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An accurate prediction of cardiovascular (CV) risk in patients with Axial Spondyloarthritis (axSpA) is a strong unmet need, as CV risk algorithms poorly perform in these subjects. The aim of this study was to establish whether the persistence of high C-reactive protein (CRP) and high disease activity may be considered predictive factors of CVD in axSpA. 295 patients without personal history of CVD, were consecutively enrolled in this study. To evaluate the relationship between CV events occurrence (fatal and non-fatal) and the persistence of increased CRP levels, ASDAS (Ankylosing Spondylitis Disease Activity Score) > 2.1, and BASDAI (Bath Ankylosing Spondylitis Disease Activity) > 4 during the follow-up, univariable and multivariable Cox Proportional Hazard Models have been performed. During follow-up (we analyzed 10-years retrospective data), 23 patients had a CV event. Multivariable Cox Proportional Hazard Models showed a strong association between CV event and the persistency of increased CRP levels (namely, percentage of visits in which CRP levels were increased) (HR = 1.03; 95%CI 1.015–1.045; p < 0.001), of ASDAS > 2.1 (HR = 1.014, 95%CI 1.000–1.028, p = 0.047), and of BASDAI > 4 (HR 1.019, 95%CI 1.006–1.033, p = 0.006) during follow-up, after adjustment for age, sex, and diabetes. This study suggests that persistence of increased CRP levels and high disease activity may be considered biomarkers to identify those axSpA patients at higher risk of CVD. Innovative axSpA-specific CV risk score, including these variables, have to be developed. [ABSTRACT FROM AUTHOR]

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still's disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis. Key points • Smoking habit resulted to be a negative prognostic factor on AOSD. • Smokers were characterised by an increased frequency of serositis and higher values of systemic score. • Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effectiveness of golimumab (GLM) in improving joint, periarticular structures and cutaneous manifestations in patients with moderate to severe psoriatic arthritis (PsA) with cutaneous psoriasis in different real-life clinical settings and 48-month drug survival. Methods: Clinical and laboratory records were collected from PsA patients treated with GLM at baseline (T0) and after 6, 12, 24, 36, and 48 months of treatment. Comparisons were performed using a paired t-test or Wilcoxon test. Drug survival rates were analyzed using Kaplan–Meier estimates. p value < 0.05 was considered statistically significant. Results: Data from 105 patients were collected. PsO occurred in 80% of patients and enthesitis in 78%, peripheral and axial arthritis in 63.8% and 35.3%, respectively, while erosions in 36.2%. The main comorbidities were cardiovascular diseases (31.4%) and metabolic syndrome (MetS) (19%). A statistically significant improvement in articular and cutaneous psoriasis was registered at T48 of GLM-therapy in clinical (DAPSA p < 0.0001; PASI p < 0.01; BASDAI p < 0.0001) and laboratory (CRP < 0.05) indexes. Gender (p = 0.652), BMI (p = 0.655), smoking habit (p = 0.466), and line of treatment (p = 0.208) did not affect treatment efficacy nor persistence. At T48, 42% of patients discontinued GLM: the most frequent reason was an insufficient response or loss of efficacy (28.6%). Conclusion: A 48-month GLM high drug persistence of PsA patients was observed in real-life, in patients presenting high disease activity, elevated prevalence of comorbidities, and more than one line of treatment at baseline. Patients' characteristics as gender, smoke, BMI, different lines of treatment, and concomitant methotrexate treatment affected treatment persistence, making GLM effective and safe in moderate-severe PsA in a long-term real-life setting. Key Points • Golimumab was effective in psoriatic arthritis, including both musculoskeletal and cutaneous manifestations. • Golimumab effectiveness and drug survival were not affected by comorbidities and patient-related characteristics. • The 4-year drug survival curves confirm the efficacy and safety of golimumab in psoriatic arthritis patients in a real-life setting. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed. [ABSTRACT FROM AUTHOR]

Introduction: The performance of seven cardiovascular (CV) risk algorithms is evaluated in a multicentric cohort of ankylosing spondylitis (AS) patients. Performance and calibration of traditional CV predictors have been compared with the novel paradigm of machine learning (ML). Methods: A retrospective analysis of prospectively collected data from an AS cohort has been performed. The primary outcome was the first CV event. The discriminatory ability of the algorithms was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), which is like the concordance-statistic (c-statistic). Three ML techniques were considered to calculate the CV risk: support vector machine (SVM), random forest (RF), and k-nearest neighbor (KNN). Results: Of 133 AS patients enrolled, 18 had a CV event. c-statistic scores of 0.71, 0.61, 0.66, 0.68, 0.66, 0.72, and 0.67 were found, respectively, for SCORE, CUORE, FRS, QRISK2, QRISK3, RRS, and ASSIGN. AUC values for the ML algorithms were: 0.70 for SVM, 0.73 for RF, and 0.64 for KNN. Feature analysis showed that C-reactive protein (CRP) has the highest importance, while SBP and hypertension treatment have lower importance. Conclusions: All of the evaluated CV risk algorithms exhibit a poor discriminative ability, except for RRS and SCORE, which showed a fair performance. For the first time, we demonstrated that AS patients do not show the traditional ones used by CV scores and that the most important variable is CRP. The present study contributes to a deeper understanding of CV risk in AS, allowing the development of innovative CV risk patient-specific models. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Both for HIT and adenovirus vector-based DNA vaccines ITT, a key role is played by the platelet-activating antibodies known as anti-PF4-polyanion complexes. Regarding the ITT case series described by Greinacher et al. [[10]], in fact, out of the 11 patients, 2 (18.2%) presented anticardiolipin antibodies, which are typical of Antiphospholipid syndrome (APS). In light of the aforementioned, an autoimmune screening may appropriately be considered on young women before administering a viral vector vaccine, in order to reduce the incidence of the ITT and avoid the vaccine underutilization. [Extracted from the article]

Introduction: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting. Methods: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model. Results: During the follow up, which lasted 25.5 (12–60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336–0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519–0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17). Conclusions: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA. Key Points • No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated. • A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment. [ABSTRACT FROM AUTHOR]

Johannes Itten, along with Walter Gropius and others, was one of the most important founders of the Bauhaus in Weimar, and a teacher at the same time. Even if Itten was not a mathematician, he had a great interest in different geometric forms, and revealed a great mathematical intuition. Itten realized "by hand" the important Fire Tower, applying translations, reductions and rotations of cubes and of portions of cone. On the occasion of the Kunstfest Weimar 2019, the organizers of the events, which were specifically dedicated to Itten, invited us to describe in mathematical language the lithograph entitled Das Haus des Weissen Mannes (1921), in which the cube is again the "protagonist" of mathematical transformations. [ABSTRACT FROM AUTHOR]

Diet is a modifiable factor implicated in chronic systemic inflammation, and the mediterranean dietary pattern is considered to be a healthy model in terms of morbidity and mortality. The main aim of this study was to evaluate the adherence to the mediterranean diet in patients with Psoriatic Arthritis (PsA) and its impact on disease activity. A cross-sectional observational study was conducted in a cohort of 211 consecutive PsA patients. We evaluated PsA activity by disease activity index for PSoriatic Arthritis (DAPSA) and composite psoriatic disease activity index (CPDAI). The NCEP-ACT III criteria were used to identify subjects with MetS, and in each subject, we evaluated body mass index (BMI). A validated 14-item questionnaire for the assessment of adherence to the mediterranean diet (PREDIMED) was recorded for all the enrolled subjects. Patients showed a median age of 55 (48–62) and disease duration was 76 (36–120) months. 27.01% of patients were classified as having MetS. The median of the mediterranean diet score (MDS) was 7 (6–9). A moderate adherence to mediterranean diet was found in 66.35% of the entire cohort; 15.64% and 18.01% of the patients showed low- and high adherence to the dietary pattern, respectively. We found a negative association between DAPSA and adherence to mediterranean diet (B = − 3.291; 95% CI − 5.884 to − 0.698). DAPSA was positively associated with BMI (B = 0.332; 95% CI 0.047–0.618) and HAQ (B = 2.176; 95% CI 0.984–3.368). Results from our study evidenced that in PsA patients, higher levels of disease activity as measured by DAPSA correlated with low adherence to mediterranean diet, suggesting potential benefit of antinflammatory properties of this dietary pattern. [ABSTRACT FROM AUTHOR]

Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate that M. tuberculosis isolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities. Some strains of Mycobacterium tuberculosis seem to be able to avoid host defense systems. Here the authors stratify patients by severity of tuberculosis and find correlations with the level of IL-1β production by macrophages exposed to these isolates. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed. [ABSTRACT FROM AUTHOR]

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-α, 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-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (β = 0.3, p = 0.001), BMI (β = 0.8, p < 0.0001), tender joint count (β = 0.23, p = 0.05), and patient pain-VAS score (β = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (β = 0.41, p < 0.0001) and BMI (β = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (β = 0.7, p = 0.003) and CRP (β = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (β = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (β = 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 Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis. [ABSTRACT FROM AUTHOR]

The increased cardiovascular (CV) risk is one of the major challenges in the management of patients with psoriatic arthritis (PsA). Recently, EULAR suggested to adapt the already available CV risk algorithms with a 1.5 multiplication factor in all the patients with rheumatoid arthritis (RA), but it is still uncertain if this adaptation could also be applied to patients with PsA. This study aims to evaluate the performance and calibration of the CV risk algorithm ASSIGN and its adaptations for RA (ASSIGN-RA) and according to EULAR recommendations in a cohort of patients with PsA (ASSIGN*1.5). Prospectively, collected data from two Italian cohorts has been analyzed. The discriminatory ability for CV risk prediction was assessed using the areas under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) test and calibration plots. For each algorithm, sensitivity and specificity were calculated for low- to high-risk cut-off (20%). One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN, 0.8160 (95% CI 0.71661 to 0.91529) for ASSIGN-RA, and 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN*1.5. HL tests did not demonstrate poor model fit for none of the algorithms. Discriminative ability and calibration were not improved by adaptation of the algorithms according to EULAR recommendations. Up to 20% of CV events occurred in patients at "low risk". No difference in performance has been observed between ASSIGN, Progetto CUORE, and QRISK2. ASSIGN could represent a useful tool in predicting CV risk in patients with PsA. Adaptation for RA or according to EULAR recommendations did not show any further improvement in performance and calibration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autoimmune diseases and autoinflammatory diseases have a number of similar etiopathogenetic and clinical characteristics, including genetic predisposition and recurrent systemic inflammatory flares. The first phase of ADs involves innate immunity: by means of TLRs, autoantigen presentation, B and T cell recruitment and autoantibody synthesis. The second phase involves adaptive immunity, a self-sustaining process in which immune complexes containing nucleic acids and autoantibodies activate self-directed inflammation. The link between autoimmunity and autoinflammation is IL-1ß, which is crucial in connecting the innate immune response due to NLR activation and the adaptive immune responses of T and B cells. In conclusion, although ADs are still considered adaptive immunity-mediated disorders, there is increasing evidence that innate immunity and inflammasomes are also involved. The aim of this review is to highlight the link between the innate and adaptive immune mechanisms involved in autoimmune diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The current prospective observational study aimed to evaluate the long-term (24 months), real-life effectiveness of ustekinumab in psoriatic arthritis (PsA). Consecutive patients with moderate-severe PsA and active psoriasis who begun ustekinumab treatment were evaluated prospectively (January 2015-March 2017). Clinimetric scores and biochemical values were assessed at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Friedman test and generalized linear models were used to compare variables over time. Regression analysis to identify determinants of minimal disease activity (MDA) at T6 and of treatment discontinuation was conducted. Sixty-five patients (43.1% men; age 49.4 ± 11.6 years) were enrolled; ustekinumab was prescribed as a first (20%), second (33.8%), third (26.5%), fourth (15.4%), or fifth (4.6%) line biological therapy. Significant decrease in tender/swollen joints, Visual Analogue Scale of pain (VASp) and general health (VASgh), Disease Activity in PsA (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), Health Assessment Questionnaire modified for spondyloarthritis (HAQ-S), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was achieved. MDA was reached by 30.7, 47.0, and 34.0% of patients respectively at T6, T12, and T24. In multivariable models, mono-oligoarthritis was independently associated to MDA at T6 (OR 9.02; 95% CI 1.41, 57.71), while baseline CRP (OR 1.12; 95% CI 1.00, 1.26) and LEI (OR 0.50; 95% CI 0.25, 0.97) to ustekinumab discontinuation. More patients used disease-modifying antirheumatic drugs at T0 (35.3%) than at T24 (8.5%). Only nine episodes of infection and no serious adverse events were registered. In a real-life clinical setting, ustekinumab was safe and effective in PsA. Comedication tapering was often possible. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with anti-tumor necrosis factor (TNF)-α agents represents the first therapeutic choice for moderate and severe forms; however, PsA patients can experience anti-TNFα failure, lack of efficacy, or adverse events. Several evidences exist on the effectiveness of switching among different TNFα inhibitors, and we reviewed the published data on the effectiveness of anti-TNFα first-, second- and third-line. Most of the studies report that the main reason for switching to a second anti-TNFα agent is represented by lack of efficacy (primary or secondary) and, more rarely, adverse events. Switchers receiving their second anti-TNFα agent have considerably poorer responses compared with non-switchers. Survival of anti-TNFα treatment appears to be superior in PsA patients when compared with rheumatoid arthritis patients. Switching from anti-TNF agents to ustekinumab or secukinumab or apremilast can represent a valid alternative therapeutic strategy. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA ( p < 0.001). The drug discontinuation rate was 5.5% with a mean of 6.8 months (range 2-10 months), and it was due to lack of efficacy, adverse events, and lost to follow-up. Nine patients (6.2%) reported the onset of mild infections resolved with antimicrobial specific oral regimen without therapy interruption. TNF-α blockers are effective in the achievement of a low disease status and safe in elderly patients with PsA. Therefore, age should not be considered a limitation to their use. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease affecting around 40% of psoriasis patients. Minimal disease activity (MDA) criteria have been proposed to identify a state of low disease activity, one of the principal goals of treatment for psoriatic disease. This study investigated treatment with ustekinumab (UST) in the context of a real-world setting. Thirty-four PsA patients who had failure or inadequate response to conventional synthetic disease-modifying antirheumatic drugs or to anti-tumour necrosis factor alpha were enrolled. Demographic and clinical features, MDA criteria, and the impact of psoriatic skin manifestations on patients' quality of life (QoL) using the dermatology life quality index (DLQI) questionnaire were evaluated at baseline and after 24-week treatment. Adverse events were recorded. At week 24, 70.5% of patients ( n = 24) achieved MDA. A sub-analysis of dermatological indices of the MDA criteria showed that the psoriasis area severity index score was significantly improved and body surface area was significantly decreased at 24 weeks compared with that at baseline (both p < 0.001). For the rheumatologic indexes, tender joint count, swollen joint count, and tender entheseal points were all significantly improved at 24 weeks of therapy (all p < 0.01 vs. baseline). Mean DLQI value decreased approximately fourfold, and there were no safety concerns. The achievement of MDA as well as the significant improvement in DLQI and lack of adverse events in the context of a real-life setting shown here confirms the efficacy and safety of UST in PsA. [ABSTRACT FROM AUTHOR]

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-FCD161IL23 CD4 T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-FIL23 - IL17A-FCD161 - and IL17A-FCD161IL23 CD4 T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4T and CD4IL23 T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA. [ABSTRACT FROM AUTHOR]

Psoriasis frequency ranges from 1 to 3 % in white population, and arthritis occurs in 10-40 % of psoriasis patients, representing a relevant health issue. Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with psoriasis, in which ocular-, intestinal-, metabolic-, and cardiovascular-related manifestations can variably coexist. In order to favor early PsA and psoriasis diagnosis, it is crucial to rule out other conditions that can resemble the disease and delay appropriate therapeutic approach. Therefore, the aim of this review is to focus on PsA and psoriasis differential diagnosis. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder occurring in patients with psoriasis. Several studies have shown an association between Psa and traditional atherosclerotic risk factors. We evaluated the relationship between small dense low-density lipoproteins particles (sd-LDL) a risk marker for atherosclerosis, sub-clinical atherosclerosis and PsA in a group of 50 patients with PsA and in 100 controls. Cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, insulin, homeostasis model assessment (HOMA), Apo B, and sd-LDL have been measured. LDL particle separation was performed and seven LDL subfractions were obtained, LDL score (percentage of sd-LDL) and mean LDL particle size were calculated. PsA patients and control group differ significantly ( p < 0.001) in triglycerides values (119.3 ± 52.0 vs 90.7 ± 40.7 mg/dL), Apo B (1.1 ± 0.2 vs 0.9 ± 0.1 g/L), insulin (8.9 ± 4.9 vs 5.8 ± 3.2 mU/L), HOMA (2.2 ± 1.7 vs 1.3 ± 0.8), BMI (27.7 ± 3.3 vs 25.8 ± 3.8). LDL score is significantly higher in PsA as compared to control (9.0 ± 10.7 vs 2.9 ± 4.7 mg/dL); and mean LDL size is significantly lower in PsA than control (268.1 ± 4.6 vs 271.2 ± 2.7 Å). These differences were confirmed when stratifying PsA patients for treatment and for disease activity. LDL score and LDL diameter significantly were correlated with the carotid IMT in patients with PsA. These findings show a novel relationship between LDL score and mean LDL size with PsA diagnosis and with sub-clinical atherosclerosis. Sd-LDL gives potentially useful information in the risk assessment for atherosclerotic disease in PsA patients. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi's criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects. [ABSTRACT FROM AUTHOR]

To evaluate the impact of anti-TNF-α therapy on the body weight of rheumatoid arthritis (RA) patients following 24 months of treatment. Data were collected on all RA patients included in the Veneto Region's Registry of Biological Therapy from January 2007 to July 2012. Inclusion criteria were: start of monotherapy with adalimumab, etanercept, or methotrexate, no previous use of biologic therapy, and at least 24 months of treatment. At baseline, 12, and 24 months, each patient completed a questionnaire about physical activity, smoking, alcohol, and food habits. One hundred and thirty-one RA patients in monotherapy with etanercept ( n = 47), adalimumab ( n = 44), and methotrexate ( n = 40) were enrolled for this study. After 24 months of therapy, there was an increase of weight only in patients treated with anti-TNF-α. Patients on etanercept and adalimumab therapy showed a risk to gain weight six times greater compared to those on methotrexate therapy. The results of present study show that the use of anti-TNF-α in RA patients can be associated to a significant increase of body weight. This increase is not shown in patients under treatment with methotrexate. A more careful evaluation of weight changes needs to be considered in RA patients under anti-TNF-α treatment. [ABSTRACT FROM AUTHOR]

The pediatric syndrome characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and adult Behçet's disease share some clinical manifestations and are both polygenic autoinflammatory disorders with interleukin-1β showing to play a pivotal role. However, the diagnosis is mostly clinical and we hypothesize that specific criteria may be addressed differently by different physicians. To determine the diagnostic variability, we compared the answers of 80 patients with a definite diagnosis of Behçet's disease (age 42.1 ± 13.7 years) obtained by separate telephone interviews conducted by a rheumatologist, a pediatrician, and an internist working largely in the field of autoinflammatory disorders. Questions were related to the age of symptom onset, the occurrence of recurrent fevers during childhood, and the association with oral aphthosis, cervical adenitis and/or pharyngitis, previous treatments, possible growth impairment, the time lapse between PFAPA-like symptoms and the onset of Behçet's disease, and the occurrence of Behçet-related manifestation during childhood. The rheumatologist identified 30 % of patients with Behçet's disease fulfilling PFAPA syndrome diagnostic criteria, compared to the pediatrician and the internist identifying 10 and 7.5 %, respectively. Most of the patients suffered from recurrent oral aphthosis in childhood also without fever (50, 39, and 48 % with each interviewer), yet no patient fulfilled the Behçet's disease diagnostic criteria. Our data suggest that physician awareness and expertise are central to the diagnosis of autoinflammatory disorders through an accurate collection of the medical history. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA. [ABSTRACT FROM AUTHOR]

Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis variably combined with T cell-mediated neurologic and cutaneous manifestations. Early and aggressive treatment with systemic corticosteroids is the mainstay of treatment for VKHD. Additional use of immunosuppressants, intravenous immunoglobulins, and tumor necrosis factor-alpha inhibitors can help the most severely affected patients and work as corticosteroid-sparing agents. We report the case of a young woman with relapsing and multiresistant VKHD who demonstrated a stable remission of both uveitis and high-frequency hearing loss following rituximab intravenous administration (1 g. twice, 2 weeks apart, and 6 months later). A complete clinical response was observed 1 month since the first infusion, and no ocular relapses were recorded during the following year; in addition, audiometry showed a high-frequency hearing recovery in the right ear. Further observational studies are required to define the role of CD20 inhibition in the management of VKHD. [ABSTRACT FROM AUTHOR]

