The Registry Study of Takayasu Arteritis in East China
The Registry Study of Takayasu Arteritis in East China
The Takayasu arteritis (TA) is a rare inflammatory large vessel arteritis which often occurs
 women in Aisa, one of which is China. The rare cases restricted the development of
 intervention strategy, especially in female patients who plan to be pregnant. So
 investigators try to recruit as many TA participants as possible to build a TA cohort so that
 investigators could manage patients much more professionally and standardized and explore the
 better interventional strategy for a better outcome as well, with full use of blood and
 vascular tissues.
1. Overview of Takayasu's arteritis.

 Takayasu arteritis (TA) is a chronic inflammatory blood vessel that seriously endangers
 human health, which affects a large variety of blood vessels, characterized by vascular
 stenosis and occlusion. The clinical manifestations of TA are hypertension, renal
 failure caused by renal artery stenosis; pulseless, syncope and cerebral infarction
 caused by carotid vessels stenosis; pulmonary infarction induced by thoracic aorta
 involvement, etc. The TA usually accompanies high morbidity, high mortality, and poor
 prognosis. TA is a rare disease which is prone to occur in Asian women, especially in
 young women (20-40 years old) in the growth period. Currently, the etiology and
 pathogenesis of TA remain unclear, and the state of the disease is often repeatedly
 active and continuously progressive. Moreover, non-effective therapy exists for the
 moment.

 2. The diagnosis and activity evaluation of TA

 At present, TA is diagnosed according to the American Society of Rheumatology (ACR)
 classification criteria for Takayasu's arteritis: ① onset at age ≤40 years; ②
 claudication of an extremity; ③ decreased brachial artery pulse; ④ >10 mm Hg difference
 in systolic blood pressure between arms; ⑤ a bruit over the subclavian arteries or the
 aorta; ⑥ and arteriographic evidence of narrowing or occlusion of the entire aorta, its
 primary branches, or large arteries in the proximal upper or lower extremities.
 Participants who meet 3 or more criteria could be diagnosed with this disease posterior
 to excluding atherosclerosis, congenital muscle fiber dysplasia, etc.

 The course of TA is often manifested as chronic, repetitive activity and continuous
 progression. The evaluation standard proposed by Kerr et al. to monitor TA activity is
 widely used clinically. Two more new emerging or aggravating clinical manifestations
 indicates disease Activity: ① systemic symptom, such as fever, bones, muscle symptoms; ②
 increased erythrocyte sedimentation rate (ESR); ③characteristics of vascular ischemia or
 inflammation: such as intermittent claudication, pulse weakening or pulseless, vascular
 bruit, vascular pain, asymmetry blood pressure, etc.; ④ abnormalities in angiography.
 Although acute phase response protein such as ESR and C-reactive protein (CRP) are
 non-specific indicators for inflammation, they are still important markers to evaluate
 the disease activity. Imaging follow-up, primarily based on magnetic resonance imaging
 (MRI) and color Doppler ultrasound, is critical in assessing TA disease activity. With
 the help of Pro. Jiang Lin and Dr. Lu Peng, investigators have established an imaging
 diagnostic team in recent years and proposed the systemic MRI scoring standard in the
 international firstly. The standard has been applied to quantitatively assess the
 vascular inflammation prior and posterior to the treatment in participants with TA.
 Recently, investigators co-operated with the Department of Nuclear Medicine and
 Radiology to employ the 18F-FDG-PET/CT to evaluate the systemic vascular inflammation
 and disease activity in participants. Moreover, investigators attempted to use
 contrast-enhanced ultrasound microbubble imaging to assess the carotid artery
 inflammation and stenosis. At present, these two technologies are still being explored.
 Therefore, it is necessary to combine the clinical manifestations, acute phase response
 proteins (ESR and CRP) and imaging to judge the TA disease activity comprehensively.

 3. Treatment of arteritis

 The treatment of TA is divided into two phases: remission induction period and
 maintenance period. The drugs are divided into three categories including
 glucocorticoids, cytotoxic drugs, and biological agents targeting inflammatory
 cytokines.

 Glucocorticoids are the basic drug for TA treatment. Most TA participants receiving high
 doses of glucocorticoids treatment could be induced remission quickly, but about 17%-29%
 of refractory participants treated with standard glucocorticoids strategy could not be
 alleviated. And the recurrence rate is up to 90% with the single glucocorticoid. About
 more than 2/3 of participants would be glucocorticoid-dependent, and more than half of
 the participants need other drugs to maintain remission. Moreover, long-term high-dose
 glucocorticoids also have many adverse effects.

