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

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

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

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

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

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

Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. METHODS: Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. RESULTS: Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. CONCLUSION: Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

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

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

Features of 847 Childhood-Onset Systemic Lupus Erythematosus Patients in Three Age Groups at Diagnosis: A Brazilian Multicenter Study.

OBJECTIVE: To evaluate demographic data and clinical and laboratory features at disease diagnosis in 3 different age groups of childhood-onset systemic lupus erythematosus (SLE): group A, early-onset (<6 years); group B, school age (≥6 to <12 years); and group C, adolescent (≥12 to <18 years). METHODS: This was a Brazilian multicenter cohort retrospective study in 10 pediatric rheumatology centers, including 847 childhood-onset SLE patients. RESULTS: Patients were divided into 3 groups: group A with 39 patients (4%), group B with 395 patients (47%), and group C with 413 patients (49%). Of 39 childhood-onset SLE patients in group A, 3 (8%) were ages <2 years, 4 (10%) were ≥2 to <3 years, and 32 (82%) were ≥3 and <6 years. A total of 74 childhood-onset SLE patients were analyzed for C1q levels, and complete C1q deficiency was observed in 3 of 74 patients (4%), all in group A. Groups were similar regarding high frequencies of female sex, nephritis, neuropsychiatric involvement, Systemic Lupus Erythematosus Disease Activity Index 2000 score ≥8, autoantibody profile, elevated acute phase proteins, and low complement levels (P > 0.05). However, the frequency of fever (78% versus 61% versus 47%; P < 0.0001), hepatomegaly (42% versus 29% versus 14%; P < 0.0001), splenomegaly (28% versus 12% versus 4%; P < 0.0001), and discoid lupus (13% versus 4% versus 4%; P = 0.020) was significantly higher in group A compared to groups B and C. The frequency of weight loss >2 kg (19% versus 28% versus 36%; P = 0.017), photosensitivity (34% versus 41% versus 51%; P = 0.006), leukopenia <4,000/mm3 (14% versus 25% versus 30%; P = 0.048), and lymphopenia <1,500/mm3 (22% versus 41% versus 47%; P = 0.011) was significantly lower in group A. CONCLUSION: Our large multicenter study identified the finding that the initial appearance of childhood-onset SLE is characterized by comparable high frequency of internal organ involvement and some distinct clinical and laboratory features in early-onset and adolescent groups.

Prospective surveillance study of acute respiratory infections, influenza-like illness and seasonal influenza vaccine in a cohort of juvenile idiopathic arthritis patients.

BACKGROUND: Acute respiratory infections (ARI) are frequent in children and complications can occur in patients with chronic diseases. We evaluated the frequency and impact of ARI and influenza-like illness (ILI) episodes on disease activity, and the immunogenicity and safety of influenza vaccine in a cohort of juvenile idiopathic arthritis (JIA) patients. METHODS: SURVEILLANCE OF RESPIRATORY VIRUSES WAS CONDUCTED IN JIA PATIENTS DURING ARI SEASON (MARCH TO AUGUST) IN TWO CONSECUTIVE YEARS: 2007 (61 patients) and 2008 (63 patients). Patients with ARI or ILI had respiratory samples collected for virus detection by real time PCR. In 2008, 44 patients were immunized with influenza vaccine. JIA activity index (ACRPed30) was assessed during both surveillance periods. Influenza hemagglutination inhibition antibody titers were measured before and 30-40 days after vaccination. RESULTS: During the study period 105 ARI episodes were reported and 26.6% of them were ILI. Of 33 samples collected, 60% were positive for at least one virus. Influenza and rhinovirus were the most frequently detected, in 30% of the samples. Of the 50 JIA flares observed, 20% were temporally associated to ARI. Influenza seroprotection rates were higher than 70% (91-100%) for all strains, and seroconversion rates exceeded 40% (74-93%). In general, response to influenza vaccine was not influenced by therapy or disease activity, but patients using anti-TNF alpha drugs presented lower seroconversion to H1N1 strain. No significant differences were found in ACRPed30 after vaccination and no patient reported ILI for 6 months after vaccination. CONCLUSION: ARI episodes are relatively frequent in JIA patients and may have a role triggering JIA flares. Trivalent split influenza vaccine seems to be immunogenic and safe in JIA patients.

Vaccination practice in children with rheumatic disease.

INTRODUCTION/OBJECTIVES: Evaluate clinical practice through assessment of vaccination card and recommendation of specific vaccines in pediatric patients with rheumatic diseases in use of different drugs and reveal the possible association between vaccination frequency and time of the clinical practice of pediatric rheumatologists in the state of São Paulo. MATERIAL AND METHODS: A questionnaire was sent to pediatric rheumatologists of the Departamento de Reumatologia da Sociedade de Pediatria de São Paulo. This instrument included questions about practice time on Pediatric Rheumatology, vaccination of patients with juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and immunization according to the treatments used. RESULTS: Vaccination card was seen by 100% of the professionals at the first visit and by 36% annually. Vaccines of live agents were not recommended for patients with JSLE, JIA, and JDM in 44%, 64%, and 48%, respectively. The professionals were divided into two groups: Group A (≤ 15 years of practice, n = 12) and B (≥ 16 years, n = 13). No statistical difference was observed in the use of live agent vaccine and vaccines with inactivated agents or protein components in the two treatment groups (P > 0.05). Moreover, the groups had similar opinion regarding severity of immunosuppression in patients with JSLE, JIA, and JDM (with or without activity) and treatment used (P > 0.05). CONCLUSIONS: The frequency of immunization by pediatric rheumatologists in São Paulo is low, especially after the first visit, and not influenced by time of professional practice.

Prática de vacinação em crianças com doenças reumáticas / Vaccination practice in children with rheumatic disease

INTRODUÇÃO/OBJETIVOS: Avaliar a prática clínica com relação à verificação do cartão vacinal e à indicação de vacinas específicas em pacientes com doenças reumáticas pediátricas em uso de diferentes drogas, e evidenciar a possível associação entre frequência de vacinação e tempo de prática clínica dos reumatologistas pediátricos do estado de São Paulo. MATERIAL E MÉTODOS: Um questionário foi enviado para os reumatologistas pediátricos do Departamento de Reumatologia da Sociedade de Pediatra de São Paulo. Esse instrumento incluiu questões sobre tempo de prática em Reumatologia Pediátrica, vacinação de pacientes com Lúpus Eritematoso Sistêmico Juvenil (LESJ), artrite idiopática juvenil (AIJ), dermatomiosite juvenil (DMJ) e imunização de acordo com os tratamentos utilizados. RESULTADOS: Cartão de vacinação foi visto por 100 por cento dos profissionais na primeira consulta e por 36 por cento anualmente. Vacinas de agentes vivos não foram recomendadas para pacientes com LESJ, AIJ e DMJ em 44 por cento, 64 por cento e 48 por cento, respectivamente. Os profissionais foram divididos em dois grupos: A (< 15 anos de prática, n = 12) e B (> 16 anos, n = 13). Nenhuma diferença estatística foi observada no uso de vacinas de agentes vivos e vacinas de agentes inativos ou componentes proteicos em relação ao tratamento nos dois grupos (P > 0,05). Além disso, os grupos foram similares em relação à opinião sobre a gravidade de imunossupressão em pacientes com LESJ, AIJ e DMJ com ou sem atividade e a terapêutica utilizada (P > 0,05). CONCLUSÕES: A frequência de vacinação por reumatologistas pediátricos de São Paulo é baixa, especialmente após a primeira consulta, e não é influenciada pelo tempo de prática profissional.

INTRODUCTION/OBJECTIVES: Evaluate clinical practice through assessment of vaccination card and recommendation of specific vaccines in pediatric patients with rheumatic diseases in use of different drugs and reveal the possible association between vaccination frequency and time of the clinical practice of pediatric rheumatologists in the state of São Paulo. MATERIAL AND METHODS: A questionnaire was sent to pediatric rheumatologists of the Departamento de Reumatologia da Sociedade de Pediatria de São Paulo. This instrument included questions about practice time on Pediatric Rheumatology, vaccination of patients with juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and immunization according to the treatments used. RESULTS: Vaccination card was seen by 100 percent of the professionals at the first visit and by 36 percent annually. Vaccines of live agents were not recommended for patients with JSLE, JIA, and JDM in 44 percent, 64 percent, and 48 percent, respectively. The professionals were divided into two groups: Group A (< 15 years of practice, n = 12) and B (> 16 years, n = 13). No statistical difference was observed in the use of live agent vaccine and vaccines with inactivated agents or protein components in the two treatment groups (P > 0.05). Moreover, the groups had similar opinion regarding severity of immunosuppression in patients with JSLE, JIA, and JDM (with or without activity) and treatment used (P > 0.05). CONCLUSIONS: The frequency of immunization by pediatric rheumatologists in São Paulo is low, especially after the first visit, and not influenced by time of professional practice.

Immunization consensus for children and adolescents with rheumatic diseases / Consenso de imunização para crianças e adolescentes com doenças reumatológicas

Crianças e adolescentes com doenças reumatológicas apresentam maior prevalência de doenças infecciosas quando comparados com a população em geral, em decorrência de atividade da doença, possível deficiência imunológica secundária à própria doença, ou uso de terapia imunossupressora. A vacinação é uma medida eficaz para a redução da morbidade e mortalidade nesses pacientes. O objetivo deste artigo foi realizar um consenso de eficácia e segurança das vacinas em crianças e adolescentes com doenças reumatológicas infantis baseadas em níveis de evidência científica. Imunização passiva para os pacientes e orientações para as pessoas que convivem com doentes imunodeprimidos também foram incluídas. Os 32 pediatras reumatologistas membros do Departamento de Reumatologia da Sociedade de Pediatria de São Paulo (SPSP) e/ou da Comissão de Reumatologia Pediátrica da Sociedade Brasileira de Reumatologia elaboraram o consenso, sendo que alguns desses profissionais estão envolvidos em pesquisas e publicações científicas nesta área. A pesquisa dos termos eficácia e/ou segurança das diferentes vacinas em crianças e adolescentes com doenças reumatológicas foi realizada nas bases de Medline e Scielo, de 1966 até março de 2009, incluindo revisões, estudos controlados e relatos de casos. O grau de recomendação e o nível científico de evidências dos estudos foram classificados em quatro níveis para cada vacina. De um modo geral, as vacinas inativadas e de componentes são seguras nos pacientes com doenças reumatológicas, mesmo em uso de terapias imunossupressoras. Entretanto, vacinas com agentes vivos atenuados são, em geral, contraindicadas para os pacientes imunossuprimidos.

Incidence of infectious diseases is higher in children and adolescents with rheumatic diseases than in the general population due to disease activity, possible immune deficiency secondary to the disease itself, or the use of immunosuppressive drugs. Vaccination is effective in reducing morbidity and mortality in those patients. The objective of this study was to establish an evidence-based consensus on the efficacy and safety of vaccination in children and adolescents with rheumatic diseases. Passive immunization of patients and guidelines for people who live with immunosuppressed patients were also included. The 32 pediatric rheumatologists of the Rheumatology Department of the Pediatrics Society of São Paulo, (SPSP, from the Portuguese), São Paulo, SP, Brazil, and/or the Commission on Pediatrics Rheumatology of the Brazilian Society of Rheumatology are responsible for this consensus; some of those professionals are involved on research and scientific publications in this field. The words efficacy and/or safety of different vaccines in children and adolescents with rheumatologic diseases were searched in Medline and Scielo data bases from 1966 to March 2009, including reviews, controlled studies, and case reports. The degree of recommendation and the scientific evidence of the studies were classified in four levels for each vaccine. As a rule, inactive and protein components vaccines are safe for patients with rheumatologic diseases, even in the presence of immunosuppressive therapy. However, live attenuated vaccines are, in general, contraindicated for immunosuppressed patients.

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

OBJECTIVE: To determine pregnancy outcome and fetal loss risk factors in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: A total of 315 female patients with JSLE followed in 12 Brazilian pediatric rheumatology centers were consecutively selected. Menarche was observed in 298 (94.6%) patients. Patients' medical records were reviewed for pregnancy outcomes and demographic, clinical, and therapeutic data. RESULTS: A total of 24 unplanned pregnancies occurred in 298 (8%) patients. The outcomes were 5 (21%) early fetal losses (prior to 16 wks gestation), 18 (75%) live births, and 1 (4%) death due to preeclampsia and premature birth. The frequencies of active diffuse proliferative glomerulonephritis, proteinuria > or = 0.5 g/day, and arterial hypertension at the beginning of pregnancy were higher in pregnancies resulting in fetal losses than in live births [60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), 60% vs 5% (p = 0.02), respectively]. JSLE pregnancies with fetal losses had a significantly higher mean SLE Disease Activity Index 2000 (SLEDAI-2K) at the start of pregnancy compared with those with live births (9.40 +/- 7.47 vs 3.94 +/- 6.00; p = 0.049). Four pregnancies were inadvertently exposed to intravenous cyclophosphamide therapy for renal involvement despite contraceptive prescriptions, resulting in fetal loss in 3 (p = 0.02). In multivariate analysis only intravenous cyclophosphamide use at start of pregnancy (OR 25.50, 95% CI 1.72-377.93, p = 0.019) remained as an independent risk factor for fetal loss. CONCLUSION: We identified immunosuppressive therapy as the major contributing factor for fetal loss in JSLE, reinforcing the importance of contraception.