Pediatric Rheumatology最新文献

{"title":"Outcome measures and monitoring framework in juvenile systemic sclerosis: bridging routine care and clinical trials.","authors":"Ivan Foeldvari, Edoardo Marrani","doi":"10.1186/s12969-026-01285-6","DOIUrl":"10.1186/s12969-026-01285-6","url":null,"abstract":"<p><strong>Introduction: </strong>Juvenile systemic sclerosis (jSSc) is an orphan multisystem autoimmune disease that can cause significant morbidity during childhood and can lead to significant worsening of quality of life. The pathophysiological features are identical with adult-onset systemic sclerosis (SSc), jSSc exhibits a distinct clinical phenotype characterized by a significantly higher prevalence of diffuse cutaneous involvement, frequent overlap syndromes, distinct autoantibody profiles, and different long-term survival trajectories. Historically, the evaluation of jSSc has relied heavily on the extrapolation of adult outcome measures, which fail to account for developmental physiology, somatic growth, and pediatric-specific feasibility constraints.</p><p><strong>Areas covered: </strong>This review provides a comprehensive overview of indicators of disease activity and severity which might be used in daily clinical practice and adapted as outcome measures in future clinical trials. It includes global outcome measures, organ-specific outcomes (including skin, pulmonary, cardiac, gastrointestinal, musculoskeletal, renal, and vascular involvement), patient-reported outcome measures (PROMs), and clinician-reported outcomes (ClinROs). The performance of adult indices within pediatric cohorts are evaluated, if applicable. Additionally, we analyze severity scores like the Juvenile Systemic Sclerosis Severity Score (J4S) alongside modern consensus metrics derived from the international Hamburg symposia. We emphasize the integration of pediatric-adapted clinical assessments, quantitative imaging, and patient and physician related outcomes.</p><p><strong>Expert opinion: </strong>The development of outcome measure in jSSc requires a paradigm shift from static severity scores to dynamic, multi-dimensional indicators capable of differentiating reversible inflammatory activity from potential permanent damage accrual. Validating pediatric-specific thresholds for physiological and cutaneous change remains an urgent priority. Over the next decade, the integration of artificial intelligence (AI)-driven quantitative imaging, decentralized home-based digital health tools, and molecular biomarkers probably will gain an essential role to optimize clinical trial readiness and personalize therapeutic strategies for children with systemic sclerosis.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"African recommendations for diagnosis and management of systemic juvenile idiopathic arthritis (sJIA) - a PAFLAR initiative.","authors":"Soad Hashad, Angela Nyangore Migowa, Ahmed Seri, Ourida Gacem, Ali Sobh, Hala Etayari, Eman A Almsillati, Angelo Ravelli, Pierre Quartier, Ayodele Faleye, Waleed Hassan, Doaa Mosad, Elisa Palalane, Temesgen Teferi, Yaninga Halwani Fuseini, Mohammed Hassan, Hanna Lishan, Wassila Messadi, Madeleine Ngandeu, Yassmin Taha, Wafa Hamdi, Samah Ismail, Hanane Lassoued Ferjani, Chafia Makhloufi Dahou, Yasmine Makhlouf, Samy Slimani, Christiaan Scott, Djohra Hadef","doi":"10.1186/s12969-026-01238-z","DOIUrl":"10.1186/s12969-026-01238-z","url":null,"abstract":"<p><strong>Objectives: </strong>To develop evidence-based recommendations for diagnosis and treatment of children and adolescents with systemic juvenile idiopathic arthritis (sJIA), taking into consideration the socioeconomic status and availability of medications in African countries.</p><p><strong>Methods: </strong>A steering group composed of five PAFLAR members formulated questions in PICO format (Patient/Population, Intervention, Comparison, Outcome), conducted a systematic literature review, and identified experts in pediatric rheumatology throughout Africa. The Delphi method was used to reach consensus among the experts on the recommendations for diagnosis and treatment of sJIA patients.</p><p><strong>Results: </strong>The online Delphi questionnaire was sent to the 22 experts selected by the steering committee, who were asked to vote for each statement and to provide their suggestions for modifications or rewording. A 100% response rate was obtained. A minimum agreement of 70% among the voting panel was required. A total of 15 recommendations were formulated, 4 regarding diagnosis and 11 regarding treatment. The percentage of agreement with the recommendations ranged from 72.7% to 95%.