Proceedings of the 24th Paediatric Rheumatology European Society Congress: Part two

P164 Evaluation of children with Behçet’s disease from regionally two different centers of a highly prevalent country Nuray Aktay Ayaz, Betül Sözeri, Mustafa Çakan, Zübeyde Gündüz, Ayşenur Paç Kısaarslan, Ruhan Düşünsel, Hakan Poyrazoğlu Pediatric Rheumatology, Kanuni Sultan Süleyman Research And Training Hospital, İstanbul, Turke; Pediatric Rheumatology, Ümraniye Research And Training Hospital, İstanbul, Turkey; Pediatric Rheumatology, Erciyes University, Kayseri, Turkey Correspondence: Nuray Aktay Ayaz Pediatric Rheumatology 2017, 15(Suppl 2):P164

recording, all participants were instructed to discriminate auditorially and visually the rare stimuli (target stimuli) from the frequent stimuli (standard stimuli) and to press the button of the mouse immediately following the target stimulus to perform ERPs and P300. Results: Neurologic involvement in BD has a wide spectrum of symptoms consisting of acute type and chronic progressive type. Subclinical neurological involvement without neurological symptoms may also be possible. We aimed to look for the presence or absence of subclinical impairment of cognitive functions in pediatric BD patients. We did not find any difference in visual processing between patients and controls. But in auditory processing, latency of P300 in Behçet patients was longer than controls. We think that this finding may be due to subtle inflammation or vasculitis in different cerebral regions of pediatric BD patients (Table 1). Conclusion: As a conclusion further evidence is needed before stating that pediatric BD patients without neurological involvement might have cognitive impairment in early periods of their disease. Disclosure of Interest None Declared. Results: The clinical picture in children with systemic vasculitis was various: hyperthermia -6 cases, weight loss 6, dorsalgia 2, skin manifestations 7 (3 hemorrhagic rash, 2 spotted hemorrhagic, 2 dry gangrene, 1 hyperemia along the vessels, 1 liverdo, 1 child with syndrome Takayasu without skin changes), 3 migrating edema, 3 nodules, 5 myalgias, 4 hyperesthesia, 6 transient arthritis, 1 pericardial effusion, 4 heart rhythm disorders, 7 hepatolienal syndrome, 1 mucosal aphthae, 4 pulmonary lesions, 1 nosebleeds, 2 menorrhagia, 4 abdominalgia, 2 Gastrointestinal bleeding, 2 arterial hypertension, 1 asymmetry of blood pressure, pulse attenuation, vascular noises, 1 stroke, 5 urinary syndrome (3 proteinuria, 1 macro, 4 hematuria, 1 macro of them), 3 patients had polyneuropathy, 2 secondary cataracts, 2 destruction of the nasal septum, 1of sinus of the nose. The time of unfolding of the symptom complex before the diagnosis of SV was 7.1 ± 3.5 months (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Laboratory changes: leukocytosis 7 cases (20,8 ± 4,3G/l), anemia -6 (in 1 case Hv 46 g/l), ESR increased in all cases 44.6 ± 13.2 mm/h, CRP 21, 2 ± 6.1 mg/l, hypereosinophilia was noted in 1 patient, hypertransaminase in 2, increased creatinine level in 2, hypercoagulation in 4, hemoculture, procalcitonin, complementation -all was normal, APLAB in 1 case revealed lupus anticoagulant, ANA, aDNA, aNRP in all patients were negative, antibodies to MP3 were positive in 2 cases (in 5 negative, in 1 there were no data), in the same patients there was RF +, markers of viral hepatitis were not detected s in any patient. To the diagnostic criteria of Takayasu's syndrome (4 criteria) corresponded 1 patient, the diagnosis was confirmed by aortography, 1 -the Churg-Strauss syndrome (4 criteria), 3 criteria had 2 patients (diagnosed with PAN). Of the patients, long-term observed as undifferentiated systemic vasculitis, 1 had 3 criteria of congruity with the diagnosis of MPA, in the 2nd 3 GPA or 5 MPA, 3 of 2 GPA or 5 MPA, in the 4th -2 criteria of PAN. Morphologically confirmed 2 cases. Certain changes did not correspond to laboratory data: destruction of the nasal septum was detected in cases of seronegative for C-ANCA, and in 1 case the clinical symptom complex complied with the PAN criteria. In seropositive patients with C-ANCA, the common clinical features were arthritis, nephritis, menorrhagia and destructive pulmonary disorders. All patients received GC, 6 cyclophosphamide, 1 mycophenolate mofetil, 1 azathioprine, 6 antimalarial, 2 plasmapheresis. In 4 cases, there is remission, 3 recurrences of vasculitis, 1 death. Conclusion: The main problems in timely diagnosis of SV are insufficient awareness of general practitioners about nosologies data, the multidimensional unfolding of the clinical symptom complex, the frequent absence of pathognomonic autoantibodies, and the difficulty in conducting morphological studies. Disclosure of Interest None Declared. Introduction: Kawasaki disease (KD) is an acute, self-limited, systemic vasculitis, predominantly involving medium-sized arteries. It mainly affects children younger than five years and it is the leading cause of acquired heart disease in children in developed countries. Of unknown pathogenesis, KD severe complication is the occurrence of coronary artery lesions. Without early treatment, there is a 15 to 25% incidence of coronary artery lesions. Management with intravenous immunoglobin (IVIG), combined with aspirin, effectively decrease the incidence of this lesions to a 4%. The long-term prognosis is determined by the initial and current level of coronary artery involvement. Methods to predict which children are at higher risk for coronary aneurysms have been sought to determine prognosis and select patients for more rigorous treatment and follow-up.
Objectives: To describe the clinical presentation and evolution in addition to laboratory findings in Mexican pediatric population who developed giant aneurysms diagnosed with KD during the past 5 years. By identifying mayor risk factors in our population, an effective score could be used to select children for evaluation of additional therapies to prevent coronary artery aneurysms that occur despite treatment with IVIG. Methods: Retrospective cohort study of the Children's Hospital of Mexico Federico Gomez, last 5 years. We reviewed the data form the clinical archives of the patients who developed giant aneurysms after the diagnosis of KD from 2011 to 2016. A total of 84 patients with KD, 7% developed giant aneurysms. The variables analyzed, apart from the typical clinical and laboratory findings of KD, include size and Z score of the aneurysms, involution through follow up, cardiac morbidity and mortality, and treatment strategy.
Results: The mean age of patients at diagnostic was 17 months, and 84% were males. Only 33% of the patients developed complete KD, while 66% were diagnosed as incomplete. All patients presented with a positive Harada score. IVIG was administer in 83% of the patients, and a second dose was needed in 33%. Infliximab was used in 33% of the patients. One patient died due to cardiogenic shock. Results from echocardiography in the follow-up show that 33% of the patients have evolved to even larger aneurysms and 50% present no changes. Of the patients with a longer follow-up, 4 years after diagnostic, 33% have developed arrhythmias and 16% myocardial infraction. All are at high risk of sudden death. Conclusion: The late diagnosis is the characteristic present in all patients which developed giant aneurysms, making imperative to identify clinical and laboratory findings that will help identify KD in Mexican pediatric population to avoid cardiac complications.

Disclosure of Interest
None Declared. Introduction: Scrotal involvement in children and adolescents with Henoch-Schönlein purpura (HSP) is generally acute, resulting in swelling, pain and/or tenderness. Data of scrotal involvement in HSP patients are limited due to the small representation of this complication in previous case series, precluding an accurate analysis of associated factors and outcomes in patients with and without this complication, and particularly using the validated HSP criteria. Objectives: To assess scrotal involvement and outcomes in children and adolescents with HSP. Methods: Two hundred ninety six patients with HSP were retrospectively evaluated. All patients fulfilled validated European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/ PRINTO/PRES) criteria for HSP patients. Of them, 150/296 (51%) were males and were assessed by demographic data, clinical manifestations, laboratory exams and treatments. Scrotal involvement was defined by the presence of scrotal edema and pain/tenderness in physical examination and/or testicular Doppler ultrasound abnormalities. Patients with only pain, petechiae or purpuric rash on scrotum were excluded. They were also divided in two groups at study entry: with and without acute scrotal involvement. Results: Acute scrotal involvement was observed in 28/150 (18%) HSP patients. Six patients (21%) had bilateral involvement. None of patients had acute scrotum as the first sign/symptom of HSP. This complication was evidenced at HSP diagnosis in 27/28 (96%) and only one of them was diagnosed at 1 year of disease duration. Recurrent scrotal involvement was identified in 2/28 (7%) HSP patients. Thirteen patients underwent testicular Doppler ultrasound and revealed acute epididymitis-orchitis in all. A short course of prednisolone/prednisone (0.5-2.0 mg/kgday) was administered in 26/28 (93%), with resolution of scrotal signs/symptoms. Further analysis of HSP patients with acute scrotal involvement (n = 27) compared to those without this complication (n = 122) at diagnosis revealed that the median of current age [4.9 (1.7-12.6) vs. 6.1 (0.9-14.8) years, p = 0.201] and purpura duration [18.5 (5-60) vs. 14 (1120) days, p = 0.101] were similar in both groups. The frequency of elevated serum IgA was significantly lower in the former group (18% vs. 57%, p = 0.017), whereas corticosteroid (93% vs. 49%, p < 0.0001) and ranitidine use (63% vs. 30%, p = 0.003) were significantly higher in the former group. The frequencies of persistent purpura, arthritis, abdominal pain and nephritis were also similar in patients with and without acute scrotal involvement (p > 0.05). Conclusion: Acute scrotal involvement was observed in almost one fifth of males with HSP. This complication was commonly evidenced at HSP diagnosis, and the recurrence was rarely seen. Scrotal signs/ symptoms improved after a prompt use of corticosteroid. Disclosure of Interest None Declared. Introduction: Henoch-Schönlein purpura (HSP) is the most common vasculitis affecting children. Renal impairment is one of severe complications among children with renal involvement that underline its early diagnosis and treatment. Antiphospholipid syndrome (APS) is an autoimmune multisystem disorder that has been shown to be associated with HPS. The association between antiphospholipid antibodies (aPL) and HSP renal involvement has not been investigated previously.
Objectives: A large body of evidence, investigated the association between aPL and renal involvement implied a wide spectrum of pathological manifestations such as renal artery stenosis, renal infarction, renal vein thrombosis and thrombotic microangiopathy. Interrelation between HPS and aPL has been reported as a complicated HSP or has been shown to be associated with central nervous system involvement in HPS cases. Although complication of HSP with aPL has been documented previously, the impact of aPL in the HPS renal manifestations and Introduction: EGPA is rare in children 1 . Patients usually have protracted asthma prodromal phase before onset of vasculitic manifestation. However in children without typical pulmonary symptoms, recognizing the condition may be challenging.
Objectives: Here we describe a case, which was previously misdiagnosed as eczema for 2 years. Results: A 6 year-old Chinese girl with history of mild allergic rhinitis developed on and off erythematous itchy skin rash since 2014. The rashes were both nodular and patches and occurred symmetrically at dorsum of feet, knees, buttocks & elbows. It came as a crop and would regress in about 2 weeks, leaving hyperpigmentation ( fig 1). There was raised IgE (1983kIU/l, <52). She was diagnosed as eczema and was given topical steroid cream. From 2015 the skin eruption became more intense and frequent. She also developed recurrent arthritis of elbows, knees and ankles. She was only referred to rheumatology by 10/2016. Joint tapping showed inflammation. Urine dipstick indicated the presence of RBC but no proteinuria. Renal function was normal. Skin biopsy revealed presence of nuclear dust and fibrin deposition in subepidermal, perivascular and interstitial tissues, compatible with Leucocytoclasia. From 11/2016 she developed moderate eosinophilia up to 2.9 x 10 9 /L (26% of circulating wcc). There was also recurrent soft tissue swelling over upper limbs, which appeared as inflammation in muscles and adjacent subcutaneous tissues in MRI. Biopsy showed eosinophil rich inflammation. There was no other cause to explain the eosinophilia. Autoantibodies profile showed strongly positive ANA, anti MPO as well as anti scl-70 antibodies. Lung function showed no impairment. Taking together her clinical features of mild allergic rhinitis, leucocytoclasia, high IgE, eosinophilia and extravascular infiltration of eosinophil and positive anti MPO, she was diagnosed EGPA. She was put on systemic prednisolone and azathioprine with good response.
Conclusion: In our case the rash and raised IgE led to the initial assumption of eczema. The diagnosis was only suspected when she developed systemic vasculitic features and eosinophilia. EGPA is extremely rare in children and there is no validated diagnostic criteria. While major classification criteria for EGPA require presence of asthma 2 , it may not be applicable in children due to the young age.
Introduction: Takayasu arteritis (TA) is an idiopathic large vessel vasculitis. The clinical features can be varying and patients may present in the acute or chronic phase with nonspecific clinical features. Tuberculosis is widely prevalent in tropical countries and has been implicated in the pathogenesis of Takayasu arteritis.
Objectives: There are many reports regarding coexisting Takayasu arteritis and active tuberculosis but none regarding Takayasu arteritis and drug resistant tuberculosis in children.
Methods: We present the case of a child who presented with nonspecific features but on investigation proved to have Takayasu arteritis associated with drug resistant TB lymphadenitis.

Results:
A 17 year old girl presented with swelling left supraclavicular region of neck, low grade fever, loss of appetite and loss of weight for 4 months. A week prior to admission to the hospital she had developed swelling of both the legs. The patient's father had been treated for pulmonary tuberculosis 2 years ago. On examination she had mild pallor, was undernourished with mild bilateral pitting pedal edema. She had multiple cervical and supraclavicular node 3x2cms which were firm, non-tender and matted.She had asymmetric pulses and discrepancy in 4 limb blood pressure. Laboratory investigations revealed anemia and elevated ESR (71 mm/ hour). Peripheral smear and iron studies were suggestive of iron deficiency. Mantoux test was positive (10mm). Echocardiogram showed left subclavian stenosis, dilated ascending aorta and normal abdominal aorta. Aortogram revealed aortic arch vessel involvement with thoracic aortic narrowing at subclavian artery and second narrowing at the level of diaphragm. Histopathology report of left cervical lymphnode biopsy showed necrotizing granulomatous lymphadenitis consistent with tuberculosis. Gene Expert detected mycobacterium tuberculosis resistant to rifampicin. The diagnosis of Takayasu with drug resistant tuberculous lymphadenitis was established.
On the advice of infectious diseases team she was commenced on Levofloxacin, Ethionamide, Pyrazinamide, Ethambutol and Inj Kanamycin for 8 months. This was followed by Levofloxacin Ethionamide and Ethambutol for further 12 months. For Takayasu arteritis she received steroids initially and then 6 cycles of monthly cyclophosphamide subsequently. This was followed by weekly oral methotrexate. The patient is well 4 years since presentation and is currently on methotrexate, aspirin and antihypertensives.
Conclusion: Co existing drug resistant Tuberculosis is possible in Takayasu arteritis particularly in tropical countries where TB is prevalent. Treatment with combination of anti-tuberculous and disease modifying agents with careful monitoring of therapy is the key to the management of such patients.

Disclosure of Interest
None Declared.
Introduction: Familial Mediterranean fever (FMF) is the most common autoinflammatory condition characterized by recurrent attacks of fever and serositis. Colchicine is the main therapeutic option for the prevention of FMF attacks. Poor compliance to colchicine can lead to life threating complications, such as amyloidosis. In addition to the recurrent disease attacks despite regular usage of colchicine in appropriate and efficacious dosage, continuous subclinical inflammation between attacks is also a treatment challenge. The colchicineresistant FMF (crFMF) is defined as 6 or more serositis attacks in the last year or 4-6 attacks during the last 3 months despite the regular usage of colchicine in the highest tolerable dose (maximum 2 mg/kg for children). IL-1 receptor antagonists (anakinra, canakinumab) have been shown to be efficient in crFMF.
Objectives: Initially we aimed to determine the crFMF patients follow up at our department. Furthermore, we tried to define the efficacy of opocalcium colchicine (OC), anakinra and Canakinumab by comparing the FMF50 scores, the complete and partial clinical responses among patients with different treatment modalities. Methods: We assessed FMF patients followed up at our department. The data of patients are taken from the patients' database. Patients who were under OC, anakinra and canakinumab are considered to be resistant to standard colchicine treatment. The FMF50 score is used to define the response to treatment. The FMF50 is defined as at least 50% improvement in five of six criteria, without worsening in any of them. Complete clinic and laboratory response is characterized by an absence of clinical features and normal laboratory findings. The partial clinical and laboratory response include 30% improvement in clinical and laboratory features. FMF50 score of crFMF patients under colchicine or other treatment modalities for at least 6 months has been determined retrospectively by using data from the patients' records. Complete or partial clinical remission has been evaluated for all crFMF patients.
Results: A total of 839 FMF patients has been assessed and 49/839 (5,8%) of them has been considered resistant. FMF50 response has been obtained in 4/49 (8.2%) patients under standard colchicine treatment; in 14/30 (46.7%) patients treated with OC, in 5/6 (83.3%) with anakinra and in 12/13 (92.3%) patients with canakinumab. The FMF50 response significantly differed according to treatment modality (p < 0.005). Clinical remission has been achieved in 10/30 (33.3%), 5/6 (83.3%) and in 11/13 (84.6%) patients treated with OC, anakinra and canakinumab, respectively. Patients treated with OC significantly differed from those treated with anti IL-1 according to complete clinical remission (p < 0.002). Laboratory remission has been obtained in 7/30 (23.3%), 4/6 (66.7%) and 11/13 (84.6%) patients treated with OC, anakinra and canakinumab, respectively. The laboratory remission was significantly different between patients treated with OC and with anti IL-1 (p < 0.0001).The most common adverse effect was diarrhea in 17/49 (34.6%), transaminases elevation in 3/49 (6%) patients and leukopenia only in 1 patient. Diarrhea was seen in 3/30 (10%) patients under OC treatment. Local allergic reactions were seen in 3/6 (50%) anakinra patients. One patient developed pneumonia while on canakinumab treatment; upper respiratory tract infection has been registered in 3/13 (23%) patients and acute gastroenteritis in one patient. All of them responded to antibiotics treatment. None of the patients developed severe adverse effect. Conclusion: The FMF50 response has not been achieved in majority of patients under OC treatment, although their drug compliance was better comparing to standard colchicum-dispert. Complete clinical remission has been obtained in minority of patients treated with OC. In contrary, FMF50 response, complete clinical and laboratory response have been detected in most of patients treated with anakinra and canakinumab. Both of anti IL-1 agents were safe and effective in crFMF patients.
Introduction: CAPS are a group of rare autoinflammatory diseases associated to NLRP3 mutations, leading to inflammasome hyperactivity and IL-1β hypersecretion. CINCA syndrome is the most severe CAPS disease characterized by central nervous system disabilities with a long-term risk of secondary amyloidosis. Amyloid deposits in AA amyloidosis are composed mainly of the serum amyloid A (SAA) protein.
Recently, we have developed a novel NLRP3 Knock In (KI) mouse model for CAPS that replicate many of the clinical and pathologic features seen in humans. NLRP3 is a main target of proton pomp inhibitors (PPIs), commonly used for the treatment of excessive acid secretion. Omeprazole (OME), a well-known PPIs, has a potential anti-inflammatory effect making him a promising drug against sepsis and other severe inflammatory conditions. Objectives: To identify alternative and repurposing drugs for the treatment of CAPS diseases. Methods: Cytokines secretion from bone marrow derived dendritic cells (BMDCs) and peritoneal macrophages (PMs) was evaluated by ELISA. We have conducted a preclinical animal study to evaluate the response of KI to OME. Hystological analysis of all organs was evaluated by hematoxylin and eosin staining. Amyloid deposition was quantified through Congo Red staining. Results: We engineered N475K mutation in the murine NLRP3 gene to obtain heterozygous KI that recapitulates CAPS syndromes. Mice developed systemic inflammation with consequent delayed growth, splenomegaly and hepatomegaly when compared to wild type (WT) controls. Hystological analysis revealed the presence of an intense acute and chronic inflammatory cell infiltrates and amyloid deposits in spleen, liver, kidneys and lungs. As in CAPS patients, KI mice showed an increase in IL-1β, IL-1α and IL-18 secretion ad a decrease level of IL1RA production, the physiological inhibitor of preformed IL-1b. OME treatment increased the lifetime of KI mice, reduced the in vitro secretion of IL-1β by BMDCs and PMs isolated from KI and restored the production of IL1RA. Remarkably, PPIs improved inflammatory condition of the organs in vivo and since the first month were able to limit the amyloid deposition in the organs of KI mice. Serum analyzes are ongoing to quantify Serum Amyloid A (SAA) protein levels.
Conclusion: PPIs are promising new drugs, economical, non toxic, available in all countries. Down-modulation of IL-1b secretion by PPIs suggest the potential use of these drugs also for the treatment of autoinflammatory disorders. Although further studies are needed, these drugs seem encouraging also to improve a severe CAPS complication, amyloidosis. Disclosure of Interest None Declared.
Introduction: Still's disease presents as a disease continuum in paediatric and adult patients (pts), denoted as systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), respectively. [1][2][3] Both SJIA and AOSD have cytokine-driven pathophysiology wherein interleukin-1 (IL-1) plays a key role. 1 Canakinumab, a selective human anti-IL1 β monoclonal antibody, is shown to be efficacious in treating active SJIA pts. 4 Objectives: To evaluate the adequacy of canakinumab dosing in pts in the AOSD age range through an exposure-response (E-R) analysis of pooled canakinumab data from SJIA pts across three age groups (grps) of children, young adolescents, and older adolescents and young adults (the latter representing AOSD population). Methods: In this pooled subgroup analysis, pharmacokinetics (PK) and efficacy data of canakinumab treated pts were included from 4 SJIA studies (NCT00426218, NCT00886769, NCT00889863, NCT00891046). Study designs for trials have been published. [4][5] Canakinumab was administered at 4 mg/kg every 4 weeks (wks) in 3 studies and 0.5-9.0 mg/ kg in 1 study. Population PK and E-R modelling was performed with dose, age and weight as covariates. PK concentrations in different age grps were predicted using the PK-binding model. Steady-state exposure metrics including trough concentration (C MINss ), peak concentration (C MAXss ) and area under the plasma concentration-time curve (AUC ss ) were derived. Of 4 SJIA studies, one study [NCT00426218] where 4 mg/ kg every 4 wks was not given, was excluded for efficacy outcomes. Efficacy endpoint was adapted American College of Rheumatology (aACR) paediatric responses over 12 wks of treatment in the 3 age grps. Safety and tolerability were also assessed by age grps. Results: PK analysis was done in 233 children (0-12 years [yrs] of age), 60 young adolescents (12-16 yrs) and 31 older adolescents and young adults (16-20 yrs; age at the time of enrolment in the first study). Steady-state canakinumab exposure showed positive trends in median exposure with increasing pts age and were comparable across age grps ( Table 2). A total of 216 children (2 to <12 yrs of age), 56 young adolescents (12 to <16 yrs) and 29 older adolescents and young adults (≥16 yrs) were analysed for efficacy outcomes. aACR response was comparable across the 3 age grps ( Table 2). The safety profile of canakinumab was similar across different age grps with infections and infestations being the most common adverse event. N, total number of patients in each age group; n, number of patients assessed for ACR variables; Q1, 1 st quartile (25 th percentile); Q3, 3 rd quartile (75 th percentile) Conclusion: A comparable canakinumab exposure-response relationship was observed across all 3 age groups. Canakinumab showed a sustained therapeutic effect and no meaningful differences in safety profiles were noted across all age grps. These analyses suggest that a canakinumab body-weight adjusted regimen at the dose of 4 mg/kg every 4 weeks offers similar safety and efficacy in AOSD pts to that observed in SJIA pts. Introduction: Although colchicine therapy has dramatically improved the prognosis of familial Mediterranean fever (FMF) by decreasing the frequency of attacks and preventing amyloidosis, 5-15% of patients are reported to be unresponsive to colchicine. Canakinumab is an anti-IL-1β monoclonal antibody. Food and Drug Administration (FDA) recently aproved this drug for familial Mediterranean fever. Little is known about the long-term efficacy and safety of canakinumab in FMF.
Objectives: To present the single center experience of colchicineresistant pediatric FMF patients who were treated with canakinumab by off-label use since 2012. Methods: The hospital files of children with FMF who were started canakinumab were retrospectively evaluated. Fifteen patients (8 girls and 7 boys) were included in the study. Initial dose of canakinumab was 2 mg/kg/8 week for patients below 40 kg and 150 mg/8 week for patients above 40 kg.Dose and frequency were adjusted according to patients'response to treatment.All patients continued colchicine treatment during canakinumab use. Clinical and laboratory data of each visit were recorded. Drug-related adverse events were recorded. Complete remission was described as no attacks and normal acute phase reactants; partial remission was defined as decrease in severity and rates of attacks and/or elevated acute phase reactants with anti-IL-1 treatment.
Results: The mean age of the patients was 14.5 ± 3.8 years, and the mean follow-up time from diagnosis was 8.5 ± 3.7 years. The duration of canakinumab use was 22.5 ± 15 months (min:9 max:55 months). Twelve patients were M694V homozygotes. One patient had nephrotic range proteinuria and renal amyloidosis proved by biopsy. Eleven patients achieved complete remission after the first dose at 2 months and 12 patients at 6 months. Canakinumab interval was shortened in 2 patients from 150 mg/ 8 weeks to 150 mg/4 weeks. Except one, all patients achieved complete remission by 12 months. This patient had bilateral sacroiliitis and HLA B27 positivity and also been treated with methotrexate, sulphasalazine, and adalimumab in the past. Nephrotic range proteinuria of the other patient with amyloidosis disappeared and re-biopsy was normal at one year of canakinumab. Two patients had mild urinary tract infections. One patient had bronchopneumonia requiring hospitalization. Two patients had teeth abscess. There were no serious adverse events such as opportunistic infections, malignancies, or deaths. There were no injection site reactions. Besides, no significant laboratory abnormalities occurred in complete blood count parameters, liver and kidney function tests. Conclusion: To the best of our knowledge, this is the longest outcome study about canakinumab use in pediatric FMF patients. The results of this study suggested that canakinumab treatment is safe and effective in FMF patients in the long-term. Disclosure of Interest: None Declared.  Introduction: Crohn disease (CD) is a chronic relapsing inflammatory bowel disease with a significant impairment of quality of life. Disease onset occurs at pediatric age in up to 20% of the cases. The use of intensified treatment approaches for patients with severe disease has been proposed previously. These approaches rely on early identification of severe disease. Therefore it is essential to establish parameters that allow prediction of severe disease course. Some parameters, including disease location, age at diagnosis and disease behavior have been proposed but no data are available about joint involvement, to predict severe digestive disease.
Objectives: To sudy the link between joint involvement and severity of intestinal Crohn's disease. Methods: We studied the link between joint involvement (JI) and therapeutic failure in a retrospective and prospective cohort of 272 pediatric patients with confirmed CD according to international criteria, followed in a French tertiary center between 2005 and 2016.
Results: JI was observed in 65/272 (23.9%) patients and occurred in 75% of cases during the first year following CD diagnosis. We found a highly significant association between JI and therapeutic failure due to digestive disease (OR = 6.2, IC [2.7 to 14.5], p < 0.0001) and introduction of biotherapy (OR = 3.2, IC [1.8 to 6.0], p = 0.0001) two and four years after diagnosis.
Conclusion: This study suggests that in pediatric patients, occurrence of joint involvement may be used as a marker to identify patients with severe CD. From a clinical point of view it indicates that patients with arthropathies should be managed with particular attention, which may justify closer follow-up visits. As joint involvement occurred during the first year after diagnosis in the large majority of patients it may allow for selection of patients that may benefit from early aggressive treatment algorithms. Disclosure of Interest None Declared.
Introduction: Macrophage activation syndrome (MAS) is the most severe complication of systemic juvenile idiopatic arthritis (sJIA). Because MAS can follow a rapidly fatal course, its prompt recognition and immediate therapeutic intervention are critical. An international collaborative effort has recently led to the publication of the 2016 classification criteria for MAS in sJIA. However these criteria are intended to serve for classification purposes and not as diagnostic tool Objectives: To develop and validate a diagnostic score for timely detection of MAS in patients with sJIA.
Methods: The clinical and laboratory features of 362 patients with sJIAassociated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. 80% of the study population was used to develop the score and the remaining 20% as a validation sample. All features associated with the diagnosis of MAS in univariate analysis (p < 0.05) were further scrutinized in multivariable logistic regression. By means of an improper linear model method, the variables that entered the best fit model were assigned a score, based on their β-coefficient weights (score 1 for β-coefficients ≤ 1, score 2 for β-coefficients > 1, score 3 for β-coefficients ≥ 2). The best cut-off that discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. The sensitivity (SE), specificity (SP), area under the curve (AUC) and kappa value of the score were calculated for both the developmental and validation samples Results: The 12 variables that were most closely associated with a diagnosis of MAS in logistic regression analysis are presented in Table 4, together with their respective score. The final score ranged from 0 to 21. A cut-off value > 7 performed best in discriminating MAS from active sJIA (SE = 84%, SP = 84%, AUC = 0,91, kappa = 0,69). The good performance of the score was confirmed in the validation sample (SE = 92%, SP = 88%, AUC = 0,90, kappa = 0,80).

