Longitudinal assessment of disease activity and muscle strength in juvenile dermatomyositis: a multicentre registry study.

OBJECTIVES: To define disease activity measures, muscle strength and functional assessments in new-onset juvenile dermatomyositis (JDM) patients, at disease onset and follow up. METHODS: A registry was set up in 18 hospitals, enrolling patients over 3-years (2015-2018). Clinical assessments were performed at baseline, and at 6, 12, 18 and 24 months after diagnosis. Disease Activity Score (DAS20), skin and musculoskeletal DAS sub-scales; Manual Muscle Test (MMT8); Childhood Myositis Assessment Scale (CMAS); Childhood Health Assessment Questionnaire disability index (CHAQ_DI 0-3) and 10 cm Visual Analog Scale (VAS) for overall wellbeing scores were compared by Poisson Model and Wald post-test for repeated measures. RESULTS: Ninety-six cases, being 61 (64%) females, median age 10 years had JDM diagnosis and 12 (13%) onset calcinosis. Mean ±SD scores at diagnosis and 6 months intervals for DAS20 (0-20) were 7.8±5, 6.3 ±4.8, 5±4, 4.9 ±5 and 0.5 ±2.3; with significant difference from baseline (p<0.01). Skin DAS subscales were 2.8±3.3, 1.8±2.9, 1,1±2.2, 0.6±1.8, 0.4±1.5. MMT (0-80) 62.6±20.4, 70.2±13.5, 73.3±11, 75.7±7.9 and 74.8±7.8, with significant difference from baseline up to 6 months (p=0.016); CMAS (0-53) 29.5±11.4, 33.1±8.3, 34.2±5.8, 34±6 and 33.3±5.4. CHAQ-DI (0-3) 1±0.9, 0.6±0.7, 0.8±0.8, 1±0.8 and 1±0.3; parents VAS 4.1±2.5, 2±2.1; 1.3±2.8, 4.1±3.1, 1.7±2.2. There was no significant difference for CMAS, CHAQ-DI and parents VAS from baseline up to 24-month assessment. CONCLUSIONS: DAS20 scores improved gradually during follow up, MMT8 improved significantly during the first 6 months and CMAS, CHAQ-DI and parents VAS scores had no significant improvement with persistent functional impairment over 2-years.

Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients.

OBJECTIVES: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients. METHODS: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots. RESULTS: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively. CONCLUSIONS: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use.

OBJECTIVE: To describe risk factors for IBD development in a cohort of children with JIA. METHODS: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR). RESULTS: Out of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89). CONCLUSION: IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

The new 2019-EULAR/ACR classification criteria specific domains at diagnosis can predict damage accrual in 670 childhood-onset systemic lupus erythematosus patients.

OBJECTIVE: To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). METHODS: This retrospective multicenter study included 670 cSLE patients with ≤5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI ≥ 1). RESULTS: Median disease duration was 2.8 (IQR 1.8-3.8) years and 200 (29.9%) patients had at least one organ damage (SDI ≥ 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI ≥ 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773-24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481-16.399, p<0.0001) at latest visit, respectively. cSLE patients with positive anti-dsDNA at diagnosis were also associated with renal damage by the latest visit (OR 2.438, 95% CI 1.114-5.3381, p = 0.021). Constitutional, hematologic, mucocutaneous, serosal, and musculoskeletal domains and specific criteria as well as other immunologic criteria were not associated with damage accrual. Median of SLEDAI-2K was significantly higher in patients with global damage (19.5 (2-51) vs 14 (0-51), p<0.001). 2019-EULAR/ACR score >25 was associated with more overall (SDI ≥ 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). CONCLUSIONS: The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25.

Impact of chronic gingivitis management on the cytokine and anti-PPAD expressions in juvenile systemic lupus erythematosus: A six-month follow-up.

