Proceedings of the 26th European Paediatric Rheumatology Congress: part 2

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic immunoinflammatory joint disease with a high degree of disability and an unfavorable prognosis. In recent decades, drugs aimed at proinflammatory cytokines, such as tumor necrosis factor (TNF), have been used very often for the treatment of JIA. The effect of these drugs on metabolic processes is not well understood. Objectives: The aim of the study was to study metabolic disorders in children with JIA receiving biological therapy. Methods: 36 children with polyarticular JIA and 20 healthy children were examined in the rheumatology department of the 4th city children's clinical hospital in Minsk. All children with JIA have long received methotrexate, non-steroidal anti-inflammatory drugs and, if necessary, glucocorticoids. In connection with the preservation of a high degree of disease activity during therapy, patients were prescribed adalimumab. All children were determined by the main indicators of the lipid spectrum of the blood. Proteins that make up lipoproteins (apoproteins ApoA, ApoB, ApoE) were determined by the immunoturbidimetric method in the research laboratory of the Belarusian Medical Academy of Postgraduate Education. Statistical data processing was carried out by traditional methods of variation statistics on a personal computer using the program Statsoft Statistica 6.0. Results: In children with JIA, the use of adalimumab showed a significant (p <0.05) decrease in the concentration of ApoA (92.3 [69.7; 99.1] mg / dl) compared with the control group (127.2 [122.1; 132.3] mg / dl) and an increase in ApoB (60.9 [48.9; 73.4] mg / dl) compared with the control group (32.1 [19.9; 50.8] mg / dl). The determination of ApoA and ApoB is used to calculate the ApoB / ApoA coefficient, which is a more reliable tool for assessing cardiovascular risk. With the ApoB / ApoA index <1, atherogenicity is regarded as low, with the ApoB / ApoA> 1, atherogenicity increases. ApoB / ApoA> 1 was established in 10 (27.8%) children with JIA. Apolipoprotein E (ApoE) plays an important role in the regulation of lipid metabolism, has a strong antiatherosclerotic effect. There is an

Introduction: Juvenile idiopathic arthritis (JIA) represents the most common pediatric chronic rheumatic disease. Children with JIA present an increased risk of infections, due to the immune-regulatory effects of disease modifying antirheumatic drugs (DMARDs); many of these infections are vaccine-preventable. Nevertheless, suboptimal vaccinations rates are reported in children with JIA. Objectives: To evaluate vaccination coverage in a population of children with JIA and to describe the prevalence of the adverse events following immunization (AEFIs) in our cohort. Methods: A single-centre retrospective study was conducted by reviewing medical records of all JIA patients, diagnosed according to ILAR criteria, admitted to the Pediatric Rheumatology Unit of University of Naples Federico II from January to December 2019. Parents were asked to provide the vaccinations records in form of the vaccination booklet. The occurrence of AEFIs was explored by telephone interviews.
Introduction: Intrarticular corticosteroid injections (IACI) are widely used in the management of patients with juvenile idiopathic arthritis (JIA). General anesthesia can be avoided in case of a small number of joints to inject or in older children. However, pain and anxiety may reduce the patient compliance to IACI, and may compromise the accuracy of the procedure. In order to overcame such problems, the use of appropriate methods of pain and anxiety control is advisable. Objectives: To assess the effectiveness and satisfaction of patients undergoing IACI with the use of topical numbing agent or under minimal sedation. Methods: Patients with JIA who underwent an IACI of up to 3 joints were recruited. Depending on age and number of joints to treat, a group of patients (group A) were injected with the application 30 minutes prior the procedure of a topical numbing agent (prilocaine+lidocaine) to the skin over the injection site. Another group of patients (group B) were treated under minimal sedation (Ketorolac/Tramadol or Morphine + Midazolam). The physician was asked to record the degree of motion and pain of the patient during the procedure and the patient (or parents for patients aged less than 4 years) was asked to report the degree of pain and satisfaction on a Visual Analogue Scale (VAS) from 0 to 10. Results: Twenty-seven patients were enrolled for a total of 30 procedures, 17 and 13 of them in group A and B, respectively. The median age at the procedure was 10 years for group A and 11 years for group B. For group A median pain scores for patients, parents and physicians were 2, 2 and 1.5, respectively. In patients of group B who underwent the IACI under Ketorolac/Tramadol the median pain scores for patients, parents and physicians were 3, 5.25 and 2.5, whereas in patients treated with Morphine median pain scores were 6, 6 and 2, respectively. Overall, we found that pain as reported by the patient/parent were higher with increase in the number of sites injected (and, consequently, duration of procedure) and age of patient. Amount of motion during procedures was overall negligible. The majority of patients/parents was satisfied for the procedures. Only 2 patients treated with Midazolam had psychomotor agitation during the IACI. Conclusion: IACI in a small number of sites without the use of general anesthesia is well tolerated by patients. The level of pain perceived from patients is irrespective of the power of the painkiller used, but seems to correlate with the duration of the procedures. It is possible that, in the paediatric age, the psychoemotional component seems to be decisive, with a progressive loss of tolerance with the increase in the number of injected joints.
for GC-MS analysis of the steroid hormone metabolites age and sexmatched healthy controls were matched to each patient. Patients were excluded if they were treated with corticosteroids in the preceding 3 months. Results: Of the 35 metabolites measured, 23 were significantly lower in JIA patients before the Etanercept treatment compared to the healthy control group. One day after the injection only 5 metabolites were still significantly lower in the JIA patients and all the other 30 metabolites normalized and were similar to the control group. Urine metabolite ratios reflecting CYP21 and 11β-HSD2 enzymatic activity indicate that these two enzyme activities were lower in JIA patients. The slowest recoveries noted were for metabolites of DHEAS and 17 OH pregnenolone. Conclusion: Prior to Etanercept treatment almost all urine adrenal metabolites were significantly lower mainly due to the active inflammatory process. Immediately after the treatment many metabolites raised to normal values as in the control group. The two adrenal enzymes that were found to be affected in JIR are CYP21 and 11β-HSD2. Blocking TN alpha immediately restore adrenal function in JIA.
Introduction: Patients with juvenile idiopathic arthritis (JIA) receive adalimumab treatment. Adalimumab is a monoclonal antibody that blocks TNF-α and is structurally and functionally similar to human IgG 1 . Nevertheless, there are reports of the development of anti-drug antibodies. The production of these antibodies may be associated with treatment failures (a decrease in the effectiveness of therapy or drug inefficiency that developed over time) and hypersensitivity reactions. To our knowledge, there is currently limited information on the availability of adalimumab antibodies (AAA) in patients with JIA. Objectives: to evaluate the prevalence rate and the clinical significance of AAA in patients with JIA on adalimumab treatment. Methods: 26 patients with JIA were examined, 17 of whom had the oligoarticular form of the disease, 7 of them with uveitis, and 9 patients had the polyarticular form of the disease, 3 of them with uveitis. Among them, there were 13 (50%) girls and 13 (50%) boys. The mean age was 11.0 ± 3.4 years; the mean disease duration was 4.1 ± 2.2 years. Patients received adalimumab (at least 1 year before the study) with concomitant administration of methotrexate (MTX) or adalimumab only -13 children who did not receive MTX for at least 3 months prior to the study as a result of either adverse events of MTX administration (5 patients) or permanent drug remission (8 patients). Before starting adalimumab therapy, all participants were treated with MTX. The mean duration of adalimumab treatment for these patients was 1.8 ± 1.0 years. The serum AAA level of antibodies was determined using the enzyme immunoassay (EIA) method. This method determines both free and bound antibodies to adalimumab at reference values less than 10 AU/ml. a and was used every 2 weeks for 3 months. The values were presented as mean ± standard deviation. Data processing and analysis were carried out using Pearson's chi-squared test and Spearman's correlation test. Results: 8 (31%) of the 26 patients enrolled in the study had AAApositive results. The mean AAA level in positive patients was 40.8 ± 20.1 AU/ml. Further disease relapses tended to occur significantly more often in AAA-positive patients than in AAA-negative ones (χ2 = 5.46, p = 0.019). Thus, 5 of 8 (62.5%) AAA-positive children had at least 1 exacerbation of the disease within 3 months, compared with 3 of 18 (16.7%) in AAA-negative ones. 7 out of 8 (87.5%) AAApositives did not take MTX for at least 3 months compared to 6 out of 18 (33.3%) in AAA-negative ones. Thus, AAAs are found to be significantly more frequent without concomitant administration of MTX in the treatment of JIA (χ2 = 6.5, p = 0.01). There were no observed adverse events or side effects during adalimumab therapy. No significant correlation was found between the presence of AAA and sex, Introduction: Advances on molecular medicine, illumination of the cytokine network and the immune pathways shed light on the etiopathogenesis for a better understanding of Juvenile idiopathic arthritis (JIA). However, the fact that the course of the disease differs individually strongly suggests the effect of external factors. Objectives: The current study was undertaken to evaluate sociodemographic and sociocultural features, parent behavior, the gestation and breastfeeding period, nutritional status of early childhood in our patients with JIA, and to determine their relationship with disease activity, damage index, remission time, and relapse rate. Methods: The study was conducted with a face-to-face questionnaire method with the parents of 171 patients with JIA and 183 healthy children. The medical patient records were reviewed. Juvenile Arthritis Disease Activity Score (JADAS) 27, Wallace clinical inactive disease criteria, Juvenile Arthritis Damage Index (JADI), and relapse rates were used to assess the general medical condition of each patient. Results: The median age of JIA patients (n = 171) was 13 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), with a female ratio of 59,1%. Age at disease onset was 7 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) years. The first remission time was 5(1-17) months. The patients were evaluated according to disease subtypes and treatment modalities. There was no difference in the duration of breastfeeding according to the distribution of the subtypes (p = 0,97). When the breastfed and formula-fed patients were compared, there was a marginally significant difference in terms of first remission time (p = 0,05), whereas there was a significant difference in relapse rate in patients who introduced to cow milk early (<12 months) (p = 0,019). The early risk factors and their relationship with the disease are presented in Table 1. Both breastfeeding durations and maternal literacy levels showed a significant difference in terms of relapse rates (p = 0,01; p=0,03, respectively). There was no significant difference in breastfeeding durations and gestational risks between the patients and the healthy group (p = 0,1; p= 0,65), respectively. However, the smoking rate among family members was significantly higher in the patient group (p = 0,03). Conclusion: In patients with juvenile idiopathic arthritis, breastfeeding rate and duration did not differ when compared to healthy controls. However, breastfeeding duration, cow's milk commence age, and maternal literacy appeared to be relevant to the relapse rates. Going to preschool both influence the remission time and relapse rate. These findings suggest a role for parental attitude and nutritional status during early childhood in the course of JIA.

Disclosure of Interest
None declared Introduction: Immunogenicity and low trough concentrations have been associated with adalimumab treatment failure in several studies of paediatric inflammatory diseases, indicating the possible value of therapeutic drug monitoring (TDM). Adalimumab efficacy may be improved by changing dose or treatment intervals based on drug concentrations. However, lack of standardization, assay heterogeneity, and paucity of research hinder the implementation of TDM in clinical practice.
Objectives: To assess the relationship of trough concentrations, immunogenicity and adalimumab response in paediatric patients with JIA. Methods: Monocentric cohort study of patients ≤18 years with JIA treated with adalimumab due to active arthritis. Clinical data and plasma samples were collected during routine follow-up. Adalimumab trough concentrations were measured by liquid chromatographytandem mass spectrometry (LC-MS/MS). Anti-adalimumab antibodies were measured in samples with trough concentrations <5mg/l. Disease activity was evaluated using the clinical Juvenile Arthritis Disease Activity Score with 71 joint count (cJADAS71). Response to adalimumab was defined as at least 50% reduction of disease activity within 3 months of therapy followed by clinical inactive disease or minimal disease activity after 6 months. The latter was defined as cJADAS71 ≤1.5 and ≤2.5, for oligoarthritis and polyarthritis, respectively, or an active joint count equal to zero when cJADAS71 was unavailable.
Results: 36 adalimumab trough samples were available from 35 JIA patients. Although there was no significant difference in median adalimumab dose, trough concentrations were significantly lower in patients with secondary failure compared to primary failure or an adequate adalimumab response (p-values <0.01). In addition, there were 11 samples with trough concentrations <5mg/l, 9 in the group with secondary failure and 2 in the group with adequate adalimumab response (Table 1). Conclusion: Adalimumab trough concentrations were significantly lower in JIA patients with secondary failure compared to primary failure or an adequate response to adalimumab. Anti-adalimumab antibodies were present in 8 out of 11 samples with trough concentrations <5mg/l. Adalimumab trough concentration measurements may identify JIA patients that would benefit from increased doses or shorter treatment intervals. In addition, JIA patients with primary failure and adequate adalimumab trough concentrations may respond better to biologic agents with other therapeutic targets. Although biologic agents have improved disease outcome of patients with JIA, concentration measurements using reliable and cost-effective methods, such as LC-MS/MS, could further improve efficacy of biologic agents and guide treat-to-target strategies. Introduction: Most studies of physical fitness (PF) in juvenile idiopathic arthritis (JIA) have shown decreased levels of maximal oxygen consumption (VO 2 max) compared to healthy peers. In JIA, boys have higher PF-levels than girls and younger children have higher levels than adolescents, congruently with data of healthy peers. Previously, we have shown that more than half of JIA-patients had below normative average of VO 2 max. However, monitoring physical activity (PA) using accelerometry, 68% of boys and 39% of girls with JIA fulfilled the recommendations of WHO of ≥1 hour of PA per day, which was comparable to normative values (61%/39%). Moreover, patients reporting engagement more than 7 hours per week in club-sports exceeded accelerometry values of healthy peers. Objectives: To explore the association between PF and specific sport habits in 10 to 16-year-old JIA-patients, related to gender, BMI, disease activity, and pain, and comparing the most fit quartile (Q4) of patients (respectively boys and girls) to the least fit quartile (Q1). Methods: Sixty patients with JIA performed an indirect ergometertest of VO 2 max (Watt max test) and answered the Physical Activity and Sport Questionnaire (PASQ). Objective PA-monitoring for one week was conducted using the GT1M accelerometer. Cut-offs for moderate-high and high intensity PA were set to >1000 and >2500 counts per minute, respectively. Disease activity was assessed with the JADAS-27, current pain and worst pain last week were measured on visual analogue scales (VAS) and in a one-week pain diary using the Faces Pain Scale-Revised (FPS-R).
Results: Girls with JIA (n=36) had lower mean PF than the boys (n= 24) (36.5±8.2/43.4±6.73 ml/kg/min), being below normative values, respectively. In both genders the most fit boys and girls (Q4; 49.3-57/ 40.9-54) had average to well-above normative average PF. The least fit boys (Q1; 33.5-37.4) all had PF-levels well-below normative average. In girls Q1-levels (18.7-30.9) were well-below to below normative average. We found significant differences between most fit (Q4) and least fit (Q1) patients regarding patient´s global wellbeing (p=0.040) and pain diary (p=0.026). These differences were not significant when separating genders, though differences were more pronounced in girls. The least fit girls (Q1) had significantly higher disease activity (JADAS-27) than the most fit girls (Q4)(p=0.019). The most fit boys and girls (Q4) engaged equally in high intensity sports (soccer: 3/24; 2/36, handball: 0/24; 2/36, gymnastics: 2/24; 4/ 36, rowing: 1/24; 0/36). However, more boys than girls played soccer (11/24; 3/36), whereas more girls preferred sports of lower intensity (riding: 8/36; 0/24). Eight of 11 boys in soccer and 2 boys in gymnastics or rowing had below average to well-above normative average of PF (Q3+Q4: 41.6-57). Three girls in gymnastics, 2 girls in soccer, and 2 girls in handball were in Q4 (40.9-54) with levels of average to well-above average PF. The third girl in soccer was in Q2 (31-36.3) with levels of well-below to below normative average. None of the riding girls were in Q4 and only 1 was in Q3 (36.3-40.8) (Below to average normative PF). Comparing accelerometer-monitored values of PA-intensity in girls with low (Q1) and high (Q4) PF, PAvalues of Q1 were significantly lower than in Q4. The same tendency was observed in boys, but not to significance. Conclusion: Our results are in accordance with most other studies of PF in JIA, adding to the knowledge of gender-specific differences in PF and type and behavior in sport activities. It emphasizes the need of regular PF-testing and guidance in high intensity PA and sport in order to improve PF and avoid the risks of inactivity and lifestyle diseases in JIA.
pg/ml), which also showed the highest the frequency of detection of its increase. It was absent in sJIA (7.52±4.74 pg/ml). The highest values of IL-17R (1849836.4±176751 pg/ml) were in the middle age group. The data obtained suggest the compensatory value of increasing IL-17R and the simultaneous initiation of inflammatory and anti-inflammatory processes during exacerbation of JIA. Assessment of the ratios of stimulating and inhibiting cytokines showed in patients with uveitis, the ratio of IFN-γ/IL-1β (4379.29 ±476.83) was higher than with other JIA (from 60.84 ± 14.92 in oJIA to 105.20± 66.01 in pJIA) and IFN-γ/IL-17R (4474.01 ±3899.19 versus from 20.14± 11.48 in oJIA to 934.55±931.37 in sJIA). An increase of IL-1β/IL-17R ratio was characteristic only for sJIA (34.12±26.17). All of these ratios increased with disease activity (r=0.22-0.37) & they did not reflect the unpleasant course of the disease. Methods: In this multicenter, case-control study, 113 fecal samples were collected from 91 children with JIA, with 72 of these samples collected from untreated children (67 of whom were treatment-naïve children). Samples from 28 children with JIA were collected during treatment with MTX as single treatment and samples from 13 children during treatment with ETN. Of those 13 children, four were treated with ETN as single treatment and nine had a combination of ETN and MTX. We compared 28 children on single treatment with MTX with 57 untreated children (52 treatment-naïve), and 13 children on treatment with ETN (nine in combination with MTX) with 62 untreated children (57 treatment-naïve). We also did pairwise comparisons of samples taken before any medication was given (n = 22) and samples taken during ongoing treatment with MTX (n = 14) or ETN (n = 8, four in combination with MTX). The microbiota was characterized by sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha diversity of the fecal samples was measured using the Chao-1 index and the Shannon diversity index. To compare these indices between treated children and untreated children, we used a logistic regression model with age at sampling as a covariate. For pairwise analyses, we used the Wilcoxon signed-rank test.
To analyze the community composition of the microbiota, principal coordinate analysis (PCoA) plots based on Bray-Curtis distances were generated for visual comparisons, and analysis of similarity (ANOSIM) was used to test for differences.
Analyses for relative abundances of taxa were performed at three taxonomic levels (phyla, families, and genera), and logistic regression with age as a covariate was used for calculations of differences between treated and untreated children, while the Wilcoxon signedrank test was used for pairwise comparisons. Significance was set to p < 0.05 and corrections for multiple comparisons were made using the Benjamini-Hochberg method.
Results: Analyses showed no significant differences in α-diversity between children treated with MTX or ETN and untreated children, and pairwise comparisons of samples before and during treatment with MTX or ETN also showed no differences. PCoA plots for children treated with MTX or ETN, in comparison with untreated children, did not show any clustering. ANOSIM showed no significant differences between treated and untreated children. PCoA plots were also made for the pairwise comparisons of children sampled before and during treatment, and according to that analysis the community compositions of microbiota did not change in any uniform way during treatment with either MTX or ETN. Furthermor, analyses of relative abundances of specific taxa did not reveal any significant results in any of the comparisons, after adjustment for multiple analyses. Conclusion: Treatment with MTX or ETN did not alter the composition of fecal microbiota in children with JIA.
Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and an important cause of shortterm and long-term disability if patients are not treated appropriately. By definition, JIA clinically presents with peripheral joint inflammation of unknown origin, persisting for at least six consecutive weeks and starting before the age of 16 years. The predominant subtypes, i.e. oligoarticular (oligo) and polyarticular (poly) JIA, have long been assumed autoimmune diseases caused by dysregulation of the adaptive immune system, with a central role for autoreactive T cells belonging to the Th1 and Th17 lineages and autoantigens that may include aggrecan, fibrillin, matrix metalloproteinase (MMP)-3 and heat shock proteins. Nevertheless, the original T cell-centered hypothesis has been challenged since it does not cover nor completely explain the full spectrum of immune-pathological phenomena observed in patients. lien.desomer@uzleuven.b Objectives: Emerging evidence suggests a potentially important role for neutrophils in JIA pathogenesis. Here, we investigated extensively the phenotypical features of neutrophils present in the peripheral blood and inflamed joints of JIA patients. Methods: Synovial fluids and parallel blood samples from patients with oligo-or polyJIA and blood samples from healthy children were collected. Multicolor flow cytometry panels allowed for in-depth phenotypical analysis of neutrophils, focusing on the surface expression of adhesion molecules, activation and maturation markers, chemoattractant-and Toll-like receptors. Multiplex technology was exploited to quantify pro-and anti-inflammatory cytokines in plasma and synovial fluids.
Results: The vast majority of synovial fluid neutrophils displayed a strongly activated, hypersegmented phenotype with decreased Lselectin (CD62L) expression and increased numbers of nuclear lobes, upregulation of adhesion molecules CD66b, CD11b and CD15 and downregulation of chemokine receptors CXCR1/2. An elevated percentage of CXCR4-expressing aged neutrophils was detected in synovial fluids from patients. Strikingly, significant percentages of synovial fluid neutrophils showed a profound upregulation of atypical neutrophil markers, including CXCR3, ICAM-1 and HLA-DR. Conclusion: Our data indicate that neutrophils present in inflamed joints of JIA patients are strongly activated cells with elevated proinflammatory and antigen presenting potential. This detailed molecular analysis supports the notion that a complex intertwining between these innate immune cells and adaptive immune events drives JIA.

Disclosure of Interest
None declared

P138
The main factors, associated with incomplete vaccination againts measels, parotitis, rubella and diphtheria in 170 juvenile idiopathic arthritis patients N. Lyubimova 1 , I. Objectives: The aim of our study was to evaluate the rate and the main factors of incomplete vaccination against measels,parotitis, rubella (MMR) and diphtheria in JIA patients. Methods: In the present study were included data 170 JIA(55 boys and 115 girls)aged from 2 to 17 years,who received scheduled vaccination before the age of 2 years and before JIA onset against measles,parotitis,diphtheria and rubella.Incomplete vaccination means the reduced number of vaccine to age.In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA.JIA categories were:oligoarthritis -73,polyarthritis -61,systemic-16 and enthesitisrelated arthritis-20.Data presented with median and 25%>75% Results: Incomplete vaccination against MMR was in 50 (42%)diphtheria in 85 (50%) of the JIA patients. The main differences in the studied groups are in the table.There were no differences in sex,JIA categories and treatment, except biologics compare to complete and complete vaccination in all vaccines.No differences in antimeasels(p=0.18),antiparotitis (p=0.1) and anti-rubella(p=0.17)vaccination between complete and incomplete vaccination group.Number of patients with protective level of anti-vaccine antibodies was similar, except parotitis(70% vs 84.2%, p=0.035).The anti-diphtheria antibodies IgG level was lower in the patients with incomplete vaccination group (0.07 IU/ml [95%CI:0.03; 0.22] vs 0.2 [95%CI:0.06; 0.4], p=0.001)as well as number of patients with protective level(34% vs 54%, p=0.002). In the multiple regression model only JIA onset age(p=0.00001)and methotrexate treatment duration(p=0.003) were predictors of incomplete vaccination against MMR and methotrexate treatment duration(p=0.005) and biologic treatment(p=0.05) for diphtheria incomplete vaccination.Incomplete MMR vaccination influence on the maintenance of the protective anti-parotitis level(p=0.036)in regression model.In correlation analysis the number of vaccination influences on anti-diphtheria antibodies level(p=0.017)and number of patients with protective level of anti-diphtheria antibodies(p=0.017). The main predictors in logistic regression for incomplete vaccination for MMR were:onset age<6 years(OR=7. 8  Conclusion: Younger onset of JIA age, longer duration of JIA and methotrexate treatment, biologics and more than 1 biologics are the main predictors of incomplete vaccination againt MMR and diphtheria. Introduction: The prevalence of autoimmune thyroid disorders (AITD) has been reported to be higher in patients with juvenile idiopathic arthritis (JIA) in comparison to the general population. Nevertheless, there is a lack of studies investigating risk factors for AITD development in children with JIA.
Objectives: To investigate the co-occurrence of JIA and autoimmune thyroiditis in southern Italy and to identify potential predisposing factors to anti-thyroid antibodies (ATA) positivity in a JIA population.
Methods: A single-centre retrospective study was conducted. All JIA patients admitted to the Pediatric Rheumatology Unit of the University of Naples Federico II, from January 2001 to December 2019, tested for ATA at least once and with a minimum of 6-months follow-up, were included. For each patient, demographic, clinical and laboratory data were extracted from clinical charts. Differences between patients affected by JIA with or without ATA were analyzed. Results: Three hundred thirty JIA patients (247 females; median age 12.5 years, IQR 9.1-16.1) were included in study. Median age at JIA onset was 4 years (IQR: 2.2-7.8). Twenty-three patients [7% (95% CI 4.5-10. 3)] presented ATA positivity. Twenty-one of them (91.3%) were females. Anti-thyroperoxidase was positive in 18/23 patients (78.2%) while 12 patients presented anti-thyroglobulin positivity (52.1%). Both antibodies were present in 8/23 (34.8%). 19 patients showed the typical ultrasound findings of autoimmune thyroiditis, resulting in a prevalence of Hashimoto's thyroiditis of 5.7% (95% CI 3.5-8.8) in our cohort. Three female patients developed subclinical hypothyroidism, whereas one male patient presented subclinical hyperthyroidism. The remaining 19 patients were euthyroid. No statistically significant difference was observed in regard to age of JIA onset, follow-up duration and JIA subtype between the patients with or without ATA. The proportion of females was marginally significantly higher (p=0.059) in the group with ATA positivity compared to children without thyroid antibodies (91.3% vs 73.6%, respectively). 56.5% of patients with ATA showed ANA positivity compared to 37.5% of patients without ATA (p=0.07). Family history for AITD was significantly higher in children with thyroid antibodies positivity (p= 0.01). Anti-TNF-alpha inhibitors were administered in only 3 children (13%) with thyroid antibodies before their detection compared to 35.5% of patients without thyroid antibodies (p=0.028). Multivariate regression analysis showed that patients with a family history for AITD were about four times more likely to develop ATA (OR 3.75, 95% CI 1.401-10.017, p=0.008) and confirmed that ATA positivity is less likely to occur in patients undergone anti-TNF-alpha therapy (OR 0.127, 95% CI 0.031-0.518, p=0.004).
Conclusion: A high prevalence of ATA positivity and Hashimoto's thyroiditis in patients with JIA was found in our wide southern Italian cohort. As expected, a positive family history of AITD was found to be associated with a higher risk to ATA development during the follow-up. This finding supports the usefulness of an active screening for AITD in JIA children, in particular in patients with relatives affected by thyroid disorders. Notably, patients treated with TNF-alpha inhibitors resulted less likely to develop thyroid antibodies. Further studies are needed to investigate the effect of anti-TNF-alpha therapy on thyroid autoimmunity in JIA.
Introduction: The knee is considered by far the joint most frequently affected at JIA onset. Nonetheless, JIA onset may present with unusual musculoskeletal involvement, eventually leading to a delay in the diagnosis and treatment.
Objectives: To identify the type and number of musculoskeletal sites affected at JIA onset in consecutive patients seen at the study center in an 8 years period.
Methods: Records of patients with new diagnosis of JIA from June 2012 to May 2020 available information in the medical history and standardized joint assessment at diagnosis, were retrospectively reviewed. Systemic JIA subtype according to ILAR classification criteria were excluded. Demographic and clinical features, including the type and number of joints at disease onset and diagnosis, were registered. Data were analyzed through descriptive statistics. Results: Of a total of 333 Caucasian patients included in the study (75.7% females), 241 patients (72.4%) had oligoarthritis, 79 (23.7%) RF-negative polyarthritis, 7 (2.1%) RF-positive polyarthritis, 1 (0.3%) psoriatic arthritis, 5 (1.5%) enthesitis-related arthritis (ERA). Antinuclear antibody (ANA) were positive in 188 patients (56.5%). The median age at onset was 4.8 years (IQR 2.3-9.3). At diagnosis 103 (30.9%) patients had only 1 active joint, 143 (43.0%) had 2-4 active joints, 87 (26.1%) had ≥ 5. As expected the knee, the tibiotalar and the wrist were the most frequently affected joints (77.2%, 41.1%, 21.0%, respectively); cervical spine was involved only in patients with polyarthritis (n=13). Notably, of 103 patients with monoarthritis at diagnosis 98 presented with large joints involvement, among which n=2 isolated elbow and n=2 isolated wrist, and 5 with small joints involvement (Table 1). No sufficient data were available regarding the involvement of tendons and bursae, since the standard joint assessment form did not include them. Nonetheless, additional 4 patients, not included in the sample analysis, had isolated tenosynovitis involvement at diagnosis (n=1 both-sided ulnar extensor tendons; n=2 isolated tenosynovitis of the flexor digiti proprius; n=1 tenosynovitis of 2 flexors digiti proprii). Conclusion: Our study confirms the knee, the tibiotalar and the wrist as the most frequently affected joints at JIA diagnosis. On the other hand, musculoskeletal sites, such as small joints of hands and feet, the hip and the shoulder, usually involved in polyarticular JIA, can be the site of disease presentation in oligo-and also mono-articular JIA. Further, JIA may present with isolated tendon involvement. Our results foster not to delay JIA diagnosis in persistent synovitis occurring in infrequent joints and to include musculoskeletal sites, other than joints, in the standard articular evaluation. This could be realized by merging clinical and imaging (i.e. ultrasound) musculoskeletal examinations in the same assessment.

