Flow Mediated Dilation in Systemic Sclerosis: Association with clinical findings, capillaroscopic patterns and endothelial circulating markers.

AIM: Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. METHODS: 57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. RESULTS: Compared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. CONCLUSIONS: FMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study.

INTRODUCTION: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. OBJECTIVE: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. METHODS: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann-Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. RESULTS: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1-2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1-3)) and T2 (median LEI 0 (IQR 1-2)). CONCLUSION: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study.

BACKGROUND: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. METHODS: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. RESULTS: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01). CONCLUSIONS: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Systemic sclerosis in a patient with Turner syndrome: A case report and a review of associated autoimmune diseases

Turner's syndrome (TS) is one of the most common sex chromosome disorders caused by numeric or structural abnormalities of the X chromosome. A case of TS and Systemic Sclerosis (SSc) is reported, along with a summary of all associated TS/autoimmune diseases described in English literature from 1948 to 2020, using a search in MEDLINE (Pubmed). A 32-year-old woman affected by TS was seen due to inflammatory arthralgia in small joints and dysphagia, as well as a two-year history of Raynaud's phenomenon and puffy hands. Biohumoural laboratory tests and severity scales revealed changes that allowed us to diagnose SSc. This case report emphasises the role played by sex hormones and chromosomal abnormalities in the pathogenesis of autoimmune disorders, and to our knowledge, this is the only case described in literature of a TS patient who developed SSc.

El síndrome de Turner (TS) es uno de los trastornos cromosómicos sexuales más comunes causados por anomalías numéricas o estructurales del cromosoma X. En este documento informamos de un caso de TS y esclerosis sistémica (SSc) y resumimos toda la asociación de TS/enfermedades autoinmunes descrita en la literatura inglesa de 1948 a 2020, encontrada buscando en MEDLINE (PubMed). Una mujer de 32 arios afectada por TS acudió a nuestra observación debido a la artralgia inflamatoria en pequenas articulaciones y disfagia y 2 anos de historia del fenómeno de Raynaud y las manos hinchadas. El laboratorio biohumoral y las pruebas instrumentales revelaron alteraciones que nos permitieron diagnosticar SSc. Nuestro informe de caso hace hincapié en el papel desempefíado por las hormonas sexuales y las anomalías cromosómicas en la patogénesis del trastorno autoinmune; y hasta nuestro conocimiento, este es el único caso descrito en la literatura de un paciente TS que desarrolló SSc.

Adipokine role in physiopathology of inflammatory and degenerative musculoskeletal diseases.

We performed a systematic literature review to summarize the underlying pathogenic mechanisms by which adipokines influence rheumatological diseases and the resulting clinical manifestations. Increasing evidence display that numerous adipokines may significantly influence the development or clinical course of various rheumatological diseases. Despite the normal anti- or pro-inflammatory role of the cytokines, the serum level varies enormously in various rheumatological diseases. The expression of high levels of pro-inflammatory cytokines such as leptin or visfatin, respectively in systemic lupus erythematosus and in rheumatoid arthritis, represents a negative prognostic factor; other adipokines such as adiponectin, broadly known for their anti-inflammatory effects, showed a correlation with disease activity in rheumatoid arthritis. In the near future pro-inflammatory cytokines may represent a potential therapeutic target to restrain the severity of rheumatological diseases. Further studies on adipokines may provide important information on the pathogenesis of these diseases, which are not yet fully understood. The mechanisms by which adipokines induce, worsen, or suppress inflammatory and degenerative musculoskeletal pathologies and their clinical significance will be discussed in this review.

Nailfold capillaroscopy : a comprehensive review on common findings and clinical usefulness in non-rheumatic disease.

Nailfold video-capillaroscopy (NVC) is a useful diagnostic tool, used to early detect abnormalities in micro-circulation, providing a qualitative description of microvascular anomalies in Raynaud's phenomenon. NVC role in the diagnosis of Systemic Sclerosis is well known. In other rheumatic conditions such as connective tissue diseases, vasculitis, and arthritis, the NVC anomalies are often included in a scleroderma like pattern. The use of NVC in non-rheumatic diseases (NRD), with remarkable microvascular damage, as diabetes, is not standardized yet, although several research studies are carrying on. The aim of this article is to provide a resume of published results in order to lay the groundwork for the employment of NVC both in the diagnosis and follow up of microvascular complication in NRD. Furthermore, we mention NVC findings in pathologies without well recognize microvascular damages in their pathogenesis : micro-vessels abnormalities may suggest a different point of view. J. Med. Invest. 68 : 6-14, February, 2021.

Pfeifer-Weber-Christian Disease: A Case Report and Review of Literature on Visceral Involvements and Treatment Choices.

Pfeifer-Weber-Christian disease (PWCD) is a rare idiopathic disease characterized by lobular panniculitis of adipose tissue with systemic symptoms and multiple organ involvement. Even though the systemic involvement is rare, it is life-threatening and represent a treatment challenge for the clinicians. We report a case of PWCD characterized by hepatic, hematologic, and renal involvement, with good response to mofetil mycophenolate and prednisone treatment. A 47-year-old female presented several months' history of painful subcutaneous nodules, fever and lymphadenopathy with recent appearing of microcytic hypochromic anemia, leucopenia with neutropenia, and increase in transaminase. Skin biopsy showed lobular panniculitis with lymph-histiocytic and neutrophilic infiltrates with necrosis of adipocytes. A combination therapy of corticosteroid with mofetil mycophenolate was effective. Moreover, we discuss the clinical manifestation and the therapeutic choices in PWCD, from classical immunosuppressive drugs to new biotechnological agents, and we provide a comprehensive review of the available literature.