Clinical correlates of a subset of anti-fibroblast antibodies in systemic sclerosis.

Anti-fibroblast antibodies (AFA) have been reported in systemic sclerosis (SSc) and are known to promote fibroblast activation. Aim of this study was to characterize the fine specificity of AFA and to analyze any correlations with clinical parameters associated to fibrosis. To this end, AFA were affinity-purified from a patient with diffuse cutaneous SSc (dcSSc) and interstitial lung disease (ILD). Panning of a phage display peptide library with purified AFA identified the motif . The peptide p121, bearing the AFA-specific motif, was used in ELISA to screen sera from 186 SSc patients and 81 healthy donors. Anti-p121 Ab serum levels were statistically higher in SSc than in healthy groups, and directly associated with dcSSc, reduced FVC (FVC < 70), and ILD. Given these clinical correlates, this study lays the groundwork for the identification of the antigen recognized by anti-p121 Ab, which might represent a novel therapeutic target for ILD.

Persistent Pancytopenia as a Long-COVID Manifestation in a Patient with Adult-Onset Still's Disease: A Case Report.

Background: Adult-onset Still's disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient's laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man's symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia.

Gastrointestinal Symptoms Impact Psychosocial Function and Quality of Life in Patients with Rheumatoid Arthritis and Spondyloarthritis: A Cross-Sectional Study.

Patients with chronic Inflammatory Arthritis (IA), such as Rheumatoid Arthritis (RA) and Spondyloarthritis (SpA) are more likely to experience psychosocial impairment. Gastrointestinal (GI) symptoms are also present, especially in Spondyloarthritis. No data are available on the relationship between gut and brain manifestations and their impact on daily activities in this setting; thus, this study aimed to assess these symptoms in an IA population and identify potential associations. IA patients and a control group were enrolled. The Patient-Reported Outcome Measurement Instrument System (PROMIS®) questionnaire was used to evaluate GI and psychosocial domains. The study included 389 subjects (238 controls and 151 with IA); demographic and clinical data were collected for each participant. IA patients reported both higher psychosocial and GI impairment compared with controls. The logistic regression model revealed a strong association between depression and belly pain (p = 0.035), diarrhea (p = 0.017), bloating (p = 0.018), and reflux (p = 0.01); anxiety was associated with belly pain (p = 0.004), diarrhea (p = 0.019), swallowing alterations (p = 0.004), flatulence (p < 0.001) and reflux (p = 0.008). Moreover, fatigue, sleep disorders, and pain interference were associated with almost all GI symptoms, whereas high physical function scores and satisfaction in social roles decreased the odds of most GI symptoms. IA patients had more significant impairment in both dimensions compared with controls. To address reported symptoms and improve the overall quality of life in rheumatologic patients, a new holistic approach is required.

Decreased Pulse Wave Velocity in a Systemic Sclerosis Population: Preliminary Results from a Cross-Sectional Study.

Systemic Sclerosis (SSc) is an autoimmune disorder characterized by organ and tissue fibrosis in which the incidence of atherosclerosis and cardiovascular events is increased, although the exact underlying mechanism remains unclear. Arterial stiffness is a marker of vascular damage that can predict cardiovascular events; therefore, this study aimed to assess the augmentation index (AIx) and pulse wave velocity (PWV), markers of stiffness, in a Systemic Sclerosis population and to detect potentially associated variables. Fourteen female Systemic Sclerosis patients and 14 age- and sex-matched controls were enrolled. Demographic, anthropometric, sero-hematological parameters and disease characteristics were collected for each participant. Arterial stiffness was evaluated using an applanation tonometry system. No differences were found between groups, except for BMI, fasting blood glucose, red blood cells count, hemoglobin, and treatment. Patients had increased augmentation index than the controls (p = 0.008). PWV was significantly decreased in SSc patients compared with the controls (p = 0.007). PWV was correlated with age (r = 0.462; p = 0.048) and BMI (r = 0.458; p = 0.050). Finally, patients with no specific auto-antibody pattern had greater AIx than those expressing anticentromere antibodies. Our study demonstrated that SSc patients had greater AIx, but lower PWV than the controls. In addition, few variables were correlated to arterial stiffness. Further studies are necessary to validate these findings and to establish medication's role in modifying cardiovascular risk.

A real-world economic analysis of biologic therapies for psoriatic arthritis in Italy: results of the CHRONOS observational longitudinal study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic, immune-mediated, spondyloarthropathy characterised by musculoskeletal signs and symptoms with associated joint pain and tenderness. The average worldwide PsA prevalence is 133/100,000, while in the Italian population is 90-420/100,000. Traditionally, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs have been used in the treatment of PsA. However, for those patients who are not adequately controlled with conventional therapies, the new biologics compounds represent a valid option. Biologic therapies have been shown to be more effective but also more expensive than conventional systemic treatments. Based on the CHRONOS study, the economic analyses presented in this paper aim to assess the annualised direct costs and the cost-per-responder of biologics in a real-world context assuming the Italian National Health System perspective. METHODS: The economic assessments were carried out on the overall cohort of patients, and on the tumour necrosis factor alpha inhibitors (TNFi) and the secukinumab subgroup, the most prescribed biologic therapies within the CHRONOS study. RESULTS: The annual economic impact of PsA in the overall group was €12,622, €11,725 in the secukinumab subgroup, and €12,791 in the TNFi subgroup. Biologics absorbed the main expenditure costs in the treatment of PsA accounting for about the 93% of total costs. At 6 months, secukinumab performed better in all the considered outcomes: cost-per-responder according to EULAR DAS28 and ACR50 response criteria were €12,661- €28,975, respectively, while they were €13,356 - €33,368 in the overall cohort and €13,138 - €35,166 in the TNFi subgroup. At 12 months secukinumab remained the subgroup with the lowest cost-per-responder ratio in EULAR DAS28 and ACR50 response criteria, while TNFi subgroup was the lowest one considered the ACR20. CONCLUSION: Despite some potential methodological limitations, our cost-per-response analysis provides physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Real-World Safety Profile of Biologics Used in Rheumatology: A Six-Year Observational Pharmacovigilance Study in the Calabria Region.

Background: The introduction of biological agents into the clinical armamentarium has modified the management of moderate-severe inflammatory arthritis (IA). However, these drugs can lead to serious adverse events (SAEs) and unpredictable adverse events (AEs) that are difficult to detect in pre-marketing clinical trials. This pharmacovigilance project aimed to study the AEs associated with biologics use in rheumatology. Methods: The current investigation is a multicenter, prospective, observational cohort study based on the Calabria Biologics Pharmacovigilance Program. Patients treated with one biologic agent from January 2016 to January 2022 were enrolled. Results: Overall, 729 (86.3%) of a total of 872 patients did not develop AEs or SAEs, whereas 143 (16.4%) patients experienced at least one AE, of which 16 (1.8%) had at least one SAE. The most common AEs were administration site conditions followed by gastrointestinal, nervous system and skin disorders. We reported a total of 173 switches and 156 swaps. Switches mainly occurred for inefficacy (136; 77.7%), whereas only 39 (22.3%) were due to the onset of an AE. Primary/secondary failure was the most frequent reason for swaps (124, 79%), while AEs onset led to 33 (21%) swaps. Conclusions: This study supports the validity of our program in monitoring and detecting AEs in the rheumatological area, confirming the positive beneficial/risk ratio of biologics.

Real-world evidence of biologic treatments in psoriatic arthritis in Italy: results of the CHRONOS (EffeCtiveness of biologic treatments for psoriatic artHRitis in Italy: an ObservatioNal lOngitudinal Study of real-life clinical practice) observational longitudinal study.

BACKGROUND: Biologics have demonstrated efficacy in PsA in randomized clinical trials. More evidence is needed on their effectiveness under real clinical practice conditions. The aim of the present work is to provide real-world evidence of the effectiveness of biologics for PsA in the daily clinical practice. METHODS: CHRONOS was a multicenter, non-interventional, cohort study conducted in 20 Italian hospital rheumatology clinics. RESULTS: 399 patients were eligible (56.9% females, mean (SD) age: 52.4 (11.6) years). The mean (SD) duration of PsA and psoriasis was 7.2 (6.9) and 15.3 (12.2) years, respectively. The mean (SD) duration of the biologic treatment under analysis was 18.6 (6.5) months. The most frequently prescribed biologic was secukinumab (40.4%), followed by adalimumab (17.8%) and etanercept (16.5%). The proportion of overall responders according to EULAR DAS28 criteria was 71.8% (95% CI: 66.7-76.8%) out of 308 patients at 6 months and 68.0% (95% CI: 62.7-73.3%) out of 297 patients at 1 year. Overall, ACR20/50/70 responses at 6 months were 41.2% (80/194), 29.4% (57/194), 17.1% (34/199) and at 1-year were 34.9% (66/189), 26.7% (51/191), 18.4% (36/196), respectively. Secondary outcome measures improved rapidly already at 6 months: mean (SD) PASI, available for 87 patients, decreased from 3.2 (5.1) to 0.6 (1.3), the proportion of patients with dactylitis from 23.6% (35/148) to 3.5% (5/142) and those with enthesitis from 33.3% (49/147) to 9.0% (12/133). CONCLUSIONS: The CHRONOS study provides real-world evidence of the effectiveness of biologics in PsA in the Italian rheumatological practice, confirming the efficacy reported in RCTs across various outcome measures.

Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study.

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy.

Satisfaction in Social Roles and Physical Function in Immune-mediated Inflammatory Diseases: A Cross-Sectional Study.

BACKGROUND: Although mood disorders have been well characterized in Immune-mediated inflammatory diseases, physical function and satisfaction in social roles have not yet been defined as independent domains. OBJECTIVE: The study aims to assess satisfaction in social roles and physical function alterations in an Immune-mediated inflammatory diseases population and identify associated characteristics. METHODS: Physical function and social roles satisfaction were evaluated through the Patient-Reported Outcomes Measurement System. Besides comparisons between groups, univariate and multivariable logistic regression were performed to identify independent predictors. RESULTS: Two hundred sixty-five Immune-mediated Inflammatory Diseases patients and 206 controls were recruited. Compared with controls, Inflammatory Bowel Diseases patients had impaired physical function (p<0.001), while Inflammatory Arthritis patients reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity and occupation were positively associated with physical function and social role satisfaction (p<0.001; p=0.001; p<0.001; p=0.001 and p<0.001; p=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002); biological treatment and ESR with social roles satisfaction (p<0.001; p=0.043; respectively). In the multivariable regression, gender remained associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction in social roles (p<0.001) and steroids for physical function (p=0.021) and social roles satisfaction (p=0.018). CONCLUSION: Immune-mediated Inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independent associated factors. Patient-Reported Outcomes should be considered in clinical management to define patients' real needs.

Fatigue and Associated Factors in an Immune-Mediated Inflammatory Disease Population: A Cross-Sectional Study.

Fatigue is a main symptom of chronic diseases, including immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD) and inflammatory arthritis (IA); however, the pathophysiological mechanisms are not completely understood. The aim of this study was to assess the prevalence of fatigue and the associated factors in an IMIDs population. A control group, IBD, and IA patients, were enrolled. The PROMIS® fatigue questionnaire was used to evaluate the symptoms. Information on demographics, anthropometrics, disease characteristics, and medications was collected for each participant. A total of 471 subjects (137 with IBD, 103 with IA, and 206 controls) were enrolled. IBD and IA patients reported greater fatigue than controls (p < 0.001, each). In univariate regression, patients with anxiety and depression were more likely to report fatigue (p = 1.40 × 10−9 and p = 3.80 × 10−11, respectively). Males, holding a high school diploma, and being employed were inversely correlated to the domain (p = 1.3 × 10−5; p = 0.003 and p = 0.005, respectively). The use of steroids and disease activity determined increased fatigue (p = 0.014 and p = 0.019; respectively). In the multivariate analysis, anxiety and depression remained associated (p = 0.002 and p = 1.3 × 10−5, respectively). IMIDs patients present increased fatigue compared with healthy subjects. Anxiety and depression are the main associated factors, suggesting a psychological component of the symptom; thus, a holistic management should be established.

