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Vasculitis is defined by a state of inflammation of the blood vessel walls. It can result in formation of either aneurysms or stenosis with ischemia and necrosis. The heterogeneity of clinical presentation depends on the type and size of the vessels involved, which leads to different patterns of organ damage. The skin is usually involved but not necessarily as a first manifestation of disease. Indeed, significant organ damage may occur at any time in the disease course and may precede other symptoms with significant morbidity and mortality, especially in case of diagnostic delay. The most common vasculitides in childhood are IgA-associated vasculitis (Schönlein-Henoch purpura) and Kawasaki disease. Other vasculitides are much rarer, often arising with insidious symp- toms that make them life-threatening. This paper aims to review the literature on paediatric vasculitides providing a practical guide to disentangle between different diagnoses. It also provides an overview that underlines the key differences in vasculitis presentation, management and follow-up.

ObjectiveTrained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production.MethodsMonocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes.ResultsGCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production.ConclusionsMyelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.

Juvenile psoriatic arthritis (JPsA) accounts for 1–7% of all cases of juvenile idiopathic arthritis (JIA) and its definition has been a matter of controversy among pediatric rheumatologists for many years. The traditional attribution of JPsA to the spondyloarthropathy group was challenged in the early 1990s, whereas the recent demonstrations of its heterogenous nature have led to questions about its identification as a distinct category in JIA classification. It has been shown that children with the phenotype of JPsA can be divided in two subgroups, one presenting with the features of early-onset ANA-positive JIA, and another that belongs to the spectrum of spondyloarthropathies. The few studies that have compared the clinical characteristics and genetic determinants of JPsA with those of the other JIA categories have obtained contrasting findings. The debate on the categorization of JPsA as a distinct entity within JIA classification is still ongoing and has prompted the revision of its current classification.

Introduction The search for biomarkers in juvenile idiopathic arthritis (JIA) is a promising and rapidly expanding field of investigation. The biomarkers identified so far may help to dissect the clinical heterogeneity of the illness, measure the level of disease activity, predict clinical remission, relapse, response to medications, course over time, complications, and forestall disease flares. Areas covered We provide a summary of the most recent advances in the development and application of biomarkers in JIA. We performed a PubMed search for significant articles combining predetermined keywords related to biomarkers in non-systemic and systemic JIA, chronic uveitis, and macrophage activation syndrome (MAS).The biomarkers available or under study are presented and discussed separately for non-systemic and systemic subtypes and for the two main disease complications, uveitis and MAS. Expert opinion The incorporation of valid and reliable biomarkers in standard clinical care may help to design better patient-tailored treatment regimens and to improve the therapeutic strategies based on the treat-to-target approach. The establishment of biomarkers that predict the risk of disease flare may lead to define the optimal modalities for treatment discontinuation after the achievement of clinical remission.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Background Hyperferritinemic syndromes are systemic inflammatory disorders characterized by a dysfunctional immune response, which leads to excessive activation of the monocyte-macrophage system with hypercytokinemia and may pursue a rapidly fatal course. Case presentation We describe two patients of 11 and 9 years of age with hyperferritinemic syndromes, one with impending macrophage activation syndrome (MAS) and one with overt MAS, who were refractory or intolerant to conventional therapies, but improved dramatically with canakinumab. Conclusions Our report indicates that canakinumab may be efficacious in the management of hyperferritinemic syndromes, including MAS.

Background: The aim of the study was to determine the effect of an educational intervention on the use of trend arrows of a real-time continuous glucose monitoring (rt-CGM) to manage daily therapy decisions in a group of adolescents with type 1 diabetes attending a camp. The secondary aim was to evaluate the variations in total daily dose (TDD) of insulin requirement. Methods: Twenty patients (15-17 years) on multiple insulin injections ( n = 8) or continuous subcutaneous insulin infusion ( n = 12) attended a training session at the beginning of the camp to learn our algorithm for the management of therapy depending on trend arrows. TDD, time in range (TIR), time above range (TAR), and time below range (TBR) (in the 24 hours and in the three hours after breakfast) before the training session (run-in) and at the end of the camp (T1) were analyzed. Results: Data showed a reduction of TAR (run-in 42.6%, T1 32.05%, P = .036) and an increase in TIR (run-in 52.9%, T1 62.4%, P = .013). Reduction of TBR (run-in 42.5%, T1 37.5%, P = .05) and improvement in TIR (run-in 49.0%, T1 57.0%, P = .02) were also observed in the post-breakfast period. Data showed a significant reduction in the TDD (run-in 52.02 ± 17.44 U/die, T1 46.49 ± 12.39 U/die, P = .024). Conclusions: Statistically significant improvement of glycemic control and reduction of TTD were observed in all patients regardless of therapy type. The improvement between run-in and T1 demonstrates the importance of patients’ education on the correct use of rt-CGM with simple algorithms for the management of therapy.

ObjectiveTo investigate the frequency in which the physician provides a global assessment of disease activity (PhGA) >0 and an active joint count (AJC)=0 in children with juvenile idiopathic arthritis (JIA) and search for determinants of divergence between the two measures.MethodsData were extracted from a multinational cross-sectional dataset of 9966 patients who had JIA by International League of Associations for Rheumatology criteria, were recruited between 2011 and 2016, and had both PhGA and AJC recorded by the caring paediatric rheumatologist at the study visit. Determinants of discordance between PhGA>0 and AJC=0 were searched for by multivariable logistic regression and dominance analyses.ResultsThe PhGA was scored >0 in 1647 (32.3%) of 5103 patients who had an AJC of 0. Independent associations with discordant assessment were identified for tender or restricted joint count >0, history of enthesitis, presence of active uveitis or systemic features, enthesitis-related or systemic arthritis, increased acute phase reactants, pain visual analogue scale (VAS)>0, and impaired physical or psychosocial well-being. In dominance analysis, tender joint count accounted for 35.43% of PhGA variance, followed by pain VAS>0 (17.72%), restricted joint count >0 (16.14%) and physical health score >0 (11.42%).ConclusionWe found that many paediatric rheumatologists did not mark a score of 0 for patients who they found not to have active joints. The presence of pain in joints not meeting the definition of active joint used in JIA was the main determinant of this phenomenon.

One of the most challenging and intriguing phenomena observed during the COVID-19 pandemic has been the multisystem inflammatory syndrome in children (MIS-C). Patients with this condition present with some clinical features similar to those of Kawasaki disease (KD) and display signs and symptoms that are uncommon or rarely occur in this disorder, such as gastrointestinal complaints and myocarditis, often leading to myocardial failure and shock. In addition, patients' age is older than that of children with classic KD. Management is based on administering intravenous immunoglobulin, glucocorticoids, and anakinra in the most severe instances. It is still debated whether MIS-C and KD are different illnesses or represent a disease continuum.

Kawasaki disease (KD) is an acute vasculitis of unknown etiology that predominantly affects children

Macrophage activation syndrome (MAS) is a serious, potentially life-threatening, hyperinflammatory condition, which belongs to the spectrum of hemophagocytic lymphohistiocytosis (HLH) and can complicate several immunologic and rheumatic disorders. MAS is characterized by a dysfunctional immune response that is similar to that seen in other forms of HLH. Because MAS may pursue a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are fundamental. Recently, a set of classification criteria for MAS complicating sJIA has been developed through a multinational collaborative effort. High-dose parenteral corticosteroids remain the mainstay of treatment of MAS.