The diagnosis and treatment of aortitis, read this article is enough

*For medical professionals only

Recently, the 9th International Forum on Rheumatism Immunization in Children and the 15th National Academic Forum on Rheumatic Immunological Diseases for Children were successfully held online, and Professor Lu Meiping of Children's Hospital Affiliated to Zhejiang University School of Medicine started from clinical cases and combined with the latest foreign guidelines and treatment recommendations, and explained the selection strategy
of multiple arteritis (TA) treatment plan for us.

Case profile

Complaint: cough, shortness of breath with chest tightness for more than half a month
.

10 months ago for "chest pain" came to the hospital, CT showed that the left hilar calcification foci, positive T-spot after admission; PPD is strong positive for
72 hours.

Physical examination: blood pressure in the extremities: right upper extremities 140/100mmHg, left upper extremities 114/84mmHg, right lower extremities 106/86mmHg, left lower extremities 92/68mmHg
.

Laboratory and imaging tests:

CRP：8.
45mg/L，ESR：32mm/h

N-terminal brain sodium peptide precursor: 16481 pg/ml, 19052.
0 pg/ml↑

• Decreased pulsation of the left radial artery;

• Grade IV systolic murmurs can be heard in the precordial area;

• Cardiac ultrasound: left atrium, left ventricular enlargement;

• Decreased left heart function: LVEF32%;

• Pulmonary hypertension: 49 mmHg
  .
  

Figure 1: Patient imaging data

Soon, the patient developed thrombosis, imaging showing complete occlusion of the descending aortic arch and collateral
circulation.

The case met the diagnostic criteria of TA, and the doctor eventually gave cardiocardiotonic, diuretic, captopril tablets, metoprolol antihypertension, bosentan to reduce pulmonary hypertension, isoniazid + rifampicin + pyrazinamide anti-tuberculosis, meprednisolone shock, tocilizumab treatment
.
This case of TA, which manifests itself as heart failure and tuberculosis infection, has triggered our thinking
.

Do you know about vasculitis and its family?

Professor Lu Meiping pointed out that the classification of vasculitis is a challenging issue
.
The classification criteria for vasculitis proposed by the American College of Rheumatology (ACR) in 1990 can help with diagnosis, but it lacks sufficient sensitivity and specificity
.
The 1994 Chapel Hill Consensus Conference (CHCC) proposed a disease definition of vasculitis, but did not reflect the histopathological characteristics
of the disease.

With the understanding of the pathogenesis of the disease, the nomenclature and definition of systemic vasculitis are constantly being updated
.
In 2012, CHCC gave vasculitis the 2012 CHCC name and classification according to the size of the main affected blood, and is currently the most widely
used.

Table 1: Classification of Systemic Vasculitis (ChapelHill, 2012)

Common knowledge about TA, all in one hand

TA refers to chronic granulomatous arteritis that mainly affects the aorta and its primary branch, mainly affects the aorta and its main branch, and is a chronic progressive, non-specific, inflammatory granuloma disease, which was first reported in 1951 as "Takayasus arteritis", called "anachronism"
.

• Infections: bacteria, viruses, tuberculosis, etc.
  ; Intestinal flora; Vascular microorganisms;

• Susceptibility gene: HLA-B52 is associated with poor prognosis; HLA-B/MICA is disease-related;

• Immune disorders;

• Estrogen: more common in women
  .
  

1.
Antihypertensive drug choice?

2．Surgery？ When？ (Surgery)

3.
Hemoptosis is related active TB infection or heart failure or pulmonary vasculitis？ (hemoptysis)

4．pulmonary hypertension？ (Pulmonary hypertension)

5.
thrombosis : Do we need use anti-coagulation treatment on TA as soon as possible？ (Thrombosis, anticoagulant?) ）

6．thrombolysis therapy？ (Thrombolysis?) ）

7．Biologics？ (Biologics)

• Can be acute onset with convulsions, hypertensive encephalopathy;

• Can conceal the onset of the disease to seek treatment for growth retardation;

• Systemic symptoms: fever, malaise, fatigue, loss of appetite, sweating, weight loss, myalgia, arthralgia or arthritis, erythema nodosum;

• Signs and symptoms of ischemia in different organs: headache, syncope, stroke, vision loss; chest pain, neck pain, abdominal pain (vascular pain); Intermittent mobility disorders of the extremities; Decreased arterial pulsation in the limbs; vascular murmur; The difference in systolic pressure between both upper extremities is greater than 10 mmHg
  .
  

