26rhk178 10.3205/26rhk178 urn:nbn:de:0183-26rhk1787 Meeting Abstract Tietz Tietz Lara Antonia LA

University Hospital Leipzig, Hospital for Children and Adolescents, Department of Pediatric Immunology, Rheumatology and Infectiology, Leipzig, Deutschland

author Dunst Dunst Franziska F

University Hospital Leipzig, Hospital for Children and Adolescents, Department of Pediatric Immunology, Rheumatology and Infectiology, Leipzig, Deutschland

author Hohmann Hohmann Tamara T

University Hospital Leipzig, Hospital for Children and Adolescents, Department of Pediatric Immunology, Rheumatology and Infectiology, Leipzig, Deutschland

author Gräfe Gräfe Daniel D

University Hospital Leipzig, Department of Diagnostic and Interventional Radiology, Leipzig, Deutschland

author Klemann Klemann Christian C

University Hospital Leipzig, Hospital for Children and Adolescents, Department of Pediatric Immunology, Rheumatology and Infectiology, Leipzig, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20260909 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0656 178 Deutsche Gesellschaft für Rheumatologie Deutsche Gesellschaft für Orthopädische Rheumatologie Gesellschaft für Kinder- und Jugendrheumatologie 54. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immunologie (DGRh), 36. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 40. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh) Deutscher Rheumatologiekongress 2026 Kinderrheumatologie Leipzig 20260909 20260912 KI.39 TextIntroduction: Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a rare ACP5-associated type I interferonopathy combining skeletal dysplasia with often severe systemic immune dysregulation. Although JAK inhibitors (JAKi) directly target interferon signalling, evidence in paediatric SPENCDI remains limited to small case series and individual reports.Methods: We retrospectively analysed a genetically confirmed paediatric SPENCDI case treated at our centre and systematically reviewed all published SPENCD/SPENCDI patients receiving JAKi. Phenotype and treatment response were assessed descriptively.Results: Our patient showed an early-onset phenotype with disproportionate short stature and progressive multisystem immune dysregulation, including constitutional symptoms, SLE-like manifestations, vasculopathic skin changes, lymphopenia, hypergammaglobulinaemia and IgA nephropathy. Initial response to ruxolitinib was limited, most likely due to underdosing in the context of advanced inflammatory disease. Following dose optimisation, however, rapid and clinically relevant improvement occurred, particularly in systemic symptoms and overall disease burden. Across the literature, we identified 14 genetically confirmed SPENCD patients, 12 of whom had been treated with JAKi. Overall, 93% experienced clinically meaningful benefit. The clearest effects were observed in immune-mediated and haematological manifestations, while skeletal disease showed little responsiveness. Haematological involvement was present in 93% of patients; partial or complete improvement was seen in most reported cases, with particularly favourable responses in AIHA, ITP and Evans syndrome. By contrast, growth remained impaired despite occasional improvement, and osteoarticular manifestations generally persisted.Conclusion: JAK inhibition appears to be a highly promising pathway-directed treatment for immune dysregulation in SPENCDI, with the strongest effects seen in systemic and haematological disease activity rather than in the skeletal phenotype. Our findings suggest that timing and adequate dosing matter and support earlier therapeutic intervention before irreversible organ damage evolves. Given the rarity of SPENCDI, international collaborative registries are needed to better define response patterns, optimal dosing and long-term outcomes.Disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Shimizu M Inoue N Mizuta M Irabu H Okajima M Honda Y Nihira H Izawa K Yachie A Wada T Successful treatment of spondyloenchondrodysplasia with baricitinib 2021 Rheumatology (Oxford) e44-e46 Shimizu M, Inoue N, Mizuta M, Irabu H, Okajima M, Honda Y, Nihira H, Izawa K, Yachie A, Wada T. Successful treatment of spondyloenchondrodysplasia with baricitinib. Rheumatology (Oxford). 