Medical Centre for Rheumatology Berlin-Buch, Berlin and
1 Institute for Radiology/Angiography, Klinikum Buch, Berlin, Germany
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Abstract |
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Methods. We describe three patients with early disease who had no haemodynamically relevant stenoses. They are compared with nine patients who were diagnosed in the stenotic/occlusive stage of the disease. All patients were German Caucasian females. Colour Doppler sonography and angiography were performed in all cases.
Results. Patients with early disease had general symptoms of fatigue and arthralgia and laboratory signs of inflammation, but neither bruits nor decrease of pulse rate. Sonography of the carotid and subclavian arteries demonstrated a characteristic, homogeneous, midechoic, circumferential thickening of the wall. At this stage of the disease it was difficult to get unequivocal results with angiography. In all nine remaining patients, sonography also demonstrated inflammation of the subclavian or carotid arteries, as did angiography in eight of these patients.
Conclusion. Sonography of the carotid and subclavian arteries aids in the detection of early Takayasu arteritis. In young females with unclear symptoms and laboratory findings of generalized inflammation, the primary extracranial branches of the aortic arch should be investigated by sonography to detect early Takayasu arteritis.
KEY WORDS: Takayasu arteritis, Ultrasonography, Colour Doppler ultrasonography, Angiography, Carotid artery, Subclavian artery, Temporal arteritis, Early disease.
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Introduction |
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We present three patients with early Takayasu arteritis in which sonography delineated characteristic long segments with homogeneous, midechoic, circumferential arterial wall thickening, which has been described as the macaroni sign [3]. This finding was decisive for the detection of Takayasu arteritis.
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Patients and methods |
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The three patients are compared with all nine consecutive patients with Takayasu arteritis who had been diagnosed during the stenotic/occlusive stage of the disease between 1994 and 2000 (group 2). All these patients had either bruits over the subclavian arteries, over the carotid arteries or over the aorta, decreased brachial artery pressure or a blood pressure difference of >10 mmHg. They all fulfilled at least three ACR criteria for Takayasu arteritis. Both sonography and arteriography demonstrated stenoses of >50% or occlusions in these patients. The stenotic/occlusive stage was defined by a stenosis of >50% or an occlusion, as stenoses of >50% are haemodynamically relevant and usually cause bruits.
All 12 patients presented at the Medical Centre for Rheumatology, Berlin-Buch. The diagnosis of Takayasu arteritis was confirmed by at least two rheumatologists who examined the patients.
Simultaneous colour Doppler and duplex sonography was performed by an experienced physician ultrasonographer (WAS) with a linear transducer (L 105, 105 MHz, length of probe 38 mm; ATL Ultramark 9 HDI; Advanced Technology Laboratories, Bothell, WA, USA). For the abdominal vessels, a 3.5 MHz curved array probe of the ATL Ultramark 9 HDI was used. If the arteries were located superficially, the 105 MHz transducer was also used for the abdominal vessels.
The intimamedia thickness of the common carotid arteries was measured as described in previous studies [4] in all 12 patients, in 12 age-matched female controls without vasculitis and in 12 consecutive female patients with active temporal arteritis (mean age 74 yr; range 6582 yr). The maximum diameter outside arteriosclerotic plaques was considered.
Sonography was performed before angiography in two cases in group 1 and in seven cases in group 2. In the three other cases, angiography had already been performed by an external institution.
In all patients who had not been investigated by an external institution, a Siemens Multiskop system (Siemens, Erlangen, Germany) was used for angiography.
Arterial involvement was recorded according to the system described by Ueno et al. [5]: type I, aortic arch and its branches; type II, involvement of the descending aorta, including the abdominal aorta and its branches; type III, combination of type I and II; type IV, additional involvement of the pulmonary artery.
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Results |
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The clinical investigation was completely normal except for a small splinter haemorrhage at the left middle finger. There were no bruits. The blood pressure at both arms was 130/85 mmHg.
