Traditional laboratory parameters and IFNγ-related biomarkers in the diagnosis and management of MAS.

Objectives: To evaluate diagnostic and prognostic significance of traditional laboratory parameters of hyperinflammation and of the IFNγ-related biomarkers interleukin-18 (IL-18), CXCL9 and neopterin in macrophage activation syndrome (MAS) secondary to Still's disease (SD).

Methods: Forty-one patients with MAS and 24 patients with active pediatric SD from six Italian centers were enrolled. Samples were obtained at baseline (at initiation or within 48 hours of initiation of specific treatments) for MAS or active SD and at T1 (5-15 days from baseline) only from MAS.

STING induces ZBP1-mediated necroptosis independently of TNFR1 and FADD.

Conditional deletion of Caspase-8 in epidermal keratinocytes (Casp8) causes necroptosis-driven lethal dermatitis. Here, we discover that Casp8 loss leads to accumulation of cytosolic DNA responsible for the activation of a cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon (IFN) gene (STING)-mediated transcriptional program. Genetic and biochemical evidence indicate that STING upregulates both Z-DNA binding protein-1 (ZBP1), and mixed lineage kinase domain-like (MLKL).

Current evidence on switching between biologic therapies for Still's disease: A systematic literature review.

Objective: Still's disease (SD) is increasingly being treated with biologic disease-modifying antirheumatic drugs (bDMARDs) according to a treat-to-target approach, with switching between these agents an integral part of this strategy. However, guidance for the clinician on switching between biologic agents in SD is limited. Here we review the evidence in the literature relating to switching between bDMARDs in SD.

Innate Lymphoid Cell Phenotypic and Functional Alterations in Patients With Systemic Juvenile Idiopathic Arthritis.

Objective: Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood disease classically attributed to innate immune cell dysregulation. This study aimed to elucidate the role of innate lymphoid cells (ILCs), including natural killer (NK) cells and helper-ILCs (hILCs), in sJIA during clinically inactive disease (CID) through phenotypic and functional analysis.

Methods: Peripheral ILCs from children with sJIA during CID receiving interleukin-1 (IL-1) inhibitors (n = 40) were analyzed by flow cytometry and compared to 23 healthy children (HC) and 22 patients with unrelated autoinflammatory diseases taking IL-1 inhibitors.

Unmet needs and research gaps in Still's disease across ages: proceedings from a pediatric and adult joint expert panel.

Background: Still's disease (SD), including systemic juvenile idiopathic arthritis (sJIA) and adult-onset SD (AOSD), is an inflammatory condition typically characterized by daily fever, arthritis, and skin rash together with neutrophilic leukocytosis, thrombocytosis, and increased acute phase reactants. The reported differences between sJIA and AOSD appear to reflect variations along an inflammatory spectrum influenced by age, rather than differences in the underlying pathology.

Methods: In February 2023, an expert meeting, including pediatric and adult rheumatologists, was held in Rome, Italy, with the aim of defining more precise and timely strategies for disease management.

Genotype-phenotype correlation in a cohort of pediatric patients with autoinflammatory diseases carrying variants.

Background: Autoinflammatory diseases (AIDs) are a group of disease characterized by excessive activation of the innate immune system with episodes of spontaneous inflammation that can affect different organs. Many monogenic or acquired autoinflammatory diseases are described in literature. More recently the concept of disease with polygenic or complex inheritance has been introduced.

Physician's global assessment of disease activity in juvenile idiopathic arthritis: consensus-based recommendations from an international task force.

Objectives: To develop consensus-based recommendations for physician's global assessment of disease activity (PhGA) scoring and to standardise definitions of disease activity.

Methods: An international task force of 34 members was assembled, and recommendations were developed in 3 phases: (1) 2 preliminary surveys of paediatric rheumatologists and a literature review; (2) 14 videoconference meetings, informed by multicriteria decision analysis and formal anonymous voting; and (3) a 2-day in-person consensus conference using structured nominal group technique discussions and formal voting. The threshold for achieving consensus was ≥78% of voting task force members.

Off-Label Use of Anakinra in Inflammatory Conditions in Neonates and Infants Up to 3 Months of Age: A Case Series and a Review of the Literature.

Background: Anakinra is an interleukin-1 receptor antagonist (IL-1Ra). Since IL-1 has been shown to play a key role in the etiology of different autoinflammatory diseases, blocking its pathway has become an important therapeutic target, even in neonates.

Aims: We aimed to report our experience in using anakinra to treat specific neonatal inflammatory conditions.

Different patterns of longitudinal changes in antinuclear antibodies titers in children with systemic lupus erythematosus and Sjögren's syndrome.

Objective: to investigate the trend of autoantibody titers during a 2-year follow-up in pediatric systemic lupus erythematosus (pSLE) and pediatric Sjögren's syndrome (pSS).

Methods: Autoantibodies testing was performed every 3-4 months during 2 years from disease onset in a cohort of children with pSLE and pSS.

Results: We enrolled 21 children with pSLE and 22 children with pSS.

EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease.

Unlabelled: 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).

Efficacy and safety of therapies for Still's disease and macrophage activation syndrome (MAS): a systematic review informing the EULAR/PReS guidelines for the management of Still's disease.

Objectives: To analyse the efficacy and safety of treatments for Still's disease and macrophage activation syndrome (MAS).

Methods: Medline, Embase and Cochrane Library were searched for clinical trials (randomised, randomised controlled trial (RCT), controlled and clinical controlled trial (CCT)), observational studies (retrospective, longitudinal observational retrospective (LOR), prospective and longitudinal observational prospective (LOP)) and systematic reviews (SRs), in which the populations studied were patients with Still's disease and MAS. The intervention was any pharmacological treatment (approved or under evaluation) versus any comparator drug or placebo, and as outcomes, any relevant efficacy and safety event.

Systemic juvenile idiopathic arthritis and adult-onset Still's disease are the same disease: evidence from systematic reviews and meta-analyses informing the 2023 EULAR/PReS recommendations for the diagnosis and management of Still's disease.

Objectives: To analyse the similarity in clinical manifestations and laboratory findings between systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD).

Methods: Three systematic reviews (SR) were performed. One included cohort studies comparing sJIA versus AOSD that described clinical and biological manifestations with at least 20 patients in each group (SR1).

Early bone marrow alterations in patients with adenosine deaminase 2 deficiency across disease phenotypes and severities.

Background: Deficiency of adenosine deaminase 2 (DADA2) is a complex monogenic disease caused by recessive mutations in the ADA2 gene. DADA2 exhibits a broad clinical spectrum encompassing vasculitis, immunodeficiency, and hematologic abnormalities. Yet, the impact of DADA2 on the bone marrow (BM) microenvironment is largely unexplored.

Management, treatment, and clinical approach of Sydenham's chorea in children: Italian survey on expert-based experience.

Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use.

Reliability of a generative artificial intelligence tool for pediatric familial Mediterranean fever: insights from a multicentre expert survey.

Background: Artificial intelligence (AI) has become a popular tool for clinical and research use in the medical field. The aim of this study was to evaluate the accuracy and reliability of a generative AI tool on pediatric familial Mediterranean fever (FMF).

Methods: Fifteen questions repeated thrice on pediatric FMF were prompted to the popular generative AI tool Microsoft Copilot with Chat-GPT 4.

Anti-Interferon-γ Therapy for Cytokine Storm Syndromes.

A vast body of evidence provides support to a central role of exaggerated production of interferon-γ (IFN-γ) in causing hypercytokinemia and signs and symptoms of hemophagocytic lymphohistiocytosis (HLH). In this chapter, we will describe briefly the roles of IFN-γ in innate and adaptive immunity and in host defense, summarize results from animal models of primary HLH and secondary HLH with particular emphasis on targeted therapeutic approaches, review data on biomarkers associated with activation of the IFN-γ pathway, and discuss initial efficacy and safety results of IFN-γ neutralization in humans.

Translation and validation in Italian of the methotrexate intolerance severity score for children and adults with arthritis.

Objectives: Methotrexate (MTX) is the most used drug to treat children and adults with arthritis and its use is burdened by adverse effects. The MTX intolerance severity score (MISS) was developed in English to identify patients who are intolerant to MTX. The aim of this study was to translate and validate the MISS in Italian.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome.

Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected.