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Objective: The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between onset of signs/symptoms and disease diagnosis. Methods: A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥ and <3 months); and C: long time interval (埵 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2K were evaluated. Results: The number of patients in each group was: A=60 (4%); B=522 (33.5%); and C=973 (62.5%). The median age at diagnosis (11.1 (4.2-17) vs. 12 (1.9-17.7) vs. 12.5 (3-18) years, P=0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4-12) vs. 6 (4-13) vs. 6 (4-12), P<0.0001) and SLEDAI-2K (18 (6-57) vs. 16 (2-63) vs. 13 (1-49), P<0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P=0.003), pleuritis (25% vs. 24% vs. 14%, P<0.0001), nephritis (52% vs. 47% vs. 40%, P=0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P=0.008), thrombocytopenia (32% vs. 18% vs. 19%, P=0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P<0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P=0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P=0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P=0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P=0.002) and low complement levels (81% vs. 81% vs. 71%, P<0.0001) compared with groups A or B. Conclusions: Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess outcomes of childhood systemic lupus erythematosus (cSLE) in three different age groups evaluated at last visit: group A early-onset disease (<6 years), group B school age (≥6 and <12 years) and group C adolescent (≥12 and <18 years). Methods: An observational cohort study was performed in ten pediatric rheumatology centers, including 847 cSLE patients. Results: Group A had 39 (4%), B 395 (47%) and C 413 (49%). Median disease duration was significantly higher in group A compared to groups B and C (8.3 (0.1–23.4) vs 6.2 (0–17) vs 3.3 (0–14.6) years, p < 0.0001). The median Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) (0 (0–9) vs 0 (0–6) vs 0 (0–7), p = 0.065) was comparable in the three groups. Further analysis of organ/system damage revealed that frequencies of neuropsychiatric (21% vs 10% vs 7%, p = 0.007), skin (10% vs 1% vs 3%, p = 0.002) and peripheral vascular involvements (5% vs 3% vs 0.3%, p = 0.008) were more often observed in group A compared to groups B and C. Frequencies of severe cumulative lupus manifestations such as nephritis, thrombocytopenia, and autoimmune hemolytic anemia were similar in all groups (p > 0.05). Mortality rate was significantly higher in group A compared to groups B and C (15% vs 10% vs 6%, p = 0.028). Out of 69 deaths, 33/69 (48%) occurred within the first two years after diagnosis. Infections accounted for 54/69 (78%) of the deaths and 38/54 (70%) had concomitant disease activity. Conclusions: This large multicenter study provided evidence that early-onset cSLE group had distinct outcomes. This group was characterized by higher mortality rate and neuropsychiatric/vascular/skin organ damage in spite of comparable frequencies of severe cumulative lupus manifestations. We also identified that overall death in cSLE patients was an early event mainly attributed to infection associated with disease activity [ABSTRACT FROM AUTHOR]

Context: Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions.Objectives: To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares.Design, Setting, and Patients: Prospective, open, multicenter, medication-withdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloid-related proteins 8 and 14 heterocomplex (MRP8/14) were determined.Intervention: Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n = 183]) or 12 months (group 2 [n = 181]) after induction of disease remission.Main Outcome Measures: Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed.Results: Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P = .86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P = .61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1 110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P = .003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90).Conclusions: In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate.Trial Registration: isrctn.org Identifier: ISRCTN18186313. [ABSTRACT FROM AUTHOR]

We evaluated the prevalence and clinical associations of amenorrhea in 298 female juvenile systemic lupus erythematosus (JSLE) patients (ACR criteria) followed in 12 Brazilian Paediatric Rheumatology centres. Amenorrhea was observed in 35 patients (11.7%) with a mean duration of 7.2±3.6 months. The hormones were performed in 32/35 patients and none of them had FSH and LH levels above and estradiol below the normal range according to pubertal changes. JSLE patients with amenorrhea were younger (15.04±2.5 versus 17.8±3.1 years; P=0.001), and had a shorter period of time between menarche and current age (3.4±2.9 versus 6.7±5.4 years; P=0.001). Interestingly, the frequency, cumulative dose, number of pulses and duration of intravenous cyclophosphamide treatment were alike in patients with and without amenorrhea (P = 0.05). In contrast, patients with amenorrhea had significantly higher SLEDAI (P = 0.01) and SLICC/ACR-DI (P = 0.024) scores compared to those without this condition. Independent risk factors identified by multivariate analysis were higher SLEDAI (OR = 1.059; CI = 1.004-1.116; P = 0.034) and SLICC/ACR-DI (OR = 2.125; IC = 1.373–3.291; P = 0.001) scores. Our data suggest that in spite of immunosuppressive therapy, JSLE patients have an adequate ovarian follicular reserve and amenorrhea is particularly associated with disease activity and damage. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "The PRINTO provisional definition of remission in juvenile dermatomyositis," by S. Garay, and colleagues, is presented.

Streptococcus mutans (SM) have three main virulence antigens: glucan binding protein B (gbpB), glucosyltransferase (Gtf) and antigens I/II (Ag I/II) envolved in the capacity of those bacteria to adhere and accumulate in the dental biofilm. Also, the glycosyltransferases 153 kDa of Streptococcus gordonii (SGO) and 170 kDa of Streptococcus sanguinis (SSA) were important antigens associated with the accumulation of those bacterias. Streptococcus mitis (SMI) present IgA1 protease of 202 kDa. We investigated the specificity and levels IgA against those antigens of virulence in samples of human colostrum. This study involved 77 samples of colostrum that were analyzed for levels of immunoglobulian A, M and G by Elisa. The specificity of IgA against extracts of SM and initials colonizators (SSA, SMI, SGO) were analyzed by the Western blot. The mean concentration of IgA was 2850.2 (±2567.2) mg/100 mL followed by IgM and IgG (respectively 321.8 ± 90.3 and 88.3 ± 51.5), statistically different (p < 0.05). Results showed that the majority of samples had detectable levels of IgA antibodies to extracts of bacteria antigens and theirs virulence antigens. To SM, the GbpB was significantly lower detected than others antigens of SM (p < 0.05). High complexities of response to Ags were identified in the samples. There were no significant differences in the mean number of IgA-reactive Ags between the antigens (p > 0.4). So, the breast milk from first hours after birth presented significant levels of IgA specific against important virulence of antigens those oral streptococci, which can disrupt the installation and accumulation process of these microorganisms in the oral cavity. [ABSTRACT FROM AUTHOR]

Background: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients., Methods: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study., Results: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types., Conclusions: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients., Trial Registration: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.

Objective: To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy., Methods: We identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells., Results: We recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5., Conclusion: These cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy., (© 2017, American College of Rheumatology.)

Objective: Asthma is under-diagnosed in many parts of the world. We aimed to assess the outcome of a capacitating program on asthma for non-specialist physicians and other healthcare professionals working in the public system in Ribeirão Preto, Brazil., Methods: A group of 16 asthma specialists developed a one-year capacitating program in 11 healthcare clinics in the Northern District of the city, which included lectures on asthma, training on inhalation device use and spirometry, and development of an asthma management protocol. Researchers visited one health unit 2-4 times monthly, working with doctors on patients' care, discussing cases, and delivering lectures. Asthma education was also directed to the general population, focusing on recognition of signs and symptoms and long-term treatment, including production of educational videos available on YouTube. Outcome measures were the records of doctors' prescriptions of individual asthma medications pre- and post-intervention., Results: Prior to the program, 3205 units of inhaled albuterol and 2876 units of inhaled beclomethasone were delivered by the Northern District pharmacy. After the one-year program, there was increase to 4850 units (51.3%) for inhaled albuterol and 3526 units (22.6%) for inhaled beclomethasone. The albuterol increase followed the recommendation given to the non-specialist doctors by the asthma experts, that every patient with asthma should have inhaled albuterol as a rescue medication, by protocol. No increase was observed in other districts where no capacitating program was conducted., Conclusion: A systematic capacitating program was successful in changing asthma prescription profiles among non-specialist doctors, with increased delivery of inhaled albuterol and beclomethasone.

Background: Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis., Methods: We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960., Findings: Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the other two treatment groups (2.45 fold [95% CI 1.2-5.0] increase with prednisone plus methotrexate; p=0.012). Median time to treatment failure was 16.7 months in patients allocated prednisone, 53.3 months in those assigned prednisone plus ciclosporin, but was not observable in patients randomised to prednisone plus methotrexate (1.95 fold [95% CI 1.20-3.15] increase with prednisone; p=0.009). Median time to prednisone discontinuation was 35.8 months with prednisone alone compared with 29.4-29.7 months in the combination groups (p=0.002). A significantly greater proportion of patients assigned prednisone plus ciclosporin had adverse events, affecting the skin and subcutaneous tissues, gastrointestinal system, and general disorders. Infections and infestations were significantly increased in patients assigned prednisone plus ciclosporin and prednisone plus methotrexate. No patients died during the study., Interpretation: Combined treatment with prednisone and either ciclosporin or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favoured the combination of prednisone plus methotrexate., Funding: Italian Agency of Drug Evaluation, Istituto Giannina Gaslini (Genoa, Italy), Myositis Association (USA)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America., Methods: Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course., Results: Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron's papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians., Conclusions: The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Objective: To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study., Methods: Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL)., Results: A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%., Conclusion: This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Purpose: Factors predicting renal function and recurrent stenosis following percutaneous renal revascularization are poorly identified. The predictive value of hemodynamic duplex ultrasound (DUS) parameters was evaluated., Methods: In a prospective observational study patients undergoing stenting of renal artery stenosis (RAS) were included. Renal resistance index (RI) and peak systolic velocity (PSV) were measured at baseline, one day, and six months after intervention., Results: At 6-months follow-up 16 (16.8%) restenosis of 105 treated renal arteries were detected. Baseline RI was 0.69 +/- 0.12 and increased significantly to 0.72 +/- 0.09 after 6 months (p < 0.0001), however, RI did not predict restenosis. PSV at baseline and age were independent predictors for increased RI at 6 months (p = 0.0078 and p = 0.0019). Diabetics had a significant higher RI before revascularization (0.74 +/- 0.08) than non-diabetics (0.68 +/- 0.12, p = 0.04). PSV after stenting was higher in patients with restenosis (1.4 +/- 0.4 m/sec vs. 1.0 +/- 0.3 m/sec, p = 0.002) and was an independent predictor for restenosis., Conclusions: Increased PSV within the stent one day after the procedure is predictive for restenosis. Patients with high grade RAS and older patients have a worse outcome. DUS is recommended to detect patients at risk for restenosis after percutaneous renal revascularization.

Objective: To describe onset features, classification and treatment of juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre registry., Methods: Inclusion criteria were onset age lower than 18 years and a diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician. Bohan & Peter (1975) criteria categorisation was established by a scoring algorithm to define JDM and JPM based on clinical protocol data., Results: Of the 189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not fit the criteria; 6.9% had features of chronic arthritis and connective tissue disease overlap. Diagnosis classification agreement occurred in 66.1%. Median onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash 83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result. Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was done in 66 cases with all parameters assessed and only aldolase resulted significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4, p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%., Conclusion: Evaluation of predefined criteria set for a valid diagnosis indicated aldolase as the most important parameter associated with definite JDM category. In practice, prednisone-methotrexate combination was the most indicated treatment.

Acute lymphoblastic leukemia (ALL) presenting with neutropenia alone is very rare. We describe a newborn with an early life-threatening infection, severe neutropenia and bone marrow findings compatible with severe congenital neutropenia (SCN). She was treated with granulocyte colony-stimulating factor (G-CSF) with complete neutrophil recovery. Three months later she developed a pro-B ALL. We identified a rare loss of 5'-MLL present at the diagnosis of SCN and ALL by FISH analysis using two different MLL (11q23) probes. Molecular analyses for SCN causing mutations (ELA-2, HAX-1 and G6PC3) and for somatic mutations of the CSF3R gene were negative. The early presence of 5'-MLL loss in bone marrow samples may favor the diagnosis of de novo ALL. Nevertheless, the genetic background for SCN is heterogeneous and a non-described mutation for SCN followed by a secondary ALL cannot be excluded. Further genetic investigation may be useful to gain insight into this rare condition in children.

