NAILFOLD VIDEOCAPILLAROSCOPY FEATURES OF PATIENTS WITH ANTISYNTHETASE SYNDROME

Background: Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). As in inflammatory myopathies, nailfold videocapillaroscopy (NVC) alterations have been sporadically described also in ASSD patients, but no elucidating data are available. Objectives: To investigate the possible specific NVC features of ASSD patients. Methods: Within the framework of a multicenter study, we retrospectively analyzed NVC images of ASSD patients, after excluding patients with overlap syndrome with systemic sclerosis. Two operators in a blind manner re-evaluated all patients with at least one image per finger. For each patient, we examined number of capillaries (mean number of capillaries per mm in the distal row), enlarged and giant capillaries, micro-hemorrhages, avascular areas, ramified capillaries, and the presence of a scleroderma (SSc)-like pattern, according to manfredi et al. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results: The NVC of 54 ASSD patients were analyzed (males/females 1/6.8, mean age 55.79, CI95% 51.9\u201359.9 years, mean disease duration 59.4, CI95% 27.9\u201390.9 months). Raynaud's phenomenon (RP) was recorded in 51.9% of patients, arthritis in 79.6%, myositis in 53.7%, and ILD in 92.6%. NVC alterations were observed in 53.7% of AASD patients. Nineteen patients (35.2%) showed a SSc-like pattern; the main features were disarrangement of hairpin and angiogenetic aspects (42.6%), avascular areas (38.9%), giant capillaries (27.6%), and microhemorrhages (20.4%). Finally, the mean number of capillaries was reduced (7.8\ub12/mm). No significant association was recorded between SSc-like pattern and the presence of arthritis, myositis, and ILD, nor with RP. Among other NVC features, angiogenesis was significantly associated to female gender (p=0.031), while microhemorrhages were inversely associated to the presence of arthritis (0.033). No association was observed between NVC features and autoantibodies profile. Of interest, in 58% of patients with ILD we observed at least a NVC alteration vs no patients without ILD (p=0.04). Finally, in patients with RP NVC alterations were recorded in 15/28 patients (53.6%) and a SSc-like pattern in 11/28 (39.3%), while only 57.9% of patients with SSc-like pattern had a clinically manifest Raynaud's phenomenon. Conclusions: Despite preliminary, the present is the first study concerning NVC in AASD patients. Regardless of the presence of Raynaud's phenomenon, NVC alterations are frequently observed; in particular, a SSc-like pattern is recorded in more than 1/3 of patients. NVC should be performed in all ASSD patients at diagnosis regardless of the presence of RP in the patient history and during follow-up. ASSD should be always considered in the screening of RP. A prospective multicenter study has been planned to identify specific patterns and possible associations between NVC findings and clinical and serological features of ASSD

Nailfold videocapillaroscopy in antisynthetase syndrome

A 57-year-old woman with a diagnosis of antisynthetase syndrome (ASSD) underwent a nailfold videocapillaroscopy (NVC) showing a scleroderma pattern. Alterations in capillary morphology have been reported in adults with inflammatory myositis (IM) but only recently have the differences in NVC findings between these two diseases been established. ASSD is currently classified as a subset of IM, for which reason only a few studies in literature evaluate its specific hallmarks, showing nonspecific features of NVC in patients with polymyositis and dermatomyositis (DM) and antisynthetase antibodies. To our knowledge, this is the first description of ASSD capillaroscopy features, and the first report of NVC in ASSD with evidence of scleroderma pattern. Further studies are needed to define clearly frequency, typical features, and possible correlation with clinical and serological data of NVC changes in ASSD, differences between microangiopathy in ASSD and systemic sclerosis or DM

20 years of experience with tumour necrosis factor inhibitors : what have we learned?