Conclusion:
The new diagnostic score, provisionally named MS score, is a powerful and feasible tool for the early detection of MAS in patients with active sJIA. Notably, the use of an improper linear model method may allow the application of the score in different settings. The MS score deserve validation in a prospective cohort of patients with sJIA-associated MAS Disclosure of Interest None Declared.
Introduction: Glucocorticoids (GCs) are first-line therapy for patients with systemic-onset juvenile idiopathic arthritis (sJIA), but approximately half of patients develop steroid dependence or resistance. Tocilizumab (TCZ) is a promising option for such intractable patients, although some continue to require high-dose GCs to maintain remission or treat persistent arthritis even under TCZ therapy. The predictors of incomplete response to TCZ in patients with sJIA remain unknown.
Objectives: To investigate the predictors of incomplete response to TCZ and their clinical course in patients with sJIA. Methods: This study was a single-center, retrospective observational study. Twenty-two patients with sJIA treated with TCZ were enrolled, and the observation period was more than 2 years. Good responder (GR) was defined as the achievement of remission with less than 0.2 mg/kg/day of prednisolone (PSL). Incomplete responder (IR) was defined as the inability to achieve remission and/or requirement for greater than or equal to 0.2 mg/kg/day PSL. Remission was defined as inactive disease according to the American College of Rheumatology. We compared the two responder groups for age at disease onset, sex, period from onset to TCZ treatment, indication of TCZ, various biomarkers at 2 years from initiation of TCZ, adjunctive immunosuppressant therapy at last visit, number of relapses under TCZ treatment, height, BMI, bone density, and Steinbrocker stage and class. Binary data were analyzed by Fisher's exact test and quantitative data were analyzed by Mann-Whitney U test.
Results: Among 22 patients (male 12, female 10, 9-18 years old), 12 patients (55%) were classified as GR and 10 patients (45%) were IR. Two IR patients presented with persistent arthritis under TCZ. There were no significant differences between the groups in age at onset, sex, and period from onset to TCZ treatment. For the indication of TCZ treatment, 8 patients could not achieve remission at onset, 12 patients relapsed with systemic manifestations with/without arthritis upon tapering of PSL, and 2 patients suffered persistent arthritis. There was no significant difference in white blood cell count and serum CRP level between the groups after 2 years of observation. However, serum CRP remained at a measurable level in 3 IR patients. Serum IL-6 in the IR group was significantly higher than in the GR group at 6 months, 1 year, and 2 years from initiation of TCZ (p = 0.008, p = 0.02, p = 0.003, respectively). ROC analysis revealed that the cut-off value of serum IL-6 at 6 months was 12.3 pg/mL (sensitivity 90%, specificity 75%, AUC 0.83) and 16.1 pg/mL (sensitivity 80%, specificity 75%, AUC 0.79) at 1 year. Serum IL-18 in the IR group was significantly higher than in the GR group at 1 and 2 years from initiation of TCZ (p = 0.001, p < 0.001, respectively). ROC analysis revealed that the cut-off value of IL-18 level at 1 year was 2328.4 pg/mL (sensitivity 70%, specificity 100%, AUC 0.91). At the last visit, adjunctive immunosuppressant use, number of relapses, and daily steroid dose were significantly greater in the IR group than in the GR group (p = 0.02, p < 0.001, p < 0.001, respectively). Six IR patients had a Steinbrocker stage of II or greater (60%), but all GR patients remained in stage I (p = 0.003). Six of 13 patients with IL-18 > 2328.4 pg/mL and/or IL-6 > 16.1 pg/mL at 1 year after TCZ initiation presented with joint destruction at the last visit.
Conclusion: Serum levels of IL-6 and IL-18 at 1 year after initiation of TCZ could predict IR and joint destruction in patients with sJIA. Disclosure of Interest None Declared.
Introduction: Canakinumab (CAN), a fully human, specific, antiinterleukin-1β monoclonal antibody, has been shown efficacious in the treatment of patients (pts) with colchicine-resistant familial Mediterranean fever (crFMF) in an open-label study. 1 Objectives: The primary objective was to demonstrate that CAN 150 mg every 4 weeks (q4w) was superior to placebo (PBO)  . After lead-in in E1, pts were randomised to CAN 150 mg q4w or PBO in E2. Pts who did not flare in the CAN group in E2 were re-randomised to CAN 150 mg q8w or CAN withdrawal/PBO in E3. In E3, dose could be escalated up to 300 mg q4w for pts with a flare. For PK/PD assessments, serum samples for CAN concentrations and total IL-1β were collected at baseline (Day 1), and trough samples at wks 1, 3, 5, 9, 13 and 17. Safety assessments included adverse events (AEs) and serious AEs (SAEs).
Results: Of the 63 crFMF pts randomised in E2, 1 PBO pt discontinued the study. The proportion of responders at Wk 16 was significantly higher with CAN vs PBO (Table 5). Of the 59 pts who continued from E2 to E3 on any treatment regimen, 19 (E2 responders) were re-randomised to CAN 150 mg q8w or PBO/CAN withdrawl in E3 while remaining pts received open-label treatment.
In E3, the proportion of pts who did not present new flares was numerically higher in the CAN vs PBO group (Table 5). In E3, 46% pts, including pts treated in open-label, maintained disease control with a prolonged dosing interval (q8w). 10% pts required up-titration to 300 mg q4w. No new safety findings or death were reported in CANtreated pts through E3 (Table 5). In crFMF pts, the serum clearance and steady-state volume of distribution of CAN (liquid-in-vial) varied according to body weight, and were estimated to be 0.14 ± 0.04 L/ day and 4.96 ± 1.35 L, respectively.  Results: Ten months old boy was admitted at our hospital due to pericarditis and fever, with no skin changes, no arthritis, and no visceromegaly but with severe inflammatory markers, including serum amyloid, and hypochromic mycrocitic anemia. All cultures were negative. He was treated with antibiotics, non-steroid anti-inflammatory drugs (NSAIDs) and prednisone, but relapsed whenever steroids were tapered. Chest CT scan had confirmed presence thick pericardial and pleural effusion while pleural punctate revealed increased number of polymorphonucler cells and increase in protein content without any evidence for infection. Since his mother had a history of neurosensorial hearing loss of undefined etiology and persistently elevated inflammatory markers we suspected on autoinflammatory disease background (possible idiopathic recurrent pericarditis). That is why we have initiated continuous treatment with ibuprofen and colchicine. DNA sample was analyzed but typical MEFV mutations in egzone 2 and 3 were not found. Since boy continued to have periodical attacks of fever and pericardial effusions, approximately on 2 weeks we were forced to add methyl-prednisolon pulses on 10 days. Unfortunately this has not stopped attacks of fever and pericarditis. . The clinical manifestations more frequently found were fever, followed by joint involvement, being more common in monogenic diseases than in polygenic disorders (Table 6). Haemoglobin levels were lower in monogenic than in polygenic diseases 9.95 g/dL ± 0.63 vs. 11.69 g/dL ± 2, ESR and CRP was higher in monogenic diseases 106 mm/h ± 68.5 and 80.5 mg/L ± 84.14 vs.  Results: A 20-months-old boy was referred to our pediatric rheumatology department with the episodes of fever, monoarthritis, and pustules on the face recurring every month since 10-months of age. Because MEFV analysis revealed M694V homozygote mutation, he was started 0.25 mg/ day colchicine by his pediatrician when he was 14-months-old. Despite the adjustment of colchicine to 0.5 mg/day, he continued to have recurrent fever and pustules. In his immunologic evaluation, white blood cell number, immunogobuline G,M,A levels, lymphocyte subgroup disturbation, phagoburst test was normal.He was given a short-course of corticsteroid because of fever and a painful erythema nodosum-like lesion when he was 26-months old. PSTPIP1 mutation was negative for PAPA. When he was 2.5 years-old, he had penile erection during an attack. Colchicine dose was increased to 1 mg/day. He experienced two more attacks of priapism with fever and pustules of the face. He was started an anti-interleukine 1 treatment, anakinra 1 mg/kg/day. He never had priapism, pustules, arthritis and fever attacks after the initiation of anakinra. After one year, anakinra was stopped. He is currently taking only colchicine since one year and doing well. Introduction: Heterozygous mutations of COPA gene have been recently linked to an autoimmune syndrome characterised by polyarthritis and lung disease with interstitial fibrosis or alveolar haemorrhages as complication (1). The gene encodes for a regulator of vesicular retrograde transport between Golgi and the endoplasmic reticulum (ER). In most cases the presenting symptoms are cough and tachypnea, that appear in the early childhood with articular manifestations appearing lately before di age of 10. At laboratory tests, autoimmunity is characterised by the presence of autoantibodies, with the majority of patients showing a frankly positive ANA titer (80%). Rheumatoid factor is reported to be raised in 43% of cases; a few patients showed also positivity for cANCA and pANCA (2). Objectives: We report one case referring to our centre of a young girl that presented at 3 year of age with polyarticular arthritis. Methods: The patient was clinically evaluated by the pediatric rheumatology unit of Istituto Giannina Gaslini. The family gave permission for publication of clinical and laboratory data and photographic images as well as molecular analysis.
Results: The patient firstly referred to our centre at 3 year of age for a polyarticular arthritis involving metacarpophalangeal joints, hip and cervical spine. Lab results were performed showing raised ESR and CRP, high titer rheumatoid factor and antinuclear antibodies positivity. For a newly-onset of a persistent cough with no evidence of infectious process a chest X-ray and then a lung CT scan was performed showing an interstitial lung disease with tree-in-a-bud appearance and air-filled cysts. In order to treat the arthritic process oral and intra-articular steroids were administered with good response. Methotrexate and abatacept used as steroid-sparing drugs failed to control disease progression. The molecular analysis of COPA gene showed the reported c.698G > A mutation. Patient intentionally discontinued therapy for 3 years as well as clinical follow-up. After that time with patient referring again at our centre, a very severe osteoarthritis with joint damage and deformities of multiple joints was found. Conclusion: COPA syndrome could be more common than thought due the autosomal dominant inheritance. When molecular diagnosis is confirmed a therapeutic aggressive approach is required to prevent permanent joint deformities and reduce the risk of life threatening complications such as pulmonary haemorrhages. Conclusion: Based on our current data the prevalence of pediatric AID in Cyprus is 0.05%, with an annual incidence of 1/10.000 in the general population. As expected, FMF is the most common diagnosis; 31% of patients have an unclassified AID. Formation of a national registry helps identifying rare disorders and acting suitably. Wider, international collaborations will further improve our knowledge and education on the pathophysiology and medical management of the AID. Disclosure of Interest None Declared.
Introduction: Antiphospholipid syndrome (APS) is a multisystem autoimmune condition characterized by vascular thromboses associated with persistently positive antiphospholipid antibodies. There is currently a paucity of data in pediatric APS and there are no validated criteria for diagnosing pediatric APS [1]. The most severe form of the disease is a catastrophic antiphospholipid syndrome (CAPS).
Objectives: The aim of our study is to present the diagnosis and the treatment of an 17-year-old patient with severe form of APS.
Methods: Retrospective analysis of patient's history.
Results: The first symptoms of the disease occurred in March 2016. The boy was admitted to clinic because of the pain on the chest for 3 weeks with growing symptoms: dyspnoea, cough, fatigue, feeling weak and lack of appetite. During the first hospitalization the pulmonary embolism was diagnosed. Additionally in blood tests elevated concentrations of D-dimer, antibodies to β2-glycoprotein I in IgM class, lupus anticoagulant, antinuclear antibodies (low titer) and antibodies to dsDNA were found. Other thrombophilic risk factors were excluded, but fact, that patient was taking dietary supplements could be important. Based on the results of the study and the observed symptoms, APS was suspected. The low molecular weight heparin (LMWH) was initially used in the treatment, but without improvement. In the following days the patient's condition was gradually deteriorated and symptoms of respiratory failure were observed. The CT pulmonary angiogram showed" image that could correspond to multiple infarct lesions". Although the patient did not meet the criteria for a catastrophic antiphospholipid syndrome, aggressive treatment: glucocorticosteroids (GC), immunoglobulins with antibiotherapy and chloroquine was used due to the deterioration of the boy's condition. The treatment resulted in a slow improvement, after four week the dose of GC was tapered and warfarin was included in the treatment, while LMWH was discontinued. After next four weeks of treatment the patient showed no symptoms of respiratory failure and moderate efford was tolerated well. Additional studies have shown low titer of anti-dsDNA antibodies, anti-cardiolipin antibodies -low profile, lupus anticoagulant was not determined due to warfarin. Control CT pulmonary angiogram showed partial regression of embolic alterations and almost complete regression of inflammatory/non-inferior lesions. Spirometry test within normal limits, moderately reduced diffusion capacity, no restriction. Six month after first symptom we have not seen signs of respiratory failure. Control of angio-CT have shown complete regression of embolic changes and further regression of inflammatory changes. Prophylaxis has continued to be recommended for warfarin. In addition to the treatment remain chloroquine and GC (10 mg/day Conclusions: Literature reports that defects in NEMO cause various abnormalities in signal transduction pathways involving NF-kB, TNF signalling and the IL-1 family protein receptors. Moreover, the association of NEMO C-terminal truncation with inflammatory disease, resulting in enhanced stimulation-induced proinflammatory gene expression and cytokine production, has been described recently.1 Our patient presents a mutation of NEMO gene involving C-terminal domain, which could be involved in the autoinflammatory manifestations as well as in the response to anti-IL-1 therapy. Informed consent to publish has been obtained from the parent. Conclusion: M694V mutation is the most common mutation followed by M680I(G/C) and E148Q. M694 mutation is shown to be associated with younger age at disease onset and severe clinical outcome. Chest pain and musculoskeletal pain were very frequent clinical features. Delay for diagnosis was found to be shorter in children compared to adults, possibly due to increase of awareness for FMF in recent years. Disclosure of Interest None Declared.
Introduction: Periodic fever syndrome with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) represents the most common periodic fever syndrome of childhood with unknown etiology. PFAPA is considered as a sporadic disease although many studies suggest that it might have a genetic cause especially due to the high rate of positive family history. However, no genetic cause has been identified. Studies show that serum levels of chemokines, immune cells chemoattractants, CXCL10 and CXCL9 are significantly increased in PFAPA patients during febrile state compared to PFAPA patients in afebrile state, patients with other hereditary periodic fever syndrome during flare and healthy controls. Furthermore, CXCL9 is increased in PFAPA patients during afebrile state compared to healthy controls. Introduction: Blau syndrome (BS) is a very rare monogenic disease resulting from mutations in the pattern recognition receptor NOD2. It is phenotypically characterized by the triad of granulomatous polyarthritis, uveitis and skin involvement. Although skin involvement occurs in 70% of cases, only very little is known about its initial clinical presentation and evolution during disease course.
Objectives: To describe the initial skin manifestations of BS. Methods: We retrospectively studied six patients from three families with a genetically confirmed BS. Data on the dermatological manifestations were collected by analysis of photographs, medical records and patient interviews.
Results: The median age at diagnosis was 16.5 years. In all patients skin manifestations were the first symptom of the disease and occurred at a median age of 1.6 years. For 3 patients the rash set on following BCG-vaccination. Skin lesions were always diffuse millimetric micropapules with normal skin colour or erythematous or pigmented without itching. The skin lesions were diagnosed as Gianotti-Crosti syndrome or atopic dermatitis before the diagnosis of BS was established. Skin lesions disappeared in three patients, one had a flare after BCG and one had a persistent rash. All skin biopsies revealed dermic granuloma without caseous necrosis. Infectious agents stains were negative. Results: We observe a 6-year-old girl. Onset of the syndrome in the age of 1: papular rash on a face and external ears followed by scars; recurrent pyretic fever. Deterioration in the condition at the age of 3: urticaria, fever with coughing and dyspnea attacks, stomatitis, conjunctivitis, stomach pain, arthralgia, Raynaud's syndrome, WBC 13 × 10 9 , ESR 35 mm/h, CRP 40 mg/l. CRP and ESR values were within normal range in-between fever attacks. In course of 3 years the patient received budesonide for bronchial asthma which gave no effect. Bronchial asthma, mucoviscidosis, primary immunodeficiency conditions, infections, connective tissues systemic diseases, ANCA vasculitis, CAPS, TRAPS, HIDS were ruled out at the age of 5. The multilayer spiral CT of lungs demonstrated interstitial alterations of S2 superior lobe of the right lung, S6 left lower lobe, with negative dynamics within 6 months of follow-up. SAVI syndrome was diagnosed. TMEM 173 mutation was not confirmed. The prescription included prednisolone 0.7 mg/kg/day, tofacitinib 7,5 mg/day. Fever, cough, dyspnea, Raynaud's syndrome, arthralgia reserved after three months of treatment, the severity of rash reduced, the levels of CRP, ESR, PLT and WBC normalized. Prednisolone was cancelled after 8 months, tofacitinib treatment was continued. After 12 months of treatment positive dynamics was observed in the multi-layer spiral CT of lungs, i.e. reduction of alterations intensity in S2 superior lobe of the right lung, as well as in the area of S6,8,9 left lower lobe. No formation of bronchi and bronchiole ectasis, honeycomb lung areas was observed. Introduction: Auto-inflammatory diseases (AInD)often first present in childhood, and the protean manifestations of fever, rash and other inflammatory symptoms can be confused with common childhood illness. Disease recognition and correct diagnosis may be delayed due to low recognition of AInD among community health care providers.
Objectives: We examined the time interval from parent-reported symptom onset to diagnosis of AInD for children seen at British Columbia's Children's Hospital (BCCH), Canada in the first year of a newly dedicated provincial tertiary-care AInD clinic. Methods: Consecutive patients seen in the AInD clinic were consented to participate in a longitudinal patient registry based at BCCH called CAN-Fever. Subjects with completed registry enrollment data were analysed, with data including demographics, diagnosis, time intervals from symptom onset (parent report) to diagnosis and from diagnosis to registry enrollment. Results: 48 patients (M:F 24:24, mean age at enrollment 8.9 y, range 1-19 y) were enrolled into CAN-Fever over 12 months in 2016. Unclassified periodic fever syndrome (n = 13) and periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome (n = 13) were the most common diagnoses; smaller numbers of patients were seen with the following: chronic recurrent multifocal osteomyelitis (9), familial Mediterranean fever (5) Introduction: Problematic issues of modern rheumatology concern not only clinical diagnostic and therapeutic issues of major and serious in its outlook and consequences of diseases. In recent years, much attention is paid to pathological conditions that are attributed to comorbid arising from the disease or the treatment used. These include modern researchers the least attention is paid to non-specific liver.
Objectives: The aim of the investigation was to study the functional state of the liver in children with systemic lupus erythematosus and juvenile rheumatoid arthritis during the administration of иasic and anti-inflammatory medications. Methods: It was analyzed the history of 26 persons 7-18 years with systemic lupus erythematosus (SLE) and 70 patients with juvenile rheumatoid arthritis (JRA) aged 7 -18 years of the duration of the underlying disease for more than three years. The functional state of the liver in children and adolescents had been studied using complex clinical laboratory, biochemical and instrumental methods (objective examination, ultrasound (US) of the liver and gallbladder, determine blood levels of bilirubin and its fractions, apolipoprotein, haptoglobin, activity of alanine transferase (ALT), aspartate transferase (AST) and γ-glutamate transferase (GGT). Results: Symptoms of liver involvement in the pathological process of increasing body size by ultrasound found in 60.0% of patients with SLE and 10.7% -with JRA. Analysis of pigment metabolism SLE patients testified to the adequacy of the liver detoxification function, but there were growth in the average total bilirubin (p <0.05), while maintaining disease activity (r = 0,63; p <0.05). High concentrations of ACT registered 12.5% in SLE and 5.0% -with JRA. The haptoglobin concentration among patients in both groups decreased significantly (p <0.05), which reflects a decrease of the protein-synthesizing liver function in patients with prolonged disease, and high level process activity. This confirms the relationship between the degree of disease activity and the level of haptoglobin in the blood of children with JRA (r = -0,96; p <0.05). Research excretory liver function by identifying one of the most sensitive markers of cholestasis -GGT serum showed that the concentration was elevated 40.0% of SLE patients. Half of patients with SLE occurres hyperinsulinemia (increased levels of over 25 mkMO/ml). It is a direct connection between the degree of disease activity and the level of serum apolipoprotein (r = 0,895; p < 0.05), ratio of ALT/RYR (r = 0,999; p <0.05), that is indicating the accumulation of signs of fibrosis formation in SLE.
Conclusion: So, the high frequency of liver involvement in the pathological process in SLE and JRA with a reduction of protein synthetic and excretory functions during long-term disease was found. The functional status of the liver are more depended on the activity of the disease. Disclosure of Interest None Declared.

P207
Investigation of the function of external respiration in children with rheumatic diseases Nataly S. Changes in the cardiovascular system in children manifested by the violations of ECG parameters (tachycardia, increased systolic index), structural changes (the mitral prolapse from first to third degree) and disorders of the intracardiac hemodynamics and the cardiac remodeling. In children with SLE and JIA the impact and minute volumes of blood decrease, the size of the left atrium and end-diastolic left ventricular size increased according to terms of disease, indicating the formation of both diastolic dysfunction and systolic. The decrease in adaptive capacity of the cardiovascular system in children with rheumatic diseases, according to test 6-minute walk, which manifested itself insufficient growth heart rate to exercise and decrease the distance that has been traveled (p <0.05). The patients' age, sex, duration of disease and its activity and duration of glucocorticoids treatment constituted fundamental relationship with the number of comorbid conditions in children with SLE. In children with JRA greatest weight in the formation of comorbidity among the studied parameters were: sex of the patient, the age of onset, number of affected joints, active process, duration of illness, duration of administration of glucocorticoids and methotrexate (p < 0,05 Objectives: To test the safety, feasibility and acceptability of Rightpath in primary care, and across two geographical areas in the UK to assess the transferability of the triage and referral guidance. Methods: Piloted first at PMSKP, with iteration of the triage guidance and process followed by roll out at a second site (South Tyneside NHS Trust). Using mixed methods, evaluation focused on key areas: Implementationworkshops with service providers (triagers and clinicians) held at two time points to refine triage guidance and process.
Trainingfor triagers based on their weekly log of triage experiences and regular case based discussions and feedback.
Evaluation -(i) Parent/patient questionnaire, incorporating the 'Friends and Family' test and 'Collaborate' (a patient reported measure of shared decision-making), completed immediately after consultation to explore expectations and satisfaction; (ii) Service providers weekly log documenting experiences and training needs; (iii) Routine patient data including demographic details, referral information, triage outcome, ultimate diagnosis/outcome and communication between triage teams and health care providers; (iv) Service providers signposted to key areas for selfdirected learning (paediatric musculoskeletal matters [PMM]www.pmmonline.org) and usage monitored. This study had ethical approval and is NIHR CRN portfolio adopted. Results: Total triaged 05/09/16 -30/04/17 (101 to Rightpath, 264 to specialist paediatric services). The most common CYP MSK referrals from primary care were knee pain, foot pain, flat feet and back pain; the most common conditions triaged to Rightpath were foot pain, knee pain, flat feet, 'clicking joints' and in-toeing. No significant pathology has been triaged inappropriately so far to Rightpath. Feedback from 66 Rightpath family participants was positive with no complaints or requests for onward specialist referral; 100% would recommend the service, with median satisfaction (1-10) scores about primary care providers being high (1='no effort made' and 9='every effort made'); 'helped understand your/your child's health issues' (8.9), 'listened to things that matter most to you about your/your child's health' (8. 9), 'included what matters most to you in choosing what to do next' (8.9). Primary care therapists and podiatry described the workload to be appropriate for their existing skills. Triage staff deemed the triage process manageable (57% of decisions 'easy/very easy') and triage guidance to be useful commenting that paediatric experience was important to support decision-making. Conclusion: Initial data shows Rightpath to be feasible, safe and acceptable. The next phase of the pilot is in progress at the second site.

Disclosure of Interest
None Declared.

P211
Hand grip strength, pinch grip strengths and manual dexterity in children and adolescents with juvenile idiopathic arthritis Ela Tarakci  Introduction: Juvenile idiopathic arthritis (JIA) is a chronic autoimmune condition of unknown etiology. JIA combine with joint pain and inflammation that affects children who are less 16 years of age and continue more 6 weeks. JIA is a chronic inflammatory disease resulting in joints arthritis and deformities in the hands and fingers. This leads to decrease of joint mobility and strength of the hands which can lead to physical and functional hand disability and subsequent reduction manual dexterity in daily living activities.
Objectives: The purposes of this study was to assessed hand grip strength, pinch grip strengths and manual dexterity in patients with JIA who have at least one affected wrist or finger joint. Methods: 40 patients with JIA aged 6-16 years (33 girls and 7 boys) diagnosed according to ILAR classification criteria were enrolled in this cross-sectional study. "Jamar Hand Dynamometer" was used to evaluate the hand grip strength, "Pinchmeter" was used to evaluate the pinch grip strengths, "Nine Hole Peg Test" (NHPT) was used to evaluate the manual dexterity. Patients were asked to take the pegs from a container, one by one, and place them into the holes on board and replace back into the container. Duration of place and replace pegs was summed up and totally record for dominant side and non-dominant side. SPSS Version 21.0 program was used for statistical analysis.
Results: The mean age was 11.62 ± 2.41 years. 55% of patients had at least one affected finger joint. 87.5% of patients had at least one affected wrist joint. Table 9 shows hand grip strength, pinch strengths and manual dexterity in patients with JIA. Grip and pinch strengths showed a significant correlation with NHPT score for dominant side (Hand grip r = -0.34 p = 0.028, palmar pinch r = -0.52 p = 0.001, tip pinch r = -0.42 p = 0.006, key pinch r = -0.34 p = 0.03). Also, only tip pinch strength showed a significant correlation with NHPT score for non-dominant side (r = -0.33 p = 0.033). Conclusion: We found correlation between manual dexterity with grip and pinch strengths in patients with JIA. Based on these results, we suppose that manual dexterity and decreased strengths of grip/ pinch should be considered to increase independence of daily life activities in patients with JIA. Introduction: Over the last ten years, several studies have shown the benefits of ultrasound (US) in assessing joints in juvenile idiopathic arthritis (JIA), without discomfort for children (1). The JIRECHO study aims to ensure a systematic ultrasound follow-up for patients with JIA within the European multicentric JIRcohort. Evaluation of the reliability in the assessment of joints by different sonographers is essential to justify a multicentric cohort. Objectives: To evaluate the intra and inter observer reliability on 10 joints between ultrasound JIA experts on children with different ages. Methods: 17 experts (10 rheumatologists, 4 radiologists and 3 pediatricians) on US from 15 different centers were invited to participate in a 2 days-reliability exercise with acquisition of images on different JIA children's group of ages. The expertise of participants being different, it was decided to work in couple during the two days. The first day, a training session was organized to be agree on different scoring; then a practical session was performed on 4 children with different age groups (2-4, 5-8, 9-12, 13-16 years) with 2 rounds, in order to obtain the intra observer reliability. The second day concerns the inter observer reliability on 4 JIA children with different ages groups. The joints examined were: elbows, wrists, MCPs II, knees and ankles (examination techniques and definition of synovitis proposed by the US paediatric OMERACT) (2)(3)(4). All parents of the children participating at the study signed an informed consent. Results: The intra observer reliability for detection of B mode and doppler synovitis was moderate for the majority of participants (k value 0.42-0.59 for 6), good for 1 (k 0.72) and fair for 1 couple (k 0.22). The inter observer reliability was highly variable and quite fair (k 0.16-0.50).  Objectives: To describe the spectrum of MRI and US features in juvenile scleroderma with musculoskeletal involvement. Methods: We describe MRI and color Doppler MSUS findings of clinically affected (with arthritis and/or LOM and/or overlying skin with edema or sclerosis) lower or upper extremities from 4 males and 2 females;2 with systemic scleroderma (ssc), 2 with linear scleroderma, 1 with generalized morphea and 1 with mixed morphea; median age 8,5 years, range 7-10,5; median time from symptom onset to MRI 11 months, range 2-24. MRI sequences; performed on a 1,5 Tesla MRI device included T1, fluid-sensitive, and T1-FS contrast-enhanced sequences. Comparisons were made to uninvolved areas of the extremity, and the contralateral extremity.

Disclosure of Interest
Results: Thickening of the dermis and infiltration of the subcutaneous fat with increase in signal intensity on fluid sensitive sequences and contrast-enhanced T1w images and hypointense signal lesions on unenhanced T1w images was apparent in 4 patients. In 2 male patients with generalized scleroderma, clinical LOM of fingers and wrists preceded skin sclerosis by 2 months. Joint and tendon sheath synovitis, indicated by initial MSUS, was detected in fluid sensitive and T1w enhanced images. The combination of tendon-sheath synovitis and muscular fascia thickening and enhancement concomitantly with contractures very characteristic of scleroderma, helped identify sclerodermatous musculoskeletal involvement in the absence of skin induration. Focal bone marrow edema depicted as high signal intensity in fluid sensitive sequences was found in 2 cases; 1 with generalized morphea without apparent overlying skin sclerodermatous lesion, 1 with linear sclerodermawith atrophic lesions in all overlying structures.
Conclusion: Musculoskeletal imaging features of juvenile scleroderma involving the skin, fascia, musculature and bones reflect pathomorphologic changes of this rare disorder and enable a complete assessment of the disease extent, including depth of infiltration and disease activity. Different imaging findings appear to reflect different subtypes of Juvenile Scleroderma. Whole depth lesions of the affected extremity in linear scleroderma, tendon sheath and joint synovitis in extremities with intact overlying skin structures in generalized morphea, bone marrow, fasciitis and skin infiltration in Systemic Scleroderma. Implementation of MSUS and MRI in Juvenile scleroderma led to earlier definition of the diagnosis and assisted the evaluation of disease extension.

Disclosure of Interest
None Declared.

Immunodeficiency and infection related arthritis P214
Commune variable immunodeficiency mimicking sarcoidosis in pediatric age: a case report Abstract withdrawn In 13 of 20 patients the duration of acute arthritis was more than six weeks and in 10 more than 6 months. In acute illness 13 of 20 patients were treated with antibiotics. All children received nonsteroidal anti-inflammatory drugs and 10 prednisone. In 13 of 20 patients intra-articular administration of methylprednisolone was performed. In the management of resistant arthritis: 13 patients were treated with sulfasalazine, 5 with methotrexate and one with cyclosporine.
In the study group the treatment was completed in 10 of 20 patients and the rest is in follow up. Six of our patients have reached adulthood. 5 of them completely recovered remain in remission without medication. One patient has been diagnosed with ankylosing spondylitis. Two of 20 patients developed psoriasis. Conclusion: In the examined period of 5 years, Yersinia infection was the cause of 17% of all ReA. Seasonal morbidity with the onset of symptoms in autumn and spring was observed. In most patients family history of spondyloarthropathies was negative.
In majority of patients YReA was associated with HLA-B27 antigen. Some patients evolve into other spodyloarthropaties. In some patients with YReA the course of the disease is prolonged or chronic and has become a significant therapeutic problem.

Disclosure of Interest
None Declared. Introduction: Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases of childhood that causes significant physical disability with high morbidity and mortality. Biologic agents are commonly used in patients with JIA as well as standard disease modifying drugs to have an acceptable quality of life, to control pain, to protect the function of joint, to ensure normal growth and to decrease the systemic complications of the disease. Choosing the most effective and safest treatment regimen is the cornerstore in management of these patients. TNF-alpha inhibitors, IL-1 ve IL-6 antagonists are commonly used biologic agents. Especially, as the firstly used biologic agent, the effectivity of TNF-alpha inhibitors is well documented. However, as these drugs act as immunosuppressant and immunomodulator, they have the risk to lead serious infections. There are studies in adults investigating the infectious complications of biologic agents and many of them reported the efficacy in treatment of adult patients with rheumatoid arthritis without any serious complications. ApoA is the main protein component of high density lipoproteins and promotes the reverse transfer of cholesterol from the walls of blood vessels to the liver. A significant (p <0.05) decrease in the concentration of ApoA in patients of all clinical groups was found in comparison with the control group. The ratio of ApoA and ApoB is a valuable indicator for assessing the atherogenic shift and the risk of cardiovascular disease, Is under genetic control and exceeds the prognostic value of the determination of individual apolipoproteins. In norm ApoA/ApoB > 1 and is considered as a low atherogenic risk factor. Among children with rheumatic fever, ApoA/ApoB <1 was found in 16.7% of patients with systemic lupus erythematosus, in 14.8 patients with juvenile idiopathic arthritis and in 12.5% of patients with juvenile scleroderma. An inverse correlation was established between the ApoA/ApoB ratio and the serum cholesterol concentration (rs = -0.31, p <0.01). ApoE is part of fatty particles of chylomicrons and very low density lipoproteins, initiating their capture and removal from the blood by interacting with a specific receptor on the surface of the liver cells. In the study, an increased level of ApoE in the blood serum of children with rheumatic diseases was found in comparison with the control group. A correlation was established (rs = 0.37, p <0.05) between the content of ApoE and total cholesterol in the blood serum. Introduction: Arthritis is the most frequent extra-intestinal manifestation of inflammatory bowel diseases (IBD) (7-21%). Onset of IBDrelated arthritis is usually before the development of gastrointestinal symptoms and hence before IBD diagnosis. Faecal calprotectin is recommended from NICE guidelines to reduce the number of useless endoscopies in patients with gastrointestinal symptoms but it is not usually performed as screening for IBD in patients with JIA. Moreover, there is no consensus about the right cut-off to obtain the better sensibility and specificity in paediatric patients.

Infections -Immunoregulation -Biomarkers
Objectives: The aim of this study was to test faecal calprotectin as a screening tool to identify JIA patients with underlying IBD. Secondary outcomes were to identify clinical or laboratory findings able to predict IBD among JIA patients as well as to define a faecal calprotectin cut-off level with the best sensibility and specificity for IBD. Among JIA subtypes, enthesitis related Arthritis (ERA) was the most frequent (4/7), followed by olygoarticular (2/7) and undifferentiated arthritis (1/7). ERA was found to be a significant risk factor for IBD (OR 69,33, 95% CI 8-538, p-value < 0,0001). Two patients with IBDrelated arthritis were receiving anti-TNFa therapy for severe arthritis when developed IBD. Only 2 patients (29%) presented diarrhea, fecal blood or abdominal pain. Three patients had growth retardation without intestinal symptoms. One patient had an arthritis uncontrolled from therapy. Faecal calprotectin was significantly higher in patients with IBD than in patients without IBD (median value 1500 mg/kg, range 60-2000, vs 20 mg/kg range 10-50, p-value < 0,0001). The cut-off value with a better sensibility and specificity was found to be 250 mg/kg or more (positive predictive value 70%; 95% CI 0. Introduction: The alarmin S100A8/A9 has long been characterized as a pro-inflammatory trigger molecule amplifying immune responses. However, recent evidence also suggests an immune-regulatory role of this protein, as observed in cancer by promoting the differentiation of myeloid-derived suppressor cells (MDSC).
Objectives: Since the molecular mechanisms involved in S100A8/A9 driven MDSC differentiation are poorly understood and the role of these cells in autoimmune diseases such as rheumatoid arthritis remain largely unknown, we analyzed the involvement of S100A8/A9 for MDSC differentiation under non-tumor conditions and evaluated their contribution during the disease development and progression of rheumatoid arthritis. Methods: To investigate the effect of S100A8/A9 on MDSC differentiation, bone marrow cells from wild type (wt), S100A9 knockout (A9ko) and S100A9 transgenic (A9tg) mice were analyzed. Accumulation of MDSC and their phenotypical characterization was performed by FACS analysis and functional characterization included arginase activity, NOand ROS-production and T cell proliferation assays. The role of S100A8/A9 and MDSC in arthritis was investigated using the collagen-induced arthritis (CIA) mouse model. Accumulation of MDSC in different organs was analyzed by FACS and systemic S100A8/A9 levels were measured by ELISA. Ex vivo functional analysis of purified MDSC was performed to assess the potential of these MDSC to inhibit T cell responses. Induction of MDSC by treatment with S100A8/A9 or pharmacological inhibition of MDSC function in CIA mice was used as proof of concept experiments. Results: Our in vitro studies reveal that prolonged stimulation of myeloid progenitor cells with S100A8 induces the differentiation of immature cells that phenotypically as well as functionally resemble MDSC. These cells comprise typical MDSC features such as co-expression and up-regulation of arginase activity and NO production as well as strong suppressive effects on the proliferation of both CD4-and CD8-positive T cells. Tolllike receptor 4 signaling was identified as the major signaling pathway of S100A8 induced MDSC differentiation. Furthermore, numbers of MDSC and their suppressive activity on a per-cell basis were decreased in cells lacking endogenous S100A8/A9 implying a dual role of this alarmin for MDSC differentiation and function.
Investigating the role of S100A8/A9 and MDSC in a mouse model of CIA, a clear correlation between disease scores, MDSC numbers and systemic S100A8/A9 levels was observed. Furthermore, disease activity was reduced in wt and A9tg mice compared to A9ko mice and was in line with a tissue-specific increased accumulation of MDSC in the lymph nodes. Next to an enhanced suppressive activity of MDSC isolated from lymph nodes of wt and A9tg mice, these MDSC promoted the accumulation of regulatory T cells (Treg) whilst suppressing the differentiation of TH17 cells. In contrast, MDSC isolated from lymph nodes of A9ko mice had no effect on Treg differentiation and did not inhibit TH17 emergence. Inhibition of MDSC function in CIA mice by administration of a nitric oxide synthase inhibitor exacerbated the disease severity while repeated treatment of A9ko CIA mice with S100A8 ameliorated arthritis symptoms that was in line with increased numbers of MDSC in the lymph nodes. Conclusion: Our in vitro results clearly show a S100A8/A9 dependent accumulation of cells that phenotypically as well as functionally resemble MDSC. In vivo data strongly support the importance of these findings. By influencing MDSC accumulation and function, S100A8/A9 is critically involved in regulating the disease outcome in rheumatoid arthritis, implying an important role of S100A8/A9 derived MDSC in regulating immune reactions during autoimmune diseases and thus a immune-regulatory role of this originally characterized pro-inflammatory alarmin.

Disclosure of Interest
None Declared.

