Microstructural Changes in the Corpus Callosum in Systemic Lupus Erythematous.

Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.

Physical Activity Influences Health-Related Quality of Life in Adults with Juvenile Idiopathic Arthritis.

This cross-sectional study aimed to evaluate the impact of physical activity and physical fitness on the health-related quality of life (HQoL) of adult patients with Juvenile Idiopathic Arthritis (JIA). Fifty-nine JIA patients and sixty healthy individuals participated in this study. All individuals had the following evaluations performed: body composition (electrical bioimpedance), physical fitness (6 min walk test (6MWT)), physical activity level (International Physical Activity Questionnaire (IPAQ)), and HQoL (Quality of Life Questionnaire in relation to Health-Short Form (SF36)). Thirty-nine (66%) JIA patients were considered sedentary compared with 15 (25%) in the control group (p < 0.01). JIA patients had a lower HQoL compared with the control group in all variables studied (p < 0.05). JIA patients who were very physically active had better HQoL conditions in the categories of functional capacity (p = 0.001), limitations by physical aspects (p = 0.003), and emotional aspects (p = 0.002) compared with sedentary patients. JIA patients had more cardiovascular abnormalities and walked shorter distances compared with healthy controls in the 6MWT. In conclusion, we observed that HQoL was reduced in adults with JIA. A high percentage of JIA patients were sedentary with lower physical fitness, but physically active patients had a better HQoL than sedentary patients. The duration of physical activity, rather than intensity, influenced the mental aspects of HQoL.

Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis.

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated into Portuguese following the standardized guidelines. We analyzed the following psychometric properties: acceptability, internal consistency, test-retest reproducibility, relative-child reliability, and external criterion and discriminant validity. We included 138 JIA patients (age: 8-18 years) and 108 relatives who took less than 5 min to answer MISS. Reproducibility tested after 15 days was good, with a kappa > 0.76. We observed good internal consistency (Cronbach's coefficient 0.75-0.87 (patients) and 0.75-0.79 (relatives)). Reliability between patients and relatives was good except for stomachache and restlessness. Cut-off points of 5 and 6 had good sensitivity (84 and 71, respectively) and specificity (80 and 87, respectively). Using a cut-off value of 6, we observed 86 (62.3%) MTX-intolerant patients. In conclusion, MISS is a viable and practical tool for routine clinical care to identify MTX intolerance in JIA. Parents do not easily identify stomachache and restlessness as adverse MTX events.

Cognitive Performance in Patients with Systemic Lupus Erythematosus Using the Ped-ANAM.

Computerized batteries have been widely used to investigate cognitive impairment (CI) in patients with SLE. The aim of this study was to evaluate the cognitive performance of patients with SLE in relation to healthy controls using the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) battery. In addition, we aimed to examine differences in Ped-ANAM scores according to age of disease onset, presence of disease activity, and disease damage. We included 201 consecutive adult-onset (aSLE) and childhood-onset SLE (cSLE) patients who were being followed at the hospital's rheumatology outpatient clinic and 177 healthy controls. We applied the percentage of correct answers on the Ped-ANAM subtests and the Performance Validity Index (PVI) metric and correlated them with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus Erythematosus Damage Index (SDI). Then, we established their relationships with neuropsychiatric systemic lupus erythematosus (NPSLE). We observed CI in a total of 38 (18.9%) SLE patients and 8 (4.5%) healthy controls (p < 0.001). CI was observed in eight (19.5%) cSLE patients and 32 (20%) aSLE patients (p = 0.8175). Individual analysis of the aSLE subtests showed a significant difference in all subtests compared to healthy controls; the greatest differences were in matching to sample (p < 0.001) and memory search ( p < 0.001). In the cSLE group, we observed a difference in the code substitution subtests (p = 0.0065) compared to the healthy controls. In the evaluation of clinical outcomes, disease activity was significantly correlated with CI in cSLE (r = 0.33; p = 0.042) and aSLE (r = 0.40; p = 0.001). We also observed an association between disease activity and neuropsychiatric manifestations (p = 0.0012) in aSLE. In conclusion, we determined that cognitive dysfunction, mainly in memory and attention, was more prevalent in patients with SLE. In both the cSLE and aSLE groups, disease activity was associated with worse cognitive function. This is the first study to use the Ped-ANAM in Brazil. Longitudinal studies are necessary to determine how the Ped-ANAM will perform over time.

