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OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

Made available in DSpace on 2021-06-25T10:38:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Healthway Objective. To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. Methods. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. Results. A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. Conclusion. The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively. UOC Clinica Pediatrica e Reumatologia IRCCS Istituto Giannina Gaslini Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili (DiNOGMI) Università degli Studi di Genova Dipartimento di Epidemiologia e Biostatistica IRCCS Istituto Giannina Gaslini Faculty of Medicine Ain Shams University Pediatric Rheumatology Division Institute of Child Health Section of Pediatric Rheumatology SRCC Children's Hospital Rheumatology Division Pediatric Department Faculty of Medicine Ramathibodi Hospital Mahidol University Pediatric Rheumatology Clinic R G Kar Medical College Division of Rheumatology IRCCS Ospedale Pediatrico Bambino Gesù Division of Pediatric Rheumatology Institute of Child Health Sir Ganga Ram Hospital Faculty of Medicine Benha University Faculty of Medicine Alexandria University Faculty of Medicine Tanta University Faculty of Medicine Cairo University Pediatric Rheumatology Division Adolescent Health Care Unit Universidade do Estado do Rio de Janeiro Department of Internal Medicine Universidade Federal do Rio de Janeiro Servicio de Inmunología y Reumatología Hospital de Pediatría Garrahan Department of Clinical Sciences and Community Health University of Milan Division of Rheumatology University Hospital Meyer Rheumatology Division National Medical Research Center of Children's Health Sechenov First Moscow State Medical University Department of Immunology Rheumatology and Allergy Queen Rania Children's Hospital Saint-Petersburg State Pediatric Medical University UOC Pediatria a Media Intensità di Cure Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Rheumatology Department Faculty of Medicine Suez Canal University Department of Pediatrics King Faisal Specialist Hospital and Research Center Dipartimento Promise G. D'Alessandro Università degli Studi di Palermo Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP UOC Pediatria Servizio di Immuno-Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Messina UO Nefrologia e Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Department of Pediatrics School of Medicine Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Pediatric Unit Ospedale Vito Fazzi Pediatric Unit AON SS Antonio e Biagio e Cesare Arrigo Children's Hospital Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP

Summary TANK binding kinase 1 (TBK1) regulates IFN-I, NF-κB, and TNF-induced RIPK1-dependent cell death (RCD). In mice, biallelic loss of TBK1 is embryonically lethal. We discovered four humans, ages 32, 26, 7, and 8 from three unrelated consanguineous families with homozygous loss-of-function mutations in TBK1. All four patients suffer from chronic and systemic autoinflammation, but not severe viral infections. We demonstrate that TBK1 loss results in hypomorphic but sufficient IFN-I induction via RIG-I/MDA5, while the system retains near intact IL-6 induction through NF-κB. Autoinflammation is driven by TNF-induced RCD as patient-derived fibroblasts experienced higher rates of necroptosis in vitro, and CC3 was elevated in peripheral blood ex vivo. Treatment with anti-TNF dampened the baseline circulating inflammatory profile and ameliorated the clinical condition in vivo. These findings highlight the plasticity of the IFN-I response and underscore a cardinal role for TBK1 in the regulation of RCD.

Objective.To revise the current juvenile idiopathic arthritis (JIA) International League of Associations for Rheumatology (ILAR) classification criteria with an evidence-based approach, using clinical and routine laboratory measures available worldwide, to identify homogeneous clinical groups and to distinguish those forms of chronic arthritis typically seen only in children from the childhood counterpart of adult diseases.Methods.The overall project consists of 4 steps. This work represents Step 1, a Delphi Web-based consensus and Step 2, an international nominal group technique (NGT) consensus conference for the new provisional Pediatric Rheumatology International Trials Organization JIA classification criteria. A future large data collection of at least 1000 new-onset JIA patients (Step 3) followed by analysis and NGT consensus (Step 4) will provide data for the evidence-based validation of the JIA classification criteria.Results.In Step 1, three Delphi rounds of interactions were implemented to revise the 7 ILAR JIA categories. In Step 2, forty-seven questions with electronic voting were implemented to derive the new proposed criteria. Four disorders were proposed: (a) systemic JIA; (b) rheumatoid factor–positive JIA; (c) enthesitis/spondylitis-related JIA; and (d) early-onset antinuclear antibody–positive JIA. The other forms were gathered under the term “others.” These will be analyzed during the prospective data collection using a list of descriptors to see whether the clustering of some of them could identify homogeneous entities.Conclusion.An international consensus was reached to identify different proposed homogeneous chronic disorders that fall under the historical termJIA. These preliminary criteria will be formally validated with a dedicated project.

