Proceedings of the 32nd European Paediatric Rheumatology Congress

Pediatric Rheumatology, 23(2): O01

Methods: Three patients with refractory JDM received a single infusion of autologous, second-generation anti-CD19 CAR T cells (1×10⁶ CAR T cells/kg; lentiviral vector), manufactured on the CliniMACS Prodigy system. Lymphodepletion was achieved using cyclophosphamide (1000 mg/m² over 2 days) and fludarabine (90 mg/m² over 3 days). B cell immunophenotyping was performed according to standard operating procedures (SOPs) before and after CAR T-cell infusion. A comparator group of five JDM patients treated with rituximab (RTX) was included.

Results: B cell reconstitution occurred at a median of 8 weeks (IQR: 8.0-12.0) post-CAR T therapy, with an immature transitional B cell phenotype. B cell subsets distribution was assessed at a median of 27.3 weeks (IQR: 22.5–40.2) after treatment, when all B cell subsets were present for each patient, and compared to pre-treatment profiles. In the RTX group, B cell phenotyping was performed at a median of 47 weeks (IQR: 33.4–50.7) post-treatment. The proportion of CD19⁺ B cells among lymphocytes was similar before and after CAR T-cell treatment (pre: 32% [IQR: 23–40], post: 21% [IQR: 20–24]). B cell subset analysis showed comparable levels of transitional, naïve and plasmablast populations pre- and post-treatment. However, there was a notable reduction in total memory B cells (MBCs) post-treatment (pre: 6.4% [IQR: 6.3–9.1], post: 3.9% [IQR: 3.1–4.0]), particularly in the switched MBC subset. Interestingly, JDM patients treated with RTX showed higher frequencies of switched MBCs during B cell reconstitution compared to those treated with CAR T cells: CAR T treated-patients 16.0 % [IQR: 8.5-18.0], RTX group 52.0% [IQR: 28.0, 60.0].

None declared

Pediatric Rheumatology, 23(2): O02

Methods: All 3 patients received a single infusion of fresh, autologous second-generation anti-CD19 CAR T product (lentiviral vector) manufactured on the Prodigy device (1x10⁶ CAR T cells/kg), after lymphodepletion with cyclophosphamide (1000 mg/m² over 2 days) and fludarabine (90 mg/m² over 3 days). 

R. Nicolai: None declared, M. Becilli: None declared, E. Marasco: None declared, P. Merli Speaker Bureau with: Miltenyi, Medac, Amgen, C. Bracaglia: None declared, F. Del Bufalo: None declared, M. Petrone: None declared, M. Cefalo: None declared, M. Algeri: None declared, F. De Benedetti Consultant with: Abbvie, Apollo, Elixiron, Kliniksa, Novartis, Roche, Pfizer, Sanofi, SOBI, F. Locatelli Speaker Bureau with: Amgen, bluebird bio, Gilead, Jazz Pharmaceuticals, Medac, Miltenyi, Neovii, Novartis, Sanofi, SOBI

Results: Gene expression analysis revealed 51 upregulated differentially expressed genes in cSLE. Sparse partial least squares discriminant analysis (sPLS-DA) revealed robust separation between cSLE and HC groups, with the strongest upregulation in IFN-I pathways (p<0.0001). Patients clustered into two groups: IFN-High (65%) and IFN-Low (35%), independent of disease activity, as validated by SLE IFN-stimulated gene (ISG) scores (AUC=1.00, p<0.0001). IFN-High patients had reduced lymphocyte counts (p=0.0048). Serum IFNα levels (p=0.0014) and reporter cell responses (p<0.0001) were significantly elevated in the IFN-High group and showed a greater reduction following anifrolumab treatment (p=0.013) compared to IFN-Low patients, supporting stratified therapy. These patterns were absent in HCs and systemic juvenile idiopathic arthritis (sJIA) disease controls, highlighting cSLE specificity. Proteomics identified LAMP3 as the most predictive biomarker for the IFN-High group (AUC=0.95, p<0.0001), validated by ELISA, with longitudinal stability regardless of disease activity across 82 data points. Cellular analysis showed increased BST2 expression in plasmacytoid dendritic cells, CD4+, and CD8+ T-cells, with functional consequences on activation, exhaustion, and abundance, indicating heightened IFN-I sensitivity in these subsets. Clustering multi-level IFN-I data revealed six patient endotypes with unique IFN-I activity and clinical phenotypes, including serum IFNα levels, ISG patterns, cell subset sensitivity to IFN-I, and profiles of disease activity, organ damage, anti-double-stranded DNA antibodies and lymphocyte counts. Thus, the impact of IFN-I signalling exists on a heterogeneous spectrum in cSLE.

None declared

Introduction: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease mainly affecting children and adolescents. It can cause pain, hyperostosis and fractures, affecting patients’ quality of life and psychomotor development. We recently identified rare P2RX7 variants in a large proportion of CNO patients (32.4% versus 4.4% of controls) and demonstrated their functional impact. CNO-associated P2RX7 variants are associated with impaired K⁺ efflux, promoting NLRP3 inflammasome activation and pro-inflammatory cytokine release. Notably, P2RX7 variants also associated with prolonged survival (reduced pyroptosis) of monocyte-derived macrophages.

Objectives: To understand how P2XR7 variants contribute to prolonged cell survival, this project investigated effects of CNO-associated P2RX7 variants on Ca²⁺ mobilisation, reactive oxygen species (ROS) production, mitochondrial integrity, and cytokine expression in THP-1 derived macrophages.

Methods: Genetically modified THP-1 monocytes were differentiated into macrophage-like cells, and used to investigate effects of CNO-associated P2RX7 variants (c.349C>T, rare gain-of-function; c.920G>A rare loss-of-function; c.489C>T common gain-of-function). Activation of the NLRP3 inflammasome (ASC speck assay), K⁺ (ELISA) and Ca²⁺ flux (flow cytometry), expression of pro- and anti-inflammatory cytokines (MSD and Luminex assays), ROS production (2',7'-dichlorofluorescein diacetate/DCFDA and Lucigenin assays) and mitochondrial function (MitoTracker) were studied. Effects of small molecule P2X7 (A-804598) and NLRP3 (MCC950) inhibitors were interrogated.

Results: Compared to cells expressing wild-type P2X7, THP-1-derived macrophages expressing CNO-associated c.349C>T and c.489C>T variants associated with increased K⁺ and sustained Ca²⁺ flux, enhanced inflammasome activation, increased IL-1β and IL-18 secretion, and reduced LDH release (approximating prolonged cell survival). Prolonged survival associated with reduced ROS content for all CNO-associated variants, reduced mitochondrial stress for the c.920G>A loss-of-function variant (superoxide production), and increased numbers of functional mitochondria for the c.349C>T and c.920G>A variants. Co-culture with the P2X7 inhibitor A-804598, across cell lines, resulted in reduced cellular K⁺ and increased Ca2⁺content, reduced inflammasome assembly, ASC speck and cytokine release, and reduced mitochondrial damage. These P2X7 inhibitor mediated effects were greater when compared to co-culture with the NRLP3 inhibitor MCC950.

Conclusion: Imbalanced K⁺ and Ca²⁺ mobilization in THP-1-derived macrophages expressing CNO-associated P2RX7 variants associates with reduced mitochondrial stress and prolonged survival. Understanding the contribution of CNO-associated variation in P2RX7 will promote the development of target-directed treatments.

None declared

Pediatric Rheumatology, 23(2): O06

None declared

A consensus developed by the Boston Children’s Hospital recommends CT evaluation for patients with sJIA showing HLADRB115 positivity, disease onset before age 2, macrophage activation syndrome (MAS) attacks and atypical rashes for sJIA. Tissue typing for HLADRB115 is also recommended for all patients diagnosed with sJIA.

Methods: Exclusion Criteria:

A total of 87 patients were included in the study.

Patients with any of the following risk factors were considered at risk and underwent thoracic CT imaging: diagnosis before age 2, Down syndrome, MAS attacks, subclinical MAS, adverse reactions to biologics, persistent cough, clubbing of fingers, and suspicious lung X-ray findings. The relationship between sJIA-LD, disease activity, HLADRB1*15 positivity and biologic agent usage was also analyzed.

Statistically significant relationships were found between lung disease and early disease onset, asymptomatic inflammation indicative of disease activity, number of MAS attacks, number of subclinical MAS attacks, adverse reactions to biologics, use of canakinumab, and HLADRB1*15 positivity.

Multivariate regression analysis identified the frequency of MAS attacks (p=0.009, OR 95% CI = 6.67 (1.82-19.08)) and subclinical MAS attacks (p=0.005, OR 95% CI = 2.28 (1.5-5.78)) as independent risk factors for lung disease. Although a strong association was found between HLADRB1*15 and sJIA-related lung disease, a direct cause-and-effect relationship could not be demonstrated.

None declared

Pediatric Rheumatology, 23(2):O08

Linear regression didn’t show the relationship between BALF IL-18 level and disease duration (p=0.15); oxygen requirement (p=0.11); dose of Anakinra (p=0.4) or plasma levels of ferritin (p=0.9), CXCL-9 (p=0.6) and IL-18 (p=0.9). There was a direct relation with daily prednisone dose (p=0.03) and number of immunosuppressive medications (p=0.0015).

Analysis of cytokines before and after BMT showed a decrease of IL18 (pre 1182 pg/mL vs post 532.99 pg/mL) and S100A8/9 (pre 10500 pg/mL vs post 3028.5 pg/mL), and no notable changes of MMP7 (pre 17589.36 pg/mL vs post 19808.8 pg/mL) in BALF 6 months after. Similar changes were observed after therapeutic whole lung lavage: level of IL18 fell from 1205 to 477.5 pg/mL.

None declared

Pediatric Rheumatology, 23(2):O09

Results: In total 187 children (119 (64%) girls and 68 (36%) boys) with non-systemic JIA, median (IQR) age 11(6.5) years, were randomized. 92 (49%) patients were allocated to the intervention group and received at least one intra-articular steroid injection, and 95 (50%) to the no-injection group. In the IA steroid injection group, mean number (SD) of joints injected at baseline were 2.7 (2.1), and the total triamcinolone hexacetonide dose 1.2 (1.0) mg/kg. The primary endpoint, the proportion of patients with sustained inactive disease at weeks 24 to 36, was 35% in the intra-articular steroid injection group compared to 33% in the control group (risk difference (RD) 0.02, 95% CI −0.12−0.15, p 0.80). The mean time to JIA-ACR inactive disease during the 48-week follow-up period was 184 days in the steroid injection group and 188 days in the no-injection group (mean difference −4.5 days, 95% CI −37.4, 28.5). JIA-ACR response rates increased in both groups during follow-up. JIA-ACR30 response rate at week 48 was 96% in the injection group and 88% in the no-injection group (RD 0.03, 95% CI −0.01, 0.08, p=0.15). JIA-ACR 50/70/90 response rates at week 48 were 96%/88%/74% in the injection group and 87%/75%/70% in the control group. Betweeen group differences were similar at week 48 for JIA-ACR50, 70 and 90 with RD (95% CI) of 0.03 (−0.01−0.07), 0.08 (−0.01−0.18) and 0.02 (−0.11−0.15), respectively. JIA-ACR core set variables showed no between-group differences at any time point (data not shown). Median (IQR) JADAS71 were 1.5 (2.2) and 2.3 (3.2) in the IA injection group and no-injection group at week 48, respectively (p=0.2). AEs/SAEs occurred in 67%/7% in the injection group and in 75%/8% in the control group. Subcutaneous atrophy occurred in 8 of 288 steroid injected joints (3%).

None declared

Pediatric Rheumatology, 23(2):O10

Results: A total of 127 patients were included. The main reason for switching to a second bDMARD was ineffectiveness, reported in 109 out of 127 patients (86%), with active uveitis accounting for 25 out of those 109 switches (23%). Adalimumab was the most frequently prescribed second-line TNFi (59%). In 25% of cases, a non-TNFi was chosen, with tocilizumab being the most common (66%). The choice of second-line bDMARD was influenced by the calendar year of prescription. Non-TNFi treatments had a median initiation year of 2021 [interquartile range (IQR) 2017–2023], compared to 2019 (IQR 2013–2022) for TNFi treatments (p = 0.03).

Time on the first TNFi did not significantly impact the likelihood of achieving CID during the second TNFi course [odd ratio (OR) 0.98, 95% confidence interval (CI) 0.79–1.21, p = 0.83]. Interestingly, the median duration of the second bDMARD (censored at discontinuation or last follow-up) was significantly longer in the TNFi group compared to the non-TNFi group [2.2 years (IQR 0.7–5.3) vs. 0.8 years (IQR 0.5–3.6); p = 0.02]. In the multivariate GEE model adjusted for propensity score quintiles, switching to a second TNFi rather than a non-TNFi was significantly associated with achieving CID (OR 5.42, 95% CI 1.91–15.40, p < 0.01). Additionally, in the same model, male sex (OR 3.37, 95% CI 1.08–10.49, p = 0.04) and switching due to an adverse event (OR 4.61, 95% CI 1.16–18.31, p = 0.03) were significantly associated with CID. Patients who switched due to active uveitis also showed a higher likelihood of achieving CID compared to those switching for active arthritis (OR 18.38, 95% CI 4.33–78.07, p < 0.01).

None declared

Pediatric Rheumatology, 23(2):O11

Methods: We included newly-diagnosed JIA patients recruited in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry between 2017 and 2024, whose parents provided Kids Disability Screen (KDS) scores for 4 or more visits. The KDS considers the help needed from parents and difficulties for run and play atributted to JIA, and has been validated against the Childhood Health Assessment Questionnaire (CHAQ)¹. Relative to the CHAQ, a KDS=0 means no impairment, >0 to 1.5 mild, >1.5 to 4.0 mild to moderate, and >4 to 10 moderate to severe impairment. Data-driven trajectories were identified with latent class trajectory analysis (LCTA), and classification trees were used to identify predictors of trajectories with persisting functional impairments.

The CAPRI JIA Registry has been funded by grants from The Arthritis Society and the Canadian Institutes of Health Research, Canada.

None declared

Pediatric Rheumatology, 23(2):O12

Results: A total of 315 children were included, median age was 13.0 years (IQR 8.3-15.9), 66% were female and 64% were Caucasian, 36% had polyarticular JIA. The majority (78%) were healthy-weight, 3% were underweight, overweight or obese accounted for 10% and 9%, respectively. Adalimumab (69%) and etanercept (22%) were the most commonly used TNFi. A total of 159 patients (50%) were TNFi responders, and 156 (50%) non-responders. At baseline the responder and non-responder groups had similar ethnicity, JIA ILAR subtypes, disease duration, laboratory findings, disease activity, time to TNFi initiation and type of TNFi received. Importantly, at baseline weight, BMI and BSA were significantly higher in non-responders (p= 0.01, 0.02, 0.01, respectively). In contrast, treatment responders received significantly higher proportion of TNFi dosing at 6 months (p= 0.01). Correlation analysis showed significant negative correlation between baseline total body weight, BMI, and BSA with the proportion of TNFi dosing received (ρ= −0.7,−0.6,−0.7, respectively), and a small but significant negative correlation between percentage change of ACR Pedi core set variables between baseline and 6-month follow-up and proportion of TNFi dosing. These findings were consistent regardless of overweight/obese status, TNFi type, or prior biologic exposure.

None declared

Pediatric Rheumatology, 23(2):O13

None declared

Pediatric Rheumatology, 23(2):O14

None declared

Pediatric Rheumatology, 23(2):O15

Objectives: i) to evaluate the diagnostic accuracy of HPO terms in a cohort of real patients, ii) to evaluate the accuracy of Phenomizer compared to different machine-learning algorithms based on a provided real-life patients’ dataset. iii) to develop a novel diagnostic tool for SAIDs.

Methods: From the Eurofever Registry, 2,866 patients diagnosed with Familial Mediterranean Fever (FMF), Cryopyrin-Associated Periodic Syndrome (CAPS), Mevalonate Kinase Deficiency (MKD), Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), or Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) were included. Eurofever clinical variables were codified with HPO terms, and missing terms were retained. The patients’ dataset was split into training (n=2,005) and test sets (n=861). Four machine learning classifiers were evaluated: Elastic Net regression (EN), k-Nearest Neighbors (kNN), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost), comparing their performance to Phenomizer.

Results: 224 Eurofever variables were codified into HPO terms. Of these, 195 had full HPO correspondence, 12 partial, and 17 no correspondence. XGBoost emerged as the best-performing algorithm in assigning the correct diagnosis to the analyzed patients, achieving an average accuracy of 0.80, and significantly outperforming Phenomizer, even when Phenomizer was trained on Eurofever HPO terms’ frequencies. The addition of the terms "fever duration" and "ethnicity" (present in Eurofever but absent in HPO) improved the algorithm accuracy, highlighting the need for new HPO codes. Finally, based on the best-performing algorithm, a user-friendly web app where clinicians can input HPO terms to receive the probability of each SAID diagnosis (among those used in the training model) was developed.

None declared

Pediatric Rheumatology, 23(2):O16

Introduction: Human ADA2 deficiency (DADA2) is an inborn error of immunity with a broad clinical phenotype encompassing vasculopathy including livedo racemosa and lacunar strokes as well as hemato-immunological manifestations. Combination of decreased serum ADA2 activity and the identification of biallelic deleterious alleles in the ADA2 gene are used for diagnosis. DADA2 carriers harbor a single pathogenic variant in ADA2 and are mostly considered healthy and asymptomatic. However, some DADA2 carriers present a phenotype compatible with DADA2 (1–4).

Objectives: We sought to investigate whether being heterozygote for specific variants in ADA2 could explain the patients DADA2 phenotype.

Methods: A HEK293T cell overexpression system was used to evaluate impact of ADA2 variants on WT ADA2 protein expression/secretion and enzymatic activity. Finngen, UK biobank and the BioMe Biobank were used to assess population genetics and evaluate correlation with DADA2 phenotypes. ADA2 enzyme activity was measured in a colorimetric assay adapted by Giusti et al (1974)

Results: In addition to diseased DADA2 carriers in literature (1–4), we report a cohort of 10 heterozygous carriers of pathogenic ADA2 variants presenting with DADA2 clinical features. To study the potential effect of heterozygous pathogenic variants in ADA2 on WT ADA2 protein expression, secretion and enzymatic activity, we performed transient transfection of each ADA2 variant together with WT ADA2 to mimic carrier status. In vitro study of the ADA2 variants identified in this patient cohort revealed that R169Q, H424N and Y453C affect secretion of WT ADA2 protein. Moreover, we demonstrate a dominant negative effect on the enzymatic activity of WT ADA2 by variants G47A, G47R, G47V, R169Q, E328K, H424N and Y453C both intracellularly and extracellularly. Data from PheWAS show that the heterozygous state for pLOF variants in ADA2 is associated with phenotypes that align with DADA2. When studying the most frequent allele, R169Q, the enriched phenotypes are even more striking, despite the overall low number of cases.

Conclusion: Here, we describe how specific heterozygous variants cause ADA2 deficiency through distinct dominant negative effects on either ADA2 enzyme activity, dimerization and/or secretion. At the molecular level, heterozygosity for these variants mimics what is observed in DADA2. We conclude that humans with heterozygous dominant negative missense variants in ADA2 are at risk of DADA2.

