Primary dental care treatment in primary Sjögren's syndrome: a possible role in improving salivary flow rate.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory chronic disorder that mainly affects exocrine glands. Additionally, oral infections can aggravate the glandular dysfunction. However, data on primary dental care (PDC) treatment in pSS are scarce. This study aimed to appraise the impact of PDC on the Xerostomia Inventory (XI), unstimulated/stimulated salivary flow rates and salivary cytokine profile in pSS. METHODS: Fifty-two pSS patients and 52 sex- and age-matched control participants without systemic autoimmune diseases were included in a prospective study. At inclusion, all participants were assessed through a standardised protocol, measurement of salivary pro-inflammatory cytokines, and underwent PDC. Dental procedures included: oral hygiene guidance, restorative treatment of caries, surgical removal of residual roots and impacted or partially erupted teeth, cysts, supra and subgingival periodontal scaling and treatment of soft tissue disorders (removal of lesions and treatment of opportunistic infections). After 3 months, the clinical/laboratorial assessments were repeated. RESULTS: At inclusion, the Decayed, Missing and Filled Teeth (DMFT) index was higher in the pSS patients than in the control group (13.3±8.2 vs. 8.6±6.2, p=0.002), whereas periodontal parameters were comparable in both groups (p>0.05). After PDC, 26.9% of pSS patients showed a reduction of at least 6 points (clinical improvement) in XI, but mean XI remained unchanged (p=0.285). PDC resulted in an increase in mean unstimulated (p<0.001) and stimulated (p=0.001) salivary flow rates in pSS, with no change in salivary cytokine profile (p≥0.05). CONCLUSIONS: PDC promoted improvement in unstimulated and stimulated salivary flow rates in pSS. This novel finding reinforces the recommendation of this strategy for pSS patients. CLINICALTRIALS: gov (Identifier: NCT03711214).

COVID-19 quarantine in adolescents with autoimmune rheumatic diseases: mental health issues and life conditions.

OBJECTIVES: To assess mental health and life conditions in adolescents with autoimmune rheumatic diseases (ARDs) and healthy controls quarantined during COVID-19 pandemic. METHOD: A cross-sectional study included 155 ARD adolescents and 105 healthy controls. Online survey included self-reported strengths and difficulties questionnaire (SDQ), and a semi-structured questionnaire with demographic data, daily home and school routine, physical activities, and COVID-19 information during the pandemic. RESULTS: Among patients, 56% had juvenile idiopathic arthritis (JIA), 29% juvenile systemic lupus erythematosus (JSLE), and 15% juvenile dermatomyositis (JDM). No differences were found regarding sex, ethnicity, and current age between ARD patients and controls (p > 0.05). Abnormal emotional SDQ (38% vs. 35%, p = 0.653) were similar in both groups. Logistic regression analyses in ARD patients demonstrated that female (OR = 2.4; 95%CI 1.0-6.0; p = 0.044) was associated with severe emotional SDQ dysfunction, whereas sleep problems were considered as a risk factor for both worse total SDQ (OR = 2.6; 95%CI 1.2-5.5; p = 0.009) and emotional SDQ scores (OR = 4.6; 95%CI 2.2-9.7; p < 0.001). Comparisons between ARD patients with and without current prednisone use showed higher median scores of peer problems in the first group [3 (0-10) vs. 2 (0-7), p = 0.049], whereas similar median and frequencies between JIA, JSLE, and JDM (p > 0.05). CONCLUSIONS: Approximately one third of JIA, JSLE, and JDM patients presented abnormal total and emotional scores of SDQ during COVID-19 quarantine. Sleep problems were the main factor associated with emotional difficulties in these ARD adolescents. The knowledge of mental health issues rates in adolescents with ARD supports the development of prevention strategies, like sleep hygiene counseling, as well as the references of the affected patients to specialized mental health services, as necessary. Key Points • One third of ARD patients presented mental health issues during COVID-19 quarantine • Sleep problems were associated with emotional difficulties. • It is necessary to warn pediatric rheumatologists about the importance of sleep hygiene counseling.

UHPLC-MS/MS Method for Determination of Hydroxychloroquine and Its Main Metabolites in Oral Fluid and Whole Blood for Therapeutic Drug Monitoring.

BACKGROUND: Hydroxychloroquine (HCQ) blood levels are used to monitor efficacy, safety, and patient adherence during treatment. Oral fluid has emerged as an alternative noninvasive, easily accessible, and low-complexity matrix for drug monitoring. However, there is no analytical method to measure HCQ in oral fluid. Therefore, we developed and validated an ultra-high-performance liquid chromatography-tandem mass (UHPLC-MS/MS) method for the measurement of HCQ and its main metabolites in oral fluid and compared to whole blood. METHODS: Ten microliters of matrices were used for sample preparation by protein precipitation with acetonitrile followed by online solid phase extraction. The validation process included assessment of lower limit of quantification, linearity, precision, recovery, matrix effect, interferences assessment, carryover, and sample dilution validation. RESULTS: The lower limit of quantification was 50 ng/mL for HCQ and metabolites in both oral fluid and whole blood. The calibration curve was linear from 50 to 2000 ng/mL (r2 = 0.999). The coefficient of variation for precision assay was 1.2% to 9.7% for intraday and 1.1% to 14.2% for interday for both HCQ and metabolites in oral fluid and whole blood samples at 150, 750, and 1250 ng/mL. The recovery was 85.3% to 118.5% for 150, 750, and 1250 ng/mL of HCQ and metabolites in both oral fluid and whole blood. Dilution factor up to 5-fold was validated for concentrations higher than the upper limit of quantification. CONCLUSIONS: The validated method is specific, precise, and accurate to determine the analytical range for therapeutic monitoring of HCQ and its main metabolites in oral fluid and blood.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

OBJECTIVE: To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS: A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS: The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION: Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

Infliximab induces increase in triglyceride levels in psoriatic arthritis patients.

OBJECTIVES: To evaluate lipid profile changes after anti-TNF therapy in patients with psoriatic arthritis (PsA). METHODS: Fifteen PsA patients (eight polyarticular, four oligoarticular, two axial, and one mutilating) under infliximab were included. None had dyslipoproteinemia or previous statin use. Total cholesterol (TC) and its fractions, inflammatory markers, and prednisone use were evaluated. RESULTS: The comparisons of lipid levels between baseline and after three months (3M) of anti-TNF therapy showed that there was a significant increase in mean triglycerides (117.8 ± 49.7 versus 140.1 ± 64.1 mg/dL, P = 0.028) and VLDL-c (23.6 ± 10.5 versus 28.4 ± 13.7 mg/dL, P = 0.019) levels. In contrast, there were no differences in the mean TC (P = 0.28), LDL-c (P = 0.42), and HDL-c (P = 0.26) levels. Analysis of the frequencies of each lipid alteration at baseline and at 3M were alike (P > 0.05). Positive correlations were found between VLDL-c and CRP (r = 0.647, P = 0.009) and between triglycerides and CRP (r = 0.604, P = 0.017) levels at 3M. ESR reduction was observed after 3M (P = 0.04). Mean prednisone dose remained stable at beginning and at 3M (P = 0.37). CONCLUSION: This study demonstrated that anti-TNF may increase TG and VLDL-c levels in PsA patients after three months.

Responsiveness to exercise training in juvenile dermatomyositis: a twin case study.