OBJECTIVE: To evaluate how chronic gingivitis treatment impacts the oral and circulating cytokine expressions after six-month follow-up in patients with juvenile systemic lupus erythematosus (jSLE) and also to evaluate the circulating expression of anti-Porphyromonas gingivalis peptidylarginine deiminase antibodies (anti-PPAD) before and after treatment. BACKGROUND: Juvenile systemic lupus erythematosus patients present a worse periodontal condition associated with higher gingival crevicular fluid (GCF) levels of interleukin (IL)-1ß, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon-γ and monocyte chemoattractant protein (MCP)-1. MATERIALS AND METHODS: Twenty-one adolescents with jSLE (mean age: 16.2 ± 1.5 years) were recruited. Participants were rheumatologically and periodontally examined. All individuals were clinically diagnosed with gingival inflammation. Chronic gingivitis treatment consisted of supragingival scaling, prophylaxis and oral hygiene instructions. The cytokine levels were determined by bead-based multiplex assays and the anti-PPAD levels by ELISA. Gingival crevicular fluid (GCF) and serum samples were collected at baseline and 6 months after treatment. RESULTS: We observed a reduction in attachment loss, SLE Disease Activity Index (SLEDAI), IL-1ß, IL-10 and MCP-1 GCF levels, and the IL-4 and IL-5 serum levels 6 months after periodontal treatment. On the contrary, a significant increase in GCF expression of IL-4, IL-12, IL-17, IFN-γ and serum levels of anti-PPAD antibody was observed. CONCLUSION: Juvenile systemic lupus erythematosus patients seem to positively benefit from periodontal treatment by a significantly reduced CAL, a GCF reduction of pro-inflammatory cytokines and an increasing of anti-inflammatory ones. However, an increase in the GCF expression of IL-17 and the serum expression of anti-PPAD antibody 6 months after periodontal treatment might negatively affect the treatment outcome of such patients in the long term.

Relapsing polychondritis in childhood: three case reports, comparison with adulthood disease and literature review.

Relapsing polychondritis (RP) is a rare autoimmune systemic disease, especially in childhood. To report three new pediatric RP cases, to provide a literature review and to compare with adulthood disease, retrospective data collection from three childhood RP cases was observed in a Brazilian Pediatric Rheumatology Division. A literature review based on a MEDLINE database search was performed. Arthritis and auricular chondritis were present in our three patients. Two cases presented with early and severe laryngotracheal chondritis, besides initial and symptomatic costochondritis. The other case developed prominent epiphyseal plate involvement. Two patients were refractory to corticosteroids and immunosuppressants and required the use of TNF-alpha inhibitors to improve the symptoms, while corticosteroids plus methotrexate induced remission in the other patient. The literature review showed 44 cases of pediatric-onset disease in English language. Arthritis and ear chondritis are the most common initial and cumulative manifestations of RP in children and adults. Nasal and laryngotracheobronchial chondritis are also common manifestations observed during follow-up in childhood. There is also an early severity of respiratory chondritis in childhood, requiring aggressive treatment with corticosteroids, immunosuppressants and biologic agents. The data presented by those 3 children, considered in conjunction with the data from the 44 published cases, may reflect some distinguishing childhood RP features, such as more severe and frequent respiratory tract involvement, symptomatic costochondritis and the atypical pattern of persistent and destructive arthritis with epiphyseal plate involvement. Response to immunosuppressants and biologic agents is anecdotal, but steroids remain the main drug during the flares.

Adherence to methotrexate in juvenile idiopathic arthritis.

Non-adherence to treatments for chronic diseases may jeopardize patients' health, increase costs of care, and cause unnecessary clinic appointments and diagnostic studies, as well as additional treatments with potentially serious side effects. Little is known about adherence to methotrexate in pediatric rheumatology. Because this medication is commonly used in JIA, we assessed adherence among children receiving methotrexate in two countries. A total of 76 outpatients (M:F 21:55) with JIA seen in Rio de Janeiro (Brazil) and in Boston (US) taking methotrexate for >2 months were enrolled. Questionnaires were completed by the parents from both centers. Non-adherence was defined as omission of ≥3 prescribed doses in the previous 8 weeks. Patients' ages ranged from 1 to 17 years. Mean time on methotrexate was 20.5 months (±25). Overall rate of non-adherence was 18%. The rate of reported non-adherence was 8% in Boston and 24% in Rio de Janeiro (P = 0.012). The main reason for non-adherence in Boston was "child refused"; in Rio de Janeiro, the main reason was inability to obtain medication. Age had a negative association with adherence (P < 0.0001). Sex, time on methotrexate, route of administration, or concomitant use of other medications were not associated with adherence. Eighteen percent of children with JIA prescribed methotrexate were non-compliant. The difference in reasons for poor adherence between patients in Rio de Janeiro and Boston suggests that different strategies may be needed to improve adherence in these 2 settings. The rate of non-adherence warrants further investigation.

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.

Automatic Quantification of Interstitial Lung Disease From Chest Computed Tomography in Systemic Sclerosis.

Background: Interstitial lung disease (ILD) is a common complication in patients with systemic sclerosis (SSc), and its diagnosis contributes to early treatment decisions. Purposes: To quantify ILD associated with SSc (SSc-ILD) from chest CT images using an automatic quantification method based on the computation of the weight of interstitial lung opacities. Methods: Ninety-four patients with SSc underwent CT, forced vital capacity (FVC), and carbon monoxide diffusion capacity (DLCO) tests. Seventy-three healthy individuals without radiological evidence of lung disease served as controls. After lung and airway segmentation, the ratio between the weight of interstitial opacities [densities between -500 and +50 Hounsfield units (HU)] and the total lung weight (densities between -1,000 and +50 HU) was used as an ILD indicator (ILD[%] = 100 × [LW(-500 to +50HU)/LW(-1, 000 to +50HU)]). The cutoff of normality between controls and SSc was determined with a receiver operator characteristic curve. The severity of pulmonary involvement in SSc patients was also assessed by calculating Z scores of ILD relative to the average interstitial opacities in controls. Accordingly, SSc-ILD was classified as SSc Limited-ILD (Z score < 3) and SSc Extensive-ILD (Z score ≥ 3 or FVC < 70%). Results: Seventy-eight (83%) SSc patients were classified as presenting SSc-ILD (optimal ILD threshold of 23.4%, 0.83 sensitivity, 0.92 specificity, and 0.94 area under the receiver operator characteristic curve, 95% CI from 0.89 to 0.96, 0.93 positive predictive value, and 0.81 negative predictive value, p < 0.001) and exhibited radiological attenuations compatible with interstitial pneumonia dispersed in the lung parenchyma. Thirty-six (38%) patients were classified as SSc Extensive-ILD (ILD threshold ≥ 29.6% equivalent to a Z score ≥ 3) and 42 (45%) as SSc Limited-ILD. Eighteen (50%) patients with SSc Extensive-ILD presented FVC < 70%, being only five patients classified exclusively based on FVC. SSc Extensive-ILD also presented lower DLCO (57.9 ± 17.9% vs. 73.7 ± 19.8%; p < 0.001) and total lung volume (2,916 ± 674 vs. 4,286 ± 1,136, p < 0.001) compared with SSc Limited-ILD. Conclusion: The proposed method seems to provide an alternative to identify and quantify the extension of ILD in patients with SSc, mitigating the subjectivity of semiquantitative analyzes based on visual scores.

Childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome: A multicenter study with 1519 patients.

OBJECTIVE: To assess childhood-onset systemic lupus erythematosus-related antiphospholipid syndrome(cSLE-APS) in a large Brazilian population. METHODS: A retrospective observational cohort study was carried-out in 27 Pediatric Rheumatology university centers, including 1519 cSLE patients. RESULTS: cSLE-APS was observed in 67/1519 (4%) and was diagnosed at disease onset in 39/67 (58%). The median disease duration was 4.9 (0-17) years. Thrombosis recurrences were evidenced in 18/67 (27%) cSLE-APS patients. The most frequent thrombosis sites in cSLE-APS patients were: venous thrombosis in 40/67 (60%), especially deep vein thrombosis in 29/40 (72%); arterial thrombosis in 35/67 (52%), particularly stroke; small vessels thrombosis in 9/67 (13%) and mixed thrombosis in 3/67 (4%). Pregnancy morbidity was observed in 1/67 (1%). Non-thrombotic manifestation associated to cSLE-APS occurred in 21/67 (31%), mainly livedo reticularis in 14/67 (21%), valvar thickening in 4/67 (6%) and valvar vegetations not related to infections in 2/67 (3%). None of them had catastrophic APS. Further analysis demonstrated that the median of SLICC/ACR-DI [1(0-5) vs. 0(0-7),p < 0.0001] was significantly higher in cSLE-APS patients compared to cSLE without APS. The frequencies of cerebrovascular disease (40% vs. 1%,p < 0.0001), polyneuropathy (9% vs. 1%,p < 0.0001), SLICC/ACR-DI ≥1 (57% vs. 27%, p < 0.0001) and intravenous cyclophosphamide use (59% vs. 37%, p < 0.0001) were significantly higher in the former group. CONCLUSIONS: Our large multicenter study demonstrated that cSLE-APS was a rare condition, occurring during disease course with a high accrual damage. Central and peripheral neuropsychiatric involvements were distinctive features of this autoimmune thrombosis.

Disease presentation of 1312 childhood-onset systemic lupus erythematosus: influence of ethnicity.

OBJECTIVE: To evaluate the influence of ethnicity in presentation of childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: This multicenter study included cSLE patients (American College of Rheumatology criteria) followed in 27 Pediatric Rheumatology services of Brazil. Ethnicities were classified in four groups according to the parents' and all four grandparents' self-reported ethnicity. The statistical analysis was performed using the Bonferroni's correction (p < 0.0027). RESULTS: According to ethnic groups, 1537 cSLE patients were classified in Caucasian (n = 786), African-Latin American (n = 526), Asian (n = 8), and others/unknown (n = 217). Comparisons between 1312 African-Latin American and Caucasian revealed similar median age at cSLE diagnosis [12.2(2.6-18) vs. 12.1(0.3-18) years, p = 0.234], time interval to diagnosis [0.25(0-12) vs. 0.3(0-10) years, p = 0.034], and SLEDAI-2K score [14(0-55) vs. 14(0-63), p = 0.781] in both groups. The mean number of diagnostic criteria according to SLICC (6.47 ± 1.911 vs. 5.81 ± 1.631, p < 0.0001) and frequencies of maculopapular lupus rash (8% vs. 3%, p < 0.0001), palate oral ulcers (17% vs. 11%, p = 0.001), tongue oral ulcers (4% vs. 1%, p = 0.001), and nonscarring alopecia (29% vs. 16%, p < 0.0001) were significantly higher in African-Latin American, whereas malar rash (45% vs. 58%, p < 0.0001) was more frequent in Caucasian. The presence of anti-phospholipid antibody (23% vs. 12%, p < 0.0001), low complement levels (58% vs. 41%, p < 0.0001), and isolated direct Coombs test (10% vs. 5%, p = 0.001) was also significantly higher in the former group. CONCLUSIONS: Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of the former group. The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients. Key Points • Our study demonstrated that disease presentation severity of African-Latin American cSLE patients is comparable with Caucasian. • Mucocutaneous manifestations and autoantibodies profile were the only distinctive features of African-Latin American cSLE patients. • African-Latin American cSLE patients had more often anti-phospholipid antibodies and hypocomplementemia. • The unique mixed background of Brazilian patients probably minimized race diversity spectrum of these patients.

Higher elastase activity associated with lower IL-18 in GCF from juvenile systemic lupus patients.

PURPOSE: Our aim was to evaluate the expression of interleukin-18 (IL-18), interleukin-l-beta (IL-1beta) and the amount of elastase activity in gingival crevicular fluid (GCF) from inflamed gingival sites in patients with juvenile systemic lupus erythematosus (JSLE), and compare these to the expression in GCF from inflamed sites in generally healthy controls. In addition, the local inflammation in periodontal tissues was related to systemic inflammation by the assessment of IL-18 levels in plasma. MATERIALS AND METHODS: GCF from 16 patients with JSLE and 14 controls were collected using a washing device. Elastase activity was measured with a specific substrate, and IL-18 and 11-1 were measured by ELISA. RESULTS: The percentage of visible plaque index, gingival bleeding index and attachment level were similar in JSLE and controls, while the percentage of probing depth greater or equal to 3 mm was significantly higher in the controls. The total amount of IL-1beta and IL-18 in GCF were significantly decreased in JSLE, while the total amount and the percentage of free elastase activity were significantly higher in JSLE when compared with the controls. The plasma levels of I1-18 and the erythrocyte sedimentation rate were significantly higher in JSLE patients. CONCLUSION: We found more active elastase in GCF from inflamed sites in JSLE patients even in the presence of significantly lower levels of IL-18 and IL-13. The increased elastase activity suggests a hyperactivity of neutrophils in JSLE, possibly generated by a priming effect caused by the higher plasma levels of IL-18 found in these JSLE patients.

Changes in periodontal and rheumatological conditions after 2 years in patients with juvenile idiopathic arthritis.

BACKGROUND: The aim of this study was to monitor changes in periodontal inflammation in patients with juvenile idiopathic arthritis (JIA) for 2 years. We investigated the influence of rheumatic disease activity and antirheumatic medication on clinical and immunological parameters of periodontal inflammation in these individuals. METHODS: Two years after a baseline examination, the periodontal and rheumatological conditions of 18 adolescents with JIA and 14 control subjects were described. The clinical periodontal inflammation was monitored by registration of visual plaque, marginal bleeding, probing depth, and clinical attachment loss (AL). Periodontal inflammation was also assessed by analysis of the cytokines interleukin (IL)-1beta and IL-18 and the collagenase matrix metalloproteinase (MMP)-8 by enzyme-linked immunosorbent assay. RESULTS: The erythrocyte sedimentation rate and clinical rheumatological parameters were significantly improved at the 2-year follow-up. The number of sites with plaque decreased, and the number of pockets >/=4 mm increased, whereas bleeding levels and the extension of AL remained unchanged. IL-1beta in gingival crevicular fluid decreased significantly in the JIA group after 2 years. No differences were observed for IL-1beta, MMP-8, or IL-18 levels between groups after 2 years. CONCLUSION: Two years after the baseline examination, no clinical or laboratory differences in periodontal inflammation could be found between JIA patients and control subjects.

Increased interleukin-18 in patients with juvenile idiopathic arthritis and early attachment loss.

BACKGROUND: Patients with juvenile idiopathic arthritis (JIA) have been shown to have incipient attachment loss (AL) more frequently than systemically healthy individuals. This study investigated neutrophil activity and proinflammatory cytokines in these patients and aged-matched controls. METHODS: Elastase activity, measured with a low molecular weight substrate (S-2484), and interleukin-1beta (IL-1beta), measured with the enzyme-linked immunosorbent assay (ELISA), were analyzed in the gingival fluid of 38 patients with JIA and 29 controls. IL-1beta and interleukin-18 (IL-18) were measured with ELISA in the serum of the same groups. Subgingival plaque was analyzed by DNA probes to detect 12 bacteria. RESULTS: Significantly elevated serum levels of IL-1beta and IL-18 were found in the JIA group. No differences were found in the gingival fluid levels of elastase and IL-1beta between groups, or in the frequency of subjects positive to most of the bacteria analyzed, except F. nucleatum, C. rectus, P. micros, and S. intermedius, which were significantly more frequent in the control group. When the JIA group was subdivided according to the presence/absence of AL, IL-18 was significantly increased in the JIA subgroup with AL compared to those without it. There were no differences in the subgingival microbiota between the subgroups. CONCLUSION: The findings of increased serum IL-18 and IL-1beta in patients with JIA accompanied by a similar subgingival microbiota suggest that the increased frequency of incipient attachment loss observed in these patients might be due to their altered systemic inflammatory response, making them more susceptible to periodontal disease.

Benign fasciculations and corticosteroid use: possible association? An update.

Fasciculations are characterized by visible subtle and fast contractions of muscle, even wormlike in movement, by the contraction of a fascicle of muscle fibers. The authors present the case study of a 28-year-old patient with the appearance of migratory and diffuse fasciculations with an onset after partial tapering off of oral corticosteroides (60 mg total dose) indicated for treatment of Minimal change Glomerulopathy. Clinical Neurological physical exam allied with an ENMG, besides other complementary laboratory exams were used for screening the above-mentioned patient. Afterwards, current research relating to the topic at hand was made in order to update the data available in the Bireme, Scielo and PubMed Data Banks using the following key words: Fasciculation's, motor neuron disease, and benign fasciculations in the Portuguese, English as well as Spanish language. Although fasciculation's are most commonly associated with Motor neuron disease as well as with certain metabolic disorders, they may also be present in individuals with absolutely no underlying pathological disorders. In our case, fasciculation potentials that have been present for six months, with no other signs of a neurogenic disorder as well as absence of laboratory findings, the patient received a diagnosis of Benign Fasciculation Syndrome (BFS).We believe that the use of corticosteroides in high doses with subsequent tapering contributed to the fasciculation's, especially due to the changes that this causes on the ionic channels. Fasciculation's are symptoms seen in a large range of conditions, and also being the main symptom of the so-called Benign Fasciculation Syndrome. We have presented an example of this clinical syndrome in a patient whose complaint was fasciculation's, with complete clinical remission of symptoms following complete tapering off of corticosteroid six months previously.

Amyotrophic lateral sclerosis: one or multiple causes?

The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

The challenge of pediatric tuberculosis in face of new diagnostic techniques.

