OBJECTIVES:Juvenile-onset systemic lupus erythematosus (jSLE) is a rare autoimmune disease. Belimumab, a monoclonal antibody targeting soluble B-lymphocyte stimulator, has been approved for paediatric use in France since 2020. This retrospective, multicentre study aimed to descriptively evaluate the real-world use, efficacy and safety of belimumab after 6 months of treatment in jSLE patients. METHODS:Patients were diagnosed with SLE according to the 2019 EULAR/ACR criteria, and belimumab therapy (intravenous or subcutaneous) was initiated before age 18. Efficacy was assessed using clinical (SLEDAI, low disease activity status, corticosteroid dose) and biological parameters (anti-dsDNA, complement, proteinuria), along with qualitative and semi-quantitative symptom analysis. RESULTS:Twenty-one patients were included. The majority received intravenous belimumab (90.5%) for articular (66.7%) or cutaneous (23.8%) manifestations. At 6 months, SLEDAI scores showed no significant reduction, although there was a trend towards lower corticosteroid use (0.53 vs 0.15 mg/kg/day) and an increase in the proportion of patients achieving low disease activity status (6.3% vs 37.5%). Marked improvement was observed in articular manifestations with 77.8% achieving complete resolution. Cutaneous, renal and haematological responses were limited. Overall, treatment was well tolerated, though psychiatric symptoms led to treatment discontinuation in one patient. CONCLUSION:This retrospective, multicentre study found that belimumab, primarily administered intravenously, was effective for articular involvement and had a corticosteroid-sparing effect in jSLE, with a favourable safety profile. Its efficacy was limited for cutaneous, renal and haematological manifestations. These findings support the potential benefit of belimumab in this population while highlighting the need for prospective, multicentre and long-term studies to confirm these observations.

Hypocomplementaemic urticarial vasculitis (HUV) is a rare small-vessel vasculitis characterized by the combination of urticarial vasculitis and hypocomplementaemia. HUV may occur in isolation or be associated with systemic diseases such as systemic lupus erythematosus (SLE). Recently, loss-of-function variants in DNASE1L3 have been reported to cause familial forms of HUV. We aimed to describe the clinical and genetic features of childhood-onset HUV cases in France. We conducted a nationwide retrospective study in France that included 10 patients with childhood-onset HUV. Ten children, all girls, were included. Their median age at onset was 9.5 years (range: 2–14 years), and the median delay between onset and diagnosis was 13 months (range: 6–55 months). Phenotypes were heterogeneous: 3 had systemic HUV syndrome (S-HUVS), all associated with DNASE1L3 deficiency, including 2 siblings; 4 had non-systemic HUVS (NS-HUVS), one of whom had a C2 deficiency; and 3 had SLE-associated HUV. Musculoskeletal features were the most common extracutaneous manifestation (9/10). The most severe manifestations were observed in children with S-HUVS, including pulmonary haemorrhage (2/3) and glomerulonephritis (2/3). Anti-nuclear antibodies were positive in 9/10 patients, anti-C1q antibodies in 6/10, and anti-neutrophil cytoplasmic antibodies in 5/10. Antihistamines were widely used in NS-HUVS, while S-HUVS and SLE-associated HUV required immunosuppressive treatments. Hydroxychloroquine was used in 8/10 patients. These 10 cases highlight the heterogeneity and potential severity of childhood-onset HUV. We report the third familial form of HUVS associated with DNASE1L3 deficiency and an extremely rare case of HUVS associated with C2 deficiency. Childhood-onset HUV is a rare disease with phenotypic and genotypic heterogeneity. Systemic HUVS, associated with DNASE1L3 deficiency but not with positive anti-C1q, is the most severe form. A genetic testing should be systematically performed in childhood-onset HUV.