Disclosure of Interest
None declared Introduction: Treatment response in JIA is currently viewed as a binary outcome: response or non-response. However, JIA is a heterogeneous disease and it is likely that different, identifiable subgroups of children and young people (CYP) may demonstrate different patterns of disease following treatment. Identifying these response subgroups can assist the tailoring of stratified treatment approaches in JIA.
Objectives: To identify subgroups of CYP defined by different trajectories of juvenile arthritis disease activity score (JADAS) components following methotrexate (MTX) initiation for JIA. Methods: MTX-naïve CYP with JIA were selected if enrolled prior to January 2018 in the BSPAR Etanercept Cohort Register or the Biologics for Children with Rheumatic Diseases Study at point of starting MTX. JADAS components (active joint count, physician's global assessment (PGA, 0-10cm), parental global evaluation (PGE, 0-10cm) and standardised ESR (0-10) were calculated based on data collected in the year following MTX initiation. Multivariate group-based trajectory models were used to explore MTX response clusters across the different JADAS components, which were log1p transformed for analysis. Optimal models were selected based on a combination of model fit (BIC, relative entropy, average posterior probabilities), parsimony and clinical plausibility. Clinical and demographic characteristics and achievement of ACR Pedi 30/90 by six months were compared across identified groups. Results: Of 658 CYP selected, the majority were female (68%) and of white ethnicity (86%), with RF-negative JIA the most common disease category (35%). Six subgroups of CYP were identified with differing patterns of disease activity following MTX initiation. Two groups improved across all JADAS components: Fast improvers (11%), and Slow improvers (16%). Persistent PGA (8%), and Persistent PGE (13%) groups maintained one persistent disease feature but otherwise improved. One group relapsed (7%) and a final group had persistent disease overall (44%). There were no differences in active joint counts at MTX initiation between subgroups and all ILAR categories were represented across each subgroup. However, CYP in persistent disease and slow improver groups had higher CHAQ, PGA and PGE scores at MTX initiation. Those with persistent disease were also older at MTX initiation. The majority of CYP fulfilled ACR Pedi 30 response (>60% across every group). ACR Pedi 90 achievement was low at 6 months for slow improvers (30%) and high in the relapse group (68%). Between 41% and 73% achieved ACR Pedi 90 response in groups with persistent disease in one JADAS component.

Conclusion:
We identify different patterns of disease activity within CYP initiating MTX, suggesting a simple responder/non-responder analysis at a set point may be over-simplistic. Commonly used response measures did not adequately describe these heterogeneous response patterns. Understanding both clinical factors associated with, and biological mechanisms underpinning, these subgroups would aid stratified medicine in JIA.
Introduction: Despite modern treatment and improved disease control, pain is the most common complaint in juvenile idiopathic arthritis (JIA). Knowledge about pain thresholds and pain sensitivity among young adults with JIA is sparse. Objectives: To study pressure pain thresholds (PPTs) in young adults with JIA, 16 years after disease onset compared with controls. Methods: Consecutive newly diagnosed children with JIA and a disease onset between 1997-2004 from Central Norway, were included in this prospective population-based long-term follow-up study. Children with onset 1997-2000 were part of the Nordic JIA cohort 1,2 . Age-and sex-matched controls were drawn from the National Population Register of Norway. Inactive disease and remission were defined according to Wallace 3,4 . At the follow-up between 2015-17, data from a clinical examination and blood tests were included in addition to an investigator-blinded quantification of PPTs. A digital algometer was used to manually apply pressure three times with an even rate at the upper and lower limb. PPTs from JIA and controls, and from subgroups of JIA defined by disease status, were compared with multilevel models in STATA.
In the control group, 71% were female and median age was 23.5 (IQR 20.2-26.7) years. Results from the multilevel regression model showed significantly lower PPTs among participants with JIA compared to controls (Table 1). In the JIA group, participants with inactive disease had lower PPTs than both JIA in remission off medication and JIA with active disease ( Table 1). The results were consistent for both upper and lower limb. Conclusion: In this long-term follow-up study of young adults with JIA, we found significantly lower PPTs compared to controls. This may indicate that young adults with JIA have altered pain sensitivity possibly due to accumulated earlier pain experiences. Introduction: Juvenile Idiopathic Arthritis (JIA) represents the most common chronic rheumatic disease in childhood. Non-steroidal antiinflammatory drugs (NSAIDs) and intra-articular steroids are the first line treatment for JIA. Systemic steroids, disease modifying antirheumatic drugs (DMARDs) and biologic drugs are used in children with severe disease. It is not possible at onset of disease to predict when a child can suspend pharmacological treatment, so children affected from JIA have to continue pharmacological treatment for several months or years. Anecdotal reports showed that rarely JIA could present renal involvement due to uncontrolled inflammation or to long exposure to drugs. Objectives: Because no cohort studies investigating renal injury in children with JIA are available, we designed this kind of study in our population. Methods: We retrospectively evaluated 110 patients suffering from JIA. JIA diagnosis was made according to ILAR criteria, treatment was assigned with ACR recommendations. For each patient we recorded the type and the duration of pharmacological treatment and the presence of renal injury. Renal injury was defined by the presence of hypertension (systolic and/or diastolic blood pressure >95 th percentile for age, sex and height), proteinuria (persistentconfirmation within 3 months-urinary protein/creatinine ratio>0.5 mg/mg for children <2 years old and >0. 2  Introduction: Juvenile idiopathic arthritis (JIA) is a pediatric rheumatic disease with partially unknown etiology and pathogenesis. Neutrophils are the most common immune cell present in synovial fluid from inflamed joints in oligoarticular JIA, but the role of neutrophils in the immunopathogenesis of oligoarticular JIA has not been investigated.
Objectives: To characterize neutrophil phenotypes and effector functions in the circulation and in the inflamed joint during active arthritis in children with oligoarticular JIA. Methods: Paired samples of blood and synovial fluid from 17 children with oligoarticular JIA were investigated regarding surface markers, phagocytic ability and oxidative burst. Healthy blood neutrophils exposed to cell-free JIA synovial fluid and healthy oral cavity neutrophils were studied as controls for synovial fluid exposure and transmigration respectively. Results: Synovial neutrophils had a shifted phenotype, characterized by high surface levels of neutrophil activation markers CD11b and CD66b, and mannose receptor CD206 and decreased levels of adhesion molecule CD62L compared to circulating neutrophils. In comparison to oral cavity neutrophils, synovial neutrophils had higher levels of CD11b and a different overall phenotype, suggesting that the phenotype shift in synovial compared to circulating neutrophils is not dependent on transmigration alone. JIA synovial fluid in itself induced activation of healthy blood neutrophils, measured as increased CD11b levels. Synovial fluid neutrophils had impaired ability to phagocytose opsonized E. coli and to produce oxygen radicals upon neutrophil activation with phorbol-myristateacetate (PMA) compared to circulating neutrophils. The impaired effector functions in synovial neutrophils was not dependent on the synovial fluid alone, as addition of cell-free synovial fluid to blood neutrophils did not alter phagocytosis and oxidative burst. Conclusion: JIA synovial fluid neutrophils are activated, have a "polarized" phenotype and impaired effector functions compared to neutrophils in the circulation. This study will help bridge the current knowledge-gap regarding the role of neutrophils in the immunopathogenesis in oligoarticular JIA.   Methods: A case report is described. Data was extracted from the medical chart of the patient and a literature review was undertaken.
Results: A 7-year-old girl was transferred to our tertiary center after being admitted for prolonged intermittent fevers, abdominal pain, fatigue and polyarthralgias. On examination, there was symmetrical proximal muscle weakness, a vasculitic lower limb rash, facial erythema with eyelid edema (Fig. 1) and oral mucositis. Initial laboratory exams revealed pancytopenia, high muscle enzymes, increased erythrocyte sedimentation rate with moderately elevated reactive C-protein, and hypocomplementemia. She also had non-nephrotic proteinuria, without hematuria.Further investigations showed a positive direct antiglobulin test, antinuclear antibodies, antidouble-stranded DNA, anti-Mi 2 and anti-Ku. Serositis (pericardial and pleural effusions, ascitis) and hepatosplenomegaly were present. Lower limb MRI documented diffuse muscle edema. The diagnosis of an overlap syndrome of jSLE and IIM was established. While being treated for concomitant bacteremia, the patient became ill-appearing, with persistent fevers, worsened cytopenias, low fibrinogen and high ferritin and triglycerides, and a Macrophage Activation Syndrome (MAS) diagnosis was assumed. The patient received antibiotics and intravenous immunoglobulin, followed by methylprednisolone pulses, IV cyclosporine (CYC), hydroxychloroquine and supportive therapy with progressive improvement. Due to hypertension (possibly related to CYC) and persistent proteinuria a renal biopsy was performed showing class IV lupus nephritis. After achieving clinical stability, CYC was switched to mycophenolate mofetil as an induction treatment, which is ongoing. Conclusion: IMM with SLE OS is uncommon, and has seldom been described in children. In addition to fulfilling SLE criteria, our patient had clinical, laboratory and imagiologic evidence of IMM. The presence of myositis specific antibodies (especially anti-Mi 2) further supports the diagnosis of an OS rather than an atypical presentation of a lupus myopathy. Juvenile dermatomyositis appears to be the IMM subtype -it is associated with anti-Mi 2, and mild heliotrope and eyelid edema are compatible. Facial rash sparing the nasolabial folds is more suggestive of SLE. MAS is a rare but life-threatening condition that should be suspected in rheumatologic conditions and might be triggered by infections or disease flares. Its identification may be particularly challenging at presentation, especially in SLE where cytopenias are common. The reported prevalence in adult SLE ranges from 0.9% to 4.6%; disease-specific criteria have been proposed. MAS has occasionally been described in IIM. In a patient with a predisposing condition, persistent fevers and illappearance must always prompt a MAS workup, since early diagnosis and treatment are paramount. Due to an early referral to a pediatric rheumatology center, the patient received a prompt diagnosis and treatment, which probably improved her prognosis. Results: Four of the five patients were female (80%) and all aged between 6 and 10 years. Four of them had calcinosis at the time of diagnosis, although they may have had symptoms for 12 to 18 months prior to diagnosis. Skin involvement was severe requiring multiple systemic and topical therapeutic agents in four out of the five patients -significantly more affected than the muscles. One patient had amyopathic subtype with normal Childhood Myositis Assessment Score (CMAS) throughout. None of them had cardiac involvement. All had weakly positive Anti-Nuclear Antibodies (ANA); but were negative for myositis antibodies except the patient with most severe skin involvement and calcinosis (patient 2), who was positive for Anti-TIF1gamma antibodies. Two of the three patients with calcinosis at onset had Cyclophosphamide as the second line agent (chosen due to calcinosis) following systemic corticosteroids with complete resolution of the lesions after six cycles at 500mg/m2. One patient responded to Infliximab, which failed to work after 20 months, following which Cyclophosphamide was tried with good response. The other two patients were given Cyclophosphamide after they failed to respond to Rituximab, which did work for muscle disease. One patient had recurrent episodes of calcinosis needing surgical curettage despite initial response to Cyclophosphamide and later IVIG.  Introduction: Systemic Juvenile Idiopathic Arthritis (sJIA) is a unique form of childhood arthritis. According to current understanding sJIA is primarily driven by innate immune mechanisms at disease onset, but can progress towards chronic destructive arthritis, which can involve T cellular immunity. For yet incompletely understood reasons, sJIA can be complicated by Macrophage Activation Syndrome (MAS), a severe hyperinflammatory condition characterized by a catastrophic cytokine storm resulting in multiple organ failure and high mortality. Objectives: The sJIA/MAS Working Party (WP) aims to promote knowledge and international multidisciplinary collaboration among experts in the field of MAS and sJIA and to foster translational research in order to improve the care and outcome of these patients Methods: Currently 60 PReS members participate to the MAS/sJIA WP. The WP arranges an annual meeting during the PReS Congress, open to all members activities. The MAS/sJIA WP core team frequently report about ongoing activities by email.

Disclosure of Interest
Results: Several studies are currently ongoing. A project aimed to establish and validate a risk score for MAS in sJIA patients using routine laboratory parameters of disease activity and severity has already completed the construction phase. Recently, building of a validation cohort comprising data form 182 patients from 10 paediatric rheumatologic centers has been accomplished and is awaiting analysis (Claudia Bracaglia). A second project focused on MAS patients with systemic thrombotic microangiopathy (TMA) has just completed the collection of 27 patients with MAS and TMA from 18 centers in 9 countries and results will soon be published (Francesca Minoia). Furthermore, the MAS/sJIA WP participated in the data collection phase of a project on the development of new criteria for primary HLH (Jan-Inge Henter and AnnaCarin Horne Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an immunological disorder characterized by clinical signs and symptoms of severe uncontrolled inflammation, due to massive release of inflammatory cytokines. A delay in diagnosis is common, and is one of the factors that determine the poor outcome. HLH is classified into primary (pHLH) and secondary (sHLH). It is important to differentiate between the two as management differs. Objectives: To describe the clinical and laboratory profile of HLH in infancy.
Methods: The electronic case files of children (age<1 year) diagnosed with HLH at the AIMS, Kochi, Kerala, between January 2012 and December 2019, was retrospectively reviewed and described. Results: Eight infants, with age range 1.5 months to 7 months, were clinically diagnosed with HLH. All were immunised and had normal development for age. None had a family history suggestive of HLH. Third degree consanguinity was present in parents of patient no.5 and second degree for patient no.7. Duration of symptoms before presentation ranged from 2 days to 68 days. Duration of follow up with us ranged from 12 days to 192 days, for those who expired. All, eight of them, had fever, anemia, thrombocytopenia, hyperferritinemia, transaminitis, raised LDH and CRP. Lymphadenopathy was present only in patient no.4. Before starting specific treatment patient no. 7 had Pseudomonas sepsis, patient no.5 had Roseomonas gilardii infection; patient no.3 and 4 were IgM CMV positive but their PCR was negative. Both of them had received prior blood transfusion. Before making a definitive diagnosis of HLH patients were treated for PUO, sepsis ? cause and acute liver failure. There was a delay in diagnosis for all patients except patient no.7. All of them were treated with HLH 2004 protocol with modification according to clinical status of the patient. Later, broad spectrum antibiotics, antifungals and antivirals were used for all. Anakinra was tried for patient no.5. Five patients (pHLH) succumbed to sepsis and MODS and three (one pHLH and two sHLH) are continuing follow up. HSCT was not done in any of them. Other clinical features are shown in Table 1. Conclusion: Making a timely diagnosis of HLH is difficult. Differentiating pHLH from sHLH is very important as the management differs. Genetic testing should be done for all infants with HLH. Negative genetic study doesn't rule out pHLH. The only curative treatment for pHLH is HSCT. sHLH infants, once their primary condition is treated, can have normal survival. Hyperbilirubinemia, splenomegaly, neutropenia, hepatomegaly, tissue hemophagocytes and hypertriglyceridemia were more common in pHLH. Health, Kolkata diagnosed as having MAS, admitted between July 2008 and April 2020 was tabulated and retrospectively analyzed . Objectives: To evaluate the clinical features, laboratory findings and outcomes in pediatric MAS, assess the response to different pharmacological therapies, and finally to identify possible factors associated with an unfavourable outcome. Methods: The data of patients diagnosed with MAS over the study period was analyzed for the clinical and laboratory features, treatment details, response to therapy and outcome. Results: 35 patients were diagnosed as having MAS. Primary illness was sJIA in 29 (82%), SLE in 5 (14%) and Kawasaki Disease (KD) in 1(4%). All had fever with varying degrees of multi systemic involvement. Hyperferritinemia was universally present. In the absence of Anakinra in India, pulse methylprednisolone with Cyclosporine was used for treating the majority.10 patients (28.5%) expired. Patients on biologics and steroids can present with a silent MAS which may be difficult to diagnose. Conclusion: MAS is a near fatal complication with protean manifestations and multi organ dysfunction. Hyperferritinemia is characteristic, higher values being associated with increased mortality. Patients resistant to steroids and cyclosporine had a poor prognosis. Early recognition with aggresive management forms the backbone of a successful outcome as reflected by improved prognosis over successive years. Late presentations with multiorgan dysfunction are associated with the poorest outcomes. Methods: Case report's description Results: A two-year-old boy presented with one month history of fever associated with limping gait, cervical lymphadenopathy and skin rash. Laboratory tests showed elevation of inflammatory markers and ferritin. By exclusion criteria, sJIA was diagnosed and steroid therapy started. After a soft tissue bacterial infection, fever relapsed and laboratory tests were consistent with MAS (day 1): Hb 8.5 g/dL, PLT 44000/mm3; FDP 1522 ug/L, CRP 100 mg/L, ferritin 2200 ug/L. High doses intravenous metilprednisolone and oral Cyclosporin A (CSA) were started. On day 2 he presented a Systemic Capillary Leak Syndrome and acute myocarditis. He was admitted into the pediatric intensive care unit (PICU) where intravenous immunoglobulin and subcutaneous Anakinra (ANA) were added. On day 4, due to an Introduction: Sjögren's syndrome is a systemic autoimmune disease characterized by dry syndrome and lymphocytic infiltration of the exocrine and extraglandular glands. Pulmonary involvement in primary Sjögren's syndrome occurs in 9-20% of patients, with very heterogeneous manifestations, and occasionally as an initial mani-festation¹. Diffuse interstitial lung involvement is one of the most characteristic pulmonary manifestations and the most frequent subtypes in lung biopsy are interstitial lymphocytic pneumonia and nonspecific interstitial pneumonia².

Disclosure of Interest
Objectives: 14-year-old girl presented to our hospital because of bilateral interstitial involvement with ground glass areas in lower lobes of both lungs on thorax and abdominal CT scan after for kidney stones follow-up. The patient had grade 1 mMRC dyspnoea and dry cough but denied having symptoms of arthralgia or arthritis, photosensitivity, oral and genital ulcers, Raynaud's phenomenon or episodes of dry mucosa. She had no history of autoimmune disease nor family antecedents of any autoimmune disease. A physical examination disclosed no finger clubbing or swollen superficial lymph nodes but indicated crackles on pulmonary auscultation. Laboratory work showed elevated acute phase reactants, positive rheumatoid factor, positive antinuclear antibodies (1/ 40), positive cytoplasmic antineutrophil antibodies (1/320) and IgG and IgA hypergammaglobulinemia. An examination for autoantibodies were negative for anti-SS-A, anti-SS-B, anti Jo-1, anticentromere and anti-scl-70 antibodies. Iontophoresis with pilocarpine and 6-minute walk test was also normal. Pulmonary function tests demonstrated a mild restrictive impairment and a reduced percent diffusion capacity for carbon monoxide of 55%. Fibreoptic bronchoscopy showed acute inflammation in bronchial mucosa. Flow cytometry of bronchoalveolar lavage and cytology showed lymphocytosis with a 15% of CD4 and 85% of CD8 lymphocytes in bronchoalveolar lavage fluid. Finally, a transbronchial lung biopsy lead to a definitive diagnosis, showing mixed interstitial inflammation and lymphocytic follicular hyperplasia with formation of germinal centers, suggestive of a lymphoid interstitial pneumonia of unreleased autoimmune etiology. Throughout time, the patient reported progression of her symptoms with increasing dyspnoea, persistent dry cough, xerostomia and arthralgia. Schirmer and Rose Bengal dye test were negative, and a salivary gland biopsy showed interstitial plasmacytosis and no IgG4 plasma cells expression which suggested Sjogren's disease. A high resolution computerized axial tomography was requested, suggesting organizing pneumonia in the context of Sjogren's disease.
Methods: Several studies indicate that lung involvement in Sjögren is more frequent in advanced stages of the disease and rarely as an initial manifestation. Sjögren's syndrome in paediatric age is rare and the subtype of secondary Sjogren's is the most common. The course is longer, and the symptoms are more heterogeneous than in adulthood 5 . The diagnosis in children is delayed, because children less frequently report dryness and frequently present with extraglandular clinical features suggestive of other autoimmune diseases. A systematic review on primary Sjögren's syndrome in male and paediatric population reported a 2.4% of pulmonary involvement in paediatric patients. 6 Pulmonary involvement is associated with an increase in the mortality of patients with Sjögren's, therefore, it is essential to periodically monitor patients with respiratory symptoms, making an early diagnosis and treatment of the disease. Results: -Conclusion: We present a case of a patient with childhood Sjögren's disease with atypical onset of disease with lung involvement. Introduction: Sarcoidosis is a multi-system disorder. Little is known about its pathogenesis. In children, the early onset sarcoidosis phenotype including Blau syndrome is more often seen. 1,2 The diagnosis of sarcoidosis is confirmed by demonstrating a typical non-caseating granuloma on a biopsy specimen. Other granulomatous diseases should be excluded, in particular mycobacterial infections, Crohn's disease and immunodeficiencies. The clinical presentation may vary depending on the organs involved and the age of the patient. 3,4 Objectives: We are reporting the case of a boy with a presentation of bone sarcoidosis at a young age. This is a rare phenotype in children.

Disclosure of Interest
Methods: Clinical details were retrospectively collated using routine clinical records. Confirmation of diagnosis was confirmed with bone biopsy.
Results: A 5 year old non-identical twin boy of Ghanaian descent born in the UK had a slowly growing, painless frontal bone mass which started to develop from 7 months of age. He was developmentally normal, with no history of fever, rashes or joint pains. Examination findings revealed frontal bossing while the remainder of the musculoskeletal examination was normal. There was no evidence of rashes, hepatosplenomegaly and ocular examination was normal.
The patient was initially referred for neurosurgical review with suspected fibrous dysplasia, after an initial MRI scan of the head revealed abnormal marrow signal and expansion of the frontal bone, with no soft tissue swelling. However, the CT scan of the calvarium was not suggestive of fibrous dysplasia. Consequently, bone biopsy was performed demonstrating inflammation with granuloma formation. He was referred to Infectious Diseases and Rheumatology. There was no travel history and no TB contact. QuantiFERON TB was negative. Infectious work-up was negative especially for mycobacterial infections. Rheumatology work-up identified on skeletal survey another bone location: a well-defined lytic lesion in the right distal fibula that was biopsied. Infection cultures and PCR were negative. Histopathology identified fibrous tissue and poorly formed granulomas. Laboratory investigations revealed a mild microcytic anaemia with iron deficiency and eosinophilia. He had normal serum calcium and vitamin D and his ESR was 25 mm/hr. ANA, ANCA and rheumatoid factor were negative, and complement C3 and C4 were normal. His serum Angiotensin Converting Enzyme (ACE) level was raised at 125 nmol/ ml/min (normal <40 nmol/ml/min). Investigations revealed mild renal impairment with normal urinary tests including normal calcium, protein and tubular proteins. Ultrasound of the kidneys was normal. Chest X-ray was normal. Lung function was performed and was normal. DLCO couldn't be performed due to low lung volume. Vascular and inflammation genetic panel identified a variant in the NEMO gene. Functional studies excluded NEMO deficiency and patient did not display any of the clinical features. However, a pattern of dysregulated T cells response was identified. He was treated with oral steroids and methotrexate. The oral steroids were successfully weaned off. He has been successfully treated with Methotrexate 10mg s/c to initially stabilise disease with no bone growth, and had no significant side effects. Repeat MRI 2 years later showed increased burden of disease with other newly affected sites however, including the right femoral diaphysis and signal changes in the left tibial metaphysis. Based on the MRI and increasing musculoskeletal pain, decision was made to escalate to anti-TNF (adalimumab) with good clinical response. Conclusion: Bone sarcoidoisis is rare in children but this should be considered in the differential diagnoses when granulomatous inflammation is identified on histopathology. Response to steroids and methotrexate is usually good but some patients will need escalation to anti-TNF.

Introduction
The most worrisome non-rheumatic condition causing persistent night pain in children which closely mimics arthritis is malignancy 1,4 . It is vital to pick up subtle clues at an early stage especially in absence of hematological manifestations , organomegaly and lymphadenopathy.

Objectives
To reveal early clinical clues in pediatric patients with predominant musculoskeletal (MSK) night pains who were initially diagnosed as suffering from some form of chronic arthritis but ultimately turned out to be affected by malignancy. Methods I gathered a data of five pediatric patients fulfilling above mentioned criteria who were seen at Dev Children's Hospital between January 2019 and March 2020. It included demographics, clinical presentation and laboratory results.

Conclusion
All above cases reemphasize the need for an extremely detailed history pertaining to characteristics of pain & pattern recognition in pediatric rheumatology. Prolonged fever , persistent MSK night pain, persistent limp, upper limb and hip joint involvement which is unlikely for JIA at onset are proven to be the earliest subtle clues which should not be missed. 1 Other constitutional symptoms, respiratory, cardiovascular, ophthalmologic or osteoarticular involvement were absent. Growth was unaffected. Auditory tests were normal. Systemic antibiotic treatment and local steroids were ineffective. Laboratory findings were unremarkable, with only mild elevation of ESR (28mm/1 st hr). ANA and ANCA were absent in repeat meausrements (3 months intervals). Cardiovascular disease was excluded. Abdominal US was normal. On the basis of relapsing bilateral auricular chondritis and confirmatory histological findings revealing inflamed cartilage from the pinna of the ear with chondrocyte degeneration, perichondrial infiltrates of lymphocytes, plasma and polymorphonuclear cells and replacement of cartilage with fibrous tissue perivascular infiltrates of polymorphonuclear cells and lymphocytes, relapsing polychondritis was diagnosed. One month NSAIDS trial, pending histology results was ineffective. Methotrexate SC and steroids 1mg/kg/d gradually tapered over a 3-month period were given with significant improvement of auricular inflammation and normalization of markers of inflammation. Auricular chondritis worsened after steroid withdrawal and adalimumab was added to treatment with significant improvement of auricular inflammation in 2 months. In the following 8 months auricular chondritis relapsed during URIs with mild elevation of ESR (25mm 1st hr) and CRP (13 mg/l). After 15 months of treatment, in an effort to prolong the intervals of adalimumab administration, bilateral auricular chondritis relapsed. After 24 months of MTX and 21 months of adalimumab administration inflammation was put in complete remission. The following year no flares or involvement of other systems were observed, under methotrexate and adalimumab treatment.
Conclusion: In this patient isolated auricular relapsing polychondritis was unresponsive to NSAIDs. Steroids and methotrexate greatly improved inflammation but did not induce complete remission. Complete remission was achieved by addition of adalimumab to methotrexate treatment, which also allowed for steroids discontinuation.

Disclosure of Interest
None declared

P173
First ever single center study revealing spectrum of rheumatic diseases in 114 children from an Indian State of Gujarat D. B. Pandya, on behalf of Dr Mehul Mitra, Pankaj Buch, Sonal Shah,

Introduction
There is very limited information and awareness about pediatric rheumatic and immunodeficiency diseases amongst primary physicians 1,2,3 in Gujarat and to make this matter even worse, we are not having a single exclusive pediatric rheumatology and immunology centre for a population of around 60 million.

Objectives
To guesstimate a status of children with rheumatic and immunodeficiency diseases in Gujarat and spectrum of these diseases at Dev Children's Hospital. Methods I gathered a retrospective data of 174 patients who attended Dev Children's Hospital between January 2019 and January 2020. Out of these, 114 children with confirmed diagnosis of inflammatory rheumatic diseases and suspected primary immunodeficiencies were included. Patients with non-inflammatory musculoskeletal(MSK) pains and non-rheumatic diseases causing MSK pains were excluded. My collected data included referral details, demographics, clinical presentation, laboratory results and diagnosis.

Results
Majority of the cases were referred by pediatricians, orthopedicians, hemato-oncologist and general physicians. Main reasons for referral were joint involvement , undiagnosed fever , multisystem disease and elevated inflammatory markers. Many physicians had put a diagnosis like rheumatoid/rheumatic arthritis, autoimmune disease or connective tissue disease. Almost 80% of patients had been evaluated with RF, ASO titer, ANA and joint imaging irrespective of clinical pattern by their primary physicians before referral. Fever , MSK involvement, extreme fatigue, constitutional symptoms, skin and mucosal involvement were prominent complaints noted by me. Family history of rheumatic, primary immunodeficiency (PID) or consanguinity was found in 1/3 of patients. Anemia of chronic disease, elevated ESR and thrombocytosis were almost universal laboratory findings in our cohort.

Conclusion
Rheumatic diseases in children are not anymore rare but due to lack of expertise and awareness , these children are not getting diagnosed. Many cases were advised unnecessary rheumatological investigations even before referral. Results: A 10-year-old female patient was referred to the rheumatology clinic at our hospital with a previous history of fever of 39°C (102.2ºC), loss of appetite, and acute polyarthritis of wrist, knees, and ankles. At that time, laboratory exams revealed a hemoglobin of 11.1 g/dL, C reactive protein 78.6 mg/L, and antistreptolysin O titers of 400 UI/mL (normal range <200UI/ml. Clinical symptoms were relieved only after using NSAIDs. After 6 months, the patient returned to our hospital with a 7-month history of weight loss and claudication related to pain and daily morning stiffness (15 minutes) on her right ankle. New laboratory findings demonstrated positive antinuclear antibodies 1:320, negative rheumatoid factor, and alpha-1-acid glycoprotein of 171 mg/dL (normal range: 44-113mg/dL). Clinical signs suggestive of chronic arthritis with exuberant swelling of the ankles were observed on physical examination (figure A). She was screened for tuberculosis (TB) and had a positive (18mm) tuberculin skin test (figure B). Chest CT revealed infiltrative soft tissue mass in the posterior mediastinum, with homogeneous contrast enhancement (figure C). Magnetic resonance imaging of both ankles was performed and demonstrated bilateral and symmetrical tibiotalar arthritis and prominent tenosynovitis of extensors, flexors, and fibularis tendons (figure D). Right ankle synovial biopsy revealed no granulomas and joint fluid culture was negative for Mycobacterium tuberculosis, confirming reactive arthritis (Poncet's) and tenosynovitis, that may follow mycobacterial infection with no infective agent in the joints. Conclusion: To our knowledge, there is no report of Poncet's disease associated with inflammatory tenosynovitis, showing the particularity of this case. The patient's symptoms resolved after two months of anti-TB therapy.
Introduction: CACP is characterized by congenital or early-onset camptodactyly (usually bilateral); non-inflammatory arthropathy (more frequently in the wrists, knees, ankles, elbows, and hips); coxa vara (reduction of the angle between the neck and shaft of the femur); and non-inflammatory pericardial effusion (a late manifestation, less frequently reported). Recognizing the radiological aspects of this syndrome and differentiating it from JIA is crucial since CACP has no effective treatment and JIA is usually treated with NSAIDs and methotrexate (2,3).
Objectives: To report a rare case of CACP syndrome mimicking JIA. Methods: Case report and literature review.
Results: A 5-year-old male patient presented with arthropathy characterized by painless progressive swelling and restricted movement of the hands, hips, knees, and ankles since the first year of life. He had a family history of camptodactyly from his paternal grandfather. On physical examination, symmetric camptodactyly of the hands and feet was observed (A). He had no history of rash or weight loss and inflammatory markers were unremarkable. The echocardiogram was normal. The pelvic radiograph showed a widening of the joint space and bilateral coxa vara. Magnetic resonance imaging (MRI) of the hips (B) and knees (C) was performed and depicted large joint effusions (arrows, B and C) with normal synovial thickness and mild synovial enhancement in all joints, without bone marrow edema-like signal. A synovial biopsy of the knee was performed and revealed mild synovial hyperplasia without inflammatory cells. The patient was diagnosed with camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP -OMIM 208250), a recently described genetic disorder with no gender predominance identified to date (1). Conclusion: An important differential diagnosis of CACP is juvenile idiopathic arthritis (JIA), a painful inflammatory chronic arthritis that can cause not only joint effusions due to synovial inflammation, but Arthritis was the most frequent extraglandular manifestation. Renal tubular acidosis represented the typical expression of renal involvement (19 cases). Neuromyelitis optica and aseptic meningoencephalitis (6 and 9 cases, respectively) were the most typical neurologic manifestations. Two cases of interstitial lung disease and one of pulmonary hypertension were reported. Almost all patients had autoantibodies, mostly ANA (200/224 patients) and anti-SSA/Ro (170/208 patients). The Schirmer test was performed in less than half of the patients, of whom 62% tested positive. A positive result of minor salivary biopsy was reported in 129/140 cases with available data. Juvenile idiopathic arthritis was the most frequently associated disease, followed by systemic lupus erythematosus (16 and 8 cases, respectively). No significant differences between patients with or without parotitis were found except that patients with parotitis showed increased levels of CRP more frequently than those without it (p= 0.00). Patients with anti-SSA/Ro had more frequently a positive Schirmer test (p= 0.04). The presence of RF was significantly associated with dry mouth (p= 0.00), arthritis (p= 0.00), and rash (p= 0.04). A positive minor salivary biopsy was more common in children with dry eyes than in those without this clinical feature (p= 0.02). Arthritis was more frequent in patients with other diseases than in those with primary SS (p= 0.00). We further investigated SS features according to the age groups (≤ 6 years, 7-11 years, ≥ 12 years). Parotid involvement was inversely proportional to the age and occurred more frequently in younger patients (79% of those ≤ 6 years; p= 0.03). Interestingly, the rate of anti-SSA/Ro positivity increased with age (97% of those ≥ 12 years; p= 0.00). Conclusion: Even though parotitis was the most frequently reported feature, a wide range of clinical manifestations in children with SS has been reported so far. A better knowledge of cSS features will help to pave the way for the development of cSS specific diagnostic criteria.

Disclosure of Interest
None declared Introduction: Pachydermodactyly (PDD) is a rare benign fibromatosis, characterized by progressive painless swelling of soft tissue of proximal interphalangeal (PIP) joints without inflammation signs. Generally PDD affects PIP joints of the fingers, rarely of the thumb. The involvement is typically symmetrical, in few cases unilateral. It usually occurs more frequently in young males. Etiology is unknown, but it arises from mechanical stimulation of periarticular skin (i.e repetitive rubbing, interlacing, and cracking of fingers). PDD has to be considered in the differential diagnosis of arthritis (i.e. juvenile idiopathic arthritis, JIA) and many syndromes (i.e. progressive pseudorheumatoid dysplasia). Prognosis is good with cessation of mechanical stimulation 1  The recurrent paroxysmal appearance of inflammatory lumps (local erythematous tender swellings, which partially respond to antiinflammatory agents), accompanied by elevated inflammatory markers during flares, suggest that FOP may be an autoinflammatory disease. The episodic formation of bone, often following a trivial injury, suggests that innate immune-related triggers induce tissue transformation through the BMP pathway. Moreover, interleukin-1β (IL-1β), a well-known mediator of the innate immune system, has been linked to HO and mineralization in mesenchymal stem cell cultures derived from human bone marrow. We hypothesized that treating FOP patients with anti-IL-1 agents could help ameliorate the progression of this devastating disease. We report our experience treating two FOP patients with anakinra and canakinumab.
Objectives: To decrease the frequency of FOP paroxysms, and/or limit the symptoms and extent of residual lesions, by using anti-IL-1 agents.
Methods: Patients' data and blood IL-1 levels were analyzed to characterize the efficacy of anti-IL-1 treatments in ameliorating the natural progression of FOP.
Results: A 13.5 year old boy and a 5 year old girl were diagnosed with FOP, both clinically and genetically (the typical R206H mutation was found). Various treatments, including high-dose corticosteroids, pamidronate infusions, celecoxib, monteleukast and sirolimus, did not change the course of the disease.
Both patients are receiving canakinumab (the male patient was initially treated with anakinra). The male patient has been treated for over 2 years. Flare rate was markedly reduced from one new lump every 8 days to approximately one every 25 days ( Figure 1). The lumps involved in almost all of these flares are the same: at the left scapular base and within the sternocleidomastoid muscle. The female patient has been treated for a year, and has not experienced any HO flares during canakinumab treatment. Temporarily withholding canakinumab in both patients, led to serious flares 8 weeks after the last dose. Notably, while undetectable levels of IL-1β (<0.125 pg/ml) were found in the three plasma samples obtained from the male patient during treatment with anakinra or canakinumab, high levels (up to 21.52 pg/ml, about 90-fold higher compared to average levels measured in healthy controls) were found in his plasma samples collected during the flare ( Figure 2). In contrast, IL-18 and IL-6 plasma levels, measured before, during and after withholding treatment, were comparable or slightly higher than those observed in healthy controls ( Figure 3A, B). Conclusion: We report here, for the first time, that anti-IL-1 agents were found efficacious in treating two FOP patients. We also found markedly increased IL-1β levels during flares, which normalized following the treatment. We suggest a role for IL-1β in the pathogenesis of this disease. Although it is too soon to conclude whether FOP may be included under the umbrella of auto-inflammatory syndromes, anti-IL-1 agents can be effective in ameliorating the natural progression of FOP. Introduction: Musculoskeletal symptoms are one of the common reasons for applying to rheumatology departments in general practice 1 . Although inflammatory causes are generally considered in the foreground, it is known that non-inflammatory causes including genetic diseases may also be responsible. The absence of signs of inflammation (morning stiffness, redness, tenderness) and normal inflammatory markers in laboratory findings may support nonrheumatologic diseases 2 .

Disclosure of Interest
Objectives: To present genetic disorders that can mimic rheumatologic symptoms and to answer when genetic diseases should be considered in the differential diagnosis in patients presenting with rheumatological complaints. Methods: We retrospectively evaluated 60 patients who applied to Hacettepe University pediatric rheumatology department with musculoskeletal compliants between January 2015 and December 2019 and had been consulted to genetics departmant. The rate and degree of consanguinity, clinical diagnosis, indication for consultation, accompanying musculoskeletal and other findings had been recorded. The diagnosis of genetic diseases were based on physical examination, radiological evaluations and genetic analysis.
Results: A total of 60 patients, 19 boys (31.6%), with a mean age 12.46 ± 1.41 years were included in the study. The rate of consanguinity was 25.0%. The most frequent referral to the genetic department was the presence of skeletal anomalies (n:12) such as camptodactyly, clinodactyly, and bone shortness accompanying joint findings. Other causes include short stature (n:4), joint deformity (n:5), joint hyperlaxicity (n:10), dysmorphic findings such as atypic facial appearance (n:9), accompanying diseases that may be part of a syndrome (n:11), genetic diagnosis suspicion according to the results of radiological examination (n:4) and joint findings without clinical and laboratory signs of inflammation (n:5). Distribution of joint involvement in 20 patients with genetic disease were hands, knees, and hips respectively. In the laboratory evaluation of patients presenting with joint swelling and arthralgia, acute phase reactants (erythrocyte sedimentation rate and C-reactive protein concentrations) were within normal reference values. One third of the patients (33.3%) had a final diagnosis of a genetic disease. The diagnoses of these patients were as follows; CACP (camptodactyly, arthropathy, coxa vara deformity and pericarditis) syndrome (n:3), trichorhinophalangeal syndrome (n:1), progressive pseudoromatoid dysplasia (n:2), LIG4 syndrome (n:1), 3M syndrome (n:1), H syndrome (n:1), SPENCD (spondyloenchondrodysplasia, n:3), and nonspecific connective tissue disease (n:8).
Conclusion: Genetic syndromes with musculoskeletal findings are often unrecognized and misdiagnosed as rheumatologic diseases leading to unnecessary procedures and treatments. Summarizing the genetic diagnosis spectrum that can be detected in these patients will increase the awareness of physicians. Results: According to the results of observation, the disease was more common in the age group of 7-11 years (65%), to a lesser extent among children in the group of 12-15 years (35%), less often in the group of 3-7 years (5%). When examining infectious agents, zoonotic infection was detected in 41% (Listeria monozytogenes, Yersinia enterocolitica). Clinical course of nodular erythema in this group was characterized by an expressed activity of the inflammatory process with multiple elements in the lower and upper extremities, joint syndrome, increased ESR to 45± 3.8 mm per hour, CRP 28± 2.5 mg\l. The disease was preceded by an episode of acute infection with an increase in body temperature, intoxication, in some cases with short-term intestinal syndrome, pharyngitis. The rashes were persistent and recurrent, with a slow regression of laboratory activity. Streptococcal etiology of nodular erythema was detected in 37% of cases. There was an increase in ESR to 25±3.8 mm per hour, CRP 15± 2.7 mg/l, a significant increase in antistreptolysin on average 480± 34% IU / ml. with an increase in individual cases to 870 IU/ml. In 13% of cases, erythema nodosum developed after an intestinal infection. Among the pathogens were identified Sh. disenteria, E. coli, Yersinia enterocolitica, enterovirus. The disease was characterized by moderate activity, a good response to etiological therapy and a short course of NSAIDs . An interesting fact was the development of nodular erythema in 4% of cases caused by the Epstein-Barr virus in groups of children from 3 to 7 years and 7-9 years. They had clinic picture with normothermia, no symptoms of intoxication, periodically occurring elements of nodular erythema on the shins, no blood changes. Therapy aimed at eliminating the virus gave a positive result and did not require specific anti-rheumatic therapy. In 5% of cases, the etiology of nodular erythema was not defined.

Conclusion:
The clinical course of nodular erythema in children depends on the infectious agent that was the trigger of the pathological process. The higher activity and duration of the disease is caused by zoonotic infection, which requires more active antiinflammatory therapy with corticosteroids, which may be associated with the activation of autoimmunity. This group of children was taken for further observation as a group at risk of developing systemic connective tissue disease. Changes in the etiological structure of nodular erythema and treatment tactics require further study. Introduction: Sjögren syndrome (SS) is a chronic autoimmune disorder characterized by inflammation of the lacrimal and salivary glands leading to oral and ocular dryness. Childhood SS is rare and poorly defined and underdiagnosed owing to the lack of childspecific diagnostic or classification criteria. Objectives: The purpose of this study is to describe 12 cases with pediatric SS in order to better clarify the characteristics of the disease in the pediatric age. Methods: We retrospectively reviewed medical records of patients (pts) with pediatric SS referring to three Italian pediatric rheumatology centers. Due to lack of childhood validated SS-specific criteria, physician diagnosis was the only inclusion criteria. Results: We collected data on 12 pts (9 females). The mean age of disease onset is 10.0 yrs (median 10.2, range 4-17). The mean age of diagnosis is 11.83 (median 11.45, range 6-18). The follow up period varied from 0.1 to 9.3 yrs (mean 3.95, median 5.0). The most common manifestations were articular involvement (mainly with arthralgia) (9/12 pts) and parotid/salivary glands swelling (8/12 pts). Xerostomia and xerophthalmia were found in 6/12 pts and in 4/12 respectively. Vaginal dryness was reported only by one pt. Fever and fatigue occurred in 3/12 and 7/12 pts respectively. We also recorded 3 cases of circulating immune complexes manifestations in 3 pts, purpura (n=2) and glomerulonephritis (n=1). We observed an endocrine involvement in 3 pts (1 metabolic syndrome, 2 autoimmune thyroiditis). Abdominal pain was found in 4/12 pts. All pts were positive for autoantibodies (positivity for ANA or anti-SSA or anti-SSB or FR) at presentation. RF test results were available in 8 pts, all positive. Positive ANA (titer>1/320) and anti-SSA were present in 10/12 pts and in 9/12 respectively. Hypergammaglobulinemia (range 1,6-8.04 g/dl) was found in 8/11 pts (1 NA). Abnormal Schirmer test was observed in the half of cases (6/12). Minor salivary gland biopsy was performed in 10 pts resulting in histological evidence of focal lymphocytic sialadenitis in 9/10. Sonographic evaluation of salivary glands was abnormal in all of the patients (10/10).
With regard to treatment, 6/12 pts received corticosteroids and eight were also treated with one or more DMARDs such a hydroxychloroquine (n=8), methotrexate (n=3), azathioprine (n=1), leflunomide (n=1). Biological therapy was used in 3 patients for systemic involvement: 1 received belimumab and then rituximab, while the other patients received rituximab. Conclusion: Xerostomia and keratoconjunctivitis sicca were not common in our series while recurrent parotid swellings were more frequent than what reported in adults. Pediatric recurrent parotitis should increase the suspicion for Sjögren syndrome. Current diagnostic criteria for SS do not include parotitis and therefore, the incidence of SS may be under-recognized in childhood. The disease is not always benign and patients with severe course may need second line treatment including immunosuppressant and biologics. Introduction: Improving our understanding of pediatric rheumatological (PR) patient population is crucial for pediatric rheumatologists to know rheumatic disease epidemiology and to raise awareness leading to early detection. We didn't find studies of PR disorders presenting in the first year of life. Objectives: The aim of this study is to assess the prevalence of PR disorders with onset in the first year of life. Methods: We retrospectively studied patients observed in our Pediatric Rheumatology Unit between January 1 st of 1987 and December 31 st of 2019. We defined acute (<2 weeks), subacute (≥2 and <6 weeks) and chronic (≥6 weeks). Results: A total of 3751 patients were observed in 32 years. Diseases' onset occurred in the first decade of life in 2290 patients (61%) and in the first year of life in 158 (4,2%). Among the latest group, chronic inflammation was the most frequent group of diagnosis (30%), followed by recurrent inflammation (23%), acute inflammation (11%), infection (9%), infiltrative/ degenerative disorders (8%) and subacute inflammation (3%). The remaining patients (16%) were diagnosed with other disorders classified as miscellaneous. Among chronic inflammation group, 14 patients were diagnosed with juvenile idiopathic arthritis (4 systemic); 14 had neonatal lupus and one patient had polyarteritis nodosa. Among recurrent inflammation group, 13 patients were later diagnosed with PFAPA (periodic fever, aphthous stomatitis, pharyngitis and adenitis), 8 were diagnosed with Behçet disease and 6 had an autoinflammatory disorder. Acute vasculitis was diagnosed in 13 patients (9 Kawasaki disease and 4 acute hemorrhagic edema of infancy). Among infectious diseases group, there were two cases of congenital syphilis with arthritis and two cases of osteomyelitis secondary to BCG vaccination. Conclusion: Rheumatological diseases presenting in the first year of life are not exceptional. Although many patients didn't have a definitive diagnosis at the beginning of the symptoms, many of them were later diagnosed with rheumatic disorders, mostly chronic inflammation (30%), which requires early diagnosis, specific treatment and long-term follow-up. Rheumatic diseases must be considered as differential diagnosis in the first year of life in order to avoid delayed intervention and long term disabilities and sequelae.  (1), on the other side measles-induced MAS has rarely been reported (2). Objectives: We present the case of a child known to have sJIA in remission, who presented a Measles primary infection and a secondary KD complicated by MAS. Methods: A 5 years old girl, not fully vaccinated and known to have sJIA in remission under Methotrexate, presented for frequent high grade fever of 3 days duration associated with flat flash red spots on the face and trunk as well as the palms and soles. A Koplik's spot was identified. Conjunctivitis and coryza were also present. Initial viral serology, including measles, returned negative. Fever persisted and on day 7, edema of both hands and feet appeared with bilateral cervical adenopathy, erythematous tonsils, gingivitis, cracked lips and hepatomegaly was noted. All cultures were negative and chest X-ray was normal. Inflammatory markers rose up. Viral serology was repeated and measles IgM came back positive. Cardiac ultrasound ruled out coronary aneurism and the ophthalmic exam showed no uveitis. KD criteria were met and 2g/kg of intravenous immunoglobulins (IVIG) were administered. After 48 hours of clinical improvement, fever reappeared and the patient returned to be ill looking although the rash regressed. We noted high ferritine(2016 ng/ml) together with low C3, decrease in platelets(170 x10 3 /ml) and elevation of hepatic enzymes, LDH and CPK, without increase in the inflammatory biomarkers. MAS was suspected and a bone marrow aspirate showed the presence of mild macrophage hemophagocytosis. Antibodies for Lupus and auto-immune myositis were all negative. Steroids were given, fever disappeared, and spectacular clinical and biological improvements were objected. 2 weeks later, desquamation of all extremities was noted. SARS-COV-2 was not investigated because historically this case presented 1 year earlier than the pandemic. Results: We hereby report, for the first time, KD and MAS triggered by Measles infection in a child with sJIA in remission. The exact mechanism involved in KD-induced MAS and Measles-induced MAS has not yet been defined but a defective immune response is suspected (3). Conclusion: Significant similarities and overlap between measles, KD, sJIA and MAS make an early diagnosis very challenging (1)(3). The recent COVID19 pandemic emphasizes how a viral illness can be responsible of KD and sometimes degenerating in MAS. We report this clinical case as an example of a Systemic Inflammatory Syndrome (SIS) taking place after a viral infection to Measles. In the era of COVID19 pandemic and secondary SIS in children, an additional challenge is present in regions lacking Measles vaccine coverage.

Disclosure of Interest
None declared

P187
The musculoskeletal manifestations of scurvy: a diagnostic challenge for the rheumatologist P2 was a 5-year-old boy, with autism spectrum disorder, malnutrition and severe food selectivity, admitted to our Unit for refusal to bear weight and bruises in lower limbs. The auxological evaluation showed a strongly dystrophic aspect. Coagulation profile and main organ function markers were normal. At nutritional biochemical parameters evaluation, iron and Vitamin C deficiencies were detected (vitamin C: 2 μmol/l). Oral vitamin C therapy was started, with prompt clinical response. P3 was a 7-year-old boy with autism spectrum disorder, admitted to our Unit for lameness and difficulty in walking for a month. At clinical examination, a mottled skin at lower limbs was noted. Joint examination was normal. Auxological parameters and main blood tests were adequate for age. Given the presence of food selectivity, he underwent serum vitamin C dosage (11 μmol/L); hence he started oral vitamin C therapy, with rapid clinical improvement. P4 was a 2 years old boy who was referred for coxalgia and fever. At clinical examination, pale skin, gingival hyperemia, and pain in mobilization of the left hip were present. Microcytic anemia was detected, but main organ and inflammatory markers were normal. No evidence of infection was present. X-ray of femur and knee showed morpho-structural alteration of the distal metaphysis bilaterally. A low intake of fruit and vegetables was reported; hence, dosage of vitamin C was performed, resulting reduced (2.5 μmol/L).
He started Vitamin C oral therapy with clinical response. P5 was a 13-year-old girl with behavioral disorder and intellectual disability, admitted for fever and right knee swelling which appeared two days after a right leg burning. C-reactive protein and ESR were elevated and ultrasound exam confirmed intra-articular knee effusion. Suspecting a septic arthritis, antibiotic therapy was started with laboratory normalization and partial clinical improvement. Considering the persistence of knee swelling after nine days of intravenous antibiotic therapy, the presence of gingival hyperemia and history of food selectivity, vitamin C dosage was practiced (12 μmol/l). Oral vitamin C was administered with complete clinical resolution.
Conclusion: Although scurvy is considered a disease of the past, it still occurs nowadays. Food selectivity associated to autism is a major risk factor for vitamin C deficiency in childhood. Rheumatologists should take into account the diagnosis of scurvy in the diagnostic approach of musculoskeletal disorders in children, especially when development disorders are present. 15.4%), juvenile dermatomyositis (n=1), sarcoidosis (n=1), granulomatous polyangiitis (GPA) (n=1), Sting-associated vasculopathy with onset in infancy (SAVI) (n=1), and oligoarticular JIA (n=1). Respiratory symptoms were present in 6 (46.2%) patients at the time of primary diagnosis. In other patients, the time period between the diagnosis of the rheumatic disease and the onset of the respiratory symptoms ranged from 1 to 12 years. Cough, the most common symptom, was present in 10 (76.9%) patients. Six patients manifested with cough and sputum. Six (46.2%) patients had shortness of breath and one patient had hemoptysis. On the physical examination of one patient, rales and clubbing were detected. High resonance computerized tomography (HRCT) was performed in all patients. HRCT findings were as follows; lymphadenopathy in 8 patients (61.5%), ground glass appearance in 10 patients (76.9%), consolidation in one patient, pleural effusion in one patient, pulmonary nodule in 4 patients (30.8%), fibrosis in one patient, cystic lesions in 3 patients (23.1%), septal thickening in 5 patients (38.5%), bronchiectasis in one patient, and reverse halo sign in one patient. In echocardiographic examination, only one patient had pulmonary hypertension.

