Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire.

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Idiopathic inflammatory myopathies: one year in review 2023.

Idiopathic inflammatory myopathies are a group of rare, autoimmune, diseases typically involving striate muscle and also variously affecting several other systems or organs, such as joints, skin, lungs, heart and gastrointestinal tract. IIM are mainly characterised by subacute onset and chronic course and are burdened by significant morbidity and mortality. Despite the rarity of these conditions, several efforts have been undertaken in the last years to better understand their pathogenesis, as well as to achieve a more precise classification and to define the optimal therapeutic approach. The aim of this review is to provide an up-to-date digest of the most relevant studies published on this topic over the last year.

Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study.

BACKGROUND: Giant cell arteritis is a critically ischaemic disease with protean manifestations that require urgent diagnosis and treatment. European Alliance of Associations for Rheumatology (EULAR) recommendations advocate ultrasonography as the first investigation for suspected giant cell arteritis. We developed a prediction tool that sequentially combines clinical assessment, as determined by the Southend Giant Cell Arteritis Probability Score (SGCAPS), with results of quantitative ultrasonography. METHODS: This prospective, multicentre, inception cohort study included consecutive patients with suspected new onset giant cell arteritis referred to fast-track clinics (seven centres in Italy, the Netherlands, Spain, and UK). Final clinical diagnosis was established at 6 months. SGCAPS and quantitative ultrasonography of temporal and axillary arteries with three scores (ie, halo count, halo score, and OMERACT GCA Score [OGUS]) were performed at diagnosis. We developed prediction models for diagnosis of giant cell arteritis by multivariable logistic regression analysis with SGCAPS and each of the three ultrasonographic scores as predicting variables. We obtained intraclass correlation coefficient for inter-rater and intra-rater reliability in a separate patient-based reliability exercise with five patients and five observers. FINDINGS: Between Oct 1, 2019, and June 30, 2022, we recruited and followed up 229 patients (150 [66%] women and 79 [34%] men; mean age 71 years [SD 10]), of whom 84 were diagnosed with giant cell arteritis and 145 with giant cell arteritis mimics (controls) at 6 months. SGCAPS and all three ultrasonographic scores discriminated well between patients with and without giant cell arteritis. A reliability exercise showed that the inter-rater and intra-rater reliability was high for all three ultrasonographic scores. The prediction model combining SGCAPS with the halo count, which was termed HAS-GCA score, was the most accurate model, with an optimism-adjusted C statistic of 0·969 (95% CI 0·952 to 0·990). The HAS-GCA score could classify 169 (74%) of 229 patients into either the low or high probability groups, with misclassification observed in two (2%) of 105 patients in the low probability group and two (3%) of 64 of patients in the high probability group. A nomogram for easy application of the score in daily practice was created. INTERPRETATION: A prediction tool for giant cell arteritis (the HAS-GCA score), combining SGCAPS and the halo count, reliably confirms and excludes giant cell arteritis from giant cell arteritis mimics in fast-track clinics. These findings require confirmation in an independent, multicentre study. FUNDING: Royal College of Physicians of Ireland, FOREUM.

The Advantages of Radiofrequency Echographic MultiSpectrometry in the Evaluation of Bone Mineral Density in a Population with Osteoarthritis at the Lumbar Spine.

BACKGROUND: Osteoarthritis (OA) in the lumbar spine can potentially lead to an overestimation of bone mineral density (BMD), and this can be a challenge in accurately diagnosing conditions like osteoporosis, where precise measurement of BMD is crucial. Radiofrequency Echographic Multi Spectrometry (REMS) is being recognized as an innovative diagnostic tool for assessing bone status. The purpose of this study was to evaluate whether the use of REMS may enhance the identification of osteoporosis in patients with osteoarthritis. METHODS: A cohort of 500 patients (mean age: 63.9 ± 11.2 years) diagnosed with osteoarthritis and having a medical prescription for dual-energy X-ray absorptiometry (DXA) were recruited for the study. All patients underwent BMD measurements at lumbar spine and femoral sites by both DXA and REMS techniques. RESULTS: The T-score values for BMD at the lumbar spine (BMD-LS) by DXA were significantly higher with respect to BMD-LS by REMS across all OA severity scores, and the differences were more pronounced in patients with a higher degree of OA severity (p < 0.001). Furthermore, the percentage of subjects classified as "osteoporotic", on the basis of BMD by REMS was markedly higher than those classified by DXA, both when considering all skeletal sites (39.4% vs. 15.1%, respectively) and the lumbar spine alone (30.5% vs. 6.0%, respectively). A similar pattern was observed when OA patients were grouped according to the Kellgren-Lawrence grading score. CONCLUSIONS: The findings from our study indicate that, in a population with varying severity levels of osteoarthritis, REMS demonstrated a higher capability to diagnose osteoporosis compared to DXA, and this could lead to earlier intervention and improved outcomes for patients with bone fragility, reducing the likelihood of fractures and associated complications.

Diagnostic accuracy of OGUS, Southend halo score and halo count in giant cell arteritis.

Objectives: Ultrasound has a paramount role in the diagnostic assessment of giant cell arteritis (GCA); Southend halo score (HS), halo count (HC), and OMERACT GCA Ultrasonography Score (OGUS) are the first quantitative scores proposed in this setting. The aim of this study was therefore to assess the diagnostic accuracy of these scores in a real-life scenario, as well as to evaluate their optimal cutoff, also with respect to disease extent, sex, and age. Methods: We retrospectively collected clinical, serological, and US findings of all patients referred for the first time to our vasculitis clinic in the suspicion of GCA. Results: A total of 79 patients were included, and a definite diagnosis of GCA was made in 43 patients. For OGUS, the ROC curve showed an optimal cut point of 0.81 (sensitivity 79.07% and specificity 97.22%). For HC and HS, the optimal cutoff values were > 1.5 (sensitivity 76.7% and specificity 97.2%) and > 14.5 (sensitivity 74.4% and specificity 97.2%), respectively. No relevant differences were assessed when patients were stratified according to disease extent, age, and sex. Compression sign (CS) was positive in 34 of 38 patients with cranial GCA and negative in all controls and LV-GCA. Conclusion: All three scores display good sensitivity and excellent specificity, although the cutoff was slightly different than proposed. In particular, for OGUS, a threshold of 0.81 could be employed for diagnostic purposes, although it was developed solely for monitoring. Due to its high sensitivity and specificity, CS should be always assessed in all patients referred with a suspicion of cranial GCA.

Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

BACKGROUND: We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. METHODS: RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. RESULTS: Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. CONCLUSION: Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

The Role of Major Salivary Gland Ultrasound in the Diagnostic Workup of Sicca Syndrome: A Large Single-Centre Study.

(1) Objective: To determine the diagnostic accuracy of major salivary gland ultrasonography (SGUS) in primary Sjogren's syndrome (SS), we used the Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system on a large single-centre cohort of patients with sicca syndrome. (2) Method: We retrospectively collected the clinical, imaging and serological data of all the patients referred with a suspicion of SS who underwent SGUS and minor salivary glands biopsy. (3) Results: A total of 132 patients were included. The SGUS scores were correlated between the two sides (p < 0.001). The diagnostic cut-off for SS (AUROC: 0.7408) was 6 for the SGUS-global sum (sensitivity: 32.43%; specificity: 96.84%). The cut-off with the highest specificity for SS diagnosis was 7. In the patients with a final diagnosis of SS, the mean SGUS score was significantly higher (p < 0.001) than that of the non-SS patients (3.73 vs. 1.32 for the SGUS-global sum). A significant correlation was demonstrated between the SGUS scores and final SS diagnosis (p < 0.001), biopsy positivity (p < 0.001), ANA positivity (p = 0.016), Ro-SSA positivity (p = 0.01), and gland fibrosis (p = 0.02). (4) Conclusions: SGUS, using the OMERACT scoring system, has moderate sensitivity and high specificity for the diagnosis of SS. The scoring showed a strong and direct correlation with all the clinical hallmarks of SS diagnosis, such as the positivity of a labial salivary gland biopsy, ANA and Ro-SSA statuses, and salivary gland fibrosis. Because of its high specificity, a SGUS-global score > 6 could be therefore employed for the diagnosis of SS in the case of ANA negativity or the unavailability of a biopsy.

