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We followed with great interest the numerous reports published by the Annals 1–9 as regards the impact of the COVID-19 pandemic on different rheumatic autoimmune systemic diseases (ASD), including the survey study by Costa et al 9 that underlined the usefulness of telerheumatology in the management of patients with psoriatic arthritis in COVID-19 era. On the same topic, the world literature encompasses a large number of anecdotal observations, cohort studies and telephone surveys.1–15 Overall, the observed prevalence of symptomatic COVID-19, usually as mild-moderate disease, in patients with chronic arthritis was comparable to that found in the general population, while worse outcomes represented almost rare events.1–15 Conversely, increased percentages of symptomatic COVID-19 were observed in patient cohorts with connective tissue diseases, especially systemic lupus or systemic vasculitis.6 7 Of note, in ASD complicated by COVID-19, the baseline use of immune modifiers, namely, conventional synthetic (csDMARD), biological (bDMARD) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD), was not associated with worse COVID-19 disease outcomes.3–5 9 10 Almost invariably these monocentre studies focused on ASD patients’ populations from limited geographical areas.1–15 Given the heterogeneous distribution of pandemic infection within the same country, we investigated the impact of COVID-19 in ASD patients’ populations from three distinct regions of Italy (northern, Emilia Romagna; central, Tuscany; and southern, Calabria), characterised by different spread of the COVID-19 pandemic, prevalent in northern Italy with a marked gradient north-south.16 Our 6-week multicentre telephone survey of 1641 unselected patients with ASD confirmed the quite benign clinical course of COVID-19 in ASD, along with the safety of baseline use of either …

OBJECTIVES: People who are exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could develop a potentially fatal disease with lung involvement and severe cytokine storm syndrome (CSS) - coronavirus disease 2019 (hereafter, COVID-19). Tocilizumab (TCZ) was administered to these subjects, despite the lack of randomised clinical trial data. Hence, summarising data on the mortality rate and related risks factors may help physicians to correctly administer TCZ. METHODS: We performed a systematic review and meta-analysis on mortality rate in TCZ- treated patients with COVID-19 according to the PRISMA guidelines. The pooled mortality rate in TCZ-treated persons was calculated and meta-regressions were done to investigate associated factors. RESULTS: We included 22 studies and 1520 TCZ-treated patients (mean age: 61 years, 95% CI: 59-64; male: 71%, 95% CI: 64-78%). The mortality estimated pooled prevalence was 19% (95% CI: 13-25, I2=100%, p

The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and referred mainly to the pre-antivirals era. Today a rational approach to the problem of hepatitis B in these patients provides for: (a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), (b) the treatment with antivirals (therapy) of active carriers, (c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, (d) the biochemical and hepatitis B surface antigen (HBsAg) monitoring (or universal prophylaxis, in case of high risk immunosuppression) in subjects with markers of previous contact with HBV (HBsAg negative and anti-HBc positive), in order to prevent reverse seroconversion. Moreover it is suggested a strict adherence to criteria of allocation based on the virological characteristics of both recipients and donors in the general setting of transplants and in liver transplantation the universal prophylaxis with nucleos(t)ides analogues (frequently combined with specific anti-HBV immunoglobulins) in HBsAg positive candidates and in HBsAg negative recipients of anti-HBc positive grafts.

Glucocorticoids (GC) are the mainstay of treatment of large-vessel vasculitis (LVV), but a sizeable number of patients relapse upon tapering the GC dose or after discontinuation of GC therapy. In addition, GC cause numerous adverse events. Therefore, in patients with longstanding disease and in those at risk for GC-related adverse events, the use of alternative therapeutic agents should be considered. Interleukin-6 (IL-6) is a key player in the pathogenesis of LVV. Preliminary data suggest the efficacy of the IL-6 receptor inhibitor tocilizumab (TCZ) in patients with LVV. We report 2 treatment-naïve patients with a recent diagnosis of LVV who received monthly TCZ infusions (8 mg/kg body weight) for 6 consecutive months as monotherapy because of relative contraindications and patients' reluctance to take GC. In both cases we observed a complete clinical response and normalisation of inflammatory markers as well as a decrease in vascular FDG uptake and SUV ratio on fluorodeoxyglucose positron emission/computerised tomography. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels rose in both patients after TCZ therapy. TCZ may be an effective alternative to GC treatment for LVV patients at risk for GC-related adverse events. Larger studies are required to confirm our findings.

Anti-TNF-α therapy has successfully been used to treat Takayasu arteritis (TA) refractory to conventional immunosuppressive treatment. However, some patients fail to respond even to TNF-α blockers. Interleukin-6 (IL-6) is a key player in the pathogenesis of TA. Preliminary data also suggest efficacy of the IL-6 receptor inhibitor tocilizumab in patients with large-vessel vasculitis. We report a patient with TA refractory to multiple conventional immunosuppressive agents and two TNF-α blockers successfully treated with monthly tocilizumab infusions (8 mg/kg body weight) for 6 consecutive months. Clinical indices of disease activity, inflammatory markers, and 18Ffluorodeoxyglucose positron emission/computerised tomography findings normalised, while the prednisone dosage could be tapered. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels raised during tocilizumab treatment consistent with the mode of action of tocilizumab. Tocilizumab holds promise for patients with refractory TA. Larger studies are required to confirm our findings.

OBJECTIVES: This paper aims to evaluate if any ultrasonographic aspect of metacarpo-phalangeal (MCP) joint can be predictors for the development of new joint damage, at single joint level, in rheumatoid arthritis (RA) patients. METHODS: Two hundred and forty MCP joints of 24 patients with RA were prospectively evaluated both clinically and by ultrasound (US) at time 0, at six months and 12 months, in order to collect the following variables: presence of synovial hypertrophy and power-Doppler (PD) vascularisation both graded on a semiquantitative (0-3) scale, and the number and dimension of bone erosions. X-ray examinations were carried out at time 0 and at 12 months and lesions were graded using the Sharp/van der Heijde (S/vdH) method at single joint level. Potential prognostic determinants for joint damage obtained at the first examination and during follow-up were entered in a conditional logistic regression analysis. RESULTS: Fifteen out of seventeen (88%) of the new eroded joints on x-rays examination had persistent PD vascularity and 14/17 (82%) had persistent synovial thickening (p=0.001 and p=0.02, vs. non-eroded joints, respectively). In multiple conditional logistic regression analysis, the most important factor associated with the development of radiological joint damage was the presence of a synovial PD score ≥2 on two or more US evaluations (OR 8.51 [95%CI 1.84-39.48] for Rx new erosions and OR 8.30 [95%CI 1.97-38.9] for increased S/vdH local joint score). Both baseline synovial score ≥2 and presence of Rx erosions were also significantly associated with the development of radiological joint damage. Two predictive models for x-ray erosions and total single joint level S/vdH damage score were constructed consisting of 2 baseline plus one longitudinal variable with a ROC AUC of 0.916 (95%CI 0.867-0.965) and 0.886 (95%CI 0.814-0.957). CONCLUSIONS: At the single joint level, the presence of US determined synovial thickness and PD signal at baseline and the persistent PD signal over time have relevant prognostic value for the development of articular damage in the same MCP joints of RA patients.

OBJECTIVES: To investigate systemic inflammation and autoimmune response to citrullinated peptides in patients with erosive and non erosive 'lone' hand osteoarthritis (HOA) with no hip/knee involvement and their relationship with radiographic structural damage. METHODS: Sera were obtained from a total of 99 patients with HOA (52 patients with erosive HOA and 47 patients with non-erosive HOA) and from 50 control subjects (NC). Hand radiographs were obtained from all patients and scored for joint damage according to the Kellgren-Lawrence and the Kallman scores. Serum levels of high-sensitivity CRP (hsCRP), IL-6, pentraxin-3 (PTX-3), anti-CCP and anti-modified citrullinated vimentin (MCV) antibodies were evaluated by a sandwich ELISA. RESULTS: Circulating levels of inflammatory biomarkers hsCRP, IL-6 and PTX3 were not significantly different in the two groups of patients with erosive and non-erosive HOA compared to NC and no significant difference was seen between non-erosive and erosive HOA. Anti-CCP positivity was detected respectively in 1 patient (2.1%) with non-erosive HOA and 1 patient (1.9%) with erosive HOA. Anti-MCV antibodies were present in 4 patients (8.5%) with non-erosive HOA, and 4 patients (7.7%) with erosive HOA. In the control group, one subject (2%) was positive for anti-CCP and 2 subjects (4%) had anti-MCV antibodies. Significant correlation was obtained only between body mass index and hsCRP concentration (r=0.4071; p

To evaluate PTX3 feasibility to provide a prognostic tool in PMR clinical practice.Circulating PTX3 levels were measured in 93 PMR patients at disease onset and during corticosteroid therapy and in 46 normal controls (NC) by ELISA.No difference in PTX3 concentrations was observed between NC and PMR either at disease onset and during follow-up or between groups of patients defined according to the presence of recurrence/relapse.PTX3 serum levels do not increase significantly in active PMR. Further studies on patients with giant-cell arteritis could evaluate whether large vessel involvement may be associated to increased PTX3 levels.

Objective: Polymyalgia rheumatica (PMR) is an inflammatory disease that tipically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synoivitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients. Methods: Synovial expression of neuropeptides was investigated by immunohistochemical analysis, in two groups of PMR patients: the first one at the onset of disease and the second one after corticosteroid treatment, and in other joint diseases, rheumatoid arthritis (RA) and osteoarthritis (OA). Results: The only significant expression of VIP wasfound in PMR and, to a lesser extent, in RA synovial tissue. In PMR, we observed VIP immunostaining both in the lining layer and in the sublining area. In patients on corticosteroid treatment VIP lining layer expression was not significantly different while VIP positive cells in the sublining area were almost absent. Conclusion: Local VIP production in PMR synovial tissue might contribute to the typical musculoskeletal discomfort and it may have a role in the immunomodulation of synovial inflammation.

Evaluation of the role of VEGF in cartilage pathophysiology.VEGF release from chondrocytes in the presence of IL-1beta, TGFbeta and IL-10 was detected by immunoassay. VEGF receptor -1 and -2 expression and VEGF ability to modulate caspase -3 and cathepsin B expression were detected by immunohistochemistry on cartilage biopsies and cartilage explants. VEGF effects on chondrocyte proliferation was analysed by a fluorescent dye that binds nucleic acids.VEGF production by osteoartritis (OA) chondrocytes was significantly reduced by IL-1beta while it was increased in the presence of TGFbeta. Cartilage VEGFR-1 immunostaining was significantly downregulated in 'early' OA patients compared to normal controls (NC). VEGFR-2 expression was negligible both in OA and in NC. VEGF decreased the expression of caspase-3 and cathepsin B, whereas it did not affect proliferation.VEGF is able to down-modulate chondrocyte activities related to catabolic events involved in OA cartilage degradation.