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

To describe the frequency and types of disease damage occurring with childhood-onset systemic lupus erythematosus (SLE) as measured by the 41-item Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and to assess the SDI's ability to reflect damage severity.Information for the SDI was prospectively collected from 1,048 childhood-onset SLE patients. For a subset of 559 patients, physician-rated damage severity measured by visual analog scale (MD VAS damage) was also available. Frequency of SDI items and the association between SDI summary scores and MD VAS damage were estimated. Finally, an international consensus conference, using nominal group technique, considered the SDI's capture of childhood-onset SLE-associated damage and its severity.After a mean disease duration of 3.8 years, 44.2% of patients (463 of 1,048) already had an SDI summary score0 (maximum 14). The most common SDI items scored were proteinuria, scarring alopecia, and cognitive impairment. Although there was a moderately strong association between SDI summary scores and MD VAS damage (Spearman's r = 0.49, P0.0001) in patients with damage (SDI summary score0), mixed-effects analysis showed that only 4 SDI items, each occurring in2% of patients overall, were significantly associated with MD VAS damage. There was consensus among childhood-onset SLE experts that the SDI in its current form is inadequate for estimating the severity of childhood-onset SLE-associated damage.Disease damage as measured by the SDI is common in childhood-onset SLE, even with relatively short disease durations. Given the shortcomings of the SDI, there is a need to develop new tools to estimate the impact of childhood-onset SLE-associated damage.

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Hindi language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). A total of 275 JIA patients (28.4% systemic, 10.9% oligoarticular, 13.8% RF negative polyarthritis, 46.9% other categories) and 98 healthy children were enrolled in three centres. The JAMAR components discriminated well healthy subjects from JIA patients. Notably, there is no significant difference between the healthy subjects and their affected peers in the school-related problems variable. All JAMAR components revealed good psychometric performances. In conclusion, the Hindi version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

OBJECTIVE: To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. STUDY DESIGN: The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. RESULTS: Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99% for a score of =123. A cutoff value of =60 revealed the best performance in discriminating pHLH from MAS. CONCLUSION: The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

Objective. To report baseline articular, functional and ocular findings of the first international prospective cohort study of Blau syndrome (BS). Methods. Three-year, multicentre, observational study on articular, functional (HAQ, Childhood HAQ and VAS global and pain), ophthalmological, therapeutic and radiological data in BS patients. Results. Baseline data on the first 31 recruited patients (12 females and 19 males) from 18 centres in 11 countries are presented. Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees. Median disease duration was 12.8 years (1.1-57). Arthritis, documented in all but one patient, was oligoarticular in 7, polyarticular in 23. The median active joint count was 21. Functional capacity was normal in 41%, mildly impaired in 31% and moderate-severe in 28% of patients. The most frequently involved joints at presentation were wrists, ankles, knees and PIPs. On radiographs, a symmetrical non-erosive arthropathy was shown. Previously unknown dysplastic bony changes were found in two-thirds of patients. Ocular disease was documented in 25 of 31 patients, with vitreous inflammation in 64% and moderate-severe visual loss in 33%. Expanded manifestations (visceral, vascular) beyond the classic clinical triad were seen in 52%. Conclusion. BS is associated with severe ocular and articular morbidity. Visceral involvement is common and may be life-threatening. Bone dysplastic changes may show diagnostic value and suggest a previously unknown role of NOD2 in bone morphogenesis. BS is resistant to current drugs, suggesting the need for novel targeted therapies.

Background: Childhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated. Methods: Cross-sectional studies of stratified random samples of 8-12-year-old children (n=10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated. Results: Overweight (odds ratio=1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio=1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/ FVC, -0.90, 95%-confidence interval: -1.33%; -0.47%, for overweight and -2.46%, 95%-confidence interval: -3.84%; -1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null. Conclusions: Our data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders., peer-reviewed

Methods Retrospective chart review of the demographic, clinical, diagnostic and genetic characteristics were studied. Results Over seven years, 12 of 1214 new cases seen in the Pediatric Rheumatology Clinic (1%) (M: F = 1:1), were diagnosed as Sarcoidosis. 11/12(91.7%) had an onset ≤4 years of age, 8/12(67%) maintained a cumulative followup of 33.7 years ( range 1-9 years). 7/12(58.3%) had received anti-tuberculous therapy prior to referral. Diagnosis was by clinical presentation ‘plus’: ACE (4/ 12), biopsy (1/12), biopsy and ACE (3/12), biopsy and mutation (1/12), mutation (2/12). 3/9(33.3%) are positive for CARD15 mutation (Blau Syndrome). 2 have sporadic mutations at R334W while 1 with a mutation at

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, 320-1110] 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.

