large vessel vasculitis is not rare, dont miss it.

1. Takayasu Arteritis (TA)
Marwa Abo Elmaaty Besar
Lecturer Of Internal Medicine
(Rheumatology Immunology Unit)
(Pediatric Rheumatology)

2. Takayasu arteritis (TA):-
• An idiopathic, granulomatous, large-vessel arteritis that predominantly
involves the aorta, its major branch arteries, and (less frequently) the
pulmonary arteries.
• Mikito Takayasu, 1908; a Japanese ophthalmologist, who first described the
arterio-venous anomalies in the retina of a patient.
• Different names
• Aortic arch syndrome, Pulseless Disease,
• Idiopathic Aortitis, Stenosing Aortitis, Aorto-arteritis,
• And Occlusive Thrombo-arteriopathy.
• The Chapel Hill Consensus Conference defined TA as
“a granulomatous inflammation of the aorta and its branches ‘usually’ occurring
in patients younger than 50 years”

3. When Rarity Maintains the Mystery
• Unfortunately, TA is still an orphan disease, and many issues remain open.
• It is the most common cause of granulomatous inflammation of large
arteries .
• Incidence:- 2/1,000,000 per year.
• Prevalence:- in Central and South America, Africa, India, and the Far East.
• Gender:- Women > Male.
• Age of onset :- from infancy to middle age, the highest; the third decade
of life, up to 90% of cases in adults.
TA is the third most common cause of vasculitis in the paediatric age group
representing the leading cause of stenotic aorto-arteriopathy and one of the most
prevalent causes of reno-vascular hypertension in childhood., associated with mortality
rates as high as 35%.
Eleftheriou D,etal 2015

4. The vascular bed:-
• The arteries involved are highly variable from patient to patient, and
geographical differences have been described.
• The subclavian arteries are the most frequent (80 % of patients)
followed by the carotids, thoraco-abdominal aorta and celiac trunk.
• Involvement of the pulmonary or coronary arteries is not rare.
• The extent of arterial disease is highly heterogeneous, ranging from a
single arterial district to a widespread disease; large arteries.
• Arterial inflammation in TA has a patchy distribution.
• Steno occlusions is the most frequent evolution, while ectasias or
aneurysms 10–25 % of patients.
Maksimowicz-McKinnon K et al 2007

5. Isolated aortitis:-
• A localized variant of GCA and TA.
• It is still unclear whether it constitutes a separate disease.
• From childhood to the seventh decade.
• Inflammation primarily localizes in large conductance arteries, such as
the aorta and its main branches.
• Usually with a focal and symmetrical pattern.
Grayson PC et al 2012

6. Histology and Pathogenesis :-
• TA is a pan-arteritis.
• TA pathogenesis is still highly mysterious.
• TA is an idiopathic condition, a heterogeneous genetic predisposition
combines with unknown environmental factors.
• Steno-occlusions are believed to derive from intimal hyperplasia and
adventitial fibrosis; local production of growth factors.
• Dilatory involvement results from medial degeneration and the action of
proteases including matrix metalloproteinases.

7. Pathogenesis

8. Red flags for infective or inflammatory
arteritis or peri-arteritis
E. Tombetti et al.2016

9. Clinical Picture:-
(i) Constitutional symptoms, “a classical systemic inflammatory syndrome”,
absent in most cases.
(Ii) Inflammatory arterial signs (tenderness over actively inflamed arteries).
(Iii)Arterial insufficiency (anisosphygmia , end-organ ischemia, systemic
hypertension , precapillary pulmonary hypertension ).
(iv)Dilative arterial disease
(v)Complication (cardiomyopathy, accelerated atherosclerosis, chronic renal
failure).
Extra-arterial
• Inflammation, involving the joints or the heart, can at times occur during active
phases.
• Other inflammatory conditions; inflammatory bowel diseases, sarcoidosis, or
relapsing poly chondritis.
Di Chio MC etal 2014

10. • Diminished or absent pulses in 84–96% of patients associated with limb claudication
and blood pressure discrepancies.
• Vascular bruits in 80–94% of patients, often multiple, and particularly affecting the
carotids, subclavian, and abdominal vessels.
• Hypertension in 33–83% of patients, generally reflecting renal artery stenosis, which is
seen in 28– 75% of patients.
• Takayasu retinopathy in up to 37% of patients.
• Congestive cardiac failure associated with hypertension, aortic regurgitation, and
dilated cardiomyopathy.
• Neurological features secondary to hypertension and/or ischaemia, including postural
dizziness, seizures, and amaurosis.
• Pulmonary artery involvement in 14–100% of patients.
Pulmonary artery disease shows little correlation with the systemic pattern of arterial
involvement.
Natraj Setty HS, etal. 2017

11. Clinical
manifestations
of
TA

12. Diagnosis:-
• Misdiagnosis due to:
• LVVs and peri-arteritis is their frequent misdiagnosis for their more
prevalent cognate non-inflammatory conditions.
• Its rarity and the frequent absence of systemic acute-phase response.
• There is no diagnostic test for TA.
• Classification criteria for TA, have a low sensitivity.

13. Laboratory And Biomarkers:-
• No specific laboratory tests.
• Acute phase reactants, (ESR) and (CRP): the most valuable non-imaging
tests used to monitor disease course,
CRP level; associated with thrombotic events.
• Normocytic, normochromic anaemia, leucocytosis, thrombocytosis, and
elevated serum amyloid A and fibrinogen, are elevated in active phase.
• Pentraxin3 (PTX-3) serum levels associated with active disease.
• Platelet to- lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio
(NLR) reflect inflammatory phase.

14. Imaging:-
• Conventional angiography, contrast-enhanced magnetic resonance
angiography (MRA), and Computed tomography angiography (CTA)
• Angiography using digital subtraction technique (DSA).
Russo and Katsicas etal.2018

15. • There are four types of vascular lesions:
1. Stenosis – most commonly affects the thoracic aorta and renal
region of abdominal aorta
2. Occlusion – affects the distal part of abdominal aorta and the
bifurcation zone
3. Dilation – predominantly spreads in the ascending aorta
4. Aneurysm – spreads in the lower part of thoracic aorta and
abdominal aorta
The 1994 International TA Conference in Tokyo established an angiographic
classification:-

16. D. Hrisrova etal2018

17. Ishikawa diagnostic criteria for Takayasu arteritis 1996
A high probability of TA is considered when
two major criteria are present
Or one major and two minor criteria
Or four minor criteria are present
De Souza АW etal.2014

18. Disease Course:-
• TA comprises an active phase with highly variable duration that
eventually subsides with residual arterial scarring.
• Monophasic illness in 20 %, to a chronic-relapsing course up to many
years.
• Morbidity and mortality are significant in TA.
• The 5-year and 10-year survival rates are 93% and 91% respectively.
Ishikawa K et al 1994
Smitienko IO etal.2008

20. TA Treatment:-
• There is no clinical measures to evaluate activity or damage in TA.
• Prevention of the progression of the arterial involvement an important
therapeutic goal, although there is no evidence-based definition of
clinically-relevant arterial progression.
• Acute-phase reactants and multi-item activity criteria do not accurately
correlate with arterial progression.
• Arterial progression:
• Serial radiological imaging; magnetic resonance and doppler
ultrasonography
• Novel biomarkers, the long pentraxin PTX3.

21. Line of management:-
• TA is still an orphan disease, no definitive advice to dosing, duration
and choice of therapeutic agents.
• Steroids are the mainstay of medical therapy of TA, usually with an
initial prednisone daily dose of 0.5–1 mg/kg.
The majority of patients relapse as steroids are tapered.
• Steroid-sparing agents such as methotrexate , azathioprine ,
mycophenolate mofetil and leflunomide.
• Cyclophosphamide , used for life threatening disease in the pre-
biologic era, is now less commonly.

22. Biologic therapies:-
• TNFα-inhibitors; are the most widely used,
• No clear differences in efficacy among various TNFα-inhibitors.
• Response, relapse and progression rate are 85–90 %, 35–60 % and
15–35 % respectively.
• IL-6 blockade with tocilizumab for refractory TA.
• Induced normalisation of systemic inflammatory responses might not
always parallel prevention of arterial progression.
• Rituximab and abatacept which tackle B and T cells may helpful.

23. Adjuvant therapy:-
• Antihypertension: beta-adrenergic blockers, calcium channel
blockers, diuretics or angiotensin converting enzyme (ACE)
inhibitors???.
• Non-immunologic therapies; aspirin and other anti-platelet agents;
reduced frequency of ischemic events in TA.
• Interventional procedures; have worse long-term patency rate in TA
than in atherosclerosis.
• Percutaneous transluminal angioplasty is used in stenotic areas.
• Endarterectomy, bypass procedures, resection of coarctation and
aneurysm regions, and aortic valve replacement
Russo RAG etal 2018

25. MAZ ET AL 2021

26. MAZ ET AL 2021

28. Reference:-
• Grayson PC et al (2012) Distribution of arterial lesions in Takayasu’s arteritis and giant cell arteritis. Ann
Rheum Dis 71:1329–1334.
• Di Chio MC, Sartorelli S, Tombetti E, Aiello P, Manfredi AA, Sabbadini MG, Baldissera E (2014) High
prevalence of inflammatory comorbidities in a 70 cases-cohort of Takayasu arteritis: not only by chance?
EULAR 2014, Paris.
• Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill
Consensus Conference nomenclature of vasculitides. Arthritis Rheum 2013;65:1–11.
• Ando M, Sasako Y, Okita Y, Tagusari O, Kitamura S, Matsuo H. Surgical considerations of occlusive lesions
associated with Takayasu’s arteritis. Jpn J Thorac Cardiovasc Surg 2000;48:173–9.
• De Souza АW, De Carvalho JF. Diagnostic and classifi cation criteria of Takayasu arteritis, Journal of
Autoimmunity, 2014, 48, 79-83.
• Russo RAG, Katsicas MM. Takayasu Arteritis. Frontiers in Рediatrics, 2018, 6(265).
• Natraj Setty HS, Vijaykumar JR, Nagesh CM, Patil SS, Jadav S, Raghu TR, Manjunath CN. J Rare Dis Res Treat.
(2017) 2(2): 63-68.
• Gubrandsson B, Molberg O, Garen T, Palm O. Prevalence, incidence, and disease characteristics of Takayasu
Arteritis by ethnic background: data from a large, population-based Cohort Resident in Southern Norway.
Arthritis Care Res. (2017) 69:278–85. doi: 10.1002/acr.22931