OBJECTIVES: To present an updated review concerning new assays for diagnosing tuberculosis based on in vitro interferon-gamma production by host T cells, and compare them with tuberculin skin test. METHODS: A literature review was carried out based on Medline and LILACS databases (2000-2008) searching for the following keywords: tuberculosis, interferon-gamma, quantiFERON, ELISPOT and T-SPOT.TB. RESULTS: These new assays proved to have, in general, equal or superior sensitivity and specificity than the tuberculin skin test not only in adults but also in children and immunosuppressed patients for the diagnosis of both latent tuberculosis infection or active disease, with some advantages such as less cross-reactivity as a result of previous BCG vaccination, less influence of anergy and better accuracy in small children. In the United States, these assays have been used instead of the tuberculin skin test and, although still very expensive, the World Health Organization will be making its economic viability a priority. CONCLUSIONS: Always having in mind the importance of clinical and epidemiological histories, these new assays based on interferon-gamma release present promising results and should be considered in tuberculosis investigation procedures for all patients, however with a special concern in the risk groups (i.e., children and immunosuppressed patients).

Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry.

OBJECTIVES: The purpose of this study was to obtain data on the association of antiphospholipid antibodies with clinical manifestations in childhood and to enable future studies to determine the impact of treatment and long-term outcome of pediatric antiphospholipid syndrome. PATIENTS AND METHODS: A European registry extended internationally of pediatric patients with antiphospholipid syndrome was established as a collaborative project of the European Antiphospholipid Antibodies Forum and Lupus Working Group of the Pediatric Rheumatology European Society. To be eligible for enrollment the patient must meet the preliminary criteria for the classification of pediatric antiphospholipid syndrome and the onset of antiphospholipid syndrome must have occurred before the patient's 18th birthday. RESULTS: As of December 1, 2007, there were 121 confirmed antiphospholipid syndrome cases registered from 14 countries. Fifty-six patients were male, and 65 were female, with a mean age at the onset of antiphospholipid syndrome of 10.7 years. Sixty (49.5%) patients had underlying autoimmune disease. Venous thrombosis occurred in 72 (60%), arterial thrombosis in 39 (32%), small-vessel thrombosis in 7 (6%), and mixed arterial and venous thrombosis in 3 (2%). Associated nonthrombotic clinical manifestations included hematologic manifestations (38%), skin disorders (18%), and nonthrombotic neurologic manifestations (16%). Laboratory investigations revealed positive anticardiolipin antibodies in 81% of the patients, anti-beta(2)-glycoprotein I antibodies in 67%, and lupus anticoagulant in 72%. Comparisons between different subgroups revealed that patients with primary antiphospholipid syndrome were younger and had a higher frequency of arterial thrombotic events, whereas patients with antiphospholipid syndrome associated with underlying autoimmune disease were older and had a higher frequency of venous thrombotic events associated with hematologic and skin manifestations. CONCLUSIONS: Clinical and laboratory characterization of patients with pediatric antiphospholipid syndrome implies some important differences between antiphospholipid syndrome in pediatric and adult populations. Comparisons between children with primary antiphospholipid syndrome and antiphospholipid syndrome associated with autoimmune disease have revealed certain differences that suggest 2 distinct subgroups.

Periodontal conditions in patients with juvenile idiopathic arthritis.

OBJECTIVE: Our aim was to compare the periodontal conditions in a group of juvenile idiopathic arthritis (JIA) patients with those in a control group of healthy subjects (CTR). MATERIAL AND METHODS: Thirty-two patients with JIA and 24 controls were selected. The measurements used to diagnose periodontal disease included plaque and bleeding scores, probing depths (PDs) and clinical attachment loss (CAL). Laboratory indicators of JIA activity included the erythrocyte sedimentation rate (ESR) and capsule-reactive protein (CRP). The Mann-Whitney test was used to evaluate the data (alpha = 0.05). RESULTS: The mean ages were 15.9 (+/- 2.7) years and 14.7 (+/- 2.3) years for groups JIA and CTR, respectively. The median ESR was 42 mm/h 13 mm/h in the CTR group (p = 0.032) and the median CRP was 1.9 and 0.4 mg/l, respectively (p = 0.001). The prevalence of patients with a proximal attachment loss of 2mm or more in the JIA group was 25% and in controls it was 4.2%. The mean percentages of visible plaque and marginal bleeding were similar in the JIA (54 +/- 22 and 30 +/- 16, respectively) and CTR groups (44 +/- 18 and 29 +/- 11, respectively). The mean percentages of sites with PD > or = 4 mm were significantly higher in the JIA group (3 +/- 4.7) than in the CTR group (0.4 +/- 1.7) (p = 0.012). The mean percentages of sites with proximal CAL > or = 2 mm were 0.7 (+/- 1.4) in the JIA group and 0.001 (+/- 0.2) in the CTR group (p = 0.022). CONCLUSION: Adolescents with JIA present more periodontal attachment loss than healthy controls, in spite of similar plaque and marginal bleeding levels.