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Objective Autoinflammatory diseases (AIDs) are characterized by recurrent sterile systemic inflammation attacks. More than half of the patients remain genetically undiagnosed with next-generation sequencing panels for common AIDs. In this study, we aimed to define phenotype-genotype correlations in a cohort of unclassified AID patients via whole exome sequencing (WES). Methods Patients with features of AIDs were included in this study followed in the Department of Pediatric Rheumatology at Hacettepe University. They were first screened for MEFV with Sanger sequencing and then WES performed for the patients with clinically insignificant results. Pre-analysis of WES data was done by considering the 13 most common AID-related genes. Further bioinformatic analysis was performed if the patient remained genetically undiagnosed. Results The median age at disease onset was 1.2 years (range 0.2–16) and at the time of study recruitment was 14 years (range 3.5–17). In our cohort, WES provided a definite or probable disease-causing variant in 4 of 11 patients (36%). Heterozygous mutations for two of these genes were previously associated with neurological defects (ADAM17, TBK1), also homozygous ADAM17 mutations were observed in one family with neonatal inflammatory skin and bowel disease. Besides, two genes (LIG4, RAG1) were associated with immunodeficiency although the patients had presented with inflammatory features. Finally, for one patient, we associated a strong candidate gene (NLRC3) with autoinflammatory features. Conclusion WES strategy is cost-effective and provides substantial results for a selected group of undefined AID patients. Our results will contribute to the spectrum of unclassified AIDs. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Herein, we report a 4-month-old male infant who presented to our hospital with an abdominal mass that was diagnosed as neuroblastoma and spinal muscular atrophy type I. We would like to discuss the course and differential diagnosis with an algorithm leading to the diagnosis in this peculiar patient. To our knowledge, coexistence of spinal muscular atrophy type I and neuroblastoma is defined for the first time in the literature. [ABSTRACT FROM PUBLISHER]

Systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are considered the same disease, but a common approach for diagnosis and management is still missing., Methods: In May 2022, EULAR and PReS endorsed a proposal for a joint task force (TF) to develop recommendations for the diagnosis and management of sJIA and AOSD. The TF agreed during a first meeting to address four topics: similarity between sJIA and AOSD, diagnostic biomarkers, therapeutic targets and strategies and complications including macrophage activation syndrome (MAS). Systematic literature reviews were conducted accordingly., Results: The TF based their recommendations on four overarching principles, highlighting notably that sJIA and AOSD are one disease, to be designated by one name, Still's disease.Fourteen specific recommendations were issued. Two therapeutic targets were defined: clinically inactive disease (CID) and remission, that is, CID maintained for at least 6 months. The optimal therapeutic strategy relies on early use of interleukin (IL-1 or IL-6 inhibitors associated to short duration glucocorticoid (GC). MAS treatment should rely on high-dose GCs, IL-1 inhibitors, ciclosporin and interferon-γ inhibitors. A specific concern rose recently with cases of severe lung disease in children with Still's disease, for which T cell directed immunosuppressant are suggested. The recommendations emphasised the key role of expert centres for difficult-to-treat patients. All overarching principles and recommendations were agreed by over 80% of the TF experts with a high level of agreement., Conclusion: These recommendations are the first consensus for the diagnosis and management of children and adults with Still's disease., Competing Interests: Competing interests: BF: AbbVie, Amgen, Biogen, BMS, Celltrion, Fresenius Kabi, Galapagos, Gilead, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche-Chugai, Sandoz, Sanofi-Genzyme, SOBI, UCB, Viatris; SM: BMS, Lilly, SOBI; JA: Sobi, Novartis, Roche, Pfizer, AbbVie, Lilly; AB: Boehringer Ingelheim, Novartis, AbbVie, Fresenius Kabi, GlaxoSmithKline; CB: SOBI; TC: AbbVie, Novartis, Roche; LD: AbbVie, Amgen, Astra-Zeneca, Boehringer-Ingelheim, BMS, Lilly, Galapagos, GlaxoSmithKline, Janssen, Kiniksa, Novartis, Pfizer, SOBI; ADB: Lenovo; EF: AbbVie, BMS, Galapagos, Lilly, Medac, Novartis, Sanofi, UCB, Pfizer, Roche, SOBI; DF: Boehringer-Ingelheim, SOBI, Novartis, Werfen Innova; MG, SGL, FM, FOR, SV: Novartis, SOBI; RG, AG: Novartis; IJ: Amgen, Lilly, Novartis, SOBI; PN: BMS, Brickell Bio, Cerecor, Exo Therapeutics, Miach Ortho, Novartis, Pfizer, SOBI, UpToDate, American Academy of Pediatrics; SO: Novartis, SOBI, Pfizer; PQ: Amgen, AbbVie, BMS, Roche-Chugai, Lilly, Novartis, Pfizer, Sanofi, SOBI, Health Events; PR: AbbVie, BMS, Janssen, Novartis, SOBI; SS: Novartis, SOBI, CSL Behring, Takeda, BioCryst, Biotest; M-ET: Boehringer-Ingelheim, Pfizer, Lilly, MSD, SOBI, Janssen, BMS, Fresenius Kabi, Galapagos, AbbVie; CW: Novartis, SOBI, UCB; LC: Meda Pharma, Angelini Pharma, Pfizer, SANOFI-AVENTIS, Fresenius Kabi, Galapagos; FDB: SOBI, Novartis, Apollo, Kiniksa, Sanofi, Roche, Elixiron, Regeneron; ADM, SB, KL, CL, ES, T-CW: none., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease of childhood; the pathogenesis is associated with T cell activation. T cell activation can be counter-balanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3, and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes., Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and synovial fluid) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups., Results: The polyarticular-JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4(p< 0.001), sPD-1(p< 0.05), and s4-1BB(p< 0.05) when compared with the other JIA subgroups and healthy controls. We analyzed the cellular surface expression of different co-IRs on the PBMCs of different JIA subtypes. Similar to plasma levels, both the percentage(p< 0.05) and the MFI (mean fluorescence intensity) (p< 0.01) of CTLA4 expression were higher in the poly-JIA subgroup., Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Biologic drugs (BD) have been game-changers in rheumatic diseases; however, severe hypersensitivity reactions concerning anaphylaxis may limit their use. Desensitisation is a crucial option that is safe and effective to maintain patients on the preferred drug. Herein we report 84 Rapid Drug Desensitisation (RDD) procedures with rituximab and tocilizumab in children with rheumatic diseases., Methods: The study was conducted as a retrospective chart review of patients who received tocilizumab or rituximab therapy between January 2010 and December 2018. The results of RDD with tocilizumab and rituximab were documented., Results: The study group consisted of 53 patients (11.6±4.5 years, 67.9% female) with rheumatic disease who had used tocilizumab (64.1%, 1007 infusions) or rituximab (35.8%, 73 infusions). Five patients (14.7%) had experienced anaphylaxis with tocilizumab and two patients (10.5%) with rituximab. Anaphylaxis was grade II in four cases whereas it was grade III in the remaining three children. Skin testing with the culprit BD performed in five children yielded positive results. We performed 65 RDDs with tocilizumab in 3 patients and 19 RDDs with rituximab in two patients. No reactions were recorded in 97.6% of the procedures. We observed one anaphylaxis during the 5th RDD of tocilizumab. After modifying the protocol, this patient continued tocilizumab RDD uneventfully., Conclusions: RDD is a groundbreaking innovation which ensures giving the full target doses while protecting the patient against severe hypersensitivity reactions (HSRs) and anaphylaxis. As BD use increases in childhood, management of HSRs to BD will become more complicated, necessitating an increased need for RDD in clinical practice.

Sarcoidosis, a multisystem disorder of unknown etiology that involves multiple organs, is rare in children. The true incidence and prevalence of childhood sarcoidosis is unknown. As in adults, many children with sarcoidosis may be asymptomatic; the disease may remain undiagnosed. A complete and systematic evaluation of the patient is essential for the sarcoidosis diagnosis in children. Here, we describe a case of 12-year-old female who presented with 2 years history of uveitis and hepatosplenomegaly. A chest computerized tomography revealed scattered peripheral pulmonary nodules and bilateral hiliar lymphadenopathy. Bone marrow aspiration and liver biopsy were not diagnostic. A lung biopsy showed non-necrotizing epithelioid cell granulomas. She was diagnosed with sarcoidosis according to demonstration of granulomatous inflammation and the exclusion of confusable entities