BACKGROUND: Patients with juvenile dermatomyositis (JDM) often present strong exercise intolerance and muscle weakness. However, the role of exercise training in this disease has not been investigated. PURPOSE: this longitudinal case study reports on the effects of exercise training on a 7-year-old patient with JDM and on her unaffected monozygotic twin sister, who served as a control. METHODS: Both the patient who was diagnosed with JDM as well as her healthy twin underwent a 16-week exercise training program comprising aerobic and strengthening exercises. We assessed one repetition-maximum (1-RM) leg-press and bench-press strength, balance, mobility and muscle function, blood markers of inflammation and muscle enzymes, aerobic conditioning, and disease activity scores. As a result, the healthy child had an overall greater absolute strength, muscle function and aerobic conditioning compared to her JDM twin pair at baseline and after the trial. However, the twins presented comparable relative improvements in 1-RM bench press, 1-RM leg press, VO2peak, and time-to-exhaustion. The healthy child had greater relative increments in low-back strength and handgrip, whereas the child with JDM presented a higher relative increase in ventilatory anaerobic threshold parameters and functional tests. Quality of life, inflammation, muscle damage and disease activity scores remained unchanged. RESULTS AND CONCLUSION: this was the first report to describe the training response of a patient with non-active JDM following an exercise training regimen. The child with JDM exhibited improved strength, muscle function and aerobic conditioning without presenting an exacerbation of the disease.

Gingival capillary changes and oral motor weakness in juvenile dermatomyositis.

OBJECTIVE: We assessed the orofacial involvement in JDM, and evaluated the possible association of gingival and mandibular mobility alterations with demographic data, periodontal indices, clinical features, muscle enzyme levels, JDM scores and treatment. METHODS: Twenty-six JDM patients were studied and compared with 22 healthy controls. Orofacial evaluation included clinical features, dental and periodontal assessment, mandibular function and salivary flow. RESULTS: The mean current age was similar in patients with JDM and controls (P > 0.05). A unique gingival alteration characterized by erythema, capillary dilation and bush-loop formation was observed only in JDM patients (61 vs 0%, P = 0.0001). The frequencies of altered mandibular mobility and reduced mouth opening were significantly higher in patients with JDM vs controls (50 vs 14%, P = 0.013; 31 vs 0%, P = 0.005). Comparison of the patients with and without gingival alteration showed that the former had lower values of median of cementoenamel junction (-0.26 vs -0.06 mm, P = 0.013) and higher gingival bleeding index (27.7 vs 14%, P = 0.046). This pattern of gingival alteration was not associated with periodontal disease [plaque index (P =0.332) and dental attachment loss (P = 0.482)]. The medians for skin DAS and current dose of MTX were higher in JDM with gingival alteration (2.5 vs 0.5, P = 0.029; 28.7 vs 15, P = 0.012). A significant association of lower median manual muscle testing with a reduced ability to open the mouth was observed in patients with JDM than those without this alteration (79 vs 80, P = 0.002). CONCLUSIONS: The unique gingival pattern associated with cutaneous disease activity, distinct from periodontal disease, suggests that gingiva is a possible target tissue for JDM. In addition, muscle weakness may be a relevant factor for mandibular mobility.

Decreased recent thymus emigrant number in rheumatoid factor-negative polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To determine TCR excision circle (TREC) levels, a marker of recent thymic emigrants, in the peripheral lymphocyte pool of rheumatoid factor-negative (RFØ) polyarticular juvenile idiopathic arthritis (JIA) children. METHODS: We studied TREC levels in peripheral blood mononuclear cells (PBMC) in 30 RFØ polyarticular JIA children with active disease and in 30 age- and gender-matched healthy controls. Signal-joint TREC concentration was determined by real-time quantitative-PCR as the number of TREC copies/microg PBMC DNA gauged by a standard curve with known number of TREC-containing plasmids. RESULTS: TREC levels in PBMC were significantly lower in JIA (4.90 +/- 3.86 x 104 TRECs/microg DNA) as compared to controls (10.45 +/- 8.45 x 104 TRECs/microg DNA, p=0.001). There was an inverse correlation between age and TREC levels in healthy children (r=-0.438, p=0.016) but not in JIA. No clinical association was observed between TREC levels and disease activity and use of oral steroids and methotrexate. CONCLUSIONS: The finding of decreased PBMC TREC levels in RFØ polyarticular JIA children is consistent with a low proportion of recent thymus emigrants. This may interfere with the equilibrium between populations of polyclonal and naïve T cells versus oligoclonal memory auto-reactive T cells and, therefore, may hinder the maintenance of immune tolerance in this disease.

Chorea in a child with Churg-Strauss syndrome.

INTRODUCTION: Churg-Strauss syndrome (CSS) is a systemic granulomatous vasculitis rarely described in children, particularly associated with neurological involvement, exceptionally chorea. To our knowledge there are only 35 children and adolescent patients with CSS described in the literature. During a 25-year period 5283 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and only one (0.02%) presented CSS. CASE REPORT: A 7-year-old boy suffered from severe asthma, eosinophilia, history of allergy, recurrent non-fixed pulmonary infiltrates, several nodular lesions in both lungs and maxillary sinusitis. Transthoracic biopsy of the right lung revealed necrotizing extravascular eosinophilic infiltrates and the diagnosis of CSS was established. During the follow-up he had persistent vasculitis skin lesions and hemichorea. Despite the treatment with immunosuppressive drugs and intravenous immunoglobulin, he died because of pulmonary abscess and sepsis. DISCUSSION: A rare case of CSS with chorea was reported, reinforcing the possibility of this disease in children with asthma, allergic rhinitis, hypereosinophilia and cutaneous vasculitis.

[Association between pulmonary hemosiderosis and juvenile dermatomyositis]. / Associação entre hemossiderose pulmonar e dermatomiosite juvenil.

INTRODUCTION: Pulmonary hemosiderosis (PH) is characterized by recurrent diffuse intra-alveolar hemorrhage associated to the presence of hemosiderin deposits inside macrophages. In the present Pediatric Rheumatology Service, during a 24 years period, 143 patients had JDM diagnosis and only one of them had associated PH (0.7%). There is no previous case report of PH and juvenile dermatomyositis (JDM) associated. CASE REPORT: A male patient, 13 years old of age had recurrent anemia, cough, hemoptysis for 8 months. He had severe anemia and lung interstitial infiltrate on radiology studies. Bronchoalveolar lavage demonstrated hemosiderin deposits inside macrophage cells and positive Perl's reaction with PH diagnosis. The treatment was initiated with corticosteroids. After one month, he developed muscle weakness, Gottron's papules and elevated serum muscle enzymes. Muscle biopsy disclosed JDM diagnosis. Due to recurrent pulmonary hemorrhage, monthly methylprednisolone and cyclophosphamide pulses and intravenous immunoglobulin (IVIG) were started and clinical remission was achieved. He developed massive pulmonary hemorrhage, death and the necropsy confirmed PH. DISCUSSION: PH had never been reported in the JDM population. The PH was a severe clinical complication and occurred previously to JDM diagnosis.

Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts "in vitro".

We examined the effects of polyarticular juvenile idiopathic arthritis (pJIA) serum on proliferation, differentiation, mineralization, and apoptosis of human osteoblast cells (hOb) in culture. The hOb were cultured with 10% serum from active pJIA and healthy controls (CT) and were tested for DNA synthesis, alkaline phosphatase (AP) activity, osteocalcin (OC) secretion, calcium levels, caspase 3 activity, and DNA fragmentation. None of the patients had used glucocorticoids for at least 1 month before the study, or any other drug that can affect bone mineral metabolism. Human inflammatory cytokine levels (IL-6, IL-8, IL-10, IL-1beta, TNF-alpha, and IL-12p70) were measured in pJIA and CT sera. Low levels of AP activity was observed in pJIA cultures compared with CT cultures (67.16 +/- 53.35 vs 100.11 +/- 50.64 mumol p-nitrophenol/h(-1) mg(-1) protein, P = 0.008). There was also a significant decrease in OC secretion (9.23 +/- 5.63 vs 12.82 +/- 7.02 ng/mg protein, P = 0.012) and calcium levels (0.475 +/- 0.197 vs 0.717 +/- 0.366 mmol/l, P = 0.05) in pJIA hOb cultures. No difference was observed in cell proliferation (323.56 +/- 108.23 vs 328.91 +/- 88.03 dpm/mg protein, P = 0.788). Osteoblasts cultured with JIA sera showed lower levels of DNA and increased fragmentation than osteoblasts cultured with CT sera. pJIA sera showed higher IL-6 values than CT (21.44 +/- 9.31 vs 3.58 +/- 2.38 pg/ml, P < 0.001), but no difference was observed related to IL-8, IL-10, IL-1beta, TNF-alpha, and IL-12p70 between pJIA and controls. This study suggests that serum from children with pJIA inhibits differentiation, mineralization and may increase apoptosis of hOb cultures, and inflammatory cytokines such as IL-6 might be a mechanism in this find. These results may represent an alternative therapeutic target for prevention and treatment of bone loss in JIA.

PDIA3, HSPA5 and vimentin, proteins identified by 2-DE in the valvular tissue, are the target antigens of peripheral and heart infiltrating T cells from chronic rheumatic heart disease patients.

Rheumatic fever (RF) is a post-infectious autoimmune disease due to sequel of group A streptococcus (GAS) pharyngitis. Rheumatic heart disease (RHD), the major manifestation of RF, is characterized by inflammation of heart valves and myocardium. Molecular mimicry between GAS antigens and host proteins has been shown at B and T cell level. However the identification of the autoantigens recognized by B and T cells within the inflammatory microenvironment of heart tissue in patients with RHD is still incompletely elucidated. In the present study, we used two-dimensional gel electrophoresis (2-DE) and mass spectrometry to identify valvular tissue proteins target of T cells from chronic RHD patients. We could identify three proteins recognized by heart infiltrating and peripheral T cells as protein disulfide isomerase ER-60 precursor (PDIA3), 78kD glucose-regulated protein precursor (HSPA5) and vimentin, with coverage of 45%, 43 and 34%, respectively. These proteins were recognized in a proliferation assay by peripheral and heart infiltrating T cells from RHD patients suggesting that they may be involved in the autoimmune reactions that leads to valve damage. We also observed that several other proteins isolated by 2-DE but not identified by mass spectrometry were also recognized by T cells. The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD.

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.

TNF receptor-associated periodic syndrome (TRAPS): description of a novel TNFRSF1A mutation and response to etanercept.

TRAPS is the most common of the autosomal dominant periodic fever syndromes. It is caused by mutations in the TNFRSF1A gene, which encodes for the type 1 TNF-receptor (TNFR1). We describe here a Brazilian patient with TRAPS associated to a novel TNFRSF1A de novo mutation and the response to anti-TNF therapy. The patient is a 9-year-old girl with recurrent fevers since the age of 3 years, usually lasting 3 to 7 days, and recurring every other week. These episodes are associated with mild abdominal pain, nausea, vomiting and generalized myalgia. Recurrent conjunctivitis and erysipela-like skin lesions in the lower limbs also occur. Laboratory studies show persistent normocytic normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein. IgD levels are normal. Mutational screening of TNFRSF1A revealed the association of a novel C30F mutation with the common R92Q low-penetrance mutation. The R92Q mutation is seen in 5% of the general population and is associated with an atypical inflammatory phenotype. The patient had a very good response to etanercept, with cessation of fever and normalization of inflammatory markers. Our report expands the spectrum of TNFRSF1A mutations associated with TRAPS, adding further evidence for possible additive effects of a low-penetration R92Q and cysteine residue mutations, and confirms etanercept as an efficacious treatment alternative.

Fatores de risco associados à calcinose na dermatomiosite juvenil / Risk factors associated with calcinosis of juvenile dermatomyositis

OBJETIVO: Identificar fatores de risco associados à calcinose em crianças e adolescentes com dermatomiosite juvenil. MÉTODOS: Prontuários de 54 pacientes com dermatomiosite juvenil foram estudados. Foram avaliados dados demográficos; características clínicas: grau de força muscular (I a V do Medical Research Council), presença de comprometimentos pulmonar (distúrbio ventilatório restritivo com presença ou ausência do anticorpo anti-Jo-1), gastrointestinal (refluxo gastroesofágico) e cardíaco (pericardite e/ou miocardite); exames laboratoriais: elevação de enzimas musculares (creatinoquinase, aspartato aminotransferase, alanina aminotransferase e desidrogenase lática) e terapias utilizadas: corticoterapia isolada ou associada à cloroquina e/ou imunossupressor. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de calcinose e foram avaliados através de análise univariada e multivariada. RESULTADOS: Calcinose foi evidenciada em 23 (43 por cento) pacientes, sendo em seis (26 por cento) antes do diagnóstico e em 17 (74 por cento) após. A análise univariada revelou que comprometimentos cardíaco (p = 0,01) e pulmonar (p = 0,02) e necessidade da utilização de um ou mais imunossupressores (metotrexato, ciclosporina A e/ou pulsoterapia com ciclofosfamida endovenosa) no tratamento da dermatomiosite juvenil (p = 0,03) foram associados com uma maior incidência de calcinose. A análise multivariada mostrou que comprometimento cardíaco (OR = 15,56; IC95 por cento 1,59-152,2) e uso de um ou mais imunossupressores (OR = 4,01; IC95 por cento 1,08-14,87) foram as únicas variáveis independentes associadas à presença de calcinose. CONCLUSÕES: O aparecimento da calcinose foi freqüente na dermatomiosite juvenil, habitualmente na evolução da doença. A calcinose foi associada aos casos mais graves, que apresentaram envolvimento cardíaco e necessitaram da utilização de imunossupressores no seu tratamento.

OBJECTIVE: To identify risk factors associated with calcinosis in children and adolescents with juvenile dermatomyositis. METHODS: A review was carried out of the medical records of 54 patients with juvenile dermatomyositis. Data were collected on demographic characteristics, clinical features: muscle strength (stages I to V of the Medical Research Council scale), pulmonary involvement (restrictive pulmonary disease with presence or absence of anti-Jo1 antibodies), gastrointestinal problems (gastroesophageal reflux) and/or heart disease (pericarditis and/or myocarditis); laboratory tests: elevated muscle enzyme levels in serum (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase and/or lactate dehydrogenase); and on the treatments given: corticoid therapy in isolation or associated with hydroxychloroquine and/or immunosuppressants. The patients were divided into two groups, depending on presence or absence of calcinosis and data were evaluated by both univariate and multivariate analyses. RESULTS: Calcinosis was identified in 23 (43 percent) patients, and in six (26 percent) patients it had emerged prior to diagnosis while in 17 (74 percent) it was post diagnosis. The univariate analysis revealed that cardiac (p = 0.01) and pulmonary (p = 0.02) involvement and the need for one or more immunosuppressor (methotrexate, cyclosporine A and/or pulse therapy with intravenous cyclophosphamide) to treat juvenile dermatomyositis (p = 0.03) were all associated with an increased incidence of calcinosis. The multivariate analysis then demonstrated that only cardiac involvement (OR = 15.56; 95 percentCI 1.59-152.2) and the use of one or more immunosuppressor (OR = 4.01; 95 percentCI 1.08-14.87) were independently associated with the presence of calcinosis. CONCLUSIONS: Calcinosis was a frequent development among these juvenile dermatomyositis cases, generally emerging as the disease progressed. Calcinosis was associated with...

Risk factors associated with calcinosis of juvenile dermatomyositis.

OBJECTIVE: To identify risk factors associated with calcinosis in children and adolescents with juvenile dermatomyositis. METHODS: A review was carried out of the medical records of 54 patients with juvenile dermatomyositis. Data were collected on demographic characteristics, clinical features: muscle strength (stages I to V of the Medical Research Council scale), pulmonary involvement (restrictive pulmonary disease with presence or absence of anti-Jo1 antibodies), gastrointestinal problems (gastroesophageal reflux) and/or heart disease (pericarditis and/or myocarditis); laboratory tests: elevated muscle enzyme levels in serum (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase and/or lactate dehydrogenase); and on the treatments given: corticoid therapy in isolation or associated with hydroxychloroquine and/or immunosuppressants. The patients were divided into two groups, depending on presence or absence of calcinosis and data were evaluated by both univariate and multivariate analyses. RESULTS: Calcinosis was identified in 23 (43%) patients, and in six (26%) patients it had emerged prior to diagnosis while in 17 (74%) it was post diagnosis. The univariate analysis revealed that cardiac (p = 0.01) and pulmonary (p = 0.02) involvement and the need for one or more immunosuppressor (methotrexate, cyclosporine A and/or pulse therapy with intravenous cyclophosphamide) to treat juvenile dermatomyositis (p = 0.03) were all associated with an increased incidence of calcinosis. The multivariate analysis then demonstrated that only cardiac involvement (OR = 15.56; 95%CI 1.59-152.2) and the use of one or more immunosuppressor (OR = 4.01; 95%CI 1.08-14.87) were independently associated with the presence of calcinosis. CONCLUSIONS: Calcinosis was a frequent development among these juvenile dermatomyositis cases, generally emerging as the disease progressed. Calcinosis was associated with the more severe cases that also had cardiac involvement and where immunosuppressors had to be included in the treatment.

Acute hemorrhagic edema of childhood.

Acute hemorrhagic edema (AHE) of childhood, a variant of Henoch-Schönlein purpura (HSP), is a rare vasculitis with benign course, generally no systemic involvement and rare flares. From January 1983 to June 2004, 4,502 patients were followed at the Pediatric Rheumatology Unit, Hospital of Clinics. Diagnosis of HSP was made in 203 cases (4.5%), of which 5 (0.1%) had AHE. All patients with AHE were male and the mean age at onset was 18 months (range: 8 to 21 months). All five cases presented vasculitis with characteristic hemorrhagic and purpuric lesions in malar region of the face, associated with painless edema of the hands and feet. Laboratory exams were normal. Upper respiratory tract infection preceding clinical manifestations occurred in four and mononucleosis in one. Treatment with corticosteroids was necessary only in one patient with necrotic lesions on the face and ears.

Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis.

OBJECTIVE: To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity. METHODS: Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokine levels (IL-1beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test. RESULTS: All the analyzed cytokine levels (IL-1, IL-1Ra, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes. CONCLUSION: Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis.

Randomized double-blind study with prednisone in Sydenham's chorea.

In this randomized, double-blind, parallel study of a group of 22 children and teenagers, prednisone efficacy in acute Sydenham's chorea was assessed. Use of prednisone (2 mg/kg/day during 4 weeks, followed by a gradual discontinuation) in the 22 patients and in a placebo group (n = 15) was evaluated by a chorea intensity score based on presence, distribution, and interference of choreic movement on daily activities. Each patient was evaluated by the same pediatric neurologist weekly during the first month, followed by evaluation on weeks 8 and 12, with further evaluations as necessary if choreic movements persisted. Although initial chorea intensity was similar in both groups, a significant difference was observed after 1 week of medication (P < 0.001) with a larger reduction in the prednisone group, that continued until the end of the study. Percentage decrease in chorea intensity scale score also was persistently and significantly (P < 0.001) greater in the prednisone group. Chorea complete remission time with prednisone (mean 54.3 days) was significantly shorter (P < 0.001) when compared with the placebo group (mean 119.9 days). Seven patients presented recurrences, with no difference between groups (13.6% and 26.7% in the prednisone and placebo groups, respectively). Severe adverse events to prednisone were not observed.