</p><p><strong>Conclusion: </strong>We present the first African recommendations for diagnosis and management of sJIA. The feedback about the application of these recommendations in pediatric rheumatology centers will serve as the basis for future revisions in the light of African-specific experiences and insights.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A big problem for little people: the impact of proposed Medicaid reimbursement cuts and the fragility of pediatric rheumatology care.","authors":"Michelle V Benjamin, Gail Kerr, S Amara Ogbonnaya, Gwenesta B Melton, Sharon Dowell, Grace C Wright, Mia T Chandler","doi":"10.1186/s12969-026-01267-8","DOIUrl":"10.1186/s12969-026-01267-8","url":null,"abstract":"<p><strong>Background: </strong>There is a significant shortage of pediatric rheumatologists in the United States with only about 420 practicing providers and more than 300,000 children with rheumatologic conditions. This shortage is compounded by regional maldistribution with large geographic areas lacking pediatric rheumatology providers and by the increasing prevalence of autoimmune diseases.</p><p><strong>Main text: </strong>Medicaid was established in 1965 to provide coverage for low-income families, children, senior citizens and people with disabilities. About 50% of children in the US are insured through Medicaid or The Children's Health Insurance Program (CHIP), programs that significantly increased access to health care for children. Pediatric subspecialists, including rheumatologists, see patients predominately covered through public insurance. However, the lower reimbursement rates have led to lower salaries for pediatric rheumatologists compared to peers with the same level of training. Medicaid cuts will potentially worsen this shortage by limiting reimbursement and recruitment of even fewer trainees. This will reduce access nation-wide and may result in worse outcomes for children living with rheumatologic conditions.</p><p><strong>Conclusion: </strong>This paper poses some potential solutions including the recent American Board of Pediatrics decision to shorten the duration of subspeciality training for pediatric rheumatology, offering loan repayment, and expanding the role of advanced practice providers. It also highlights the importance of leveraging advocacy groups to fight for policies that promote the health and well-being of children living with rheumatologic conditions and advocate for policies that sustain reimbursement for specialty care.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence to treat-to-target recommendations in juvenile idiopathic arthritis in clinical practice.","authors":"S De Roock, P C E Hissink Muller, R S M Yeung, S J Vastert, D A Marshall, S M Benseler, J F Swart","doi":"10.1186/s12969-026-01265-w","DOIUrl":"https://doi.org/10.1186/s12969-026-01265-w","url":null,"abstract":"<p><strong>Objective: </strong>To assess adherence to Treat-to-Target (T2T) recommendations for juvenile idiopathic arthritis (JIA) in clinical practice.</p><p><strong>Methods: </strong>A nested cohort study in the multicenter international prospective UCAN JIA cohort was performed. Patient characteristics, clinical features, classification, disease activity as measured by number of active joints (AJC), Physician Global Assessment (PhGA) and Patient Global Assessment (PPGA) and treatment at baseline and six-months visit was assessed. Data were compared to published, consensus-based T2T recommendations. Logistic regression with step-wise selected variables identified factors related to the decision to change therapy.</p><p><strong>Results: </strong>A total of 476 children were included, 62% female, median age was 10.0 years. At baseline, anti-inflammatory medications (NSAID) and/or intra-articular injections were started in 53%, conventional synthetic anti-rheumatic drugs (csDMARD) in 37% and biologic therapies in 11%. At six-months, 248 patients (52%) had inactive arthritis based on AJC. PPGA was not collected for 35% of patients. In children with arthritis, treatment change as suggested in the recommendations were only made in 33%. Patients that had no treatment change were more often already treated with a csDMARD or biological or had limited number of joints affected. Multivariate logistic regression showed that the decision to change treatment at six-months was significantly related to PhGA, prior treatment changes and use of csDMARD or biological since baseline.</p><p><strong>Conclusion: </strong>PPGA is not consistently collected, hampering measurement-based care and T2T. PhGA and prior treatment steps are underlying current treatment decisions, but often not according to the T2T cut-offs and time-points that have been agreed upon in consensus.