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Abstract Objective To evaluate the influence of environmental factors and prematurity relating to juvenile dermatomyositis (JDM), its course and refractoriness to treatment. Methods A case-control study with 35 patients followed up at a tertiary hospital and 124 healthy controls, all residents of São Paulo. Patients were classified according to monocyclic, polycyclic or chronic disease courses and refractoriness to treatment. The daily concentrations of pollutants (inhalable particulate matter-PM10, sulfur dioxide-SO2, nitrogen dioxide-NO2, ozone-O3 and carbon monoxide-CO) were provided by the Environmental Company of São Paulo. Data from the population were obtained through a questionnaire. Results Fifteen patients had monocyclic courses, and 19 polycyclic/chronic courses. Eighteen patients were refractory to treatment. Maternal occupational exposure to inhalable agents (OR = 17.88; IC 95% 2.15–148.16, p = 0.01) and exposure to O3 in the fifth year of life (third tertile > 86.28µg/m3; OR = 6.53, IC95% 1.60–26.77, p = 0.01) were risk factors for JDM in the multivariate logistic regression model. The presence of a factory/quarry at a distance farther than 200 meters from daycare/school (OR = 0.22; IC 95% 0.06–0.77; p = 0.02) was a protective factor in the same analysis. Prematurity, exposure to air pollutants/cigarette smoke/sources of inhalable pollutants in the mother’s places of residence and work during the gestational period were not associated with JDM. Prematurity, maternal exposure to occupational pollutants during pregnancy as well as patient’s exposure to ground-level pollutants up to the fifth year of life were not associated with disease course and treatment refractoriness. Conclusion Risk factors for JDM were maternal occupational exposure and exposure to O3 in the fifth year of life.

BackgroundLupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement.MethodsThirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3−CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels.ResultsPatients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = −0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls.ConclusionThis study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell–based.

Characterising the response to SARS-CoV-2 post vaccination is critical in the appraisement of the induced immune response, performance and protective potential. Here the authors present data from a phase 4 clinical trial in autoimmune rheumatic disease patients 6 months post second dose of Sinovac-CoronaVac inactivated vaccine that show a marked reduction in antibody particularly in males or those under treatment with immune targeting therapies but saw no rise in COVID-19 disease.

Abstract Background The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28–59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusion Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

ObjectivesTo prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19.MethodsA longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%.ResultsThe median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8–10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6–60.9) vs. 41.5 (21.6–54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household’s members in the residence (p = 0.68). The frequency of slight to extreme problems (level ≥ 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14–5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05).ConclusionWe longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.

The COVID-19 pandemic impacts on eating habits among adolescents may be more relevant in pediatric patients with immunocompromised chronic diseases. This case-control study conducted between June and October 2020 aimed to: (i) describe dietary patterns of adolescents with chronic conditions compared to healthy controls and (ii) determine associations between food consumption, health-related quality of life (HRQL) and sleep quality during the COVID-19 pandemic. Participants (184 immunocompromised and 58 healthy adolescents, aged 14.3 [SD 2.5]) responded to HRQL and sleep validated instruments (PedsQL and PSQI) and three 24 h food recalls via online software. Adjusted linear and logistic regressions were used to assess differences in dietary patterns and associations between food consumption (according to Nova classification) and HRQL and sleep quality. Adolescents with gastrohepatic, rheumatic, and kidney diseases had an improved dietary pattern vs. their healthy peers, showing greater consumption of unprocessed and minimally processed foods (unstandardized coefficient (b) = 7.35%[95%CI 1.59; 13.1]; b = 15.10%[95%CI 7.00; 23.1]; and b = 11.2%[95%CI 5.68; 16.8]), and lower consumption of ultraprocessed foods (b = −7.53%[95%CI-12.90; −2.18]; b = −11.4%[95%CI-18.90; −3.94]; b = −10.8%[95%CI-16.00; −5.68]). Consumption of culinary ingredients was associated with reduced psychological HRQL in controls (standardized coefficient (β) = −0.26[95%CI-0.52; −0.004]), and processed food consumption was associated with improved sleep latency in immunocompromised participants (β = 0.16[95%CI 0.01; 0.31]). These findings suggest diet quality may play a role in HRQL and sleep quality in this population, and may be relevant for clinical practitioners and policy makers when considering the importance of dietary quality in immunocompromised youths.

Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. FH deficiency is a rare condition that causes unregulated C3 consumption, leading to an increased susceptibility to infections and glomerulopathies. Our previous studies have demonstrated a FH deficient patient carrying a c.452G > A, p.R127H FH mutation which leads to a misfolded protein and its retention in the endoplasmic reticulum. In his cultured fibroblasts, FH-delayed secretion was partially rescued when treated with curcumin, and once secreted, exhibited normal regulatory function. Here, we report a childhood-onset systemic lupus erythematosus (cSLE) in this FH deficient patient and the results of experimental treatment with curcumin aiming to rescue FH secretion and regulatory activity.

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p

Objectives: To evaluate mortality in adolescents and young adult patients with chronic diseases followed in a Latin American tertiary hospital. Methods: A cross‐sectional retrospective study was performed in a tertiary/academic hospital in the state of São Paulo, Brazil. Death occurred in 529/2850 (18.5%) adolescents and young adult patients with chronic diseases, and 25/529 (4.7%) were excluded due to incomplete medical charts. Therefore, 504 deaths were evaluated. Results: Deaths occurred in 316/504 (63%) of early adolescent patients and in 188/504 (37%) of late adolescent/young adult patients. Further comparisons between early adolescents (n = 316) and late adolescent/young adult patients (n = 188) with pediatric chronic diseases at the last hospitalization showed that the median disease duration (22.0 [0–173] vs. 43.0 [0–227] months, p

Abstract Background To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups. Conclusions To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Objective: The objective of this study was to evaluate the health‐related quality of life in children and adolescents with autoimmune hepatitis. Methods: A cross‐sectional assessment with the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy controls. Demographic data, prednisone dose, disease remission state, disease severity, and abdominal pain were also evaluated. Results: Based on the child self‐reports, physical, emotional, school, and total scores were significantly lower in autoimmune hepatitis patients when compared with controls (p 0.05). Autoimmune hepatitis patients who received a prednisone dose below 0.16 mg/kg/day at the time of the interview showed significantly higher physical scores than those who received a dose similar to or above 0.16 mg/kg/day (87.5 [50–100] vs. 75 [15.63–100], p = 0.006). Conclusions: Reduced scores in the physical, emotional, and school domains were observed in pediatric autoimmune hepatitis patients compared to control patients. Abdominal pain and corticosteroid dose negatively influenced the health‐related quality of life in children and adolescents with autoimmune hepatitis. Resumo: Objetivo: Avaliar a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune (HAI). Métodos: Foi concluída uma avaliação transversal com o Inventário Pediátrico de Qualidade de Vida 4.0 (PedsQL 4.0) para 80 pacientes com hepatite autoimune e 45 controles saudáveis. Os dados demográficos, a dose de prednisona, o estado de remissão da doença, a gravidade da doença e dor abdominal também foram avaliados. Resultados: Com base nos autorrelatos das crianças, os escores físico, emocional, escolar e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Com base nos relatos dos pais, apenas os escores físico e total foram significativamente menores em pacientes com hepatite autoimune em comparação com os controles (p < 0,05). Uma análise adicional em pacientes com hepatite autoimune com dor abdominal no mês passado revelou escores médios físico, social e total significativamente menores (p < 0,05). Nenhuma diferença foi observada com base no estado de remissão da doença ou na gravidade da doença (p > 0,05). Os pacientes com hepatite autoimune que receberam uma dose de prednisona abaixo de 0,16 mg/kg/dia no momento da entrevista mostraram escores físicos significativamente maiores que os que receberam uma dose semelhante ou acima de 0,16 mg/kg/dia [87,5 (50‐100) em comparação com 75 (15,63‐100), p = 0,006]. Conclusões: Escores reduzidos nos domínios físico, emocional e escolar foram observados em pacientes pediátricos com hepatite autoimune em comparação com pacientes do grupo de controle. Dor abdominal e dose de corticosteroide influenciaram negativamente a qualidade de vida relacionada à saúde em crianças e adolescentes com hepatite autoimune. Keywords: Quality of life, Autoimmune hepatitis, Childhood, Adolescence, Chronic disease, PedsQL 4.0, Palavras‐chave: Qualidade de vida, Hepatite autoimune, Infância, Adolescência, Doença crônica, PedsQL 4.0

OBJECTIVES: Previous studies focusing on pediatric patients hospitalized with severe coronavirus disease 2019 (COVID-19) have been limited to small case series. We aimed to evaluate the characteristics of a large population of pediatric patients with severe COVID-19 and compare them with patients with severe cases of influenza and other respiratory viruses (ORV). METHODS: We performed a cross-sectional study of Brazilian data from the National Epidemiological Surveillance Information System, gathered from January 1st to July 14th, 2020. The sample included 4,784 patients (2,570 with confirmed COVID-19, 659 with influenza, 1,555 with ORV). Outcome measures included clinical features, preexisting comorbidities, pediatric intensive care unit admissions, need for ventilatory support, and death. RESULTS: Compared with the influenza and ORV groups, the COVID-19 group had a higher proportion of newborns and adolescents, as well as lower frequencies of fever, cough, dyspnea, respiratory distress, and desaturation. Although use of invasive ventilatory support was similar among groups, death rate was highest for COVID-19 (15.2% vs. 4.5% vs. 3.2%, p

Abstract Objective To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni’s correction (p 0.0033). Conclusions Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.

Abstract 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

Abstract Objective To characterize scrotal involvement in children and adolescents with IgA vasculitis. Methods A cross-sectional retrospective study included 296 IgA vasculitis (EULAR/PRINTO/PRES criteria) patients, 150/296 (51%) were males and assessed by demographic/clinical/laboratory and treatments. Scrotal involvement was defined by the presence of scrotal edema and/or pain/tenderness in physical examination and/or testicular Doppler ultrasound abnormalities. Results Scrotal involvement was observed in 28/150 (19%) IgA vasculitis patients. This complication was evidenced at IgA vasculitis diagnosis in 27/28 (96%). Acute recurrent scrotal involvement was observed in 2/150 (1%) and none had chronic subtype. Further analysis of patients with scrotal involvement at first episode (n = 27) compared to those without this complication (n = 122) revealed that the median age at diagnosis [4.0 (2.0–12) vs. 6 (1.3–13) years, p = 0.249] was similar in both groups. The frequency of elevated serum IgA was significantly lower in IgA vasculitis patients with scrotal involvement versus without this manifestation (18% vs. 57%, p = 0.017), whereas glucocorticoid (93% vs. 49%, p

Abstract Background Association between periodontal disease and dyslipidemia was recently reported in healthy adults. However, a systematic evaluation of concomitant periodontal diseases and lipid profile was not carried out in juvenile dermatomyositis (JDM). A cross-section study was performed in 25 JDM patients and 25 healthy controls, assessing demographic data, periodontal evaluation, fasting lipoproteins and anti-lipoprotein lipase antibodies. Disease parameters, laboratorial tests and treatment were also evaluated in JDM patients. Results The mean current age was similar in patients and controls (11.5 ± 3.75 vs. 11.2 ± 2.58 years,p = 0.703). Regarding lipid profile, the median triglycerides [80(31–340) vs. 61(19–182)mg/dL,p = 0.011] and VLDL[16(6–68) vs. 13(4–36)mg/dL,p = 0.020] were significantly higher in JDM patients versus controls. Gingival vasculopathy pattern was significantly higher in the former group (60% vs. 0%,p = 0.0001), as well as the median of gingival bleeding index (GBI) [24.1(4.2–69.4) vs. 11.1(0–66.6)%,p = 0.001] and probing pocket depth (PPD) [1.7(0.6–2.4) vs.1.4(0–2.12)mm,p = 0.006]. Comparison between JDM patients with and without dyslipidemia revealed that the median of dental plaque index (PI) [100(26.7–100) vs. 59(25–100)%,p = 0.022], PPD[1.9(0.6–2.4) vs. 1.4(1.2–1.8)mm,p = 0.024] and clinical attachment level (CAL) [1.31(0.7–1.7) vs. 0.8(0.6–1.7)mm,p = 0.005] were significantly higher in patients with dyslipidemia. Further analysis between JDM patients with and without gingivitis revealed that the median of current age [12.4 (8.3–18.4) vs. 9.2 (5.5–17.5) years, p = 0.034] and disease duration [7.09 ± 3.07 vs. 3.95 ± 2.1 years, p = 0.008] were significantly higher in the former group. Conclusion Our study showed that gingival inflammation seems to be related to dyslipidemia in JDM patients, suggesting underlying mechanisms for both complications.

Objective: To describe the characteristics of children and adolescentes with chronic diseases of outpatient clinics at a tertiary university hospital. Methods: A cross‐sectional study was performed with 16,237 patients with chronic diseases followed‐up in one year. The data were collected through the electronic system, according to the number of physician appointments in 23 pediatric specialties. Patients were divided in two groups: children (0–9 years) and adolescents (10–19 years). Early (10–14 years) and late (15–19 years) adolescent groups were also analyzed. Results: Of the total sample, 56% were children and 46% were adolescents. The frequencies of following pediatric specialties were significantly higher in adolescents when compared with children: cardiology, endocrinology, hematology, nephrology/renal transplantation, neurology, nutrology, oncology, palliative and pain care, psychiatry, and rheumatology (p

Abstract Objective To evaluate alcohol, smoking and/or illicit drug use, and history of bullying in adolescent childhood-onset systemic lupus erythematosus and healthy controls. Methods 174 adolescents with pediatric rheumatic diseases were selected. All of the 34 childhood-onset systemic lupus erythematosus patients and 35 healthy controls participated in this study. A cross-sectional study included demographic/anthropometric data and puberty markers assessments; structured questionnaire and CRAFFT screening interview. Results McNemar tests indicated an excellent test–retest reliability of the structured questionnaire (p = 1.0). The median current age was similar between childhood-onset systemic lupus erythematosus patients and controls [15 (12–18) vs. 15 (12–18) years, p = 0.563]. The median of menarche age was significantly higher in childhood-onset systemic lupus erythematosus patients compared to controls [12 (10–15) vs. 11.5 (9–15) years, p = 0.041], particularly in those that lupus had occurred before first menstruation [13 (12–15) vs. 11.5(9–15) years, p = 0.007]. The other puberty marker and sexual function parameters were similar in both groups (p > 0.05). Alcohol use was similar in both childhood-onset systemic lupus erythematosus patients and controls (38% vs. 46%, p = 0.628). A trend of lower frequency of CRAFFT score ≥2 (high risk for substance abuse/dependence) was evidenced in childhood-onset systemic lupus erythematosus patients compared to controls (0% vs. 15%, p = 0.053). Bullying was reported similarly for the two groups (43% vs. 44%, p = 0.950). Further analysis in lupus patients regarding alcohol/smoking/illicit drug use showed no differences in demographic data, puberty markers, history of bullying, sexual function, contraceptive use, disease activity/damage scores, clinical/laboratorial features and treatments (p > 0.05). Conclusion This study showed high frequencies of early alcohol use in lupus adolescents and healthy controls, despite of a possible low risk for substance abuse/dependence in childhood-onset systemic lupus erythematosus patients.

Abstract Introduction One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. Case reports Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. Discussion Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients.

ABSTRACT Objective: To describe the clinical and angiographic characteristics of Takayasu's arteritis in Brazilian children and adolescents. Methods: A retrospective data collection was performed in 71 children and adolescents followed in 10 Brazilian reference centers in Pediatric Rheumatology. The evaluation was carried out in three different time points: from onset of symptoms to diagnosis, from the 6 th to 12th month of diagnosis, and in the last visit. Results: Of 71 selected patients, 51 (71.8%) were girls. The mean age of onset of symptoms and of time to diagnosis was 9.2 (± 4.2) years and 1.2 (± 1.4) years, respectively. At the end of the study, 20 patients were in a state of disease activity, 39 in remission and 5 had evolved to death. The most common symptoms in baseline assessment, second evaluation, and final evaluation were, respectively: constitutional, musculoskeletal, and neurological symptoms. A decrease in peripheral pulses was the most frequent cardiovascular signal, and an increase in erythrocyte sedimentation rate was the most frequent laboratory finding in all three evaluation periods. The tuberculin test was positive in 41% of those tested. Stenosis was the most frequent angiographic lesion, abdominal artery was the most affected segment, and angiographic type IV the most frequent. Most (90%) participants were treated with glucocorticoids, 85.9% required another immunosuppressive drug, and 29.6% underwent angioplasty. Conclusion: This is the largest study on juvenile-onset Takayasu arteritis, and a high number of patients under the age of 10 years, with predominance of constitutional symptoms early in the disease, was observed.

Resumo Introdução Ictiose arlequim é uma doença cutânea congênita grave, autossômica e rara, caracterizada por ressecamento excessivo da pele e hiperqueratose. A associação de ictiose com esclerose sistêmica foi descrita em apenas três crianças. Ainda não foi descrito nenhum paciente com morfeia generalizada (MG) associada à ictiose arlequim. Relato de caso: Menina de quatro anos e seis meses de idade com diagnóstico de ictiose arlequim baseado em espessamento cutâneo difuso, com fissuras, descamação, eritema e sangramento da lesão desde as primeiras horas de vida. A paciente foi tratada com acitretina (1,0 mg/kg/dia) e creme emoliente. Aos três anos e nove meses, desenvolveu contraturas musculares com dor à movimentação e limitação nos cotovelos e joelhos e placas esclerodérmicas difusas no abdômen, nas costas, na região suprapúbica e nas extremidades inferiores. A biópsia de pele mostrou epiderme retificada e hiperqueratose leve, derme reticular com linfócitos, infiltrado mononuclear perivascular e perianexial e esclerose da derme reticular e glândula sudorípara rodeada por um tecido colágeno denso, compatível com esclerodermia. A paciente preencheu os critérios para o subtipo MG. Metotrexato e prednisona foram introduzidos. Aos quatro anos e três meses, apresentou novas lesões esclerodérmicas, associando-se azatioprina à terapêutica anterior, sem resposta após dois meses. Discussão: Um caso de ictiose arlequim associada à MG foi descrito. O tratamento dessas duas condições é um desafio e requer uma equipe multidisciplinar.

RESUMOObjetivo:Avaliar a qualidade de vida relacionada à saúde (QVRS) em pacientes pediátricos com hanseníase.Métodos:Estudo transversal com 47 pacientes com hanseníase e 45 indivíduos saudáveis. A QVRS foi mensurada pelo Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) e os domínios físico, emocional, social e escolar foram avaliados. Os pacientes com hanseníase foram classificados pelos critérios de Ridley e Jopling e avaliados de acordo com manifestações clínicas musculoesqueléticas, laboratoriais e exames radiográficos.Resultados:A média de idade atual foi similar em pacientes com hanseníase e controles [12(6-18) vs. 15(5-18) anos, p = 0,384], assim como frequências do sexo feminino (p = 0,835) e classes socioeconômicas brasileiras média/baixa (p = 1,0). De acordo com a autoavaliação da criança relacionada com as atividades escolares, esse domínio foi significativamente menor nos pacientes com hanseníase em relação aos controles de 13-18 anos [75(45-100) vs. 90(45-100), p = 0,021]. Os outros domínios foram semelhantes em ambos os grupos (p > 0,05). Pelo menos uma manifestação musculoesquelética (artralgia, artrite e/ou mialgia) foi observada em 15% dos pacientes com hanseníase e nenhuma nos controles (p = 0,012). Uma comparação mais detalhada entre pacientes com hanseníase mostrou que a mediana do domínio de capacidade física [81,25(50-100) vs. 98,44(50-100), p = 0,036] e de atividades escolares pela autoavaliação da criança [60(50-85) vs. 80(45-100), p = 0,042] era significantemente menor nos pacientes com manifestações musculoesqueléticas em comparação com a dos pacientes sem essas manifestações. (1) Nenhuma diferença foi evidenciada entre os outros parâmetros de QVRS em ambos os grupos relatados pelos pacientes e pais (p > 0,05).Conclusões:Diminuições dos domínios capacidade física e escolar foram observadas em pacientes com hanseníase pediátrica e manifestações musculoesqueléticas.

RESUMOObjetivoAvaliar as dimensões do fígado e do baço em pacientes com lúpus eritematoso sistêmico de início pediátrico (LESp) e controles saudáveis.MétodosForam submetidos a uma ultrassonografia do abdome 30 pacientes com LESp e 30 voluntários saudáveis controle. Foram feitas duas medições do fígado no lobo hepático esquerdo (craniocaudal e anteroposterior) e três no lobo hepático direito (LHD) (craniocaudal posterior [CCP-LHD], craniocaudal anterior e anteroposterior). Foram também avaliadas três medidas das dimensões do baço: longitudinal, transversal e anteroposterior. Foram avaliados dados demográficos, clínicos e laboratoriais, SLEDAI-2K, ECLAM, SLAM e tratamento.ResultadosA idade média foi semelhante nos pacientes com LESp e controles (170,31 ± 27,81 vs. 164,15 ± 39,25 meses; p = 0,486). A média da dimensão CCP-LHD foi significativamente maior no grupo LESp em comparação com os controles (13,30 ± 1,85 vs. 12,52 ± 0,93, p = 0,044). Não houve diferenças nos outros parâmetros biométricos do fígado e do baço (p > 0,05). Uma análise especifica realizada apenas nos pacientes com LESp de acordo com a dimensão CCP-LHD ≥ 13,3 cm versus < 13,3 cm mostrou que a mediana do SLEDAI-2K [8 (0-18) vs. 2 (0-8), p = 0,004], ECLAM [4 (0-9) vs. 2 (0-5), p = 0,019] e SLAM [5 (1-13) vs. 2 (0-14), p = 0,016] era significativamente maior em pacientes com maior dimensão CCP-LHD, do mesmo modo que a frequência de nefrite (77% vs. 29%, p = 0,010). As enzimas hepáticas foram semelhantes nos dois grupos (p > 0,05). Foi observada uma correlação positiva entre o SLEDAI-2K e a dimensão CCP-LHD (p = 0,001, r = +0,595). Evidenciou-se uma correlação negativa entre a duração da doença e a dimensão longitudinal do baço (p = 0,031, r = −0,394).ConclusãoOs dados levantam a possibilidade de que a atividade da doença pode levar a uma hepatomegalia subclínica e localizada durante o curso da doença. A duração da doença resultou em atrofia do baço em pacientes com LESp.

Introdução: As manifestações clínicas da deficiência de imunoglobulina A (DIgA) incluem infecções recorrentes, atopia e doenças autoimunes. No entanto, para o nosso conhecimento, as avaliações concomitantes de doenças autoimunes e autoanticorpos em uma coorte de pacientes com DIgA com idade atual > 10 anos e seus parentes não foram feitas. Objetivos: Avaliar doenças autoimunes e presença de autoanticorpos em pacientes com DIgA e seus parentes de primeiro grau. Métodos: Estudo transversal feito em 34 pacientes com DIgA (idade atual > 10 anos) e em seus parentes de primeiro grau. Todos foram acompanhados em um centro terciário brasileiro para imunodeficiência primária: 27 crianças/adolescentes e sete de seus parentes de primeiro grau com diagnóstico tardio de DIgA. Doenças autoimunes e autoanticorpos (anticorpos antinucleares, fator reumatoide e antitireoglobulina, antitiroperoxidase e anticorpos antiendomísio da classe IgA) também foram avaliadas. Resultados: Doenças autoimunes (n = 14) e/ou autoanticorpos (n = 10, quatro deles com autoanticorpos isolados) foram observadas em 18/34 (53%) dos pacientes e seus parentes. As doenças autoimunes mais comuns encontradas foram tireoidite (18%), artrite crônica (12%) e doença celíaca (6%). Os autoanticorpos mais frequentes foram anticorpos antinucleares (2%), antitireoglobulina e/ou antitireoperoxidase (24%). Nenhuma diferença significativa foi observada no sexo feminino, idade no momento do diagnóstico e idade atual em pacientes com DIgA com e sem doenças autoimunes e/ou presença de autoanticorpos (p > 0,05). As frequências de imunodeficiência de primárias na família, autoimunidade em família, atopia e infecções recorrentes foram semelhantes em ambos os grupos (p> 0,05). Conclusão: Doenças autoimunes e autoanticorpos foram observadas em pacientes com DIgA durante o acompanhamento, o que reforça a necessidade de um acompanhamento rigoroso e contínuo durante a adolescência e a idade adulta.

OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3′ non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p

ABSTRACT Human toxocariasis is a parasitic zoonosis mainly caused by Toxocara canis or Toxocara catiand is acquired by ingestion of the parasite’s embryonated eggs. Arthralgia and/or arthri-tis were reported in up to 17% of the cases, generally with acute duration (less than 6weeks). However, to our knowledge, chronic polyarthritis, as the isolated presentation ofToxocara infection, was not reported. One of the 5809 patients that was followed up at ourservice (0.017%) had chronic polyarthritis as the single manifestation of toxocariasis and wasdescribed herein. A 3-year-old girl was referred to our service with severe painful chronicpolyarthritis for a period longer than 10 weeks and morning stiffness of 30 min. Dog contactexposure history in the recreational areas of neighborhood was reported. Her exams showedhigh levels of eosinophils in peripheral blood (29%), bone marrow aspirate revealed markedeosinophilia (32%) and Toxocara enzyme-linked immunosorbent assay (Elisa) was positive(1:1280). She was treated with paracetamol (40 mg/kg/day) and thiabendazole (25 mg/kg/day)for 10 days, and all manifestations reduced. After eight months of follow-up, she was onclinical and laboratorial remission. In conclusion, we described a case of chronic polyarthri-tis, as isolated manifestation of toxocariasis, mimicking juvenile idiopathic arthritis andleukemia. Importantly, this zoonosis should be considered in patients with arthritis andeosinophilia.

Resumo A piomiosite é uma infecção piogênica da musculatura esquelética, decorrente da disseminação hematogênica e geralmente acompanhada de formação de abscesso localizado. Esta infecção da musculatura é raramente descrita em adultos com lúpus eritematoso sistêmico (LES) e, até onde se sabe, ainda não o foi em pacientes com LES juvenil (LESJ). De nossos 289 pacientes com LESJ, uma apresentou piomiosite. Diagnosticada com LESJ aos 10 anos de idade e após seis anos de tratamento com prednisona, azatioprina e hidroxicloroquina, a paciente foi hospitalizada em razão de um histórico de 30 dias de dor insidiosa na coxa esquerda, sem relato algum de trauma aparente ou febre. O exame físico mostrou músculos sensíveis e com endurecimento lenhoso. Os exames laboratoriais revelaram anemia, aumento de reagentes de fase aguda e enzimas musculares normais. A tomografia computadorizada da coxa esquerda mostrou coleção no terço médio do vasto intermédio, sugerindo estágio purulento de piomiosite. Iniciou-se tratamento com antibiótico de largo espectro, que levou à resolução clínica completa. Em suma, descreveu-se o primeiro caso de piomiosite em pacientes com LESJ encontrado neste serviço. Este relato reforça que a presença de dor muscular localizada em pacientes imunocomprometidos, ainda que sem aumento de enzimas musculares, deve sugerir o diagnóstico de piomiosite. Recomenda-se tratamento imediato com antibióticos.

A doença de Kikuchi-Fujimoto (DKF) é uma linfadenite necrosante histiocítica autolimitante de origem desconhecida. É digno de nota que a DKF era apenas pouco frequentemente comunicada em pacientes com lúpus eritematoso sistêmico (LES), com rara ocorrência em pacientes com LES juvenil (LESJ). Até onde vai nosso conhecimento, ainda não foi estudada a prevalência de DKF na população pediátrica lúpica. Assim, em um período de 29 anos consecutivos, 5.682 pacientes foram acompanhados em nossa instituição e 289 (5%) satisfaziam os critérios de classificação do American College of Rheumatology para LES; um sofria DKF isolado (0,03%) e apenas um padecia de DKF associada a diagnósticos de LESJ; este caso foi descrito no presente artigo. Uma jovem com 12 anos de idade apresentava-se com febre alta, fadiga e linfadenopatia cervical e axilar. Os anticorpos antinucleares (ANA) estavam negativos, com imunologia positiva para IgM e IgG antivírus do herpes simples tipos 1 e 2. As imagens obtidas por tomografia por emissão de pósitrons com flúor-18-fluoro-desoxi-glicose/tomografia computadorizada (PET/TC) demonstraram linfadenopatia difusa. A biópsia dos linfonodos axilares demonstrou linfadenite necrosante com presença de histiócitos, sem doença linfoproliferativa, compatível com DKF. Transcorridos 30 dias, a paciente apresentou regressão espontânea, não havendo necessidade de tratamento. Nove meses depois, a paciente exibia erupção malar, fotossensibilidade, úlceras orais, linfopenia e ANA 1:320 (padrão nuclear homogêneo). Nessa ocasião, a aplicação do Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (Índice de Atividade de Doença/LES 2000) teve um escore igual a 10, e a jovem foi tratada com prednisona (1,0 mg/kg/dia) e hidroxicloroquina, demonstrando melhora progressiva dos sinais e sintomas. Em conclusão, DKF é doença benigna e rara em nossa população lúpica pediátrica. Também queremos enfatizar a relevância do diagnóstico de doenças autoimunes durante o acompanhamento de pacientes com DKF.

Gengivite e periodontite são doenças periodontais imunoinflamatórias caracterizadas por infecções localizadas crônicas geralmente associadas a uma inflamação insidiosa. Essa revisão narrativa discute doenças periodontais e mecanismos que influenciam a resposta imune e a autoimunidade na área das doenças reumáticas pediátricas (DRP), particularmente a artrite idiopática juvenil (AIJ), lúpus eritematoso sistêmico juvenil (LESJ) e dermatomiosite juvenil (DMJ). Foi notada maior frequência de gengivite nessas doenças em comparação com controles sadios, enquanto casos de periodontite foram achados raros. Em pacientes com AIJ, a gengivite e a periodontite estavam relacionadas a fatores mecânicos, artrite crônica com incapacitação funcional, desregulação da resposta imunoinflamatória, dieta e medicamentos, principalmente corticosteroides e ciclosporina. Em pacientes com LESJ, a gengivite estava associada a períodos mais longos da doença, doses elevadas de corticosteroides, hiperativação dos linfócitos B e elevação da imunoglobulina G. São escassos os dados sobre doenças periodontais na população com DMJ; nos pacientes ativos, foi observado um padrão gengival singular, caracterizado por eritema gengival, dilatação dos capilares e formação arbustiforme. Em conclusão, gengivite foi a doença periodontal mais comum em pacientes com DRP. A associação observada com a atividade da doença reforça a necessidade de futuros estudos, com o intuito de determinar se a resolução dessa complicação irá influenciar o curso ou a gravidade da doença.

Cryptococose é uma infecção fúngica causada pelo Cryptococcus neoformans, geralmente associada com imunodeficiências e drogas imunossupressoras, e foi raramente descrita em pacientes com lúpus eritematoso sistêmico (LES), particularmente em LES juvenil (LESJ). De janeiro de 1983 a Junho de 2011, 5,604 pacientes foram seguidos em nosso Hospital Universitário e 283 (5%) casos preencheram critérios de classificação diagnóstica do Colégio Americano de Reumatologia para LESJ. Apenas um (0.35%) destes apresentou meningite criptocócica. Esta paciente teve diagnostico de lúpus aos 10 anos de idade. Aos 15 anos, ela apresentou cefaleia, náuseas e vômitos durante 5 dias, sem febre, após viagem a região de cavernas. Neste momento, ela estava em uso de prednisona 10 mg/dia, azatioprina e hidroxicloroquina. Foi realizada punção lombar e a tintura da Índia foi positiva para cryptococo, a cultura do liquido cerebroespinhal também foi positiva para Cryptococcus neoformans e a pesquisa de antígeno cryptocócico sérico foi positiva em título de 1:280. Azatioprina foi suspensa e anfotericina B liposomal (3 mg/Kg/dia) foi iniciada. No entanto, quatro dias após ela desenvolveu amaurose e coma. A tomografia computadorizada de crânio demonstrou áreas isquêmicas e nódulos sugestivos de infecção fúngica. Após quatro dias, ela desenvolveu sepse grave e vancomicina e meropenem foram iniciados, entretanto foi a óbito devido choque séptico. Portanto, meningite cryptocócica foi uma rara e grave infecção oportunista em uma população de lúpus juvenil. Este estudo reforça a importância do diagnóstico precoce e da pronta introdução de agentes antifúngicos, principalmente em pacientes com história de contato com excrementos de pássaros.

INTRODUÇÃO: A reumatologia pediátrica (RP) é uma especialidade emergente, com número restrito de especialistas, e ainda não conta com uma casuística brasileira sobre o perfil dos pacientes atendidos e as informações sobre a formação de profissionais capacitados. OBJETIVO: Estudar o perfil dos especialistas e dos serviços em RP e as características dos pacientes com doenças reumáticas nessa faixa etária a fim de estimar a situação atual no estado de São Paulo (ESP). PACIENTES E MÉTODOS: No ano de 2010 o departamento científico de RP da Sociedade de Pediatria de São Paulo encaminhou um questionário respondido por 24/31 especialistas com título de especialização em RP que atuam no ESP e por 8/12 instituições com atendimento nesta especialidade. RESULTADOS: A maioria (91%) dos profissionais exerce suas atividades em instituições públicas. Clínicas privadas (28,6%) e instituições (37,5%) relataram não ter acesso ao exame de capilaroscopia e 50% das clínicas privadas não tem acesso à acupuntura. A média de tempo de prática profissional na especialidade foi de 9,4 anos, sendo 67% deles pós-graduados. Sete (87,5%) instituições públicas atuam na área de ensino, formando novos reumatologistas pediátricos. Cinco (62,5%) delas têm pós-graduação. Dois terços dos especialistas utilizam imunossupressores e agentes biológicos de uso restrito pela Secretaria da Saúde. A doença mais atendida foi artrite idiopática juvenil (29,1%-34,5%), seguida de lúpus eritematoso sistêmico juvenil (LESJ) (11,6%-12,3%) e febre reumática (9,1%-15,9%). Vasculites (púrpura de Henoch Schönlein, Wegener, Takayasu) e síndromes autoinflamatórias foram mais incidentes nas instituições públicas (P = 0,03; P = 0,04; P = 0,002 e P < 0,0001, respectivamente). O LESJ foi a doença com maior mortalidade (68% dos óbitos), principalmente por infecção. CONCLUSÃO: A RP no ESP conta com um número expressivo de especialistas pós-graduados, que atuam especialmente em instituições de ensino, com infraestrutura adequada ao atendimento de pacientes de alta complexidade.

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria) were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years). In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively). Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively). Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42) and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72) were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study emphasizes the importance of investigating leukemia in patients presenting with musculoskeletal manifestations and, in particular, limb pain associated with thrombocytopenia.

OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p>0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding, and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population.

ABSTRACT Objective: To evaluate alcohol/tobacco/illicit drug use and sexual function in adolescent juvenile idiopathic arthritis (JIA) and healthy controls. Methods: 174 adolescents with pediatric rheumatic diseases were selected. A cross-sectional study with 54 JIA patients and 35 controls included demographic/anthropometric data and puberty markers assessments, physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk and a questionnaire that evaluated sexual function, bullying and alcohol/tobacco/illicit drug use. Clinical/laboratorial data and treatment were also assessed in JIA. Results: The median current age was similar between JIA patients and controls [15(10–19) vs. 15(12–18) years, p = 0.506]. Frequencies of alcohol/tobacco/illicit drug use were high and similar in both JIA and controls (43% vs. 46%, p = 0.829). However, age at alcohol onset was significantly higher in those with JIA [15(11–18) vs. 14(7–18) years, p = 0.032], particularly in polyarticular onset (p = 0.040). High risk for substance abuse/dependence (CRAFFT score ≥ 2) was found in both groups (13% vs. 15%, p = 1.000), likewise bullying (p = 0.088). Further analysis of JIA patients regarding alcohol/tobacco/illicit drug use showed that the median current age [17(14–19) vs. 13(10–19)years, p < 0.001] and education years [11(6–13) vs. 7(3–12)years, p < 0.001] were significant higher in those that used substances. Sexual activity was significantly higher in the former group (48% vs. 7%, p < 0.001). A positive correlation was evidenced between CRAFFT score and current age in JIA patients (p = 0.032, r = +0.296). Conclusion: A high risk for substance abuse/dependence was observed in both JIA and controls. JIA substance users were more likely to have sexual intercourse. Therefore, routine screening is suggested in all visits of JIA adolescents.

ABSTRACT Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC.

Abstract Objective: To assess esophageal involvement (EI) in juvenile localized scleroderma (JLS) population and the possible association between this gastrointestinal manifestation and demographic data, clinical features, laboratory exams, treatments and outcomes. Methods: For a period of 30 years, 5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology Division. EI was defined by the presence of symptoms (solid/liquid dysphagia, heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia) and confirmed by at least one EI exam abnormality: barium contrast radiography, upper gastrointestinal endoscopy and 24-hour esophageal pH-monitoring. Results: JLS was observed in 56/5881 patients (0.9%), mainly linear morphea subtype. EI was observed in 23/56(41%) of JLS patients. Eight(35%) of 23 EI patients with JLS were symptomatic and presented heartburn(5/8), solid and liquid dysphagia(3/8), nausea and epigastralgia(1/8). The frequency of any cumulative extracutaneous manifestations (calcinosis, arthritis/arthralgia, central nervous system, interstitial pneumonitis, mesangial nephritis and/or arrhythmia) was significantly higher in JLS patients with EI compared to those without this complication (56% vs. 24%, p = 0.024). No differences were evidenced in demographic data, JLS subtypes and in each extracutaneous manifestation in both groups (p > 0.05). The frequency of methotrexate use was significantly higher in JLS patients with EI compared to those without (52% vs. 12%, p = 0.002). Autoantibody profile (antinuclear antibodies, anti-SCL-70, rheumatoid factor, anticentromere, anti-cardiolipin, anti-Ro/SSA and anti-La/SSB) was similar in both groups (p > 0.05). Conclusions: Our study demonstrated that EI was frequently observed in JLS patients, mainly in asymptomatic patients with linear subtype. EI occurred in JLS patients with other extracutaneous manifestations and required methotrexate therapy.

ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA), 47 with ankylosing spondylitis (AS), 36 with juvenile idiopathic arthritis (JIA), 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35%) male and mean disease duration of 15 ± 10 years. Sixty-four (33%) patients were receiving adalimumab, 59 (30%) etanercept and 71 (36%) infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5%) patient had localized fungal infection (vaginal candidiasis). None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

Abstract Objectives: To evaluate, in an endemic country, the long-term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers. Methods: This was a retrospective cohort that included JIA patients eligible to anti-TNF therapy. Patients were screened for LTBI prior to anti-TNF using tuberculin skin test (TST), chest X-ray and history of exposure to TB. Subjects were regularly followed at 2-month intervals. Results: Sixty-nine JIA patients with current age of 17.4 ± 5.8 years, mean disease duration of 5.0 ± 4.9 years were included. Forty-seven patients received a single anti-TNF, while 22 patients switched to another anti-TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST-positive and history of TB exposure and two had solely TST-positive. No active TB was diagnosed during the study period (median of follow-up was 3.8 years). Conclusion: Long-term evaluation revealed that LTBI screening and primary prophylaxis before anti-TNF treatment was effective in a high-risk country and TST was the most sensitive parameter to identify these patients.

ABSTRACT Childhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory brain disease of unknown etiology. Of note, brain hemorrhage has been rarely reported in cPACNS patients, generally associated with a delayed clinical diagnosis, or with a diagnosis only at necropsy. We present the case of a boy with cPACNS that previously suffered an ischemic stroke. At the age of 7 years and 10 months, he presented a sudden and severe headache, vomiting and reduction in consciousness level (Glasgow coma scale 7), requiring prompt tracheal intubation. Brain computed tomography demonstrated intraparenchymal hematoma in the right parieto-occipital lobe and a small focus of bleeding in the right frontal lobe, vasogenic edema, herniation of the uncus and a 10 mm deviation to the left from the midline. C-reactive protein (9.2 mg/dL) and von Willebrand factor (vWF) antigen (202%) were elevated. Decompressive craniotomy was performed and methylprednisolone and cyclophosphamide were administered. One week later, the patient had left hemiparesis without other sequelae. Importantly, motor deficits have been improving progressively. Our case reinforces the inclusion of this vasculitis as a differential diagnosis in children and adolescents with CNS hemorrhage.