Axial spondyloarthritis: one year in review 2023.

Axial spondyloarthritides (axSpA) are a group of systemic autoimmune diseases, characterised by an inflammatory involvement of the axial skeleton, which, in the earlier phases, cannot be detected by conventional radiology, but only by magnetic resonance imaging, thus defining the so-called non-radiographic axSpA (nr-axSpA). The initial osteitis then tends to complicate into bone reabsorption and aberrant bone deposition, which then determines the ankylosis of the axial skeleton in the latest phases of the disease.Peripheral joints may also be affected, enthesitis being its more characteristic manifestation. The radiographic form corresponds to ankylosing spondylitis which, with psoriatic arthritis, is the best-known subtype of SpA. AxSpA are rarely associated to laboratory abnormalities and are usually complicated by the presence of both extra-articular manifestations (particularly acute anterior uveitis, psoriasis and inflamatory bowel disease) and comorbidities, with a subsequent higher risk for patients of an impaired quality of life.In this paper we reviewed the literature on axSpA of 2021 and 2022 (Medline search of articles published from 1st January 2021 to 31st December 2022).

Psoriatic arthritis: one year in review 2022.

Psoriatic arthritis is a systemic autoimmune disease, in which a characteristic heterogeneous inflammatory involvement of entheses and both peripheral and axial joints tends to be associated with different clinical features, in particular skin or nail psoriasis, but also inflammatory bowel diseases, or acute anterior uveitis. Patients with PsA are at higher risk of developing comorbidities, in particular metabolic syndrome, with a significant impact on their quality of life. Although the advanced knowledge in the pathogenetic mechanisms of PsA helped in developing an abundant therapeutical armamentarium, the available drugs might still show a suboptimal efficacy. However, the frontier of "personalised medicine" could promote further future improvement in the quality of care of patients. In this paper we reviewed the literature on PsA of 2020 and 2021 (Medline search of articles published from 1st January 2020 to 31th December 2021).

One year in review 2021: axial spondyloarthritis.

Axial spondyloarthritides (axSpA) are a group of systemic inflammatory rheumatic diseases with a broad spectrum of clinical manifestations and typical imaging features, rarely accompanied by laboratory abnormalities. They can be classified into a so-called non-radiographic form (nr-axSpA), unlike the radiographic one, because magnetic resonance imaging may show specific inflammatory lesions when conventional radiology is not able to highlight them. Inflammatory involvement of the axial skeleton tends to associate typically with new bone formation and peripheral joints may also be affected. Patients with axSpA are at higher risk of developing some typical extraarticular manifestations, particularly, acute anterior uveitis, psoriasis and inflammatory bowel disease. In this paper we review the literature on axSpA of 2019 and 2020 (Medline search of articles published from 1st January 2019 to 31st December 2020).

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

One year in review 2019: psoriatic arthritis.

Psoriatic arthritis (PsA) is an inflammatory arthritis belonging to spondyloarthritides (SpA), a group of rheumatologic diseases characterised bya wide spectrum of different clinical manifestations that tend to associate with various comorbidities and that may significantly compromise the quality of life of patients. Nowadays, it is well known how PsA may manifest in different clinical domains, in particular peripheral articular and periarticular involvement, axial involvement, skin and nail psoriasis. Moreover, the majority of patients with PsA develop comorbidities such as inflammatory bowel diseases, uveitis, but also cardiovascular diseases, psychiatric or pulmonary pathologies. The therapeutical armamentarium of PsA has been enriched during the last years, in relation to an advance in the knowledge of the immunological mechanisms at the basis of the disease; in particular, the future frontier of "personalised medicine" could lead to a further improvement in the quality of care of this group of patients. In this paper we review the literature on PsA of 2019 (Medline search of articles published from 1st January 2019 to 31st December 2019).

Management of epilepsy in brain tumors.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

One year in review 2017: spondyloarthritis.

The term spondyloarthritis (SpA) represents a condition characterised by a broad spectrum of clinical manifestations, laboratory abnormalities and imaging features; in particular, SpA is an inflammatory condition in which both peripheral and axial joints might be affected. The majority of people with this disease have either psoriatic arthritis or axial spondyloarthritis, which includes ankylosing spondylitis. Less common subgroups are enteropathic SpA, which is associated with inflammatory bowel diseases (Crohn's disease and ulcerative colitis), reactive arthritis, which can occur in people following gastrointestinal or genitourinary infections and undifferentiated SpA, that does not meet the diagnostic criteria of the other subgroups at onset, but that may evolve to do so later. Very interestingly, much of the emerging data show how SpA, during its course, tends to associate with the development of some comorbidities; in particular, with cardiovascular diseases, diabetes mellitus, osteoporosis and depressive disorders. Healthcare professionals in non-specialist settings do not always recognise the signs and symptoms of SpA, particularly spinal symptoms, which may be mistakenly attributed to other causes of low back pain, thus leading to significant delays in diagnosis and treatment of the disease itself and of its related comorbidities, with consequent disease progression and disability, compromising the health-related quality of life of patients. In this paper we reviewed the literature of the past year (Medline search of articles published from 1st March 2016 to 28th February 2017) with the aim of approaching the spectrum of SpA from some different points of view, to try to give the reader an insight into this clinically challenging group of rheumatic pathologies.

One year in review 2016: pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic synovial inflammation leading to joint destruction and bone erosions. Although the pathogenic mechanisms underlying the disease are not fully elucidated, it is known that genetic susceptibility and environmental factors trigger an abnormal autoimmune response. Potentially, any organ and tissue could be affected by RA and the increased cardiovascular (CV) risk represents the major complication responsible for a worse prognosis. In this setting, the shared pathogenic mechanisms between RA pathogenesis and accelerated atherosclerosis further strengthen the rationale for a treat-to-target strategy with synthetic and biologic disease modifying anti-rheumatic drugs. The aim of this review is to provide the novel insights, regarding the pathogenesis of RA, published over the last year.

One year in review 2015: idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) are a group of rare acquired muscle diseases that mainly affect skeletal muscles. Recently, novel insights into the pathogenesis, diagnosis and treatment of these complex diseases have been provided. Herewith we provided an overview of the most significant literature contributions published over the year.

Altered immunoregulation in rheumatoid arthritis: the role of regulatory T cells and proinflammatory Th17 cells and therapeutic implications.

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder.

Occult radiological sacroiliac abnormalities in patients with inflammatory bowel disease who do not present signs or symptoms of axial spondylitis.

OBJECTIVES: To investigate radiological sacroiliac abnormalities in IBD patients without musculoskeletal symptoms and to determine the clinical and familiar differences between IBD patients with and without radiologic sacroiliac joint (SIJ) abnormalities. Subsequently, the patients with x-ray alterations were followed for 3 years in order to assess the onset of chronic inflammatory back pain (IBP). METHODS: 81 patients (55 Crohn-CD- and 26 ulcerative rettocolitis-UC) with remittent and low active IBD, from a tertiary referral centre of Gastroenterology Unit, were studied using SIJ x-rays. Differences in IBD clinical variables (activity and duration of CD and UC, extra-intestinal involvement, treatment with surgery and not, ESR and CRP levels), familiarity (for psoriasis, IBD, spondyloarthritis, coeliac syndrome), between patients with SIJ x-ray findings and without were investigated. Patients with radiological sacroiliac joint abnormalities were followed up clinically for 3 years and the onset of symptoms of chronic (higher than 3 consecutive months) IBP was investigated. RESULTS: 22/81 patients (27.1%) showed radiological SIJ abnormalities at baseline: isolated sclerosis in 17/22 (77.3%) and localised erosions in 12/22 (54.5%). Radiological SIJ involvement did not correlate with IBD clinical and familial variables. All patients were HLA B27 negative. At 3 years, 4/22 patients (18.1%) presented chronic IBP symptoms with bone oedema at MRI. CONCLUSIONS: In IBD, occult radiological SIJ alterations might precede the onset of axial symptoms but, in the absence of clinical signs, it is not possible to identify some IBD features or familiar predisposition that might be more frequent when SIJ abnormalities are involved. Clinical follow-up might be useful in these patients for a diagnosis of axial spondyloarthritis onset.

Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience.