P222
In active juvenile idiopathic arthritis the HLA-DR associated network module may drives the functionally dichotomic pathogenic immune subsets from a common Introduction: We have previously identified T cell subsets in both Teff (CPLs) and Treg (iaTreg) compartments that are HLA-DR positive, antigen experienced, pro-inflammatory, correlating with disease activity and sharing strong TCR oligoclonality with synovial T cells. Their phenotype and association with clinical fate inspired out current hypothesis that these functionally discordant cells may originate from a common precursor. Objectives: To understand the pathogenicity drivers, find key genes, modulated pathways or network of gene associated with pathogenic HLA-DR positive subsets. Methods: Next generation RNA sequencing was performed on sorted CPLs (CD3 + CD4 + CD14 -HLADR + CD25/CD127 Teff gate) and iaTregs (CD3 + CD4 + CD14 -CD25 hi CD127 lo Treg gate) from 8 active disease juvenile idiopathic arthritis (JIA) patients. CPLs and iaTregs were sorted using flow cytometer, RNA was extracted and and library was prepared for RNA-sequencing. The paired end RNA sequencing was performed using illumina HI-Seq platform. Raw reads were aligned using STAR aligner and reads were summarised at gene level using featureCount programme. Raw read counts were further analysed in R statistical programming environment. Results: Comparative gene expression analysis, between CPLs vs iaTreg and that of the common pool of Teff vs Treg, and pyhlogenetic association analysis suggests that Teff and Treg converges to a common branch from where iaTreg and CPLs have emerged. TCR sequence oligoclonality in CPLs/iaTregs versus that of the common Teff/Treg pool reinforce the possibility of a common precursor. Furthermore, Weighted gene correlation network analysis (WGCNA) identified strongly coordinated HLA-DR gene network module and suggests its potential role as the driver of pathogenic T cell subsets from HLA-DR negative subsets. Gene set enrichment analysis suggest that HLA-DR module genes are involved in TNF-a signalling, Inflammatory response, complement, and apoptosis. Transcription factors (TFs) gene regulatory network (TF-GRN) analysis is performed to identify the key regulatory molecules driving the convergence of HLA-DR negative Teff and Treg population to HLA-DR positive pathogenic CPL and iaTreg population. Global TF-GRN network analysis identified FOXP3, CEBP, SPI and E2F1 as key transcription factor driving the Teff, Treg to pathogenic iaTreg and CPLs. Intriguingly, as both subsets transit in the inflamed synovium, these data underscore a potential role of the microenvironment in shaping two functionally dichotomic populations from a common precursor. Introduction: S100A8/A9 heterodimers are efficient and reliable biomarkers for monitoring disease activity in inflammatory disorders like juvenile idiopathic arthritis. On a molecular level these proteins are characterized as endogenous alarmins that, upon release by activated or necrotic phagocytes, amplify inflammation by directly binding to Toll-like receptor (TLR) 4. Surprisingly, we now identified an additional immune-regulatory function of S100A8 in developing monocyte-derived dendritic cells (moDCs).
Objectives: This study aims to analyze immune-regulatory mechanisms of S100A8 proteins in human DCs. Methods: Monocytes isolated from human blood donors are differentiated to immature moDCs with or without exposure to S100A8. After subsequent LPS-induced maturation specific linage marker as well as activation marker expression on the cell surface is determined by flow cytometry. In addition, cytokines and chemokines, secreted during development are analyzed by Luminex cytokine arrays. The metabolic state of moDCs is examined by using Seahorse XFp Analyzer assays. On a functional level the ability of these cells to induce autologous CD4 + , CD8 + , and γδ T-cell proliferation is investigated. Finally, to identify molecular mechanisms leading to an immuneregulatory phenotype, the mRNA expression of moDCs is analyzed by genome-wide gene expression arrays. Results: Our results clearly demonstrate that early exposure to S100A8 interferes with in-vitro differentiation of moDCs. Compared to controls S100A8-exposed moDCs show dramatically reduced surface expression of co-stimulatory molecules after LPS-induced maturation. In addition, early treatment of moDCs with S100A8 alters the secretion pattern of immune-regulatory cytokines and chemokines depending on the developmental state of moDCs. S100A8-induced effects on moDC maturation are not limited to TLR4 stimulation but rather trigger a common state of unresponsiveness. Furthermore, essential biochemical processes like mitochondrial respiration and glycolytic function are diminished in S100A8-treated moDCs. As a consequence, S100A8-exposed moDCs have a reduced potential to induce autologous CD4 + , CD8 + , and γδ T-cell proliferation. We can show that these broad differences are mainly caused by reduced surface expression of co-stimulatory molecules on S100A8-treated moDCs. Mechanistically, genome-wide gene expression analysis reveals dramatic differences in gene expression between S100A8-exposed and conventionally differentiated moDCs. We demonstrate that S100A8 pre-treatment of moDCs significantly blocks LPS-induced gene expression during moDC activation. Interestingly, in-silico analysis of transcription factor networks predicts NFκB and C/EBPδ as master regulators of S100A8-induced effects in developing moDCs. C/EBPδ on protein level, indeed, shows reduced expression in S100A8differentiated moDCs prior and after LPS-induced maturation when compared to conventionally differentiated moDCs.
Conclusion: Taken together, our results demonstrate a novel regulatory mechanism of innate immunity to prevent overwhelming immune responses. C/EBPδ seems to be a novel master regulator in this process. Keeping in mind that S100A8 and S100A9 are highly abundant in synovial fluid and tissue of JIA, dysregulated repression of detrimental adaptive immune responses might represent a novel pathomechanism of this chronic inflammatory disease. Therefore, S100A8-differentiated immune-suppressive DCs potentially represent a promising therapeutic tool to treat auto-immune diseases in the future. Disclosure of Interest None Declared. Introduction: Juvenile idiopathic arthritis (JIA) is a term that encompasses a group of arthritides that vary in pattern of joint inflammation and presentation (1). The distinct characteristics found in these subtypes are likely to be a result of genetic and environmental variations. Each subtype has been found to respond differently to the different DMARD and biologic regimes currently available, based on the unique immunological mechanism involved in each subtype. New evidence shows use of proteins found in serum, as bio and prognostic markers for some JIA subtype, such as MMP-3 in ERA (2)  SF cellular composition has a long established use in differentiating between inflammatory and infective arthritis in adults, due to a firm understanding that cell count correlates directly with final diagnosis (6). Although we are increasingly finding new patterns of protein expression in SF of children with JIA there has been no satisfactory documentation of a diagnostic cell count profile similar to that available for adults. Current SF analysis in paediatrics uses adult reference ranges, which does not take into account the differing disease process in JIA compared with adult onset arthritis. We hypothesise that cytoanalysis of synovial fluid from children with JIA can be used to diagnose which subtype of JIA the patient will develop and further provide prognostic value. This study will look at the cytoanalysis of 200 patients with JIA and compare the subtypes of each patient and their SF cell composition. We aim to demonstrate a clear pattern of cell composition, which is distinct between the subtypes, thus providing a reference for paediatric cytoanalysis of SF that can be used as a tool in establishing the final diagnosis. Introduction: Systemic onset Juvenile Idiopathic Arthritis (sJIA) is an acquired autoinflammatory disease, characterized by arthritis, spiking fever, rash and elevation of serum S100-proteins and interleukin (IL)-18, reflecting an IL-1 pathway activation. Although it is known that sJIA patients with active disease often display marked neutrophilia, the role of neutrophils in sJIA is yet to be unravelled. Objectives: To dissect the role of neutrophils in the inflammatory cascade of sJIA. Methods: Clinical lab values were collected of 50 new-onset sJIA patients at onset and during therapy, whom most were treated with hrIL1RA (anakinra) monotherapy. In a subgroup of 23 patients, serum levels of S100A12 and Mrp8/14 were analysed by ELISA and other immune compounds by Luminex multiplex immunoassay. RNA-sequencing of peripheral blood derived neutrophils from 3 sJIA patients with active disease without medication and 3 healthy donors (HDs) was performed. Further exploration of neutrophil phenotype and function was assessed in 9 sJIA patients with active disease, 9 patients in remission and 20 HDs. The percentage of immature neutrophils, defined as granulocytes with banded nucleus and decreased CD16 expression, was calculated. Surface marker expression of activation markers ex vivo and ROS production and release of secretory vesicles after in vitro stimuli were measured by flow cytometry Results: Neutrophil counts were elevated in 40/50 patients at onset, and these levels decreased within days after the start of anakinra to return to normal ranges in all patients with clinically inactive disease. Neutrophil counts correlated to inflammatory markers CRP (R 2 = 0.335, p < 0.001), ferritin, (R 2 = 0.308, p < 0.001), Mrp8/14 (R 2 = 0.470, p = 0.003) and S100A12 (R 2 = 0.276, p = 0.037) Further, neutrophil related proteins as neutrophil collagenase (p < 0.001), sICAM (p < 0.001), E-selectin (p = 0.002) and elastase (p = 0.005) were significantly increased in onset versus remission. RNA-sequencing revealed a distinct transcriptome in active sJIA neutrophils compared to HDs, with specific upregulation of immune-related processes. sJIA neutrophils showed increased expression of genes encoding for S100-proteins, inflammasome components, NFκB-pathway, IL1-and IL18-related proteins. As IPA analysis identified LPS as the most significant upstream regulator of the differentially expressed genes, we compared our dataset to two known sepsis gene sets. Indeed, a remarkably strong enrichment was observed (NES = 3.6-3.9, p < 0.001), which suggests a profound overlap between the transcriptome of neutrophils from sJIA and sepsis patients. The percentage of immature neutrophils was significantly higher in active sJIA, which is in line with findings in sepsis patients (p = 0.001). The expression of CD64, known to increase after stimulation and CD35, a marker of secretory vesicle release, were significantly increased in active sJIA compared to HDs (p = 0.004 and p = 0.010, respectively). CD62L, which is shed upon activation, was decreased in active sJIA (p = 0.014). A significant increase in the release of secretory vesicles (p = 0.010) and a trend for increased ROS production (p = 0.081) after stimulation with fMLP was observed in active sJIA. Introduction: The identity of antigenic trigger(s) of T cell-dependent autoimmunity in Juvenile Idiopathic Arthritis (JIA) has remained elusive. Nevertheless, T cells are major effectors in the perpetuation of synovitis. Unraveling inflammatory pathway(s) elicited by jointinfiltrating T cells therefore remains paramount.
Objectives: Biological evaluation of the synovial environment is a sound approach towards an improved understanding of disease activity in inflammatory arthritides. Here, we examined a T cellmediated, but TCR-independent, inflammatory pathway underlying synovitis in JIA.
Methods: Research protocols were approved by Institutional Review Boards of the University of Pittsburgh. Synovial fluid (SF) samples were obtained from children with oligoarticular or RF neg polyarticular JIA who were undergoing arthrocentesis. Blood samples from healthy children, and JIA patients were also obtained as internal reference  for cell phenotyping. Cell-free SF and plasma were used in multiplex humoral profiling, and the corresponding cell preparations were used in multicolor cytometry. Receptor cross-linking bioassays were performed using SF mononuclear cells, and molecular outcomes were examined in multiplex platforms.
Results: Humoral profiling of SF showed dominance of five cytokines including IL-17. Cell phenotyping showed predominance of T cells doubly negative (DN) for CD4 and CD8 coreceptors, and also lacked expression of the CD28 costimulatory molecule. These unusual T cells expressed high levels of CD31, an adhesion molecule known to facilitate transmigration of innate cells into sites of injury. Bioassays using CD31 + CD28 null DN T cells isolated from SF showed CD31 ligation alone was sufficient to induce intracellular expression of the same cytokines observed in SF humoral profiling. These bioassays also showed phosphorylation of four signaling intermediates, and the direct trans-activation of IL-17 gene promoter. Such cellular outcomes were blocked by a novel oxidoreductase mimic, which as originally designed as scavenger of tissue-destructive superoxide. In addition to DN T cells, phenotyping of SF cells showed abundance of fibrocyte-like cells (FLC). FLC expressed high levels of IL-17 receptor A (IL-17RA) and CD38, a ligand of CD31. Exposure of FLC to recombinant IL-17 resulted in the induction of several downstream effectors including TNFα, IL-6, and MMPs. These IL-17-mediated responses by FLC were dampened by the oxidoreductase mimic comparable to, and in many cases, better than those seen with the biologics IL6i and TNFi. Conclusion: CD31 + CD28 null DN T cells are a unique subset of cells that shape the inflammatory environment of arthritic joints in JIA. These cells may interact with non-hematopoetic CD38 + IL17RA + FLC, creating a local inflammatory circuit that is IL-17mediated, but totally independent of TCR triggering. Interruption of this DN T cell-FLC communication by an oxidoreductase mimic indicates inflammatory signaling in marked departure from the autoantigen paradigm. The data also provide rationale for translational efforts to explore a potential therapeutic application of this oxidoreductase mimic as a DMARD for JIA. Introduction: Earlier we established 10 joint juvenile arthritis disease activity score (JADAS10) cut-off levels for inactive disease (ID), low disease activity (LDA) and moderate disease activity (MDA) [1]. These were slightly different from cut-off levels proposed by Consolaro et al. [2].Several definitions of high disease activity (HDA) in juvenile idiopathic arthritis (JIA) exist [3][4][5].
Objectives: The aim was to validate previously established JADAS10 cut-off levels [1] and compare them to the cut-off values suggested by Consolaro et al. [2]. Another aim was to analyze the proportions of HDA patients in a random JIA population when using the criteria defined by Bulatovic´C´alasan et al. [4] and Consolaro et al. [5].
Methods: Data on the recent visit of the patients diagnosed with non-systemic JIA during two years (n = 337) was collected. Area under the ROC-curve (AUC) was determined. Correct classification rates (CCR) and too high and too low classification rates were counted using our previously defined cut-off values [1] and, for comparison, the cut-off values proposed by Consolaro et al. [2].
Results: Based on relatively high CCRs, the cut-offs validated in this study seemed feasible. Changing the cut-off value for LDA to 1.0 in both oligoarthritis and polyarthritis, as suggested by Consolaro et al. [2], lowered the correct classification rate of LDA and led to increase in the number of patients with LDA classified as having ID ( Introduction: Patient reported outcomes are increasingly being recognized as important instruments in the assessment of juvenile idiopathic arthritis (JIA) disease course. Analysis of these outcomes gives insight into factors that are important to patients and which should therefore have a bearing on the treatment decisions in the management of JIA.
Objectives: To identify factors that are associated with patient reported satisfaction in JIA. Methods: A cross-sectional cohort of 239 anonymized JIA patients enrolled in PharmaChild in our centre and who completed at least one juvenile arthritis multidimensional assessment report (JAMAR) was evaluated. In case a patient completed more than 1 JAMAR, the first was analysed. Primary outcome was the patient' s satisfaction with their current condition. First, every item of the JAMAR, as well as JIA subtype, demographics and disease activity parameters was analysed in univariate analysis, Introduction: Juvenile idiopathic arthritis (JIA) is the most common disease causing chronic anterior uveitis in childhood. The onset of ocular inflammation is insidious and often asyntomatic; uveitis can worsen over time and lead to sight-threatening complications, such as posterior synechiae, band keratopathy, cataract, glaucoma, ocular hypotonia, phtisis bulbi, and cystoid macular edema. Despite recent advances in the treatment of JIA-associated uveitis, ophthalmologic disease still represents a common cause of eye-related morbidity. Objectives: To investigate the frequency and risk factors of complications of uveitis in children with JIA. Methods: A retrospective study was conducted on patients with JIA who were seen at study centers from January 1987 to October 2016. Inclusion criteria were a diagnosis of JIA based on ILAR criteria and a disease category of persistent oligoarthritis, extended oligoarthritis, RF-negative polyartrhritis, psoriatic arthritis and undifferentiated arthritis. Patients without uveitis who had a disease duration of less than 6 months were excluded. In all patients who developed uveitis, we reviewed all ophthalmologic evaluations to verify whether they had or did not have ocular complications, including posterior synechiae, band keratopathy, cataract, glaucoma, ocular hypotonia, phtisis bulbi, and cystoid macular edema. Predictors of ocular complications included age at onset of arthritis and uveitis, ILAR category, antinuclear antibody (ANA) status, disease duration at onset of uveitis, follow-up duration after diagnosis of uveitis and type of complication. Results: A total of 1425 patients were included in the study; of them, 336 (23.6%) had uveitis. After a median of 2.1 years after the onset of uveitis, 104/336 (31.0%) patients with this condition developed at least one of these complications: posterior synechiae (n = 75; 22.3%), band keratopathy (n = 41; 12.2%), cataract (n = 40; 11.9%), glaucoma (n = 11; 3.3%), and cystoid macular edema (n = 12; 3.6%). The comparison of children with and without ocular complications showed that those with complications had a younger age at uveitis onset and a shorter disease duration before the onset of uveitis (p = 0.042 and p = 0.024, respectively). ILAR category and ANA status were comparable between patients with and without complications (P = 0.62 and P = 0.29, respectively). The age at onset of arthritis was also similar in the two groups (P = 0.73) (Table 14). Conclusion: Around one quarter of our patients with select categories of JIA developed uveitis. Children with a younger age at onset of uveitis and a shorter duration of articular disease before the onset of uveitis had a higher risk of developing ocular complications. This finding highlights the need for a particularly strict ophthalmologic monitoring in younger children and in the earlier disease stages.  Introduction: The child/parent overall well-being and pain are essential patient-reported outcomes (PRO) in juvenile idiopathic arthritis (JIA).

Disclosure of Interest None Declared
Objectives: To study determinants and any discordance between child/parent overall well-being and pain and physician global assessment (GA) of disease activity in children with JIA.
Methods: The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) study is aimed to obtain information on the frequency of JIA subtypes in different geographic areas, the therapeutic approaches, and the disease and health status of children with JIA currently followed worldwide. More than 9137 children with JIA from 118 pediatric rheumatology centres in 49 countries were collected so far. We have investigated the determinants and any discordances of the GA visual analogue scale (VAS) (range 0-10) between child/parent and physician. The PRO was reported by the parent(s) in children <10 years of age, otherwise by the child. Discordance was defined as high for a VAS difference >3, moderate for a VAS difference >1 and ≤3, and in agreement for a VAS difference <1. Correlations was assessed with Spearman correlation coefficient r. The countries were divided in eight geographical areas.
Results: Child/parent and physician GA score was available in 8615/9137 (94.3%) of the EPOCA participants. Primarily pain, but also the health-related quality of life (HRQL), were determinants of the child/parent score of general well-being, while the most important determinants of the physician GA were the number of active joints, pain, ESR and morning stiffness. The overall correlation between the child/parent and the physician GA was moderate r = 0.54, but ranged from 0.28 to 0.94 in different countries. The correlation between the child/parent GA and the pain score was high, r = 0.75. The overall agreement between child/parent and physician GA was ≤1 in 5,218 (60.6%). When the child/parent GA was higher than the physician, the scores on pain and adverse effect on HRQL were significantly higher, also the number of children with morning stiffness was higher (Table 15). When the physician GA was higher than the child/ parent, the active joint count was higher. The discordance was highest for JADAS scores >6. Geographical differences were found, with the highest proportion of discordantly higher child/ parent scores compared to the physician in Northern and Central European regions. Values are the median (1 st , 3 rd quartile), unless indicated n (%). JADAS10, Juvenile arthritis disease activity score based on 10 joints; CGA, child/parent global assessment of overall well-being (range 0-10); PGA, physician global assessment of disease severity (range 0-10).
Conclusion: The child/parent overall well-being is mainly determined by pain, while the number of joints was a main determinant of the physician GA VAS. Worldwide differences in PRO and physician GA VAS determinants and discordances were found.

Disclosure of Interest
None Declared. Objectives: 1) To study the long-term changes in self-reported orofacial symptoms, 2) To define the impact of orofacial symptoms on OHRQOL.
Methods: Consecutive patients were invited to participate in this study. Inclusion criteria were: 1) JIA diagnosis, 2) ≤20 years of age. At baseline (T0), the patients completed the euroTMjoint patient questionnaire that incorporates six domains related to the orofacial area. Among others, pain frequency was assessed using a 5 point Likert scale (0="Never", 1="Less than once a week", 2="Several times a week", 3="Several times a day", 4="All the time"). A 100 mm VAS was used to assess orofacial functional disability (0="Not affected", 100="Severely affected").  Active Joints 0 (0, 1) 1 (1, 4) 1 (0, 2) 2 (1, 6) 0 (0, 1) patients with orofacial functional disability at T0 also reported disability at T1. Changes were as follows: 27% (7/26) reported an improvement of orofacial functional disability, 42% (11/26) reported the same level of orofacial functional disability, and 31% (8/26) reported a worsening of orofacial functional disability at T1. Global ratings of self-reported perception of oral health, and the extent to which the orofacial conditions affected the overall well-being and general quality of life were significantly reduced in patients in pain (p < 0.0001) compared to asymptomatic patients. 16% (10/61) of the patients with orofacial pain and/or functional disability reported that the condition had "Some" (Likert scale score 2) negative impact on the overall quality of life. 7% (4/61) reported that the orofacial condition reduced general quality of life "A lot" (1/61, score 3) and "Very much" (3/61, score 4).
Conclusion: This study shows: 1) Self-reported orofacial pain and functional disability were common findings in a cohort of JIA patients followed over two years. 2) These symptoms seem to persist over time in most patients. 3) Orofacial pain and functional disability significantly reduce OHRQOL. 4) General quality of life is substantially affected in 23% of the patients with orofacial symptoms.

Disclosure of Interest
None Declared.

P237
Can we predict clinically inactive disease in patients with juvenile idiopathic arthritis?
Stephanie J. W. Introduction: It is currently impossible to predict the prognosis of juvenile idiopathic arthritis (JIA) patients at diagnosis. Correct prediction of disease prognosis would enable physicians to stratify patients and make optimal use of existing effective medication.
Objectives: To predict inactive disease in a cohort of JIA patients, using clinical data, gut microbiota composition and a large panel of inflammation related compounds in plasma.
Methods: We analysed a cohort of 152 treatment-naïve JIA patients enrolled within 6 months after the onset of disease. No systemic JIA patients were enrolled. We collected clinical parameters regarding disease activity, a faecal sample to determine the gut microbiota composition and blood to analyse a large panel of cytokines and chemokines using Luminex technology. Patients were followed up every 6 months and additionally in case of flare, for 2 years. Disease activity was determined using the Wallace criteria. The prediction model was developed using clinical data only, clinical and microbiota data, or clinical and Luminex data. Variables were selected in univariate analysis. All models contained treatment and time elapsed since baseline as potential confounders. The models were developed in two thirds of patients and validated in the remaining one third of patients. The split in training and test data was performed 10 times and model performance was averaged over the different splits. Various models were tried. A repeated measurements analysis was performed using generalized estimating equations (GEE). Cox proportional hazards models of time to first inactive disease and time to inactive disease using recurrent events were fitted as well. We also performed logistic regression of inactive disease at 6 months and 12 months. Additionally, to reduce the heterogeneity underlying JIA, all models were refitted in the subgroups of oligoarticular patients and polyarticular rheumatoid factor (RF) negative patients. Results: The majority of patients was female (121, 80%) and presented with at most 4 active joints at baseline (109, 72%). The median juvenile arthritis disease activity score (JADAS)-71 was 13 (1 st quartile, 3 rd quartile: 8, 19). The clinical GEE model showed moderate performance in training data (area under the curve [AUC] 0.70), but poor performance in test data (AUC 0.65). Similar or poorer performance was observed for the microbiota and Luminex GEE models, as well as for the Cox regression. The logistic regression of the 6 months and 12 months outcome did slightly better with an AUC of 0.74 in training data and 0.66 in test data for both the clinical and the microbiota model. The highest AUCs were obtained when analysing oligoarticular patients and polyarticular RF negative patients separately, using GEE. The AUC of the oligoarticular microbiota model was 0.79 in training data and 0.69 in test data. Higher JADAS-71 score and a higher relative abundance of the operational taxonomic unit Mogibacteriaceae were associated with lower odds of inactive disease. The best model in polyarticular patients was the Luminex model with an AUC of 0.79 in training data and 0.69 in test data. Longer duration of morning stiffness and a higher plasma concentration of CXCL-9 were associated with decreased odds of inactive disease, whereas a higher haemoglobin level was associated with increased odds of inactive disease at follow up.
Conclusion: Prediction of the prognosis in JIA is challenging. In this well-defined inception cohort of JIA patients, we were unable to predict disease inactivity with satisfactory accuracy, using clinical data, gut microbiota composition and a panel of cytokines and chemokines. This is potentially due to the heterogeneity underlying JIA. Indeed, predictive accuracy of the models increased when oligoarticular and polyarticular RF negative patients were considered separately.

Disclosure of Interest
None Declared Introduction: Juvenile Idiopathic Arthritis (JIA) is hallmarked by a disturbed immunological balance between regulatory T cells (Treg) and effector T cells (Teff). Restoring this balance by enhancing the suppressive function or number of Treg might therefore be a promising novel therapeutic strategy. The transcription factor FOXP3, is essential for Treg function and development. We have previously demonstrated that the acetylation of FOXP3 prevents its degradation, thereby resulting in increased FOXP3 protein levels. The lysine deacetylase SIRT1 can deacetylate FOXP3 and therefore promote its degradation. Therefore, inhibitors of SIRT1 could lead to increased FOXP3 expression. Interestingly, a rather specific SIRT1 inhibitor, and well known food additive, is Vitamin B3, also known as nicotinamide (NAM). Therefore, NAM has the potential to stabilize FOXP3 expression and positively influence regulatory T cell function. Translating these laboratory findings into clinical practice could result in a novel therapeutic strategy. We envision that NAM, when combined with established immunosuppressive treatment, could help regain immunological balance in JIA. NAM is well known as a dietary supplement and has been extensively studied in a variety of diseases in both children and adults. However, the safety, tolerability and optimal dosing of NAM in children with JIA is still unknown. Therefore, before such a therapeutic strategy can be tested in a placebo-controlled trial, we need to gain detailed information on dosing, tolerability, and surrogate parameters of effectiveness in JIA.

