Takayasu arteritis in a Brazilian multicenter study: children with a longer diagnosis delay than adolescents.

OBJECTIVES: To evaluate and compare demographic, clinical, laboratory and angiographic data of Brazilian children and adolescents with Takayasu's arteritis. METHODS: In this Brazilian multicentre, retrospective study which included 10 paediatric rheumatology centres, we identified 71 children and adolescents with Takayasu's arteritis which were diagnosed before their 19th birthday. The patients' demographic, clinical, laboratorial and angiographic data were recorded. The participants were divided into two groups: children, defined by the WHO as younger than 10 years old (group 1: 36 patients) and adolescents, defined as individuals aged 10 to 19 years old (group 2: 35 patients). Features of both groups concerning disease manifestations were compared. RESULTS: A total of 21 (58.3%) patients in group 1 and 30 (85.7%) patients in group 2 were girls (p=0.01). The mean age at disease onset, the mean time to diagnosis, and the mean follow-up time were 5.7 and 12.7, 1.8 and 0.7, 7.2 and 3.6 years, respectively, in groups 1 and 2 (p<0.001, 0.001 and <0.001). At initial evaluation, constitutional symptoms (77.5%) were the most predominant symptoms and decreased peripheral pulses (85.9%) was the most predominant clinical sign without differences between groups. The main laboratory findings were increased erythrocyte sedimentation rate followed by leukocytosis. Anaemia, thrombocytosis and higher platelet levels were significantly more frequent in group 1 (p=0.031, 0.001 and 0.018). Angiographic data were similar in both groups. CONCLUSIONS: Children presented more laboratory abnormalities but clinical and angiographic characteristics were similar to those presented by the adolescents. Diagnosis delay is longer in younger patients.

Hereditary autoinflammatory syndromes: a Brazilian multicenter study.

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.

Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea.

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.

Decreased recent thymus emigrant number in rheumatoid factor-negative polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To determine TCR excision circle (TREC) levels, a marker of recent thymic emigrants, in the peripheral lymphocyte pool of rheumatoid factor-negative (RFØ) polyarticular juvenile idiopathic arthritis (JIA) children. METHODS: We studied TREC levels in peripheral blood mononuclear cells (PBMC) in 30 RFØ polyarticular JIA children with active disease and in 30 age- and gender-matched healthy controls. Signal-joint TREC concentration was determined by real-time quantitative-PCR as the number of TREC copies/microg PBMC DNA gauged by a standard curve with known number of TREC-containing plasmids. RESULTS: TREC levels in PBMC were significantly lower in JIA (4.90 +/- 3.86 x 104 TRECs/microg DNA) as compared to controls (10.45 +/- 8.45 x 104 TRECs/microg DNA, p=0.001). There was an inverse correlation between age and TREC levels in healthy children (r=-0.438, p=0.016) but not in JIA. No clinical association was observed between TREC levels and disease activity and use of oral steroids and methotrexate. CONCLUSIONS: The finding of decreased PBMC TREC levels in RFØ polyarticular JIA children is consistent with a low proportion of recent thymus emigrants. This may interfere with the equilibrium between populations of polyclonal and naïve T cells versus oligoclonal memory auto-reactive T cells and, therefore, may hinder the maintenance of immune tolerance in this disease.

Inflammatory myopathies in childhood: correlation between nailfold capillaroscopy findings and clinical and laboratory data.

OBJECTIVE: Nailfold capillaroscopy is an important tool for the diagnosis and follow-up of patients with rheumatic diseases, in particular dermatomyositis and scleroderma. A relationship has been observed in adults between improved capillaroscopic findings and reduced disease activity. Our aim was to correlate disease activity (clinical and laboratory data) and nailfold capillaroscopy findings in 18 patients with inflammatory myopathies. METHODS: This prospective study included 13 juvenile dermatomyositis patients (Bohan and Peter criteria) (mean age of 8.8 years) and five patients with overlap syndrome (mean age of 15.7 years). We evaluated disease activity (skin abnormalities and muscle weakness, muscle enzymes and acute phase reactants) and its correlation with nailfold capillaroscopy findings (dilatation of isolated loops, dropout of surrounding vessels and giant capillary loops). We used a microscope with special light and magnification of 10 to 16X. RESULTS: Eighteen patients underwent a total of 26 capillaroscopic examinations, seven of them on two or more occasions (13 were performed during the active disease phase and 13 during remission). Twelve of the 13 examinations performed during the active phase exhibited scleroderma pattern and 8 of the 13 examinations performed during remission were normal. Therefore, in 20 of the 26 examinations clinical and laboratory data and nailfold capillaroscopy findings correlated (p = 0.01). CONCLUSIONS: Nailfold capillaroscopy is a non-invasive examination that offers satisfactory correlation with disease activity and could be a useful tool for the diagnosis and follow-up of inflammatory myopathies.

Prospective nailfold capillaroscopy evaluation of Raynaud's phenomenon in children and adolescents.

OBJECTIVE: To evaluate prospectively the clinical features and nailfold capillaroscopy findings of a cohort of children and adolescents who presented Raynaud's phenomenon (RP) without criteria for autoimmune rheumatic diseases. METHODS: 40 children and adolescents with isolated RP were included. Evidence of systemic autoimmune rheumatic diseases (SARD) was ruled out by thorough clinical and laboratory examination. Concomitantly we also performed wide-field nailfold capillaroscopy evaluation using an optical microscope with magnifications of 10 and 16X. All patients were prospectively re-evaluated within a mean interval time between evaluations of 1.6 years. RESULTS: Thirty (75%) out of 40 patients were female with a mean age of 14.6 years and mean follow-up time of 4.2 years. The mean age of disease onset was 10.4 years and the mean time until diagnosis was 1.4 years. Fourteen out of 40 patients (35%) presented antinuclear antibodies (ANA). Five (12.5%) patients had altered nailfold capillaroscopy at first examination: four presented non-specific microangiopathy and one presented scleroderma pattern. At the re-evaluation three patients (7.5%) presented nailfold capillaroscopy alterations (two SD pattern and one non-specific microangiopathy). The two patients who showed scleroderma pattern at the nailfold capillaroscopy presented along the follow-up a diagnosis of mixed connective tissue disease and hypothyroidism, respectively. One 10 year-old girl with normal nailfold capillaroscopy and presence of autoantibodies (ANA 1/640, nuclear homogeneous pattern, anti-native DNA 1/80) was diagnosed with systemic lupus erythematosus after 1 year of initial evaluation. None of the other children presented diagnosis of SARD along the follow-up. CONCLUSIONS: Primary Raynaud´s phenomenon remained the diagnosis in most cases in this series of children and adolescents presenting with initial RP complaint. Nailfold capillaroscopy and determination of autoantibodies were useful ancillary tools in the investigation of possible evolution towards SARD.

[Nailfold capillaroscopy in children and adolescents with rheumatic diseases]. / Capilaroscopia periungueal em crianças e adolescentes com doenças reumáticas.

Nailfold capillaroscopy is a simple, noninvasive and inexpensive method which allows a functional and morphological study of the capillary network through direct visualization of the distal row of periungueal capillaries of the fingers. This method has been used as a diagnostic auxiliary in diseases such as scleroderma, dermatomyositis, systemic lupus erythematosus and mixed connective tissue disease. It has also been used to differentiate between active and non active diseases, especially dermatomyositis, and to distinguish between primary and secondary Raynaud's phenomenon. Most reports of nailfold capillaroscopy are qualitative and semi-quantitative. Manuscripts describing quantitative methods (video-capillaroscopy) are scarce, particularly in childhood. The authors did a literature review based on Medline, Lilacs and Pubmed data using the keywords: nailfold capillaroscopy, colagenosis, Raynaud, children and adolescents.

Pregnancy outcome in juvenile systemic lupus erythematosus: a Brazilian multicenter cohort study.

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.

Inflammatory myopathies in childhood: correlation between nailfold capillaroscopy findings and clinical and laboratory data

OBJECTIVE: Nailfold capillaroscopy is an important tool for the diagnosis and follow-up of patients with rheumatic diseases, in particular dermatomyositis and scleroderma. A relationship has been observed in adults between improved capillaroscopic findings and reduced disease activity. Our aim was to correlate disease activity (clinical and laboratory data) and nailfold capillaroscopy findings in 18 patients with inflammatory myopathies. METHODS: This prospective study included 13 juvenile dermatomyositis patients (Bohan and Peter criteria) (mean age of 8.8 years) and five patients with overlap syndrome (mean age of 15.7 years). We evaluated disease activity (skin abnormalities and muscle weakness, muscle enzymes and acute phase reactants) and its correlation with nailfold capillaroscopy findings (dilatation of isolated loops, dropout of surrounding vessels and giant capillary loops). We used a microscope with special light and magnification of 10 to 16X. RESULTS: Eighteen patients underwent a total of 26 capillaroscopic examinations, seven of them on two or more occasions (13 were performed during the active disease phase and 13 during remission). Twelve of the 13 examinations performed during the active phase exhibited scleroderma pattern and 8 of the 13 examinations performed during remission were normal. Therefore, in 20 of the 26 examinations clinical and laboratory data and nailfold capillaroscopy findings correlated (p = 0.01). CONCLUSIONS: Nailfold capillaroscopy is a non-invasive examination that offers satisfactory correlation with disease activity and could be a useful tool for the diagnosis and follow-up of inflammatory myopathies.