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149118744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the 33rd European Paediatric Rheumatology Congress.","authors":"","doi":"10.1186/s12969-026-01260-1","DOIUrl":"10.1186/s12969-026-01260-1","url":null,"abstract":"","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 Suppl 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-related quality of life in childhood arthritis: the impact of generic versus disease-specific instruments.","authors":"Jelleke B de Jonge, Sytze de Roock, Nele Grundhoefer, Deborah A Marshall, Sebastiaan J Vastert, Rae S M Yeung, Susanne M Benseler, Joost F Swart","doi":"10.1186/s12969-026-01274-9","DOIUrl":"10.1186/s12969-026-01274-9","url":null,"abstract":"<p><strong>Background: </strong>Health-related quality of life (HRQoL) data provided by children with arthritis and their parents is critically important to enable co-design of care and shared decision making. However, there is significant heterogeneity in how HRQoL is captured, as both generic (EQ-5D-Y-5L) and disease-specific instruments (JAMAR) are available. This study aimed to examine the concordance of the JAMAR and EQ-5D-Y-5L questionnaires in childhood arthritis.</p><p><strong>Methods: </strong>The international UCAN CAN-DU study prospectively enrolled consecutive children with arthritis across Canada and the Netherlands. This study included patients in whom corresponding JAMAR and EQ-5D-Y-5L questionnaires were completed on the same date by either the patients or their parents. The concordance of the questionnaire responses was measured by comparing the answers given to five specific JAMAR domains corresponding to the EQ-5D-Y-5L dimensions (anxiety/depression; mobility; pain/discomfort; self-care; usual activities). The impact of disease activity was assessed. Spearman's correlation explored the association between global scales from the JAMAR and the EQ-5D-Y-5L.</p><p><strong>Results: </strong>The study included 678 children with JIA; 63% were female; the median age at first questionnaire was 11.9 years (interquartile range: 6.2-15.1). Concordances between JAMAR and EQ-5D-Y-5L responses were found in 84% of the questions across all domains (84%, 82%, 85%, 87%, and 82% for anxiety/depression, mobility, pain/discomfort, self-care, and usual activities, respectively). In a state of inactive disease, generic and disease-specific instruments converged across all domains except for pain/discomfort. Comparison of global assessment scales revealed a high correlation between the EQ-5D-Y-5L and the JAMAR (Spearman's correlation: R = -0.72, p < 0.001).</p><p><strong>Conclusions: </strong>Patients and parents provided different responses to generic and disease-specific HRQoL instruments. The concordance was reduced in all domains except for pain/discomfort when children were experiencing high disease activity, highlighting the perceived conceptual differences and limitations of HRQoL instruments.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of persistent oxidative stress markers with coronary artery abnormalities in Kawasaki disease patients on follow-up.","authors":"Rajni Kumrah, Taru Goyal, Manphool Singhal, Prateek Bhatia, Vignesh Pandiarajan, Ankur Kumar Jindal, Rakesh Kumar Pilania, Deepti Suri, Surjit Singh, Amit Rawat","doi":"10.1186/s12969-026-01249-w","DOIUrl":"10.1186/s12969-026-01249-w","url":null,"abstract":"<p><strong>Background: </strong>Kawasaki disease (KD) is associated with long-term vascular sequelae, including persistent endothelial abnormalities. Data on laboratory-based markers of oxidative stress during long-term follow-up of KD patients from developing countries are limited. This study aimed to evaluate extracellular nitric oxide metabolites and neutrophil-derived reactive oxygen species (ROS) in patients with KD during follow-up and to explore their associations with coronary artery abnormalities (CAAs).</p><p><strong>Methods: </strong>In this prospective, single-centre study, 62 children with KD and 20 age- and gender-matched healthy controls (HC) were enrolled. KD patients were stratified into three groups based on time since diagnosis and further categorised by the presence or absence of CAAs. Serum nitrite and nitrate levels were measured as indicators of extracellular nitric oxide metabolism. Neutrophil ROS production was assessed using a dihydrorhodamine-123 flow cytometric assay.</p><p><strong>Results: </strong>Serum nitrite levels were comparable across the 3 groups (Group 1: 3.46 ± 1.64; Group 2: 5.04 ± 2.55; Group 3: 5.22 ± 3.00) and HC (3.33 ± 1.98) (p = 0.06). The serum nitrate levels in KD patients across all three groups (Group 1: 63.07 ± 41.32; Group 2: 58.63 ± 27.12; Group 3: 64.57 ± 26.36) were also comparable to HC (57.49 ± 8.68) (p = 0.43). In subgroup analysis, serum nitrate levels and serum nitrite levels in KD patients with CAAs and without CAAs were comparable (Group 1: p = 0.60; Group 2: p > 0.99; Group 3: p = 0.10) and (Group 1: p > 0.99; Group 2: p > 0.99; Group 3: p = 0.90), respectively. Neutrophil ROS production (ΔMFI) was increased in KD patients, with a significant rise observed in the intermediate follow-up group 2 (> 1.5-3 years) compared with healthy controls (p = 0.03). No significant correlations were found between oxidative stress markers and systemic inflammatory parameters.</p><p><strong>Conclusion: </strong>Children with KD exhibit persistent oxidative stress during follow-up, as evidenced by increased neutrophil ROS production, indicating ongoing cellular oxidative activity. Elevated ROS may serve as an accessible biomarker for CAAs and long-term cardiovascular risk in KD patients on follow-up.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-life physical activity and risk of juvenile idiopathic arthritis: a longitudinal ABIS cohort study using a symptom-free baseline design.","authors":"Noman Sohail, Erik Kindgren, Johnny Ludvigsson","doi":"10.1186/s12969-026-01266-9","DOIUrl":"10.1186/s12969-026-01266-9","url":null,"abstract":"<p><strong>Background: </strong>The role of physical activity (PA) in the development of juvenile idiopathic arthritis (JIA) remains unclear, and the evidence addressing this question is limited. Therefore, this study aimed to investigate the longitudinal association between early-life PA and the risk of JIA, using a symptom-free baseline design to minimize bias from early disease manifestations.</p><p><strong>Methods: </strong>A total of 16,415 participants were included from the All Babies in Southeast Sweden cohort. PA was assessed at age 5, 8, and 10-12 years using a composite Total Activity Score by categorizing participants into less active and highly active groups based on z-score threshold. Incident JIA cases (n = 88) were identified through Swedish National Patient Registers. At each age, individuals with a diagnosis of JIA prior to or at the time point were excluded. Participants reporting joint symptoms (pain, swelling, limited mobility, or limping) were excluded to create a symptom-free baseline population. Remaining participants were followed for incident JIA. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence interval. All models were adjusted for sex, parental education, and family history of rheumatic disease.</p><p><strong>Results: </strong>After exclusions, 6832 participants were identified at age 5, 3885 at age 8, and 4445 at age 10-12. A total of 62, 56, and 40 incident JIA cases during follow-up were identified in the respective age-specific cohorts. Higher PA was consistently associated with a reduced risk of JIA across all age groups, with HRs ranging from 0.72 to 0.88 in unadjusted models, and 0.76 to 0.91 in adjusted models. However, none of the associations reached statistical significance.</p><p><strong>Conclusion: </strong>Our findings suggest that PA in childhood does not increase the risk of JIA although any potential protective association is likely modest. The use of a symptom-free cohort strengthens causal interpretation by minimizing reverse causation.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological manifestations and vasculopathy in PLCG2-associated antibody deficiency and immune dysregulation (APLAID): a case series.","authors":"Kosar Asna Ashari, Rebecca MacRae, David P Hoytema van Konijnenburg, Craig D Platt, Maryam Ashoor, Alfred P See, Agnieszka Kielian, Amy Danehy, Riten Kumar, Elliot James, Kristin Houghton, Sheri Harder, Mark P Gorman, Stacy A Kahn, Ankana Daga, Sadaf H Hussain, Alicia M Johnston, Alicia Casey, Jodie D Ouahed, Wai Wong, Kathy Jenkins, Susan Prockop, Esraa Eloseily, Kimberly Risma, Michael J Ombrello, Fatma Dedeoglu, Milena M Andzelm","doi":"10.1186/s12969-026-01227-2","DOIUrl":"10.1186/s12969-026-01227-2","url":null,"abstract":"<p><strong>Background: </strong>Autosomal dominant pathogenic variants in PLCG2 are associated with autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID), characterized by immunological abnormalities and multi-system inflammation. Descriptions of associated neurological manifestations and vascular anomalies are limited. We describe three patients with APLAID, vasculopathies, neuroinflammation, and cerebral vascular tortuosity. These cases highlight underrecognized and clinically important manifestations of APLAID.</p><p><strong>Case presentations: </strong>All three patients had de novo variants in PLCG2 and early systemic inflammatory and immunodeficiency findings within the spectrum of APLAID (e.g. immune laboratory abnormalities, skin and gastrointestinal inflammation, and frequent infections). Additionally, they had notable neurological and vascular findings. Patient #1 (PLCG2 c.3420T > A; p.Asp1140Glu) is a female who had focal seizures at 16 months old. Magnetic resonance imaging (MRI) revealed right parietal leptomeningeal enhancement with white matter changes. MR angiography (MRA) showed cerebrovascular tortuosity and stenoses without evidence of vasculitis. She had extensive veno-lymphatic malformation in the thorax, abnormal renal vasculature, inferior vena cava (IVC) atresia, and bilateral pulmonary vein stenosis (PVS). Patient #2 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at four years old had an episode of status epilepticus. MRI revealed a right parietal infarct with surrounding leptomeningeal enhancement and MRA demonstrated abnormal caliber of the right middle cerebral artery (MCA), arterial tortuosity, and carotid aneurysms. His course was complicated by aortic root dilation and bilateral PVS. Patient #3 (PLCG2 c.2122G > C; p.Ala708Pro) is a male who at 16 months had a right sided focal motor seizure. MRI demonstrated infarct with associated sulcal enhancement predominantly in the left cerebral hemisphere. MRA found excessive vascular tortuosity and fenestrations. He has a dilated aortic root and ventricular septal defect (VSD).</p><p><strong>Conclusion: </strong>We present three cases of APLAID complicated by significant cerebrovascular tortuosity and seizure and two with cerebral ischemia. The etiology of stroke and/or seizures in these patients is unclear, but vasculopathy leading to perfusion deficits, neuroinflammation, or thrombosis due to underlying thrombotic diathesis or abnormal vascular anatomy may have contributed. We recommend all patients with APLAID undergo monitoring for neurologic manifestations. Additionally, we highlight important vasculopathic findings such as PVS, where early recognition for directed treatment is critical.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal Aicardi-Goutières syndrome presenting with macrophage activation syndrome-like hyperinflammation and severe congenital glaucoma: a case report.","authors":"Murat Konak, Banu Bozkurt, Gülay Ceylaner, Müşerref Kasap Cüceoğlu, Fatih Mehmet Akif Özdemir, Buket Kara, Osman Selçuk Duysak, Saime Sündüs Uygun","doi":"10.1186/s12969-026-01264-x","DOIUrl":"10.1186/s12969-026-01264-x","url":null,"abstract":"<p><strong>Background: </strong>Neonatal-onset Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy that may mimic congenital infection and can present with severe multisystem inflammation. The distinction between primary hemophagocytic lymphohistiocytosis (HLH) and AGS-associated macrophage activation syndrome (MAS)-like hyperinflammation can be challenging in neonates.</p><p><strong>Case presentation: </strong>We report a term neonate presenting with cholestatic jaundice, a generalized blueberry muffin-like ecchymotic-purpuric rash, cytopenias, hyperferritinemia, hepatosplenomegaly, intracranial calcifications, and severe bilateral congenital glaucoma. Extensive infectious evaluation was negative. The patient fulfilled five of eight HLH-2004 criteria, consistent with a severe MAS-like hyperinflammatory phenotype. Dexamethasone and intravenous immunoglobulin had been initiated at the referring center for presumed virus-associated HLH but were not continued after transfer to our unit. With persistent disease activity, negative microbiological studies, and neuroimaging strongly suggestive of a type I interferonopathy, ruxolitinib was initiated on day of life (DOL) 34 before molecular confirmation. Exome sequencing subsequently identified homozygous pathogenic variants in RNASEH2B and CYP1B1, supporting AGS type 2 and primary congenital glaucoma (glaucoma 3 A), respectively. Serial laboratory data showed sustained improvement after initiation of JAK1/2 inhibition, although the observational nature of a single case and other immunomodulatory exposures limit causal attribution.</p><p><strong>Conclusions: </strong>This case illustrates the clinical overlap between neonatal AGS and MAS-like hyperinflammation, underscores the potential role of early mechanism-based therapy in selected critically ill neonates with suspected interferonopathy, and emphasizes the importance of comprehensive genomic evaluation when severe ocular disease accompanies AGS. The identified CYP1B1 variant provides a strong molecular explanation for the patient's congenital glaucoma.</p>","PeriodicalId":54630,"journal":{"name":"Pediatric Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148882527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}