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Das muskuloskeletale System unterliegt in Kindheit und Jugend bis zum Erreichen der Endgrose einem ausgepragten Langenwachstum. Zusatzlich muss sich das muskuloskeletale System kontinuierlich an die aktuellen auf Muskel und Knochen einwirkenden Beanspruchungen adaptieren. Uber die funktionelle Muskel-Knochen-Einheit wird im Sinne eines Regelkreises der Knochenaufbau und -abbau angepasst. Im Rahmen chronischer Erkrankungen (neurologische Erkrankungen, Knochenstoffwechselstorungen, rheumatisch-entzundliche Erkrankungen) aber auch im Rahmen einer kurzfristigen Immobilitat kommt es haufig direkt oder indirekt zu Veranderungen der funktionellen Muskel-Knochen-Einheit, der Gelenke oder der Bewegungsmuster, was letztlich in einer „Bewegungsstorung“ bzw. in veranderten Bewegungsmustern mundet. Unabhangig von der zugrunde liegenden Ursache scheinen die reduzierte Beweglichkeit, das veranderte Bewegungsmuster und die teilweise resultierende Immobilitat die Teilhabe der Betroffenen am Leben deutlich zu reduzieren, weswegen diesem Symptom eine hohe Wichtigkeit aus Sicht der Patienten zugeschrieben wird. Eine gezielte Diagnostik mit funktioneller Analyse der vorliegenden Bewegungsstorung erscheint unabdingbar, um ein interdisziplinar individuelles Betreuungskonzept, basierend auf der zugrunde liegenden Erkrankung, anbieten und dessen Wirksamkeit beurteilen zu konnen sowie die Lebensqualitat und Teilhabe der Betroffenen zu erhalten.

Entzundlich-rheumatische Erkrankungen im Kindes- und Jugendalter stellen in der Versorgung von akuten Traumata eine besondere Herausforderung dar. Bei Kindern und Jugendlichen haben sich die medikamentosen Behandlungsstrategien modifiziert. Welche Besonderheiten sind beim jungen Rheumatiker zu berucksichtigen, wenn ein Trauma zu einem operativen Verfahren zwingt? Uber eine Literaturrecherche werden Empfehlungen fur die Praxis erarbeitet. Die gelenkbetonten Veranderungen beim jungen Rheumatiker unterscheiden sich im Hinblick auf die unterschiedlich veranderten entzundlich-rheumatischen Destruktionen. Das Ausmas der entzundlich-destruktiven Veranderungen diktiert das operative Vorgehen. Konsequenzen ergeben sich in der Beachtung der Begleitmedikation im Hinblick auf die Vermeidung eines schubauslosenden Geschehens und einer Gewebeinfektion. Die Knochenfestigkeit zwingt zur individuellen Wahl von Implantaten und ggf. Dauer der Nachbehandlung. In den fruhen Stadien des Entzundungsprozesses unterscheiden sich die Vorgehensweisen bei Traumata nicht vom Gesunden, in spateren (Larsen-Dale-Eeck-Stadium III) schon. Ein interdisziplinares Konzept kann Nachteile in der Therapie der Grunderkrankung vermeiden helfen. Aufgrund der besonderen dysplastischen Anatomie und Gewebeveranderungen stellen Traumata bei dieser Klientel eine besondere Herausforderung dar.

Juvenile Idiopathic Arthritis (JIA) patients living in areas with high prevalence of tick-borne-encephalitis-virus-(TBEV)-infection are recommended for administration of inactivated TBE-vaccination. However, there are serious concerns regarding protective vaccine-induced immune responses against TBEV in immunocompromised patients. The present study aimed to analyze the humoral and cellular immune response to TBE-vaccination in previously TBE-vaccinated JIA patients compared to healthy controls (HC) including investigation of IgG-anti-TBEV avidity, neutralization capacity, cellular reactivity by IFNgamma-ELISPOT and cytokine secretion assays. Similar IgG-anti-TBEV antibody concentrations, neutralization titers and cellular reactivity were found between JIA and HC. The number and the early timing of booster vaccinations after primary vaccination had the most prominent effect on neutralizing antibodies in JIA and on IgG-anti-TBEV concentrations in both JIA and HC. Administration of booster vaccinations made it more likely for JIA patients to have IgG-anti-TBEV concentrations ≥165 VIEU/ml and avidities >60%. TNF-alpha inhibitors had a positive and MTX administration a negative effect on humoral immune responses. In conclusion, irrespective of having JIA or not, vaccinated children showed similar humoral and cellular immunity against TBEV several years after primary TBE-vaccination. However, in JIA, booster vaccinations mounted a significantly higher humoral immune response than in JIA without boosters. Our results highlight the need for timely administration of boosters particularly in JIA. Although immunosuppressive treatment at vaccinations in diagnosed JIA had a negative effect mainly on TBEV-specific cellular immunity, most JIA patients mounted a favorable humoral immune response which was maintained over time. Thus, successful TBE-vaccination seems highly feasible in JIA patients with immunosuppressive regimens.

Adalimumab (ADA) has become a valuable treatment option for juvenile idiopathic arthritis (JIA). The importance of combination with methotrexate (MTX) is unclear.Data from the German Biologics in Paediatric Rheumatology (BIKER) registry are reported. Response to treatment was analysed using JIA American College of Rheumatology (ACR) scores, 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and improvement of functional status and ACR inactive disease criteria. Compa-risons between rates of adverse events (AEs) and serious adverse events (SAEs) provided data for the safety assessment.Overall, 584 patients with non-systemic JIA started ADA therapy, 61% of whom received concomitant MTX treatment at baseline. The latter patients were younger (p 0.001), with shorter disease duration (p = 0.001), more frequently had antinuclear antibodies (p = 0.04), and had higher baseline JADAS10 scores (p = 0.03). In patients with ADA monotherapy, enthesitis-related arthritis (p = 0.004) and presence of human leucocyte antigen-B27 (p = 0.008) were documented more often. Mean treatment duration in both cohorts was 15 months. Comparable last follow-up rates for JIA ACR 30/50/70/90% response, JADAS minimal disease activity, JADAS remission, and ACR inactive disease were, respectively, 75/72/64/49%, 66%, 46%, and 58% for ADA monotherapy, and 77/72/61/45%, 64%, 48%, and 55%, for ADA + MTX. During 1082 patient-years (PY) of ADA exposure, 725 AEs (67/100 PY), including 57 SAEs (5.3/100 PY), were reported. Serious infections were reported in 10 patients (0.9/100 PY) and 11 (1.0/100 PY) had varicella infections/zoster reactivation. Rates of AEs, SAEs, infectious events, and serious infections did not differ between the cohorts. Elevated transaminases (p = 0.005) and gastrointestinal events (p 0.0001) were reported more often in the combination cohort. Two pregnancies and no deaths were reported.ADA demonstrated an acceptable risk profile and high percentages of patients in both cohorts showed sufficient treatment response. No differences in treatment response or adherence to treatment were found.

Background:Juvenile idiopathic arthritis (JIA) associated uveitis is an extra-articular manifestation of the JIA disease that may cause vision-threatening complications and an uncontrolled uveitis may even lead to blindness. Uveitis occurs in up to 20% of patients with JIA, depending on the JIA category. The majority of patients develop uveitis within the first two years after JIA symptom onset, but uveitis can continue into adulthood.Objectives:The main objective of this study was to analyze the risk for uveitis events after discontinuing disease-modifying antirheumatic drugs (DMARD) in patients with extended oligoarthritis and rheumatoid factor (RF)-negative polyarthritis.Methods:Data of the two ongoing multicenter biologic registers: German Biologics in Pediatric Rheumatology (BiKeR) and the Juvenile arthritis Methotrexate/Biologics long-term Observation (JuMBO) were used to analyze the adverse-event (AE) and events of special interest (ESI) reports about uveitis events during treatment and after discontinuation of DMARDs. Biker started recruitment of children and adolescent patients with JIA exposed to biological (b) or conventional (cs) DMARD’s in 2001. The patients were further followed in JuMBO after reaching the age of 18 or transitioning to an adult rheumatologist. Disease characteristics, treatment data, AE’s and ESI’s were reported by the pediatric or adults rheumatologist, respectively.Results:A total of 2,041 patients with RF-negative polyarthritis (n=1,280) or extended oligoarthritis (n=761) were included into the analyses. The mean follow-up of this study was 7.6 years (SD 5.3). About half of the patients were enrolled in BiKeR with start of etanercept (1,137, 55.7%), followed by 635 (31.1%) patients with start of methotrexate (MTX) monotherapy or adalimumab (ADA, n=198, 9.7%). A history of uveitis was reported for 238 (11.7%) patients at enrolment in BiKeR. More patients with a history of uveitis treated with ADA were included in BiKeR initiating ADA (n=98 of 238, 41.2%). Patients with uveitis had a lower age at JIA onset in comparison to patients without uveitis (mean 3.6 (SD 3.0) versus 7.0 (SD 4.5) years). A total of 142 recurrent (84% of 169) uveitis events were reported in 93 patients and for 27 patients (1.3% of 2,041) was an incident uveitis reported during follow-up. More than one uveitis event was reported for 32 patients with a maximum number of 4 uveitis flares in 3 patients. Nineteen uveitis flares (11.2% of 169) were reported for patients after the age of 18. The longer the time since DMARD discontinuation the fewer uveitis events occurred. Uveitis events were significantly more often reported in the first 24 months after MTX discontinuation (2 at last MTX intake had a higher likelihood for uveitis events (OR=1.40, 95%CI: 1.02 to 1.92).Conclusion:This is the first study that analyzed the risk of uveitis after DMARD withdrawal. Uveitis relapses are common. Patients who discontinued DMARD therapy were at high risk for uveitis within the first 3 to 24 months after discontinuation. Rheumatologists and ophthalmologists should be aware about this risk which should lead to a regular uveitis screening after DMARD withdrawal.Disclosure of Interests:Jens Klotsche: None declared, Ariane Klein: None declared, Martina Niewerth: None declared, Tilmann Kallinich: None declared, Daniel Windschall: None declared, Johannes-Peter Haas: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, Abbvie, SOBI, Roche, Novartis, Toni Hospach: None declared, Frank Dressler: None declared, Kirsten Minden: None declared, Gerd Horneff: None declared

Background:Various treatment strategies are used for children with newly diagnosed polyarticular JIA. MTX is usually prescribed, sometimes in combination with high-dose intravenous glucocorticoid pulses (HDGC) or multiple intra-articular GC injections (IAGC). These different approaches were considered in the German consensus-based treatment protocols for polyarticular JIA1, they were also the leading therapies in patients with rheumatoid factor-negative polyarthritis (RF- PA) included in the JIA inception cohort ICON.Objectives:To compare the effectiveness of three different treatment strategies in nearly DMARD-naïve patients with RF- PA.Methods:Patients with RF- PA who were included in the ICON cohort and received one of the following treatments within the first three months were considered for the analysis: Group 1: MTX + IAGC in >4 joints, Group 2: MTX + HDGC, Group 3: MTX, no IAGC in >4 joints, no HDGC. Propensity score-adjusted group differences in outcomes after one and two years were analysed by linear and logistic regression analyses.Results:The analysis included data from 150 patients (79% female, mean age 6.7±4.8 years) enrolled in ICON 1.6±1.9 months after the diagnosis of RF- PA, of whom 52 were in Group 1, 54 in Group 2 and 44 in Group 3. Disease activity did not differ significantly between the groups at treatment start (cJADAS-10 16.7±4.7, 15.8±5.7, 15.9±6.5, respectively).Of the total group, at 1- and 2-year follow-up (FU), 60.9%/60.1% and 52.3%/58.8% of patients had inactive disease (cJADAS ≤1/Wallace criteria2), 21.3% and 35.6% were in remission off drug2, and mean cJADAS-10 scores were 2.6±3.9 and 3.0±3.5, respectively. 60.5% and 67.0% had no functional limitations (CHAQ=0).Patients in Group 1 more often had an inactive disease (according to Wallace2) at the 1-year FU and tended to have inactive disease more often at 2-year FU than patients in Group 3 (78.1% vs. 45.2%, p=0.025; 73.3 vs. 49.1%, p=0.075, respectively). Group 2 patients (inactive disease in 56.1% and 53.4% at 1- and 2-year FU) did not differ significantly from either Group 1 or Group 3. In addition, Group 1 patients had a significantly better quality of life than patients of Group 2 at the 2-year FU (mean PedsQL 4.0 total score 90.4±9.3 vs. 83.8±11.2, p=0.031). At that time, Group 3 patients had a mean PedsQL 4.0 total score of 85.0±14.6, which was not significantly different from either Group 1 or 2.On the other hand, Group 1 patients tended to develop new uveitis more frequently within the first two years of treatment than patients in Groups 2 and 3 (13% vs. 2.2% and 3.6%, p=0.101 and 0.131, respectively). At the 2-year FU, patients in Group 1 also had a significantly lower mean height SDS than patients of Group 3 (-0.3±1.1 vs. 0.2±1.1, p=0.038). Mean height SDS was lowest (-0.5±0.8) in patients in Group 2 and significantly lower than in Group 3 (0.019). Mean body mass index SDS also differed significantly between the groups at 2-year follow-up. The mean BMI SDS was highest in Group 1 patients (0.2±0.8), differing significantly from Group 2 (-0.3±0.7, p=0.014) and Group 3 (-0.4±1.1, p=0.023).There were no significant differences in inactive disease (according to cJADAS) and functional status (CHAQ) between the three groups at 1- and 2-year FU. Over time, treatments were very different in the three groups. In Group 3, biologics were used significantly more often over time than in group 1 (54.0% vs. 18.3%, p=0.014), and Group 2 patients received bDMARDs in 36.1%.Conclusion:While patients with numerous early joint injections seem to achieve inactive disease more frequently and earlier, they have a slightly smaller body height and tend to develop uveitis slightly more often than patients with more intensive DMARD therapy. However, the differences are small between the groups. Further comparative effectiveness studies with higher patient numbers are needed to identify particularly effective and safe treatment strategies.References:[1]Horneff et al. Pediatric Rheumatology 2017;15:78.[2]Wallace et al. Arthritis Care Res (Hoboken) 2011;63:929-36.Acknowledgements:The ICON study is funded by a research grant of the Federal ministry of education and research (BMBF, FKZ 01ER0812, FKZ 01ER1504A-C).Disclosure of Interests:Kirsten Minden Speakers bureau: Pfizer, Abbvie, Consultant of: Novartis, Tobias Schwarz: None declared, Frank Dressler: None declared, Ivan Foeldvari Consultant of: Gilead, Novartis, Pfizer, Hexal, BMS, Sanofi, MEDAC, Johannes-Peter Haas: None declared, Gerd Horneff Speakers bureau: Pfizer, Consultant of: Novartis, Toni Hospach Consultant of: Novartis, Jasmin Kümmerle-Deschner: None declared, Kirsten Moenkemoeller: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, AbbVie, SOBI, Roche, Novartis, Klaus Tenbrock: None declared, Martina Niewerth: None declared, Claudia Sengler: None declared, Dirk Foell: None declared, Jens Klotsche: None declared

Background:Although children and adolescents are less likely to develop COVID-19 and generally show milder disease courses, it is unclear what impact the SARS-CoV2 infection has on children and adolescents with rheumatic and musculoskeletal disease (RMD). Due to their underlying disease as well as therapeutic immunosuppression these patients may be at higher risk of being more severely affected by SARS-CoV2. Furthermore, SARS-CoV2 infection might trigger a flare of the underlying disease.Objectives:To evaluate clinical characteristics and disease course of COVID-19 in children and adolescents with RMD and to analyze possible effects of SARS-CoV2 infection on the underlying disease under different therapeutic regimens.Methods:Data from juvenile patients with RMD recorded via the SARS-CoV2 questionnaire within the National Pediatric Rheumatology Database and the registry for hospitalized children and adolescents with COVID-19 of the German Society for Pediatric Infectious Diseases were analyzed. In addition to age, sex and diagnosis, information was collected about the date and method of a positive SARS-CoV2 testing, reason for testing, on clinical manifestations, disease course, treatment and outcome of COVID-19, on drug therapy at the time of virus detection, on disease activity (NRS 0 – 10, 0 = best) of the underlying disease at the last visit before and after the SARS-CoV2 infection.Results:From April 17th 2020 until January 25th 2021, data of 67 patients with RMD and confirmed SARS-CoV2 infection were collected. Mean age was 13.5 ± 3.9 years with equal sex distribution. The majority of patients were diagnosed with juvenile idiopathic arthritis (JIA, 64%), 12 (18%) patients had an autoinflammatory disease (FMF, CAPS, PFAPA, TRAPS) and 5 (7%) a connective tissue disease. Fifty-two patients (78%) were treated with a disease modifying antirheumatic drug (DMARD), 39% with a biological DMARD and 9% systemic glucocorticoids at the time of SARS-CoV-2 infection. Nineteen patients (28%) were tested for SARS-CoV-2 because of typical symptoms, the majority (67%) because of contact to an infected person. PCR was used most often (in 60 %).52 patients (78%) developed symptoms of COVID-19, 15 patients remained asymptomatic. The most common symptom of COVID-19 was rhinitis (42%) and fever (38%), followed by fatigue (34%), taste/smell disorder (33%), sore throat (27%) and cough (23%).Disease severity was graded as mild in 44 of 52 (85%) symptomatic patients, only two patients were hospitalized, one of whom required intensive care and died of cardiorespiratory failure 3 days after symptom onset. In 22 of 26 (85%) SARS-CoV2-positive patients, no relevant increase in disease activity (difference in NRS ≤ 1 before/after infection) of the underlying disease was observed 31 days after symptom onset (median, IQR 17-52 days). One patient, who had paused tocilizumab for 2 doses, experienced a flare of his seronegative polyarthritis 2 months after asymptomatic SARS-CoV-2 infection.Conclusion:In our cohort, the clinical picture of COVID-19 in children and adolescents with RMD was similar to that of healthy peers. The majority of patients showed mild disease course with good outcome under various medications, however, one patient with a severe course of COVID-19 died. In addition, SARS-CoV2 infection does not appear to have a relevant impact on the underlying disease activity, whereas discontinuation of therapy might pose a risk of flare.Disclosure of Interests:None declared.

Background:In patients with JIA, growth impairment and variance in body composition are well-known long-term complications that may be associated with prolonged drug therapy (e.g. glucocorticoids) as well as impaired physical and psychosocial well-being. An increased accumulation of body fat represents a significant risk factor for metabolic abnormalities and a modifiable variable for a number of comorbidities. Recently, evidence has emerged in favour of the potential negative influence of overweight on the course of the disease and treatment response [1].Objectives:The study aimed a) to estimate the prevalence of underweight, overweight and obesity in children and adolescents with JIA compared to the general population, and b) to investigate correlates of patients’ weight status.Methods:A cross-sectional analysis of physicians’ recorded body weights and heights of patients with JIA enrolled in the NPRD in the year 2019 was performed. Underweight (BMI 90th) and obesity (BMI >97th) were defined according to age- and sex-specific percentiles used in the German reference system. For comparison with data from the general population [2], sex- and age-matched pairs of 3-17-year-old patients and controls were generated. A multinomial logistic regression analysis was performed to examine the association between weight status and patients’ clinical and self-reported outcomes.Results:In total, data from 6.515 children and adolescents with JIA (age 11.2 ± 4.1 years, disease duration 4.9 ± 3.8 years, 67% girls, 40% persistent oligoarthritis) were included. Of these, 3.334 (age 5.9 ± 2.1 years, 52.5% girls) could be considered for matched-pair analysis. Compared with the general population, patients underweight, overweight and obesity rates were 10.6% (vs. 8.1%), 8.8% (vs. 8.5%) and 6.1% (vs. 5.7%), respectively. No significant sex differences were found in either group. Largest difference in prevalence was registered for underweight, specifically in the age group 3-6 years (12.9% patients vs. 5.9% controls). Similar to the general population, higher rates of overweight were observed in adolescent patients than in affected children (19.1% age group 11-13 vs. 8.4% age group 3-6). While the highest underweight prevalence was registered in patients with RF+ polyarthritis (16%), patients with Enthesitis-related arthritis (22%), psoriatic arthritis (21%) and systemic JIA (20%) showed the highest overweight rates (including obesity). Younger age (OR = 0.51, 95% CI = 0.31-0.83), more frequent physical activity (OR = 0.92, 95% CI = 0.85-0.99) and high parental vocational education (OR = 0.39, 95% CI = 0.18-0.80) were independently associated with a lower likelihood of being overweight/obese.Conclusion:The overall prevalence of underweight, overweight and obesity in children and adolescents with JIA is comparable to that found in the general population. Behavioural health promotion, including regular physical activity, as part of the treatment strategy in JIA should preventively already begin at preschool age and necessarily be made accessible to patients of all educational levels.References:[1]Giani T et al. The influence of overweight and obesity on treatment response in juvenile idiopathic arthritis. Front Pharmacol 2019;10:637.[2]Schienkiewitz A et al. BMI among children and adolescents: prevalences and distribution considering underweight and extreme obesity. Bundesgesundheitsbl 2019;62:1225–1234.Acknowledgements:The National Paediatric Rheumatological Database has been funded by AbbVie, Chugai, Novartis and GSK.Disclosure of Interests:Florian Milatz: None declared, Jens Klotsche: None declared, Martina Niewerth: None declared, Jana Hörstermann: None declared, Daniel Windschall: None declared, Frank Weller-Heinemann Speakers bureau: Pfizer, AbbVie, SOBI, Roche and Novartis., Frank Dressler: None declared, Rainer Berendes: None declared, Johannes-Peter Haas: None declared, Gerd Horneff: None declared, Kirsten Minden Speakers bureau: Pfizer, AbbVie, Consultant of: Novartis

ZusammenfassungHäufig werden Nachhol-, Auffrisch- und Indikationsimpfungen bei Patienten mit Autoimmunerkrankungen insbesondere unter Immunsuppression in Sorge vor Schüben der Grunderkrankung oder aufgrund von Unwissenheit über die meist gute Impfantwort über Jahre hinweg verschoben. Zum Zeitpunkt der Transition in die Erwachsenenrheumatologie besteht die Gelegenheit, die Vorgeschichte des Patienten aufzuarbeiten und den aktuellen Impfstatus zu überprüfen. Mögliche neue Motivation für Impfungen in diesem Lebensabschnitt stellen geplante Auslandsaufenthalte, eine Ausbildung im Gesundheitssystem oder ein Kinderwunsch dar. Um die Akzeptanz für Impfungen zu erhöhen, empfiehlt sich eine individualisierte Impfberatung unter Berücksichtigung des persönlichen Risikos einer schwer verlaufenden Infektion, die Messung von Ausgangsimpftitern, um unnötige Boosterungen zu vermeiden und – im Falle von Lebendimpfungen – der Einsatz von Impfstrategien, die ermöglichen, das Risiko für einen Schub der Grunderkrankung bzw. eine Erkrankung durch den Impfstamm zu minimieren. Aus diesem Grund werden hier immunologisch basierte Algorithmen als Diskussionsgrundlage vorgeschlagen, damit auch Patienten mit seltenen Erkrankungen und/oder immunsuppressiver Therapie nicht durch das Raster der Impfempfehlungen fallen.

Hintergrund: Bei verschiedenen chromosomalen Storungen wird ein erhohtes Risiko fur eine Juvenile Idiopathische Arthritis (JIA) vermutet. Vor allem bei Patienten mit einem Morbus Down (Trisomie 21) und einer JIA besteht daruber hinaus eine Unsicherheit bezuglich der geeigneten Therapie mit DMARDs, weil auch das Risiko bezuglich einer AML erhoht ist. Methode: In einer retrospektiven Fall-Kohorte eigener Patienten wurde das typische Verteilungsmuster und die Entzundungsaktivitat bei Patienten mit Trisomie 21 und JIA (T21-JIA) sowie deren Ansprechen und Nebenwirkungen von MTX im Vergleich zu JIA-Patienten mit seronegativer polyartikularer JIA (SNP-JIA) untersucht. Ergebnisse: Die elf eingeschlossenen T21-JIA Patienten (6 weibl./5 mannl.) hatten bei Diagnosestellung JIA ein mittleres Alter von 6 Jahren (1–13 Jahre). 9 T21-JIA Patienten (82%) hatten einen polyartikularen Verlauf und wurden mit MTX behandelt. T21-JIA Patienten hatten bei Diagnosestellung eine signifikant hohere Anzahl aktiver und schmerzhafter Gelenke (T-21 JIA 19,9 (± 10,9) vs. SNP-JIA 15,5 (± 6,5)) und prasentierten sich in 7 von 10 (70%) Fallen als SNP-JIA (gemas ILAR-Klassifikation, erwartet: 13–15%). Ein T21-JIA Patient hatte eine systemische, einer eine persistierende- und 2 eine extended oligoartikulare JIA. Im Verlauf entwickelten 81% der T21-JIA Patienten Gelenkskontrakturen. Kein T21-JIA Patient hatte im Verlauf eine Uveitis. Das Ansprechen auf MTX und die Frequenz von unerwunschten Arzneimittelwirkungen (UAW) war bei T21-JIA Patienten mit denen einer gematchten Vergleichstichprobe vergleichbar. Schlussfolgerung: T21-JIA Patienten zeigen gehauft einen polyartikularen Verlauf mit einer hoheren Anzahl betroffener Gelenke und ausgepragteren Bewegungseinschrankungen im Erkrankungsverlauf. Das Ansprechen und die UAW einer MTX-Therapie bei Patienten mit T21-JIA entspricht dem von JIA-Patienten mit einem normalen Karyotyp. Auch bei anderen chromosomalen Aberrationen namentlich Turner- (Monosomie XO), Klinefelter- (Poly-X, XXY) und Di George Syndrom (del 22q11.2) wird ein erhohtes Risiko fur das Auftreten einer JIA vermutet.

Background Vitamin D has been shown to have immunomodulatory properties in addition to its well-established role in the maintenance of mineral homeostasis and bone health. Conflicting data have been available regarding vitamin D status in children and adolescents with juvenile idiopathic arthritis (JIA) and its influence on the disease. Objectives To determine 25–0 hour-vitamin D3 (25-OHD) levels in patients with JIA, and to evaluate whether 25-OHD levels are associated with disease activity and disease course. Methods Serum 25-OHD levels were determined in a pair of serum samples from patients with JIA who were enrolled in the JIA inception cohort study ICON and prospectively followed for three years. The frequencies of 25-OHD deficiency (defined as Results In 360 patients with early JIA (48% OA, 27% rheumatoid-factor negative polyarthritis), 25-OHD levels were determined twice: after a median disease duration of 6.6 and of 13.0 months. The mean 25-OHD level of all JIA samples was insufficient (22.1 ng/ml, SD 7.8), but significantly higher than that of the control population (18.4 ng/ml, SD 10, p An insufficient mean 25-OHD level was found in 40% of JIA patients and in 25% in both samples each, sufficient levels in 13% and 7%, respectively. There were no significant differences in 25-OHD levels among the JIA categories. Disease activity, measured by the cJADAS-10, was inversely correlated with the first 25-OHD level (β=−0.20, 95% CI −0.37,–0.03, p=0.018), especially in 141 DMARD-naive patients (β=−0.26, 95% CI −0.44,–0.01, p=0.041). Up to the 3-year-follow-up, 17% (61/360) developed uveitis, and 30% (52/173) of OA patients an extended OA. While 20% (17/87) of those with 25-OHD deficiency at both measurements were affected by uveitis, this applied to only 9% (2/23) in those with sufficient levels. Multivariable regression analysis revealed that the 25-OHD level was significantly associated with the risk to develop uveitis (Hazard ratio 0.95, 95% CI 0.91,0.99, p=0.008). Twelve out of 29 (41%) patients with OA and two deficient vitamin D levels, but only 2 of 14 (14%) with two sufficient 25-OHD levels developed extended OA during the first 3 years (p=0.034). Conclusions Overall, vitamin D levels were higher in JIA patients than in matched controls. JIA patients with higher disease activity had lower 25-OHD levels. In particular, complicated courses with uveitis or the development of polyarthritis seem to be associated with lower 25-OHD levels. Further studies are needed to substantiate these results. Acknowledgements ICON is funded by the Federal Ministry of Research (FKZ:01ER0812) Disclosure of Interest C. Sengler: None declared, J. Zink: None declared, J. Klotsche: None declared, D. Foell: None declared, M. Niewerth: None declared, I. Liedmann: None declared, G. Horneff Grant/research support from: Abbvie, Pfizer, Roche, Chugai, MSD, J.-P. Haas: None declared, K. Moenkemoeller: None declared, A. Thon: None declared, K. Minden Grant/research support from: Pfizer, Abbvie, Roche

In der differenzialdiagnostischen Abklarung von Arthralgien und/oder Arthropathien bei Kindern und Jugendlichen sind auch einige z. T. sehr seltene monogenetische Erkrankungen in Betracht zu ziehen. Zunachst autoinflammatorische Erkrankungen wie das Cryopyrin assoziierte periodische Syndrom (CAPS), die pyogene Arthritis mit Pyoderma gangranosum und Akne (PAPA-Syndrom) und die Infantile Sarkoidose (Blau Syndrom); daruber hinaus genetisch bedingte Veranderungen in Regulations- und Strukturgenen des Bindegewebes wie die Progressive Pseudorheumatische Arthropathie des Kindesalters (PPAC), das Camptodaktylie-Arthropathie-Coxa vara-Perikarditis-(CACP) – Syndrom, die Multizentrische Carpotarsale Osteolyse (MCTO), die Spondyloenchondrodysplasie (SPENCD) und das Camurati-Engelmann Syndrom (CAEND). Die Vorliegende Ubersicht im Rahmen des Schwerpunktheftes gibt einen Uberblick uber diese seltenen Erkrankungen.

Background Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. Methods In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) (https://aid-register.de). Data for this retrospective TCZ study were documented by 13 centers. Results From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1–18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. Conclusion Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. Trial registration The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

OBJECTIVE: To determine whether systemic juvenile idiopathic arthritis (JIA) susceptibility loci that were identified by candidate gene studies demonstrate association with systemic JIA in the largest study population assembled to date. METHODS: Single-nucleotide polymorphisms (SNPs) from 11 previously reported systemic JIA risk loci were examined for association in 9 populations, including 770 patients with systemic JIA and 6,947 controls. The effect of systemic JIA-associated SNPs on gene expression was evaluated in silico in paired whole genome and RNA sequencing data from the lymphoblastoid cell lines (LCLs) of 373 European subjects from the 1000 Genomes Project. Responses of systemic JIA-associated SNPs to anakinra treatment were evaluated in 38 US patients for whom treatment response data were available. RESULTS: We found no association between the previously reported 26 SNPs and systemic JIA. Expanded analysis of the regions containing the 26 SNPs revealed only 1 significant association: the promoter region of IL1RN (P < 1 × 10(-4) ). Systemic JIA-associated SNPs correlated with IL1RN expression in LCLs, with an inverse correlation between systemic JIA risk and IL1RN expression. The presence of homozygous IL1RN high expression alleles correlated strongly with a lack of response to anakinra therapy (odds ratio 28.7 [95% confidence interval 3.2-255.8]). CONCLUSION: In our study, IL1RN was the only candidate locus associated with systemic JIA. The implicated SNPs are among the strongest known determinants of IL1RN and interleukin-1 receptor antagonist levels, linking low expression with increased systemic JIA risk. Homozygous high expression alleles predicted nonresponsiveness to anakinra therapy, making them ideal candidate biomarkers to guide systemic JIA treatment. This study is an important first step toward the personalized treatment of systemic JIA.

Background There is increasing experience with Etanercept (ETA) in juvenile idiopathic arthritis in the BIKER Registry. Objectives To report on practice changes ETA utilization and outcome over a period of 16 years. Methods 6 cohorts of pts were created according to inclusion period. Patients9 and disease characteristics,the utilization of DMARDs, steroids, NSAIDs were analysed. Efficacy was judged by PedACR30/50/70/90, JADAS and ACR-remission. Results Records from 2105 JIA pts treated with etanercept with at least a baseline and one follow up form were analysed. Most pts were females (67%). The median age of disease onset increased from 5.9 years in the early to 9.3 years in the later cohorts while age at start of treatment remained stable (about 13 years). Median disease duration markedly decreased from 5.3 to about 2 years. Most pts had RF neg. polyJIA followed by extended oligoarthritis. In the more recent cohorts the rate of enthesitis related arthritis increased and the rate f systemic JIA decreased (table). At registry start, 20% of newly enrolled pts belonged to the systemic JIA category compared to Conclusions In recent years, children have been treated earlier, received less concomitant treatment with NSAIDS, corticosteroids as well as DMARDs. More recent cohort of patients had less severe disease at baseline, but also showed a markedly better outcome already at one year of treatment reflected by higher rates of patients with no active joint, a CHAQ DI of 0, a JADAS-MDA, and ACR-Remission. These data suggest that early disease control and better pre-selection of patients who need biologics are important to improve outcome and safety in children with JIA. Disclosure of Interest G. Horneff Speakers bureau: Abbvie, Pfizer, Roche, Novartis, MSD, K. Minden Speakers bureau: Abbvie, Pfizer, Roche, Genzyme, Pharm-Allergan, I. Foeldvari: None declared, G. Ganser: None declared, J. Haas: None declared, J. Brunner: None declared, I. Becker: None declared

Background Since the approval of Adalimumab (ADA) for treatment of juvenile idiopathic arthritis (JIA), it has become a valuable option, which significantly improved the outcome of patients. Objectives To report efficacy (as observed) and safety of ADA in clinical practice. Methods Data from the German BiKeR register from 2011 to 2016 are reported. Baseline patient characteristics, treatment response and safety data were compared. Treatment response was analyzed using JIA-ACR criteria, JADAS score and improvement of functional status (Childhood Health Assessment Questionnaire disability index, CHAQ), JIA-ACR-scores, JADAS10-minimal disease activity (MDA), JADAS-remission and ACR-inactive disease criteria were analysed. Results 589 non-systemic JIA patients exposed to Adalimumab with at least one follow-up report were identified in the German BIKER registry, representing 1143.9 patient years (PY) of exposure to ADA and 1206.5 observation years including 90 days after discontinuation. At Baseline, 58.2% received combination with methotrexate (MTX). Patients on combination treatment had more frequently ANA, less frequently HLA-B27, had higher JADAS 10 and more often received systemic steroids (9.9% vs. 22.2%, p=0.0002). ADA dosage was 0.8mg/kg in both cohorts. At month 12 JIA-ACR 30/50/70/90 and JADAS-MDA/-remission/ACR-inactive disease was reached by 66/63/49/33/50/24/27% on monotherapy with ADA and 68/63/45/28%/50/28/27 on combination of ADA and MTX (not significant). Response rates at month 24 were 67/66/54/35/65/32/29% on ADA monotherapy and 67/61/46/31/57/35/30% on ADA+MTX combination cohort (not significant). The rate (/100PY) of all adverse events (AE)/serious AE/infections/serious infections/uveitis events was 52.3/2.2/16.4/4.6 upon monotherapy and 65.3/5.1/2.3/16.4/6.2 upon combination. Only rates for any AE were significantly higher upon combination (p=0.008) as well as rate of elevated transaminase (p=0.01). Rate of patients with an uveitis event was higher upon combination (9.6% vs. 5.3%, p=0.007) Conclusions Adalimumab demonstrated high response rates and an acceptable risk profile. Efficacy and safety of monotherapy was not inferior to combination therapy with MTX. Disclosure of Interest A. Klein: None declared, K. Minden Speakers bureau: Abbvie, Pfizer,Roche,Genzyme,Pharm-Allergan, I. Foeldvari: None declared, G. Ganser: None declared, J. Haas: None declared, R. Trauzeddel: None declared, A. Hospach: None declared, F. Weller-Heinemann: None declared, G. Horneff Grant/research support from: Abbvie, Chugai, Novartis, Pfizer,Roche

Hintergrund Die Glukokortikoidtherapie beim Kawasaki-Syndrom wird seit Jahren kontrovers diskutiert.

In der Rheumatologie zeigt der zunehmende Einsatz von Kombinationstherapien aus „disease modifying drugs“ (DMARDs) und Biologika auch bei schwer verlaufenden rheumatischen Grunderkrankungen im Kindes- und Jugendalter Erfolge. Diese Strategie steigert jedoch die medikamentenspezifischen infektiologischen Risiken. Zusatzlich bedingen viele Erkrankungen per se bereits ein erhohtes Infektionsrisiko. Einige Patienten weisen weitere immunologische oder organische Komorbiditaten auf, wie beispielsweise einen Komplementmangel oder eine pulmonale Gerusterkrankung, wodurch die Infektanfalligkeit zusatzlich steigt. Die hier vorgeschlagene Checkliste mit gezielten apparativen und immunologischen Vorsorgeuntersuchungen basiert auf einer „State-of-the-art-Auswertung“ der verfugbaren Literatur und eigenen Erfahrungen. Sie soll helfen, Risikofaktoren aufzudecken. Eine zusammenfassende Beurteilung von Grunderkrankung, Komorbiditaten und Wirkungsweise der Medikation ermoglicht somit 1) eine individuelle Risikostratifizierung der geplanten Immunsuppression und 2) eine Beurteilung der infektiologischen Gefahrdung des Patienten.

The goal of modern antirheumatic therapy is to achieve an optimized disease control. This is individually achieved by an intensified immunosuppression (IS) frequently combining different immunosuppressive agents. Intensified IS should be accompanied by a standardized protocol to monitor immunological changes in the patient. This should include checklists (see Part 1 Screening during intensified IS in children and adolescents). An individual risk stratification according to the planned IS allows a prediction of infectious disease risks for the patient and, thus, individual infection prophylaxis. In addition, standardized management of patients with fever while receiving intensified IS may prevent further complications.

Congenital anomalies of the kidneys and urinary tract (CAKUT) are among the most common anomalies in newborn infants, and may cause chronic renal disease in newborns. We investigated the sensitivity and specificity of different ultrasound-based screening strategies for CAKUT.Newborns (n = 4331) were analyzed for CAKUT in at least one ultrasound examination as a part of the Survey of Neonates in Pomerania (SNiP), a 7-year population-based study on neonates in Western Pomerania (Germany). Intrauterine ultrasound examinations were compared with early postnatal ultrasound findings (from days 3 - 7 of life) and pathological findings within the first 6 months of postnatal life.Cases of CAKUT were detected in 309 (3.7 %) kidneys in one ultrasound examination at the following points of time at least: (i) prenatally in 56 newborns (18.2 %), (ii) 3 - 7 days postnatally in 201 newborns (65.2 %) and (iii) in 52 newborns (17 %) during the 6-month follow-up. The prevalence was significantly higher in male infants, and hydronephrosis was found to be the most frequent obstructive nephropathy (83.3 %). Significant co-morbidity was observed with CNS malformations. The diagnostic sensitivity was significantly higher in postnatal ultrasound screening (79.6 vs. 18.2 % prenatally), while the specificity was above 99 % at all time points.This study demonstrates a high prevalence of CAKUT and demonstrates the importance of combined prenatal and postnatal ultrasound examinations for early CAKUT diagnosis.ZIEL:: Angeborene Fehlbildungen der Nieren und ableitenden Harnwege (CAKUT) gehören zu den häufigsten neonatalen Anomalien und können zur Entstehung chronischer Nierenerkrankungen und Niereninsuffizienz führen. In dieser Studie haben wir Sensitivität und Spezifität der verschiedenen ultraschallbasierten Screening-Ansätze untersucht.Im Rahmen des über 6 Jahre durchgeführten Survey of Neonates in Pomerania (SNiP) erhielten Neugeborene (n = 4331) mindestens eine Ultraschalluntersuchung der Nieren und ableitenden Harnwege im Rahmen der zweiten Vorsorgeuntersuchung (U2) zwischen dem 4.–7. Lebenstag. Intrauterine Ultraschallergebnisse wurden mit den postnatalen Ergebnissen und eventuellen weiteren Auffälligkeiten in den ersten 6 Lebensmonaten verglichen.Bei 309 (3,7 %) Nieren wurde in einer der folgenden Ultraschalluntersuchungen eine CAKUT diagnostiziert, (i) pränatal bei 56 Neugeborenen (18,2 %), (ii) 4 – 7 Tage postnatal bei 201 (65,2 %) und (iii) während der ersten 6 Lebensmonate bei weiteren 52 (17 %) Neugeborenen. Es zeigte sich eine signifikant höhere Prävalenz bei männlichen Neugeborenen. Eine angeborene Hydronephrose war die am häufigsten gefundene obstruktive Nephropathie (83,3 %). Eine signifikante Komorbidität zeigte sich mit Auffälligkeiten des ZNS. Die diagnostische Sensitivität des postnatalen Screenings war signifikant höher (79,6 vs. 18,2 % pränatal), die Spezifität war zu allen Screeningzeitpunkten über 99 %.Diese Studie zeigt eine hohe CAKUT-Prävalenz und demonstriert die Wichtigkeit eines Ultraschallscreenings zur Früherkennung einer angeborenen Fehlbildung der ableitenden Harnwege.

Juvenile idiopathic arthritis (JIA) summarizes a group of inflammatory diseases of childhood. The etiology remains still unclear. In JIA, T cells have been demonstrated to play key roles in the pathogenesis. T-cell proliferation in JIA may be different in the peripheral blood (PB) and the synovial fluid (SF). The aim of this study is to demonstrate the turnover of T cells in the PB and SF of patients with persistent oligoarticular JIA (oJIA) compared to controls. Matched pairs of samples were investigated derived from PB and SF of nine patients with persistent oJIA. The cells from PB and SF were determined by flow cytometry. The majority of the PBMC and IAMC were in phase G0/G1, with fewer than 1% in S phase. In the SF, the percentage of cells in the S phase are higher than in the PB. The percentage of cells in the S phase in SF are equal to the result in the control group. In conclusion, the turnover of synovial T cells in persistent oJIA is higher than in the PB.

Inhibitoren von Tumornekrosefaktor α (TNFα) und andere Biologika haben die Therapieoptionen bei juveniler idiopathischer Arthritis erheblich erweitert. Die Wirksamkeit von Etanercept und Adalimumab wurde in randomisierten kontrollierten klinischen Studien nachgewiesen. Die Langzeitsicherheit bleibt Gegenstand laufender Untersuchungen. Die U.S. Food and Drug Administration berichtete im August 2009 uber insgesamt 48 bosartige Tumoren bei mit Infliximab, Etanercept oder Adalimumab behandelten Kindern und Jugendlichen, was Fragen bezuglich eines erhohten Malignomrisikos aufwirft. Lymphome machten mit 50% den grosten Anteil der 48 Malignome aus. Die Indikation fur die Anwendung von TNF-Inhibitoren ist unter Berucksichtigung von Risikofaktoren sorgfaltig zu prufen. Dies gilt insbesondere fur nicht zugelassene Substanzen, nicht zugelassene Indikationen und fur Kombinationsbehandlungen mit TNF-Inhibitoren und Immunsuppressiva. Andererseits soll aufgrund der aktuellen Datenlage bei keinem Patienten, der die entsprechenden Voraussetzungen erfullt, eine notwendige Therapie beendet oder nicht begonnen werden. Eine adaquate Aufklarung, Uberwachung und Langzeitdokumentation der Behandlung im Register der Gesellschaft fur Kinder- und Jugendrheumatologie werden dringlich empfohlen.

Neonatal health is of major concern to parents, midwives, physicians and society as a whole, yet a prospective population-based birth cohort to collect comprehensive data on multiple issues including medical, social, environmental and genetic aspects remains to be established in Germany. The survey of newborns in Pomerania (SNiP) described in this paper attempts to take up this goal. The objectives of SNiP are to establish (a) a population-based birth cohort providing detailed information about neonatal health, morbidity and mortality, (b) a biobank with newborn DNA and serum from cord blood, placenta tissue samples and DNA obtained from oral mucosal swabs of the mothers, (c) a prospective study design by re-examination of the SNiP population prior to attendance at primary school. From March 2003 until November 2008 all childbearing mothers in a well-defined region in North-Eastern Germany were asked to participate with their newborns. Detailed data on health status of the newborn, pregnancy, medical and family history, socio-economic status and maternal life style were obtained via face-to-face interview, standardised questionnaires and medical records. Placental tissue samples, cord blood plasma and DNA were continuously collected; sampling of maternal DNA from mouth swabs started in 2007. As a result, during the study period n = 6747 births and n = 6828 babies were enrolled. A population coverage of 95% was achieved. The active participation rate was 75%. A non-responder analysis revealed no meaningful selection bias. Thus, SNiP is a population-based, representative study in Germany that is able to describe the health and living conditions of newborns and their families comprehensively. It can contribute to existing knowledge and to similar cohort studies since data are accessible by researchers.

ZusammenfassungDie juvenile Psoriasis-Arthritis (jPsA) wird als eine Kategorie der juvenilen idiopathischen Arthritis (JIA) definiert und weist unterschiedliche klinische Manifestationsformen auf. Die größte Gruppe bilden Patienten mit einer asymmetrischen Arthritis im Schulalter, gefolgt von Kindern mit Oligoarthritis und Beginn im Kleinkindalter. Bei zehn bis 20 Prozent besteht eine symmetrische Polyarthritis. In der Klassifikation nach ILAR von 2002 gelten Ausschlusskriterien, die insbesondere Jungen mit einer Spondylarthropathie betreffen. Dadurch ergeben sich Schwierigkeiten im Vergleich mit früheren Studien sowie bei Lanzeitstudien. Die Spondylitis psoriatica stellt eine typische Manifestation der adulten Psoriasis-Arthritis dar. Die Erkrankung dieser Patienten muss im Kindesalter jedoch oft als undifferenzierte Arthritis klassifiziert werden. Die Therapie der jPsA erfolgt multidisziplinär entsprechend den Richtlinien der JIA. Die medikamentöse Behandlung schließt neben der dermatologisch topischen Versorgung die Gabe von NSAR, intraartikuläre Steroidinjektionen und je nach Verlauf auch Basismedikamente und/oder Biologika mit ein. Wichtige Bestandteile der Therapie sind Physio- und Ergotherapie sowie Hilfsmittelversorgung. Im Hinblick auf den chronischen Verlauf ist auch eine psychosoziale Betreuung von Kind und Familie erforderlich. Primär muss von einem lebenslänglichen Verlauf ausgegangen werden, weshalb beim Übergang ins Erwachsenenalter auch eine betreute Transition der Patienten in die Erwachsenenrheumatologie erfolgen sollte. Die Prognose hängt entscheidend von einer frühzeitigen konsequenten Therapie ab. Anhaltenden Remissionen stehen progredient destruktive Verläufe gegenüber. Neben einer Übersicht zum Thema werden Daten aus den Langzeitverläufen von 79 Patienten mit einer jPsA vorgestellt und diskutiert. Die ILAR-Klassifikation der jPsA bietet eine gute Klassifikationsgrundlage, definiert jedoch einige Ausschlusskriterien, die angesichts unserer Analysen zuviele Patienten aus dieser Gruppe ausgrenzen.

BACKGROUND: The official birth statistics are regarded as a reliable data source on births and birth rate in the German population. However, they show methodological limitations with respect to the identification of first-time mothers and the number of children per mother. The mothers’ social and economical background is not assessed. The goal of the present analysis was (a) to describe demographic and socio-economic variables of all births in a defined region over a fixed time-frame and (b) to make a comparison on the basis of parity and gravidity. METHOD: From 2004-2007 4 982 children were born in the region and data from n=4 788 children were assessed (96%); n=3 505 (73%) of these mothers consented to a more detailed assessment. RESULTS: The fertility rate in the SniP region is low. There are fewer children per 1 000 women and born per women in general. The average age of primiparae was 25 and 26 years. As can be expected there is a significant difference between primiparae and multiparae with respect to age. There is also a difference in occupational status. 17% of the primiparae have been multigravidae. CONCLUSIONS AND DISCUSSION: For the first time in Germany, the SNiP collected comprehensive population-based data on the age and socio-demographic variables of children and their mothers in a defined geographical region. A significant discrepancy for average age of primiparae between the study results and the official statistics is discussed in the light of methodological and regional issues. Our results require the continuation of comprehensive population-based data assessment. Furthermore, the SniP region could serve as a model region for future research. In international comparisons Germany?s reproductive behaviour has proved to be unfavourable, which is accentuated in the region under examination.

ZusammenfassungDie Therapie rheumatischer Erkrankungen bei Kindern und Jugendlichen hat in den vergangenen Jahren erhebliche Fortschritte gemacht. Dennoch leidet mehr als die Hälfte der Betroffenen beim Eintritt in das Erwachsenen-alter an einer aktiven Erkrankung oder an den Folgen der Erkrankung. Dies macht einen rehabilitativen Therapieansatz erforderlich. Ziel ist es, bleibende Bewegungseinschränkungen des Bewegungsapparates und/oder Fehlstellungen zu behandeln, eine altersgerechte Entwicklung zu fördern, sozial-psychologische Überlastung zu mildern und den besonderen Schulungs- oder Beratungsbedarf, besonders bei Jugendlichen im Umgang mit der Erkrankung und bezüglich der Schul- und Berufsausbildung, zu decken.Geschildert werden zwei Modelle zur Rehabilitation rheumakranker Kinder- und Jugendlicher: das Projekt zur Rehabilitation schulpflichtiger Kinder und Jugendlicher des Landes Brandenburg und das Rehabilitationsprogramm am Deutschen Zentrum für Kinder-und Jugendrheumatologie in Garmisch-Partenkirchen.

BACKGROUND AND OBJECTIVE: Population-based data on smoking behavior in Germany of women before or during pregnancy have been lacking. Smoking rates of these women have now been recorded over a period of 3 years against the background of growing tobacco control activities in Germany. METHODS: The study was conducted between 4/2003 and 3/2006 in the context of a prospective population-based survey about perinatal morbidity and mortality (Survey of Neonates in Pomerania - SNiP). This survey registers all newborns and their mothers in one defined region. Of the women eligible for the study 2 297 (68.1%) participated after delivery by giving data about their smoking behavior beforer and during pregnancy. RESULTS: 61.2% of the women had smoked at some time, 46.6% had smoked before, 24.2% into the 4. month and 20.5% into the last 4 weeks of pregnancy. Smoking rates remained unchanged over the 3 years that were studied. The rates of smokers who had quit byt the time of delivery varied according to the length of school education: (>10 years: 30%; 10 y: 59%; 24 years: 45%; 25-30 y: 65%

Impfungen stellen bei Kindern und Jugendlichen mit rheumatischen Erkrankungen ein besonderes Problem dar. Wirkungen und Nebenwirkungen von Impfungen sind fur dieses Patientenkollektiv leider nur unzureichend untersucht, und spezifische Impfempfehlungen fehlen. Die bei diesen Patienten haufig erforderliche immunsuppressive Therapie schafft zusatzliche Unsicherheit. Hinzu kommen Bedenken bezuglich impfassoziierter Reaktivierungen der Grunderkrankung. Die bestehenden Unsicherheiten im Umgang mit Impfungen fuhren zu einer erheblichen Praxisvariation unter den Kinderarzten und Impflucken bei den betroffenen Kindern und Jugendlichen. So ist jeder dritte Patient mit juveniler idiopathischer Arthritis unzureichend geimpft, was sogar Standardimpfungen mit Totimpfstoffen wie Tetanus/Diphtherie einschliest. Nach aktuellem Stand des Wissens ist der Nutzen vieler Impfungen gerade bei Patienten mit Autoimmunerkrankungen deutlich hoher als deren Risiko zu veranschlagen. Gerade Patienten mit immunsuppressiver Therapie benotigen einen besonderen Schutz vor Infektionen. Kinder und Jugendliche mit rheumatischen Erkrankungen sollten deshalb – soweit moglich – nach den STIKO-Empfehlungen geimpft werden. Dabei muss der Zeitpunkt der anstehenden Impfung sorgfaltig in Abhangigkeit von der Krankheitsaktivitat und Therapie gewahlt werden.

Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy.A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution.A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008).Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex, intrauterine position and a positive family history for congenital hip anomalies. METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256 neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound results of 1043 term and since October 2003 33 preterm neonates were analysed. Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when reaching their corrected term gestational age. Ultrasound was applied with a 7.5 MHz linear scanner and results were classified according to Graf. Chi-square and Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 % bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than in males (3.2 %). There was no significant difference in intrauterine position or positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of fathers and 2.4 % of siblings positive. There was a higher incidence for congenital hip dysplasia in preterms with 6.1 %, which is not significant due to the limited number. DISCUSSION: Current screening methods miss up to 18 % of newborns with severe hip dysplasia. We were able to demonstrate that screening for congenital hip dysplasia with ultrasound is a diagnostic tool even during the first days of life. There is a significantly higher incidence of congenital hip dysplasia in females, but in contrast to other studies we found no significant difference in intrauterine position or familial history. Earlier diagnosis and therapy on the base of relevant risk factors might correspond with an improved prognosis and outcome. Further studies are warranted to evaluate the significance in preterm neonates.

The diagnostic biochemical hallmarks of Smith-Lemli-Opitz syndrome (SLOS) are elevated concentrations of the cholesterol precursors 7- and 8-dehydrocholesterol (7- and 8-DHC). We describe a patient with classical SLOS phenotype and oesophageal achalasia, which has not been reported in SLOS patients before. Plasma 7-DHC and 8-DHC were only marginally elevated. The diagnosis was confirmed by sterol analysis in cultured skin fibroblasts and mutation analysis.

Growth factor deprivation-induced apoptosis plays an important role in several cellular systems. However, knowledge of the molecular mechanisms involved are restricted to a few murine models or tumor cell lines. Therefore, we aimed studying signaling pathways leading to apoptosis in activated human peripheral T cells after IL-2 withdrawal. Lymphoblasts from patients with CD 95 (Fas/APO-1)-deficiency revealed that functional CD95 was not required to induce apoptosis after IL-2 withdrawal. Moreover, apoptosis induction in response to various cytotoxic stimuli was found to be mediated in the absence of functional CD95 but was affirmatorily influenced by IL-2 signaling. Immunoblots showed no downregulation of Bcl-2 or Bcl-xL and no upregulation of Bax, whereas decreased mitochondrial membrane potential was readily measurable 24 h after cytokine deprivation. Tetrapeptide inhibitors showed limited efficacy in preventing apoptosis whereas the caspase inhibitor zVAD-FMK potently blocked induction of apoptosis. Cleavage of different fluorogenic substrates revealed multiple caspase enzyme activities in lymphoblasts, which were not negatively affected by the fas mutation. Starting at 8 h after IL-2 withdrawal, upregulation of active caspase-3 but not of caspase-8 could be detected. Taken together, our data argue for molecular mechanisms of cytokine deprivation-induced apoptosis in activated human lymphocytes independent of CD95.

The expression of m-fas/apo1 (CD95) and its soluble form (s-fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m-fas/s-fas transcripts was calculated by densitometry of fas-specific RT-PCR products. An inverted ratio of m-fas/s-fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m-fas/s-fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m-fas/s-fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA-JCA which is not limited to the affected joints.