OBJECTIVES: To report methodology and overall clinical, laboratory and radiographic characteristics for Henoch-Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) classification criteria. METHODS: The preliminary Vienna 2005 consensus conference, which proposed preliminary criteria for paediatric vasculitides, was followed by a EULAR/PRINTO/PRES - supported validation project divided into three main steps. Step 1: retrospective/prospective web-data collection for HSP, c-PAN, c-WG and c-TA, with age at diagnosis

International audience; The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy. The cross-sectional study involved 54,178 children (aged 8-12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested. The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5-24.5% and 1.4-45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0-71% for a positive skin-prick test to one or more seasonal allergens and 0-41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens. Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.

International audience; RATIONALE: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. OBJECTIVES: To investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. METHODS: Cross-sectional studies of random samples of 8- to 12-year-old children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 31,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). MEASUREMENTS AND MAIN RESULTS: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient rho = 0.50, P = 0.006, and rho = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (rho = 0.47, P = 0.01). CONCLUSIONS: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.

Musculoskeletal examination(MSKe) is a neglected clinical skill in paediatric practice and this could contribute to delayed or missed rheumatologic diagnosis in children. paediatric Gait Arms Legs Spine (pGALS), a simple format of MSKe, targeted at non specialists has been shown to be acceptable and valid. Its potential as a clinical tool in populations underserved by paediatric rheumatologists, such as India, has yet to be explored. This information could be used to design curricula and teaching methods to students and practitioners in such areas.

The occurrence of Erythema Multiforme (EM) like lesions in lupus has been reported in 98 patients to date but only in 9 children below 18 years.

Description MG, now a 10 year old female, was seen with a history of recurrent fevers since 1 month of life with bilateral knee effusions noted at 1.5 years of age, in the year 2002. This was initially treated as ANA negative oligoarticular JIA, requiring intra-articular steroid injections twice. She has never had a history of skin manifestations or uveitis. Over time, the knees showed increasing bogginess without restriction of activity. Six years after being lost to follow up, in mid 2008, at the age of 8 years, she presented with features of cardiac failure, arrhythmias (ventricular premature beats) and arthritis of the elbow joint. Investigations showed normal blood counts, normal eye examination and raised ESR. The 2D Echo showed dilated cardiomyopathy with a 20% ejection fraction with an abnormal myocardial echogenicity. Recurrent fevers since early childhood with arthritis and cardiomyopathy lead to a suspicion of an autoinflammatory syndrome. Further investigations showed a normal serum ACE and the DNA analysis showed a punctual mutation at G464W in exon 4 of the CARD15 gene. Liver and cardiac biopsies were deferred due to poor cardiac function. An identical genetic mutation was found in the mother who had a history of recurrent fevers, abdominal pain and respiratory symptoms that had never been investigated. Since then, MG has been on tapering oral steroid (started at 1mg/kg/ day), injectable Methotrexate (1517.5 mg/m) and anti-failure line of therapy. Initially, her symptoms improved with only a marginal improvement in the cardiac function. In early 2009, mild hypertension was documented and in September 2009, carotid pulsations were found reduced. By mid 2010, she had severe hypertension (230/120 mmHg), uncontrolled on multiple antihypertensives, with renal and carotid bruits. Digital Subtraction Angiography showed generalized narrowing of the aorta, carotids, left subclavian artery and bilateral renal arteries, suggestive of an aortoarteritis. The cerebral circulation was maintained normally with diffuse collaterals. The ultrasound abdomen showed a contracted left kidney with the right kidney perfusion maintained with an accessory artery with multiple renal hypo-echogenecities. The renal function and calcium excretion were normal with negative ANCAs. Three years into follow-up after diagnosis of aortoarteritis, on continuing therapy, she remains asymptomatic with an improvement in her cardiac function to an ejection fraction of 55%. Intervention such as stenting of the stenosed major vessels has currently been deferred due to the widespread nature of the aortoarteritis being aided with diffuse collateral circulation maintaining normal function.

Systemic-onset Juvenile Idiopathic Arthritis (SOJIA) is not rare in India, where biotherapies are unaffordable.Data on its course, outcome and complications are scarce.

Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA), whose prompt recognition and treatment are critical. However, early diagnosis of MAS is often challenging and none of the current diagnostic criteria is satisfactory. An international project aimed to develop a new set of classification criteria for MAS was recently started.

Description A 10 year old female, born of third degree consanguinity was referred for abnormal skeletal findings and suspected arthritis. On examination she had camptodactyly of all digits. Facial dysmorphism, camptodactyly, skeletal findings and subnormal intelligence were suggestive of the Guadalajara Syndrome. Facial dysmorphism (midfacial hypoplasia, hypertelorism, long neck, small, posteriorly rotated ears) and subnormal intelligence were compatible with Type I variant but muscle (gluteal hypoplasia), genital (labial hypoplasia) and skeletal findings (brachydactyly, simian creases, osteopenia and pelvic hypoplasia) were seen as has been described in the Type II variant. Other additional findings (not reported on OMIM to date), were a cervical rib, flattened thenar eminences, divarication of rectii and exomphalos. Short stature and microcephaly, known to be common to both the variants, were also noted. Conclusions This child had overlapping features of both types of variants of the Guadalajara Syndrome. Her subnormal intelligence and craniofacial features were that of Type I while musculoskeletal findings were that of Type II. This leaves us to speculate that the two variants are probably not distinct entities but there exists a continuing spectrum in the syndrome.

Methotrexate (MTX), the disease modifying antirheumatic drug (DMARD) of first choice in juvenile idiopathic arthritis (JIA), is not effective in 45-50% of patients with polyarticular course JIA. In developed countries, when MTX fails, the next step is to start biologicals. In resource limited settings this step is constrained by prohibitive cost and children failing MTX run the risk of poor disease control or steroid overuse. There is paucity of data on use of other DMARDs or their combinations in such children. MTX and leflunomide (LEF) are known to have differing and complementary actions in modifying the immune response and this combination has been studied in adults. Their combined cost is a fraction of the cost of biologicals.

Blau syndrome is an autosomal dominant monogenic granulomatous disease associated with gain of function mutations at or near the NACHT domain of NOD2; it is the only form of granulomatous arthritis with a known gene mutation. Although its phenotype has been amply described as a triad of arthritis, uveitis and dermatitis in case series and retrospective cohorts, prospective studies on natural history and outcome have not been done.

Results 20 patients (male-12, female-8) were diagnosed as having definite or probable juvenile dermatomyositis based on the Bohan and Peter criteria.. The mean age at diagnosis was 7.02 years(range 3 to 15.25 years) and the mean duration of disease prior to diagnosis was 7.5 months (range 3 weeks-2 years).The most frequent symptoms at presentation were typical skin rash(100%), proximal muscle weakness(20/20-100%), fatigue(16/2080%), fever(13/20-65%) and arthralgia(11/20-55%).Dysphagia was seen in 5/20(25%), cutaneous ulcers in 4/20 (20%), calcinosis in 3/20(15%), lipodystrophy in 2/20 (10%) and pyogenic infections in 2/20 (10%). Hirsutism was seen in 3/20(15%) and vitiligo in 1/20(5%). One of the patients had associated insulin dependent diabetes mellitus and chronic hepatitis. None of the patients in the cohort presented with or developed cardiomyopathy. All patients presented with at least one of the four serum muscle enzyme levels elevated. Interestingly, a normal range of creatine kinase (CK.) was seen in 11/20 (55%) of the patients. Electromyography was done in 4 patients and muscle biopsy done to confirm the diagnosis in one patient. Magnetic resonance imaging of the thigh muscles was used to as an aid to diagnosis in 10/ 20 patients and was abnormal in all Pulse steroids were used to induce remission in 10 patients and as a rescue for relapses in one patient. IVIG was used as rescue therapy in 2 children with good results. All patients received oral steroids and methotrexate as the standard maintanence treatment. Hydroxychloroquine was added in patients with dominant cutaneous manifestations. 4 children with inadequate response, ulcerative disease or hepatotoxicity received Azathioprine (4/4), cyclosporine (1/4), cyclophosphamide(1/4) as additional therapy. One child with extensive calcinosis is being treated with monthly IVIG, diltiazem and colchicine. The total follow-up period was 62.24 patient-years (range0.58 to 12.17 years). A monocyclic course was seen in 15/20(75%), relapsing course in 3/20 (15%) and a chronic progressive course in 2/20(10%).No mortality has been reported till date.