Inflammatory diseases of the aorta
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Aortitis is a term which encompasses inflammatory changes to the aortic wall from various pathogenic etiologies. Large vessel vasculitis, such as Takayasu arteritis and giant cell arteritis represent the most common entities; however, there is also an association with other rheumatological diseases. Chronic idiopathic periaortitis represents a distinct disease entity and infectious aortitis is a rare but life-threatening disease. Due to the diverse clinical pictures vascular surgeons often face a significant challenge in terms of making an accurate initial diagnosis. Treatment requires an interdisciplinary approach. This article describes the pathogenesis of the various forms of aortitis as well as the diagnostic methods and treatment approaches.
KeywordsPathogenesis Vasculitis Arteritis Aortic infection Rheumatic diseases
Entzündliche Erkrankungen der Aorta
Unter dem Begriff der Aortitis werden entzündliche Veränderungen der Aortenwand verschiedener pathogenetischer Ursachen zusammengefasst. Großgefäßvaskulitiden, wie die Takayasu-Arteriitis und die Riesenzellarteriitis, stellen die häufigsten Erkrankungen dar, es findet sich aber auch eine Assoziation mit anderen rheumatologischen Krankheiten. Die chronische idiopathische Periaortitis stellt eine eigene Entität dar. Eine infektiöse Aortitis ist eine seltene aber lebensbedrohliche Situation. Für den Gefäßmediziner ist es auf Grund des vielgestaltigen klinischen Bildes oft schwierig, eine exakte Erstdiagnose zu stellen. Die Behandlung erfordert eine interdisziplinäre Zusammenarbeit. Dieser Beitrag soll Ursachen, diagnostische Methoden und Therapieansätze der verschiedenen Aortitiden darstellen.
SchlüsselwörterPathogenese Vaskulitis Arteriitis Infektion der Aorta Rheumatische Erkrankungen
Inflammatory changes to the aortic wall can be caused by a multitude of different diseases. The broad spectrum of pathogenic factors and nonspecific clinical presentation often delay initial diagnosis; however, a precise determination of the underlying pathology is essential for successful management. The aim of this article is to describe the pathogenesis, symptoms and diagnosis of aortitis and equip the reader with the knowledge required to perform adequate treatment following an appropriate diagnostic work-up.
Definition and classification
Forms of underlying rheumatic diseases associated with inflammatory lesions of the aorta
Systemic lupus erythematosus
HLA B27-associated spondyloarthropathies
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis
Panarteritis nodosa syn.
Differential diagnosis of mid-aortic syndrome
Abdominal aortic coarctation
Neurofibromatosis (Recklinghausen disease)
Giant cell arteritis
American College of Rheumatology criteria for the classification criteria of Takayasu arteritis which is highly probable in the presence of three or more criteria (sensitivity 91 % and specificity 98 % )
Age at disease onset < 40 years
Claudication of the extremities
Weak brachial artery pulse
Blood pressure difference > 10 mmHg between arms
Auscultable stenotic bruits over the subclavian artery or abdominal aorta
Pathognomonic angiographic findings
Diagnostic criteria for Takayasu arteritis according to Ishikawa whereby the presence of two major criteria or one major and two minor criteria is highly suggestive for Takayasu arteritis
Symptoms consistent with Takayashu arteritis
Lesion in the mid-portion of the left subclavian artery
Lesion in the mid-portion of the right subclavian artery
Erythrocyte sedimentation rate ≥ 20 mm/h
Aortic valve insufficiency
Lesion in the pulmonary artery
Lesion in the mid-portion of the common carotid artery
Lesion in the region of the distal brachiocephalic trunk
Lesion in the region of the descending thoracic aorta
Lesion in the region of the abdominal arteries
Lesion in the region of the coronary arteries
Giant cell arteritis (synonyms: Horton’s disease and temporal arteritis)
American College of Rheumatology (ACR) criteria for giant cell arteritis and three out of five criteria need to be fulfilled for diagnosis
Age at initial manifestation > 50 years
New onset of headache
Temporal artery anomaly
Elevated erythrocyte sedimentation rate
Pathological temporal artery biopsy
Other underlying rheumatic diseases
Rational laboratory diagnostics in the case of suspected aortitis
Basic laboratory tests
Complete blood count (including differential blood count), uric acid, creatine kinase, alkaline phosphatase, creatinine, gamma-glutamyl transferase, aspartate aminotransferase, total protein, protein electrophoresis, coagulation
Erythrocyte sedimentation rate, C‑reactive protein
Antinuclear antibodies (ANA)
Special laboratory tests
Antineutrophil cytoplasmic antibodies (ANCA)
Double-stranded DNA antibodies (dsDNA-Ab)
Complement, HLA typing
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 . In addition to monitoring clinical symptoms the ESR is a good follow-up parameter . 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.  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 . A randomized trial that combined steroids with infliximab also revealed no advantages compared with placebo . 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 . 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.
Chronic idiopathic periaortitis
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].
Inflammatory aortic aneurysm
The term inflammatory aneurysm was first used by Walker in 1972 [cited in 27] who described a group of aortic aneurysms intraoperatively characterized by a thickened wall, marked perianeurysmal and retroperitoneal fibrosis and adhesions to adjacent organs. Inflammatory aneurysms account for approximately 3–11 % of all AAAs and are predominantly seen in males. The average age of onset is striking in that it is 5–10 years lower that in patients with non-inflammatory aneurysms . Likewise, the proportion of smokers in this group was significantly higher at 77–100 % . There is evidence that a familial tendency to aneurysm formation is found 10 times more frequently in patients with inflammatory aneurysm, leading to the assumption of a genetic predisposition .
