Behçet's syndrome (BS) is a rare systemic vasculitis, characterized by a wide range of different clinical involvements and unpredictable phases of recurrence and remission. BS can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B^*51, the cause behind the onset and progression of the disease remains currently not fully understood. Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders. Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. This review summarizes current evidence on the main genetic, environmental and immunological factors contributing to BS development.

Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of interleukin-1(IL-1)β that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients’ quality of life. IL-1β blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1β antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.

Objectives Behçet’s syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria. In search of novel biomarkers for BS diagnosis, we determined the profile of plasmatic circulating microRNAs (ci-miRNAs) in patients with BS compared with healthy controls (HCs). Methods ci-miRNA profile was evaluated by microarray in a screening cohort (16 patients with BS and 18 HCs) and then validated by poly(T) adaptor PCR (PTA-PCR) in a validation cohort (30 patients with BS and 30 HCs). Two disease control groups (30 patients with systemic lupus erythematosus (SLE) and 30 patients with giant cell arteritis (GCA) were also analysed. Results From the microarray screening, 29 deregulated (differentially expressed (DE)) human ci-miRNAs emerged. A hierarchical cluster analysis indicated that DE ci-miRNAs clearly segregated patients from controls, independently of clinical features. PTA-PCR analysis on the validation cohort confirmed the deregulation of miR-224-5p, miR-206 and miR-653-5p. The combined receiver operating characteristic (ROC) curve analyses showed that such ci-miRNAs discriminate BS from HCs (and BS with active vs inactive disease), as well as BS from patients with SLE and GCA. The functional annotation analyses (FAAs) showed that the most enriched pathways affected by DE ci-miRNAs (ie, cell–matrix interaction, oxidative stress and blood coagulation) are related to thrombo-inflammatory mechanisms. Accordingly, the expression of the three ci-miRNAs from the validation cohort significantly correlated with leucocyte reactive oxygen species production and plasma lipid peroxidation. Conclusions The ci-miRNA profile identified in this study may represent a novel, poorly invasive BS biomarker, while suggesting an epigenetic control of BS-related thrombo-inflammation.

To describe frequency, preventability and seriousness of adverse drug reactions (ADRs) in children as cause of emergency department (ED) admission and to evaluate the association between specific factors and the reporting of ADRs. A retrospective analysis based on reports of suspected ADRs collected between January 1st, 2012 and December 31st, 2016 in the ED of Meyer Children’s Hospital (Italy). Demographics, clinical status, suspected drugs, ADR description, and its degree of seriousness were collected. Logistic regression was used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of potential predictors of ADR seriousness. Within 5 years, we observed 834 ADRs (1100 drug-ADR pairs), of whom 239 were serious; of them, 224 led to hospitalization. Patients were mostly treated with one drug. Among patients treated with more than one drug, 78 ADRs presented a potential interaction. The most frequently reported ADRs involved gastrointestinal system. The most frequently reported medication class was antinfectives. Risk of serious ADR was significantly lower in children and infants compared to adolescents (ROR 0.41 [95% CI: 0.27–0.61] and 0.47 [0.32–0.71], respectively), and it was significantly increased in subjects exposed to more than one drug (ROR 1.87 [1.33–2.62] and 3.01 [2.07–4.37] for subjects exposed to 2 and 3 or more drugs, respectively). Gender, interactions and off-label drug use did not influence the risk of serious ADRs. Active surveillance in pharmacovigilance might represent the best strategy to estimate and characterize the clinical burden of ADRs in children.