RESUMEN
OBJECTIVE: Takayasu Arteritis (TA) is a rare disease that mainly affects large elastic arteries. It is more frequently seen in Asia, the Mediterranean basin, South Africa and Latin America. We have characterized its clinical manifestations and identified the cardiovascular mortality predictors in a cohort of 110 Mexican Mestizo patients. MATERIAL AND METHOD: Retrospective review of 110 charts of TA patients complying with the American College of Rheumatology (ACR) criteria, seen in a single hospital between 1976 and 2003. Demographic, clinical, and radiological characteristics were described. With the use of actuarial table analysis at 2, 5, and 10 years, and Kaplan Meier methods applying t function for probability, plus Cox regression analysis, the following factors were identified as mortality predictors: systemic arterial hypertension, coronary heart disease and aortic valve regurgitation. Informed consent and approval from the institutional Internal Review Board (IRB) were obtained. RESULTS: We observed a slowly progressive widespread obstructive arterial disease with cardiovascular (48%), neuro-ophthalmic (36%), and skin morbidity (13%). Systemic hypertension and heart disease were significant mortality predictors. Twenty-six percent of cases died due to myocardial infarction, chronic renal failure, stroke, or surgical complications. CONCLUSION: TA in Mexican Mestizos shows a clinical pattern similar to the one recognized in the Far East. Management strategies must be directed at reducing the identified mortality risk factors.
Asunto(s)
Indígenas Norteamericanos , Arteritis de Takayasu/etnología , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , México/epidemiología , Pronóstico , Estudios Retrospectivos , Arteritis de Takayasu/mortalidad , Arteritis de Takayasu/fisiopatología , Adulto JovenRESUMEN
OBJECTIVE: To describe the clinical, laboratory, and radiographic manifestations of Takayasu arteritis (TA) in a cohort from the US, evaluate the response to interventions, remission and relapse rates, and disease progression, and compare these observations with those from other cohorts in the US, Japan, India, Italy, and Mexico. METHODS: Seventy-five patients were retrospectively studied using a uniform database that included clinical, laboratory, and imaging data. Vascular imaging studies were performed at least yearly to monitor disease progression. RESULTS: Common manifestations at disease onset included loss or asymmetry of pulses (57%), limb blood pressure discrepancy (53%), and bruits (53%). Eleven percent of patients were asymptomatic prior to disease diagnosis. Initial angiographic studies showed aortic abnormalities in 79% of patients and frequent involvement of the subclavian (65%) and carotid (43%) arteries.Ninety-three percent of longitudinally followed patients attained disease remission of any duration, but only 28% sustained remission of at least 6 months' duration after prednisone was tapered to <10 mg daily. Both angioplasty and vascular surgery were initially successful, but recurrent stenosis occurred in 78% of angioplasty and 36% of bypass/reconstruction procedures. More than two-thirds of patients had difficulty performing routine daily activities and approximately one-fourth of all patients were unable to work. Our cohort was similar to the National Institutes of Health, Italian, Japanese, and Mexican cohorts in terms of the predominance of female subjects and disease manifestations, but differed from the Indian cohort in that the latter group had a higher frequency of male subjects, abdominal aorta and renal artery involvement, and hypertension. CONCLUSION: Although improvement of symptoms in TA usually follows glucocorticoid therapy, relapses usually occur with dosage reduction. Attempts to restore vascular patency are often initially successful, but restenosis occurs frequently. Chronic morbidity and disability occur in most patients with TA in the US.
Asunto(s)
Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Arteritis de Takayasu/patología , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Reestenosis Coronaria/tratamiento farmacológico , Reestenosis Coronaria/etnología , Reestenosis Coronaria/prevención & control , Quimioterapia Combinada , Femenino , Humanos , India/etnología , Italia/etnología , Japón/etnología , Estudios Longitudinales , Masculino , México/etnología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/etnología , Resultado del Tratamiento , Estados Unidos/etnologíaRESUMEN
Takayasu's arteritis (TA) is a primary vasculitis that causes stenosis or occlusion, rarely aneurysm and distal ischemia. This study was undertaken to examine cardiovascular damage using echocardiography and determine the causes of morbid-mortality in Mexican Mestizo patients with TA. Seventy-six patients were studied by transthoracic echocardiography. Left ventricular diameters, parietal thickness, systolic function, and wall motion were analyzed, also, valvular lesions and aorta features were assessed. Thickness of the interventricular septum was 12 mm +/- 3 (8-19), and that of posterior wall was 12 mm +/- 2 (9-18). The average left ventricular diastolic diameter was 47 mm +/- 7 (33-68) and the left ventricular systolic diameter 32 mm +/- 8 (16-64). The left ventricular ejection fraction was of 57 +/- 11%. Left ventricular concentric hypertrophy was found in 28 (50%) of the 56 hypertensive patients. The five-year survival of patients with left ventricular concentric hypertrophy was 80%, compared to 95% in patients without hypertrophy (P = 0.00). Abnormal wall motion was found in 15 patients. Thirty-one patients had aortic regurgitation, 19 had mitral regurgitation, 13 had tricuspid regurgitation, and 10 and pulmonary hypertension. Six patients had aneurysms of ascending aorta and 7 stenosis of descending aorta. Thirteen of 76 patients died (17%), 85% were hypertensive, and 9% also had acute myocardial infarction (AMI). Echocardiography, a noninvasive technique, shows a great utility in detection and follow-up of cardiovascular manifestations in patients with TA. New techniques, more sensitive toward detecting the early stages of left ventricular dysfunction, are promising to limit left ventricular hypertrophy development.
Asunto(s)
Ecocardiografía , Arteritis de Takayasu/diagnóstico por imagen , Arteritis de Takayasu/fisiopatología , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/fisiopatología , Humanos , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , México/epidemiología , Persona de Mediana Edad , Contracción Miocárdica , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Índice de Severidad de la Enfermedad , Volumen Sistólico , Análisis de Supervivencia , Tasa de Supervivencia , Arteritis de Takayasu/etnología , Arteritis de Takayasu/mortalidad , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
OBJECTIVE: The aim of the present work was to study the association between HLA alleles and Takayasu's arteritis in Mexican Mestizo patients. METHODS: The study included 26 Mexican Mestizo patients with Takayasu's arteritis and 99 healthy unrelated individuals. HLA-A, -B and -DR alleles were determined by polymerase chain reaction PCR-SSP RESULTS: Increased gene frequencies were demonstrated for HLA-B15(p=0.009,pC=0.020,OR=3.24,EF=11.9%) and HLA-B52 (p=0.008, pC=0.027, OR=5.16, EF=7.7%), and a decreased frequency for the HLA-A24 allele in patients compared to normal controls (p=0.035, pC=NS, PF=11.1%). When HLA typing was correlated to clinicalfeatures in 24 cases, wefound an increasedfrequencies of HLA-DR14 in patients with systemic arterial hypertension (p=0.005, pC=0.004, OR=24.6, EF=38.3%) and HLA-A2 on patients with pulmonary involvement (p=0.034, pC=0.036, OR=3.67, EF=40.4%) when compared to patients without these clinical manifestations. CONCLUSION: These data confirm HLA-B52 as a relevant susceptibility allele for Takayasu's arteritis and suggest that HLA-B15 could be important as a marker of the disease in Mexican patients. Other class I and/or class II alleles could also be relevant as markers for the clinical features present in these patients.
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Antígenos HLA/genética , Indígenas Norteamericanos/genética , Arteritis de Takayasu/genética , Adolescente , Adulto , Anciano , ADN/análisis , Etnicidad/genética , Femenino , Frecuencia de los Genes , Prueba de Histocompatibilidad , Humanos , Inmunogenética , Masculino , México/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Arteritis de Takayasu/etnología , Arteritis de Takayasu/patologíaRESUMEN
We performed HLA Class I and Class II typing in 16 patients (15 women, one man) with a confirmed diagnosis of Takayasu arteritis. We did not find any of the previously described associations with HLA-B52, and/or HLA-DRB1*1301 alleles. However, in our patients, HLA-DRB1*1602 and HLA-DRB1*1001 were significantly increased. The association of Takayasu arteritis with Amerindian and Asian HLA-DRB1 alleles (DRB1*1602 and DRB1*1001) in the Colombian mestizo patients reported here, and with HLA-B*3906 previously reported in Mexicans, suggest the possibility that some HLA and disease associations are markers for ethnicity of a population carrying a disease gene which is present in an admixed population with the disease.
