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Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part three

Genoa, Italy. 28 September – 01 October 2016

Poster Session: Miscellaneous rheumatic diseases

P381 Transient periosteal hyperostosis with dysproteinemia (Goldbloom syndrome): two cases report

Riccardo Papa1, Alessandro Consolaro1, Francesca Minoia1, Roberta Caorsi1, Gianmichele Magnano2, Marco Gattorno1, Angelo Ravelli1, Paolo Picco1

1Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy; 2Radiologia, Istituto Giannina Gaslini, Genoa, Italy
Presenting author: Riccardo Papa

Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrome (GS), is a rare pediatric disease characterized by recurrent crisis of bone pain, fever, increased inflammatory markers and dysproteinemia. From 1966 only few cases have been reported in the English literature.

Objectives: To better define the clinical and epidemiological features of GS.

Methods: We report clinical, laboratory and radiological features of our patients in Table 1, comparing with the English literature.

Results: Case 1 was a 9-year-old girl who presented daily crisis of bone pain at the lower limbs, associated with fever spikes, limping and nocturnal awakenings. Physical examination was normal. Laboratory tests showed mild anemia, thrombocytosis, increased inflammatory markers and high antibody levels against streptolysine O and DNase-B (ASO 4280 IU/ml and ADN-B 6310 UI/ml, respectively). Throat swab was positive for group A β-hemolytic streptococcus (GAS). Unusual dysproteinemia, characterized by hypoalbuminemia with increased a1, a2 and g globulinemia, was noted. X-ray evaluation of the lower limbs showed increased bone density at femurs and tibias with signs of periostitis: on STIR sequence MRI these bones presented areas of hyperintense signal. Bone biopsy revealed a thickened periosteum that was strongly adherent to the underlying tissue. Histopathologic study showed signs of chronic inflammation. Steroid treatment was started, leading to a prompt resolution of the clinical picture within few days.

Case 2 was a 6-years-old girl who developed, two weeks after an untreated febrile pharyngitis, daily attacks of severe pain at ankles with fever. Joint examination was normal. Throat swab was positive for GAS. In the following weeks, recurrent crisis of bone pain persisted with a severe weight loss. She was hospitalized and laboratory tests showed mild anemia, thrombocytosis and unusual dysproteinemia with hypoalbuminemia and high a1, a2 and g globulinemia. Inflammatory markers and antibodies against GAS were elevated (ASO 775 IU/ml, AND-B 1660 U/ml). STIR sequence MRI showed hyperintense areas at the femurs, tibias, humerus and ulnas, associated with a thickened pretibial soft tissue. Bone marrow biopsy showed signs of chronic inflammation. A short cycle of steroids was administered with rapid resolution of symptoms, turning off inflammatory markers. Immaging became normal after three months.

Conclusion: Our patients fulfill the GS features with evidence of previous GAS infection. Our patients lived in the same area of Northern Italy and presented the onset of GS a week apart. Our experience suggests that a timely diagnosis and a short cycle of steroid may rapidly change the history of GS.

Disclosure of Interest: None Declared

Table 1 (abstract P381). Main features of our patients with English literature review

P382 Diagnosis of acute rheumatic fever with the 2015 revision of Jones criteria

Roberto Pillon1, Denise Pires Marafon2, Lidia Meli2, Claudia Bracaglia2, Andrea Taddio1,3, Fabrizio De Benedetti2

1University of Trieste, Trieste, Italy; 2Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy; 3Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy
Presenting author: Roberto Pillon

Introduction: In 2015 the historic Jones criteria for the diagnosis of Acute Rheumatic Fever (ARF) were revised introducing two different sets of criteria for low-risk and for moderate/high-risk populations (according to ARF incidence). In Italy the exact ARF incidence is unknown but small regional or local reports suggest an incidence of 2-5/100.000 per year, suggesting that our population might be considered at moderate risk for ARF.

Objectives: To evaluate the performance of the revised Jones criteria in a retrospective population and to compare it with the performance of the previous version of Jones criteria.

Methods: We conducted a retrospective study on 288 patients with ARF (108 female; median age 8.5 years, IQR 7.1-10.3) diagnosed from 2001 to 2015 in a Pediatric Rheumatology Division by pediatric rheumatologists, discharged with an ICD 9 code consistent with ARF. We retrospectively applied the two sets (for low-risk and for moderate/high-risk) of the 2015 revised Jones criteria and the 1992 version of the Jones criteria.

Results: Of 288 patients, 253 (87.8%) met the 1992 version of the Jones criteria, 237 (82.3%) met the revised criteria for low-risk populations and 259 (89.9%) for moderate/high-risk populations. None of these differences was significant. Prevalence of major and minor criteria is shown in Table. With the exception of difference in arthritis, the 1992 version and the 2015 revised version did not show major differences. Of the 288 patients with a clinical diagnosis of ARF 29 did not meet any version of the Jones criteria. Patients in this group presented with isolated chorea or silent carditis without other manifestations.

Prevalence of the clinical characteristics and comparison among the 1992 version of Jones criteria and the 2015 revised Jones criteria (low risk and moderate-high risk populations):

  1992 version 2015 low risk 2015 mod-high risk 1992 version vs 2015 low risk* 1992 version vs 2015 mod-high risk*
Total of patients 253 237 259 0.08 0.51
MAJOR CRITERIA Arthritis 94 (37.2) 88 (37.1) 209 (75.3) 1.0 <0.0001
Erythema marginatum 3 (1.2) 3 (1.3) 3 (1.2) 1.0 1.0
Chorea 48 (19) 49 (17) 49 (17) 0.73 0.91
Carditis 230 (90.9) 247 (85.8) 247 (85.8) 0.51 0.39
MINOR CRITERIA ESR/CRP 218/236 (92.4) 208/259 (80.3) 226/259 (87.3) 0.0026 0.13
Fever 140 (55.3) 157 (54.5) 196 (68.1) 0.65 0.0004
Arthralgia 186/249 (74.7) 166/235 (70.6) 8/257 (3.1) 0.36 <0.0001
Prolonged PR 38 (15) 34 (14.3) 35 (13.5) 0.90 0.70

Values are expressed in Number (percentage). *p value (Fisher Exact test)

Conclusion: The revised Jones criteria for low-risk populations are slightly more sensitive than the 1992 version of Jones criteria, while the revised Jones criteria for moderate/high populations are slightly less sensitive than the 1992 version. In this population, the revised criteria did not substantially modify the diagnosis of ARF. Approximately 10% of patients presented with isolated chorea or silent carditis.

Bibliography:

1. Gewitz M, et al. Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography: A Scientific Statement From the American Heart Association. Circulation. 2015.

2. Breda L, et al. Population-Based Study of Incidence and Clinical Characteristics of Rheumatic Fever in Abruzzo, Central Italy, 2000-2009. The Journal of Pediatrics 2012

Disclosure of Interest: None Declared

P383 Restrospective view of primary raynaud’s phenomenon in childhood

Enes Turan, Sara Sebnem Kilic

Pediatric Rheumatology, Uludag University Medical Faculty, Bursa, Turkey
Presenting author: Sara Sebnem Kilic

Introduction: Raynaud’s phenomenon (RP) refers to transient vasospasm of peripheral arteries and arterioles, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or emotional stress. The diagnosis of RP can be made on the basis of the patient’s clinical symptoms. Primary RP occurs without underlying disease and is considered a benign. Connective tissue diseases are the most common cause of secondary RP. Objectives: Detailed history, physical, and laboratory findings of the patients with primary RP were evaluated restrospectively.

Methods: Data collection was performed via the patient files. The study was approved by the Ethical Committee of the Uludag University Faculty of Medicine.

Results: Out of the 58 patients, 38 were girls whereas 20 were boys. The patients’ boy/girl ratio was 1.9 (38/20) and their ages ranged from 6 to 21 years (median:16 years). The median age at onset of complaints due to RP was 13 (minimum:2, maximum:17), median age at diagnosis:15 (minimum:3, maximum:17). In 37.9% cases (n = 22) There were similar complaints in first-degree relatives in 37.9% of patients. The most common symptom was feeling cold in the extremities ends (100%), followed by pain (87%) and tingling sensation (70.7%). While 38 patients(65.5%) had biphasic colour changes, 20 (34.5%) had triphasic colour changes. Triphasic colour change was statistically significant with high incidence (p = 0.026) in cases with ANA positivity and family history. Low titer positive ANA was present in 14 patients(24.1%). Presence of migraine in 29,3% of the cases was the most common disease associated with RP. Migraine was significantly more frequent in the girls compared to the boys (p = 0.02). Furthermore, cases with migraine had a significant lower hemoglobin levels and significant higher mean platelet volume. Apart from preventive measures, calcium channel blockers (CCB) were the most used drugs (n = 32, 55.2%) and were beneficial in 78.1% (25 out of 32). Nitroglycerin patch was applied to the rest of patients (n = 26, 44.8%), which was useful to relieve the symptoms in 50% of them. Sildenafil was used in one patient who was resistant to both of the drugs and the result was positive.

Conclusion: There is very limited data concerning childhood RP. In previous studies conducted in children there is no data on association between RP and migraine. Anemia in patients with RP was thought to be a predisposition to migraine development. Calcium channel blockers were found to be more effective than nitroglycerin patch treatment. Further studies with a greater number of patients are required in order to confirm our results.

Disclosure of Interest: None Declared

P384 Prevention of Sjögren’s syndrome by immunosuppressants in children with positive anti-ro antibodies and chronic nonspecific complaints

Yasuhiko Itoh, Tomoko Shigemori, Shingo Yamanishi, Hidehiko Nagasaki

Department of Pediatrics, NIPPON MEDICAL SCHOOL, Tokyo, Japan
Presenting author: Yasuhiko Itoh

Introduction: Anti-Ro antibodies are found in children with either Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) or, occasionally, chronic nonspecific complaints such as fatigue and low-grade fever. We have reported that about 10% of children with chronic nonspecific complaints and with positive antinuclear antibodies were positive for anti-Ro antibodies.

Objectives: Although a few of them showed positive lip biopsy findings equivalent to that of SS (subclinical SS), the majority of such children exhibited no evidence of SS. To clarify the pathogenic role of anti-Ro antibodies in various conditions and the future development of dryness, those children have been followed for more than 10 years, both clinically and immunologically.

Methods: The patients included in this study were as follows: 1) 27 children with chronic nonspecific complaints, with anti-Ro antibodies, and with negative lip biopsies; 2) 10 children with chronic nonspecific complaints, with anti-Ro antibodies, and with positive biopsies; 3) nine children with SLE and with positive anti-Ro antibodies; 4) three children with MCTD and with positive anti-Ro antibodies. They have been followed for more than 10 years. Anti-Ro antibodies were measured by using either the Ouchterlony, ELISA, western immunoblot or, in some cases, RNA-immunoprecipitation methods.

Results: Twenty-three out of 27 patients in group 1 showed no evidence of SS even after more than 10 years. Most of the patients in group 2 who had not been treated by immunosuppressants have gradually developed dryness. On the other hand, patients who had been treated have developed no or little dryness. Patients in the groups 3 and 4 have developed no dryness.

All patients in groups 3 and 4 had been treated by immunosuppressants against their basic diseases and developed no dryness. In the same way, most patients with only nonspecific complaints treated with immunosuppressants did not develop dryness.

Conclusion: These results suggest that there may be a chance to prevent SS with immunosuppressants in children with positive anti-Ro antibodies as long as the treatment is initiated before they develop dryness.

Disclosure of Interest: None Declared

Poster Session: Psycho-social aspects and rehabilitation

P385 Invention of rehabilitative games using the leap motion controller for hand rehabilitation in children with juvenile idiopathic arthritis and investigation of its’ effectiveness

Ela Tarakci1, Nilay Arman1, Devrim Tarakci1, Yusuf S. Akgul2, Ozgur Kasapcopur3

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Istanbul University, Istanbul, Turkey; 2Department of Computer Engineering, Gebze Institute of Technology, Kocaeli, Turkey; 3Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Ela Tarakci

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease. Depending on the underlying pathologies, the common symptoms of this disorder are the limitations of the upper extremity joint movement angles, muscle imbalance and the functional limitations caused by the contracture due to these patients. By utilizing exciting new sensor technologies, such as Microsoft Kinect, Nintendo Wii and Leap Motion, practical game based rehabilitation applications have been becoming popular in the current.

Objectives: The aim of this study was to investigation of effectiveness of invented rehabilitative games using The Leap Motion Controller (LMC) for hand rehabilitation in patients with JIA.

Methods: 18 patients with JIA (14 girls, 4 boys), age range 8-18 participated in this study. Range of motion (ROM) of hand, grip strength, functional ability, fatique and quality of life were assessed with a goniometer, hand dynamometer, Childhood Health Assessment Questionnaire (CHAQ), Numeric Rating Scale (NRS), and the Pediatric Quality of Life Inventory (PedsQL), respectively. In order to improve hand functions, two games were invented with hand free LMC by our team. One of the games, “Leapball” was invented as picking the ball and throw to the basket. The game is to ensure the activities of repeated hold and release by simulating the hand grip function. The other game, “CatchAPet” is to intend touching the rabbits going out its burrow for simulating wrist flexion and extension. The patients completed a 8 week individually planned leap motion based exercise programme 3 times a week at the department of physical therapy and rehabilitation. Duration of the each treatment session was 30-45 minutes. Parameters of the games (Time, size of ball, speed of rabbits) were adjusted according to patient’s functional ability and progressed during the treatment.

Results: The mean age and duration of disease was 12.22 ± 3.30 (age range 8-18), 7.28 ± 4.22 years, respectively. The means of the pre/post treatment scores of NRS fatigue were 6.11 ± 1.53 / 2.22 ± 1.21, PedsQL-patients 63.71 ± 18.13 / 85.93 ± 12.08, PedsQL-parents 57.63 ± 18.88 / 80.80 ± 13.21, CHAQ-total 1.36 ± 0.67 / 0.30 ± 0.28, CHAQ-pain 31.94 ± 30.49 / 6.94 ± 11.77, and CHAQ-well being scores were 55.28 ± 19.28 / 21.94 ± 15.44, respectively. Table 2 shows ROM of wrist flexion and extension, fingertip to palm distance, hand grip and pinch grips scores for pre and post treatment. Significant statistical differences were found between pre and post-treatment all outcomes. (p < 0.001).

Conclusion: The study demonstrated that participating in a 8-week individually planned leap motion based exercise programme improves the range of motion of hand, grip strength, fatigue, physical function and the quality of life in patients with JIA. We think that improvements of the results may base on realistic animations of hand, virtual environments, patient motivation, consistent visual feedback and feasible and easy progression options of the invented games.

Disclosure of Interest: None Declared

Table 2 (abstract P385). ROM of wrist flexion and extension, fingertip to palm distance, hand grip and pinch grips scores for pre and post treatment

P386 Lupus and you: developing a workshop for young people with lupus and their families

Emily Wilson1, Hanna Lythgoe1, Eve Smith1,2, Jenny Preston1,3, Michael W. Beresford1,2,3

1Department of Paediatric Rheumatology and Psychology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 2Department of Women’s and Children’s Health, Institute of Translational Medicine, Liverpool, UK; 3UK Experimental Arthritis Treatment Centre for Children, University of Liverpool, Liverpool, United Kingdom
Presenting author: Emily Wilson

Introduction: Lupus is a severe, autoimmune disease, potentially affecting any organ in the body. It is very rare in children and young people. As a regional service and the UK’s only ‘Centre of Excellence for Childhood Lupus’, our patients live across a large geographical catchment area. Many of the patients accessing our service report never having had the chance to meet another young person with the condition and how isolating this could feel. The mental health needs of young people with chronic health conditions are well known and potentially debilitating.

Objectives: We aimed to develop a series of day-long multidisciplinary “Lupus and You” workshops to be attended by young people with lupus and their families, within the Lupus Centre at Alder Hey Children’s Hospital. We wanted to continue to be responsive to the ongoing needs of our patients whilst also looking to intervene proactively to support them in developing resilience and coping strategies to minimise the impact of their condition on their lives.

Methods: 7 families participated in the first workshop which focused on two main themes; managing fatigue and research participation.

Fatigue was one of the most commonly reported concerns identified by young people and their parents on a routinely completed pre-clinic screening tool. A recent survey of young people with lupus suggested patients wanted to know more about research participation.

All participants completed a range of standardized measures to capture psychological well-being (including fatigue, emotional well-being, resilience and quality of life) at the time of attendance. Evaluations forms were given out to all attendees in order to review the day and identify areas for consideration within future workshops.

Results: Participants participated in exercises designed to facilitate sharing of difficulties as well as examples of strategies utilized to manage fatigue. The team’s psychologist, physiotherapist and occupational therapist also shared ideas and strategies for families to consider. Information about local and national research in paediatric lupus was shared in an interactive session.

High levels of fatigue were identified amongst lupus patients (mean score on the fatigue severity scale 5.1 (range 4 – 5.8) where people scoring above 3 points are considered to suffer with fatigue). Young people and their families reported increased confidence in managing fatigue when pre- and post-workshop data were compared.

Otherwise there was considerable variation in the extent to which young people were coping with having lupus. The results will be reviewed with the individuals and their parents in order to inform ongoing intervention and support.

Feedback from workshop evaluations indicated that attendees found the activities to be helpful and convenient to attend. Support for siblings, medication, and knowledge of common symptoms were identified as potential topics for future workshops.

Conclusion: The “Lupus and You” workshop allowed young people with lupus and their families to share experiences of managing this chronic illness, to develop supportive relationships whilst also developing resilience and practical strategies for living their lives fully despite their ongoing health needs.

Workshops such as this could be used as a forum to facilitate collection of important data from patients with rare diseases, whilst simultaneously benefitting patients and their families.

The workshops are being considered as part of a stepped-care model of psychological support offered to lupus patients.

Disclosure of Interest: None Declared

P387 Development and usability testing of an ipad and desktop psycho-educational game for children with juvenile idiopathic arthritis and their parents

Lynn R. Spiegel1,2, Jennifer Stinson3,4, Mark Connelly5, Adam Huber6, Nadia Luca7, Argerie Tsimicalis8, Stephanie Luca9, Naweed Tajuddin3, Roberta Berard10, Julie Barsalou11, Sarah Campillo12, Brian Feldman1, Shirley Tse1, Paul Dancey13, Ciaran Duffy14, Nicole Johnson7, Patrick McGrath15, Natalie Shiff16, Lori Tucker17, Charles Victor18

1Rheumatology, Hospital for Sick Children, Toronto, Canada; 2Pediatrics, University of Toronto, Toronto, Canada; 3Child Evaluative Health Sciences, The Hospital for Sick Children, Toronto, Canada; 4Lawrence S. Bloomberg Faculty of Medicine, University of Toronto, Toronto, Canada; 5Psychology, University of Kansas Medical Center, Lawrence, KS, United States; 6Rheumatology, IWK Health Center, Halifax, Canada; 7Rheumatology, Alberta children’s Hospital, Calgary, Canada; 8Ingram School of Nursing, Mcgill University, Montreal, Canada; 9Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Canada; 10Rheumatology, Children’s Hospital of Western Ontario, London, Canada; 11Rheumatology, CHU Ste-Justine, Montreal, Canada; 12Rheumatology, Montreal Children’s Hospital, Montreal, Canada; 13Pediatrics, Memorial University of Newfoundland, St John’s, Canada; 14Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 15Research, Innovation and Knowledge Translation, IWK Health Center, Halifax, Canada; 16Pediatrics, University of Florida, Gainesville, FL, United States; 17Rheumatology, BC Children’s Hospital, Vancouver, Canada; 18Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
Presenting author: Lynn R. Spiegel

This abstract is not included here as it has already been published.

P388 Icancope: user-centred design and development of a smartphone app to support self-management for youth with arthritis pain

Lynn R. Spiegel1,2, Chitra Lalloo3,4, Lauren Harris4, Joseph Cafazzo5, Lori Tucker6, Kristin Houghton6, Brian Feldman1,7, Nadia Luca8, Ronald Laxer1,9, Jennifer Stinson3,4

1Pediatrics, University of Toronto, Toronto, Canada; 2Rheumatology, The Hospital for Sick Children, Toronto, Canada; 3Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada; 4Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada; 5Centre for Global eHealth Innovation, University Health Network, Toronto, Canada; 6Pediatrics, University of British Columbia, Vancouver, Canada; 7Rheumatology, Hospital for Sick Children, Toronto, Canada; 8Rheumatology, Alberta Children’s Hospital, Calgary, Canada; 9Rheumatology, The Hospital for Sick Children, Toronto, Canada
Presenting author: Lynn R. Spiegel

This abstract is not included here as it has already been published.

P389 Use of the Xbox Kinect virtual gaming system to improve upper extremity functions and activity performance in patients with with juvenile idiopathic arthritis

Nilay Arman1, Ela Tarakci1, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy And Rehabilitation, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: Juvenile idiopathic arthritis (JIA) is most common chronic rheumatic disease in childhood. The upper extremity involvement in JIA causes muscle imbalance, joint destruction, pain, stiffness and limitations on activities of daily living (ADL) in varying degrees. It has been reported that improvements of upper extremity functions were achieved by video-based games (VBG) in various disease groups.

Objectives: The aim of this preliminary study was to investigate effects of client-centered task-oriented activity training (TOAT) with VBG on upper extremity functions and activity performance in children with JIA.

Methods: 23 patients (19 girls, 4 boys) with JIA (7 oligoarticular, 16 polyarticular) have upper extremity involvements, participated in this study. Muscular strength was measured by using a portable digital handheld dynamometer. Also, hand grip and pinch strength evaluations was done by a dynamometer and pinchmeter. ADL was evaluated by Duruoz Hand Index (DHI) and Childhood Health Assessment Questionnaire (CHAQ). Activity performance was performed by Jebsen Hand Function Test (JHFT). Also, activity performance and satisfaction were measured by The Canadian Occupational Performance Measure (COPM). Five most important problems of activity performance were determined with the patient and his/her parents. Fatigue severity was measured by Numeric Rating Scale (NRS). We have created training protocol with Xbox 360 games. We prefered ‘Dance Central2’, one of the Xbox 360 games, for warming (macerana dancing, 10 minutes). Other games, ‘Fruit Ninja’, ‘Table Tennis’, ‘Boxing’, ‘Volleyball’, ‘Darts’ and ‘Bowling’ were selected appropriately for TOAT according gto 5 most important limited ADL of each patient that determined with COPM. The games were set as client-centered for 45-60 minutes by the physiotherapist. All the participants completed 8 weeks (3 times in a week) of client-centered TOAT with Xbox 360 Kinect™ games.

Results: The mean age and duration of disease was 12,26 ± 3,09 (age range 8-18), 6,78 ± 4,16 years, respectively. 20 of patients had bilateral involvement of upper extremity. Wilcoxon test showed significant statistically differences pre and post-treatment, in almost all the values, except some scores of subtasks of JHFT (p < 0.001). All muscles strength of upper extremities were statistically significant increased (p < 0.001). Table 3 shows the scores of functional ability, fatigue, grip and pinch strength and activity performance outcomes pre and post-treatment.

Conclusion: Our Kinect Xbox 360 protocol that inclued client-centered TOAT has showed improvements on upper extremity functions and activity performance in patients with JIA. We think that TOAT with VBG improves the activity performance and physical functions via being stimulative and interactive in order to provide feedback and to increase interest and motivation. Xbox Kinect virtual gaming system is more fun and provides motivation, and may be a preferable method of treatment for patients with JIA but further studies are needed to compare with the potential benefits of VBG and conventional therapy in patients with JIA.

Disclosure of Interest: None Declared

Table 3 (abstract P389). Scores of outcome measures pre and post-treatment

P390 The truth, the whole truth and nothing but the truth: methotrexate and compliance; the JIA patient perspective

Madeleine Rooney1, Roisin Campbell2, Catherine Wright3

1Center Experimental Medicine, QUEENS UNIVERSITY BELFAST, Belfast, United Kingdom; 2Pharmacy, Belfast Hospital Trust, Belfast, United Kingdom; 3Arthritis Care, Belfast, United Kingdom
Presenting author: Roisin Campbell

Introduction: Methotrexate is the first-choice disease-modifying drug (DMARD) for the treatment of JIA. It is accepted as an effective drug that induces remission in more than 70% of patients. Serious adverse effects are infrequent and usually transient due to rigid monitoring guidelines. However the impact on the quality of a child’s and their family lives has yet to be adequately researched.

Objectives: The aim of this research was to investigate the JIA patient’s perspective and tolerance and compliance of oral or parental Methotrexate in accordance with BSPAR guidelines.

Methods: Children between 10-17 years of age with a diagnosis of JIA (all sub-types included) attending the Paediatric Rheumatology Day Ward were asked to complete an adapted MISS (Methotrexate Intolerance Severity Score) questionnaire during their routine medicines reconciliation and compliance interview, carried out by the paediatric rheumatology pharmacist. A total of 15 questionnaires were completed.

Arthritis Care, host activity weekends for children between 10 – 17 years of age with a diagnosis of JIA, during one such weekend they devoted a group session to discussing and completing the adapted MISS questionnaire. To date a total of 15 questionnaires have been completed in the two different settings and with two interviewees of differing provenance.

Results: Results

Venue MISS score range MISS average score
Rheumatology Day Ward 0 – 8 3.6
Activity Weekend 4 - 32 19

The children were asked “choose one word to describe how you feel about taking Methotrexate”.

Children attending Rheumatology Day Ward examples – Fine, Ok, Necessary, Annoying.

Children at the Activity Weekend examples – Evil, Depressed, Stressed, Sore, Terrible, Hate.

Conclusion: The MISS questionnaire is a well -designed validated tool widely used by Paediatric Rheumatology teams to assess Methotrexate tolerance in JIA patients. Anticipatory nausea and behavioural effects of Methotrexate are not clinically evident during physical assessment but may be detected by the MISS questionnaire. However this research poses the question how much value can we place upon the results we receive if they are so profoundly affected by the environment in which they are completed and the person who is requesting the information.

The narrow score range and low average MISS score obtained when completed with the rheumatology pharmacist creates the impression that Methotrexate is a well-tolerated drug which young patients find at worst “annoying”. Is it safe to dismiss this as the Hawthorne effect? (or should we say young patients simply trying to please us?).

Yet the dramatically higher average score and broad score range obtained at the Activity weekend indicate that Methotrexate has a significant detrimental effect on young patients creating a greatly anticipated stressful event every week.

Arthritis Care, activity weekends create an environment where young patients are free to express themselves in their own language and allow their anger and emotions to be expressed away from reproachful and anxious parents.

These findings challenge the validity of this questionnaire if it is so dependent on the environment and the questioner. Our preliminary finding demonstrate the need for further research in this field and highlight the already underestimated degree of morbidity and non-compliance associated with MTX in children with rheumatic diseases.

Disclosure of Interest: None Declared

P391 Fatigue in patients with juvenile idiopathic arthritis: relationship to perceived health, physical health, self-efficacy, and participation

Wineke Armbrust1, Otto Lelieveld2, Jolanda Tuinstra3, Nico Wulffraat4, Joyce Bos2, Jeanette Cappon5, Marion van Rossum5, Mariët Hagedoorn6

1Beatrix Children’s Hospital, Department of Pediatric Rheumatology and immunology, Groningen, Netherlands; 2Center for Rehabilitation, Groningen, Netherlands; 3Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; 4Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, Netherlands; 5location: Dr. Jan van Breemenstraat, Reade, Center for Rehabilitation and Rheumatology, Amsterdam, Netherlands; 6Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Presenting author: Wineke Armbrust

Introduction: Fatigue is present in 60-75% of patients with JIA. Fatigue is multidimensional, meaning that it can be physical or mental in its manifestation and cause. The causes and consequences of fatigue are not well known.

Objectives: To assess the presence and severity of fatigue in patients with JIA, including factors presumed associated with fatigue (e.g., disease activity, disability, pain, physical activity, exercise capacity, and self-efficacy), and whether fatigue is related to participation in physical education classes, school attendance, and sports frequency.

Methods: Eighty patients with JIA (age 8-13) were included. Primary outcome measurements were fatigue (multi dimensional Pediatric-Quality-of-Life-Inventory (PedsQl)-Fatigue-scale) and energy level (uni dimensional VAS scale (0-10; 0 meaning respectively lowest an highest energy)). Predictors of fatigue were disease activity (PGAS (0-10 cm)), disability(CHAQ), physical activity (accelerometer), exercise capacity (Bruce test) and self-efficacy (Childhood Arthritis Self-Efficacy Scale). Consequences of fatigue were school attendance and participation to physical education class and sports using a questionnaire.

Results: Median age was 9.8 years [8.7; 11.0], disease duration was 2.95 years [1.22; 6.19], disease activity was .03 [.00;.90] and 60 patients were on medication. Sixty percent of patients with JIA suffer from daily low-energy levels; 27% suffer from very low-energy levels more than half the week. Fatigue measured with the PEDsQL was higher compared to the norm-population (77.5 compared to 80.5). High fatigue was correlated with low energy levels (P < .01). Patients who reported higher levels of fatigue showed higher disability (P < .01), higher pain (p < .01), lower exercise capacity p = .05), lower physical activity (<.01), and lower self-efficacy scores (P < .01). Disability (p = .01) and low self-efficacy (p = .04) were main predictors of fatigue in a multivariate model. Self-efficacy was a predictor of fatigue but did not act as moderator. Low energy levels were correlated with high disability (p < .01), pain (p = .01), a lower PAL (p < .01), and being on medication (p = .03). Low energy levels were best predicted by disability (p < .01)and low physical activity (p < .01) in a multidimensional model. Fatigue was a predictor for sports frequency (p = .01) but not for school attendance (p = .08).

Conclusion: Fatigue is present in more than half of the patients with JIA. Uni- and multidimensional measurements can be used to determine the level of fatigue. However, related factors were different for both measurements as single correlations as well as in a prediction model, indicating that they are not interchangeable. Interventions aimed at reducing perceived disability, stimulating physical activity, and enhancing self-efficacy might reduce fatigue and thereby enhance participation.

Trial registration identifying number: R@W Trial number ISRCTN92733069

Disclosure of Interest: None Declared

Table 4 (abstract P391). Patient characteristics and outcome measurements of 80 (52 female) patients

P392 Nurses’ experiences of meeting children afraid of needlestick

Anna Vermé1, Ylva Lampela2

1Pediatric Rheumathology, Karolinska, Sweden; 2Youth clinic, Södersjukhuset, Stockholm, Sweden
Presenting author: Anna Vermé

Introduction: Regardless where nurses work they meet both adults and children who are scared of needle stick. Both the empirical and the literature reveals that the meeting with the children who are afraid of needle stick can be challenging and difficult to manage. According to competence description to pediatric nurses work to ensure that blood tests, examinations and treatments are tailored to the individual child. When meeting with children who are afraid of needle stick and meeting their families, it is important that the nurse takes into account several factors: the child’s age, developmental stage, previous experience and the situation the child is in. The parents’ past experiences and feelings about needle stick can affect how the child reacts to different procedures.

