Do Ultrasound Lung Abnormalities Correlate to Biomarkers and Male Gender in Rheumatoid Arthritis Patients? A Monocentric Cross-Sectional Study.

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. Methods: We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters p 0.0001), rheumatoid factor IgM (PLUS p 0.0006, PAUS p 0.02, LUS-T p 0.001) and ACPA (p 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 (p 0.02). The male gender was predictive of all LUS evaluations (p 0.001, 0.05, 0.001, respectively), which were higher than in women (p 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS (p < 0.05). Conclusions: We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex.

Is Active Synovitis of Metacarpophalangeal Joints a Neuropathic Condition in Rheumatoid Arthritis Patients? Results from an Ultrasound Study of Palmar Digital Nerves.

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, primarily characterized by pain. A significant proportion of patients report symptoms suggestive of neuropathic pain. The objectives of this study were to investigate the presence of an increased cross-sectional area (CSA) of the palmar digital nerves by ultrasound in patients with active synovitis of the metacarpophalangeal joints and to identify potential predictors of such an increase. (2) Methods: An ultrasound examination of the clinically most affected hand (from the second to the fifth metacarpophalangeal joint) was performed. The presence of synovitis was scored using a 0-3 semiquantitative method for each joint. The CSA of each pair of palmar digital nerves was measured. (3) Results: A significant correlation was found between the sum of the CSAs of the nerves and the Clinical Disease Activity Index (CDAI) (r = 0.387), as well as with the ultrasonographic grading of synovitis (r = 0.381) both at the patient and the joint level. These two variables, aimed at measuring disease activity, along with male gender, are the only predictors of the CSA of the palmar digital nerves. (4) Conclusions: Synovial inflammation of the metacarpophalangeal joints is, therefore, a condition that can influence the CSA of the palmar digital nerves and may partially explain neuropathic pain in patients with RA.

Sex Bias in Diagnostic Delay: Are Axial Spondyloarthritis and Ankylosing Spondylitis Still Phantom Diseases in Women? A Systematic Review and Meta-Analysis.

Diagnostic delay (DD) is associated with poor radiological and quality of life outcomes in axial spondyloarthritis (ax-SpA) and ankylosing spondylitis (AS). The female (F) population is often misdiagnosed, as classification criteria were previously studied mostly in males (M). We conducted a systematic review to investigate (i) the difference in DD between the sexes, the impact of HLA*B27 and clinical and social factors (work and education) on this gap, and (ii) the possible influence of the year of publication (before and after the 2009 ASAS classification criteria), geographical region (Europe and Israel vs. extra-European countries), sample sources (mono-center vs. multi-center studies), and world bank (WB) economic class on DD in both sexes. We searched, in PubMed and Embase, studies that reported the mean or median DD or the statistical difference in DD between sexes, adding a manual search. Starting from 399 publications, we selected 26 studies (17 from PubMed and Embase, 9 from manual search) that were successively evaluated with the modified Newcastle-Ottawa Scale (m-NOS). The mean DD of 16 high-quality (m-NOS > 4/8) studies, pooled with random-effects meta-analysis, produces results higher in F (1.48, 95% CI 0.83-2.14, p < 0.0001) but with significant results at the second analysis only in articles published before the 2009 ASAS classification criteria (0.95, 95% CI 0.05-1.85, p < 0.0001) and in extra-European countries (3.16, 95% CI 2.11-4.22, p < 0.05). With limited evidence, some studies suggest that DD in F might be positively influenced by HLA*B27 positivity, peripheral involvement, and social factors.

Post-COVID-19 and Post-COVID-19 Vaccine Arthritis, Polymyalgia Rheumatica and Horton's Arteritis: A Single-Center Assessment of Clinical, Serological, Genetic, and Ultrasonographic Biomarkers.

