Quarterly Medical ReviewUpdate on Takayasu's arteritis
Section snippets
Genetics
Genetic studies demonstrated HLA-B*52, and to a lesser extent B*67 in Japan, as the most important HLA alleles associated with TAK in different ethnicities [11], [12], [13]. The role of fine epitope specificities of HLA alleles in pathogenesis is highlighted by the fact that HLA-B*51 and B*52, with only two amino acid differences in antigen-binding groove, are associated with completely different diseases: B*51 with Behcet's disease as an autoinflammatory disorder, B*52 with TAK of a
Classification
A set of classification criteria for TAK was established by the American College of Rheumatology (ACR) in 1990 [19] and criteria defined by Ishikawa et al. is also used in Japan [20]. Although ACR criteria have not been criticized as much as other criteria sets for small-vessel vasculitis (SVV) with over 90% sensitivity and specificity, the control group formed mainly of other SVV, which have limited overlapping vascular and clinical features with TAK. Therefore, usefulness of this criteria may
Prevalence and ethnicity
According to Japanese nation-wide registry, there were at least 5881 TAK patients in Japan in 2011 and the prevalence is thought to be > 0.004%. A systematic review collected only 197 patients from 7 Arab countries with a population of approximately 80 million, demonstrating a low prevalence [24]. The demographical and clinical findings of TAK in Arabs is reported to be similar to other series, with the course of the disease “quite stable” in about 50% of patients and the overall mortality is low
Clinical course
New clinical series published recently better characterized the natural course of TAK. Grayson et al. demonstrated that among 6 different vasculitides, TAK has the highest rate of new, severe manifestation (ischemic, vascular) incidence (44%) [8]. Clinical features of “vascular symmetry” in TAK are investigated in 2 separate studies from USA and France [26], [27]. Cluster analysis revealed that TAK lesions mostly develop in a symmetric manner in paired vascular territories and disease extension
Prognosis
In a limited number of series, mortality seems to range between 3–15% in TAK [4]. In one of the largest series with a long-follow-up from Mayo Clinic, USA, overall survival was much better compared to earlier series (97% at 10 and 86% at 15 years) [6]. However, mortality was still increased compared to the general population (SMR: 3.0). Disease phenotype and severity of disease expression due to ethnicity, differences in medical therapy (e.g. less frequent use of glucocorticoids and cytotoxic
Assessment of disease activity with new outcome tools
The most commonly adopted approach for disease assessment in TAK is the simple definition of “active disease” originally used in a study from US National Institute of Health (NIH) as the presence of constitutional symptoms, new-bruits, elevated APRs or new angiographic features [39]. A literature search performed for TAK have shown that items in NIH series were preferred by most studies to define “active” disease [40].
The Birmingham Vasculitis Activity Score (BVAS) is a validated-tool for small
Imaging in TAK
Imaging in TAK has relied on conventional angiography, which demonstrates mainly luminal blockage rather than vessel wall involvement [48], [49]. Computerized tomography (CT) provides excellent anatomical characterization of structural aortic changes, but is limited in its assessment of early disease activity [50]. MR angiography can show vessel wall thickening and oedema, however this correlates poorly with clinical activity or APR and is shown to have a limited role for long-term follow-up
Biomarkers
Acute-phase response (erythrocyte sedimentation rate [ESR] and C-reactive protein) is frequently advocated for disease assessment in TAK, despite being shown to be neither sensitive nor specific enough to monitor disease activity [2]. Serum autoantibodies such as anti-endothelial antibodies, circulating endothelial cells and serum biomarkers such as VEGF, IL-6, IL-8, IL-18, matrix metalloproteinase-9 and adipokines are also investigated [73], [74], [75], [76], [77], [78].
Recently Pentraxin3
Damage assessment and patient reported outcomes
One of the major difficulties in LVV is the differentiation between activity vs. damage. A vascular stenosis may be due to the inflammation if it is taking place in an acute phase-elevated state, however may also be a sign of an ongoing narrowing of the vessel wall in longstanding disease. The role of atherosclerosis in this process is also not clarified. Damage is not a well-studied domain in LVV, with also a not fully-published, new instrument from India [7], [81]. Further research is needed
Treatment
Like in all orphan diseases, the rarity of TAK is a major limitation for randomized controlled trials (RCT) and, except an ongoing one, there are no RCTs published in TAK [40], [87]. Therefore, treatment choices are mainly determined by observational studies and the clinicians’ decision based on expert opinion [82]. This lack of studies can partly be explained with the low incidence [13], and unlike SVV, lack of international collaborative studies. This is reflected in EULAR guidelines for the
Conclusion
Although outcome measures are not clearly validated, progress in the assessment of Takayasu's arteritis is reflected in recent studies when clinical, acute-phase response and serial non-invasive imaging is shown to reflect a good prognosis in patients treated with biological agents with no long-term increase in damage [81], [97]. Recent progress in management also requires better disease assessment tools for clinical studies [87].
Complementary references
Three important new papers have been published since the review was written, please refer to [98], [99], [100].
Disclosure of interest
the authors declare that they have no conflicts of interest concerning this article.
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