Background Anifrolumab is approved for adults with moderate-to-severe active systemic lupus erythematosus (SLE) based on Randomised clinical trials (RCTs). While randomised pivotal RCTs have demonstrated their efficacy and safety, real-world evidence (RWE) remains limited.Objectives To describe the clinical characteristics, effectiveness and safety of anifrolumab in clinical practice and to assess findings from published observational studies.Methods Multicentre study of patients with SLE classified according to EULAR/American College of Rheumatology (ACR) 2019. Data were collected from medical records up to 30 April 2025. Variables included demographic characteristics, clinical and serological features, prior and concomitant therapies, disease activity indices including the SLE Disease Activity Index 2000 (SLEDAI-2K), SLE Disease Activity Score (SLE-DAS) and Physician Global Assessment (PGA), damage and disease control measures including the Systemic Lupus International Collaborating Clinics/ACR Damage Index, Lupus Low Disease Activity State (LLDAS) and Definitions of Remission in SLE (DORIS) remission and the association with adverse events (AEs). A review of published observational studies was also conducted.Results We included 206 patients (183 women; mean age 44.6±12.6 years) from 54 Spanish centres. The most common indications for anifrolumab were cutaneous (61.7%), musculoskeletal (48.5%) and haematological (27.2%).A rapid and sustained improvement was observed in disease activity (SLEDAI-2K, SLE-DAS, PGA), LLDAS, DORIS remission, serological markers (anti-double-stranded DNA, C3/C4) and corticosteroid tapering. Organ damage remained stable. After a mean follow-up of 7.5±5.3 months, the most frequent AEs were herpes zoster (n= 5), respiratory infections (n= 6) and headache (n= 3). Twenty patients discontinued treatment. These results were consistent with published observational studies.Conclusion In this large RWE cohort, anifrolumab demonstrated early and sustained clinical benefit, a favourable safety profile and a significant corticosteroid-sparing effect. These findings reinforce the evidence from CT and support the incorporation of anifrolumab into routine care for patients with SLE.

OBJECTIVES:This study aimed to develop consensual definitions and semiquantitative scoring for structural damage on ultrasound and to test the reliability of individual components of a global Outcome Measures in Rheumatology ultrasound joint damage score (GLODS) in rheumatoid arthritis (RA). METHODS:A Delphi survey including statements on normal ultrasound appearance of joint features, scanning technique, new definitions, and scoring systems for 3 components of structural damage (bone erosions, cartilage change, and joint malalignment) was circulated among task force members. After agreement (≥75% of grades 4-5 on a 1-5 Likert scale) was achieved on the statements, datasets of ultrasound images representing various grades of the above-mentioned structural damage components were created and used in 2 web-based exercises. Finally, the metacarpophalangeal joints 1 to 5 of 7 patients with RA were scanned with ultrasound, twice on the same day by 7 task force members for detecting and scoring the 3 components using the consensus-based semiquantitative GLODS. Intraobserver and interobserver reliability of the new scoring system was measured by weighted kappa. RESULTS:Agreement on a total of 9 statements was reached in 4 Delphi rounds. Intraobserver and interobserver reliability for the individual components ranged from good to excellent in both the web-based (0.72-0.97) and the live exercises (0.68-0.89). Intraobserver and interobserver reliability of the total GLODS was shown to be excellent (0.92) and good (0.69), respectively. CONCLUSIONS:Ultrasound is a reliable tool for evaluating bone erosions, cartilage change, and joint malalignment in the hand joints of patients with RA. These features can be reliably integrated into a global ultrasound score.

Objectives . To assess whether the ultrasound-measured response to targeted therapy in rheumatoid arthritis (RA) differs between women and men. Methods . The GENder on UltraSound (GENUS) was a multicentre, observational, prospective study. We included RA patients who initiated or switched targeted therapy, gender-balanced and women and men matched by age. Blinded clinical, laboratory, and ultrasound assessments were performed at baseline and three months. We obtained global scores for B-mode synovitis, Doppler synovitis, and the Global EULAR-OMERACT Synovitis Score. The primary outcome was the change in global ultrasound scores from baseline to three months after initiation or switching of targeted therapy. Results . A total of 185 patients were included [92 (49.7%) women, 93 (50.3%) men]. At three months, 174 patients [90 (51.7%) women, 84 (48.3%) men] were evaluated, while 11 patients were lost to follow-up. Most clinical, laboratory, and ultrasound variables showed significant improvement from baseline to three months in both women and men (p<0.01), with a large effect size (Wilcoxon signed-rank test r ≥ 0.5) for most variables in both genders. At three months, there were no significant differences in changes in clinical, laboratory, or ultrasound variables between genders (p>0.05), and the effect size was small (Wilcoxon rank-sum test r < 0.2) for all variables. In multivariate regression analysis, no significant differences in ultrasound scores between women and men were observed after adjustment for potential confounders (p > 0.05). Conclusions . These results suggest that the short-term ultrasound-assessed response to targeted therapy in RA patients is similar in women and men.

IgA-mediated vasculitis (IgAV) is a complex inflammatory disease. Unravelling its genetic background would allow us to identify genetic biomarkers that may be used as additional tools in its daily management, helping to solve the clinical challenge that this vasculitis entails. C5 is a potent immune mediator that is proteolytically processed to generate C5a, a potent anaphylatoxin that exerts its function via C5aR1. C5 downstream variants (rs3761847 and rs10818488) have been recently related to IgAV pathogenesis. Additionally, C5a and C5aR1 dysregulation contributes to the development of inflammatory diseases, and, particularly, elevated C5a plasma levels have been observed in IgAV patients in the acute stage. Accordingly, we aimed to evaluate the influence of C5 and C5AR1 on the pathophysiology of IgAV. Eight C5 (rs10760128, rs74971050, rs4310279, rs7868761, rs10818495, rs10156396, rs3815467, and rs16910280) and three C5AR1 (rs10853784, rs11673071, and rs11670789) tag variants were genotyped in 342 Caucasian IgAV patients and 723 ethnically matched healthy controls. No statistically significant differences were observed when C5 and C5AR1 frequencies were compared between IgAV patients and healthy controls. Likewise, similar C5 and C5AR1 frequencies were observed amongst IgAV patients stratified according to IgAV severity (presence/absence of nephritis). Furthermore, no C5 and C5AR1 differences were disclosed when IgAV patients were stratified according to demographic and clinical IgAV characteristics other than nephritis (age at disease onset, presence/absence of joint and gastrointestinal manifestations) and sex. Our results suggest that C5 and C5AR1 are not related to IgAV pathogenesis and, therefore, these genes may not be useful as IgAV genetic biomarkers.

Introduction:Immunoglobulin A vasculitis (IgAV) is an inflammatory disease mediated by B cells. Nuclear factor kappa B (NF-κB) is essential for B-cell development and maturation and plays a key role in autoimmunity and inflammation. In particular, the NF-κB canonical activation pathway genes NFKB1 (encoding NF-κB1) and NFKBIA (encoding NF-κB inhibitor alpha) have been identified as risk loci for several immune-mediated diseases, but their role in IgAV remains unclear. This study aimed to determine whether NFKB1 and NFKBIA represent novel genetic risk factors for IgAV pathogenesis. Methods:The NFKB1 promoter variant -94 ins/del ATTG (rs28362491), six tag NFKB1 polymorphisms (rs77830930, rs1598856, rs7340881, rs4648055, rs4648090, and rs230547), and seven tag NFKBIA variants (rs3138055, rs696, rs1022714, rs2233419, rs2233415, rs1050851, and rs1957106) were genotyped in 343 Caucasian IgAV patients and 764 healthy, ethnically matched controls using TaqMan probes. Patients were stratified according to age at disease onset and the presence or absence of renal, articular, and gastrointestinal manifestations. Genotype, allele, and haplotype frequencies were compared between patients and controls, as well as across clinical subgroups. Results:No statistically significant differences were found in genotype or allele frequencies of NFKB1 or NFKBIA between IgAV patients and healthy controls. Likewise, haplotype frequencies of both genes were similar across groups. No associations were observed when patients were stratified by clinical features, including renal involvement, age at onset, or articular/gastrointestinal symptoms. Conclusion:Our findings do not support a major role for the NFKB1 or NFKBIA variants studied in IgAV susceptibility or severity. These results suggest that if NF-κB signaling contributes to IgAV pathogenesis, it likely involves other biological mechanisms.

Background: Anifrolumab (ANI) is a human monoclonal antibody that binds to the type I interferon receptor subunit 1 (IFNAR1), thus blocking the biological activity of type I IFNs. ANI was approved by Spanish authorities on June 1, 2023. Its use is indicated in adults with moderately to severely active autoantibody-positive systemic lupus erythematosus (SLE) in combination with standard treatment. Objectives: To describe in Spanish clinical practice since its approval a) SLE profile of patients, b) effectiveness and c) safety. Methods: Descriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding were collected from medical records (June 2023-January 2024). Demographic features, clinical and laboratory variables, previous and concomitant therapy, activity index (SLE-DAS, SLEDAI-2k, PGA), organic damage index (SLICC SDI) and safety were assessed. Results: Baseline characteristics of patients and therapy before ANI are summarized in Table 1. A total of 91 patients (82 women/9 men), mean age 32.7±11.5 years (range 15-59 years) (38 hospitals) were included.The main reason for starting ANI was: skin activity (n=60, 65.9%), joint activity (n=52, 57.1%), hematological activity (n=25, 27.5%), renal activity (n=2, 2.2%), corticosteroids dependence (n=5, 5.5%) and serious side effects with belimumab (BLM) (n=2, 2.2%).All patients received 300 mg/4 w of ANI except one patient who received a loading dose (900 mg/4 w x3 months and after 300 mg/4 w) due to renal involvement.Concomitant treatments with ANI were: corticosteroids (n=78), antimalarials (n=68), mycophenolate mofetil (MMF) (n=23), methotrexate (MTX) (n=13), azathioprine (AZA) (n=5), tacrolimus (n=5), leflunomide (LFN) (n=2), rituximab (RTX) (n=1), cyclophosphamide (CYM) (n=1), sulfones (n=2) and anakinra (n=1).A rapid and maintained significant decreases in SLE-DAS, SLEDAI-2k, PGA and anti-dsDNA antibodies were observed from 1 month until the last visit. Complement C3 and C4 levels also increased significantly (Figure 1). No increase in the chronicity index was observed.After a follow-up of 4.8±3.6 months the main side effects observed were: herpes zoster (n=3), arterial hypotension (n=2), headache (n=2), suppurative hidradenitis (n=1), influenza A pneumonia (n=1), skin reaction (n=1), herpes simplex virus infection and urinary infection (n=1). In follow-up, 7 patients discontinued treatment due to primary failure (n=3), secondary failure (n=2), severe pneumonia (n=1), arterial hypotension (n=1). Conclusion: In our cohort of SLE patients in a real-world setting, ANI has showed a rapid effectiveness, and a relatively good safety. Therefore, ANI seems to be a good choice to treat patients refractory to other therapies. ANI in severe and refractory patients even was used combined with other biologic therapy. REFERENCES: [1] Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019 Sep;78(9):1151-1159. Acknowledgements: NIL. Disclosure of Interests: Vanesa Calvo-Río Abbie, Lilly, Grünenthal, AMGEN, MSD, Novartis, Galápagos, Vifor, GSK, Otsuka, Janssen, M. Retuerto-Guerrero: None declared, Judit Font: None declared, Ivette Casafont-Solé: None declared, A. Mayo-Juanatey: None declared, Juan Jose Alegre Sancho: None declared, Dalifer Freites: None declared, Cristina Hormigos: None declared, Noemí Garrido-Puñal: None declared, Guillermo Gonzalez Arribas: None declared, Juan Roberto Miguelez Sanchez: None declared, Andrea García-Valle: None declared, Marta Ibañez: None declared, Fernando Lozano Morillo: None declared, Ángel García Manzanares: None declared, S. Sandoval-Moreno: None declared, Josefina Cortés-Hernández: None declared, Deseada Palma Sanchez: None declared, Leticia Lojo: None declared, Evelin Cecilia Cervantes Pérez: None declared, Paz Collado: None declared, Cristina Arciniega Larios: None declared, Luis Sala Icardo: None declared, Eztizen Labrador-Sánchez: None declared, Cilia Peralta-Ginés: None declared, Nahia Plaza-Aulestia: None declared, Miguel Medina Malone: None declared, Jose Rosas Gómez de Salazar: None declared, Montserrat Corteguera: None declared, Laura Cebrián-Méndez: None declared, Fred Antonio Anton Pages: None declared, Jose Ramón Lamúa Riazuelo: None declared, Maria Dolores Fábregas Canales: None declared, María José Alados Hernández: None declared, Marta Garijo Bufort: None declared, Anna Pàmies: None declared, Luis Sarabia De Ardanaz: None declared, Rodrigo Aguirre-del-Pino: None declared, Jose Angel Cabezas Lefler: None declared, Alvaro Seijas-Lopez: None declared, Maria del Carmen Carrasco Cubero: None declared, Ana Lopez-Ceron Cofiño: None declared, Vera Ortiz-Santamaria: None declared, Santos Castañeda: None declared, Carmen Bejerano: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers-Squibb, Janssen, Lilly, Novartis, UCB, and MSD, Abbvie, MSD, Roche.Figure 1Evolution of C3, C4 and anti-dsDNA levels and activity and organ damage indices after starting anifrolumab. Table 1Clinical manifestations and treatments received before starting anifrolumabClinical manifestations before ANIN (%)Therapy before ANIN (%)Concomitant therapy with ANIN (%)articular87 (95.6%)oral steroids88 (96.7%)oral steroids78 (85.7%)cutaneous75 (82.4%)antimalarials88 (96.7%)antimalarials68 (74.7%)hematological57 (62.6%)BLM73 (80.2%)MMF23 (25.3%)oral ulcers47 (51.6%)MMF46 (50.5%)MTX13 (14.3%)alopecia46 (50.5%)AZA38 (41.7%)AZA5 (5.5%)renal30 (33%)RTX34 (37.3%)tacrolimus5 (5.5%)serositis28 (30.8%)MP boluses32 (35.1%)leflunomide2 (2.2%)neuropsychiatric12 (13.2%)CYM19 (20.9%)sulfones2 (2.2%)digestive6 (6.6%)tacrolimus9 (9.9%)RTX1 (1.1%)Abbreviations in alphabetical order: ANI: anifrolumab; AZA: azathioprine; BLM: belimumab; CYM: cyclophosphamide; MMF: mycophenolate mofetil; MP: methylprednisolone; MTX: Methotrexate; RTX: rituximabCYM1 (1.1%)anakinra1 (1.1%)

Background: Autoinflammatory syndromes (AIS) are a group of inherited diseases characterized by increased systemic inflammation caused by disorders in the innate immune system. They include both monogenic Mendelian diseases and more complex polygenic entities, which have mutations in genes involved in the control of various inflammatory pathways and present with periodic or persistent clinical pictures. They are characterized by a pediatric onset and diagnosis, although there is an increasing number of reported cases of late onset in adulthood. The heterogeneous nature of these diseases, which in many cases present with mild symptoms, often leads to diagnostic delays. Therefore, it is important to be aware of the peculiarities of these syndromes and to maintain a high clinical suspicion to reach a final diagnosis. Objectives: To describe the clinical and therapeutic characteristics of adult patients with AIS. Methods: Descriptive, observational, and retrospective study. Patients over 16 years of age with a high clinical suspicion of AIS were included from a database of a rheumatology department of a non-reference center (hospital, level 2) from 2005 to 2023. Variables collected: sex, age and symptoms at debut, age at diagnosis, delay time to diagnosis, genetic mutation, clinical characteristics, treatments, and laboratory parameters such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ferritin. Descriptive statistics were expressed as mean (standard deviation, SD) or median (interquartile range, IQR) to describe continuous variables, and percentages for categorical variables. The diagnosis was made by diagnostic classification criteria (Yamaguchi 1992 for adult Still's disease and Eurofever 2015 for tumor necrosis factor receptor-associated periodic syndrome (TRAPS) mutations), or by genetic study. Patients with a positive genetic study and those with an inconclusive study having ruled out infectious, autoimmune, or neoplastic causes were included. Results: Eight patients with a diagnosis of suspected AIS were analyzed. The mean age was 55.5 ±20.3 years, with no gender predominance (50% male), and the majority were Caucasian. Adult Still's disease was the most frequent AIS, 3 patients (37.5%). The mean age at symptom onset was 40 ±23 years, with a mean age at disease diagnosis of 45.6 ±20.7. The onset of symptoms or characteristic signs of the disease occurred in adulthood in 7 (87.5%) of the cases. Only one patient had clinical onset in the pediatric age group. Overall, a mean delay in final diagnosis of 5.7± 5 years was observed. The main characteristics of the included AIS are listed in Table 1. Elevation of acute phase reactants was collected in 7 (87.5%) of the cases. The mean value was 187 ±110 mg/L for CRP and 95.2 ±38 mm/h for ESR. Median ferritin was 923.5 ng/mL (329-15410). All patients, but one, were taking corticosteroids. Interleukin-1 inhibitor (IL-1-i) therapy was reported in half of the study population (4 patients). Three of these four patients underwent an IL-1-i switched from Anakinra to Canakinumab due to intolerance to daily injection in the patient with pediatric debut and secondary therapy failure in the other two cases. To date, all patients included in the study have had adequate control of disease activity. Conclusion: We describe a representative sample of AIS that showed up in daily clinical practice from a non-expertise centre. It is important to maintain a high suspicion for early identification of AIS, as usual antirheumatic therapy is not effective and almost al need systemic steroids. Prescription of IL-1-I usually achieves adequate disease control. The increasing identification of AIS in adulthood forces the adult rheumatologist to open mind regardless of where he or she works. Further studies are needed to improve the understanding of adult AIS. REFERENCES: NIL. Table 1. Main characteristics of autoinflammatory syndromes (AIS). Acknowledgements: NIL. Disclosure of Interests: None declared.

Background: Ultrasound (US) is a suitable imaging technique to study of arthritis in the paediatric population. However, its application in juvenile psoriatic arthritis (JPsA) is challenging due to the multiple domains it presents. Objectives: To investigate what and how many joints and periarticular structures should be included in early US evaluation of JPsA in clinical practice, to determine the inter-observer reliability of US-detected findings and to analyze concordance between clinical and US assessment for arthritis. Methods: Multicentre study including children with JPsA, both early PsA (onset less than one year) and chronic disease affected by an outbreak. The main outcome measure was the prevalence of US-detected abnormalities, which were assessed bilaterally in a blinded way using B-mode and Power Doppler technique. As, so far, there has been no approach to assess paediatric PsA, we decided to use a combination of the PsASon-Score13 (US composite score for the assessment of inflammatory and structural pathologies in psoriatic arthritis) (1) plus reduced joint assessment for the US detection of synovitis in JIA (2) to determine the maximum number of structures that could be affected by JPsA. The presence of US-detected synovitis was defined using the OMERACT definition developed for children with JIA, whereas for definition of US-enthesitis and for tenosynovitis we use the one developed in adults. To determine the inter-observer reliability a set of 78 static images was included in this study.Descriptive statistics were used to summarize the data. Concordance and interobserver reliability of US-detected abnormalities were estimated using the kappa index adjusted for low prevalence, with its 95% confidence intervals. Results: Forty-eight children (71% girls) with a mean age at inclusion 11±4 years were included. Most of them were under therapy. Both US and clinically, arthritis was recorded more frequent than enthesitis and tenosynovitis. However, US was superior to clinical assessment to detect enthesitis, particularly in the distal patellar ligament and Achilles tendon (US 27% and 19%, respectively vs clinical assessment 6% and 4% of 48 patients, respectively). Ultrasonography detected a small number of tenosynovitis, but no findings were recorded on clinical examination.Synovitis involvement of the knee and the dorsal recess of the first metatarsophalangeal (MTP1) was the most frequently detected finding both US and clinically. US detected more synovitis within the small finger joints in the hand than the clinical examination. The presence of US-detected abnormalities in feet joints (except MTP1) were uncommon. Overall, the concordance between clinical and US evaluation for presence/absence of joint involvement was good (> 70%) for most of the joints assessed, except for MTF1 (62%). Overall, interobserver agreement was moderate for presence/absence of US-detected synovitis and enthesitis on B-mode (Fleiss’ kappa 0.69; 95% CI 0.62-0.77 and Fleiss’ kappa 0.52; 95% CI 0.34-0.77, respectively). Conclusion: The study shows a higher frequency of abnormalities detected by US only in 9 of the joints included in the PsASon-Score and in one of the entheses included in the same score. Therefore, unlike in adults, such an exhaustive assessment could be avoided in JPsA. This is the first attempt to draw up an imaging approach for early JPsA considering the characteristics of the disease as well as the feasibility of US assessment in clinical practice. REFERENCES: [1] Ficjan A et al. Ultrasound composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis (PsASon-Score). Arthritis Research & Therapy 2014;16:476[2] Collado P et al. Reduced joint assessment vs comprehensive assessment for ultrasound detection of synovitis in juvenile idiopathic arthritis. Rheumatology 2013;52:1477 Acknowledgements: This work has been supported by a scientific grant from Sociedad Española de Reumatología Pediátrica (SERPE). Disclosure of Interests: None declared.

Objectif: une revue systématique visant à évaluer l’apport de l’échographie dans la détection de l’enthésite chez les patients porteurs d’arthrite juvénile idiopathique (AJI). Méthodes: une recherche bibliographique a été menée dans les bases de données PubMed et Embase pour la période comprise entre janvier 1966 et mai 2021 ; les articles qui répondaient aux critères d’inclusion selon la définition de l’enthésite échographique et les propriétés métrologiques étudiées ont été sélectionnés. Nous avons évalué les caractéristiques cliniques de la population cible, le design de l’étude, le type et le nombre d’enthèses examinées, la définition et le système de cotation de l’enthésite échographique ainsi que les propriétés métrologiques définies par le filtre OMERACT (vérité, discrimination et faisabilité). La qualité méthodologique des études a été analysée au moyen de l’échelle QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). Résultats: cinq publications remplissaient les critères d’inclusion (26 à 146 patients et 1 à 10 sites d’enthèse examinés bilatéralement). Toutes les études étaient axées sur enthèses des membres inférieurs. Les lésions élémentaires incluses dans la définition de l’enthésite chez l’adulte ont été généralement évaluées. Peu d’études ont rapporté la fiabilité de l’échographie et aucune n’a évalué sa sensibilité au changement. Les anomalies échographiques des enthèses étaient visibles chez 9,4% à 53% des patients atteints d’AJI et 20% à 83% des cas d’arthrite liée à l’enthésite (ERA). Il n’a été retrouvé aucune anomalie significative chez les sujets sains. L’exploration échographique a été faiblement corrélée à l’examen clinique. La qualité globale des études était faible, en raison notamment de l’absence de test de référence. Conclusion: l’échographie est un outil qui affiche une bonne sensibilité pour la détection des anomalies des enthèses dans l’AJI. D’après les données actuelles, il n’existe pas de définition échographique standardisée de l’enthésite dans la population pédiatrique. Par ailleurs, les critères de validité externe et interne de l’échographie n’ont pas été établis. [[[en]]]ABSTRACT Objective: A systematic review to assess the value of ultrasonography (US) for detecting enthesitis in juvenile idiopathic arthritis (JIA). Methods: PubMed and Embase databases were searched for articles published from January 1966 to May 2021; we selected those meeting the inclusion criteria according to the US definition of enthesitis and metric properties studied. We assessed the clinical features of the population, study design, the type and number of entheses examined, the definition and scoring system of US enthesitis and metric properties according to the OMERACT filter (truth, discrimination, feasibility). The quality of the studies was evaluated with the Quality Assessment of Diagnostic Accuracy Studies 2. Results: Five publications met the inclusion criteria (26 to 146 patients and 1 to 10 bilaterally examined entheses). All studies focused on lower-limb entheses. The elementary lesions included in the definition of adult enthesitis were generally assessed. Few studies reported US reliability, and none evaluated sensitivity to change of US. US revealed entheseal abnormalities in 9.4% to 53% of JIA patients and 20% to 83% of enthesitis-related arthritis cases. No significant abnormalities were found in healthy children. US findings were poorly correlated with clinical examination. The overall quality of the studies was low, mainly because of the lack of a reference standard. Conclusion: US is a sensitive tool to detect entheseal abnormalities in JIA. The current evidence highlights that a standardized US definition of enthesitis in children is lacking and US criteria and discriminant validity have not been established.

Background: Nailfold Videocapillaroscopy (NVC) is a valuable tool in the differential diagnosis of Raynaud's phenomenon (RP), present in certain Rheumatic diseases (RD). Knowing that many people have cardiovascular risk factors (CVRF), the main objective was to demonstrate that CVRF and carotid plaques produce NVC alterations. Methods: Cross-sectional unicentric study carried out from 2020 to 2023. Four groups were formed: subjects with RD and RP, participants with RD without RP, subjects with RP without RD and finally participants without RP or RD (study group). Each subject exhibiting CVRF presented only a single risk factor. The variables collected were: sociodemographic, CVRF (diabetes, tobacco, alcohol (ALC), obesity (OBE), dyslipidemia and arterial hypertension (AH)), diseases, RP, treatments, tortuosities and NVC alterations (ramified capillaries, enlarged capillaries, giant capillaries, haemorrhages and density loss) and carotid ultrasound (CU). Results: 402 subjects were included (76 % women, mean age 51 +/- 16 years), 67 % had CVRF, 50 % RP and 38 % RD. Tortuosities were present in 100 % of CVRF participants. A statistically significant association was found between the presence of CVRF and all the NVC alterations: ramified capillaries (OR = 95.6), enlarged capillaries (OR = 59.2), giant capillaries (OR = 8.32), haemorrhages (OR = 17.6) and density loss (OR = 14.4). In particular, an association was found between giant capillaries with AH (p = 0,008) and OBE (p (0,001), and haemorrhages and density loss with ALC and OBE (p < 0,001). On the other hand, 40 subjects presented CU plaques (9.9 %), associated with enlarged capillaries (OR = 8.08), haemorrhages (OR = 4.04) and ramified capillaries (OR = 3.01). The pathological intima-media thickness was also associated with haemorrhages (OR = 3.14). Conclusions: There is a clear association between CVRF and ultrasound atherosclerotic findings in carotid with NVC alterations. These findings are of special interest for a correct NVC interpretation and to avoid false positives in the diagnosis of primary and secondary RP.

Background: Immunoglobulin A Vasculitis (IgAV) is an inflammatory disease caused by the accumulation of immune complexes of IgA in the walls of small blood vessels of skin, joints, gut, and kidney [1,2]. Likewise, Immunoglobulin A Nephropathy (IgAN) is characterized by the deposition of IgA immune complexes, although IgAN is limited to the kidney. Interestingly, the nephritis caused by IgAV (IgAVN) is indistinguishable from IgAN. One factor that many nephropathies share, including IgAN, is the activation of the NLR family pyrin domain-containing 3 (NLRP3) protein, one of the best-understood members of the inflammasome [3]. NLRP3 is also known for activating Caspase 1, an enzyme that cleaves inflammatory precursors involved in several nephropathies, and its levels have been linked to acute kidney injury and the pathogenesis of IgAV [4,5]. Accordingly, it is plausible to consider that these molecules could play a role in the discrimination of these diseases. Objectives: The aim of this work was to assess whether NLRP3 and CASP1 could be considered as genetic biomarkers for the differential diagnosis of IgAV and IgAN. Methods: 342 patients with IgAV (of which 116 developed IgAVN), the largest series of Caucasian patients with IgAV ever assessed for genetic studies, and 96 Caucasian patients with IgAN, were recruited for this study. Seven single nucleotide polymorphisms (SNPs) within NLRP3 (rs4925648, rs4925659, rs10159239, rs10754558, rs4353135, rs35829419, and rs10733113) and 2 CASP1 SNPs (rs488992 and rs501192) were genotyped using TaqMan Probes. p values < 0.05 after Benjamini-Hochberg correction for an FDR of 5% were considered statistically significant. Results: No statistically significant difference was found in NLRP3 and CASP1 genotype and allele frequencies between patients with IgAV and patients with IgAN (Table 1). Likewise, no statistically significant differences were observed in genotype and allele frequencies in NLRP3 and CASP1 when comparing IgAVN patitents with IgAN patients (Table 1). Additionally, the same outcome was achieved when comparing the haplotype frequencies of IgAV and IgAVN patients to those of IgAN patients (Table 2). Conclusion: Our results suggest that neither NLRP3 nor CASP1 is useful for discriminating between IgAV and IgAN, nor between IgAVN and IgAN, indicating that these diseases could be similar in the inflammasome context. REFERENCES: [1] Arthritis Rheum. 2013 Jan;65(1):1-11. [2] Clin Exp Rheumatol. 2013 Jan-Feb;31(1 Suppl 75):S45-51. [3] Medicina (Kaunas). 2022 Dec 30;59(1):82. [4] Kidney Dis (Basel). 2023 Jun 24;9(6):443-458. [5] Ann Palliat Med. 2021 Jun;10(6):6687-6693. Acknowledgements: This research was funded by European Union FEDER funds and "Fondo de Investigaciones Sanitarias" from "Instituto de Salud Carlos III" (ISCIII, Health Ministry, Spain), grant number PI18/00042 and PI21/00042. JCB-L is a recipient of a PFIS programme fellowship from the ISCIII, co-funded by the European Social Fund ("Investing in your future"), grant number FI22/00020. MSM-G is supported by funds of "Fondo de Investigaciones Sanitarias" from ISCIII, grant number PI18/00042.VP-C is supported by funds of IDIVAL, grant number NVAL23/02. RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF ("Investing in your future"), grant number CPII21/00004. Disclosure of Interests: None declared.

Background: Immunoglobulin A Vasculitis (IgAV) is an inflammatory disease caused by the accumulation of immune complexes of IgA in the walls of small blood vessels [1]. It has been shown that these immunocomplexes activate the mannan-binding lectin and the alternative complement pathway [2]. Moreover, the presence of complement system components has been observed in skin and kidney biopsies in IgAV patients [3]. In this context, C5a (a protein fragment cleaved from C5 complement factor), together with its receptor, C5aR1, have been proposed as therapeutic targets in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [4], another small-vessel vasculitis [1]. Nevertheless, the molecular mechanisms by which the complement is involved in IgAV are poorly understood. Objectives: The aim of this work was to determine whether C5 and C5AR1 represent novel genetic risk factors for IgAV. Methods: 346 patients with IgAV, the largest series of Caucasian patients with IgAV ever assessed for genetic studies, and 723 healthy ethnically matched controls, were recruited for this study. Among the IgAV patients, 117 presented nephritis (IgAVN). Eight tag single nucleotide polymorphisms (SNPs) within C5 (rs10760128, rs74971050, rs4310279, rs7868761, rs10818495, rs10156396, rs3815467, and rs16910280) and 3 C5AR1 tag SNPs (rs10853784, rs11673071, and rs11670789) were genotyped using TaqMan Probes. p values < 0.05 after Benjamini-Hochberg correction for an FDR of 5% were considered statistically significant. Results: No statistically significant difference was found in C5 and C5AR1 genotype and allele frequencies between patients with IgAV and healthy controls (HC) (Table 1). Likewise, no statistically significant differences were observed in genotype and allele frequencies of C5 and C5AR1 when IgAV patients were stratified according to the severity of the disease, represented by the presence or absence of renal manifestations (Table 1). In addition, no statistically significant differences were shown among IgAV patients stratified according to other clinical aspects, such as the age at disease onset or the presence/absence of articular and gastrointestinal manifestation in C5 and C5AR1 (Data not shown). Furthermore, no differences in the haplotype frequencies of C5 and C5AR1 were observed between IgAV patients and HC (Table 2), and between stratified IgAV patients according to the severity of the disease (Table 2) as well as to other clinical manifestations (Data not shown). Conclusion: Our results suggest that C5 and C5AR1 do not seem to be involved in the pathogenesis of IgAV. REFERENCES: [1] Arthritis Rheum. 2013 Jan;65(1):1-11. [2] Front Immunol. 2022 Oct 3:13:921864. [3] Autoimmun Rev. 2017 Dec;16(12):1246-1253. [4] Immunobiology. 2023 Sep;228(5):152413. Acknowledgements: This research was funded by European Union FEDER funds and "Fondo de Investigaciones Sanitarias" from "Instituto de Salud Carlos III" (ISCIII, Health Ministry, Spain), grant number PI18/00042 and PI21/00042. JCB-L is a recipient of a PFIS programme fellowship from the ISCIII, co-funded by the European Social Fund ("Investing in your future"), grant number FI22/00020.VC-R is a recipient of a grant for research activity intensification provided by the Spanish Rhemathology Foundation. MSM-G is supported by funds of "Fondo de Investigaciones Sanitarias" from ISCIII, grant number PI18/00042.VP-C is supported by funds of IDIVAL, grant number NVAL23/02. RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF ("Investing in your future"), grant number CPII21/00004. Disclosure of Interests: Joao Carlos Batista-Liz: None declared, Vanesa Calvo-Río Abbvie, Lilly, Grünenthal, AMGEN. MSD, Novartis, Galapagos, Vifor, GSK, and Otsuka, María Sebastián Mora-Gil: None declared, Belén Sevilla-Pérez: None declared, José Luis Callejas: None declared, María Teresa Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Javier Narváez: None declared, Luis Martín-Penagos: None declared, Lara Belmar-Vega: None declared, Cristina Gomez-Fernandez: None declared, Luis Caminal-Montero: None declared, Paz Collado: None declared, Patricia Quiroga Colina: None declared, Esther Vicente-Rabaneda: None declared, Esteban Rubio-Romero: None declared, Manuel León Luque: None declared, Juan María Blanco-Madrigal: None declared, Eva Galíndez-Agirregoikoa: None declared, Santos Castañeda: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD, Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD, Abbvie, MSD, and Roche, Verónica Pulito-Cueto: None declared, Raquel López-Mejías: None declared.

Background Several studies have suggested a potential role for ultrasonography (US) in detecting enthesitis in children, thus enhancing the accuracy of the classification of juvenile idiopathic arthritis (JIA) and improving the therapeutic approach. Because of no consensual definition of ultrasonographic enthesitis in children, the pediatric sub-taskforce of the OMERACT working group posed the research question of whether there are sufficient data to support the role of US in the diagnosis and follow-up of enthesitis in JIA, particularly enthesitis related arthritis (ERA). Objectives We performed a systematic literature review (SLR) to assess the value of US for detecting enthesitis in JIA. The main objectives were to determine: i.which elementary lesions have been evaluated by US in JIA patients; ii.which definitions and scoring systems were used; and iii.the measurement properties of US in evaluating enthesitis in JIA according to the OMERACT Filter 2.1 Instrument Selection Algorithm (OFISA). Methods PubMed and Embase databases were searched for articles published from January 1966 to May 2022; we selected those meeting the inclusion criteria according to the US definition of enthesitis and metric properties studied. We assessed the clinical features of the population, study design, the type and number of entheses examined, the definition and scoring system of US enthesitis and metric properties according to the OMERACT filter (truth, discrimination, feasibility). The quality of the studies was evaluated with the Quality Assessment of Diagnostic Accuracy Studies 2. Results Five publications met the inclusion criteria (26 to 146 patients and 1 to 10 bilaterally examined entheses)[1-5]. All studies focused on lower-limb entheses. The elementary lesions included in the definition of adult enthesitis were generally assessed. Few studies reported US reliability, and none evaluated sensitivity to change of US. US revealed entheseal abnormalities in 9.4% to 53% of JIA patients and 20% to 83% of enthesitis-related arthritis cases. No significant abnormalities were found in healthy children. US findings were poorly correlated with clinical examination. The overall quality of the studies was low, mainly because of the lack of a reference standard. Conclusion US could be a sensitive tool to detect entheseal abnormalities in JIA. Nevertheless, the current evidence highlights that a standardized US definition of enthesitis in children is lacking and US criteria and discriminant validity have not been established. References [1] ousse-Joulin S, Breton S, Cangemi C et al. Ultrasonography for detecting enthesitis in juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011 Jun;63(6):849-55. [2] Shenoy S, Aggarwal A. Sonologic enthesitis in children with enthesitis-related arthritis. Clin Exp Rheumatol. 2016 Jan-Feb;34(1):143-7. [3] Guo R, Cao L, Kong X, Liu X et al. Fever as an initial manifestation of enthesitis-related arthritis subtype of juvenile idiopathic arthritis: retrospective study. PLoS One. 2015 Jun 1;10(6):e0128979. [4] Laurell L, Court-Payen M, Nielsen S et al Ultrasonography and color Doppler of proximal gluteal enthesitis in juvenile idiopathic arthritis: a descriptive study. Pediatr Rheumatol Online J. 2011 Aug 11;9(1):22. [5] Weiss PF, Chauvin NA, Klink AJ et al. Detection of enthesitis in children with enthesitis-related arthritis: dolorimetry compared to ultrasonography. Arthritis Rheumatol. 2014 Jan;66(1):218-27. Acknowledgements: NIL. Disclosure of Interests None Declared.

ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.

Background Juvenile psoriatic arthritis (JPsA) is one of the least common subtypes of JIA. Information on JPsA is mainly clinical, but scarce regarding the impact of musculoskeletal involvement on children’s quality of life. Objectives To describe the clinical and ultrasound (US) characteristics of children with JPsA, and to assess their impact using a composite quality of life index, the PsAID (Psoriasis Arthritis Impact of Disease). Methods A multicentre cross-sectional observational study recruited consecutive JPsA patients, from January-2020 to May-2022. Inclusion criteria: 1/ age at onset ≤ 16 years, 2/ diagnosis by the prescribing physician based on one of the 2 JPsA diagnostic classification systems (ILAR or Vancouver). All were assessed clinically and US (independently) and completed two questionnaires: PsAID (1) and Child Health Assessment Questionnaire (CHAQ, to measure physical disability). Statistics included correlation Spearman (rho) and PsAID was identified as the dependent variable. Results The 48 children included (mean age at inclusion 11±4 years), 71% girls, 67% had oligoarthritis and 80% psoriasis in a first or second-degree relative. Mostly arthritis started before the psoriasis. The median time lag between the diagnosis and the onset of specific musculoskeletal manifestations was 1 year; interquartile range 0.5-2. ANA and HLAB27 were present in 19 (40%) and 5 (10%) of the children, respectively. A history of axial inflammatory symptoms was present in 3 (5%) patients, and unilateral sacroiliitis was confirmed by MRI in only one patient. Psoriasis and dactylitis were the most frequent manifestations identified (≥50%), while uveitis was less common (12%). Twenty-eight (58%) patients used methotrexate, 21 used anti-TNF agents and 14 needed corticosteroid infiltration. The population showed low clinical activity in the DAPSA composite activity index (md 3.5; range 0-25). Similarly, US showed a low number of affected joints but US was slightly superior to clinical examination, while US was clearly superior to detect enthesitis and tenosynovitis, particularly tendons of the fingers. The PsAID index (median 0.4; range 0-9.2) showed low correlation with CHAQ (r 0.3) and high with DAPSA (r 0.7); however, the correlation between PsAID and total joint count was low for both clinical and US assessment (r 0.4). The correlation between PsAID and total joint count was moderate for clinical (r 0.5) and low for US (r 0.4). Children with the presence of enthesitis and clinical dactylitis had a higher mean PsAID score than those without (dactylitis; p=0.002, and enthesitis; p<0.001). Conclusion The study supports the existence of an atypical pattern of late-onset JPA characterised by a predominance of girls with peripheral involvement and little uveal involvement. Based on our results, dactylitis and enthesitis have a greater impact on the child’s quality of life than joint involvement per se. Studies with a larger sample size and/or disease activity are needed to confirm these findings. Reference [1]Gossec L, et al. A patient-derived and a patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriasis Arthritis Impact of Disease, PsAID questionnaire, a 13-country EULAR initiative. Ann Rheum Dis 2014;73:1012 Acknowledgements Sociedad Española de Reumatología Pediátrica (SERPE) Disclosure of Interests None Declared.