The potential role of the COVID-19 vaccine and infection to induce autoimmunity is currently underestimated despite the literature emphasizing arthralgia as a common adverse event. We aimed to study the impact of rheumatological complications post-COVID-19 (PC) and post-COVID-19 vaccine (PCV), comparing undifferentiated arthritis (UA) to Polymyalgia Rheumatica, Horton's Arteritis (PMR-HA) and isolated arthritis to UA with "connective-like" accompanying symptoms. We retrospectively included 109 patients with at least 6 months of follow-up, analyzing serum biomarkers, joint ultrasound (US), lung HRCT, DLCO, and HLA haplotypes. There were 87 UA patients showing increased gastrointestinal and lung involvement (p = 0.021 and p = 0.012), higher anti-spike protein IgG levels (p = 0.003), and anti-SARS-CoV-2 IgG positivity (p = 0.003). Among them, 66 cases progressed to ACR-EULAR 2010 early arthritis after 3 months, whereas PMR-HA patients were more commonly PCV (81.8%, p = 0.008), demonstrating higher CRP (p = 0.007) and ESR (p = 0.006) levels, a lower rate of ANA positivity (p = 0.005), and a higher remission rate after six months (p = 0.050). In UA patients, the prevalent HLA was DRB1*11 and C*07 (36.8% and 42.1%). Serum calprotectin, interleukin-6, and C*07 (p = 0.021, 0.041, 0.018) seemed more specific for isolated UA. Conversely, "connective-like" arthritis showed poorer DLCO (p = 0.041) and more frequent US synovitis (p = 0.041). In conclusion, UA is a frequent common PC and PCV complication and may persist over time when compared to PMR-HA.

Correction: Benucci et al. Predicting Loss of Efficacy after Non-Medical Switching: Correlation between Circulating TNF-α Levels and SB4 in Etanercept to SB4 Switchers and Naïve Patients with Rheumatic Disease. J. Pers. Med. 2022, 12, 1174.

The authors wish to make the following correction to this paper [...].

Do new and old biomarkers of early undifferentiated arthritis correlate with Arthritis Impact Measurement Scales?

OBJECTIVES: In early undifferentiated arthritis (EUA), the relationship between inflammatory biomarkers and disability is still unclear. The aim of this study was to correlate inflammatory biomarkers with the Arthritis Impact Measurement Scales (AIMS) in EUA. METHODS: Seventy patients with EUA were compared with 20 patients with established rheumatoid arthritis (RA). The association of AIMS [mobility, physical impairment (PI), dexterity, household activities, activities of daily living (ADL), social activity, pain, anxiety, depression] with serum laboratory [phase acute reactants, calprotectin, interleukin-6, tumour necrosis factor (TNF)-α, rheumatoid factor, anti-nuclear and anti-citrullinated peptide antibodies, HLA-DRB], clinical [Clinical Disease Activity Index (CDAI), fatigue, pain and stiffness NRS], x-ray and ultrasound biomarkers was analysed with non-parametric Spearman's rank correlation and Mann-Whitney U tests. RESULTS: No differences in AIMS were found between EUA and established RA patients, or between EUA patients that evolved into early RA (n=17) and those that remained EUA (n=53) at six months of follow-up. In EUA, erythrocyte sedimentation rate correlated with mobility impairment, PI and depression (p=0.04, p=0.03 and p=0.022, respectively), TNF-α correlated with PI (p=0.01) and calprotectin with anxiety (p=0.02). HLA-DRB1*11-positive EUA patients had lower ADL deficiency (p=0.006), depression (p=0.0004) and anxiety (p=0.01). CDAI correlated with PI (p=0.01) and pain (p=0.01), fatigue with PI (p=0.0001) and ADL (p=0.009), stiffness with PI (p=0.01), and Power Doppler ultrasound synovitis with PI (p=0.02) and pain (p=0.007). CONCLUSIONS: In EUA, physical and mood disorders are associated with new and old inflammatory serological, clinical and imaging biomarkers. HLA-DRB1*11-positivity may be protective against these disease-related features.

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

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

Two Novel Technologies for the Detection of Anti-cardiolipin and Anti ß2-Glycoprotein Antibodies in the Real Life: Chemiluminescent in Comparison to the Addressable Laser Bead Immunoassays.

In the present study, we evaluated two novel technologies, the chemiluminescent immunoassay (CIA) QUANTA Flash on BIO-FLASH (Inova Diagnostics, San Diego, CA, USA) and the addressable laser bead immunoassay (ALBIA) on BioPlex™ 2200 (Bio-Rad, Hercules, CA, USA) for the detection of anti-cardiolipin IgG/IgM (aCL) and anti-ß2-glycoprotein IgG/IgM (aß2GPI) antibodies. The study was performed on 134 samples from consecutive patients (59 males and 75 females, mean age 54 ± 10 years) who consulted a rheumatologist because thrombosis and/or pregnancy complications were present or another immunological disease (Sjogren's syndrome, inflammatory arthritis). Fourteen patients of the total fulfilled 25the Sydney criteria for APS and for these patients previous results of aPLs were available. Sera were tested for aCL and aß2GPI of IgG and IgM isotypes using CIA (BIO-FLASH) and ALBIA (BioPlex™ 2200). Overall agreement between CIA and ALBIA ranged from 88.1% (aCL IgG) to 97.8% (aß2GPI IgG). Cohen's kappa coefficient ranged from 0.53 to 0.91, implying moderate to almost perfect agreement. Almost perfect agreement was found between BioPlex™ 2200 and BIO-FLASH aß2GPI IgG and aCL IgM with Cohen's kappa of 0.91 and 0.88, respectively. On the other hand, moderate agreement was found between BioPlex™ 2200 and BIO-FLASH aCL IgG and ß2GPI IgM assays with Cohen's kappa of 0.57 and 0.53, respectively. The two novel technologies look promising and comparable but further studies with larger cohorts are needed to contribute to the better understanding of the new aPLs antibodies assays performance.

Tocilizumab modulates serum levels of adiponectin and chemerin in patients with rheumatoid arthritis: potential cardiovascular protective role of IL-6 inhibition.

OBJECTIVES: Adipokines play an important role in the pathophysiology of rheumatoid arthritis (RA), provide a link between the disease and overweight, contributing to explain the enhanced cardiovascular (CV) risk and influence the response to disease-modifying anti-rheumatic drugs. The aim of this study was to determine the possible effects of intravenous (IV) tocilizumab (TCZ), an interleukin-6 receptor antagonist, on serum levels of leptin, adiponectin, resistin, visfatin, and chemerin. METHODS: Forty-four RA patients with active disease (DAS28-ESR ≥3.2) were treated with IV TCZ (8 mg/kg) once every 4 weeks for six months: 20 patients received TCZ as monotherapy and 24 in association with methotrexate (MTX). At baseline and monthly, before each infusion, body mass index, DAS28-ESR and Health Assessment Questionnaire (HAQ) were recorded. The laboratory parameters, including the adipokines serum levels were collected at baseline and after six months. RESULTS: At the end of the follow-up, ESR, CRP, DAS28-ESR and HAQ resulted significantly improved in patients received TCZ as monotherapy or combined with MTX. Lipid profile showed only a significant increase of total cholesterol. A significant reduction of chemerin and an increase of adiponectin were observed in the whole population and in the subgroups of the patients analysed (TCZ mono or combined therapy) without any significant correlations with clinical and biochemical parameters. No changes in the leptin and resistin levels were detected. CONCLUSIONS: TCZ is able to regulate serum levels of chemerin and adiponectin in RA patients, independently of the disease treatment response, which contributes to explain the CV safety of TCZ.

The profiling of axial spondyloarthritis patient candidate to a biologic therapy: Consensus from a Delphi-panel of Italian experts.

OBJECTIVE: The project aimed to collect expert consensus statements for the profiling of patients with axial spondyloarthritis (axSpA) candidate to biologic agents (bDMARDs) treatment, in order to better define the drivers for the best treatment choice. METHODS: The 6 more interesting topics about axSpA patient profiling were identified by the project steering committee and a panel of axSpA Italian experts. A systematic literature review (SLR) was performed for each of the selected topics according to the PICO format. Two rounds of a modified Delphi process were conducted. In the 1st round, the steering committee evaluated the results of the SLR in order to formulate statements for each topic. In the 2nd round, the experts panel discussed, rephrased when needed, and voted the level of agreement (on a 5-point Likert-type scale) for each statement. Consensus was defined as ≥66% agreement. RESULTS: The topics selected for the analysis were the differential efficacy of available bDMARDs on enthesitis/dactylitis, uveitis, radiographic progression and cardiovascular involvement, and the clinical response in non radiographic-axSpA and in patients receiving a second-line bDMARD. The Delphi rounds formulated 19 statements, all reaching the defined level of consensus in a second round including 25 rheumatologists highly skilled in the management of axSpA. CONCLUSION: Identified consensus statements can help clinicians to apply to routine-care settings the results from clinical studies and international recommendations, providing a guide for individualization of treatment strategy in axSpA patients.

Factors correlated with the improvement of endothelial dysfunction during Abatacept therapy in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis patients are exposed to a high risk of cardiovascular morbidity and mortality even in the early phases of the disease. METHODS: We evaluated carotid common carotid intimal media thickness (ccIMT) intimal thickness and brachial flow-mediated dilation (FMD) of 45 rheumatoid arthritis patients without known cardiovascular risk factors or heart disease on a stable dose of prednisone 5.2±1.2 mg/day and Methotrexate 11.5±2.1 mg at baseline (T0) and after 12 months (T1) of treatment with Abatacept 125 mg/week. The comparison between T0 and T1 (t- and Mann-Whitney test), correlation (Spearman r), and predictivity (linear regression) of FMD, ccIMT vs clinical and laboratory parameters (disease activity 28 score, tumor necrosis factor alpha [TNFα], interleukin-6, erythrocyte sedimentation rate, C-reactive protein (CRP), CD3+, CD3+/CD4+, CD3+/CD8+, CD19+(B), CD20+(B), NK CD3-CD56+CD16+, CD14+ HLA DR+, CD4+CD28+, CD4+CD28, rheumatoid factor IgM, IgA, RF IgG, anti-citrullinated peptide antibodies) were also evaluated. RESULTS: During Abatacept treatment, ccIMT and FMD remained stable and disease activity 28 score, CRP, erythrocyte sedimentation rate, and interleukin-6 decreased significantly (p=0.0001, 0.002, 0.0002, 0.0001 respectively). At T0, only ccIMT resulted as correlated with baseline TNFα values (p=0.0245) in an inverse proportion. At T1, ccIMT correlated with CD3/CD8+ lymphocytes number (p=0.0351) and FMD with CRP (p=0.0075). In regression analysis, baseline ccIMT and FMD had a low predictivity for TNFα (p=0.011) and CRP (p=0.049) at T1, respectively. CONCLUSION: This study shows that the endothelial function remained stable during Abatacept treatment.

Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what's on the horizon?

OBJECTIVE: The main objective was to determine the prevalence of anti-dense fine speckled (DFS70) antibodies in a stable population of undifferentiated connective tissue disease (UCTD) to better define their potential role. METHODS: Immunological and clinical records of 91 long-standing UCTD patients were studied. DFS pattern was determined using the IIF ANA test on HEp-2 cells and anti-DFS70 antibodies were tested by chemiluminescence assay and by DFS70 line immunoassay. RESULTS: Twelve (13.2%) of 91 serum samples were positive for anti-DFS70 antibodies by chemiluminescence assay and line immunoassay. There was no statistical significance between the prevalence of anti-ENA and anti-DNA autoantibodies in patients with and without anti-DFS70 antibodies. No differences were found in the clinical characteristics of both groups. The presence of the anti-DFS70 antibodies was related to the younger age class. CONCLUSION: The high prevalence of anti-DFS70 antibodies in the UCTD patients suggested the potential role of these autoantibodies as a marker in the evolution of UCTD to CTD.

