Search

Objective. To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD). Methods. An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding. Results. pSpA is the most common extraintestinal manifestation in IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several “red flags” guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed. Conclusions. Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

This cross-sectional online study was designed by the study group on Capillaroscopy and Microcirculation in Rheumatic Diseases (CAP) of the Italian Society of Rheumatology (SIR) to provide an overview of the management of nailfold capillaroscopy in Italian rheumatology centers. Therefore, SIR distributed the survey to its members in July 2021, and each center’s physician with the most expertise in capillaroscopy completed the questionnaire. The survey was completed by 102 centers, with at least one representative from each Italian region. Ninety-three centers perform capillaroscopy, and 52 (56) conduct more than 200 investigations annually. Seventy-eight (84%) of respondents have more than five years of experience with the technique, and 75 centers (80.6%) have received certification from specific national or international training courses. In 85 centers, a videocapillaroscope with 200x magnification is employed (91.4%). The average waiting period for the examination is 2.4 months, and less than 3 months in 64 of the locations (68.8%). The study demonstrates that capillaroscopy is an integral part of both the diagnostic phase of Raynaud’s phenomenon and the monitoring of autoimmune connective tissue diseases (CTDs). However, the reporting methods and timing of patient followup are heterogeneous.

Interstitial lung disease (ILD) is a relevant cause of morbidity and mortality in patients with autoimmune rheumatic diseases (ARDs). In the last years, an acute exacerbation (AE) - defined as an acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality - has been reported to occur in virtually all ILD types, including ARD-ILD. The aim of this review is to describe the available and investigational treatments in patients affected by AE-ARD-ILD in light of the very low quality of evidence available. Currently, management consists of efforts to identify reversible triggers of respiratory decline, such as drugs effective in ARDs and infections, including opportunistic infections, together with supportive treatments. AE-ILD, AE-ARD-ILD and acute respiratory distress syndrome share histopathologically similar findings of diffuse alveolar damage in most cases. Identification of triggers and risk factors might contribute to early diagnosis and treatment of AE-ILD, before the alveolar damage becomes irreversible. In patients with acute respiratory distress syndrome, the role of steroids and immunosuppressants remains controversial. Also, many uncertainties characterize the management of AE-ARD-ILD because of the lack of evidence and of an unquestionable effective therapy. At this time, no effective evidence-based therapeutic strategies for AE-ARD-ILD are available. In clinical practice, AE-ARD-ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. Randomized controlled trials are needed to better understand the efficacy of current and future drugs for the treatment of this clinical relevant condition., Competing Interests: Declaration of competing interest The Authors have no Conflict of Interest related to this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To provide a comprehensive overview of peripheral spondyloarthritis (pSpA), focusing specifically on its occurrence and management in patients with inflammatory bowel disease (IBD)., Methods: An exhaustive literature search was conducted in PubMed, Embase, Cochrane Database of Systematic Reviews, and Google Scholar to identify relevant studies on pSpA in IBD patients. Titles, abstracts, and full-text articles were screened for relevance. Data on study design, patient characteristics, diagnostic criteria, main findings, and conclusions were extracted from selected articles. Study quality was assessed using appropriate checklists. Information was synthesized narratively to summarize current understanding., Results: pSpA is the most common extraintestinal manifestation in IBD, with a median prevalence of 16%. It worsens quality of life and requires collaboration between gastroenterologists and rheumatologists for optimal diagnosis and treatment. Several "red flags" guide appropriate specialist referral of IBD patients with suspected pSpA. Once the diagnosis is confirmed, the choice of therapy depends on IBD phenotype and patterns of articular/axial involvement. Anti-tumor necrosis factor (TNF) drugs are first-line biologics, with interleukin (IL)-12/23 and IL-23 inhibitors as alternatives for anti-TNF failure. Small molecules like apremilast and Janus kinase inhibitors also have utility. Recommended treatment algorithms exist, but more randomized controlled trials are needed., Conclusions: Early identification of pSpA is crucial in IBD patients to enable timely intervention, prevent structural damage, and minimize disability. A multidisciplinary, holistic approach addressing musculoskeletal and extra-musculoskeletal manifestations is key to optimal patient outcomes.

