No changes in N-terminal pro-brain natriuretic peptide in a longitudinal cohort of patients with systemic sclerosis-associated pulmonary arterial hypertension on therapy with bosentan

Abstract AIM: The aim of this study was to evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) and changes after therapy with bosentan. METHOD: Twenty-one patients with SSc-PAH on bosentan therapy were enrolled. PAH was diagnosed by right heart catheterization. NT-proBNP levels, 6-min walking test (6MWT), Doppler echocardiography to estimated systolic pulmonary arterial pressure (sPAP), New York Heart Association (NYHA) functional class for dyspnea and carbon monoxide lung diffusion capacity (DLco) were recorded at baseline, and after 1 and 2 years. Fifty-two SSc patients without PAH were also evaluated as controls. RESULTS: NT-proBNP plasma levels were significantly higher in SSc-PAH at 385 pg/mL (SD ± 427) than in SSc without PAH and 72 pg/mL (SD ± 52, P < 0.001) at baseline, but did not significantly change following bosentan therapy at 1 year (330 pg/mL [SD ± 291] and 2 years (374 pg/mL [SD ± 291]). However, NYHA class significantly improved at 2 years (P = 0.01) as well as 6MWT (P = 0.04). NT-proBNP levels were positively correlated only with sPAP but not with DLco, NYHA class or 6MWT. CONCLUSIONS: NT-proBNP levels were found to be significantly higher in SSc-PAH at baseline. Serial assessment of NT-proBNP in SSc-PAH patients on bosentan therapy showed no relation to the clinical improvement. This suggests that NT-proBNP may lack 'sensitivity to change', but further studies are warranted to assess the role of NT-proBNP as a biomarker of the therapeutic response in larger cohorts of SSc patients

Refractory knee giant cell tumor of the synovial membrane treated with intra-articular injection of Infliximab: A case series and review of the literature

Giant cell tumor (GCT) of the synovial membrane, also known as pigmented villonodular synovitis, causes a progressive, relapsing and destructive arthropathy affecting one or more synovial joints. Systemic therapy can be combined to intra-articular treatments, including surgical synoviectomy, especially when monoarticular. Despite that, the synovial membrane commonly grows again with clinical relapse. Here, we report three case of patients diagnosed with GCT of the knee who had an early relapse of the disease even after surgical synoviectomy. All of them underwent intra-articular therapy with infliximab and subsequent synoviectomy to eradicate residual tissue. A complete remission of CGT was achieved without relapse occurring during the follow-up. These preliminary data need to be confirmed by further clinical trials; however, intra-articular therapy with infliximab might be deemed a potential option to treat CGT of a single joint

Use of biologics and other novel therapies for the treatment of systemic sclerosis

INTRODUCTION Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy, inflammation and fibrosis. These three main disease-determining pathways are the target of the currently available treatments used to possibly modify the progression of disease-related manifestations, although this synergy has not been fully applied on SSc joint, skin or lung involvement yet. Areas covered: we describe the current status of SSc treatment/therapy performing a literature search in MEDLINE/Pubmed and Thomson Reuter's Web of Science for articles published until March 2016. Moreover, ongoing registered clinical trials (RCTs) on SSc were searched through clinicaltrials.gov website. Expert commentary: presently, promising drugs are under evaluation to target the different pathogenic pathways of systemic sclerosis: Tocilizumab and Abatacept for skin and lung fibrosis; Riociguat and Selexipag are approved for pulmonary arterial hypertension but promising anti-fibrotic effects are now being studied. Finally, several anti-fibrotic molecules are currently involved in RCTs, such as Nintedanib, IVA-337, Terguride

Body mass index and adipokines/cytokines dysregulation in Systemic Sclerosis

Body fat has regulatory functions through producing cytokines and adipokines whose role in the pathogenesis of systemic sclerosis (SSc) is currently emerging. Changes in body mass, either over- or underweight, entail a dysregulation of the cytokine/adipokine network that may impact upon SSc disease activity. We evalu- ated serum levels of adipokines and cytokines in SSc patients and correlated them to clinical features and body mass index (BMI) categories. The study included 89 SSc patients and 26 healthy donors (HD). Serum levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-10 and IL-17A were measured by multiplex immunoassay and correlated to BMI and disease-specific features. Student’s t-test or analysis of variance (ANOVA) were used for comparisons between groups. Spearman’s or Pearson’s tests were used for cor- relation analysis. Serum levels of TNF-α, IL-2, leptin and resistin were significantly higher in SSc than in HD. Leptin levels were significantly higher in interstitial lung disease (ILD)- and pulmonary arterial hypertension (PAH)-SSc subgroups. The high- est levels of IL-17A, IL-2, IL-10, leptin and visfatin were detected in SSc patients with obesity (p < 0.01). Conversely, underweight SSc patients showed the highest TNF-α levels (p < 0.05). Adipokines, IL-2, IL-10 and IL-17A were found to be increased in SSc patients with obesity, but whether or not they play a role in the pathogenesis of the disease remains to be investigated. Intriguingly, underweight patients had the highest TNF-α levels, suggesting a potential role of TNF-α in inducing the cachexia observed in long-lasting disease

Nailfold Videocapillaroscopy Alterations in Dermatomyositis and Systemic Sclerosis: Toward Identification of a Specific Pattern

The term scleroderma pattern typically defines capillary abnormalities of scleroderma spectrum disorders, mainly systemic sclerosis (SSc) and dermatomyositis (DM). Our study aimed to investigate differences in nailfold videocapillaroscopy (NVC) between DM and SSc, with a cross-sectional and longitudinal evaluation. METHODS: NVC features of 29 consecutive patients with DM were compared with 90 patients with SSc categorized into the 3 subsets of scleroderma pattern: early, active, and late. Twenty patients with DM and all with SSc were also longitudinally reevaluated after 30 months of followup. RESULTS: At baseline, all SSc groups showed giant capillaries, with significant differences with DM only for early and active pattern. Ramified capillaries were significantly more frequent and severe in DM than in early and active patterns, while DM showed an opposite trend compared with late pattern. Capillary loss was lower in early pattern and higher in active and late, compared with DM. Finally, giant-ramified capillaries were almost exclusive of DM. During followup, NVC showed a different evolution in DM and SSc. In DM we recorded a reduction of giant capillaries, while ramified capillaries increased both in DM and in early and active SSc pattern. The number of capillaries recovered in DM; conversely, capillary loss slightly worsened in all SSc patterns. Giant-ramified capillaries significantly decreased in patients with DM, remaining rare in patients with SSc. CONCLUSION: Our study strengthens the specificity of DM and SSc microangiopathy and points out the need for large prospective studies to confirm our results and possibly to revise current terminology by distinguishing between "scleroderma" and "dermatomyositis" patterns

Validation study of predictive value of capillaroscopic skin ulcer risk index (CSURI) in scleroderma patients treated with bosentan

In this validation study, the predictive value of capillaroscopic skin ulcer risk index (CSURI) in scleroderma patients treated with bosentan has been investigated. Seventy-six consecutive SSc patients treated with bosentan 125 mg bid were enrolled in a multicentre study. The area under the curve was 0.69 (95%CI 0.57-0.79, p=0.0019) and, at the validated cut-off value of 2.96, sensitivity was 86.1%, specificity 60.0%, positive and negative likehood ratio 2.15 and 0.23, while negative and positive predictive values were 82.1% and 64.6%, respectively. CSURI showed a lower negative predictive value in the bosentan group when compared with the control group, while the positive predictive value was similar

Capillaroscopic Skin Ulcers Risk Index (CSURI) calculated with different videocapillaroscopy devices: how its predictive values change

Digital ulcers (DU) occur in about 50% of systemic sclerosis (SSc) patients. Scleroderma DU are responsible for chronic pain and disability with the need of systemic and local treatments. Recently, capillaroscopic skin ulcer risk index (CSURI) has been validated as useful tool in predicting the appearance of new scleroderma ulcers and/or persistence of non-healing lesions, within 3 months from capillaroscopy evaluation

Orofacial Manifestation of Systemic Sclerosis: A Cross-Sectional Study and Future Prospects of Oral Capillaroscopy

Background and objectives: oral alterations in Systemic Sclerosis (SSc) patients are widespread and include microstomia, periodontitis, telangiectasias, mandibular resorption, bone lesions, and xerostomia. This cross-sectional study aims to evaluate the differences between SSc patients (cases) and healthy subjects (controls) regarding oral manifestations, quality of life (QoL), and microcirculation alterations. Methods: plaque index (PCR), periodontal index (PSR), DMFT, salivary flow rate, and buccal opening were measured by expert clinicians. S-HAQ test, the Self-Rating Anxiety State (SAS), the Self-Rating Depression Scale (SDS), and the WHOQOL-BREF test were administered to patients to evaluate their QoL. Microvascular alterations were assessed by oral videocapillaroscopy, performed on gingival and labial mucosa. A statistical analysis was conducted to find significant differences between healthy people and SSc patients. Results: 59 patients were enrolled in this study. Standard salivary flow is significantly more frequent in controls, while xerostomia, reduced flow, microstomia, lip retraction, and periodontitis are significantly more frequent in the cases. Gingival capillaroscopy showed differences concerning loop visibility, thickening of the gum, tortuosity of gingival loops, and reduced gingival density. Labial capillaroscopy demonstrates that visibility of the labial loops, the labial ectasias, and the tortuosity of the loops are significantly associated with the presence of scleroderma. Hand and facial deformities, hypomobility of the tongue, cheeks, lips, microstomia, and xerostomia significantly compromised the quality of life of SSc patients, which was significantly worse among them. Moreover, oral videocapillaroscopy could be a proper diagnostic method to detect oral microcirculation alterations. SSc patients often present ectasias, rarefaction of the reticulum, microhemorrhages, and megacapillaries, which negatively impact their oral health. Conclusions: periodontitis, reduced salivary flow, and microstomia could be considered SSc oral manifestations. Joint deformities, facial appearance, and comorbidities significantly reduce the QoL of SSc patients compared to healthy subjects. Oral videocapillaroscopy could be an innovative and reliable technique to detect oral microcirculation anomalies