Takayasu arteritis (TA) is a large vessel vasculitis affecting mainly the aorta and its major branches. TA occurs most commonly in female patients in the second and third decades of life, but has also been reported in children as young as 24 months of age 1. The disease is more frequent in Asian populations, but has been reported in patients of all ethnical background. Descriptions of TA in the pediatric age are scanty. Moreover, treatment options have been limited so far, with few reports focusing on immunosuppressive treatment (2 methotrexate, 1 cyclophosphamide) in pediatric TA 234.

The aim of the present report was to describe four cases of pediatric TA seen in a French tertiary pediatric rheumatology center, with an emphasis on both medical and surgical management, as well as providing a recent review of the literature. A representative clinical history is detailed below, while Table 1 summarizes the characteristics of the patients.

PH, male, with unremarkable family or past medical history, at the age of 11 years was admitted for the occurrence of arterial hypertension (180/100 mm Hg) with the presence of headache and vomiting for the previous 2 days. His parents reported a history of fatigue, myalgia, frontal headache and weight loss (9 kg) for the previous 2 months. On admission he was alert, afebrile and in no acute distress. BP was 170/105 mm Hg. All his pulses were felt and symmetric. Fundoscopy was normal. No abdominal bruit was present. The rest of his physical examination was normal. Investigations on admission revealed anemia (Hb 79 g/L), thrombocytosis (platelet count 738 G/L), ESR 125 mm/h, CRP 80 mg/L. The rest of laboratory investigations, including serum creatinine, electrolytes, autoantibodies, and urinalysis, were normal, as well as ECG and chest X-ray. An echocardiogram showed mild thickening of the left ventricle. A renal color Doppler ultrasound examination revealed a right renal artery stenosis with a small ipsilateral kidney (70 mm vs 104 mm for the left kidney). An angio-MRI demonstrated a thrombosis in the left common carotid artery, a 70% stenosis of the left subclavian artery, a 80% stenosis of the brachiocephalic artery, a thrombosis in the descending thoracic aorta, and a right renal artery thrombosis and stenosis (Figure 1). The boy was given prednisone 2 mg/kg per day, antihypertensives (amlodipine 5 mg/day, enalapril 10 mg/day), as well as low-dose aspirin. After 2 weeks, ESR fell to 26 mm/h and BP to 156/68 mm Hg. Surgery was planned, but the patient relapsed at the prednisone dose of 5 mg per day, so that daily dosage was increased up to 40 mg (1 mg/kg/d), and another immunosuppressive (mycophenolate mofetil, MMF, 250 mg bid) was added. Six months later he underwent revascularization bypass surgery of brachiocephalic trunk (a femoral vein was used as a graft between ascending aorta and right carotid artery). He was discharged two weeks after surgery on prednisone 10 mg/day, MMF 250 mg bid, 4 antihypertensive drugs (enalapril 10 mg/day, nicardipine 60 mg/day, labetalol 400 mg/day, and clonidine 0.3 mg/day) and low-dose aspirin. At last visit at 14 years of age, BP was controlled (135/65 mmHg) by three medications; he was taking prednisone 7.5 mg per day, MMF (750 mg bid), and low-dose aspirin. His last investigation showed ESR 28 mm/h, Hb 115 g/dL, platelet count 557 G/L, and a normal renal function. His last MRI angiogram showed normal visualization of the brachiocephalic trunk and right internal carotid artery. Neurological examination was normal, but periodic headaches were still present.

Takayasu arteritis has been rarely reported in childhood. A common clinical mode of disease presentation in our patients was arterial hypertension (2/4 cases), together with nonspecific symptoms (headache, fatigue, myalgia, weight loss). Symptoms due to ischemia, which are frequent in adults, have been seldom reported in children. However, although true claudication (upon effort) was present only in one patient, we have observed ischemic findings (chest, limb, and abdominal pain) in three of our four patients. The disease is also called 'pulseless disease', since peripheral pulses are often absent due to vascular obstruction; however, this feature was present only in one of our patients. In addition, an abdominal bruit can often help in the diagnosis, but this was noted in only 1/4 of our cases.

The largest series of TA in children has been reported by Hong et al., who described 70 cases 5; the male to female ratio was 1:4.4 and the youngest patient was 3 years old. Arterial hypertension was seen in 65/70 patients (93%). In another report of 31 children with TA from South Africa 6, arterial hypertension was the most common presenting feature, followed by cardiac failure, bruits, and absent pulses. Jain et al 7 from India reported 24 children with TA; again, arterial hypertension was the commonest mode of presentation, seen in 83% of patients; the male to female ratio was 1:5. In a Turkish multicenter serie, TA represented 1.5% of pediatric vasculitides 8. Among these patients, 71.4% described constitutional symptoms. Hypertension was the leading feature, and renal involvement was present in 86% of cases. Half of the patients had involvement of both thoracic and abdominal aorta. Table 2 summarizes clinical findings of main published series, as well as our own data.

The diagnosis of TA is based on characteristic findings of diseased aorta and its major branches seen on angiography. This is demonstrated by luminal abnormalities such as stenosis or aneurysmal dilatation of the aorta, its major branches, and the pulmonary arteries. With regard to imaging studies, traditionally the angiographic patterns have been divided in: type I, affecting the aortic arch; type II, the thoracic and abdominal aorta; type III, the aorta both above and below the diaphragm; and type IV, the aorta and the pulmonary arteries. In our cases type I was the predominant pattern, whereas in two series type II was the predominant one 79.

Ultrasonography and positron emission tomography are new, promising techniques to assess large-vessel vasculitides. Color-coded Doppler sonography can facilitate an accurate diagnosis of Takayasu arteritis by the characteristic appearance. Homogeneous circumferential intima-media thickening of the common carotid arteries is a specific ultrasonographic finding in patients with Takayasu arteritis 101112. More recently MRI has been used to establish the diagnosis of TA in children, to monitor disease activity and to guide treatment. Early in the disease of TA, smooth muscle thickened vessel walls, which may be the only manifestation of vascular inflammation, may be not detected by conventional angiography but MRI can visualize the thickened vessel wall directly, and in addition it can show other signs of active inflammation such as mural edema with T2-weighted imaging and increased wall vascularity with enhanced imaging 1314. For one patient in our series MRI was used to establish the diagnosis of TA and for follow-up. Table 3 summarizes the evolution of vascular involvement in our patients, as studied by echodoppler, MRI and/or angiography.

The authors declare that they have no competing interests.

SAA and RC wrote the manuscript, MFD and LD retrieved data from charts, and XB and PC conceived and supervised the study. All authors read and approved the final manuscript.