The laboratory data were typical for generalized inflammation. The ESR was 92 mm/h, C-reactive protein concentration (CRP) was 36 mg/l (normal value <6), there was thrombocytosis of 595 g/l, and - and
-globulins were elevated:
2 globulin was 15.2% and
-globulin 21.4%. Slight leucocytosis of 12.6x109/l and slight anaemia (haemoglobin 7.4 mmol/l) were found. Other laboratory data, including titres of several viruses, rheumatoid factor, antinuclear antibodies (ANA), extractable nuclear antigens (ENA) and antineutrophil cytoplasmic antibodies (ANCA) did not reveal any relevant abnormalities.
The patient had no risk factors for cardiovascular disease.
As the diagnosis was still unclear, colour Doppler sonography of the cervical region was performed to look for inflammatory changes. It revealed a characteristic, homogeneous, midechoic, circumferential thickening of the wall of the entire left common carotid artery with 30% stenosis (Fig. 1A and B
). The maximum diameter of the artery wall was 2.5 mm and the minimum lumen diameter was 4.6 mm. The systolic flow velocity was slightly increased, to 150 cm/s. The diastolic flow velocity was normal. The wall of the right proximal common carotid artery was also thickened, with a minimum lumen of 5.0 mm. There were also slight, haemodynamically irrelevant stenoses of the right subclavian and the right axillary artery.
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Angiography had been performed at an external institution before sonography was done. Angiography showed only a smaller left carotid artery (Fig. 1C). This finding had been misinterpreted as a hypoplasia of this vessel. No involvement of the aorta or the renal, mesenteric and coeliac arteries was found by ultrasound, angiography, or magnetic resonance angiography.
The stenoses of both carotid arteries, the right subclavian and right vertebral artery were less than 50%. Thus, the patient was classified as having prestenotic stage Takayasu arteritis with type I involvement of the vascular system.
Other investigationsradiography of the chest, the paranasal sinuses, ECG, cerebral magnetic resonance imaging (MRI), sonography of the abdomen, of the left elbow, and of the thyroid, gynaecological investigation, fundoscopy and bone densitometrywere normal.
The patient was treated with a daily dose of 30 mg prednisolone and 150 mg azathioprine, with good effect on arthralgias, fatigue and malaise. ESR and CRP returned to normal. Prednisolone was then reduced within 3 weeks to 10 mg for 6 months. The dose was lower than is generally suggested for the treatment of Takayasu arteritis, as guidelines for the treatment of early Takayasu arteritis have not yet been developed. The extracranial arteries of the aortic arch were investigated 6 months after the start of treatment. The thickening of the wall of the left common carotid artery decreased from 2.5 to 1.5 mm. Thus, there was only a minimal abnormality left in this region. The other arteries had been involved to a lesser extent without significant change compared with the first investigation. Fourteen months after the start of treatment, the minor mural thickening of the left common carotid remained, but a typical macaroni sign, as seen in Fig. 2, with a 40% stenosis, could now be demonstrated in the right common carotid artery.
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Patient 2.
A 27-yr-old female had complained of arthralgias for 3 yr. At first her knees, ankles and mandibular joints were affected. Later she also had pain of the wrists and headache. Within the last 3 months she had lost 4 kg. She had low-grade fever with temperatures up to 38.2°C.
The clinical investigation was completely normal except for a funnel chest. There were no bruits. The blood pressure at both arms was 110/65 mmHg.
The laboratory data were typical of severe generalized inflammation. The ESR was 120 mm/h and CRP 246 mg/l. There was a leucocytosis of 12.5x109/l and severe anaemia (haemoglobin 5.2 mmol/l), due to both inflammation and iron deficiency. Albumin was reduced (26 g/l). 2-Globulin and
-globulins were elevated (17.0 and 23.9% respectively). ANA were slightly positive, with a titre of 1:80 and a fine speckled fluorescence. Several virus titres were investigated. A recent parainfluenza virus infection was suspected. Other laboratory data, including ENA, ANCA and rheumatoid factor, did not reveal any relevant abnormalities.
The patient had no risk factors for cardiovascular disease.
When sonography of the thyroid was performed to search for a focus of the inflammation, the investigator (AN) realized that the wall of the right common carotid artery was thickened. Thus, colour Doppler sonography of the cervical region was added. A characteristic, homogeneous, midechoic, circumferential, 6-cm-long thickening of the wall of the proximal right common carotid artery was found (Fig. 2A and B
). The maximum grade of the stenosis was 40%. The maximum diameter of the artery wall was 3.0 mm and the minimum lumen was 5.0 mm. Additionally a small, 1-cm-long wall thickening with a maximum diameter of 2.0 mm was found at the right proximal subclavian artery. There were no increased blood-flow velocities in the stenoses.
Angiography was performed after sonography to evaluate the distribution of the disease. The narrowing of up to 40% of the right proximal common carotid artery and the slight stenosis of the right proximal subclavian artery were confirmed (Fig. 2C). Additionally, arteriography showed slight, haemodynamically irrelevant stenoses of the right proximal vertebral artery and the left proximal common carotid artery. No involvement of the aorta or the renal, mesenteric and coeliac arteries was found by either sonography or angiography. Thus, the patient was classified as having prestenotic stage Takayasu arteritis with type I involvement of the vascular system.
Additionally a small pericardial effusion and bronchitis due to Klebsiella pneumoniae were diagnosed. The bronchitis was treated with ciprofloxacin. Therapy with prednisolone was started. The patient received 100 mg/day for 3 days followed by 60 mg/day for 1 week; the dose was then reduced by 10 mg/day each week until it reached 20 mg/day. The dose was then reduced according to clinical and laboratory parameters. Fever, arthralgia, and laboratory signs of inflammation decreased quickly with treatment. Additionally, methotrexate at a weekly dose of 15 mg was started. With a daily dose of 15 mg of prednisolone, the patient again had arthralgia and low-grade fever as well as elevated CRP and ESR. The extracranial arteries of the aortic arch were again investigated by sonography 8 weeks after start of treatment. The stenoses of both carotid arteries had now become haemodynamically relevant, with increased systolic and diastolic blood flow velocities of 250 and 100 cm/s respectively. Corresponding to this ultrasound finding, new bruits could be heard over the carotid arteries. The minimal lumen of the right carotid artery decreased from 5 cm to 3.8 mm. The degree of stenosis was now estimated at 55%. It was the same 8 months after the start of treatment.
Patient 3.
A 36-yr-old female complained of myalgia and weakness of the arms and legs and morning stiffness of 12 h, and had had xerophthalmia for 2 yr. The left knee-joint had been swollen 9 months ago. She had a 15-yr history of arterial hypertension that was treated with a daily oral dose of 10 mg of lisinopril and a 15-yr history of smoking (10 cigarettes per day).
The clinical investigation was normal except for a slight arthritis of the right knee, varicosis, and 16 of 18 positive tender points for the classification of fibromyalgia. There were no bruits. The blood pressure was 140/80 mmHg at the right arm and 135/75 mmHg at the left arm.
The laboratory data were typical of generalized inflammation. The ESR was 60 mm/h and CRP was 40 mg/l. 2-Globulin was slightly elevated (11.8%). Other laboratory data, including red and white blood cell count, ANA, ENA, ANCA and rheumatoid factor, did not reveal any relevant abnormalities.
Colour Doppler sonography of the cervical region was performed to look for inflammatory changes as the diagnosis was unclear. A 1-cm-long homogeneous, circumferential midechoic wall thickening of the right distal common carotid artery and the carotid bulb with a 40% stenosis and a maximum diameter of the intimamedia complex of 3.9 mm was found. A slight wall thickening was also found at the left carotid bulb. There was no increased blood-flow velocity at the stenoses. The subclavian, axillary and vertebral arteries were normal.
Angiography was performed after sonography to evaluate the distribution of the disease. As the arterial wall thickening was limited mainly to the carotid bulb, no stenosis could be demonstrated by angiography, but the carotid bifurcations were rather narrow. No involvement of the aorta and its primary branches was found by either sonography or angiography. Thus, the patient was classified as having prestenotic stage Takayasu arteritis with type I involvement of the vascular system.
Echocardiography demonstrated hypertrophy of the interventricular septum, with a diameter of 16 mm. Otherwise, colour Doppler echocardiography was normal.
ECG, radiography of the chest, hands, feet and knees and sonography of the abdomen and the thyroid, submandibular and parotid glands were normal.
Treatment was the same as for patient 2. Myalgia, weakness, morning stiffness and the laboratory features of inflammation disappeared quickly with therapy. The wall thickening of the right common carotid artery increased after 8 weeks to a maximum of 4.5 mm and 55% stenosis, with a slight increase in blood-flow velocities (systolic flow 150 mm/s, diastolic flow 50 mm/s). No murmurs could be heard by auscultation. After 5 months of treatment, the grade of stenosis improved. It was 40% at the right common carotid artery, with a maximum diameter of the intimamedia complex of 3.5 mm, and 30% at the left common carotid artery, with a maximum diameter of the intimamedia complex of 3.2 mm.
Patients with diagnosis of Takayasu arteritis at the stenotic/occlusive phase
These nine females are described in more detail in Table 1. In all patients, sonography demonstrated a characteristic homogeneous wall thickening of either the carotid or the subclavian arteries. In one patient (patient 6), angiography demonstrated involvement of only the descending aorta and the coeliac, and femoral arteries, but sonography also showed a small, 12-mm-long wall thickening with a maximum diameter of 3.5 mm of the right subclavian artery without a haemodynamically relevant stenosis. Renal artery stenosis could be demonstrated in one of the two cases by sonography. Coeliac artery stenosis was seen in all three cases by sonography. Sonography failed to show the characteristic wall thickening in the renal and coeliac arteries. On the other hand, smooth, homogeneous wall thickening could be demonstrated at all other involved arteries.
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Discussion |
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Takayasu arteritis is not usually diagnosed before stenoses or occlusions are present. In a study of 32 US American patients, multiple vascular bruits were found in 94% and absent pulses in 50% of the patients [6].
Sonography and angiography are complementary methods in the diagnosis of Takayasu arteritis. Angiography shows changes in the lumen in many arteries, whereas sonography shows changes mainly of the arterial wall in a small number of important arteries. Sonography is superior to angiography in the detection of smaller carotid lesions. Inflammatory wall thickening of the carotid arteries could be documented in 19 of 23 patients by sonography, whereas angiography detected pathologies in only 13 of these patients [3]. In another study, sonography found pathological wall thickening in 28 of 44 carotid arteries of 22 patients with Takayasu arteritis. Angiography detected a stenosis in only 21 of these 44 arteries [7]. In six instances, sonography detected marginal but definite blood flow in severe stenoses that angiography had failed to reveal [7].
Sonography of the carotid and subclavian arteries can be used to detect early Takayasu arteritis, but also to monitor disease progression and the effects of therapy. It is a quick, non-invasive technique without any radiation. The characteristic wall thickening of the carotid arteries and of the arteries of the limbs can even be evaluated by grey-scale ultrasonography [3], whereas colour Doppler and duplex sonography are superior for other vessels and for the evaluation of flow characteristics.
In all our patients, the carotid or subclavian arteries were involved. Angiography showed involvement of these arteries in eight of nine patients with late disease. The pattern of arterial involvement in Takayasu arteritis depends on ethnological factors. The aortic arch and its branches are involved more frequently in Caucasian patients [1, 6, 8, 9] and in patients from east Asian countries [1012] and Mexico [13, 14] than in patients from India [15], Bangladesh [16] and Kuwait [17], who more often have exclusive involvement of the descending aorta and its branches.
In a recently published study from Belgium, sonography of the common carotid, subclavian and common femoral arteries demonstrated typical changes in 42 of 43 patients [9]. In another study, pathological findings were also demonstrated by transcranial Doppler sonography [13].
MRI has also been used as a non-invasive method of describing pathological changes in the large arteries, including the vessel walls, in Takayasu arteritis [18]. Contrast enhancement of the thickened aortic wall in Takayasu arteritis correlated with the CRP level and the ESR in most patients [19].
One case with early Takayasu arteritis detected by abdominal computed tomography has been described. This patient had an inflammatory wall thickening of the superior mesenteric artery. Sonography confirmed this finding. Additionally, inflammatory wall thickening of both common carotid arteries was found in this patient [20]. In a 16-yr-old girl with fever of unknown origin, an aortic aneurysm was detected by ultrasonography, which helped to establish the diagnosis of Takayasu arteritis [21].
Two primary large-vessel vasculitides are distinguished: Takayasu arteritis and temporal arteritis. In our three patients with early Takayasu arteritis, the diagnosis of temporal arteritis was highly improbable. According to Michel et al. [22], the age barrier of 4050 yr between the two entities is almost absolute. Our patients had no other important discriminatory variables, such as tender scalp or shoulder stiffness. Involvement of the common carotid arteries is very rare in temporal arteritis. Colour Doppler sonography of the temporal arteries was normal in all three patients.
In acute temporal arteritis, colour Doppler sonography of the temporal arteries reveals a characteristic dark (hypoechoic) swelling of the wall which is due to oedema [23]. Additionally, inflammatory stenoses and occlusions can be demonstrated by ultrasound. The sensitivity and specificity of sonography are similar to those of histology of the temporal arteries [24]. In 7% of patients with polymyalgia rheumatica and no clinical signs of temporal arteritis, sonography aided in establishing the diagnosis of concomitant giant cell arteritis [25]. About 6% of patients with temporal arteritis had symptomatic large-vessel involvement [26]. This subset has been described as large-vessel giant cell arteritis [27]. In most of these patients inflammation is localized to the axillary and brachial arteries. The ultrasound image in large-vessel giant cell arteritis is comparable to that of the temporal arteries in classic temporal arteritis with dark (hypoechoic) wall thickening [28]. We have also described a patient with both Wegener's granulomatosis and vasculitis and perivasculitis of the left internal carotid artery. This coincidence is extremely rare [29]. The ultrasound image of the wall thickening in this patient and in the patients with Takayasu arteritis is brighter than that of those with temporal arteritis and large-vessel giant cell arteritis. Thus, sonography is an additional diagnostic tool to differentiate between temporal arteritis and Takayasu arteritis. The reason for the different appearance of the artery wall remains unclear. We think that it is due to the fact that temporal arteritis is a much more acute disease than Takayasu arteritis. Thus, we conclude that in giant cell arteritis there is more mural oedema, which results in the darker image.
In rheumatology, sonography is an evolving technique, particularly for musculoskeletal indications. It provides information additional to that provided by the patient's clinical status and helps in the evaluation of the progression of the disease [30, 31], but in most cases it is not possible to establish a definite diagnosis with this imaging method. The situation is different with respect to the large-vessel vasculitides, such as Takayasu arteritis and temporal arteritis. In these diseases, characteristic findings can be detected by sonography. For Takayasu arteritis, this non-invasive, repeatable, fast method helps in the establishment of early disease in the prestenotic stage, even before angiography. In young females with unclear symptoms and laboratory findings of generalized inflammation, the primary extracranial branches of the aortic arch should be investigated by sonography to detect early Takayasu arteritis.
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Notes |
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References |
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