Disclosure of Interest
Three patients underwent open lung biopsy, and diagnosis was made with pathological examination of the lung tissue. Of these three patients, two (15.4%) had lymphocytic interstitial pneumonia (LIP), and one patient had chronic inflammation and focal fibrosis. Infectious lung disease was not detected in any patient. Ten patients (76.9%) had interstitial lung disease associated with rheumatic disease, one patient had pulmonary hemorrhage, one patient had pulmonary involvement of GPA, one patient had pulmonary involvement of sarcoidosis. There was no statistically significant difference between the first and last spirometry and DLCO values during the follow-up period. Mortality was 7.5% (1/ 13) in this cohort. Active disease was significantly associated with abnormal TC, HDL, and TG levels (p=0.04*), (p=0.03*) and (p=0.04*) respectively. Multivariate analysis of the factors affecting abnormal cholesterol level revealed that SLE is a significant predictor of abnormal cholesterol level . Presence of jSLE increase risk of abnormal cholesterol 9 times more than cases without jSLE. The overall percent predicted was 80%. Active disease is a significant risk factor for abnormal TG with increased risk of abnormal TG by 3.2 among cases with active disease than cases with inactive disease. The overall percent predicted was 75.6%. Conclusion: children with rheumatic diseases showed significant lipid profile abnormalities. Abnormal TC, HDL and TG are significantly associated with active disease. Presence of jSLE increase risk of abnormal cholesterol. Active disease is a significant risk factor for abnormal TG. Therefore, lipid levels should be monitored regularly and managed in patients with paediatric rheumatic diseases to minimize the longterm risk of CVD. Methods: Non-experimental, cross-sectional and descriptive study. A confidential survey was conducted online, aimed at residents and attendings who deal with musculoskeletal pain. Were addressed with the definitions of arthralgia, arthritis, myalgia, allodynia and hyperesthesia (between five to seven options) with only one correct answer. Correct definitions: arthralgia (pain localized to the joint or periarticular structures, as a only manifestation); arthritis (Criterion one or criterion two: 1 -Joint swelling or intra-articular effusion / 2 -Limitation of joint mobilization associated with at least one of the following: a) Pain b) Tenderness c) Swelling d) Heat); myialgia (pain with muscular origin or referred to muscle, regardless of its etiology); allodynia (pain resulting from usually non-painful stimulus); hyperesthesia (coexistence of allodynia plus hyperalgesia -exaggerated responses to tactile and thermal nociceptive and nonnociceptive stimuli

Introduction
The association of pure red cell aplasia (PRCA) with thymoma led to the discovery of the autoimmune mechanisms involved in the pathogenesis of this rare disease. Till date many adult case reports have revealed a strong link between PRCA and autoimmune diseases, endocrine disorders, rheumatic diseases, autoinflammation and immune dysregulation. [1][2][3][4][5] Objectives To stimulate a search for the genetic and immunological roots for a 2.5 years old girl with syndromic face, pure red cell aplasia, type 1 diabetes and polyarthritis. Methods This is a story of a 2.5 years old girl with pure red cell aplasia, type 1 diabetes and polyarthritis. She was normal till 7 months of age. At the age of 8 months, she was diagnosed with type 1 diabetes. She was evaluated by her paediatrician in view of generalized hypotonia, deformed pinna, low set ears, midfacial hypoplasia, blue sclera, umbilical hernia and retracted eyelids. She had multiple episodes of seizures during next few months. To me, she was presented with one year history of polyarthritis with severe pallor requiring frequent blood transfusions. Family history was inconclusive. Musculoskeletal examination showed polyarthritis involving right knee, bilateral ankles, fingers and toes. Further examination revealed haemolytic facies and hepatosplenomegaly. I was not able to make out any facial dysmorphism mentioned earlier by her paediatrician. Results: Table 1 Conclusion Early age of onset, pure red cell aplasia, autoimmune and endocrine manifestations with some doubtful facial dysmorphism inspired me to suspect some known or unknown immune dysregulation syndrome in this child. Genetic analysis would be the best possible option in this scenario if financial condition permits. Introduction: Galactosialidosis (GS) is a rare inherited lysosomal storage disorder (LSD) which is characterized by a defect in the lysosomal glycoprotein catabolism. Here we report, for the first time, a case of a child affected by GS who presented with recurrent episodes of extensive joint inflammation in both knees. Knowledge on GS related inflammatory joint pathology is lacking, which hampers evaluation of possible mechanisms that could give an explanation for the significant arthritic joint abnormalities as observed in our patient.
Objectives: The aim of this study is to describe the clinical presentation as well as the laboratory, radiologic and microscopic features of this extremely rare presentation of GS. Furthermore, we conduct a literature review on LSD's complicated by arthritis in order to evaluate potential mechanisms that could explain the extensive inflammatory joint swelling observed in our patient.
Methods: In this study we present a 12-year-old Turkish boy who was diagnosed with GS (late infantile form) at 17 months of age. From the age of 8 years, the boy presented with episodes of inflammatory joint pathology of the knee. Informed consent was obtained. Alongside the case report, a literature review using Medline was conducted. An extensive list of known LSD's was combined with the terms: "arthritis", "joint inflammation", "synovitis" and "synovial inflammation". Cases in which joint inflammation was based on a probable cause other than the underlying LSD were excluded. Results: In the present case, owing to comprehensive examinations (i.e. laboratory tests, imaging and microscopic examination) multiple possible causes for the recurrent inflammatory joint pathology could be rejected (i.e. no signs of infectious arthritis, reactive arthritis, osteoarthritis, arthritis secondary to a malignancy or crystal induced arthritis). A diagnosis which could explain the clinical picture is the JIA subtype: ANA negative oligo-articular JIA. However, microscopic examination showed numerous foamy macrophages with extensive vacuolization in the synovial tissue of the inflamed joint, which is not associated with JIA. Given the evidence of storage products within the macrophages of the inflamed synovial tissue and no conclusive diagnosis, GS itself should be considered as the primary cause for the recurrent arthritis. An in-depth literature review using Medline for data on inflammatory joint pathology in LSD's showed that 7 LSD subtypes (i.e. Fabry disease, Farber lipogranulomatosis, Gaucher disease type 1, Mucopolysaccharidosis IX, a-Mannosidosis, Fucosidosis and Cystinosis) could present with disease related arthritis. Multiple potential arthritic mechanisms secondary to storage product accumulation in LSD's have been described, such as: dysregulation of innate immunity and increased upregulation of numerous pro-inflammatory proteins. Conclusion: Given the evidence of storage products within macrophages of the inflamed synovial tissue and the absence of other etiological clues, our hypothesis is that GS itself is the primary cause for the inflammatory joint pathology in our patient. Although, GS cannot be linked directly to joint inflammation, lysosomal defects have been associated to pro-inflammatory effects that possibly could result in arthritic disease. Future identification of other patients with GS is required to support the hypothesis of an arthritic clinical phenotype of GS and to assess underlying pathophysiology. Introduction: Joint pain (JP) is a relatively common complaint among children and adolescents. A painful joint in children for many years continues to maintain the status of the most common symptom of juvenile arthritis. However this symptom should not always be interpreted as a manifestation of rheumatic diseases.
Objectives: The aim of current review is to debate of the structure in children with the chief complaint of JP.
Methods: We retrospectively analysed our series of 600 children which attending outpatient department with complaint about pain lasting longer than two months in one or more joints. The clinical, instrumental and laboratory pictures were collected. Special attention was paid to certain aspect of medical complaints, a complete and accurate history and physical examination. Different categories as possible etiologies of JP in children were systematize and detailed.
Results: All children were divided into several groups based on their anatomical and physiological characteristics of osteoarticular system: the first group consisted of 240 children under 6-7 years old, the second group -220 children 7-12 years old, the third group -140 children over 12 years old.
Research suggests that more preschool children were experience bilateral lower extremity pain by "post-walk genesis" due to natural hypermobility, immaturity of sensory innervation of the joints and imbalance of the leg muscles (e.g. growing pains). The second most common cause of JP was associated with intra -or postinfectious factor (viral, streptococcal and chronic focal of infection). The frequency of juvenile arthritis and other rheumatic diseases in children of this age group did not exceed 10%. Special attention was paid to fever, chills, malaise, nightpain and constitutional symptoms with changes in blood lab tests to exclude osteomyelitis (inc specific cause), malignancies manifestation and other bone tumors (less 5%).
The most common causes of joint pain of school-age children were hypermobility syndrome and enthesopathy (primary, secondary). Secondary enthesopathy were result of changes in nutrition, rapid growth and excessive exercise. Also enthesopathy were manifestation of endocrine, gastrointestinal or infectious diseases. The proportion of children with the onset of chronic inflammatory arthropathy also did not exceed 10%. Hypermobility child's syndrome was characterized by harmless pain (inc low back pain), linked to physical activity (less morning stiffness).
Over the past decade, we've seen a gradual increase in the number of children (95% were girls) with knee pain by diagnosed patellofemoral and mediopatellar plica syndromes, patellar tendinitis or idiopathic cause. In most cases children was complicated by syndrome of increased anxiety. The share of true chronic inflammatory arthropathies, including spondylitis, in children of this age group did not exceed 10%. Fibromyalgia were diagnosed less 5%. Introduction: A significant part of patients in rheumatologist's practice is children and teenagers with complaints of pain. The further volume of examination and the choice of treatment course depends on the capability of the rheumatologist to define the inflammatory and non-inflammatory genesis of pain. That makes the problem of differential diagnosis very important.
Objectives: To conduct a comparative analysis of patients with a principal pain complaint to determine if there are significant differences in the groups with the inflammatory and noninflammatory pain genesis. Methods: The retrospective study included children who consulted a rheumatologist in the outpatient clinic in the period 2018-2020 without preliminary selection (n = 176). Of them there were selected children with principal pain complaint (n = 120). According to the diagnosis, the children were divided into 2 groups: those who have inflammatory genesis of pain (A, n =59) and those with noninflammatory genesis of pain (B, n =61). The group A included children with such diagnoses as: reactive, poststreptococcal and juvenile idiopathic arthritides. The group B included children with arthralgia, chronic pain syndrome, orthopedic pathology, fibromyalgia. Results: 1. Groups A and B differ in the average age of the first complaints onset (t-criterion for equality of means) with a high degree of statistical significance (Group A = 7,4 years; Group B = 9,3 years; p = 0.019). Which means that in Group A more often than in Group B first complaints appear in the age between 1 to 10 while in Group B more often than in Group A it happens in the age between 11 to 16. 2. There was a statistically significant difference in the means between Groups A and B in time between the onset of first complaints and the first visit to a rheumatologist (p = 0.03) Also in favor of this conclusion speaks the fact that in Group A the number of visits to a rheumatologist in the same year when the first complaints appear is almost 2 times higher than in Group B. 56% of cases in Group A consulted the rheumatologist the same year when the first complaints appeared in comparison to Group B where only 31% of patients did the same. Below is the table with distribution of cases by the number of years between the first complaints onset and the first visit to a rheumatologist in both groups: Conclusion: In children with arthritides, the first pain complaints appear at an earlier age (an average of 7.4), and in Group B (an average of 9.3). Patients with arthritis more often visit a rheumatologist earlier (within 1 year after the first complaints) than those with non-inflammatory genesis of pain complaints.

Introduction:
The most common cause of recurrent musculoskeletal pain is growing pain (GP) in children. Differential from rheumatic diseases could be challenging in some cases since there are no diagnostic criteria for GP. Objectives: To analyze GP characteristics in a large cohort of patients in comparison with other non-inflammatory and inflammatory diseases causing limb pain, and to simplify the GP's diagnosis process by using machine learning (ML) techniques.
Methods: This is a multicenter cross-sectional study. Introduction: It is a well-known fact that the period of intensive growth in children is associated with the processes of active bone mass accumulation and coincides with them in time. One of the most distinctive indicators of an increase in the disease incidence among children for the recent decade (+105,3%) can be found in the skeletal disorders resulting from disrupted calcium metabolism and vitamin D deficit. The latter is widespread in Ukraine as it is observed in 92% of schoolers.
Objectives: Establish the specifics of the structural and functional status of the bone tissue in children during the growth spurt, taking account of the degree of vitamin D3 sufficiency.
Methods: The examination covered 147 children aged 9-17 who were divided into three groups depending on the presence of the growth spurt (GS) and its intensity: group 1 -35 children who had become 8-12 cm taller for the year in question; group 2 -32 children who had become taller by 12 cm or more, group 3 -80 children who had experienced no growth spurt. Inclusion criteria were the following: no chronic somatic or endocrine pathologies, no musculoskeletal disorders or mineral homeostasis disruptions; physical exertion corresponding to their age; the children had not been taking any complexes of vitamins and minerals, including vitamin D 3 for 6 months before the examination. Conclusion: Children aged 9-17 showed deficiency of vitamin D 3 reaching 100% which had no correlation with the presence or intensity of the growth spurt. In children who experienced growth spurt, a reduced BMD proved more frequent and correlated with the spurt intensity, however, it did not depend on sufficiency of vitamin D 3. Therefore, during the growth spurt, disrupted mineralization of the bone tissue was influenced not only by the vitamin D deficit but also by the correlation between the bone tissue mineralization rate and intensity of growth in the children. Methods: A self-reported 25 question online survey on QOL of patients with sJIA and AOSD was developed by the non-profit organizations, the Autoinflammatory Alliance, KAISZ/VAISZ, ENCA and sJIA Foundation in English and translated to Dutch. Respondents were recruited by convenience sampling through online social media posts. Data on flares, triggers, family history, and correlation of symptoms with labs were collected in addition to detailed information on QOL during and in-between flares.
Results: Between 2017 and 2019, there were 109 responses; 54 were from parents of children with sJIA, 18 from adults with sJIA, and 37 from adults with AOSD. Interestingly, adults (whether diagnosed with sJIA or AOSD) were more likely to report pain, fatigue, joint swelling or arthritis, nausea & vomiting, and diarrhea during flares than children. Adults were also more likely to describe flares >one month. 80% of patients reported being "greatly" or "severely" limited during flares. Between flares, 20% reported being "greatly" or "severely" limited while 59% were "somewhat" limited. 80% felt their condition affected their studies, job, and career, including 66% of children with sJIA, 100% of adults with sJIA, and 92% with AOSD.
Respondents were asked open-ended questions regarding their experience with disease flares and impact on their lives, and specifically how sJIA and AOSD affected work, career and schooling. Responses regarding the disease experience were classified into 7 theme areas: 1) experience with disease onset and process of diagnosis; 2) health care access, quality, and drug safety concerns; 3) physical impact of the disease including pain and chronic fatigue; 4) social impact of the disease; 5) mental health and emotional impact of the disease; 6) impact on work, career, and employment; and 7) broad impact on life and lifestyle. Responses regarding effect on work, career, and schooling were categorized into 3 theme areas: 1) physical impact negatively influencing school/work productivity; 2) lost work and wages, including unemployment and needing disability benefits, and parents missing work to care for the child; and 3) the socialemotional impact as well as negative effects on mental health. About half of patients regardless of age reported the name sJIA did not represent well the disease, specifically that it did not emphasize the systemic symptoms, and that the disease gets confused with other types of arthritis. Adult patients with sJIA did not like to have juvenile in the name. Conclusion: Children and adults with sJIA and AOSD report high levels of QOL limitation and effect on school, work, and career, both during and between flares. Our qualitative data emphasizes the importance of multidimensional evaluation of disease with ongoing input from the patients, which will provide a foundation for asking more relevant research questions to foster better care and improve QOL. Results: In total 111 participants were included in the study : 62 Juvenile idiopathic arthritis (JIA) patients, and 49 their parents. The mean age of the patients was 13.7 ± 2.3 years. Significant differences were found between patients and healthy children in such HRQoL survey categories like "Autonomy" and "Financial resources" (p < 0.05). Although quality of life in children's with Juvenile idiopathic arthritis was lower than in healthy children in HRQoL survey category "Self perception" (p < 0.05). After analyzing data no significantly differences were found between patients and parents' assessment scores in HRQoL survey categories (p > 0.05). Conclusion: Juvenile idiopathic arthritis has a moderate negative influence on HRQoL survey categories "Self perception", "Autonomy" and "Financial resources" (p < 0.05) according KIDSCREEN-52 queationnaire. Introduction: Juvenile Dermatomyositis (JDM) is often first identified by parents and carers as the red facial rash develops. The rash can progress and lead to young people being misdiagnosed with eczema, scarlet fever or psoriasis. However, over time the obvious signs of JDM can become "invisible" as treatment calms the rashes and masks the outward signs of JDM, until a flare occurs, when the rashes can be a marker for disease activity or progression. As part of a larger study, children around the United Kingdom were asked to discuss their views on whether they wanted people to be able to see their JDM. Objectives: To understand the implications for children and young people from having a disease that has visible and invisible phases and whether they want others to see their JDM, or not. Methods: Children and young people around the United Kingdom who were already consented and enrolled into the UK Juvenile Dermatomyositis Cohort and Biomarker Study were asked to complete a bespoke questionnaire. There was a mix of open and closed questions, and it was administered in paper format to all children and young people between the ages of 8 and 19 years of age for self-completion, either on the paper forms, or via a secure web-based software system. The questionnaires were administered at the end of 2018. Numeric data were described and qualitative data were analysed using standard content analysis. Results: 246 questionnaire packs were sent out, with 127 (52%) being returned. Of these 4 could not be used due to practical reasons, such as only demographic data being completed, which left a sample of 123. 98 (80%) of the 122 who responded said other people could not see their JDM, with only 11 (9%) saying it was visible and 13 (11%) saying they did not know if others can see it. 1 did not respond to the question as said their JDM has gone away. They were then asked whether it was a good or bad thing for others to be able to see their JDM or for others not to be able to see it. 41 young people left comments as to why it was a good thing, 36 left comments as to why it was a bad thing and 14 left comments to why they said don't know, table 1 presents the top ranking response for the three multichoice answers. Conclusion: This study has highlighted the disparity between young people wanting others to see their JDM so that they gain more understanding and empathy from those around them, but equally, wanting their JDM to be invisible, so that they feel the same as their peers. Whilst many paediatric rheumatic conditions are in fact invisible, our data illustrate that JDM often gives children and young people a taste of both visible and invisible phases of disease activity. As one young person said "It's not good, nor badit's good that it's invisible sometimes so I can blend in without the disabled stereotype. However, sometimes it needs to be seen so I can be understood and not challenged".
Disclosure of Interest: None declared Multidimensional Assessment Report (J-FiMAR) which includes comprehensive patient self-report questionnaire and numerical rating scales to measure pain, fatigue, headache, sleep quality, physical function, psychological state, health-related quality of life, satisfaction with illness course. The J-FiMAR has been devised according to the Outcome measure in Rheumatology (OMERACT) guidelines. Discriminant ability of the multidimensional tool was evaluated by testing it in a control group including healthy controls and patients affected by active juvenile idiopathic arthritis (JIA). The psychosocial consequences of chronic pain were evaluated by using the Children Depression Index (CDI) and the Multidimensional Anxiety Scale for Children (MASC). The objective sleep quality was measured by overnight polysomnography. Results: Table 1 shows characteristics and the most represented somatic symptoms in our cohort of JFS patients at the study enter. Polysomnography was performed in 21 patients with sleep disturbance; 8/21 (38.1%) showed an electroencephalographic pattern of alpha wave intrusion in slow wave sleep (SWS). The presence of objective sleep disorders was significantly correlated to CDI score rs -0,775 (p≤0,0001) and MASC 0,61 (p=0,005). From November 2016 to April 2020 J-FiMAR was completed by 43 JFS patients (F 35 (81.4%), median age 14.7 years [7.1-17.6], median disease duration 1.9 years [0.1-7.8]) in 125 visits. All patients filled out the questionnaire in a short time (<15 minutes) and considered it simple and easy to understand. JFS patients showed significantly higher score for pain, fatigue, poor physical function and measure of psychological distress than healthy controls and JIA patients (p<0.05 for each item). Conclusion: JFS patients presented significantly higher pain experience, functional disability, and impaired quality of life than patients with active JIA. A relevant percentage of JFS patients experience sleep disturbances, which were correlated with mood and anxiety disorders. Our multidimensional tool was feasible and able to quantify global JFS severity. This multidimensional tool, by measuring the main domains affected by the disease, could be promising to individualize treatment strategy and to test its efficacy.
Disclosure of Interest: None declared Introduction: Fatigue is a subjective state of overwhelming, sustained exhaustion and decreased physical and mental capacity, which is not relieved by rest. Fatigue is the most common complaint in children and teens with an autoinflammatory disease, besides the disease related flares. The purpose for this study was to show that fatigue is a serious issue for children and young people with autoinflammatory diseases. We hypothesized that age, gender and/ or the type of autoinflammatory disease could have differing effects on the fatigue experience. Objectives: We aimed to investigate fatigue in children and young people (CYP) with autoinflammatory disease, including how this affected them on a daily basis. Methods: CYP with autoinflammatory diseases were invited to complete an online survey, providing details about their fatigue and how it affected them. The survey was developed by the non-profit organizations Autoinflammatory Alliance and KAISZ/VAISZ, in English. Respondents were recruited by convenience sampling through online social media posts. Data on age, gender and disease were collected in addition to information on their experience of fatigue on school and social interaction. A total of 114 CYP (age range 7-18 years) with an autoinflammatory disease responded to the survey (52% female). Results: The majority of respondents (81%) reported experiencing both mental and physical fatigue. Respondents were asked how much their fatigue affected them, on a scale of 0 to 10; overall, the mean fatigue score was 6.6. However, young people aged 15 or over reported a significantly higher impact than those aged 11-14 years (mean 7.5, p=0.012). Different autoinflammatory diseases were surveyed: CRMO 25%, CAPS 20%, PFAPA 12% also Unclassified SAID (uSAID) with 23%.
In the open-response portion of the survey, 81% of respondents reported that fatigue was physical, as well as mental, in their experience. Most (89%) reported that someone had doubted their fatigue in the past; 29% had found their teachers had doubted them, 26% had friends who doubted them, and 24% reported that they felt their doctors had doubted them. Children and young people also felt a number of activities made their fatigue worse (table 1)." Conclusion: CYP with autoinflammatory diseases experience physical and mental fatigue. Health professionals and teachers should listen to patients reporting fatigue, validate their experience, and help find ways to support them. Identifying resources to help the patients with fatigue, and referrals to therapy and mental health resources as needed may help the patients to better cope and manage their chronic disease. Further studies will include patient engagement in designing questionnaires about all aspects of life and autoinflammatory disease will help our understanding of these complex conditions and how they affect patients.  Introduction: Scleromyositis is the most common overlap syndrome but is rarely observed in childhood. This disorder involves two different autoimmune diseases: systemic scleroderma (SSc) and polymyositis (PM). Objectives: To describe the clinical course of a SSc/PM syndrome in a young girl. Methods: Case report Results: An 11-year-old female was admitted to the Neurological Unit of our hospital for creatine phosphokinase (CPK) increase and hypertransaminasemia associated to sporadic episodes of right calf pain. Familiarity for muscular dystrophy was reported in the maternal branch. Muscle tone and trophism were preserved at initial neurological evaluation. Laboratory investigation confirmed increased muscle enzyme levels, including CPK (x70) (CK-MM 94.5%, CK-MB 5.5%), aldolase (x7), cardiac troponin (x10) and myoglobin (x10). Suspecting a primary muscle disease, she underwent a total body STIR-MRI which showed a diffuse edema of gluteus medius bilaterally and a muscle biopsy revealing a marked muscle damage with dystrophic aspects and normality of the tested proteins. A genetic extended panel for congenital myopathies resulted negative. After 4 months, a new clinical examination showed the occurrence of general skin induration, sclerodactyly and tightening of the face skin.
Appearance of dysphagia was also reported, and muscle enzyme increase persisted. In suspicion of an SSc/PM overlap syndrome, she was referred to our Unit. Nailfold capillaroscopy showed capillary dilatation and branching, megacapillaries and diffuse microhemorrhages. Reduction of esophageal contractions amplitude and hypotensive lower esophageal sphincter pressure were observed at esophageal manometry test. High-resolution CT of lungs and pulmonary function testing were normal. Skin biopsy showed sclerodermiform findings. Immunological studies revealed a positivity of antinuclear antibody (1:320) and anti-Ku. Anti-PM-Scl resulted negative. An oral corticosteroid therapy (prednisone, 1.5 mg/kg/day) was started in association with subcutaneous Methotrexate (15 mg/m 2 /week) and intravenous immunoglobulins (IVIG) (2gr/kg every two weeks). Improvement of skin manifestation, joint mobility, as well as normalization of serum CPK levels were observed. Over 3 months, prednisone and IVIG were slowly discontinued up to the ongoing dosage of 0.9/mg/day and 2 gr/kg every 4 weeks, respectively. MTX is still ongoing at the same dosage.
Conclusion: The diagnosis of overlap connective tissue disease syndromes may be challenging in pediatric age. Different symptoms may be prevalent at different stages throughout the course of the disease. In our patient, a localized myositis preceded the SS onset by about four months. Even though the use of high dose of corticosteroids is associated to a higher incidence of renal crisis in patients with cSS, a combined therapy with high doses of oral steroids, IVIG and MTX was safe and effective in skin, muscle and joint symptoms in our patient. Results: A total of 336 images were obtained from 118 healthy children included in the study and 708 capillary measurements were made. Capillary density was significantly higher in Group 4 than in Groups 1 and 2. Arterial width was significantly lower in Group 1 as compared to Group 3 and 4, and in Group 2 as compared to Group 4. Apical loop width and capillary distance were significantly lower in Group 1 compared to Group 2 and 3 and 4. There was no significant difference between the age groups in terms of capillary length and venous width. There was no difference between the groups in terms of capillary morphology. In total 336 image evaluations, capillary tortuosity was <50% in 67.8%, and > 50% in 4.2%, and capillary crossing were <50% in 52.5% and> 50% in 3.4%. While the enlarged capillary was 4.7% and the avascular area was 4.2%, capillary branching, capillary meandering, microhemorrhage, and giant capillary were not detected in any case. There was a good level of agreement between the researchers, as 20 cases with 120 capillaries were evaluated with a good level of agreement (Table 1).
Conclusion: This is the first study to evaluate capillary morphology in healthy Turkish children. This study also adds that some special forms such as enlarged capillary and avascular area, which is always named as pathological in adult age, can be seen in healthy children. These data will be guiding in capillaroscopic studies in various patient groups, particularly in children with collagen vascular diseases.    Methods: 308 patients with JIA were tested for HLA-B27. They were divided into 2 groups: 1) HLA-B27 positive and 2) HLA-B27 negative.
Conclusion: patients with HLA-B27 positivity were characterized by male predominance, more often hip involvement, higher laboratory activity and the need for more frequent use biologics. The rate of axial involvement wasn't different in HLA-B27 positive and negative patients, that needs further study and creating more accurate classification criteria for JSA.
Disclosure of Interest: None declared Introduction: Although gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in juvenile SpA (jSpA) patients is still largely unknown, mostly due to the lack of reliable non-invasive tests.
Objectives: We performed a cross-sectional study of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with jSpA, other forms of juvenile idiopathic arthritis (JIA) and noninflammatory (NI) conditions. Methods: fCAL was measured by commercially available assay in stool samples of enthesitis related (ErA), psoriatic (PsA) and patients with other JIA subtypes (oligo-and poly-articular) who fulfilled ILAR criteria, as well as in children with NI causes of musculoskeletal pain (NI-MSD), regardless of the gastrointestinal (GI) symptoms (Table 1). fCAL was compared among different groups of patients and correlated with demographic data, clinical characteristics, treatment modalities and disease activity measured by jSpADA. The values were also dichotomized to <50 mg/kg, 50-200 mg/kg, and >200 mg/kg, which was regarded as normal, slightly increased and increased, respectively. Ileocolonoscopy was performed in one patient.

Conclusion:
Our study has shown that fCAL levels are significantly higher in ErA patients compared to other JIA (p=0.03) and/or NI-MSD (p=0.03) patients. Moreover, almost a third of patients with ErA had levels of fCAL above the range regarded as normal, which adds to the number of evidences for a gut inflammation in this particular type of JIA. Besides, the fCAL levels were higher in those with axial involvement, which further suppots the association of gut and axial inflammation in children with ErA. Although endoscopy remains a gold standard for the diagnosis of gut inflammation, fCAL can help to select children with ErA who might benefit from this invasive procedure, regardless of the GI symptoms, as shown in one patient with the highest fCAL concentration in our study. Moreover, fCAL levels seems not to be influenced by disease characteristic and/or concomitant therapy intake. Therefore, fCAL should be a part of diagnostic workup in children with any type of JIA, but most importantly in those with ErA.  evaluate potential predictor variables of Magnetic Resonance Imaging (MRI) SIJ remission Methods: Retrospective review of prospectively collected data. We included patients with ERA (according to ILAR criteria) continuously treated with anti-TNF agents for ≥ 12 months who had at least two MRIs of the sacroiliac joints performed before starting anti-TNF therapy (baseline) and during the follow up ( > 12 months after anti-TNF treatment). SI joints were examined using T1-weighted images, T2 fastsuppressed and short-tau inversión recovery. The SPARCC-SIS was scored by two pediatric radiologists. SPARCC-SIS assessed the presence, depth and intensity of bone marrow edema (BME) on consecutive six slices in the iliac and sacrum bones . Scoring is composed by: BME (0-48), BM intensity (0-12), BM depth (0-12    Introduction: Several paediatric patients manifest conditions commonly misdiagnosed as spider bites, which however, can include other arthropods bites; bacterial, viral, and mycotic infections; vasculitis; dermatological diseases; miscellaneous conditions as drug reactions, chemical injuries. Objectives: In Italy, spiders which are likely to be associated with severe toxin mediated tissue damage are uncommon, especially in urban zones. However, a minor trauma may be a precipitating factor for pyoderma gangrenosum particularly over the legs, in association with inflammatory bowel disease, haematologic diseases and Juvenile Idiopathic Arthritis (JIA). Methods: We describe a 11-years old boy with pyoderma gangrenosum complicated spider bite in association with systemic JIA (sJIA). The patient was in clinical remission after the start of the sJIA, occurred two months before, still treated with tapering doses of steroids and canakinumab, with the normalization of inflammatory parameters (CRP, ESR, SAA, ferritin) and clinical manifestations. Only a mild arthritis of the knee persisted and for this reason he was still treated with steroids. Furthermore, he developed hyperglycemia, requiring insulin treatment. The first dermatological manifestation which he referred was a red dot of the leg skin. In a few days, the erythema enlarged, involving an area of 7 x 7 cm, with oedema, pain, and blisters, evolving in a necrotic lesion, with purulent exudate, surrounded by a haemorrhagic zone. Results: Haematological controls revealed neutrophilic leucocytosis, increased CRP and procalcitonin. He started treatment with intra venous administration of teicoplanin plus ceftriaxone, with no resolution of the clinical manifestations and the reduction of leukocytosis, CRP, procalcitonin. A culture swab was performed and was positive for Pseudomonas Aeruginosa, confirmed by PCR on the culture. He started ciprofloxacin and surgical curettage of the lesion, with the resolution of the lesion and the normalization of biochemical parameters.
Conclusion: The aspect of the lesion and its evolution were evocative of a spider bite suggested by anamnestic records, complicated by a pyoderma gangrenosum secondary to Pseudomonas Aeruginosa. The underlying disease, the immune suppressive treatment, with steroids and biological drugs, the hyperglycaemic pattern of the patient allowed the severe evolution of the spider bite. Children in treatment with immune suppressive and/or biologic drugs are at high risk of infections. Skin lesions, as arthropods bites, can be a facility for superinfection, with possible haematological and systemic diffusion.

Introduction
The strict application of the ILAR 1 requirement for the presence of documented arthritis for the diagnosis of sJIA, early in the disease course, may result in unnecessary delays in initiating appropriate treatment. In preliminary PRINTO 2 classification criteria for sJIA, this mandatory requirement of documented arthritis has been modified.

Objectives
To measure performance of preliminary PRINTO classification criteria for sJIA in our Indian cohort. Methods I gathered a data of seven sJIA patients who attended dev children's hospital between Jan 2019 and Jan 2020. My data included demographics,clinical presentation, laboratory parameters and outcome of these patients. All these patients were diagnosed at an early stage by clinical judgement irrespective of fulfilment of ILAR criteria. I applied preliminary PRINTO classification criteria for all.

Results
Average age of selected children (4 girls and 3 boys) was 5.1 years. Conclusion A preliminary PRINTO classification criteria for sJIA has been validated in our cohort. There are many raised inflammatory markers in most of these patients other than WBC count. These markers should be considered to be added in supportive laboratory criteria to be more specific towards the diagnosis. It is important to add PID in exclusion list especially in a case of sJIA with MAS at onset. 3 Trial registration identifying number  Leningrad's Regional Children' Two patient stopped treatment within 6 months from therapy start: due to primary inefficiency (1) and allergic reaction (1). Five (5/11) patients were-co-administered with cDMARDs, other 5with oral GC, and 6 subjects had been previously exposed to other biologic drugs. Whole 5 patients stopped therapy due to secondary inefficiency: 2 patients were switched on TOC, other children were switched on ETA (1) Introduction: Systemic juvenile idiopathic arthritis (sJIA) is a rare, complex auto-inflammatory disease with significant morbidity including fever, rash, serositis and articular problems. With the availability of interleukin-1 (IL-1) and IL-6 inhibitor treatment, morbidity has significantly reduced and the outcome for sJIA patients has improved. However, differences in access to care and differences in treatment strategies between countries in and outside of Europe remain a concern.
Objectives: The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) consortium aimed to develop best practices for paediatric rheumatic diseases in order to decrease differences in care between European countries. Here, we present the final results of the literature review and a series of consensus meetings on defining overarching, diagnostic and therapeutic recommendations for diagnosis and treatment of sJIA.
Methods: The SHARE methodology has been previously published, including the use of the EULAR standardized operating procedure for developing best practice recommendations. As per these guidelines, a methodologist provided supervision during the process and consensus meetings.  Conclusion: HScore seems to perform slightly better than MS-score for the diagnosis of MAS in our cohort.

Introduction
Early inhibition of IL-1 is discussed to play an important role in the disease course of sJIA 1 . Assuming that pretreatment with other DMARDs leads to a later start of therapy with canakinumab, this analysis evaluates the effectiveness of canakinumab as first-line vs. second-line DMARD.

Objectives
To evaluate the effectiveness of canakinumab as first used biological DMARD in sJIA compared to canakinumab in sJIA-patients pretreated with other DMARDs. Methods SJIA-patients documented in the German Biologic Registry for Pediatric Rheumatology (BiKeR), who were exposed to canakinumab, were identified. For the first-line (FL) group DMARD naïve patients were selected, prior treatment with corticosteroids and/or NSAIDs was allowed. Patients receiving any DMARD prior to canakinumab entered the second-line (SL) group. Both groups were compared in a retrospective intention-to-treat-analysis. Effectiveness

Conclusion
Canakinumab treatment showed good effectiveness in sJIA both as first-and second-line DMARD. After 6 months the use of canakinumab as first-line DMARD is associated with higher response rates compared to second-line use. Our data support the hypothesis that early treatment with canakinumab is associated with good therapeutical response and a positive effect on the disease course of sJIA. Results: A total of 11 children (9 girls) with SLE were identified. Median age of symptom onset and diagnosis was 14 years(range 8-17 years) and 11 years respectively. The presenting manifestations were fever(5), oral ulcers(3), alopecia(3), malar rash(4), photosensitivity(5), renal involvement (5), seizures(1) and gastrointestinal complaints (1) apart from some unusual manifestations of isolated peripheral arthritis(1), isolated bilateral pleural effusion(1), macrophage activation syndrome(2). Laboratory investigations: Hemogram revealed anemia in 8 children and thrombocytopenia in 5. Urine examination showed nephrotic range proteinuria in 1 child and subnephrotic proteinuria in 2.
Microscopic hematuria was noted in 2 pateints. Renal function tests were deranged in 2 cases. ANA, Anti dsDNA positivity and hypocomplimentemia were present in all. Renal biopsy was done in 4 patients, 2 had class IV, one class III and one had class V lupus nephritis. All patients were initiated on hydroxychloroquine and photoprotection. Children with renal involvement were given pulse methylprednisolone followed by tapering doses of oral prednisolone and intravenous, monthly cyclophosphamide. Azathioprine was used as maintenance therapy in all. Subcutaneous weekly methotrexate was used in 2 patients. One child (MAS) died during disease course. Disease continues to be in remission in rest. Conclusion: We found a significant female preponderance in our study group. Renal involvement was the commonest presentation. Some unusual presentations were also seen. Early recognition of SLE is critical for timely initiation of appropriate treatment. This is the first report of a cohort of Pediatric SLE from this part of India. Introduction: Autoantibodies in AHAI may be IgG/IgM/IgA. AHAI can be divided into primary or secondary (e.g. SLE, lymphoproliferative diseases, infections, medications). It is also classified based on the temperature at which the antibody reacts to erythrocytes, and can be warm (IgG or IgA) or cold (IgM or C3). In warm AHAI, the antibodies react at temperatures ≥37ºC, not activating the complement system and not undergoing agglutination in vitro. In cold AHAI, antibodies react at temperatures below 37ºC, activating the complement system with in vitro agglutination.Mixed AIHA (warm and cold) is rare and occurs in <10% of AIHA cases and can occur at any age, but is extremely rare in children. The prevalence of the mixed form is less than 1/1,000,000 patients with AHAI.
Objectives: To report a rare case of mixed AHAI and idiopathic intracranial hypertension(IIH) in a 15-years old female patient with a previous diagnosis of SLE and APS. Methods: Case report and literature review.
Results: A 15-years old female adolescent previously diagnosed with SLE/APS since 2017 was in remission on hydroxychloroquine(400mg);azathioprine(150mg);aspirin(100mg);vitaminD3(1.000IU);calcium(1g), and sunscreen. In April 2020 , she had a relapse presenting with fatigue, myositis, headache, hypocomplementemia, and severe autoimmune hemolytic anemia (Hb of 4g/dL) (SLEDAI-2K=18 points). Mixed AHAI was diagnosed base on a Direct/Indirect Coombs test 4/4+;DirectAntiglobulinTesting showing anti-IgA(weak),anti-IgM(3+/4+),anti-IgG(3+/4+),anti-C3c(weak),anti-C3d (3+/4+);IgG1/3subclasses with a reaction of 1:100(2+/4+);an eleven cell antibody panel positive revealing a cold and warm antibody, and adsorption technique revealing a cold and warm autoantibody. Chest CT showed bibasilar subsegmental atelectasis, head CT/MRI was normal and LP showed a high opening pressure of 45cmH2O with a normal cell count. After the procedure, the patient reported improvement in the pain and was diagnosed with IIH. The patient was screened for secondary causes for AHAI (table 1) due to the unusual mixed type pattern and serology was positive for Chlamydia trachomatis (IgM) and Mycoplasma pneumoniae (indeterminate-IgM/positive-IgG) suggesting a recent infectious trigger causing reactivation of the underlying disease with a probable cross-reactivity. The patient treated with 10-days of clarithromycin. Before the infectious screening came back negative, AHAI was treated with a single dose of IVIG(1g/kg) and then, with 3-days of methylprednisolone(1g/day). Azathioprine was replaced by mycophenolate mofetil. Due to headache recurrence, acetazolamide(500mg/day) was started, and the patient referred no pain. The patient was discharged with a resolution of the symptoms. Objectives: To our knowledge, the association of GBS and BBE has been described in adults only. Methods: We here describe a child presenting at SLE disease-onset with an overlap of peripheral (GBS) and central (BBE) nervous system manifestations, highlighting the possible association between these two entities in children.
Results: An 11-year-old healthy girl presented with acute ataxia, ophtalmoparesis and altered level of consciousness, rapidly followed by areflexia, facial paresis, swallowing difficulties, sensory deficits, paresis in all four limbs and respiratory insufficiency. These symptoms were accompanied by pleuro-pericardial serositis, proteinuria and hypertension. Immunological investigations revealed the presence of positive ANA and ds-DNA antibodies. The renal biopsy showed a stage III lupus nephritis. Hence, the clinical, laboratory findings and biopsy report led to the diagnosis of pSLE. Brain and spine MRI did not show any abnormalities; diffuse slowing compatible with nonspecific encephalopathy was seen on EEG. Nerve conduction studies (NCS) confirmed the clinical suspicion of acute polyradiculoneuropathy with proximal interruption of motor nerve conduction, compatible with Guillain-Barré-like syndrome. CSF analysis (performed twice) remained normal. The patient was treated with glucocorticoids, intravenous immunoglobulins, cyclophosphamide as well as plasmapheresis. The neurological and physical symptoms improved gradually with complete neurological recovery four months after onset. Conclusion: Overlapping forms of BBE/GBS have never been described in association to SLE in children. Our patient's presentation and evolution fulfilled the criteria for such an overlap, occurring at pSLE onset. Although SLE and BBE/GBS are rare entities, our case suggests that there may be a common underlying immune background. This association should be recognized early for rapid and appropriate treatment initiation.

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Infantile antiphospholipid antibody syndrome: acquired and de novo APL appearance in four infants T. Giani 1 , G. Ferrara 2 , A. Mauro 3 , R. Cimaz 4 Introduction: Antiphospholipid syndrome (APS) is a rare condition in the neonatal age. In most cases it is considered a passively acquired autoimmune disease, due to a transplacental passage of maternal antiphospholipid antibodies (aPL). Exceedingly unusual is the de novo production of aPL in newborns and infants. Objectives: To describe four infants who developed an early brain stroke with increased and persistent levels of aPL, even after six months of life. Methods: We reviewed the clinical charts of four such infants, followed from diagnosis up to two years after the disappearance of aPL. Conclusion: Common characteristics of these four children are the development of brain stroke and the increased and persistent aPL levels even after six months of life. This opens the window on a gray zone related to the origin of these antibodies (maternal or neonatal) and on their role in the pathogenesis of the infantile brain stroke. patients had over 20% of their monitoring completed but only 2 had over 80%. Aspects of monitoring that were more time intensive or were required less regularly were most frequently overlooked. There was a statistically significant increase in the percentage of completed monitoring in those patients for whom the Lupus Checklist was used compared to patients where a checklist was not used (p=0.00).
Conclusion: There is significant room for improvement in the monitoring of these patients with JSLE in the rheumatology clinic. This audit illustrates that more diligent use of the Lupus Checklist and an overall improvement in sustained use of the checklist will help to improve monitoring of these patients. Evidence suggests that checklists are underutilised in medicine and wider implementation of this simple tool could improve patient outcomes. 3,4,5 Interventions such as in person or electronic reminders, or audits with feedback to physicians could improve usage over time. The application of the Lupus Checklist or a similar document in other paediatric clinics is important for comprehensive monitoring of a condition as complex as JSLE and has the potential to prevent ongoing damage and medication toxicity in this high-risk population.
juvenile onset and this cluster have may more severe kidney, neuropsychiatric or hematological involvement.
Objectives: The aim of this study was to assess the clinical and laboratory characteristics, disease activity, and treatment response of patients with juvenile SLE (jSLE).
Methods: This is a retrospective study involving patients between 1 July 2016 and 1 January 2020. The data of patients diagnosed with jSLE and followed up for a minimum of 6 months, were collected. The SLEDAI-2K scores at initiation and at the follow-up (1st, 3rd, 6th, and 12th months of treatment) were examined. The SLEDAI-2K score was considered to be ≤4, for disease remission status.
Results: A total of 49 children were included in to the study. The female/male ratio was 4.4/1 and the median age of the patients at the diagnosis was 13 (IQR: 11.1-15.2) years. The median follow-up of patients was 19 (IQR: 12-25) month. Four of the patients were diagnosed with monogenic SLE. Two siblings were diagnosed with c3 deficiency and two were diagnosed with familial chilblain lupus. The most common clinical findings were found musculoskeletal complaints (69.4%), malar rash (51%), oral ulcers (38.8%), and fever (30.6%), respectively in over all the group. The frequency of involvement of the system and organs was as follows; mucocutaneous 77.6%, musculoskeletal 69.4%, renal 44.9%, hematological 34.7%, serous membranes 16.3%, neuropsychiatric 12.2%, respectively. All patients had anti-nuclear antibody positivity, while 46.9% had anti-ds DNA, 14.3% had anti-Sm and 8.2% had antiphospholipid antibody positivity. While all patients received hydroxychloroquine treatment, 22.4% of the patients were received were mycophenolate mofetil, 22.4% were azathioprine, 14.3% cyclophosphamide, 12.2% methotrexate and 10.2% were rituximab. The median SLEDAI-2K score was 14 (IQR: 10-18.5) at admission, besides it was found to 6 (IQR: 4-12), 4 (IQR: 2-6), 2 (IQR: 0-6) in the 1st, 6th and 12th months of treatment, respectively. While 98% of the patients had active disease at admission, 67.3% at 1 months, 32.7% at 6 months and 22.4% at 12 months still had active disease (SLEDAI-2K >4). Patients with initially high SLEDAI-2K scores had significantly lower remission rates in the first month (p=0.003). It was observed that patients with high SLEDAI-2K scores in admission were more resistant to conventional immunosuppressive treatments and the use of rituximab was more frequent in these patients. At least one major organ (renal, hematological, neurological) were affected in 57% of patients. The remission rate of these patients at 6 months was found significantly decreased compared to the others (p <0.005). Renal biopsy was performed in 21 patients (42.9%). 12 of them had type 4 lupus nephritis (LN), 5 had type 2, 2 had type 3, and 1 had type 5. It was observed that patients with renal involvement were the group that reached remission latest. Conclusion: The presence of high initial SLEDAI-2K scores and the major organ involvement have poor predictive value to achieve inactive disease. A two year old girl of consanguineous parents presented to hospital at 13 months of age with fever and erythematous macular rash on her cheeks which spread to her nose, chin, and ears. The rash started a month prior, and progressed over her entire body. A skin swab grew staphylococcus aureus but the rash didn't respond to topical antibiotics. Review of systems was unremarkable except for longstanding oral thrush and diaper rash. Birth and family history were unremarkable. On exam she had a diffuse, erythematous, morbilliform eruption over her face and body. She had facial swelling, orbital edema and vasculitic oral ulcers. She had leukopenia mainly neutropenia, low hemoglobin, with normal platelets. Her liver enzymes and erythrocyte sedimentation rate (ESR) were high while C-reactive protein, immunoglobulins, C3 and C4 were normal. Cultures were negative, however she was positive for adenovirus, mycoplasma and EBV (EBV load was 6000 IU/ml ). Autoimmune hepatitis work up was negative. The direct coombs test, antinuclear antibodies (1:640), Ro, RNP and SmD were positive. CH50 came low as well as C1q level of 4 mg/dL (normal range 12-22 mg/dL). Lymphocyte subsets showed reduced CD4 and NK cells. Bone marrow aspiration showed active marrow. Skin biopsy showed chronic non-specific inflammation (immunofluorescence and electron microscopy were not available). Echocardiogram showed dilatation of the left coronaries. She was treated with intravenous immunoglobulin (IVIG) for Kawasaki disease with no improvement. Therefore pulse steroid 30mg/kg followed by 2 mg/kg was initiated. Her rash, facial swelling and abnormal blood counts improved dramatically. Whole Exome sequence showed homozygous variant c.469G>T p.G157C at the C1qA gene. While tapering steroids she flared so subcutaneous methotrexate was started. Unfortunately, she continued to have rash, leukopenia and high liver enzymes, so treatment was switched to mycophenolate mofetil and hydroxychloroquine. However she did not improve and started to have recurrent bacterial and viral infections that included cellulitis, gastroenteritis and upper respiratory tract infection. We started her on regular IVIG, which helped with infections and allowed for weaning of steroids. However she developed alopecia and lower limb spasticity with delayed walking. MRI brain and spine was normal. Upon reanalysis of the WES, two other homozygous mutations at KIF1C and APG7 were identified and associated with spastic paraplegia, but reported as variants of unknown significant. Fresh frozen plasma (FFP) transfusions were started, initially weekly, then every two weeks and subsequently every four weeks. The rash disappeared, leukopenia and ESR improved and we were able to discontinue steroids Conclusion: Early-onset SLE with a severe course of disease raises the possibility of a genetic etiology. We are reporting, for the first time, a rare missense mutation G>T in exon 3 of the C1qA gene that resulted in an amino acid substitution that is pathogenic. Interestingly, she had other mutations associated with neurological manifestation that never reported together before and altered her phenotype. She has responded well to FFP as has been reported in a few case reports Results: A total of 148 pSLE under the age of 13 years were included, 30% (n = 44) were males. The overall mean age at diagnosis was 7.6 ± 3.5 years and median disease duration was 9.5 (5-13) years. HUV was diagnosed in 34.5% (n = 51) of pSLE cohort. pSLE with UV were more likely to be males (57% vs 15%; P < 0.001), diagnosed at a younger age (5.9 vs 8.5 years; P < 0.001), have a family history of SLE (53% vs 36%; P = 0.044) and have conjunctivitis more frequently (32% vs 5.3%; P < 0.001) than pSLE without UV. pSLE with UV were also less likely to have CNS involvement (7.6% vs 20%; P = 0.045) and hematological manifestations such as leukopenia (9.4% vs 24%; P = 0.028) and thrombocytopenia (5.7% vs 18%; P = 0.045). In addition, pSLE with UV were more likely to be associated with low C3 complement count (94% vs 66%; P < 0.001) and positive cytoplasmic ANCA (11% vs 0%; P = 0.022).However, the pSLE with UV cohort were less likely to be associated with ANA (65% vs 83%; P = 0.016), DsDNA (56% vs 72%; P = 0.042) and perinuclear anti-neutrophil cytoplasmic antibodies (33% vs 55%; P = 0.047). Conclusion: We report a high occurrence of HUV in pSLE cohort (34.5%) associated with unique demographic, clinical features and laboratory features. The debate regarding whether HUV is a rare subset or unusual type of SLE, or is a separate entity altogether, continues. However, the overlap in clinical, laboratory and genetic mutation supports the notion that HUV and SLE fall into the same spectrum of autoimmune disease with similar disease pathogenesis. However, further studies are needed to reach clear conclusions regarding the relationship between HUV and SLE.    Introduction: The last decade has brought a lot to the approaches to the diagnosis and treatment of juvenile arthritis. In Russia, the actualization of the problem of diagnosis and treatment of JIA required the development of federal standards, which provide the most detailed algorithms for medical care, both at the stage of inpatient and outpatient care. In the regions of the Russian Federation, the effective use of these documents required a whole range of additional educated activities, both with students of medical universities, as well as with the medical and nursing community, in addition, a set of work was carried out to create a regional regulatory framework. In the total biological therapy pool, 67% of patients receive TNF-alpha inhibitors, antibodies to IL-6 receive 27% of patients, antibodies to IL-1 -6,25%. It is worth noting that when using biological agents in 60% of cases, the criterion of an inactive disease was achieved by 4-5 months, which was characterized by the absence of acute inflammatory symptoms, normalization of ESR and CRP. Monitoring of patients with JIA receiving biological agents required the conduct of a number of educational activities for medical personnel, the creation of an additional methodological base. For further training of young specialists at the regional medical university, a program of an additional educational course in pediatric rheumatology was developed and introduced. A regional patient organization was established and also required a set of information activities by the medical community.
Conclusion: In the Saratov region of the Russian Federation, about 20% of patients with JIA receive biological therapy, which corresponds to the average indicators according to the literature. In the structure of the biological drugs used, the group of TNF-alpha inhibitors is preserved -67%. The introduction of modern methods of treatment using biological agents in JIA has significantly increased the effectiveness of treatment, but it required the organization of additional information support for medical personnel.
Disclosure of Interest: None declared Introduction: Immunogenicity and development of anti-drug antibodies have been associated with treatment failure and adverse events during biologic treatment. Anti-drug antibodies (ADAs) have been reported in 21% of Juvenile Idiopathic Arthritis patients treated with Adalimumab. However, their role in reducing adalimumab efficacy is still debated due to conflicting results. No study has been directed toward identification of neutralizing ADAs in paediatric rheumatic disorders. Objectives: Aim of our study was to detect ADAs, along with their clinical relevance, using a new theranostic peptide-base assay in a cohort of children with inflammatory chronic diseases on Adalimumab treatment. Methods: Six candidate Adalimumab derived peptide antigens (HC-CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR 2, LC CDR3) have been developed and optimized to be tested. Their performance has been compared with commercial ELISA kit and a SPR-based optical assay (Biacore®). Assays have been performed in sera of a cohort of children receiving Adalimumab due to an inflammatory chronic disease. Mean age, disease duration, concomitant treatment with methotrexate (MTX), ANA positivity, disease activity parameters and scores at the time of ADA determination have been recorded. Chisquare, and Fisher exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for entered variables. Results: Eighteen (14 F, median age 12.6, range 3.8-16, yrs) patients were enrolled: 16 affected by Juvenile Idiopathic Arthritis, 7 of whom complicated by JIA -associated chronic uveitis, and 2 patients affected by chronic idiopathic uveitis. Peptide assay revealed ADAs in 8 children, Biacore in 6, commercial Elisa in 5. Of note, we found total concordance among the 3 tests just in 2 patients. No significant correlation has been proven among the 3 ADA determinations. Biacore and ELISA determination showed significant concordance (r s : 0.72, p<0.006). The presence of HC CDR3 and LC CDR 3 resulted significantly correlated with disease activity (r s : 0.57, p<0.05), and, inversely, with disease remission on treatment (r s = -0.523, p<0.05). No patient experienced severe adverse events and no correlation with ADAs has been revealed Conclusion: In chronic rheumatic disorders, novel reliable methods are urgently required to guide clinical decision and support decisions about switching within or between drugs in refractory children. The 3 different methods, since based on different antigenic probes, detect different antibody populations. The present peptide-based assays might contribute to identify neutralizing ADAs in patients treated with Adalimumab. Further validation in larger cohort is required. Introduction: Non-bacterial multifocal osteomyelitis (NBO) is a rare polygenic autoinflammatory disease, which is difficult to diagnose and treat. Because of combination of bone lesions with arthritis and/ or axial skeleton damage in most cases the diagnosis of juvenile idiopathic arthritis (JIA) or juvenile ankylosing spondylitis (JAS) may be establish as a concurrent diagnosis, so this allows to legal use of Biologics (BA) for the treatment. Objectives: To analyze the single center experience of clinical and laboratory features of multifocal NBO in patients (pts) who were treated by BA for the last 8 years.