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Antígenos HLA-DR , Indígenas Sudamericanos/genética , Arteritis de Takayasu/etnología , Arteritis de Takayasu/genética , Adolescente , Adulto , Alelos , Colombia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
Takayasu arteritis (TA) is characterized by a 'pulseless' condition and occurs frequently in young females from Asian and South American countries. It has been associated with Mayor Histocompatibility Complex (MHC) genes in different populations. Recent data indicate direct participation of HLA-B alleles in the susceptibility to the disease. This fact was explored in an associative study with TA to establish if some region in the exon 2, intron 2 or in the exon 3 of HLA-B alleles is common in the alleles associated with TA and at the same time to know if a specific sequence or an epitope, more than an allele, would be responsible for the susceptibility to this vasculitis. We studied HLA-B alleles of 12 Mexican patients with TA using PCR-SSP and sequencing. The analysis by PCR-SSP in 12 patients showed that five of them showed the B*15 allele, three the B*40 allele and two the B*39 allele, the remaining two presented the B*44 allele. Sequence analysis enabled us to define that the B*39 subtypes are B*3908; B*15 subtypes are B*1510, B*1515, B*1522 and B*1531; and the B*40 subtypes are B*4005 and B*4008. An individual with B*51 (B*5107) and another with B*52 (B*5201) alleles were also identified. The sequences of the intron 2 seem be heterogeneous. Analysis at the 63 and 67 positions of HLA-B alleles showed that 9 of them have similarity in some of these positions with the residues detected in the B*5201 and B*3902 alleles associated with TA in Asian populations. The results indicate that there is heterogeneity in the alleles associated with TA in Mexicans but, in spite of that heterogeneity, the alleles associates can be separated into three groups: B*39, B*15 and B*40, whose subtypes are rare and apparently of recent generation in Mexico, probably by recombination events at intron 2 level. The sequences analysis also shows that most of the alleles detected in the Mexican patients share two epitopes described in the susceptibility alleles in Asian populations, suggesting that these epitopes could be responsible for the susceptibility to develop the disease in spite of the allele in which are found.
Asunto(s)
Antígenos HLA-B , Análisis de Secuencia de ADN , Arteritis de Takayasu/genética , Alelos , Epítopos , Predisposición Genética a la Enfermedad , Humanos , México , Reacción en Cadena de la Polimerasa/métodos , Estudios Seroepidemiológicos , Arteritis de Takayasu/etnologíaRESUMEN
Dentro de las vasculitis primarias, las que afectan grandes arterias son raras. Una, la arteritis inespecífica llamada "Takayasu", parece ser común en México. Dada su morbilidad cardiovascular se ha estudiado con predilección en nuestro hospital. Objetivo. Reseña de las condiciones habituales de diagnóstico en 65 casos consecutivos con panaortografía definitiva. Material y métodos. Serie de casos, estudio retrolectivo, descriptivo, observacional. Estadística descriptiva. Resultados. La morbilidad de la enfermedad es cardiovascular y neurooftálmica, solo un cuarto de los casos tiene datos que sugieren inicio sistémico, la enfermedad crónica provoca hipertensión arterial sistémica, isquemia en distintos territorios y obvias deficiencias de pulsos, diferencia en la tensión arterial e insuficiencia cardiorrenal. En el laboratorio son útiles la biometría hemática, la eritrosedimentación, y la determinación de fibrinógeno y PCR. No hay tratamiento definido. Conclusión. Es necesario un índice de sospecha y maniobras diagnósticas específicas para reconocer la Arteritis de Takayasu. Se requiere un estudio multicéntrico para definir la terapéutica médico-quirúrgica en esta arteritis primaria
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Arteritis de Takayasu/fisiopatología , Arteritis de Takayasu/epidemiología , Arteritis de Takayasu/etnología , Glucocorticoides/uso terapéutico , México/epidemiologíaRESUMEN