The clinical manifestations of TA vary greatly depending on the affected vascular site, and the clinic is divided into four types
according to the different lesion sites.

Table 2: Clinical classification and clinical features of TA

At present, the diagnosis of TA internationally is based on the TA classification standards developed by ACR in 1990 and the criteria for TA classification by the European Union of Rheumatology (EULAR)/International Organization for the Study of Childhood Rheumatology (PRINTO)/European Society for Pediatric Rheumatology (PRES) on TA classification, including:

(1) The age of onset ≤ 40 years old;

(2) Intermittent limb claudication;

(3) Decreased pulsation of one or both brachial arteries;

(4) The difference between systolic blood pressure of both upper extremities > 10 mmHg;

(5) One or both sides of the subclavian artery or abdominal aorta smell and murmur;

(6) Angiography abnormalities, found that the first-level branch of the aorta or the proximal aorta of the upper and lower extremities are stenosis or occlusion, the lesions are often focal or segmental, and except for arteriosclerosis, fibromuscular dysplasia or similar reasons, angiography is often replaced
by MRA, CTA and so on in recent years.

3 or more of the above 6 must be met to diagnose TA
.

Figure 2: 2010 EURAR/PRINTO/PRES DIAGNOSTIC CRITERIA FOR CHILDREN

• Systemic infectious diseases: HIV, brucellosis, endocarditis;

• Infectious aortic arteryitis: syphilis, tuberculous aortic artery;

• Autoimmune diseases: primary systemic vasculitis, rheumatic fever, systemic lupus erythematosus, sarcoidosis, Behcet's disease, giant cell arteritis;

• Non-inflammatory diseases: congenital coarctation of the aorta, Marfan syndrome
  .
  

Table 3: Comparison of different imaging techniques of TA

Trade-offs in the treatment of TA

Professor Lu Meiping pointed out that with the improvement of diagnosis level and understanding, the incidence of TA has increased year by year, and TA treatment often requires multidisciplinary cooperation, involving renal immunity, rheumatic immunity, cardiovascular immunity, imaging and other specialties, especially severe disease identification
.
The current routine treatment regimen for children is a combination of glucocorticoids and immunosuppressants, and in refractory cases, the use of biologics should be considered as soon as possible to prevent ischemic damage
to the terminal organs.
When arterial stenosis is severe, surgical treatment
is required.

Early diagnosis and prompt, correct management are essential
to reduce morbidity and organ damage.

Non-surgical treatment includes: 1.
Glucocorticoid therapy: prednisone, methylprednisone; 2.
Immunosuppressants: cyclophosphamide, methotrexate and azathioprine; 3.
Biologics; 4.
Blood vessel dilvation, anticoagulation
.
Surgical treatment includes: 1.
percutaneous intraluminal angioplasty; 2.
surgical treatment: artificial vascular reconstruction, endometrial thrombotomy
.
It is particularly important to note that surgical treatment should be performed
during a stable period of remission.

1.
Hormone-based medication

• It is recommended to start using glucocorticoids in large doses instead of small doses of glucocorticoids;

(Large dose: equivalent to prednisone 40 ~ 60 mg / day; Once the disease is controlled, the hormone dose is reduced to 15 to 20 mg/day within 2 to 3 months, and ≤10 mg/day after 1 year)

• Glucocorticoid shock therapy when there is organ damage or life-threatening;

• In children, low-dose corticosteroids are recommended to be given orally
  after glucocorticoid shock therapy.
  

2.
Immunosuppressants: early treatment with immunosuppressants is recommended

• MTX: 10-15mg/㎡/w, not more than 20mg/w, total course of treatment 18-24 months;

• Relatively infrequently used drugs: azathioprine (AZA): 2 mg/kg/d, mycophenolate mofetil 20-30 mg/kg;

• CTX: Not used anymore
  .
  

3.
For patients with relapse or refractory nature, the addition of biological agents is recommended

• Clinical remission rate of biologics is 80%, compared to tocilizumab, more use of TNF inhibitors (infliximab and adalimumab);

• Small molecule-targeted drugs such as JAK inhibitors, reported on a case-by-case basis, are worth looking forward to
  .
  