Disclosure of Interest
Methods: The study involved a retrospective cohort of multifocal NBO pts treated by different BA in our clinic from 2013 to 2020. All of them underwent standard rheumatological examination. In order to examine all localizations of the bone damage, a scintigraphy and/ or "whole body" MRI scan was performed.
Results: Among the whole group of pts with NBO (n=40) we identified 13 pts treated by BA (TNF-inhibitors only). The majority were girls (n=9, 69 %). Age at disease onset was 10.2 years in average (Me 10.2 range 1.3-16.5). For legal reason of BA administration, we classified our patients according to rheumatological features as JIA or JAS. 7 pts had JIA (5 girls), 6 pts had JAS (4 girls). Among 13 pts 9 had oligoarthritis (69%), 4 had polyarthritis of low limbs (hip, knee, ankle). Axial involvement was represented by active erosive sacroiliitis with deep bone marrow edema on MRI scan in 9 pts (69%), active spondylitis of several bodies in thoracic spinein 2; erosive arthritis with partial ankyloses of facet joints of neck in 3 pts, multiple syndesmophytes in 1 girl. We found that definite axial lesions in NBO developed in very young children (in 2 y.old at minimum), much earlier than in "idiopathic" JAS. HLA B27 was presented in 5 pts (39%), 5 pts had ANA in high titer (all of those HLA B27-negative). The pts had bone lesions in different parts of skeleton: vertebral bodies -5 pts, clavicle -1, sternum, ribs -1, extremities bones, metaphysic mostly (tibial, fibular -7 pts), sacroiliac region -4 pts. Extraskeletal manifestations were observed in 3 pts, one in each condition -uveitis, psoriasis pustulosus, acnae conglobate. In a girl with very severe course of disease, not responded to any therapy NBO was combined with familial Mediterranean fever. High level of laboratory activity were detected before biologics in 10 pts (77%): ESR acceleration up to 60 mm/h, increase of CRP up to 80 mg/l. Treatment included NSAIDS (all), methotrexate (7 pts), sulfasalazine (6 pts, but it was withdrawn in all pts), bisphosphonates (1 pt), prednisolone (3 pts). Because of high activity of NBO with appearance of new bone lesions and persistent arthritis TNF inhibitors were administrated: etanercept in 10 pts, adalimumab -4 (2 as first line, 2second line), golimumab -1. At the start of BA the average age was 13.7 years (range 7.2-17.9); mean disease duration was 3,4 years (range 0.3-8.1). There were 2 cases of withdrawals. Due to inefficacy etanercept was switched to adalimumab. Disease activity decreasing was reached in the most of the patients (12 from 13). Among them 2 pts developed the whole remission with resolving of active arthritis and bone marrow edema spots. Skin lesions (psoriasis pustulosis and acnae conglobate) were significantly improved. There were no adverse events during the TNF therapy. Conclusion: Our experience of the therapy with TNF inhibitors in patients with high NBO activity has shown that this is a good and safe therapeutic option that is expected to prevent progression and bone destruction. . AE were reported for 71.7% of patients, most within 24 to 48 hours after the first or second injection: flu-like symptoms (57.5%), hypocalcaemia (37.5%) and hypophosphatemia (20%). Underweight patients (body mass index < 18.5 kg/m²) accounted for 50% of hypocalcaemia. The frequency of all the AE not significantly decreased with the reduction of the first dose. Only one serious hyponatremia occurred corresponding to a patient with renal failure before treatment. Conclusion: Our results were similar to those previously published: bisphosphonates are safe for osteoporosis in children. In the literature, SAE are very rare in children, being limited to anecdotal osteopetrosis in cases of higher doses and long-term treatment, and delayed bone healing. Anecdotal osteonecrosis of the jaw in adults has never been described in children. The use of bisphosphonates beforehand requires dietary measures (vitamin D and calcium supplementation). Furthers systematic collection on efficacy and safety parameters for each Bisphosphonates drug should confirm these data. Introduction: The use of biosimilars in rheumatology has increased significantly over the last 5 years and has resulted in considerable cost savings.

Disclosure of Interest
Objectives: To assess the effectiveness and tolerability of the Adalimumab biosimilar ABP 501 in patients with JIA. Methods: A database of patients prescribed Adalimumab in our service has been screened to identify patients with JIA, who switched from the originator to the biosimilar. Only patients who had a clinical review since they had started the biosimilar were included. A paired-samples t-test was conducted to compare the number of active joints at the clinic appointment before and after the initiation of the biosimilar treatment. The frequency and type of side effects, the clinical response and the number of patients who switched back to the originator have been collected. Results: Sixty-one patients who switched to the biosimilar ABP 501 between February 2019 and February 2020 were included. They were comprised of 30 enthesitis-related arthritis (ERA), 13 polyarthritis, 9 oligoarthritis, 6 psoriatic and 3 systemic JIA patients. Their baseline characteristics and outcomes are summarised in Table. The mean duration of follow-up after the switch to biosimilar was 10 months (range 2-23). Eleven patients (18%) reported side effects; the most common side effect (n=7, 63.6%) was injection site reactions and the remaining 4 consisted of anaphylaxis, druginduced lupus, dizziness and bone pain, respectively. Seven patients (11.5%) reverted to the Adalimumab originator, 4 as a result of side effects, 3 because of ineffectiveness and one patient for both reasons. In addition, 3 patients were changed to a different biologic, one patient due to allergy to both the originator and biosimilar and the other two patients had active disease on the originator and biosimilar Adalimumab. Two patients stopped the biosimilar and remained off any biologic, in the first case this was due to a side effect and in the second case it was patient's choice. On the whole, 78.7% of patients had remained on ABP 501 at their last visit. There was no significant difference in the active joint count before the biosimilar was started (mean 0.55+/-1.11) and after the switch (mean 0.6+/-1.59), (p= 0.855).  Introduction: Golimumab (GOL) is approved for polyarticular juvenile idiopathic arthritis (pJIA) in patients of ≥2years but long-term safety data are limited.
Objectives: Prospective monitoring of long-term safety and effectiveness of GOL in routine care using the BIKER-registry. Methods: Baseline demographics, clinical characteristics, disease activity and safety parameters were compared to a contemporary 1:2 matched control cohort using alternative TNF inhibitors or methotrexate without exposure to a biologic. Efficacy outcomes were JADAS10, joint counts and functional status. Safety assessments were based on adverse events (AE) reports.
Results: In this ongoing study, 65 pts initiating GOL were matched to 130 with alternative TNFi and 65 biologic-naïve pts. Pts starting GOL had a longer disease duration (p<0.0001) and use of GOL was significantly more often second line (84.6% vs 22.3%, p< 0.0001) and thus disease activity was lower at baseline. Pts in the GOL cohort used less corticosteroids, otherwise patients were comparable with pts treated with other TNFi (Table 1).
In GOL treated ps a marked clinical response was noted at 6 months and beyond, indicating the effectiveness of GOL in the treatment of pJIA. A significant decrease of the mean JADAS 10 11.3 to 5.3 (p= 0.0008) after 6 months of treatment was observed, as well as JIA ACR 30/50/70/90 response rates of 61/59/42/29%. JADAS remission and minimal disease activity was observed in 27% and 53.7% after 6 months and in 39% and 54% after 12 months of treatment.
Rates of AE, SAE and infectious AE were comparable in the GOL cohort (87.5/100PY, 3.4/100PY and 11.1/100PY), the alternative TNFi cohort (92.3/100PY, 2.9/100PY and 9.7/100PY) and the MTX only cohort (121.2/100PY, 2.1/100PY and 18.5/100PY). SAE reported in the GOL cohort were flares of uveitis and of JIA (each 1) and fibromyalgia syndrome (1). SAE reported in the alternative TNF cohort was two serious infections (both influenza), one knee ligament injury, one flare of arthritis and one hyperventilation . No case of pregnancy, malignancy or death was reported.
Conclusion: Golimumab seems an effective in treatment of pJIA. Tolerability was acceptable and comparable to alternative TNFi or MTX. Recruitment to the project is ongoing.

Trial registration identifying number: EUPAS20781
Disclosure of Interest None declared Introduction: Methotrexate (MTX) is one of the most commonly used disease-modifying anti-rheumatic drug in rheumatology practice. It has some side effects that can impair quality of life. The most common of them is associated with the gastrointestinal tract.
Objectives: The aim of the study is to evaluate and compare the frequency of methotrexate intolerance in adult and pediatric patients.
Methods: Patients with rheumatologic diseases followed in Hacettepe University Pediatric Rheumatology and Rheumatology departments who used oral or parenteral methotrexate for at least 3 months were included in the study. Methotrexate intolerance was assessed using 'Methotrexate Intolerance Severity Score (MISS) questionnaire. The MISS questionnaire consisted of 5 parts: abdominal pain, nausea, vomiting, fatigue and behavioral symptoms. The patients scored the severity of each symptom separately; 0: no symptoms, 1: mild symptoms, 2: moderate symptoms, 3: severe symptoms. A total score of 6 or more was defined as MTX intolerance. Visual analogue scale (VAS) ranging from 0 cm to 10 cm was performed to each patient concurrently with the MISS questionnaire. In the pediatric patient group, MISS questionnaire and VAS assessment were applied to both patients and families.
Results: A total of 100 patients, 50 of whom were children, enrolled in the study. The mean age for children and adults were 11.78 (± 3.4) and 52.9 (± 11.8) respectively. The most frequent diagnosis of patients was juvenile idiopathic arthritis (78.0%) in children and rheumatoid arthritis in adults (68.0%). The mean MTX dose in adults and pediatric group was 12.5 (±3) mg vs 14.5 (± 3.6) mg (p: 0.004). The prevalence of MTX intolerance in children and adults were 66.0% (n:33) and 14.0% (n:7) respectively. The mean MISS score in the pediatric group was higher compared with the adults (12.4±9.4 vs 1.84±4.5, p<0.001). Similarly, the mean VAS scores were higher in pediatric group (1.2±2.4 vs 4.2±3.2 (p<0.001)). There was a strong correlation between MISS and VAS scores between family and child evaluations (p <0.01, r = 0.95 / p <0.01, r = 0.94). Abdominal pain, nausea, vomiting and behavioral symptoms were observed more frequently in children compared to adults. Results: 3(4%) out of 73 patients were diagnosed with psoriasis denovo. One patient was treated with ADA (a girl with undifferentiated arthritis who had positive HLA-B 27, ANF and family history of psoriasis -her grandmother had psoriasis), 2 patients were treated with ETA (both female, one patient had undifferentiated arthritis, the other had enthesitis-related arthritis; both patients had positive HLA -B 27 and ANF negative). 2 patients achieved significant improvement after changing TNFalpha inhibitor (1-ADA, 1-ETA), 1 patient (was treated with ETA) had significant improvement after discontinuation of biological therapy.
Conclusion: This single-center observational study demonstrates the possibility of developing psoriasis de-novo in patients with JIA receiving TNF-alpha inhibitors. Although more extensive research is needed, our data suggest that discontinuing the TNF-alpha inhibitor or switching to another TNFalpha inhibitor in patients with psoriasis de-novo should be considered as a treatment strategy in such cases. Objectives: Long-term surveillance of patients newly initiating TOC treatment for at least 5 years compared to a cohort of patients newly initiating a comparator biologic using the BIKER-registry. Methods: Baseline demographics, clinical characteristics and disease activity, efficacy and safety parameters were compared. Efficacy outcomes were JADAS10, joint counts and functional status Safety was assessed by adverse events (AE) reports. Results: 161 patients with 161 matched controls have been recruited. Patients starting on TOC were older at treatment start (12.1 vs. 10.1 years (y); p<0.0001) and had a longer disease duration (p< 0.0001). TOC was significantly more often a second line biologic (p< 0.0001). Baseline JADAS10 (17+/-10 vs 15+/-6), CHAQ-DI (0.63+/-0.63 vs 0.65+/-0,64), ESR 18+/-15 mm/h vs. 21+/-21 mm/h and active joint counts (7+/-7 vs. 6+/-5) were comparable. Upon TOC a substantial response with a significant reduction in JADAS 10 from 16.8 to 3.4 (p<0.0001) after 12 months of treatment was observed. There were no significant differences between patients from the TOC cohort and their matched controls in the JIA ACR 30/50/70/90 criteria, JADAS 10, JADAS remission and minimal disease activity was reached by comparable numbers (TOC 37% and 58%; control cohort 37% and 60%). The total number of AE was comparable (TOC cohort n=201 AE; (77/ 100PY); control cohort n=207; (65/100PY; RR 1.2; 95%CI 0.99-1.4). More serious AE (SAE) were reported with TOC. Serious infections were documented at lower frequency with TOC. Uveitis events were documented at significantly higher frequency with TNF inhibitors most likely due to a selection bias (Table 1). SAE with TOC were depression (n=3) in 2 with suicidal intent, exacerbation of JIA (n=2), septic arthritis, gastrointestinal infection, abdominal pain, colitis, paronychia and fracture. SAE in the control cohort were depression, osteomyelitis, gastrointestinal infection and disease flare. No significant differences regarding cytopenias and elevated transaminases were observed. No gastrointestinal perforation, no vascular events and no deaths occurred. Conclusion: TOC was effective and comparable to treatment with alternative biologics. Tolerability was acceptable. As TOC was given as a second-line biologic in the vast majority of patients comparisons between the 2 cohorts have to be interpreted carefully. Observation is ongoing. Conclusion: In this retrospective cohort study in pediatric patients on RTX-treatment, we found undetectable low drug levels in ADApositive patients, indicative for their neutralizing capacity. Consequently, the lack of B-cel depletion leads to reduced treatment efficacy. Patients with SLE seem more susceptible to develop ADA. If ADA are detected, continuation of treatment seems non-effective and changing medication is advised. Certainly when considering that, in this study, anaphylactic reactions only occurred in ADA-positive patients.

Disclosure of Interest
None declared Objectives: The aim of this study was to evaluate retrospectively the long-term efficacy and safety of adalimumab in patients with JIAassociated uveitis. Methods: We have retrospectively analysed nineteen JIA patiens data with associated uveitis from our centre registry between 2010 and 2020, treated with adalimumab after failure of treatment with corticosteroids and metotrexate. Demografic data and blood samples were collected at different time points while uveitis activity was evaluated by slit-lamp biomicroscopy. Adverse events were recorded. Results: Registry records provided 10 years follow up of 19 JIA patients data with associated uveitis. Eleven patients were females (57.90 %) diagnosed as oligo/extended oligoarticular JIA while eight (42.10 %) were males diagnosed as enthesitis related arthritis (ERA). Before adalimumab was prescribed, all patients were previously treated with metotrexate during 3.5 years in avarage dose of 10 mg/ m 2 weekly. The mean uveitis duration, before adalimumab administration was 9 months. Ten years long follow up period have showed that there were no new relapsis of uveitis while patients were receiving adalimumab and metotrexate. All of our patients were able to gradually tapper and stop treatment with topical steroids two months after adalimumab commencing. Seven patients were able to stop biological treatment after 4.3 years of adalimumab usage. Uveitis relapsed three monts after the adalimumab discontinuation only in one patient. Two patient were lost to follow up during the transitional period. No serious adverse events were recorded. Conclusion: During the long term follow up period adalimumab have shown good efficacy and safety profile in JIA patients with active inflammatory ocular disease. Introduction: Post-streptococcal syndrome is a systemic immunemediated complication of beta-haemolytic streptococci infection, mostly seen as post-streptococcal arthritis, rheumatic fever or glomerulonephritis. Uveitis is an uncommon manifestation of this syndrome.

Disclosure of Interest
Objectives: Case report Methods: Case report Results: A previously healthy 7-year-old female was admitted at the emergency department with prolonged fever, arthritis and red eye. She had a 4-month history of febrile episodes every two weeks, with axillary temperature ranging from 37,8 to 39ºC. Migratory arthralgia affecting both knees and tibiotarsal joints showed up two months after the fever onset and worsened in the previous week, with refusal to walk. Non-painful bilateral red eye for several weeks was mentioned. Other symptoms were absent. Recent infections were denied and family history was irrelevant. Physical examination revealed lower limb muscular atrophy, knees pain and impaired function and bilateral tibiotarsal arthritis with inability to walk. Ophthalmological observation showed a bilateral non-granulomatous anterior uveitis. Sequential laboratory work up revealed a maximum eritrocitary sedimentation rate of 135 mm/h, maximum c-reactive protein of 5,3 mg/dL, microcytic hypochromic anemia, positive antistreptolysin O titer (ASOT) (initial result of 1250 that increased to 2500 in 4 weeks and later decreased to 500) and negative anti-nuclear antibodies. Cardiac involvement was excluded. The diagnosis of rheumatic fever with concomitant poststreptococcal uveitis was assumed and the patient was treated with oral and topical ophthalmic corticosteroids with prompt clinical resolution of fever, acute polyarthritis and uveitis. No relapse occurred in a 5-year follow-up. Conclusion: Juvenile idiopathic arthritis (JIA) is the most common cause of uveitis in childhood. Although our patient clinical course could initially raise the possibility of systemic JIA (sJIA), the criteria that define this entity weren't all present and clinical and laboratory findings were more supportive of rheumatic fever. Besides, uveitis occurs exceptionally in sJIA, which turned this diagnosis even less reasonable. In our Rheumatology Unit, among 563 patients diagnosed with JIA in 32 years, 89 had uveitis. However, in the group of 51 patients with sJIA only one had ocular involvement, a boy with isolated vitritis. Post-streptococcal uveitis (PSU) typically presents as bilateral, non-granulomatous anterior uveitis, as described in this case. As streptococcal infection is very common among children and many patients may experience subclinical infection. PSU should be considered in all patients with uveitis along with positive ASOT and negative routine investigations for other causes. Although PSU has been described in literature, to the best of our knowledge, this is the first reported case of concomitant rheumatic fever and PSU.  . ADA was first tapered to every 3 weeks by 76% of the responders and then to every 4 weeks by 49% before discontinuing. Fewer respondents used or tapered IFX, TOC or ABA. Around 65% tapered the interval and 20% tapered the dose and interval for ABA, 26% for TOC and 37% IFX There were differences in the duration of tapering prior to discontinuation of specific medications. For ADA it was 6 months in 62%, 12 months in 36% ,and 24 months in 10%. For IFX it was 6 months in 27%, 12 months in 45%, and 24 months in 33%. For TOC it was 40% after 4 weeks, 87% after 6 weeks and 53% after 24 weeks. For ABA i.v. it was 30% after 8 weeks, and 90% after 12 weeks. If combination therapy was used, 36% tapered the bDMARD first, 62% csDMARD first, and 12% both simultaneously.
Conclusion: This is the first survey to describe "real world" medication tapering and discontinuation practices of pediatric rheumatologists and ophthalmologists globally. Most physicians start to taper medication after 24 months of remission on medication and discontinue after the 6 to 12 months of tapering.

Acknowledgement:
We would like to thank all the participating colleagues, who took time to fill out our surve  Introduction: JIA-associated uveitis (JIA-U) occurs in 10-20% of children with Juvenile Idiopathic Arthritis (JIA) and typically asymptomatic, and sight-threatening complications occur in 50% of children, (i.e. cataracts, vision loss). Frequent ophthalmic examinations are important for early diagnosis and monitoring of uveitis activity. Even after uveitis is controlled, risk of disease exacerbation still exists. Therefore, frequent ophthalmic screening and monitoring is important for detection and management of JIA-associated uveitis (JIA-U). S100 proteins, cytokines, and chemokines detected in aqueous humor of patients with uveitis are also detected in tears. Biomarker discovery using tears is promising since collection is noninvasive, feasible, well-tolerated, and close to the target organ. Objectives: We aim to determine if S100 proteins, cytokines, and chemokines levels differ in tears of children with JIA and JIA-U and in children with JIA-U by uveitis activity. Methods: Tears were collected using Schirmer strips from children ≥5 years old with oligo-or polyarticular RF negative JIA with (JIA-U) and without uveitis (JIA-no-U), and in children with JIA-U at time of active and inactive eye disease. Activity was defined by Standardization of Uveitis Nomenclature (SUN) criteria. Active uveitis was anterior chamber inflammation grade ≥0.5+ cells. S100A8, A9, and A12 were measured by ELISA, and IL-18, IL-8, IP-10, MCP-1, RANT ES, and sICAM-1 by Luminex assays. Biomarker levels were compared in children with 1) JIA-no-U (n=8) to active JIA-U (n=8), and 2) JIA-U (n=8) at time of active and inactive uveitis.

Disclosure of Interest
Results: Children with JIA-no-U and JIA-U were matched by JIA subtype and arthritis activity. They had primarily oligoarticular JIA (63%), active arthritis (25%), and were on systemic medication (75%). At time of active uveitis, 75% had grade 0.5+, and 25% had 1+ and mean interval between time of active and inactive disease was 11 months. We found that levels of biomarkers in tears of children with JIA-no-U compared to active JIA-U were similar. Although not statistically significant, levels of S100A12 (mean difference 12,190 pg/ML [95% CI -4847 to 29,227], P= 0.14) and sICAM-1 (5329 pg/ML [95% CI -5372 to 16,031], P=0.28) were higher when uveitis was active compared to inactive. Conclusion: Our results suggest that S100A12 and sICAM-1 are potential biomarkers of uveitis activity in JIA-U, but not uveitis diagnosis. Thus, neutrophils may play a role in the pathogenesis of anterior uveitis which has been reported in an animal model of acute anterior uveitis. Identifying biomarkers using tears provides a noninvasive and objective method of monitoring uveitis. Limitations are our heterogeneous cohort that varied by arthritis severity and immunosuppression, and minimally active uveitis. We were underpowered to detect statistically significant differences and continue to collect tears prospectively in children with JIA-U with goal of n=28. Despite low uveitis activity, we were still able to detect differences. Further studies in larger and diverse cohorts are necessary to assess the role of S100A12 and sICAM-1 in JIA-U. Objectives: To report an extremely rare presentation of GPA in a 12 year old with acute digital ischemia.

Methods:
A 12 year old boy, with a background of poorly controlled type 1 diabetes and hypothyroidism, initially presented to hospital unwell with diabetic ketoacidosis. Treatment was initiated promptly with good response. Furthermore, he was found to have weight loss, productive cough and hearing loss over the past 3 months. He was haemodynamically stable, but very pale and cachectic. He had reduced air entry and crackles on the right. There was hypertonia and clonus in his lower limbs. Blood tests showed microcytic hypochromic anaemia (Hb 82g/L), normal white cell count, thrombocytosis and raised inflammatory markers (CRP 138mg/L and ESR 68 mm/hr). His chest x-ray showed enlargement of the right hilum with consolidation/ atelectasis extending into the middle and lower lobes. MRI scans of head and spine were normal apart from fluid opacification in the paranasal sinuses. He was screened for infections including Tuberculosis and started on intravenous antibiotics. On day 13, he developed painful bluish discolouration of his left hand, particularly his thumb, index and middle fingers. His left radial and brachial pulses weren't palpable. A heparin infusion was started.
A Doppler scan showed occlusion of radial and ulnar arteries proximal to the wrist with no clear thrombus.
He had a CT thoracic aorta with contrast which showed proximal left radial artery occlusion and distal ulnar artery occlusion with no evidence of proximal embolic source or vasculitis. It showed multiple perihilar masses (lymph nodes) in the right lung and peripheral parenchymal masses in both lungs, suggestive of atypical infection or connective tissue disease. Blood tests still showed raised inflammatory markers(CRP 107mg/L, ESR 86 mm/hr and platelets 658 10 9 /L). An autoantibody screen showed positive ANCA with strongly positive anti PR3(>100 U/mL); other autoantibodies, including ANA, ds DNA and anti-phospholipid antibodies, were negative. He developed further ischaemia with bluish, painful discoloration of his right foot, especially right great toe, with a weakly palpable dorsalis pedis pulse. Doppler scan revealed occlusion/narrowing of the posterior tibial artery 6cm proximal to the ankle. Following vascular team advice, he was started on ilioprost infusion to aid reperfusion of the extremities involved, with good results. Based on clinical and lab features of systemic inflammation, evidence of upper airway involvement(bilateral conductive hearing loss and sinusitis on MRI scan), parenchymal lesions on CT chest and strong PR3 positivity, a diagnosis of GPA was made.
Results: Our patient responded well to therapy including multiple pulses of high dose methylprednisolone and cyclophosphamide, with improvement of all organs involved and no further digital ischemia.
Conclusion: Although GPA is very rare in children, it is associated with high morbidity and mortality. Many studies show that the spectrum of paediatric GPA is not vastly different from adults, except for higher gender bias towards female, more constitutional and musculoskeletal symptoms and higher risk of subglottic stenosis.
Although there are a handful of case reports of digital ischaemia in adults with GPA, to our knowledge this is the first case report of acute digital ischaemia in paediatric GPA. Early diagnosis and prompt treatment with a multidisciplinary team approach is paramount for good outcome. Introduction: Adenosine deaminase-2 deficiency (DADA2) is a monogenic vasculitis syndrome whose presentation ranges from recurrent fevers and livedo reticularis to systemic vasculitis, hematologic and immunologic abnormalities, and early-onset stroke. It is characterized by biallelic loss-of-function mutations in the encoding gene of ADA2 protein and low levels of ADA2 enzymatic activity in the peripheral blood. The genotype and phenotype features of DADA2 has a wide spectrum. Treatment with anti-TNF inhibitors is effective in controlling vascular inflammation and reducing strokes.

Disclosure of Interest
Objectives: To describe two sisters with different presentations of DADA2 and a deletion mutation on exon 7 of the ADA2 gene. Methods: Medical data was used to describe the clinical manifestations of two siblings. Parental informed consent was obtained.
Results: Patient 1: A 10-year-old female had presented with fever, rash, arthralgia, hepatosplenomegaly, and coombs positive autoimmune hemolytic anemia (AIHA) at the age of 7 years. She had been followed with a suspected diagnosis of systemic lupus erythematosus (SLE) and steroids, azathioprine, mycophenolate mofetil had been used. Her ANA and complement levels were normal. Because of unmet classification criteria of SLE, genetic testing had been done, and no mutation found in the ADA2 gene. Cranial MR and MR angiography was normal. She was referred to our clinic after 2.5 years of the first manifestation. Physical examination revealed Raynaud phenomenon on both hands and feet, livedo reticularis, arthritis, and splenomegaly. Laboratory tests indicated an increase in acute phase reactants, CD19, CD20, and switched memory B cell lymphopenia, and hypogammaglobulinemia. Because of prolonged fevers, a thorax CT was obtained and aneurisms of the renal artery were seen. Abdominal CT angiography indicated multiple aneurysms of both renal, intercostal, and hepatic arteries. Repeated genetic analysis of the ADA2 gene showed a homozygous deletion mutation on exon 7. She has been followed on anti-TNF and IV immunoglobulin without severe symptoms for a year. Patient 2: The older sister had been followed with a diagnosis of familial Mediterranean fever with E148Q heterozygous mutation because of recurrent fever, abdominal pain, erysipelas-like erythema, elevated acute phase reactants, and splenomegaly. She did not have any other cutaneous or systemic findings. Because of parental consanguinity, the ADA2 gene was analyzed and a homozygous deletion mutation on exon 7 was found. She has been followed without any symptoms after anti-TNF treatment. Throat swab was negative. Abdomen ultrasound showed bowel wall thickening, testis ultrasound was normal. HSP diagnosis was confirmed. Methylprednisolone iv was administered for three days, then oral prednisone was started. Purpuric lesions, abdominal pain persisted, so we decided to add MMF (600mg/ m 2 /day) and prednisone was tapered in a month.
Results: Thanks to MMF vasculitis lesions and abdominal symptoms disappeared in few days. MMF was continued for a month, tapered in 6 months. There was no evidence of relapse in a 6 months follow up. Conclusion: These cases suggest that MMF may be useful to induce and maintain remission of recurrent HSP with gastrointestinal involvement. Multicenter clinical trials with long-term follow up to confirm the efficacy of MMF in the treatment of HSP with gastrointestinal involvement are needed. Introduction: Henoch-Schönlein purpura (HSP), the most common childhood vasculitis. Cholecystitis is extremely rare in patients with HSP. This is the first case of a Libyan child presenting with HSP complicated by calculus cholecystitis HSP nephritis. Objectives: our aim is to present an unusual case of gall bladder involvement in an 8-year-old Libyan female affected by HSP. Methods: a case reports study Results: : we report an unusual case of gall bladder involvement in an 8-year-old Libyan female with HSP. She was referred to a rheumatology clinic due to HSP with chronic calculus cholecystitis and distended small bowel with fluid-like fecal material with no evidence of intussusception on an abdominal ultrasound. The patient had a one-month history of abdominal pain, purpuric lesion on lower limbs and swelling in both feet. She was admitted 3 times to another hospital before being referred to the rheumatology clinic. An abdominal sonography revealed a distended small bowel with fluid-like fecal material with no evidence of intussusception and chronic calculus cholecystitis; they treated her with Urosdoxycholic acid tab at 250mg per day and ibuprofen syrup. Then referred to our rheumatology clinic. After 40 days, she showed a purpuric rash over her lower extremities, mainly over her thighs and buttocks, microscopic hematuria, no arthritis, no fever, no abdominal pain; her blood pressure was normal at90\55mmHg, and she had normal laboratory tests (CBC, WBC 7.7, HGB 10.8, Platelets 356 ESR 20ml\hour, CRP 1mg\dl was negative, C3 was 150mg\dl within normal range 90-180mg\dl, C4 was 35.4 mg\dl within normal range 10-40, ANCA, ANA, as well AntidsDNA Ab yielded negative, Antistreptolysin-O (ASO) titer was 250 Todd , LFT included total bilirubin , direct , indirect GPT,GOT, U\E, creatinine ) except urine routine showed mild microscopic hematuria RBC 100 HPF , protein was Nil ) urine for pro-tein\creatinine ratio was 0.16 normal range <0.5 ). An abdominal sonography showed multiple stones, with faint acoustic shadow, the largest of which were 7mm, no signs of acute inflammation. We initially treated her with oral prednisolone tab at 1mg\kg\day and enalopril tab 2.5mg once per day, All clinical manifestations resolved within one week, including normal gallbladder sonography finding, besides microscopic hematuria RBS was 80-85HPF; she had nephrotic syndrome urine protein\creatinine ratio was 1.99 (normal range is < 0.5) in spite of taking prednisolone tab for 4 weeks. The treatment with MMF 30 mg/kg/day commenced and the oral prednisolone (2 mg/kg/every other day for 2 months only) after treatment with MMF for two months, microscopic hematuria continued for 3 months and recovery from nephrotic syndrome within 2 weeks. After six months, MMF was discontinued and there was no clinical or laboratory abnormalities. The patient achieved complete remission at the end and after discontinuation of the therapy. There was no evidence of recurrence over one-year follow-up. Conclusion: Physicians should be aware that HSP might present initially as calculus cholecystitis. Repeat abdominal ultrasonography is essential in order to detect complications in patients with HSP. MMF was found to be a useful immune-suppressant and effective for maintenance of remission in HSP patients. Introduction: Takayasu's arteritis (TA) is extremely rare, especially in childhood, and its occurrence with inflammatory bowel disease (IBD) is even rarer. There have been suspected associations between TA and IBD in adult literature, but only a few paediatric case reports. Objectives: We describe a case of a girl (X) with Pakistani origin, diagnosed with indeterminate pan colitis, age 4 following her presentation with abdominal pain, weight loss, blood and mucus PR. Rescoping 2 years later, as steroid dependant, confirmed ulcerative colitis and she subsequently went into remission with Sulfasalazine and Azathioprine. Age 12, X presented with 3 months history of right sided neck pain, fatigue, pain in her lower limbs, intermittent fevers, night sweats and weight loss but no changes in her bowel symptoms. On examination she was pale, tachycardic at 135 bpm, BP 101/61 mmHg with no discrepancy between limbs. She had right sided torticollis despite full range of neck movements. Methods: X was admitted for pain management and noted to have raised inflammatory markers, anaemia and thrombocytosis. She had a neck ultrasound which revealed evidence of large vessel arteritis. CT angiogram showed arteritis of the thoracic aorta with aneurysmal change with involvement of the proximal arch vessels and proximal superior mesenteric artery; consistent with a diagnosis of Takayasu arteritis. MRI confirmed the findings. X was started on IV pulsed Methylprednisolone 30mg/kg for 3 days followed by weaning dose of oral Prednisolone, weekly SC Methotrexate and low dose Aspirin therapy. Treatment was switched to Mycophenolate Mofetil and later Tocilizumab, due to inadequate control of TA with SC Methotrexate, suggested by blood tests and serial US of large artery walls. Her disease remains stable and Prednisolone has been weaned to 5mg daily. Results: The exact causative mechanism for both IBD and TA is unclear; however there may be genetic markers which link both diseases. A significantly higher proportion of patients with IBD and TA were HLA-B52 positive compared to TA alone. Other genetic markers including HLA-DR2 and IL-12B have also been shown to be present in both diseases. There are reports that Infliximab has been effective to treat combined IBD and TA; this could support the theory that TNF-alpha may have a role in both conditions leading to mucosal and vessel inflammation. There is currently no NHS England funding pathway for anti-TNF alpha medications for TA, however Tocilizumab can be used. Conclusion: TA and IBD is extremely rare and requires a high degree of suspicion. Ongoing symptoms of pain, weight loss, fever and high inflammatory markers, in patients with otherwise well controlled IBD, should raise suspicion of alternative pathologies such as Takayasu arteritis. Neck and back pain in this child aided the journey to a diagnosis of TA due to direct pressure effects of enlarged arteries, but these symptoms are unusual. Early diagnosis and prompt treatment are likely to reduce morbidity and mortality in these patients who already suffer a high disease burden.

Disclosure of Interest
None declared

P286
Kawasaki disease in early infancy -case series K. Rücklová 1,2 , Š. Introduction: Kawasaki disease in infants typically presents as an incomplete or atypical form, which often results in delayed diagnosis and treatment thereby increasing the risk of coronary artery involvement. Objectives: To draw attention to diagnostic and therapeutic challenges posed by patients with Kawasaki disease manifesting at very early age. Methods: Medical reports and laboratory and echocardiographic findings of three infants treated at our centre for Kawasaki disease presenting below four months of age were analyzed retrospectively. Results: The first patient presented at the age of almost four months with fever and shock that required inotropes and artificial ventilation. Due to the atypical presentation the diagnosis was delayed until day seventeen of the illness when the patient developed giant coronary aneurysms and severe mitral valve insufficiency. Another patient manifested at three months of age and fulfilled most of the clinical criteria and received appropriate treatment already on the fifth day of the illness. He exhibited multiple risk factors for an adverse outcome including low age, very high CRP, thrombocytopenia, hyponatremia and hypalbuminemia with pronounced vascular leakage. After administration of IVIG and corticosteroids his clinical condition improved significantly. He was afebrile but his CRP remained mildly elevated and he experienced another flare of the disease within four weeks after the initial treatment with newly formed giant coronary aneurysms. He received adalimumab and pulsed methylprednisolone that finally terminated the inflammation. The last patient manifested at two months with a complete form of Kawasaki disease that prompted timely IVIG treatment. Despite repeated administration of IVIG only partial improvement was achieved and the patient developed giant coronary aneurysms during the second week of illness. Further therapeutic decision was complicated by the patient´s concurrent primary CMV infection. Conclusion: The first case demostrates a diagnostic challenge posed by patients presenting with Kawasaki disease shock syndrome. The second patient shows the need for very close follow-up of high risk patients. Even though our patient was afebrile after the initial treatment, his CRP remained elevated and the inflammatory process continued requiring biological therapy and escalation of antiaggregation to anticoagulation. The last patient emphasizes the importance of treating both Kawasaki and the concurrent illness that may potentiate the vasculitis as a trigger. Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237. Objectives: Case description Methods: A previously healthy 10 years-old girl presented high grade fever for 4 days, pharyngitis and vomiting. After 24 hours, she developed diffuse maculo-papular rash and oedema on extremities. She presented progressive worsening of general conditions and bilateral bulbar conjunctivitis, mucositis with strawberry-like tongue and left cervical lymph nodes enlargement. On admission remarkable laboratory tests were increased C reactive protein (CRP), neutrophilic leucocytosis, low sodium and albumin, increased gGT and gallbladder hydrops on abdominal ultrasound. Suspecting Kawasaki disease 2 gr/ kg IVIG were administered with salicylic acid (50 mg/kg/day). Nevertheless, she presented persistent remitting fever, low consciousness, diffuse vasculitic rash, worsening of mucositis and pericardial and pleural effusion. Lab tests showed low haemoglobin, platelets and fibrinogen (9,3 g/L, 65.000/ml and 1.05 g/L, respectively), ferritin 16.492 g/L, SGOT 487 U/L, SGT 351 U/L, triglycerides 345 mg/dl , Ddimers 10.353 microgr/L and soluble interleukin-2 receptor (sIL-2R), 6464 kU/L. Active haemophagocytosis was retrieved in bone marrow and cerebrospinal fluid (CSF) so MAS was diagnosed. Three consecutive iv methylprednisolone pulses (30 mg/kg) were administered followed by dexamethasone 10 mg/m2/day and cyclosporin A 2 mg/ kg/day as well as plasma infusions and oxygen supplementation (6 l/ min) for 48 hours. Parvovirus B19 (HPVB19) DNA was found in peripheral blood, bone marrow and CSF, while other microbiological analysis (EBV, CMV, HHV6, VZV, Influenza A-B, Measles, Adenovirus, HSV) were negative. The patient progressively improved with reduction of fever, oedema of extremities and skin rash and after 6 days presented extensive desquamation on hands, feet and limbs. Lab tests slowly improved and normal values were achieved on day 23. Echocardiogram did not show any coronary aneurism or dilatation, cerebral MRI was normal and neurological impairment gradually disappeared. Primary HLH mutations for UNC13D, STXBP2, STX11, RAB27a, SH2D1A, XIAP were not found. Corticosteroids and Ciclosporin were gradually tapered and discontinued after 7 and 12 months respectively, whilst acetylsalicylic acid was stopped after 2 months. Results: MAS is a relatively infrequent complication in KD and may be associated with severe course and poor outcome. Several potential infectious agents have been suggested as trigger factors of both MAS and KD, such as Epstein Barr virus, Influenza virus etc. and, more recently, the SARS-COV-2 epidemic has been associated with severe forms of systemic inflammatory syndrome resembling KD and MAS.
Conclusion: To the best of our knowledge, this is the first case in which demonstration of HPVB19 DNA in peripheral blood, bone marrow and CSF during acute phase strongly suggests a direct role of the virus in triggering both KD and MAS rather than an antibody or immune-complex mediated mechanism.

Introduction
There is a limited awareness about vasculitis amongst primary physicians in our region. There is not a single exclusive pediatric rheumatology center in our region catering around 20 million people. [1][2][3] Objectives To unveil characteristics of vasculitis in children in our region. Methods I gathered a data of 27 children with confirmed diagnosis of some form of vasculitis who attended Dev Children's Hospital between January 2019 and January 2020. It included demographics, clinical presentations, laboratory results, treatment and follow up.

Results Conclusion
The most common vasculitis in our cohort is Kawasaki disease. The number of incomplete KD patients was almost same as complete KD. Almost all our KD patients responded to IV Ig. None of the children with KD developed coronary artery abnormalities. Gastrointestinal complications were seen to be associated with four patients of IgA vasculitis at onset. Two children with IgA vasculitis developed renal complication within 3 months of disease onset. Trial registration identifying number Introduction: Kawasaki disease (KD) is an acute, immune-mediated multisystem vasculitis of unknown etiology that most frequently affects infants and young children. Immunological abnormalities during the acute phase of KD have been described extensively and coronary artery aneurysms (CAA) identified as a main long term complication. The occurrence of non-cardiac, autoimmune complications in patients with history of KD was rarely reported. Objectives: Our aim was to evaluate the presence of autoimmune diseases (AID) in patients after KD diagnosis and to compare clinical, demographic and laboratory characteristics between patients who developed AID (group 1) and patients who did not (group 2). Methods: A single-center, retrospective cohort study with longitudinal follow-up of all children newly diagnosed with KD between June 2006 and December 2018 was performed. In total, 151 children (91 males and 60 females, median age 3.4 years) with KD were enrolled. Range of follow up was from 1 to 13 years after KD (mean follow-up 16.8 months). Results: Of 151 children with KD, 16 (10.6%) developed AID after KD including: 6 juvenile idiopathic arthritis (JIA), 6 macrophage activation syndrome (MAS), 3 coeliac diseases, 1 ulcerative colitis, 1 psoriasis, 1 hypothyroidism and 1 demyelination. Three patients presented with more than one AID. The mean time interval between diagnosis of KD and diagnosis of AID was 30.5 months (range 0.2 − 149 months). We found no difference in age distribution, clinical characteristics and incidence of CAA between the two groups. Group 1 had significantly lower median serum sodium (135 vs 137 mmol/L, p = 0.002), lower median platelet count ( 262 vs 363 x10 9 /L, p = 0.026) and higher neutrophil to lymphocyte ratio (9.4 vs 4, p = 0.009). There was also significantly higher percentage of IVIG resistance in group 1 (37.5% vs 12.6%, p = 0.022). Moreover, we found that children with KD had twice as many AID compared to CAA on long term follow-up (10,6% and 5,3% respectively). Conclusion: In our cohort, children with KD had twice as many AID when compared to CAA on long term follow up. Monitoring of children after KD for AID should be considered, especially in patients who were resistant to IVIG treatment. Additional studies are necessary to clarify the possible role of sodium, platelet count and neutrophil to lymphocyte ratio for risk stratification of AID after KD. Introduction: The clinical presentation of Granulomatosis With Polyangiitis (GPA) is often heterogeneous, with frequent involvement of the respiratory tract, the kidney, the skin and the joints. GPA vasculitis is rare in childhood but cohort studies performed during the last decade have clarified their phenotype, patterns of renal involvement and their prognostic implications, and outcome. We provided preliminary data on demographic characteristics and organ manifestations of Russian cohort in one center. Objectives: To describe demographic characteristics, presenting clinical features, and initial treatments in patients with granulomatosis with polyangiitis (Wegener's) (GPA). Methods: The European Medicines Agency (EMA) classification algorithm was applied. The EMA algorithm was used to uniquely distinguish children with GPA from children with other vasculitis, whose diagnoses had been classified according to both adult-and pediatric-specific criteria. Descriptive statistics were used for comparisons. Results: In total, 15 patients (67% female) fulfilled the classification criteria for GPA (n = 15). The median time to diagnosis was 3.5 months (ranging to 24 and 46 months, respectively). The median age was 13 years. Pulmonary manifestations were in 53 % (n=8) of patients (alveolar hemorrhage (n=2), dyspnea (n=5), chronic cough (n=4), pleural effusion (n=1), lung nodules or cavity (n=3), lung infiltration (n=6). Renal pathologic features were found in 53% (n=8). Eye involvement was in 33 % (n=5), ENT involvement was in 67 % (n=10), cutaneous involvement was in 26 % (n=4), CNS involvement was in 6% (n=1), cardiovascular involvement was in 6% (n=1), musculoskeletal involvement was in 60% (n=9), gastrointestinal involvement was in 13 % (n=2), fever, fatigue were in 87 % (n=13). All patients with GPA for induction remission received combination therapy with corticosteroids plus immunosuppressive agents Objectives: The aim of this study was to investigate the value of erythrocyte glutathione S-transferase (e-GST) activity as an early predictor of nephritis development in HSP.
Methods: Ninety-seven children with HSP were enrolled into the study. The control group consisted of 52 children without clinical and laboratory signs of inflammation. In all patients e-GST activity was determined spectrometrically for three times during six-month period and corelated with clinical characteristics of the disease, routine blood and urine laboratory findings as well as with e-GST activity in healthy children.
Results: At the beginning of the disease the e-GST activity values were significantly higher in the group of HSP patients who developed proteinuria above 0.15 g/dU and/or haematuria above 5 E/mm 3 (i.e. HSPN) during six-month follow-up period, compared to the group of HSP patients without nephritis during same time span: median (interquartile range) 5,70 U/g Hb (4,38-7,50 U/g Hb ) compared to 3,10 U/g Hb (2,20-4,20 U/g Hb ); P<0,001. Similar results were obtained after the comparison of the patients with HSPN and control group: 5,70 U/g Hb (4,38-7,50 U/g Hb ) vs. 3,13 U/g Hb (1,91-4,20 U/g Hb ); P< 0,001. There were no statistically significant differences between the group of HSP patients without nephritis and a control group (P= 0,837). After the period of three and six months, a decrease of e-GST activity was observed in the HSPN patients, but it was still significantly higher compared to the group of HSP patients without nephritis (P<0,001 / P<0,001).
In the ROC analysis of the e-GST activity determination value in the prediction of HSP nephritis, for the e-GST values >4,1 U/g Hb a significant area under the curve (AUC) of 91.1% (P < 0.001) and sensitivity of 90.5% and specificity of 72.7% was found at the beginning of the study. The sensitivity of the nephritis detection tests decreased, and the specificity increased during the follow-up period. No significant correlation between e-GST activity and severity of skin changes, abdominal pain and arthralgia/arthritis, or used therapy was found. Among the routine laboratory tests, a consistent, statistically significant, positive correlation was found only between e-GST activity and the number of erythrocytes per mm 3 in urine samples.
Conclusion: e-GST activity is a reliable, independent marker of early nephritis risk assessment in children with HSP. As a sensitive and specific, feasible and inexpensive laboratory test, it has potential practical utility in the diagnostic algorithm and monitoring of the children with HSP. tertiary hospitals in Croatia. The average annual incidence of IgAV was calculated with the population census data from 2011 as the denominator. To investigate the spatial distributions of IgAV, a choropleth map was created based on the raw and Bayesian adjusted incidence data.

Disclosure of Interest
Results: A total of 402 domestic patients were included in the study, of which 223 (55.47%) were male, and 179 (44.53%) were female, with a median age of 6.42 (4.5 to 9.08) years. The estimated average annual incidence was 8.4 with a 95% confidence interval between 6.51 to 10.66 per 100 000 children. As expected, the raw data showed that the highest number of cases was detected in administrative areas with a higher population. A statistically significant higher percentage of patients came from the continental (69.15%), when compared to the Mediterranean part (30.85%), p< 0.001. Box maps and standard deviation maps showed with incidences higher (hot-spots) and lower (cold-spots) than the average annual incidence. However, when the standardized average annual incidence was plotted, the spatial distribution correlates with the location of higher incidence levels. Therefore, the spatial distribution pattern showed the existing of hot-spot clusters with higher incidences around large cities both in the continental, and Mediterranean part of Croatia.
Conclusion: This pilot study investigated the usefulness in expanding the epidemiological toolbox with applying spatial analyses. The results of this study suggested that the IgAV incidence might be clustered in space. However, for a more definitive conclusion, a geostatistical analytical approach is needed to evaluate the significance of observed clusters. SUPPORT: Croatian Science Foundation project IP-2019-04-8822. The study was carried out in the pediatric Rheumatology Unit of the Institute of Child Health Kolkata, India. 33 children aged between 6 weeks to 7 years with KD were included who received IFX after 1-2 doses of IVIG due to persistent fever/ increasing CAA or developing new CAA. Patients were analyzed for response in terms of achievement of defervescence in hours, normalization of CRP and improvement in echocardiographical findings specially CAAs. Children with severe CAAs were followed up by echocardiography weekly upto 6 weeks, monthly upto 3 months, and then 6 monthly.

Disclosure of Interest
Results: IFX was used in 1) IVIG resistant fever(23/33) and 2) increasing CAAs post IVIG (15/33). Overlapping indications ie. IVIG resistance with increasing CAAs were also present (7/33).IFX was administered at 5mg/kg and defervescence was achieved within 24 hours in all of the 23 resistant cases along with normalization/ drastic fall in CRP. 2 children whose fever persisted was later diagnosed as Systemic Arthritis and hence excluded from the study. Diminution in size of aneurysm was seen in 80 % (12 out of 15) cases on follow up, giant aneurysms being converted to medium or small sized aneurysms over 6 to 18 months. Interestingly 50% reduction in the aneurysm size was noted in 60% (n=9) within first 6 months of administration. We present a case of acute severe postinfectious glomerulonephritis in a TRAPs patient, presumably poststreptococal. This is to our best knowledge the first case reported and questions arise on the possible association of this severe event to TRAPs syndrome, ongoing treatment or just an unfortunate coincidence. Differential diagnosis was mandatory to discard a rapidly progressive glomerulonephritis and renal amyloidosis in this context. Mild and generally transient proteinuria and creatinine clearance reduction have been reported in association with canakinumab treatment but to no acute glomerulonephritis has been previously described. Methods: With a fever child was admitted to the infectious department, after the treatment with improved condition discharged home. In a 3 month, and than after 4 months the same episodes of a sudden fever and skin rush were observed, with nausea, vomiting, diarrhea. Child was excluded with common causes of prolonged infection disease. At the age of 1,6 together with fever and rush, episode of arthritis appeared. Child was admitted to the rheumatologist and confirmed with systemic JIA, treated with high dose of steroids. In a next 2 years involvement of both knee and ankle joints was observed, fever appeared at least once in 2-3 months and was treated with steroids. At the age of 5, child got long therapy with steroids, but frequency of fever episodes was high, followed by typical inflammatory signs in laboratory investigations, in periods between fever attacksall laboratory and instrumental results were normal. At the age of 8 -13 years, episodes of fever became rare, 2-3 times a year, and less severe. At the age of 13 treatment was added with metotrexate, as joint syndrome was still ongoing, steroids were stopped. Patients condition remain stable, with minimal arthritis of knee joint, fever was occurred once in a year, and at the age of 18 patient was transferred to adult rheumatologist. At the background of an argument between the patient and a doctor, he didn't come to his office for regular check-ups and discontinued treatment by himself. At the age of 20 new episodes of a fever started to appear, with rush, arthritis. Episodes of vomiting and diarrhea appeared as well. Patient by himself started to take steroids, but took them just during fever attacks. Patient started to suffer from muscle weakness and mother admitted that son became depressed, refused even from small walks. At the age of 24, during fever attack acute cerebrovascular accident happened. After the stroke, patient developed neurological symptoms that accompanied periodic fever, he got poor memorizing, difficulties with speech. Rheumatologist initiated systemic steroids, metotrexate, recommended pulse therapy with steroids. Patient refused from pulse therapy and didn't continue systematically treatment. At the age of 25,5 patient developed second acute cerobravascular accident during fever episode. This time patient was admitted to the ICU for long time, after the treatment discharged home with severe neurological complications. After the second stroke he got inversion of the day/night sleep, slept 18-20 hours a day, didn't recognize and communicate with no one, except mother and still had periodic fever and arthritis. Patient totally refused from the treatment and was deeply depressed.

Disclosure of Interest
Results: Ptient came to the center of orphan disease and was examined by genetic and pediatric rheumatologist, prescribed with additional investigations and mutation V377I was detected, as well high level of mevalonic acid in urine and decreased activity of mevolanatkinase. Patient was recommended to initiate treatment with anakinra and canakinumab. In a 4 months after the treatment was initiated, neurological symptoms normalized, disappeared fever and arthritis. Conclusion: Adequate and in a timely manner diagnostic measures of the periodic fever syndrome with deficiency of mevalonatkinase allows initiate appropriate treatment, improve quality of patients life and avoid dozen complications. Estimation of the correct diagnose in case of our patient was late for 25 years. Introduction: HIDS is a rare genetic inflammatory disease (autosomal recessive), characterized by periodic episodes of fever accompanied by other symptoms such as joint pain, skin rash and abdominal pain. The fever episodes have a duration of 4-6 days, they begin from the first year of life and appear periodically throughout the whole life. The mutation in the case of HIDS leads to a decrease in the activity of mevalonate kinase, an enzyme important for cholesterol synthesis, and febrile episodes can further decrease this activity. Thus, during these episodes high levels of mevalonic acid can be found on blood serum and urine.
Objectives: Case presentation, a child with HIDS Methods: A 12-year-old female patient, whose parents refer for recurrent episodes of fever (38-39.5ºC), that are accompanied with diffuse joint disease, skin rash, oral aphthous lesions and abdominal pain. The episodes had begun nearly at 18-months-old with a duration of 3-5 days up to 6-years-old. Then again at 11-years-old. The fever episodes did not improve with the use of antibiotics, NSAIDs, CS or antipyretics. The mother had a normal pregnancy, the child was born on term and the psycho-motor development was conform the age. Results: In the examination performed during the febrile episodes the patient did have joint pain on pressure, non itchy skin rash in the abdomen and inferior limbs, appearing during the fever but that endure even outside the febrile episodes. Aphthous lesions can be seen on tongue and soft palate. Moreover, non painful, mobile nodules of 1-1.5 cm can be palpated in the cervical, axillary and inguinal area. Spleen at the level of iliac crest. In the laboratory evaluation: inflammatory anemia in the blood test and a mild leukocytosis, (WBC 14x103, RBC 3.12x106, HgB 9.7mg/dl, MCV 86 fl, ESR 40mm/h). The biochemical profile within range. In the blood and urine culture no pathogenic increases were found. Febrile infectious antigens were negative. Bone marrow examination was normal. Immunological evaluation: FR neg, AAN neg, ENA neg, ANCAp/c neg, C3-C4 within the range, PCR 9.6(<5UI/ml). Protein electrophoresis revealed an increase in ά1.
Immunoelectrophoresis revealed an increase in IgD 350UI/ ml(100UI/ml). Blood ferritin level was 60mg/dl (20-50mg/dl). Head MRI was normal. In the abdominal CT with contrast infusion, cervical, axillary and inguinal nodules of 1-2 cm can be seen, liver of 16cm without any visible lesions and homogenous spleen of 13.4cm. The data of lymphocyte immunophenotyping of peripheral and central blood within the range, no pathological lymphocytic populations were found. Nothing abnormal was found during nodule biopsy. HLA-B27 neg, HLA-B51neg. The level of mevalonic acid in urine resulted 130.8 mmol/ml (<69mmol/ml). Discussion: For the case the diagnostic differentiation between several diseases was made, including lymphoproliferative disorders (the data of bone marrow examination, biopsy and lymphocyte immunophenotyping did not support the diagnosis), infectious diseases (the data of febrile antigens were negative and febrile episodes were not affected by use of antibiotics), JRA-Still's disease (blood ferritin slightly increased and recurrent febrile episodes that resolve by themselves), inflammatory connective tissue disease ( FR, AAN, ENA, HLA-B27, HLA-B51 neg).
Conclusion: Since all other diseases were ruled out and both the level of IgD in blood and the level of mevalonic acid in urine were found to be elevated, besides the periodic febrile episodes and clinical symptoms, the patient was diagnosed with HIDS. In all patients with periodic febrile episodes the electrophoresis of immunoglobulins should be performed and also the evaluation of mevalonic acid both in blood and urine. Introduction: The COVID-19 disease identified and reported from Wuhan, Hubei, China. At the time being, the disease is a pandemic and has involved the entire world.
Objectives: The aim of this study is reporting the planning and actions after the COVID-19 epidemic for prevention of spread of the disease, supporting patients, and managing the disease at our center's outpatient clinic as a referral center for children suffering rheumatic diseases. Methods: Since the first report of disease, we tried to reply to the patients' questions in a virtual social network. We were following lab data, radiograms, sonograms, CT scans, and MRI results in this network and provided solutions for the management of the children's problems without need to encountering. Results: In cases that were controlled and their diseases were in remission, we invited one of the patient's parents to come and receive the prescriptions. We put some instructive short films about COVID-19 in the virtual network and in LED screens of our outpatient hospital clinic to provide useful information. About the turn rating system (queuing system) we omitted manual turn-taking stands to prevent virus transmission. In the peak of the epidemic, we stopped outpatient clinics for three weeks. After that, we started clinics with the least number of patients and the most standard protection measures for physicians, patients, and other staff. All people were triaged in the hospital yard before entering the waiting hall of the clinic by taking their temperature and screening questions. If they didn't have a fever and symptoms compatible with the disease, we let the patient and only one compeer enter the clinic hall with giving a free three-layer surgical mask to each of them. We requested the physicians to increase the time of their clinics to distance the appointments of the patients and to prevent overcrowding in the clinic. Each clinic was held with the presence of the attending physician and only one fellow physician. Gowns, protective glasses and face shields, surgical masks, and latex gloves were provided for secretaries and the other staff in the clinic. In the first eight weeks, daily disinfection was performed for all the surfaces of the clinic and after that, a disinfecting tunnel at the door of the clinic was added. With the screening of about 100 staff in the clinic, we found only one IgM positive person for COVID-19 during the first eight weeks who was one of the secretaries without any signs and symptoms and were quarantined at home. Among the physicians, 6 of them (8 percent) developed COVID-19 disease with laboratory confirmation. All of the involved physicians were working in the private section as well as a state-run system. From about 200 patients with different rheumatic diseases came to the clinic in eight weeks, 11 of them (5.5%) were in the relapse of their disease which in comparison to the same time in the last year, 26 from 760 patients (3%), a remarkable increase (almost double) is seen for which different causes can be considered. Most of the patients who came to the clinic in the COVID-19 outbreak were those who had to come due to the severity of their disease. In the patients who came before the epidemic, the most causes were musculoskeletal pains such as hypermobility and skeletal benign reasons and rheumatic diseases were in the next rank but in the epidemic outbreak, the prior group came in a lower number. Follow up on the patients after the epidemic will reveal this matter better. Conclusion: Employing personal and patient protective equipments, patients' triage, postponement of face-to-face appointments, social distancing, telemedicine, and using the virtual social networks may be effective policies in outpatient clinics in the COVID-19 outbreak. Objectives: To report a case of SARS-COV-2-related Kawasaki-like disease with severe cardiac involvement. Methods: case report description.
Results: A 10-year-old previously healthy girl presented progressively worsening abdominal pain, high grade fever for 3 days and vomiting. Lab tests showed WBC 11680/mmc, N 9370/mmc, Creactive protein (CRP) 329 mg/L, procalcitonin (PCT) 0,74 ug/L, PT-INR 1,35 and elevated D-dimer and fibrinogen levels (817 ug/L and 9,45 g/L respectively). Abdomen ultrasound revealed lymphadenopathies and hyperechogenic mesentery in the right lower quadrant, although the appendix was not visualized. She underwent laparoscopy showing moderate quantity of free fluid and appendectomy was performed. Thereafter she continued to complain of high-grade fever, abdominal pain and diarrhoea, despite broad-spectrum antibiotics. Blood, urine and stool cultures were negative. Bilateral non-exudative conjunctivitis was present. Moreover, the lab tests showed persistent marked elevation of CRP (370 mg/L), WBC 15590/mmc, N 14070/mmc, hypoalbuminemia (23 g/L), elevated ferritin and triglycerides (458 ug/L and 221 mg/dl). By taking into consideration the concomitant SARS-COV-2 pandemic, nasopharyngeal and rectal swabs were taken with negative results. Conversely, serological test showed anti-SARS-COV-2 IgG antibodies and absence of IgM. The family medical history showed that the mother had presented fever, cough, ageusia and anosmia one month before, preceded by a contact with a SARS-COV-2 positive case, while the patient was asymptomatic at that time. Suspecting a KD-like disease she was referred to our Paediatric Rheumatology Unit: cardiological assessment revealed negative Twaves in V4-V5-V6 on EKG while standard and advanced echocardiography showed mild mitral and tricuspid insufficiencies, mild dilatation of the left main coronary artery (LMCA, z score +2), normal global function (FEVS 2D 58%) but reduced longitudinal strain (GLS -16%). Lab tests confirmed myocardial injury with troponin (TnI) 100,1 ng/l and brain natriuretic peptide (P-BNP) 593 ng/L. A single infusion of intravenous immunoglobulin 2 g/kg associated with methylprednisolone (1 mg/kg/day) led to a rapid clinical improvement with apyrexia and resolution of abdominal pain and conjunctivitis. Blood test confirmed gradual normalization of inflammatory markers, ferritin, troponin and BNP and EKG showed positive T-waves. Shortly after the discharge, while she was on prednisone 0.5 mg/kg/day and acetylsalicylic acid 100 mg/day, she referred some episodes of heart pounding, lasting about ten minutes with spontaneous resolution. Three weeks after onset, cardiac MRI was normal, however, speckle tracking echocardiography showed persistent dilatation of LMCA and reduction of global longitudinal strain (GLS -14%). 24-hour EKG-Holter detected episodes of supraventricular tachycardia and several ventricular and supraventricular extrasystoles. Thus, oral atenolol therapy was started. Conclusion: In our patient SARS-COV-2 induced a possible postinfectious antibody or immune-complex mediated reaction that led to KD-like disease with acute surgical abdomen presentation and persistent myocardial damage and arrythmias. Speckle tracking echocardiography appears more reliable than MRI in early detection of myocardial damage in patients with preserved left ventricular ejection fraction.

Introduction
Recently reports from Europe and North America have described clusters of children and adolescents with a multisystem inflammatory condition with some features similar to those of incomplete Kawasaki disease. [1][2][3] Objectives To unveil characteristics of systemic inflammatory syndrome (SIS) in children during COVID-19 pandemic in India Methods This is a case series which included three such pediatric patients who were evaluated between April 2020 and May 2020 at five different hospitals from an Indian state of Gujarat. Our electronic data included demographics, clinical presentation, laboratory results and follow up. Objectives: We report the case of a child with a severe systemic inflammatory syndrome following an asymptomatic COVID-19 infection.

Results
Methods: A 9-year-old male was admitted to the Pediatric Emergency Unit due to fever and abdominal pain. Symptoms started 7 days before admission, with fever, vomiting and non-bloodydiarrhea. Family history revealed that the father had been admitted to a COVID-19 Sub-Intensive Unit with bilateral interstitial pneumonia until 7 days before the onset of symptoms in the child. On the basis of familial history and because of the presence of fever, patient entered the COVID-19 pathway and was isolated. He had no chronic underlying disease nor history of previous hospitalization. At admission, he appeared stable. Body temperature was 38.1°C, O2 saturation was 98% in ambient area, blood pressure was 106/60 mm Hg, heart rate was 140 bpm, respiratory rate was 21 breaths per minute. On examination he was alert, there were no cough, runny nose or other respiratory symptoms. No conjunctivitis, rash or peripheral edema was detected. He had mild hepatomegaly. Results: The patient underwent blood and microbiological exams including blood specimens for cultures and nasopharyngeal swabs for SARS-COV2 nucleic acid (by RT-PCR-assay). At baseline, leukocytosis with neutrophilia and relative lymphopenia were found. Hemoglobin was below the normal range, while platelets count was normal. Inflammatory markers were strongly elevated, particularly CRP(420.8 mg/L), ferritin(4488 ng/mL), D-dimer(5106 ng/ mL). Several significantly altered parameters suggested liver function abnormality, with hypertransaminasemia, acute renal injury, with elevated blood urea nitrogen and serum creatinine, and myocardial injury, with elevated high sensitivity cardiac troponin (434 ng/L) and brain natriuretic peptide (825 pg/mL). Lymphocyte subsets were within the normal range, while NK cells were slightly reduced. Patient was also tested for respiratory syncytial virus (RSV) and for influenza viruses A and B, resulted all negative. Bacteria and fungi blood cultures were sterile, as well as urine and stool cultures. He was tested for COVID-19 antibodies which showed positivity of both IgG and IgM (qualitative test), confirmed by a quantitative analysis which showed a high level of IgG (5066 AU/ml) and a weak positivity of IgM (0.532 AU/mL). Echocardiography showed no ventricular dysfunction, no dilatated coronaries or pericoronary iperechogenicity. Chest CT on the 2 nd day showed two small bilateral areas of atelectasis associated to minimal pleural effusion more evident on the right side. The diagnosis of Hyperinflammatory syndrome COVID-19 related was made.
Conclusion: Because of the high levels of BNP and troponin, IV methylprednisolone (5 mg/kg/day) and subcutaneous heparin (100 U/kg/day) were started after 24 hours since admission. Search for COVID-19 on nasopharyngeal swabs collected for 3 consecutive days resulted negative, The patient gradually recovered and fever disappeared after 48 hours. He presented no vomiting or diarrhea during the hospital stay, nor respiratory symptoms. Laboratory exams dramatically improved. According to his clinical and laboratoristic improvement, methylprednisolone was tapered to 3mg/kg/day and he started oral prednisone 1.25 mg/Kg/day four days after. He was discharged with steroid and heparin therapy and a close follow-up was planned.

Disclosure of Interest
None declared Campatodactly-arthropathy -coxavara-pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by a mutation in the gene proteoglycan 4(PRG4) affecting lubricin production, which is an essential protein for joint function. We present this case of a female child to describe the clinical, laboratory and radiological findings of CACP syndrome that should help in differentiation of CACP syndrome from other childhood inflammatory arthritis. Objectives: To increase the awareness of this familial condition to prevent confusion with other inflammatory conditions Methods: A case report Results: an 8-year-old female patient was referred to the Rheumatology clinic with complaints of joint deformities of her fingers namely campatodactly was noticed through the first year of life that treated surgically, while other joint involvement at age 3 was starting to have multiple joints swelling, she was the products of 3 rd degree consanguineous marriage and other 2 siblings are healthy, she was referred as a case of poly juvenile idiopathic arthritis. She has normal intelligence with normal school performance, she's able to perform all daily activities except that she has difficulty in the traditional cross sitting.At the time of our assessment, articular findings revealed bilateral flexion deformity of proximal interphalangeal joints and limited flexion and extension of both wrist joints, additionally there was a thickened rubbery synovium, significant knee joints swelling with moderate to large effusion associated with it, significant limitation of hip joint movements mainly in the internal and external rotation as well as abduction, and she was unable to sit crosslegged , although she didn't have joint tenderness or hotness , she had sometimes a non-specific diffuse joint pain . Moreover , she had normal cardiac examination and echocardiography study , her ophthalmological assessment was normal , however ; her height was below 3 rd percentile , there were no other associated systemic involvement. Her laboratory tests revealed that she had normal inflammatory marks (ESR, CRP) and the result of rheumatoid factor test was negative, she had low vitamin D and slightly elevated alkaline phosphatase level, her PTH, serum calcium and phosphate were within normal range. Regarding her radiological findings , her x ray showed that there were pictures of bilateral coxa vara with a short femoral neck and flat, irregular femoral head and intra-osseous cysts, increased joint space and abnormal modeling acetabulum with small iliac wings. Other joints (knees, ankle, elbow and wrist) showed soft tissue swelling consistent with thick cartilage. Her hand xray showed a soft tissue swelling around the interphalangeal and wrist joints , periarticular osteopenia and flexion deformities of the interphalangeal joints, affecting the 5 th joints bilaterally .A bilateral hip MRI showed effusion. Patient was treated at the referral hospital with a (NSIDs) and antirheumatic drugs , however ; they were ineffective.We treated her in the rheumatology clinic with vitamin D and calcium supplements as a treatment for osteopenia. We believe that synovial biopsy is not indicated in the correct clinical and radiological setting for atypical presentation, thus it is recommended if genetic testing is not affordable.
Conclusion: CACP syndrome should be considered in juvenile patients presenting with non-inflammatory arthropathy . We hope that this report will increase the awareness of this familial arthropathy condition and the clinical characteristics and the radiological findings well facilitate the differentiation from the common childhood rheumatic diseases. Introduction: Capillaroscopy is a tool that helps to assess microcirculation (MC) by observing the shape, density, structure, and alterations in the capillaries of the nailfold. MC has an important association with rheumatic diseases (RD), which is why it has become an important tool in rheumatology, and is considered a low-cost, non-invasive method. Raynaud's phenomenon (RP), a clinical condition commonly found in patients with RD, requires capillaroscopic evaluation to differentiate primary RP from the secondary, and it also helps to monitor the activity of the disease, assess response to treatment and prognosis. To date, there are no standardized capillaroscopic patterns in pediatric populations. Objectives: Describe qualitative and quantitative capillaroscopic differences between pediatric RD patients with RP and those without RP. Methods: Patients from the pediatric rheumatology department of a tertiary center in Monterey, Nuevo León, Mexico from July 2017 to March 2020 were included. Eight fingers, excluding the thumb, taking for analysis the most representative 1 mm image of each finger with x200 videocapillaroscope (Optilia), all measurements were taken by the same observer. Demographic data captured to describe the diagnosis, age, and RP presence. Capillaroscopy data, qualitative data: pattern, density, abnormal shapes, microbleedings and edema; for quantitative characteristics length, width, inter capillary distance, afferent diameter and efferent diameter were obtained. Results: Sixteen patients were included, of which 13 (81.2%) were female, the mean age was 12 years, RP was present in 12 (75%) patients. Regarding the diagnoses in the RP group, we found Systemic Lupus Erythematosus (5/12), Juvenile Idiopathic Arthritis (3/12), undifferentiated connective tissue disease (1/12), systemic sclerosis (1/12), IgA vasculitis (1/12) and primary RP (1/12); in the group without RP the diagnosis where psoriatic arthritis (1/4), psoriasis (1/4), localized scleroderma (1/4) and polymyositis (1/4). Among the quantitative characteristics, we found a greater length in R2, R4, R5, L4 and L5 of the patients with RP. Similarly, we observed a difference in the afferent diameter of R3, R4, R5, L2, L3, L4 and L5, being bigger in patients with RP. In L4 we found a difference in length, afferent and efferent diameter, being greater in those patients with RP, on the contrary, the width is usually smaller. Conclusion: We found both qualitative and quantitative differences in patients with RP versus those without RP, mainly in afferent diameter for all fingers, and in L4 we found a difference in most of the measurements. This study shows the quantitative data of the videocapilaroscopic analysis, and therefore it is proposed as a possible tool for the diagnosis and monitoring of RD in pediatric patients. Despite finding capillaroscopic alterations in both, the sample size in this cohort is small, so studies with a greater sample must be done, as well as studies with controls on healthy children, to make more conclusions. Introduction: Clinical examination may not detect mild degrees of synovitis that can be present in subjects deemed to be in clinical remission and with negative inflammatory markers. In adults, ultrasound (US) Power Doppler positivity in patients with RA in clinical remission has been suggested by some authors to have a predictive value for flare. In pediatrics there are less definite data, in relation to difficulties in practical application of US and physiological changes in growing joints. In asymptomatic JIA children with a normal joint examination the long term significance of subclinical arthritis detected by US is not clear. Objectives: Aim of the present study is to review published articles related to the predictive value for flare of subclinical synovitis assessed by ultrasound in juvenile idiopathic arthritis (JIA) in clinical remission. This could have implications in the practical management both for adjustments in drug treatments and for the timing of clinical surveillance during follow-up. Methods: Medline, Embase and Cochrane databases were searched from 1990 to 2020 by two authors, using PICO methodology to build the following strategy. Population: JIA patients, aged ≤ 16 years, in clinical remission. Interventions: Clinical assessment plus ultrasound. Comparison: Clinical assessment only. Outcome: Clinical flare. Reviews and case series < 10 patients were excluded. The study is built and reported according to PRISMA guidelines. Results: The search found a total of 208 records. After removing duplicates, 168 articles were selected by title and abstract, and of those 163 were excluded since they did not meet the PICO inclusion criteria. Five articles were identified suitable for analysis. One of these, after reading the full text, lacked detailed data related to US findings at baseline and was therefore excluded. We considered four articles comprising a total of 202 patients with JIA in clinical remission from at least 3 months. Because of the small number of the articles and data heterogeneity meaningful statistical analysis could not be performed. Two of the articles found US subclinical signs of synovitis to be predictive for flare, with a five times higher risk (with Power Doppler signal as an important feature), while in the other two articles baseline US abnormalities could did not predict a clinical flare. The articles differed for protocols, definitions, and length of follow-up. Conclusion: US has an expanding role in pediatric rheumatology. Although its usefulness in the early diagnostic phase may be questionable, a more interesting use could be applied during followup, for the possibility of identifying subclinical inflammatory signs predictive of a future flare. The small number of studies available, data heterogeneity, and conflicting results however do not allow yet any definite conclusions in this regard. The indications of the ETN currently cover the JIA of polyarticular evolution, that is to say the polyarticular, extended oligoarticular forms and the systemic forms become polyarticular, the form associated with enthesopathies and psoriatic arthritis Objectives: To analyze the effectiveness of Etanercept, as well as its tolerance in juvenile idiopathic arthritis (JIA). Methods: We carried out a retrospective study of children diagnosed with JIA according to the ILAR classification criteria and treated with Etanercept at the pediatric center of Setif University Hospital since 2015. 15 children were included and judged at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years on epidemiological criteria, efficacy criteria (Joint scores, uveitis, SV, CHAQ) and the occurrence of possible Side effects . We defined the improvement of 30% (ACR 30), 50% (ACR 50), 70% (ACR 70), 90% (ACR 90), and 100% (ACR 100) as the improvement of minus 3 out of 6 criteria of 30%, 50%, 70%, 90%, 100%; patients must not have an aggravation of more than 30% from one of the 6 criteria. Results: The epidemiological characteristics were as follows: 9 girls and 6 boys, 7 have a polyarticular form, 5 have an oligoarticular form, 2 cases with psoriatic arthritis, and only one case of arthritisassociated enthesitis (ARF). ACR 30 is obtained in 75%, 84%, 88% of cases respectively at 3 months, 6 months, 1 year. The most marked responses were obtained in the polyarticular, oligoarticular and and arthritis-related enthesitis. for psoriatic arthritis = 72%. Complete remission was maintained in the majority of the patients for varying durations depending on the outcomes. Furthermore, no clinical or biological undesirable effects have been noted. Conclusion: Etanercept has a spectacular efficacy in children suffering from juvenile idiopathic arthritis, particularly in polyarticular, oligoarticular forms and IBAs. His overall tolerance is very good.

Disclosure of Interest
None declared

Introduction
There is very limited information and awareness about juvenile idiopathic arthritis (JIA) amongst primary physicians in Gujarat and to make this matter even worse, we are not having a single exclusive pediatric rheumatology center for a population of around 60 million. [1][2][3] Objectives To study characteristics of twenty seven JIA children managed at Dev Children's Hospital. Methods I gathered a data of 27 pediatric patients with confirmed diagnosis of JIA who were seen at Dev Children's Hospital between January 2019 and January 2020. It included demographics, clinical presentation, laboratory results and treatment. All cases were reclassified according to preliminary PRINTO JIA classification. 4

Results Conclusion
Most common JIA sub-type in our cohort is RF positive JIA. Knee is the most common affected joint irrespective of JIA sub-type. Only one patient showed eye involvement. Most of the patients have been given steroids at onset. One patient with RF positive JIA and two patients with systemic JIA have been given intravenous tocilizumab infusion. Anti-inflammatory diet and yoga were advised for almost all patients of more than 5 years of age.  (1) . Objectives: We present a challenging case of Paediatric Mixed Connective Tissue Disease (MCTD) with Sjogren overlap resistant to standard treatment and requiring the addition of Rituximab to control recurrent debilitating parotitis. Methods: We conducted a retrospective case review using electronic patient record.

Results:
A 15 year old female, first presented at the age of 7 with Raynaud's phenomenon and a high ANA 1:5120 was referred from local hospital. Double stranded DNA was negative, ENA typing revealed anti U1-RNP positive. She then developed symptoms of Parotitis and arthritis when oral steroids were commenced. A lower lip biopsy revealed periductal lymphocytic infiltrate admixed with scattered plasma cells. USS of parotid glands showed bilateral chronic sialadenitis in submandibular and parotid glands. Increased vascularity in submandibular glands bilaterally may represent acute on chronic inflammation. She did not have dry mouth, pain with swallowing or dry eyes. Her capillary folds were abnormal. She was commenced on Hydroxychloroquine whilst awaiting Biopsy, which was consistent with Sjogren's syndrome. Methotrexate was added, which soon led to transaminitis and she also continued to have flares and Methotrexate was switched to Azathioprine. This helped with her symptoms but led to Neutropenia. Eventually decision was made to switch to Mycophenolate Mofetil (MMF). Initially MMF helped her with arthritis and energy levels improved but after a year of being on MMF her disease started to flare, requiring oral steroids, and leading to cushingoid facies. Her Lipase was elevated and Amylase was borderline elevated. Due to ongoing disease activity with recurrent and painful parotitis, decision was made to use Rituximab. She gradually recovered from this. Since Rituximab infusion in January 2019 her disease has been continuously in remission and she has recently started to wean MMF down. Conclusion: We report the successful use of rituximab in a difficult to treat patient with Sjogren-MCTD overlap (2) . Rituximab was chosen due to the well-established role of B cell hyperactivity in the immunopathogenesis of primary Sjogren disease (3) . Rituximab has mixed results in the management of primary Sjogren syndrome in adults.
There is no evidence of the use of rituximab in paediatric Sjogren but it was successful at controlling paediatric Sjogren syndrome in our patient and allowed weaning of long-term DMARD.
Introduction: The prognosis for JIA regarding joint destruction and disability has changed significantly during the last two decades due to the emergence of effective anti-inflammatory treatment regimens.
However, approximately 50% of the patients will need ongoing medication far into adult life. The prospect of having a long lasting chronic disease requiring continuing medication, with possible side effects, frequent clinical controls and periods of pain can, by itself, for some patients lead to a passive and inactive lifestyle overshadowing the primary positive effect of the anti-inflammatory medication. In these cases, it can be difficult for the patient (child or adolescent) to resume a normal physically and mentally active lifestyle so important in childhood and youth and of great importance for general health in adulthood.
Recently a Danish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) was published, and we now have an internationally validated tool for assessment of our patients' life circumstances and their personal view of the burden of their disease. Using this tool, in combination with structured clarifying talks between nurse and/or physiotherapist and patient (and parents according to age of the patient) we aim to uncover unmet special needs that we may help to fulfil in the municipal system, in schools, in sports clubs or in other institutions. This structured approach may also by itself help the patient and the family to gain constructive insight in their life situation, with a chronically ill member, and find possible hitherto unknown resources.
Objectives: The purpose of this project is to investigate the effect of a structured multifaceted treatment of juvenile idiopathic arthritis, focusing on lifestyle and physical activity in parallel with antiinflammatory medication. We hypothesize that this strategy will help patients to obtain an early and robust rehabilitation and thus get the full benefits of the effective medicine currently available.
Methods: This is a prospective, non-randomized intervention project. A pilot design is chosen with the purpose of early evaluation of practical circumstances. Inclusion criteria: -Danish speaking patients with JIA, followed in the outpatient clinic at the Pediatric Department at Slagelse Hospital having a low objective clinical disease activity and a high subjective burden of disease according to JAMAR We aim to include 20 patients. Intervention: structured clarifying talks between patient (and parents according to age of the patient) and the caregiving nurse or physiotherapist with the purpose of uncovering unmet needs special needs are sought fulfilled by individual agreements between patients/families and the municipal system, with schools, with sports clubs or with other institutions. The staff in the rheumatology clinic shall be drivers in this process. Endpoints: -Change in JAMAR score at 3 and 6 months after inclusion; the patient will serve as his/her own control. Conclusion: DISCUSSION: The use of intra-muscular or intra-synovial triamcinolone acetate is approved in children from 6 years. There are few cases described that develop a secondary Cushing syndrome. We found a systematic review describing 18 cases of Cushing after infiltrations and injuries in scars. Although there are no clear recommendations regarding its use in paediatrics, we must be cautious, use the lowest effective dose and adequately monitor these patients. Introduction: Some patients with systemic juvenile idiopathic arthritis (sJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected sJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained sJIA remission off-treatment, the procedure-related morbidity was high. Objectives: We try to demonstrate that haplo-identical allogenic HSCT in refractory sJIA can be an alternative treatment for refractory sJIA Methods: We report the case of a child who was successfully treated with haplo-identical allogenic HSCT. Results: A girl presented sJIA since the age of 15 months with a severe disease course. She was refractory to the combination of methotrexate and steroids to anti-interleukin(IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors and thalidomide. Therefore allogenic HSCT was considered. In the absence of any possible HLA matched donor, a multidisciplinary team assessed carefully risks and benefits of an alternative graft. Given the high disease burden and treatment related toxicity the indication for a haploidentical HSCT from her mother was validated. The patient was. treated with intensive immunosuppression and received a T replete bone marrow graft at the age of 3.7 years. Conditioning contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine, as well as Cyclophosphamide at D+3 and +4 post HSCT for GHVD prophylaxis, followed by Cyclosporine A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft versus host disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child was alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, sJIA was in complete remission, off immunosuppressive drugs. Conclusion: Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical donor, in patients with inflammatory diseases such as sJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory diseases.

Disclosure of Interest
None declared

AB036
Analysis of published randomized controlled trials in pediatric patients with rheumatic inflammatory diseases treated with biologics T. Welzel 1,2 , C. Winskill 3 , N. Zhang 3 , A. Woerner 2 , M. Pfister 1,3 coronary aneurisms, with evidence of giant CAAs (LMCA, LAD, RCA z score: 12.7, 15.1, 10.4). The anakinra dosage was increased to 4 mg/ kg/day and anticoagulant therapy with warfarin was started. Echocardiography showed a significant reduction of CAAs (LMCA, LAD, RCA z score: 10.1, 12.29, 7.9) 6 days after, with complete resolution of giant CAA (LMCA, LAD, RCA z score 7.4, 9.4, 7.17) 13 days after. Therapy with sc Anakinra (4 mg/kg/day) was continued for a month, then it was gradually tapered down and completely stopped after 4 months. Follow up is still ongoing but serial echocardiographies confirmed a persistent positive remodelling of all CAAs.
Conclusion: It has been reported that therapy with Anakinra in refractory KD leads to a rapid and sustained improvement in clinical and biological inflammation. However, its effects on the size of CAAs are still unclear. In our patient with refractory KD, subcutaneous Anakinra was quickly effective in controlling the systemic and laboratory inflammatory aspects of the disease and, at a higher dose, led to a rapid and significant reduction of CAAs with complete resolution of giant aneurisms. No side effects were reported. Therefore Anakinra can represent a valuable and safe treatment approach in refractory KD patients, reducing cardiovascular damage. Further studies are needed to reach a standardized treatment protocol to better define the optimal dosage, duration and tapering of Anakinra therapy, facilitating improvement and uniformity of care.