Introduction Skin ulcers (SU) represent one of the most frequent manifestations of systemic sclerosis (SSc), occurring in almost 50% of scleroderma patients. SSc-SU are often particularly difficult to treat with conventional systemic and local therapies. In this study, a preliminary evaluation of the role and effectiveness of blue light photobiomodulation (PBM) therapy with EmoLED ® in the treatment of scleroderma skin ulcers (SSc-SU) was performed. Methods We retrospectively analyzed 12 consecutive SSc patients with a total of 15 SU on finger hands. All patients were treated with adequate systemic therapy and local treatment for SU; after a standard skin ulcer bed preparation with debridement of all lesions, EmoLED ® was performed. All patients were locally treated every week during 2 months of follow-up; SU data were collected after 4 weeks (T4) and 8 weeks (T8). Eight SSc patients with comparable SU were also evaluated as controls. Results The application of EmoLED ® in addition to debridement apparently produced faster healing of SU. Complete healing of SU was recorded in 41.6% cases during EmoLED ® treatment. Significant improvements in SU area, length, and width, wound bed, and related pain were observed in EmoLED ® patients from T0 to T8. Control subjects treated with standard systemic/local therapies merely showed an amelioration of SU area and width at the end of the follow-up. No procedural or post-procedural adverse events were reported. Conclusions The positive clinical results and the absence of side effects suggest that EmoLED ® could be a promising tool in the management of SSc-SU, with an interesting role to play in the healing process in addition to conventional systemic and local treatments.

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ObjectivesMixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. Aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile. Methods All MCV patients referring to participating centres were assessed with an interview-based survey about vaccination,reasons for not getting vaccinated, adverse events (AE), and disease flares within a month after vaccination. Results.A total of 416 patients were included in the study. Among participants, 7.7% did not get vaccinated, mainly for fear related to vaccine side-effects (50%) or medical decision (18.8%). They were more frequently treated with chronic glucocorticoids or rituximab (p=0.049 and p=0.043, respectively). Mild and self-limiting AE were recorded in 31.7% of cases, while post-vaccination vasculitis flares were observed in 5.3% of subjects. Disease relapses were mainly observed in patients with peripheral neuropathy or skin vasculitis (40% and 25%, respectively). Conclusions.Vaccination against SARS-CoV-2 has been performed in a high percentage of MCV patients with encouraging safety profile. Vasculitis flares rate was in line with that observed for other autoimmune diseases, despite patients with purpura or peripheral neuropathy seem to be at risk for symptoms' exacerbation. Patients' hesitancy, rituximab and glucocorticoids treatment were the main reasons for delaying vaccination.

OBJECTIVE To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc). METHODS In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment. RESULTS Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants’ total hours of sleep. Patients in the control group more frequently required additional analgesic therapy. CONCLUSIONS Topical CBD may be a valuable tool to treat pain related to digital ulcers in patients with SSc.

We reviewed 11 patients with systemic sclerosis-related ILD who were referred to our Scleroderma Unit from January 2020 to January 2021 and started Nintedanib. Nonspecific interstitial pneumonia (NSIP) was prevalent (45%), usual interstitial pneumonia (UIP) and UIP/NSIP pattern were both 27%. Only one patient had a history of smoking. Eight patients were on mycophenolate mofetil (MMF), eight were treated with corticosteroids (mean dose 5 mg/day of Prednisone or equivalent), and three were on Rituximab. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 to 2.5. Two patients had to reduce their daily dose to 200 mg/day for severe diarrhoea. Nintedanib was generally well tolerated.

BackgroundSystemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs (1,2). One of the most common and severe SSc manifestations is interstitial lung disease (ILD) (3).ObjectivesEvaluate tolerability and safety profile of Nintedanib in patients with SSc-related ILD.MethodsWe enrolled 11 consecutive patients (6 female, 5 male, Mean age 62.7 ± 8 SD, disease duration (from the first Non-Raynaud symptom) 8 years (± 7SD) who referred to our Scleroderma Units during the last twelve months. Patients fulfilled EULAR/ACR classification criteria (4) for SSc. Patient was assessed by means of clinical evaluation (baseline and every three months), High Resolution computed tomography (every six month, or sooner), respiratory function test (every three to six months), laboratory work up, nailfold videocapillaroscopy, echocardiogram, and clinical questionnaires (BORG and mMRC).ResultsNSIP was the most frequent HRCT pattern (5 pts, 45%), followed by UIP and UIP/NSIP pattern (respectively 3 pts & 3 pts, 27%). 9 patients showed more than 20% of HRCT pulmonary fibrosis involvement. Only 1 patient had a history of smoking. mRSS was 9.23 (±10SD) points with any significant improvement during the twelve months follow-up (10 ±10SD). 8 pts were on Micophenolate Mophetil (MMF) (7 of them on MMF + steroids), 8 patients were on steroids (mean dose 5 mg/day of Prednisone or equivalent), 3 on rituximab. Main FVC was 2347 ml [+/- 1051 ml] (61.3% predicted) remaining stable. The mmRC decrased from 2.36 at baseline to 2.27 at the end of the follow up and Borg ameliorated from 7.27 at baseline to 6. Two patients were on oxygen therapy (O2 3l/min) with any significant airflow adjustment. Three patients reported irrepressible diarrhea, one patient had a partial intestinal obstruction, one had pulmonary arterial hypertension worsening with an immediate drug withdraw, one patient presented nausea, one irritability. Three patients had a clinical irrelevant weight loss (less than 2 Kg).Conclusionwe report a preliminary real-life experience on the use of Nintedanib in SSc-related patients, focusing in particular to its tolerability and safety profile. Nintedanib is well tolerated with a low rate of definitive discontinuation due to SAE. Diarrhea is a very frequent adverse event (approximately 5 episodes a day) and had led to dose reduction and/or treatment re-challenge in the majority of patients. Diarrhea seems to ameliorate reducing daily dose of MMF (1 gram/day) or precribing loperamide along with diosmectite and probiotics. FVC, mRSS, HRCT and capilalroscopy pattern remained stable. Further studies are desirable to confirm the usefulness of Nintedanib in progressive ILD, but based on our experience we support the combined use of the anti-fibrotic therapy plus immunomodulatory drugs in early stages of SSc-related ILDReferences[1]LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol [Internet] 1988 [cited 2015 Nov 19];15:202-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3361530[2]TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol [Internet] 1961 [cited 2016 May 23];84:359-71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13778561[3]Hoffmann-Vold AM, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol Lancet Publishing Group; 2020;2:e71-83.[4]Van Den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis BMJ Publishing Group; 2013;72:1747-55.Disclosure of InterestsNone declared

BackgroundIntravenous iloprost (ILO) is used in the treatment of refractory Raynaud phenomenon and scleroderma (SSc) digital ulcers. To date, there are no recommended imaging modalities to monitor ILO vascular effects. So far few studies explored ultrasound (US) as a tool to assess vascular subcutaneous involvement in patients affected by SSc.ObjectivesWe aim to evaluate the acute vascular effects of intravenous ILO infusion by power Doppler US (PDUS) examination at periungual (PU) and finger pulp (FP) subcutaneous areas in a consecutive series of SSc patients.MethodsTen consecutive SSc patients who met the ACR/EULAR criteria for SSc referring to our tertiary center for ILO infusions were enrolled in the study.FP and PU vascularization of the 1st, 2ndand 3rdfinger of the dominant hand were evaluated before and after ILO infusion (dosage 0.5-2.0 ng/kg/min for 4-6 hours) using an Esaote MylabClassC, (Genoa, Italy) machine equipped with a 22-8 Mhz multifrequency linear probe. All the exams were performed after at least 30 minutes of acclimation in a room with an ambient temperature ranging from 20 to 22C by the same operator (PM). All the images with the highest presence of PD signal were stored for subsequent examination by a rheumatologist (ST) blind to the sequency of the images.The presence of PD signal in every image was scored according to a semiquantitative 0-3 scale (grade 0 no vessels; grade 1: 1-2 visible vessels; grade 2: 3 to 5 vessels, and grade 3 more than 5 vessels). The value of each finger (FP & PU) were summed up to obtain a total patient PD score and values before and after ILO treatment were compared by T-test for paired samples. Single fingers PD improvements after infusion were summed obtaining total improvement respectively for the PU and FP areas.ResultsClinical and laboratory features of the enrolled patients are reported in Table 1. Mean total PU PD score was 4.2±2.2 at T0 and increased to 7.3±2.5 after treatment(p=0.012).Mean FP total PD score was 2,2±1,81 at T0 and remained unchanged (2,8±1,68) at T1 (p= 0,475). The median number of fingers/patient with PU PD improvement after treatment was 2 (1-3), while the median number of fingers/patient with FP PD improvement was 0,5 [0-3].ConclusionPDUS examination of the PU area could demonstrate an ILO acute effect in SSc patients with long-lasting disease.References[1]Schioppo, T., Orenti, A., Boracchi, P., De Lucia, O., Murgo, A., Ingegnoli, F., 2018. Acute and chronic effects of two different intravenous iloprost regimens in systemic sclerosis: a pragmatic non-randomized trial. Rheumatol. Oxf. Engl. 57, 1408–1416.https://doi.org/10.1093/rheumatology/key113Table 1.Clinical, laboratory and power doppler ultrasound characteristics of our patients, before and after iloprost treatment. SD: standard deviation; ERA: endothelin receptors antagonists; CCB: calcium channel blockers; PDE5i: Phosphodiesterase type 5 inhibitors; ENA: extractable nuclear antigen; ACA: Anti-centromere antibody; RNA: ribonucleic acid; PD: power doppler; PU: periungual; FP: finger pulp.number (%)Mean ± SDMedian (range)P valueTotal patients10 (100%)\\\Age (years)\56,5±14,5456,5 (32-79)\SexMaleFemale2(20%)8(80%)\\Iloprost therapy duration (years)\10,57±8,1610 (0,2-25)\Concomitant vasoactive therapy\\\ERA6(60%)CCB3 (30%)PDE5i0Infusion rate (ml/h)17,1±6,916,5 (10-30)\ENA antibodies\\\Topoisomerase I6 (60%)Negative2 (20%)ACA1 (10%)RNA polymerase III1 (10%)Cutaneous subset of disease\\\Diffuse8(80%)Limited2(20%)Ultrasound PD features\\0,012Total PU PD T04,2±2,20,475Total PU PD T17,3±2,49Total FP PD T02,2±1,81Total FP PD T12,8±1,68PU PD improvement1,9±0,882 (1-3)\1 finger4 (40%)2 fingers3 (30%)3 fingers3 (30%)FP PD improvement0,9±1,10,5 (0-3)\0 finger5 (50%)1 finger2 (20%)2 fingers2 (20%)3 fingers1 (10%)FigureAcknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundMixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterized by heterogeneous clinical manifestations mainly involving skin, kidney and peripheral nervous system.Despite reassuring safety data from EULAR Coronavirus Vaccine (COVAX) physician-reported registry, a significant proportion of patients with autoimmune diseases reported unwillingness to get vaccinated against SARS-CoV-2 infection in the preliminary results of the COVAD study, due to concerns about the lack of long-term safety data, and fear of associated side effects and disease flare.ObjectivesAims of this multicentre Italian study were to investigate the prevalence of vaccination against SARS-CoV-2 in Italian population of MCV patients, to explore the reason for the missed vaccination, and to investigate short and long-term side effects of the vaccine, including vasculitis flare.MethodsAll MCV patients referring to 12 Italian centres were investigated about vaccination and possible both short- (within 48 hours) and long-term (within 30 days) adverse events (AE), classified according to FDA Toxicity Grading Scale for preventive vaccine clinical trials, and possible disease flares. Patients with MCV related to lymphoproliferative disorders or connective tissue diseases were excluded from the study.The baseline variables were expressed as percentages or mean±standard deviation. The differences between continuous variables were analysed using the Mann–Whitney nonparametric test. The chi-squared test, or Fischer’s exact when appropriate, were used for categorical variables (absolute numbers and percentages) regarding baseline characteristics.ResultsA total of 416 patients, 69.2% females and 30.8% males, with a mean age of 70.4±11.7 years, were included in the study.Only 7.7% of patients were not vaccinated, mainly for fear of adverse events (50%) or for medical decision (18.8%). Corminaty was the vaccine most frequently used (80.5%). Interestingly, 6 patients (1.44%) were with a heterologous vaccination (usually AstraZeneca-Corminaty).Considering ongoing treatment, not vaccinated subjects were more frequently treated with chronic glucocorticoid therapy and/or Rituximab (p=0.049 and p=0.043 respectively).AE were recorded in 31.7% of cases, mainly mild and self-limiting (grade 1). More severe adverse events, such as flare of vasculitis, were observed in 5.3% of cases.AE were not associated with the kind of vaccine used and with the clinical manifestations of vasculitis. Patients with active MCV showed a lower frequency of short-term (within 48 hours) adverse events, but patients affected by peripheral neuropathies or skin vasculitis frequently showed a flare of their symptoms, recorded in 40% and 25% of cases, respectively. Finally, patients under glucocorticoid treatment were more prone to develop a vasculitis flare within a month after vaccination.ConclusionVaccination in MCV patients has been performed in a high percentage of patients showing a good safety. Other than patients’ fear, treatments with rituximab and glucocorticoids are the main reasons for delaying vaccination, and it should be considered by the physician before starting therapy. Vasculitis flares were observed in about 5% of cases, in line with that observed in other autoimmune diseases. Specific attention should be reserved to people with purpura or peripheral neuropathy, for the increased risk of exacerbation of their symptoms.References[1]Visentini M et al Flares of mixed cryoglobulinaemia vasculitis after vaccination against SARS-CoV-2 2021[2]Machado PM et al Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine COVAX physician-reported registry 2021[3]Sen P et al COVAD Study Group. COVID-19 vaccination in autoimmune disease COVAD survey protocol 2022[4]Scarpato S et al Italian Group for the Study of Cryoglobulinaemia GISC. Provisional recommendations for SARS-CoV-2 vaccination in patients with cryoglobulinaemic vasculitis 2021Disclosure of InterestsNone declared