Objective: To describe a patient who had polyarteritis nodosa with central nervous system involvement mimicking infectious meningoencephalitis., Design: Case report., Setting: Pediatric intensive care unit of a university hospital., Patient: A 9-yr-old boy with prolonged fever, headache, decreased level of consciousness, neck stiffness, and papilledema., Results: Cerebrospinal fluid examination showed pleocytosis and a high protein level. After neurologic deterioration resulted from the initial treatment with antibiotic, the combination of clinical and laboratory findings with neuroradiologic features led to suspected systemic vasculitis. The patient was treated subsequently with corticosteroid, which resulted in great improvement. Biopsy of a skin lesion confirmed the diagnosis of polyarteritis nodosa., Conclusions: Critical care physicians must recognize neurologic manifestation patterns of systemic vasculitides because appropriate diagnosis and therapy result in significantly improved morbidity and mortality.

In this study we have optimised the enzyme immunoassay (ELISA) to quantify CD59 antigen in human serum or plasma. The glycosyl-phosphatidylinositol (GPI)-linked form of CD59 is known to complex with serum high-density lipoprotein. For ELISA optimisation, therefore, we investigated the effect of detergents, added to the sample diluent, on the determined values of CD59. Values obtained in the presence of octyl-glucoside (OG) for 20 adults aged 18-35 years and 17 children 1-5 years old were, respectively, 33-119 ng/ml (mean +/- S.D.: 66+/-22 ng/ml) and 37-143 ng/ml (76+/-33 ng/ml). These results were higher than those measured without OG and were in contrast with published results showing absence, or eight to nine times lower levels, of the protein in serum. A known range for serum concentrations of CD59 in healthy individuals will establish an important reference point for clinical work and for the investigation of diseases involving the complement membrane attack complex (MAC) and its regulation.

Cockroach allergy has been recognized as an important cause of asthma. Exposure to high levels of cockroach allergens in the home is a major risk factor for symptoms in sensitized individuals. Previously identified allergens from Blatella germanica and Periplaneta americana include Bla g 2 (inactive aspartic proteinase), Bla g 4 (calycin), Bla g 5 (glutathione-S-transferase), Bla g 6 (troponin), the Group 1 cross-reactive allergens Bla g 1 and Per a 1, Per a 3 (arylphorin), and Per a 7 (tropomyosin). The primary site of cockroach allergen accumulation is the kitchen. However, lower levels of allergen can be found in bedding, on the bedroom floor, and in sofa dust. Strategies for decreasing exposure to cockroach have been investigated. The results suggest that a sustained decrease in cockroach allergen levels is difficult to accomplish, even after successful extermination of cockroach populations. The use of recombinant cockroach allergens may lead to the development of new approaches to asthma treatment in the future.

Background: Fanconi's anemia (FA) is a rare recessive chromosomal instability disorder, characterized by progressive bone marrow failure and congenital defects. Patients with FA present with recurrent infections, particularly those of the respiratory tract., Objective: The aim of the present study was to evaluate whether patients with FA have altered antibody-mediated immune responses., Methods: A group of 12 patients with FA, 5-32 years old (6 males) was studied. Serum levels of IgG, IgM, IgA and IgG subclasses, isohemagglutinin titers and specific IgG antibodies to poliovirus and measles were determined using standard methods. Immediate skin tests to common inhalant allergens were performed, and total and specific serum IgE was quantitated using a fluoroenzymatic assay (Uni-CAP, Pharmacia). Antipneumococcal antibodies were measured by ELISA before and 4-8 weeks after immunization with pneumococcal vaccine (Pneumo 23, Pasteur Mérieux Connaught). Responses to serotypes 1, 3, 5, 6B, 9V and 14, which are the most prevalent in our country, were studied., Results: Ten patients had elevated IgE levels in sera, and 7 of them had detectable specific IgE and positive immediate skin tests. An inadequate response to pneumococcal vaccination was found in 2 of the 12 patients. Isohemagglutinin titers and levels of IgG, IgM, IgA and IgG subclasses and antipoliovirus and antimeasles antibodies were within the normal limits for age in all patients. Two patients had undetectable IgG4 levels (below 5 mg/dl)., Conclusions: The results indicate that a proportion of patients with FA (2/12) in our study had inadequate responses to pneumococcal vaccination. No other significant abnormalities of the immune system were found in these patients., (Copyright 2001 S. Karger AG, Basel)

We report the cross-cultural adaptation and validation into Brazilian-Portuguese of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children regardless the underlying disease. The Brazilian CHAQ was revalidated, while the CHQ has been derived from the Portuguese version. A total of 471 subjects were enrolled: 157 patients with JIA (27% systemic onset, 38% polyarticular onset, 9% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 314 healthy children. The CHAQ discriminated clinically healthy subjects from JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and lower overall well-being scores when compared to their healthy peers. Also the CHQ discriminated clinically healthy subjects from JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being score when compared to their healthy peers. In conclusion the Brazilian versions of the CHAQ-CHQ are reliable and valid tools for the combined physical and psychosocial assessment of children with JIA.

Asthma and allergy are the most common diseases associated with cockroach infestation of houses in the United States and other parts of the world. Sensitization and exposure to cockroach allergens is associated with increased asthma morbidity in the United States, especially among lower socioeconomic groups, including African American and Hispanic populations. Exposure to cockroach allergens in the first 3 months of life has been associated with repeated wheezing and asthma. The principal domestic cockroach species are Blattella germanica and Periplaneta americana. Both species produce several potent allergens, including Bla g 2 (inactive aspartic proteinase), Bla g 4 (calycin), Bla g 5 (glutathione-S-transferase), the group 1 cross-reactive allergens Bla g 1 and Per a 1, and tropomyosin. Structural homology between tropomyosins from cockroaches, mites, and shrimp may explain clinical cases of the oral allergy syndrome. The 3-dimensional structures of several cockroach allergens are known, and biologically active recombinant allergens have been produced in high-level expression vectors. The use of recombinant cockroach allergens should allow mechanisms of cockroach-induced asthma to be investigated and may lead to the development of new approaches to asthma treatment. Environmental allergen measurements of Bla g 1 and Bla g 2 have allowed exposure levels that cause allergic sensitization to be established. Abatement studies have shown that a sustained decrease in cockroach allergen levels is difficult but can be accomplished by professional application of insecticides, together with rigorous household cleaning. Cockroach asthma is an important public health problem that affects patients who are the least likely to be compliant with treatment with asthma medications or environmental control. Patient education, improvements in the housing stock, and improvements in environmental and immunologic treatment strategies are likely to be the most successful approaches to reduce the prevalence of cockroach-induced asthma.

Rhinosinusitis is a disease that has attracted increasing attention both in terms of triggering factors and of treatment evolution, with its possible complications and repercussions. Follow-up of chronic cases almost always requires imaging evaluation and computed tomography (CT) has been considered the 'gold standard' for these cases, for which the exam must often be repeated more than once. This fact implies submitting the patient to a greater radiation load and, in the case of some children, to repeated sedation, causing possible damage to the patient, concern to the parents and to the physician when he requests this procedure. In the present study, the authors propose a reduced CT technique compared to the standard exam, with a smaller number of slices, to be used for the initial evaluation of a case and for the follow-up of chronic cases, with the standard examination reserved for cases requiring the best possible anatomical detailing, such as surgical cases. The standard technique involves 2-mm thick sections spaced 5 mm apart. In the reduced technique, the spacing is 10 mm, with a consequent reduction in the number of sections. Twenty-one children aged 4-13 years were submitted for the examination. The advantages of the proposed method reside in the reduction of the radiation load to which the patient is exposed, in its better agility, with a reduced time of execution and a consequent increase in collaboration on the part of the child, and in the reduction on cost of the procedure. It is also a technique of easy execution that does not require specific technical training.

OBJECTIVE: The aim of this study was to describe the clinical manifestations and to assess the occurrence of atypical arthritis in ARF patients attending a Pediatric Rheumatology Clinic at the University Hospital of Ribeirão Preto. METHODS: We have studied retrospectively the records of 120 attacks of ARF in 109 children, 3-13 years old, who attended our clinic from January 1990 to December 1995. All children fulfilled the Jones criteria. RESULTS: 77% of the attacks involved arthritis, 62% carditis, 32% chorea, 2.5% subcutaneous nodules and 1.3% erythema marginatum. The number of involved joints was 1 in 3 episodes of ARF, 2-5 in 52, 6-10 in 30 and more than 10 in 5. Arthritis was considered atypical in 43 (47%) of the 92 ARF episodes with arthritis, based on the following criteria: involvement of unusual joints (cervical spine in 24 children, hip in 15, small joints of the hand in 12 or feet in 13); monarthritis (3); duration longer than 3 weeks (26); incomplete response to salicylates (18). Association of these atypical features were frequently present. For instance, considering the 24 episodes with cervical spine involvement, the duration of arthritis was longer than 3 weeks in 13 cases, 10 had insufficient response to salicylates and the hip joint was also involved in 7. Time to reach diagnosis was longer than 4 weeks in 59% of the patients presenting with atypical arthritis compared to 35% in the other patients (p=0.04). Different diagnosis were considered at the beginning of the disease in 40% of the 120 episodes and in 65% of the ones presenting with atypical arthritis (p=0.03). CONCLUSION: We conclude that atypical arthritis was present in a significant proportion of ARF episodes, adding an extra dilemma to the diagnosis of this intriguing disease.

Values of complement lytic activity of classical and alternative pathways, assessed by measuring the time required to lyse 50% of target red blood cells, and the concentration of complement components C3, C4 and factor B were estimated in the sera of 103 healthy children aged 3 to 14 y. Age-dependent variations were seen in the C3 and factor B concentrations, but not in C4, with the highest values found among 5-6-y-old children. Variations in classical and alternative lytic activity were not detected in this group of children, although the values are significantly different from our previously published data on adults, using the same kinetic assay (1). We also evaluated the relationship between the lytic activity of the classical (CPT) and alternative pathways (APT) and the levels of complement components. There were significant correlations between: APT and factor B, APT and C3, C3 and C4, C3 and factor B, and C4 and factor B concentrations. The normal ranges measured here can be used in the initial screening of Brazilian children presenting diseases involving the complement system. This study also contributes to a better understanding of the complement system ontogeny.

Background: Cockroaches produce several proteins that induce IgE antibody responses. Although cockroaches are abundant in warm and humid areas, sensitization to cockroach allergens has not been investigated in Brazil., Objective: The aims of this study were to investigate the frequency of cockroach allergy among patients with asthma, rhinitis, or both in Brazil and to identify American cockroach allergens., Methods: Skin tests using cockroach extracts were performed on children and young adults with asthma, rhinitis, or both. A Periplaneta americana complementary (c)DNA library was screened by using IgE antibodies from Brazilian patients allergic to cockroaches. Reactivity of an mAb directed to Dermatophagoides pteronyssinus tropomyosin against cockroach tissue was examined by immunofluorescence., Results: Cockroach allergy was present in 55% and 79% of the patients, as determined by using skin prick tests alone or combined prick and intradermal tests, respectively. Five cDNA clones reacted with IgE antibody and contained the same sequence. A representative clone (1300 bp), pa 12, coded for a protein that reacted with 50% of the sera from patients allergic to cockroaches on plaque immunoassay and showed a high degree of homology to tropomyosins, particularly those from invertebrates. P americana tropomyosin showed 80%, 81%, and 82% sequence identity to tropomyosins from D pteronyssinus, D farinae, and shrimp, respectively, which have been previously defined as important allergens. An mAb directed against D pteronyssinus tropomyosin, which also recognizes shrimp tropomyosin, showed binding to cockroach striated muscle., Conclusion: Our results support the recommendation that cockroach extracts should be routinely used for the evaluation of patients with asthma, rhinitis, or both in Brazil. The identification of P americana tropomyosin as an important allergen will make it possible to investigate cross-reactivity among cockroaches, mites, and food derived from invertebrates.

The haemolytic activity of complement was evaluated in the serum of healthy children from birth to 2 years of age using the kinetic method for the determination of the time needed to lyse 50% of target red cells (t 1/2). No sex-linked differences were observed in any of the age groups studied and the lowest lytic activity levels for both complement pathways were detected in neonates. The two pathways, however, showed different maturation patterns, i.e., lytic activity levels similar to those of adults were reached between the 1st and 3rd month of life (classical pathway) and around the 13th month (alternative pathway). In the age group of 7 to 24 months, the lytic activity of the classical pathway was higher than in adults. The present data permitted us to establish normal ranges of t 1/2 values for the classical and alternative pathways in serum of healthy neonates and children aged 1 to 24 months.