RESUMO
OBJECTIVE: To evaluate the prevalence of genetic defects in clinically suspected autoinflammatory syndromes (AIS) in a Brazilian multicenter study. METHODS: The study included 102 patients with a clinical diagnosis of Cryopyrin Associated Periodic Syndromes (CAPS), TNF Receptor Associated Periodic Syndrome (TRAPS), Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD) and Pediatric Granulomatous Arthritis (PGA). One of the five AIS-related genes (NLRP3, TNFRSF1A, MEFV, MVK and NOD2) was evaluated in each patient by direct DNA sequencing, based on the most probable clinical suspect. RESULTS: Clinical diagnoses of the 102 patients were: CAPS (n = 28), TRAPS (n = 31), FMF (n = 17), MKD (n = 17) and PGA (n = 9). Of them, 27/102 (26 %) had a confirmed genetic diagnosis: 6/28 (21 %) CAPS patients, 7/31 (23 %) TRAPS, 3/17 (18 %) FMF, 3/17 (18 %) MKD and 8/9 (89 %) PGA. CONCLUSION: We have found that approximately one third of the Brazilian patients with a clinical suspicion of AIS have a confirmed genetic diagnosis.
Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Brasil , Proteínas de Transporte/genética , Proteínas do Citoesqueleto/genética , Feminino , Humanos , Masculino , Mutação , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína Adaptadora de Sinalização NOD2/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Pirina , Receptores Tipo I de Fatores de Necrose Tumoral/genéticaRESUMO
To identify the underlying mechanism of amenorrhea in juvenile systemic lupus erythematosus (JSLE) patients, thirty-five (11.7%) JSLE patients with current or previous amenorrhea were consecutively selected among the 298 post-menarche patients followed in 12 Brazilian pediatric rheumatology centers. Pituitary gonadotrophins [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] and estradiol were evaluated in 32/35 patients, and prolactin and total testosterone in 29/35 patients. Patient's medical records were carefully reviewed according to demographic, clinical and therapeutic findings. The mean duration of amenorrhea was 7.2 ± 3.6 months. Low FSH or LH was observed in 7/32 (22%) JSLE patients and normal FSH or LH in 25 (78%). Remarkably, low levels of FSH or LH were associated with higher frequency of current amenorrhea (57% vs. 0%, P = 0.001), higher median disease activity (SLEDAI) and damage (SLICC/ACR-DI) (18 vs. 4, P = 0.011; 2 vs. 0, P = 0.037, respectively) and higher median current dose of prednisone (60 vs. 10 mg/day, P = 0.0001) compared to normal FSH or LH JSLE patients. None of them had decreased ovarian reserve and premature ovarian failure. Six of 29 (21%) patients had high levels of prolactin, and none had current amenorrhea. No correlations were observed between levels of prolactin and SLEDAI, and levels of prolactin and SLICC/ACR-DI scores (Spearman's coefficient). We have identified that amenorrhea in JSLE is associated with high dose of corticosteroids indicated for active disease due to hypothalamic-pituitary-ovary axis suppression.
Assuntos
Amenorreia/sangue , Hormônios/sangue , Lúpus Eritematoso Sistêmico/sangue , Adolescente , Amenorreia/diagnóstico , Criança , Pré-Escolar , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Hormônio Luteinizante/sangue , Menarca , Prednisona/uso terapêutico , Estudos Retrospectivos , Testosterona/sangue , Adulto JovemRESUMO
OBJECTIVE: To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients' medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. RESULTS: A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria > or = 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. CONCLUSION: We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Complicações na Gravidez , Resultado da Gravidez , Adolescente , Adulto , Antirreumáticos/efeitos adversos , Criança , Estudos de Coortes , Ciclofosfamida/efeitos adversos , Feminino , Morte Fetal , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Gravidez , Gravidez não Planejada , Índice de Gravidade de DoençaRESUMO
El término leucemia mieloide aguda describe un grupo heterogéneo de desórdenes clonales de células progenitoras hematopoyéticas, con un espectro de características morfológicas, inmunofenotípicas, citogenéticas y moleculares, y un comportamiento clínico similar. La clasificación de la OMS para neoplasias hematológicas define las características morfológicas, teniendo en cuenta, de manera simultánea, las características inmunofenotípicas, citogenéticas y de biología molecular, para establecer el linaje de las células y el estado de maduración. Las anormalidades genéticas son los parámetros más importantes para el tratamiento y el pronóstico del paciente.
Assuntos
Leucemia Mieloide , Biologia Molecular , ImunofenotipagemRESUMO
Introducción: La leucemia neutrofílica crónica es un desorden mieloproliferativo poco frecuente (sólo se han descrito 143 casos)que se caracteriza por esplenomegalia, leve leucocitosis, marcada neutrofilia sin basofilia, cromosoma Filadelfia BCR/ABL negativos y anormalidades cromosómicas hasta en el 10 porciento de los casos; en el caso clínico descrito se encontró tetrasomía 8. El diagnóstico diferencial de la leucemia neutrofílica crónica es difícil e incluye la reacción leucemiode, la leucemia mieloide crónica y la policitemia vera. Descripción del caso: apaciente de 73 años con síntomas clínicos y hallazgos hematopatológicos de leucemia neutrofílica crónica, con tetrasomía 8 en el estudio citogenético. Discusión: de junio de 1977 a junio de 2003, en el Instituto Nacional de Cancerología se diagnosticaron 318 casos de leucemia mieloide crónica. entre los pacientes afectados se encontró uno que cumplió con todos los criterios clínicos, genéticos y patológicos para ser clasificado como víctima de una leucemia neutrofílica crónica. Este es nuestro primer caso de leucemia neutrofílica crónica que se presenta la anormalidad cromosómica tetrasomía 8