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PURPOSE OF REVIEW Despite immunology and translational therapeutics advances in inflammatory arthritis over the past two decades, the enthesis, which is the epicentric of the spondyloarthritis family pathological process, retains many mysteries because of tissue inaccessibility that hampers direct immune study. As entheses are subject to almost continuous mechanical stress and spondyloarthritis is linked to microdamage or injury and joint stress, it is cardinal to understand the physiological changes occurring within the entheses not only to be able to differentiate disease from health but also to understand the transition normal physiology break down and its merges into spondyloarthritis-related disease. RECENT FINDINGS Imaging has played a major role in understanding the enthesis in human. Remarkable insights from enthesis functioning and microdamage in normal and with ageing including those linked to body mass index is emerging. The impact of mechanical stress and degenerative conditions on the development of the secondary entheseal vascular changes is not understood. Of note, ultrasound studies in psoriasis have shown higher power Doppler changes compared to controls pointing towards a role for vascular changes in the development of enthesitis in psoriatic arthritis. SUMMARY The literature pertaining to normal entheses changes with age, microdamage and vascular changes in health is providing a roadmap for understanding of the enthesis and its potential role in evolution of spondyloarthritis including psoriatic arthritis.

Objective: Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis. Methods: Serum levels of TNF-?, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria. Results: Patients of the two groups were not significantly different for levels of TNF-?, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (? = 0.3, p = 0.001), BMI (? = 0.8, p < 0.0001), tender joint count (? = 0.23, p = 0.05), and patient pain-VAS score (? = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (? = 0.41, p < 0.0001) and BMI (? = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (? = 0.7, p = 0.003) and CRP (? = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (? = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (? = 0.46, p = 0.004) but not in group 2. Conclusions: Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease.Key PointsoLevels of TNF-?, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis.oThere is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA.oThere is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis.

Dactylitis, one of the most typical features of psoriatic arthritis (PsA), is the diffuse swelling of the digits and is determined by the involvement of different anatomic structures, including: the subcutaneous fibrous tissue “accessory pulley” system; flexor tendons, with their related structures; the articular synovium; the small enthesis of the hands. Dactylitis is currently considered both a marker of disease activity and severe prognosis and its importance in PsA is emphasized by the inclusion in the classification criteria of PsA. This review focuses on the role of imaging in the management of PsA patients with dactylitis in clinical practice and in a research setting. Furthermore, imaging could be a valuable tool to assist in unravelling some of the underlying mechanisms of the onset and chronicization of dactylitis in PsA patients.

Introduction: To assess clinical and ultrasound effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath for the treatment of psoriatic dactylitis compared to systemic treatment (ST) alone. Methods: In this observational, multicentre, prospective study, 88 cases of symptomatic hand dactylitis were evaluated clinically and sonographically by high-frequency ultrasound (US) probe in both greyscale (GS) and power Doppler (PD). The presence of flexor tenosynovitis (FT), soft tissue oedema (STO), peritendon extensor inflammation and synovitis was assessed (including DACtylitis glObal Sonographic—DACTOS—score) before treatment, at 1-month (T1) and 3-months (T3) follow-up. LT was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Patients continued the same baseline csDMARDs and/or corticosteroid therapy during the whole follow-up period. US response was defined for DACTOS score < 3 and US remission for DACTOS score = 0. Results: At T3 evaluation the ST group showed a significantly higher persistence (grade > 1) of FT and STO (p < 0.001 for all) and MCP synovitis (p = 0.001). US remission was achieved only in the LT group (at T3 31% vs. 0, p < 0.001). The percentage of patients with DACTOS < 3 was significantly greater in the LT group compared with ST group, at both T1 (49% vs. 5%, p < 0.001) and T3 evaluation (76% vs. 7%, p < 0.001). In multiple conditional logistic regression analysis, the only factor associated with US remission was LT (T3 odds ratio = 41.21, p < 0.001). Conclusions: US confirmed the effectiveness of steroid injection for dactylitis by demonstrating that it involves the resolution of extra-articular inflammation, in particular FT and STO.

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); pgroup A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

Objective: the aim of this pilot study was to test the short-term effect of oral supplementation with a sodium hyaluronate with a large spectrum of molecular weights (FS-HA&reg, ) on the symptoms and functionality of knee osteoarthritis (OA). Methods: 60 subjects affected by clinical and/or radiological diagnosis of symptomatic knee OA were consecutively enrolled in a randomized, double blind, placebo-controlled, clinical trial. At randomization visit, at day 28 (visit 2), and day 56 (visit 3), the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the Lequesne Functional Index (LFI) and the Visual Analogue Scale (VAS) for pain (VAS-p) were administered to the enrolled patients. Then, patients were asked how many times they used rescue medications (non-steroidal antinflammatory drugs &ndash, NSAIDs and/or anti-pain drugs) during the previous 4 weeks. Finally, the range of knee joint motion (ROM) was also instrumentally measured. Results: In FS-HA&reg, treated subjects, VAS-p, pain and total WOMAC score, LFI and ROM significantly improved compared to the baseline values (p &lt, 0.05). At 60 days, the VAS-p and the pain WOMAC score were significantly lower after FS-HA&reg, treatment when compared with placebo as well (p &lt, 0.05). The FS-HA&reg, treated subjects significantly reduced the weekly use of NSAIDs and/or antipain drugs when compared to the placebo-treated ones (p &lt, 0.05). Conclusion: the oral supplementation with a FS-HA&reg, characterized by a large spectrum of molecular weight was associated with a short-term improvement in symptomatology and functionality of osteoarthritis-affected knees, and associated with a reduction in the use of NSAIDS and anti-pain drugs.

Objective The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a PsA dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders. Methods Forty-six consecutive patients with symptomatic PsA hand dactylitis were enrolled. A total of seventy-three dactylitic digits were evaluated clinically and sonographically before and after treatment in this observational and prospective study. Clinical assessment included the Leeds Dactylitis Index-basic (LDI-b) score and visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). Sonographic lesions were investigated using high-frequency ultrasound with grey scale and power Doppler features according to the DACTOS score. Correlations between the DACTOS score and the clinical parameters were assessed at baseline, 1 month (T1) and 3 months (T3). Results We observed significant improvements in all of the assessed clinical parameters and the DACTOS scores after dactylitis treatment. There was a statistically significant correlation between the variation of all clinical parameters (VAS-p, VAS-FI and LDI-b) and the DACTOS score at T1 and T3 evaluations. We found statistically significant differences in the DACTOS score between clinical responder and non-responder groups (P Conclusion The DACTOS score performs well in real-life clinical settings in terms of sensitivity to change and correlations with clinical features in PsA dactylitis.

ObjectivesDactylitis is one of the most typical features of psoriatic arthritis (PsA), with a high lifetime prevalence and inclusion in PsA clinical indices. Musculoskeletal ultrasonography (Msk-US) can readily detect inflammatory involvement of finger anatomical structures particular to dactylitis and monitor therapeutic effects. In this study, we aim to identify the characteristic lesions in PsA dactylitis of the hands, assess the reliability of Msk-US in scoring those lesions and develop a DACTylitis glObal Sonographic (DACTOS) score.MethodsAfter a systematic literature review on the use of Msk-US in PsA dactylitis, 12 rheumatologists participated in a three-round Delphi procedure and consensus meeting to agree on the sonographic elementary lesions characterising dactylitis and on the composition of a global sonographic score. Then, a web-based and a patient-based intra-rater and inter-rater reliability exercise was performed to assess those lesions included in the score.ResultsDACTOS score was obtained by summing the scores of each lesion selected in the Delphi survey: subcutaneous soft tissue oedema, flexor tenosynovitis, peritendon extensor inflammation and synovitis. The DACTOS score ranges from 0 to 25. In the reliability exercises, we obtained moderate-to-excellent agreement for the sonographic lesions included in the score.ConclusionsThe novel DACTOS score is a reliable measure to interpret the multiple characteristic sonographic features of dactylitis. The DACTOS score provides a useful global analysis of dactylitis of the hand and can represent a support to clinical diagnosis as well as a useful tool for the management and research in patients with PsA with dactylitis.

This observational and prospective study evaluated the clinical correlations of sonographic lesions in consecutive psoriatic arthritis (PsA) dactylitis cases. Eighty-three dactylitic digits were evaluated clinically and sonographically before treatment and at one-month (T1) and three-month (T3) follow-up. Clinical evaluation included the Leeds Dactylitis Index-basic (LDI-b) score and the visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). High-frequency ultrasound with grey scale (GS) and power Doppler (PD) assessed flexor tenosynovitis (FT), soft tissue oedema (STO), extensor tendon paratenonitis, and joint synovitis. There was a statistically significant correlation between the clinical parameters (VAS-p, VAS-FI, and LDI-b) and FT and STO at T1 and T3. We found statistically significant improvement in FT and STO for the cases with clinically meaningful treatment responses (p &lt, 0.001). After a multiple conditional logistic regression analysis, the only variables that correlated with a T1 clinical response were the resolutions of PD FT (OR 15.66) and PD STO (OR 6.23), while the resolution of PD FT (OR 27.77) and of GS STO (OR 7.29) correlated with a T3 clinical response. The clinical improvements of active dactylitis are linked to the regression of sonographic evidence of extracapsular inflammation (particularly FT and STO).

Introduction: Metabolic Syndrome (MetS) is strictly interconnected with systemic inflammation, and increased evidence has described a close link between this condition and Psoriatic Arthritis (PsA). Areas covered: This review summarizes main studies exploring clinical aspects and prevalence of MetS in PsA cohorts. Further, there is accumulating evidence showing shared inflammatory pathways between MetS, its components, and PsA. Expert opinion: The high prevalence of MetS in PsA highlights the need for screening, evaluation, and close monitoring of MetS and its components (namely, diabetes mellitus, obesity, hypertension, and dyslipidemia) in psoriatic patients. Further studies should focus on the pathogenetic link between MetS and PsA. More studies are required to identify appropriate algorithms for the assessment and management of MetS in PsA patients.

To evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB).We studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed.A final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61-1.27) and 1.15 (CI, 0.67-1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59-3.19) and 3.77 (CI, 0.53-26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68-1.25).A large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

Introduction: In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)–signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). Areas covered: The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their post-hoc analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA. Expert opinion: In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.

Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis.One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones.Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade 2, soft tissue edema and subcutaneous PDUS signal (p 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p 0.001).Digital tenderness and pain are linked to US tenosynovitis of grade 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.

Objective.To use ultrasonography to study whether the duration of psoriatic dactylitis was associated with different patterns of extracapsular and synovial-based involvement.Methods.One hundred cases of hand dactylitis from 85 patients with psoriatic arthritis (PsA) were consecutively enrolled in a multicenter cross-sectional study and divided into 2 groups according to dactylitis duration (shorter or longer than the median: 20 weeks). All dactylitis fingers were investigated using high-frequency ultrasound both in greyscale (GS) and power Doppler (PD), evaluating the presence of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDS), extensor tendon involvement, and joint synovitis.Results.Cases with a shorter dactylitis duration (< 20 weeks) had a significantly higher prevalence of GS flexor tenosynovitis of grade > 2, PD flexor tenosynovitis, soft tissue edema, and subcutaneous PDS (p = 0.001, p < 0.001, p < 0.05, and p = 0.001, respectively). However, the presence of synovitis in GS and PD mode (in both cases at proximal interphalangeal level) was more frequent in patients with longer dactylitis duration (p < 0.001). When detected in the chronic form, flexor tenosynovitis was grade 2 or lower.Conclusion.In a large cohort of PsA hand dactylitis, we found a predominant extracapsular inflammation (flexor tenosynovitis and soft tissue edema) in early cases and a high prevalence of joint synovitis at proximal interphalangeal level in the chronic form. However, longitudinal imaging studies are needed to clarify these aspects.

Objective: To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST). Methods: Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3). Results: The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001). Conclusions: For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis.Key Points• Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone.• The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3.• A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference.• For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.

Aim: To define and score finger soft tissue oedema in psoriatic dactylitis by ultrasound.Material and methods: A systematic literature review (SLR) on ultrasound-detected finger soft tissue oedema was performed. Subsequently, based on the SLR, a Delphi survey was developed and circulated among a group of 13 expert sonographers, in order to obtain agreement on detection, definition and scoring of finger oedema by B-mode and power Doppler ultrasound. Agreement was considered achieved when each statement was approved by >75% of participants.Results: At the first Delphi round, 91 % agreement was obtained for the scanning technique to adopt, including the most appropriate area to evaluate. At the second round, 76% agreement was achieved on the definition of soft tissue finger oedema. At the third round, 76% agreement was obtained for B-mode and power Doppler scores. The volar aspect of the finger and comparisons with the contralateral side were agreed to be the most appropriate in terms of scanning technique. Agreed ultrasound definition of finger soft tissue oedema was “abnormal hypoechoic/anechoic areas, diffused or localized within the subcutaneous tissue between the epidermidis and the tendon-related anatomic structures (i.e. flexor tendon sheath, peritenonium, tendon pulleys), with local thickening, with or without local abnormal Doppler signal, visualised in two perpendicular planes and not evident on the contralateral side”. Semiquantitative (0-3) scores for both B-mode and power Doppler were agreed to be the most appropriate to be used.Conclusion: Our work produced, for the first time, technical indications, definition and scoring for the ultrasound assessment of soft tissue oedema in psoriatic dactylitis

Psoriatic arthritis (PsA) can start in subjects aged over 60 years, defined as late-onset PsA. In late-onset PsA, the weight of family history and genetic background appears less significant when compared with younger onset PsA, whereas obesity and smoking have been suggested as potential risk factors. In patients with late-onset PsA, erosive polyarticular or oligoarticular patterns are more frequent than other phenotypes. Laboratory findings usually show an increase in levels of acute phase reactants, including erythrocyte sedimentation rate and C-reactive protein. The drugs used for the management of young PsA subjects represent the same therapeutic armamentarium used in patients with late-onset disease. However, in elderly subjects, these anti-inflammatory, immunomodulatory and immunosuppressive therapies, including newer biologic therapies, represent an important challenge due to age aspects, increased frequency of comorbidities and associated polypharmacotherapy. There is a need for more evidence around treatment strategy for these patients in order to identify the best balance between the benefits and risks of pharmacological agents. This is important for establishing how treatment should ideally be tailored to the characteristics of any single patient and to the presence of complex age- and disease-related aspects. The objective of this review is to focus on pathogenetic, clinical and therapeutic aspects of late-onset PsA and the management of elderly PsA patients.

Background:Axial Spondyloarthritis (axSpA) can be distinguished in radiographic axSpA (r-axSpA) and non-radiographic (nr-axSpA). Secukinumab (SEC) is a novel treatment for axSpA, but data from real-life are still missing.Objectives:1)to evaluate the effectiveness and safety of a wide cohort of axSpA patients on SEC followed in 8 Italian Rheumatologic centers for 24-months;2)to compare the features and disease-activity indices of SEC-treated axSpA patients subdivided in naïve biological drugs (group A) and in TNF-inhibitors failure patients (group B).Methods:Consecutive patients with active axSpA (diagnosis according Assessment of SpondyloArthritis International Society ASAS criteria), who started SEC treatment, were evaluated prospectively.Data on disease characteristics, previous/ongoing treatments and imaging were collected. Disease-activity/functional/clinical scores and biochemical values were recorded at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Effectiveness was evaluated over-time with descriptive statistics. Anova (Kruskal Wallis) and generalized linear models were used to compare variables over-time. Infections,adverse events were collected.Results:One-hundred-seven patients [49.53% men; median age 49years; median treatment duration 18.5years] were enrolled;53(49.53%) had HLA-B27, 47.66% were r-axSpA and 52.34% nr-axSpA. Signs of sacroiliitis were present on MRI in 97 (90.65%) and X-rays in 51 (47.66%). SEC was prescribed as first line biologic treatment in 32 (29.9%) patients and as second or more line biological treatment in 75 (70.1%) patients (Figure 1). In all population significant decrease was achieved in:Visual Analogue Scale of pain and general-health; Leeds Enthesitis Index;Health Assessment Questionnaire modified for spondyloarthritis (HAQ-s);Bath Ankylosing Spondylitis Functional Index (BASFI);C-reactive protein. Bath Ankylosing Spondylitis Metrology Index and Erythrocyte-sedimentation-rate not significantly decreased. Effectiveness was associated to an improvement in Ankylosing Spondylitis disease activity score (ASDAS) [T0=3.4 (2.9-3.9) vs T24=1.9 (1.2-2.7);p=0.02] and in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [T0=6.6 (5.0-7.8) vs T24=3.2 (2.0-5.0);p=0.03].At T0 group B had a longer disease duration (p=0.04),a greater prevalence of peripheral arthritis (p=0.02),enthesitis (p=0.04) and psoriasis (p=0.05) and was mostly male (p=0.05),while no significant difference was observed for functional and disease-activity indices and signs of sacroiliitis on MRI/X-rays. At T24 group A showed better physical functioning and lower disease activity compared to group B [HAQs A vs. B=0.1(0.0-0.5) vs 0.3(0.1-0.8); BASFI A vs B=1.6(0.8-4.8) vs 4.0(2.5-4.6); BASDAI A vs B=2.2(1.0-3.8) vs 3.9(2.7-5.0);ASDAS A vs B=1.3(1.0-2.2) vs 2.1(1.6-2.9)].After T24 of treatment 70.2% of Group A and 68.4% of Group B had a low disease activity,accordingly to ASDASGroup A and B were similar (log-rank test=0.81;p=0.69).Conclusion:In a real-life clinical setting,SEC was safe and effective in axSpA, as shown by a significant decrease of BASDAI and ASDAS over a 24-months follow-up.Disclosure of Interests:Mariagrazia Lorenzin: None declared, Augusta Ortolan: None declared, Maria Sole Chimenti: None declared, Antonio Marchesoni Grant/research support from: AM has received honoraria and speaker fees from Abbvie, Pfizer, MSD, UCB, Novartis, Janssen, Eli-Lilly., Ennio Lubrano: None declared, Leonardo Santo Speakers bureau: Speaker from Jansen, Novartis, Pfizer, UCB, MSD, Sanofi, Angelo Semeraro: None declared, Carlo Salvarani: None declared, Nicolò Girolimetto: None declared, Emanuela Praino: None declared, Giulia Lavinia Fonti: None declared, Rosario Foti: None declared, Antonio Carletto: None declared, Andrea Doria Grant/research support from: ADhas received honoraria and speaker fees from Novartis, Abbvie, Pfizer, MSD, Janssen., Roberta Ramonda Grant/research support from: RR has received honoraria and speaker fees from Novartis, Abbvie, Pfizer, MSD, Janssen.

The letter by Akpabio and colleagues1 raises an important question and describes an interesting scenario related to their geographical area. However, this scenario can easily be applied to several other experiences. In fact, the situation described by Akpabio and colleagues1 with regard to rheumatological centres being located in great urban areas as compared with the shortage of these specialists within their periphery is quite frequent. The impact of the COVID-19 pandemic on everyday practice gives us an opportunity to speed up the development of the process already known as telemedicine, which may be an attempt to correct some of these disparities. The authors of the letter indicate many and relevant suggestions which we find very adequate and deserve immediate consideration. In particular, during this phase, we feel that it is necessary to manage this development. What can this mean? First of all, it should be outlined that telemedicine does not mean reduced need for specialists. Each one of us has experienced the burden of this approach. Telemedicine, as compared with the traditional inperson medical consultation, means greater effort in terms of more complex visit planning, of time spent, of organisation (detailed patient charts …

We read with interest the article by Gupta et al 1 who reported the management of treatments for rheumatic diseases during COVID-19 pandemic among practitioners in India. In this study, the authors showed that about half of the physicians would reduce the use of biological disease-modifying antirheumatic drugs (bDMARDs) or defer specific drugs such as rituximab.1 Choices were apparently made considering possible relationships between drug mechanism of action and effect on the viral infection.1 During COVID-19 pandemic, telemedicine is emerging as a possible tool for reducing the risk of contagion and viral spread,2–4 and a useful strategy for the management of chronic diseases.5 6 As of 29 April 2020, the outbreak of COVID-19 generated 201 505 confirmed cases in Italy, with 2405 confirmed cases in Naples Metropolitan area. The objective of our study was to evaluate telemedicine when offered as part of routine care for the follow-up of patients …

Background:Dactylitis is a common feature of PsA, occurring in 16 to 49% of PsA patients,mostly in early disease.Objectives:To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath for the treatment of active dactylitis in PsA patients as compared to systemic treatment (ST) alone.Methods:73 hand dactylitis were assessed in a prospective observational study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for pain (VAS pain),functional impairment (VAS-FI).In accordance with EULAR and GRAPPA recommendations, steroidinjectionwas proposed to all patients. Patients who refused LT were treated with oral NSAIDs. The patients of the two groups continued baseline therapy with csDMARDs or corticosteroids. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3) by assessors blinded to this study.Results:The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group as compared to the ST group, both at T1 (p Table 1.Variation of clinical parameters during follow up.T0baselineT11 monthT33 monthsT0 vs T195% CIT0 vs T395% CIVAS - PAINLT6.89±1.931.97±1.621.34±1.484.92(4.17; 5.67)5.55(4.76; 6.32)ST6.03±2.435.49±2.535.0±2.650.54(-0.23;1.32)1.03(-0.02; 2.07)Mean differences (95% CI)0.87(-1.89; 0.16)3.51(2.53; 4.49)3.66(2.67; 4.65)VAS - FILT7.87±1.532.76±1.871.68±1.545.11(4.49; 5.72)6.18(5.52; 6.84)ST6.89±1.926.14±2.255.74±2.630.74(0.23; 1.26)1.14(0.32; 1.97)Mean differences (95%CI)0.98(-1,79; 0,17)3.38(2.42; 4.34)4.05(3.06; 5.05)Finger circumference (cm)LT7.17±0.576.61±0.596.55±0.540.56(0.46; 0.65)0.62(0.52; 0.73)ST7.05±0.806.90±0.896.88±0.910.15(0.06; 0.25)0.17(0.07; 0.27)Mean differences (95%CI)0.12(-0.44; 0.21)0.29(-0.07–0.69)0.33(-0.02 -0.68)LDI-bLT12.31±0.039.91±7.151.25±4.358.40(5.73;11.06)11.05(8.22; 13.89)ST14.97±11.079.88±10.9810.04±11.095.10(1.63; 8.55)4.93(1.54; 8.32)Mean differences (95%CI)2.67(-1.82; 7.16)5.97(1.58; 10.35)8.79(4.74;12.83)VAS, visual analogue scale; VAS-FI, Visual analogue scale for functional impairment; LDI-b, Leed’s dactylitic index basic; LT, local treatment group; ST, systemic treatment group.Table 2.Percentage of Significant response and Remission of dactylitis.T1 1 monthT3 3 monthsSignificant response, n (%)LT33 (86.8%)36 (94.7%)ST6 (17.1%)11 (31.4%)p value< 0.001< 0.001Remissionn (%)LT1 (2.8%)7 (18.4%)ST0 (0%)0 (0%)p valuens0.012Values are presented as number of dactylitic fingers achieving response/remission. p values < 0.05 were considered statistically significant.Conclusion:For the first time, we show the effectiveness of steroid injection into the digitalflexor tendon sheathin improving clinical aspects and symptoms of hand psoriatic dactylitis.References:[1]Gladman DD, Ziouzina O, Thavaneswaran A, Chandran V. Dactylitis in psoriatic arthritis: prevalence and response to therapy in the biologic era. J Rheumatol. 2013;40:1357-9.Disclosure of Interests:None declared

Background:The association between PsA and cardiovascular disease is generally thought to be greater than the risk between psoriasis and cardiovascular disease. Vascular calcifications (VC) are considered an early marker of atherogenesis and accurate VC scores including Carotid, Aortic and Lower limbs vascular Calcifications (CALC) were published2. PsA localises to entheses that are sites of high physical stressing, analogous to artery bifurcations which are sites of high vascular stress. Entheseal calcification is a feature of the post-inflammatory changes. We hypothesised that there may be common “deep koebernisation” responses in the entheses and vessels in PsA as a common biomechanical response specifically linking PsA with cardiovascular diseaseObjectives:To quantify non-coronary VC in a consecutive series of PsA patients using CALC score (CALCs) and compare PsA patients with CV risk factors to the group without. To independently evaluate sonographic entheseal changes including new bone formation and to determine if the magnitude of vascular and entheseal lesions was linkedMethods:122 adult PsA patients diagnosed according to the CASPAR criteria underwent US assessment for the presence of VC according to CALCs. Carotids arteries intima-media thickness (IMT) was also measured. Blinded to this US assessment, further US imaging of 12 large entheseal sites was performed. The presence of enthesophytes was scored dichotomously for each site and summed up to generate the ARES score. Enthesophytes were scored semiquantitatively in a 0-3 scale according to previous studies3to generate RESS score. Enthesal inflammatory changes were identified according with OMERACT definitionsResults:Overall, 83 patients were female (68%), mean age 58.6±10.3 y and mean PsA duration 9.5±7.0 y. PsA with obesity, metabolic syndrome and hypertension presented higher IMT values. The IMT scores correlated significantly with entheseal thickness (p< 0.001). A statistical significant correlation was found between CALCs with enthesophytes scores ARES and RESS (spearman rho = 0.665, p < 0.001 and 0.634, p < 0.001 respectively). CALCs, ARES and RESS were significantly increased in patients with CV risk factors or an history of CV events, compared with patients without (table 1). No significant correlation was found between CALCs and PsA duration (Spearman rho = 0.132, p = 0.135)PATIENTS, N. (%)CALCsARESRESSHypertension50 (41%)8.18 ± 6.20 **6.55 ± 2.59 **12.06 ± 5.91 **No hypertension72 (59%)3.82 ± 4.24 **4.79 ± 2.61 **8.05 ± 5.40 **Positive history of CV events16 (13%)11.5 ± 5.34 **7.56 ± 2.50 *13.56 ± 4.97 *No CV events106 (87%)4.70 ± 5.02 **5.16 ±2.64 *9.06 ± 5.86 *Obesity31 (25%)6.55 ± 5.036.63 ± 1.86 *12.03 ± 4.96 *No obesity91 (75%)5.48 ± 5.775.32 ± 2.85 *9.17 ± 6.07 *Hyperuricemia14 (11%)11.86 ± 8.15 *7.43 ± 2.56 *15.00 ± 5.33 **No hyperuricemia108 (89%)4.65 ± 4.55 *5.23 ± 2.68 *8.97 ± 5.69 **Dyslipidemia54 (44%)7.47 ± 6.43 **5.90 ± 2.7010.84 ± 6.13 *No Dyslipidemia68 (56%)3.92 ± 4.03 **5.11 ± 2.738.59 ± 5.58 *Diabetes11 (9%)10.09 ± 7.29 *7.18 ± 2.14 *14.55 ± 5.20 *No diabetes111 (91%)5.08 ± 5.16 *5.31 ± 2.73 *9.14 ± 5.79 ** = pConclusion:In PsA patients vascular and entheseal calcifications are significantly correlated. Patients with CV risk factors and/or history of CV events have higher values of CALCs, ARES and RESS. This suggests possible commonalites between entheses and vessels that might represent a deep Koebnerisation response in arteries and entheses. This raises the possibilities that the primary joint inflammatory responses and what is viewed as a comorbidity are closely linkedReferences:[1]Eder L, et al. J Rheumatol Suppl. 2019;95:20-27.[2]Flore R, et al. Eur Rev Med Pharmacol Sci. 2018;22(3):736-742.[3]Aydin SZ, et al. Rheumatol Int. 2016;36(3):397-404.Disclosure of Interests:Ilaria Tinazzi: None declared, Giorgia Citriniti: None declared, Nicolò Girolimetto: None declared, Federica Martinis: None declared, Carlo Salvarani: None declared, Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Pierluigi Macchioni: None declared

Objectives: To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis. Methods: Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment. Results: The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons). Conclusions: Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.

Introduction: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. Areas covered: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. Expert opinion: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated

The aim of this study was to evaluate the prevalence of MetS and its components and the level of serum uric acid in patients with PsA and in those with PsA sine psoriasis. A secondary aim of the study was to investigate on correlations of MetS in all study population. Consecutive PsA patients underwent assessment of disease activity and metabolic parameters. Blood samples were collected after 12 h of overnight fasting and analyzed for glucose, lipid profile, serum uric acid, and acute-phase reactants. The NCEP-ACT III criteria were used to identify subjects with MetS. Forty-two patients (52.5%) were classified as having PsA with clinically evident psoriasis (group 1) and 38 (47.5%) as having PsA sine psoriasis (group 2). Group 1, when compared to group 2, showed a significant increase for the frequency of MetS (p = 0.006) and for mean values of diastolic blood pressure (p = 0.0116) and of serum uric acid (p = 0.04). We then aimed at defining determinants of MetS in the entire study population. In the multivariate analysis, three variables reached statistical significance: presence of psoriasis (OR 0.14; p = 0.01), increase of one unit of BMI (OR 1.26; p = 0.001), and smoking habit (OR 5.93; p = 0.02). In our study, the occurrence of MetS and mean levels of serum uric acid were higher in PsA patients with clinical evident psoriasis compared to sine psoriasis PsA. The results also show the potential role of BMI, psoriasis, and smoking as important determinants in the development of MetS in PsA patients.

Introduction: The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases. Areas covered: We searched in the PUBMED database and review published data on the efficacy and safety profile of the small molecules, inhibitor of phosphodiesterase 4, apremilast, and of JAK/STAT pathways, tofacitinib, in PsA. Moreover, we report data on the other JAK inhibitor, baricitinib, and the A(3) adenosine receptors agonist, CF101, emerging by studies conducted in psoriasis patients. Expert opinion: In Psoriatic Arthritis, apremilast appears promising for PsA and recent studies have shown a good efficacy and an acceptable safety profile. Data on tofacitinib in PsA are limited. Studies on the small molecules, baricitinib and CF101 are still incomplete and limited to trials conducted in Rheumatoid Arthritis and in psoriasis. Further studies on small molecules and on their underlining mechanisms are advocated in PsA.

The improved recognition of pathogenetic molecular mechanisms has led to the use of drugs targeting cytokines in different inflammatory arthropathies as well psoriatic arthritis (PsA). In particular, the progress in knowledge on tumor necrosis factor (TNF)-α in the pathogenesis of PsA has changed the therapeutic approach by use of direct and receptor cytokine antagonists. Currently, infliximab (IFX), adalimumab, etanercept, golimumab and certolizumab pegol represent the five anti-TNF-α available for the treatment of PsA. This review describes evidence on treatment aimed at neutralizing TNF-α in PsA patients, from the first study in 2000 until today, mainly derived from randomized clinical trials. In comparison with traditional therapies, anti-TNF-α agents have shown to have more efficacy both in treating clinical aspects, including enthesitis, dactylitis, joint pain and swelling, axial involvement, nail and skin lesions, and in reducing radiographic progression. Moreover, anti-TNF-α agents have been demonstrated to be reasonably safe in PsA, as confirmed by data derived by different registries.