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Objective A working group was established to develop a core domain set (CDS) for Chronic Nonbacterial Osteomyelitis (CNO) and Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) following the OMERACT filter 2.1. Methods A scoping review to identify disease-related manifestations was performed, followed by a special interest group (SIG) session at OMERACT2020 to begin the CNO/SAPHO CDS framework. Results Candidate items were identified from the scoping review and most fell under Life Impact and Pathophysiology Manifestation core areas. A SIG agreed on the need to develop a CDS for CNO and SAPHO (100%) and for children and adults (91%). Conclusion Based on candidate items identified, qualitative research and Delphi surveys will be performed as next steps.

Objective To assess the first-year features of patients with chronic nonbacterial osteomyelitis (CNO). Methods Patients with a diagnosis of CNO, disease duration of under 13 months, and first registration in the German National Pediatric Rheumatologic Database (NPRD) between 2009 and 2018 were included in this cross-sectional analysis. Results Of 774 documented patients, 62.8% were female, and all patients had a median age of 11 years. The most affected clinical sites were the tibia (29.7%), pelvis (28.0%), and femur (27.8%). HLA-B27 was positive in 48 of 314 analyzed patients (15.3%). In 406 patients, an X-ray was performed at the first visit; X-ray results showed osteosclerosis/−lysis in 34.0% and hyperostosis in 14.5% of the patients. MRI scans (focal and whole-body scans) were performed in 648 patients, and 81.5% showed a positive TIRM/STIR signal. A total of 84.7% of the patients were administered nonsteroidal anti-inflammatory drugs, 9.6% were administered oral glucocorticoids, 10.8% were administered disease-modifying anti-rheumatic drugs (DMARDs), and 6.1% were administered bisphosphonates. An evaluation of the patient’s questionnaire showed an overall well-being (NRS 0–10) of 2.0. The PedCNO disease “activity” score revealed a 70% improvement in variables in 43% of patients in the initial 1-year follow-up. Copresentation with diagnostic criteria of pediatric enthesitis-related arthritis was rare. Conclusion To our knowledge, the NPRD cohort seemed to be the largest cohort of children and adolescents suffering from CNO worldwide. Most patients were treated effectively with NSAIDs, and only a small group of patients was administered additional medication. The patient-defined measures of disease activity had a moderate impact on patients’ daily lives. Trial registration Not applicable.

Objective.The autoinflammatory bone disorder chronic nonbacterial osteomyelitis (CNO) covers a wide clinical spectrum, ranging from mild self-limited presentations to chronically active or recurrent courses, which are then referred to as chronic recurrent multifocal osteomyelitis (CRMO). Little is known about treatment options and longterm outcomes. We investigated treatment responses and outcomes in children with CNO.Methods.A retrospective chart review was conducted in a tertiary referral center, covering 2004–2015. Disease activity was measured at 0, 3, 6, 12, and 24 months after treatment initiation, and at the last recorded visit.Results.Fifty-six patients with CNO were identified; 44 had multifocal CNO. Fifty percent of patients relapsed after a median of 2.4 years, and as few as 40% remained relapse-free after 5 years. Nonsteroidal antiinflammatory drugs were used as first-line treatment in 55 patients, inducing remission after 3 months in all individuals with relapse rates of 50% after 2 years. Further treatment included corticosteroids (n = 23), tumor necrosis factor-α (TNF-α) inhibitors (n = 7), and bisphosphonates (n = 8). While 47% of patients with CNO relapsed within 1 year after corticosteroid therapy, favorable outcomes were achieved with TNF-α inhibitors or bisphosphonates (pamidronate).Conclusion.CNO is a chronic disease with favorable outcomes within the first year, but high relapse rates in longterm followup. Particularly, patients with CRMO with long-lasting, uncontrolled inflammation were at risk for the development of arthritis. Our findings underscore the importance of a timely diagnosis and treatment initiation. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

IgG4-related disease (IgG4-RD) is an inflammatory disorder characterized by tumor-like swelling in one or more organs, elevated serum IgG4 levels, and histological alterations with infiltration of IgG4-positive plasma cells. IgG4-RD is rare and likely underdiagnosed in children. We report a case of a 16-year-old girl with IgG4-positive colitis that developed weeks after IgG4-related ophthalmic disease and discuss diagnosis and treatment in the context of the literature available. Since the pathophysiology of IgG4-RD is unknown, treatment options are empiric and, for the most part, untargeted. Systemic corticosteroid treatment is the basis of anti-inflammatory treatment in IgG4-RD and induced early remission in our patient. During corticosteroid taper, the patient developed weight loss and intestinal inflammation. Histopathological assessment of the intestinal walls confirmed IgG4-positive colitis. Immune-modulating treatment with non-biologic (e.g., methotrexate (MTX) and mycophenolate mofetil) or biologic (rituximab) disease-modifying antirheumatic drugs has been reported in treatment refractory or corticosteroid-dependent patients. The patient responded to treatment with anti-inflammatory therapy with food rich in TGF-β2 (modulen) and MTX. This is one of the first pediatric patients reported with IgG4-related colitis extending the phenotype of pediatric IgG4-RD. International collaboration to prospectively document clinical presentation and treatment responses may help to further establish the phenotype and treatment options and to raise awareness for IgG4-RD.

Non-infectious uveitis is associated with visual impairment and blindness. Non-biologic treatment for non-infectious uveitis is not based on strong evidence. A retrospective chart review was conducted to investigate treatment response to high-dose intravenous methylprednisolone (IVMP) in children with non-infectious uveitis. Fifty-six patients (93 eyes affected) were included. In 29% uveitis was associated with juvenile idiopathic arthritis. Uveitis predominately affected the anterior segment, was bilateral and recurrent. Complications were common and included visual loss, synechiae, cataract and/or retinal lesions. Patients received up to 5 IVMP at monthly intervals. Visual acuity improved at 3 and 6 months. Anterior chamber cells, synechiae, keratic precipitates, papillary and/or macular edema improved at 3 months. Children treated with ≥3 IVMP (vs 1 IVMP) experienced trends towards fewer relapses, fewer cataracts and less frequently required treatment with biologic agents. High-dose IVMP induce rapid improvement in children with non-infectious uveitis. Prospective randomized trials are required to confirm results.

Background Intraocular inflammation accounts for up to 10-15% of total blindness cases [1]. The incidence of uveitis in children ranges around 4.9/100.000, and a significant number of patients develop chronic courses and irreparable complications [2]. An impressive 74% of children with juvenile idiopathic arthritis (JIA)-associated uveitis are legally blind at diagnosis [3]. This underscores the importance of timely diagnosis and effective anti-inflammatory treatment. Objectives To evaluate the clinical response to high-dose intravenous methylprednisolone (IVMP) in children and adolescents with autoimmune uveitis. Methods A retrospective chart review was conducted in two tertiary referral centers in Germany (TU Dresden and University of Wurzburg) to investigate treatment responses to IVMP (10-30mg/kg/day on three successive days with a total of one to five IVMP at monthly intervals) in children and adolescents ( Results Fifty-six patients (93 affected eyes) with a median age of 7.4 (range: 2.5-16.7) years were included. In 29% of patients uveitis was associated with JIA. Uveitis was predominately located in the anterior segment (43%), bilateral (66%) and recurrent (43%). Complications occurred in 77% of patients and included visual loss, synechiae, cataract and/or retinal lesions. Patients with active uveitis received between 1 and 5 IVMP. Visual acuity improved significantly (0.52±0.33 to 0.69±0.30 at 3 months (p Conclusion High-dose IVMP induces rapid improvement in children with autoimmune uveitis. Data suggest improved outcomes in children treated with three or more courses of IVMP when compared to one course (without reaching statistical significance). Prospective randomized trials in larger cohorts are required to confirm results. References [1] Nussenblatt RB. The natural course of uveitis. Int Ophthalmol. 1990; 141:303–8. [2] [2] Paivonsalo-Hietanen T et al. Uveitis in children: population-based study in [3] Finland. Acta Ophthalmol Scand. 2000; 78(1):84-8. [4] [3] Woreta F at el. Risk factors for ocular complications and poor visual acuity at presentation among patients with uveitis associated with juvenile idiopathic arthritis (JIA). Am JOphthalmol 2007; 143:647–55. Disclosure of Interests Anja Schnabel: None declared, Elisabeth Unger: None declared, Normi Bruck: None declared, Annette Holl-Wieden: None declared, Henner Morbach: None declared, Reinhard Berner Grant/research support from: Local Principal Investigator in a Clinical Trial on Canakimumab for sJIA supported by Novartis (Trial Registration: NCT00886769, NCT00889863, NCT00426218 and NCT00891046) Local Principal Investigator in a Clinical Trial DAP-PEDOST-11-03 supported by Merck (Trial Registration EUDRACT 2013-000864-28), Anna Leszczynska: None declared, Christian Hedrich Grant/research support from: Novartis Pharmaceuticas for Research study on effector T cells in psoriasis, Speakers bureau: In 2016: Roche Pharmaceuticals, RheumatoLogisch, Dresden, Germany; Novartis, Advisory board > Travel costs.