4.
Drug adjustment in patients with recurrence:

• Minor recurrence, it is recommended to increase to the last effective dose;

• Severe recurrence, it is recommended to restart hormone therapy
  according to the new disease.
  

Inflammation of the walls of blood vessels is the main cause of thrombosis, and anti-inflammatory is key
.

• Anticoagulation is not routinely used and antiplatelet therapy is not required in all patients with TA;

• For severe arterial stenosis, severe involvement of intracranial or vertebral basilar arteries, combined with coronary heart disease or cerebrovascular disease, etc.
  ;

(Aspirin 75-300 mg/day; Aspirin in children is dosed at 3 to 5 mg/kg/day [≤75 mg/day]).

• Remission without hormoneization: discontinuation of hormonal therapy (other immunosuppressant therapy can still be continued);

• Persistent remission: remission of the condition for at least 6 months / reaching an individualized target hormone amount;

• Remission: absence of active signs and symptoms, normal ESR and CRP; absence of progressive vascular stenosis or dilation;

• Refractory: despite standard treatment, it does not induce remission;

• Mild relapse: disease activity that does not meet the criteria for severe relapse;

• Severe recurrence:

a.
Clinical features of ischemia (stroke, limb claudication, etc.
)

b.
Progressive aortic or large vasodilature, stenosis, or dissection caused by arterial inflammation

At least 2 of the following 4 criteria have had a recent episode or worsen:

1.
Symptoms of ischemia or inflammation of blood vessels: limb beating, pulse reduction or disappearance, vascular murmur or pain, blood pressure asymmetry;

2.
Exclude systemic symptoms caused by other reasons: fever, arthralgia, scleritis, etc.
;

3.
Angiography (CTA/MRA, etc.
): showing worsening of vascular lesions or the formation of new vascular lesions;

4.
Elevated inflammatory indicators (erythrocyte sedimentation, C-reactive protein, fibrinogen
).

summary

Finally, Professor Lu Meiping pointed out that TA is a common macrovasculitis in children and has a potential life threat
.
Early diagnosis and intervention are essential for long-term prognosis
.
Recent advances in early diagnosis and effective treatment options have significantly reduced the mortality and complication rate of TA
.

• Hormones are the first-line treatment of the disease, with high-dose hormones preferred as the initial treatment, if necessary, high-dose shocks;

• TNF, IL-6, interferon (IFN) pathway and other immune inflammatory mechanisms involved in the disease, severe patients or hormone dependents, it is recommended to add biological agents;

• Unlike anticoagulation, aspirin is used for severe arterial stenosis, severe intracranial or vertebrobasilar arteries, and concomitant coronary heart disease or cerebrovascular disease
  .
  

• Surgical treatment should be performed
  during a stable period of remission.
  

• Chief physician and doctoral supervisor

• Director of the Department of Rheumatology and Immunoallergy at the Children's Hospital Affiliated to Zhejiang University School of Medicine

• Deputy Leader of the Rheumatology Group of the Pediatric Branch of the Chinese Medical Association

• Vice Chairman of the Children's Allergy Immunorheumatism Branch of the Asia-Pacific Medical Bio-Immunization Society

• He is the executive director of Zhejiang Immunology Society and the chairman of the Rheumatology and Immunology Professional Committee

• Vice Chairman of the Rheumatology Branch of Zhejiang Mathematical Medicine Association

• Standing committee member of the Rheumatology Branch of Zhejiang Medical Association and Medical Doctor Association

• Leader of the rheumatology group of the Pediatric Branch of Zhejiang Medical Association

• 2006.
  1-2007.
  7 Postdoctoral Fellowship at the Canadian University of Saskatchewan

• He has presided over a number of projects such as the National Natural Science Foundation of China, the Provincial Natural Science Foundation of China, and the Provincial Science and Technology Department

• Won 1 Provincial Science and Technology Progress Award

[1] EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008.
Part II: Final classification criteria，Ann Rheum Dis,2010 May; 69(5):798-806.
doi: 10.
1136/ard.
2009.
116657.

[2]European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides - the SHARE initiative; Rheumatology (Oxford), 2019 Apr 1; 58(4):656-671.
doi: 10.
1093/rheumatology/key322.

[3]2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis； Arthritis Care Res (Hoboken)，2021 Aug; 73(8):1071-1087.
doi: 10.
1002/acr.
24632.
Epub 2021 Jul 8.

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