Abstract
Behçet’s syndrome (BS) is a systemic vasculitis characterized by a relapsing and remitting course. It can involve the skin, mucosa, joints, vessels (arteries and/or veins), eyes, and nervous ...and gastrointestinal systems, and so is referred to as a syndrome rather than as a unique and nosologically distinct condition. These involvements may present alone or co-exist in the same patient. Although all the possible combinations of the above-mentioned manifestations may occur, clusters of commonly co-existing involvements (also referred to as ‘disease phenotypes’) have been suggested, namely ‘mucocutaneous and articular’, ‘peripheral vascular and extra-parenchymal neurological’ and ‘parenchymal neurological and ocular’ phenotypes have been described. Patient-specific demographic and genetic features have been described as positively or negatively associated with specific disease phenotypes. This review will focus on the different clinical features of Behçet’s syndrome, summarizing current evidence on the distinct disease manifestations as well as the major phenotypes.
Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more ...frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion (
) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents "
" a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets.
The first 1000 days of life -including pregnancy and the first 2 years after birth- represent a critical window for health interventions. This systematic review aimed to summarize the evidence on the ...relationship between traffic-related air pollutants exposure in the first 1000 days of life and the development of wheezing and asthma, with a particular focus on windows of exposure.
Medline and Embase were searched from January 2000 to May 2020 to retrieve population-based birth-cohort studies, including registries, providing quantitative information on the association between exposure to traffic-related air pollutants during pregnancy or early life, and the risk of developing wheezing and asthma in childhood. Screening and selection of the articles were completed independently by three reviewers. The quality of studies was assessed using the Newcastle-Ottawa scale.
Out of 9681 records retrieved, 26 studies from 21 cohorts were included. The most common traffic-related air pollutant markers were particulate matter (PM) and nitric oxides (NOx). The variability in terms of pollutants, exposure assessment methods, and exposure levels chosen to present the results did not allow a meta-analysis. Exposure to PM and NOx in pregnancy (10 cohorts) was consistently associated with an increased risk of asthma development, while the association with wheezing development was unclear. The second trimester of pregnancy seemed to be particularly critical for asthma risk. As for exposure during early life (15 cohorts), most studies found a positive association between PM (7/10 studies) and NOx (11/13 studies) and the risk of asthma development, while the risk of wheezing development was controversial. The period of postnatal exposure, however, was less precisely defined and a partial overlap between the period of exposure measurement and that of outcome development was present in a consistent number of studies (14 out of 15) raising doubts on the associations found.
Traffic-related air pollution during pregnancy is associated with an increased risk of asthma development among children and adolescents. The relationship between exposure in the first two years of life and the development of wheezing and asthma needs to be confirmed in studies with more precise exposure assessment.
To evaluate the efficacy and safety of secukinumab in Behçet's patients with active mucocutaneous and articular manifestations refractory to previous treatments.
We retrospectively evaluated 5 ...patients treated with the IL17-inhibitor secukinumab and diagnosed with Behçet according to ISG/ICBD criteria. All patients had active mucocutaneous and articular manifestations refractory to colchicine, conventional DMARDs and at least one anti-TNFα agent. Four patients received secukinumab in the dose of 150 mg/monthly since also fulfilling the criteria for ankylosing spondylitis, while the fifth patient received secukinumab 300 mg/monthly because she met psoriatic arthritis criteria. Achievement of response was based on the number of oral ulcers, BASDAI and ASDAS for articular involvement, and BDCAF for Behçet activity. Complete response was defined as: i) decrease ≥50% in the number of oral ulcers; ii) BASDAI index <4; iii) ASDAS index <1.4; iv) decrease of 50% or more in BDCAF index.
The patient starting secukinumab 300 mg/month successfully achieved complete response within 3 months. Complete response was maintained during all 9-months follow-up. Among the 4 subjects starting secukinumab 150 mg/month, two achieved complete response at month 6, but one relapsed. This patient and the two who not achieved complete response at month 6 were switched to secukinumab 300 mg/month. Within 3 months from the dosage increase, all three subjects successfully (re)achieved complete response.
Our study suggested for the first time that secukinumab (either 150 mg and 300 mg/month) improved active mucocutaneous manifestations refractory to previous treatments, while secukinumab 300 mg/monthly resulted superior in inducing articular and complete response in Behçet's patients.
•Secukinumab is effective for Behçet's mucocutaneous and articular manifestations.•Secukinumab 300 mg is superior to 150 mg for inducing articular and complete response.•Due to secukinumab safety concerns in IBD, attention must be paid in entero-Behçet.
Behçet's syndrome (BS) is a multisystemic vasculitis, characterized by different clinical involvements, including mucocutaneous, ocular, vascular, neurological, and gastrointestinal manifestations. ...Based on this heterogeneity, BS can be hardly considered as a single clinical entity. Growing evidence supports that, within BS, different phenotypes, characterized by clusters of co-existing involvements, can be distinguished. Namely, three major BS phenotypes have been reported: (a) the mucocutaneous and articular phenotype, (b) the extra-parenchymal neurological and peripheral vascular phenotype, and (c) the parenchymal neurological and ocular phenotype. To date, guidelines for the management of BS have been focused on the pharmacological treatment of each specific BS manifestation. However, tailoring the treatments on patient's specific phenotype, rather than on single disease manifestation, could represent a valid strategy for a personalized therapeutic approach to BS. In the present literature review, we summarize current evidence on the pharmacological treatments for the first-, second-, and third-line treatment of the major BS phenotypes.
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.
BACKGROUND:
Temporal lobe epilepsy (TLE) surgery is associated with the best seizure outcome in adults, although its long-term results remain suboptimal. Retrospective pediatric studies suggest ...better figures whose determinants are poorly understood.
OBJECTIVE:
To conduct a systematic review and meta-analysis of studies on the efficacy of TLE surgery in children (age younger than 18 years) and adults.
METHODS:
We searched MEDLINE, Embase, and Cochrane Library for TLE surgery original research from January 1, 1990, until May 12, 2020. The outcome measures were seizure freedom since surgery and seizure freedom either at last or longest follow-up. We meta-analyzed the proportion of children and adults achieving either Engel I/International League Against Epilepsy (ILAE) 1 or Engel IA/ILAE 1A outcome by follow-up duration, type of surgery, histopathology, neuroimaging, quality of the studies, and publication period. We used a random effects model with Freeman-Tukey double arcsine transformation of proportions.
RESULTS:
From 40 409 records identified, we included 277 studies (30 848 patients). The proportions of patients achieving Engel I/ILAE 1 and Engel IA/ILAE 1A outcomes were 0.74 (95% CI, 0.69-0.78) and 0.61 (0.48-0.74) for children and 0.69 (0.67-0.71) and 0.56 (0.52-0.60) for adults. Histopathology significantly influenced Engel I/ILAE 1 outcome in adults but not in children (
P
< .0001), while the type of surgery significantly influenced Engel I/ILAE 1 outcome in children but not in adults.
CONCLUSION:
The proportion of seizure freedom after TLE surgery was higher in children, although not significantly. Histopathology and the surgical approach can influence seizure outcome, with age-related variability.
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.
Background
General practitioners often deal with patients suffering acute musculoskeletal disorders. Paracetamol, non-steroidal anti-inflammatory drugs, and opioids are the most prescribed ...medications, according to pain intensity and patient’s features. Combinations of different analgesics can be adopted to enhance pain relief, but only one fixed-dose combination has been recently launched to treat acute musculoskeletal pain.
Objective
This study aimed to investigate the effectiveness of ibuprofen plus paracetamol (fixed-dose) combination compared to other analgesics in preventing musculoskeletal pain persistence.
Setting
Italian outpatients’ data extracted from a national general practice database.
Method
A retrospective cohort study was conducted on the Health Search Database. Patients prescribed with analgesics for acute musculoskeletal painful conditions were considered (i.e., non-chronic painful conditions, identified using a query validated by two expert General Practitioners (GPs)). For each patient, the first prescription of an analgesic was defined as index date. A new GP’s visit related to musculoskeletal disorders in the first 3 months following the index date was defined as “pain persistence”.
Main outcome measure
Risk of pain persistence among users of the ibuprofen plus paracetamol combination compared to other systemic analgesics.
Results
Overall, 102,216 patients were treated with systemic analgesics for acute musculoskeletal disorders. Most patients were middle-aged or elderly women. 939 (0.92%) patients were prescribed with the fixed-dose ibuprofen plus paracetamol combination for a mean duration of 7.23 ± 2.68 days, mainly for low back pain and cervicalgia. Musculoskeletal pain persistence was found in 22,125 (21.65%) patients. Compared to other systemic analgesics, the ibuprofen plus paracetamol combination resulted significantly more effective in preventing pain persistence (adjusted hazard ratio 0.72, 95% confidence interval 0.61–0.85).
Conclusion
These findings suggest that the fixed-dose ibuprofen plus paracetamol combination might be effective in controlling musculoskeletal pain persistence.
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