Prevalence and characteristics of subclinical giant cell arteritis in polymyalgia rheumatica.

OBJECTIVE: The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. METHODS: This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent US of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. RESULTS: We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. CONCLUSION: More than a fifth of the pure PMR patients had US findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Tocilizumab Vs Methotrexate in a Cohort of Patients Affected by Active GCA: A Comparative Clinical and Ultrasonographic Study.

Introduction: No head-to-head study has assessed the superiority of tocilizumab versus methotrexate in giant cell arteritis (GCA), and few studies have demonstrated its effectiveness in terms of ultrasonographic findings, but without a control group. The primary endpoint was to assess whether tocilizumab was superior to methotrexate in inducing normalization of US findings, whereas the secondary endpoint was to assess the effectiveness of precocious withdrawal of glucocorticoids. Methods: We prospectively enrolled all the patients with active GCA at our clinic. The inclusion criteria were clinical diagnosis of GCA; active disease; and clinical, laboratory, and US data, evaluated using the halo count (HC) and OMERACT GCA Ultrasonography Score (OGUS). Evaluations were repeated at 3, 6, and 12 months. Results: Twenty patients were treated with Tocilizumab and 9 with Methotrexate. All but three tocilizumab-treated patients achieved remission at six months, whereas at 12 months, all patients were in glucocorticoid-free remission. Up to three of the nine methotrexate patients experienced a lack of efficacy or minor relapses. Tocilizumab-treated patients showed a statistically significant difference between baseline and all follow-ups in terms of OGUS and HC, whereas the difference in the Methotrexate group was significant after 1 year. The mean glucocorticoid dosage significantly decreased in both groups. No severe adverse events or major relapses were reported. Conclusion: Our study demonstrates the superiority in terms of rapidity of a tocilizumab-based scheme over a methotrexate-based scheme in inducing clinical and US remission. Precocious withdrawal of glucocorticoids did not increase the risk of relapse.

Baricitinib retention rate: 'real-life' data from a mono-centric cohort of patients affected by rheumatoid arthritis.

Objectives: The aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection. Materials and methods: Patients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort's demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks. Results: Ninety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p < 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation. Conclusion: Our data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Introduction: The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Materials and methods: Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Results: Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. Discussion: This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

Anti-Cytosolic 5'-Nucleotidase 1A in the Diagnosis of Patients with Suspected Idiopathic Inflammatory Myopathies: An Italian Real-Life, Single-Centre Retrospective Study.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies were proposed as a biomarker for the diagnosis of inclusion body myositis (IBM), but conflicting specificity and sensitivity evidence limits its use. Our study aimed to assess the diagnostic accuracy of anti-cN1A in a cohort of patients who underwent a myositis line immunoassay for suspected idiopathic inflammatory myopathies (IIM). We also assessed the agreement between two testing procedures: line immunoassay (LIA) and enzyme-linked immunoassay (ELISA). MATERIALS AND METHODS: We collected retrospective clinical and serological data for 340 patients who underwent a myositis antibody assay using LIA (EUROLINE Autoimmune Inflammatory Myopathies 16 Ag et cN-1A (IgG) line immunoassay) and verification with an anti-cN1A antibody assay using ELISA (IgG) (Euroimmun Lubeck, Germany). RESULTS: The serum samples of 20 (5.88%) patients (15 females, 5 males, mean age 58.76 ± 18.31) tested positive for anti-cN1A using LIA, but only two out of twenty were diagnosed with IBM. Seventeen out of twenty tested positive for anti-cN1A using ELISA (median IQR, 2.9 (1.9-4.18)). CONCLUSIONS: Our study suggests excellent concordance between LIA and ELISA for detecting anti-cN1A antibodies. LIA may be a rapid and useful adjunct, and it could even replace ELISA for cN1A assay. However, the high prevalence of diseases other than IBM in our cohort of anti-cN1A-positive patients did not allow us to consider anti-cN1A antibodies as a specific biomarker for IBM.

Clinical, laboratory and ultrasonographic findings at baseline predict long-term outcome of polymyalgia rheumatica: a multicentric retrospective study : Polymyalgia rheumatica predicted by ultrasonographic findings polymyalgia rheumatica outcome predicted early by ultrasound.

To assess the rate of PMR who, during the follow-up, undergo a diagnostic shift as well as to assess which clinical, laboratory and US findings are associated to a diagnostic shift and predict the long-term evolution of PMR. All PMR followed-up for at least 12 months were included. According to the US procedures performed at diagnosis, patients were subdivided into four subgroups. Clinical data from follow-up visits at 12, 24, 48 and 60 months, including a diagnostic shift, the number of relapses and immunosuppressive and steroid treatment, were recorded. A total of 201 patients were included. During the follow-up, up to 60% had a change in diagnosis. Bilateral LHBT was associated with persistence in PMR diagnosis, whereas GH synovitis and RF positivity to a diagnostic shift. Patients undergoing diagnostic shift had a higher frequency of GH synovitis, shoulder PD, higher CRP, WBC, PLT and Hb and longer time to achieve remission, while those maintaining diagnosis had bilateral exudative LHBT and SA-SD bursitis, higher ESR, lower Hb and shorter time to remission. Cluster analysis identified a subgroup of older patients, with lower CRP, WBC, PLT and Hb, lower PD signal or peripheral synovitis who had a higher persistence in PMR diagnosis, suffered from more flares and took more GCs. Most PMR have their diagnosis changed during follow-up. The early use of the US is associated with a lower dosage of GCs. Patients with a definite subset of clinical, laboratory and US findings seem to be more prone to maintain the diagnosis of PMR.

Immunological Pathways in Sarcoidosis and Autoimmune Rheumatic Disorders-Similarities and Differences in an Italian Prospective Real-Life Preliminary Study.

BACKGROUND: The pathogenesis of sarcoidosis involves T cells and B lymphocytes that produce autoantibodies. We compared the expression of different T and B cell subsets in sarcoidosis and three B-mediated rheumatic diseases that can affect the lungs in an attempt to identify similarities and differences that distinguish these diseases. METHODS: The study included patients referred to Siena University Hospital's respiratory disease and rheumatology units. Patients were enrolled prospectively and consecutively. Healthy volunteers were also included. Multicolor flow cytometry was performed on phenotype T and B cell subsets. Multivariate analysis was carried out to reduce the dimensionality of the data. RESULTS: Fifteen patients had a diagnosis of sarcoidosis, fourteen idiopathic inflammatory myopathies (IIM), five granulomatosis with polyangiitis (GPA), ten microscopic polyangiitis (MPA), and seven were controls. Thirty-five T and B cell subsets were phenotyped, 15 of which were significantly different in sarcoidosis, B-mediated rheumatic disorders, and controls. Principal components analysis distinguished the four groups of patients with a total explained variance of 54.7%. A decision tree was constructed to determine which clustering variables would be most useful for distinguishing sarcoidosis, IIM, MPA, and GPA. The model showed regulatory T helper cells (Th-reg) > 5.70% in 91% of sarcoidosis patients as well as Th-reg ≤ 5.70 and Th17 > 43.27 in 100% of MPA. It also showed Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≥ 7.81 in 100% of GPA patients, and Th-reg ≤ 5.70, Th17 ≤ 43.27 and Tfh-reg ≤ 7.81 in 100% of IIM patients. CONCLUSION: The immune cell profile sheds light on similarities and differences between sarcoidosis and B-mediated rheumatic diseases. Sarcoidosis and autoimmune diseases show similar patterns of cellular immune dysregulation, suggesting a common pathogenic pathway that may provide an opportunity for further understanding autoimmunity and exploring biological therapies to treat sarcoidosis.

Intra-articular injections of biological disease-modifying anti-rheumatic drugs in inflammatory arthropathies: An up-to-date narrative review.

INTRODUCTION: Since the 1990s thebiological disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionized the treatment of chronic dysimmune inflammatory arthropathies such as Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondylarthritis. Nevertheless, despite a full treatment regimen, mono- and oligoarticular persistence of the synovitis is sometimes observed. The intra-articular (IA) use of bDMARD drugs could resolve the persistent joint inflammation and result in a reduction in the degree of immunosuppression of individuals; moreover, the use of these drugs intra-articularly could be associated with a reduction in the treatment-related costs. METHODS: We extensively searched via PubMed and Google Scholar articles using as keywords "etanercept", "infliximab", "adalimumab", "certolizumab", "golimumab", "tocilizumab", "ixekizumab", "secukinumab", "rituximab" each combined with "intra-articular injection". RESULTS: We found and evaluated 161 papers, and then we selected 24 that were highly related to the topic of the present work. The articles examined a total of 349 patients, 85 males (M), and 168 females (F), mean age of 44.75±12.09 years old and considered 556 treated joints. Three hundred and forty-one patients were affected by Rheumatoid Arthritis, 198 by Psoriatic Arthritis, 56 by Axial Spondylarthritis, 26 by Juvenile Idiopathic Arthritis, 19 by Undifferentiated Arthritis, 1 by arthritis associated with inflammatory bowel disease and 9 patients by an unspecified inflammatory articular disorder. All patients were treated intra-articularly with a TNFα inhibitor among Adalimumab, Etanercept or Infliximab. Side effects were documented in 9 out of 349 (2.57%) treated patients and all were mild or moderate. In some cases the effectiveness of IA bDMARDs treatment was maintained for several months, however in the few published randomized controlled trials(RCTs) the corticosteroids (GCs) appeared to act better when administered intra-articularly compared to bDMARDs. CONCLUSIONS: The IA use of bDMARDs seems to be weakly effective in the management of resistant synovitis and not superior to GCs injections. The treatment's main limit appears to be the poor persistence of the compound in the joint.

Prevalence of myositis specific and associated antibodies in a cohort of patients affected by idiopathic NSIP and no hint of inflammatory myopathies.

The presence of interstitial lung disease (ILD) is a common and fearsome feature of idiopathic inflammatory myopathies (IIM). Such patients show radiological pattern of non-specific interstitial pneumonia (NSIP). The present study aimed to assess the prevalence of myositis-specific and myositis-associated antibodies (MSA and MAA) in a cohort of patients with a previous diagnosis of NSIP and no sign or symptom of IIM. Secondly, it will be assessed whether patients displaying MSA and/or MAA positivity have a worse or a better outcome than idiopathic NSIP. All patients affected by idiopathic NSIP were enrolled. MSA and MAA were detected using EUROLINE Autoimmune Inflammatory Myopathies 20 Ag (Euroimmun Lubeck, Germany), line immunoassay. A total of 16 patients (mean age 72 ± 6.1 years old) were enrolled. Six out of 16 patients (37.5%) had significant MSA and/or MAA positivity: one displayed positivity of anti-PL-7 (+ +), one of anti-Zo (+ +), anti-TIF1γ (+ + +) and anti-Pm-Scl 75 (+ + +), one of anti-Ro52 (+ +), one of anti-Mi2ß (+ + +), one of anti-Pm-Scl 75 (+ + +) and the latter of both anti-EJ (+ + +) and anti-Ro52 (+ + +).Two out of 7 seropositive patients showed a significant impairment of FVC (relative risk 4.8, 95% CI 0.78-29.5; p = 0.0350). Accordingly, among the 5 patients that started antifibrotic treatment during the observation time, 4 were seronegative. Our findings highlighted a potential autoimmune or inflammatory in idiopathic NSIP patients and also in those without significant rheumatological symptoms. A more accurate diagnostic assessment may ameliorate diagnostic accuracy as well as may provide new therapeutic strategy (antifibrotic + immunosuppressive). A cautious assessment of NSIP patients with a progressive and non-responsive to glucocorticoids disease course should therefore include an autoimmunity panel comprising MSA and MAA.