Objectives: To describe nurses’ experiences of meeting children scared of needle stick and meeting their families.

Methods: The study was qualitative and the collected material was analyzed using qualitative content analysis. Five nurses who worked in child care 3-42 years participated in the study.

Results: The results were reported as three categories and eleven subcategories. The categories were: Challenging encounters with children who are afraid of needle stick, Cooperation and Child different reactions. The meeting was affected by various things such as the nurse’s own experience of meeting children who are afraid of needle stick, the circumstances and the nurse’s ability to build trust and confidence. A working relationship with colleagues, children and parents was crucial so the situation would be as good as possible.

Conclusion: Fear of needle stick is a common phenomenon, especially in pediatrics. Sharing experiences and gaining knowledge on this subject make it easier for nurses who feel insecure about meeting children who are afraid of needle stick and their families. We also hope that this work will lead to discussions on this topic in the working groups who in their daily work meet children who are afraid of needle stick.

Disclosure of Interest: None Declared

P393 The first transition clinic from pediatric to adult rheumatology in Turkey

Ayse Huri Ozdogan1, S Ugurlu1, K Barut2, A Androvic2, O Kasapçopu3

1Department of Adult Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey; 2Department of Pediatric Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey; 3Department of Pediatric Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey
Presenting author: Ayse Huri Ozdogan

Introduction: -

Objectives: To assess the outcome of the first transition clinic from pediatric to adult rheumatology in İstanbul, Turkey

Methods: A transition outpatient clinic has been started in 2014 in Cerrahpaşa Medical Faculty with the contribution of 2 adult and 4 pediatric rheumatologists who get together once every 2 to 3 months. Patients who have been followed in the pediatric rheumatology clinic were asked to attend the transition OPC after the age of 18. These patients are seen by all the attending physicians initially in the pediatric clinic. A standardized form is filled for all which includes information on diseases history, last physical and laboratory examinations, and treatment. The next appointment is given for the adult rheumatology clinic where they are seen by one of the adult rheumatologist who have attended the first visit. All patients seen in the transition clinic during this 2 year period were contacted to assess the follow-up and outcome.

Results: Since 2014, 82 patients (52 F, 30 M) were seen in the transition OPC. The mean age was 21 years (18-24). The diagnoses of the patients were FMF in 44, JIA in 28, BD in 3, SLE in 2, vasculitis 2 and others 3. Fifty six patients were regularly attending the adult rheumatology clinic (68%), whereas 3 were being followed in another center, 9 never attended to a visit in the adult clinic and 14 were lost to follow up. The attendance rate was somewhat higher in girls compared to boys (71% vs 60%). Their main complaints were the crowdness of the adult clinics (8 patients) and insufficient attention (7 patients).

Conclusion: These are the preliminary results of the first transition clinic from pediaitric to adult rheumatology from Turkey. Compared to well established clinics from other countries like Canada, the attendance rate and the age at transition are comparable. In order to increase the attendance and the overall satisfaction of the patients the programme needs to be improved.

Disclosure of Interest: None Declared

P394 The use of a screening tool to support children and young people with lupus and their families in prioritising issues for discussion in clinic appointments

Emily Wilson1, Jody Etheridge1, Eve Smith1,2, Katie Dobson1, Sue Kemp1, Michael W. Beresford1,2

1Department of Paediatric Rheumatology and Psychology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 2Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Presenting author: Emily Wilson

Introduction: Patients attending the UK’s only ‘Centre of Excellence for Childhood Lupus’ at Alder Hey Children’s Hospital, Liverpool, routinely attend clinic appointments every three months. During these appointments there is pressure for clinicians to review complex medical presentations and treatment in a timely manner. As a service we recognise the importance of holistic, multi-disciplinary care and the need to consider the priorities of patients and their families in relation to the illness and its management.

The challenges faced by patients in asking questions and asserting influence over a medial consultation are widely acknowledged and so a ‘screening tool’ was developed to facilitate this process.

Objectives: To develop a screening tool to facilitate conversations with young people with lupus and their families in order to identify areas of concern that they would like to discuss within or outside of a given clinic appointment.

Methods: Immediately prior to each clinic appointment, patients with juvenile-onset systemic lupus erythematosus (‘lupus’) and the parent or guardian accompanying them were asked to complete a bespoke screening questionnaire.

The tool was developed through detailed consultation with patients, parents and multi-disciplinary team members (nursing, occupational therapy, physiotherapy and psychology). Several versions were developed to enable the tool to be utilised by children of different ages as well as their parents. Parents of all children were encouraged to identify issues that concerned them about their child but also areas in which they felt they were struggling themselves regarding their child’s condition.

The completed tools were brought into the consultation for consideration by the attending clinicians and team. Where appropriate, the screening questionnaires influenced the topics of conversation within the appointment, otherwise, plans were made to contact the multi-disciplinary team separately.

The completed questionnaires formed part of the patients’ case notes. Data were also collated and used to inform wider service development within the lupus service.

Results: Completed screening tools were reviewed over a 10-month period. 36 were completed (19 young people, 17 parents).

Amongst the young people, the most frequently reported concerns were: fatigue (81%), appearance (58%), pain (53%) and exercise (53%). Parents were most concerned for their children regarding: fatigue (65%), pain (65%), emotions (59%), sleep (59%) and support from school or college (53%). In terms of areas in which parents were concerned about themselves, most frequently reported were: concerns regarding the future (82%), feeling upset regarding their child’s condition (59%), supporting their child (59%) and having adequate support from others (59%).

Conclusion: The questionnaires have received positive feedback from patients, parents and staff in terms of their ease of completion and their utility in terms of highlighting issues for further discussion either within clinic or otherwise. They have also helped especially to normalise the role of psychological well-being in the management of lupus.

The data have been used to influence service development including:

  • Development of a ‘health passport’ document to facilitate communication between family, hospital and school

  • Development of a workshop for patients with lupus and their families focussing on fatigue management

  • Development of a future workshop for patients and their families focussing on transition, the future and becoming a young adult with lupus.

Disclosure of Interest: None Declared

P395 “On the journey diagnosed with juvenile idiopathic arthritis (JIA)”– a bag with relevant information that generates trust

AnnaCarin Horne, Karin Palmblad, Malin Höglund

Pediatric rheumathology, Karolinska Hospital, Stockholm, Sweden
Presenting author: Malin Höglund

Introduction: When a child is diagnosed with juvenile idiopathic arthritis (JIA) a lot of questions evolve among family members and the social surrounding. The initial information provided by the doctor may be overwhelming and it may be hard to take in all the details. Many seek additional information from literature or from the internet but feel overwhelmed by all the different information available.

Objectives: To provide parents and children with correct information included in an information bag and to evaluate the response on this initiative.

Methods: “On the journey diagnosed with JIA” is a information bag created in collaboration between the pediatric rheumatology unit at Astrid Lindgren Children’s Hospital, the Swedish Rheumatism Association, Young Rheumatic Patients, and AbbVie Sweden. The information bag contains informative brochures, lists of adequate web sites with balanced information, and information from parent and patients associations. In addition, a calendar is provided to encourage self-management of the disease. All information is carefully checked by the clinic and based on medically correct information. The bag is a compliment to the information that the family receives at the clinic; a way for the patient and family to continue the journey at their own pace back home. The pilot project consisted of 20 bags that were handed out at the pediatric rheumatology clinic at Astrid Lindgren Children’s Hospital to children newly diagnosed with JIA. The children were between 2-17 years old. After a month an assistant nurse at the clinic contacted the family by mail or by phone to evaluate how the bag had been used. The families were asked whether the information added value and if they found answers to any questions that arose after the doctor’s visit.

Results: All of the 20 families were positive to the bag and its content. They found that the information helped them to explain about JIA to people around them, in school or preschool, or on activities after schools. The content of the bag had increased understanding and knowledge of what the disease means for the child in everyday life. The material had also helped the parents to get a good basic information so that they then had a better perspective on all the information online and in social media.

Conclusion: The information bag has been an appreciated complement to the information given at the hospital and will now be implemented as a tool provided to children diagnosed with JIA at Astrid Lindgren Children’s Hospital.

Disclosure of Interest: A. Horne: None Declared, K. Palmblad: None Declared, M. Höglund Grant / Research Support from: Travel grant from AbbVie

P396 Psychological peculiarities in patients with cryopyrin-associated periodic syndromes and systemic juvenile idiopathic arthritis

Natalia Stepanenko, Svetlana Salugina, Evgeny Fedorov, Irina Nikishina, Maria Kaleda

Nasonova Research Institute of Rheumatology, Moscow, Russian Federation
Presenting author: Natalia Stepanenko

Introduction: Cryopyrin-associated periodic syndromes (CAPS) and systemic juvenile idiopathic arthritis (sJIA) formally belong to the same group of autoinflammatory diseases (AID) and have a number of clinical similarities, and approaches to therapy. At the same time CAPS (cryopyrin-associated periodic syndromes) refer to AID group, associated with NLRP3 gene mutation with multiorgan damage and involvement of the central nervous system (CNS) that can result in the development of cognitive functions and determine certain psychological peculiarities.

Objectives: to carry out a fundamental psychological testing aimed at identifying peculiarities of the emotional sphere and cognitive deficits in patients with CAPS and systemic juvenile idiopathic arthritis (sJIA).

Methods: A detailed psychological examination was performed under a single diagnostic plan: 12 patients consecutively admitted to the clinic: 6 patients with CAPS (4 - MWS, 2 - CINCA-NOMID), aged from 9 to 17 years, 4 males, 2 females; average disease duration of 9 years and 6 patients with sJIA aged from 7 to 16 years, 4 males, 2 females; average disease duration of 7 years.

Methodology: clinical interview, 8-Luscher color test, Spielberger - Khanin test to identify the level of anxiety, CMAS, methods of pathodiagnostic survey.

Results: CAPS patients showed a reduction of attention functions in a part of concentration and distribution (by 66.7%), insufficient attention efficacy (increase in the time consumed in vigorous activities) in 83.3%, the low-speed entry (50%), reduced level of performance efficiency in 83.3%. Irregularities in the process of memorization, short-term memory (16%) and storage of data (long-term memory, LTM) were observed in a half. The concreteness of ideation which did not meet the age norm and reduced level of factuality were observed (50%).

An increased level of personal anxiety (66.7%), dissatisfaction with their appearance (50%), difficulty in communicating with agemates (50%), reduced level of social adaptation were observed in the emotional sphere (7%). Patients with sJIA showed the reduction of focus functions - in a part of concentration (50%), the distribution of attention (16.7%), insufficient attention efficacy (33.3%), and low speed entry (16.7%). Abnormalities in the short-term memory link were observed in 33.3%, long-term – in 16.7%. The thinking processes did not show reducing level of factuality in 33.3% and specificity of ideation inconsistent with age norm. In the emotional sphere there were revealed an increased level of personal anxiety (50%), difficulty in communicating with agemates (83.3%), dissatisfaction with appearance and reduced level of social adaptation - in a half.

Conclusion: Differences in the psychological status of patients with CAPS and sJIA were revealed. CAPS patients showed the most dramatic abnormalities in the cognitive functioning - in all functions of attention, memory and thinking, which may be indicative of the major organ damage. Disturbances in the emotional sphere are dominated in patients with sJIA (difficulty in communicating with agemates and low social adaptation). Dissatisfaction with their own appearance is equally characteristic of both groups. Clinical and psychological status of patients with CAPS and sJIA requires further study at a greater volume of material to identify sustainable patterns of regularities, assess the impact of targeted therapies and develop psychocorrective programs for cognitive and emotional disorders.

Disclosure of Interest: None Declared

P397 The perceptions of patients with juvenile idiopathic arthritis about “having a rheumatic disease” and “doing exercise” via metaphors

Nilay Arman1, Ela Tarakci1, Kenan Barut2, Amra Adrovic2, Sezgin Sahin2, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: A metaphor is considered the strongest device for an individual to comprehend and explain a hypothetical or an abstract, complex fact in a high level. Metaphors shape our perceptions, beliefs, attitudes and thoughts and they may influence the actions we take in the real world. Metaphors are among the most powerful cognitive tools to understand children with chronic disease. Juvenile idiopathic arthritis (JIA) affects social, emotional, and cognitive development of children, because it is a chronic disease in childhood. Understanding the perceptions about their disease helps to accomplish cognitive barriers of the rehabilitation in children. However, in the literature, no study has been found about perceptions about their disease in children with arthritis.

Objectives: The aim of the study was to understand the perceptions of patients with JIA about having a rheumatic disease and doing exercise via metaphors.

Methods: The population of the study included 20 (16 girls and 4 boys) patients with JIA. Each patient with JIA was asked to complete the blanks in the sentences, “Having a rheumatic disease is like a/an.....................because..................” and “Doing exercise is like a/an.....................because..................” The data were analysed using qualitative (content analysis) method.

Results: The mean age of the patients was 11.35 ± 2.20 (age range 8-18). According to the findings of the study, patients with JIA identified 24 metaphors (15 metaphors for “having a rheumatic disease”, 9 metaphors for “doing exercise”) in total. The metaphors for “having a rheumatic disease” developed by patients with JIA were analysed and interpreted at two categories: animals and objects. While the animal metaphors indicated three characteristics as “slow-moving”, “coping difficult” and “frightening” for “having a rheumatic disease”. The object metaphors indicated five characteristics as “Chaotic”,“ Stiffness”, “Formidable”, “Puffy” and “Uncertainty” for it. The metaphors for “doing exercise” indicated three characteristics as “Beneficial for Health”, “Tedious” and “Hard”.

Conclusion: As a result, the metaphors can be used as a strong research tool in understanding, revealing and explaining the cognitive images of patients with JIA about their disease and doing exercise. This study showed that patients with JIA prefered different metaphors for explaining their perceptions of disease and exercise but the reasons were similar. According to their metaphors, “Having a rheumatic disease” is similar to solving a difficult problem, “Doing exercise” is necessary for getting better but it requires the responsibility.

Disclosure of Interest: None Declared

P398 The effects of kinect based dance therapy on lower extremity functions of a patient with oligo articular jia: case report

Nilay Arman1, Ela Tarakci1, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: Juvenile idiopathic arthritis (JIA) is characterized by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and activity restriction. In the literature, some evidence reports that patients with JIA are physically less active when compared with healthy children. Active video gaming such as Xbox 360 Kinect is a promising physical activity alternative given that children are encouraged to move whilst engaging in an activity they enjoy.

Objectives: The purpose of this case report is to describe effects of Kinect based dance therapy (KBDT) on lower extremity functions of a patient with oligo articular JIA.

Methods: The patient was 18-year-old girl with oligo articular JIA. She had left hip arthritis. So, she had dissatisfaction about her appearance during the walking because of limitation of hip range of motion and increased anterior pelvic tilt. Also, she complained of pain and fatigue at rest and during the walking. Pain during rest and activity was assessed using a 0-to-10 Numeric Rating Scale (NRS). Fatigue severity was also measured by NRS with higher scores indicating high fatigue, Active and passive Range of motion (ROM) of lower extremity was measured using a standard goniometer. Muscular strength was estimated at maximal isometric force for the muscles of the lower extremities by using a portable digital handheld dynamometer. Static balance was measured by using the Functional Reach Test (FRT) and Lateral Reach Test (LRT). Functional ability was assessed by Childhood Health Assessment Questionnaire (CHAQ). Functional capacity was assessed by 6 minutes walking test (6MWT). The total distance was recorded during walking for 6 minutes. Our KBDT program was composed of “Dance Central 2”. Dance Central 2 is a rhythm game developed exclusively for the Xbox 360 Kinect. During the game, players perform given dance moves similar to a mirror, which are tracked by the Kinect. The more accurately the player performs the move, the more points he/she scores. Higher difficulties increase move complexity. 4-5 different dances that included weight bearing and balance actions for lower extremity were selected for our KBDT program. She completed 8 weeks (3 times in a week) of her specific KBDT program.

Results: Pain scores of NRS-rest and NRS-activity and NRS-fatigue were 5 point before the treatment. After treatment NRS-activity was 1 point, both NRS-rest and NRS-fatigue were 0 point, Active ROM of Hip flexion was 70, hip extension 20, abduction 20, internal rotation 30, and external rotation was 30 degrees before the treatment. After the treatment, Active ROM hip flexion was 90, hip extension 35, abduction 45, internal rotation 45, and external rotation was 40 degrees. FRT scores of pre and post-treatment were 36 and 45 cm respectively. LRT scores of pre and post-treatment were 22 and 30.5 cm respectively. Pre and post-treatment scores of 6MWT were 406 and 522 meters, respectively. CHAQ total, CHAQ-walking, CHAQ- activities scores were 1.12, 2 and 2 before the treatment respectively. All CHAQ scores dropped to 0 after the treatment. Also, all muscle strength scores of both lower extremities were improved after the treatment.

Conclusion: In this study, we found clinically significant improvements of lower extremity functions, functional capacity, pain and fatigue for a patient with oligo articular JIA. This indicates that repeated actions with visual and auditory feedback provided by Kinect-based virtual reality may increase patient focus and motivation and thereby improving the quality of movements. This case report describes a novel approach to rehabilitation of patients with JIA but further investigation into the effectiveness of KBDT for children with JIA is warranted.

Disclosure of Interest: None Declared

P399 AJIados, a francophone patient association for adolescents and young adults with JIA

Laurence Toumoulin1, Johnny Frossard1, Stephanie Archimbaut1, Anne Paitier1, Rolande Guastalli1, Severine Guillaume Czitrom2

1AJIADOS, Le Kremlin Bicetre Cedex, France; 2Service de Medecine des Adolescents, CHU DE BICETRE, Le Kremlin Bicetre Cedex, France
Presenting author: Severine Guillaume Czitrom

Introduction: Adolescent departments in France are usually devoted to the care of mental health disorders. Yet, there is a huge need for chronic organ-diseases care, focused on adolescents specifically. Adolescence is often a difficult period but chronic organ-disease as JIA, may amplify the troubles, thus requiring a particular effort.

Objectives: Improve the daily life of adolescents and young adults with JIA with practical actions.

Methods: We chose to start with the improvement of patient education in adolescents and young adults having juvenile idiopathic arthritis in France. We created the first patient association “AJIados” involved in adolescent/ young adults in France.

Results: AJIados supports different actions : (i) collective meetings between the young people, between their parents/families, between them and caregivers. We organize 4 times a year, collective assemblies on various themes, generally chosen by the patients; all together, we create small documents to help solving practical problems (school, physiotherapy, living with a uveitis…) and distribute them across our country as well as in the Maghreb. We also send to interested people our newsletter every 3 months. Our efforts have had a great success with always more adolescents and families; (ii) we organized nice encounters with key figures in french sport and music, who are vectors of hope and will go on this way; (iii) we created a web-site (www.ajiado.org) to help patients in their daily life: there are 5 modules (a forum, a tool box, news on research as well as surveys, an agenda with referral caregivers that is built and improved by the patients themselves and a growing part devoted to patient education).

Conclusion: Presently, the success is « au rendez-vous » with the adolescents and young adults, justifying to pursue all our efforts.

Disclosure of Interest: None Declared

P400 Health-related quality of life in Thai children with juvenile idiopathic arthritis

Sirirat Charuvanij, Chollada Chaiyadech

Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Presenting author: Sirirat Charuvanij

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic disease resulting in pain and disability. There has been no study focusing on health-related quality of life (HRQOL) among Thai children with JIA.

Objectives: To describe HRQOL and determine factors influencing the HRQOL of Thai JIA patients.

Methods: A cross-sectional descriptive study was conducted in JIA patients and their parents followed up at a pediatric rheumatology clinic, Siriraj Hospital, Bangkok, Thailand. HRQOL was measured by using the Pediatrics Quality of Life (PedsQL) 4.0 generic core scale, Thai version, during January 2015-December 2015. Suboptimal HRQOL is defined as a PedsQL total mean score of < 78.6.1

Results: Sixty-five patients and their parents were included. Thirty-three patients were female (50.8%). Mean age of patients was 9.6 ± 3.9 years and the median of duration of the disease was 1.1 (0.0-9.43) years. Systemic JIA was the most common JIA subtype (40%). The median of Juvenile Arthritis Disease Activity Score-71 (JADAS-71) was 7 (0-27.2). Forty-nine (75.4%) patients were having active disease. The median of total PedsQL score reported by patients was 80.6 (36.9, 100); physical functioning score 78.1 (34.4, 100), emotional functioning score 85 (35, 100), social functioning score 90 (30, 100), school functioning score 80 (25, 100). There were 25 (45.4%) patients classified as having suboptimal HRQOL. The median of total PedsQL scores reported by parents was 71.7 (33.3, 100); physical functioning 75.0 (0, 100), emotional functioning 80 (40, 100), social functioning 85 (25, 100) and school functioning 65 (25, 100). Suboptimal HRQOL was identified in 39 (60%) patients based on parent reports. There was positive correlation between total PedsQL scores reported by children and their parents (rs = 0.662). There were no statistically significant factors associated with suboptimal HRQOL reported by children. Non- oligoarthritis; OR 3.8 (95%CI: 1.0, 14.6), joint pain; OR 4.1 (95%CI: 1.4, 11.5), limping; OR 4.7 (95%CI: 1.2, 18.7), wrist arthritis; OR 8.6 (95%CI: 1.0, 72.1), elevated erythrocyte sedimentation rate: OR 2.8 (95%CI: 1.0, 7.9), elevated C- reactive protein: OR 3.2 (95%CI: 1.1, 9.2), active disease; OR 4.9 (95%CI: 1.2, 16.8), high disease activity (JADAS-71 ≥ 10.5); OR 12.6 (95%CI: 2.6, 60.9) and oral steroid use; OR 3.2 (95%CI: 1.0, 10.3) were associated with suboptimal HRQOL reported by parents. However, only high disease activity influenced on the suboptimal HRQOL by multiple logistic regression analysis; adjusted OR 20.2 (95%CI: 1.4, 291.7).

Conclusion: Almost half of Thai JIA patients had suboptimal HRQOL. The physical functioning score was the lowest aspect. The factor associated with suboptimal HRQOL reported by parents was high disease activity.

Trial registration identifying number: N/A

Disclosure of Interest: None Declared

P401 Attitude surveys of pediatric and non-pediatric rheumatologists regarding transition of care

Takako Miyamae, Hisashi Yamanaka

Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
Presenting author: Takako Miyamae

Introduction: The goal of planned adolescent healthcare transition procedures is to optimize the functioning and well-being of all young people, including those with special healthcare needs. In this regard, the transitioning of young people with childhood-onset rheumatic diseases to adult healthcare is increasingly important, as many of these patients might continue to have active disease or considerable sequelae well into their adult lives.

Objectives: Attitude surveys of pediatric and non-pediatric rheumatologists about transition procedures were performed.

Methods: Overall, 28 operation commissioners of the Pediatric Rheumatology Association of Japan and 37 non-pediatric rheumatologists belonging to the Institute of Rheumatology, Tokyo Women’s Medical University participated in the surveys. Experiences of adult patients with childhood-onset rheumatic diseases, ideal medical care for adults, and factors contributing to challenges associated with the transition to adult care were examined.

Results: In total, 19% of pediatric rheumatologists still see their patients as adults, whereas 62% of non-pediatric rheumatologist have experiences with childhood-onset patients. Transition to non-pediatric medical care was supported by 81% and 95% of pediatric and non-pediatric rheumatologists, respectively. A preparatory step of visiting both a pediatrician and a non-pediatrician is recommended by some physicians. Two major factors, incomplete facilitation of personal independence to make the transition to adult care and the sharing of pediatric rheumatology knowledge and skills with non-pediatric rheumatologists, particularly with respect to autoinflammatory disorders, were identified as contributing to challenges associated with successful transition. Overall, 33 of 37 (89%) non-pediatric rheumatologists required education about childhood-onset rheumatic diseases.

Conclusion: Key elements for effective transitions include the development of education programs to help pediatric patients manage their illness independently and to share pediatric rheumatology knowledge within the non-pediatric rheumatology community.

Disclosure of Interest: None Declared

Poster Session: New diseases

P402 Interstitial lung disease with TMEM173 mutations is associated with a strong IFN-stimulated protein induction in situ

Cecile Picard1,2, Guillaume Thouvenin3, Caroline Kannengiesser4, Jean-Christophe Dubus5, Nadia Jeremiah6, Frédéric Rieux-Laucat6, Bruno Crestani7, Véronique Secq8, Christelle Ménard9, Martine Reynaud-Gaubert10, Françoise Thivolet-Bejui1, Philippe Reix11, Alexandre Belot2,12

1Pathology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France; 2Inserm U1111, Lyon, France; 3Pediatric Pulmonology, Assistance publique-Hôpitaux de Paris, Paris, France; 4Genetic, Assistance publique-Hôpitaux de Paris, Paris, France; 5Assistance publique-Hôpitaux de Marseille, Marseille, France; 6Institut Imagine, hôpital Necker, Paris, France; 7INSERM, Unité 1152, Université de Paris Diderot, Paris, France; 8Pathology, Assistance publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France; 9Pediatric Pulmonology, Assistance publique-Hôpitaux de Paris, hôpital Armand Trousseau, Paris, France; 10Pulmonology Department, CHU Nord, Assistance publique-Hôpitaux de Marseille, Marseille, France; 11Pediatric Pulmonology, Nephrology and Dermatology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France; 12Pediatric Rheumatology, Nephrology and Dermatology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France
Presenting author: Cecile Picard

Introduction: Inherited inflammatory syndromes related to the transmembrane protein 173 (TMEM173) gene gain-of-function mutation were described so far by the triad early-onset systemic inflammation, marked cutaneous vasculopathy and pulmonary fibrosis, with variable clinical expression even in familial cases (1,2). Recently, we have reported that TMEM173 mutations can be associated to inaugural lung interstitial disease (ILD) with late-onset systemic symptoms (3).

Objectives: To investigate pathological features of the lung disease of STING-associated ILD.

Methods: Clinical and biological data, chest HRCT and lung biopsies were collected retrospectively in 2 children and one adult with TMEM173 mutation. Paraffine-embedded tissues were stained for IFNa (clone MMHA-2), CXCL10, IFNAR1 and MxA and compared to healthy controls and non genetic ILD (systemic sclerosis).

Results: Initial presentation was related to symptoms suggestive of pulmonary fibrosis for all patients. Few systemic features appeared later on life and skin damage was mild, delaying the evocation of a systemic disease. Classical causes of familial interstitial lung disease were all excluded genetically and all three patients had an already known genetic variant of TMEM173. Cystic lesions on HRCT predominated in upper lobes with relative preservation of lower lobes. Immunohistological analysis showed fibrosis with destruction of alveolar architecture associated with follicular lymphoid infiltrates (neolymphogenesis) containing a majority of B cells CD20+. The overall architecture differs from other common ILD. Intra-alveolar infiltrate was made of macrophages and cholesterol crystal clefts was noticed for the 3 patients. Interestingly, there was no evidence for vasculopathy or microangiopathy. By contrast, a huge induction of IFN-related protein in the lung section of patients was observed as compared with controls. A strong interferon signature was found in all three cases.

Conclusion: The diagnosis of STING-related lung fibrosis should be considered as a differential diagnosis of ILD in children even with no or mild systemic features. The pathological study may represent a useful procedure to support the diagnosis.

Written informed consent were obtained from all the participants of the study.

References

1. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014 Aug 7;371(6):507–18.

2. Crow YJ, Casanova J-L. STING-associated vasculopathy with onset in infancy--a new interferonopathy. N Engl J Med. 2014 Aug 7;371(6):568–71.

3. Picard C, Thouvenin G, Kannengiesser C, Dubus JC, Jeremiah N, Rieux-Laucat et al. Severe pulmonary fibrosis as the first manifestation of interferonopathy (TMEM173 mutation). Chest. 2016 Accepted/In Press

Disclosure of Interest: None Declared

P403 The characteristic features of the patients with deficiency of adenosine deaminase 2 (DADA2)

Ezgi Deniz Batu1, Hafize Emine Sonmez1, Abdulsamet Erden2, Ekim Z. Taskiran3, Omer Karadag2, Umut Kalyoncu2, İbrahim Oncel4, Berkan Kaplan5, Zehra Serap Arici1, Cagri Mesut Temucin5, Haluk Topaloglu4, Yelda Bilginer1, Mehmet Alikasifoglu3, Seza Ozen1

1Department of Pediatrics, Division of Rheumatology, Ankara, Turkey; 2Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey; 3Department of Medical Genetics, Ankara, Turkey; 4Department of Pediatrics, Division of Neurology, Ankara, Turkey; 5Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Presenting author: Ezgi Deniz Batu

Introduction: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease resulting from a loss-of-function mutation in CERC1 gene encoding for ADA2 protein. The patients present with systemic inflammation and vasculopathy.

Objectives: We aimed to present the characteristics of the pediatric DADA2 cases.

Methods: The clinical and laboratory features of thirteen pediatric patients (8 M, 5 F), who were diagnosed with DADA2 at Hacettepe University Pediatric Rheumatology Department between 2014-2016, have been summarized. Mutations in CECR1 were detected by Sanger sequencing.

Results: Eleven patients were homozygous for G47R mutation in CECR1 gene, one was compound heterozygous for G47R and G47V while one patient was heterozygous for G47R. Seven of these patients had been followed up in our clinic with the diagnosis of polyarteritis nodosa (PAN). There was consanguinity in four cases, and two patients were siblings. The median (min-max) age at onset of the symptoms and diagnosis was 5.5 (1.4-19) and 120 (36-211) months, respectively. All patients suffered from recurrent episodes of fever with elevated acute phase reactants. Skin manifestations were as follows: livedo reticularis (n = 13), erythema nodosum (n = 4), and necrotic ulcers (n = 2). Neurological and musculoskeletal involvement was in the form of myalgia (n = 5), arthralgia (n = 10), arthritis (n = 5), stroke (n = 8), strabismus (n = 3), peripheral neuropathy (n = 6), and spinal cord atrophy (n = 1). One patient had been diagnosed with core myopathy through muscle biopsy which was thought as a co-incidental finding. Optic neuritis was detected in one patient. There was Raynaud’s phenomenon in two patients. Four patients had aneurysms in different middle-sized arteries (hepatic artery, renal artery, and superior mesenteric artery). One patient had intestinal perforation and ileostomy at the age of eight. As renal involvement, one patient had focal segmental glomerulosclerosis (collapsing variant), one mesangial proliferative glomerulonephritis (renal subcapsular hematoma after renal biopsy), and one had renal amyloidosis. There was testicular torsion in one patient. Three patients had positive antinuclear antibody while there was low levels of immunoglobulin M in two patients. Two adult patients died soon after diagnosis of DADA2. One patient was asymptomatic on only colchicine for almost 10 years. One responded to mycophenolate mofetil treatment. Rest of the patients responded well to anti- tumor necrosis factor therapy (etanercept).

