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Objective. To describe an intensive and multimodal ultrasound (US) training program focused on Achilles enthesitis and to illustrate the learning curve of trainees without experience. Methods. Three medical students (trainees) and two rheumatologists experienced in musculoskeletal US (trainers) were involved in the training program, which encompassed one preliminary theoretical-practical meeting and five scanning sessions (two patients per session). The students and one expert performed the US examination of the Achilles enthesis bilaterally. The trainees acquired representative images and assessed the presence of Outcome Measures in Rheumatology (OMERACT) US abnormalities of enthesitis. The experts provided feedback addressing trainees’ misinterpretations, and the quality of the acquired images was evaluated. A dedicated questionnaire was used to evaluate the students’ confidence. After each session, five sets of static images (total=100 images of most commonly scanned entheses) were provided and scored by the students according to OMERACT US definitions. Total agreement and prevalence and bias adjusted kappa (PABAK) were used to evaluate the concordance between the trainees and the expert sonographer. Results. The total agreement and PABAK significantly improved between the first and fifth scanning sessions (76.2% versus 92.9%, p

Objective. The aim of the present review was to highlight gender and sex differences in spondyloarthritis (SpA) to achieve a better awareness of the unmet needs of women with SpA. Methods. A literature search of PubMed was performed, including manuscripts in English published in the last twenty years, to select and analyze articles related to SpA and sex and gender differences in epidemiology, genetics, immunology, clinical features, and response to treatment. Results. Women and men with SpA have different disease phenotypes, and this heterogeneity mirrors anatomical, physiological, and hormonal differences, as well as peculiar variability in response to treatment. These underestimated differences, which include several biological factors and intertwined social factors, contribute to diagnostic delay and increased disease burden in women with SpA. Conclusions. This review elucidates gender differences in SpA and raises awareness about the need for gender-related stratification of SpA patients with the concomitant implementation of SpA gender differences in future research and upcoming clinical trials. A deeper knowledge of SpA in women is indispensable to pave the way for real personalized medicine for SpA patients to reduce misdiagnosis and delay in intercepting the disease.

Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause, almost exclusively occurring in people aged over 50 and often associated with giant cell arteritis. The evidence that PMR occurs almost exclusively in individuals aged over 50 may indicate that age-related immune alterations in genetically predisposed subjects contribute to development of the disease. Several infectious agents have been investigated as possible triggers of PMR even though the results are inconclusive. Activation of the innate and adaptive immune systems has been proved in PMR patients as demonstrated by the activation of dendritic cells and monocytes/macrophages and the altered balance between Th17 and Treg cells. Disturbed B cell distribution and function have been also demonstrated in PMR patients suggesting a pathogenesis more complex than previously imagined. In this review we will discuss the recent findings regarding the pathogenesis of PMR.

The gastrointestinal tract regulates the trafficking of macromolecules between the environment and the host through an epithelial barrier mechanism and is an important part of the immune system controlling the equilibrium between tolerance and immunity to non-self-antigens. Various evidence indicates that intestinal inflammation occurs in patients with rheumatic diseases. In many rheumatic diseases intestinal inflammation appears to be linked to dysbiosis and possibly represents the common denominator in the pathogenesis of different rheumatic diseases. The continuative interaction between dysbiosis and the intestinal immune system may lead to the aberrant activation of immune cells that can re-circulate from the gut to the sites of extraintestinal inflammation as observed in patients with ankylosing spondylitis. The exact contribution of genetic factors in the development of intestinal inflammation in rheumatic diseases needs to be clarified.

Objective: Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren's syndrome (pSS)., Methods: In both pSS and non-pSS sicca syndrome patients, we examined Trm frequency, cytokine production in salivary glands (SG) and peripheral blood (PB). We also analysed Trm-related gene expression in SG biopsies through bulk and single-cell RNA sequencing (scRNAseq). Additionally, we investigated Trm properties in an immunisation-induced animal model of pSS (experimental SS, ESS) mouse model and assessed the effects of Trm inhibition via intraglandular anti-CD103 monoclonal antibody administration., Results: Transcriptomic pSS SG showed an upregulation of genes associated with tissue recruitment and long-term survival of Trm cells, confirmed by a higher frequency of CD8 + CD103 + CD69 + cells in pSS SG, compared with non-specific sialadenitis (nSS). In SG, CD8 + CD103 + Trm contributed to the secretion of granzyme-B and interferon-γ, CD8 + Trm cells were localised within inflammatory infiltrates, where PD1+CD8+ T cells were also increased compared with nSS and MALT lymphoma. scRNAseq of PB and pSS SG T cells confirmed expression of CD69, ITGAE, GZMB, GZMK and HLA-DRB1 among CD3 + CD8 + SG T cells. In the SG of ESS, CD8 + CD69 + CD103 + Trm producing Granzyme B progressively expanded. However, intraglandular blockade of CD103 in ESS reduced Trm, reduced glandular damage and improved salivary flow., Conclusions: CD103 + CD8 + Trm cells are expanded in the SG of pSS and ESS, participate in tissue inflammation and can be therapeutically targeted., Competing Interests: Competing interests: RT has filed provisional patents surrounding technology for targeting DCs for antigen-specific tolerance (US patent 9017697 B2: 2006, PCT/AU2013/000303) and is developing immunotherapy to target DCs to suppress autoimmune disease in collaboration with CSL. AB-M and AB are employees of CSL. The other 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., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Geographic origin may represent a variable capable of influencing health status. This study aims to investigate the presence of differences of disease severity in Italian patients with fibromyalgia from different macro-regions., Methods: This retrospective, cross-sectional study involved patients included in the Italian Fibromyalgia Registry. Three geographical macro-regions were identified, comprising patients from Northern Italy, Central Italy and Southern Italy. Clinical differences (evaluated through PolySymptomatic Distress Scale [PSD], revised Fibromyalgia Impact Questionnaire [FIQR] and modified Fibromyalgia Assessment Status [FASmod]) among the geographical macro-regions were studied using one-way analysis of variance (ANOVA) and the Scheffé's test., Results: A total of 6095 patients (5719 females and 376 males) were included, with 1957 from Northern Italy, 2979 from Central Italy and 1159 from Southern Italy. All studied clinical indices showed a trend indicative of greater disease severity in Southern Italy, followed by Northern Italy and then Central Italy (mean values for PSD: 19.97 ± 6.20 in Northern Italy, 18.61 ± 7.12 in Central Italy, 23.01 ± 5.66 in Souther Italy). These differences were statistically significant for the overall scores of all studied indices, evaluated with ANOVA (all p < 0.001) and in the head to head comparisons, evaluted with Scheffé's test., Conclusions: Geographic background is significantly associated with variations in the severity of fibromyalgia in Italian patients., Significance Statement: This is the first study to demonstrate geographical origin-dependent intra-national differences in the severity of fibromyalgia. The results confirm the necessity of considering fibromyalgia within the context of the biopsychosocial model and of implementing healthcare policies targeted towards the most underserved regions., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Objective: To describe an intensive and multimodal ultrasound (US) training program focused on Achilles enthesitis and to illustrate the learning curve of trainees without experience., Methods: Three medical students (trainees) and two rheumatologists experienced in musculoskeletal US (trainers) were involved in the training program, which encompassed one preliminary theoretical-practical meeting and five scanning sessions (two patients per session). The students and one expert performed the US examination of the Achilles enthesis bilaterally. The trainees acquired representative images and assessed the presence of Outcome Measures in Rheumatology (OMERACT) US abnormalities of enthesitis. The experts provided feedback addressing trainees' misinterpretations, and the quality of the acquired images was evaluated. A dedicated questionnaire was used to evaluate the students' confidence. After each session, five sets of static images (total=100 images of most commonly scanned entheses) were provided and scored by the students according to OMERACT US definitions. Total agreement and prevalence and bias adjusted kappa (PABAK) were used to evaluate the concordance between the trainees and the expert sonographer., Results: The total agreement and PABAK significantly improved between the first and fifth scanning sessions (76.2% versus 92.9%, p<0.01, and 0.5 versus 0.79, p<0.01) and between the first and fifth static image sets (64.5% versus 81.9%, p<0.01, and 0.29 versus 0.74, p<0.01). Image quality did not significantly improve (p=0.34). A significant increase in trainees' confidence was registered (p<0.01)., Conclusions: The described training program rapidly improved the students' performance in the US assessment of Achilles enthesitis, appearing to be an effective starting model for the future development of pathology-oriented teaching programs for the US in rheumatology.

Background: Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients., Methods: A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention., Results: In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis., Conclusion: This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA., (© 2024. The Author(s).)

Objective: The aim of the present review was to highlight gender and sex differences in spondyloarthritis (SpA) to achieve a better awareness of the unmet needs of women with SpA., Methods: A literature search of PubMed was performed, including manuscripts in English published in the last twenty years, to select and analyze articles related to SpA and sex and gender differences in epidemiology, genetics, immunology, clinical features, and response to treatment., Results: Women and men with SpA have different disease phenotypes, and this heterogeneity mirrors anatomical, physiological, and hormonal differences, as well as peculiar variability in response to treatment. These underestimated differences, which include several biological factors and intertwined social factors, contribute to diagnostic delay and increased disease burden in women with SpA., Conclusions: This review elucidates gender differences in SpA and raises awareness about the need for gender-related stratification of SpA patients with the concomitant implementation of SpA gender differences in future research and upcoming clinical trials. A deeper knowledge of SpA in women is indispensable to pave the way for real personalized medicine for SpA patients to reduce misdiagnosis and delay in intercepting the disease.

Objectives: Conflicting results about clinical and subclinical atherosclerosis in systemic sclerosis (SSc) and the associated risk factors have been reported. Hence, we aimed to determine the prevalence of clinical and subclinical atherosclerosis in a large number of Italian SSc patients and the associated risk factors., Methods: This study included 613 SSc patients from 11 Italian tertiary Rheumatologic Units. All patients underwent full history taking, clinical examination, and relevant laboratory and radiological investigations. Doppler ultrasonography (US) of the common carotid and upper and lower limbs was performed to measure carotid and femoral intima-media thickness (cIMT and fIMT), and carotid and peripheral atheroma plaques. Doppler US of the brachial artery was performed to measure flow-mediated dilatation (FMD)., Results: Patients were mostly women (91.4%) with a median age of 61 years (range, 20-100); a median disease duration of 14 years (range, 0-77) from the onset of the first non-Raynaud's phenomenon (RP); 9.3% had a history of clinical atherosclerosis (9 stable/unstable angina, 21 myocardial infarctions, 24 heart failure, 3 strokes, 8 transient ischaemic attack, 6 intermittent claudication, 10 atrial thrombo-embolism). In 37.1% of patients, subclinical atherosclerosis was detected, after excluding those with a history of clinical atherosclerosis. The prevalence of clinical and subclinical atherosclerosis was higher than that reported by the European Society of Cardiology and observational studies that enrolled Italian healthy individuals as a control group, respectively., Conclusions: A higher prevalence of clinical and subclinical atherosclerosis was detected in SSc Italian patients and correlated with traditional and SSc-related risk factors.

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest for this work., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly., Methods: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis., Results: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations., Conclusion: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted., (© 2024 American College of Rheumatology.)

Objectives: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients., Methods: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events., Results: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported., Conclusions: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Objectives: Recent evidence suggests that innate lymphoid cells (ILCs) might be involved in rheumatoid arthritis (RA) pathogenesis and individuals at risk of RA exhibited an increased frequency of ILC1. JAK3 participates in ILC1 and ILC3 differentiation. Tofacitinib and the Janus Kinase (JAK) 3 inhibitor, PF-06651600, impair the ability of human intraepithelial ILC1 (iILC1) to produce IFN-γ and the proliferation of ILC1 and ILC3. Our study aims to evaluate the ex vivo effects of tofacitinib in RA patients and to investigate if ILC1s and ILC3s are specific targets of tofacitinib in RA., Methods: Twenty RA patients starting tofacitinib and 10 RA patients starting anti-TNFα were enrolled. Peripheral blood mononuclear cells (PBMCs) from RA patients, collected before and three months after therapy, were cultured to evaluate ILC1 and ILC3 frequencies and the respective production of IFN-γ and IL-17 by flow cytometry analysis. PBMCs of RA patients were in vitro cultured with tofacitinib to evaluate the dose effects on ILC frequencies., Results: RA patients showed a significant expansion of ILC1 but not ILC3. Unlike anti-TNFα treated patients, in whom no reduction in ILCs was reported, after three months of tofacitinib therapy the overall ILC frequency was reduced, as well as the ILC1 ability to release IFN-γ. In vitro treatment of PBMCs with tofacitinib demonstrated a dose-dependent reduction in the frequency of ILCs compared to untreated cells., Conclusions: Our preliminary results demonstrate that tofacitinib modulates the innate immune response by reducing the frequency of ILC1 cells and their production of IFN-γ.

Objectives: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations., Methods: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected., Results: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult., Conclusions: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We studied high-resolution impedance manometry (HRiM) findings in dermatomyositis (DM) to detect oesophageal dysmotility, even in asymptomatic patients, and correlated the alterations to clinical and serological disease domains., Methods: We performed a cross-sectional study of DM patients, enrolled between December 2021 and December 2022. All patients underwent rheumatological, laboratory and HRiM assessment. HRiM findings were compared with different clinical and serological profiles., Results: The study population consisted of 15 DM patients (13 women and 2 men, age 54±15.2 years). The mean disease duration was 6.6 years. According to HRiM findings, three different groups of oesophageal disease severity were identified (in order of severity G0, G1 and G>1, 5 patients per group). G>1 group was significantly associated with MDA5 antibodies (80% vs. 20%, p<0.05). Interstitial lung disease (ILD) did not show any significant association with HRiM findings. However, a diffusing lung capacity for carbon oxide (DLCO) < 80% was present in 100% of G>1 (p<0.05). No associations between dysphagia, creatine kinase (CK) level, muscle weakness, skin, articular involvement and treatment were found., Conclusions: Oesophageal involvement is frequent and should be evaluated in the comprehensive work-up of DM. We used for the first time HRiM in DM, which proved to be an accurate and objective technique in assessing oesophageal disease, even in the subclinical stage. Interestingly, the MDA5-positive group had a higher burden of HRiM pathological findings, suggesting a greater severity of oesophageal involvement, often asymptomatic.

Large-vessel vasculitis (LVV) are autoimmune and autoinflammatory diseases focused on vascular inflammation. The central core of the intricate immunological and molecular network resides in the disruption of the "privileged immune state" of the arterial wall. The outbreak, initially primed by dendritic cells (DC), is then continuously powered in a feed-forward loop by the intimate cooperation between innate and adaptive immunity. If the role of adaptive immunity has been largely elucidated, knowledge of the critical function of innate immunity in LVV is still fragile. A growing body of evidence has strengthened the active role of innate immunity players and their key signaling pathways in orchestrating the complex pathomechanisms underlying LVV. Besides DC, macrophages are crucial culprits in LVV development and participate across all phases of vascular inflammation, culminating in vessel wall remodeling. In recent years, the variety of potential pathogenic actors has expanded to include neutrophils, mast cells, and soluble mediators, including the complement system. Interestingly, new insights have recently linked the inflammasome to vascular inflammation, paving the way for its potential pathogenic role in LVV. Overall, these observations encourage a new conceptual approach that includes a more in-depth study of innate immunity pathways in LVV to guide future targeted therapies.

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.)

Jellyfish envenomation is a common problem in coastal areas all over the world; usually symptoms are self-limited with no long-lasting complications. Despite that, some jellyfish species, mainly populating the Indian Ocean, are renown to be potentially lethal and in some cases may cause severe myopathy. We report the first case of rhabdomyolysis following a jellyfish sting in the Mediterranean Sea. A 17-year-old patient was admitted to the intensive care unit of our hospital in life-threatening conditions. He was dyspnoeic and dysphagic with pain and functional impairment of upper and lower limbs. The evidence of a red mark in his face and the clinical presentation, coupled with the diagnostic test performed, allowed the diagnosis of toxidrome from jellyfish venom. Treatment with hydration, ventilatory support and steroids led to a progressive improvement of patient conditions. Our case report stresses the importance of prompt identification and treatment of potential rhabdomyolysis determined by jellyfish and rises awareness on the presence of such venomous species in the Mediterranean Sea., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still's disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients., Methods: Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters., Results: K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients., Conclusions: Four patient clusters in Still's disease may be recognised by a multidimensional characterisation ('Juvenile/Transitional', 'Uncomplicated', 'Hyperferritinemic' and 'Catastrophic'). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Psychosocial factors are recognised as important determinants of pain experience in patients with inflammatory arthritides. Among them, pain catastrophising, a maladaptive cognitive style, observed in patients with anxiety and depressive disorders, garnered specific attention. Here, we evaluated pain catastrophising (PC) and its related domains (Rumination, Magnification, and Helplessness), in psoriatic arthritis (PsA) and axial spondyloarhtiritis (axSpA) participants, to assess its impact on disease activity. Furthermore, we analysed possible correlations of PC-Scale (PCS) with those psychometric domains which have been already related to catastrophisation in patients with chronic pain. Lastly, we aimed to define the relationship between PCS and the different variables included in the composite indices of disease activity., Methods: A multi-centre, cross-sectional, observational study has been conducted on 135 PsA (age 56 (47-64) years, males/females 40.74/59.26%; Disease Activity in Psoriasic Arthritis (DAPSA) 13.34 (5.21-22.22)) and 71 axSpA (age 49 (37-58) years, males/females 56.34/43.66%; Bath Ankylosing Spondylitis Arthritis Activity (BASDAI) 4.17 (2.1-6.3)) participants. Multivariable regressions and correlations were performed to evaluate the relationship between pain catastrophising and both disease activity and patient-reported outcomes., Results: The adjusted linear regression model showed a positive association between PCS and DAPSA as well as between PCS and BASDAI; PCS negative impacts on the subjective domains of disease activity scores., Conclusions: This study suggests the role of PC, independently of inflammation, in disease perception and achievement of remission or low disease activity in chronic arthritides.

Background and Objectives : Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods : We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results : In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 ± 11.0 vs. 19.05 ± 8.83; p < 0.05), pain (NRS: 5.55 ± 1.2 vs. 2.9 ± 1.09; p < 0.05), and PSST score (24.4 ± 4.0 vs. 16.2 ± 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 ± 9.72 vs. 22.7 ± 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 ± 1.09 vs. 4.5 ± 1.07; p < 0.05) and in the PSST scale (16.2 ± 2.36 vs. 20.4 ± 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions : Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma.