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Jornal Vascular Brasileiro

versão impressa ISSN 1677-5449versão On-line ISSN 1677-7301

J. vasc. bras. vol.8 no.1 Porto Alegre jan./mar. 2009  Epub 20-Mar-2009

http://dx.doi.org/10.1590/S1677-54492009005000008 

REVIEW ARTICLE

 

Macrovascular involvement and systemic sclerosis

 

 

Emmanuelle Tenório Albuquerque Madruga GodoiI; Alexandre Domingues BarbosaII; Juannicelle Tenório Albuquerque Madruga GodoiIII; Mariana Atanásio Morais RamosIII; Jocelene Tenório Albuquerque Madruga GodoiIV; Silvio Romero de Barros MarquesV;Ângela Luzia Branco Pinto DuarteVI

I MSc., Internal Medicine, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil. Specialist, Angiology, SBACV
IIStudent, Specialization in Rheumatology, UFPE, Recife, PE, Brazil
IIIMedical student, UFPE, Recife, PE, Brazil
IVProfessor. Associate physician. Head, Department of Clinical Medicine, UFPE, Recife, PE, Brazil
VProfessor, Vascular Surgery Service, Hospital de Clínicas, UFPE, Recife, PE, Brazil
VIProfessor. Head, Rheumatology Service, Hospital de Clínicas, UFPE, Recife, PE, Brazil

Correspondence

 

 


ABSTRACT

The objectives of this article are to review aspects described in the literature on macrovasculature involvement in systemic sclerosis and to assess occurrence and distribution of macrovascular alterations in patients with systemic sclerosis using Doppler ultrasound and ankle-brachial index. In addition, the article evaluates the association of these findings with demographic characteristics, clinical form, clinical course of the disease, Raynaud’s phenomenon, digital changes, limb ulcers, reabsorption of phalanges, amputation, and risk factors and antecedents of atheromatous disease. A prospective, case series study of 20 patients was performed. The sample was comprised of 19 women, with a mean age of 46.30 years. All patients had objective Raynaud’s phenomenon, 85% were diffuse, 55% had digital pulp changes, 15% current limb ulcer, 25% reabsorption of phalange, no amputations, and 70% presented one to four risk factors. Studies were performed by color Doppler ultrasound of the aortic and carotid arteries and lower and upper limb arteries to assess thickening of the intima-media complex, presence of plaques and aneurysms. Ankle-brachial index was also performed in lower limb arteries. Ankle-brachial index was normal in all patients, but 12 (60%) had macrovascular disease assessed by Doppler ultrasound, nine (45%) of these in the aorta, six (30%) in the carotid arteries, one (5%) in the upper limb arteries, and seven (35%) in lower limb arteries. There was an association between macrovascular disease and digital pulp changes (p = 0.0045). Macrovascular disease was identified in 60% of the patients by Doppler ultrasound, but not by ankle-brachial index, which was normal in all patients. There was a significant association between macrovascular disease and current digital pulp changes, which did not occur with the other variables.

Keywords: Systemic sclerosis, Doppler effect, atherosclerosis.


 

 

Introduction

Systemic sclerosis (SS) is a connective tissue disease, little frequent and of unknown etiology. It preferentially affects women, at a 3:1 ratio, between 35-60 years, and is not frequent in children and men younger than 30 years.1,2 In Brazil, the data on incidence and prevalence under investigation by the Group of Systemic Sclerosis of Pronuclear Project (GEPRO), implemented in 2003, are not available yet.3

SS affects multiple organs, including skin, cardiovascular system, lungs, gastrointestinal tract and kidneys, whose histopathological exam has shown edema of the endothelial cells and/or intimal hyperplasia of the microvasculature. Raynaud's phenomenon (RP) and digital ulcers are common examples of this type of impairment. Both structural and functional changes contribute to vasculopathy in SS.4-6

SS is divided into two groups: diffuse and limited form; the former is more severe (with visceral and vascular manifestations) and the limited form is less complex.7,8

Vascular changes are more evident in the limited form (severe RP, telangiectasias and a primary type of pulmonary hypertension in late disease). Anti-centromere antibody is a known risk factor for digital ischemia and it mainly occurs in the long-term limited form.9,10

Although the microvascular disease is one of the SS markers, there may be impairment of macrocirculation. Such impairment has not been widely recognized, although some authors, in descriptive studies, suggest a more than casual association.11-13 This article aimed at reviewing the aspects present in the literature about impairment of macrovasculature and description of occurrence and distribution of macrovascular changes in patients with SS at Hospital das Clínicas (HC), Universidade Federal de Pernambuco (UFPE) using Doppler ultrasonography and ankle-brachial index (ABI).

 

Microvascular disease in SS

Vascular dysfunction is an essential element in SS,14,15 and an active vascular system, with prevalence of vasoconstriction, is frequently associated with a significant morbidity in disease course.16

Perivascular inflammatory infiltrates and endothelial apoptosis with reduced angiogenesis have been observed in early stages of SS; however, terminal stages are characterized by excessive accumulation of protein in the extracellular matrix of the skin and internal organs. Surprisingly, despite insufficient angiogenesis, a vascular endothelial growth factor, which serves to protect against digital ulcers, is increased, but its prolonged expression can have a paradoxical effect, determining formation of irregular vessels similar to those seen in SS.17,18

RP is considered as the most frequent and early manifestation of SS, and may occur in up to 95% of patients.19 It is characterized by reversible episodes of vasospasm in the limbs, associated with change in typical color in hands and/or feet, usually after contact with cold or emotional stress. In its primary form, such event is benign and with no tissue damage.20

In RP secondary to SS, characteristic vascular changes are added to arterial vasospasm, which can cause irreversible tissue damage, such as reabsorption of pulp and distal phalange, limb scars and gangrene. Such vascular lesions are mainly characterized by myointimal proliferation, by exuberant activity of fibroblast and endothelial dysfunction, present in small arteries and microcirculation, in the early stages of the disease.21,22

Peripheral microangiopathy in SS is well documented by capillaroscopy, which is an established method to evaluate the morphological component in RP. A known pattern, called scleroderma, is observed in 83-97% of patients23 and is characterized by presence of dilatation (ectasia) and capillary distortion associated with areas of complete devascularization, in addition to diffuse reduction in number of loops.22 Such pattern is not exclusive of SS; it may also be found in patients with dermatomyositis and mixed disease of the connective tissue. Laser Doppler has been used as a new technique to quantify flow in the microcirculation of patients with SS.24

Traditionally, vascular involvement in SS has predominantly been microvascular, associated with unbalance between vasoconstriction and vasodilatation, the former being predominant.15 Although RP is the most frequent vascular manifestation, recent studies have also shown increasing macrovascular impairment in sclerodermic patients.4,5,25,26 Detection of vascular involvement is a crucial element in SS, as it is frequently associated with significant morbidity and mortality in disease course.27,28

An important reduction in arterial compliance of sclerodermic patients is related to vessel elasticity, and it can be a consequence of changes in the connective tissue and reflect increased cardiovascular risk.19,29

 

Macrovascular disease

Atherosclerosis, which is the main cause of macrovascular disease (MVD), has been associated with SS. Its early identification influences reduction in morbidity and mortality rates in such patients.26

It is a systemic disease characterized by formation of cholesterol plaques at the intimal layer level. All arteries can be affected, but the clinical consequences are more important in the impairment of coronary, carotid and lower limb arteries. Chronic obstructive arterial disease, along with heart failure and ischemic stroke, is one of the three clinical manifestations of the same physiopathologic process: atherothrombosis.30

Peripheral arterial disease (PAD), of an atheromatous origin, is more frequent in the lower limbs and in men aged between 50-70 years, although it has been diagnosed in younger individuals. Its prevalence varies according to diagnostic method and population under investigation.31

Intermittent claudication (IC) of the lower limbs is the characteristic clinical manifestation of PAD and a consequence of tissue ischemic process. Claudication occurs when the metabolic need of the tissue is higher than that received by blood transport.32,33 Pain at rest occurs when blood inflow is not sufficient to maintain basal metabolism. The collateral network, which reduces symptoms, is developed with walking exercises.32 Studies have shown a more prevalent IC in patients with SS than in the general population.26,34 In PAD classification, proposed by Fontaine in 1954, IC corresponds to stage II.32,35

Risk factors for atheromatous PAD are the same of atherosclerosis, especially smoking, hypertension, diabetes mellitus (DM) and dyslipidemia.30,36

 

Atherosclerosis and SS

Change in macrovasculature associated with dyslipidemia has been described in collagen diseases. In systemic erythematosus lupus (SEL), presence of self-antibodies against lipoprotein lipase (anti-LPL), an enzyme that hydrolyses triglycerides, determines increase in serum levels and early atherosclerosis. Presence of anti-LPL IgG in patients with SS is associated with high levels of triglycerides, more extensive cutaneous fibrosis, pulmonary fibrosis, cardiac involvement and anti-topoisomerase I.37

Lippi et al.,38 in preliminary studies on the lipid profile of patients with SS, showed that lipoprotein-a (Lpa) can act in synergism with other prothrombotic conditions known in the pathogenesis of varied vascular changes. Such changes predispose to development of thrombotic complications, stressing the importance of identification and occasional treatment of this subgroup of patients.

 

Diagnostic methods of MVD

A proper anamnesis can be responsible for PAD diagnosis in 90% of cases, so questionnaires such as Edinburgh's and that of the World Health Organization (WHO) have a high positive predictive value.36,39,40

ABI is a simple, non-invasive method that has high predictive value for PAD and is significantly associated with risk of cardiovascular mortality. Such index can also be used as a good PAD indicator in patients with SS.10,26,41 The highest systolic pressure of each ankle is divided by the highest brachial systolic pressure.42 Thus, ABI is equal to the highest systolic pressure in the ankle divided by the highest brachial systolic pressure.

ABI normal value ranges between 0.9 and 1.3, which is associated with clinical status of lower limb arteriopathy (LLA)35 (Table 1). ABI reduction indicates impairment of lower limb arteries, and values equal or lower than 0.9 are associated with a significant increase in cardiovascular risk, especially myocardial infarction and stroke, regardless of other risk factors.41

 

 

The treadmill test consists of walking on an electric treadmill and can be performed by most patients suffering from arteriopathy. The walking perimeter at claudication onset and the maximal perimeter where the patient stops walking due to pain are recorded. ABI is measured before and immediately after the patient stops walking. In a normal individual, ABI increases with effort, but is reduced in a patient with PAD. Such reduction is directly proportional to the degree of arterial lesion and inversely related to degree of compensation by the collateral network.35,36,43

Doppler ultrasonography is a non-invasive, high-resolution method that enables detailed assessment of the macrovasculature and combines three components: B mode, pulsed Doppler and color.

B mode (Figure 1A) provides real-time two-dimensional images. It is used for anatomical assessment of the vessel, enabling to locate it in soft tissues, measure its diameter and visualize irregularities (plaques or thrombi) in its lumen. Pulsed Doppler (Figure 1B) allows for assessment of flow velocity. It can quantify velocity and evaluate flow pattern, which ranges according to type of artery, either high or low resistance. Color mode (Figure 1C) enables velocity data to be determined as a map, with codified colors overlapping the B mode ultrasound image. Image color is based on flow direction.44-46

 



 

Thickening of the intimal-medial complex is a non-invasive and early marker of arterial wall change, easily measured in the carotid artery, using B-mode ultrasound. Its use in research has been growing, and measurement can be performed in two ways: manual measurement in multiple sites of the extracranial carotid artery, in anterior and/or posterior walls, and measured by an automatic acquisition program in the posterior wall of the distal segment of the common carotid artery. Thickening can reflect an increased overall cardiovascular risk. Epidemiologic evaluation of data indicates that increased intimal-medial complex (larger than 1 mm) is accepted as thickening and can be a major risk of myocardial infarction and/or cerebrovascular disease.46-48

Conventional and digital arteriography is an invasive method, considered as the gold standard for the diagnosis of MVD, as it enables construction of a detailed and reliable arterial map. Because there are less invasive diagnostic methods, its preferential use is for the treatment of arterial lesions.49

Magnetic angiographic resonance (MAR) enhances blood flow, as it suppresses the signs generated by static tissues and increases signals of circulating blood. After obtaining many independent images, there is a sum or recombination of data to obtain conventional angiographic image. MAR has the following advantages: not invasive, does not involve exposure to ionizing radiation and can be performed without use of contrast mean - although it uses gadolinium, which is an intravenous contrast mean with minimal side effects, for a better definition and shorter examination time.50

Helical (or spiral) CT increased indications of CT in vessel assessment. This technique was enhanced with the development of multi-slice CT, which is a noninvasive method of great value for investigation of vascular diseases. Its disadvantages are use of iodinated intravenous contrast mean and use of ionizing radiation; the dosage commonly used is higher than helical CT. Presence of multiple detectors, ranging between 6 and 64, enables a high temporal and spatial resolution, a wide study in a few seconds and a screening from the aorta to the most distal arteries.51

 

MVD and SS

SS is characterized by complex fibrotic lesion of the connective tissue and changes in vascular bed, including proliferation of the intimal layer and fibrous thickening of the medial layer. Some possible mechanisms are responsible for ischemia, including vasospasm, endothelial damage and abnormalities of homeostasis. Extension of vascular involvement has been better defined, not only at the level of internal organs, but also in the periphery.16,52

In SS the characteristic pattern of microvasculature includes endothelial dysfunction and coagulation disorders. Similar changes have also been observed in patients with MVD secondary to atherosclerosis. Such pathogenic findings can suggest association between atherosclerosis and SS.26

MVD in SS has been described in case reports and post-mortem retrospective studies, reflecting the lack of identification of such pattern and the lack of knowledge of its prevalence.34 Changes in macrovasculature associated with dyslipidemia have been described lately.37,38

Youssef et al.53 studied patients with severe MVD of the upper limbs and minimal cardiovascular risk factors. An important luminal narrowing due to cellular material was identified in a sample of a patient's impaired ulnar artery, with no evidence of atheroma.

In a study of 53 sclerodermic patients, Veale et al.34 used the IC questionnaire developed by the WHO to determine prevalence of symptomatic MVD in SS. IC was found in 10 (21.7%) patients: two in the diffuse form and eight in CREST. In a comparison of the population of such study with the population studied in Edinburgh, where IC was 4.6%, Veale et al.34 observed a higher prevalence of IC in the population with IC. The following risk factors were identified: hypertension in four patients, smoking in seven and hypercholesterolemia in two; none of them were diabetic or were using corticosteroid. Also in that study, 70% of claudicating sclerodermic patients had symptomatic ischemic heart disease, with angina or current or past acute infarction, when compared with 19.4% of patients without IC.

In a retrospective cohort study during 1974-90, Youssef et al.4 evaluated prevalence of MVD in the upper limbs of women with SS, with minimal duration of 5 years, compared with a control group that had no SS. PAD occurred in 18 (58%) patients and in only three (9.6%) controls (relative risk = 6.0) and was associated with severe morbidity. Histological examination of patients with PAD suggested discrete intimal thickening in the ulnar artery.

Stafford et al.,25 in a retrospective cohort study of 20 sclerodermic patients and 20 controls, analyzed the Doppler results of lower limbs, neck arteries and abdomen, correlating them with risk factors for atherosclerosis (hypertension, hyperdyslipidemia, smoking and DM). IC was more frequent in sclerodermic patients. Ulnar artery disease occurred in 10/19 (53%) patients and was bilateral in 6/10 (60%). Absence of association between SS and arterial disease of the lower limbs was another finding of that study. The authors stressed that ulnar arterial disease has important consequences in reversibility or irreversibility of digital ischemia.

Ho et al.,26 in a case control study of 54 sclerodermic patients and 43 controls, evaluated prevalence of MVD. All patients were submitted to a conventional screening for risk factors of atherosclerosis. Carotid Doppler and ABI were used to identify MVD. There was no significant difference in relation to risk factors between groups. About 64% of patients that had carotid disease, compared with 35% of the control group (p = 0.007). Nine (17%) patients had ABI lower than 0.9, compared with no patients in the control group (p = 0.003). There were no correlations between macrovascular impairment and duration of disease or SS clinical form.26

Using angiography of 29 patients, 14 with acrosclerosis and 15 with proximal ascending sclerosis, Stucker et al.54 found stenosis of lower limb arteries in 27/29 (93%). Frequency of arterial occlusion reduced from 90% of digital arteries to 31% of ulnar artery and there was no impairment of the radial artery. RP intensity was not correlated with angiographic findings; however, these were correlated with extension of cutaneous sclerosis and with serological findings.

Wan et al.10 retrospectively evaluated ABI measurement in 119 sclerodermic patients, 91 with the limited form and 28 with the diffuse form. ABI was measured as usual, and the normal reference value was 1.0. ABI was lower than 1.0 in 14 patients (12%), 11 with the limited form and three with the diffuse form.

From 1992 to 2000, Dick et al.55 evaluated 26 of 1,400 patients with SS submitted to arteriography or angioplasty due to critical limb ischemia, taking into account age, gender and cardiovascular risk factors (smoking, hypertension, DM and hypercholesterolemia). Upper limb angiography showed isolated distal disease in 86% of patients with or without cardiovascular risk factors, such as smoking. In the lower limbs, there was a highly significant association between risk factors and MVD, and inversely proportional between absence of such factors and distal disease (below the knee). The authors concluded that indication of upper limb angiography is not dependent on risk factor, while their presence is required for the lower limbs.

In a retrospective study of 15 sclerodermic patients with intense RP characterized by refractory digital ulcers, positive Allen's test and occlusive ulnar arterial disease using angiography, Taylor et al.5 found occlusion in all patients, which was bilateral in nine. Eight patients were submitted to revascularization, and histological examination of the ulnar artery sample showed fibrosis of the intimal layer, lumen narrowing, slight hypertrophy of the muscle layer and normal adventitia, consistent with the histological findings of microvascular disease, suggesting that vasculopathy is not atherosclerotic.

Cheng et al.19 performed a study on the biomechanical properties (elastic and muscular) and thickening of the intimal-medial complex of the carotid and femoral arteries of 19 patients with diffuse SS, 33 with limited SS and 21 controls. They observed progressive and significant reduction (p < 0.001) in the elastic property of the carotid artery of sclerodermic patients with the limited form in relation to the control group.

In a case control study of 45 sclerodermic patients evaluated by ultrasound for thickening of the intimal-medial complex of the carotid arteries and identification of risk factors (hypertension, obesity, DM, smoking, dyslipidemia), Beyne-Rauzy et al.56 did not find any significant difference regarding such factors. In the same group of patients, Leger et al.57 found arterial abnormalities in 23/45 (51.1%) using Doppler ultrasonography; 14/23 (61%) in the upper limbs, 3/23 (13%) in the lower limbs and 6/23 (26%) in both. In both studies, conducted at the same center, carotid disease seems to be less frequent and peripheral MVD of the limbs is more frequent in the sclerodermic group.

In a cross-sectional study of 221 patients with symptomatic arterial disease of the lower limbs (IC in 93%), sociodemographic aspects, risk factors for atherosclerosis, RP, another arterial disease and vascular surgical procedure were evaluated. There was significant difference in patients with RP and heart disease (6/8, 75%) when compared with controls (64/179, 35.8%). Olmedo et al.58 concluded that, in atherosclerotic patients with high morbidity and mortality, presence of RP represents a five-fold increase in heart disease and, surprisingly, SS was more frequent than expected, suggesting a bidirectional relation between SS and atherosclerosis.

Hasegawa et al.59 evaluated the macrovasculature of eight sclerodermic patients with digital ulcers and gangrene using lower and limb arteriography and correlating them with the profile of self-antibodies and cardiovascular risk factors. Macrovascular involvement was detected in 7/8 (87.5%) of sclerodermic patients, and the authors concluded that macrovascular involvement, detected through arteriography, is not rare in patients with SS and digital ulcers or gangrene.

 

Methods

To illustrate this topic, a prospective case study series of 20 patients (19 women), mean age 46.30 years was conducted at HC, UFPE. The study was approved by the human research ethics committee of Centro de Ciências da Saúde of UFPE. Its main goal is to evaluate occurrence and distribution of macrovasculature changes in a population with SS using Doppler ultrasonography and ABI. Association between these findings and demographic characteristics, clinical form, time of disease course, RP, digital changes, limb ulcers, phalange reabsorption and amputation, as well as risk factors and history of atheromatous disease was also evaluated. Diffuse clinical form was present in 85% of patients. All had RP, 55% had changes in digital pulps, 15% had current limb ulcer, 25% had phalange reabsorption, and there was no amputation (Table 2).

 

Results

Risk factors for atherosclerosis - one to four factors - were present in 70% of the population. Aorta, carotid arteries and lower and upper limb arteries were evaluated by Doppler ultrasonography to detect thickening of the intimal-medial complex, presence of plaques and aneurysms (Table 3). In lower limb arteries, ABI was also performed. ABI was normal in all patients; however, 12 (60%) of them had MVD, nine (45%) in the aorta, seven (35%) in lower limb arteries, six (30%) in carotid arteries and one (5%) in upper limb arteries. There was association between MVD and changes in digital pulps (p = 0.0045) (Table 4). Doppler ultrasonography identified MVD in 60% of patients with SS. No patient had normal ABI. There was significant association between MVD and current changes in digital pulps, and there was no association between MVD and risk factors (Table 5).

 

 

 

 

 

 

Discussion

In this study, MVD, which was evaluated by Doppler ultrasonography, was present in 60% of the population, differently from ABI, which was normal in all patients. Youssef et al.4 identified MVD in 58% of patients with SS using the combination of Doppler ultrasonography, arteriography, history of IC and changes in pulses. MVD was identified in only 10% of the control group in this study. Leger et al.,57 using Doppler ultrasonography and ABI, found peripheral arterial abnormalities in 51.1% of sclerodermic patients and 6.7% of patients in the control group.

Ho et al.26 identified changes in the ABI of 17% patients with SS and none in the control group. Wan et al10 talso found ABI changes in 14 (12%) patients; however, the authors defined values lower than 1.0 as normal. Caso tivéssemos utilizado essa mesma referência, 15% dos nossos pacientes teriam o ITB alterado. In case the same reference had been used, 15% of our patients would have altered ABI. A cut-off point lower than 0.9 (95% sensitivity and 100% specificity when compared with arteriography, which is the diagnostic gold standard) was used because it was adopted in most studies.26,35,41

There were no changes in ulnar arteries. Stafford et al.25 showed MVD due to impairment of ulnar arteries in 53% of sclerodermic patients, which was bilateral in 60%. Taylor et al.5 identified ulnar artery occlusion in 15 sclerodermic patients, which was bilateral in nine. Leger et al.57 found MVD in patients with SS, 31% in the upper limbs and 6% in the lower limbs, which are the opposite of the results found in this study. It is worth stressing that involvement of upper limb arteries was very low in this study, differently from the findings of other authors,5.58 who believe such involvement is a marker of MVD in SS. The ulnar arteries were evaluated by ultrasonography and had preserved flows and conserved walls. Segmental findings and digital lesions may not have been identified because arteriographic study was not used.

There was no significant association between MVD and age, gender, ethnicity, disease course and clinical form of SS, in addition to RP and risk factors for atheromatous disease. Wan et al.10 and Ho et al.26 did not find association between MVD and limited and diffuse clinical forms, which had the same prevalence.

In this population, there was no association between MVD and risk factors for atheromatous disease, either grouped or isolated. Stafford et al.25 found association of MVD with smoking and hypertension. Wan et al.10 found an association between smoking and ABI reduction.

In the present study, there was a significant association between MVD and changes in digital pulps, as aspect that has not been described in the reviewed literature. Macrovascular involvement can be added to microvascular changes characteristic of SS, exacerbating existing distal hemodynamic disorders, responsible for changes in digital pulps.

An aspect to be stressed is the fact that PAD is predominantly atheromatous and more prevalent in elderly men. This population was mainly comprised of women aged 30-59 years (except for a 73-year-old female patient) and with no significant association with risk factors for atheromatous disease. Such findings suggest that MVD showed in this study is a consequence of SS.

It is worth stressing that MVD in this population was less clinically significant than in other studies,54,55 as none of our patients was claudicating, had ABI change or significant involvement of arteries, as shown by Doppler ultrasonography.

Macrovascular involvement is responsible for increased morbidity in sclerodermic patients. Association between SS and dyslipidemia has been described and suggests a relation between SS and atherosclerotic disease, although the classical atheromatous lesion is not histologically confirmed. Because MVD symptoms are similar to those of atheromatous disease, knowledge of the latter enables early diagnosis, proper treatment and improvement in quality of life of sclerodermic patients with this type of involvement.

 

Conclusion

MVD was identified in 60% of patients using Doppler ultrasonography, but not by ABI, which was normal in all patients. There was a significant association between MVD and current changes in digital pulps, which did not occur with the other variables.

 

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Correspondence:
Dra. Emmanuelle Tenório A. M. Godoi
Rua Marquês de Tamandaré, 162/1402, Poço da Panela
CEP 52061-170 - Recife, PE, Brazil
Email: godoiemmanuelle@hotmail.com

Manuscript received January 9, 2008, accepted November 12, 2008.

 

 

No conflicts of interest declared concerning the publication of this article.
This work was conducted at the rheumatology Service, Hospital das Clínicas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco (UFPE) and at the Radiology Sector of Hospital Agamenon Magalhães, Recife, PE, Brazil.

 

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