Conclusion: ADA2 protein is a growth factor for endothelial cells and leukocytes and is important for stabilization of endothelial cells. For this reason, it causes autoinflammatory symptoms as well as vasculitis symptoms similar to PAN. ADA2 deficiency is a recently defined disease and the data about its phenotype increases with the introduction of new cases with different symptoms. This is the first description of spinal cord atrophy, core myopathy, and mesangial proliferative glomerulonephritis in DADA2 patients. Similar to the patients in the literature, most of our patients responded to etanercept therapy. Our cases suggest the diverse phenotype of DADA2.

Disclosure of Interest: None Declared

P404 Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND): preliminary results of a proof-of-concept trial with anakinra

Lien Van Eyck1,2, Ellen De Langhe3, Isabelle Jéru4,5, Erika Van Nieuwenhove1,2, Vasiliki Lagou2,6, Paul J. Baker7,8, Jocelyn Garcia-Perez1,2, James Dooley1,2, Lien De Somer9, Raf Sciot10, Pierre-Yves Jeandel11, Julia Ruuth-Praz4,5, Bruno Copin5, Myrna Medley-Hashim12, Andre Megarbane13, Sinisa Savic14, An Goris6, Serge Amselem4,5, Adrian Liston1,2, Seth Masters7,8, Carine Wouters1,9

1Department of Immunology and Microbiology, University of Leuven, Leuven, Belgium; 2Translational Immunology Laboratory, VIB, Leuven, Belgium; 3Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium; 4Université Pierre et Marie Curie-Paris, UMR_S933, Paris, France; 5Service de Génétique et d’Embryologie médicales, Assistance Publique Hôpitaux de Paris, Hôpital Trousseau, Paris, France; 6Department of Neurosciences, University of Leuven, Leuven, Belgium; 7Inflammation division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; 8Department of Medical Biology, University of Melbourne, Parkville, Australia; 9Department of pediatrics, University Hospitals Leuven, Leuven, Belgium; 10Department of pathology, University Hospitals Leuven, Leuven, Belgium; 11Département de Médecine Interne, Hôpital Archet 1, Nice, France; 12Department of Life and Earth Sciences, Lebanese University, Beirut, Lebanon; 13Al-Jawhara Center, Arabian Gulf University, Manama, Bahrain; 14Department of Clinical Immunology and Allergy, St James’s University Hospital, Leeds, United Kingdom
Presenting author: Lien Van Eyck

Introduction: Recently, we identified a S242R mutation in pyrin in 12 patients from a three-generation Belgian family suffering from childhood-onset recurrent episodes of severe neutrophilic dermatosis, arthralgias/myalgias and systemic inflammation. The mutation results in the loss of a 14-3-3 binding motif at phosphorylated S242, resulting in continuous pyrin-inflammasome activation and excessive IL-1β production. Because of the genetic causation by pyrin mutation and the characteristic features of systemic inflammation and dermatosis, we termed this disease pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). We found additional patients in Lebanon, France and UK, where one patient received treatment with the IL-1 receptor antagonist monoclonal antibody (mAb) anakinra leading to a resolution of symptoms and normalisation of inflammatory markers.

Objectives: To assess the efficacy of the IL-1 receptor antagonist mAb anakinra (Sobi) in controlling the clinical and biochemical consequences of constitutive activation of the pyrin inflammasome in patients with PAAND.

Methods: Three Belgian patients with the S242R pyrin mutation are treated with daily subcutaneous injections of Anakinra 100 mg for 12 weeks. Previous therapy with TNF-antagonists was stopped and concomitant immunosuppressive treatment was limited to low-dose corticosteroids. Clinical cutaneous, articular/muscular manifestations and inflammatory markers are assessed at baseline, and after 2, 4, 8 and 12 weeks. In addition presence of cytokines and activated caspase1 as well as inflammasome activation in vitro are assessed at baseline, 4 and 12 weeks.

Results: At baseline, all three patients manifested neutrophilic dermatosis in the form of severe cystic acne and sterile abscesses, diffuse myalgias and arthralgias, fatigue and night sweats, and abdominal pain associated with diarrhea. Inflammatory markers were increased and mild anemia was present.

At the time of writing, i.e. two weeks after the start of anakinra treatment inflammatory markers were normalized in all three patients. All patients showed manifest improvement of the cutaneous manifestations, reduction of the gastro-intestinal pain with normalization of the stools and a reduction of the musculoskeletal pain. Night sweats had disappeared, but fatigue was still present.

Conclusion: PAAND is a new autosomal dominant autoinflammatory disease caused by a specific S242R mutation in MEFV leading to constitutive activation of the pyrin-inflammasome. The clinical phenotype is dominated by severe neutrophilic dermatosis and systemic inflammation. Treatment with Anakinra resulted in suppression of clinical manifestations and control of inflammatory markers, endorsing the key pathogenic role of IL-1 in PAAND.

Disclosure of Interest: None Declared

P405 A fourteen-year-old girl with immunoglobulin G4-related disease

Nami Okamoto1, Yuko Sugita2, Kousuke Shabana2, Takuji Murata2, Hiroshi Tamai1

1Department of Pediatrics, Graduate School of Medicine, Takatsuki-city, Japan; 2Pediatrics, Osaka Medical and Pharmaceutical University, Takatsuki-city, Japan
Presenting author: Nami Okamoto

Introduction: We will report a girl with immunoglobulin G4-related disease (IgG4-RD), a newly recognized disorder that share particular pathologic (infiltration of IgG4-rich plasma cells or fibrosis), serologic (elevated serum IgG4), and clinical features (multifocal phymatoid or hypertrophic lesions).

Objectives: Child patient with IgG4-RD is very rare and its pathophysiology is thought to be different from adult cases1). We will report our patient whom treated with mycophenolate mofetil (MMF) for the purpose.

Methods: Retrospective analysis based on charts.

This report was approved by Ethics Committee of Osaka Medical and Pharmaceutical University.

Results: She complained exophthalmos when she was twelve years old. MRI was performed at former hospital that revealed tumefaction of lacrimal gland and salivary gland. Serum IgG4 concentration was significantly high (1090mg/dl) and biopsy specimen from salivary gland showed infiltration of IgG4-positive plasma cells (>50%). She was diagnosed as IgG4-RD and oral prednisolone (1mg/kg) was administered. Because of steroid-induced glaucoma, the disease control was difficult to manage and she was introduced to our hospital at age of thirteen. Laboratory data: WBC 10020/μl, PLT 31万/μl, CRP 0.01mg/dl, ESR 23mm/1h, IgG 2960mg/dl, IgA 45mg/dl, IgM 115mg/dl, IgE >5000Iu/ml, IgG4 1370mg/dl, CH50 41 U/ml, C3 90mg/dl, C4 15.6 mg/dl, AST/ALT 13/22U/L, γGTP 19U/L, BUN 15mg/dl, CRN 0.54mg/dl, autoantibodies negative, no abnormality in urine test. Abdominal CT and MRI were performed that showed IgG4-related cholangitis, cholecystitis and nephropathy. Bile duct wall was edematous and wall thickening was exhausted, so we diagnosed her status as CS-resistant. We prescribed MMF (800mg/kg) and she was responded clinically and serologically. Her disease activity has been controlled well since then. IgG4-RD is a male dominant disease and peak age is between forties and seventies in adults. Among pediatric patient of IgG4-RD, girls are double to boys and their age ranged from two to seventeen. Despite the recognition that pediatric IgG4-RD shows different characteristics, little was known about the pathogenesis, adequate therapy and prognosis yet. Though corticosteroid (CS) therapy was effective for most patients, half of them experienced relapse or recurrence with reducing CS2). CS-sparing agents that include azathioprine, rituximab, cyclophosphamide and MMF are required for them. But it is not clear when it should be started and which agent would be adequate as a maintenance therapy.

Conclusion: Our patient with pediatric IgG4-RD who was resistant to CS monotherapy responded to MMF. Further study about children with this rare disorder and confirming the response to maintenance therapy is necessary in worldwide.

References:

1) Karim F, et al. IgG4-related disease: a systematic review of this unrecognized disease in pediatrics. Ped Rheumatol. 2016;14:18.

2) Sekiguchi H, et al. Immunoglobulin G4-related disease: Retrospective analysis of 166 patients. Arthritis Rheumatol. 2016 Mar 18. doi:10.1002/art.39686. [Epub ahead of print]

Disclosure of Interest: None Declared

P406 Autoimmune damage of CNS - a newly recognized clinical manifestation of autoimmune polyendocrine syndrome type 1?

Juliana Ferenczová, Erika Banóova, Pavol Mrážik, Veronika Vargova

Department of Paediatrics and Adolescent Medicine, Šafárik University and children faculty hospital in košice, Košice, Slovakia
Presenting author: Veronika Vargova

Introduction: Autoimmune polyendocrine syndrome (APS) type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autosomal recessive disease. The classic features are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Several non-classic presentations of the disease have been described over the last few years.

Objectives: Authors present a case of 14-year old girl with prolonged seizures as a new serious non-classic presentation of APS type 1.

Methods: case report

Results: Patient was diagnosed with a mucocutaneous candidiasis and hypoparathyroidism at the age of 3 years. APS 1 was diagnosed at 9 years of age shortly after diabetes mellitus type 1 had been recognized. Mutational analysis of the AIRE gene showed R257X (c.769C > T) mutation. Typical symptoms of Addison disease - weakness, fatigue and hyperpigmentation - developed at 13 years of age. At 14 years she was admitted to hospital for prolonged seizures. Hypoglycemia and hypocalcemia were excluded as a cause of the seizures. EEG showed finding non-specific for epilepsy. Examination of the CSF was performed to exclude infection (herpetic viruses, etc.). MRI angiography did not show vasculitis or other organic changes of cerebral vessels. Specific autoantibodies for autoimmune encephalitis turned out to be positive in CSF (antiGAD65 > 2000 MU/L) as well as in blood (>2000 MU/L). Immunosuppressive treatment (glucocorticoids and i.v. immunoglobulins) in combination with antiepileptics resulted in a clinical course without seizures.

Conclusion: Differential diagnosis of autoimmune damage of CNS is a new challenge for pediatric rheumatologists. Autoimmune GAD65-positive encephalitis should be considered a new component of the clinical spectrum of APS in patient with new onset neuropsychiatric symptoms.

Disclosure of Interest: None Declared

Poster Session: Spondyloarthritis (SpA) and enthesitis related arthritis (ERA)

P407 Color Doppler us as an alternative to MRI for detecting sacroiliitis - a pilot study

Dubravko Bajramovic1, Ksenija Stekic Novacki1, Kristina Potocki1, Marijan Frkovic2, Marija Jelusic2

1Department of radiology, University Hospital Center Zagreb, Zagreb, Croatia; 2Department of pediatrics, University Hospital Center Zagreb, Zagreb, Croatia
Presenting author: Dubravko Bajramovic

Introduction: Considering that the ultrasound is a validated method for assessing inflammation activity in peripheral joints our aim in this pilot study was to determine whether the ultrasound/Color Doppler could be used to diagnose sacroiliitis in juvenile SpA patients.

Objectives: To determine the value of ultrasound/Color Doppler in diagnosing acute sacroiliitis in comparison with the established method which is considered a standard - the MRI. To compare data collected from our jSpA patients with previously published predisposing factors for the development of sacroiliitis.

Methods: We performed ultrasound/Color Doppler and MRI of sacroiliac joints using a standardized protocol on 112 patients observed for jSpA. All patients had low back pain and clinically suspected acute sacroiliitis. Out of 112 patients 43 were male and 69 female with average age of 13.9. Patients age at the beginning of the disease, number and sequence of joint involvement, history of rheumatic diseases in the family and results of HLA serotyping were recorded. All ultrasound and MRI examinations were performed by two MSK radiologists with an experience in imaging methods and protocols for rheumatic diseases.

Results: Active disease or acute sacroiliitis was noted using ultrasound/Color Doppler examination in 31 patients while 81 showed no signs of synovitis. MRI detected 28 patients with active disease. Only eight patients had ultrasound signs of disease activity confirmed on MRI. Based on preliminary results sensitivity of ultrasound/Color Doppler examination in detecting acute sacroiliitis in jSpA patients is 28.6% and specificity is 72.6%. Positive predictive value is 0.26 while negative predictive value is 0.75. Out of 41 patients with sacroiliitis confirmed on the MRI (both active and chronic) 27 of them had positive HLA- B27 serotyping, 9 had hip joint inflammation at the disease onset and only 5 had positive family history of rheumatic diseases.

Conclusion: MRI is a method of choice for detection of acute sacroiliitis but due to the waiting lists it can take a substantial amount of time before the examination can be performed. In order to get the diagnostic information as soon as possible ultrasound examination is often indicated. Ultrasound is an available, cheap and relatively easy method to perform and it doesn’t have the harmful effects of radiation which is especially important in the pediatric population. In sacroiliac joints imaging ultrasound has serious limitations due to the complex joint anatomy and a relatively small imaging “window” that enables us to visualize and analyze only the dorsal aspect of the joint. Evaluator has to make sure to that the Doppler signals acquired are the result of the increased vascularization within the synovia in the intraarticular space and not the result of imaging of the blood vessels in the periarticular soft tissues. Optimizing the image parameters is extremely important as well as imaging experience. As our preliminary results show using ultrasound CD as an alternative to MRI is questionable due to the low sensitivity and specificity of the method resulting from the limitations mentioned. Ultrasound is not the adequate method for demonstrating acute sacroiliitis and patients with high clinical suspicion of sacroiliitis should perform MRI in order to confirm the diagnosis.

Disclosure of Interest: None Declared

P408 Longterm experience of biologics therapy in juvenile spondyloarthritis: focus for the drug survival

Irina Nikishina, Olga Kostareva, Svetlana Arsenyeva, Maria Kaleda, Anna Shapovalenko

V.A.Nasonova research Institute of Rheumatology, MOSCOW, Russian Federation
Presenting author: Irina Nikishina

Introduction: Juvenile spondyloarthritis (JSpA) included several subtypes of juvenile arthritis, the main of there are follows: juvenile onset of ankylosing spondylitis (JAS), enthesitis-related arthritis (ERA), juvenile psoriatic arthritis (JPsA). Biologics, TNF-inhibitor mostly, provided excellent progress in JSpA outcome for the last 15 years. Drug survival is a general marker of the treatment success as it depends of its efficiency and safety.

Objectives: To compare drug survival of biologics depending on the subtype in JSpA patients (pts) in real clinical practice of single center.

Methods: The study involved a prospective cohort of JSpA pts treated by different TNF-inhibitors in our clinic from 2004 to 2016. Analyze included drug survival with Kaplan-Meier, reasons of withdrawals and adverse event (AE) rates.

Results: 177 JSpA pts, treated with one or more biologics were analyzed. At the start of biologics pts average age was 13.19 ± 3.7 years (range 3.58-17.9); mean disease duration was 50,4 month (range 2-163). JSpA subtypes were as follows: JAS, fulfilled to modified New-York criteria - 48(26%), ERA - 106(60%) and JPsA - 23(13%), diagnosed according to ILAR (2001) criteria, 149(83%) were HLA-B27positive. 24(13,4%) had uveitis. In total, 205 treatment series, including 79 for etanercept (185 patient-year PY), 73-adalimumab (160 PY), 53-infliximab (182 PY) were evaluated. There were 62 cases of withdrawals. Reasons for withdrawals were AE in 7,32% (95%CI 4.49-11.72), inefficacy -i10.73% (95%CI 7.19-15.71), others – 11,71% (95% CI 8-16,83), basically due to organizational difficulties of biologics access in adult life. AE were developed after at mean 1.63 years (range 0.74-3,36). AE were included: etanercept – 3 cases of uveitis de novo (1.62 per 100 PY); infliximab – 6 infusion reactions (3.3 per 100 PY), 1 psoriasis de novo, 1 severe skin disorder, 1 toxic hepatitis, 2 tuberculosis; adalimumab – 2 psoriasis de novo, 1 tuberculosis. AE as a reason of Infliximab withdrawal was observed more often than under adalimumab or etanercept (18.9% vs 2.74% and 3.8% respectively, p < 0.05). Due to inefficacy Infliximab was cancelled more often than adalimumab (16.9% vs 6.85%, p < 0.05). Etanercept was rare withdrawn due to organization problem in compare to infliximab and adalimumab (6.3% vs 16.98% and 13.7%, p < 0.05). Long-term drug survival of TNF-inhibitors was 78% for ERA, 64% for JAS and 57% for JPsA. Drug survival for etanercept were 95% and 35% after 1 and 5 years, infliximab – 90% and 38%, adalimumab – 97% and 32%, respectively. The average survival rate of etanercept and adalimumab was higher in ERA vs JAS and JPsA (84% vs 68% and 67% respectively), but for infliximab it was similar in all JSpA subtypes.

Conclusion: Our experience of long-term study of TNF-inhibitors in JSpA demonstrated the best rate of drug survival for etanercept in pts with different subtype of JSpA, especially in ERA. Infliximab mostly withdrawn due to AE and inefficacy, but adalimumab cancelled more often because of organizational reasons, especially in adult life.

Disclosure of Interest: None Declared

P409 Concomitant MRI features of sacroiliitis increase specificity for diagnosis of juvenile spondyloarthritis

Lennart Jans1, Nele Herregods1, Jacob Jaremko2, Rik Joos1, Joke Dehoorne1

1Ghent University Hospital, Gent, Belgium; 2University of Alberta, Edmonton, Canada
Presenting author: Lennart Jans

This abstract is not included here as it has already been published.

P410 Is contrast necessary to detect sacroiliitis on MRI in juvenile spondyloarthritis?

Nele Herregods1, Jacob Jaremko2, Xenofon Baraliakos3, Joke Dehoorne4, Rik Joos4, Lennart Jans1

1Department of Radiology and Medical Imaging, Ghent University Hospital, Ghent, Belgium; 2Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Canada; 3Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany; 4Department of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium
Presenting author: Nele Herregods

This abstract is not included here as it has already been published.

P411 Performance of disease activity measures in juvenile spondyloarthritis in a placebo controlled trial with infliximab

Sofia Ramiro1, Julio C. Casasola-Vargas2, Désirée van der Heijde1, Robert Landewé3, Ruben Burgos-Vargas2

1LUMC, Leiden, Netherlands; 2Hospital General de Mexico, Mexico, Mexico; 3ARC, Amsterdam, Netherlands
Presenting author: Ruben Burgos-Vargas

Introduction: Several outcome measures in trials with juvenile-onset spondyloarthritis (Jo-SpA) have been borrowed from trials in juvenile idiopathic arthritis and from adult spondyloarthritis, but a proper psychometric analysis has never been conducted in patients with Jo-SpA.

Objectives: To assess discriminatory aspects of several disease activity outcome measures and response criteria for Jo-SpA.

Methods: Data from a previously reported 12-week RCT comparing infliximab (IFX) and placebo (PBO) in patients <18 years with Jo-SpA and onset <16 years of age were analyzed. The primary endpoint of the trial was the number of active joints (both swollen and tender). Several other disease activity measures and response criteria were also tested (Table 5). Statistics to determine how well disease activity measures could discriminate between IFX and PBO included ‘standardized mean difference’ (SMD) and ‘Guyatt’s effect size. Both statistics are standardized measures to compare change from baseline per group. For categorical response criteria, the chi-square test (χ2) was used. Higher numbers indicate better discriminatory capacity.

Results: Patients were randomised to IFX (n = 12) and PBO (n = 14). Of the continuous measures, the ASDAS showed the best and very good discrimination between IFX and PBO (SMD:1.98; Guyatt: 4.28) (Table 5). The physician’s global, CRP, JADAS and JSpADA also discriminated well. The BASDAI (or its separate items), BASFI and spinal mobility measures performed worse. Of the response criteria ASAS40 (IFX 55% vs PB = 0%, χ2 10.05) and ACR Pedi 90 (IFX 67% vs PBO 7%, χ2 10.12) discriminated best between IFX and PBO. ASDAS response criteria (ASDAS-MI: IFX 63% vs PBO 0%, χ2 8.65, ASDAS-CII IFX 88% vs PBO 20%, χ2 8.10) and ACR Pedi 30-70 also performed well.

Conclusion: Of all continuous measures tested in adult axial SpA the ASDAS discriminates best between active treatment and PBO in patients with Jo-SpA. But the child specific JSpADA also performs well.

Of all response criteria tested the child-specific ACR Pedi 30 to 90, as well as the adult ASAS40 and ASDAS response criteria work well. One of these measures should be used as primary endpoint in trials with Jo-SpA.

Disclosure of Interest: None Declared

Table 5 (abstract P411). Discrimination between patients on infliximab and placebo at week 12

P412 Efficacy and safety of adalimumab in pediatric patients with enthesitis related arthritis

Ruben Burgos-Vargas1, Shirley M. Tse2, Gerd Horneff3, Kristina Unnebrink4, Jaclyn K. Anderson5

1Hospital General de Mexico, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico; 2University of Toronto, The Hospital for Sick Children, Ontario, Canada; 3Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany; 4AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; 5AbbVie Inc, North Chicago, IL, United States
Presenting author: Ruben Burgos-Vargas

This abstract is not included here as it has already been published.

P413 Evaluation of DMARDs effectiveness on ERA patients

Aysenur Paç Kisaarslan1, Betül Sözeri1, Zübeyde Gündüz1, Gökmen Zararsız2, Hakan Poyrazoğlu1, Ruhan Düşünsel1

1Pediatric Rheumatology, Erciyes University, Kayseri, Turkey; 2Bioistatistic, Erciyes University, Kayseri, Turkey
Presenting author: Aysenur Paç Kisaarslan

Introduction: Therapeutic options for Enthesitis Related Arthritis (ERA) include monotherapy or combination therapy with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents. Until today, the approach to managing ERA is guided in large part by evidence from studies in adults with SpA and other forms of JIA.

Objectives: This study aim is determined whether effectiveness of DMARDs in ERA patients.

Methods: Fiftytwo ERA patients who satisfied ILAR criteria were enrolled in the study. The patients with psoriasis, inflammatory bowel disease, reactive arthritis and undifferentiated arthritis were exculuded. Patient information was obtained from the records. Registered data included demographic features, medical history, initial and following physical examination, initial juvenile spondyloarthritis disease activity index(JSpADA), initial laboratory tests, radiographic tests, JADI -A (Juvenil Arthritis Demage Index-articulary) and JADI-E(extraarticulary) on last admission, and all of medical treatment.

Results: We evaluated response of DMARDs in 52 patients. Twenty-seven patients (52%) achieved remission with DMARDs, while 25(48%) patients were not achived remission with DMARDs. Diagnosis of age, gender, family history of AS, inflammatory back pain, shoulder, hip, small joint involvement, sacroileitis with physical examination, enthesitis, presence of uveitis, presence of HLA-B27, initial high AFR levels, initial JSpADA score, last JADI-A score did not determinated risk factor on unresponsiveness of DMARD(HR:1, p > 0.05). Although it was not statistically significant, sacroileitis determinated with MRI increased 2.84 fold on unresponsiveness of DMARD with cox-regression analysis (p > 0.05). DMARD effectiveness decreased 50% at 20th month in this group with Kaplan-Meier analysis.

Conclusion: There are no significant differencies periferic between axial involvement treated with DMARD in our study. Therefore we believe that DMARDs kept up to date.

Disclosure of Interest: None Declared

P414 Assessment of entheseal ultrasonography in patients with juvenile fibromyalgia

Kazutaka Ouchi, Shinji Akioka, Hiroshi Kubo, Norio Nakagawa, Hajime Hosoi

Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan
Presenting author: Kazutaka Ouchi

Introduction: Fibro myalgia (FM) is characterized by widespread chronic musculoskeletal pain with fatigue, poor sleep, frequent psychological difficulties, and multiple tender points on physical examination. In adult cases, American College of Rheumatology 2010 (ACR2010) criteria was proposed as clinically useful tool, and the analyses of the underlying disease of FM based on this criteria demonstrated that some FM cases are complicated with SpA, one of which pathogenesis is enthesitis. Here, we examined ultrasound findings on entheses of juvenile FM patients.

Objectives: To identify the ultrasound (US) picture of peripheral entheses in juvenile patients with FM.

Methods: A single-center study was performed in 8 patients with definite juvenile FM according to suggestive symptom (a widespread pain resulting in school absenteeism). US assessment of the following four entheses was performed bilaterally by a senior rheumatologist: distal Achilles tendon, distal and proximal patellar tendon, and quadriceps tendon.

Results: The patients were 6 women and 2 men with a mean age of 14 ± 1 years. Total 64 entheses was examined. Inflammatory enthesitis was detected in 36 entheses (56.3%), and enthesopathy detected in 8 entheses (12.5%). All of patients had at least one lesion: inflammatory enthesitis was detected in 8 patients (100.0%), and enthesopathy detected in 6 patients (75.0%).

Conclusion: All juvenile FM cases were found to have enthesitis by US. Our result showed that a part of juvenile FM patients are probably complicated with enthesitis.

Disclosure of Interest: None Declared

P415 Epigenetic regulation of PTPN12 gene could influence the immunopathogenesis of juvenile spondyloarthritis and give rise to new therapeutic options

Lovro Lamot1,2, Fran Borovecki2, Sanja Kapitanovic3, Kristina Gotovac2, Mandica Vidovic1, Mirta Lamot1, Edi Paleka Bosak1, Miroslav Harjacek1

1Clinical Hospital Center Sestre Milosrdnice, Zagreb, Croatia; 2University of Zagreb School of Medicine, Zagreb, Croatia; 3Ruđer Bošković Institute, Zagreb, Croatia
Presenting author: Lovro Lamot

Introduction: Gene expression profiling of juvenile spondyloarthritis (jSpA) patients revealed aberrant expression of some genes, but the mechanism of this expression alterations remained unknown (1).

Objectives: To discover epigenetic modifications with effect on regulation of 4 genes (TLR4, NLRP3, CXCR4, PTPN12) differentially expressed in jSpA patients.

Methods: DNA methylation analysis was performed in promotor region of differentially expressed genes by methylated DNA Immunoprecipitation (meDIP). Based on literature search, 4 microRNAs (miR-150, miR-146a, miR-181a, miR-223) included in regulation of differentially expressed genes were selected and their expression was analyzed using RT-PCR with predeveloped Taqman microRNA assays. Both analysis were performed in 7 newly diagnosed untreated jSpA patients and 7 matched healthy children.

Results: Statistical analysis revealed no difference in methylation of promotor sites for examined genes, but PTPN12 showed trend towards higher methylation (p = 0,076), compared with control group. There was no statistical difference in expression of selected miRs between two groups.

PATIENTS 1 2 3 4 5 6 7
PTPN12 (fold enrichment) 0,43 1,01 0,54 1,84 1,06 5,08 0,55
0,95 0,57 1,08 0,81 0,886 1,26 0,586
CONTROLS 1 2 3 4 5 6 7

Conclusion: jSpA is a multifactorial disease in which a complex interplay occurs between the immune system and environmental factors on a predisposing genetic background. One of the most important mechanisms by which environment can influence processes inside of an organism is gene regulation via epigenetic modifications. Therefore, we investigated possible influence of DNA methylation and posttranscriptional modifications on the genes differentially expressed in jSpA patients. The results didn’t indicate any statistically significant abundance of miRs with described role in expression of examined genes, nor hypermethylation of their promotor sites, but there was a clear trend of higher methylation of PTPN12 in jSpA patients, while lack of statistical significance could be attributed to small number of study participants. This observation can easily explain decrease of PTPN12 expression in treated and untreated jSpA patients. PTPN12 expressed in dendritic cells is identified as a key regulator of dendritic cell migration as well as T cell-dependent immunity and autoimmunity (2). It is also a negative regulator of inflammation and intestinal cell migration, as well as a positive regulator of osteoclast activity, all of which are processes important for the pathophysiology of jSpA. Results of our study are in concordance with previous epigenetic studies of this gene in human breast cancer patients, which showed PTPN12 can be silenced by methylation. Interestingly, more recent study pointed to the potential of 5-Azac, a DNA hypomethylating agent, in increasing PTPN12 expression, and highlighted the therapeutic potential of this mechanism in treatment of breast cancer (6). Therefore, it is tempting to speculate the results of our study could after confirmation in larger cohorts give rise for new treatment options in jSpA patients as well.

References:

1. Lamot L, et al. Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis. PLoS One. 2014 Dec 15;9(12):e115416.

2. Inmoo Rhee, et al. Control of dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells. Mol Cell Biol. 2014 Mar;34(5):888-99.

3. Thummuri D, et al. Epigenetic regulation of protein tyrosine phosphatase PTPN12 in triple-negative breast cancer. Life Sci. 2015 Jun 1;130:73-80.

Disclosure of Interest: None Declared

P416 Anti-tumor necrosis factor therapy in patients with enthesitis-related arthritis

Ricardo A. Russo, María M. Katsicas

Immunology & Rheumatology, Hospital de Pediatría Garrahan, Buenos Aires, Argentina
Presenting author: Ricardo A. Russo

Introduction: Enthesitis-related arthritis (ERA) is a category of Juvenile idiopathic arthritis considered to be a form of Juvenile Spondyloarthropathy (jSpA). Tumor necrosis factor (TNF)-blocking strategies have proven effective in the treatment of jSpA1-2.

Objectives: To assess effectiveness of anti-TNF treatment in a cohort of patients with ERA; to search for associations between clinical features at treatment onset and inactive disease (ID).

Methods: Retrospective review of prospectively collected data. Patients with ERA (according to ILAR criteria) continuously treated with anti-TNF agents for ≥ 3 months were included. At visit 0 (baseline) and every 3 months thereafter Information was collected on therapeutic agents used and the following disease activity measures: joint count, pain score (0-10), presence of active enthesitis (AE), sacroiliac pain (SIP) or lumbar limitation (LL), wellbeing according to the patient using a visual analogue scale (VASp, 0-10), disease activity according to the physician (VASphy, 0-10), JADAS-102, JSpADA3, and ESR. Functional capacity was also assessed through the use of CHAQ. Occurrence of ID (defined as JADAS-10 £ 1 or as per Wallace et al4) and clinical remission (CR)4 was recorded. ANOVA and Mann-Whitney U test were used for comparisons between visits, while associations were analyzed with chi square and Sperman’s rank correlation.

Results: 30 patients fulfilled inclusion criteria. Patients were followed at a specialized clinic during the period 2002-2015.They were all male, 43% HLA-B27 positive; median age at start of TNF-blocker therapy was 13 years, disease duration 3.5 years; median observation period was 18 months. Twenty-seven (90%) children showed peripheral arthritis while 22 (73%) exhibited sacroiliitis on MRI/Xrays at start of therapy. Patients received etanercept (23, 2 were later switched to adalimumab and 1 to infliximab), adalimumab (5), or infliximab (2). At baseline patients showed (medians): active joints (AJ) 4, pain 1.5, VASp 2, VASphy 2, JADAS-10 9.75, JSpADA 2.5, ESR 16.5 mm/h, and CHAQ 0.25. AE was present in 4 (13%), SIP in 7 (23%), and LL in 12 (40%) children. All patients showed JSpADA > 0 and 29 (97%) children had JADAS > 1 at entry. At 3 months JADAS-10 decreased to 5.5 (p = 0.007) and JSpADA to 1.25 (p = 0.002); 6 (21%) patients achieved ID. At 12 months patients showed AJ 0 (p = 0.01), pain 0 (p = 0.009), VASp 0 (p = 0.0005), VASphy 0.75 (p = 0.0001), JADAS-10 3 (p = 0.0001), JSpADA 1 (p = 0.0004), ESR 6 mm/h (p = 0.02), and CHAQ 0 (p = 0.12). AE was present in 0 (p = 0.08), SIP in 0 (p = 0.01), and LL in 6 (24%) (p = 0.03) patients. ID was recorded in 22 (73%) and CR in 9 (30%) children during the observation period. Achievement of ID at 12 months was associated with baseline presence of active sacroiliitis (p = 0.02).

Conclusion: In this retrospective cohort of ERA patients on TNF-blockers a significant and progressive reduction in disease activity measures was observed. Patients with baseline axial involvement appear to benefit most from this therapy.

References

1. Hugle B, Burgos-Vargas R, Inman RD, et al. Long-term outcome of antitumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis. Clin Exp Rheumatol 2014;32:424-31.

2. Consolaro A, Ruperto N, Bazso A, et al. Development and validation of a composite disease activity score for Juvenile Idiopathic Arthritis. Arthritis Care Res 2009;658-66.

3. Weiss P, Colbert RA, Xiao R, et al. Development and Retrospective Validation of the Juvenile Spondyloarthritis Disease Activity Index. Arthritis Care Res 2014;66:1775-82.

4. Wallace CA, Ruperto N, Giannini EH. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004;31:2290-4.

Disclosure of Interest: None Declared

P417 An audit to determine the characteristics of axial symptoms and imaging studies in children/adolescents with juvenile-onset spondyloarthritis/enthesitis related arthritis described in the literature

Ruben Burgos Vargas1, Ana L. Ortiz-Peyegahud2

1Rheumatology, Mexico, Mexico; 2Hospital General de Mexico, Mexico, Mexico
Presenting author: Ruben Burgos Vargas

Introduction: Peripheral arthritis and enthesitis characterize the onset and course of JoSpA/ERA. Axial symptoms (ax-symp) are rare at onset and increasingly frequent in patients at risk of ankylosing spondylitis (AS). Unfortunately, most papers, including those mentioning the distinctive term “inflammatory back pain” (IBP) lacked of precision about symptoms.

Objectives: To identify the elements that define ax-symp in children and adolescents with joSpA/ERA.

Methods:

We extracted information regarding ax-symp, clinical signs, and imaging studies referring to spinal and sacroiliac joints and entheses in joSpA/ERA patients from series of cases, case-control and cohort studies appeared in PubMed from 1966 to 2016.

Results: 58/1405 articles mentioned scarce, ambiguous, and non-specific clinical and imaging data about the involvement of the spine and sacroiliac joints and entheses. Only nine studies described timing; five referred to IBP characteristics, and four to imaging data. The analysis suggests ax-symp occur within five years from onset in up to 50% of the patients; radiographic sacroiliitis is seen and AS diagnosis is made 7.5 to 15 years after onset; syndesmophytes are rare before the of 20 years. MR studies seem to add nothing new yet.

Conclusion: Few papers describe timing and characteristics of ax-symp and radiographic sacroiliitis in children with joSpA/ERA evolving to AS. In contrast, most papers, including AS, do not present enough support to confirm ax-symp in joSpA/ERA patients, including those with AS; the effect of these factors may increase the proportion of false positives in the clinic and in clinical trials.

Disclosure of Interest: None Declared

P418 Juvenile-onset Ankylosing Spondylitis(JAS) and its bone metabolism

Zhang Pingping1, Mou Yikun1, Qi Jun2, Jiang Yutong2, Gu Jieruo2

1Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; 2Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Presenting author: Zhang Pingping

Introduction: Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease which characteristically involves the axial skeleton, enthesis regions or peripheral joints.As a chronic disease, AS generate high socioeconomic costs and AS cases require lifelong treatment. Severe pain and spine destruction causes high prevalence of work-related disabilities and a decrease in quality of life, which is a huge burden for the case, their families and the society.According to their onset age,the patients was classified to, Juvenile-nset Ankylosing Spondylitis (JAS), whose onset symptoms before the age of 16 years, and Adult-onset Ankylosing Spondylitis(AAS). Clinical phenotype and prognosis of JAS is different from AAS, but up to now scarce information about JAS was reported, especially the related bone metabolism mechanism.

Objectives: To analyse bone metabolic index(BMI) changes on patients with Juvenile-onset Ankylosing Spondylitis(JAS)and their relations with clinical index.

Methods: To collect the clinical data of JAS,such as C-reactive protein (CRP), blood sedimentation (ESR),the disease activity index (BASDAI),functional index (BASFI) and bone mineral density (BMD), detect the serum bone metabolism index,such as Wnt-3a, BMP-2, Dkk-1, 25 (OH) D and ICTP, then group these data and do statistical analysis.

Results: Osteopenia and VitD lack were widespread in JAS. Compared with controls, The elevated Wnt-3a and reduced Dkk-1 levels were not significant in JAS (P > 0.05), and there was no significant correlation between the two indexes and other BMI, course, clinical inflammation index, BASDAI and BASFI.However,the serum ICTP and BMP-2 were increased significantly in JAS, and both the CRP and BMP-2 were positive related with serum Wnt-3a(r was 0.271 and 0.250 respectively, P < 0.05).Correlation analysis shew there was positive correlation between serum 25 (OH) D and hip BMD in JAS(r = 0.383, P < 0.01), and there was negatively correlation between ICTP and BASDAI (r = -0.405 and -0.273 respectively, P < 0.05).Besides,regression analysis shew that both serum 25 (OH) D and the disease course were independent prognostic factors of patients’ hip BMD decreasing, where as CRP and ICTP were also independent prognostic factors of patients’ BASDAI. BMI in JAS with different clinical phenotypes were compared, BMP-2 level was much higher in JAS with hip joint involvement than other groups(P = 0.032), while there was no significant difference in serum 25(OH)D,ICTP,Wnt-3a and Dkk-1 level in all groups(P > 0.05).

Conclusion: Bone metabolism imbalance exists in JAS,and BMP pathway played an important role in the JAS with hip lesions and deserves further research.

Disclosure of Interest: None Declared

Poster Session: Systemic JIA II

P419 Identification of best cut-off points and clinical signs for discrimination of rheumatic mask of hematooncology disease and systemic onset of juvenile idiopathic arthritis

Mikhail M. Kostik1, Shilova Ekaterina1, Ilia Avrusin1, Yuriy Korin1, Olga Kopchak2, Eugenia Isupova1, Irina Chikova1, Panova Tatyana3, Margarita Dubko1, Vera Masalova1, Ludmila Snegireva1, Tatyana Kornishina1, Olga Kalashnikova1, Vyacheslav Chasnyk1

1Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation; 2Pediatry, Kirov’s regional children’s hospital, Kirov, Russian Federation; 3Pediatry, Leningrad regional children’s clinical hospital, Saint-Petersburg, Russian Federation
Presenting author: Mikhail M. Kostik

Introduction: Systemic onset of juvenile idiopathic arthritis (SoJIA) is a diagnosis of exclusion and required a broad spectrum of differential diagnosis. Patients with malignant hematooncology diseases (HOD) can have the similar to SoJIA symptoms as fever, lymphadenopathy, hepatosplenomegaly, joints pain and arthritis, increased ESR, CRP, anemia and should be discriminated from SoJIA. Due to presence of rheumatic masks children with HOD can be admitted to rheumatologic department.

Objectives: The aim of our study was to find the best cut-off points and clinical signs allowed to discriminate patients who have the rheumatic masks of HOD from patients with SoJIA.

Methods: In the retrospective study were included 86 patients with SoJIA and 21 children with HOD who were admitted in the rheumatology department due to rheumatic masks with initial provisional diagnosis - SoJIA. The HOD group was presented with patients with acute lymphoblastic leukemia (n = 18), neuroblastoma (n = 1) and lymphomas (n = 2). We evaluated the presence of main clinical signs in both groups and detected the best cut-off points of qualitative variables with ROC-analysis 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 no differences in onset age, presence of hepatosplenomegaly, lymphadenopathy, lung, CNS involvement, levels of hemoglobin, AST, LDH, ALP, GGTP, ferritin and sodium levels between both groups (table). The main diagnostic signs, allowed to discriminate HOD from SoJIA were: number of active joints ≤3 (DOR = 4.4 (95%CI:1.5-13.2), p = 0.005), CRPБ < 15 mg/l (DOR = 5.6 (95%CI:1.7-18.4), p = 0.002), PLT ≤ 307x109/l (DOR = 22.9 (95%CI:4.9-107.0), p = 0.0000001), WBC ≤ 8.9x109/l (DOR = 50.2 (95%CI:6.3-401.3), p = 0.0000001), albumin > 43.3% (DOR = 28.8 (95%CI:5.6-149.2), p = 0.000001), no fever (DOR = 37.3 (95%CI:7.2-192.8), p = 0.0000001), no rash (DOR = 39.8 (95%CI:8.4-188.5), p = 0.0000001), night bone pain (DOR = 2364.3 (95%CI:92.9-60169.9), p = 0.0000001), any bone and joint pain (DOR = 227.6 (95%CI: 12.5-4158), p = 0.0000001), pathologic fractures (DOR = 32.7 (95%CI:1.6-661.0), p = 0.0004).

Parameters HOD (n = 21) SJIA (n = 86) p
WBC, x109/l 7.4 (5.3-8.3) 14.6 (9.3-18.5) 0.002
PLT, x109/l 175 (109.5-249) 436 (256-583) 0.00001
CRP, mg/l 12.3 (5.9-48.8) 57 (18-113) 0.005
Active joints, n 1 (1-3) 4 (2-13) 0.006
Fever, n (%) 11/21 (52.4) 82/84 (92.6) 0.0000001
Rash, n (%) 2/21 (9.5) 67/83 (80.7) 0.0000001
Night pains, n (%) 12/21 (57.1) 0/86 (0) 0.0000001
Bone pains, n (%) 20/21 (95.2) 0/86 (0) 0.0000001
Pathological fractures, n (%) 3/21 (14.3) 0/86 (0) 0.0004

Conclusion: The found diagnostic criteria can help physicians to discriminate HOD patients with “rheumatic masks” into the group of patients with suspected SoJIA.

Disclosure of Interest: None Declared

P420 The ability of tocilizumab induces the remission in systemic juvenile idiopathic arthritis: the main predictors

Mikhail M. Kostik, Irina Chikova, Eugenia Isupova, Margarita Dubko, Vera Masalova, Ludmila Snegireva, Tatyana Kornishina, Tatyana Likhacheva, Olga Kalashnikova, Vyacheslav Chasnyk

Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation
Presenting author: Mikhail M. Kostik

Introduction: Systemic juvenile idiopathic arthritis (SJIA) is one of the most striking forms of juvenile arthritis, required biologic administration due to failure of corticosteroids (CS) and DMARDs. Currently there are two strategies in treatment SJIA with biologic: blockade of IL-1 and IL-6. Despite similar efficacy and safety profile in latest ACR recommendations blockade of IL-6 recognized as second-line biologic treatment after using the anakinra. The question about first line biologic treatment in SJIA is still open.

Objectives: The aim of our study was to evaluate outcomes and find predictors of remission in SJIA children, receiving TCZ therapy.

Methods: Our retrospective study was included 48 active SJIA children who fall CS, methotrexate (MTX), cyclosporine A (CsA) and their combination in whom TCZ was initiated in dosage 12 mg/kg if weight was < 30 kg and 8 mg/kg if weight ≥ 30 kg. The duration of study was limited the 1st and last TCZ infusions. We evaluated clinical and laboratorial signs, attributed to SJIA, such as presence of fever, hepatosplenomegaly, serositis, rash, lymphadenopathy, active joints, the levels of Hb, WBC, PLT, granulocytes, LDH, and macrophage activation syndrome (MAS). We check the granulocytes levels throw 1 and 2 after 1st TCZ infusion. The efficacy of TCZ was measured throw changes of SJIA attributed signs, symptoms, dynamic of concomitant treatment and achievement the remission according to C. Wallace (2004) criteria.

Results: The main demographic parameters (Me; IQR) included the age-9.9 (5.-12.7) years and delay of TCZ-27.0 (5.9-89.7) months. The treatment before TCZ included CS-38 (79.2%), MTX-40 (83.3%), CsA-18 (37.5%) and their combination. The macrophage activation syndrome (MAS) in past medical history before TCZ was in 14 (29.2%).

During the trial CS successfully discontinued 25 (65.8), CsA 8/18 (44.4%), MTX 12/40 (30.0%) patients. In 7 children TCZ was discontinued due to stable remission with median duration 640 days. After TCZ initiation 6 children have experienced MAS, but all of them had MAS before TCZ, so no “new cases” were observed on TCZ. 5 children early withdrew during the trial due to adverse events (infusion reaction, MAS) and 2 children died (1 severe uncontrolled MAS, 1 amyloidosis).

During the TCZ treatment 40 (83.3%) achieved the remission in 138.5 (56.0; 255.0) days. Patients, who achieved remission had milder disease course, presented in less frequent hepatosplenomegaly, lung, heart and CNS involvement, hemorrhagic syndrome and MAS. They had higher Hb (p = 0.02) and lower WBC (p = 0.048), granulocytes (p = 0.015), ESR (p = 0.034), CRP (p = 0.05), LDH (p = 0.0003), ferritin (p = 0.0007). The main predictors of achievement inactive disease, calculated with Cox-regression models, presented in the table.

Conclusions: We found clinical and laboratorial criteria for SoJIA remission during the tocilizumab treatment.

