OBJECTIVE: Cyclophosphamide (CYC) is used in clinical practice off-label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). METHODS: This was an international, open-label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. RESULTS: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). CONCLUSION: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health-related quality of life than CYC treatment.

• MeSH
• cyklofosfamid terapeutické užití   MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   MeSH
• indukce remise metody   MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• polyarteritis nodosa farmakoterapie   MeSH
• předškolní dítě MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• práce podpořená grantem MeSH

OBJECTIVES: To describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs). METHODS: Clinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases. RESULTS: This study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%). CONCLUSION: This study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

• MeSH
• antagonista receptoru pro interleukin 1 terapeutické užití   MeSH
• antirevmatika terapeutické užití   MeSH
• chronická nemoc MeSH
• dědičné zánětlivé autoimunitní nemoci farmakoterapie   genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• genetická variace genetika   MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• kolchicin terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rodokmen MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVES: To provide an overview of the paediatric rheumatology (PR) services in Europe, describe current delivery of care and training, set standards for care, identify unmet needs and inform future specialist service provision. METHODS: An online survey was developed and presented to national coordinating centres of the Paediatric Rheumatology International Trials Organisation (PRINTO) (country survey) and to individual PR centres (centre and disease surveys) as a part of the European Union (EU) Single Hub and Access point for paediatric Rheumatology in Europe project. The survey contained components covering the organization of PR care, composition of teams, education, health care and research facilities and assessment of needs. RESULTS: Response rates were 29/35 (83%) for country surveys and 164/288 (57%) for centre surveys. Across the EU, approximately one paediatric rheumatologist is available per million population. In all EU member states there is good access to specialist care and medications, although biologic drug availability is worse in Eastern European countries. PR education is widely available for physicians but is insufficient for allied health professionals. The ability to participate in clinical trials is generally high. Important gaps were identified, including lack of standardized clinical guidelines/recommendations and insufficient adolescent transition management planning. CONCLUSION: This study provides a comprehensive description of current specialist PR service provision across Europe and did not reveal any major differences between EU member states. Rarity, chronicity and complexity of diseases are major challenges to PR care. Future work should facilitate the development, dissemination and implementation of standards of care, treatment and service recommendations to further improve patient-centred health care across Europe.

• MeSH
• biologické přípravky terapeutické užití   MeSH
• biomedicínský výzkum statistika a číselné údaje   MeSH
• dítě MeSH
• dostupnost zdravotnických služeb organizace a řízení   normy   MeSH
• lidé MeSH
• mezisektorová spolupráce MeSH
• monitorování léčiv metody   MeSH
• poskytování zdravotní péče organizace a řízení   normy   MeSH
• přechod k lékaři pro dospělé organizace a řízení   normy   MeSH
• průzkumy zdravotní péče MeSH
• revmatické nemoci terapie   MeSH
• revmatologie výchova   organizace a řízení   normy   MeSH
• služby zdravotní péče o dítě organizace a řízení   normy   MeSH
• spotřeba léčiv statistika a číselné údaje   MeSH
• standardní péče MeSH
• studium lékařství organizace a řízení   normy   MeSH
• výzkum zdravotnických služeb metody   MeSH
• zdravotnické služby - potřeby a požadavky statistika a číselné údaje   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

INTRODUCTION: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. METHODS: The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. RESULTS: The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. CONCLUSION: The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.

• MeSH
• dědičné zánětlivé autoimunitní nemoci komplikace   diagnóza   MeSH
• dítě MeSH
• dospělí MeSH
• familiární středomořská horečka komplikace   diagnóza   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nedostatek mevalonátkinázy komplikace   diagnóza   MeSH
• odchylka pozorovatele MeSH
• periodické syndromy asociované s kryopyrinem komplikace   diagnóza   MeSH
• počítačová simulace MeSH
• registrace MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH

OBJECTIVES: Autoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency. METHODS: We developed the ADDI by consensus building. The top 40 enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions, which were then formally weighted in a scoring system derived using decision-making software, known as 1000minds. RESULTS: More than 80% of the experts and patients completed the online surveys. The preliminary ADDI contains 18 items, categorised in the following eight organ systems: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example, chronic musculoskeletal pain. CONCLUSIONS: An instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building. Patients fulfilled a significant role in this process.

• MeSH
• dědičné zánětlivé autoimunitní nemoci komplikace   MeSH
• dítě MeSH
• dospělí MeSH
• horečka komplikace   MeSH
• konsensus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• přehledová literatura jako téma MeSH
• průzkumy a dotazníky MeSH
• senioři MeSH
• stupeň závažnosti nemoci * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH

OBJECTIVES: Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa). METHODS: A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis. RESULTS: A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available. CONCLUSIONS: We suggest that the methodological template we propose could be applied to trial design for other rare diseases.

• MeSH
• Bayesova věta MeSH
• cyklofosfamid terapeutické užití   MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• kyselina mykofenolová analogy a deriváty   terapeutické užití   MeSH
• lidé MeSH
• polyarteritis nodosa farmakoterapie   MeSH
• randomizované kontrolované studie jako téma MeSH
• výsledek terapie MeSH
• vzácné nemoci farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The objective of this study was to evaluate the clinical features, disease activity, treatment and outcome of childhood TA in a tertiary UK centre. METHODS: We analysed a retrospective case series of children fulfilling the TA classification criteria of the European League against Rheumatism, the Paediatric Rheumatology European Society and the Paediatric Rheumatology International Trials Organisation. Data regarding demographics, clinical features, treatments and outcomes were recorded. Descriptive statistics are expressed as median and range. Fisher's exact test was used for group comparisons. The Paediatric Vasculitis Activity Score (PVAS), Paediatric Vasculitis Damage Index (PVDI), Disease Extent Index-Takayasu (DEI.Tak) and Indian Takayasu Arteritis Activity Score (ITAS2010) were calculated retrospectively. RESULTS: A total of 11 children (64% female) with age at diagnosis of 11.8 (1.3 to 17) years were identified over a 23-year period. The median time to diagnosis was 17 (0 to 132) months. The most common clinical features at presentation were arterial hypertension (72.7%), systemic features (36%) and cardiovascular (45%), neurological (36%), pulmonary (27%), skin (9%), renal (9%) and gastrointestinal (9%) involvement. At presentation, PVAS was 5/63 (1 to 13); DEI.Tak was 7/81 (2 to 12) and ITAS2010 was 9/57 (6 to 20). Treatment included corticosteroids (81.8%), combined with methotrexate in most cases (72.7%). Cyclophosphamide (36.4%) and biologic agents (45.5%) were reserved for severe and/or refractory cases. PVDI at latest follow-up was 5.5/72 (3 to 15). Mortality was 27%. Young age at disease onset (<5 years old) and permanent PVDI scores≥3 were significantly associated with mortality risk (P=0.024). CONCLUSION: TA is a rare and potentially life-threatening large-vessel vasculitis. Improved awareness of TA is essential to secure a timely diagnosis. Although the evidence base for the treatment of TA in children is weak, we found that it is essential to treat it aggressively because our data emphasise that the mortality and morbidity in the paediatric population remains high.

• MeSH
• centra terciární péče * MeSH
• diagnostické zobrazování metody   MeSH
• dítě MeSH
• endovaskulární výkony metody   MeSH
• imunosupresivní léčba metody   MeSH
• incidence MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Takayasuova arteriitida diagnóza   farmakoterapie   epidemiologie   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Spojené království MeSH

BACKGROUND: Rare chronic childhood vasculitides lack a reliable disease activity assessment tool. With emerging new treatment modalities such a tool has become increasingly essential for both clinical practice and therapeutic trials to reproducibly quantify change in disease state. OBJECTIVE: To develop and validate a paediatric vasculitis activity assessment tool based on modification of the Birmingham Vasculitis Activity Score (BVASv.3). METHODS: A paediatric vasculitis registry was reviewed to identify clinical features missing in the BVASv.3. A modified nominal group technique was used to develop a working version of the Paediatric Vasculitis Activity Score (PVAS). Prospective validation provided tool reliability, reproducibility and responsiveness to change. Training of assessors was done according to the BVAS principles. RESULTS: BVAS items were redefined (n=22) and eight paediatric items added in Cutaneous (n=4), Cardiovascular (n=3) and Abdominal (n=1) sections. The final PVAS has 64 active items in nine categories. The principles of new/worse and persistently active disease were retained as were the overall score and weighting of categories. The median PVAS in 63 children with systemic vasculitis was 4/63 (0-38/63). There was a high interobserver agreement for the overall as well as for subsystem scores (linear-weighted-κ ≥0.87). PVAS correlated with physician's global assessment (p<0.01); treatment decision (p=<0.01) and erythrocyte sedimentation rate (ESR) (p=0.01). In response to treatment, 15/19 patients assessed demonstrated a significant fall in PVAS (p=0.002), with good agreement among assessors for this change. CONCLUSIONS: The PVAS validity in children with systemic vasculitis was demonstrated. Like the BVAS, we anticipate that the PVAS will provide a robust tool to objectively define disease activity for clinical trials and future research.

• MeSH
• chronická nemoc MeSH
• dítě MeSH
• glukokortikoidy terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• odchylka pozorovatele MeSH
• předškolní dítě MeSH
• reprodukovatelnost výsledků MeSH
• stupeň závažnosti nemoci * MeSH
• vaskulitida diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH