Zusammenfassung Die medikamentöse Behandlung der juvenilen Psoriasisarthritis und der Enthesitis-assoziierten Arthritis unterscheidet sich teilweise von der anderer Formen der juvenilen idiopathischen Arthritis. Standen bisher vor allem als biologische „disease modifying antirheumatic drugs“ (bDMARD) v. a. Tumornekrosefaktor-α Inhibitoren zur Verfügung, gab es in den letzten Jahren einige vielversprechende Entwicklungen, die teilweise auch die Zulassung in diesen Indikationen erreicht haben. Der Fokus dieses Artikels liegt auf den neueren Biologika – Hemmer von Interleukin (IL) 17 und IL 12/23 bzw. IL23, sowie der small molecules mit Inhibition von Januskinasen, Tyrosinkinase 2 und Phosphodiestase-4 und was bei deren Einsatz zu beachten ist. Der Einsatz der Medikamente bringt für mehr Patienten das Therapieziel Remission in erreichbare Nähe. Register unterstützen beim Erkenntnisgewinn bei der Langzeitbehandlung.
Pediatric high-grade glioma (pedHGG) can occur as first manifestation of cancer predisposition syndromes resulting from pathogenic germline variants in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1, and PMS2. The aim of this study was to establish a generalized screening for Lynch syndrome and constitutional MMR deficiency (CMMRD) in pedHGG patients, as the detection of MMR deficiencies (MMRD) may enable the upfront therapeutic use of checkpoint inhibitors and identification of variant carriers in the patients' families. We prospectively enrolled 155 centrally reviewed primary pedHGG patients for MMR-immunohistochemistry (IHC) as part of the HIT-HGG-2013 trial protocol. MMR-IHC results were subsequently compared to independently collected germline sequencing data (whole exome sequencing or pan-cancer DNA panel next-generation sequencing) available in the HIT-HGG-2013, INFORM, and MNP2.0 trials. MMR-IHC could be successfully performed in 127/155 tumor tissues. The screening identified all present cases with Lynch syndrome or CMMRD (5.5%). In addition, MMR-IHC also detected cases with exclusive somatic MMR gene alterations (2.3%), including MSH2 hypermethylation as an alternative epigenetic silencing mechanism. Most of the identified pedHGG MMRD patients had no family history of MMRD, and thus, they represented index patients in their families. Cases with regular protein expression in MMR-IHC never showed evidence for MMRD in DNA sequencing. In conclusion, MMR-IHC presents a cost-effective, relatively widely available, and fast screening method for germline MMRD in pedHGG with high sensitivity (100%) and specificity (96%). Given the relatively high prevalence of previously undetected MMRD cases among pedHGG patients, we strongly recommend incorporating MMR-IHC into routine diagnostics.
ObjectiveThe Paediatric Rheumatology International Trials Organisation (PRINTO) recently undertook an effort to better harmonize the pediatric and adult arthritis criteria. These provisional criteria are being refined for optimal performance. We aimed to investigate differences between patients who did and did not fulfill these PRINTO criteria among youth diagnosed with juvenile spondyloarthritis (SpA) that met axial juvenile SpA (axJSpA) classification criteria.MethodsThis was a retrospective cross-sectional sample of youth diagnosed with juvenile SpA who met the axJSpA classification criteria. Demographics, clinical manifestations, and physician and patient-reported outcomes were abstracted from medical records. Magnetic resonance imaging (MRI) scans underwent central imaging review by at least two central raters. Differences between groups were compared using Wilcoxon signed-rank test or chi-square test, as appropriate.ResultsOf 158 patients who met axJSpA criteria, 107 patients (68%) met the PRINTO provisional criteria for enthesitis/spondylitis-related arthritis. A total of 41 patients (26%) did not fulfill any of the three major PRINTO criteria due to lack of peripheral disease manifestations. Demographics, prevalence of inflammatory or structural lesions on MRI, family history of SpA, and duration of pain were not statistically different between those who did and did not meet PRINTO criteria. Those who fulfilled the PRINTO criteria had significantly more peripheral arthritis, enthesitis, and HLA-B27 positivity but reported less sacral/buttock pain.ConclusionPhenotypic differences of children with axJSpA between those who were and were not classified by the PRINTO criteria were primarily due to peripheral disease manifestations and HLA-B27 positivity. Modification of the PRINTO provisional criteria may facilitate capture of youth with primarily axial disease.
Für die oligoartikuläre Form der juvenilen idiopathischen Arthritis (JIA) wurden im Rahmen eines konsentierten Prozesses Protokolle entwickelt, welche die Klassifikation, Überwachung und Therapie betreffen (ProKind Rheuma). Durch die Autorengruppe wurden 23 Statements formuliert und diese im Rahmen eines Online-Survey zur Beteiligung unter den ärztlichen Mitgliedern der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR) zirkuliert. An der Beantwortung des Surveys nahmen insgesamt 80 der insgesamt 124 Kinder- und JugendrheumatologInnen teil; dies entspricht einem Anteil von knapp 65
