|Year : 2019 | Volume
| Issue : 1 | Page : 2-3
Challenges in assessing the disease activity of takayasu arteritis
Durga Prasanna Misra1, Anupam Wakhlu2
1 Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India
|Date of Web Publication||14-Mar-2019|
Dr. Durga Prasanna Misra
Department of Clinical Immunology and Rheumatology, C-Block, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareily Road, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Misra DP, Wakhlu A. Challenges in assessing the disease activity of takayasu arteritis. Indian J Rheumatol 2019;14:2-3
The assessment of ongoing disease activity versus damage in Takayasu arteritis (TA) remains a challenge for rheumatologists. Since the disease process ensues in the large vessels, most of which are inaccessible to histopathological analysis, except during surgical procedures, the identification of active vasculitis using peripheral blood markers or imaging remains, as of now, the only feasible option. The difficulties with these modalities are exemplified by analysis of concordance between histopathology of arterial tissues in patients undergoing bypass procedures, wherein >40% of patients continued to demonstrate active vasculitis despite clinical inactivity. Similar discordance of disease activity with erythrocyte sedimentation rate (ESR) has also been noted.
In this context, the recent paper by Devarasetti et al. discussing the role of pentraxin 3 (PTX3) as a marker of disease activity in TA is relevant. While plasma PTX3 was higher in patients with TA than in healthy controls, it could also distinguish active disease from grumbling or inactive disease (by patient global assessment), with better performance (area under the receiver operating characteristic curve [AUC]) than ESR or C-reactive protein (CRP). The interpretation of the study was limited by relatively small number of patients and the lack of longitudinal follow-up and imaging, which might have helped assess the sensitivity of this biomarker to changes in disease activity. Other studies discussed by the authors had also previously shown the potential of this biomarker as an indicator of disease activity in TA; however, this was the first such report from India.
Recent efforts have attempted to identify peripheral biomarkers for the assessment of disease activity in TA, with mixed results. A study of 34 TA patients with clinically inactive disease compared to 22 healthy controls revealed higher circulating levels of tumor necrosis factor-alpha, interleukin (IL)-17F, IL-21, and IL-23 in the patients with TA, suggesting underlying subclinical inflammation. Another study analyzed S100 proteins, identified as markers of disease activity in other rheumatic diseases, in the peripheral blood of TA patients, and failed to identify a significant difference between those with active and inactive TA. This was in contrast to that in giant cell arteritis (GCA), another variant of large-vessel vasculitis (LVV), and the study was limited by small number of TA patients. The hypothesis-free approaches of metabolomics and proteomics hold promise for assessing disease activity in TA with interesting preliminary results. The levels of metabolites glutamate and n-acetyl glycoprotein were found to reasonably distinguish patients with active and inactive TA. Yet another study utilizing proteomics of the peripheral blood proposed a score generated using a composite of eight peripheral blood proteins, as discriminatory between active and inactive TA, with an AUC of 0.9.
Imaging modalities may also help assess disease activity in TA. Contrast-enhanced magnetic resonance angiography, utilizing novel contrast agents such as gadofosveset trisodium, or computerized tomographic angiography using intravenous contrast, may help delineate active disease due to uptake of contrast in the inflamed vessel wall., Nuclear medicine imaging modalities such as positron emission tomography–computerized tomography (PET-CT) theoretically should help image areas of the vasculature which have increased metabolism (due to inflammation) subsequent to 18-fluorodeoxyglucose (18-FDG) uptake. Recent literature on the use of PET-CT as a disease activity assessment tool in TA has provided interesting insights. It has been shown that uptake of 18-FDG may identify a population of active TA which have normal levels of CRP, thereby providing complementary information to that provided by peripheral blood inflammatory markers. A recent study proposed a quantitative score of vascular inflammation using PET-CT (the PET vascular activity score [PETVAS]). In this study of 30 patients with GCA and 26 with TA, positivity on PET-CT could help distinguish patients with active LVV from mimics of LVV, such as atherosclerosis. Interestingly, nearly 60% of patients who were clinically in remission demonstrated increased vascular metabolic activity on PET-CT, and those with a higher PETVAS score despite clinical inactivity were more likely to relapse on longitudinal follow-up. Patients on glucocorticoid therapy tended to have lower PET-CT vascular uptake, suggesting that this may not be as reliable for the assessment of disease activity in those on corticosteroids. It may be worthwhile evaluating the role of PET-CT using isotopes tagged to specific proteins, such as 14-3-3, which can localize to sites of inflamed aortic tissue.
While challenges abound in the assessment of TA disease activity, the future holds promise of a breakthrough utilizing the help of both biomarkers and imaging parameters. Recent efforts have focused on the design of a composite disease activity score for the assessment of TA and GCA, utilizing both clinical and angiographic parameters. Such a score requires validation across populations as well as may benefit from further inclusion of recently identified peripheral blood biomarkers.
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