Objectives:
We aim to gain more information regarding the mechanistic effect of NAM on the function, FOXP3 expression, and cytokine expression of Treg and Teff in both blood and synovial fluid of JIA patients and healthy controls. In addition, in preparation of a phase III clinical trial, we want to acquire essential data on pharmacokinetics/dynamics, safety, feasibility and tolerability of NAM in the proposed dose in children with JIA.
Methods: Human peripheral blood T cells of healthy controls (N = 3) and synovial fluid of oligo-JIA patients (N = 5)were isolated and cultured in the presence of NAM in different concentrations for 4-7 days. The percentage of FOXP3+ cells and proliferation index of CD4+ and CD8+ T cells was determined using Flow cytometry. To assess Treg function, isolated human T cells were cultured with NAM after which Treg were sorted and their function was analyzed using a suppression assay.
Results: In vitro NAM treatment of human T cells significantly increased both the percentage of FOXP3+ cells and the FOXP3 mean fluorescent intensity. Furthermore, the suppressive function of Treg treated with NAM was increased. Importantly, this was confirmed in cells isolated from the synovial fluid of JIA patients. In addition to the effect on regulatory T cells, NAM reduced the proliferation of CD4+ and CD8+ T cells.
Conclusion: Collectively, these data demonstrate that NAM treatment in vitro results in more Treg with an increased suppressive capacity.
In addition, NAM directly suppressed the proliferation of Teff cells. Therefore, NAM treatment could rebalance the active adaptive immune system in patients with JIA by suppressing immune activation and increasing tolerance. Hence, NAM treatment as an adjuvant therapy has the potential to benefit patients with JIA and potentially other autoimmune diseases. To directly test this hypothesis we are now conducting a phase I/II trial as a run-up for a phase III trial in which we will test whether NAM treatment is useful in a strategy of maintaining disease remission after stopping DMARD or biologicals.

Disclosure of Interest
None Declared. Pts with pJIA are more likely to have neutropenia in the first months of therapy, pts with sJIA in achieving remission. 5 pts with sJIA had neutropenia upon MAS that was not related to TCZ. Rates of infections during period of normal neutrophil counts were comparable to those observed ±15 days around grade 1-4 neutropenia, with no trend toward increased risk with higher grade neutropenia. MTX use wasn't significantly associated with lowest observed neutrophil count (p > 0.5).
Older age was associated with lowest level of neutrophils (p < 0.05). Combined use of GC and TCZ exposure were associated with normal level of neutrophils (p > 0.5). Previous BA didn't increase the risk of neutropenia (p > 0.5). All cases of neutropenia were recorded in pts with response to therapy more than 50% ACRpedi criteria. Conclusion: Our data show, that there are different kinds of neutropenia phenomenon: 1. "benign", transient neutropenia -a predictor of high efficiency of TCZ, developes primarily in the first few days after infusion; 2. neutropenia as a phenomenon of "redundancy" of therapy (more resistent) and requires correction of the dose of TCZ and concomitant therapy; 3. neutropenia, as a risk of manifestation of MAS, mainly due to an inadequate effect or its "exhaustion", is associated with other markers of MAS. We didn't observe association between neutropenia and increased risk of infections. The neutropenia should be constantly monitored with subsequent individual correction of therapy.

Disclosure of Interest
None Declared.  Results: Growth retardation at the baseline (SDS < -2) was detected in 29 patients (23%). By 24 months of BT, the number of children with short stature decreased to 19 (15%). Dynamics of growth rate and growth rate SDS are presented in the Table 18. Growth rate prior BT in all groups are comparable (p > 0.05). The lowest growth rate was observed in children with sJIA. In all patient receiving BT, the growth rate increased and remained higher than growth rate at the baseline. Growth rate in children receiving tocilizumab (group II) by 12 months of treatment and in children receiving adalimumab (group III) by 6 months of therapy is significantly higher comparing to other groups (p <0.05). In group 1, the mean growth SDS at the baseline was -1.96 ± 0.52. By 24 months of BT growth SDS increased to -1.61 ± 0.39 which was comparable to baseline (p = 0.058). In group 2, the mean growth SDS at the baseline was -0.51 ± 0.37. By 24 months of BT growth SDS significantly increased to -0.16 ± 0.30 (p = 0.043). In group 3, the mean growth SDS at the baseline was -0.35 ± 0.34. By 24 months of BT growth SDS amounted -0.22 ± 0.34 which was comparable to baseline (p = 0.108). In group 4, the mean growth SDS at the baseline was -0.63 ± 0.29. By 24 months of BT growth SDS significantly increased to -0.31 ± 0.31 (p = 0.020). In group 5, the mean growth SDS at the baseline was -0.06 ± 0.22. By 24 months of BT growth SDS amounted 0.08 ± 0.21, which was comparable to baseline (p = 0.088). Conclusion: Treatment with biological therapy increases growth rate not only in the first 6 month, but in the subsequent period of treatment. The highest growth rate is observed in children receiving tocilizumab and adalimumab. The higher growth rate results in increased growth SDS by 24 months of treatment. BT in children with severe JIA and impaired growth leads to a decrease of incidence and severity of short stature.

Disclosure of Interest
None Declared. Introduction: Current delivery routes and doses of corticosteroid (CS) treatment in juvenile idiopathic arthritis (JIA) are principally based on clinician and patient preference, rather than scientific evidence. A clinical trial is needed in the future to ascertain the most effective routes and doses of CS in JIA. Objectives: To explore families' experiences of four CS delivery routes in JIA and to assess their views regarding feasibility of a future trial evaluating the most effective routes and doses of CS. Methods: Semi-structured interviews with a purposive sample of young people and their parents (N = 28; 9 young people and 19 parents), recruited from four UK Paediatric Rheumatology providers. Data were analysed using thematic analysis informed by the Framework Approach.
Results: Families had first-hand experience of oral prednisolone (n = 10), intravenous (IV) methylprednisolone (n = 7), intra-articular (IA) injections (n = 14) and intra-muscular (IM) injections (n = 3). The majority of families (n = 13/15) had experience of at least two delivery routes. Parents and young people tended to view oral prednisolone as less suitable for more advanced JIA and IA was viewed as less appropriate for patients with poly or systemic arthritis. Young people were more likely than their parents to report willingness to participate in a trial of CS. Overall, participants tended to be more willing to participate at time of diagnosis than at time of JIA flare; previous positive and negative experiences of delivery routes influenced perceptions of future treatment efficacy. Key barriers to participation identified by both parents and young people included: the perception that some delivery routes would be more or less appropriate due to factors such as age and JIA sub-type; being randomly allocated to receive a treatment, rather than the treatment being clinician-informed; concerns regarding the quality of care they would receive as a trial participant. Conclusion: Recruitment of children and young people with flaring JIA to a future trial will likely be more challenging than recruitment at diagnosis. The findings can be used to inform the design of a future trial of CS. In order to optimise the recruitment process for a future trial, clinicians will need to provide families with comprehensive information on treatment arms, the rationale for randomisation (including emphasising equipoise), and reassurance of quality of care whether they participate or not. Doing so would reduce families' anxieties, improve informed consent and potentially optimise recruitment. Researching families' perspectives about future paediatric rheumatology trials can help to assess the feasibility of these trials and optimise their design.

Disclosure of Interest
None Declared. The first biologic was defined as the first biologic treatment claim for the patient. Switchers were defined as patients with a claim for a different bDMARD than the index bDMARD within a grace period of 90 days after the end of days-supply of the previous bDMARD claim. Patients who discontinued had no claim for another bDMARD within a grace period of 90 days after the end of days-supply of the previous bDMARD claim.
Results: The study included 91 patients treated with abatacept from the PharMetrics and 137 from the MarketScan database. In both databases, patients treated with abatacept were older, more likely to be female and less likely to have baseline uveitis than those treated with other bDMARDs (Table 19). Differences between the two treatment cohorts for most characteristics were consistent between the two databases. However, patients treated with abatacept were more likely to have baseline asthma and less likely to be on non-bDMARDs than those with other bDMARDs in the MarketScan database. In both databases, the rate of those who switched to a non-bDMARD and the discontinuation rate were all slightly lower and the number of patients who stayed on index drug was higher among abatacept-treated patients compared with patients on other bDMARDs (Table 19).  Introduction: Juvenile Idiopathic Arthritis (JIA) is a common chronic childhood illness that can negatively impact health-related quality of life (HRQL). Adolescents are expected to assume greater responsibility in disease management as they mature. However, the vast majority of adolescents with JIA do not receive comprehensive self-management education. Internet-based interventions provide an innovative approach to improve the accessibility and acceptability of self-management programs for adolescents with chronic illnesses. Objectives: A randomized control trial was conducted to determine the effectiveness of an Internet-based self-management intervention. We hypothesized that youth with JIA in the Internet selfmanagement intervention (Teens Taking Charge or TTC) group will demonstrate: (a) reduced pain and improved HRQL (primary outcomes); (b) reduced emotional (anxiety and depression) symptoms; and (c) Increased treatment adherence, pain coping, JIA-specific knowledge, and self-efficacy compared to adolescents in the control group (static web-based education). Methods: Participants were between 12-18 years old with JIA across 11 pediatric centers in Canada. Teens participated with a parent/ caregiver. Teens in the intervention reviewed 12 modules focused on disease education, self-management strategies and social support. Teens in the control condition reviewed standard disease education modules without self-management skills or social support. As part of the 3-month program, teens had monthly telephone check-ins with health coaches, but only intervention participants reviewed modules with their coach. Parents in both groups reviewed modules focused on promoting independence and disease self-management in their teen. Teens and parents completed outcome measures at 4 time points: baseline, at program completion (3-months), 6-months, and 12-months after the program. Results: In total, 333 teens (n = 109 male, n = 224 female; mean age = 14.5, SD = 1.7) and 306 parents (n = 52 male, n = 254 female) were enrolled. Of the 164 participants in the intervention group, 62.8% (n = 103) completed the study over an average 189.8 days (SD = 113.5). Of the 169 control participants, 87.0% (n = 147) completed the study over an average 123.6 days (SD = 70.6). Results indicated that average weekly pain interference in enjoying daily life (p = 0.004) and PedsQL treatment problems (p = 0.010) improved significantly in the intervention group as compared to the control group. Improvements in selfefficacy, disease knowledge, health related quality of life and pain coping were shown at 3-month follow-up, when compared to baseline for both intervention and control groups. There were no changes in either group for anxiety, depression or adherence. Conclusion: Teens with JIA overall are satisfied with using an online program for education and learning self-management skills, with improvement in pain interference and HRQOL deriving in part from increased knowledge and self-efficacy. Education and nonspecific factors (e.g., feeling part of a community) may be key determinants of improving important patient reported outcomes through the online self-management program. Disclosure of Interest None Declared. Introduction: We have previously reported 54-week results of ACUTE-JIA trial, comparing 3 treatment arms without initial oral steroids; single methotrexate (MTX), synthetic combination DMARDs of methotrexate, sulfasalazine and hydroxychloroquine (COMBO), and infliximab plus methotrexate (TNF) in very early, DMARD-naïve polyarticular JIA (juvenile idiopathic arthritis). Prior to study onset, the mean duration of arthritis was 1.9 months (SD 0.1) [1] The extension trial included follow-up visits at 3 and 5 years. We present now 3-year results. Objectives: To detect potential clinical differences at 3 years between the initial treatment arms. Methods: Open label extension study. 60 patients continued on their originally randomized treatment until they failed the strategy or achieved inactive disease (ID) on medication for at least 6 months. When applicable, data was analyzed both on-group (within original treatment arm) and on-strategy (within treatment strategy, last observation carried forward if switch of strategy was chosen), using χ 2 , nonparametric testing and regression analyses. ACRp 30-100 (onstrategy) and achieving (ID) were assessed. Results: All 60 patients in the original trial completed the 3-year follow-up. 50 patients (83%) switched treatment strategies. Changes were due to ID in 27 (45%), inefficacy in 20 (33%) and adverse events Data are n (%) unless indicated otherwise *p < 0.05 for the difference between the two treatment groups in each of the two databases in 3 (5%). TNF was not discontinued in any patients due to inefficacy, although in 4 infliximab was switched to other anti-TNFs due to sideeffects or patient preference. At 3 years, 8 patients (40%) on TNF, 6 (30%) on COMBO and 6 (30%) on MTX arm were still receiving the original drug strategy. 21 patients (35%) were receiving biological therapy, including 13 failures from COMBO and MTX arms. ACRp100 (on-strategy) was achieved in 80% of those receiving TNF, 40% on COMBO and 35% on MTX (p = 0.008). ACRp90 was achieved in 90% on TNF, 50% on COMBO and 50% on MTX (p = 0.025); ACRp70 in 95%, 55% and 50% (p = 0.028); and ACRp50 and 30in 100%, 55% and 50% (p = ns), respectively. At 3 years, 16 patients (80%) receiving TNF, 11 (55%) COMBO and 6 (30%) MTX reached ID (on-strategy, p = 0.008). When the number of patients reaching ID in each original group was assessed between groups, no differences were detected (p = 1.000). However, mean time spent in ID (on-group) was 23.5 months on TNF, 16.3 on COMBO, and 14.7 on MTX (p = 0.029). Strategy and ID correlated strongly based on Spearman's rho (p = 0.002). Furthermore, when adjusted with duration of biologic treatment in each group, time spent in ID was higher in those receiving TNF than COMBO (p = 0.001) or MTX (p < 0.001).
Conclusion: Clinical inactivity in JIA seemed to correlate with both on-going and early initial drug treatment. Although very early firstline infliximab was highly effective to control the activity of JIA and protective against long-term damage, it was not able to completely turn off rheumatic activity. In most patients, JIA flared after discontinuation of anti-TNF agents.  Introduction: Methotrexate (MTX) is widely adopted as a first line treatment in moderate to severe forms of juvenile idiopathic arthritis (JIA), when NSAIDs and intra-articular corticosteroid injections are not sufficient to control joint disease. MTX is generally prescribed at 10-15 mg/m 2 weekly and its administration can be either oral or parenteral (subcutaneous (SC) or intramuscular). Contrasting evidence is available in the literature about the difference in efficacy and safety of MTX, according to the route of administration. Objectives: Aim of the study is to compare the efficacy of oral versus SC MTX in inducing sustained disease remission in children with oligoarticular JIA enrolled in two prospective cohorts. Methods: Children with oligoarthritis included in 3 prospective studies were considered for inclusion: a) the TRIMECA trial (1), b) the MD-Paedigree study (2), c) the PharmaChild registry. Patient evaluated at the IRCCS Istituto Giannina Gaslini and at the Ospedale Pediatrico Bambino Gesù were included if they had received methotrexate treatment as a first line systemic medication within 6 months after disease onset and if a follow up of at least 12 month after treatment initiation was available. Patients were then grouped according to the route of MTX administration. Baseline demographic and disease features were compared between the 2 groups. Efficacy was assessed by comparing the rate of inactive disease (ID) and clinical remission on medication (CRM) at 12 months, the rate of patients changing the route of MTX administration or requiring a biologic medication due to treatment failure. Safety was assessed by comparing the frequency of treatment interruption due to side effects of MTX. Results: 79 patients were included in the study: 43 received oral MTX, 36 received SC MTX. At treatment initiation, disease duration was not different in the two groups; children receiving SC MTX were older at baseline (4.6 yrs vs. 2.5 yrs) and at disease onset (4.2 yrs vs. 2.3 yrs). Disease activity was comparable in the 2 groups, with a median of 2 active joints in both groups. Median MTX dose was 14.4 mg/m 2 for oral MTX group and 15.2 mg/m 2 for SC MTX (Mann-Whitney U test, p < 0.01). At 12 months, children receiving SC MTX achieved more frequently ID (84.9% vs 43.8%, Chi squared test p < 0.001) and CRM (54.5% vs 28.3%, p = 0.002). Patients in SC MTX group were more often prescribed a biologic medication (22.9% vs 6.5%, p = 0.024), but none of them were switched to the oral administration while 37% of children in oral MTX group were turned to SC MTX. One patient in both groups had MTX treatment suspended due to side effects. Introduction: Patient self-report of pain using multi-dimensional assessment is best practice, although uncertainty about which pain aspects are prioritised in guiding pain management decisions may prevent the uptake of this approach in paediatric rheumatology. Objectives: To determine which features of multidimensional pain information from individuals with Juvenile Idiopathic Arthritis (JIA) were viewed as most salient by pain experts and paediatric rheumatology healthcare professionals. Methods: Participants were recruited via online advertisements posted by their professional organisations to take part in two separate group workshops. Workshops were hosted at an international conference on pain and a national conference on paediatric rheumatology. Participants were asked to rank order nine vignette scenarios from 'highest pain' to 'lowest pain' using patient data collected with an electronic multidimensional pain assessment tool (My Pain Tracker). The pain components collected by the tool were developed by children with JIA and included pain intensity, severity, location and spread (demonstrated through colour/shading), pain quality descriptors (including symbols such as fire and sharpness) and emotions. Participants were asked to explain their individual reasoning for their rankings of pain experiences aloud within workshops. Recordings were transcribed and analysed using content analysis. Results: Nineteen participants took part: nine paediatric pain experts and ten paediatric rheumatology healthcare professionals. The high prioritisation of pain intensity and severity was uncontentious between and within groups. Differences between groups emerged in the prioritisation of specific pain location information. For pain experts, the number of sites affected was important. However, for healthcare professionals, localised pain around specific joints was seen as high priority. This suggests that this group of participants couple pain information with disease activity indicators to guide pain management decisions in children with JIA. Despite the importance of location information for both groups, spread of pain (e.g. radiating pain demonstrated through the use of colour) was not important for either group. Another area of disparity was in the prioritisation of pain emotion. Both groups talked about needing further confirmatory evidence for them to interpret emotion scores with confidence as this component could often be inconsistent with other pain information. However, for pain experts, data about function and interference was important and for healthcare professionals, corresponding information about disease activity was valuable. Lastly, qualitative descriptors of pain were a low priority for both groups unless children used the 'fire' symbol. This again suggests that evidence of inflammatory pain processes were viewed as significant.
Conclusion: Not all of the pain components collected by My Pain Tracker are used to inform pain management decisions, although children identify these as important in helping them to effectively communicate about their pain experiences. Results demonstrate which pain facets are most salient in the visualisation of electronic multi-dimensional pain data. Our findings will be incorporated into interpretive guidelines for such assessments in children with musculoskeletal pain. Disclosure of Interest None Declared. Introduction: Despite the introduction of new and effective biological disease-modifying anti-rheumatic medication, children with juvenile idiopathic arthritis still report pain and discomfort during every day life. Pain has been found to be a major contributor to morbidity in this group of children. Objectives: We wanted to access the effect of pain and disease activity on perceived health and strain on the family. Methods: Inclusion criteria were age 6-16 years and JIA with active disease or in remission on medication. During routine visits at pediatric rheumatology clinic, the parents and child were asked to fill out validated questionnaires -Juvenile Arthritis Multidimensional Assessment Report (JAMAR), Well-being index WHO-5 (score 5-25) and to answer questions about social status and activities of daily living. For assessment of disease activity "Juvenile arthritis disease activity score" (JADAS-27) was completed. Results: Data is reported as median (minimum; maximum): From December 2016 to April 2017, 92 consecutive JIA patients met the inclusion criteria. 13 were excluded due to other significant disease or inability to communicate in Danish, 7 declined to participate. A total of 51 patients completed the questionnaires. Patient characteristics are seen in Table 20. Disease activity according to JADAS27 was 2. (0;16.6). Days spent in relation to care of arthritis or arthritis related symptoms in a year was 12 (0;104). The parents reported need of special assistance in relation to arthritis symptoms in 30% of school children with JIA and 15% of children with JIA in day-care. In children in need of special attention or extra follow-up visits, there was pronounced diversity with regards to how the families perceived this as stressful or not. Thus 19 out of 51 parents reported a score of 4 or above (on a 0-10 VAS scale) when asked whether finding help for follow up or home-care was difficult or not median 3 (0; 6.9). Pain during the previous week (according to JAMAR) was VAS 1.5 (0; 7.9). In psychological well-being according to WHO-5 they generally performed well 76 (36;100), no patients were at high risk of depression, but a small group of patients (9%) were found to have low mood and at moderate risk of depression.
There was no correlation between pain, disease activity and low WHO-5 score or the number of days spend taking care of the arthritis. Conclusion: Self-reported maximum pain and disease activity did not explain the variance in family time spend on JIA related disease and disease management. Despite a high score in well-being compared to general childhood population, a small group of JIA patients are still at moderate risk of depression. Disclosure of Interest None Declared.

biologics in England and
Wales is dependent on adherence to the interim policy statement, there is no obligation for UK clinicians to follow NICE guidance. Understanding current prescribing patterns in children and young people (CYP) with JIA is a necessary precursor to development of targeted early treatment pathways (treat-to-target regimes). Objectives: 1. To describe prescribing patterns in CYP presenting to UK paediatric rheumatology (PRh) teams with a new diagnosis of JIA, with reference to the national treatment guidelines. 2. To collate opinion regarding targeted early treatment pathways in CYP with new-onset polyarticular-pattern JIA.

Methods:
In March 2016, 19 UK-based PRh consultants (1 representative from each NHSE PRh provider) were invited to complete an online survey.
Respondents were asked to provide data regarding numbers of patients diagnosed between 2015 and 2016 with oligoarticular and polyarticular-pattern JIA, current treatment approaches (with reference to national treatment guidelines) and opinion regarding targeted treatment pathways and earlier use of biologics. Results: 14/19 (74%) responders from England (n = 12), Scotland (n = 1) and Northern Ireland (n = 1) returned the questionnaire. The median number of patients per centre with new-onset oligoarticular and polyarticular-pattern JIA was 19 (IQR 14-40) and 10 (IQR 6-20) respectively. 85% respondents reported 'always' or 'mostly' treating patients according to the NHSE interim policy. oligoarthritis, 9 (43%) polyarthritis, one rheumatoid factor positive disease and one psoriarthritis. None had uveitis. The SandRA-system automatically sends text messages (questions) to the patient's/parent's cell phone every two weeks for six months. The questions concern medication, possible side-effects and laboratory results. The follow-up parameters we collected at routine visits (0, 3 and 6 months).
The outcome was evalueted with clinical criteria of remission, JADAS-10 and CHAQ. Results: Of the 21 patients 15 were female (76%). Mean age was 8,6 years (SD 4,2 years). One patient was ANAab positive and one rheumatoid factor and ACPA positive. HLAB27 positivity was found in 7 patient (37%). 95% of parents found SandRA-system easy to use. 3 parents (14%) wished more direct contacts with the clinic. 12 (57%) considered SandRAas a useful additional tool and 76% were interested to use it in the future. At 6 months after drug treatment initiation, 11 (52%) patients were in clinical remission. JADAS-10 was 8,2 and 3,1 in the baseline and in the 6 months visit, respectively (P < 0,001) (Table 21).
Conclusion: SandRA was considered as a promising tool in enhancing the adherence to treatment and thus, achieving remission in JIA among families and health care workers. Next, we plan to introduce a 6-12 months randomized controlled study. Presumably some modifications will be made in the system, for example timing of the questions needs adjustment. Other digital methods than text messages might also improve participation of teenagers.

Disclosure of Interest
None Declared.

P257
Adipokines in juvenile idiopathic arthrtis, are they usefull as inflammatory activity markers? Esmeralda  Anthropometric, clinical and treatment data were recorded and Juvenile Arthritis Disease Score 27 (JADAS27) was calculated for each patient. Acute phase reactants, including high sensitive RCP (hsCRP), TNF -α and IL-6, and adipokines as leptine, adiponectine and resistine were determined. Activity, inactivity and remission were defined using Wallace criteria (2011).
No differences in mean adipokines levels were found between different JIA subtypes, depending on received treatments, neither between active and inactive/in remission patients (Table 22). In bivariant analysis possitive relation between resistine and hsCRP (Rho 0,40; p < 0,001), between resistine and IL-6 (Rho 0,40; p < 0,001) and between adiponective and TNF -α (Rho 0,29; p 0,009) were found. Afterwards, a multivariate analysis was performed using JADAS27 as dependent variable. We found a direct relation to IL-6 (ß 0. Introduction: In recent studies the immunological situation in the intestinal canal in children with JIA have been discussed in aspects of dysbiosis of microflora, increased permeability and an aberrant regulation of lymphocytes in the mucosa. JIA is also associated with an increased risk of other autoimmune diseases such as type 1 diabetes mellitus and thyroid disorders. It has been suggested that children with JIA also have an increased risk of developing celiac disease but no population based studies have been made and exclusion of IgA deficiency has not always been part of the protocol. Objectives: To study the prevalence of celiac disease in a population based cohort of children with JIA, by screening for IgA anti-TG2 antibodies, total IgA and IgG anti-TG2 antibodies and to study levels of those antibodies in the different categories of the disease. Methods: Every child diagnosed with JIA in three Swedish counties (Uppsala, Gävleborg and Dalarna), with disease onset between January 1, 2007 and December 31 2014, were included prospectively. Classification according to the ILAR criteria and analysis of IgA, IgG anti-TG2 antibodies and total IgA from serum samples were performed. Children with IgA anti-TG2 antibodies above 3 U/mL and children with IgA deficiency in combination with IgG anti-TG2 antibodies above 3 U/mL were referred to the pediatric gastroenterology unit for further investigation with gastroscopy and small intestine biopsy.
Results: 216 children with JIA were included and analysis of IgA and IgG anti-TG2 antibodies was performed on 214 of these children. Three children had a diagnosis of celiac disease prior to the diagnosis of JIA but by screening the cohort we found three additional children with raised levels of IgA anti-TG2 antibodies. Small intestinal biopsy confirmed the diagnosis of celiac disease for all of them. One of these children had gastrointestinal symptoms prior to our screening, but the other two children were asymptomatic. Total serum level of IgA was analysed in 213 children and two children had an IgA deficiency (0.94%). One of the children with IgA deficiency had a raised IgG anti-TG2 level and was referred to the pediatric gastroenterology unit, but small intestinal biopsy showed no signs of celiac disease.
In this population based study we found a point prevalence of 2.8% (n = 6) for celiac disease in children with JIA, and the prevalence increased by screening. Levels of IgA correlated with age at sampling.

Conclusion:
The present study does not support a higher occurrence of celiac disease in JIA compared to healthy children but it reminds us that screening for celiac disease can detect asymptomatic cases. We believe that all children with JIA should be screened for celiac disease.

Disclosure of Interest
None Declared. Introduction: Early onset ANA-positive JIA has been suggested as a potential subgroup of JIA. It must be proved whether this subgroup is a separate entity regarding basic characteristics, disease mechanisms, uveitis, prognosis, risk for damage and need for treatment. Objectives: To describe early onset ANA-positive JIA as a subgroup of JIA with data from the Swedish Paediatric Rheumatology Registry and compare the study group with the remaing group of JIA. Methods: The Swedish Paediatric Rheumatology Registry started in 2009. The national coverage is above 60% for all JIA and above 90% for JIA treated with antirheumatic drugs. We have identified a subgroup of JIA with positive ANA and onset ≤ 6 years of age with exclusion of ERA, RF pos arthritis and systemic JIA and used data in the registry to describe the selected group regarding sex, treatment, uveitis and JADAS. Results: 334 patients with early onset ANA positive JIA where identified out of 2667 patients with JIA. In 1464 patients there were missing data on ANA in the registry. 78% in the study group were females (64% in remaining group). The mean age at onset was 2.7 years (8.2 years in remaining group). Uveitis at any time in 17% (2% in remaining group) but data missing in 58% (87% remaining group). Treatment with methotrexate at any time in 74% (remaining group 62%) and biologics 54% (remaining group 43%). No differences in JADAS from onset during first 15 months could be found. Conclusion: Early onset ANA-positive JIA patients extracted from the Swedish Paediatric Rheumatology Registry have most but not all cases of uveitis. There are no big differences in treatmen with methotrexate Methods: Patients with JIA and clinical involvement of TMJ consecutively seen at the study center in September-December 2016, with at least 8 years of age, were asked to identify the daily activities most affected by TMJ arthritis. From the collected items, we asked them to select the most relevant and representative of "TMJ well-being/worsening" in their daily life. We included in the JATA the items that were most frequently selected and a patient's global assessment (GA) of TMJ (VAS 0-10; 0 = worst; 10 = best). Finally, we asked to a subgroup of patients that underwent to intraarticular corticosteroid injection (IACI) of one or both TMJ to complete the report, based on their abilities before the therapeutic intervention (VAS 0-10; 0 = totally unable, 10 = fully able). Clinical TMJ assessment, dental and TMJ magnetic resonance (MR) reports just before TMJ IACI were blindly reviewed and associated to a score, based on the presence/absence of pathological features: clinical severity (CS) of TMJ, as presence (1) or absence (0) of swelling + pain on motion/tenderness + limited-range-ofmotion (range 0-3); dental-score, as presence (1) or absence (0) of cavities + insufficient hygiene + pain on TMJ palpation + pain on muscle palpation + lateral deviation/micrognatia (range 0-6); MRscore, as presence (1) or absence (0) of joint effusion + synovial pannus + enhancement + condylar deformities + erosions + bonemarrow oedema (range 0-6). Correlations between JATA-score (range 0-30) and clinical, dental, and MR scores were calculated using Spearman coefficient test (statistical significance: p <0.05).
Results: Twenty (77%) out of the 26 eligible JIA patients eligible identified daily activities most relevantly affected by TMJ involvement. Then, the items most frequently selected were included in the JATA (Table 23). Eight patients (100% female, 62.5% with persistent oligoarthritis and 12.5% with extended oligoarthritis, polyarticular RFnegative, and polyarticular RF-positive, respectively) filled the JATA questionnaire reporting their abilities and global assessment on TMJ before TMJ IACI. The time to complete each questionnaire varied around 3-5 minutes. The median (IQ) JATA-score was 14.8 (11.9-17.8), JATA-GA 5 (3-5.5), CS-TMJ 2 (1.8-2), dental-score 1 (1-2.5), and MRscore 5 (3.5-5), respectively. Statistically significant correlation was found only between JATA-score and CS-TMJ (p = 0.04). . This project is a collaboration between European and Latin American (LA) countries that aims to identify the specific needs for optimal care in Juvenile Idiopathic Arthritis (JIA) patients in different continents. The delay in diagnostic and treatment of JIA may cause permanent joint damage, which will negative impact the present and future life of the patients. In order to avoid the burden of disease, it is extremely important to optimise health care providing satisfactory access to the specialist, implementing multidisciplinary team follow up, as well as to provide easy access to adequate treatment. The quality of these variables will show how efficient the health care is. The first LA country to join this initiative was Brazil, followed by Argentina, Chile and El Salvador. Objectives: To identify which health care aspects needs improvement in order to plan further optimal care to children with JIA in LA countries. However, the families that replied this survey may present a bias to urban population, where the pediatric rheumatology centers are. Conclusion: The families view is an important tool to identify the topics on standard of care that need improvement, in order to achieve a high quality health care in any region of the world. The results of the first LA countries that participated in the SHARE LA project showed satisfactory follow up with pediatric rheumatologists. However, it is needed that more LA countries join the survey in order to achieve a more reliable   Table 25 shows the participant centers and the number of answered surveys of each one of them. Twelve rheumatology centers from seven states of the country participated in the survey. After the first appointment with the pediatric rheumatologist, families view showed regular follow up, with good access to rheumatic medications and satisfactory uveitis screening. However, some families had to wait a long time for the first appointment with the specialist, and also had to travel very long distances to the rheumatology center. Conclusion: The difference in the quantity of answered questionnaires among Brazilian regions reflects the distribution of rheumatology centers in the country. It is well known that there are extensive areas of the country that don't have a rheumatology center nearby. For this reason, it's difficult to the patient to reach the specialist in the beginning of the disease in some areas. Once the patients have reached the rheumatology care, they had a satisfactory follow up with the specialist. Disclosure of Interest None Declared. Objectives: To investigate the presence of anti-CCP antibodies in a cohort of JIA patients collected in the Stockholm area, Sweden (the JABBA cohort). Furthermore, to define the ACPAs presence and to correlate their occurrence to clinical parameters recorded in the Swedish juvenile arthritis quality register. Methods: Detection of anti-cyclic citrullinated peptide antibodies was performed for 352 JIA patients and 66 age and sex matched healthy controls using anti-CCP2 ELISA (Euro-Diagnostica). ACPAs were analysed in 81 patients with CCP2 reactivity ranging from ≥24AU/ml (n = 11), 24 > CCP2 ≥ 14 AU/ml (n = 7), 14 > CCP2 ≥ 10 AU/ml (n = 8) and CCP2 < 10 AU/ml (n = 55). Additionally, 191 healthy controls were analysed for the presence of ACPAs. For ACPA analysis, a multiplex analytic microarray system (Phadia AB, Uppsala, Sweden) that analyzes  Introduction: There is a worldwide variation in the incidence of juvenile idiopathic arthritis (JIA) which may be affected by genetic and environmental factors. The incidence of autoimmune diseases like type I diabetes or inflammatory bowel disease has increased during the last decades in Finland and all over the world.
Objectives: The aim of this study was to assess the annual incidence of JIA in Finland. We also aimed to study trends in the incidence of JIA in Finland.    5-3,8). Following the switching of the route of MTXadministration, patients were followed-up every 3 months for at least two years. Results: Switching from SC to PO route of MTX-administration was effective in 26/27 patients (96%). Only one patient returned to SC-MTX due to the appearance of a disease flare 7 months after switching. One more 13 year-old female patient returned to SC-MTX after 1 month PO-MTX due to worsening of nausea. With regard to tolerability of switching, while on SC-MTX, seventeen of the remaining 25 patients (68%) were presenting with persistent gastrointestinal symptoms, dizziness and/or behavioral symptoms occurring before (anticipatory/associative) MTX-administration. In 15/17 (88%) of patients these complaints subsided completely after switching whereas in 2/19 (12%) the complaints improved but did not disappear.

Conclusion:
Our results indicate that in JIA patients on longstanding clinically inactive disease under monotherapy with SC-MTX, switching from SC to PO route of MTX-administration is effective in the vast majority of patients. Additionally, due to the high degree of tolerability after PO administration switching to PO route seems to be easily achievable with concomitant improvement of patients' and families' dissatisfaction and subjective complaints due to injections (not measured with a validated tool in this study). According to our previous findings, MTX withdrawal in JIA patients in longstanding remission is accompanied by a 50% relapse rate. In conclusion, switching from SC to PO route of Methotrexate administration offers a safe treatment modality to reassure the continuation of disease remission with an acceptable improvement of the patients' quality of life.

Disclosure of Interest
None Declared.  Introduction: Juvenile systemic sclerosis (JSS) is a rare disease with possible vital organ involvement and severe complications. Cardiac involvement in particular tends to result in severe clinical complications, such as congestive heart failure, arrhythmias, and sudden cardiac death. Cardiac manifestations that often begin during the early stages of the disease but remain clinically asymptomatic at onset. Therefore, the identification of high-risk patients would benefit from early medical intervention for cardiac complications. New echocardiography modalities, like two-and three-dimensional (2D, 3D) speckle tracking (STE) employing strain analysis, provide an assessment of myocardial deformation in the early stage of the disease.
Objectives: We aimed to use the (2D with 3D) STE for the detection of subclinical cardiac involvement of the ventricles in patients with JSS. Therefore, the identification of high-risk patients would benefit from early medical intervention for cardiac complications. Methods: We assessed patients with JSS together with age-and sexmatched controls. All the target patients met the Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for JSS. A complete medical history was taken and physical examination and laboratory evaluation performed for each patient at the time of enrollment. All images were acquired with a Philips iE33 echocardiographic system (Philips Medical Systems, Andover, MA, USA), using an X3-1 matrix-array transducer. According to the international recommendations, 3D left and right ventricle (LV, RV) full volume sweeps were acquired from four views, during an end-expiratory breath-hold when possible: the apical view, the sagittal (to outline the tricuspid valve), the four-chamber (to outline the apex), and the coronal (to outline the RV outflow tract). Results: We assessed 21 patients with JSS and 19 healthy controls. The mean ages of the JSS patients and healthy controls at the time of study were 15.38 ± 2.74 and 14.33 ± 3.48 years, respectively. The mean disease duration was 2.65 ± 2.6 years (range: 0.6 -10 years). The left ventricular end diastolic volume (LVEDV), end systolic volume (LVESV) and ejection fraction (EF) were different between patients and control group (99.2 ± 23.8 vs. 52 ± 23.8, 40.6 ± 16.0 vs 20.2 ± 17.4, 59.2 ± 7.5 vs 65.6 ± 5.2). Global longitiduinal strain (GLS), Global circumferential strain (GCS) were lower in patients (18.4 ± 4.7 vs 22.4 ± 3.7 and 26.4 ± 5.8 vs 31.4 ± 3.5), peak systolic strain values of right ventricular septal (RVLS septal) and free wall (RVLS freewall) were lower in patients with JSS (18.1 ± 6.8 vs 24.8 ± 6.0, 22.8 ± 5.9 vs 28.0 ± 6.9). 3D measurements of RVEDV, RVESV, RVSV (88.2 ± 31,3 vs 50.8 ± 23.5, 43.1 ± 17.6 vs 19.0 ± 12,2 and 45.0 ± 16.2 vs 31,7 ± 12,6) were higher in patients with JSS. RVLS freewall were lower in JSS patients having interstitial lung fibrosis, arthritis, muscle weakness, weight loss, high level of anti-Scl 70 antibodies than the JSS patients without these variables. We found that a GCS < 34.5% could identify patients for LV dysfunction with a sensitivity of 93.3, specificity of 92.9 and RVEF < 60.7% could identify patients for RV dysfunction with a sensitivity of 92.9 and specificity of 21.4%. Conclusion: Currently, there is a lack of data on the presence and development of functional myocardial dysfunctions in JSS patients. Our results highlight key advantages of 3D STE for the tracking of early systolic dysfunction in patients with JSS, which may be useful in the clinical setting. More aggressive immunosuppressive treatment may be recommended to prevent progression of myocardial dysfunction, as shown with new echocardiography modalities like 2D and 3D STE.

Disclosure of Interest
None Declared.

P274
The relationship between hand grip strength, pain level and hand functionality in children with juvenile scleroderma Arzu Dag 1 , Ela Tarakci (Table 26). Conclusion: In this study, it is demonstrated that increases in hand functionality values are especially directly related with pain level rather than hand-key-palmar and tip grip strength. Pain has been determined as the most influential factor in the daily use of the hand. Therefore it was determined that pain is the fist symptom to be treated using hand effectively in daily life activities in children with JS, with espeailly in JSS.

Disclosure of Interest
None Declared.

P275
Long term outcome of juvenile localized scleroderma: data from a single pediatric rheumatology center Introduction: Juvenile Localized Scleroderma (JLS) comprises a group of autoimmune fibrosing conditions involving skin and subcutaneous tissues after initial inflammatory reaction. The treatment of JLS is challenging for pediatric rheumatologists and, to date, available data on long-term outcome are partial and incomplete.
Objectives: to evaluate the long-term outcome of patients with JLS based on clinical form, type and time of treatment and to identify possible predictors of outcome, that can guide the treatment choice at diagnosis. Methods: a retrospective study with collection of clinical, radiological and laboratory data from patients with JLS, followed at the Paediatric Rheumatology Unit of the University Hospital of Padua has been performed. We included all patients that had at least 6 months follow-up and had been evaluated at least once in the last 2 years. For each patient, clinical assessment of the disease activity and of severity of tissue damage and functional impairment was performed by using the LoScat score combined with thermography. Univariate tests and a multivariate model were used for statistical analysis.
Results: 133 patients entered the study: 84.6% of patients had a partial remission of disease (inactive disease on treatment) within the first year of follow-up, 55.6% had a complete remission (inactive disease and more than 2 years without any treatment) within 5 years of follow-up and 85.7% within 7 years of follow-up; 12.5% has a still active disease after over 10 years of follow-up and all them have the linear subtype. 59.5% of patients had no relapses in the disease course, 22.2% had at least one relapse on average 20 months after discontinuation of treatment, and 12.7% presented repeated relapses. Overall, 18.3% of patients did not respond to topical or systemic therapy. 49.2% of all patients developed only a mild tissue damage, 25.4% moderate and 23% reported a severe residual skin involvement. Only 2.4% patients have no aesthetic sequelae. Up to 19.8% present a functional limitation and, in particular, linear scleroderma and pansclerotic morphea are those associated with more severe aesthetic and functional sequelae. The entity of tissue and functional damage does not change over time and is not related to the duration of follow-up: 27.8% of patients with <2 years of followup has a marked damage, 20.6% in those with a follow-up of 5-10 years and 25% with a follow-up > 10 years. A delay in systemic treatment is associated with a worse outcome in terms of activity duration and number of disease relapses. Conclusion: The majority of patients with JLS achieves complete remission and do not present disease relapses. Patients with the linear subtype have more aggressive disease course with active disease after more than 10 years and more disease relapses as compared to other forms. The entity of skin and subcutaneous tissue damage seems to establish at the early stages of the disease and to remain stable over time. A delay in the start of treatment is related to a worse outcome. A close follow-up is mandatory in particular during the first 2 years after discontinuation of treatment when disease relapses occur more frequently.

Disclosure of Interest
None Declared.

P276
Update on the juvenile systemic sclerosis inception cohort project. characteristics of the first 97 patients at first assessment. www.juvenile-scleroderma.com Abstract withdrawn Introduction: Juvenile dermatomyositis (JDM) is a rare disease characterized by chronic inflammation of muscle and skin [1]. Systemic capillary leak syndrome (SCLS) is a rare life-threatening condition, characterized by sudden onset of hypotension, hypoalbuminemia and hemoconcentration due to vascular endothelium alterations that cause leakage of plasma and protein into the interstitial space leading, in some cases, to hypovolemic shock and death [2]. Plasma leakage into muscle and fascia can cause increased intra compartmental pressure inducing rhabdomyolysis and compartment syndrome [3]. Objectives: We describe three cases of JDM complicated by SCLS requiring intensive care and aggressive immunosuppressive treatment.
Methods: Data on clinical and laboratory parameters were collected from three patients evaluated at our Pediatric Rheumatology Unit in the last five years.
Results: All the patients were male, aged between 3 and 13 yearsold, diagnosed with JDM according to Bohan and Peter criteria [2]. All the patients presented with acute onset of unexplained edema associated with hypotension, myalgias with rhabdomyolisis, neutrophilic leukocytosis, hyponatriemia, hypoalbuminemia and hemoconcentration (Table 27). They developed SCLS while on high dose MPDN therapy. Two of these patients (case 1 and 3) needed pediatric intensive care support. One patient developed an acute compartment syndrome of the upper extremities that needed emergency fasciotomy. All patients had an optimal response to intravenous immunoglobulin therapy (IGIV) with complete recovery of the SCLS. Conclusion: SCLS is a rare but life-threatening condition calling for early detection and treatment. The pathogenesis of this disorder seems to be related to abnormalities in vascular endothelial growth factor (VEGF), endothelial cell apoptosis and increased expression of pro-inflammatory molecules [4]. More recently SCLS has been reported in association with autoimmune disease [5]. A confirmation of the possible immunologic pathogenesis of this disorder is the reported efficacy of the IVIG treatment which recently revealed to be a promising therapy for SCLS [6]. Our patients with JDM developed SCLS while on high dose MPDN therapy, confirming that corticosteroids cannot prevent this complication that should be suspected in a JDM patient with an atypical course characterized by acute unexplained onset of edema and myalgias with rhabdomyolysis, neutrophilic leukocytosis, hypoalbuminemia, hemoconcentration and hypotension. In these cases, intensive symptomatic treatment and prompt intravenous immunoglobulin (IVIG) administration are mandatory.

Informed consent
The subject's and parents' written consent was obtained according to the Declaration of Helsinki. Duration of untreated illness was designated as the time from first sign of rash or weakness to a diagnostic visit. Laboratory, muscle and cutaneous inactivity were defined as normal muscular enzymes values, absence of muscle symptoms and normal Childhood Myositis Assessment Scale (CMAS), when available, and absence of skin rashes respectively. Results: 55 of the 87 (63%) patients were girls. Gottron's papules were the most common skin rash at diagnosis (89.5%). Heliotrope rash was present in 67%. Eighty seven percent patients presented muscle symptoms (82% hips, 76% shoulders, 61% axial). CMAS was available in 26 patients at diagnosis with a median value of 34/52 (minimum 9/52). Baseline demographic data and laboratory findings are described in Table 28. Eighty eight percent patients had Von Introduction: There is growing evidence for an involvement of interferons (IFNs) in the chronic inflammation that characterizes juvenile dermatomyositis (JDM). Additional information is needed to support the hypothesis of a pathogenic role of IFNs in JDM in order to provide the rationale for therapies aimed at specifically targeting type I IFN and/or type II IFN pathway in JDM.
Objectives: The aim of this study was to investigate muscle expression of type I (IFNα/β) and type II (IFNγ) IFN inducible genes in muscle biopsies of JDM patients and their correlations with clinical and histological aspects of the disease. Methods: In a retrospective cohort of patients diagnosed with JDM (n = 35), expression of the six genes part of the so called type I IFN score (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1), as well as of IFNγ and of CXCL9, CXCL10, CXCL11, CIITA, were analysed by real-time PCR on snap-frozen muscle biopsies and compared with biopsies from Duchenne muscular dystrophy (DMD) patients (n = 24) and 4 healthy controls (HC). Expression levels of CXCL9, CIITA (genes specifically induced by IFNγ) and IFNγ itself were used to generate a type II IFN score. We also analyzed mRNA expression of the pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). Patient charts were reviewed to record clinical features at diagnosis and long term outcomes: physician's global assessment of disease activity, serum levels of muscle enzymes, erythrocyte sedimentation rate, C-reactive protein level, antinuclear antibodies status, time to inactive disease and time to prednisone (or equivalent) dose 0.2 mg/kg/ daily, and relapses. We furthermore evaluated typical histological aspects of JDM (inflammatory infiltrate, necrosis, perifascicular atrophy and fibrosis) on tissue sections of the muscle biopsies.
Results: JDM patients treated (n = 12) with systemic glucocorticoids before biopsy were excluded from analysis, because expression levels of the studied genes were markedly reduced compared to untreated patients. The type I IFN score and type II IFN score were significantly higher in the muscle of untreated JDM patients (n = 23) compared with controls (p < 0.0001, p < 0.001 respectively). Expression of TNFα, but not of IL-1β and IL-6, was significantly (p < 0.05) higher in untreated JDM muscle biopsies compared with those of controls. Type I IFN score correlated with inflammatory infiltrate and necrosis, while the type II IFN score correlated with inflammatory infiltrate, perifascicular atrophy and fibrosis. Type I IFN score, type II IFN score and TNFα expression significantly correlated with physician's global assessment at diagnosis (r = 0.38, r = 0.42, r = 0.62, respectively). When analyzing correlations with long term outcomes, we found that patients with elevated type II IFN score reached clinically inactive disease significantly later than patients with low type II IFN score (log-rank chi square value = 10.1, p < 0.01).  Introduction: Children with juvenile dermatomyositis (JDM) are at risk of growth failure and delayed puberty because of inflammatory disease activity and side effects of corticosteroid treatment. Knowledge on growth and pubertal development in JDM is very limited.
Objectives: To study growth and puberty in a multicenter longitudinal prospective cohort of children with JDM. Methods: Anthropometric and pubertal data in children ≤18 years with recent onset or flare of JDM from 31 countries were studied. Growth failure was defined as parent-adjusted z-score < -1.5, and height deflection z-score < -0.25/year. Delayed menarche was defined as age of menarche >15 years. Late and delayed pubertal onset was defined as age at Tanner B2 > 11 years and >13 years for girls, respectively, or age at Tanner T2 > 12 and >14 years for boys, respectively. Delayed puberty was defined as a delay in pubertal onset, pubertal tempo or menarche.
Results: Height and weight from four follow-up visits during two years in 196/275 (71.3%) of the children included in the original JDM study were analyzed. There was a significant reduction in parent-adjusted height z score over time in females (p < 0.0001) and males (p = 0.001) with significant gender difference (p < 0.05), but also catch-up growth at the final study visit were seen. Median body mass index (BMI) z score peaked at 6 months (p < 0.0001) and was still significantly above baseline with no gender difference at the final study visit at a median of 26 months after baseline (p = 0.007). Females with a disease duration ≥12 months after onset had significantly lower parent-adjusted height z score (p = 0.002) with no catch-up growth. Delayed pubertal onset, pubertal tempo and delayed menarche was found in a substantial number of the participants as shown in the Methods: In the PRINTO JDM trial, children aged 18 years old or younger with newly diagnosed and untreated probable or definite JDM were enrolled. All patients received three daily pulses of intravenous methylprednisolone at onset, and then they were randomized to one of the following three different treatment groups: prednisone (PDN), prednisone plus ciclosporin (PDN + CSA) and prednisone plus methotrexate (PDN + MTX). In our study, we considered patients who had a complete HRQoL assessment at onset through the Child Health Questionnaire (CHQ). We compared quality of life among the responders (PRINTO20-50-70) belonging to the three treatment groups, and between responder and not responder patients. Moreover we compared the affected patients to healthy children.
Results: Out of a total of 139 patients enrolled in the PRINTO JDM trial, 129 (92.8%) were retained for the analysis (41.9% males and 58.1% females; median age 7.4 years). At baseline, patients with JDM showed poorer scores in quality of life (PhS = 15.6 and PsS = 40.0) than healthy children. In particular, "Physical Summary score" (PhS) turned out to be significantly lower than 2 standard deviations with respect to the mean value of the healthy children with no difference among the 3 treatment groups (PDN, PDN + MTX, PDN + CSA). Less compromised scores were observed for the PsychoSocial summary Scale, with values between 1 and 2 standard deviations below the mean values of healthy children.
We found similar values between «responder 20» and «not responders». A statistically significant improvement was observed after 6 months of treatment both in the PhS and in the PsS subscales (P < 0.0001) irrespective of the treatment group, and in all items of the CHQ with the exception of the GBE (Global behavior parameter). A significant improvement over time was observed regardless of the treatment group and the level of response (PRINTO 20, 50, 70). "Responder" patients showed PhS values significantly higher than "not responder"; on the contrary, PsS values did not reveal a significant difference between "responders" and "not responders", despite an improvement over time.
Conclusion: Children with new-onset JDM, treated with PDN alone or in combination with other therapies, showed a significant improvement in quality of life during a two-year follow-up. According to the "PRINTO 20-50-70" criteria, "responder" patients showed a statistically significant improvement in the PhS score compared to the "not responders". Introduction: Juvenile dermatomyositis (JDM) is a rare condition with a wide severity range, from self-limiting to life threatening. Its treatment will vary between different pediatric rheumatology centers as no uniform therapeutic protocols are available, especially based on the severity of disease presentation. Previous studies have documented the improvement of disease prognosis, but the impact of the most recent treatment strategies on side effects and cumulative damage is still insufficiently documented.
Objectives: To compare the treatment approach based on the disease severity, the side effects and the cumulative damage of children with JDM followed in two large European tertiary care centers. Results: A total of 127 patients were included, 88 at GOSH and 39 at IGG. Demographic data, including age of onset and disease duration at first visit, were almost identical between patients followed at the two centers. Based on the physician clinical judgment, we divided our patients into Mild, Moderate or Severe disease activity. At GOSH and IGG the Mild and Moderate patients were initially treated with corticosteroids (88% vs 100%) and methotrexate (98% vs 100%), then at GOSH azathioprine (37%), and anti-TNF (31%) were used in the second year of follow up, whilst cyclosporine (50%) and iv immunoglobulin (33%) were preferred at IGG. Children with Severe disease activity at GOSH also received iv cyclophosphamide (67%), whilst cyclosporine (46%) and iv immunoglobulin (23%) were administrated at IGG. The corticosteroid toxicity has been the most frequent side effect reported in both centers in 25% and 43.6% of patients, followed by sickness due to methotrexate showed in 25% and 20.5% of children at GOSH and IGG respectively. At GOSH there were more reports of increased blood pressure (6.8% vs 2.5%) and mood swing (10.2% vs 2.5%). At IGG increased body hair (30.8% vs 3.5%) and raised liver enzymes (10.2% vs 5.7%) were more commonly seen. Vertebral fracture occurred in 3.5% and 2.5% of patients at GOSH and IGG respectively. The percentage of patients with evidence of damage (MDI ≥ 1) in any organ or system at baseline, 6, 12 and 24 months of follow up was 9%, 13.6%, 12.3%, 12.6% at GOSH and 5.1%, 5.5%, 11.4%, 8.8% at IGG. The details of the most common signs of cumulative damage are shown in the table.
Conclusion: xIn spite of the differences in the treatment approach, the frequency of damage was low (< 16%) in both patient cohorts. The side effects of treatment were mostly transient and never lifethreatening. The commonest side effects were due to corticosteroids: treatment protocols that reduce the use of corticosteroids would be beneficial.

Disclosure of Interest
None Declared. Introduction: Linear scleroderma of the face (LSF) is a very disabling condition and, to date, standardized and validated methods for assessing and monitoring the disease progression are lacking. The Cone Beam Computed Tomography (CBCT) is an imaging technique, currently used in dentistry and maxillofacial surgery, with good sensitivity for both soft and bony tissues, it is fast to be performed therefore does not require patient sedation. Of interest, the radiation exposure is 50 times lower than a traditional CT scan, being the ideal technique for a repeated use. Objectives: Given the young age of the majority of the patients with LSF and the need for a combined bone and soft tissue evaluation, we investigated whether CBCT may represent a potential reliable tool for assessing the patients and for monitoring the course of LSF over time. Methods: Ten consecutive patients with LSF, aged 3-21 years, and 5 age-matched healthy controls underwent CBCT assessment. The transverse sections of CBCT scan, in digital format, were analyzed according with three arbitrarily selected anatomic levels: mandibular condyle (MC), floor of the maxillary sinus (MS) and mandibular foramen (MF). Measurements of both affected and unaffected side of the face were made by a standardized methodology. From the intersection axes, an origin point was generated and from this one, 30°a nd 60°lines, crossing bony and soft structures, were drawn. For each given degree, the soft tissue thickness and the total thickness (bony and soft tissues) of the right and left side were calculated by using the software Onis 2.4 free edition. Twenty-four measures for each subject (two for each side, right and left, of the three transverse sections) were therefore evaluated. Five raters, all physicians, after a one-hour training session, evaluated LSF patients' and controls' CBCTs twice and blindly one from the other. The intra-rater reliability was assessed by the repeatability coefficient and the inter-rater reliability by the Intraclass Correlation Coefficient (ICC) and interpreted as follows: ICC values range 0.75-1 excellent reliability, 0.4-0.74 good reliability, <0.4 poor reliability. All statistical analyses were performed by using IBM SPSS (Vers. 18.0). Results: CBCT was fast and well tolerated by the patients even the youngest.
The intra-rater concordance resulted optimal as the repeatability coefficient ranged between 0.77 and 0.99. The inter-rater concordance for the total thickness, among the assessors, was also excellent with mean ICC value of 0.75 (SD 0.16) for patients and 0.89 (SD 0.09) for controls. The mean ICC for the soft tissue thickness was 0.49 (SD 0.24) for patients and 0.66 (SD 0.28) for controls, respectively. 58.3% of the measurements for patients and 91.2% of those for controls showed excellent ICC results (> 0.75). The best performances were obtained at the level of the MF and MC sections.
Conclusion: CBCT has shown to be a reliable method to assess and monitor skin and bone changes in patients with linear scleroderma of the face. It is a fast, reproducible and reasonably safe technique.
Although it is not reliable for the assessment of lesions on the forehead, CBCT is indicated for the assessment of the remaining parts of the face. A prospective validation to confirm its relevance in evaluating the disease progression is ongoing.

Disclosure of Interest
None Declared.
Introduction: The unilateral manual muscle test (MMT-8) and the childhood myositis assessment scale (CMAS) are regarded as important measures of muscle strength and function/endurance in juvenile dermatomyositis (JDM). However, due to ceiling effects the tests are known to have low sensitivity and specificity in detecting mild muscle weakness that is often predominant in long term JDM. Isokinetic knee extension is a more objective evaluation of muscle power and endurance. Objectives: To explore the association between the MMT-8, CMAS, and an isokinetic knee extension test in JDM patients with long term disease.
Methods: JDM patients and gender-and age-matched controls from the general population were examined. Patients were divided into active and inactive disease by the PRINTO criteria (2012) [1]. Height and weight were measured, and MMT-8 (0-80) was scored in both groups; CMAS (0-52) in patients only. An isokinetic knee-extension device with an attached force transducer (HBM U2AC2, Darmstadt, Germany) was used to measure maximal voluntary contraction (MVC) force as a measure of muscle strength. At 30% of the MVC force, the participants then performed repetitive one-leg knee extensions at 0.25Hz to exhaustion. Exercise volume (mass derived from the 30% MVC force x number of repetitions) was used as a measure of muscle endurance. Values represent averages of right and left leg. Results: Forty-five patients (60% women) and 50 controls participated in the study. Mean disease duration from symptom onset was 20.6 (11.9) years, 28 (62%) patients had inactive disease and 11 (24%) were on medication. Muscle strength (MMT-8 and MVC force) and endurance (exercise volume) were reduced in patients compared to controls and in patients with active compared to inactive disease. CMAS was not statistically different between the patient groups (   Specific goals of the project were identified by consensus. Via an online survey among pediatric rheumatologists and neurologists (67 participants) using different case scenarios, various approaches were identified. These approaches were harmonized. A final consensus meeting took place in January 2017 (13 participants). By means of nominal group technique individual statements were developed. Consensus was considered to be achieved if more than 80% of participants supported a statement.
Results: Overall, ten individual statements were developed, each with a consensus of 92-100%, regarding (1) diagnosis of JDM, (2) case definitions for the application of the protocols, (3) initial diagnostic work-up, (4) monitoring and documentation, (5) treatment targets for a treat-totarget strategy, (6) supportive measures, (7) explicit definition of a treatto-target strategy, (8) different glucocorticoid treatment options, including intermittent intravenous methylprednisolone pulse therapy and high-dose oral glucocorticoid therapy and suggestions for tapering, (9) initial glucocorticoid-sparing treatment, and (10) treatment in case of refractory disease. Conclusion: We developed individual statements regarding the management of JDM by means of a consensus process among JDM experts in Germany. These statements and resulting treatment protocols may be applied to patients with active moderately severe and severe JDM. Long-term goals of the project include the establishment of a documentation platform for JDM in Germany, the participation in international registries and further optimization of these protocols.

Disclosure of Interest
None Declared.

P288
Anti Introduction: Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune-mediated disease characterized by proximal muscle weakness, elevated levels of muscle enzymes, and rashes typically heliotrope rash and Gottron's papules. Other clinical features that may contribute to major morbidity include calcinosis, skin ulceration, treatment-resistant rash, and internal organ involvements of the gut, lungs, and brain. Serologic investigation has been explored in JDM in order to define subgroups that can help us predict clinical course, treatment and prognosis. Autoantibodies directed against the Ku autoantigen are one of myositis associated antibodies found in adult patients with systemic sclerosis (SSc) and have been associated with myositis overlap and interstitial lung disease (ILD). However, there is a paucity of data on the clinical correlates of anti-Ku antibodies in the paediatric autoimmune conditions. Objectives: The aim of this study was to review clinical phenotype, prognosis and treatment of anti-Ku antibodies in two paediatric cases with juvenile dermatomyositis-scleroderma overlap. Methods: 380 of the patients enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS) were tested for autoantibodies (at the time of this study) and we found only two cases who have anti-Ku positivity as myositis-associated autoantibodies (MAA). The review of patient medical notes were performed with the comparison between disease characteristics of anti-Ku antibodies in our patients and other case studies. Results: We report a 10 year old male with anti-Ku associated myositis/ scleroderma overlap syndrome characterized by destructive myopathy, sclerodermatous rashes, joint restriction, oesophageal dysmotility, interstitial lung disease (ILD) and possible cardiac involvement. The patient initially presented at the age of 8 as a hyperpigmented lesion over the chest and abdomen which developed into a widespread tightening and thickening of the skin. He was started on high dose intravenous steroid, subcutaneous methotrexate injection and courses of Rituximab and cyclophosphamide infusion. His clinical progression has gradually improving after six doses of cyclophosphamide. Another case review is a 10 year old girl with a three year history of gradual tightening of her fingers, progressing to her elbows, shoulders, hips, knees and back. She also complained of Raynaud phenomenon with progressive muscle weakness. After seven years of treatment with steroid and methotrexate, her disease had still active and required more aggressive treatment. Similar to previous adult cohort studies, anti-Ku positive patients are associated with more severe muscle weakness, articular symptoms, Raynaud phenomenon and a tendency to develop ILD.
To the best of our knowledge, this report is one of the youngest anti-Ku positive patients with juvenile dermatomyositis-scleroderma overlap. Conclusion: Our review suggests that anti-Ku antibodies might be used to identify individuals with juvenile dermatomyositis-scleroderma overlap whose disease will progress to severe muscle weakness and systemic internal organ involvements, particularly interstitial lung disease. Prompt aggressive treatment should be managed according to the severity of symptoms in order to improve clinical outcome and prevent serious complication. Our report underscores the screening for anti-Ku antibodies at diagnosis in JDM patients presenting with scleroderma features such as Raynaud phenomenon to guide further investigation and initiate appropriate treatment.
The written informed consent for the publication of these details was obtained from the participants.

Disclosure of Interest
None Declared.

P289
Capillary microscopy in juvenile dermatomyositis is not strongly correlated to clinical and laboratory markers of disease Introduction: Juvenile dermatomyositis is an auto-immue inflammatory vasculopathy of uncertain aetiology that affects skin and striated muscle. It is historically diagnosed by proximal muscle weakness, characteristic skin lesions and evidence of muscle inflammation. It has an incidence in UK and Ireland of approximately 1.9 per million [1]. In recent years, myositis autoantibodies have been identified that may play a role in further distinguishing subtypes of inflammatory myositis. They can be broadly divided into myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) [2]. Conclusion: Myositis auto-antibodies were present in a significant number of our cohort, MSA accounting for the majority (73%). Anti MDA 5 antibody accounted for 38% of those with a positive result and 12% of the overall cohort. This is slightly higher than previously quoted studies in Caucasian/UK populations [3]. The presence of anti MDA 5 is known to be associated with a more aggressive clinical course with more pronounced interstitial lung disease, arthritis and cutaneous manifestations such as skin ulcerations. This was reflected in our population of MDA 5 positive patients.
[1] Symmons DP, Sills JA, Davis SM.  Objectives: The objectives of the case report are to describe a patient with sJIA complicated with MAS who developed a TRALI following transfusion of a whole blood derived platelets from a male donor. Methods: Case report.
Results: A six-year-old girl with sJIA complicated by MAS received a whole blood derived filtered and irradiated platelets from a male donor due to profound thrombocytopenia. Approximately one hour post-infusion, she started coughing and rapidly became progressively dyspnoeic. Physical examination of the patient revealed tachycardia, tachypnoea and diffuse bilateral crepitations throughout her lungs. Hypoxemia was evident with a SpO2 persistently below 90% and increasing oxygen requirements. Administration of intravenous furosemide and hydrocortisone had no effect on her symptoms. Urgent chest radiograph showed bilateral nonhomogenous opacities but no cardiomegaly, and she was promptly intubated and placed on mechanical ventilation for two days. No evidence of acute heart failure secondary to an ischemic event or circulatory overload was found so a diagnosis of transfusion-associated circulatory overload (TACO) was unlikely. Other risk factors that might contribute to acute lung injury including sepsis were excluded. The patient's pulmonary condition rapidly improved clinically and a radiograph taken 24 hours post-event showed marked resolution of the airspace shadowing. She was extubated and transferred out of the intensive care unit one day later, with no further pulmonary sequalae. Based on relevant criteria, a blood immunology studies were performed in order to detect HLA class I, class II, and/or granulocyte antibodies in donor's and patient's plasma. The presence of anti-human neutrophil antigen 3b (anti-HNA-3b) in patient's plasma and no detectable HLA class I, class II, and granulocyte antibodies in donor's plasma indicates that in our patient TRALI might resulted from the reverse mechanism in which the recipient has granulocyte antibodies that match residual donor white blood cells.
Conclusion: Although acute hypoxic pulmonary failure has been described rarely in children with sJIA complicated with MAS, it is important to consider TRALI in transfusion settings in these children.

Disclosure of Interest
None Declared. Introduction: An increasing body of evidence, in humans and in animals, support the hypothesis that IFNg plays a pivotal role not only in the pathogenesis of primary HLH, but also of secondary HLH (sHLH). Nevertheless, few data demonstrating the activation of the IFNg pathway in target tissues of patients during the active phase of the disease are available.
Objectives: To analyse the mRNA expression of IFNg and IFNg inducible genes in the liver and in the blood from a patient with sHLH and to measure the circulating levels of CXCL9, in order to evaluate whether the IFNg pathway is up-regulated.
Methods: A Caucasian boy presented with systemic inflammation and progressive worsening of general conditions at age of 17. At this time bone marrow (BM) was negatıve. Glucocorticoid treatment was started but a first relapse occurred during tapering. Ten months later, a third episode with progressıve multiple organ failure, and subsequent ICU admission, occurred. Laboratory parameters and BM were consistent with HLH. Analysis of primary HLH-related genes showed a heterozygous mutation (R928C) in UNC13d gene. Eight years later, he presented with progressive increasing in ferritin and transaminase (max value 2300 and 2450 of ferritin and ALT, respectively). No fever was present and general conditions were excellent. Blood count and acute phase reactant were normal. Bone marrow aspirate showed some activated macrophages. Liver biopsy showed acute hepatitis with massive infiltration from macrophages showing active haemophagocytosis. Results: One liver biopsy specimen was snap-frozen for gene expression by Real-Time PCR and compared with tissue expression in a normal liver tissue. The expression of IFNg was strongly up-regulated (approximately 80 fold). Furthermore, we found that all IFNg inducible genes analysed (CXCL9, CXCL10, CXCL11 and IDO) were highly upregulated (from approximately 200 to 380 fold). In contrast, we did not observe marked up-regulation of the expression of pro-and anti-inflammatory cytokines (IL-1b, TNFa, IL-6, IL-18, IL-8, IL-10). Analysis of blood samples showed that the expression levels of CXCL9 and CXCL10 were higher (about 10 fold) while the expression levels of IFNg were lower, compared to those observed in blood from healthy donors (n = 2). Circulating plasma levels of CXCL9 were high during the active phase of the disease and paralleled the increase (max levels 6000 pg/ml) and the decrease in ferritin levels respectively during worsening and the subsequent progressive clinical improvement during treatment. Introduction: The term scleroderma means "sclerosis", stiffening of the "dermis" and the skin. Scleroderma has two main forms: systemic sclerosis (adults suffer more frequently) and localized sclerodermamore often revealed in children.Both types of scleroderma are rare in children, the annual incidence of systemic scleroderma (SSCL) makes up 1 cases per 1 million children, whereas the incidence of local scleroderma (lSCL) makes up 1-3 cases per 100.000 children. Aggressive form of the disease and early involvement of the internal organs may resul in severe disability and even fatal outcome in children. The percentage otf the lethal cases is lower when the progression of the disease is slow.
Objectives: In our work, we have presented a very rare case of congenital scleroderma. Patient F.D. was charged in Scientific center of pediatrics and children surgery at the age of 2.5 months old.
Methods: The child's health status at the first admission was of moderate severity due to skin syndrome. Child gained weight in compliance with the age. The facial features are sharp, the mimicry is poor.
On the lower extremities, in the region of the shin, the external surface of the thighs, on the lower part of the trunk the skin was tight and stiffened with a dense consistency, was not folded,the surface of the skin was glistering. Under the skin, as a result of the subcutaneous adipose tissue atrophy, there was tuberosity, painless. Cyanotic feet.Joints were the normal shape and size and there was limitation of knee and hip joints motion due to the fibrosclerotic changes of periarticular tissues. Heart tones were clear, rhythmic. Enlargement of the liver: +1.0 + 1.5 + 1.5. These changes are common for following nosologies: SCL, phenylketonuria, sclera. To clarify the diagnosis, it was necessary to exclude feniketonuria, detect ANA, the consultation of a neurologist, a dermatologist. Whole blood parameters were within references. Results: 71 items in 13 domains were scored. 6 Items were not scored as they were felt not to represent an outcome measure or non-feasible and and 6 items received a median score less then 4.    11.1% of our patients. During the outbreaks of activity a marked increase of RFA, ferritin and platelets has been observed. As for the treatments administered, only a small number of patients did not require biological treatment, while more than 30% received more than one, the anti-IL-1 and anti-IL-6 drugs were the most frequently administered. Currently, more than 50% of patients receive biological treatment.

Disclosure of Interest
None Declared.

P307
The disease burden of sJIA for patients and caregivers: an international health-related quality of life survey and retrospective chart review Abstract withdrawn Objectives: The aim of our study was to find the best cut-off points and clinical signs allowed to discriminate patients who with ALL from patients with SoJIA depending the presence of MAS.
Methods: In the retrospective study were included 119 patients with SoJIA and 21 children with ALL who were admitted in the rheumatology department due to rheumatic masks with initial provisional diagnosis -SoJIA. We evaluated the presence of main clinical signs and detected the best cut-off points of qualitative variables with ROCanalysis and analysis of sensitivity and specificity. We calculated the diagnostic odds ratios (DOR) for identification the best cut-off parameters. For comparison of two independent groups was used Mann-Whitney test, chi-square test and Fisher's exact test.
Results: There were differences in some parameters between three groups ( Introduction: The optimal duration of treatment in patients with JIA, especially systemic JIA (SJIA), is a major concern for parents and physicians alike. Innovative medicines have managed to fully control this otherwise potentially lethal condition; however questions regarding duration and cessation of treatment remain unanswered.
Objectives: The aim of this study was to describe the long-term outcome of children with sJIA treated with anti-IL1β monoclonal antibody (canakinumab-CAN-), in which treatment was discontinued, following sustained clinical remission; and to identify potential relapse associated risk factors. Methods: Single center retrospective case study including patients with SJIA (based on ILAR criteria) who had received CAN from January 2008 to January 2017. All subjects had clinically inactive SJIA (clinical remission on medication-CRM-Wallace criteria) for two years under CAN. Patients were monitored for up to three years following attempt of CAN withdrawal. Demographics, clinical and laboratory parameters were recorded. We also collected data on medication exposure as well as clinical outcome measures. Data were analyzed using SPSS 19.0. Differences were tested with the Mann-Whitney U test using level of significance p < 0.05. Results: In a total of 12 (7 girls) patients with inactive SJIA, (mean age of 8.5 years), CAN treatment was discontinued. Mean disease duration at the time of CAN initiation was 3.8 years (range from 1 to 7 years). All patients were on steroids when biologics were started (<1mg/kg prednisolone), which were discontinued within three months. Ten (80%) patients were on methotrexate (12.5mg/m 2 ), one on leflunomide (20mg). They remained on the same dose of DMARDS throughout the study period. 75% of patients had received at least one other biologic before starting CAN (2 anti-TNFα, 1 abatacept, 2 tocilizumab, 3 anakinra). Two (12.5%) patients had received at least two biologics prior to CAN. One patient had received three biologics. All patients received 4mg/kg CAN at monthly intervals for at least two years. Mean duration of treatment was 28 months (range 26-40 Among the initial symptoms the most frequently were: hematological disturbances -76,4% (thrombocytopenia -35,3%, leukopenia-41,2%, anaemia -47%), constitutional disturbances (76,47% patients), fever (58,8%), articular syndrome -70,9% (arthralgia-47,05%, polyarthritis -23,5%), typical cutaneous manifestations (malar rush) -52,94%, nephritis (53%), neurological disorders (23,5%), less than 10% had Raynaud's phenomenon, stomatitis, stomach-ache. Two male patients (11,7%) had macrophage activation syndrome (MAS) in the first 6 months of the disease. Another two male patients over 10 years old had severe presentations of SLEthe combination of nephritis and central nervous system affliction. In one case of early onset in boy SLE started with MAS and further severe skin and mucose lesions with typical for Ro-associated vasculitis had delayed (in 1,08 year) nephritis. All patients had immunological markers, including ANA (100% of cases), dsDNA (47%). The therapy depends on disease severity: 100% patients were treated by corticosteroids, 94% used cytostatic treatment (47,05% azathioprine, cyclophosphamide -35,2%, methotrexate, cyclosporine, mycophenolate mofetil had 5,8% equely). 76,5% recieved Plaquenil, 47,1% -IVIG. In 17,6% cases required Rituximab. Despite serious course of disease remission was achieved on the treatment and ANA inversion to negative was found in 9,1% cases. Conclusion: SLE is rarely diagnosed among boys and, in spite of the severity of clinical manifestations the delay of diagnosis is more significant. The most common symptoms in male patients are hematological and articular signs. Frequent nonspecific constitutional disturbances among the first symptoms without adequate laboratory examination result in delay of timeous diagnosis. More than the half cases suffered by nephritis and quarter by central nervous system involvement. The severity of clinical presentations requires aggressive treatment strategy that leads to good results in most cases.

Disclosure of Interest
None Declared. Introduction: Systemic lupus erythematosus (SLE) is a clinically diverse, autoimmune disease characterized by the development of autoantibodies, multi-organ involvement, and a chronic disease course. Renal involvement is one of the most common manifestations of SLE, and lupus nephritis (LN) has a higher prevalence in childhood-onset SLE (cSLE), occurring in up to 60% of patients during the disease course. The outcome in cSLE with nephritis is worse than in those without it, and the initial presentation at onset has been reported as predictive for renal involvement.
Objectives: To analyze the clinical presentation at onset of cSLE and to identify clinical features associated with different histological findings at kidney biopsy. Methods: We retrospectively analyzed the records of patients with LN followed from 1994 to 2017 at Ospedale Maggiore Policlinico of Milan, who underwent a renal biopsy in the first 2 years since the disease onset. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used for measuring disease activity at onset of cSLE. The WHO classification of LN was used to grade histological findings. We considered renal involvement mild if the histological class was II or III (16 patients), and severe if it was IV or V (14 patients).
Continuous variables were compared between the two groups with the Student's t-test, whereas categorical variables were compared with the chi-squared test. In all analyses, P < 0.05 was taken to indicate statistical significance. Results: Among 45 children with LN who underwent a renal biopsy in the first 2 years since the disease onset, 15 were excluded because of incomplete data, thus a total of 30 patients was finally enrolled. Among the 30 patients selected, the distribution of histological class was: Class II: 5 patients (16.7%), Class III: 11 patients (36.7%), Class IV: 12 patients (40%) and Class V: 2 patients (6.7%). The mean disease duration since disease onset until renal biopsy was 10 and 19 months for mild and severe involvement respectively. The mean SLEDAI score at onset was 31 for the mild subgroup and 25 for the severe subgroup. Neurological manifestations were more frequent in children with higher histological classes at renal biopsy. Among the activity indices at onset, hematuria was more frequent in the patients in the mild group than in those in severe group (P = 0.02), as well as pyuria (P = 0.01).
Patients with the development of severe renal involvement presented more frequently with hypertension, compared to those who developed a mild involvement (35.7% vs 18.7%, respectively, P = 0.294).
Other demographic and clinical characteristics at disease onset are shown in Table 35. F/M: female to male ratio. Neurological manifestations: Seizure, Cerebrovascular accidents, and Organic brain syndrome. Hypertension (PAs > 140, PAd > 90) Conclusion: As expected, the disease duration is higher in the group with more severe histological findings, even if it is not statistically significant in our population, probably due to the small sample size and high dispersion of the results. Pyuria and hematuria were most frequently observed among the group with mild involvement at kidney biopsy, whereas hypertension and neurological manifestations are more represented in the severe group. The SLEDAI score at onset was higher in children with mild kidney involvement. Further data collection is still ongoing on prospective cases.

Disclosure of Interest
None Declared. Introduction: High-mobility group box 1 (HMGB1) is a highly conserved ubiquitous nuclear protein with key functions including regulation of DNA binding, transcription, repair and recombination. Extracellular Introduction: Fabry disease is an X-linked lysosomal storage disorder that share similar organ involvement pattern with systemic lupus erythematosus (SLE). Mutations in GLA gene decrease the activity of lysosomal alpha galactosidase enzyme and responsible from the clinical manifestations. Decreased enzyme activity results with accumulation of a ganglioside; globotriaosylceramide inside of the endothelial cells and this accumulation impairs the normal functioning of these cells. Although previously reported as an X-linked recessive disease, currently Fabry disease is classified under the group of X-linked diseases owing to presence of clinical manifestations also in females. A more quiescent and nonspecific disease course are encountered particularly in females and children. Hence, delay in diagnosis and treatment is frequently observed. Presence of autoantibodies in Fabry disease and co-occurence of Fabry disease and SLE are reported previously in various case reports.
Objectives: In this study, we aimed to screen Fabry disease in all ANA positive juvenile SLE patients that were diagnosed according to ACR 1997 criteria. All subjects were also interrogated in terms of clinical manifestations of Fabry disease. Methods: From January 2016 to June 2016, 76 ANA positive juvenile SLE patients were enrolled consecutively in the study. All patients had met the 1997 revised criteria of American College of Rheumatology for classification of SLE. All of the patients or parents gave written consent for participation. Since the majority of the patients were female, initially GLA gene was searched for mutations causing Fabry disease. Mutation positive subjects were further evaluated for storage of globotriaosylceramide in lysosomes (lyso*Gb3). Results: Of the 76 subjects, 12 were male and 64 of them were female. While the mean onset of the disease was 11.6 ± 3.6 years, the mean duration of disease was 4.4 ± 2.9 years. Parental consanguinity was present in 25% (n = 19) of the patients. Fourteen subjects have been reporting burning sensation in hands and feet; two patients hypohidrosis and 11 patients gastrointestinal manifestations. There were no cornea verticillata and angiokeratomas in any of the patients. A heterozygous p.D313Y has been found in 2 female subjects. These subjects were further investigated for lyso*Gb3 levels in dry blood samples. Lyso*Gb3 levels were found to be also normal in these two subjects and we have excluded Fabry disease. Conclusion: Fabry disease may occasionally manifests with nonspecific features particularly in females. Hence, the diagnosis is delayed and the patients receive treatments due to various misdiagnoses. Although coexistence of SLE and Fabry disease previously has been reported in case reports, a systematic screening of juvenile SLE for Fabry disease has not been performed up to date. However, we have not detected any Fabry disease in our juvenile SLE cohort. In conclusion, we do not suggest screening Fabry disease in patients with SLE. Disclosure of Interest None Declared.
Introduction: Capillaroscopy findings can be qualitatively described as: normal, microangiopathy (non-specific abnormalities) or scleroderma pattern. Capillary abnormalities, described in varying prevalence in patients with systemic lupus erythematosus (SLE), are mainly described as microangiopathy Objectives: To describe capillary characteristics in a cross-sectional tertiairy cohort of patients with childhood-onset SLE (cSLE) by quantitative and qualitative assessment Methods: Nailfold videocapillaroscopy (NVC) was performed in cSLEpatients (onset < 18 years) with a x200 magnification lens (Optilia). All fingers except the thumb were examined with 4 images per finger. Introduction: Kidney involvement is a common manifestation in systemic lupus erythematosus (SLE), the incidence being 50% to 75% of childhood-onset SLE (cSLE) patients. Lupus nephritis (LN) encompasses a clinical spectrum from microscopic glomerular haematuria, cellular casts and minimal proteinuria to a myriad of life-threatening disorders.
Objectives: The aim of this study was to assess the clinicopathological characteristics and treatment outcomes in children with lupus nephritis in a paediatric nephrology department for 13 years.
Methods: This study was based on the lupus nephritis cohort, which included 19 hospitalised patients from the Department of Nephrology, Emergency Clinical County Hospital for Children Cluj Napoca, Romania, from 2003 till 2016. In this cohort were included detailed demographic data, ethnicity, age of LN onset, time between onset and diagnosis, clinical laboratory results, renal biopsy result and medication information. Eligible patients were diagnosed with childhood-onset lupus nephritis prior to 17 years of age, using revised American College of Rheumatology (ACR) SLE classification criteria and SLICC criteria. The activity of disease was assessed according to SLE Disease Activity Index scale (SLEDAI). Renal biopsy was performed before the initial induction therapy in 13 patients and the results were classified using ISN/RPA. Partial and complete renal response were categorised based on EULAR/ERA-EDTA recommendations of LN. Another patient was on 6 weekly concomitant IVIG for autoimmune myositis and they never developed hypogammaglobulinaemia. Complete B cell depletion (<0.0001 x10*9/L) using very sensitive flow cytometry was achieved in 9/14 (64%) of patients, however a significant proportion 4/15 (36%) remained B cell detectable. Neutropenia (<1.5x10*9/L) was identified in one SLE patient (1/14, 7.1%) post-RTX. They had normal levels pre-RTX, which dropped to 0.34x10*9/L, 5 months post-RTX. Conclusion: The findings provide a useful insight into the use of RTX in paediatric rheumatology patients. The incidence of hypogammaglobulinaemia attributable to RTX is significant (21.4%). Neutropenia was identified in a single patient (7.1%). It isn't possible to definitively ascertain whether this was due to disease activity or RTX. No patient with hypogammaglobulinaemia or neutropenia suffered with a serious infection, requiring hospitalisation. We did not feel IVIG replacement was indicated. This study does not support the use of prophylactic/routine IVIG replacement therapy during/after RTX. We would recommend checking blood cell counts and immunoglobulin levels following each dose of RTX and at least monthly for 3 months following the last dose of RTX. Certainly, checking and considering IVIG replacement would be sensible in any patient presenting with serious infection following 3 months of RTX. The limitations of this study include the retrospective design, small sample size and single centre experience. Biologic registries to gather long-term safety data are essential. Current guidelines also recommend women of childbearing potential should use effective contraception while on RTX and for 12 months following treatment.

Disclosure of Interest
None Declared. Introduction: The spectrum of diseases that biologic agents are used in treatment of juvenile rheumatic diseases has been increasing gradually since the first approval of etanercept for JIA in 1999. Inadequate response to synthetic disease-modifying antirheumatic drugs (DMARDs) is the most frequent reason of biologic agent introduction. These agents significantly improved the outcome of not only JIA patients but also other rheumatic diseases. There is still lack of data regarding the safety of these therapies in juvenile rheumatic diseases. Objectives: We aimed to report our single center experience regarding the usage indications and long term safety of various biologic agents in Turkish children.

Methods:
We have included all the patients treated with biologic agents at least 6 months due to various rheumatic diseases from January 2003 to October 2016. Demographic characteristics, diagnosis and all adverse events (AEs) were obtained from medical records of the patients. Results: Overall, 502 patients (281 female) with rheumatic diseases have been received biologic therapy since 2003. The most frequent diagnosis was juvenile idiopathic arthritis (n = 393), followed by autoinflammatory diseases (n = 55), uveitis (n = 20), connective tissue diseases (n = 18), vasculitis (n = 12), inflammatory bowel disease (n = 3), idiopathic recurrent pericarditis (n = 1). While the median age at disease onset was 5.4 years (range 1 month-17.6 years), median age at onset of biologic therapy was 10 years (range 1 -20 years). Among the patients treated with biologic agents, 355 subjects (70.8%) showed complete response to the first agent and so, used only one biologic drug: 244 etanercept, 35 adalimumab, 21 anakinra, 20 infliximab, 13 rituximab, 12 canakinumab, 9 tocilizumab, 1 belimumab. However, 29.2% of the subjects (n = 147) switched to another biologic agent due to side effect or inefficacy. Of the 147 subjects who switched, 58 (39.4%) finally remained on adalimumab therapy, 37 (25.2%) patients on canakinumab, 24 on tocilizumab (16.3%), 21 on etanercept (14.3%), 5 (3.4%) on infliximab and 2 (1.4%) on anakinra after various biologic drugs. At least one AE occured in 177 subjects (%35.2) and 53 patients (%10.5) had at least one serious AE. While 21 patients received prophylaxis for tuberculosis, only six patients developed tuberculosis disease on biologic therapy. Conclusion: We have observed, the usage of biologic therapies with a wide range of indications in Turkey. The frequency of AEs and SAEs are similar with the previous studies. Other than tuberculosis disease, these agents seem fairly safe in juvenile rheumatic diseases. We recommend close screening of patients on biologic therapy particularly in countries where tuberculosis disease is still widespread as in Turkey. Objectives: To optimise PVA-based HF-MNs array properties to improve its rigidity and develop a special HF-MNs patch design loaded with the required MTX dose and evaluate its efficiency to deliver MTX in an in-vivo setting. Methods: HF-MN arrays composed of 11 x 11 MNs of conical shape with MNs measuring (729.5 ± 11.2 um) in height, 300 um in-width at the baseplate and interspacing 200-250 um were fabricated as per [3] and optimised to form a stronger HF-MNs array. The fabricated HF-MNs arrays were characterised in terms of their mechanical strength, swelling capacity and permeability to MTX in an in-vitro setting employing Franz-type diffusion cells.The optimised HF-MNs arrays were then used to build up a novel HF-MNs patch loaded with MTX dose of 0.5 mg/kg. The ability of the fabricated HF-MNs patch to deliver MTX in an in-vivo setting was evaluated using Sprague Dawley rats (n = 6). One patch was applied onto the back of each rat with 20 μl of deionised water added into the MTX wafer reservoir and then removed after 24 hours. 200 μL blood samples were collected over 48 hours from application at predetermined time intervals and then analysed for MTX and its polyglutamates (PGs) content.
Results: The optimised HF-MNs arrays showed superior properties in terms of their mechanical strength and swelling capacity in comparison with those reported in previous study [3]. Upon applying the HF-MNs patch onto skin at the back of the rat, MNs were inserted into skin without breaking or bending. Furthermore, upon removing the patch. Also, it was noticed that HF-MNs completely swelled and the MTX wafer was dissolved indicating that the HF-MNs after insertion into skin imbibed skin interstitial fluid forming continuous conduits between the dermal microcirculation and an attached MTX wafer reservoir within the patch. This allowed the drug to be delivered in a controlled sustained manner. Interestingly, the HF-MNs arrays were removed intact from skin and no marks of irritation or severe inflammation were observed at the application site.
Conclusion: The optimised PVA-based HF-MNs with the novel patch design has shown to be a promising, minimally invasive transdermal drug delivery system which could be used to deliver MTX efficiently to JIA patients. However, further investigation is required to prove its efficiency and safety and advantage in comparison with other administration routes (oral, subcutaneous) after single and multiple application using larger number if rats Introduction: Kawasaki disease is the second most common primary vasculitis in children. The incidence of Kawasaki disease varies depending on ethnicity, with the highest incidence in the Japanese population (265/100 000 children under 5 years of age). The  Introduction: IgA vasculitis is the most often vasculitis in the paediatric population, presenting predominantly with palpable purpura, arthritis, abdominal pain and renal involvement. in Zagreb and 10 and 20 in Split. The peak incidence of IgA vasculitis was observed in February and October in Zagreb (26 and 25 patients), but with a stable number of patients from August until June. In Split peak incidence was in November (23 patients) with a predominance of disease in the period from October until February and lower number of patients in rest of the year. All of the patients in both centres presented with a characteristic rash. Introduction: The cytomegalovirus (CMV, human herpesvirus 5, HHV-5) is a common pathogen that is widespread all over the world. The seropositivity of CMV reaches a level of around 60% in highly developed countries, but stands at more than 95% in the developing world. The primary infection in immunocompetent patients is self limited or asymptomatic. CMV, like all herpes viruses, can establish long lasting latent infections. The possibility of the reactivation of the infection in patients receiving immunosuppressive therapy is a diagnostic and therapeutic challenge. There are few studies of CMV infection in patients with GPA. Latest reports indicate that those studies that do exist have reported a high risk of the heavy course of the disease and a poor prognosis, especially if the diagnosis of CMV is delayed.
Objectives: This study presents a patient suffering from granulomatosis with polyangiitis (GPA) which was complicated with CMV pneumonia. Methods: Retrospective analysis of patient's history.
Results: The diagnosis was made using the GPA criteria: pulmonary involvement (nodules, cavities, fixed pulmonary infiltrates), histopathology showing granulomatous inflammation within the wall of the artery, an ANCA positive result and renal involvement (proteinuria). The initial therapy involved a combination of glucocorticosteroids (GC), Cyclophosphamide and IVIG with initial remission of symptoms. During maintenance therapy with Azathioprine and low-dose GC, exacerbation was observed. High-resolution computed tomography (HRCT) of the lungs revealed widespread pulmonary infiltrates. A bronchoscopy with an endobronchial ultrasound (EBUS) revealed alveolar bleeding in the both lungs. CMV DNA was detected by the PCR method of analysing bronchoalveolar lavage and a lung tissue sample. The specific IgM and IgG antibodies in the sera were also detected. Furthermore, DNA of the human cytomegalovirus in the urine was found. Plasma CMV-DNA viral was not detected. Differential diagnoses were conducted but all tests were negative. Following the diagnosis of CMV pneumonia, the patient was started off on a course of Ganciclovir and the administration of GC was continued without Azathioprine. After two weeks of receiving Ganciclovir, the patient was examined and the DNA of the human CMV was not found in the urine or plasma. The specific IgM and IgG antibodies in the sera were still detected. After one month of antiviral therapy, immunosuppressive treatment (Cyclophosphamidum) was restored. At this time the patient's condition was good and their effort tolerance was normal.
Conclusion: In presented case study, the correlation between GPA, immunosuppressive therapy and CMV infection was a threat to health and life of our patient. Currently, no guidelines exist concerning the monitoring and treatment of CMV infections in paediatric patients with rheumatic diseases. In light of current knowledge, Introduction: Kawasaki disease (KD) is a predominantly medium vessel vasculitis with a predilection for the coronary arteries. Proposed etiology include a host of infectious causes including bacterial, viral and fungal agents (superantigen theory) coupled with genetic predisposition and autoimmunity. Co-occurrences of associated infections are described but relatively infrequent. Objectives: We report a case of Kawasaki disease with concurrent salmonella infection and a dengue positive serology Methods: A two-year-old male child presented with a history of fever for 7 days, irritability and abdominal distension since 2 days. Physical examination revealed evidence of non-purulent bulbar conjunctivitis, erythematous cracked lips with mucositis, dorsal edema of feet and hepato splenomegaly. Investigations revealed anemia, leucopenia, thrombocytopenia with elevated acute phase markers with hypoalbuminemia and transaminitis. His ultrasonography of abdomen showed organomegaly, gall bladder hydrops with evidence of ileoileal intussusception. Blood culture grew salmonella typhi.Also a dengue serology (IgM) came positive. Antibiotics along with supportive care was commenced in view of the positive blood culture. Suspecting an incomplete Kawasaki disease, a 2 D echocardiogram was ordered which revealed significant dilatation of coronaries (LAD2.8 mm Z score 3.7, LMCA 4.8mm Z score 6.5, RCA 2.1 mm Z score 0.8). With no improvement and persistent fever spikes after 72hours, he was treated with intravenous immunoglobulin (2 gms/kg) with a significant clinical improvement within 24 hours of the commencement infusion.Repeat echocardiogram at 8 weeks showed complete resolution of coronary dilatation. Results: Conclusion: Few case reports of KD with dengue fever has been reported. However, none with blood culture proven salmonella has been reported so far. Dengue positive serology in addition was extremely striking. Such a rarity coupled with features of both small vessel vasculitis (intussusception) and medium vessel vasculitis (KD) makes this case extremely unique. It is rare to have two diseases present at the same time with an additional inflammatory manifestation. Whether salmonella typhi with a positive dengue serology was a coexisting infection or the potential organism triggering the development of KD is debatable. However, this case concurs with the theory regarding the possible role of microorganisms in the etiology of KD.

Disclosure of Interest
None Declared. Introduction: Kawasaki disease (KD) is a predominantly medium vessel vasculitis with a predilection for the coronary arteries resulting from an interaction of a host of infections (superantigen theory), genetic predisposition and autoimmunity. Co-occurrences/associated unusual infections with KD has not been reported so far. Objectives: We describe two cases of KD with amoebic liver abscess and one case with salmonella typhi managed at a tertiary care centre in Western India Methods: Case 1 A 4-year-old male child was referred with persistent fever for eighteen days and abdominal pain. Ultrasonography abdomen had revealed an abscess (4cm x 4.8cm x 3.8cm) involving the right hepatic lobe. He had received multiple antibiotics and amoebicidal drugs. Clinical examination revealed mucositis, pedal edema, and bulbar conjunctivitis. Laboratory findings revealed anaemia, neutrophilic leucocytosis, thrombocytosis, elevated acute phase reactants and hypoalbuminemia. A transthoracic 2 D echocardiogram showed significantly dilated coronary arteries with right coronary artery aneurysm (RCA-Z score 4.31), left main coronary (LMCA-Z Score 3.22), left anterior descending artery (LAD-Z score 2.55). Immunohemagglutination (IHA) test for IgG Amoeba antibody was positive.

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With no response to antibiotics and the positive cardiac findings, IVIG was administered at 2 gm/kg with complete resolution of symptoms. Case 2 A 5-year-old female child presented with fever of 7 days, mucositis with a strawberry tongue, left anterior cervical lymph node enlargement (>1.5 cm), and pedal edema. A history of a macular rash and non-purulent conjunctival congestion was elicited. Laboratory findings were suggestive of KD; 2D ECHO showed (LMCA-Z score 0.06), (LAD -Z score of 1.91) and RCA -Z score of 5.97). IVIG was administered with a diagnosis of KD. Post IVIG, with persistent fever spikes and tender hepatomegaly, USG showed a 7.4 X 6.5 X 6.4 cm liquefied abscess. IHA for IgG amoeba antibody was positive. Percutaneous drainage of 200ml fluid with an 'anchovy sauce' like appearance with parenteral amoebicidal led to resolution of symptoms. Case 3