None declared

Pediatric Rheumatology, 23(2):O17

Objectives: This study aims to develop a lipid-substituted polyethyleneimine-based lipopolymer (PEI-C) system for safe and efficient siRNA delivery to immune cells, specifically targeting NLRP3 to suppress inflammatory responses in autoinflammatory disorders.

Methods: We designed three siRNAs targeting murine Nlrp3 and complexed them with PEI-C to formulate lipopolymer nanoparticles (LPNPs). These LPNPs were used to transfect RAW264.7 murine macrophages stimulated with lipopolysaccharide (LPS). 24 hours post-transfection, Nlrp3 gene expression and IL-1β secretion were quantified using RT-qPCR and ELISA, respectively. The most effective siRNA sequence (siNlrp3-3) was further tested in vivo using an LPS-induced inflammation mouse model. IL-1β levels were measured in the spleen, liver, lung, kidney, heart, and bone marrow 24 hours post-treatment. In addition, ex vivo studies were conducted using LPS-stimulated PBMCs from healthy human donors transfected with LPNPs containing a human-specific siNLRP3.

Results: In vitro, siNlrp3 LPNPs effectively silenced Nlrp3 expression in LPS-stimulated RAW264.7 cells, resulting in a marked reduction in IL-1β secretion compared to scrambled control (CsiRNA) LPNPs. Among the three tested sequences (siNlrp3-1, siNlrp3-2, and siNlrp3-3), siNlrp3-3 outperformed the other 2 sequences. Based on this outcome, siNlrp3-3 LPNPs were evaluated in an LPS-induced inflammatory mouse model (n=5), where IL-1β levels were measured 24 hours post-treatment in different tissues, including spleen, liver, lung, kidney, heart, and bone marrow. Reductions of IL-1β levels were observed in the liver and bone marrow, with significant decreases in the spleen (p=0.0086) and lung (p=0.0030). To assess translational relevance, siNLRP3 LPNPs were tested ex vivo in LPS-stimulated human PBMCs (n=15), leading to a significant reduction in IL-1β secretion compared to CsiRNA LPNPs (p=0.0107).

Conclusion: Our study demonstrates that PEI-C–based LPNPs offer a robust, non-viral delivery system for siRNA-mediated silencing of NLRP3, leading to effective suppression of IL-1β in murine and human immune models, highlighting the therapeutic potential of siRNA nanomedicine in autoinflammatory diseases, especially where conventional therapies fall short.

M. Nasrullah: None declared, A. P. Rajendran: None declared, B. Bulut: None declared, M. Romano: None declared, L. Piskin: None declared, S. Suresh: None declared, M. Osman: None declared, H. Ostergaard: None declared, E. Demirkaya: None declared, H. Uludağ Shareholder with: The lipopolymer, PEI-C, is being commercialized with a different brand name via a U. of Alberta spin-off company, RJH Biosciences Inc. (Edmonton, AB). H.U. has ownership of patents on the indicated lipopolymers and own shares in RJH Biosciences Inc.

Pediatric Rheumatology, 23(2): O18

Introduction: MAS is a life-threatening complication of Still’s disease, characterized by interferon-gamma (IFNg)-driven macrophage activation and systemic hyperinflammation. Emapalumab binds free and receptor-bound IFNg, providing rapid and targeted neutralization of IFNg. Emapalumab achieved rapid control of MAS in a pooled patient population from two single-arm interventional studies (NI-0501-06¹ and NI-0501-14 [EMERALD]).

S. Vastert Grant/Research Support with: Sobi, Consultant with: Sobi, Novartis, Speaker Bureau with: Sobi, Novartis, J. Antón Grant/Research Support with: Sobi, Speaker Bureau with: Sobi, P. Quartier: None declared, B. Fautrel Grant/Research Support with: AbbVie, Eli Lilly & Co, MSD, Pfizer, Consultant with: AbbVie, Alternative, Biogen, BMS, Celgene, Celltrion, Chugai, Eli Lilly & Co, Fresenius Kabi, Galapagos, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche, Room, Sandoz, Sanogi-Genzyme, UCB, P. Brogan Speaker Bureau with: Sobi, E. Behrens Grant/Research Support with: Sobi, Consultant with: Sobi, Ab2Bio, M. Elder: None declared, F. Minoia Consultant with: Sobi, Novartis, Speaker Bureau with: Sobi, Novartis, P. Dolezalova Speaker Bureau with: Sobi, Novartis, Pfizer, Medac, R. Biesen: None declared, M. Shimizu Grant/Research Support with: Medical and Biological Laboratories Co., Ltd, U. Ullmann Consultant with: Sobi, A. Mahmood Consultant with: Sobi, A. Danquah Employee with: Sobi, E. Burillo Employee with: Sobi, M. Petrimpol Employee with: Sobi, S. Mallett Consultant with: Sobi, B. Jamieson Employee with: Sobi Inc., A. Grom Grant/Research Support with: National Institutes of Health, Novartis, SJIA FOundation, Sobi, Consultant with: Kiniksa, Novartis, Sobi, F. De Benedetti Grant/Research Support with: Abbvie, Apollo, Elixiron, Kiniska, Novartis, Sanofi, Sobi, Consultant with: Abbvie, Apollo, Elixiron, Kiniska, Novartis, Sanofi, Sobi

Pediatric Rheumatology, 23(2):O19

None declared

Pediatric Rheumatology, 23(2):O20

Results: Among the 61 patients who received IL-1 inhibitors, we identified 34 responders and 27 non-responders. A higher baseline physician global score was observed in non-responders (mean 7.2 vs 5.5; p = 0.006). Responders trended towards a higher neutrophil count at baseline, but this was not significant (mean 11,560 cells/µL vs 9,160; p= 0.09). There were no significant differences in the baseline joint count, arthritis joint count at one month, or in days to initiation of therapy between responders and non-responders. There were 30 total patients who received IL-1 inhibitors with existing baseline biosamples; of these, 17 were responders and 13 were non-responders. At baseline, median IL-18 levels were higher in non-responders (46,823 pg/mL; range 4,612-157,713) vs responders (23,435; range 1,485- 150,479), but this difference was not significant (p=0.65). Luminex data revealed decreased baseline CCL25 (p=0.019) and MCP-1 (p=0.05) levels in non-responders when compared to responders. Finally, we performed blood transcriptional profiling using Nanostring. A 29 gene score previously associated with response to canakinumab showed no significant difference between responders and non-responders. However, baseline gene expression levels of genes associated with canakinumab non-response - STAB1, CD163, and VCAN – were significantly higher in non-responders compared to responders. A composite geomean score of these three genes >545 yielded 78% sensitivity and 93% specificity for IL-1 inhibitor non-response. 

Conclusion: In the FROST cohort, non-responders to IL-1 inhibitors by CID or LDA had higher baseline physician global scores and significantly decreased CCL25 and MCP-1 levels compared to responders. We also validated a previously described IL-1 non-response gene expression signature of STAB1, CD163, and VCAN. These findings support the hypothesis that subgroups of sJIA patients with different immunologic phenotypes exist, and that immune phenotyping could assist in predicting IL-1 inhibitor non-response.

M. Matt: None declared, M. Marques: None declared, L. Auld: None declared, G. Tomlinson: None declared, Y. Kimura: None declared, M. Ombrello: None declared, G. Schulert Grant/Research Support with: IpiNovyx, Consultant with: Novartis and Sobi

Pediatric Rheumatology, 23(2):O21

None declared

Pediatric Rheumatology, 23(2): O22

None declared

Pediatric Rheumatology, 23(2): O23

Results: We conducted 3 focus groups with the help of one of our child representatives from the Steering Group who co-led the sessions. In total 10 children (aged 8-13 (M = 10.51, SD = 1.60); 58.33% were female), with a range of different rheumatological conditions (JIA (N=5), JDM (N=2) and other conditions such as Behcet’s, fever syndromes, CRMO, and Scleroderma (N=5)) participated in the sessions. They discussed challenges and implications in relation to having a health condition, especially around taking medicines, and sometimes not understanding side effects. Most prominently, children were very encouraging and provided hints and tips on how to support their ‘friend’ when it comes to blood tests, taking medicines, and doing regular exercises. They explored advantages of telling their friends, and how informing school is important to get extra help where needed. The children voiced how they really enjoyed the opportunity to meet others during the focus groups, and some even swapped contact details to stay in touch.

None declared

Pediatric Rheumatology, 23(2): O24

None declared

Pediatric Rheumatology, 23(2): O25

Methods: Muscle biopsies from three JDM patients recruited from the JDCBS and three age-matched controls were analyzed using the Nanostring GeoMx Digital Spatial Profiler. Regions of interest (ROIs) included muscle fibres, immune-infiltrated muscle, and CD68+ macrophage-enriched regions. Differential gene expression, pathway enrichment, and pathway clustering analyses were performed. Findings were validated in a bulk RNA-sequencing dataset (JDM n=4; controls n=5; PMID: 34997119) and a cohort of 19 JDM cases from the JDCBS using immunohistochemistry (IHC) for myxovirus-resistant-protein A (MxA, an IFN-driven protein marker) and histochemistry (HC) with COX-SDH staining (indicating mitochondrial deficiency).

Results: Spatial transcriptomics identified 448 differentially expressed genes (|LogFC|>1.5, FDR <0.05) between JDM and control muscle regions, with pathway analysis revealing concurrent IFN pathway activation and mitochondrial dysfunction. To quantify these patterns across ROI types, two gene expression scores were calculated: a 15-gene IFN score was elevated across all JDM regions (Kruskal-Wallis p=0.0034), while a 41-gene mitochondrial score showed significant suppression of genes associated with mitochondrial function (ANOVA p<0.0001), most marked in CD68+ macrophages. These mitochondrial abnormalities were confirmed in bulk RNA-sequencing from 5 additional JDM cases, demonstrating consistent suppression of oxidative phosphorylation pathways, linked to both nuclear-encoded and mitochondrial-encoded gene transcription. Critically, IFN and mitochondrial signatures were clinically distinct: mitochondrial dysfunction was evident even in patients with minimal weakness or lower IFN activity. This was further validated in 19 JDM cases, where IHC demonstrated no association between MxA and COX-SDH scores (U-statistic permutation test, p=0.657), reinforcing that mitochondrial defects could occur independently of IFN-associated inflammation. Importantly, higher MxA expression was associated with more severe muscle symptoms, while mitochondrial deficiency showed no such association.

A. Syntakas: None declared, M. Kartawinata: None declared, H. Nguyen: None declared, C. Papadopoulou: None declared, M. Al-Obaidi: None declared, C. Pilkington: None declared, Y. Glackin: None declared, C. Mahony: None declared, A. Croft: None declared, S. Eaton: None declared, M. Cortina-Borja: None declared, N. Evans: None declared, A. White: None declared, M. Mshanga: None declared, M. Mshanga: None declared, O. Ogunbiyi: None declared, A. Merve: None declared, L. Wedderburn Grant/Research Support with: Pfizer, Consultant with: Pfizer and Cabaletta, M. Wilkinson: None declared

Pediatric Rheumatology, 23(2): O26

The task force devised 33 statements including 4 overarching principles. Major themes endorse the importance of acknowledging that pediatric Behcet disease can be a challenging diagnosis, as symptoms emerge gradually over time. It's crucial to consider genetic or genomic conditions in the differential diagnosis, especially for patients with early-onset or family history of Behcet-like disease. In these cases, evaluation should include genetic testing using NGS-based autoinflammatory gene panels or WES or WGS as well as screening (immune-phenotyping) for immune dysregulation, and disease-associated comorbidities. Monoclonal Anti TNFs should be used as a first-line biologic treatment for patients with severe major organ such as ocular, neuro, vascular and GI involvement. Close monitoring for disease progression and complications is essential as well as the access to specialized, multidisciplinary care at referral centers.

None declared

Pediatric Rheumatology, 23(2): O27

None declared

Pediatric Rheumatology, 23(2): PT001

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Pediatric Rheumatology, 23(2): PT002

None declared

Pediatric Rheumatology, 23(2): PT003

Construct validity of JADAS and its components (joint counts, physician, and patient global assessment) were evaluated through Spearman’s rank correlation and Cohen’s weighted kappa with adult measures of disease activity (DAS28/SDAI/CDAI). Convergent validity of the JADAS with Health Assessment Questionnaire (HAQ) scores was tested using Spearman’s rank correlation. Criterion and discriminant validity were assessed through the sensitivity and specificity of the JADAS at detecting clinically inactive disease between versus adult constructs, respectively. Differences in optimal JADAS cut-offs relating to i) the achievement/non-achievement of DAS28 EULAR response criteria and ii) clinically important differences in HAQ scores between two clinical visits were assessed via ROC curve analysis.

High construct validity of the JADAS10 was demonstrated, particularly against the SDAI (correlation coefficient: 0.95; kappa: 0.72 (0.70-0.74) and CDAI (correlation coefficient: 0.96; kappa: 0.72 (0.70-0.74). Correlation between JADAS10 and DAS28 was lower (correlation coefficient: 0.69; kappa: 0.51 (95% CI 0.48-0.54). Similar correlations were seen for JADAS27 and JADAS71.

High convergent validity of the JADAS10 and HAQ was observed (correlation coefficient: 0.64), with clinical significant differences in JADAS 10 scores between those with low/mild disability (JADAS10 cut-off: < 2.95), moderate disability (JADAS10 cut-off: 2.95-4.85) and high disability (JADAS10 cut-off: >4.85).

High criterion validity of the JADAS10 was demonstrated, with sensitivities of detecting clinically inactive disease according to the CDAI at 88%, SDAI at 86%, and lower with the DAS28 at 64%. High discriminant ability was also demonstrated with specificities of excluding clinically inactive disease according to the CDAI at 97%, SDAI at 97% and DAS28 at 96%.

The JADAS10 had moderate to high classification ability at detecting DAS28 EULAR response between two-time points, with a change of 1.9 for moderate response and 4.3 for good response. The results were similar for all JADAS versions. AUC values were 0.73 for detecting moderate DAS28 EULAR response, and 0.74 for good response.

None declared

Pediatric Rheumatology, 23(2): PT004

Clinical features used for ILAR JPsA classification were clustered: an active joint count and the presence or absence of psoriasis, dactylitis and nail abnormalities. We tested two methods of including CYP (those with a JPsA diagnosis vs. those with JPsA, ERA or undifferentiated JIA who fulfilled ILAR JPsA criteria) and two timeframes for accumulation of clinical features (within one vs. two years of disease onset). Latent class analysis was used to identify one to ten clusters, with optimal models selected based on statistical fit (AIC, BIC), entropy and likelihood ratio testing. Differences in outcomes between clusters were tested via Chi-squared, Mann-Whitney U-tests and Kruskall-Wallis tests.

None declared

Pediatric Rheumatology, 23(2): PT005

Introduction: Psoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar traits that differ by age of onset.¹ PsA and psoriasis (PsO) share comparable pathology and clinical features in children and adults. While interleukin (IL)−23 is a key cytokine in PsA and PsO pathophysiology, no approved pediatric treatment selectively targets IL-23 signaling. Guselkumab (GUS), a fully human IL-23p19-subunit inhibitor, was shown safe and effective in adult PsO and PsA in the phase 3 VOYAGE (V)1/2 and DISCOVER (D)1/2 trials, respectively, with consistent clinical benefits and safety in pediatric PsO in the phase 3 PROTOSTAR study.

Objectives: As jPsA is rare and shares similarities with adult PsO and PsA, extrapolation based on similarity of GUS systemic exposure and clinical response across Phase 3 populations of children with PsO, adults with PsO, and adults with PsA was used to establish GUS efficacy and safety in jPsA. This FDA-endorsed² extrapolation method was previously applied to support the use of ustekinumab in jPsA.³

H. Crauwels Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, S. Ringold Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, S. Howard Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, B. Van Hartingsveldt Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, V. Smith Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, M. Jett Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, T. Baguet Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, E. Adamson Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, S. Chakravarty Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson, J. Leu Shareholder with: Johnson & Johnson, Employee with: Johnson & Johnson

Pediatric Rheumatology, 23(2): PT006

At week 12, 171 of the 176 patients had measurements of both s-adalimumab and number of active joints, and median (IQR) s-adalimumab was 14.3 mg/L (9.5-17.8). 57/171 (33%) patients had >1active joint, 114/171 (67%) had no active joints. In patients with >1 active joint median s-adalimumab was 12.1 mg/L (IQR 7.6-16.0) and in patients with no active joints s-adalimumab was 15.1 mg/L (IQR 10.1-19.5) (p=0.01).

At week 48, 153 of the 176 patients who started adalimumab at baseline had measurements of both s-adalimumab and number of active joints, and median (IQR) s-adalimumab was 14.9 mg/L (10.1-20). 20/153 (13%) patients had >1 active joint, 133/153 (87%) had no active joints. In patients with >1 active joint median s-adalimumab was 12.9 mg/L (IQR 7.7-17.4) and in patients with no active joints s-adalimumab was 15.5 mg/L (IQR 10.7-20.6) (p=0.14).

None declared

Pediatric Rheumatology, 23(2): PT007

Introduction: A 156-week (W), open-label, 2 part study (12W core and 144 W extended)¹ evaluated the efficacy and safety of sarilumab [3/4mg/kg every 2 weeks] in two weight groups (Group A/B: body weight ≥30kg/≥10kg–<30kg) of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).

Methods: This 156 W study assessed the efficacy and safety of sarilumab in patients with pcJIA aged 2-17 years, who received the selected dose identified after core phase of part 1.¹ Efficacy was evaluated by improvements in specified disease activity levels at W48, 96 and 156. Safety was assessed by reported adverse events (AEs) for up to 3 years.

Results: Ninety-three patients received ≥1 dose of the selected dose (primary safety population) during the 156 W study phase. The primary efficacy population (73 patients who received the selected dose from baseline [BL]) had mostly RF-negative pJIA (48/73 [65.8%]), a high cJADAS-10 (mean±SD: 20.1±4.1) and CHAQ-DI (mean±SD: 1.24±0.66). At BL, 14/73 (19.2%) had ≥1 prior bDMARD, 62/73 (84.9%) were receiving csDMARD, and 10/73 (13.7%) systemic glucocorticoid (GC). Improvements in specified disease activity levels as assessed by cJADAS-10≤2.5 (W48/96/156: 70.3%/72.9%/81.8%), clinically inactive disease (CID) per Wallace criteria¹ (W48/96/156: 70.3%/78.9%/84.4%), CID per Wallace criteria with no GC use (W48/96/156: 60.9%/70.2%/78.1%), and clinical remission [inactive disease per Wallace criteria ≥6 consecutive months] (W48/96/156: 51.6%/64.6%/77.4%) were observed in patients with available measurement at each visit. Functional ability of patients, as assessed by the CHAQ-DI score, improved with a mean change of −0.96, −1.01, and −1.13 from BL to W48, W96, and W156 respectively. Treatment-emergent AEs (TEAEs) were reported in 89/93 (95.7%) patients with any exposure to the selected dose. Among these, 6/93 (6.5%) patients had ≥1 serious TEAE (core-treatment phase: 1 patient; W12 to W52: 3 patients; after W52: 2 patients). All serious TEAEs were unrelated to the study drug. In patients with grade 3/4 neutropenia (35/41, 85.4%), the incidence of infections was comparable to those without grade 3/4 neutropenia (50/60, 83.3%) following exposure to any sarilumab dose (N=101).

F. De Benedetti Grant/Research Support with: AbbVie, Novartis, Novimmune, Pfizer, Roche, Sanofi, SOBI, and UCB, Consultant with: Novartis, Roche, and SOBI, I. Penadés Grant/Research Support with: AbbVie, Bristol-Myers Squibb, Clementia, MSD, Novartis, Pfizer, Roche, and Sanofi, Speaker Bureau with: AbbVie, Novartis, Roche, and SOBI, Advisory Boards with: AbbVie and Novartis, I. Nikishina Speaker Bureau with: AbbVie, Ipsen, Janssen, Novartis, Pfizer, and R-Pharm, I. Foeldvari Speaker Bureau with: Boehringer, Lilly, Mitsubishi, Advisor with: Boehringer, Lilly, Mitsubishi, A. Spindler Speaker Bureau with: Eli Lilly, A. Kozlova: None declared, N. Rubio-Pérez Speaker Bureau with: AbbVie and Roche, P. Quartier Consultant with: AbbVie, Chugai-Roche, Lilly, Novartis, Novimmune, Sanofi (also member of a data safety monitoring board), and SOBI, Speaker Bureau with: AbbVie, Bristol-Myers Squibb, Chugai-Roche, Novartis, Pfizer, and SOBI, Z. Żuber: None declared, R. Barria Consultant with: Tecnofarma, Speaker Bureau with: Pfizer and Roche, D. Clemente Speaker Bureau with: Novartis and Roche, G. Cornejo Grant/Research Support with: Bristol-Myers Squibb, Parexel, and Sanofi, K. Marzan Grant/Research Support with: Novartis, Pfizer, and Sanofi, N. Liu Shareholder with: Sanofi, Employee with: Sanofi, J. Msihid Shareholder with: Sanofi, Employee with: Sanofi, L. Araujo Shareholder with: Sanofi, Employee with: Sanofi, V. Batarilo Shareholder with: IQVIA (supporting current analysis for Sanofi), Employee with: IQVIA (supporting current analysis for Sanofi), S. DiMartino Shareholder with: Regeneron, Employee with: Regeneron, B. Akinlade Shareholder with: Regeneron, Employee with: Regeneron, L. Baret-Cormel Shareholder with: Sanofi, Employee with: Sanofi

Pediatric Rheumatology, 23(2): PT008

Results: In total, 186 families participated in the study. Children and caregivers used effective pain coping strategies more often than catastrophizing. Discordance between the patient or parent and physician global assessment of less than +/−10 mm was seen in 51% of the children and 52% of the parents. When a discordance of more than +/−10 mm was seen, it was mainly positive, i.e. the patients' and parents' perception of the disease state was higher than the physician's. A global assessment discordance of +/- 30 mm or greater was seen in 17% of the children and 11% of the parents. In the patients, the lower the active joint count (AJC) (p=0.006) and the higher the pain assessment (p<0.001), the greater the discordance between patient and physician global assessment. In parents, the lower the AJC (p<0.001) and the higher the parent proxy pain assessment (p<0.001) and catastrophizing score (p=0.005), the greater the discordance between parent and physician global assessment.

None declared

Pediatric Rheumatology, 23(2): PT009

None declared

Pediatric Rheumatology, 23(2): PT010

The model was developed using multivariate logistic regression with bootstrap resampling and the Lasso (Least Absolute Shrinkage and Selection Operator) method for variable selection.

None declared

Pediatric Rheumatology, 23(2): PT011

Results: The median IL-18 level at onset was 59.215 pg/ml (IQR 14.261–630.037). MAS was present in 23 (35%) patients at disease onset. Sixty-one patients were treated with anakinra and 3 with canakinumab. IL-18 levels significantly decreased during treatment (median pg/ml: T0 59.215; T3 1.984; T6 1.100; T12 788). However, patients with active disease (AD) had consistently higher IL-18 levels than those in clinical inactive disease (CID) at all time points. Patients with AD at 12 months had significantly higher IL-18 levels at baseline compared to those who achieved CID. IL-18 levels >45.000 pg/ml at onset predicted AD at 12 months with an area under the curve (AUC) of 78% (Se 91%, Sp 53%, p=0,001). Regarding disease course, 54% patients had a monocyclic, 26% a polycyclic, and 20% a chronic-persistent course. After treatment initiation, IL-18 levels significantly decreased in mono-/poly-cyclic course patients, but remained stable over-time in those with a chronic-persistent course. IL-18 levels >45.000 pg/ml at disease onset predicted a chronic-persistent course (AUC 72%, p=0,01, Se 91% Sp 56%). Furthermore, IL-18 levels >15,000 pg/ml at three months (T3) more accurately predicted a persistent course, yielding an AUC of 91% (p<0.0001; se 90%, sp89%). Additionally, elevated IL-18 levels at baseline were strongly associated with MAS development (AUC 81%, p=0.004, Se 100%, Sp 77%).

None declared

Pediatric Rheumatology, 23(2): PT012

None declared

Results: SD joints contained a dominant population of clonally expanded CD4⁺ T cells with a Tph phenotype, characterized by high IL-21 and CXCL13 expression and potent B cell helper activity. Single-cell transcriptomics revealed a diverse CD4⁺ T cell compartment, with a striking convergence of Tph and regulatory T cell gene programs, particularly in SD. A subset of these cells showed transcriptional hallmarks consistent with differentiation from Tph precursors. In vitro, IL-1β and IL-18 compensated for limited CD28 co-stimulation signals to induce proliferation and synergistically with IFN-α promoted upregulation of effector Tph gene signatures. These in vitro derived IL-1β- or IL-18-induced gene signatures were enriched in Tph cells within the SD SF scRNA-seq dataset.

J. Dirks: None declared, J. Fischer: None declared, L. Harrer: None declared, C. Bracaglia Consultant with: SOBI and Novartis, Speaker Bureau with: GSK, G. Prencipe: None declared, M. Pardeo Consultant with: SOBI and Novartis, A. Holl-Wieden: None declared, H. Girschick: None declared, C. Kessel: None declared, H. Morbach Speaker Bureau with: Novartis

Pediatric Rheumatology, 23(2): PT014

Introduction: The outcome of Still’s disease (SD) has significantly improved in the past 15 years due to new therapeutic options¹, treatment strategies based on early biologic initiation (window of opportunity)^2,3 and a treat-to-target approach⁴. Nonetheless, a substantial proportion of patients still experiences a refractory course, severely impacting their quality of life. Recent reports have also highlighted an increasing occurrence of severe SD-associated lung disease (SD-LD)⁵. Treatment strategies in these cases are not standardized and are affected by medication availability and clinician experience.

Results: A total of 206 physicians completed the survey, predominantly pediatric rheumatologists (91%), from 56 countries. Methotrexate was the most common 1^st-line choice for SD-refractory arthritis, followed by anti-TNF agents and intra-articular steroids. JAK inhibitors (JAK-i) were considered mainly as 2^nd- or 3^rd-line option. If systemic symptoms co-occurred, 62% of respondents would modify their strategy, favoring methylprednisolone (MPN) pulses, JAK-i and ciclosporin. In SD patients with recurrent/refractory MAS, ciclosporin, anakinra, and MPN pulses were the most frequently selected medications. Treatment decisions were mainly guided by clinical severity, inflammatory markers, history of ICU admission and concomitant complications. Biomarkers played a minor role, partly due to limited access, reported by 22% of clinicians. For SD-LD, 41% would continue ongoing biologics, 30% withdraw and 29% decide case by case. Factors influencing withdrawal included persistent disease activity, history of adverse reactions and impending MAS. HLA genotyping was rarely considered relevant. The most used 1^st-line agents for SD-LD included JAK-i, mycophenolate mofetil, and ciclosporin and only 8% would add Pneumocystis Jiroveci prophylaxis. Most respondents (82%) would consider Hematopoietic Stem-Cell Transplantation (HSCT) in difficult-to-treat SD patients, particularly for refractory MAS or SD-LD.

G. Rogani: None declared, F. Baldo: None declared, C. Bracaglia: None declared, D. Foell: None declared, M. Gattorno Grant/Research Support with: Novartis, Consultant with: Novartis, SOBI, Speaker Bureau with: Fresenius Kabi SwissBioSim GmbH, Novartis, SOBI, M. Jelusic: None declared, J. Anton: None declared, P. Brogan Speaker Bureau with: SOBI, S. W. Canna Grant/Research Support with: Simcha Therapeutics, Consultant with: AB2Bio; Bristol-Myers Squibb(BMS); Novartis, Speaker Bureau with: SOBI, R. Q. Cron Grant/Research Support with: Sobi, Consultant with: AbbVie/Abbott; American Board of Pediatrics; AS2 Biotherapeutics; CareerPhysician; Neurogene; Pfizer; Sobi; VIDA Ventures, F. De Benedetti Grant/Research Support with: AbbVie; Apollo; Elixiron; Kiniksa; Novartis; Sanofi; Sobi, Consultant with: AbbVie; Apollo; Elixiron; Kiniksa; Novartis; Sanofi; Sobi, A. Grom Grant/Research Support with: Novartis; Sobi, Consultant with: Novartis; Sobi, M. Heshin Bekenstein: None declared, A. Horne: None declared, R. Khubchandani: None declared, M. Mizuta: None declared, S. Ozen Speaker Bureau with: Novartis, Pfizer, Sobi, P. Quartier Dit Maire Grant/Research Support with: Amgen; Bristol-Myers Squibb(BMS); Lilly; Novartis; Pfizer; Sanofi; Sobi, Consultant with: AbbVie/Abbott; Amgen; Bristol-Myers Squibb(BMS); Lilly; Novartis; Pfizer; Sanofi; Sobi, Speaker Bureau with: Chugai-Roche; Novartis; Pfizer, A. Ravelli Grant/Research Support with: AbbVie; Alexion; Bristol-Myers Squibb(BMS); Galapagos; Johnson & Johnson, Novartis; Pfizer; Roche; SOBI, Consultant with: AbbVie; Alexion; Bristol-Myers Squibb(BMS); Galapagos; Johnson & Johnson, Novartis; Pfizer; Roche; SOBI, Speaker Bureau with: AbbVie; Alexion; Bristol-Myers Squibb(BMS); Galapagos; Johnson & Johnson, Novartis; Pfizer; Roche; SOBI, M. Shimizu: None declared, G. Schulert Grant/Research Support with: IpiNovoyx, Consultant with: Novartis; SOBI, C. Scott: None declared, R. Sihna: None declared, N. Ruperto Consultant with: Abbvie; AClaris; AlfaSigma; Amgen; AstraZeneca; Aurinia; Boehringer-Ingelheim; Bristol Myers and Squibb; Eli Lilly; Galapagos; Genentech; Guidepoint; Idorsia; Janssen; Novartis; Pfizer; Roche; Sanofi; Takeda, Speaker Bureau with: Abbvie; AClaris; AlfaSigma; Amgen; AstraZeneca; Aurinia; Boehringer-Ingelheim; Bristol Myers and Squibb; Eli Lilly; Galapagos; Genentech; Guidepoint; Idorsia; Janssen; Novartis; Pfizer; Roche; Sanofi; Takeda, J. Swart: None declared, B. Fautrel Grant/Research Support with: AbbVie; Eli Lilly&Co.; MSD; Pfizer, Consultant with: AbbVie; Amgen; Biogen; BMS; Celltrion; Chugai; Eli Lilly&Co.; Fresenius Kabi; Galapagos; Janssen; Medac; MSD; Nordic Pharma; Novartis; OW KIN; Pfizer; Roche; Sandoz; Sanofi-Genzyme; SOBI; UCB; Viatris, S. Vastert Grant/Research Support with: SOBI, Consultant with: Novartis; SOBI, Speaker Bureau with: Novartis; SOBI, F. Minoia: None declared

Pediatric Rheumatology, 23(2): PT015

Results: Flow cytometry analysis of SJIA neutrophils showed variable levels of more immature CD10- neutrophils, but with increased abundance in association with flares. Immature neutrophils, and in particular CD10-CD16- neutrophils, were highly enriched in the LDG population compared to the NDG population. To examine the transcriptional diversity of these populations, we captured paired LDG and NDG populations from 3 patients with SJIA, compared to total neutrophils from 2 healthy control children. We sequenced 34,442 NDG, 25,979 LDG, and 10,200 control neutrophils. Integrated analysis revealed 24 transcriptionally distinct clusters, which contained cells from each sample; there were no patient-specific or LDG-specific clusters. Both NDG and LDG showed increased abundance of more transcriptionally active clusters (3, 17) with high NEAT1 expression, as well as interferon-stimulated gene (ISG) high expressing cluster 1. Patient LDG samples showed an increased abundance of more immature neutrophil clusters 21 and 24, including PADI4 expression associated with NETosis. Performing pathway analysis on LDG to NDG transcriptomes, we found significant enrichment in pathways in innate immune response (z-score 16.7, adjusted p=3.75e-7) and antibacterial humoral response (z-score 59.8, adjusted p=2.49e-4), with differentially expressed genes including CD177, DEF4A, PADI4, and S100A12.

None declared

Pediatric Rheumatology, 23(2): PT016

Results: RNA expression of classical complement protein C1q is upregulated in both whole blood and isolated CD14+ monocytes from active SD patients compared to those with inactive disease (NanoString: C1QB 43 vs. 11, p<0.01; C1QC 24 vs. 6, p<0.01; Monocytes: C1QB log₂FC 3.6, p<0.01; C1QC log₂FC 3.9, p<0.01) and to active non-systemic JIA patients (C1QB 43 vs 15, p<0.01; C1QC 24 vs 8, p<0.01). Moreover, whole blood C1QB and C1QC expression levels positively correlate with the IFN-score (r=0.34, p=0.01), plasma levels of IL18 (r=0.5, p<0.01) and IFN related chemokines CXCL9 (r=0.4, p<0.01) and CXCL10 (r=0.6, p<0.01) in SD. Protein analysis revealed elevated levels of C1q, C3a, and C5a, as well as enhanced classical complement activity in active SD compared to inactive SD (94% vs 74%, p<0.01) and active non-systemic JIA patients (94% vs 81%, p=0.02). Furthermore, in vitro stimulation of healthy control monocytes with IFNγ robustly and specifically induces C1q mRNA expression. Flow cytometry analysis confirmed that IFNγ stimulation promotes the emergence of a distinct monocyte subset characterized by high C1q expression.

F. Huijsmans: None declared, A. Bodelón de Frutos: None declared, L. Sijbers: None declared, S. Benseler: None declared, J. Swart: None declared, R. Yeung: None declared, B. Vastert Grant/Research Support with: SOBI, Consultant with: Novartis and SOBI, J. van Loosdregt: None declared

Pediatric Rheumatology, 23(2): PT017

None declared

Pediatric Rheumatology, 23(2): PT019

None declared

Pediatric Rheumatology, 23(2): PT020

Objectives: In the present study, we investigated whether and how the inflammatory environment in SD versus JIA synovial fluid (SF) may differentially impact T helper (Th) cell polarization and activation.

Results: Both SD and JIA SF represents a highly pro-inflammatory environment. Compared to JIA, SD SF was hallmarked by significant overexpression of IL-1β, IL-18, GM-CSF, S100A9 and MPO. Soluble FasL and IL-17A were elevated by trend in JIA SF. SD SF selectively induced significant elevation of CD4 T cellular ICOS expression and CXCR3^posCCR6^pos Th cell expansion, while JIA SF increased CXCR3^negCCR6^pos Th cell numbers. CCR6^pos Th cell expansion was sensitive to IL-1 blocking treatment in in vitro experiments. Furthermore, SD SF selectively supported the prevalence of recombinant cytokine induced (Th1-like) T follicular/peripheral Th (Tf/ph) phenotypes. These phenotypic data were supported by cytokine and transcription factor expression profiles assessed at protein and gene expression level. Tf/ph prevalence upon exposure to SD SF was associated with several inflammatory mediator levels in SF, but IL-1β, IL-18 and GM-CSF, in particular. Spiking JIA SF with a cocktail of these cytokines recapitulated some T cellular phenotypic features as observed in T cell cultures with SD SF.

None declared

Pediatric Rheumatology, 23(2): PT021

None declared

Pediatric Rheumatology, 23(2): PT022

Introduction: Mevalonate kinase deficiency (MKD) is a monogenic autoinflammatory disease caused by loss of function mutations in MVK gene which results in reduced isoprenoids synthesis due to impaired mevalonate kinase enzyme. The mevalonate pathway controls the innate immune response via protein geranylgeranylation. Impairement of geranylgeranylation results in overproduction of pro-inflammatory cytokines, increased pyrin inflammasome. Past research shows that monocytes display inflammasome dysregulation and aberrant innate immune responses.

Methods: Nineteen MKD patients were included our study, and peripheral blood mononuclear cells (PBMCs) were obtained during remission (n=12) and flare (n=7) phases and patients with hypercholesterolemia using statins (n=7) and healthy controls (10). The flow cytometer was used to evaluate classical CD14++CD16- monocytes and intermediate CD14++CD16+ monocytes and non-classical CD14+CD16+ monocytes. Plasma cytokine levels as well as post-LPS stimulation cytokine production was examined via Legend Plex™ Inflammation Panel 1. Lastly, gene expression of pattern recognition receptors MAVS, AIM2, MDA5, DDX58, STING, cGAS, IL-33R, IL-17R, TLR2, TLR3, TLR7 and TLR9 were evaluated with real-time qPCR.

Results: A decrease in the frequency of CD14++CD16- classical monocytes was observed in MKD patients during flare and remission. Intermediate and non-classiacl monocytes did not show significant difference. Serum IL-18 and IL-6 levels were increased in MKD patients with disease flare compared to healthy controls. After LPS stimulation, IL-1β, IL-6, IL-8, IFN-α2, IFN-γ and MCP-1 cytokine levels were found to be significantly lower in PBMCs of MKD patients in flare compared to healthy controls. DDX58 (RIG-I) gene expression was significantly decreased in MKD patients in the flare and remission period compared to healthy controls.

None declared

Pediatric Rheumatology, 23(2): PT024

None declared

Pediatric Rheumatology, 23(2): PT025

None declared

Pediatric Rheumatology, 23(2): PT026

None declared

Pediatric Rheumatology, 23(2): PT027

Objectives: We found two variants of uncertain significance (VUS) via whole exome sequencing in two families with BD-like complaints and evaluated their possible pathogenic impact through in silico and in vitro investigations.

Conclusion: Our findings show that nucleotide changes in the MRTF-A gene, initially classified as VUS, actually lead to increased activity of the MRTF-A protein, enhancing gene expression. Given its crucial role as a transcriptional co-activator of Serum Response Factor and its established link to actin cytoskeleton dynamics, the observed hyperactivation likely disrupts these cellular processes. The clinical presentation in individuals carrying these variants, mimicking aspects of Behçet's disease, points toward a novel potential monogenic mimicker of BD. This is because reduced G-actin levels, a consequence of such defects, promote the translocation of MRTF-A into the nucleus, thereby increasing its activity. Consequently, gain-of-function variants of MRTF-A may exhibit effects analogous to those observed in actin depolymerization disorders, such as WDR1 deficiency, a recognized monogenic mimic of Behçet's disease, thereby reinforcing the hypothesis that cytoskeletal imbalance may play a role in the pathogenesis of Behçet's disease spectrum disorders.

None declared

Pediatric Rheumatology, 23(2): PT028

Introduction: Cherubism (OMIM 118400) is characterized by destructive bilateral jawbone expansion due to inflammatory fibrous lesions. Recently, autosomal recessive loss-of-function variants in the OGFRL1 (opioid growth factor receptor-like 1) gene were identified in two families from Syria and India with cherubism. These families carried homozygous frameshift mutations, presumed highly pathogenic. Despite attempts to model the disease in OGFRL1 knockout mice, the human phenotype could not be replicated.

Results: The younger brother developed recurrent fevers, developmental delay, sterile pyogenic arthritis, and severe abscesses post-vaccination at the age of 1, along with jawbone osteitis and diffuse CRMO lesions. Imaging revealed mandibular osteosclerosis with heterogeneous osteolytic lesions and multifocal metaphyseal involvement on whole-body MRI. A major inflammatory syndrome was noted (leukocytes 16,000, CRP 180 mg/L, ESR 110 mm). The older brother displayed a milder phenotype with post-vaccination abscesses and osteoarticular pain starting at age 10. MRI identified a single epiphyseal-metaphyseal lesion in the right clavicle, suggesting CRMO. Inflammatory markers were moderately elevated (CRP 7 mg/L, ESR 40 mm). Cherubism-related features were absent. WGS revealed a rare missense variant in OGFRL1 exon 7, p.(Arg241His), predicted deleterious in silico in both brothers. Proteomics analysis of the younger brother highlighted a higher abundance of proteins involved in osteoclast differentiation (NOTCH2, EFNA2, FOSL2, PIAS3), cartilage development (FOSL2, RUNX3, DLX2), and immune function (TXN, ITGB2/ITGAL, HERC1, ULBP1). Conversely, anti-inflammatory proteins BCHE, SIGLEC5, and SIGLEC14 were less abundant.

Conclusion: This report extends the spectrum of OGFRL1-related disorders to include a phenotype combining cherubism and CRMO. Unlike previously reported cases, our patients exhibit CRMO, pyogenic arthritis, and skin pathergy. We investigated the KEGG pathways involving significant proteins and known cherubism-related genes. Our results suggest that the OGFRL1 mutation in our patients may affect the MAPK signaling pathway, shedding light on the potential molecular mechanisms underlying this condition. Consent to published had been obtained.

None declared

Pediatric Rheumatology, 23(2): PT029

Introduction: Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disorder, characterized by recurrent episodes of systemic inflammation. Although this largely is an autosomal recessive condition, a subset of heterozygous carriers of MEFV mutations exhibit a clinical phenotype consistent with FMF. The mechanisms underlying this phenomenon remain poorly understood.

For transcriptome profiling, total RNA from pooled groups (heterozygous FMF, homozygous FMF, healthy carriers) was extracted (Norgen Kit), followed by globin mRNA depletion (Qiaseq Fast Select) and library preparation (Qiaseq Stranded mRNA Kit). Libraries were sequenced on an Illumina NextSeq 500/550 (2×74 bp paired-end reads). Reads were aligned to hg19 (CLC Genomic Workbench), with differential expression analyzed via a negative binomial Generalized Linear Model (TMM-normalized; adjusted *p*<0.01, |log₂FC|>1). REACTOME pathways were assessed using ExpressAnalyst.

Protein studies utilized healthy donor-derived monocytes/PBMCs. Monocytes (isolated with Miltenyi Kit) and PBMCs were stimulated with IFN-α (1000 U/mL), and lysates were immunoblotted for IRF-3, ISG15, Pyrin, STAT1, AIM2, caspase-5, and β-actin. CXCL10 in supernatants was quantified via Luminex (Bio-Rad).

Results: We included 10 familial Mediterranean fever (FMF) patients (6 males/4 females; median age 9–11 years) and 5 healthy heterozygous carriers (1 male/4 females). All patients were treatment-naïve, with normal acute-phase reactants. Transcriptomic profiling of PBMCs identified 147 differentially expressed genes (DEGs; FDR ≤0.001, |Fold Change (fc)|≥2) between heterozygous FMF patients and healthy carriers (96 upregulated and 51 downregulated genes), including upregulated interferon-stimulated genes (STAT1, STAT2, IRF7, ISG15, IFIT2, IFIT3, USP18). Gene Ontology revealed enriched type I interferon responses, cytokine signaling, and inflammatory pathways (p-adj <0.01), with JAK-STAT signaling implicated. REACTOME analysis confirmed pronounced type I interferon activation (p-adj <0.01), particularly in IFN-α/β clusters. STRING network analysis highlighted interactions among innate immune genes (STAT1, IRF7, ISG15, OAS1).

Inflammasome-associated genes (CASP5, GBP1, NLRC4) and MEFV (encoding Pyrin) were upregulated in heterozygous FMF (p-adj <0.05). Compared to homozygous patients, heterozygotes exhibited heightened cytokine signaling and persistent interferon-related gene expression. Kinetic analysis of IFN-α-stimulated monocytes/PBMCs from healthy donors demonstrated time-dependent increases in CXCL10 secretion and elevated expression of Pyrin, STAT1, ISG15, AIM2, and caspase-5, while IRF3 remained unchanged. These findings support a model wherein chronic type I interferon signaling acts as a “second hit” in heterozygous MEFV carriers, driving mutant Pyrin overexpression and inflammasome activation, thereby precipitating the FMF phenotype.

Conclusion: These findings suggest that type I IFN signaling acts as a critical ‘second hit,’ amplifying Pyrin expression in heterozygous individuals and enabling disease manifestation despite a single MEFV mutation. This study offers an explanation for the much-debated issue of the carriers expressing disease phenotypes in diseases such as FMF, and presents novel insights for precision diagnosis and therapeutic intervention. 

None declared

Pediatric Rheumatology, 23(2): PT031

Results: From July 2022 to March 2025 the WBCT was performed in 32 pts (15 female/17 male) with a verified FOP. 31/97% pts have «typical» c.617G>A (p.Arg206His) and 1 pt have ultra-rare (p.Gly356Asp) heterozygous missense substitution in the ACVR1 gene. All pts have congenital malformed great toes as a classic phenotypical FOP features. In 18 pts WBCT was done twice (9 female/9 male), in 4 pts 3 times (2 female/2 male), in 1 male pt – 4 times. HO volume was calculated in 23 pts (repeated in 13). WBCT was repeated after 1-year period. At the moment of first performed WBCT the median age of pts was 10 [interquartile range (IQR) 7;16] years, the median CAJIS was 7 [IQR 5;11], the median HO volume (n=23) was 89.7 [IQR 9.2;297.1]. We detected significant correlation between HO volume and CAJIS (r=0.554, p=0.006) and between age and CAJIS (r=0.554, p=00009). At the moment of second examination with WBCT the median age of pts was 11 [IQR 8;15] years, the median CAJIS was 7,5 [IQR 4;11], the median HO volume (n=13) was 89,7 [IQR 49,3;352,3]. We detected significant correlation between HO volume and CAJIS (r=0.741, p=0.003) and between age and CAJIS (r=0.656, p=0.003). Pts were compared into 4 age groups (at the moment of performing WBCT): 0-5 y.o. (n=5); 5-10 y.o. (n=12); 11-15 y.o. (n=6); >16 y.o.(n=9). Significant association with CAJIS was detected in two age groups: 5-10 y.o. and >16 y.o. (p=0.04). Tendency to significant association with HO volume was detected in other two age groups: 0-5 y.o. and 11-16 y.o. (p=0.08).

None declared

Pediatric Rheumatology, 23(2): PT032

Groups:

Rheumatic diseases, incl. autoimmune and autoinflammatory conditions (n = 188, 72.3% ♀, mean age (M) = 13.6, SD = 3.7).

Chronic pain, incl. complex regional pain syndrome (n = 123, 82.9% ♀, M = 13.9, SD = 2.4).

Post-infectious conditions, incl. SARS-CoV-2, EBV, and others (n = 22, 68.2% ♀, M = 15, SD = 3.6).

ME/CFS (n = 13, 84.6% ♀, M = 15.4, SD = 2.2).

Results: Fatigue severity varied between groups. Rheumatic disease patients reported the lowest sum scores (M = 22.23, SD = 10.26; mean item score (MIS) = 2.22), followed by patients with chronic pain (M = 29.09, SD = 10.44; MIS = 2.91). Higher scores were found in post-infectious conditions (M = 39.75, SD = 7.51; MIS = 3.98), while patients with ME/CFS showed the highest (M = 42.54, SD = 7.21; MIS= 4.25).

When asked about the most appropriate wording for their fatigue (exhausted or tired), descriptions varied between groups. Among those with rheumatic diseases, 56.80% described themselves as exhausted, 36.80% as tired, and 6.40% chose both. In the chronic pain group, a similar pattern emerged, with a stronger tendency toward exhausted (65.45%), followed by tired (28.18%) and both (6.36%). Patients with post-infectious conditions showed a preference for exhausted (90.48%), with 4.76% each choosing tired or both. All patients with ME/CFS (100%) identified exhausted as the most accurate description of their experience.

Fatigue is a relevant and variable symptom across pediatric chronic conditions. The findings emphasize the need for diagnosis-specific assessment and targeted management strategies in clinical care.

None declared

Pediatric Rheumatology, 23(2): PT033

BMD z-scores for chronological age, height age, and bone age were recorded as −0.16±1.25, −0.10±1.34, and −0.31±1.29, respectively. The prevalence of vertebral fractures was 3.5% (n=4).

No significant associations were found between disease severity parameters, including inflammatory markers(CRP, ESR, SAA), MEFV gene mutations, and PRAS score, and bone health outcomes(BMD and vertebral fractures)(p > 0.05 for all).

Analysis of treatment subgroups revealed no significant effect of colchicine on BMD or vertebral fracture risk (p>0.05 for all). On the other hand, patients treated with anti-IL-1 treatment showed significantly higher BMD values adjusted for both bone age and calendar age(p=0.037 for both). However, no significant difference was observed in vertebral fracture risk(p=0.634) or height age–adjusted BMD(p>0.05) in this group.

None declared

Pediatric Rheumatology, 23(2): PT035

We observed an increased level of RANTES in children with complications compared to those without complications (0.752 vs 0.389, p=0.028), and when considering the number of [0, 1, or >1] (0.389 vs 0.675 vs 0.824 respectively, p=0.022) complications. Conversely, CXCL10 was decreased in children with complications (2.82 vs 2.99 p=0.010), and when stratified by the number of complications (2.991 vs 2.881 vs 2.785 respectively p=0.004).

There were several significant correlations between the level of candidate biomarkers and ocular parameters: RANTES levels were positively correlated with the presence of complications (ρ=271, p=0.005) and glaucoma (ρ=306, p=0.015), while CXCL10 was negatively correlated with the presence of complications(ρ=0.27; p=0.005, the number of complications (ρ=0.31, p=0.006), and the presence of macular oedema/and papillitis (ρ=245, p=0.031). Moreover we found a positive correlation between S100A9 and the presence of cataract (ρ=384, p=0.003) and a negative correlation with uveitis activity (ρ=292, p=0.007). 

None declared

Pediatric Rheumatology, 23(2): PT036

Methods: This was a single-center cross-sectional study including children ≤18 years, diagnosed with CNO, acute infectious osteomyelitis (AOM) and bone malignancy from June 1, 2018 to May 31, 2024. Patients with other mimicking conditions, immunodeficiency, sickle cell disease, or those previously included in the original development cohort were excluded. Patients were divided into two groups: a CNO group and a non-CNO group (AOM and bone malignancy), from the latter a representative, random, sample was selected (www.random.org). Demographic, clinical, laboratory, imaging and pathology data were collected at disease onset. EULAR/ACR criteria were retrospectively applied to the entire cohort, independently from the initial diagnosis. Patients with an aggregate score ≥ 55 points were classified as having CNO. A sensitivity analysis was also conducted where patients with criteria with missing data were excluded. Classification results using the new criteria were compared with the final clinical diagnosis based on physician assessment (criterion standard). The same analysis was applied to Jansson and Bristol criteria. From contingency tables, sensitivity and specificity were calculated.

None declared

Pediatric Rheumatology, 23(2): PT037

Methods: Tsc2 deletion was induced in male and female Mx1-Cre⁺ Tsc2 fl/fl mice (C57BL/6, 4-11 weeks of age) by intraperitoneal injection of 250 µg poly(I:C) on days 0, 2, and 4. Tissues were collected and analyzed on day 25 by flow cytometry, complete blood count, histology and Olink-based cytokine profiling. In vivo MRI scans of the brain were conducted in seven males on days 0, 4 and 24 as an exploratory study after findings in brain histology.

Results: Mx1-Cre⁺ Tsc2 fl/fl mice of all age groups and both sexes developed hemophagocytosis in bone marrow and hepatosplenomegaly with disruption of normal lymphoid follicle formation in the spleen – phenotypes not apparent in poly(I:C)-treated Mx1-Cre^- littermate controls. While anemia was detected in the blood, leukocytopenia was observed only in the bone marrow. Weight loss and joint swelling were not observed. By flow cytometry, F4/80⁺ macrophages were highly increased in bone marrow and Ly6G⁺ neutrophils were increased in the spleen. Pro-inflammatory Ly6C^hi CX3CR1^- monocytes were increased, whereas Ly6C^lo CX3CR1⁺ monocytes were diminished in both marrow and spleen. Natural killer (NK) cell proportions were lower in both compartments. Cytokine analysis in serum from 24 mice revealed an upregulation of macrophage-associated inflammatory markers such as CCL4, CCL5 and CXCL1, while the anti-inflammatory cytokine CCL22 was decreased. Histology of brain tissue revealed a greater abundance of F4/80⁺ macrophages, particularly in the choroid plexus. However, hydrocephalus or other evidence of CNS-MAS was not observed by MRI.

F. Bauer Grant/Research Support with: German Academic Scholarship Foundation and German Society of Internal Medicine (merit-based scholarships), J. Kuehn: None declared, R. Darbousset: None declared, H.-M. Lorenz: None declared, P. Lee Consultant with: Pfizer (reviewing of a slide deck), P. Nigrovic: None declared

Pediatric Rheumatology, 23(2): PT038

None declared

Pediatric Rheumatology, 23(2): PT039

None declared

Pediatric Rheumatology, 23(2): PT04

Results: A total of 635 patients with JIA were identified, 187 (29.4%) of whom had JIA-U (Table 1). The overall cohort was predominately white (73.7%) and female (74.9%), with 298 (46.9%) being identified as MTX-NR. Average MTX oral and subcutaneous dose was similar at 16.5 mg/m² (SD 6.6) and 17.4 mg/m² (SD 5.7), respectively. White race was associated with MTX-NR on bivariate (X²=20.0, p=0.0012) and multivariate (OR 2.429, CI 1.512-3.904) analysis, with no other significant clinical variables identified. Of the 187 JIA-U patients, 91 (48.6%) were identified as being MTX-NR (Table 2). Of the 91 JIA-U MTX-NR, a majority were non-responders due to arthritis activity (61.5%), followed by both CAU and arthritis activity (26%) and isolated CAU activity (12%). In contrast to the overall cohort, MTX intolerance (MTX-IT) was associated with MTX-NR (X²=9.3, p=0.00023) in the JIA-U group. The most common reason for MTX-IT being GI symptoms (76.2%), followed by laboratory abnormalities (11.9%). The most initiated biological DMARD in MTX-NR patients was adalimumab (37.9%). No significant differences in predictors of response were found between JIA and JIA-U groups across clinical and demographic variables.

None declared

Pediatric Rheumatology, 23(2): PT041

Methods: The study was planned as a case-control study. The data of 102 patients (<18 years of age) who were followed up in tertiary center between January 2015 and January 2023 were reviewed using electronic medical records. Patients were divided into 3 groups as JIA, idiopathic uveitis and uveitis associated with JIA (JIA-U), 34 patients from each group. Then, pairwise comparison was made between these three groups. Demographic and clinical characteristics of the patients, recurrence frequency, treatments, various familial and environmental factors (smoking exposure during pregnancy, breast milk use), and Mediterranean diet compliance were assessed with KIDMED questionnaires¹ during outpatient clinic visits. Air quality indexes and air pollutants data were recorded for the place of residence one year before the last uveitis attack, and for the place of residence of those without remission of the attack and those with a diagnosis of JIA.

There were no significant differences between the groups in demographic factors such as parental consanguinity, parental age and number of siblings, except for maternal smoking during pregnancy (p<0.001). However, caesarean section rates were significantly higher in the idiopathic uveitis groups compared with JIA and JIA-U (p=0.007). The Mediterranean diet quality scores were evaluated between patient groups, the median KIDMED score differed significantly between JIA-U and idiopathic uveitis (p=0.007).

Environmental factors including air pollutants (PM10, PM2.5, SO2) and weather parameters (precipitation, daily maximum temperature, daily diurnal temperature difference, average relative humidity) were found to influence disease severity and frequency. In particular, air pollutants (PM10, PM2.5, SO2) above defined thresholds were associated with an increased risk of disease, while SO2 showed a potentially protective effect. Statistical analysis of total precipitation, daily maximum temperature, and daily diurnal temperature difference across the three groups revealed significant differences, with the most pronounced variations observed in the uveitis group, evident throughout the year and in the last 3 months.

None declared

Pediatric Rheumatology, 23(2): PT044

Objectives: We aimed to assess the pathogenicity of an undescribed NM_138636.5: c.1027G>C (p.D343H) variant of TLR8 in two kindreds and describe its clinical presentation.

Methods: We performed in silico analyses of the c.1027G>C variant, reported the genetic and clinical familial segregation and explored the impact of the variant on the NF-κB pathway using a luciferase reporter assay.

Results: Familial segregation revealed an X-linked transmission of the disease, and genetic assessment found a c.1027G>C variant of TLR8. This variant was predicted pathogenic by CADD score and AlphaMissense. This mutation was not disclosed in healthy genetic database, but another variant at the same position was recorded in a healthy female, carrying c.1028A>T, p.D343V variant. As both variants were located on the same residue, we explored the impact on the protein function using a NF-κB reporter luciferase assay. After TLR stimulation, both variants presented an increased NF-κB activity compared to wild type TLR8 and were activated at lower concentration. Interestingly, p. D343H variant exhibits a marked loss of ligand specificity and unexpectedly responds to R837, a specific agonist of TLR7. Location of the mutation was shown to be in the site of interaction with degraded RNA, which likely explains TLR8 overactivation (4).

From a clinical perspective, female carriers were mainly asymptomatic, as previously described (2,3). Several symptoms presented by the patients were evocative of ADA2 deficiency and were reported as polyarteritis nodosa diagnoses with thrombotic vasculitis, livedo or erythema nodosum, and infectious manifestations that could be fatal. Moreover, vasculitis, uveitis, neutrophilic dermatitis and polychondritis were as many manifestations compatible with UBA1 somatic mutation and could be evocative of another somatic disease, the VEXAS syndrome. These manifestations, associated with the effect of TLR8 variants on hematopoietic stem cells, provide promising clues to understand how NF-κB overactivation in myeloid cells contributes to these phenotypes (1,3).

None declared

Pediatric Rheumatology, 23(2): PT045

Results: We identified 40 DEGs (fold change>1.5, P<0.05) in the cis-female cSLE cohort vs. HCs (defining a post-pubertal cSLE signature) that overlapped with the transgender cohort (on GAHT). Specifically, in the XY TF group (on E vs. GnRHa), there were 24 upregulated/1 downregulated DEGs, including TLR2 (upregulated, p= 0.0077), and IL1R2 (upregulated, p= 0.048 which overlapped with the cSLE signature. Similarly, in the XX TM group (on T vs. GnRHa), there were 6 upregulated/4 downregulated overlapping DEGs, including IL15 (upregulated, p= 0.019). PEA revealed DEGs linked to the inflammatory response processes, cell migration/activation and lipid regulation.

Additionally, we discovered 63 X-linked DEGs (P <0.05) in the GAHT vs. GnRHa groups across both XX and XY backgrounds, however, these did not overlap with the cSLE signature, suggesting a lesser impact of sex hormones on X-linked transcripts related to cSLE susceptibility. However, the X-linked non-coding RNA X-inactive specific transcript (XIST) and the XIST antisense non-coding RNA TSIX, were both significantly increased in cSLE vs. HCs (p=0.018 and 0.0007). XIST correlated negatively with cSLE interferon scores (p=0.0010, r=−0.38) and X-linked TLR7 expression (p=0.0004, r=−0.40), but TSIX did not, supporting a role for X chromosome inactivation in controlling the pathogenic mechanisms associated with cSLE in females.

Conclusion: This analysis demonstrated unique inflammatory transcriptomic changes (DEGs) induced by GAHT in transgender adolescents, which overlapped with cis-female cSLE adolescents, as well as sex hormone-independent associations between XIST expression and inflammatory cSLE pathogenic mechanisms. To our knowledge, this is the first exploration of the impact of sex hormones disaggregated from their corresponding sex chromosomal background in driving transcriptomic changes potentially relevant for understanding female cSLE pathogenesis.

None declared

Pediatric Rheumatology, 23(2): PT046

To confirm these findings, we analysed data from the largest MIS-A published cohort to date (11 patients). TCR Vβ repertoire screening was performed in MIS-A patients and control cohorts including patients with COVID-19 associated myocarditis, post BNT162b2 mRNA vaccine-related myocarditis, and flu associated myocarditis. We found an expansion of Vβ21.3+ T cells in 6/11 MIS-A patients versus 3/15 control patients. 

None declared

Pediatric Rheumatology, 23(2): PT047

None declared

Pediatric Rheumatology, 23(2): PT048

Introduction: Juvenile idiopathic arthritis is the most common rheumatic disease in childhood and adolescence. Previous studies have shown an immunological imbalance leading to chronic inflammation of affected joints. Granzymes are secreted by cytotoxic immune cells, in particular CX3CR1 expressing CD8+ T cells, and are capable of extracellular matrix degradation and remodeling^{1, 2}. Whether granzymes are involved in JIA pathogenesis is not yet understood.

Methods: We collected peripheral blood mononuclear cells (PBMC), plasma, synovial fluid cells (SFC) and synovial fluid (SF) from 27 patients with JIA. Samples were frozen at −80 °C until the time of analysis. We performed flow cytometry based immunephenotyping of PBMC (n=45) and SFC (n=31) and Legendplex^TM multiplex cytokine analysis in plasma and SF.

None declared

Pediatric Rheumatology, 23(2): PT049

Results: We identified significant upregulation (log2 fold change ≥1) of endogenous retroviruses (ERV1, ERVL, ERVK families), LTR retrotransposons, and LINE elements during MIS-C flares compared to remission. Notably, LTR161-ERV1 and LTR108e_Mam-ERVL were among the highest expressed elements (log2FC=2). T2T alignment exclusively uncovered additional TE transcripts, including unknown and poorly characterized elements (e.g., UCON61, UCON63), further emphasizing genomic regions traditionally underrepresented in reference genomes. Elevated TE expression coincided with significantly increased cytokine levels, including IL-6 (median flare: 484.81 vs remission: 2.40 pg/mL, adjusted p=0.019), IFN-γ (median flare: 2184.48 vs remission: 70.71 pg/mL), VEGF (median flare: 179.74 vs remission: 134.78 pg/mL, adjusted p=0.024), and CCL2 (median flare: 531.99 vs remission: 219.58 pg/mL, adjusted p=0.024). These cytokines are known to promote inflammatory responses and immune cell recruitment, potentially contributing to the transcriptional activation of TEs observed during MIS-C flares.

None declared

Pediatric Rheumatology, 23(2): PT050

Introduction: The lining layer of the synovial membrane is increasingly recognised as a key tissue niche determining joint health, producing synovial fluid components, including proteoglycan-4 (PRG4), to nourish and lubricate the joint(1-3). The rare monogeneic condition Camptodactyly-Arthropathy-Coxa Vara-Pericarditis (CACP) syndrome, caused by mutations in the PRG4 gene, manifests with progressive arthropathy of the large joints arising in early childhood, demonstrating a critical for PRG4 in mediating normal joint homeostasis(4).

Results: Single cell and spatial transcriptomic analyses of CACP syndrome synovium demonstrated an increased proportion of myofibroblasts and extracellular matrix deposition, which we validated at the protein level in human and mouse tissue using IF staining and flow cytometry, in accordance with the clinical manifestation of this condition. Interestingly, we observed multi-nucleated macrophages in the hyperplastic synovial lining layer in CACP syndrome, an uncommon feature of joint pathology. These lining layer macrophages displayed polarisation towards an SPP1+ program, which is associated with fibrosis in the fibrotic liver and lung, and in vitro stimulation determined SPP1 expression to be directly regulated by PRG4. 3D imaging analysis of synovial lining macrophages in Prg4-knockout mice demonstrated altered morphology, suggesting impaired capacity to undergo immunoregulatory efferocytosis of synovial fluid debris.

Conclusion: We demonstrate that PRG4 suppresses the emergence of a pro-fibrotic SPP1+ macrophage program in the synovial lining, which, in the absence of PRG4, promotes differentiation of myofibroblasts that drive synovial fibrosis, leading to restricted movement in the joints of individuals affected by CACP syndrome. Our further work aims to characterise defects in efferocytic capacity of lining macrophages in the absence of PRG4 and elucidate the role of efferocytosis in the healthy and inflamed synovium.

None declared

Pediatric Rheumatology, 23(2): PT051

Objectives: To investigate whether the introduction of submaximal treadmill fitness testing could increase PA levels, estimated peak oxygen uptake (VO_2peak), walking distance, physical function, and health-related quality of life (HRQoL) in adolescents with JIA. Also, to examine associations between PA levels, VO_2peak and walking distance.

Methods: A longitudinal clinical study with a pre-test (visit 1) and post-test (visit 2) design was conducted. The planned test interval was 3-6 months. Adolescents aged 10-18 years with non-systemic JIA were recruited at Oslo University Hospital between June 2019 and September 2021. The intervention included a submaximal treadmill test during routine physiotherapy assessments. The test involved walking at a self-selected pace on a treadmill with a 0% incline for 4 minutes, followed by a 5% incline for the next 4 minutes. Estimated VO_2peak was calculated based on walking speed, age, sex, and heart rate increase. PA was measured using the International Physical Activity Questionnaire (IPAQ). Physical function and HRQoL were assessed using the Juvenile Arthritis Multidimensional Assessment Report.

Results: Thirty-four participants were initially enrolled in the study; however, only 24 completed the follow-up assessments within 3-11 months after visit 1. The COVID-19 pandemic adversely affected recruitment efforts and led to the cancellation of several planned follow-up tests. Between visits, there was no significant change in PA levels measured by IPAQ. However, significant improvements were observed in estimated VO_2peak (2.4 mL∙kg⁻¹∙min⁻¹, p=0.012) and walking distance (31 meters, p=0.038). Moderate, positive correlations were found between vigorous PA and estimated VO_2peak at both visits (Visit 1: rho=0.36, p=0.035; Visit 2: rho=0.51, p=0.01), and between vigorous PA and walking distance at Visit 2 (rho=0.42, p=0.04). Additionally, there were significant correlations between moderate-to-vigorous PA and estimated VO_2peak (rho=0.43, p=0.04), and between total PA and estimated VO_2peak (rho=0.41, p=0.049) at Visit 2. Even if changes in PA levels, physical function and HRQoL were non-significant, there were positive trends, indicating that our study was underpowered.

Conclusion: Submaximal treadmill fitness testing may enhance estimated VO_2peak and walking distance in adolescents with JIA. While no significant changes in PA levels or HRQoL were observed, the positive trends and correlations indicate that fitness testing could be a valuable tool in clinical practice to motivate increased PA.

None declared

Pediatric Rheumatology, 23(2): PT052

Methods: Data fields were compared from existing International Ped-APS Registry and CARRA Registry, which identifies patients with APS within the lupus cohort. The 2023 ACR/EULAR APS classification criteria were reviewed and systematic literature review of pediatric APS between 2003-2024 was conducted to identify potential data elements for future registries (Figure 1). Delphi surveys were completed by physicians with APS experience, which included pediatric rheumatologists, med/peds rheumatologists, adult rheumatologists, and pediatric hematologists representing 12 countries and two caregiver representatives. Items were scored from 1 (not important) to 9 (very critical). Consensus “in” was reached for core items scored > 7 by > 70% of experts, as well as all items included in the adult 2023 APS Classification Criteria. Consensus “out” was reached for items with average score < 5. The remaining items were labeled “equivocal” for voting at a hybrid consensus meeting. During the meeting, items with >80% agreement were included in the final dataset (either Core or Expanded), and items failing to meet consensus were either excluded or revised and re-evaluated when appropriate. Items scoring >6 were eligible for either Core or Expanded datasets. Items scoring > 5 but < 6 were only voted upon for the Expanded dataset.

Results: A total of 32 experts completed the first-round Delphi survey, and 26 participated in the second round. Two caregiver representatives completed a modified version of the survey. Of 316 total candidate items, 72 reached consensus “in,” 87 were rated “out,” and 157 were classified as “equivocal.” These equivocal items were reviewed and voted upon by 19 experts during a hybrid consensus meeting. Based on >80% agreement thresholds, additional items were included. Ultimately, a final dataset comprising 60 core and 22 expanded data elements was established. These were categorized under 18 thematic domains, including demographics, thrombotic and non-thrombotic features, laboratory parameters, comorbidities, therapies, and outcomes. The resulting dataset reflects both expert consensus and parent perspectives and is intended to support consistent international data collection in future pediatric APS research initiatives.

None declared

Pediatric Rheumatology, 23(2): PT053

None declared

Pediatric Rheumatology, 23(2): PT054

Introduction: The transition from pediatric to adult rheumatology care presents a vulnerable phase for young people with chronic inflammatory arthritis. Disruptions during this process may compromise therapeutic continuity, health status, and long-term participation. Despite growing awareness of transition challenges, real-world data on care continuity and psychosocial outcomes remain limited.

The InfoTrans project is funded by the Innovation Fund of the Federal Joint Committee (G-BA), grant number 01VSF20012.

None declared

Pediatric Rheumatology, 23(2): PT055

None declared

Pediatric Rheumatology, 23(2): PT056

either as officially appointed representative or as recognized leading experts. Via a survey we asked for the number of pediatric rheumatologists who care for children in the different countries. We also gathered information on the training and the recognition of pediatric rheumatology as a subspecialty. Finally, we asked for the actual time and effort spent in the care for children with RMDs (full time, part time approximately 25-75%, or less).

Finding the exact number of pediatric rheumatologists in Europe is challenging. Our survey suggests that there are approximately 600 certified pediatric rheumatologists across Europe, but their training varies substantially. It is a major task for EULAR and PReS to provide guidance and standards.

The European Syllabus for Training in Paediatric Rheumatology Syllabus, approved by the European Academy of Paediatrics - Union Européenne des Médecins Spécialistes (EAP-UEMS) should be the basis for optimized training programs in Europe.

None declared

Pediatric Rheumatology, 23(2): PT057

None declared

Pediatric Rheumatology, 23(2): PT058

This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 121E690.

None declared

Pediatric Rheumatology, 23(2): PT059

None declared

Pediatric Rheumatology, 23(2): PT061

The forms of AIDs included: type I Interferonopathies - 14, genetically undefined AIDs −13, adenosine deaminase 2 deficiency (DADA2) – 5, PSTPIP1-associated syndrome (PAID) - 4, SAMD9 deficiency - 2, SOCS1 haploinsufficiency – 2, SAMD9L deficiency - 1, A20 haploinsufficiency (HA20) - 1, proteasome-associated autoinflammatory syndrome (PRAAS) – 1, IL-18–mediated PAP and recurrent MAS −1, NLRP1- associated autoinflammation with arthritis and dyskeratosis (NAIAD) – 1, RELA haploinsufficiency −1, NEMO-NDAS – 1, C1q deficiency – 1.

JAKinibs were used as monotherapy in 19 cases, and in combination with other immunosuppressive therapy (steroids, anti-IL1, anti-TNFα and others) - in 29. Before initiation of JAKinibs therapy, 27 patients received therapy with other immunosuppressive drugs which was not effective

24 patients had autoinflammatory, 22 – autoinflammatory and hematological and 2 - hematological manifestations.

Tofacitinib was used in 32/48 cases, and ruxolitinib - in 16/48. Average initial dose was 0.9±0.2 mg/kg. Median duration of therapy – 3.0 years (0.3; 10.0). Median age of initiation of therapy – 5.0 years (0.5; 17.0).

JAKinibs therapy led to a complete remission in 23/48 cases, partial remission in 20/48, and had no effect in 5/48.

Side effects that were attributed to JAKinibs were noted in 8/48 patients and included infections in 5, lymphopenia in 2, hepatotoxicity in 1, none of them were severe and led to discontinuation of treatment.

None declared

Pediatric Rheumatology, 23(2): PT062

S. Palmeri: None declared, M. Ponzano: None declared, G. Recchi: None declared, C. Conti: None declared, S. La Bella: None declared, D. Sutera: None declared, M. Bustaffa: None declared, C. Matucci-Cerinic: None declared, R. Bertelli: None declared, F. Penco: None declared, I. Prigione: None declared, R. Papa: None declared, I. Ceccherini: None declared, S. Volpi Consultant with: Boehringer, Speaker Bureau with: Speaker fee from SOBI, R. Caorsi Consultant with: SOBI, M. Gattorno Consultant with: Novartis, Sobi, Fresenius Kabi, Kiniksa, Speaker Bureau with: Novartis, Sobi, Fresenius Kabi, Kiniksa

Pediatric Rheumatology, 23(2): PT063

Results: Children with KD demonstrated a significantly higher risk of developing pediatric rheumatic diseases compared to controls. JIA incidence was markedly elevated at 2 years (117.83 vs. 9.41 per 100,000 person-years; HR 12.51, 95% CI: 2.43-64.50, p=0.003), with this significance persisting throughout the 20-year follow-up (HR 4.38, 95% CI: 1.59-12.09, p=0.004). SLE showed consistently significantly higher incidence from early follow-up (HR 15.01, 95% CI: 1.56-144.30, p=0.019) at 2 years, through 15 years (HR 5.01, 95% CI: 1.01-24.80, p=0.049), though not at 20-years. HSP risk was elevated at 2 years (HR 5.01, 95% CI: 1.45-17.30, p=0.011), with an approximately two-fold increased risk thereafter, without statistical significance.

None declared

Pediatric Rheumatology, 23(2): PT064

Methods: Children with JIA presenting to Cincinnati Children’s Hospital Rheumatology clinics and able to tolerate a MSUS were eligible for this study. During a study visit, clinical information including the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS-10), serum, SF -following a clinically indicated arthrocentesis-, and MSUS images were collected. MSUS examination of 10 joints (bilateral wrist, knee, ankle, 2^ndand 3^rd MCPs) was performed by MSUS-expert pediatric rheumatologist. B-mode and Power Doppler (PD) mode MSUS images were scored by pediatric MSUS experts using a reliable joint-specific semiquantitative MSUS scoring system (MSUS-10, graded 0-normal to 3-severe). Synovitis on MSUS was defined as MSUS findings of grades >=2. MSUS-10 count resulted from the sum of the positive MSUS joints for synovitis (MSUS-10 count range 0-10). SF was collected from a subset of participants that received a clinically indicated knee joint injection after MSUS of the knee (MSUS-knee) was completed. MSUS-knee score (range 0-6) assess severity of knee joint recess distention at 3 different anatomic locations. To evaluate the association of MSUS findings with biomarkers of inflammation, the following biomarkers in serum and SF were measured: TNFR1, IL-6, IL-10, MCP-1, ANG-1, ANG-2, MMP-2, MMP-8, CCL18, CCL20, IFNg, IL-17a, IL-2Ra, IL-23, IL-18, resistin, CXCL9, VEGF, TIMP-1 by Luminex, and S100A12, S100A8/A9 by ELISA. Descriptive statistics were done. Spearman correlation (r_s) was used to assess the relationship between MSUS, clinical variables, and biomarkers.

A total of 28 children [mean age 11.8 (SD 5.60)] with JIA (oligoarticular JIA 54%, pJIA 32%) contributed 32 SF samples. MSUS-knee score median was 5 (IQR 4-6). MSUS-knee score was <=4 in 37% of the knees while 31% had a score of 6 (severe findings of MSUS synovitis). Moderate to strong associations between the MSUS-knee score and Ang-2 [0.40 (0.06-0.66), p 0.021], VEGF [0.39 (0.04-0.65), p 0.028], IL-2Ra [0.66 (0.2-0.88), p 0.008] were found. Additionally, Ang-2, VEGF, and IL-2Ra levels were significantly higher in children with MSUS-knee score of 6 when compared to those with a MSUS-knee score <=4 (p-value <0.05). Ang-2, VEGF, and IL-2Ra levels were significantly higher in children with oligoarticular course-JIA when compared with children with pJIA (p-value <0.05).

None declared

Pediatric Rheumatology, 23(2): PT065

Introduction: Musculoskeletal ultrasound (MSUS) can be used to evaluate the presence and severity of joint inflammation in juvenile idiopathic arthritis (JIA). Two measures have been proposed for the assessment of MSUS-based JIA disease activity using a 10 joint examination protocol: MSUS10-count and MSUS10-score. The association of the MSUS10-count and MSUS10-score with clinical and patient-reported outcomes (PRO) measures is not known

Methods: Children with a history of polyarticular JIA (pJIA) presenting to Cincinnati Children’s Hospital Rheumatology clinics were enrolled. During a study visit, clinical and PRO data (including the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS-10) score, the Pediatric Quality of Life Inventory generic core (PedsQL-gen) and rheumatology module (PedsQL-rhe)) and a MSUS of 10 joints (MSUS10, bilateral wrists, knees, ankles, 2nd and 3rd MCPs) were collected. B-mode MSUS images were scored by pediatric MSUS experts, who were blinded to clinical information using joint-specific semiquantitative MSUS scoring systems (range 0-normal to 3-severe). Synovitis on MSUS was defined as B-mode findings of grades > 2 for a given joint. The MSUS10-score was calculated from the sum of graded inflammation per joint as per MSUS. To correct for biasing joints with more MSUS views (2 views for MCP, 3 for wrist and knee, and 4 for ankle), the contribution from each joint was weighted equally (range: 0-120). MSUS10-count reflects the total number of joints with MSUS-confirmed inflammation (range 0-10). Descriptive statistics were done. Spearman correlation (r_s) was used to assess the relationship between MSUS, clinical, and PRO measures variables.

Results: Sixty children with pJIA were enrolled [mean age 13.6+3.6; median cJADAS 3.5 (IQR: 1-9.5)]. The median MSUS10-count was 1 (IQR: 0-3) and the MSUS10-score was 6 (IQR: 0-16). PRO suggest moderately reduced quality of life (mean+SD; PedsQL-gen 76.1+18.8; PedsQL-rhe 77.8+15.2). There were moderately strong correlations of MSUS10-count with cJADAS (r_s:0.38, p=0.003), PedsQL-gen (r_s:−0.31, p=0.05) and PedsQL-rhe (r_s:−0.38, p=0.016). Similar results were observed for the MSUS10-score: cJADAS(r_s:−0.42, p=0.001), PedsQL-gen (r_s:−0.35, p=0.027) and PedsQL-rhe (r_s:−0.41, p=0.008). The correlations between MSUS10-count and MSUS10-score was 0.90 (p<0.001).

Conclusion: There was moderate association between MSUS10-count and the MSUS10-score using the MSUS-10 joint examination in pJIA with clinical measures of JIA activity and PRO. This supports the construct validity of both MSUS10 measures (count, score). Further research is needed to delineate the preferred MSUS-based activity measure for JIA.

None declared

Pediatric Rheumatology, 23(2): PT066

Results: Two hundred and sixty-nine autoinflammatory bone disease patients were evaluated. Fifty-one patients with cutaneous manifestations [46 CNO and 5 Majeed syndrome] were included in this study. Cutaneous manifestations preceded bone symptoms in 21 (41.2%) patients. The mean diagnostic delay was 16.1 ± 11.7 months in those with cutaneous manifestations and 25.3 ± 9.9 months in those with bone involvement (p=0.02). The most common skin lesions were acne (n=26), pustules (n=23), and papules (n=10). In a comparison of patients with and without acne, patients with acne had more frequent male sex and higher ESR, CRP levels (p=0.01, p=0.03, and p=0.04, respectively). In a comparison of patients with and without pustules, patients with pustules had younger age at symptom onset and age at diagnosis and higher ESR and CRP levels (p=0.04, p=0.04, p=0.04, p=0.02, p=0.03, respectively). In patients with CNO, the mean time to remission was 2.1 ± 0.7 years for cutaneous manifestation and 2.9 ± 1.4 years for bone involvement (p=0.04).

None declared

Pediatric Rheumatology, 23(2): PT067

Introduction: Familial Mediterranean fever (FMF) is an autoinflammatory disease most commonly associated with biallelic mutations in the MEFV gene. Patients carrying the same pathogenic variant in MEFV can exhibit a broad spectrum of clinical phenotypes. Identifying factors contributing to this clinical variability is essential for understanding disease mechanisms. DNA methylation has been proposed as a potential modifier of MEFV mutations and clinical presentation. However, prior studies exploring this hypothesis included heterogeneous cohorts, lacked genome-wide methylation analyses, and yielded inconsistent findings. 

Results: We identified 22 differentially methylated CpG sites in FMF patients compared with healthy controls. Of these, 18 were hypomethylated—including a CpG site within the MEFV gene—and four were hypermethylated. Notably, several differentially methylated CpGs were located in genes encoding zinc finger proteins, a family of transcriptional regulators. Of the 22 CpGs, 13 were found on chromosome 16, where MEFV is located. Three hypomethylated CpGs were within 1.1 kb of the MEFV transcription start site, two of which overlapped with enhancer regions, suggesting a potential regulatory role. Cell-type–specific analysis revealed significant differential methylation in NK cells, CD8⁺ T cells, and CD4⁺ T cells in FMF patients compared with controls.

Conclusion: Our findings suggest that DNA methylation changes may contribute to the pathogenesis of FMF. The enrichment of differentially methylated sites near MEFV on chromosome 16 and in immune cell subsets supports a role for epigenetic regulation in disease expression. These results highlight DNA methylation as a potential modifier of FMF and a promising target for future biomarker development and personalized therapeutic strategies.

None declared

Pediatric Rheumatology, 23(2): PT068

Introduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disorder caused by mutations in the MEFV gene, characterized by recurrent fever, abdominal pain, and serositis attacks. Chronic inflammation may lead to metabolic disturbances, increasing the risk of growth retardation and malnutrition. 

Objectives: This study aims to evaluate the impact of MEFV genotypes on malnutrition in pediatric FMF patients by comparing nutritional status and anthropometric measurements across different genotypes. Furthermore, we aim to investigate the relationship between genotype and malnutrition to identify high-risk populations. To date, only a limited number of studies have examined the relationship between genotype and malnutrition in this specific population.

Results: A total of 224 patients were enrolled in the study. Female patients accounted for 56.7% (n = 129) of the study cohort.The mean age was 11.9 (7.6–15.0) years; age at diagnosis was 7.0 (4.0–10.0) years; disease duration was 3.0 (2.0–6.0) years; and colchicine treatment duration was 24.0 (12.0–48.0) months. It was determined that 17% (n=38) of the patients had at least one comorbid condition, while 67.4% (n=151) had a families with intermediate socioeconomic status. Among the patients, 46% (n=104) carried at least one M694V mutation in the MEFV gene, and 12.5% (n=28) were diagnosed with colchine resistant FMF. Patients with at least one M694V mutation in exon 10 exhibited significantly higher rates of mild and moderate malnutrition (59.7% and 18.8%, respectively) compared to those without the mutation (16.0% and 5.3%, p<0.001). Additionally, patients with homozygous M694V mutations in exon 10 demonstrated significantly lower mid-upper arm circumference z-scores and height-for-age z-scores (median [IQR]: 2 [2–2] and −1.86 [−2.96–−0.72], respectively) compared to non-carriers (3 [3–3] and −0.72 [−1.24–−0.12], p=0.002 and p=0.004, respectively).The PYMS and STRONGkids total scores were significantly higher in patients with colchine resistant FMF (1.03 ± 0.74 and 0.96 ± 0.42, respectively) than in those without (0.37 ± 0.62 and 0.35 ± 0.49, p<0.001 for both). Furthermore, a statistically significant positive correlation was observed between SAA levels and both PYMS and STRONGkids scores (r=0.204, p=0.002 and r=0.229, p=0.001, respectively).

None declared

Pediatric Rheumatology, 23(2): PT069

This study is supported by the Foundation for Research in Rheumatology 

None declared

Pediatric Rheumatology, 23(2): PT070

Introduction: Behçet’s disease (BD) is a chronic, complex inflammatory disorder with unclear multifactorial pathogenesis.¹ Recently, monogenic disorders mimicking BD have emerged, whose identification may improve understanding of pathogenesis and allow tailored therapies.^2,3

None declared

Pediatric Rheumatology, 23(2): PT071

Introduction: DNASE1L3 deficiency is a rare genetic disorder that typically presents with features of systemic autoimmunity, particularly early onset systemic lupus erythematosus (SLE) and hypocomplementemic urticarial vasculitis syndrome (HUVS). The disease is based on loss-of- function mutations in the endonuclease DNASE1-like 3 (DNASE1L3), which is secreted by immune cells and typically degrades chromatin into small fragments and effectively dismantles neutrophil extracellular traps (NETs). The persistence of undigested chromatin and cell-free DNA can result in the formation of autoantibodies such as anti-dsDNA antibodies and is implicated in the development of various autoimmune diseases including SLE. Additionally, the presence of anti-DNASE1L3 autoantibodies detected in patients with idiopathic SLE correlates with disease severity, suggesting that DNASE1L3 plays a critical role in NET associated autoimmune disease.

T. Avcin Consultant with: Octapharma, Speaker Bureau with: Novartis, Octapharma, Pfizer, Takeda, M. Bizjak: None declared, T. Vesel Tajnsek: None declared, B. Jenko Bizjan: None declared, B. Cugalj Kern: None declared, C. Lood Shareholder with: Redd Pharma, Grant/Research Support with: Archon, Boehringer-Ingelheim, Gilead Sciences, Neutrolis, Pfizer, Redd Pharma, Consultant with: Citryll, Redd Pharma, R. Lambalot Shareholder with: Neutrolis, Employee with: Neutrolis, A. Prasanna Shareholder with: Neutrolis, Employee with: Neutrolis, G. Gouya Shareholder with: Neutrolis, Consultant with: Neutrolis, A. Hakkim Shareholder with: Neutrolis, Employee with: Neutrolis, T. Fuchs Shareholder with: Neutrolis, Employee with: Neutrolis, A. Reiff Shareholder with: Neutrolis, Employee with: Neutrolis

Pediatric Rheumatology, 23(2): PT072

None declared

Pediatric Rheumatology, 23(2): PT073

Methods: A total of 64 patients with childhood-onset lupus and 47 healthy controls were included in this study, along with an independent validation cohort of 38 additional patients. DNA was isolated from PBMCs in the study cohort and from whole blood in the validation cohort to assess DNA methylation using the Infinium MethylationEPIC v2.0 array (Illumina). Quality controls and statistical analyses were performed using minfi and limma R packages. Methylation differences among groups were tested through linear regression, adjusting for age, sex, medication use, and cell subset compositions. Differences in clinical manifestations were assessed using Fisher’s exact tests. Gene ontology enrichment analyses were performed with Metascape and GREAT.

Results: Case-control differential DNA methylation analysis revealed significant hypomethylation in interferon-regulated genes in lupus, such as DTX3L, PARP9, IFI44L, and MX1. The enrichment analysis confirmed the presence of type I interferon signature-related biological processes, consistent with adult-onset lupus. Hypomethylation in genes related to B cell activation and cellular senescence was correlated with more active disease, as measured by SLEDAI scores. K-means clustering analysis of patients based on DNA methylation patterns identified 3 distinct lupus clusters. Cluster 1 was characterized by the enrichment of hypomethylated genes involved in cell adhesion and response to growth factor pathways; Cluster 2 exhibited hypomethylation in genes related to regulation of cell differentiation and cell fate determination; and Cluster 3 was enriched in response to oxidative stress and Rap1 signaling pathway in hypomethylated genes. Sex-based analysis revealed hypomethylation in males at sites enriched in immune response pathways, with over 80% of differentially methylated positions in male individuals with childhood-onset lupus validated in the replication cohort.

None declared

Pediatric Rheumatology, 23(2): PT074

Objectives: This study investigated genetic variability of TLR7 and associations with disease outcomes in 319 jSLE patients enrolled in the UK JSLE Cohort Study.

Methods: Sequence capture enrichment (NimbleGen/Roche), followed by next-generation sequencing (MiSeq2500/Illumina) was performed. Allele frequencies were extracted from Allele Frequency Aggregator, 1000 genomes, and the Genome Aggregation Database. Haplotype analyses and linkage disequilibrium parameters were investigated using SNPstats, and associations with organ domain involvement (pBILAG-2004) were analysed. Functional impacts of TLR7 variants were studied in HEK293T cells following transfection with reporter plasmids including the TLR7 promoter and plasmids carrying the TLR7 cDNA sequence. Transcription factor recruitment was evaluated through chromatin immunoprecipitation (ChIP). Messenger RNA (mRNA) stability was investigated through the transcriptional inhibitor 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB).

Results: Three jSLE-associated variants with a minor allele frequency ≥5% and an in silico predicted impact on gene function were retrieved: rs2302267/n.−20T>G (promoter); rs179008/c.32A>T/p.Gln11Leu (loss-of-function); and rs3853839/c.*881C>G (3’ untranslated region/UTR). Among girls carrying rs3853839 GC/GG, JSLE risk was increased in African/Caribbean girls (OR: 1.8; 95% CI: 1.2-2.9) and reduced in those of European ancestry (OR: 0.5; 95% CI: 0.4-0.7). The SLE-associated rs2302267 minor G allele associated with reduced leukopenia. The non-random rs79008/rs3853839 T-C/TT-CC haplotype associated with increased overall disease activity, and activity in the constitutional and musculoskeletal domains. Two SNPs lacked functional data in the literature: rs2302267/n.−20T>G and rs3853839/c.*881C>G. To study rs2302267, cells were transfected with reporter plasmids and promoter luciferase activity was reduced for the minor G allele when compared to the major T allele. Recruitment of the negative transcriptional regulator transcription factor 7-like 1 (TCF7L1) was higher for the G allele, suggesting reduced TLR7 expression and a protective effect against leukopenia. Cells transfected with TLR7 expression plasmids carrying the rs3853839 minor G allele showed increased TLR7 and IFN expression. As 3’UTRs are involved in fine-tuning gene expression through microRNAs, mRNA stability was investigated and found to be elevated in transcripts carrying the rs3853839 G variant.

Conclusion: Common TLR7 variants may influence jSLE risk and organ involvement in an ancestry-specific manner, supporting the rationale for genetic risk stratification and future consideration of TLR7-targeted treatments.

None declared

Pediatric Rheumatology, 23(2): PT077

E. Ogbu Grant/Research Support with: Supported by the Lupus Research Alliance Empowering Lupus Research Career Development Award, Consultant with: Cartesian Therapeutics, C. Treutel: None declared, A. Merritt: None declared, M. Wagner: None declared, H. Brunner Grant/Research Support with: Supported by National Institutes of Arthritis and Musculoskeletal Skin Diseases under Award Number P30AR076316, Consultant with: Abbie, Astra Zeneca-Medimmune, Merck, Novartis, R-Pharm, Sanofi, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lily, EMD Serono, Genzyme, GlaxoSmithKline, F.Hoffmann-La Roche, Johnson &Johnson, Speaker Bureau with: GlaxoSmithKlein, Novartis, Roche (speaker bureau includes symposia and expert witness for all)

Pediatric Rheumatology, 23(2): PT079

None declared

Pediatric Rheumatology, 23(2): PT080

None declared

Pediatric Rheumatology, 23(2): PT081

Results: Monocyte Siglec-1 expression, measured by flow cytometry was significantly elevated at disease onset in children with juvenile dermatomyositis JDMS (n=14) compared to controls (n=20): Siglec-1% AUC=0.986 (95% CI: 0.957–1, p<0.001); Siglec-1 ΔMFI AUC=1.0 (95% CI: 1–1, p<0.001). Expression levels substantially reduced with treatment in newly diagnosed patients-Siglec-1%: Friedman χ²(2)=13.55, p=0.001; Siglec-1 ΔMFI: Friedman χ²(2)=18.00, p<0.001-and in relapsed cases-Siglec-1 ΔMFI: Friedman χ²(2)=6.50, p=0.039. Monocyte Siglec-1 expression also remained significantly higher in patients in remission (n=27) compared to controls (Siglec-1 ΔMFI: AUC=0.681, 95% CI: 0.528–0.835, p=0.035). Isolated skin disease activity had an independent effect on monocyte Siglec-1 levels (Siglec-1%: U=61.0, p<0.05; Siglec-1 ΔMFI: U=77.0, p<0.05), whereas calcinosis did not (Siglec-1%: U=32.5, p=0.372; Siglec-1 ΔMFI: U=37.0, p=0.576). Clinical markers of muscle disease activity such as CMAS, MMT8, and MDAS, showed moderate correlations with Siglec-1 expression (r=0.4–0.52, p<0.05), while skin disease activity exhibited only weak correlations (r=0.2–0.3, p<0.05).

None declared

Pediatric Rheumatology, 23(2): PT082

Results: 216 patients had an HRCT result at time of the inclusion in the cohort. 76 of them were HRCT+. In both groups around 70% of the patients had diffuse subset. Median age at the time of the first non-Raynaud´s presentation was 10.8 and 11.3 in the HRCT+ versus HRCT- group. Median disease duration was around 2 years. Significantly more patients had decreased FVC<80% (44% versus 25%, p=0.011) and DLCO<80% (62% versus 36%, p=0.004) in the HRCT + then HRCT- group. Median MRSS was lower in the HRCT+ then HRCT- group (8.5 versus 12.5, p=0.031). Lower number of patients had sclerodactyly in the HRCT+ then HRCT- group (68% versus 81%, p=0.039). Nailfold capillary changes occurred more often in the HRCT+ then in HRCT- group (88% versus 73%, p=0.042). In the HRCT+ group pulmonary hypertension occurred more frequently (14% versus 2%, p=0.001). Oesophageal involvement was more frequent in the HRCT+ group (58% versus 34%, p=0.001). We could not find any significant difference regarding antibody profile, cardiac, renal and musculoskeletal 

None declared

Pediatric Rheumatology, 23(2): PT083

Data were analyzed using SPSS (v.27). Non-normally distributed variables were assessed with the Mann-Whitney U test, while categorical data were compared using the Chi-square or Fisher’s exact tests. Statistical significance was set at p<0.05.

Joint involvement was more prevalent in JDM (p=0.019), whereas cardiac involvement was more common in ADM (p=0.038). Calcinosis occurred in 33.3% of JDM cases but only in one ADM case (p<0.001). Among the myositis-specific and myositis-associated antibodies, Anti-NXP2 and Anti-TIF1g were more prevalent in JDM, whereas Anti-Mi2, Anti-Jo1 and Anti-SSa were more common in ADM.

Acute phase reactants were higher in ADM at both diagnosis and last visit (p<0.005 for all). While MRI was more frequently utilized to demonstrate myositis in JDM cases, biopsy, EMG and PET/CT were more commonly employed in ADM (p<0.001 for all)

Glucocorticoids were initiated in nearly all patients (>98%) in both groups. At follow-up, most ADM patients remained on treatment, while only 11.6% of JDM patients were still receiving steroids (p<0.001). Malignancy was observed in 26.2% of ADM cases, whereas no such association was found in JDM (p<0.001). The hospitalization and mortality rates were higher in the ADM group (p<0.001 for both).

These differences emphasize that JDM should not be approached merely as the pediatric form of ADM, but as a distinct clinical entity requiring tailored management strategies.

None declared

Pediatric Rheumatology, 23(2): PT084

This study was supported by The Scientific and Technological Research Council of Türkiye (TÜBİTAK) under the 2219 International Postdoctoral Research Fellowship Programme.

None declared

Pediatric Rheumatology, 23(2): PT085

Results: A cohort of 33 patients was analyzed (7 males, 21%), with 3 having a family history of SLE. The mean age at diagnosis was 13.8 years (SD 2.7), with a mean follow-up of 14.4 years (SD 5.0). Median transition was 4 months (IQR 2-10). Transition occurred over several joint visits with both pediatric and adult rheumatologists. A psychologist was regularly included in the transition. Cumulatively, the most frequent clinical classification criteria were malar rash (24/33), arthritis (21/33) and photosensitivity (15/33). Lupus nephritis was biopsy-proven in 11 patients (class III: 3; IV: 6; V: 2). Frequent laboratory criteria included anti-dsDNA antibodies (28/33) and cytopenia (26/33), mostly leukopenia (23/33). Hemolytic anemia was seen in 9 patients, mostly autoimmune, and one microangiopathic due TTP. Secondary APS was diagnosed in one patient. Damage (SDI ≥1) occurred in 15/33 patients, with SDI ≥2 in 6: Most frequent damage types included cataract (4/15); deforming arthritis (3/15); osteoporosis with fracture, muscle atrophy, nephrotic-range proteinuria (2/15 each). In 10/15 patients, damage was observed at pediatric age (<18 years). Damage-free survival (DFS) was 71% at 5 years and 59% at 10 years, much lower in those with lupus nephritis. Renal disorder and photosensitivity were more frequent in the damage group (p=0.026 and p=0.016). No differences were observed in disease activity (at diagnosis or one year after) or most treatments, except cyclophosphamide, which was more common in the damage group (10/15 vs. 1/18, p=0.026).