Correlation between HLA haplotypes and the development of antidrug antibodies in a cohort of patients with rheumatic diseases.

INTRODUCTION: The aim of this study was to investigate the correlation between human leukocyte antigen (HLA) haplotypes and the development of antidrug antibodies (ADAs) in a cohort of patients with rheumatic diseases. PATIENTS AND METHODS: We evaluated the presence of ADAs in 248 patients with inflammatory rheumatic diseases after 6 months of treatment with anti-TNF drugs: 26 patients were treated with infliximab (IFX; three with rheumatoid arthritis [RA], 13 with ankylosing spondylitis [AS], 10 with psoriatic arthritis [PsA]); 83 treated with adalimumab (ADA; 24 with RA, 36 with AS, 23 with PsA); 88 treated with etanercept (ETA; 35 with RA, 27 with AS, 26 with PsA); 32 treated with certolizumab (CERT; 25 with RA, two with AS, five with PsA); and 19 treated with golimumab (GOL; three with RA, seven with AS, nine with PsA). Serum drug and ADA levels were determined using Lisa-Tracker Duo, the ADA-positive samples underwent an inhibition test, and the true-positive samples underwent genetic HLA typing. To have a homogeneous control population, we also performed genetic HLA typing of 11 ADA-negative patients. RESULTS: After inhibition test, the frequency of ADAs was 2/26 patients treated with IFX (7.69%), 4/83 treated with ADA (4.81%), 0/88 treated with ETA (0%), 4/32 treated with CERT (12.5%), and 1/19 treated with GOL (5.26%). The frequency of HLA alleles in the examined patients was HLA-DRß-11 0.636, HLA-DQ-03 0.636, and HLA-DQ-05 0.727. The estimated relative risks between the ADA-positive patients and the ADA-negative patients were HLA-DRß-11 2.528 (95% CI 0.336-19.036), HLA-DQ-03 1.750 (95% CI 0.289-10.581), and HLA-DQ-05 2.424 (95% CI 0.308-15.449). CONCLUSION: This is the first study that shows an association between HLA and genetic factors associated with the occurrence of ADAs in patients with rheumatic diseases, but the number of samples is too small to draw any definite conclusion.

Musculoskeletal ultrasonography for psoriatic arthritis and psoriasis patients: a systematic literature review.

Objective: To systematically review the role of musculoskeletal US in patients suffering from PsA or psoriasis (Pso) in terms of prevalence, diagnosis, prognosis, monitoring and treatment. Methods: A systematic literature review was conducted through medical databases (MEDLINE via PubMed, Embase) and the grey literature up to September 2015 to inform a new study of the Musculoskeletal Ultrasound Study Group of the Italian Society for Rheumatology. All articles reporting data on musculoskeletal US in PsA or Pso were included and extracted according to the underlying clinical question. Results: A total of 86 publications were included. The prevalence of US abnormalities showed a wide range for each examined feature (e.g. 37-95% for entheses thickness of the lower limbs). The performance of US for diagnosis of disease or elementary lesions was variable across studies, but no study evaluated the overall performance of US in addition to clinical findings for diagnosing PsA. Considering US in defining PsA and Pso prognosis, several works focused on US of entheses of lower limbs in Pso, while for the monitoring of PsA activity five different scoring systems were identified. Last, the results of the role of US in guiding intra-articular interventions were controversial for the clinical outcomes, but in favour of US for accuracy. Conclusion: despite the recognized importance of US in the management of PsA and Pso, this review clearly demonstrated the need of pivotal research in order to optimize the use of US in the diagnosis and monitoring of psoriatic disease.

Safety, efficacy and immunogenicity of switching from innovator to biosimilar infliximab in patients with spondyloarthritis: a 6-month real-life observational study.

Biosimilar infliximab (INX) was recently approved by the European Medicine Agency for the treatment of rheumatoid arthritis, ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis, psoriatic arthritis (PsA), and psoriasis on the grounds that its pharmacokinetics, safety, and efficacy were comparable to those of innovator INX. The aim of this study was to investigate the real-life efficacy, safety, and immunogenicity of switching from innovator to biosimilar INX in patients with spondyloarthritis (SpA). Forty-one patients attending three Italian rheumatology centres with a previous diagnosis of SpA and clinically inactive or moderate disease activity (ASDAS-CRP < 2.1; 22 with AS, five with enteropathic arthritis, 10 with PsA, and four with undifferentiated SpA), who had been treated for more than 6 months with innovator INX in accordance with the ASAS/EULAR guidelines, were switched to biosimilar INX for pharmaco-economic reasons (Tuscany Law No. 450 of 7 April 2015) and followed up for 6 months. A record was kept of their BASDAI, BASFI, ASDAS-CRP, DAS28-CRP (in the presence of peripheral disease), MASES, VAS pain scores, the duration of morning stiffness, and adverse events (AEs). At the time of the switch, the patients had a median age of 50.9 years (range 23-80), a median disease duration of 124.5 months (range 14-372), and a median duration of treatment with innovator INX of 73.7 months (range 6-144). After 6 months of biosimilar INX therapy, there were no statistical differences in their median BASDAI (2.73 ± 1.5 vs. 2.6 ± 1.3, p = .27), BASFI (2.34 ± 1.3 vs. 2.17 ± 1.2, p = 0.051), ASDAS-CRP (1.35 ± 0.3 vs. 1.28 ± 0.2, p = 0.24), DAS28-CRP (2.66 ± 0.67 vs. 2.67 ± 0.35, p = 0.92), MASES (0.35 ± 0.7 vs. 0.17 ± 0.4, p = 0.08), or VAS pain scores (18 ± 14.7 vs. 16.7 ± 11.3, p = 0.55), whereas the median duration of morning stiffness had significantly decreased (7.2 ± 6.9 vs. 5.8 ± 6, p = 0.02). Furthermore, there was no change in circulating INX (4.22 ± 2.89 vs 4.84 ± 2.86 µg/mL, p = 0.80) or anti-INX antibody levels (27.76 ± 17.13 vs 27.27 ± 17.28 ng/mL, p = 0.98). The switch from innovator to biosimilar INX in this Italian multicentre SpA cohort was not associated with any statistically significance differences in efficacy, adverse events or anti-drug antibody level.

Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy and tolerability.

BACKGROUND: Oral glucocorticoids (GCs) have been shown to be effective in reducing the inflammatory symptoms of rheumatoid arthritis, but their use is not supported by evidence in spondyloarthritis (SpA). Modified-release (MR) oral prednisone taken at bedtime has been shown to be more effective than immediate-release prednisone taken in the morning. The efficacy of low-dose MR prednisolone in patients with SpA is unknown. PATIENTS AND METHODS: This single-center cohort study retrospectively assessed the effectiveness and safety of 12-week low-dose MR prednisone (5 mg daily, bedtime administration) in GC-naïve adult patients with symptomatic axial SpA. A 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or a final BASDAI score of <4 according to disease activity at baseline was chosen as the primary outcome parameter after MR prednisone. RESULTS: Fifty-seven patients were evaluated; of them, 41 had an active disease (BASDAI score of ≥4) at baseline. MR prednisone significantly reduced BASDAI (from 5.5±2.6 to 3.0±2.8, P<0.001) as well as inflammatory symptoms, pain, fatigue and morning stiffness. The overall response rate after MR prednisone was 52.6% (53.7% in patients with active SpA and 50.0% in patients with low-active disease; nonsignificant). At multivariable analysis, none of the considered clinical findings independently predicted the response to MR prednisone in subjects with active SpA. Overall, seven patients (11.8%) had nonserious adverse drug reactions after MR prednisone. CONCLUSION: In patients with symptomatic SpA and naïve to GCs, low-dose MR prednisone reduced the symptoms and clinical indexes of disease activity and showed a positive safety profile.

Occult spondyloarthritis in inflammatory bowel disease.

Spondyloarthritis (SpA) is a frequent extra-intestinal manifestation in patients with inflammatory bowel disease (IBD), although its real diffusion is commonly considered underestimated. Abnormalities in the microbioma and genetic predisposition have been implicated in the link between bowel and joint inflammation. Otherwise, up to date, pathogenetic mechanisms are still largely unknown and the exact influence of the bowel activity on rheumatic manifestations is not clearly explained. Due to evidence-based results of clinical studies, the interest on clinically asymptomatic SpA in IBD patients increased in the last few years. Actually, occult enthesitis and sacroiliitis are discovered in high percentages of IBD patients by different imaging techniques, mainly enthesis ultrasound (US) and sacroiliac joint X-ray examinations. Several diagnostic approaches and biomarkers have been proposed in an attempt to correctly classify and diagnose clinically occult joint manifestations and to define clusters of risk for patient screening, although definitive results are still lacking. The correct recognition of occult SpA in IBD requires an integrated multidisciplinary approach in order to identify common diagnostic and therapeutic strategies. The use of inexpensive and rapid imaging techniques, such as US and X-ray, should be routinely included in daily clinical practice and trials to correctly evaluate occult SpA, thus preventing future disability and worsening of quality of life in IBD patients.

Ultrasonographic wrist and hand abnormalities in early psoriatic arthritis patients: correlation with clinical, dermatological, serological and genetic indices.

OBJECTIVES: The aims of our study are to describe the wrist and hand ultrasound (US) abnormalities compared to clinical examination in early psoriatic arthritis (ePsA) and to analyse their correlation with clinical, dermatological, serological and genetic indices. METHODS: We analysed 1120 fingers and 224 wrists of 112 early PsA, with MyLab70 Xview (Esaote, linear probe) ultrasound (US). Power Doppler active synovitis (AS), erosions, finger tendons tenosynovitis or peritendinitis (TP) and pseudotenosynovitis (PT), were compared to clinical (BASDAI, SHAQ), dermatological (PASI and psoriasis aspects), serological (ESR, CRP, ACPA) and genetic (HLA haplotypes) indices. RESULTS: All US abnormalities were present: AS was more frequent at wrists (50/224 [22.3%]), followed by hand PT (68/1120 [6,1%]) and TS (29/1120 [2.6%]), while erosions were rare (10/1120 [0.8%]). US abnormalities were independent of ePsA clinical indices (except erosions - even if represented only in a low percentage - that correlated to BASDAI [p<0.05]), while they were associated to several dermatological (except PASI), serological and genetic parameters: psoriasis (all p<0.0001), palmoplantar psoriasis (wrist and hand AS p<0.0005 and p<0.005, respectively), hand psoriasis (all p<0.0001), nail dystrophy (hand AS p<0.05, PT p<0.0001, erosions p<0.0001); positive CRP (all p<0.0001), ESR (wrist and hand AS p<0.005 and <0.0005, respectively, TS, PT and erosions p<0.0001) and ACPA - even if represented only in 1.78% of patients - (wrist and hand AS and TS p<0.0001, PT p<0.5); HLA-B27 (wrist and hand AS p<0.0001, TS p<0.01, PT p<0.05), -B35 (wrist and hand AS p<0.01 and p<0.05, respectively), -B38 (wrist and hand AS p<0.0001, TS p<0.0001, PT p<0.005), -CW6 (wrist AS p<0.05), -DR4 (wrist and hand AS p<0.0001, TS p<0.0001, PT p<0.005). CONCLUSIONS: US abnormalities of hand and wrist were independent of clinical ePsA indices (except erosions), while they correlated to dermatological (except PASI), serological and genetic parameters of disease.