POS1344 EVALUATING THE MULTIVISCERAL INVOLVEMENT ON ADULT-ONSET STILL'S DISEASE TO RETRIEVE IMAGING-BASED DIFFERENCES IN PATIENTS WITH AND WITHOUT MACROPHAGE ACTIVATION SYNDROME; RESULTS FROM A SINGLE-CENTRE OBSERVATIONAL STUDY

Background:Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder usually affecting young adults, burdened by life-threatening complications, mainly macrophage activation syndrome (MAS), a secondary form of hemophagocytic lymphohistiocytosis [1]. In this context, the importance of an accurate assessment of AOSD is suggested to promptly recognise the multivisceral involvement of the disease which is associated with life-threatening complications. The assessment of the most aggressive subsets of the disease could guide the clinicians when to apply additional resources but avoiding unnecessary expenditures in patients with a less severe clinical picture.Objectives:In this study, we aimed at describing the multivisceral involvement of the disease to retrieve imaging-based differences in AOSD patients with and without MAS.Methods:The present evaluation has been designed as a cross-sectional study to descriptively compare the multivisceral involvement in AOSD patients with and without MAS. Patients admitted to our Institution, who underwent a total body CT scan, were selected from our historical cohort and assessed. Clinical and CT scan characteristics of AOSD patients with and without MAS were compared. Clinical and CT scan characteristics of AOSD patients with and without MAS were analysed by parametric or non-parametric t tests for all continuous variables, and chi squared test was used for categorical ones, as appropriate. Furthermore, possible correlations among radiological outcomes with laboratory markers and systemic score were estimated by using a point-biserial coefficient correlation.Results:This study evaluated 39 AOSD patients (men 64.1%), mean age of 48.8±16.6 years). Out of those, 14 patients (35.9%) were complicated by MAS. These patients showed higher values of ferritin [AOSD: 770.0 (1306.5) ng/mL vs MAS: 2926.3 (4918.5) ng/mL p=0.003] and systemic score (AOSD: 4.6±1.4 vs MAS: 6.9±1.7, p<0.0001). AOSD patients with MAS presented a higher prevalence of lung disease than others (AOSD: 56.0% vs MAS 85.7% p=0.048). Lung disease correlated with the systemic score (coefficient 0.491, p=0.003). AOSD patients with MAS were more frequently characterised by hepatomegaly (AOSD: 12.0% vs MAS: 50.0% p=0.019) and splenomegaly (AOSD: 16.0% vs MAS 50.0% p=0.033), respectively, than others. Hepatomegaly correlated with CRP (coefficient 0.421, p=0.016), ferritin (coefficient 0.397, p=0.020), and systemic score (coefficient 0.391, p=0.022). Furthermore, the presence of splenomegaly correlated with the systemic score (coefficient 0.439, p=0.009). CT scan features of abdominal effusions were more frequently observed in AOSD patients with MAS than those without this complication (AOSD: 12.0% vs 57.1% p=0.007). Finally, a higher percentage of AOSD patients with MAS showed a significant lymph node enlargement, either mediastinal or abdominal, than others on CT scan (AOSD: 36.0% vs MAS 71.4% p=0.048). The presence of lymphadenomegaly correlated with the systemic score (coefficient 0.368, p=0.032).Conclusion:Our findings showed a higher prevalence of multiorgan involvement in AOSD patients with MAS, suggesting imaging-based differences, although other studies are needed to fully assess this issue. Pulmonary disease, hepatomegaly, splenomegaly, lymph nodes enlargement, and abdominal effusions were associated with these more aggressive patients.References:[1]Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun. 2018 Sep;93:24-36.Disclosure of Interests:None declare

The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed

The new Italian SIDAPA Baseline Series for patch testing (2023): an update according to the new regulatory pathway for contact allergens

Allergic contact dermatitis (ACD) is a common inflammatory skin disease caused by delayed hypersensitivity to chemical and biotic contact allergens. ACD significantly affects the patients' quality of life negatively impacting both occupational and non-occupational settings. Patch testing is the gold standard diagnostic in vivo test to precise the ACD etiology and to correctly perform prevention. According to the Italian Medicines Agency (AIFA) legislative decree no. 178 of 29th May 1991, allergens are defined as medicines and therefore they are subject to strict regulation. In 2017, AIFA (decree no. 2130/2017) started a procedure to regulate contact allergens on the Italian market and actually the contact allergens temporarily authorized are reported in AIFA decree no. 98/2022, valid until November 2023. The availability on the market of contact allergens to diagnose ACD and continuous updating on the basis of new epidemiological trends are mandatory, jointly with the continuous update of the baseline and integrative series for patch testing. For this reason, the scientific community represented in Italy by the Skin Allergies Study Group of SIDeMaST (Italian Society of Dermatology and Venereology) and SIDAPA (Italian Society of Allergological, Occupational and Environmental Dermatology) are constantly working, in close relationship with the European scientific communities with large expertise in this important sector of the modern Dermatology. Herein, we report the setting up of regulatory legislation by AIFA and the new Italian Adult Baseline Series for patch testing

Tendon Fascicle-Inspired Nanofibrous Scaffold of Polylactic acid/Collagen with Enhanced 3D-Structure and Biomechanical Properties

Surgical treatment of tendon lesions still yields unsatisfactory clinical outcomes. The use of bioresorbable scaffolds represents a way forward to improve tissue repair. Scaffolds for tendon reconstruction should have a structure mimicking that of the natural tendon, while providing adequate mechanical strength and stiffness. In this paper, electrospun nanofibers of two crosslinked PLLA/Collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were developed and then wrapped in bundles, where the nanofibers are predominantly aligned along the bundles. Bundle morphology was assessed via SEM and high-resolution x-ray computed tomography (XCT). The 0.4-micron resolution in XCT demonstrated a biomimetic morphology of the bundles for all compositions, with a predominant nanofiber alignment and some scatter (50-60% were within 12° from the axis of the bundle), similar to the tendon microstructure. Human fibroblasts seeded on the bundles had increased metabolic activity from day 7 to day 21 of culture. The stiffness, strength and toughness of the bundles are comparable to tendon fascicles, both in the as-spun condition and after crosslinking, with moderate loss of mechanical properties after ageing in PBS (7 and 14 days). PLLA/Coll-75/25 has more desirable mechanical properties such as stiffness and ductility, compared to the PLLA/Coll-50/50. This study confirms the potential to bioengineer tendon fascicles with enhanced 3D structure and biomechanical properties

FRI0006 ASSESSING PRO-INFLAMMATORY PROPERTIES OF H-FERRITIN BY EX VIVO AND IN VITRO OBSERVATIONS

Background:The concept of 'hyperferritinemic syndrome' has recently been proposed, suggesting high levels of ferritin as pathogenic pro-inflammatory mediator [1] Ferritin is an intracellular iron storage protein, comprising 24 subunits, heavy (H) and light (L) based on molecular weight. The H-/L subunits ratio may be different in tissues, since the ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be observed in different tissues, according to pathophysiologic status [1].Objectives:We aimed to assess the presence of H- and L-ferritin as well as of CD68/H-ferritin and CD68/L-ferritin in bone marrow (BM) biopsies of adult macrophage activation syndrome (MAS) patients. In the same patients, we matched the findings of BM biopsies with sera to identify the main represented subunits of ferritin. Furthermore, we evaluated effects of ferritin, L-ferritin, and H-ferritin on human monocytes, assessing pro- and anti-inflammatory cytokines, and expression of NLRP3 inflammasome. Finally, we checked the ability of monocytes, which were treated with ferritin, to stimulate or not the proliferation of peripheral blood mononuclear cells (PBMCs).Methods:Immunofluorescence analysis was performed to investigate the tissue presence of L- and H-ferritin in BM biopsies as well as of CD68/H-ferritin and CD68/L-ferritin. Liquid chromatography mass spectrometry (LC-MS/MS) based proteomics was performed to identify L- and H-ferritin in sera proteins. Human monocytes were cultured with M-CSF for 7 days and, after that, treated with ferritin, H-ferritin, and L-ferritin at 10nM, for 120 and 240 minutes. After stimulation, IL-1β, IL-6, IL-10, IL-12, IFN-γ, TGF-β, TNF, and VEGF were assessed by RT-PCR and, in case of positive finding, evaluated by western blot. NLRP3 inflammasome was also assessed. Finally, the proliferation of PBMCs when co-cultured with ferritin-treated monocytes was tested by a specific proliferation assay.Results:Immunofluorescence showed an increased H-ferritin expression in the BMs of MAS patients, whereas L-ferritin did not. Conversely, LC-MS/MS identified that the L-ferritin was the dominant form, after stringent probability matching.In vitro, H-Ferritin induced a significant increased expression of IL-1β, IL-6, IL-12, and TNF after 240 minutes. Ferritin also induced a significant increased expression of IL-1β, IL-6, IL-12, and TNF after 240 minutes. Effects on pro-inflammatory cytokines were more marked with H-ferritin than ferritin. Conversely, no significant effects were retrieved analysing IFN-γ, IL-10, TGF-β, and VEGF after 240 minutes, after ferritin and H-ferritin stimulation. Furthermore, both ferritin and H-ferritin induced a direct effect on NLRP3 inflammasome. Finally, monocytes, which were treated with H-ferritin, stimulated the proliferation of co-cultured PBMCs.Conclusion:In our work, results showed the presence of H-ferritin and CD68/H-ferritin cells in BM biopsies of MAS patients, by immunofluorescence. Conversely, LC-MS/MS identified L-ferritin in sera proteins of those patients. Furthermore, pro-inflammatory effects of ferritin and, particularly, of H-ferritin on human monocytes were observedin vitro, increasing pro-inflammatory cytokines and NLRP3 inflammosome. Finally, H-ferritin-treated monocytes stimulated the proliferation of co-cultured PBMCs.References:[1]Rosario C, et al. BMC Med 2013; 11:185.Disclosure of Interests:Piero Ruscitti Grant/research support from: Pfizer, Speakers bureau: BMS, MSD, Ely Lilly, SOBI, Paola Di Benedetto Grant/research support from: Paola Di Benedetto received grant from Dompè outside this work., Onorina Berardicurti: None declared, Noemi Panzera: None declared, Federica Sensini: None declared, Paola Cipriani Grant/research support from: Actelion, Pfizer, Speakers bureau: Actelion, Pfizer, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfize