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Background Chronic nonbacterial osteomyelitis (CNO)is the most common autoinflammatory bone disorders in childhood (1). CNO remains a diagnosis of exclusion because of the absence of specific clinical or laboratory findings.An important role in the diagnosis could be provided by whole body imaging techniques as TC-99 bone scintigraphy and/or whole body MRI. The treatment is not standardized;non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, bisphosphonates and tumour necrosis factor neutralizing agents have been used until now with variable response (2). Objectives To describe clinical, biological and radiological response to treatment with IL-1 receptor antagonist (anakinra) in a cohort of patients with CNO. Methods Seven patients with CNO refractory to NSAIDs, glucocorticoids and bisphosphonate (pamidronate) were treated with anakinra for at least 6 months in our institution. Response of treatment was evaluated assessing clinical manifestations (pain, local swelling, functional impairment), laboratory findings (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR] and serum amyloid A level [SAA]) and number of bone lesions on TC-99 bone scintigraphy at the start of treatment and in a 6 months follow-up. Results Seven patients (4 females and 3 males) were included in this study. The median age at diagnosis was 9.7 years (IQR 7.8-14.7) and the median age before starting anakinra treatment was 13.3 years (IQR 8.0-15.9). All the patients were treated with NSAIDs and bisphosphonates as first-line therapy. Glucocorticoid therapy was required in one patients with concomitant recurrent fever and pleural effusion. These patients did not respond satisfactorily and we decide to use anakinra (2 mg/kg/day) to control disease activity. At the start of treatment 7/7 patients (100%) had pain, 3/7 (43%) local swelling and 5/7 (71%) functional impairment; at 6 months of follow up 6/7 patients (86%) were completely asymptomatic, with one patient complaining of arthralgia. Before starting anakinra the median CRP, ESR and SAA were 2.7 mg/dl (IQR 1.7-4.9) 26 mm/h (IQR 12-46) and 53 mg/dl (IQR 27-112); at 6 months 5/7 patients (71%) have normalized CRP, ESR and SAA, 2/7 had a decrease in inflammatory markers. Before anakinra 59 osseous lesions were detected on TC-99 bone scintigraphy. After 6 months of therapy 24/59 lesions (40%) had completely resolved, 1/59 lesions (2%) had partially improved and 29/59 lesions (49%) remained stable. In two patients with persistent high biological inflammatory markers, new lesions (14) developed during treatment. Conclusions Our data suggest that anakinra appears effective in CNO patient, who have not responded to standard of care, in controlling symptoms and laboratory findings, although subclinical bone inflammation was still detectable by bone scintigraphy after 6 months of treatment. Long-term follow-up studies with a larger number of patients are needed. References Sara M. Stern, Polly J. Ferguson. Autoinflammatory Bone Diseases. Rheum Dis Clin N Am 39 (2013) 735-749. H J Girschick, P Raab, S Surbaum, A Trusen, et al. Chronic non-bacterial osteomyelitis in children. Ann Rheum Dis 2005;64:279-285. Disclosure of Interest None declared

Background Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown ethiology. The clinical manifestations of CRMO are highly variable. One to 20 sites can be affected at one time. Since CNO is a systemic disorder that can affect multiple skeletal sites, whole-body imaging techniques (Tc-99 bone scintigraphy or MRI) provide major contribution to the initial diagnostic approach, as well as during follow-up (1-2). Objectives To evaluate typical patterns of bone involvement on MRI in paediatric patients with CRMO. Methods We retrospectively reviewed 112 MRI performed at the diagnosis and during follow-up from 2010 to 2014 of 40 children with CRMO. Thirty-two patients underwent bone biopsy that confirmed the diagnosis. 28/40 (70%) underwent one or more WBMRI. Coronal STIR images were obtained in all children. Additional sequences were performed in doubtful cases. Results A total of 360 lesions were detected. Lesions were multifocal in 36/40 patients (90%) and were symmetric in at least one localization in 24/40 patients (60%). In 30/40 patients (75%) lesions were located on the metaphyses of long bones (especially femur and tibia) close to one or both sides of an epiphyseal or apophyseal growth plate and/or on pelvic bones (particularly on the sacro-iliac joints and close to the triradiate cartilage) and/or on clavicle/sternum. The spine was involved in 14/40 (34.1%) patients, in all but 2 in combination to the submentioned locations. No patients had carpal or head bone involvement, 16/40 had tarsal involvement. Conclusions MRI, and particularly WBMRI, should be considered the diagnostic modality of choice in patients with clinical multifocal pain. Simmetricity, multifocality and particularly specific patterns of lesions appear highly suggestive of CRMO. References De Somer L. et al. Total body MRI, a guide to diagnosis in patients with osteo-articular pain and inflammation. Arthritis Rheumatol. 2014 March;66(S3):S119 Falip C. et al. Chronic recurrent multifocal osteomyelitis (CRMO): a longitudinal case series review. Pediatr Radiol. 2013 Mar;43(3):355-75. Disclosure of Interest None declared

Background Autoinflammatory disorders (AIDs) represent a group of complex diseases characterized by periodic or chronic systemic inflammations with involvement of various organs and systems in the absence of evidence of autoimmunity or infections. Mutations in more than 15 genes, affecting several distinct pathways, have been associated with autoinflammatory recessive/dominant syndromes [1]. The molecular genetic analysis of these diseases based just on the candidate gene has low efficiency and it9s time consuming and expensive. Next Generation Sequencing (NGS) has emerged in the last year as new diagnostic tool in this field. Objectives To share data obtained by the application of NGS in a cohort of patients affected by an AIDs of undefined origin evaluated at our center. Methods In this study we enrolled 145 patients evaluated at our center from 2010 to 2014,affected by undefined AIDs. In order to improve variant detection, to reduce diagnosis time and to correlate phenotype of patients with their genotype on multiple genes, we developed NGS approaches starting with 11 genes (divided into two panels), already known to be involved in AID (Panel 1: MVK, MEFV, NRLP12, NRLP3, NOD2, TNFRSF1A and PSTPIP1; Panel 2: IL1RN, LPIN2, IL36RN, PSMB8). Targeted resequencing was performed using a uniquely customized panel and analyzed with the MiSeq® sequencing platform (Illumina, San Diego, CA). All variants identified have been confirmed by Sanger sequencing and,when possible,family members were tested to study the segregation of identified variants. Results NGS analysis led to the identification of 61 patients with different variants in the genes of panel 1, with a detection rate of 42%. 36% of the patients showed variants in the NLRP3 gene, 19% in NOD2, 31% in NLRP12, 23% in MEFV, 8% in MVK and TNFRSF1A, 6% in PSTPIP1. Some of these variants are novel and others are already known or polymorphisms. In 29% of patients the combination of variants in two different genes was found. Several variants are of unknown pathogenic significance,while some of them are described as risk factors. We performed 15 familial study to unravel the segregation of some variants. Conclusions NGS leads to the identification of many genetic variants that could be associated with disease susceptibility. The major challenge is in the interpretation of the clinical relevance of identified variants, particularly of variants that are found at low, but >1%, frequency in various populations. These may function as susceptibility alleles to inflammation rather than disease-associated mutations [2]. Some patients show variants in multiple analyzed genes: it can be assumed that different variants in different genes may cooperate to determine a pathological phenotype.This will necessitate large-scale population studies, in vitro functional assay and careful correlation of genetic information with phenotypic data [3]. Crucial is close collaboration with clinicians. References Martinon F, Aksentijevich I. New players driving inflammation in monogenic autoinflammatory diseases. Nat Rev Rheumatol 2015 Jan;11(1):11-20. Shinar Y, et al. Guidelines for the genetic diagnosis of hereditary recurrent fevers. Ann Rheum Dis 2012 Oct;71(10):1599-605. Aksentijevich I, Kastner D. Genetics of monogenic autoinflammatory diseases: past successes, future challenges. Nat Rev Rheumatol 2011 Jul 5;7(8):469-78. Disclosure of Interest None declared