65 % of patients, causing not inconsiderable comorbidities. In such situations the use of other steroid-sparing substances can be considered. Three randomized placebo-controlled studies on the use of methotrexate in giant cell arteritis yielded conflicting results, while one meta-analysis found a certain advantage conferred by 10–15 mg/week in terms of reducing recurrence rates and steroid dosage [15]. A randomized trial that combined steroids with infliximab also revealed no advantages compared with placebo [7]. A reduction in steroid maintenance dose in patients with Takayasu arteritis was possible with both azathioprine (2 mg/kg body weight/day) and methotrexate (20–25 mg/week [8, 31]). To date, cyclophosphamide has been tested only in a small study on adults with steroid-refractory Takayasu arteritis. The administration of low-dose acetylsalicylic acid (75–150 mg/day) reduced the manifestation of cardiovascular and cerebrovascular events in giant cell arteritis patients [14, 19].

Interventional and conventional surgical management of arterial occlusion or aneurysms are guided by clinical symptoms and the basic principles of arteriosclerosis treatment. Although the results of reconstructive interventions are good, the need for surgical revision is significantly increased in the long term [4]. Several authors recommend performing revascularization when inflammatory activity is at its lowest [4, 16]. The restenosis rate following interventional procedures, such as angioplasty or angioplasty and stents is higher compared with surgical procedures [4, 12, 17, 23]. Data on the use of drug-eluting stents or drug-eluting balloons are lacking. Due to the rareness of the disease there is a simple lack of evidence to make specific recommendations on the selection of surgical or endovascular procedures, the type of stents or stent grafts to be used or resection in the case of aneurysms.

Since this disease was first described evidence has grown to suggest that inflammatory abdominal aortic aneurysms (IAAA) are not, as originally assumed, a distinct entity but belong to a group consisting of three symptom complexes with the same etiology: (1) inflammatory AAA, (2) idiopathic retroperitoneal fibrosis (Ormond’s disease) and (3) a combination of these two [6, 25].