Background Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease characterised by a highly heterogeneous presentation. Specific genetic variations predispose patients to the disease, and rare monogenic forms caused by single-gene variations have been identified in a small percentage of patients, often with early disease onset. In this study, we used exome sequencing in a large cohort of patient with juvenile-onset SLE to gain insight into the genetic basis of juvenile SLE (jSLE). Methods Patients were selected if disease onset occurred before the age of 18. We performed exome sequencing on 263 individuals across 172 distinct families. The majority of cases were solo exomes (n = 118), while others included affected duos, trios, or multiplex families (n = 18 + 5 + 1), as well as classical trios with unaffected parents (n = 30). Findings A molecular diagnosis consistent with the clinical presentation was established in 17 patients from unrelated families (10%). Among them, we identified pathogenic or likely pathogenic variants in genes previously associated with monogenic lupus, including a novel C1QA variant as well as other lupus-associated genes (COPA, ADAR, TLR7, IKZF3, RELA, PTPN11, SERPING1). Strikingly, exome sequencing also revealed variants in immunodeficiency-associated genes (IRAK4, USB1), autoinflammatory disorders (PSTPIP1) and unexpected candidates like ETV6, and MAN1B1 revealing previously unrecognised pathways in SLE development. Syndromic features and very early-onset (before the age of 5) were strongly associated with a higher diagnostic yield, reaching nearly 33% in these subgroups. Interpretation This study expands our understanding of causes of lupus, highlighting its genetic heterogeneity. It also supports the systematic use of genetic testing in cases of juvenile lupus, especially those with very early onset or syndromic features, regardless of the clinical presentation. Given the range of unexpected molecular diagnoses identified in this study, pangenomic analysis such as exome or genome sequencing appears to be the most appropriate approach in these cases. Funding This work was supported by: The Institut National de la Santé et de la Recherche Médicale (INSERM); Government grants managed by the Agence Nationale de la Recherche (ANR) as part of the “Investment for the Future” program: Institut Hospitalo-Universitaire Imagine (ANR-10-IAHU-01), Recherche Hospitalo-Universitaire (ANR-18-RHUS-0010); The Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH); The Fondation pour la Recherche Médicale (FRM: EQU202103012670, FDM202006011291); French and European grants managed by the ANR: ANR-14-CE14-0026 (Lumugène), ANR-21-CE17-0064 (SOCSIMMUNITY); The National Reference Center for Rheumatic, Autoimmune and Systemic Diseases in Children (RAISE).

Juvenile idiopathic arthritis (JIA) is characterised by arthritis onset before the age of 16, persisting for at least 6weeks without a known cause. Symptoms include joint swelling, inflammatory pain (worse at night and in the morning), or also back, heel, or buttock pain. Timely diagnosis and referral to a paediatric rheumatologist are crucial to reduce errors, invasive procedures, and long-term complications. Around 5000 children under 16 are affected by JIA in France. The current international classification recognises 7 subgroups: the systemic form, oligoarthritis, polyarthritis without rheumatoid factor, polyarthritis with rheumatoid factor (juvenile rheumatoid arthritis), enthesitis associated with JIA (juvenile spondyloarthropathy), JIA associated with psoriasis and undifferentiated JIA. A new classification divides JIA into 5 groups: the systemic form, early-onset oligo- and polyarthritis with anti-nuclear antibodies (associated with a risk of chronic anterior uveitis), polyarthritis with rheumatoid factor, juvenile spondyloarthropathy and non-groupable forms. JIA management involves a multidisciplinary team led by a paediatric rheumatologist, using targeted therapies (biologics, small molecules) and numerous health professionals (physiotherapist, occupational therapist, etc.), improving overall outcomes. Physicians (paediatricians or general practitioners) play a vital role in overall management, ensuring treatment compliance, monitoring effectiveness, and managing infection risks. This includes updating vaccination schedules and addressing febrile episodes. We present recent international recommendations including the "treat-to-target" approach, consisting in setting precise objectives at the beginning and during the evolution, which involves regularly assessing the patient's situation to adapt treatments, control inflammation and disease complications, limit the toxicity of treatments. This strategy aims to achieve, ideally in a few months an inactive disease or complete remission. Regarding systemic JIA (or pediatric Still's disease), we pay attention to particularly severe clinical forms in very young children, which may be life-threatening by major activation of the immune system (macrophage activation syndrome) or secondary pulmonary involvement. For non-systemic forms, i.e. oligoarthritis, polyarthritis, enthesitis related JIA (or juvenile spondylarthropathies) and JIA associated with psoriasis, we specify the state of current knowledge and uncertainties regarding prognosis and therapeutic choices.

Background: Systemic sclerosis encompasses a range of disorders characterized by vascular and connective tissue abnormalities. Although rare in pediatrics, juvenile systemic sclerosis (jSSc) is a severe and life-threatening condition that significantly impacts children's development. This study aimed to provide an overview of JSSc in France over the past decade. Methods: Patients with disease onset before the age of 16 were included following a request for observations sent via email to member practitioners of the SOFREMIP (French pediatric Rheumatology society). Results: Our study included 18 patients from 8 different French centers. While our cohort exhibited a balanced distribution between limited and diffuse subsets of the disease, we observed a higher prevalence of the diffuse subset in children above the age of 10. Skin induration was the most reported symptom, while Raynaud's phenomenon was present in 61% of the children at initial clinical evaluation. All children tested positive for antinuclear antibodies, with anti-Scl70 being the most common specificity, even among children with limited cutaneous subsets. Interestingly, we found a high sensitivity of the ACR / EULAR criteria for diagnosing jSSc in our cohort with 83% of patients meeting these criteria, except for 3 children who presented with overlap syndromes. Despite the frequent use of corticosteroids at the onset, no deaths or renal crises were reported. Three patients received treatment with biological agents, specifically Rituximab and Tocilizumab. Conclusion: JSSc is a rare but severe disease requiring rapid, specialized, and multidisciplinary care. Further studies are needed to validate proper diagnosis criteria including overlap syndromes and evaluate the use of biotherapies in children.

Paediatric-onset anti-nuclear antibody-associated immune thrombocytopenic purpura (ITP-ANA+) is a pre-lupus condition. Interferon signature (IS) is a reliable method to measure interferon-stimulated gene expression which is commonly raised in systemic lupus erythematosus (SLE) and in adult pre-lupus cases. Between 2022 and 2024, IS analysis was performed on 61 children, 17 with ITP-ANA+, 15 with ITP-ANA-, 15 with SLE and 14 with juvenile idiopathic arthritis. IS was positive in 14/17 children (82%), with a median score of 17 (1.2-143). This median IS was significantly higher than in the ITP-ANA- group (2.8, 1-41, p = 0.03) and lower than in the SLE group (37.5, 2.1-129, p = 0.04). Among ITP-ANA+ children, IS elevation was associated with age >10 years at ITP diagnosis, newly diagnosed or persistent ITP, positive anti-extractable nuclear antigen antibodies and the absence of hydroxychloroquine treatment. Hydroxychloroquine significantly reduced IS values in three children with pre- and post-treatment scores available. The involvement of type I interferon signalling in childhood ITP-ANA+ highlights a distinct pathogenic pathway and IS appears as a pertinent biomarker to identify patients at risk of progression to SLE. The introduction of hydroxychloroquine in these patients could help prevent the high morbidity of SLE at adult age.

Rare diseases (RD) have progressively emerged as public health priority in many countries. Epidemiological data are still lacking and the extraction of data from the public health system remains insufficient. In France, RD database set up in 2013 as Banque Nationale de Données de Maladies Rares (BNDMR). Patients’ information is provided by physician at each consultation and RD are classified according ORPHAcode. The status of each diagnosis can be entered as ‘confirmed’, ‘probable’ or ‘under investigation’, as well as related families. We aimed to test the reliability and quality of data for epidemiology by analyzing the data from a RD caused by autosomal dominant inheritance and with a univocal genetic diagnosis: TNF receptor-associated periodic syndrome (TRAPS). Patients were extracted on January 2023 and genetic files were retrieved from January to march 2023. All patients registered with a diagnosis of TRAPS were included. We identified 132 patients who fulfilled inclusion criteria, among which 31 were excluded (missing data and duplicates). We analyzed 101 patients and their sequences of TNFSRSF1A gene. Pathogenic and likely pathogenic variants were found in 69

OBJECTIVES:Childhood-onset systemic lupus erythematosus (cSLE) is a rare autoimmune disease with significant morbidity. Although B cell-depleting agents show promise for refractory cSLE, there is limited research on rituximab therapy in children. This study aimed to retrospectively assess the indications, efficacy, and safety of RTX in cSLE, using data from the Juvenile Inflammatory Rheumatism (JIR) cohort database. METHODS:A national retrospective study analysed data from the JIR cohort for cSLE patients treated with RTX from July 2009 to June 2023. RESULTS:Forty-one patients received RTX over 14 years; 85.4% were girls and mean age at diagnosis was 11.7 years. RTX was administered on average 16 months post-diagnosis. At treatment initiation, 87% either had received or were receiving corticosteroids, 21% NSAIDs and 82% immunosuppressants. Main indications for RTX were lupus nephritis (51.2%), persistent polyarthritis (19.5%) and refractory cytopenias (12.2%). Significant improvements in disease activity were observed at 3 and 6 months post-RTX infusion, indicated by the SLEDAI-2K score (P < 0.001), along with a notable reduction in corticosteroid usage (from 0.93 mg/kg to 0.39 mg/kg; P = 0.001) and improvements in relevant biomarkers. Adverse effects occurred in 17% of patients, with 7.3% experiencing anaphylactic reactions. One year following the last infusion, 52.5% of the paediatric subjects did not necessitate an increase in their baseline immunosuppressive therapy or the initiation of a novel treatment modality. CONCLUSIONS:RTX in refractory cSLE reduced disease activity and steroid dependence with an acceptable safety profile. Further research and international collaboration are needed to validate these findings.

Non-infectious paediatric granulomatous uveitis (PGU) is a rare disease that is idiopathic in more than half of affected children. The diagnosis of definite ocular sarcoidosis (OS) must be supported by the presence of non-caseating granulomas detected in biopsy, and is therefore a challenge in children with PGU. This study investigated the utility of minor salivary gland biopsy (MSGB) in the diagnosis of definite OS in PGU. Twenty-six consecutive children with PGU diagnosed between 2018 and 2023 and with a systematically performed MSGB within 3 months of the diagnosis were enrolled. The median age at PGU diagnosis was 11.6 (4.2–16.5) years, and 54

PURPOSE:Fractures in infants younger than 1 year without an obvious accidental cause raise suspicion of child abuse, warranting a skeletal survey. However, adherence to child abuse screening guidelines remains suboptimal. This study aimed to identify factors associated with skeletal survey completion in infants with fractures in the absence of a clear accidental context. METHODS:A retrospective chart review was conducted on children younger than 1 year with at least one fracture, identified over a 6-year period (2017-2023) at a French tertiary children's hospital. Infants with fractures due to obstetric trauma or road traffic accidents were excluded. Multivariate logistic regression was used to determine factors associated with skeletal survey completion. RESULTS:A total of 312 children were included, of whom 97 (33%) underwent a skeletal survey. Among those children, additional fractures were detected in 16 (16.5%). Skeletal surveys were more frequently performed in boys (odds ratio [OR]: 3.82, 95% confidence interval [CI]: 1.66-8.84), younger infants, and those with an inconsistent or evolving trauma explanation (OR: 17.18, 95% CI: 1.86-158.26) or no reported explanation (OR: 16.56, 95% CI: 6.30-43.54). CONCLUSIONS:Only one-third of infants were screened for occult fractures, but the factors associated with skeletal survey completion aligned with established clinical guidelines. Long-term follow-up is necessary to assess whether the two-thirds of children who were unscreened were later identified as victims of child abuse.

Introduction Systemic Lupus Erythematosus (SLE) can be diagnosed using the 2012 criteria of the Systemic Lupus International Collaborating Clinics (SLICC) and, more recently, the 2019 criteria of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR). Hematological involvement is scored differently by these classifications. Our objective was to compare both criteria in a cohort of children with autoimmune cytopenia (AIC)-associated SLE.Method We included 79 patients with childhood-onset AIC as the first manifestations of SLE.Results The median age at SLE diagnosis was 14.5 years (1.1-21.4 years). The SLICC criteria were fulfilled by 76/79 (96%) patients and the EULAR/ACR criteria by 72/79 (91%) patients during follow-up. The SLICC and EULAR/ACR criteria were discordant (not concomitantly fulfilled) in 25/79 (32%) patients. Non-hematological clinical manifestations were more frequently observed in SLE diagnosis when the criteria were concordant (30/54, 56%) than when they were not (5/25, 20%) (p = 0.004). In 16/25 (64%) discordant patients, the SLICC criteria allowed earlier diagnosis of SLE. Finally, the attribution of a maximum weight of 6 to the hematological involvement of the EULAR/ACR criteria increased the sensitivity thereof from 63/79 (80%) to 76/79 (96%) in our population.Conclusion The SLICC 2012 and EULAR/ACR 2019 criteria do not effectively diagnose SLE in children when AIC is the predominant feature. The SLICC criteria appear to be more effective in this population of SLE patients. An increase in the maximum weight of hematological involvement to 6 increases the sensitivity of the EULAR/ACR criteria for SLE diagnosis in children.

Introduction: Anakinra has dramatically improved the management of systemic juvenile idiopathic arthritis (SJIA) over the last decade. Nevertheless, management remains inconsistent; corticosteroids are still frequently used. We analyzed the course of SJIA in children treated with anakinra according to the time of treatment initiation after Methods: Children with SJIA treated with anakinra between 2006 and 2020 were included in this single-center, retrospective observational study. Results: Twenty-four children received anakinra at a median time of 58 (range 12-2940) days after SJIA onset, all after failure of nonsteroidal anti-inflammatory drug (NSAID) treatment. Eighteen were males and the median age at disease onset was 6.04 (range 0.8-13) years. The median follow-up time was 3.5 (range 0.5-10.8) years after treatment initiation. At the last follow-up, remission attributable to anakinra was observed in 18/24 (75%) children and treatment-free remission was observed in 12 (67%). For each child, the response to anakinra was the same at 3 months and at the last follow-up. The 15 children treated with anakinra within the first 3 months after disease onset exhibited better remission (93%) than did the 9 children treated after 3 months (44%) (p = 0.015) and the former received fewer corticosteroids (7% versus 67%) (p = 0.004). One child with long-standing disease died of the disease. Conclusions: Early anakinra initiation within the first 3 months of SJIA onset after NSAID failure ensures longterm remission and reduces corticosteroid use. Anakinra should not be continued for more than 3 months in nonresponding children.

Les maladies auto-immunes (MAI) pédiatriques touchent plus fréquemment l’adolescente contrairement aux maladies auto-inflammatoires monogéniques qui concernent principalement le plus jeune enfant. De nombreuses situations peuvent faire évoquer une MAI, mais la prescription d’un bilan auto-immun sera réalisée le plus souvent sans urgence et après avoir éliminé les causes infectieuses et néoplasiques. Cet article détaille les principaux éléments orientant vers une MAI en rhumatologie–médecine interne pédiatrique et discute l’intérêt des anticorps anti-nucléaires. Le bilan devra toujours être accompagné d’une bandelette urinaire en cas de suspicion de connectivite ou de vascularite. L’association avec un déficit immunitaire devra être recherchée. Enfin, en cas d’auto-immunité biologique sans contexte clinique évident, il faudra contrôler et suivre régulièrement l’enfant en cas de positivité persistante afin de déceler précocement une MAI débutante.

Abstract Background Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS). Methods This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study. Results 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab. Conclusion This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

Objectives: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu’s arteritis (TAK) in a European population.Methods: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK.Results: We identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (p<0.05). Children presented with significantly more systemic symptoms; i.e., fever (p<0.05), fatigue (p<0.001), weight loss (p<0.001), abdominal pain (p<0.05), and myalgia (p<0.05) while adults had more upper limb claudication (p<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (p<0.01), upper and lower limbs (p<0.001) while children had more kidney lesions (p<0.05). Children TAK had more frequent (p<0.01) and higher (p<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (p=0.001) and less biotherapy (p<0.010) at diagnosis. Relapses (p<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults.Conclusion: Paediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment.

Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS'CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer >= 1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period.

Background Despite guidelines, poor access to appropriate care for juvenile idiopathic arthritis (JIA) patients remains a global issue. Prompt referral to a pediatric rheumatology (PR) center and effective care is known to be critical for changing the natural history of the disease and improving long-term prognosis. This project assesses socio-economic factors of delayed referral to a pediatric rheumatologist (PRst) for JIA patients in France and Switzerland within the Juvenile Inflammatory Rheumatism (JIR) Cohort. Methods All patients diagnosed with JIA, presenting at one center of the JIRcohort in France or Switzerland with additional data on referral pathway were included. Patient characteristics at first visit to the PR center, dates of visits to healthcare providers during referral, and parent characteristics were extracted from the JIRcohort database. Results Two hundred fifty children were included. The overall median time to first PR assessment was 2.4 months [1.3; 6.9] and ranged widely across the JIA subtypes, from 1.4 months [0.6; 3.8] for children with systemic juvenile idiopathic arthritis (sJIA) to 5.3 months [2.0; 19.1] for children with enthesitis-related arthritis (ERA). A diagnosis of ERA and an appointment with an orthopedist during the referral pathway were significantly associated with a longer time before the first PR visit (hazard ratio HR 0.50 [95% CI: 0.29; 0.84]) and HR 0.68 [95% CI: 0.49; 0.93], respectively) in multivariable analysis. Having a mother with a post-graduate educational attainment level was tendentially associated with a shorter time before the first PR visit, (HR 1.32 [95% CI: 0.99; 1.78]). Conclusions Time to first PRst visit was most often short compared to other studies and close to the British recommendations. However, this time remained too long for many patients. We observed no social inequities in access to a PRst, but we show the need to improve effective pathway and access to a PR center for JIA patients.

MARSHALL SYNDROME. Marshall syndrome also known as PFAPA syndrome belongs to the group of autoinflammatory diseases. The acronym reflects the main clinical features of the disease: periodic fever, aphthous stomatitis, pharyngitis, and adenitis. It is the most common autoinflammatory disease, beginning between 1 and 5 years of age. There is little or no impact on growth, but the recurrence of febrile seizures can compromise the quality of life of patients. Clinical diagnosis meets positive and exclusion criteria. Putting it correctly allows a reassuring framework of care and avoids many unnecessary antibiotic treatments. Corticosteroid therapy is the reference treatment for the crisis. Tonsillectomy associated with adenoidectomy can be discussed but is not systematically recommended in this pathology, which is generally benign and most often heals spontaneously with age.

The paradigm type I interferonopathy Aicardi-Goutières syndrome (AGS) is most typically characterized by severe neurological involvement. AGS is considered an immune-mediated disease, poorly responsive to conventional immunosuppression. Premised on a chronic enhancement of type I interferon signaling, JAK1/2 inhibition has been trialed in AGS, with clear improvements in cutaneous and systemic disease manifestations. Contrastingly, treatment efficacy at the level of the neurological system has been less conclusive. Here, we report our real-word approach study of JAK1/2 inhibition in 11 patients with AGS, providing extensive assessments of clinical and radiological status; interferon signaling, including in cerebrospinal fluid (CSF); and drug concentrations in blood and CSF. Over a median follow-up of 17 months, we observed a clear benefit of JAK1/2 inhibition on certain systemic features of AGS, and reproduced results reported using the AGS neurologic severity scale. In contrast, there was no change in other scales assessing neurological status; using the caregiver scale, only patient comfort, but no other domain of everyday-life care, was improved. Serious bacterial infections occurred in 4 out of the 11 patients. Overall, our data lead us to conclude that other approaches to treatment are urgently required for the neurologic features of AGS. We suggest that earlier diagnosis and adequate central nervous system penetration likely remain the major factors determining the efficacy of therapy in preventing irreversible brain damage, implying the importance of early and rapid genetic testing and the consideration of intrathecal drug delivery.