TNF inhibitors are biologic DMARDs approved for the treatment of active RA in mid-1990s. They still represent a valuable therapeutic option to control the activity, disability and radiographic progression of the disease. In the context of TNF inhibitors, there are currently several molecules and different administration routes that provide optimal treatment personalization, allowing us to respond to a patient's needs in the best possible way. The increasing use of TNF inhibitors has not only improved the management of RA, but it has also helped in our understanding of the pathogenetic mechanisms of the disease. This review focuses on the basis of this targeted therapy and on the knowledge gained from their use about therapeutic effects and adverse events. Effectiveness analysed from drug registries and safety issues are presented together with recent data on infections (in particular, Mycobacterium tuberculosis and hepatitis B), cancer (lymphoma, skin cancers) and cardiovascular risk

Nailfold videocapillaroscopy in antisynthetase syndrome

A 57-year-old woman with a diagnosis of antisynthetase syndrome (ASSD) underwent a nailfold videocapillaroscopy (NVC) showing a scleroderma pattern. Alterations in capillary morphology have been reported in adults with inflammatory myositis (IM) but only recently have the differences in NVC findings between these two diseases been established. ASSD is currently classified as a subset of IM, for which reason only a few studies in literature evaluate its specific hallmarks, showing nonspecific features of NVC in patients with polymyositis and dermatomyositis (DM) and antisynthetase antibodies. To our knowledge, this is the first description of ASSD capillaroscopy features, and the first report of NVC in ASSD with evidence of scleroderma pattern. Further studies are needed to define clearly frequency, typical features, and possible correlation with clinical and serological data of NVC changes in ASSD, differences between microangiopathy in ASSD and systemic sclerosis or DM

Liposomes loaded with everolimus and coated with hyaluronic acid: A promising approach for lung fibrosis

Chronic lung allograft dysfunction (CLAD) and interstitial lung disease associated with collagen tissue diseases (CTD-ILD) are two end-stage lung disorders in which different chronic triggers induce activation of myo-/fibroblasts (LFs). Everolimus, an mTOR inhibitor, can be adopted as a potential strategy for CLAD and CTD-ILD, however it exerts important side effects. This study aims to exploit nanomedicine to reduce everolimus side effects encapsulating it inside liposomes targeted against LFs, expressing a high rate of CD44. PEGylated liposomes were modified with high molecular weight hyaluronic acid and loaded with everolimus (PEG-LIP(ev)-HA400kDa). Liposomes were tested by in vitro experiments using LFs derived from broncholveolar lavage (BAL) of patients affected by CLAD and CTD-ILD, and on alveolar macrophages (AM) and lymphocytes isolated, respectively, from BAL and peripheral blood. PEG-LIP-HA400kDa demonstrated to be specific for LFs, but not for CD44-negative cells, and after loading everolimus, PEG-LIP(ev)-HA400kDa were able to arrest cell cycle arrest and to decrease phospho-mTOR level. PEG-LIP(ev)-HA400kDa showed anti-inflammatory effect on immune cells. This study opens the possibility to use everolimus in lung fibrotic diseases, demonstrating that our lipids-based vehicles can vehicle everolimus inside cells exerting the same drug molecular effect, not only in LFs, but also in immune cells

Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis

Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SSc(Fib+)) with that obtained from six SSc patients without pulmonary fibrosis (SSc(Fib-)) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SSc(Fib+ )patients and SSc(Fib- )patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SSc(Fib+ )patients compared with SSc(Fib- )patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SSc(Fib+ )patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease

Ultrasound imaging for the rheumatologist XXVIII. Impact of sonographic knee joint involvement in recent-onset inflammatory polyarthritis

Objective. To assess the impact of the knee joint inflammation, detected by ultrasonography (US), on functional disability in patients with recent-onset inflammatory polyarthritis (IP). Methods. We included patients who had IP for less than 12 months and who had more than 5 swollen joints. All patients were assessed clinically at baseline. US was used to identify joint inflammation at multiple joint sites including: hands, wrists, elbows, shoulders, knees, ankles and feet. Joint group involvement was defined when at least one joint showed intra-articular signs of inflammation (synovial fluid abnormalities and/or synovial hypertrophy), according to the OMERACT definitions. Functional disability was measured using the health assessment questionnaire (HAQ) score. All patients with complete clinical and US data were included in the analysis. Results. Patients with US knee involvement showed more active and severe disease at baseline. The mean difference of HAQ between patients with and without US knee inflammation was 0.42 (95%CI 0.22, 0.62; p<0.001). This difference was still clinically and statistically significant even after controlling for disease extension and pattern of joint involvement. US shoulder involvement was also significantly and independently associated with higher mean HAQ scores. Conclusion. US knee involvement is associated with higher disability in IP at first presentation. US is a good tool to help in the differentiation of patients with recent-onset IP with different disease severity