Transition From Pediatric to Adult Rheumatology Care: An Exploratory Study From Latin America.

BACKGROUND/PURPOSE: Adequate transition from pediatric to adult care is associated with better adherence to treatment and better outcomes in pediatric patients with chronic diseases. There are little data on transition programs, outcomes, use of transition guidelines, and available tools in pediatric rheumatology centers from Latin America (LATAM). In this study, we described the characteristics of transition programs from 3 pediatric rheumatology centers. We also introduced results of the first survey examining the transition experience in countries from LATAM. METHODS: The experience and implementation process of transition programs from 3 pediatric rheumatology centers were described. A survey based on a questionnaire created by Chira et al (J Rheumatol. 2014;41:768-779) from the Childhood Arthritis and Rheumatology Research Alliance was also administrated to pediatric rheumatology centers from LATAM. RESULTS: A total of 49 (68%) pediatric rheumatologists answered the survey. Most centers do not have an official and written transition program and reported a need for more tools and resources in their services to facilitate the transition experience. CONCLUSIONS: Transition guidelines culturally tailored to developing countries are needed in LATAM.

Is positron emission tomography/magnetic resonance imaging a reliable tool for detecting vascular activity in treated childhood-onset Takayasu's arteritis? A multicentre study.

OBJECTIVES: Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu's arteritis (c-TA) under immunosuppressive therapy. METHODS: A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. RESULTS: Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76-3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P < 0.001). A positive correlation between SUVmax and CRP levels (ρ = 0.528, P = 0.029) was seen. CONCLUSION: A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.

Selenium nutritional status and its association with SLEDAI-2K, HOMA-IR and lipid profile in Juvenile Systemic Lupus Erythematosus patients.

OBJECTIVES: To assess nutritional status regarding selenium in adolescents with Juvenile Systemic Lupus Erythematosus (jSLE) and analyze possible associations with disease activity, insulin resistance and lipid profile. METHODS: This was an observational, cross-sectional study of 31 female adolescents with jSLE and 31 healthy female volunteers as a comparison group. We obtained demographic, anthropometric (weight, stature, waist, and neck circumferences), and clinical data (disease activity measured by SLEDAI-2K) from both groups; laboratory data including: lipid profile, plasma selenium, erythrocyte glutathione peroxidase activity (GPx), plasma malondialdehyde (MDA), ultrasensitive C-reactive protein (usCRP), insulin levels, and glycemia (Homeostasis Model Assessment for Insulin Resistance-HOMA-IR). RESULTS: Mean age at diagnosis of jSLE group was 15.9±1.7 years, with mean disease duration of 3.6±2.6 years. 48% of patients and controls had below-reference Se levels (≤46mcg/L). GPx was more frequently below reference levels (<4.171U/L) in the jSLE group, compared to controls. A ROC curve was used to assess the power of the variables to discriminate between both groups; insulin (AUC = 0.712; CI 95% 0.584-0.840), waist-to-height ratio (AUC = 0.704; CI 95% 0.572-0.837), and HOMA-IR (AUC = 0.689; CI 95% 0.556-0.822) were the variables with the greatest discriminatory power. Linear regression showed an independent inverse association between Se levels and c-LDL; no such correlation was found for GPx activity. SLEDAI-2 K and HOMA-IR showed no association with levels of Se and GPx activity. CONCLUSIONS: Approximately, 50% of jSLE adolescents had below reference Se levels. The frequency of inadequate GPx values was higher in patients, compared to controls. There was an independent inverse association between Se and c-LDL levels in both groups; this was not the case for HOMA-IR and SLEDAI-2K. The data show the importance of assessing Se nutritional status in jSLE patients.

Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). METHODS: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. RESULTS: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. CONCLUSION: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

BACKGROUND: Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. OBJECTIVE: To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. CONCLUSIONS: jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.

Neutrophilic dermatosis: a new skin manifestation and novel pathogenic variant in a rare autoinflammatory disease.

Sideroblastic anaemia, B-cell immunodeficiency, periodic fever and developmental delay (SIFD) is caused by mutations of TRNT1, an enzyme essential for mitochondrial protein synthesis, and has been reported in 23 cases. A 6-month-old girl was evaluated with recurrent fever, failure to thrive, skin lesions and anaemia. She received blood transfusions and empirical antibiotics. Skin lesions, previously interpreted as insect bites, consisted of numerous firm asymptomatic erythematous papules and nodules, distributed over trunk and limbs. Skin histopathology revealed an intense dermal neutrophilic infiltrate extending to the subcutaneous, with numerous atypical myeloid cells, requiring the diagnosis of leukaemia cutis, to be ruled out. Over the follow-up, she developed herpetic stomatitis, tonsillitis, lobar pneumonia and Metapneumovirus tracheitis, and also deeper skin lesions, resembling panniculitis. Hypogammaglobulinaemia was diagnosed. An autoinflammatory disease was confirmed by whole exome sequencing: heterozygous mutations for TRNT1 NM_182916 c.495_498del, p.F167Tfs * 9 and TRNT1 NM_182916 c.1246A>G, p.K416E. The patient has been treated with subcutaneous immunoglobulin and etanercept. She presented with developmental delay and short stature for age. The fever, anaemia, skin neutrophilic infiltration and the inflammatory parameters improved. We describe a novel mutation in SIFD and the first to present skin manifestations, namely neutrophilic dermal and hypodermal infiltration.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with childhood systemic lupus erythematosus: a real-world interventional multi-centre study.

OBJECTIVE: This study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: Volunteer cSLE patients aged 9-20 years and healthy controls (HC) were enrolled to receive a two- or three-dose qHPV vaccination schedule from March 2014 to March 2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose. In each study visit, disease activity and adverse events following vaccination were analyzed, and a serum sample was collected for testing antibody concentrations. Participant recruitment was conducted in 15 Brazilian paediatric rheumatology units. Of the 256 cSLE patients included, 210 completed the two- or three-dose schedules; 15 had previously received one dose, and 18 had received two doses of the vaccine. The analysis was based on intention-to-treat so that participants who did not complete the entire study protocol were also included. RESULTS: No severe adverse events were related to the vaccination. Disease activity was generally low and remained stable or even improved. The HC presented 100% seropositivity to HPV16 and HPV18, whereas the two- and three-dose cSLE groups presented 93% and 83% versus 97% and 91%, respectively. One year after the first dose, seropositivity of the three-dose cSLE group was 91% to HPV16 and 84% to HPV18. CONCLUSIONS: HPV vaccination in cSLE patients is safe and immunogenic. Since the seropositivity to HPV16 and HPV18 was higher for the three-dose schedule group, this regimen should be recommended for cSLE patients.

Anthropometric Evaluation and Assessment of Food Intake of Parents of Pediatric Patients with Chronic Rheumatic Diseases.

INTRODUCTION: Parents' eating behavior, lifestyle, and food choices can interfere with their children's eating habits, bringing new perspectives for the development of beneficial interventions in the context of chronic rheumatic diseases. OBJECTIVES: The objective is to evaluate BMI, dietary intake, physical activity, and biomarkers of lipid metabolism in parents of children and adolescents with chronic rheumatic diseases and to verify the association with those of their children. METHODS: This is a cross-sectional study with 91 parents, and their respective children diagnosed with juvenile idiopathic arthritis (n = 30, 33.0%), juvenile systemic lupus erythematosus (n = 41, 45.0%), and juvenile dermatomyositis (n = 20, 22.0%). Anthropometric and dietary data, physical activity, lipid profile, and apolipoproteins A-I and B were evaluated. RESULTS: In total, 67% of parents and 27.5% of children were overweight; 80% of overweight children/adolescents also had parents with the same nutritional diagnosis. We found a moderate association of total fat intake (Cramer's V test = 0.254; p = 0.037), and a weak association of saturated fat intake (Cramer's V test = 0.219; p = 0.050) and cholesterol intake (Cramer's V test = 0.234; p = 0.025) between parents and their children. A high prevalence of dyslipidemia was observed for parents (82.4%) and children (83.5%), however, with no association between both. A weak association was found between parents and children (Cramer's V test = 0.238; p = 0.024) for triglycerides, and no association was found between parents and children concerning physical activity. CONCLUSION: The high frequency of overweight and dyslipidemia observed in parents, combined with the association between the fat intake by parents and their children with chronic rheumatic diseases, points to the importance of intervention strategies with the engagement and participation of families.

Unexpected relevant role of gene mosaicism in patients with primary immunodeficiency diseases.

BACKGROUND: Postzygotic de novo mutations lead to the phenomenon of gene mosaicism. The 3 main types are called somatic, gonadal, and gonosomal mosaicism, which differ in terms of the body distribution of postzygotic mutations. Mosaicism has been reported occasionally in patients with primary immunodeficiency diseases (PIDs) since the early 1990s, but its real involvement has not been systematically addressed. OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs. METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics. RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time. CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.

Nutritional intervention in patients with juvenile systemic lupus erythematosus: protective effect against the increase in fat mass.

Patients with juvenile systemic lupus erythematosus (JSLE) usually have an increase in fat mass and decrease in lean body mass. The purpose of this study was to assess the effect of a nutritional intervention on changes in body composition and food consumption of adolescents with JSLE compared with a control group and its variation over time and to assess the association of total fat mass with clinical parameters. This randomized controlled study evaluated 31 girls. Body composition and food intake were evaluated at baseline. The patients were randomly allocated into a nutritional intervention group and a control group. The intervention group received monthly nutritional guidelines for 9 months. After this period, evaluations were repeated. The carbohydrates intake decreased in the intervention group compared with the control group (p = 0.031) at the end of the study period. Additionally, a significant decrease was observed in the intake of energy (p = 0.023), carbohydrates (p = 0.031), protein (p = 0.024), total fat (p = 0.027), saturated fat (p = 0.012), and trans fat (p = 0.029) in the intervention group between baseline and the end of the study. There was an average increase of 3.7 kg (95% CI 0.8-6.5) in the total fat mass (p = 0.013) and 0.36 kg/m2 (95% CI 0.10-0.62) in the appendicular fat mass (p = 0.007) in the control group during the study period; this finding was not observed in the intervention group. A 9-month nutritional intervention in JSLE patients improved their eating habits and protected against the excessive gain of weight and body fat.

Takayasu arteritis in childhood: misdiagnoses at disease onset and associated diseases.

Juvenile-Takayasu arteritis (j-TA) is a difficult diagnosis and some patients develop uncommon manifestations and associated diseases that may contribute to the delayed diagnosis. Our aim was to identify the misdiagnoses, the associated diseases and the atypical manifestations observed in a j-TA Brazilian multicentre study. 71 children and adolescents who met the classification criteria for j-TA were included. The misdiagnoses, the associated diseases and the atypical manifestations were evaluated. 19 (26.8%) patients had misdiagnoses. The most common of them was aortic coarctation in six (8.4%) patients, followed by rheumatic fever in five (7.0%) and one patient presented with both former diagnoses. Limb pain (two patients), spondyloarthropathy, juvenile idiopathic arthritis (JIA), spinal arteriovenous malformation, polyarteritis nodosa (PAN) and fever of unknown origin (FUO) were other misdiagnoses. Patients who had misdiagnoses previously to j-TA diagnosis presented a trend to have a longer diagnosis delay. 11 (15.5%) patients had 14 TA-associated diseases, such as pulmonary tuberculosis (5 patients), rheumatic fever (2 patients), spondyloarthropathy, polyarticular JIA, Crohn's disease, Prader-Willi disease, diabetes mellitus, Moyamoya and primary immunodeficiency. 7 (9.9%) patients presented 10 atypical manifestations, such as pyoderma gangrenosum, erythema nodosum, myositis, chorea, enthesitis, episcleritis, uveitis, hepatomegaly, splenomegaly and necrosis of extremities. Our study emphasizes the main misdiagnoses, associated diseases and atypical manifestations that occur in patients with j-TA and warns of the features that may alert paediatricians to this diagnosis, such as constitutional symptoms and elevated inflammatory markers.

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy.

Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1α, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments.

Lipid profile among girls with systemic lupus erythematosus.

The aim of the study was to describe biomarkers of lipid metabolism associated with increased cardiovascular risk and their correlation with disease variables and markers of inflammation in adolescent females with systemic lupus erythematosus (SLE). This cross-sectional controlled study evaluated 33 adolescent females with juvenile SLE and 33 healthy controls. Anthropometric data, SLE disease activity index (SLEDAI), medications, proteinuria, ultra-sensitive C-reactive protein (us-CRP), lipid profile (total cholesterol, LDL-c, HDL-c and triglycerides), apolipoproteins A and B (Apo A-I and B), paraoxonase, and myeloperoxidase were evaluated. Median age of the patients and the median disease duration were 16.7 years and 54 months, respectively. SLEDAI scores above 4 were observed in 11 (33.3 %) patients. Moreover, 12 (36.4 %) patients were overweight, and 5 (15.2 %) had low height for age ratios. Dyslipidemia was observed in 13 (39.4 %) patients and in 7 (21.2 %) controls with a decrease in HDL-c concentrations in SLE patients even after adjustment for their nutritional status. In the group with SLE, us-CRP concentrations were inversely correlated with LDL-c/ApoB ratio (p = 0.031). After multivariate regression analysis, the SLE group showed lower concentration of Apo A-I and a decreased LDL-c/ApoB ratio. SLE adolescent females with low disease activity, with preserved kidney function and on low dose of corticosteroids, regardless of nutritional status and food intake, have proatherogenic lipid biomarkers, which may contribute to an increased atherosclerotic risk.

Subclinical Pulmonary Hypertension in Childhood Systemic Lupus Erythematosus Associated with Minor Disease Manifestations.

The aim of this study was to evaluate pulmonary hypertension (PH) in 852 childhood-onset systemic lupus erythematosus (cSLE) patients. This was a large multicenter study conducted in 10 Pediatric Rheumatology Services of São Paulo state, Brazil. PH was defined as systolic pulmonary artery pressure >35 mmHg and/or measurement of the mean pulmonary artery pressure >25 mmHg and/or diastolic pressure >15 mmHg by transthoracic echocardiogram. Demographic data, clinical manifestations, disease activity score (SLEDAI-2K), disease damage score (SLICC/ACR-DI) and treatments were also evaluated. Statistical analysis was performed using Bonferroni correction (p < 0.002). PH was observed in 17/852 (2%) cSLE patients. Effort dyspnea occurred in 3/17, chest pain in 1/17 and right ventricle dysfunction in 3/17 cSLE patients. None had pulmonary thromboembolism or antiphospholipid syndrome. Further comparison between 17 cSLE with PH and 85 cSLE control patients without PH with similar disease duration [15 (0-151) vs. 15 (0-153) months, p = 0.448], evaluated at the last visit, revealed higher frequencies of fever (47 vs. 9%, p < 0.001), reticuloendothelial manifestations (41 vs. 7%, p < 0.001) and serositis (35 vs. 5%, p = 0.001) in the former group. Frequencies of renal and neuropsychiatric involvements and antiphospholipid syndrome, as well as the median of SLEDAI-2K and SLICC/ACR-DI scores, were comparable in both groups (p > 0.002). Normal transthoracic echocardiography was evidenced in 9/17 (53%), with median cSLE duration of 17.5 months (1-40) after PH standard treatment. PH was a rare manifestation of cSLE occurring in the first two years of disease. The majority of patients were asymptomatic with mild lupus manifestations. The underlying mechanism seemed not to be related to pulmonary thromboembolism and/or antiphospholipid syndrome.

Evans Syndrome at Childhood-Onset Systemic Lupus Erythematosus Diagnosis: A Large Multicenter Study.

BACKGROUND: Evans syndrome (ES) in childhood-onset systemic lupus erythematosus (cSLE) patients has been rarely reported and limited to small populations. PROCEDURES: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services including 850 patients with cSLE. ES was assessed at disease diagnosis and defined by the combination of immune thrombocytopenia and autoimmune hemolytic anemia. RESULTS: ES was observed in 11 of 850 (1.3%) cSLE patients. The majority of them had hemorrhagic manifestations (91%) and active disease (82%). All patients with ES were hospitalized and none died. Comparisons of cSLE patients with and without ES at diagnosis revealed similar frequencies of female gender, multiorgan involvement, autoantibodies profile, and low complement (P > 0.05). Patients with ES had a lower frequency of malar rash (9% vs. 53%, P = 0.003) and musculoskeletal involvement (18% vs. 69%, P = 0.001) than those without this complication. The frequencies of intravenous methylprednisolone (82% vs. 43%, P = 0.013) and intravenous immunoglobulin use (64% vs. 3%, P < 0.0001) were significantly higher in the ES group, with similar current prednisone dose between groups (1.1 [0.76-1.5] vs. 1.0 mg/kg/day [0-30], P = 0.195). CONCLUSIONS: Our large multicenter study identified ES as a rare and severe initial manifestation of active cSLE with good outcome. Diagnosis is challenging due to the lack of typical signs and symptoms of lupus and the requirement to exclude infection and primary immunodeficiency.

Characterization of chronic arthritis in a multicenter study of 852 childhood-onset systemic lupus erythematosus patients.

Chronic arthritis (CA) is an unusual condition in childhood-onset systemic lupus erythematosus (cSLE) and data in children is very limited. The aim of the study is to assess CA in a large population of cSLE patients, in a multicenter cross-sectional study including 852 cSLE patients followed in ten Pediatric Rheumatology referral services in state of São Paulo, Brazil. CA was observed in 32/852 (3.7 %) cSLE patients mostly in hands and ankles. Chronic monoarthritis was diagnosed in four cSLE patients, oligoarthritis in nine and polyarthritis in 19. In the latter group, six had rhupus syndrome. Two oligoarticular patients had Jaccoud's arthropathy. CA was an isolated manifestation observed at disease onset in 13/32 (41 %) cSLE patients, and juvenile idiopathic arthritis (JIA) was the first diagnosis in 18/32 (56 %). The comparison of last visit of patients with CA and without this manifestation revealed higher frequency of splenomegaly (28 vs. 11 %, p = 0.002). The median of SLICC/ACR-DI score [1(0-9) vs. 0(0-7), p = 0.003] was significantly higher in CA patients compared to patients without this manifestation, likewise the frequency of musculoskeletal damage (31 vs. 9 % p = 0.001). Frequencies of treatment with nonsteroidal anti-inflammatory drugs (75 vs. 26 %, p < 0.0001), hydroxychloroquine sulfate (87 vs. 59 %, p = 0.001) and methotrexate (47 vs. 22 %, p = 0.001) were significantly higher in CA patients. This large multicenter study allowed us to characterize CA as a rare and early manifestation of cSLE, frequently mimicking JIA at disease onset. It is predominantly polyarticular, involving more often hands and ankles and it is associated with significant musculoskeletal accrual damage.

Sleep, quality of life and mood of nursing professionals of pediatric intensive care units.

OBJECTIVE: To assess sleep, quality of life and mood of nursing professionals of pediatric intensive care units. METHOD: Quantitative, cross-sectional and descriptive study. Professionals grouped by morning, afternoon and evening shifts were assessed by means of the instruments: Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Generic questionnaire for the assessment of quality of life (SF-36); Beck Depression Inventory; Beck Anxiety Inventory; State-Trait Anxiety Inventory. RESULTS: Sample consisted of 168 professionals, with prevalence of neutral typology (57.49%). There was no statistical significance regarding sleep, despite scores showing a poor quality of sleep and excessive daytime sleepiness for the three shifts. Quality of life did not reveal any statistical significance, but in the field "social role functioning" of the evening shift, a lower score was observed (p<0.007). There was no statistical significance regarding levels of anxiety and depression. CONCLUSION: The results suggest that these professionals may present sleeping problems, but they do not have lower scores of quality of life or mood disorders. Likely explanations for these findings may include an adaptation to their work type over time and the fact that working with children is rewarding. OBJETIVO: Avaliar sono, qualidade de vida e humor em profissionais de enfermagem em Unidades de Terapia Intensiva Infantil. MÉTODO: Estudo quantitativo, transversal e descritivo. Profissionais agrupados por turnos matutino, vespertino e noturno foram avaliados pelos instrumentos: Questionário de identificação Matutinidade-Vespertinidade; Índice de qualidade do sono de Pittsburgh; Escala de sonolência Epworth; Questionário genérico de avaliação de qualidade de vida - SF-36; Inventário de depressão de Beck; Inventário de ansiedade de Beck; Inventário de ansiedade Traço-Estado. RESULTADOS: Amostra composta por 168 profissionais, predominando tipologia neutra, 57,49%. Não houve significância estatística quanto ao sono, apesar dos escores mostrarem qualidade ruim e sonolência diurna excessiva para os três turnos. A qualidade de vida não denotou diferença estatística, mas no domínio "aspecto social" do turno noturno, observou-se escore pior (p<0,007). Não houve significância estatística nos níveis de ansiedade e depressão. CONCLUSÃO: Os resultados sugerem que estes profissionais podem apresentar problemas no sono, entretanto não apresentam escores mais baixos de qualidade de vida ou transtornos do humor. Possíveis explicações para estes achados são que haja uma adaptação ao regime de trabalho ao longo do tempo e que trabalhar com crianças seja recompensador.

Chronic Spontaneous Urticaria: A Survey of 852 Cases of Childhood-Onset Systemic Lupus Erythematosus.

BACKGROUND: Data regarding the prevalence of chronic spontaneous urticaria (CSU) in childhood-onset systemic lupus erythematosus (cSLE) patients and possible associated factors are limited to a few case reports. The objectives of this study were to assess CSU in a large cSLE population, in order to evaluate the demographic data, clinical manifestations, disease activity/damage, laboratory abnormalities and treatment. METHODS: A retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services and included 852 cSLE patients. CSU was diagnosed according to the guidelines of the European Academy of Allergy and Clinical Immunology, the Global Allergy and Asthma European Network, the European Dermatology Forum and the World Allergy Organization. Patients with CSU (evaluated at urticaria diagnosis) and patients without CSU (evaluated at the last visit) were assessed for lupus clinical/laboratory features and treatment. RESULTS: CSU was observed in 10/852 cSLE patients (1.17%). The median of cSLE duration at urticaria diagnosis was 0 (-3 to 5) years. Comparison of cSLE patients with and without CSU revealed a greater frequency of constitutional symptoms (40 vs. 8%, p = 0.006), reticuloendothelial system involvement (30 vs. 3%, p = 0.003), mucocutaneous (90 vs. 28%, p < 0.0001) and musculoskeletal manifestations (50 vs. 6%, p < 0.0001) and methylprednisolone pulse therapy use (60 vs. 9%, p < 0.0001) in the former group. The frequency of immunosuppressive treatment was lower in patients with CSU (p = 0.018). The median SLE Disease Activity Index 2000 (12 vs. 2, p < 0.0001) and erythrocyte sedimentation rate (40 vs. 19 mm/1st hour, p = 0.024), was higher in patients with CSU. CONCLUSIONS: To our knowledge, this is the first study with evidence that CSU may be linked to cSLE. We also demonstrated that this particular skin manifestation occurs predominantly at disease onset and is associated with lupus moderate/high disease activity without major organ involvement.

Fatigue in children with juvenile idiopathic arthritis: reliability of the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale".

The aim of the study was (1) to translate the "Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale" (PedsQL-Fatigue) into Brazilian Portuguese language and culture and evaluate its reliability and (2) to measure fatigue among patients with juvenile idiopathic arthritis (JIA): (1) Translation of the PedsQL-Fatigue by two bilingual researchers; (2) Backtranslation into English assessed by the authors of the original version; (3) Pilot study with five patients followed in the Pediatric Rheumatology Outpatient Clinic and their parents; and (4) Field study and assessment of measurement properties (internal consistency, reproducibility, and construct validity). In this stage, the scale was administered to 67 patients with JIA and 63 healthy individuals, aged from 2 to 18 years old, matched by age (from 2 to 4, 5 to 7, 8 to 12, and from 13 to 18 years old). Cronbach's alpha coefficient ranged from 0.6 to 0.8 for children and parents, indicating the instrument's good internal consistency. The scale's construct validity was confirmed by a satisfactory Spearman's coefficient between the PedsQL-Fatigue and the generic PedsQL 4.0 (0.840 for the children and 0.742 for the parents). Reproducibility was also adequate (0.764 for the children and 0.938 for the parents). No differences were found between the scores obtained by the JIA group and control group, though lower scores were observed among patients with clinically active JIA when compared to those without clinical activity. The PedsQL-Fatigue is a valid and reliable tool, and that can be used to measure fatigue among patients with JIA.

Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline--a longitudinal analysis after using TNFa blockers.

Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.