Background: Progressive pulmonary fibrosis (PPF) has been associated with a worse prognosis, even when interstitial lung disease (ILD) is related to rheumatic diseases. Since many differences are detectable among rheumatic diseases in prevalence and features of ILD, we aimed to investigate features of PPF in different rheumatic diseases, namely rheumatoid arthritis (RA) and primary Sjogren's syndrome (pSS). Methods: In an Italian multicentre cross-sectional study, consecutive pSS or RA patients with a diagnosis of ILD from at least two years were enrolled. For each patient, demographic, clinical, and serological data, other than chest high-resolution computed tomography and lung function tests, were recorded at the enrolment and after 2 years. Results : Among 232 patients, namely 156 RA-ILD and 76 pSS-ILD, a PPF was recorded in 38.8% of cases, without differences between the two diseases. Analysing patients with a PPF, usual interstitial pneumonia was significantly more frequent in RA than pSS (71.4% and 44.4%, respectively; p = 0.019), while ILD preceded the diagnosis of the rheumatic disease in 29.1% of RA and 89.5% of pSS ( p < 0.001). Finally, RA patients were significantly younger than pSS at the diagnosis of the rheumatic disease ( p < 0.001). Conclusions: In conclusion, although there is a similar prevalence of PPF in RA-ILD and pSS-ILD, we demonstrated for the first time that the two conditions differ in terms of radiological patterns and demographic and clinical features, suggesting that specific factors related to such diseases might influence the lung involvement over time. Prospective studies could investigate if these specificities could induce different responses to the treatment.

Objective: Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD., Methods: We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort., Results: Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD., Conclusion: We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD., (This article is protected by copyright. All rights reserved.)

Objective: Evaluation of effectiveness of non-mucosa-sparing (eg, reboot) surgery in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), poorly responders to mAb therapy, who failed repeated comprehensive endoscopic surgeries. Methods: Retrospective observational study. Patients who were under mAb for a comorbid condition but still had no control over their CRSwNP were included. Data collected were preoperative tissue eosinophilia, nasal polyp score (NPS), 22-item sinonasal outcome test (SNOT-22), visual analog scale (VAS) for nasal symptoms, Lund-Kennedy score for nasal crusts (LK-c) and synechiae (LK-s), and Lund-Mackay score (LMS). The same data were also collected postoperatively (at 12 months), besides LMS, and compared. Results: Overall, 20 patients were included. Pre-reboot scores were: NPS = 4.95 ± 1.70; SNOT-22 = 63.90 ± 19.15; VAS-global = 7.06 ± 1.50; LM = 19.0 ± 4.01; LK-c = 1.10 ± 0.64; and LK-s = 1.30 ± 0.73. Tissue biopsies revealed a high density of eosinophils in all cases, ≥10/HPF (range 10-60). Mean postoperative outcomes were: NPS = 0; SNOT-22 = 17.90 ± 6.80; VAS-global = 1.91 ± 1.17; LK-c = 1.45 ± 0.51; and LK-s = 1.50 ± 0.61. The difference of mean pre- and postoperative scores was significant for both NPS, SNOT-22 and VAS-global ( P < .001). No differences were observed for LK-c and LK-s ( P > .05). Nasal specimens showed markedly reduced tissue eosinophils (100% of cases). Conclusion: Reboot sinus surgery might be an effective solution for recalcitrant CRSwNP patients unresponsive to mAbs and multiple sinus surgeries., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Pulmonary involvement is one of the most common extra-articular manifestations of rheumatoid arthritis (RA), a systemic inflammatory disease characterized by joint swelling and tenderness. All lung compartments can be interested in the course of RA, including parenchyma, airways, and, more rarely, pleura and vasculature., Areas Covered: The aim of this paper is to review the main RA lung manifestations, focusing on pathogenesis, clinical and therapeutic issues of RA-related interstitial lung disease (ILD). Despite an increasing number of studies in the last years, pathogenesis of RA-ILD remains largely debated and the treatment of RA patients with lung involvement is still challenging in these patients., Expert Opinion: Management of RA-ILD is largely based on expert-opinion. Due to the broad clinical manifestations, including both joints and pulmonary involvement, multidisciplinary discussion, including rheumatologist and pulmonologist, is essential, not only for diagnosis, but also to evaluate the best therapeutic approach and follow-up. In fact, the coexistence of different lung manifestations may influence the treatment response and safety. The identification of biomarkers and risk-factors for an early identification of RA patients at risk of developing ILD remains a need that still needs to be fulfilled, and that will require further investigation in the next years.

Lung involvement represents a fearful complication in rheumatoid arthritis (RA), potentially involving all compartments of the pulmonary system. Regarding interstitial lung disease (ILD), the HRCT represents the gold standard technique for its diagnosis; however, the examination is burdened by radiation exposure and high costs. In addition, although some risk factors for ILD are known, no algorithms exist to know which patients to submit to HRCT and when. In this context, lung ultrasound (LUS) showed promising results for at least 10 years, demonstrating correlation with high resolution computed tomography (HRCT) findings in other rheumatic diseases. Here, LUS may represent a screening test providing additional information to clinical examination and pulmonary function tests. The data deriving from LUS experience in other rheumatic diseases could steer the future towards the use of this technique also in RA patients, and in this review, we report the most relevant literature regarding LUS in RA-ILD.

Background: Interstitial lung disease (ILD) represents a frequent cause of morbidity and mortality in primary Sjogren syndrome (pSS). However, the prevalence and behavior of pSS-ILD remains incomplete, largely based on retrospective heterogeneous studies., Aim of the Study: To investigate the prevalence of progressive pulmonary fibrosis (PPF) in a multicentric cohort of patients with pSS-ILD. Additionally, this study explored possible correlations between PPF and clinical, demographic, and serological features of pSS., Methods: All consecutive patients with pSS-ILD were enrolled in a 6-month period. Clinical, demographic, and serological features of pSS, other than functional and radiological lung features, were collected. Clinical behaviors of ILD other than PPF were also investigated., Results: Seventy-two patients were enrolled. A fibrosing ILD pattern was observed in 65.3% of patients with pSS-ILD; among them, 55.3% showed a PPF. The radiologic pattern (NSIP, UIP, or others) was not associated with PPF; in particular, patients with PFF had UIP in 42.3% of cases and NSIP in 57.7%, without a significant difference with respect to the non-PPF group ( p = 0.29). Shorter pSS disease duration, higher age at pSS diagnosis, and lower frequency of antinuclear antibodies were correlated with the PPF subgroup. However, multivariate analysis did not confirm these associations., Discussion: This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up., Conclusions: This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up.

Objectives: We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in rheumatoid arthritis (RA) patients with particular regards to difficult-to-treat subgroups., Methods: The diffusion of Janus kinase inhibitors (JAKi) for the treatment of RA has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities., Results: Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients., Conclusions: In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.

Objective: To evaluate patient-reported outcomes (PROs) after initiation of tumor necrosis factor inhibitor (TNFi) treatment in European real-world patients with psoriatic arthritis (PsA). Further, to investigate PRO remission rates across treatment courses, registries, disease duration, sex, and age at disease onset., Methods: Visual analog scale or numerical rating scale scores for pain, fatigue, patient global assessment (PtGA), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) from 12,262 patients with PsA initiating a TNFi in 13 registries were pooled. PRO remission rates (pain ≤ 1, fatigue ≤ 2, PtGA ≤ 2, and HAQ-DI ≤ 0.5) were calculated for patients still on the treatment., Results: For the first TNFi, median pain score was reduced by approximately 50%, from 6 to 3, 3, and 2; as were fatigue scores, from 6 to 4, 4, and 3; PtGA scores, from 6 to 3, 3, and 2; and HAQ-DI scores, from 0.9 to 0.5, 0.5, and 0.4 at baseline, 6, 12, and 24 months, respectively. Six-month Lund Efficacy Index (LUNDEX)-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 24%, 31%, 36%, and 43% (first TNFi); 14%, 19%, 23%, and 29% (second TNFi); and 9%, 14%, 17%, and 20% (third TNFi), respectively. For biologic-naïve patients with disease duration < 5 years, 6-month LUNDEX-adjusted remission rates for pain, fatigue, PtGA, and HAQ-DI scores were 22%, 28%, 33%, and 42%, respectively. Corresponding rates for patients with disease duration > 10 years were 27%, 32%, 41%, and 43%, respectively. Remission rates were 33%, 40%, 45%, and 56% for men and 17%, 23%, 24%, and 32% for women, respectively. For patients aged < 45 years at diagnosis, 6-month LUNDEX-adjusted remission rate for pain was 29% vs 18% for patients ≥ 45 years., Conclusion: In 12,262 biologic-naïve patients with PsA, 6 months of treatment with a TNFi reduced pain by approximately 50%. Marked differences in PRO remission rates across treatment courses, registries, disease duration, sex, and age at onset of disease were observed, emphasizing the potential influence of factors other than disease activity on PROs., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old., Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected., Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi ( p  = 0.02), JAKi ( p  < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi ( p  = 0.013)., Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Manfredi, Fornaro, Bazzani, Perniola, Cauli, Rai, Favalli, Bugatti, Rossini, Foti, Conti, Lopalco, Scalvini, Garufi, Congia, Gorla, Gremese, Atzeni, Caporali, Iannone and Sebastiani.)

Objectives: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis., Methods: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance., Results: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities., Conclusions: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs., (© 2023. The Author(s).)

Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA., Methods: A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: "early PsA," "axial-PsA," "extra-articular manifestations and comorbidities," "therapeutic goals." Relevant articles from the literature (2016-2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated., Results: Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for "early PsA"; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for "axial PsA"; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for "comorbidities and extra-articular manifestations"; target and tools, treat-to-target strategy, role of imaging for "therapeutic goals." The final document consisted of 49 statements., Discussion: The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease., Competing Interests: SD’A received consulting and speaking fees from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer and UCB. MB had the following financing relationships with subjects with commercial interests in the health sector: BMS, Janseen, Novartis, Lilly, Abbvie, Pfizer, and Galapagos. LD received consultation honoraria from Abbvie, Amgen, Astra-Zeneca, Biogen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Janssen, Kiniksa Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, Swedish Orphan Biovitrium (SOBI), Takeda, and Vifor Pharmaceuticals. The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unrestricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Kiniksa, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI. CD has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow and Sanofi; grant support from AbbVie and Novartis. FF received consulting/speaker fee or research support from AbbVie, Amgen, Alfa-Sigma, Biogen, Bristol-Myers Squibb, Eli-Lilly, Galapagos, Janssen, Lilly, Novartis, and Pfizer. MGa received consulting and speaking fees from Abbvie, Pfizer, Novartis, Galapagos, Janssen, MSD, Lilly, Astra Zeneca. RGe received consulting and speaking fees from AbbVie, Alfasigma, BMS, MSD, Pfizer, Roche. MGo received consulting and speaking fees from AbbVie, Amgen, Lilly, Novartis, Pfizer. EG received consulting/speaker fee or research support from AbbVie, Eli-Lilly, Galapagos, Janssen, Novartis, and Pfizer. FI received honoraria or consulting fees from Abbvie, Eli-Lilly, Galapagos, Janssen, and Pfizer. BL received speaker fee or research support from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer, and Bristol. CM received speaker’s bureau or grants from Abbvie, Amgem, BMS, Galapagos, Lilly, Novartis, and Pfizer. RR received consulting/speaker fee or research support from AbbVie, Novartis, Janssen, Eli-Lilly, Amgen, and Pfizer. MR received advisory board honoraria, consultancy fees and/or speaker fees from Abbvie, BMS, Eli-Lilly, Galapagos, Menarini, Novartis, Pfizer, Sandoz, Theramex, UCB. MS received consulting/speaker fees or research support from Bristol-Myers Squibb, Janssen, Eli-Lilly, Pfizer, Galapagos, and Boehringer-Ingheleim. CSe received consulting/speaker fee or research support from AbbVie, Amgen, Alfa-Sigma, Biogen, Eli-Lilly, EUSA-Recordati, Galapagos, Janssen, Novartis, Pfizer, SOBI. AM received consulting/speaker fee from Abbvie, Eli-Lilly, Janssen, Novartis, and UCB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 D’Angelo, Atzeni, Benucci, Bianchi, Cantini, Caporali, Carlino, Caso, Cauli, Ciccia, D’Agostino, Dagna, Dejaco, Epis, Ferrucci, Franceschini, Fusaro, Gabini, Gerli, Giacomelli, Govoni, Gremese, Guggino, Iagnocco, Iannone, Laganà, Lubrano, Montecucco, Peluso, Ramonda, Rossini, Salvarani, Sebastiani, Sebastiani, Selmi, Tirri and Marchesoni.)

Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown., Objectives and Methods: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients., Results: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern., Conclusion: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms' evaluation might underestimate the prevalence of progressive lung disease but increases the value of results.

In the field of encapsulation, microcapsules containing perfume have emerged as effective vehicles for delivering active ingredients across various applications. The present study employed a multivariate analysis framework to examine polyacrylate microcapsules for household products synthesized using different acrylate monomers. The advanced multivariate approach allowed us to quantify critical properties such as the Molecular Weight between Cross-links ( MW c ), mechanical attributes, Encapsulation Efficiency ( EE ), and On-Fabric delivery . It is worth noting that the mechanical properties were gauged using a novel nanoindentation technique, which measures the Rupture Force per unit diameter ( RFD ). Both Encapsulation Efficiency and On-Fabric delivery were assessed using GC-MS. Our findings identified the optimal microcapsule system as one synthesized with 100% aromatic hexafunctional urethane acrylate, showcasing a 94.3% Encapsulation Efficiency and an optimal RFD of 85 N/mm. This system achieved an exemplary On-Fabric delivery rate of 307.5 nmol/L. In summary, this research provides crucial insights for customizing microcapsule design to achieve peak delivery efficiency. Furthermore, by designing acrylic monomers appropriately, there is potential to reduce the amount of active ingredients used, owing to enhanced delivery efficiency and the optimization of other microcapsule properties. Such advancements pave the way for more environmentally friendly and sustainable production processes in the fast-moving consumer goods industry.

This is the first report comparing EULAR and national treatment recommendations for PsA patients across Europe, and the first this decade to compare ASAS-EULAR and national treatment recommendations in axSpA patients. An electronic survey was completed from October 2021-April 2022 by rheumatologists in 15 European countries. One and four countries followed all EULAR and ASAS-EULAR recommendations, respectively. Five countries had no national treatment recommendations for PsA and/or axSpA, but followed other regulations. In several countries, national treatment recommendations predated the most recent EULAR/ASAS-EULAR recommendations. Entry criteria for starting biologic/targeted synthetic disease-modifying anti-rheumatic drugs varied considerably. In several countries, for PsA patients with significant skin involvement, interleukin-17 inhibitors were not given preference. The positioning of Janus Kinase inhibitors differed and Phosphodiesterase-4 inhibitors were not in use/reimbursed in most countries. This study may motivate European countries to update their national treatment recommendations, to align them better with the latest international recommendations., Competing Interests: BM, research grant from Novartis (for the present manuscript, paid to employer), Centre for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY) is funded as a Centre for Clinical Treatment Research by The Research Council of Norway (project 328657); MØ, Funding for the present manuscript from Novartis (paid to institution), The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG, research grants from Abbvie, BMS, Merck, Novartis, UCB, consulting fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, UCB, support for attending meetings and/or travel from UCB; MJN, grant from Novartis (payment to institution), consulting fees from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), support for attending meetings and/or travel from Janssen, UCB (payment to institution), participation on a Data Safety Monitoring Board or Advisory Board from Eli-Lilly, Janssen, Novartis, Pfizer (payment to institution), scientific member of the SCQM registry and the EuroSpA collaboration (unpaid), ASAS-EULAR taskforce member (unpaid); AC, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Merck-Sharp & Dohme, Novartis; BMö, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Novartis, Pfizer, support for attending meetings and/or travel from Abbvie, Janssen, Novartis, Pfizer; LMØ, research grant from Novartis (for the present manuscript, paid to employer); JZ, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Eli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, support for attending meetings and/or travel from Abbvie, Pfizer, Astra Zeneca, participation on a data safety monitoring board or advisory board from Abbvie, UCB, Sobi; BGli, Research grants from Pfizer, AbbVie, BMS (payments made to institution); AM; payment for work done in relation to research questions for this project from the University of Aberdeen, speakers fees for educational events from Galapagos; KL, Honoraria for lectures from Pfizer, Abbvie, Novartis, Janssen, support for attending meetings from Abbvie, Pfizer; DN, Consulting fees from BMS, Lilly, MSD, Novartis, Pfizer, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, support for attending meetings and/or travel from Pfizer; BGu, consulting fees from Novartis, speaker bureaus from Novartis, Nordic Pharma; FI, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, BMS, Galapagos, Eli-Lilly, Pfizer, UCB, support for attending meetings and/or travel from Pfizer, UCB; PH, research grant (payments made to employer) from Novartis; TKK, consulting fees from AbbVie, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Grünenthal, Janssen, Sandoz, participation on a data safety monitoring board or advisory board from Abbvie, grants or contracts from AbbVie, BMS, Galapagos, Novartis, Pfizer, UCB; AMR, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Amgen, Novartis, support for attending meetings and/or travel from Amgen, Nordic, Theramex, grants or contracts from Novartis, Pfizer, Amgen, Astra Zeneca, Abbvie, MSD, Lilly, Boehringer Ingelheim; CC, None; ZR, Consulting fees from AbbVie, Janssen, Novartis, MSD and Lek Sandoz, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Eli Lilly, Janssen, Abbvie, Pfizer, Boehringer Ingelheim, support for attending meetings and/or travel from Gedeon Richter, Pfizer, SOBI (payments made to employer), participation on data safety monitoring board or advisory board from Abbvie, Pfizer, Astra Zeneca, Janssen, Eli Lilly, Novartis and Boehringer Ingelheim; ICF, consulting fees from Pfizer, Galapagos, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from BMS, Eli-Lilly, Gilead, Janssen, Novartis, MSD, Pfizer, GSK, support for attending meetings and/or travel from Pfizer, Eli-Lilly; JKW, Research support from Abbvie, Amgen, Eli Lilly, Novartis, Pfizer (unrelated to the present work, payment made to Lund University), speakers bureaus from Abbvie and Amgen (payed to Skåne University Hospital), acting co-chair of the Swedish Society for Rheumatology's working group annually updating Swedish treatment recommendations for axial spondyloarthritis and psoriatic arthritis (unpaid, fiduciary assignment); JV, support for the present manuscript from the Czech Ministry of Health–Conceptual Development of Research Organization 00023728 (Institute of Rheumatology), payment to institution, consulting fees from Eli Lilly, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Biogen, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, support for attending meetings and/or travel from Abbvie (payment to institution), participation on a data safety monitoring board or advisory board from Abbvie, Gilead, Pfizer, UCB, grants or contracts from Abbvie (payment to institution); AGL, Consulting fees from Jansen-Cilag A/S, Lilly Nordics, UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis Healthcare A/S, Pfizer, support for attending meetings and/or travel from Pfizer, UCB, participation on a data safety monitoring board or advisory board from Jansen-Cilag A/S, Lilly Nordics, UCB; MH; None; SV, None; AMH, Research grant from MSD, grant for attending meeting from Janssen, Pfizer, support for travel cost from Janssen; GG, None; MS, support for the present manuscript from Lilly and Boehringer-Ingelheim, payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing or educational events from Pfizer, Boehringer-Ingelheim, GSK, participation on data safety or advisory board from Janssen-Cilag, support for attending meetings and/or travel from Janssen-Cilag; MvdS, Research support/grant from UCB, Eli Lilly, Novartis, Janssen (payments made to institution, AMR Medical Research BV), consulting fees from Novartis, UCB, Abbvie (payments made to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, UCB, Janssen (payments made to institution), support for attending meetings and/or travel from UCB; EKK, None; MJS, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Lilly, Novartis, Pfizer, support for attending meetings and/or travel from Janssen, Viatris, Medac and receipt of equipment, materials, drugs, medical writing, gifts or other services from Vifor; CM, None; MT, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Amgen, Boehringer, Pfizer, Sanofi-Aventis, Roche, Lek-Sandoz, Janssen, Medis, Novartis, participation on data safety or advisory board from Astra Zeneca, Eli Lilly, Janssen, Boehringer, MSD, Novartis, Roche; FDG, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, payment for expert testimony from Abbvie, Galapagos, Janssen, and support for attending meetings and/or travel from Pfizer, Astra Zeneca; DDG, None; MLH, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer, Medac, Sandoz, research grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordstar (payment to institution). MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis., (© 2023 The Author(s).)

Background: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce., Methods: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old., Results: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors., Conclusions: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Early diagnosis of interstitial lung diseases secondary to connective tissue diseases is critical for the treatment and survival of patients. The symptoms, like dry cough and dyspnea, appear late in the clinical history and are not specific, moreover, the current approach to confirm the diagnosis of interstitial lung disease is based on high resolution computer tomography. However, computer tomography involves x-ray exposure for patients and high costs for the Health System, therefore preventing its use for a massive screening campaign in elder people. In this work we investigate the use of deep learning techniques for the classification of pulmonary sounds acquired from patients affected by connective tissue diseases. The novelty of the work consists of a suitably developed pre-processing pipeline for de-noising and data augmentation. The proposed approach is combined with a clinical study where the ground truth is represented by high resolution computer tomography. Various convolutional neural networks have provided an overall accuracy as high as 91% in the classification of lung sounds and have led to an overwhelming diagnostic accuracy in the range 91%-93%. Modern high performance hardware for edge computing can easily support our algorithms. This solution paves the way for a vast screening campaign of interstitial lung diseases in elder people on the basis of a non-invasive and cheap thoracic auscultation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD)., Methods: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member., Results: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks., Conclusions: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD., Competing Interests: Competing interests: GEF: Consulting fees/honoraria: Pfizer, Abbvie, Novartis, UCB, AENorasis, Janssen, Pharmaserv-Lilly. EN: speaker fees/honoraria: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly, Fresenius. Research funding: Pfizer, Lilly. MD: none SZ: consulting fees: UCBDC: None. LA: has received consulting fees and/or research funding from Astra-Zeneca, GSK, Pfizer. FA: none. GMNB: has received consulting fees/honoraria as speaker from Gilead, ViiV Healthcare, Janssen, MSD, Roche, Moderna unrelated to this work. JWJB: none PB: none CAC: none SG-D: none MCK: none KL: has received consulting/speaker fees from Pfizer, Viatris, Celltrion outside of the submitted work. ML: none. JM: none GN: consulting fees/honoraria as speaker from AbbVie, Amgen, Boehringer Ingelheim, Janssen, Miltenyi Biotech, Lilly, Pfizer, Roche unrelated to this work. EP: consulting fees/honoraria as speaker from Bayer, Menarini, Grifols, Zambon, Pfizer, Chiesi, Teva, Shire, Shionogi, Insmed, Boehringer-Ingelheim, unrelated to this work. JvR: none MS: consulting fees: BMS, Boehringer-Ingheleim, Eli Lilly, Celltrion, Amgen, Pfizer, Janssen Cilag. AS: has received consulting fees/honoraria as speaker from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Pfizer, Roche unrelated to this workAdT: none JG: speaker fees/honoraria: Abbvie, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB. Research funding: Abbvie, Astrazeneca, Galapagos, Gilead, Gritstone, Janssen, Moderna, Novovax, PfizerKH: honoraria from Abbvie; grant income from Pfizer and BMS., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the rate of progression towards specific autoimmune diseases (SADs) of a prospective, multi-centre cohort of patients classifiable as interstitial pneumonia with autoimmune features (IPAF)., Methods: IPAF patients were enrolled based on specific research criteria, and jointly followed by rheumatologists and pulmonologists for at least one year with clinical check-ups, serological exams including autoimmunity, capillaroscopy and high-resolution computed tomography (HRCT). Diagnostic assessment was repeated at least once a year, or earlier when deemed useful., Results: We enrolled 191 IPAF patients through 95 different combinations of IPAF criteria. Of these, 24.1% progressed towards SAD, mainly in connective tissue diseases but also in microscopic polyangiitis. The IPAF patients who progressed were younger than stable IPAF patients (63±10 years vs. 68±9 years, p=0.002) and had a longer follow-up (36.9±18.7 vs. 29.3±15.7 months, p=0.007), but similar severity. No parameters were associated with overall progression, but some parameters were associated with the development of specific diagnoses: Sjögren's syndrome with positivity for SSA (p=0.007, χ2 7.4); idiopathic inflammatory myopathy with mechanic's hands (p=<0.0001, χ2 12.6), organizing pneumonia pattern (p=0.01, χ2 6.1), positivity for anti-Pm/scl (p=0.04 χ2 4.1) and anti-MDA5 (p=0.04, χ2 4.2); systemic sclerosis with palmar telangiectasias (p=<0.0001 2 18.3), positivity for anti-Scl70 (p=<0.0001 χ2 12.5) and anti-PM/Scl (p=0.001 χ2 10.1)., Conclusions: IPAF patients had a rate of progression towards SAD similar to that reported in previous studies on undifferentiated connective tissue diseases, thus including some patients in which lung involvement could represent the first or even the sole clinical manifestation of a SAD.