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4CD25, CD4CD25 FOXP3 and CD4CD25 CD127 Treg, and either mean fluorescence intensity (MFI) of FOXP3 on CD4 Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4CD25 helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4CD25 FOXP3 and CD4CD25 CD127 Treg cells and brighter MFI of IL-6Rα were observed both on CD4CD25- and CD4CD25 T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients. [ABSTRACT FROM AUTHOR]

Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis with exudative retinal detachments, often associated with neurologic and cutaneous manifestations. Therapy relies mainly on the use of corticosteroids, administrated as oral or intravenous high-dose pulses, and immunosuppressants. However, since macular edema and retinal detachment can often be refractory to systemic therapies, intravitreal triamcinolone acetate has been used successfully. Herein, we report the first case of refractory bilateral panuveitis in a young patient with VKHD successfully treated with dexamethasone intravitreal implant. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the influence of metabolic syndrome (MetS) on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α with a follow-up period of 24 months. A cohort of PsA patients was assessed at the University Federico II of Naples and at University of Padova. For the aim of the present study, patients' data were collected at baseline (T0), at 12 months (T1) and at 24 months (T2). Assessment of metabolic and disease activity parameters was performed at each visit. The NCEP-ACT III criteria were used to identify subjects with MetS and the MDA criteria to evaluate the disease activity. On the basis of the exclusion and inclusion criteria, 330 subjects were included in the study; 134 patients (40.7 %) were classified as not having MetS and 196 (59.3 %) as having MetS. An inverse association was found between presence of metabolic syndrome and the probability of achieving MDA. Univariate analysis indicated that patients with metabolic syndrome were less likely to achieve MDA than patients without metabolic syndrome (OR 0.45, p < 0.001). This inverse association remained statistically significant in the multivariate regression model (OR 0.56, p < 0.001). Metabolic syndrome is associated with a lower probability of achieving MDA in PsA patients in therapy with anti-TNF-α. [ABSTRACT FROM AUTHOR]

Autoinflammatory disorders (AIDs) are a novel class of diseases elicited by mutations in genes regulating the homeostasis of innate immune complexes, named inflammasomes, which lead to uncontrolled oversecretion of the proinflammatory cytokine interleukin-1β. Protean inflammatory symptoms are variably associated with periodic fever, depicting multiple specific conditions. Childhood is usually the lifetime in which most hereditary AIDs start, though still a relevant number of patients may experience a delayed disease onset and receive a definite diagnosis during adulthood. As a major referral laboratory for patients with recurrent fevers, we have tested samples from 787 patients in the period September 2007-March 2014, with a total of 1,328 AID-related genes evaluated and a gene/patient ratio of 1.69. In this report, we describe our experience in the clinical approach to AIDs, highlight the most striking differences between child and adult-onset AIDs, and shed an eye-opening insight into their diagnostic process. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), formerly known as familial Hibernian fever, is the most common autosomal dominant autoinflammatory disease, resulting from mutations in the TNFRSF1A gene, encoding the 55-kD tumor necrosis factor receptor. The pathophysiologic mechanism of TRAPS remains ambiguous and only partially explained. The onset age of the syndrome is variable and the clinical scenery is characterized by recurrent episodes of high-grade fever that typically lasts 1-3 weeks, associated with migrating myalgia, pseudocellulitis, diffuse abdominal pain, appendicitis-like findings, ocular inflammatory signs, and risk of long-term amyloidosis. Fever episodes are responsive to high-dose corticosteroids, but different classes of drugs have been reported to be ineffective. The use of etanercept is unable to control systemic inflammation, while interleukin-1 blockade has been shown as effective in the control of disease activity in many patients reported so far. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of classic cardiovascular risk factors, due to an imbalance between pro- and anti-inflammatory adipokines. Tumor necrosis factor (TNF)-α is a pro-inflammatory adipocytokine mainly produced by monocytes and macrophages with a central role in inflammatory responses, but it also induces adipocytes apoptosis, promotes insulin resistance, and stimulates lipolysis. The aim of this study was to evaluate the impact of therapy with etanercept (ETN), adalimumab (ADA), and methotrexate (MTX) on MetS components in a cohort of PsA patients with a follow-up period of 24 months. A retrospective study has been conducted in a cohort of PsA patients. On the basis of the inclusion criteria, we identified the first 70 consecutive patients, respectively, on ADA, ETN, and MTX, for a total of 210 patients achieving PsARC criteria during the observation period. As part of the routine clinical practice, assessment of metabolic parameters and of disease activity was recorded at baseline (T0), at 12 months (T1), and at 24 months (T2). The results show that when the specific components of the MetS were considered, taking also into account by regression analysis the effect of the confounding factors, the patients on etN and ADA show a significant improvement of the metabolic syndrome components (in detail, waist circumference, triglycerides, high-density lipoprotein cholesterol, and glucose) as compared to the MTX group. In conclusion, these data suggest that the biologic treatment in PsA can no longer be taken into consideration only for its positive effect on articular and cutaneous symptoms but also on the various aspects of this complex picture. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α is an essential cytokine for the host defense, and its depletion by treatment may facilitate the risk of infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in patients with PsA and concomitant latent tuberculosis infection (LTBI) comparing their outcome with non-infected PsA patients. This is a retrospective study in 321 patients with PsA, attending the Psoriatic Arthritis Clinic at the University Federico II of Naples, who had an inadequate response to DMARDs and started therapy with TNF-α blockers. We identified 40 patients with LTBI, who were included in this study along with 40 not infected PsA patients as control group. At baseline (T0) and every 3 months for 2 years (T2), data concerning PsA activity were registered. All patients underwent chest X-ray every 6 months (or 12 if appropriate). In each group, 22 patients were on etanercept therapy, 14 on adalimumab, and 4 on infliximab. Anti-TNF-α therapy was effective in both group of patients, and no statistically significant differences were found in the analysis of the study variables between the two groups from T0 to T2. No serious adverse events occurred in both groups, and no patient was withdrawn from therapy. Our experience suggests that anti-TNF-α treatment is effective and safe in PsA patients with concomitant LTBI. Therefore, neither LTBI nor chemoprophylaxis seems to influence the course of anti-TNF-α therapy. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a gluten-sensitive enthesopathy occurring in genetically predisposed individuals that is caused by a permanent intolerance to gluten. The major environmental factor associated with the risk of developing celiac-related complications is persistent exposure to dietary gluten. The aim of this study was to determine the prevalence of lower limb enthesopathy in CD patients at first diagnosis compared with CD patients on a gluten-free diet (GFD). Fifty-five untreated CD patients (group A) and 55 CD patients on a GFD from at least 1 year (group B), matched for age and sex, attending gastroenterology outpatient clinic of the University Federico II of Naples, were enrolled in this study. All patients underwent clinical and ultrasonography examination. Among group A, 27 (49.8 %) patients presented at least one entheseal alteration as compared with 15 patients (27.2 %) of group B (prevalence rate ratio 1.83, I.C. 95 % = 0.48-7.01; p < 0.001). The Glasgow ultrasound enthesitis scoring system (GUESS) was significantly higher in patients of group A than in patients of group B. In conclusion, our study shows that enthesopathy is more frequent in untreated CD subjects with positive anti-tissue transglutaminase antibodies title, as compared to those on GFD and absence of serum anti-tissue transglutaminase antibodies title. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin and/or nail psoriasis. TNF-α, in addition to its pro-inflammatory role, is an essential cytokine for the host's defense, and its depletion by treatment may facilitate the risk of viral infections or their reactivation. The aim of this study was to evaluate the efficacy and safety of TNF-α blockers in PsA patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter study carried out in four Italian centers specialized in the diagnosis and treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy, data concerning PsA activity and liver tests were registered. A total of 15 PsA patients with concomitant HCV infection were included in the study. At baseline, 13 patients had low viral load, and liver enzyme tests were within the normal range. During the observation period, these values remained stable. On the other hand, at baseline, a high viral load with slightly increased values of AST and ALT was detected in one patient. At T6 and T12, these values decreased. The remaining patient, at baseline, had low viral load, but with slightly increased AST and ALT values that normalized during the observation period. This is the greatest sample size available in the literature on this topic. The data suggests that anti-TNF-α agents are effective and safe in PsA patients with concomitant HCV. We suggest that the use of anti-TNF-α agents, accompanied by close monitoring, could be a therapeutic option. [ABSTRACT FROM AUTHOR]

Looking to the sustained psoriatic arthritis (PsA) joint as a model of local human inflammation, this study was designed to assess the T lymphocyte signal transduction pathways potentially involved in this chronic immune-mediated inflammatory process, as characterized by direct ex vivo analysis of T helper (Th)-17 T effector (Teff) cell phenotypes in synovial fluid (SF) and peripheral blood (PB) of clinically active PsA patients. The reverse-phase protein arrays (RPPA) technique was employed to identify STAT3, STAT1, JAK1, JAK2, PKCδ and ERK1/2 phosphoprotein levels on total T cell lysates in SF samples of PsA patients. Frequencies of T CD4IL-17A-F and T CD4IL-23R Th17 cells were quantified in SF and matched PB of PsA patients by flow cytometry and compared with PB of healthy controls (HC). Increased levels of JAK1, STAT3, STAT1 and PKCδ phosphoproteins were found in SF T cells of PsA patients, compared with PB of HC. The expansion of T CD4IL-17A-F cells, as well as of T CD4 cells expressing IL-23Rp19 (T CD4 IL-23R), considered as the pathogenic phenotype of effector Th17 cells, was found to be confined to the joints of PsA patients, as the frequencies of both populations were significantly higher in SF than in matched PB, or in PB of HC. In conclusion, T lymphocyte signal transduction pathway mapping revealed an enhanced activation of JAK1/STAT3/STAT1 and PKCδ phosphoproteins that may drive the local inflammatory process, characterized by the in vivo expansion of T CD4IL-17A-F and T CD4IL-23R Th17 Teff cells in SF of clinically active joints of PsA patients. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus (PF) and Behçet's disease (BD) are immune-mediated conditions which are usually treated with corticosteroids, immunosuppressants, and, when refractory, with biologic agents. In both diseases, interleukin (IL)-6 serum levels are increased driving the immune-mediated inflammatory process. Tocilizumab is a humanized monoclonal antibody, targeting IL6-receptor, used in the treatment of rheumatoid arthritis. Besides the current indication, it has been recently administered to patients with refractory immune inflammatory diseases as an off-label treatment. Here, we report the case of a woman affected with PF and BD, who did not respond to corticosteroids, immunosuppressants, and biologic agents including adalimumab, anakinra, and infliximab. A complete, long-lasting, clinical, and serological remission was achieved only with tocilizumab. To the best of our knowledge, the association between PF and BD has never been reported. Moreover, only two cases of BD and no cases of PF treated with tocilizumab have been described to date. A literature review on the use of biologic agents on patients with PF and BD was also carried out. [ABSTRACT FROM AUTHOR]

The objective of the study was the evaluation of arterial stiffness, a cardiovascular risk factor, in patients with psoriatic arthritis (PsA). Twenty PsA patients classified on the basis of the CASPAR criteria (M/W, 14/6; mean age, 38.6 years; range, 22-53), attending our out-patient clinic, and 20 healthy control subjects (M/W, 14/6; mean age, 38.7 years; range, 22-53) matched for age, weight, height and with similar cardiometabolic profile entered the study. An exclusion criterion was the presence of known cardiovascular risk factors. Central hemodynamic parameters and aortic pulse wave velocity (aPWV) were assessed non-invasively by a SphygmoCor device. A significantly higher aPWV was recorded in PsA patients when compared to controls. The difference remained statistically significant after adjustment for age, weight, height, heart rate (HR) and central mean pressure (mean±SE; PsA, 8.3 ± 0.2 versus control, 6.8 ± 0.2 m/s; p < 0.0001). Among PsA patients, aPWV was related to known duration of disease ( r = 0.63; p = 0.003). This result was confirmed after adjustment for the main confounders ( β = 0.011; p = 0.013). These results support the concept of psoriatic disease as a systemic condition involving not only the skin, joints and gastrointestinal tract but also arterial vessels. The involvement of the vascular system indicates the presence of pathogenetic mechanisms that could accelerate the atherosclerotic process in this condition. [ABSTRACT FROM AUTHOR]