Chronic anterior uveitis is a common complication of juvenile idiopathic arthritis (JIA). Leflunomide is a frequently used alternative to methotrexate in the treatment of joint manifestations of JIA. However, very little is known on the effect of leflunomide treatment on concurrent chronic uveitis in JIA.

Background Biological disease modifying antirheumatic drugs (bDMARD) had great impact on the medical management of patients with juvenile idiopathic arthritis (JIA). Many patients nowadays enter adulthood in clinical remission, with normal function and without long-term sequelae. There is little information to what extent the early use of bDMARDs affects the long-term outcome of patients with JIA. Objectives To investigate if the 10-year outcome after JIA onset is associated with the time lag between JIA disease onset and first bDMARD use. Methods Outcome variables were examined in patients prospectively observed in the national JIA biologic register BiKeR and its follow-up register JuMBO since initiation a bDMARD therapy. Analyses included patients with at least one visit in JuMBO. Assessed parameters were JADAS3–10, C-HAQ, joint surgery (replacements, synovectomies), eye surgery and patient-reported outcomes. To analyze the influence of the time lag between JIA onset and first use of bDMARD, patients were assigned to one of the following three groups (G1: ≤2 year = early therapy, G2: intermediate, G3: ≥5 years = late). A general propensity score was estimated to adjust for baseline differences between the three groups. Mixed models were used to determine the association of the three groups and outcomes. Surgeries were analyzed by Cox regression analyses. Results 609 patients were ever treated with a bDMARD and successfully transferred to JuMBO. Most (91%) patients were enrolled in BiKeR on etanercept followed by adalimumab (6%), 93% had previously received a conventional synthetic (cs) DMARD. 27.9% had RF negative polyarthritis and 19.5% enthesitis-related arthritis. The first csDMARD was started 0.4 years after disease onset in the early bDMARD group (n=142), and 1.2 and 3.1 years after JIA onset in the in-between group and late group (n=274), respectively. At their last follow-up (10.2±6.2 years after JIA onset), the patients9 mean age was 21.2 years. The clinical outcome 10 years after disease onset could be investigated in 478 patients. Patients with early biologic treatment were significantly more often in drug-free JADAS remission (15%) for at least 12 months, had more often an inactive disease (JADAS3–10≤1, 27.6%) and no functional limitations (58.6%) compared to late treatment start. There was no significant difference in the patient-reported outcome measures. Among all 609 patients, 35 (5.8%) patients had undergone joint replacement, 100 (16.4%) synovectomy and 19 (3.2%) eye surgery. Patients on bDMARD in follow-up had a lower likelihood for joint replacement (HR=0.25, p=0.003) or synovectomy (HR=0.26, p Conclusions Patients who started with cs and bDMARDs within the first two years of disease are significantly more often in drug-free remission in adulthood and have less sequelae than those who started later. The data emphasize the importance of a fast disease activity control and may support the idea of a window of opportunity for JIA. Disclosure of Interest None declared

Background Since the approval of first biologics for JIA, such treatments in Germany are monitored prospectively by the BiKER registry. Methods sJIA pts documented in BIKER exposed to Etanercept (ETA), Tocilizumab (TOC) or IL-1inhibitors were identified. A 6-month therapy period was chosen as a meaningful time for early efficacy judgement. Intention to treat analysis (ITT) of JADAS10 was performed. Discontinuation due to inefficacy/intolerance was calculated as non-response. Results 205 sJIA patients (51% male) received 269 treatment courses with biologics (TOC 71, Anakina 36, Canakinumab 19, ETA 143). Median age and disease duration (ETA 3.3;TOC 3.3;IL-1i 3.0) were comparable. The choice of drug was influenced by the availability. ETA was started in 80% of pts before 2008 while in the TOC cohort all pts and in the IL-1i cohort 74% started therapy after 2008. Pre-treatment consisted of steroids in all pts, MTX in the ETA/TOC/IL-1i cohort in 88%/83%/76% and biologics preexposure was used in 2%/66%/86%. Concomitant treatment with systemic steroids was significantly less frequent with TOC (44%, p Systemic manifestations were present at baseline in: 8% ETA, 96% TOC and 38% IL-1i cohort. The mean±SD baseline JADAS was higher in the ETA cohort (20.7±9.1) than in the TOC cohort (16.2±10.6) or IL-1i cohort (7.8±8.9). At month 6, a marked decrease of the JADAS was noted in all cohorts. ITT analysis revealed a significant advantage of TOC and Il-1i over ETA (table). Significantly more pts reached a JADAS-Remission (JADAS≤1) upon TOC (OR/95CI 3.85/1.68–8.83/p Conclusions A high proportion of pts showed a significant response to treatment especially with TOC or with IL-1i. After 6 months on treatment JADAS remission criteria were reached by up to 50% of patients while 60% to 65% reached JADAS minimal disease activity desoite much less steroids and DMARD used with TOC or IL-1i. ETA has been used in earlier times but it is less effective and it9s use in sJIA has markedly decreased in Germany. Disclosure of Interest None declared

Background High plasticity was described for Th1 and Th17 cells depending on the local cytokine milieu and regulation by Tregs. Pathogen-induced human Th17 cells and Tregs are strongly regulated by IL-1beta. So far, the influence of IL-1beta on FoxP3 methylation and stability of the Treg lineage has not been investigated. Further, whether inhibition of IL-1beta and its receptor is able to promote FoxP3 demethylation and to conserve Treg functions, such as suppression of Th17 and Th1 functions, has not been assessed in healthy humans, as well as in patients with autoimmune arthritis. Objectives Thus, the present study aimed to investigate in vitro nTreg and iTreg functions in lymphocytes obtained from stored routine blood samples of patients with juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) in different disease activity states. Methods Proportions of peripheral nTregs and cultured iTregs from stored routine blood samples taken from JIA, RA patients and healthy, age-matched controls (HC) and intracellular cytokine production were analyzed by flow cytometry. Suppressive function of iTregs under in vitro inhibition of IL-1beta was studied by suppression assays. FOXP3 expression and methylation were analyzed by quantitative PCR and bisulfite pyrosequencing. Results Lower proportions of nTregs were found in samples of JIA patients with acute disease flare (mean 2.3% of CD4+ T cells) compared to HC (4.1%) (p Conclusions Induction of Tregs seems to be different depending on disease activity status in autoimmune arthritis. DNA methylation at the FOXP3 promoter and enhancer regions may influence expression of FoxP3 in Tregs and, thus, modify their phenotype. Although IL-10 was not markedly influenced by IL-1beta-dependent mechanisms, our findings indicate that suppressive iTreg functions may be restored by selective blockade of IL-1beta. Disclosure of Interest None declared

Background Since the approval of first biologics for treatment of JIA, surveillance in Germany is monitored prospectively by the BIKER registry. Objectives To evaluate the safety of Tocilizumab (TOC), IL-1 inhibitors (Anakinra & Canakinumab) and Etanercept (ETA). Methods Safety assessments were based on adverse events reports. Results 205 sJIA pts received 269 treatment courses with biologics (TOC 71, Anakina 36, Canakinumab 19, ETA 143 and 57 pts. received MTX only. Median age was lower In the MTX cohort (4.8y) than with ETA (8.2); TOC (9.6); IL-1i (8.2) as was the disease duration. ETA was started in 80% of pts before 2008 while in the TOC cohort all pts and in the IL-1i cohort 74% started therapy after 2008. Pre-treatment consisted of systemic steroids in 75% starting MTX and in all patients starting biologics. Initial concomitant treatment with systemic steroids was significantly less frequent with TOC (44%, p Conclusions Higher rates of safety signals, especially infections were noted upon treatment with TOC and IL-1i. Beside infections, disease reactivation and MAS, further adverse events were rare and overall tolerability was acceptable. However, steroids were markedly spared upon IL6- and Il-1 inhibitors. Disclosure of Interest G. Horneff Grant/research support from: Abbvie, Roche, Chugai, Pfizer, A. Schultz: None declared, A. Hospach: None declared, G. Ganser: None declared, I. Foeldvari: None declared, A. Thon: None declared, R. Trauzeddel: None declared, F. Weller: None declared, K. Minden: None declared, J. Haas: None declared