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium.

Objectives: Interstitial lung disease (ILD) has been described as a possible pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV), mainly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Aim of this cross-sectional Italian national study was to describe demographic, clinical and serological profile of ILD related to MPA and GPA and investigate possible correlations between radiologic patterns of ILD and vasculitis features., Methods: We enrolled 95 consecutive patients with AAV-ILD, 56 affected by MPA (58.9%) and 39 by GPA (41.1%)., Results: NSIP was the most frequently detected ILD pattern, observed in c-ANCA patients in 60.9% of cases, followed by UIP pattern mainly observed in p-ANCA patients (47.7%, p=0.03). ILD represented the first clinical manifestation, preceding vasculitis diagnosis in 22.1% of cases and, globally, ILD was already detectable at AAV diagnosis in 66.3% of patients. The diagnosis of ILD preceded that of AAV in 85.7% of p-ANCA positive-patients, while only one patient with c-ANCA developed ILD before AAV (p= 0.039). Multivariate analysis confirmed the correlation of UIP pattern with p-ANCA-positivity and a diagnosis of ILD before AAV, also when adjusted for age and sex., Conclusions: Our study confirms that UIP is a frequent pattern of lung disease in AAVILD patients. Our results also suggest that ILD can represent an early complication of AAV but also occur in the course of the disease, suggesting the need of a careful evaluation by both pulmonologist and rheumatologist to achieve an early diagnosis. Further prospective studies are needed to define ILD prevalence and evolution in AAV patients.

Objectives: Mixed 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. The 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: Hepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide., Methods: A PubMed search was performed to select eligible studies in the literature, up to July 2022., Results: Some studies have analyzed clinical manifestations in HBV-related CV and have investigated the role of antiviral therapy with nucleotides analogues (NAs). Clinical manifestations of CV vary from mild to moderate (purpura, asthenia and arthralgias) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, and non-Hodking lymphoma). NAs therapy leads to suppression of HBV-DNA; therefore, it is capable of producing clinical response in the majority of patients with mild to moderate symptoms., Conclusion: Antiviral therapy with NAs is the first choice for HBV suppression and control of mild to moderate disease. In severe vasculitis (glomerulonephritis, progressive peripheral neuropathy and leg ulcers), rituximab alone or with plasma-exchange is always indicated in combination with antiviral therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor GG declared a shared affiliation with the author MV at the time of review., (Copyright © 2023 Mazzaro, Bomben, Visentini, Gragnani, Quartuccio, Saccardo, Sebastiani, Filippini, Lauletta, Monti and Gattei.)

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV., (© 2022. The Author(s).)

Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD)., Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests., Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46-75.78) treated with JAKi. The median follow-up was 19.1 months (11.03-34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%)., Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up.

Measurement of the surface free energy (SFE) of a material allows the prediction of its adhesion properties. Materials can have microscale or sub-microscale surface inhomogeneities, engineered or random, which affect the surface macroscopic behaviour. However, quantitative characterization of the SFE at such length scales remains challenging in view of the variety of instruments and techniques available, the poor knowledge of critical variables and parameters during measurements and the need for appropriate contact models to derive the SFE from the measurements. Failure to characterize adhesion correctly may result in defective components or lengthy process optimization costing billions to industry. Conversely, for planar and homogeneous surfaces, contact angle (CA) measurements are standardized and allow for calculating the SFE using for example the Owen-Wendt model, relying only on the properties of the probing liquids. As such, we assessed and report here a method to correlate quantitative measurements of force-distance curves made with an atomic force microscope (AFM) and with silica and polystyrene (PS) colloidal probe pairs, with quantitative CA measurements and CA-derived SFE values. We measured five surfaces (mica, highly oriented pyrolytic graphite, thermally grown silica on silicon, silicon, and silicon with a super-hydrophobic coating), ranging from hydrophilic to super-hydrophobic, and found an excellent classification of the AFM measurements when these are represented by a set of principal components (PCs), and when both silica and PS colloidal probes are considered together. A regression of the PCs onto the CA measurements allows recovery of the SFE at the length scale of the colloidal probes, which is here ca. 1 micron. We found that once the PC-regression model is built, test sets of only ten AFM force-distance curves are sufficient to predict the local SFE with the calibrated silica and PS colloidal probes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients., Methods: High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables., Results: We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36-120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56-55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05-0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06-0.82) and the flatness (HR 0.42, 95% CI 0.18-0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82-2.83) was also retained as a confounder., Conclusion: Radiomic analysis may predict RA-ILD patients' mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Venerito, Manfredi, Lopalco, Lavista, Cassone, Scardapane, Sebastiani and Iannone.)

While precision medicine is still a challenge in rheumatic disease, in recent years many advances have been made regarding pathogenesis, the treatment of inflammatory arthropathies, and their interaction. New insight into the role of inflammasome and synovial tissue macrophage subsets as predictors of drug response give hope for future tailored therapeutic strategies and a personalized medicine approach in inflammatory arthropathies. Here, we discuss the main pathogenetic mechanisms and therapeutic approaches towards precision medicine in rheumatoid arthritis from the 2022 International GISEA/OEG Symposium.

Competing Interests: MS reports payments or honoraria for lectures and presentations from Bristol Myers Squibb, Pfizer, and Boehringer-Ingelheim and fees for participation on Advisory Board from Bristol Myers Squibb, Lilly, Amgen, Janssen, Boehringer-Ingelheim, and Celltrion. AM reports payments or honoraria for lectures and presentations from Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim and reports fees for participation on Advisory Board from Bristol Myers Squibb, Lilly, and Boehringer-Ingelheim.

Competing Interests: MS has received payments or honoraria for lectures or presentations from BMS, Pfizer, and Boehringer-Ingelheim; and fees for participation on advisory boards from BMS, Lilly, Amgen, Janssen, Boehringer-Ingelheim, and Celltrion. CS declares participation on an advisory board for Lilly. AM has received payments or honoraria for lectures or presentations from BMS, Lilly, and Boehringer-Ingelheim; and fees for participation on advisory boards from BMS, Lilly, and Boehringer-Ingelheim.

This cross-sectional online study was designed by the study group on Capillaroscopy and Microcirculation in Rheumatic Diseases (CAP) of the Italian Society of Rheumatology (SIR) to provide an overview of the management of nailfold capillaroscopy in Italian rheumatology centers. Therefore, SIR distributed the survey to its members in July 2021, and each center's physician with the most expertise in capillaroscopy completed the questionnaire. The survey was completed by 102 centers, with at least one representative from each Italian region. Ninety-three centers perform capillaroscopy, and 52 (56) conduct more than 200 investigations annually. Seventy-eight (84%) of respondents have more than five years of experience with the technique, and 75 centers (80.6%) have received certification from specific national or international training courses. In 85 centers, a videocapillaroscope with 200x magnification is employed (91.4%). The average waiting period for the examination is 2.4 months, and less than 3 months in 64 of the locations (68.8%). The study demonstrates that capillaroscopy is an integral part of both the diagnostic phase of Raynaud's phenomenon and the monitoring of autoimmune connective tissue diseases (CTDs). However, the reporting methods and timing of patient followup are heterogeneous.

The term "axial spondyloarthritis" (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium.

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations' development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients' quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium.