Although TA has a worldwide distribution, the disease is thought to be more prevalent in Asian, Middle-East, and Central and South American countries than in North America [6–8] or Europe [3], with some differences in the characteristics of the disease among the various ethnic backgrounds [3, 7, 9, 10]. The greatest frequency of the disease is observed in Japan [11, 12]. Conversely, the incidence of the disease is as low as 0.3–2.6 cases per million per year in the USA, Sweden, Germany and UK [3], suggesting that TA is one of the most infrequent form of vasculitis. One of the typical epidemiological features of TA is the marked predominance of the disease in women, with a F/M sex-ratio known to vary from 29/1 to 1.2/1 [3]. This very wide range may reflect either biases in case collection or differences between ethnic groups. Most TA patients have disease onset during the second or third decade of life. However, neither the occurrence of TA in patients over 50 years nor in children is uncommon [3, 13].

Because biopsy of involved vessels is not usually performed in TA, the diagnosis mostly relies on clinical features and vascular imaging. Pathologic findings in the pulmonary arteries have been poorly documented [14] and most available data originate from other arteries. Active inflammation in TA is typically indicated by the presence of mononuclear cells within the vascular wall, predominantly lymphocytes and macrophages. These cells are mostly recruited in the media and adventitia through the vasa vasorum. Because TA is a granulomatous vasculitis, giant cells and granulomas are commonly found in the media during active inflammation. Intimal proliferation contributes to the development of stenotic arterial lesions. At a more advanced stage, pathologic features include vascular wall fibrosis, while the destruction of the elastic lamina and the muscular media can lead to aneurismal dilation of the affected vessel. Retrospectively, dense scar tissue remains as an indication of prior vasculitis.

While our knowledge of the pathogenesis of TA has considerably improved during the last decade, the exact pathogenic sequence and natural history of vascular lesions remain unknown. By using cluster analysis we have recently shown that paired vascular beds usually clustered with their contralateral counterparts, while vascular lesions extended contiguously in the aorta [15]. Cell-mediated mechanisms are thought to be of primary importance in TA (Fig. 11.1). Therefore, it is currently hypothesized [15] that an unknown stimulus triggers the expression of the 65 kDa Heat-shock protein in the aortic tissue which, in turn, induces the Major Histocompatibility Class I Chain-Related A (MICA) on vascular cells. The γδ T cells and NK cells expressing the NKG2D receptors recognize MICA on vascular smooth muscle cells and release perforin, resulting in acute vascular inflammation. Pro-inflammatory cytokines and chemokines are therefore released and increase the recruitment of mononuclear cells within the vascular wall. Then, T cells infiltrate and recognize one or a few antigens that could be presented by a shared epitope, which is associated with specific major Histocompatibility Complex alleles on the dendritic cells, these latter being activated through their Toll-like receptors. Th1 lymphocytes drive the formation of giant cells through the production of interferon-γ, and activate macrophages with release of vascular endothelial growth factor (VEGF) resulting in increased revascularization and platelet derived growth factor (PDGF), resulting in smooth muscle migration and intimal proliferation. Th17 cells induced by the IL-23 microenvironment may also contribute to vascular lesions through activation of infiltrating neutrophils. Although being very controversial, dendritic cells may cooperate with B lymphocytes and trigger the production of anti-endothelial cell auto-antibodies resulting in complement-dependent cytotoxicity against endothelial cells.

The clinical course of TA is classically thought to progress through three distinct stages: first, an early phase with prominent constitutional and systemic symptoms such as fatigue, weight loss, fever, and arthralgia; second a vascular phase occurring months or years later, with clinical manifestations of ischemia due to stenotic or occlusive lesions, or related to aneurysms; and third, a late phase (also called “burnt out phase”) with fibrotic and fixed vascular abnormalities [6]. While more than 90 % of patients have vascular signs or symptoms during the course of the disease, it is now well recognized that the systemic and vascular phases may overlap, and that a significant proportion of patients may never exhibit any constitutional symptom [3, 6].

The clinical presentation of TA is heterogeneous, and comprises many non-specific findings such as constitutional symptoms (fatigue, fever and weight loss), musculoskeletal features (arthralgia, arthritis), cardiac and vascular features (vascular bruit, blood pressure asymmetry, claudication of extremities, carotodynia, hypertension, valvular involvement with aortic regurgitation, Raynaud’s phenomenon, pericarditis), neurologic features (headache, visual disturbance, stroke or transient ischemic attacks, seizures), dermatologic manifestations (erythema nodosum, pyoderma gangrenosum).

Pulmonary artery involvement of TA is believed to occur in 15–65 % of patients [11, 14, 16–22]. It may occasionally be the revealing [23, 24] or foreground feature of the disease [23, 25, 26]. Clinical signs of pulmonary involvement in TA are usually non-specific and therefore may lead to delayed diagnosis [3, 27]. These mostly include chest pain, cough, signs of pulmonary hypertension such as dyspnea, fatigue, angina, syncope [28–31], and hemoptysis [32, 33], with rare cases of pulmonary hemorrhage [34–36]. The exact frequency of pulmonary hypertension is unknown in TA, and is mostly due to pulmonary stenosis or left heart involvement [37]. However, other causes, including pulmonary capillary haemangiomatosis have been occasionally reported [38]. In a study of 76 Mexican TA patients [39], 10 (13 %) developed pulmonary hypertension using transthoracic echocardiography. Pulmonary artery hypertension was observed in 20 % of patients with pulmonary artery involvement among patients with pulmonary artery involvement reported in a Chinese study published in 1994 [19]. Pulmonary hypertension in TA was statistically associated with disease activity in a Korean series of 204 patients [40], those with active disease (defined as patients having an elevated ESR or CRP level, thickened arterial wall with mural enhancement on CT or MR angiography, and carotidynia at the time of the initial diagnosis) had a higher incidence of pulmonary hypertension than those with inactive disease. In a Japanese study [41], a significant correlation was found between plasma endothelin-1 levels, which is involved in the pathogenesis of pulmonary hypertension, and erythrocyte sedimentation rates. Occasionally, clinical and radiographic features mimicking pulmonary embolism may be the first manifestation of Takayasu’s arteritis [42–44], and pulmonary infarction may occur in this setting [45–47]. Rarely, coronary artery to pulmonary artery collaterals may develop and induce coronary steal and myocardial ischemia [48, 49].

Dealing with TA patients is challenging because there is no sensitive or specific biologic markers for diagnosis and monitoring disease activity in TA [50]. It is well known that clinical assessment alone may underestimate disease activity [6, 51] and current disease activity criteria (Table 11.2) are non-validated [6]. Previous studies have shown that ESR and CRP did not correlate with clinical features in about 50 % of cases [6, 7]. Interleukin-6, RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted), and Pentraxin-3 blood levels are believed to correlate with disease activity, but these markers are not widely available [52, 53].

Because the clinical presentation and results of laboratory tests are typically nonspecific, accurate diagnosis of TA commonly depends on imaging studies. While conventional angiography has for long been the “gold standard”, this imaging modality is now outdated, while Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) angiographies are increasingly used (Figs. 11.2, 11.3 and 11.4). These latter offer several advantages, including their non-invasiveness and their capability to demonstrate both mural and luminal changes in the pulmonary arteries, which is of major interest in TA because luminal changes may be delayed [22, 23, 54, 55]. Recently, pulmonary perfusion MRI has been shown to be a new alternative for the evaluation of pulmonary perfusion in TA [22, 56]. In a Japanese study [56], pulmonary MR perfusion images were acquired in 21 TA patients. The presence of perfusion abnormality was determined in both lobe-based (n = 126) and patient-based (n = 21) analyses. Sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated using perfusion scintigraphy as a standard reference. For lobe-based analysis, sensitivity was 91.7–95.8 %, specificity was 92.2–93.7 %, and PPV and NPV were 73.3–76.7 % and 97.9–99.0 %, respectively. For patient-based analyses, sensitivity was 100 %, specificity was 72.7 %, and PPV and NPV were 76.9 and 100 %, respectively. Therefore MR perfusion imaging appeared to be a valuable, non-invasive method to estimate pulmonary artery involvement in TA patients. Pulmonary perfusion scintigraphy has been shown effective to detect presence of pulmonary artery involvement in TA [13, 17, 18, 20, 57] and correlates well with pulmonary angiography [58]. Another convenient way to assess vascular involvement in TA is peripheral vascular Doppler. Unfortunately, vascular Doppler is only suitable for following peripheral disease progression and not pulmonary involvement in TA. ¹⁸F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning has been proposed as a new way of assessing disease activity in TA, but its role in the diagnostic and follow-up strategy remains controversial [59].

The most characteristic imaging findings of pulmonary involvement in TA include wall thickening and enhancement in early phases, stenotic or occlusive changes during the vascular phase, and fibrotic and/or calcified stenosis or occlusion in the chronic phase. These lesions mainly involve the segmental and subsegmental arteries, and less commonly the lobar or main pulmonary arteries [60–62]. Unilateral occlusion of a pulmonary artery can occur in advanced cases. Therefore, late-phase TA should always be considered in cases of chronic pulmonary artery obstruction of unknown origin [60]. Occasionally, TA may mimic unilateral pulmonary artery agenesis in children [63]. While being frequent in the aorta and its main branches, vascular dilatation and aneurysms in the pulmonary arteries are uncommon findings among TA patients [14, 16, 19, 21]. In a Chinese study performed in 1994 [19], pulmonary artery involvement was assessed by conventional digital subtraction angiography arteriography in 45 (33.8 %) of 133 patients. Stenosis and/or occlusion of segmental and/or lobar pulmonary arteries, and subsegmental branches, were the basic angiographic findings. Pulmonary artery branches in the upper lobes were more commonly affected than those in the lower and middle lobes. Bilateral lesions were more common than unilateral ones. Single lobar and segmental lesions were rare. No main pulmonary artery involvement was detected. In a Japanese study published in 1992 [14], 21 of 30 patients (70 %) had pulmonary artery involvement at pulmonary arteriography. Abnormalities were most common in upper lobe pulmonary arterial branches and segmental branches, followed by subsegmental branches. Systemic artery-pulmonary artery communications were seen in 6 patients (20 %). While regional hypoperfusion due to pulmonary arteritis may occasionally be seen on lung CT-scan [64], involvement of the lung parenchyma is atypical in TA, and alternative diagnoses should also be considered [65–67].

Corticosteroids are usually considered the mainstay of medical treatment in active TA with early phase or vascular phase manifestations [68, 69]. However, approximately 40–50 % of patients require additional immunosuppressive agents to achieve and maintain remission [3, 7, 70]. Corticosteroids and other immunosuppressive agents have been shown effective to treat pulmonary involvement of TA, as these regimen may reverse pulmonary artery stenosis [28, 71]. Azathioprine [72], methotrexate [73], mycophenolate mofetil [74, 75], cyclophosphamide [76], and anti-TNFα agents [20, 77, 78] have all been recognized effective in open-label trials but no randomized controlled trial data are available. Therefore, the therapeutic choice should be mainly guided by the individual benefit-risk ratio. There is no specific recommendations for the treatment of TA-associated pulmonary hypertension, therefore the latter should be treated according to the current standard of care, while it may occasionally be intractable [29].

Treatment with corticosteroids and immunosuppressive agents is not mandatory during the late phase, as only limited improvement, if any, can be achieved for fibrotic and fixed vascular abnormalities. However, both angioplasty and stenting [28, 79, 80] or vascular bypass [31, 81] may be necessary in TA patients when symptomatic and/or hemodynamically significant stenoses, including pulmonary arterial stenoses, have occurred. Pulmonary artery bypass has been shown effective for in-stent stenosis following angioplasty for isolated pulmonary TA [82]. Bronchial artery embolization may be considered in case of intractable hemoptysis [83].

The early, intermediate and long term outcome of angioplasty and vascular bypass procedures in TA is generally considered satisfactory [51, 71, 82, 84–95], even for treatment of pulmonary artery involvement where available experience is more limited [80].

Comparison of survival between TA series is likely biased because different enrollment criteria and care strategies have been used. In most series from developed countries, the 5 and 10-year survival rates are of ≈95 and ≈90 %, respectively [3, 6–8, 96–98]. Park et al. [96] underlined that major prognostic factors in TA were presence of valvular heart disease, cerebrovascular accidents, congestive heart failure, ischemic heat disease, retinopathy and renovascular hypertension [96]. However, the exact prognostic value of pulmonary involvement in TA remains currently unknown.

Behçet’s disease (BD) is a multisystem and chronic disease of unknown etiology characterized by relapsing manifestations, including oral and genital ulcers, uveitis, and vasculitis, cutaneous, articular and central nervous system involvement.

BD’s vasculitis is particularly distinctive because both veins and arteries can be affected, mainly in the form of arterial aneurysms and of venous or arterial thrombosis. Pulmonary involvement in BD can almost be summarized as pulmonary artery aneurysm and pulmonary thrombosis. Parenchymal manifestations are less documented and can be either isolated or associated with pulmonary arterial involvement, therefore being a direct consequence of parenchymal ischemia.