Parameters OR (95% CI) p HR p
CRP ≤ 82.0 mg/l** 7,9 (1,4-45,3) 0,016* 1,17 0,66
ESR ≤ 32 mm/h** 17,0 (0,9-314,3) 0,014* 0,85 0,62
Ferritin ≤ 273ng/ml** 56,5 (2,8-1124,9) 0,0001* 2,6 0,02
LDH ≤ 676 U/l** 113,6 (5,3-2451,8) 0,000014* 3,18 0,029
PLT > 335x109/l** 5,0 (0,9-28,9) 0,11* 2,54 0,007
Age of 1st TCZ infusion ≤ 11y.** 2,6 (0,6-12,4) 0,24* 1,44 0,3
Decreaed WBC in 2 weeks > 11%** 13,0 (1,4-124,3) 0,03* 6,03 0,019
Decreased Granulocytes in2 weeks > 12%** 14,0(1,1-185,5) 0,05* 4,7 0,13
MAS before TCZ 0,17 (0,04-0,87) 0,037* 0,7 0,34

Me (IQR), * Fisher’s exact test, ** AUC – area under the curve

Conclusion: We found clinical and laboratorial criteria for SoJIA remission during the tocilizumab treatment.

Disclosure of Interest: None Declared

P421 Efficacy and safety of canakinumab in patients with systemic juvenile idiopathic arthritis: results from an open-label long-term follow-up study

N. Ruperto1, H. I. Brunner2, P. Quartier3, T. Constantin1, E. Alexeeva1, R. Schneider2, I. Kone-Paut1, K. Schikler2, K. Marzan2, N. Wulffraat1, S. Padeh1, V. Chasnyk1, C. Wouters1, J. B. Kuemmerle-Deschner1, T. Kallinich1, B. Lauwerys4, E. Haddad2, E. Nasonov1, M. Trachana1, O. Vougiouka1, K. Leon5, A. Speziale6, K. Lheritier6, E. Vritzali6, A. Martini1, D. Lovell2 and PRINTO/PRCSG

1PRINTO-Istituto Gaslini, Genoa, Italy; 2PRCSG, Cincinnati, OH, United States; 3Necker-Enfants Malades Hospital, Paris, France; 4Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 6Novartis Pharma AG, Basel, Switzerland
Presenting author: N. Ruperto

Introduction: Canakinumab (CAN), a highly selective human anti-IL1 β monoclonal antibody, had demonstrated its efficacy and safety in patients (pts) with active systemic juvenile idiopathic arthritis (SJIA) in a comprehensive global clinical program consisting of one phase II and two phase III trials.1,2 However, limited data was available on long-term efficacy and safety of CAN in SJIA.

Objectives: To assess long-term efficacy and safety of CAN treated SJIA pts over a 5-year (yr) follow-up observational period.

Methods: This was an open-label extension (OLE) study of SJIA pts participating in the global clinical trials of CAN.3 Pts, 2 to <20 yrs of age at the time of enrollment in study, received subcutaneous CAN 4 mg/kg every 4 weeks. Baseline was defined as the starting point of the extension trial. Efficacy assessments were done every 3 months, including adapted paediatric response criteria (aACR), clinical inactive disease and clinical remission on medication (continuous 12 months of clinical inactive disease). Safety assessments included adverse events (AEs) and serious AEs (SAEs).

Results: Overall, 147 pts to the OLE study had a median treatment duration of 3.2 yrs; total treatment exposure was approximately 365 pt-yrs. Of 147 pts, 100 (68%) completed 96 weeks of treatment, whereas 47 (32%) pts discontinued the study. Another 25 pts (17%) discontinued the study after Week 96. Of the 107 pts with an aACR 30 at entry to the OLE study, 61.7%, 79.4% and 86.0% have had aACR 100, 90 and 70 responses, respectively at last assessment. At baseline, 32.7% of patients were with inactive disease which increased up to 60% - 70% between Week 36 and Week 168. Clinical remission on medication was achieved in 43% pts. In total, 137 (93.2%) pts reported at least 1 AE during the 3.2 years median exposure in the study corresponding to 2.009 AEs/100 pt-days (733.6 AEs/100 pt-years) with infections (202.7 per 100 pt-years) being the most common AE. Overall, 47 (32.0%) pts had at least 1 SAE corresponding to 0.089 SAE/100 pt-days (32.6 SAE/100 pt-years) with the most common being JIA (14 pts) denoting disease flares or worsening of SJIA. Ten patients (6.8%) with a total of 12 MAS events were reported as SAE and 7 patients among them discontinued the study. No deaths were reported.

Conclusion: In patients previously treated with CAN in pivotal trials, response to treatment was sustained or improved during long-term treatment in the OLE study. Safety profile of CAN was consistent with safety findings from previous studies.

References:

1. Ruperto N, et al. N Engl J Med. 2012;367(25):2396-406.

2. Ringold S, et al. Arthritis & Rheum. 2013;65(10):2499-512.

3. Ruperto N, et al. Ann Rheum Dis. 2015;74(2):608.

Trial registration identifying number: NCT00891046

Disclosure of Interest: N. Ruperto Grant / Research Support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, Speaker Bureau of: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CDPharma, Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and Vertex, H. Brunner Consultant for: Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK and BMS, Speaker Bureau of: Novartis and Roche, P. Quartier Grant / Research Support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer and SOBI, Consultant for: Abbvie, Novartis, Servier and SOBI, Speaker Bureau of: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer and SOBI, T. Constantin: None Declared, E. Alexeeva Grant / Research Support from: Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb and Centocor, Speaker Bureau of: Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac and Pfizer, R. Schneider Consultant for: Novartis, Novimmune, Sobi and Innomar Strategies, I. Kone-Paut Grant / Research Support from: SOBI, Novartis and Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie and Roche/Chugai, K. Schikler Consultant for: Novartis, Novimmune, SOBI and Innomar Strategies, K. Marzan Grant / Research Support from: Novartis, Abbvie, N. Wulffraat Grant / Research Support from: Novartis, S. Padeh: None Declared, V. Chasnyk: None Declared, C. Wouters Grant / Research Support from: GSK, Novartis and Roche, J. Kuemmerle-Deschner Grant / Research Support from: Novartis, Consultant for: Novartis, SOBI and Baxalta, T. Kallinich Grant / Research Support from: Novartis, Speaker Bureau of: SOBI, Novartis, BMS and Roche, B. Lauwerys: None Declared, E. Haddad: None Declared, E. Nasonov: None Declared, M. Trachana Grant / Research Support from: Novartis, Abbvie, Bristol Meyers, Consultant for: Novartis, Roche and Pfizer, O. Vougiouka: None Declared, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, E. Vritzali Employee of: Novartis, A. Martini Grant / Research Support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, Speaker Bureau of: Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier and Takeda, D. Lovell Grant / Research Support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene and Jannsen, Speaker Bureau of: Genentech, Roche and Novartis

P422 Phagocyte involvement in systemic onset juvenile idiopathic arthritis

Nienke Ter Haar1,2, Rianne Scholman1, Wilco de Jager1, Tamar Tak1, Pieter Leliefeld1, Bas Vastert2, Sytze de Roock1,2

1Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands; 2Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands
Presenting author: Nienke Ter Haar

Introduction: Systemic onset Juvenile Idiopathic Artritis (sJIA) is a systemic autoinflammatory disease, characterized by arthritis, spiking fever and rash and elevation of serum S100-proteins and interleukin(IL)-18, reflecting IL-1 pathway activation. The exact role of monocytes and neutrophils in the inflammatory cascade of sJIA is still to be unravelled.

Objectives: To dissect the role of monocytes and neutrophils in the inflammatory cascade of sJIA.

Methods: In a prospectively followed cohort of 23 new-onset sJIA patients, we evaluated cell counts, serum levels of cytokines, chemokines and other analytes at disease onset and during inactive disease. Cytokine concentrations in supernatant and serum were determined by multiplex immunoassay. We determined neutrophil activation ex vivo (phenotype and cell membrane markers) and after stimulation (ROS-production and degranulation) of cells derived from sJIA with active disease (n = 10) or in clinically inactive disease (n = 6), compared to healthy donors (HDs, n = 16). To investigate the role of monocytes, we assessed cytokine production of peripheral blood derived mononuclear cells (PBMC) from active and remission sJIA patients and HDs (n = 6 for all groups) after stimulation with TLR-4 activating S100-proteins (+/- ATP) or other TLR-ligands.

Results: Twenty-one of 23 patients with onset sJIA had elevated neutrophil counts, while monocyte counts were elevated in only 5/23 patients. Among the inflammatory markers that were significantly elevated in serum of onset sJIA patients, we observed multiple neutrophil specific proteins like elastase and neutrophil collagenase, indicating the importance of this cell type.

Neutrophils from active sJIA patients showed an activated phenotype, reflected by higher ex vivo cell membrane expression of FC-gamma receptors (CD32 and CD64), markers of secretory vesicles (CD35) and specific granules (CD66b). Further, on cytospins of acute onset patients, this hyperactivated state was confirmed, including granulocyte precursors, vacuolization and toxic granules. ROS production and degranulation were also enhanced in active sJIA, both with medium control and after short in vitro stimulation. This activated phenotype was most prominent in patients with a short, fever-dominant disease, while it was less prominent in patients with >1 month active disease, or with a more articular phenotype at disease onset. Neutrophil phenotype normalized when patients improved to clinically inactive disease.

In contrast to the hyperactivated status of neutrophils in active sJIA, PBMC from these patients produced less Il-1b, IL-18, IL-6 and TNF-a upon TLR-stimulation compared to PBMC from patients with clinically inactive disease or HDs, suggesting tolerance after exposure to high TLR4 stimulating S100-levels in vivo. RNA-sequencing of FACS sorted monocytes ex vivo and after LPS stimulation is currently undertaken and will reveal pathways involved in this ‘tolerance’ phenotype.

Conclusion: We show here that monocytes from active new-onset sJIA patients produce less cytokines upon TLR stimulation, while the neutrophils are hyperactivated, reflected by increased cell membrane activation markers, ROS production and degranulation. The exact role of both cell types in relation to the increased S100 protein levels and the IL-1 / IL-18 activaion is currently under investigation.

Disclosure of Interest: None Declared

P423 Biomarkers in systemic onset juvenile idiopathic arthritis: prediction of therapy response

Nienke Ter Haar1,2, Rianne Scholman1, Wilco de Jager1, Ariane de Ganck3, Nadia Ryter4, Miha Lavric5, Dirk Foell5, Sytze de Roock1,2, Bas Vastert2

1Laboratory for Translational Immunology, Utrecht, Netherlands; 2Pediatric Rheumatology, UMCU, Utrecht, Netherlands; 3Biogazelle NV, Zwijnaarde, Belgium; 4BÜHLMANN Laboratories AG, Basel, Switzerland; 5Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany
Presenting author: Nienke Ter Haar

Introduction: Systemic onset juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease, characterized by fever, rash and arthritis. The IL-1 pathway and IL-6 pathway are crucial disease mechanisms in sJIA, exemplified by the excellent responses to IL-1 and IL-6 blocking therapy. However, so far it has not been feasible to base treatment choice on the individual inflammatory characteristics of a patient. In addition, we cannot predict in which patients we can safely stop therapy when inactive disease is reached.

Objectives: We aim to find biomarkers to predict: which sJIA patients will respond to IL-1 blockade at disease onset, and which patients will maintain clinical remission when IL-1 blockade is stopped after reaching clinically inactive disease.

Methods: In our center, patients are treated with recombinant human IL-1 receptor antagonist (rhIL1RA) as first-line therapy. If the response to rhIL1RA is insufficient, either low dose corticosteroids are added or the patients are switched to alternative biologicals. If patients are in inactive disease at time point three months after start of rhIL1RA, we attempt to taper and stop rhIL1RA.

Biomarker discovery was performed in the serum of patients at onset (before start of rhIL1RA) and at time point 3 months in patients with clinically inactive disease on rhIL1RA, using cytokine analysis (Luminex multiplex assay), determination of S100A12 and Mrp8/14 (ELISA) and miRNAs (qPCR). To determine differences between the groups, we used the Mann-Whitney U test, with false discovery rate (FDR) correction by Benjamini-Hochberg methodology.

Results: In total, serum of 19 patients at disease onset and 20 patients at inactive disease was available. Fifty-five proteins and 10 miRNAs were significantly different between patients at onset and at inactive disease after FDR-correction. Proteins included known biomarkers as S100A12, Mrp8/14, IL-6 and IL-18, but also novel markers including metalloproteinases and angiogenesis-related proteins.

Within the onset patients, thirteen patients had a complete response with rhIL1RA monotherapy (GR), while five patients needed additional therapy/switch of therapy (NR) because of persistent fever (n = 2), arthritis (n = 2) or both fever and arthritis (n = 1). One patient had a partial response on rhIL1RA monotherapy. On univariate (uncorrected) testing, 3 proteins and 35 miRNAs were significantly different between GR and NR. After FDR-correction none remained significant, which can be explained by the low number of patients, especially in the NR group.

In the stop-prediction part of this study, ten patients flared during tapering or after stopping of therapy, while nine patients remained in remission. One patient preferred to continue rhIL1RA and could therefore not be categorized in a response group. The PCA of the Luminex data showed that patients that will flare cluster separately from patients that will maintain clinical remission. On univariate analysis, 16 proteins and 2 miRNAs were significantly different, however none were significant after FDR correction.

Conclusion: This study aimed to find novel biomarkers for the prediction of treatment response to rhIL1RA in new-onset sJIA patients. Although no markers were significant after FDR correction, the results still provide potentially interesting biomarkers that need further analysis and modeling. A soon-to-start prospective study on optimisation of stop-strategy of rhIL1RA, will provide the opportunity to validate the predictive value of these biomarkers.

Disclosure of Interest: None Declared

P424 Impact of systemic juvenile idiopathic arthritis/Still’s disease on adolescents as evidenced through social media posting

Renee F. Modica1, Kathleen G. Lomax2, Pamela Batzel3, Armelle Cassanas3, Melissa E. Elder1

1Department of Pediatrics, University of Florida, Gainesville, FL, United States; 2Immunology and Dermatology Medical Affairs, Novartis Pharmaceuticals Corp, East Hanover, NJ, United States; 3Treato, Princeton, NJ, United States
Presenting author: Renee F. Modica

Introduction: Systemic juvenile idiopathic arthritis (SJIA)/Still’s disease is a rare form of chronic arthritis in paediatrics. The patient perspective of living with the disease is not well understood, particularly among adolescent age patients.

Objectives: The objective was to understand the adolescent SJIA experience as shown by their own social media posts.

Methods: English posts from SJIA patients were reviewed on public social media sites.

Results: 71 posts with a date range of 2009-2015 on 15 sites were reviewed in Nov 2015. 24 unique authors were identified: 17 SJIA patients (40 posts) and 7 mothers of SJIA patients (12 posts). Patients were aged 13-20 years. Several patients posted about similar diagnostic experiences marked by 5 stages: (1) misunderstood with their pain and fatigue being overlooked until a crisis occurs, (2) dismissed as ‘fakers,’ where their initial misdiagnosis is often ‘growing pains’ or ‘fake pains’, (3) misdiagnosis, often as cancer, when the symptoms acutely worsen (4) testing stage that leads to an SJIA diagnosis, and (5) focus on the difficulties of dealing with a chronic invisible disease where they feel ashamed of their arthritis and distressed at being different from their peers. Many adolescent patients, looking back at the onset of the disease when they were children, describe themselves as a “sleeping child” rather than the typical active, playing child. Patients describe trying to hide their illness from friends, but express their concerns more openly online. Patients also describe anger directed at SJIA which is described as a powerful external enemy attacking their body, using terms like “bulldozer,” “dragon,” and “monster.” Many posters used superhero language or imagery in their social media posts to help them “fight” the disease and their struggle. Mothers of SJIA patients also used warrior-child imagery and language in their posts. Some SJIA patients also posted about the risk of death, or shared stories abo