BACKGROUND: Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments. METHODS: Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months. RESULTS: In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months. CONCLUSION: The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.

Angiotensin II type 2 receptor (AT2R) as a novel modulator of inflammation in rheumatoid arthritis synovium.

Despite increasing evidence suggesting that angiotensin II type 2 receptor (AT2R) may regulate tissue inflammation, no study has yet analyzed its possible implication in rheumatoid arthritis (RA) synovitis. In this study, we investigated the expression and function of AT2R in synovial tissue and cultured fibroblast-like synoviocytes (FLS) from RA patients. AT2R expression was strongly increased in RA compared with osteoarthritis (OA) synovium, as well as in in cultured RA-FLS respect to OA-FLS and healthy FLS. Treatment with pro-inflammatory cytokines was able not only to boost AT2R expression in RA-FLS and OA-FLS, but also to induce its de novo expression in healthy FLS. The stimulation of AT2R with the specific agonist CGP42112A significantly reduced gene expression of interleukin (IL)-1ß and IL-6 and activation of NF-κB in RA-FLS, while opposite effects were elicited by AT2R small interfering RNA. Moreover, AT2R agonism efficiently decreased RA-FLS proliferation and migration either at baseline or under pro-inflammatory cytokine challenge. In conclusion, AT2R is strongly expressed in key effector cells of rheumatoid synovitis, namely RA-FLS, and the activation of AT2R with a specific agonist may effectively dampen their pro-inflammatory and aggressive behavior. AT2R agonism might represent a novel therapeutic strategy for patients with RA.

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

Epilepsy is the most common comorbidity in patients with brain tumors. STUDY AIMS: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.

Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis.

OBJECTIVE: The interferon-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases, but not in healthy subjects. This leaking leads to loss of tolerance toward this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated. METHODS: IFI16 protein and anti-IFI16 antibody levels were assessed by enzyme-linked immunosorbent assay in serum samples from 154 RA patients and 182 healthy controls, and in synovial fluid (SF) samples from 21 RA patients and 25 patients with osteoarthritis (OA). RESULTS: Mean serum levels for both IFI16 and anti-IFI16 antibodies were higher in RA patients than in healthy controls, with a direct correlation between IFI16 concentration and anti-IFI16 antibody titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for rheumatoid factor (RF)/anti-cyclic citrullinated peptide antibody (anti-CCP). The latter group was found to be positive for anti-IFI16 antibodies as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 antibodies were higher in RA patients when compared with control OA patients. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 antibodies, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 antibodies, sex, and smoking habit. CONCLUSION: Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/anti-CCP-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as a new clinical biomarker of RA should be verified with additional studies.

Cardiovascular disease in systemic sclerosis.

Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc.

Disease activity improvement in rheumatoid arthritis treated with tumor necrosis factor-α inhibitors correlates with increased soluble Fas levels.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia. Tumor necrosis factor-α (TNF-α) plays a pivotal role in RA by interfering with the Fas-Fas ligand (FasL) proapoptotic pathway. We investigated the circulating levels of soluble Fas (sFas) and soluble FasL (sFasL), and their possible correlation with disease activity and improvement after anti-TNF-α treatment in RA. METHODS: Serum levels of sFas and sFasL were measured by quantitative ELISA in 52 patients with RA before and after 3 months of anti-TNF-α treatment (adalimumab, n = 32; infliximab, n = 20). Disease activity measures [Disease Activity Score at 28 joints-erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (CRP)] were recorded before and after treatment. Forty age-matched and sex-matched healthy subjects served as controls. RESULTS: No significant differences in serum sFas levels were detected between anti-TNF-α-naive patients with RA and controls. After anti-TNF-α treatment, serum sFas levels significantly increased in patients with RA compared to both anti-TNF-α-naive patients and controls. Increased sFas levels inversely correlated with disease activity variables (DAS28-ESR: r = -0.739, CRP: r = -0.636, both p < 0.001). No significant differences in sFasL levels were detected in patients with RA before and after anti-TNF-α treatment. CONCLUSION: In RA, an increase in sFas levels closely correlates with improvement in disease activity induced by TNF-α inhibitors, suggesting their ability to modulate Fas-mediated synoviocyte apoptosis.