Cross-cultural adaptation and initial validation of the Brazilian-Portuguese version of the pediatric automated neuropsychological assessment metrics.

Automated neuropsychiatric batteries have been used in research and clinical practice, including for chronic diseases, such as Systemic Lupus Erythematosus. The Pediatric Automated Neuropsychological Assessment Metrics battery (Ped-ANAM), originally developed for use in American-English speaking individuals, allows tracking of cognitive functions. It can be applied to people over 9 years old. The aim of this study was to translate and present initial validation data from the Ped-ANAM into Brazilian-Portuguese. We translated the battery according to Beaton's guidelines. Psychometric properties were tested, internal consistency was analyzed by Cronbach's alpha coefficient, test-retest reliability by the intraclass correlation coefficient (ICC). Further, we measured the test execution speed at both times as a temporal stability. Principal component analysis (PCA) was used for structural validity. Evidence of construct validity was assessed through assessment of the relationships with the Wechsler Intelligence Scales. All participants prior to the start of study related activities signed an informed consent form approved by the local ethics committee. A sample of 230 individuals [mean (range) of age: 23 (9 to 60) years; 65% females] was included; a subset of 51 individuals [mean (range) of age: 18 (9 to 57) years, 59% female] completed the Ped-ANAM twice to assess test-retest reliability, and another subset of 54 individuals [mean (range) of age: 20.4 (7 to 62) years; 67% female] completed the Wechsler Intelligence Scales for Children and Adult for assessment of the Ped-ANAM's construct validity. Our results suggest that the internal consistency of the Ped-ANAM (Cronbach's α = 0.890) and its subtest test-retest reliability were excellent (ICC: 0.59 to 0.94). There was no clustering in the Principal Components Analysis, suggestive of non-grouping of the evaluated variables. Construct validity assessment to the Wechsler Scales showed expected ranges of low to strong correlations (Spearman correlations: ρ = 0.40 to ρ = 0.69). We concluded that, based on the results of this study, a cross-culturally validated Brazilian-Portuguese version of the Ped-ANAM has been developed and it is a reliable tool for the screening cognitive function.

Longitudinal comparison of IL-6, IL-10, and IL-12 cytokine profiles in adult and childhood-onset systemic lupus erythematosus.

Objective: To compare the levels of Th1 (IL-12) and Th2 (IL-6 and IL10) cytokines over a two-year period among systemic lupus erythematosus patients with childhood-onset (cSLE), adult-onset (sSLE), and healthy controls, and correlate with their clinical, laboratory, and treatment manifestations. Methods: The study included 63 patients with cSLE [57 (90%) women; mean age 19.7 ± 4.3 years (range = 10-29); mean disease duration 7.3 ± 4.2 years (range 2-15)], 67 patients with aSLE [65 (97%) women; mean age of 39.9 ± 11.8 years (range 21-68); disease duration 7.7 ± 3.1 years (range 4-16)], and 40 healthy controls [36 (90%) women; mean age of 29.6 ± 10 years (range 12-49)]. cSLE and aSLE patients were paired by disease duration. Clinical and laboratory manifestations, disease activity (SLEDAI), cumulative damage (SDI), and current drug exposures were evaluated. Symptoms of anxiety and depression were evaluated by the Beck inventory (BAI and BDI, respectively). Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by the ELISA test. Data were collected at four different time points (TI, TII, TIII, and TIV) and compared by non-parametric tests. Results: IL-6 levels were significantly higher in aSLE patients compared to healthy controls at times I, II, and III (TI p = 0.013, TII p = 0.015, TIII p = 0.004, and TIV p = 0.634). However, no difference was observed between cSLE patients and healthy controls (TI p = 0.223, TII p = 0.613, TIII p = 0.341, and TIV p = 0.977). In addition, no difference was observed between aSLE and cSLE patients (TI p = 0.377, TII p = 0.123, TIII p = 0.105, and TIV p = 0.591). The levels of IL-12 were significantly higher in cSLE patients compared to healthy controls at all time points (TI p = 0.04, TII p < 0.001, TIII p = 0.015, and TIV p = 0.021). aSLE patients showed significantly elevated levels when compared to healthy controls at time III and IV (TI p = 0.752, TII p = 0.827, TIII p = 0.011*, and TIV p < 0.001*). cSLE patients showed significantly higher levels than aSLE patients at times I and II (TI p = 0.07*, TII p < 0.001*, TIII p = 0.998, and TIV p = 0.140). In aSLE patients, IL-6 was associated with headache (p = 0.006), arthritis (p = 0.044), and nephritis (p = 0.012); IL-10 was associated with nephritis (p = 0.043), hypocomplementemia (p = 0.001), and disease activity (p = 0.001); in these patients, IL-12 was associated with alopecia (p = 0.025) and leukopenia (p = 0.044). In cSLE patients, IL-6 was associated with arthritis (p = 0.022) and malar rash (p = 0.012). Conclusion: aSLE and cSLE patients with long disease duration present similar levels of cytokines, despite differences in clinical activity patterns over time.

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.

The importance of transition from pediatric to adult rheumatology care in juvenile idiopathic arthritis.

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic inflammatory condition in childhood. The long-term morbidity, mortality, and quality of life have improved with the earlier use of disease-modifying drugs (DMARDs) and the availability of biology disease-modifying drugs (bDMARDs). Despite the improvement of treatment, around 50% of the patients reach adulthood with articular and/or extra articular disease activity. A careful planned transition from pediatric to adult care is necessary to reduce the loss of follow-up that is associated with stopping medications, flares, and disability due to untreated arthritis or uveitis.Areas covered: This narrative review provides an overview of the importance of transition in JIA Articles were selected from Pubmed searches.Expert opinion: JIA patients, family, and healthcare workers have to be trained to provide an effective transition plan, based on local and national policies. Important aspects such as expectations, maturation, disease characteristics, disease activity, adherence, disability, and psychological aspects among others have to be considered and addressed during the transition phase to improve self-esteem, self-assurance, and quality of life.

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.

Trisomy X in a patient with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, chronic and systemic autoimmune disease generally with a more severe clinical phenotype than the adult-onset SLE. In both conditions, it is known that females are predominantly affected; therefore, the possible overlap of SLE and sex chromosomal abnormalities has attracted attention. Our case report describe the clinical manifestations and immunological profile of a Brazilian female with cSLE and trisomy X. The 22 year-old patient, diagnosed with cSLE at age of 11, present some features related to 47, XXX, such as difficulties at school and communication, although this was not enough to investigate for chromosome abnormalities. Cytoscan HD array screening allowed the comprehensive diagnosis for this patient. We also characterized her ancestral composition, showing that she has 6.2% higher African component than the mean from health subjects from the same geographical area. This report reinforces the role of the X chromosome dose effect for sex bias in SLE, as well as the importance of African ancestry composition in cLES. It also throws lights upon the application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data.

Familial Aggregation of Childhood- and Adulthood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To assess the familial occurrence of systemic lupus erythematosus (SLE) in a large Brazilian cohort. METHODS: Consecutive patients with SLE were recruited and stratified according to age at disease onset into childhood-onset SLE or adult-onset SLE. Each patient was personally interviewed regarding the history of SLE across 3 generations (first-, second-, and third-degree relatives). Recurrence rates were analyzed for each degree of relation. RESULTS: We included 392 patients with SLE (112 with childhood-onset SLE and 280 with adult-onset SLE). We identified 2,574 first-degree relatives, 5,490 second-degree relatives, and 6,805 third-degree relatives. In the combined overall SLE cohort, we observed a familial SLE recurrence rate of 19.4 in first-degree relatives, 5.4 in second-degree relatives, and 3.0 in third-degree relatives. Recurrence rates were higher for first- and second-degree relatives of patients with childhood-onset SLE than for first- and second-degree relatives of patients with adult-onset SLE (25.2 versus 18.4 for first-degree, and 8.5 versus 4.5 for second-degree), while in third-degree relatives, recurrence rates were higher in adult-onset SLE than in childhood-onset SLE (P = 2.2 × 10-4 for differences in recurrence proportions between childhood-onset SLE and adult-onset SLE). There were no phenotypic differences in patients from multicase versus single-case families, and there was no sex-skewing observed in the offspring of patients with SLE. CONCLUSION: The greater decline in SLE recurrence rate by generation in childhood-onset SLE versus adult-onset SLE suggests a more polygenic and epistatic inheritance and suggests that adult-onset SLE may be characterized by fewer risk factors that are individually stronger. This finding suggests a higher genetic load in childhood-onset SLE versus adult-onset SLE and a difference in the genetic architecture of the disease based on age at onset.

Symptomatic polyautoimmunity at diagnosis of 1463 childhood-onset lupus: A Brazilian multicenter study.

OBJECTIVE: To evaluate symptomatic polyautoimmunity (PA) at childhood-onset systemic lupus erythematosus(cSLE) diagnosis, and its association with demographic data, disease activity, clinical manifestations and laboratorial abnormalities in a large Brazilian cSLE population. METHODS: A multicenter retrospective study was performed in 1463 cSLE(ACR criteria) patients from 27 Pediatric Rheumatology services. Symptomatic PA was defined according to the presence of more than one concomitant autoimmune disease(AD) and symptomatic multiple autoimmune syndrome(MAS) was defined as three or more AD. An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. RESULTS: At cSLE diagnosis symptomatic PA was observed in 144/1463(9.8%) and symptomatic MAS occurred in solely 10/1463(0.7%). In the former group the more frequently observed associated AD were Hashimoto thyroiditis n = 42/144(29%), antiphospholipid syndrome n = 42/144(29%), autoimmune hepatitis n = 26/144(18%) and type 1 diabetes mellitus n = 23/144(15.9%). Further comparisons between cSLE patients with and without PA showed a higher median age(p = 0.016) and lower mean SLICC criteria (p = 0.039) in those with PA. Additionally, these cSLE patients had less renal involvement(35% vs. 44%, p = 0.038) and red blood cell cast(6% vs. 12%, p = 0.042) and more antiphospholipid antibodies(29% vs. 15%, p < 0.0001). CONCLUSIONS: Approximately 10% of cSLE had symptomatic PA at diagnosis, particularly endocrine autoimmune disorders and antiphospholipid syndrome. Lupus was characterized by a mild disease onset and MAS was infrequently evidenced. Further studies are necessary to determine if this subgroup of cSLE patients have a distinct genetic background with a less severe disease and a better long-term outcome.

Diffuse alveolar hemorrhage in childhood-onset systemic lupus erythematosus: a severe disease flare with serious outcome.

OBJECTIVE: To evaluate prevalence, clinical manifestations, laboratory abnormalities and treatment in a multicenter cohort study including 847 childhood-onset systemic lupus erythematosus (cSLE) patients with and without diffuse alveolar hemorrhage (DAH), as well as concomitant parameters of severity. METHODS: DAH was defined as the presence of at least three respiratory symptoms/signs associated with diffuse interstitial/alveolar infiltrates on chest x-ray or high-resolution computer tomography and sudden drop in hemoglobin levels. Statistical analysis was performed using Bonferroni correction (p < 0.0022). RESULTS: DAH was observed in 19/847 (2.2%) cSLE patients. Cough/dyspnea/tachycardia/hypoxemia occurred in all cSLE patients with DAH. Concomitant parameters of severity observed were: mechanical ventilation in 14/19 (74%), hemoptysis 12/19 (63%), macrophage activation syndrome 2/19 (10%) and death 9/19 (47%). Further analysis of cSLE patients at DAH diagnosis compared to 76 cSLE control patients without DAH with same disease duration [3 (1-151) vs. 4 (1-151) months, p = 0.335], showed higher frequencies of constitutional involvement (74% vs. 10%, p < 0.0001), serositis (63% vs. 6%, p < 0.0001) and sepsis (53% vs. 9%, p < 0.0001) in the DAH group. The median of disease activity score(SLEDAI-2 K) was significantly higher in cSLE patients with DAH [18 (5-40) vs. 6 (0-44), p < 0.0001]. The frequencies of thrombocytopenia (53% vs. 12%, p < 0.0001), intravenous methylprednisolone (95% vs. 16%, p < 0.0001) and intravenous cyclophosphamide (47% vs. 8%, p < 0.0001) were also significantly higher in DAH patients. CONCLUSIONS: This was the first study to demonstrate that DAH, although not a disease activity score descriptor, occurred in the context of significant moderate/severe cSLE flare. Importantly, we identified that this condition was associated with serious disease flare complicated by sepsis with high mortality rate.

Prevalence and features of metabolic syndrome in childhood-onset systemic lupus erythematosus.

To estimate the prevalence and features of metabolic syndrome (MetS) in childhood-onset systemic lupus erythematosus (cSLE), we performed a cross-sectional study of 76 consecutive cSLE patients and 54 healthy controls, age and sex matched. All individuals were assessed for anthropometric and MetS features according to World Health Organization (WHO), NCEP Adult Treatment Panel III (NCEP-ATP III), and International Diabetes Federation (IDF) criteria. The cSLE patients were further assessed for clinical and laboratory manifestations, disease activity (Systemic Lupus Erythematosus Disease Activity Index), cumulative damage (Systemic Lupus International Collaborating Clinics (SLICC)), and current and cumulative drug exposures. Sixty-nine (90.8%) patients were female with mean age of 16.8 years [standard deviation (SD) ±4.0 years]. Mean disease duration was 4.8 years (SD ± 4.1). Based on the WHO MetS criteria, MetS was observed in two (2.6%) cSLE patients. We observed high prevalence of the MetS in cSLE patients according to NCEP-ATP III MetS criteria (18.4%) (p = 0.002) and according to IDF MetS criteria (17.1%) (p = 0.003). We did not observe MetS in the control group. No difference in cSLE patients <18 and ≥18 years was observed. We observed an association between the presence of MetS and SLICC scores in cSLE <18 years and cumulative corticosteroid dose adjusted by weight in cSLE ≥18 years. This study showed that MetS is frequently observed in cSLE using NCEP-ATP III MetS criteria and IDF MetS criteria. The identification of MetS is important to indicate cardiovascular morbidity and mortality in cSLE.

Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey.

The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4-519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.

Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus.

BACKGROUND: To our knowledge there are no studies assessing anti-Ro/SSA and anti-La/SSB autoantibodies in a large population of childhood-systemic lupus erythematosus (cSLE) patients. METHODS: This was a retrospective multicenter cohort study performed in 10 Pediatric Rheumatology services, São Paulo state, Brazil. Anti-Ro/SSA and anti-La/SSB antibodies were measured by enzyme linked immunosorbent assay (ELISA) in 645 cSLE patients. RESULTS: Anti-Ro/SSA and anti-La/SSB antibodies were evidenced in 209/645 (32%) and 102/645 (16%) of cSLE patients, respectively. Analysis of cSLE patients with and without anti-Ro/SSA antibodies revealed higher frequencies of malar rash (79% vs. 71%, p=0.032), photosensitivity (73% vs. 65%, p=0.035), cutaneous vasculitis (43% vs. 35%, p=0.046) and musculoskeletal involvement (82% vs. 75%, p=0.046) in spite of long and comparable disease duration in both groups (4.25 vs. 4.58years, p=0.973). Secondary Sjögren syndrome was observed in only five patients with this antibody (2.5% vs. 0%, p=0.0035), two of them with concomitant anti-La/SSB. The presence of associated autoantibodies: anti-Sm (50% vs. 30%, p<0.0001), anti-RNP (39% vs. 21%, p<0.0001) and anti-ribossomal P protein (46% vs. 21%, p=0.002) was also significantly higher in patients with anti-Ro/SAA antibodies. Further evaluation of cSLE patients with the presence of anti-La/SSB antibodies compared to those without these autoantibodies showed that the frequency of alopecia (70% vs. 51%, p=0.0005), anti-Sm (59% vs. 31%, p<0.0001) and anti-RNP (42% vs. 23%, p<0.0001) were significantly higher in the former group. CONCLUSIONS: Our large multicenter cohort study provided novel evidence in cSLE that anti-Ro/SSA and/or anti-La/SSB antibodies were associated with mild manifestations, particularly cutaneous and musculoskeletal. Secondary Sjögren syndrome was rarely observed in these patients, in spite of comparable frequencies of anti-Ro/SSA and/or anti-La/SSB reported for adult SLE.

Bilateral spontaneous chylothorax after severe vomiting in children / Quilotórax bilateral espontâneo após vômitos excessivos em criança

Abstract Objective: To report the case of a child with bilateral chylothorax due to infrequent etiology: thoracic duct injury after severe vomiting. Case description: Girl, 7 years old, with chronic facial swelling started after hyperemesis. During examination, she also presented with bilateral pleural effusion, with chylous fluid obtained during thoracentesis. After extensive clinical, laboratory, and radiological investigation of the chylothorax etiology, it was found to be secondary to thoracic duct injury by the increased intrathoracic pressure caused by the initial manifestation of vomiting, supported by lymphoscintigraphy findings. Comments: Except for the neonatal period, chylothorax is an infrequent finding of pleural effusion in children. There are various causes, including trauma, malignancy, infection, and inflammatory diseases; however, the etiology described in this study is poorly reported in the literature.

Resumo Objetivo: Relatar o caso de uma criança com quilotórax bilateral devido a etiologia pouco frequente: lesão do ducto torácico após quadro de vômitos excessivos. Descrição do caso: Menina, sete anos, apresentava edema facial crônico iniciado após quadro de hiperemese. À avaliação, também apresentava derrame pleural bilateral, com líquido quiloso obtido na toracocentese. Após extensa investigação clínica, laboratorial e radiológica da etiologia do quilotórax, foi definido ser secundário a lesão do ducto torácico por aumento da pressão intratorácica pela manifestação inicial de vômitos, corroborado por achados de linfocintilografia. Comentários: À exceção do período neonatal, o quilotórax é achado infrequente de efusão pleural em crianças. As causas são diversas, incluindo trauma, neoplasia, infecção e doenças inflamatórias; contudo, etiologia como a aqui descrita é pouco relatada na literatura.

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. RESULTS: 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). CONCLUSION: Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment.

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus / Associação entre desempenho acadêmico e disfunção cognitiva em pacientes com lúpus eritematoso sistêmico juvenil

Abstract Objective To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Methods Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p < 0.05) was adopted. Results 41 patients with a mean age of 14.5 ± 2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p = 0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p = 0.037) and symptoms of depression were observed in 1 patient (2.43%). Conclusion Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment.

Resumo Objetivo Determinar se há associação entre o perfil de disfunção cognitiva e os resultados acadêmicos em pacientes com lúpus eritematoso sistêmico juvenil (LESj). Métodos Foram selecionados pacientes com idade de início da doença ≤ 18 anos e com escolaridade mínima do quinto ano do Ensino Fundamental seguidos em um hospital universitário. A avaliação cognitiva foi feita de acordo com as recomendações do Colégio Americano de Reumatologia (ACR). Os sintomas de ansiedade e depressão foram avaliados pelas escalas Beck, a atividade da doença foi avaliada pelo Systemic Lupus Erythematosus Disease Activity Index (Sledai) e o dano cumulativo pelo Systemic Lupus International Collaborating Clinics (Slicc). Também foram avaliados a presença de autoanticorpos e o uso de medicação. Adotou-se nível de significância de 5% (p < 0,05). Resultados Foram incluídos 41 pacientes com média de 14,5 ± 2,84 anos. Disfunção cognitiva foi observada em 17 (41,46%). Observou-se pioria significativa no desempenho de matemática em pacientes com disfunção cognitiva (p = 0,039). Sintomas de ansiedade foram observados em oito pacientes (19,51%) e estavam associados à percepção visual (p = 0,037) e sintomas de depressão foram observados em um paciente (2,43%). Conclusão Pacientes com LESj com disfunção cognitiva apresentam pior desempenho acadêmico em matemática em relação a pacientes sem disfunção cognitiva.

Bilateral spontaneous chylothorax after severe vomiting in children. / Quilotórax bilateral espontâneo após vômitos excessivos em criança.

OBJECTIVE: To report the case of a child with bilateral chylothorax due to infrequent etiology: thoracic duct injury after severe vomiting. CASE DESCRIPTION: Girl, 7 years old, with chronic facial swelling started after hyperemesis. During examination, she also presented with bilateral pleural effusion, with chylous fluid obtained during thoracentesis. After extensive clinical, laboratory, and radiological investigation of the chylothorax etiology, it was found to be secondary to thoracic duct injury by the increased intrathoracic pressure caused by the initial manifestation of vomiting, supported by lymphoscintigraphy findings. COMMENTS: Except for the neonatal period, chylothorax is an infrequent finding of pleural effusion in children. There are various causes, including trauma, malignancy, infection, and inflammatory diseases; however, the etiology described in this study is poorly reported in the literature.