Our understanding of the processes that underlie aneurysm formation has significantly increased in recent years. It is becoming apparent that a combination of genetically predisposing factors and certain pathophysiological factors cause aneurysm genesis through inflammatory degradation of the aortic wall. Thus, according to current knowledge, it is likely that inflammatory AAA does not represent a separate disease entity but is a particularly extreme variant of this inflammatory process . Although the etiology of the clearly antigen-triggered inflammatory response has not been fully elucidated as yet, possibilities include degradation products from lipids deposited in the wall, elastin degradation products or infectious triggers (e.g. Chlamydia pneumoniae, herpes simplex virus and cytomegalovirus) [11, 22, 27, 28]. These lead in the further course to the disintegration of the extracellular matrix via the release and activation of proteolytic enzymes from immune cells, e. g. metallomatrix proteases. Classically, bacterial pathogens are not detected on histopathological and microbiological analysis of the aneurysm wall . The onset of inflammatory aneurysms is virtually always associated clinically with abdominal, back or flank pain (65–90 %), which are seen significantly less frequently in non-inflammatory aneurysms (8–18 % ). Lack of appetite and weight loss are seen in almost 50 % of patients. In addition, the ESR is generally strikingly elevated (40–88 %). Although leukocytosis and fever are seen in isolated cases they do not represent typical elements of the clinical picture . The occurrence of comorbidities, such as arteriosclerosis, coronary heart disease, hypertension and diabetes is the same as in patients with non-inflammatory aneurysms; however, ureteral involvement in periaortic inflammation, which is seen in up to 50 % of patients and not infrequently causes chronic obstructive postrenal renal dysfunction (18–21 %), is clinically indicative.
Inflammatory AAA is diagnosed intraoperatively in the majority of cases, although both CT  and ultrasound (halo) show good diagnostic accuracy . According to Sterpetti et al. ureteral involvement is best assessed using a combination of excretory pyelography and CT . The inflammatory periaortic mass can also be well visualized using contrast-enhanced MRI, whereby this method yields other data necessary for perioperative planning to a lesser extent . The inflammatory etiology of inflammatory aortic aneurysms makes primarily drug-based therapy with corticosteroids appear reasonable. Indeed, there are individual reports on the complete resolution of clinical symptoms and all inflammatory changes to the aortic wall and retroperitoneum under steroid therapy ; however, a reduction in aneurysm diameter has not been observed. If the role of arteriosclerotic changes in the formation of inflammatory aneurysm are taken into consideration, the resulting reduction in risk factors assumes crucial importance. Abstention from tobacco use in particular appears to have a positive effect on disease course . The indications for surgical treatment are assessed in much the same way as in non-inflammatory aneurysms, whereby the frequent onset of pain tends to prompt early surgery.
The strategy of open aortic repair differs from non-inflammatory aneurysms in that dissection should be kept to a minimum. Attempts to detach inflammatory adhesions involving adjacent organs, such as the duodenum, sigmoid colon, vena cava or ureters from the aneurysm can cause damage to these organs and initially contributed to significantly higher morbidity and mortality compared with non-inflammatory aneurysms [1, 21]. As early as in 1985, Crawford et al. recommended infradiaphragmatic cross-clamping to create a proximal anastomosis . The inflamed wall can easily tear and should be reinforced with polytetrafluoroethylene (PTFE) pledgets. Thus, improvements in surgical techniques have led to a gradual reduction in the mortality rate, which was virtually comparable with non-inflammatory AAA in the 1990s (6.8–11 %; [26, 28, 32]). Anatomy permitting, there appear to be no other obstacles to endovascular treatment. Initial reports show good results in terms of mortality and morbidity, comparable with those achieved with endovascular treatment of arteriosclerotic aneurysms [13, 28]; however, it remains unclear why a regression in fibrotic periaortitis is seen significantly less frequently following endovascular treatment . It is possible that the endografts themselves are capable of triggering an inflammatory reaction in the aortic wall and directly adjacent structures, as observed following treatment of non-inflammatory aneurysms. Thus, the indications for EndoVascular Aneurysm Repair (EVAR), at least in IAAA with ureteral involvement, should be considered from a critical perspective . A systematic review of the Cochrane working group on this topic is underway.
Ormond’s disease (retroperitoneal fibrosis)
This disease is characterized by the same clinical, radiological and etiological features as IAAA, differing only in that there is no aneurysm formation . The overlap and possible combinations in the severity of individual symptoms are by nature fluid. Obstructive ureteral complications, which can usually be managed by placement of a splinting catheter, take the foreground. Otherwise, treatment is limited to the use of corticosteroids in combination with immunosuppressants, such as azathioprine, cyclophosphamide and methotrexate, although it is difficult to predict individual responses to these drugs .
Non-infectious inflammatory processes of the aorta and its branches are associated with severe sequelae. Initially, diagnosis may be challenging due to the nonspecific clinical presentation. Thus, particularly in surgical disciplines it is of crucial importance to “think of it in the first place.” Prompt intensive drug treatment can reduce long-term morbidity in many cases. Vascular surgery plays a crucial role within the interdisciplinary treatment team.
Compliance with ethical guidelines
Conflict of interest
I. Töpel, N. Zorger and M. Steinbauer state that there are no conflicts of interest.
The accompanying manuscript does not include any studies on humans or animals.
The supplement containing this article ist not sponsored by industry.
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