Takayasu arteritis is characterized by a "pulseless" condition and occurs frequently in young females from Asian and South American countries. This disease has been found to be linked with major histocompatibility complex (MHC) antigens in Japanese individuals. In the present study we compared gene frequencies of class I, class II, and class III MHC genotypes in patients with Takayasu arteritis and ethnically matched healthy controls. Serological typing was confirmed by molecular typing at the DNA level. We found significant increases in the frequencies of human leucocyte antigen (HLA)-DR6 and HLA-B62 in patients compared to the healthy controls (P corrected [C] = 0.0007, relative risk [RR] = 5.08; PC = 0.05, RR = 3.13 respectively). However, since the number of patients was considerably lower than the number of controls this can be considered as a tendency and not a true association. On the other hand, we found a significantly decreased frequency of HLA-DR4 in patients compared to healthy controls (PC = 0.04, RR = 0.34). At the DNA level, all DR6-positive individuals were HLA-DRB1*1301 whereas controls were HLA-DRB1*1301 (4.2%). Takayasu arteritis in Mexicans is probably associated with the HLA-DR6 (DRB1*1301) gene.
Asunto(s)
Antígenos HLA-DR/genética , Antígeno HLA-DR6/genética , Arteritis de Takayasu/genética , Adulto , Estudios de Casos y Controles , Etnicidad/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígenos HLA-B/genética , Antígeno HLA-B15 , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Humanos , México/epidemiología , Arteritis de Takayasu/etnologíaRESUMEN
OBJECTIVES: To review our experience in clinical diagnosis of the non-specific arteritis called Takayasu's arteritis (TA), and to assess its possible relationship with previous mycobacterial infections as judged by delayed hypersensitivity skin test. METHODS: We examined 44 consecutive patients in Mexico City. All of them fulfilled the ACR criteria for the classification of TA and had a characteristic panaortogram in the absence of any other arterial or systemic disease. RESULTS: Forty-three of our patients were Mexican mestizos; only one had a Caucasian appearance. 38 were women, and the age at diagnosis ranged from 15 to 64 years with a mean of 32 and a median of 35. Age at onset of the symptoms was under 30 years in most cases. Five patients had type I disease, and 4 had type II. Most had a diffuse arteritis (type III), and in seven cases involvement of the pulmonary artery (type IV) was recognized. All patients showed abnormal peripheral pulses and blood pressure differences, 35 had systemic arterial hypertension and 7 pulmonary hypertension. A noisy vascular auscultation was very common and cardiac ailments were also found in many cases. Systemic complaints such as fever, weight loss and malaise were present in the active stages of the disease. Arthritis did occur in a single case, arthralgia was frequent and inflammatory nodules involving the shin, perimalleolar area, and the antero-external surface of the distal leg were also common. Polyclonal hypergammaglobulinemia was a frequent finding in active and inactive cases; leukocytosis with neutrophilia, accelerated ESR and high fibrinogen, however, did occur when the disease was active. Eight of our patients had a previous diagnosis of tuberculosis, and 81% developed a delayed skin reactivity to PPD (2U old tuberculin). None had a bacteriologic diagnosis of tuberculosis or mycobacterial disease. CONCLUSION: Non-specific arteritis, or Takayasu's disease, frequently affects young women of colored race in Mexico. Late diagnosis is common and cardiovascular features dominate the clinical picture. Arterial compromise is widespread and may involve the pulmonary artery and its branches. Most cases are inactive and morbidity results from systemic arterial hypertension and heart disease; active cases have systemic complaints and laboratory abnormalities suggestive of ongoing inflammation. The close relationship between Takayasu's arteritis and previous contact with Mycobacterium tuberculosis was again confirmed in our series, although further studies are necessary to clarify this probable relationship.