2021 Feb 1;60(2):e44-e46. DOI: 10.1093/rheumatology/keaa356 http://dx.doi.org/10.1093/rheumatology/keaa356 Li W Wang W Wang W Zhong L Gou L Wang C Ma J Quan M Jian S Tang X Zhang Y Wang L Ma M Song H Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China 2022 Front Immunol 825367 Li W, Wang W, Wang W, Zhong L, Gou L, Wang C, Ma J, Quan M, Jian S, Tang X, Zhang Y, Wang L, Ma M, Song H. Janus Kinase Inhibitors in the Treatment of Type I Interferonopathies: A Case Series From a Single Center in China. Front Immunol. 2022 Mar 28;13:825367. DOI: 10.3389/fimmu.2022.825367 http://dx.doi.org/10.3389/fimmu.2022.825367 Chougule A Taur P Gowri V C O. E. Consortium; Desai MM. SPENCD Presenting with Evans Phenotype and Clinical Response to JAK1/2 Inhibitors-a Report of 2 Cases 2023 J Clin Immunol 331-334 Chougule A, Taur P, Gowri V; C. O. E. Consortium; Desai MM. SPENCD Presenting with Evans Phenotype and Clinical Response to JAK1/2 Inhibitors-a Report of 2 Cases. J Clin Immunol. 2023 Feb;43(2):331-334. DOI: 10.1007/s10875-022-01400-8 http://dx.doi.org/10.1007/s10875-022-01400-8 Gernez Y Narula M Cepika AM Valdes Camacho J Hoyte EG Mouradian K Glader B Singh D Sathi B Rao L Tolin AL Weinberg KI Lewis DB Bacchetta R Weinacht KG Case report: Refractory Evans syndrome in two patients with spondyloenchondrodysplasia with immune dysregulation treated successfully with JAK1/JAK2 inhibition 2024 Front Immunol 1328005 Gernez Y, Narula M, Cepika AM, Valdes Camacho J, Hoyte EG, Mouradian K, Glader B, Singh D, Sathi B, Rao L, Tolin AL, Weinberg KI, Lewis DB, Bacchetta R, Weinacht KG. Case report: Refractory Evans syndrome in two patients with spondyloenchondrodysplasia with immune dysregulation treated successfully with JAK1/JAK2 inhibition. Front Immunol. 2024 Jan 29;14:1328005. DOI: 10.3389/fimmu.2023.1328005 https://doi.org/10.3389/fimmu.2023.1328005 Romano M Geerlink A Demirkaya E Berard RA Garcia-Bournissen F Pharmacokinetics of Baricitinib in Cerebrospinal Fluid and Plasma in a Patient with SPENCD 2024 J Clin Immunol 78 Romano M, Geerlink A, Demirkaya E, Berard RA, Garcia-Bournissen F. Pharmacokinetics of Baricitinib in Cerebrospinal Fluid and Plasma in a Patient with SPENCD. J Clin Immunol. 2024 Mar 8;44(3):78. DOI: 10.1007/s10875-024-01680-2 http://dx.doi.org/10.1007/s10875-024-01680-2 Dri J Dos Santos E Pereyra M Guillamondegui MJ Ballester C Tolin A Gatica C Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases 2024 Arch Argent Pediatr e202303031 Dri J, Dos Santos E, Pereyra M, Guillamondegui MJ, Ballester C, Tolin A, Gatica C. Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases. Arch Argent Pediatr. 2024 Feb 1;122(1):e202303031. English, Spanish. DOI: 10.5546/aap.2023-03031.eng http://dx.doi.org/10.5546/aap.2023-03031.eng Liu C Xie Z Wang M Chu J Yang L Zhang K Huang L Tu S Cai H Wu Z Wang L Wang N Case Report: Successful treatment of spondyloenchondrodysplasia with immune dysregulation using tofacitinib and ruxolitinib: a report of two pediatric cases 2025 Front Pharmacol 1588003 Liu C, Xie Z, Wang M, Chu J, Yang L, Zhang K, Huang L, Tu S, Cai H, Wu Z, Wang L, Wang N. Case Report: Successful treatment of spondyloenchondrodysplasia with immune dysregulation using tofacitinib and ruxolitinib: a report of two pediatric cases. Front Pharmacol. 2025 Jul 25;16:1588003. DOI: 10.3389/fphar.2025.1588003 http://dx.doi.org/10.3389/fphar.2025.1588003 Pandurangi S Soucy N Moreda CM Singh V Wysocki CA Dual Targeted Therapy with Baricitinib and Anifrolumab in Infantile Spondyloenchondrodysplasia with Immune Dysregulation 2025 J Clin Immunol 155 Pandurangi S, Soucy N, Moreda CM, Singh V, Wysocki CA. Dual Targeted Therapy with Baricitinib and Anifrolumab in Infantile Spondyloenchondrodysplasia with Immune Dysregulation. J Clin Immunol. 2025 Nov 8;45(1):155. DOI: 10.1007/s10875-025-01954-3 http://dx.doi.org/10.1007/s10875-025-01954-3 Firat Senturk E Ayvaz BB Firtina S Ugurlu S A rare case of late-onset spondyloenchondrodysplasia with immune dysregulation presenting as adult-onset monogenic lupus 2025 Lupus 108-114 Firat Senturk E, Ayvaz BB, Firtina S, Ugurlu S. A rare case of late-onset spondyloenchondrodysplasia with immune dysregulation presenting as adult-onset monogenic lupus. Lupus. 2025 Jan;34(1):108-114. DOI: 10.1177/09612033241301506 http://dx.doi.org/10.1177/09612033241301506 0 0 0 0