Historically, osteomyelitis was considered an infectious disorder. More recently, inflammatory mechanisms were recognized causing a significant proportion of pediatric osteomyelitis. This study was to compare characteristics of children with chronic non-bacterial (CNO) and bacterial osteomyelitis (BOM). A chart review of osteomyelitis patients from the departments of pediatrics, pediatric surgery, orthopedic surgery, and oral and maxillofacial surgery was conducted in a tertiary referral center, covering the years 2004–2014. Institutional incidences of CNO (n = 49) and BOM (n = 56) were comparable. Differentiation between CNO and BOM based on clinical or laboratory findings was mostly impossible. However, children with BOM more frequently presented with local inflammatory signs (47 vs. 68 %, p = 0.040), fever (12 vs. 38 %, p = 0.003), and abscesses (0 vs. 39 %, p < 0.001). Peripheral arthritis (14 vs. 0 %, p < 0.001), inflammatory bowel disease (10 vs. 2 %, p = ns), and hyperostosis (29 vs. 4 %, p = 0.001) were more common in CNO. Whole-body MRI was performed in 76 % of CNO patients, unveiling multifocal lesions in 80 % (CRMO). Though considered a rare disorder, institutional incidences of CNO were comparable to BOM, and the discrimination between CNO and BOM solely based on clinical aspects was mostly impossible. This is of special interest, since a correct and timely diagnosis is of utmost importance for long-term outcomes in both disorders. Whole-body MRIs should be considered in chronic osteomyelitis to (1) detect clinically inapparent lesions in CNO and (2) indirectly exclude (usually unifocal) chronic bacterial infections. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, covering a clinical spectrum with asymptomatic inflammation of single bones at the one end, and chronic recurrent multifocal osteomyelitis (CRMO) at the other end. The exact molecular pathophysiology of CNO remains largely unknown. Provided familial clusters and the association with inflammatory disorders of the skin and intestine suggest a genetic predisposition. Recently, profound dysregulation of cytokine responses was demonstrated in CRMO. Failure to produce antiinflammatory cytokines interleukin (IL)-10 and IL-19 contributes to activation of inflammasomes and subsequent IL-1β release. In IL-10–deficient and in CNO-prone chronic multifocal osteomyelitis mice, IL-1β was linked to bone inflammation. Further, alterations to the gut microbiome were suggested in contributing to IL-1β release from innate immune cells in mice, offering an interesting target in the search for molecular mechanisms in CNO. Here, we summarize clinical presentation and treatment options in CNO/CRMO, current pathophysiological concepts, available mouse models, and promising future scientific directions.

Entzundungen der knochernen Strukturen konnen im Kindes- und Jugendalter zur erheblichen Einschrankung der Lebensqualitat sowie zu psychischen und korperlichen Schaden fuhren. Entgegen der Annahme ausschlieslich infektioser Ursachen der Osteomyelitiden (OM) gewinnen zunehmend die nichtinfektiosen, (auto-)inflammatorischen Ursachen an Bedeutung. Die haufigste autoinflammatorische Knochenerkrankung ist die chronische nichtbakterielle Osteomyelitis (CNO), die vorwiegend das knocherne Skelett betrifft, aber auch inflammatorische Veranderungen an Haut, Darm und Gelenken verursachen kann. Das breite klinische Spektrum reicht von zeitlich limitierten Knochenentzundungen an einzelnen Knochen bis zu chronisch aktiven oder rekurrierenden Verlaufen mit symmetrischem Befall mehrerer Knochen. Der Beitrag fasst Daten bezuglich der Differenzialdiagnose infektioser und nichtinfektioser OM zusammen und gibt evidenzbasierte Empfehlungen zu Differenzialdiagnostik und Therapie der CNO.

The pathophysiology of chronic nonbacterial osteomyelitis (CNO) remains incompletely understood. Increased NLRP3 inflammasome activation and IL-1β release in monocytes from CNO patients was suggested to contribute to bone inflammation. Here, we dissect immune cell infiltrates and demonstrate the involvement of monocytes across disease stages. Differences in cell density and immune cell composition may help to discriminate between BOM and CNO. However, differences are subtle and infiltrates vary in CNO. In contrast to other cells involved, monocytes are a stable element during all stages of CNO, which makes them a promising candidate in the search for "drivers" of inflammation. Furthermore, we link increased expression of inflammasome components NLRP3 and ASC in monocytes with site-specific DNA hypomethylation around the corresponding genes NLRP3 and PYCARD. Our observations deliver further evidence for the involvement of pro-inflammatory monocytes in the pathophysiology of CNO. Cellular and molecular alterations may serve as disease biomarkers and/or therapeutic targets.

Author(s): Fotis, Lampros; Shaikh, Nur; Baszis, Kevin; French, Anthony; Tarr, Phillip; Grevich, Sriharsha; Lee, Peggy; Ringold, Sarah; Leroux, Brian; Leahey, Hannah; Yuasa, Megan; Foster, Jessica; Sokolove, Jeremy; Lahey, Lauren; Robinson, William; Newsom, Joshua; Stevens, Anne; Karasawa, Rie; Tamaki, Mayumi; Tanaka, Megumi; Sato, Toshiko; Yudoh, Kazuo; Jarvis, James N; Moncrieffe, Halima; Bennett, Mark F; Tsoras, Monica; Luyrink, Lorie; Xu, Huan; Prahalad, Sampath; Morris, Paula; Dare, Jason; Nigrovic, Peter A; Rosenkranz, Margalit; Becker, Mara; O’Neil, Kathleen M; Griffin, Thomas; Lovell, Daniel J; Grom, Alexei A; Medvedovic, Mario; Thompson, Susan D; Zhu, Lisha; Jiang, Kaiyu; Wong, Laiping; Buck, Michael J; Chen, Yanmin; Moncrieffe, Halima; Brungs, Laura; Liu, Tao; Wang, Ting; Jarvis, James N; Alsaeid, Khaled; Alfailakawi, Jasim; Alenezi, Hamid; Alsaeed, Hazim; Beukelman, Tim; Natter, Marc; Ilowite, Norm; Mieszkalski, Kelly; Burrell, Grendel; Best, Brian; Bristow, Helen; Carr, Shannon; Dennos, Anne; Kaufmann, Rachel; Kimura, Yukiko; Schanberg, Laura; Blier, Peter R; Boneparth, Alexis; Wenderfer, Scott E; Moorthy, L Nandini; Radhakrishna, Suhas M; Sagcal-Gironella, Anna Carmela P; von Scheven, Emily; Gedik, Kader Cetin; Siddique, Salma; Aguiar, Cassyanne L; Erkan, Doruk; Cohen, Ezra; Lee, Yvonne; Dossett, Michelle; Mehta, Darshan; Davis, Roger; Gilbert, Mileka; Goilav, Beatrice; Meidan, Esra

Chronic non-bacterial osteomyelitis (CNO) is an auto-inflammatory disorder that affects the skeletal system. Interleukin (IL-)10 is an immune-modulatory cytokine that controls inflammation, and limits inflammatory cytokine responses. Dysregulation of IL-10 expression has been shown to result in autoimmune and infectious diseases. We investigated IL-10 expression by monocytic cells from CNO patients and controls. In response to stimulation with LPS, IL-10 expression from CNO monocytes was reduced (p

Because of its distinct clinical and laboratory features, reflecting systemic inflammation, sJIA can be distinguished from other forms of JIA which usually present as a milder phenotype. The exact pathophysiology of sJIA, however, remains unknown. Profound dysregulation of innate pro- and anti-inflammatory cytokines, and rapid clinical response to cytokine blocking strategies in sJIA patients suggest impaired control mechanisms in innate immune cells contributing to sJIA pathogenesis. Endogenous TLR ligands, such as S100 protein complexes, enhance the pro-inflammatory phenotype. Associations with polymorphisms in cytokine genes and their receptors suggest a genetic component. Furthermore, genetic associations that have been reported in familial hemophagocytic lympohistiocytosis also exist in patients with sJIA-associated macrophage activation syndrome, a severe complication of sJIA. Reported mutations in single genes, however, are too weak to confer sJIA, suggesting a multi-factorial mode of inheritance. We provide an overview of current pathophysiological concepts, state-of-the-art treatment regimens, and unanswered questions in sJIA.

Background Wheezing is a common symptom in infants and toddlers. Usually it occurs due to viral infection of the lower airways and no further diagnostic procedures are necessary. However in rare cases, other reasons such as anatomical malformation have to be considered. Case presentation We report about an infant with recurrent episodes of wheezy bronchitis, which persisted despite adequate therapy. Bronchoscopy and computed tomography of the lung with three-dimensional reconstruction revealed a rare bronchial branching anomaly - the so called “bridging bronchus”. In contrast to previous case reports, this infant showed no additional malformations, which seems to be important for the prognosis. Conclusion To the best of our knowledge this is the first report about a patient with a bridging bronchus in its “original form” without associated anomalies of the trachea-bronchial system or other organs.

Introduction: Chronic non-bacterial osteomyelitis (CNO) is an inflammatory, non-infectious disorder of the skeletal system with unknown aetiology. Therapeutic options are NSAIDs, steroids and DMARDs (MTX or sulfasalazine). However, a considerable number of patients have a severe disease course and bisphosphonates[for full text, please go to the a.m. URL], 43. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 29. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 25. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Gotzes Titel macht neugierig, da er fast alle wichtigen Schlagworter der Asthetik des Widerstands zitiert, die die literaturwissenschaftlichen Untersuchungen der letzten Jahre inspiriert haben. Doch unglucklicherweise lenkt er dadurch die Erwartungshaltung des Lesers in eine Richtung, die von den tatsachlichen Schwerpunkten der vorliegenden Arbeit nicht erfullt wird.