The CHRONOS Real-World Evidence of Biologic Treatments in Psoriatic Arthritis in Italy: A Post Hoc Gender Analysis.

Background: Phenotypic features and outcome differences between sexes have been reported in psoriatic arthritis (PsA). However, little is known about sex differences in effectiveness of biologics in clinical practice. Methods: Post hoc gender analysis of the CHRONOS, a multicenter, noninterventional, retroprospective Italian real-world study assessing 6-month and 1-year effectiveness of biologics for PsA. Results: Eligible patients were 399, 43.1% men. Sociodemographic characteristics, type of arthritis, baseline Disease Activity Score 28 joints (DAS28), and duration of biologic treatment were rather homogeneous. More men were overweight/obese and naive to biologics. The most frequently used biologics were TNF-inhibitors and secukinumab in both sexes. DAS28 responders were 72.7% (women) and 70.5% (men) at 6 months, and 68.0% in both sexes at 1 year. American College of Rheumatology (ACR) response showed a trend for men versus women to achieve more frequently ACR50 (32.6% vs. 26.5% at 6 months; 34.9% vs. 20.0% at 1 year) and ACR70 (22.3% vs. 12.4% at 6 months and 25.0% vs. 13.0% at 1 year). Global satisfaction with treatment at enrollment and after 6 months was slightly higher among men [mean (standard deviation) Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) score: 68.6 (18.6) and 69.9 (18.2), respectively] than women [65.3 (18.2), 66.2 (18.5)]. Conclusions: Overall response to biologics for PsA was rather favorable. With similar baseline disease severity, men appear to have a somewhat earlier and better response with higher treatment satisfaction.

Psychometric evaluation of an Italian custom 4-item short form of the PROMIS anxiety item bank in immune-mediated inflammatory diseases: an item response theory analysis.

BACKGROUND: There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)'s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons' responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs. METHODS: We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease (n = 246), rheumatological (n = 100) and dermatological (n = 43) diseases, and healthy volunteers (n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form. RESULTS: Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach's α = 0.93, McDonald's ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs. control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group (ps < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves (p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson's r = 0.98) and led to similar results. DISCUSSION: The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients.

An Italian Disease-Based Registry of Axial and Peripheral Spondyloarthritis: The SIRENA Study.

Introduction: Data about the clinical presentation and management of early and mild spondyloarthritis (SpA) are limited. Objectives: The objective of this study was to describe the baseline characteristics of disease-modifying antirheumatic drug (DMARD)-naïve patients with axial or peripheral SpA. Methods: The Spondyloarthritis Italian Registry: Evidence from a National Pathway (SIRENA) study is an ongoing, Italian, multicenter, prospective registry of patients with a first or newly confirmed diagnosis of SpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. To be included, patients had to be naïve to conventional, targeted, and biological DMARDs for SpA. Patients were enrolled between June 2017 and June 2019 and classified into groups according to disease presentation: predominantly axial or peripheral manifestations. The study is ongoing, and patients are being followed for 2 years, with an evaluation every 6 months according to clinical practice. Differences in baseline demographics, lifestyle, and clinical characteristics between axial and peripheral SpA were evaluated. Results: In this study, 350 patients were enrolled, of which 123 (35.1%) were axial and 227 (64.9%) were peripheral patients. Patients with axial SpA were significantly younger at enrollment (median age: 44 vs. 53 years), had significantly more anxiety/depression (13 vs. 2.6%), and expressed higher disease activity compared to patients with peripheral SpA. Patients with peripheral SpA had significantly more cardiometabolic disorders (33 vs. 18.7%), skin psoriasis (65.2 vs. 21.1%), and nail psoriasis (35.5 vs. 17.1%) than patients with axial SpA. Dactylitis, enthesitis, and fibromyalgia were observed, respectively, in 17.6, 51.2, and 5.7% of patients with axial SpA and 24.3, 40, and 3.1% of patients with peripheral SpA. In both disease groups, women tended to report depression, joint tenderness, and higher disease activity more frequently than their male counterparts. At inclusion, a new diagnosis of SpA was performed in 58% of axial and 77% of peripheral patients, with a median time from symptom onset to diagnosis of 36 and 24 months, respectively. At baseline, most patients with axial SpA (77%) started a biological DMARD, while over half of the peripheral patients started a conventional DMARD. Conclusions: Based on a well-characterized clinical registry of SpA, we provided real-world insights on the clinical features of DMARD-naïve SpA patients, pointing out major differences between axial and peripheral disease in terms of clinical characteristics and treatment pattern. Future prospective evaluations within the SIRENA study will improve knowledge on SpA and contribute to defining the best therapeutic approach.

Quality of life and therapeutic management of axial spondyloarthritis patients in Italy: a 12-month prospective observational study.

OBJECTIVES: To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA). METHODS: QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables. RESULTS: 413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-axSpA). Nr-axSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-axSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS. CONCLUSIONS: We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-axSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.

Dissecting the clinical heterogeneity of adult-onset Still's disease: results from a multi-dimensional characterization and stratification.

OBJECTIVES: To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. METHODS: AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. RESULTS: Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724 (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively]. CONCLUSION: Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.

Use of Ultrasonography to Discriminate Psoriatic Arthritis from Fibromyalgia: A Post-Hoc Analysis of the ULISSE Study.

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray-scale (GS; B-mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS- and PD-mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B- and PD-mode, respectively, 3.5 being the best cut-off GS-score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B-mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B-mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.

The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts' Consensus.

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients.

Management of psoriatic arthritis in rheumatology and dermatology settings: sub-analysis of the Italian population from the international LOOP study.

Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of dermatology/rheumatology specialist settings on diagnosis and therapeutic approach in PsA patients. This cross-sectional multicounty study in Italy involved twenty-eight rheumatology or dermatology clinics. Patients with suspected or confirmed PsA were examined by both a dermatologist and a rheumatologist. A total of 413 patients were enrolled and 347 (84%) were diagnosed with PsA. The majority of patients were enrolled from a rheumatology setting (N = 224, 64.6%). Patients with PsA in the dermatology settings had significantly higher disease activity, including skin involvement and musculoskeletal symptoms. Time from PsA onset to diagnosis was 22.3 ± 53.8 vs. 39.4 ± 77.5 months (p = 0.63) in rheumatology and dermatology settings; time from diagnosis to initiation of csDMARD was 7.3 ± 27.5 vs. 19.5 ± 50.6 months, respectively (p < 0.001). In contrast, time from diagnosis to bDMARD use was shorter in dermatology settings (54.9 ± 69 vs. 44.2 ± 65.6 months, p = 0.09, rheumatology vs. dermatology), similar to the time taken from first csDMARDs and bDMARDs (48.7 ± 67.9 vs. 35.3 ± 51.9 months, p = 0.34). The choice to visit a rheumatologist over a dermatologist was positively associated with female gender and swollen joints and negatively associated with delay in time from musculoskeletal symptom onset to PsA diagnosis. This study highlights a diagnostic delay emerging from both settings with significantly different therapeutic approaches. Our data reinforce the importance of implementing efficient strategies to improve early identification of PsA that can benefit from the integrated management of PsA patients. Key Points • A diagnostic delay was observed from both dermatology and rheumatology settings with significantly different therapeutic approaches. • Shared dermatology and rheumatology clinics offer the combined expertise to improve in the early identification and management of PsA.