Managing Adult-onset Still's disease: The effectiveness of high-dosage of corticosteroids as first-line treatment in inducing the clinical remission. Results from an observational study

To assess the effectiveness of the treatment with high dosage of corticosteroids (CCSs), as first-line therapy, in inducing remission in naïve Adult-onset Still's disease (AOSD) patients compared with low dosage of CCSs, after 6 months. To further evaluate the rate of patients maintaining the remission and the rate of CCSs discontinuation, after additional 12 months of follow-up.A retrospective evaluation of patients prospectively followed was designed to compare the rate of clinical remission in naïve AOSD patients treated with high dosages of CCSs (0.8-1 mg/kg/day of prednisone-equivalent) or low dosage of CCSs (0.2-0.3 mg/kg/day of prednisone-equivalent), after 6 months. An additional analysis was performed to compare the rate of monocyclic pattern between these groups, after further 12 months of follow-up.The clinical remission was achieved in a higher percentage of patients treated with the first-line treatment with high dosage of CCSs than treated the first-line treatment with low dosage of CCSs. At the end of 18 months of follow-up, a larger percentage of patients treated the first-line treatment with high dosage of CCSs was classified as monocyclic pattern and discontinued CCSs when compared with patients treated the first-line treatment with low dosage of CCSs. Patients defined as CCSs non-responder were treated with methotrexate (MTX)+CCSs or with combination therapy CCSs+MTX+biologic drug. The clinical remission was observed in a percentage of these patients.We showed the effectiveness of the first-line treatment with high dosage of CCSs in inducing clinical remission in naïve AOSD patients when compared with the first-line treatment with low dosage of CCSs. The first-line treatment with high dosage of CCSs was also associated with the achievement of monocyclic pattern and CCSs discontinuation, after 18 months of follow-up

SAT0601 RELATIONSHIP BETWEEN BODY MASS INDEX AND NAILFOLD CAPILLAROSCOPY IN PRIMARY AND SECONDARY RAYNAUD'S PHENOMENON

Background:Raynaud's phenomenon (RP) is a diffuse clinical manifestation (3-5% of general population) RP is often secondary to autoimmune systemic diseases, while the condition is classified primary if no underlying disorders can be found. A lower body mass index (BMI) was associated with a greater risk of developing RP, perhaps due to greatest sensivity to cold temperaturesObjectives:The objective of our study was to evaluate the association of BMI with clinical and capillaroscopic features in primary and secondary RP.Methods:Consecutive patients at the first access to a Rheumatology Outpatient Clinic over a 13 months period were screened to RP; nailfold videocapillaroscopy (NVC)was carried out and qualitative and quantitative assessment was performed. Diagnosis of RP was defined in patients who identified color pictures of witnessed attacks.Patients enrolled were screened for secondary causes of RP. RP was classified as primary when no abnormalities were found. Weight and height were collected in clinical records and patients were divided in 3 groups according to their BMI: underweight (BMI25 kg/m2). Chi-square test to compare categorical variable and Parametric Student t-test to comparing mean values of normally distributed data were used. p<0.05 was considered to be statistically significant.Results:RP was diagnosticated in 100 of 1416 patients (7.06%). Of these, 73 (10 M, 63F) accepted to undergo NVC. An autoimmune disease was found in 35 patients (47.9%), of which 2 were underweight, 14 normal weight and 19 overweight. Of 38 patients with primary RP,3 were underweight, 23 normal weight and 12 overweight. BMI was significantly higher in secondary RP (p=0.03). Overweight patients with secondary RP were older (p=0.01), but with a disease duration not statistically significant longer (p=0.26). In secondary RP, avascular areas and neoangiogenesis were founded only in overweight patients. Moreover,in secondary RP overweight was correlated with decreased capillary density (p=0-04). There was not association between BMI and capillaroscopic abnormalities in primary RP.Conclusion:In our study BMI was correlated with microvascular changes only in patients with secondary RP. Our findings may suggests a role for obesity in the microcirculatory disfunction in the autoimmune diseases. Further studies are needed to generalize results and to find a causative role.References:[1]Lemmens HA. Vasa Suppl. 1987;18:10–4.[2]Le RoyEC,MedsgerTA.ClinExpRheumatol 1992;10;485-8[3]O Keeffe ST et al Journal Rheumat 1992:19:1415-7[4]Fraenkel L. Curr Rheumatol Rep. 2002;4(2): 123–8.[5]MaundrellA et al NY:Spinger New York 2015 p 21-35[6]Giurgea G. etalArthritis Rheumatol Vol. 67, No. 1, January 2015, pp 238–242[7]A.Eman et al. Ab / Atherosclerosis 287 (2019) e123-288Disclosure of Interests:Rosella Tirri: None declared, Marco Barba: None declared, Ranieri Formica: None declared, Rosaria Irace: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvi

Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: A new potential target for antifibrotic therapy

Background: Fibrosis may be considered the hallmark of systemic sclerosis (SSc), the end stage triggered by different pathological events. Transforming growth factor-β (TGF-β) and platelet-derived growth factor BB (PDGF-BB) are profibrotic molecules modulating myofibroblast differentiation and proliferation, respectively. There is evidence linking CD248 with these two molecules, both highly expressed in patients with SSc, and suggesting that CD248 may be a therapeutic target for several diseases. The aim of this work was to evaluate the expression of CD248 in SSc skin and its ability to modulate SSc fibrotic process. Methods: After ethical approval was obtained, skin biopsies were collected from 20 patients with SSc and 10 healthy control subjects (HC). CD248 expression was investigated in the skin, as well as in bone marrow mesenchymal stem cells (MSCs) treated with TGF-β or PDGF-BB, by immunofluorescence, qRT-PCR, and Western blotting. Finally, in SSc-MSCs, the CD248 gene was silenced by siRNA. Results: Increased expression of CD248 was found in endothelial cells and perivascular stromal cells of SSc skin. In SSc-MSCs, the levels of CD248 and α-smooth muscle actin expression were significantly higher than in HC-MSCs. In both SSc- and HC-MSCs, PDGF-BB induced increased expression of Ki-67 when compared with untreated cells but was unable to modulate CD248 levels. After CD248 silencing, both TGF-β and PDGF-BB signaling were inhibited in SSc-MSCs. Conclusions: CD248 overexpression may play an important role in the fibrotic process by modulating the molecular target, leading to perivascular cells differentiation toward myofibroblasts and interfering with its expression, and thus might open a new therapeutic strategy to inhibit myofibroblast generation during SSc

Short-Facelift Approach in Temporal Artery Biopsy: Is It Safe?

Giant cell arteritis (GCA) is a quite common panarteritis of the elderly that affects medium- and large-size arteries. Despite the increasing role of imaging with advancing technology, the gold standard for the diagnosis of GCA is still the temporal artery biopsy. A described complication of superficial temporal artery biopsy (STAB), for which incidence is not clear, is the accidental damage of the frontal branch of the facial nerve. In this paper, we described the short-scar facelift surgical approach for STAB on 23 consecutive patients who underwent unilateral superficial temporal artery biopsy for GCA suspicion. We collected data in terms of postoperative complications, biopsy specimen length, biopsy result and cosmetic appearance of the scar. In our experience, this surgical approach combines the advantage of avoiding incisions within the dangerous anatomical area, minimizing the risk of facial nerve damage, with an acceptable complication rate and a good final aesthetic result which avoids visible scarring

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease

OBJECTIVES: Behçet's disease has been historically classified as a Th1 disease. The recently described IL-17/IL-23 pathway seems to play an important role in many inflammatory diseases and in the intestinal abnormalities of AS and CD. The aim of the present study was to evaluate the IL-17/IL-23 axis in parallel with Th1 and IL-27 response in the intestine of patients with BD and gastrointestinal abnormalities. METHODS: Quantitative TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) was utilised for all determinations on ileal biopsy specimens obtained from BD, AS and CD patients. The serum levels of Th1 and Th17 cytokines were evaluated by enzyme-linked immunosorbent assay. RESULTS: A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease. CONCLUSIONS: Although BD shares clinical manifestations with both CD and AS, the immunologic abnormalities seen in the intestine are quite different, indicating that other immune mechanisms should be taken into account