 Recently, targeted biological agents have been attempted to treat refractory, recurrent
 TA and glucocorticoid-dependent remission induction TA participants. Compared with
 conventional drugs, targeted biological agents work faster and could bring disease
 remissions for 70%-90% of refractory participants. However, the long-term use of
 biological agents would threaten the low-immunity participants with the risk of
 infections and cancer. Moreover, the effect on the reproductive system is unclear for
 the moment; in addition, these drugs are expensive and mainly used in refractory and
 critically ill participants.

 The combination of glucocorticoids combining with immunosuppressive agents such as
 cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, etc. are the
 commonly used remission induction strategy clinically. However, large amounts of
 clinical evidence demonstrate that TA participants receiving glucocorticoids with the
 immunosuppressive agents would also face the histopathological activities lesions in the
 future. In the long-term follow-up, the relapse rate is much higher, and the mortality
 rate is significantly higher than that of healthy people.

 In summary, the current commonly used drugs for TA treatment could not meet the needs of
 the clinical setting, and TA participants lack a universally effective treatment
 strategy.

 4. Pregnancy of TA participants

 TA often occurs in women of childbearing age, so reducing the risk of maternal pregnancy
 caused by pregnancy in TA participants is one of the investigators' focuses in recent years.
 At present, there are no relevant guidelines for the pregnancy of TA participants, and
 doctors instruct them to take pills and monitor disease activity mainly basing on the
 doctor's clinical experience. Usually, investigators do not recommend the TA participants in
 active phase to conceive, not only because that the use of hormones and cytotoxic drugs could
 influence the development of the fetus, but also because that the stenosis or occlusion of
 the distal artery would increase the cardiac load so as to cause congestive heart failure,
 pre-eclampsia as well as fetal growth restriction and stillbirth. A case-control study in
 Brazil recruiting 89 TA and 89 healthy pregnant women discovered that the risk of gestational
 hypertension and low birth weight was much higher in TA than that in healthy controls.
 Moreover, the perinatal mortality rate is much higher in TA pregnant participants as well. A
 retrospective study in France including 96 TA pregnant women, 240 cases of pregnancy events,
 revealed that TA did not affect the pregnancy outcomes, but increased the risk of
 complications such as pregnancy hypertension with the elevating of the disease activity.
 Therefore, there is a lack of large-scale evidence-based medical proof uncovering the
 relationship between the pregnancy outcome and maternal risk in participants of TA. Here, the
 present follow-up registration also extends to the service of pregnant TA participants, which
 is designed to guide the treatment of pregnant participants and monitor maternal safety.

 This objective of this study is to record the related materials of the follow-up of TA
 participants and the pregnancy course, to direct the standardized medication, to monitor the
 changes of disease conditions, and to provide the better prognosis and pregnancy outcome for
 TA participants.
Inclusion Criteria

 -  onset at age ≤40 years;

 -  claudication of an extremity;

 -  decreased brachial artery pulse;

 -  >10 mm Hg difference in systolic blood pressure between arms;

 -  a bruit over the subclavian arteries or the aorta;

 -  angiographic evidence of narrowing or occlusion of the entire aorta, its primary
 branches, or large arteries in the proximal upper or lower extremities.

 -  Patients should meet at least 3 of the above 6 articles.

 -  Sign the informed consent

 Exclusion Criteria

 -  autoimmune diseases, such as ANCA-associated vasculitis, systemic lupus erythematosus,
 Behcet's disease, rheumatoid arthritis, ankylosing spondylitis, etc.;

 -  complicated medical abnormal conditions, un-related with TA but engendering the
 unpredictable risks, such as severe, progressive, or uncontrollable kidney, liver,
 blood, gastrointestinal, pulmonary, heart, neuron or others

 -  malignant tumors;

 -  serious acute or chronic infections;

 -  high risk of tuberculosis infection such as clinical, radiological or laboratory
 evidence of active or occult tuberculosis, or the history of active tuberculosis;

 -  Having received or plan to receive plasma exchange or lymphocyte replacement or
 immunoabsorption therapy within 1 year.

 -  Preparing to receive an attenuated vaccine during the trial;

 -  Having received or plan to receive an organ transplant;

 Exit criteria

 -  participants require to withdraw during the study;

 -  participants who believe that they need to withdraw due to clinical adverse events;

 -  Participants can not or does not comply with the requirements of the research
 protocol;