None declared

Pediatric Rheumatology, 23(2): PT086

Methods: We included patients newly diagnosed with JSSc, per PRES/EULAR/ACR criteria¹ and/or EULAR PRES adult SSc criteria², at our Centre from 2007 onward. Demographic and clinical data were retrospectively collected from medical records. Cardiologic assessment included conventional echocardiography, strain rate echocardiography (STE), and CMR with contrast and optional T1/T2 mapping.

Results: 32 patients, 18 (56.3%) females, mean age at onset 10.7 years (range 4.2–15.9), were enrolled. Seventeen had diffuse JSSc, 7 limited, 5 sine scleroderma, and 3 overlap syndromes. Four patients (12.5%) had symptomatic cardiac involvement: three had left ventricular dysfunction and arrhythmias requiring ICD placement; one had pulmonary hypertension with right ventricular dysfunction; all had unfavorable outcomes (3 transplants, 1 death). Standard echocardiography and EKG were performed in all but resulted altered only in the symptomatic patients. STE revealed GLS abnormalities in 7/26 (26.9%) of patients undergoing this assessment: 3 symptomatic with Left Ventricular Ejection Fraction (LVEF) reduction and 4 asymptomatic. CMR was performed in 21 patients, including two symptomatic, and was abnormal in 7 (33%). CMR-measured LVEF was reduced in two with known dysfunction. Fibrosis (LGE+) was found in 4: two symptomatic, two asymptomatic with normal LVEF and GLS. T1/T2 mapping was abnormal in 3 of 9 in whom was performed, all asymptomatic with no prior cardiac findings. Abnormal left atrial strain was available for 10 patients and found altered in 1 asymptomatic patient with known reduction of GLS.

None declared

Pediatric Rheumatology, 23(2): PT087

Introduction: Nailfold videocapillaroscopy (NVC) represents a reliable, non-invasive tool for the diagnosis of several adult rheumatic diseases, and the assessment of peripheral microvascular abnormalities may serve as a potential biomarker of disease severity in these patients¹. However, data on NVC findings and their clinical significance in pediatric patients are limited.

Raynaud’s phenomenon (PRP) and connective tissue diseases (CTDs). In juvenile CTDs, we aimed to assess potential associations between NVC features and clinical or organ involvement.

Methods: NVC was performed in patients followed at the Paediatric Rheumatology Unit of our hospital for PRP or a definite diagnosis of CTD. For each child, 32 images were acquired, and microvascular alterations were analysed and classified as either non-specific or scleroderma patterns (early, active, and late) by two independent observers. A semi-quantitative rating scale from 0 to 3 was adopted to score six capillary abnormalities² (enlarged capillaries, giant capillaries, microhaemorrhages, loss of capillaries, microvascular disarray, and capillary ramifications) and calculate an average score. The capillary density score was identified as “avascular score”.

Results: A total of 800 NVC images from 50 subjects (30 females; mean age 16.4±4.0 years) were evaluated. Scleroderma pattern was significantly more frequent in juvenile systemic sclerosis (jSSc) compared to both juvenile dermatomyositis and PRP (p=0.003 and p<0.001, respectively). In terms of capillaroscopic alterations, differences were observed only in PRP vs. jSSc for reduction of capillary density (p<0.001) and presence of giants (p=0.01). Scleroderma pattern was associated with skin sclerosis (21/25 vs. 0/9; p<0.001), digital ulcers (8/25 vs. 0/9; p=0.07) and gastrointestinal involvement (17/25 vs. 1/9; p=0.006). Avascular score was higher in children with interstitial lung disease (ILD) than in those without (p<0.05). Patients with severe reduction of capillary density (≤4/mm) were more likely to have ILD (5/10 vs. 4/13; p=0.02). Multivariate logistic regression analysis showed that the association between severe reduction of capillary density and ILD was independently of the presence of scleroderma pattern (OR 3.2; 95%CI 0.9-11.6) and skin fibrosis (OR 2.7; 95%CI 0.8-9.3).

None declared

Pediatric Rheumatology, 23(2): PT089

NIH Intramural Research Program (IRP). This work could not have been accomplished without the aid of the following organizations: The NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the Arthritis Foundation (AF), and the Cure JM Foundation (Cure JM). We would also like to thank all participants and hospital sites that recruited patients for the CARRA Registry.

This study utilized data collected in the CARRA Registry. The views expressed are the authors’ and do not necessarily represent the view of CARRA.

B. Yi: None declared, M. Sherman: None declared, K. Ardalan Grant/Research Support with: Rheumatology Research Foundation, Childhood Arthritis & Rheumatology Research Alliance/Arthritis Foundation, Chan Zuckerberg Initiative, Cure JM Foundation, Patient-Centered Outcomes Research Institute, National Institutes of Health/Technical Resources International., Consultant with: Cabaletta Bio (scientific advisory board, paid consulting), Childhood Arthritis & Rheumatology Research Alliance (Vice Chair JDM Committee paid consultant position), Paid Instructor with: Rheumatology Research Foundation Pediatric Visiting Professorship travel reimbursement and honorarium 2024-2025, American College of Rheumatology travel reimbursement for invited speaker 2024, SingHealth - honorarium (paid to my institution, not directly to me) for grant pre-review program, S. Kim: None declared, S. Tarvin: None declared, H. Kim Grant/Research Support with: Intramural Research Program of the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) (AR041215)., Consultant with: Juvenile myositis expert panel member for Cabaletta Bio (unpaid), part of NIAMS CRADA with provision of drug (deucravacitinib) with Bristol Myers Squibb, previous part of NIAMS CRADA with study support and drug (baricitinib) with Eli Lilly and Company., B. Feldman: None declared

Pediatric Rheumatology, 23(2): PT090

None declared

Pediatric Rheumatology, 23(2): PT091

None declared

Pediatric Rheumatology, 23(2): PT092

Results: The study included 24 participants: nine homozygous patients, four heterozygous symptomatic patients, five asymptomatic heterozygous carriers, one asymptomatic homozygous individual, and five healthy controls. Among those with the G47R mutation (n=9), four were homozygous, two heterozygous with symptoms, and three heterozygous without symptoms. Of the heterozygous symptomatic individuals, three exhibited a vasculitic phenotype with stroke; two had the G47R/- mutation, one had H335R/-. miR-185-5p expression was significantly elevated in homozygous and heterozygous patients with clinical findings compared to carriers and healthy controls (p=0.018). Furthermore, patients with severe disease showed higher miR-185-5p expression than those with mild/moderate or no symptoms (p=0.062). Stroke patients had markedly increased expression compared to non-stroke individuals (p<0.001).

This project was supported by Hacettepe University BAP Coordination Unit (Project No: 323S389) and the TÜBİTAK under the 1002-B support program. ‘We would like to express our sincere gratitude to the Scientific and Technological Research Council of Turkey (TÜBİTAK) for their invaluable support.’

None declared

Pediatric Rheumatology, 23(2): PT093

Methods: Retrospective-prospective, observational, international multicenter study, supported by the 2020 PRINTO/PReS grant. KD patients, diagnosed according to the AHA criteria were enrolled from April 2022 to January 2024. Retrospective data were also collected for patients diagnosed from January 1^st, 2015.

Results: 723 KD patients were included across 19 paediatric rheumatology units. 62.0% (448) were male, with a median age of 2.40 years (IQR 1.19–4.30). The cohort comprised 57.9% (418) Caucasian, 20.5% (148) Indian, 14.2% (102) Asian, 5.3% (38) African, and 2.4% (17) Hispanic patients. Complete KD was diagnosed in 396 patients (54.8%), incomplete KD in 296 (41.0%), and atypical features were noted in 18 (2.5%). KD shock syndrome was observed in 12 patients (1.7%). Coronary ectasia was observed in 87 cases (12%), and coronary aneurysms in 181 (25.1%). IVIg resistance rate was 19.8% (143). No significant differences in ethnicity or age were observed between IVIg responders and non-responders. However, extremity desquamation (p=0.017), musculoskeletal signs (p=0.006), cardiac involvement (p < 0.001), longer fever duration (p<0.001) and long-term sequelae (p<0.001) were significantly more common in the IVIg-resistant group. Higher ESR (p = 0.002), neutrophil count (p=0.021), ALT (p=0.001), and AST (p<0.001) values were more commonly observed in IVIg-resistant patients. The Kobayashi score demonstrated a balanced accuracy of 55.3% with sensitivity and specificity of 71.3% and 39.2%, respectively. The Kawanet score showed a balanced accuracy of 53.3% with a sensitivity and specificity of 16.1% and 90.4%, respectively. When analysed across the three main ethnic subgroups—Caucasian, Indian, and Asian—the performance of both scores remained consistent with that observed in the overall cohort.

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Pediatric Rheumatology, 23(2): PT094

Results: Among 148 patients (83% female, median age at diagnosis 13.1 years [IQR 10.9–14.6], median follow-up duration 6.1 years [IQR 3.2 - 8.6]), 135 (91%) achieved at least one cLLDAS episode. Of these, 67 (49.6%) experienced 91 flare episodes, with 20 (29.9%) having more than one flare. Median duration of initial cLLDAS before first flare was 17.2 months (IQR 7.2-30.0), while median duration of subsequent cLLDAS remained similar before flares (14.4 months, IQR 10.3–18.5, p=0.958).

Kaplan-Meier analysis demonstrated significantly shorter flare-free intervals among patients with neuropsychiatric involvement (log-rank p=0.003), discoid rash (p = 0.040) and photosensitivity (p=0.005). Cox regression identified neuropsychiatric involvement (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.35–4.69, p=0.004) and photosensitivity (HR 2.13, 95% CI 1.21–3.73, p=0.008) as independent predictors of time to flare. The duration in first cLLDAS did not correlate with duration of first flare (p=0.683) nor flare severity (p=0.942).

Poisson regression showed shorter duration in first cLLDAS (Incidence Rate Ratio [IRR] 1.05 per decreasing month, 95% CI 1.03-1.06, p<0.001) and older age at diagnosis (IRR 1.53 per increasing year, 95% CI 1.29-1.80, p<0.001) were associated with higher flare rate when accounting for follow-up duration.

None declared

Pediatric Rheumatology, 23(2): PT095

Anemia is present in more than 50% of cases and several patients with DADA2 present with pure red cell aplasia and transfusion dependence, mimicking Diamond-Blackfan anaemia. Hematopoietic stem cell transplant may be needed to treat refractory cytopenia. Bone marrow biopsy typically demonstrates hypoplasia of the affected lineage(s), suggesting a defect in cell production.

The objectives of the present work are: (i) to quantify and characterize hematopoietic progenitor cells on bone marrow samples of DADA2 patients, (ii) to test the apoptosis of CD34+cells, (iii) to explore if in the bone marrow there is an inflammatory milieu by testing the presence of proinflammatory cytokines in BM plasma and (iv) to assess the effect of anti-TNFα, human recombinant ADA2 or Eltrombopag on the growth of BM patients’ progenitors.

BFU-E (Burst-Forming Unit-Erythroid) and CFU-GM (Colony-Forming Unit-Granulocyte Macrophage) were analyzed by flow cytometry. Apoptosis and pro-inflammatory cytokines were measured by flow cytometry.

None declared

Pediatric Rheumatology, 23(2): PT096

Introduction: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive monogenic vasculitis syndrome.It typically presents in early childhood with clinical features such as vasculitis, stroke, hematological abnormalities, and immune dysregulation.Diagnosis of DADA2 is based on the presence of pathogenic variants in the ADA2 gene and low serum ADA2 enzyme activity.However, due to the high cost and time-consuming nature of genetic testing, enzymatic activity measurement is increasingly important, particularly for screening and differential diagnosis in symptomatic patients.

Results: Among 83 symptomatic patients, ADA2 enzyme levels varied significantly based on genetic findings. Patients with biallelic ADA2 variants (n=26) had a median enzyme level of 6.6 U/L (range: 2.8–16.4; IQR: 4.5–8.8), while monoallelic variants (n=10) had a higher median 9 U/L (range: 5.8–27.4; IQR: 6.5–12.3). Patients without any detected pathogenic variants detected (n=47) showed the highest median ADA2 levels at a median 13.1 U/L (range: 3–30.2; IQR: 8.9–17.7). The difference among these three groups was statistically significant (p < 0.001). Comparison between symptomatic (n=10) and asymptomatic (n=10): monoallelic carriers revealed no significant difference in enzyme levels (median 9 U/L vs. 11.2 U/L, p=0.65). In evaluating the diagnostic performance of ADA2 enzyme activity, a threshold of <8 U/L predicted the presence of biallelic mutation with a sensitivity of 79% and a specificity of 69.2%.

None declared

Pediatric Rheumatology, 23(2): PT097

Results: 401 patients from the UK JSLE Cohort Study were included, contributing 4,602 visits. In univariable PWP analyses of patients who had attained either cCR and cCR-0, each unit change in both anti-dsDNA (cCR model HR 1.0004, 95% CI 1.0001–1.0007, p=0.0035, cCR-0 model HR 1.0004, 95% CI 1.0001–1.0007, p=0.0048) and ESR levels (cCR model HR 1.0046, 95% CI 1.0028–1.0063, p<0.0001, cCR-0 model HR 1.0050, 95% CI 1.0032–1.0070, p<0.0001) was associated with significantly increased risk of subsequent flare. In contrast, C3 and C4 levels were not statistically significantly associated with flare risk (p>0.05). In the multivariable model, both anti-dsDNA and ESR remained independently associated with risk of subsequent flare in the cCR (anti-dsDNA: HR 1.0005, 95% CI 1.0001–1.0008, p=0.0078; ESR: HR 1.0041, 95% CI 1.0020–1.0063, p=0.0002) and cCR-0 (anti-dsDNA: HR 1.0004, 95% CI 1.0000–1.0008, p=0.0188; ESR: HR 1.0045, 95% CI 1.0023–1.0067, p<0.0001) models. In the univariable model of patients in cLLDAS, ESR was also significantly associated with subsequent risk of flare (HR 1.0047, 95% CI 1.0029–1.0065, p<0.0001).

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Pediatric Rheumatology, 23(2): PT098

Results: There were 546 IgAV patients with a male dominance. A total of 40 (7.3%) patients had a relapse related to IgAV after an asymptomatic period of at least 6 months (Group 1). Patients’ characteristics and laboratory features were presented in Table 1. Male predominance, diarrhoea, bloody stool, bloody vomiting, gastrointestinal involvement, testicular involvement, WBC, creatinine, and pediatric vasculitis assessment scale (PVAS) at first visit were significantly higher, while mean age at diagnosis of IgAV was significantly lower in Group 1 than Group 2 (p=0.033, p=0.015, p=0.013, p=0.045, p=0.047, p=0.003, p=0.012, p=0.012, p=0.000, and p=0.015, respectively). The most recurrent clinical finding was purpuric skin eruption (65%) (Table 2). Recurrence free survival of Group 1 was illustrated in Fig1. Logistic regression analysis for the prediction of recurrence of IgAV was shown in Table 3. Male sex, diarrhoea, testicular involvement, Hb value, and PVAS were found as independent risk factors for the prediction of IgAV recurrence in the long-term follow-up (p=0.033, p=0.015, p=0.003, p=0.025, and p=0.005, respectively).

None declared

Pediatric Rheumatology, 23(2): PT099

Among patients with CAA, the proximal RCA showed the highest initial Z-score (median 3.48 [IQR 2.6–7.6]). Despite a frequent transient increase in coronary Z-scores around day 7 to 14 after ANK initiation, the median time to normalization across all coronary segments was 5 days (IQR 0–181; n=13). At last follow-up, only 3 patients had persistent CAA.

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Pediatric Rheumatology, 23(2): PT100

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Pediatric Rheumatology, 23(2): P003

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Pediatric Rheumatology, 23(2): P004

Results: This study included 1205 PFAPA patients. Tonsillectomy was recommended for 332 patients, and 167 underwent the procedure. After tonsillectomy, 69.5% of patients experienced complete resolution of symptoms, while 26% had partial recovery. Overall, 89.2% of patients were satisfied with the procedure. The absence of exudative tonsillitis during attacks, along with the presence of pharyngitis or abdominal pain, were significant factors influencing a decision to recommend tonsillectomy. Multivariate analysis showed exudative tonsillitis was a negative predictor (p=0.012), while pharyngitis (p < 0.001) and abdominal pain (p < 0.001) were positive predictors. Longer attack duration was also associated with tonsillectomy (p=0.043).

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Pediatric Rheumatology, 23(2): P005

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Pediatric Rheumatology, 23(2): P006

Considerably less information is available on arbovirus in children with KD. However, some observational studies have reported an overlap between KD outbreaks and seasonal peaks of arboviral infections, suggesting the possible role of these pathogens as triggers of KD.

In the beginning of the year 2025, there was a massive outbreak of Chikungunya infection on the Reunion Island with many children affected. Paediatric presentations for Chikungunya infection usually include high fever, skin, joint and neurological manifestations.

Although Kawasaki disease is known to be triggered by certain virus, no cases of kawasaki-like disease have been yet described in these patients. 

Two weeks after the beginning of the fever, he developped inflammation of both cervical and inguinal lymph nodes which a pustular raash that led him to the emergency room Saint Pierre University Hospital in La Reunion. At arrival he had a major blood inflammation with a CRP of 284mg/l with anemia 11g/L and hepatic cytolysis (<2N). During his hospitalisation, in addition to his fever, the other major criteria of kawasaki disease were rapidly observed: supracentimetric cervical and inguinal lymphnode, cheilitis with strawberry tongue, conjunctival hyperemia and erythematous rash all over his body.

Blood tests revealed : anemia 11g/dl, negative EBV PCR, negative viral multiplex PCR, negative Chikungunya/Leptospirosis/Dengue PCR.

The Chikungunya serology came back positive with a profile suggesting a recent infection: IgM positive at 20 and IgG positive at 2.9. Dengue serology was negative. COVID serology was positive for IgG not IgM.

Bacteriological and mycological swab from the pustules was positive for Candida albicans. A Chest X-ray showed no infectious focus or effusion. Urinalysis showed aseptic leukocyturia. A cardiac ultrasound was then performed, showing dilation of both coronary arteries with Z-score>2.The patient was administered intravenous immunoglobulin (IVIG) 2g/kg, corticosteroids 2mg/kg/j IV and aspirin. The fever and all of the other symptoms resolved after 1 dose of IVIG. The CRP went down quickly and was negative 6 days after the begining of IVIG.

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Pediatric Rheumatology, 23(2): P002

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Pediatric Rheumatology, 23(2): P007

Conclusion: Though this is a small retrospective observational study, we demonstrate 84% of children with PFAPA reported improvement or cure following tonsillectomy + colchicine.

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Pediatric Rheumatology, 23(2): P008

Introduction: Chronic Nonbacterial Osteomyelitis (CNO) is an aseptic inflammatory skeletal disease, that primarily affects the pediatric population and rarely adults^(1,2). The presentation of CNO is tipically non-specific, with local bone pain, and sometimes with other clinical features including low grade fever, swelling, warmth, focal tenderness, and unspecific radiological findings. For this reason, the diagnostic process is one of exclusion⁽²⁾. First-line therapeutic agents are non-steroidal anti-inflammatory drugs (NSAIDs) while use of corticosteroids, disease-modifying antirheumatic agents and anti-TNF agents have also been reported. In refractory cases, there is increasing evidence on the use of bisphosphonates⁽³⁾.

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Pediatric Rheumatology, 23(2): P009

Methods: A systematic search of the literature was conducted in PubMed/Medline, Cochrane, and Web of Science databases according to the PRISMA guideline. The search involved the articles published in English up to March 1^st, 2025, with no filter set for publication date. Papers detailing FMF patients less than 18 years of age with clinical neurological involvement or assessing neurological outcomes were selected. All study designs were considered, including case series and case reports. When there was a clear distinction between patients aged less than 18 years and adults only pediatric patients were included in the dataset. Given the multiple classification criteria available for FMF, all patients diagnosed based on the authors’ decision were included. Non-peer reviewed content such as congress abstracts, papers published in languages different than English, and papers not distinguishing between pediatric and adult patients were excluded. The following data were extracted from the articles: first author name, demographic data, study design, FMF classification criteria, characteristics of neurological involvement, MEFV genotype, diagnostic work-up, treatment, and outcome.

Results: Sixty-four studies, comprising 4753 children with FMF, were included. Approximately 33.9% of them had some degree of neurological involvement and were categorized into six groups: headache, seizures, demyelinating disorders, cochlear/vestibular involvement, optic nerve/retinal abnormalities, and other manifestations. Headache emerged as the most common neurological symptom in children with FMF, affecting 766 (female to male ratio: 1.28) out of 3143 children (24.4%) and was often associated with FMF flares, with frequencies ranging from 4.8% to 58.8%. Reports describe various headache phenotypes, spanning from migraine with and without aura (107 children diagnosed with migraine, 73 with probable migraine) to tension-type headaches (TTH) and secondary headache syndromes such as pseudotumor cerebri and cerebral vasculitis. Seizures were reported in 127 (female to male ratio: 0.78) out of 1890 patients from 12 studies. Reports and cohort studies describe a spectrum of seizure types that mostly occur during FMF flares and are rarely accompanied by electroencephalographic abnormalities. Indeed, febrile seizures emerged as relevant manifestations, as expected in children with FMF since they have more and high fever during childhood, with frequencies ranging from 1% to 15.2%. Demyelinating disorders, such as multiple sclerosis, were rarely reported, mostly in female adolescents with the homozygous M694V MEFV genotype. A few studies have shown that cochlear and retinal involvement due to chronic and recurrent inflammation may contribute to sensorineural hearing loss and retinal abnormalities. However, the causality of neurological involvement in children with FMF has not been shown and a report bias cannot be ruled out. 

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Pediatric Rheumatology, 23(2): P010

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Pediatric Rheumatology, 23(2): P011

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Pediatric Rheumatology, 23(2): P012

Results: Among 117 patients (44.4% female), 73 (62.4%) and 84 (71.8%) achieved FMF50 response at 3 and 6 months, respectively. The ISSF, AIDAI, and Pras scores were significantly higher in non-responders (p<0.001). Elevated CRP (OR 1.035, 95% CI 1.002–1.070, p=0.038), ISSF (OR 1.703, 95% CI 1.135–2.557, p=0.010), and AIDAI (OR 1.253, 95% CI 1.053–1.491, p=0.011) at three months were significantly associated with FMF50 non-response at sixth month. Multivariate analysis identified high ISSF (OR 1.745, 95%CI 1.129–2.698, p=0.012) and AIDAI (OR 1.265, 95%CI 1.056–1.514, p=0.011) as independent predictors. Although the TURPAID score was not significantly associated with the FMF50 response, patients with higher TURPAID scores tended to have lower FMF50 achievement rates. APRs were significantly correlated with ISSF, Pras, and AIDAI. Kappa coefficients revealed poor agreement among the activity scores (Kappa values = 0.157 to –0.048).

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Pediatric Rheumatology, 23(2): P013

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Pediatric Rheumatology, 23(2): P014

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Pediatric Rheumatology, 23(2): P015

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Pediatric Rheumatology, 23(2): P016

Results: In total, 2249 patients (1519, FMF; 271, TRAPS; 254, CAPS; 205, MKD) from 32 countries were included in the study. 51.9% (n=1168) were male and 64.4% were Caucasian-European (n=1448). The median age at disease onset was 3.1[IQR 1-7.8] overall and, 3.6 [IQR 1.6-8] for FMF, 4.4 [IQR 1-13.4] for TRAPS, 1.2 [IQR 0-6.1] for CAPS and 0 [IQR 0-2.6] for MKD. The median age at diagnosis was 8 [IQR 4.1-16.5] overall and, 7 [IQR 4-13.2] for FMF, 16.1 [IQR 6.2-38.4] for TRAPS, 12.3 [IQR 4.3-30.5] for CAPS and 7.4 [IQR 3.7-15.2] for MKD. The median diagnostic delay in years was 2.9 [IQR 1-8.3] overall and, 2.3 [IQR 0-5.7] for FMF, 5.8 [IQR 1.4-21] for TRAPS, 5.8 [IQR 2-20] for CAPS and 5 [IQR 1.6-14.2] for MKD. Frequency of having at least one concomitant disease was 17.7% (n=399) and 14.9% (n=334) had at least one complication. Diagnostic delay was shorter in patients with FMF compared to others (p<0.001). There was no statistically significant difference in diagnostic delay between males and females (2.9 [IQR 1-8.2] and 3 [IQR 1-8.7] years, respectively, p=0.82). However, diagnostic delay was significantly higher in patients with at least one concomitant disease (4.2 [IQR 1.4-10.2] vs 2.7 [IQR 1-7.9] years, p<0.001) and patients with at least one complication (8.2 [IQR 2.4-24.2] vs 2.6 [IQR 1-6.5] years, p<0.001).

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Pediatric Rheumatology, 23(2): P017

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Pediatric Rheumatology, 23(2): P018

Introduction: Recognizing the value of predictive models in guiding treatment strategies, we developed the PREDICT-crFMF score—a novel tool designed to predict colchicine resistance in children with FMF. This model was externally validated in a large, independent cohort, demonstrating robust performance with a sensitivity of 82% and specificity of 79%.

Objectives: To prospectively validate the PREDICT-crFMF score and assess its performance in predicting colchicine resistance based on patients’ baseline characteristics.

Methods: Data from patients presenting for the first time after the introduction of the PREDICT-crFMF scoring system were analyzed. Preliminary findings from two tertiary pediatric rheumatology centers were reviewed. Eligible patients were diagnosed after 2022, were under 18 years of age at diagnosis, and had a minimum follow-up of 6 months. The score's performance was evaluated using a predefined cut-off value of 9, derived from logistic regression modeling.

Results: Between January 2023 and December 2024, 83 patients were admitted to the paediatric rheumatology outpatient clinics and newly diagnosed with FMF. Among these, 73 patients (88%) showed a favorable response to colchicine treatment, while 10 patients (12%) met the criteria for colchicine-resistant FMF (cr-FMF), having experienced more than three clinically and laboratory-confirmed inflammatory attacks within a six-month period despite regular colchicine use. Approximately half (43.4%) of the entire cohort and 60% of the cr-FMF patients were female.The cr-FMF group and the responsive group were similar in terms of age at diagnosis (p = 0.75). The follow-up period was significantly longer in the resistant FMF group (p = 0.03).At least one pathogenic exon 10 mutation was found in 90.4% (n=74) of the patients. All patients with colchicine resistance had exon 10 homozygous or compound heterozygous mutations on exon 10. In colchicine-responsive patients, 50.7% had exon 10 homozygous or compound heterozygous mutations on exon 10 and 49.3% had other exon mutationson MEFV gene.

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Pediatric Rheumatology, 23(2): P019

Introduction: Heterozygous pathogenic mutations in the TNFAIP3 gene lead to haploinsufficiency of the A20(HA20)protein,which is associated with a complex inflammatory disorder at the intersection of autoinflammation and autoimmunity.To date there is little data available regarding paediatric presentation.

Methods: We conducted a retrospective analysis of HA20 patients in France, utilizing both the SOFREMIP(Francophone Society of Paediatric Rheumatology and Inflammatory Medicine)mailing list and data from the referent.Inclusion criteria were disease onset <18 years, the presence of a TNFAIP3 mutation,and the reasonable exclusion of other similar conditions.Data on demographics, clinical and laboratory features,disease progression and treatment efficacy were analysed and compared to previous reports in literature.

Results: We included 20 patients(45%female,90% Caucasian)from 13 non-consanguineous families, carrying distinct TNFAIP3 mutations.The median age at disease onset was 4 years(1 month–17 years).Age at onset was significantly lower in boys compared to girls(2.5 vs. 6 years,p = 0.004).Clinical presentations varied widely among patients and among siblings carrying the same mutation.At disease onset,65% of patients presented with oral ulcers and 20% with genital ulcers.Over the disease course,these proportions increased to 80% and 60%,respectively.Other frequent features included fever(70.6%)and gastrointestinal manifestations, such as abdominal pain(63.2%),diarrhoea(45%),and colitis(20%).Arthralgia was significantly more frequent in children with disease onset <5 years of age(p = 0.015).Acute-phase reactants were moderately elevated during flares(medianCRP 93 mg/L vs. 7 mg/L out of flares).None of the patients suffered from a definitive rheumatic autoimmune disease, although 40%of patients had positive ANA titers,and 14.3% tested positive for rheumatoid factor.Colchicine monotherapy was effective in 20% of patients.Among biological DMARDs,infliximab was the most effective,with a 100% response rate (4/4 patients).

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Pediatric Rheumatology, 23(2): P021

Methods: This study is part of the Juvenile Inflammatory Rheumatisms (JIR)-CliPS project, an international cross-sectional online survey led by the JIR-network (www.jircohorte.org) and conducted on 5 JIR medical conditions by a consortium of pediatric and adult rheumatologists and immunologists from Europe and beyond. Questionnaires on diagnosis, treatment and follow-up were sent to physicians taking care of PFAPA patients. Data were exported on September 18, 2024, yielding 313 responses from 41 countries. After excluding incomplete or irrelevant entries, 164 responses specifically addressing CS use in PFAPA were analyzed. The current analysis focused on 15 questions on CS use in patients with PFAPA. Analyses were conducted to explore associations between responses and factors such as professional experience, Gross Domestic Product (GDP), and Health Assessment Questionnaire (HAQ) indices.

Regarding CS prescription practices during flares, 60% (n=99) administered CS once or twice per flare. Child-friendly formulations, such as oral solutions, were available to 73% (n=119) of participants. Nearly half (49%, n=80) reported using CS no more than 5–10 times annually. Most participants (81%, n=133) observed clinical improvement within 3–4 hours of administration, or at most within 12 hours. Six CS formulations were identified and standardized for analysis, with no significant preference differences linked to professional experience. 32% (n=53) routinely prescribed CS at flares, while 68% (n=111) did so non-routinely. Complex Medical Reasons (such as combinations involving attack frequency and severity) tend to appear more frequently in high GDP categories. (p<0.05).

Criteria for nonresponse to CS included the need for more than two doses (50.6%, n=83), lack of fever improvement within 24 hours (38.4%, n=63) or 12 hours (36.6%, n=60), recurrence of fever after CS administration (35.4%, n=58), and the requirement for more than one dose of CS (12.8%, n=21). Regarding indications for alternative treatments, 57% (n=93) cited severe attacks, 36% (n=59) flare intervals shorter than two weeks, 27% (n=44) highlighted flare intervals shorter than three weeks or attacks persisting beyond three weeks, and 4% (n=6) noted attacks lasting over one year.

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Pediatric Rheumatology, 23(2): P022

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Pediatric Rheumatology, 23(2): P023

Methods: This study is part of the Juvenile Inflammatory Rheumatisms (JIR)-CliPS project, an international cross-sectional online survey led by the JIR-network (www.jircohorte.org) and conducted on 5 JIR medical conditions by a consortium of pediatric and adult rheumatologists and immunologists from Europe and beyond. Questionnaires on diagnosis, treatment and follow-up were sent to physicians taking care of PFAPA patients. The current analysis focused on 12 questions on genetic testing in patients suspected of PFAPA. We analyzed the responses according to the participant's professional profile and geographical origin. Based on the results, we propose a decision algorithm for genetic testing in patients suspected of PFAPA.

Two thirds of the participants reported occasionally performing genetic tests, 15% never, 8% always, and 12% often. Sixty-one percent favored autoinflammatory gene panels, and 20% preferred single-gene tests (Table 1). The choice of the test did not significantly differ according to the country’s GDP. Physicians with < 10 years of experience preferred single-gene tests compared to those with > 10 years (21 vs. 7, p<0.001). Atypical presentation was the most reported reason for performing a genetic test. A variant of unknown significance (VUS) was considered as a causative variant in 73% of the responders, mainly based on expert opinion and compatible clinical findings. Based on the results we have drawn a flowchart representing the different strategies used by the participants.

Trial registration identifying number: Funding

This article/publication is based upon work from COST Action CA21168 – Improving outcome of Juvenile Inflammatory Rheumatism via universally applicable clinical practice strategies (JIR-CliPS), supported by COST (European Cooperation in Science and Technology) - www.cost.eu.

H. Sönmez Grant/Research Support with: This article/publication is based upon work from COST Action CA21168 – Improving outcome of Juvenile Inflammatory Rheumatism via universally applicable clinical practice strategies (JIR-CliPS), supported by COST (European Cooperation in Science and Technology) - www.cost.eu., C. Vinit: None declared, N. Toplak: None declared, O. Boyarchuk: None declared, M. Gattorno: None declared, G. Ozomay Baykal: None declared, K. Pateras: None declared, E. Batu: None declared, F. Hofer: None declared, C. JURCUT: None declared, M. Rodrigues: None declared, O. Gillaux: None declared, K. Laskari: None declared, M. Santos Faria: None declared, R. Craveiro da Costa: None declared, M. Hofer: None declared

Pediatric Rheumatology, 23(2): P024

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Pediatric Rheumatology, 23(2): P025

There are few series describing the clinical and genetic characteristics of FMF, as well as its management and progression in Spain.

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Pediatric Rheumatology, 23(2): P026

In recent years, interleukin-18 (IL-18) has attracted attention as a promising biomarker of inflammatory activity, a tool for patient stratification, and a potential therapeutic target in various immune-mediated inflammatory diseases.

Elevated IL-18 levels were found in 60 (77%) patients (me 357.8 [215.3; 1032.9] pg/mL), including 27 (68%) in remission (me 309.4 [207.9; 443.8]) and 28 (76%) with active disease (me 418.5 [249.6; 1385.6]). IL-18 levels were higher in patients with active disease, though the difference was not statistically significant. Elevated IL-18 levels were more frequent in FMF (81%) compared to CAPS (69%) and TRAPS (42%) (p=0.03). Median IL-18 levels were significantly higher in FMF (553.1 [308.9; 1516.4]) than in CAPS (347.5 [216.3; 396.1]) and TRAPS (178.6 [156; 278.4]) (p<0.05), and higher in CAPS than in TRAPS (p=0.028). In active disease, IL-18 levels were higher in FMF than in CAPS (p=0.003). No significant differences were observed between groups during remission. Comparing ferritin and IL-18 levels in active vs. remission subgroups, IL-18 elevation was observed in 76% of patients with low ferritin (<20 ng/mL) during active disease and 65% in remission. However, the differences were not statistically significant.

Among CAPS patients, higher IL-18 levels were found in those with low ferritin (median 380.6 [303.5; 640.2] pg/mL) compared to those with normal ferritin levels (median 216.8 [153.1; 333.2] pg/mL). This association was not observed in FMF or TRAPS.

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Pediatric Rheumatology, 23(2): P027

Introduction: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease caused by mutations in the MEFV gene. While the clinical phenotype is well characterized in homozygous or compound heterozygous patients (confirmed FMF, cFMF), some heterozygous individuals also present with FMF-like symptoms requiring treatment (symptomatic heterozygotes, HetFMF). The distinction between these two populations and their clinical trajectories remains poorly understood.

Fever duration was similar (2–3 days). Compared to cFMF, HetFMF patients had lower frequencies of abdominal pain (75% vs 90%, p=0.04), chest pain (33% vs 62.5%, p=0.001), myalgia (36.6% vs 65.6%, p<0.01), and erysipelas-like erythema (8.6% vs 26.6%, p=0.007). Orchitis and purpura were reported only in cFMF. During attacks, aphthous ulcers (14% vs 11%) and pharyngitis (20% in both) were reported with similar frequency. Cervical lymphadenopathy was also observed in both groups.

Between flares, HetFMF more often had aphthous ulcers (19.4% vs 9.4%, p=0.01) and reported fewer triggers: no trigger 62% vs 47% (p<0.05). Stress (22% vs 35%), exertion (9% vs 20%), sleep deprivation (4% vs 13%) were more frequent in cFMF. M694V was the most common mutation in both groups. C-reactive protein levels during attacks were elevated in both groups, with no significant difference (median CRP: 50 vs 89 mg/L). Colchicine duration was shorter in HetFMF (median 48 vs 96 months, p<0.001). High-dose colchicine was less frequent (54.5% vs 89.1%, p<0.001), and interruptions over one year were more common (10.4% vs 1.6%).

Clustering analysis identified five groups. Cluster 1 (C1): homozygous genotype, very symptomatic attacks requiring colchicine and anti-IL1 therapy. C2: highly symptomatic, heterogeneous genotype, only partial response to colchicine. C3: predominantly HetFMF, variable attack frequency, moderately symptomatic, well response to high-dose colchicine. C4: HetFMF, few or no symptoms, no specific treatment. C5: moderately symptomatic form, predominantly HetFMF, requiring colchicine, often high doses.

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Pediatric Rheumatology, 23(2): P028

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Pediatric Rheumatology, 23(2): P029

Results: The FMF-QoL was applied to 187 patients with FMF and 50 control subjects. The median age (IQR) was 13 (10.3-15.8) years for the FMF group and 11 (9-13) years for the control group. The female/male ratio was 90/97 (48.1% female) in the patient group and 25/25 (50% female) in the control group. Forty-three (22.9%) patients with FMF were resistant to colchicine. The total median FMF quality of life score was 16 (9-32) for colchicine-resistant FMF patients, 20.5 (10.2-31) for patients receiving only colchicine treatment, and 9.5 (6-14) for the control group. The quality-of-life score was statistically significantly lower in the control group compared to the patient group (p=0.00). The Kaiser-Meyer-Olkin (KMO) measure was 0.668, indicating sampling adequacy. Bartlett’s test of sphericity was significant (p < 0.001), confirming the data’s suitability for factor analysis. Most items loaded strongly (>0.50) on the first component, which appeared to represent a general quality of life dimension. The FMF-QoL scale showed good internal consistency with a Cronbach’s alpha of 0.75.

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Pediatric Rheumatology, 23(2): P030

Introduction: Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). Janus kinase (JAK) inhibitor ruxolitinib has been reported to control disease progression in such patients through targeting type I IFN signaling.₁ Recurrent viral infections are known side effects of JAK inhibitors.₂

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