Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

In this open study, longterm treatment with ET-1 receptor antagonist in combination with iloprost was found to interfere with progression of nailfold microvascular damage in patients with SSc, as assessed by NVC over a 3-year followup period.

Objective. To investigate the timing of transition through different patterns of nailfold microvascular damage in patients with systemic sclerosis (SSc).Methods. In this medium-term longitudinal study, 38 SSc patients (median disease duration 12 months) with the early scleroderma pattern of microangiopathy seen on baseline nailfold videocapillaroscopy (NVC) were followed up by NVC for a median of 84 months. The evolution of the NVC pattern over time was monitored and recorded.Results. At the end of followup, the NVC pattern was still that of early scleroderma in 47% of the patients. The active scleroderma pattern was seen in 34%, the late scleroderma pattern in 13%, and a normal pattern in 5%. The mean ؎ SD time of progression from the early to the active pattern and from the early to the late pattern was of 28 ؎ 20 months and 36 ؎ 29 months, respectively. In the subgroup of patients whose microangiopathy progressed from the early to the late NVC pattern, the time of progression from the early to the active pattern was only 8 ؎ 1 months (P ‫؍‬ 0.01), demonstrating that there is a subset of patients with rapid progression of microangiopathy. Clinical symptoms progressed in accordance with the nailfold morphologic changes in 60% of the SSc patients.Conclusion. The results of this longitudinal study demonstrate dynamic transition of microvascular damage through different NVC patterns of microangiopathy in ϳ50% of SSc patients. It is recommended that patients exhibiting rapid progression from the early to the active NVC pattern (<1 year) should be monitored closely, since the evidence suggests that they are at risk of rapid progression to the advanced (late) NVC pattern of microangiopathy that is associated with further clinical manifestations of SSc.

The interaction between a fluid flow and a transversely isotropic porous medium is described. A homogenized model is used to treat the flow field in the porous region, and different interface conditions, needed to match solutions at the boundary between the pure fluid and the porous regions, are evaluated. Two problems in different flow regimes (laminar and turbulent) are considered to validate the system, which includes inertia in the leading-order equations for the permeability tensor through a Oseen approximation. The components of the permeability, which characterize microscopically the porous medium and determine the flow field at the macroscopic scale, are reasonably well estimated by the theory, both in the laminar and the turbulent case. This is demonstrated by comparing the model's results to both experimental measurements and direct numerical simulations of the Navier-Stokes equations which resolve the flow also through the pores of the medium

This study demonstrates a relationship between nailfold microangiopathy severity, DT and FBP in SSc patients.

Longterm treatment of SSc patients with ET-1 antagonism, in combination with ILO, seems to increase fingertip blood perfusion, as well as both capillary dilation capacity and number.

summaryThe objective of this prospective study was to investigate the transition from primary (PRP) to secondary (SRP) Raynaud's phenomenon (RP), in a large cohort of patients affected by isolated RP. A total of 2065 patients with RP were investigated by clinical interview, laboratory examinations, and nailfold videocapillaroscopy (NVC). Patients with negative NVC at first visit were yearly followed to monitor either the appearance of specific morphological alterations at NVC, or clinical manifestations of an underlying disease. Capillary abnormalities at NVC were scored, as well as the qualitative patterns of microangiopathy (Early, Active and Late). NVC was found negative at first visit in 1500 subjects; among them, 412 patients were evaluable and they were followed for a mean time of 5±4 years (range 2-13 years). Sixty-eight patients (16%) achieved a diagnosis of SRP during follow-up, showing normal or not specific capillary alterations at NVC 4% of patients (the diagnosis was undifferentiated connective tissue diseases), Early scleroderma-pattern 57%, Active sclerodermapattern 7%, Late scleroderma-pattern 12%, and scleroderma-like pattern 18% of patients. The time of transition from normal/not specific capillary alterations to Early scleroderma-pattern was 4.4±3.8 years. Enlarged capillaries (diameter between 20 and 50 microns) and mild reduction of capillary density were found the more frequent markers at first NVC visit in patients who progressed to a scleroderma pattern (P=0.01). This study demonstrates in a large cohort, that almost 16% of patients initially diagnosed as affected by RP with negative NVC may transit to SRP during a mean follow-up of 4.4 years. PRP patients showing major notspecific alterations of nailfold capillaries at first NVC should be strictly monitored at least once a year since at higher risk of transition to SRP.

Background Aromatases increase estrogen synthesis in inflammatory tissues whereas vitamin D (calcitriol, 1,25-dihydroxyvitamin D3, 1,25(OH)2D3) seems to decrease the aromatase expression at least in human cancer cells (BCa cells) (1). Interestingly, the aromatase activity is increased together with the estrogen synthesis in the synovial tissue of rheumatoid arthritis (RA) patients, especially at the level of macrophages (2-4). Objectives To evaluate in cultures of human activated macrophages the influence exerted by calcitriol on aromatase expression, as a new target for 1,25(OH)2D3cell modulation of proinflammatory cytokine production (5). Methods Cultures of human monocytic THP-1 were activated to macrophages and treated for 24 hours with 1,25(OH)2D3 (10-8M), alone or in combination with 17b-estradiol (E2, 10-8M), in order to evaluate the effects on the intracrine estrogen metabolism (aromatase-driven) and cytokine synthesis. Untreated human macrophages were used as controls (basal condition). P450-aromatase synthesis was evaluated by immunocytochemistry (ICC) and western blot analysis (WB). The expression of P450-aromatase gene (CYP19A1) was investigated by real-time PCR (RT-PCR). Macrophage proinflammatory cytokines IL1-β, IL-6 and TNF-α were evaluated by ELISA and WB. Results Interestingly, 1,25(OH)2D3 downregulated P450-aromatase synthesis, CYP19A1-gene expression, and proinflammatory cytokine production (IL1-β, IL-6 and TNF-α) in basal conditions when compared to 1,25(OH)2D3-untreated macrophages. However and interestingly, the treatment with 1,25(OH)2D3significantly reduced the increase in P450-aromatase (p<0.001), CYP19A1 gene expression (p<0.001) as well as IL-1bβ, IL-6, TNF-α production (p<0.001) induced by estrogen treatment vs. estrogen-treated (but 1,25(OH)2D3-untreated) macrophages. Conclusions Our data suggest that 1,25(OH)2D3 may downregulate the proinflammatory cytokine production in human activated macrophages by significantly decreasing the aromatase activity, especially in presence of an enhancing estrogenic milieu. Interestingly, this latter hormonal metabolic condition is observed in the synovial tissue and fluid of RA patients of both sexes (2,3). References Krishnan AV et al. Endocrinology 2010;151:32-42. Cutolo M et al. Autoimmun Rev. 2011;2 [Epub ahead of print]. Cutolo M. Rheumatology (Oxford) 2009;48:210-12. Le Bail J et al. Steroids. 2001;66:749-57. Zwerina K et al. Ann Rheum Dis. 2011;70:1122-9. Disclosure of Interest None Declared