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Objective. To verify if tocilizumab (TCZ) is associated with an increased risk of cardiovascular (CV) events compared with etanercept (ETN) in rheumatoid arthritis (RA). Methods. This is a retrospective cohort study on administrative healthcare databases (AHD) in Italy. Patients were identified using a validated algorithm based on AHD. Exposure to specific drugs was estimated by the drug prescription recorded in the AHD. The occurrence of acute CV events (myocardial infarction, stroke, other CV events) was derived from the hospital discharge forms. The association between TCZ or ETN and CV events was estimated using competing risk models, adjusting for pre-specified confounders. Results. We identified 1,752 subjects with RA, 1,086 treated with ETN and 666 with TCZ. TCZ did not increase the overall risk of acute CV events, even when adjusted for pre-specified confounders (hazard ratio HR 0.95, 95% confidence interval 95%CI 0.54-1.66), specifically of acute myocardial infarction (HR 0.39, 95%CI 0.15-1.06), stroke (HR 1.44, 95%CI 0.24-8.68) or other CV event (1.07, 95%CI 0.59-1.92). Conclusion. RA patients with TCZ do not have a medium-term excess of CV risk in patients compared with ETN.

OBJECTIVES: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). METHODS: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. RESULTS: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. CONCLUSIONS: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.

Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with skin psoriasis and manifests a wide clinical phenotype, with proposed differences between sexes. Current treatments are based on traditional disease-modifying anti-rheumatic drugs (DMARD), and biologic agents and studies have reported different clinical response patterns depending on sex factors. We aimed to identify sex differences in drug retention rate in patients with PsA and performed a systematic research on MEDLINE, EMBASE and Cochrane databases (1979 to June 2015) for studies regarding effectiveness (measured as drug retention rate) in PsA in both traditional DMARDs and biologics. Demographic data as well as retention rates between sexes were extracted. From a total 709 retrieved references, we included 9 articles for the final analysis. Only one study reported data regarding DMARDs, while eight studies reported retention rate for anti-tumor necrosis factor (TNF) biologics, mainly infliximab, adalimumab and etanercept. No differences were reported in retention rates between sexes for methotrexate, while women manifested lower retention rates compared to men with regard to anti-TNF. We highlight the need to include sex differences in the management flow chart of patients with PsA.

Objective To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard Methods We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. Results 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. Conclusion US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis.

Objective: The aims of our study were to investigate the prevalence of ultrasound (US) abnormalities in the foot of patients with rheumatoid arthritis (RA) and to compare them with the clinical findings. Methods: One hundred RA patients were enrolled in the study. Bilateral US examination of metatarsophalangeal (MTP) joints, proximal interphalangeal (PIP) joints, midfoot joints (talonavicular, calcaneo-cuboid, medial, intermediate and lateral navicularcuneiform and cuneiform-metatarsal joints and cuboid-4th and 5th metatarsal joints) were examined for synovitis and erosion. In addition the plantar fascia and the insertion of the anterior and posterior tibialis and peroneous brevis tendons were imaged. Results: Effusion with synovial proliferation was visualised only at MTP joints in 84 out of 200 (42%) feet, at MTP plus at least one joint of the midfoot in other 41 out of 200 (20%) feet (making a total of 125 out of 200 (62%) MTP joints) exclusively in one or more joints of the midfoot in 7 out 200 (3%) feet, in the PIP joint of the 2nd and 3rd toes in 3 (1.5%) and 4 (2%) feet respectively, while no effusion with synovial proliferation was visualised in the PIP joint of the 4th and 5th toes. Synovitis was present most frequently in the 2nd MTP joint whilst erosions were most frequently imaged in the 5th MTP joint. Conclusion: US examination appears to be a useful imaging technique to study joint and tendon involvement of the foot in RA patients. Moreover, US examination of the foot is more sensitive than clinical examination in the detection of joint inflammation and allows for a better understanding of the features and the progression of the disease. © Clinical and Experimental Rheumatology 2011.

Objectives. To investigate the ability of ultrasonography (US) to detect synovitis in metatarsophalangeal joints (MTP) in patients with suspicion of early arthritis, and to discriminate between diagnoses. Methods. Patients referred to early arthritis clinics for differential diagnosis were enrolled, and clinical and laboratory measures were recorded. Ultrasonography of MTPs was performed searching for synovial hypertrophy (SH), joint effusion (JE) and power Doppler (PD), graded from 0 to 3 on a semi-quantitative scale. Patients were classified according to definite classification criteria, or as undifferentiated arthritis or non-inflammatory pathology. US findings were compared across different diagnoses and diagnostic accuracy was calculated taking clinical diagnosis as reference.Results. Out of 427 patients (71% rheumatoid arthritis (RA), 20% undifferentiated arthritis (UA), 15% spondyloarthritides (SpA), 13% non-inflammatory), 307 (71.9%) showed SH, 120 (25.5%) JE, 77(18.0%) PD. RA patients had median JE, SH and PD scores significantly higher than non-inflammatory and other diseases. Patient with UA and SpA had higher scores of SH and JE compared to non-inflammatory, no significant differences were present among different diagnosis. In RA, SH and JE were more frequently detected in the second MTP, and PD in the fifth. Crystal-related arthritis showed a tendency towards a more frequent involvement of the first MTP. The diagnostic accuracy of single US measures was moderate, but the detection of a PD of 2 or more provided a high specificity for the diagnosis of RA. Conclusions. US can be used as additional information in patients evaluated in an early arthritis setting. High scores of JE, SH and PD, together with the pattern of involvement are suggestive of RA.

The aims of our study were to investigate the prevalence of ultrasound (US) pathologic abnormalities and to compare them with the clinical findings in the knee of rheumatoid arthritis (RA) patients. One hundred RA patients were enrolled in the study. Bilateral US examination of the knee was performed to visualise the presence of effusion, synovial proliferation, bone erosions, femoral cartilage abnormalities, quadricipital and/or patellar enthesopathy. The popliteal fossa and the calf region were also evacuate to detect popliteal cyst. We observed joint effusion in 140 out of 200 (70%) knees. Synovial hypertrophy was present in 115 out of 140 (82%) knees associated with effusion and in 22 out of 115 (19%) knees intra-articular power Doppler (PD) signal was found. Hyperechoic spots within the cartilage layer, suggestive of pyrophosphate crystals deposit, were detected in the knees of 3 patients. US signs of quadricipital and/or patellar enthesopathy were detected in 53 out 200 (26%) knees. Bone erosions were visualised in 16 out 200 (8%) knees. Popliteal cyst was found in 66 out of 200 (33%) joints. US examination of the knee is more sensitive than clinical examination in the detection of joint inflammation and allows for the identification of different patterns of pathologic changes at knee level, including morphostructural changes at both cartilage and tendon level.

Psoriatic arthritis (PsA) is an arthropathy associated to psoriasis, which is part of the spondyloarthropathy family, and which may present with various forms, from mono-oligoarthritis to symmetric polyarthritis mimicking rheumatoid arthritis. In longstanding disease, the symmetric polyarthritis is the most common pattern of PsA, involving small joint of hands, feet, wrists, ankles and, very frequently, knees. Other common features are represented by the inflammation of enthesis and tendons. Ultrasound (US) examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 10-14 MHz. One-hundred and sixty-six knee joints were investigated in a total of 83 patients. Prior to US assessment, all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (detected by palpation and/or active or passive mobilisation of the knee), and knee swelling. Sixty-two (74.7%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 70 (84.3%) knee joints. In the 59% of the patients we noticed synovial hypertrophy. Enthesitis was present in 39.7% of the subjects studied. This study demonstrated that US detected a higher number of inflamed knee joints and enthesis with respect to clinical assessment in PsA patients.

The knee is a frequent target for gout and calcium pyrophosphate dihydrate (CPPD) disease with involvement of both articular and peri-articular structures. The aims of the present study were to investigate the relationship between clinical and ultrasound (US) findings and to describe the prevalence and distribution of crystal deposits in the knee in patients with gout and CPPD disease. Thirty patients with gout and 70 patients with CPPD disease were enrolled in the study. Prior to US assessment all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/ absence of pain, tenderness (evocated by palpation and/or active or passive mobilisation of the knee), and knee swelling. US examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 9 MHz. Two hundred knee joints were investigated in a total of 100 patients. Fifty-one (25.5%) knee joints were found clinically involved, while at least one US finding indicative of joint inflammation was obtained in 73 (36.5%) knee joints. The most frequent US finding indicative of knee joint inflammation was joint effusion, detected in 21 (35%) out of 60 knees and in 52 (37%) out of 140 knees, in gout and CPPD disease, respectively. Ten (17%) out of 60 knees and 21 (15%) out of 140 knees were found positive for synovial hypertrophy with or without intra-articular power Doppler, in gout and CPPD disease respectively. Sonographic evidence of crystal deposition within joint cartilage (hyaline and fibrocartilage) was more frequently seen than in the soft tissue in the knee. This study demonstrated that US detected a higher number of inflamed knee joints than clinical assessment in patients with crystal related arthropathies and that the distribution of crystal deposits at joint cartilage level permitted distinction between gout and CPPD disease. Further studies are required to investigate both sensitivity and specificity of US features indicative of crystal aggregates at both tendon and entheseal level.

Systemic lupus erhthematosus (SLE) is an autoimmune multisystem disorder characterised by frequent musculoskeletal manifestations. Joint involvement in SLE is usually not erosive or destructive but some patients develop hand erosive arthritis or deforming arthropathy of the hand (respectively "rhupus" hand and Jaccoud arthritis). To date, few studies, evaluated joint and tendon involvement in SLE patients by US. We studied wrist and hand structure, using ultrasound, in 50 patients affected by SLE, detecting inflammatory joint involvement in 80% of them at the wrist and in 50% at the hand. Tenosynovitis was visualised in 14 patients, while structural damage was present in 12% of the SLE group. Those results reinforce the importance of including musculoskeletal ultrasound in the patient assessment, especially in those cases in which physical examination is not conclusive.

Objective. To study the frequency and features of joint and tendon involvement in the hand of patients with primary Sjögren's syndrome (pSS) by musculoskeletal ultrasound (US) examination. Methods. Forty-eight patients with pSS diagnosed according to the preliminary classification criteria proposed by the American-European Classification Criteria Group were enrolled in the study. Bilateral US examination of the 1st-5th metacarpophalangeal (MCP), 2nd-5th proximal interphalangeal (PIP) joints and of flexor tendons were performed. A semi-quantitative grading method (0 to 3) for scoring joint effusion, synovial proliferation and intra-articular power Doppler (PD) signal was used. Results. We observed clear evidence of inflammatory arthritis in 9 (18.7%) patients. Bone erosions at MCP and/or PIP joint were visualized in 6 out of 48 (12.5%) patients. In 10 (20.8%) patients we imaged flexor tenosynovitis which appeared more frequent than in healthy subjects even if no statistically significant difference was detected. Conclusion. US examination appears to be a useful imaging technique to study joint and sofi tissue involvement in connective tissue diseases. The presence of bone erosions in pSS patients is unexpected. Future studies will hopefully concentrate more on defining the erosive capability of connective tissue disorders together with inflammatory involvement of tendons. © Copyright Clinical and Experimental Rheumatology 2009.

Three-dimensional (3D) US is a new sonographic modality which represents a promising tool in the assessment of joint and periarticular tissues abnormalities in rheumatic diseases. The available literature has recently underlined its advantages mainly related to the virtual operator independence due to image acquisition of infinite 3D data sets obtained by transducer automated sweeping. Shortening of the US examination time represents another notable advantage over conventional two-dimensional (2D) US. The aim of the present study was to investigate the validity of 3D US in assessing Achilles tendon enthesitis by comparing it with 2D US. US examinations were performed by using a Logiq 9 (General Electrics Medical Systems, Milwaukee, WI) equipment with a high-frequency (8-15 MHz) volumetric probe. One hundred and eighty-six Achilles tendon enthesis of 93 SpA patients were examined. The analysis of each basic US finding demonstrated from good to excellent agreement rates between 3D and 2D US, both in dichotomous assessment of sonographic lesions and in the use of semi-quantitative grading. Excellent agreement between the two modalities was demonstrated in the assessment of both inflammatory changes and structural lesions. Our study for the first time demonstrated that 3D US is a valid imaging modality for the assessment of Achilles tendon enthesitis.

In the rheumatology literature, most of the available evidence on three-dimensional ultrasound (3D US) is related to the acquisition process and highlights the virtual operator independence and shortening of the US examination time. The main aim of this study was to compare 3D US using a high-frequency volumetric probe and conventional 2D US at the wrist and hand in patients with rheumatoid arthritis (RA). The 3D US examinations were performed using a Logiq 9 (General Electrics Medical Systems, Milwaukee, WI) with a high-frequency (8-15 MHz) volumetric probe. Overall, there is good-to-excellent agreement between the two modalities relating to both joint inflammation and bone erosion. This study is an initial step towards establishing a methodology necessary for developing multi-centre US studies which are aimed at assessing hand involvement in patients with RA.

The knee joint is a frequent focus of attention for rheumatologists when assessing patients presenting to a clinic and may represent underlying intra-articular inflammatory pathology or involvement of the surrounding soft tissues. This study describes the correlation between clinical and ultrasound findings in patients presenting with a variety of rheumatic disorders and knee pain. US imaging provides for a sensitive and detailed identification of different intra- and peri-articular pathology responsible for knee pain.

Objective To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients. Methods The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P Results Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage. Conclusion We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.

Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.

Objective To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD). Methods The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2). Results 445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005). Conclusion In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility

ObjectiveThese analyses aim to comparatively evaluate the persistence on treatment of different biological disease-modifying antirheumatic drugs (bDMARDs) when administered in monotherapy compared with combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA) patients receiving first-line biologics.DesignThis is a retrospective observational study on Administrative Healthcare Databases.MethodsData were extracted from healthcare databases of the Lombardy Region, Italy (2004–2013), as a part of the RECord-linkage On Rheumatic Diseases study, on behalf of the Italian Society for Rheumatology. Analyses included patients with RA starting first-line approved course of bDMARDs and evaluated drug survival by using Cox proportional hazard models. Results are presented as HRs and 95% CI, crude and adjusted for prespecified confounders (age, sex, disease duration, Charlson Comorbidity Index (CCI), previous infections, use of concomitant glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs)).Results4478 patients with RA were included (17.84% monotherapy). Etanercept, adalimumab and infliximab were the most prescribed first-line biologics. bDMARD monotherapy was associated with longer disease duration, higher CCI, lower glucocorticoids and NSAIDs use. Compared with monotherapy, combination associated with a lower risk of failure (adjusted HR 0.79, 95% CI 0.72 to 0.88). Among monotherapies, considering etanercept as reference, adalimumab (1.28, 95% CI 1.03 to 1.59) and infliximab (2.41, 95% CI 1.85 to 3.15) had higher risk of failure. Concomitant methotrexate (0.78, 95% CI 0.70 to 0.87), leflunomide (0.80, 95% CI 0.65 to 0.98) or csDMARD combinations (0.77, 95% CI 0.68 to 0.87) reduced the risk of bDMARD withdrawal.ConclusionAdalimumab and infliximab monotherapies show lower retention rate compared with etanercept. The relatively small number of therapeutic courses different from tumour necrosis factor (TNF) inhibitors makes more difficult to achieve conclusive results with other biologics. Concomitant methotrexate, leflunomide and csDMARDs combination associate with longer survival on bDMARD. Our data confirm the effectiveness of the current practices in the choice of etanercept as first-line anti-TNF monotherapy and strengthen the currently recommended use of bDMARDs in combination with csDMARDs.

Objectives Hepatitis B (HBV) infection, which is prevalent worldwide, is also frequently seen in patients with rheumatoid arthritis (RA). The Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) endorsed a national consensus process to review the available evidence on HBV management in RA patients and to produce practical, hospital-wide recommendations. Methods The consensus panel consisted of infectious disease consultants, rheumatologists and epidemiologists and used the criteria of the Oxford Center for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results A core-set of statements has been developed to help clinicians in the management of patients with RA and HBV infection. Vaccination and prophylaxis of RA patients treated with biological drugs have been also discussed. Conclusions HBV infection is not rare in clinical practice; a screening for HBV in all patients with early arthritis is not universally accepted, while it is considered mandatory before starting any immunosuppressive or hepatotoxic treatment. In fact, a specific risk, associated with the use of biologic treatments, exists for patients with HBV infection, although longitudinal studies of viral reactivation are generally reassuring. RA patients with HBV infection should be referred to the hepatologist and correctly classified into active or inactive carriers. Patients with active hepatitis B should undergo antiviral treatment before starting immunosuppressive treatments. Occult HBV carriers should be monitored or receive prophylaxis on the basis of the risk of reactivation associated with the administered treatment.

Item does not contain fulltext OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p

Objectives: To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis. Methods: In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (

Objective. The aim of this study was to develop and validate an algorithm to assist the attribution of neuropsychiatric (NP) events to underlying disease in SLE patients. Methods. Phase 1 identified and categorized candidate items to be included in the algorithm for the attribution of an NP event to SLE and their relative weights through a literature-informed consensus-driven process. Using a retrospective training cohort of SLE, phase 2 validated items selected in phase 1 and refined weights through a data-driven process, fitting items as independent variables and expert evaluation (clinical judgement) as reference standard in logistic models. Phase 3 consisted of a validation process using an external multicentre retrospective SLE cohort. Results. Phase 1 identified four different items: timing of the NP event, type of event, confounding factors and favouring factors. The training and validating cohorts included 228 and 221 patients, respectively. Each patient experienced at least one NP event characterized using the ACR case definition. In these samples, items selected in phase 1 showed good performance in discriminating patients with NPSLE: the area under the receiver operating characteristic curve using dichotomous outcomes was 0.87 in the training set and 0.82 in the validating set. Relevant cut-offs of the validated score identify events with a positive predictive value of 100% (95% CI 93.2, 100) and 86.3% (95% CI 76.2, 93.2) in the training and validating cohorts, respectively. Conclusion. A new algorithm based on a probability score was developed and validated to determine the relationship between NP events and SLE.

Objectives To investigate whether children with juvenile idiopathic arthritis (JIA) in clinical remission have subclinical synovial disease on ultrasound, and whether ultrasound abnormalities predict an early flare of synovitis. Methods Thirty-nine consecutive children who had clinically defined inactive disease (ID) for a minimum of 3 months underwent ultrasound assessment of 52 joints. All joints were scanned for synovial hyperplasia, joint effusion, power Doppler (PD) signal and tenosynovitis. Patients were then followed clinically for up to 2 years until a flare of synovitis occurred in one or more joints, or until the 2-year visit if the disease remained in clinical remission. Results Synovial hyperplasia, joint effusion, PD signal and tenosynovitis in at least one joint were detected in 76.9%, 66.7%, 33.3% and 15.4% of patients, respectively. During the 2-year follow-up, 24 patients (61.5%) experienced sustained ID, whereas 15 patients (38.5%) had a flare of synovitis in a total of 45 joints after a median of 10.6 months (range 6.3–13.7 months). At study entry, the rate of synovial hyperplasia, joint effusion and tenosynovitis was comparable between patients with persistent ID and patients with synovitis flare, whereas patients with persistent ID had a greater frequency of PD signal than patients with synovitis flare. Only 17 of the 45 flared joints had ultrasound abnormalities at study entry. Conclusion The authors found that ultrasound-detected synovial abnormalities are common in children with JIA in clinical remission. However, the presence of ultrasound pathology did not predict an early flare of synovitis in the affected joints.

Objectives: To investigate the prevalence of ultrasound (US) detectable inflammation in hips of patients with ankylosing spondylitis (AS) and the relationship between US and measures of disease activity and severity. Methods: Consecutive patients with AS attending the rheumatology units involved in this study were enrolled. Clinical and demographical data were recorded. US examination of bilateral hips was performed at the same time, evaluating anterior longitudinal scan to search for synovial hypertrophy (SH), joint effusion (JE) or power Doppler (PD) positive synovitis. Results: A total of 56 patients were included, median age (interquartile range, IQR) 49 (39, 59.5), median disease duration 98 (72, 204) months, 80.3% were treated with TNF-α inhibitors, median BASDAI 2.65 (1.96, 3.95), 30.3% had hip tenderness. US JE was found in 26.7% of patients, US SH in 16%, no patient had detectable PD. The concordance between clinical findings and US abnormalities was moderate, with a kappa of 0.44. Patients with detectable US abnormalities had higher median visual analogue scale (VAS) pain and C-reactive protein (CRP), while there was no significant association with other measures of disease activity and disability. In the subgroup of patients with no hip tenderness, US alterations were still significantly related to higher CRP levels, while in patients with hip tenderness and no US abnormalities CRP was not higher than in the asymptomatic patients. Conclusions: US assessment of hip joint in AS patients can be considered of value, as suggested by the correlation with relevant clinical and laboratory measures. In asymptomatic patients, US examination might provide further information on subclinical involvement. © Clinical and Experimental Rheumatology 2012.

Introduction: In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.Methods: Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.Results: Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.Conclusion: In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.Trial registration number: Current Controlled Trials ISRCTN2486111.

Psoriatic arthritis (PsA) is an arthropathy associated with psoriasis, which is part of the spondyloarthropathy family, and which may present with various forms, from mono-oligoarthritis to symmetric polyarthritis mimicking rheumatoid arthritis. In longstanding disease, the symmetric polyarthritis is the most common pattern of PsA, involving the small joints of hands, feet (the involvement of which seems to be very common, ranging from 50 to 100% of patients), wrists, ankles and knees. Other common features are represented by the inflammation of enthesis and tendons. Its exact prevalence, in Italy, should be about 30% in psoriatic subjects or 0.42% when considering the general population. The aims of our study were to investigate, by US examination, the prevalence and the features of foot involvement in PsA and to describe their correlations with clinical findings. Ultrasound (US) examinations were performed using a Logiq 9 (General Electric Medical Systems, Milwaukee, WI) equipped with a multifrequency linear probe, working at 14 MHz. One hundred and eighty feet were investigated in a total of 101 patients. Prior to US assessment, all patients underwent a clinical examination by an expert rheumatologist who recorded the presence/absence of pain, tenderness (detected by palpation and/or active or passive mobilisation of the feet) and swelling. US finding indicative of metatarsophalangeal joint inflammation were obtained in 77 (76.2%) patients, while only 34 (33.7%) patients were positive to the clinical examination. This study demonstrates that US detected a higher number of inflamed joints with respect to clinical assessment in PsA patients.

Objective: To assess the impact of the knee joint inflammation, detected by ultrasonography (US), on functional disability in patients with recent-onset inflammatory polyarthritis (IP). Methods: We included patients who had IP for less than 12 months and who had more than 5 swollen joints. All patients were assessed clinically at baseline. US was used to identify joint inflammation at multiple joint sites including: hands, wrists, elbows, shoulders, knees, ankles and feet. Joint group involvement was defined when at least one joint showed intra-articular signs of inflammation (synovial fluid abnormalities and/or synovial hypertrophy), according to the OMERACT definitions. Functional disability was measured using the health assessment questionnaire (HAQ) score. All patients with complete clinical and US data were included in the analysis. Results: Patients with US knee involvement showed more active and severe disease at baseline. The mean difference of HAQ between patients with and without US knee inflammation was 0.42 (95%CI 0.22, 0.62; p

Objective. To investigate the prevalence and severity of sonographic-detected abnormalities in knee osteoarthritis (OA) and to correlate ultrasound (US) findings with clinical data. Methods. Outpatients with chronic, painful knee OA according to the ACR criteria were consecutively recruited and underwent clinical and US examinations. An expert rheumatologist recorded the presence of knee joint pain, swelling and tenderness, patient's global assessment of knee pain using visual analogue scale (VAS), and Lequesne Index of severity for knee OA.A second rheumatologist, blinded to the clinical data, performed the knee US examination using a Logiq9 machine equipped with a 12MHz linear probe and registering the presence of joint effusion, synovial proliferation, power Doppler (PD) signal, Baker's cyst, osteophytes and femoral cartilage abnormalities. Results. One hundred and sixty-four knees of 82 patients (53 women, 29 men) were studied; mean age was 63.2 ±8.1 SD years, mean disease duration was 4.3±5.6 SD years. All patients complained of at least one knee joint pain during physical activity. Mean patient's VAS for knee pain was 48.4±19.9 SD mm, mean Lequesne Index was 8.2 ±4.4 SD. Knee swelling was present in 39% of the patients and tenderness was found in 65.8%. US showed: joint effusion in 43.3% of the patients, synovial proliferation in 22.1%, PD signal in 2.9%, Baker's cysts in 6.6%, cartilage abnormalities in 79%, osteophytes in 100%. In all patients US findings were present at least at the level of one knee. Statistically significant correlations were demonstrated between a composite inflammatory score and both VAS (p=0.004) and Lequesne Index (p

In order to identify rate and stability of remission induced by low-dose prednisone comedication in early rheumatoid arthritis (RA), we evaluated patients with early RA (

Objectives. This study aimed to evaluate the usefulness of a systematic musculoskeletal ultrasonographic (US) assessment in the detection of residual disease activity in patients with early RA who achieved clinical remission. Methods. We prospectively studied 106 early RA patients receiving conventional DMARDs according to a disease activity score (DAS)-steered therapeutic protocol over a 24-month period. Standard evaluation included clinical, laboratory, functional and systematic (44 joints) US assessment. US indexes of grey scale (GS) and power Doppler (PD) synovitis were correlated with clinical evaluation, laboratory indexes and clinical outcome. Clinical remission was defined when DAS was < 1 .6 at two consecutive visits 3 months apart. Results. US examination was significantly more sensitive than clinical examination, both in active disease and in remission. In patients with an active disease, both clinical and US indexes correlated with CRP, whereas in remission only PD still remained significantly correlated. In clinical remission, 95% of the patients showed residual GS synovitis, and 41% of them showed a positive PD signal. Positive PD signal, even in a single joint, resulted the main predictor of relapse within 6 months, both in univariable and multivariable logistic regression analysis. Conclusions. In a cohort of early RA patients treated with conventional DMARDs, US-GS can detect residual disease activity more sensitively than clinical examination both in active disease and in remission. Moreover, PD-positive synovial hypertrophy identifies an ongoing inflammation even during remission and predicts short-term relapse.

Objectives To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region. Design Case–control and cohort diagnostic accuracy study. Methods In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region. Results The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%). Conclusions AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.

Objective. To determine the presence and clinical significance of antibodies to cyclic citrullinated peptides (anti-CCP) in psoriatic arthritis (PsA). Methods. We performed a cross-sectional study on 102 outpatients (56 men) with PsA consecutively recruited from a tertiary referral center. Median disease duration was 36 months (interquartile range 21-81). All patients were investigated for peripheral joint and axial involvement, enthesitis, and dactylitis. Laboratory investigations included anti-CCP, assessed by enzyme-linked immunosorbent assay and IgM rheumatoid factor (RF). Plain radiographs of pelvis, wrists, hands, and feet were performed in all cases. Results. Anti-CCP were detected in 16/102 patients, 8/68 with symmetric polyarthritis, 1/8 with asymmetric polyarthritis, 2/20 with mono-oligoarthritis, 1/2 with mutilating arthritis, and 0/4 with exclusive axial or distal interphalangeal (DIP) involvement. The male:female ratio as well as frequency of dactylitis, enthesitis, and nonexclusive axial or DIP joint involvement were similar in the anti-CCP positive and negative groups. Anti-CCP positive patients were more frequently treated with disease modifying antirheumatic drugs and showed higher number of involved joints, and higher frequency of erosive arthritis and positive RF. Using multiple logistic regression, anti-CCP (but not RF) were significantly associated with erosive arthritis (odds ratio 9.8; 95% confidence interval 1.87-51.8) and ≥ 10 involved joints (17.99; 3.6-89.2). Conclusion. Anti-CCP can be found in a small but significant proportion of patients with a clinical picture of PsA and are associated with erosive arthritis and multiple joint involvement.

The aim of the present study was to perform an immunohistological assessment of the synovial tissue from involved small joints in rheumatoid arthritis (RA) and to explore the reliability of a mini-invasive ultrasound (US)-guided technique of small joint synovial biopsy for the histopathological assessment. Synovial tissue collected during arthrotomic surgery of small joints in nine patients served as the gold standard for the validation of the histological assessment. Small hand-joint synovial biopsies from an additional nine patients with erosive RA were obtained by a mini-invasive US-guided procedure, performed percutaneously by the portal and rigid forceps technique. Using digital image analysis, the area fractions of synovial macrophages (CD68 cells), T cells (CD3 cells) and B cells (CD20 cells) were measured in all high-power fields of every sample at different cutting levels. The representative sample was defined as the minimal number of high-power fields whose mean area fraction would reflect the overall mean area fraction within a percentage mean difference of 10%. For each patient, a range of three to five large samples for surgical biopsies and a range of 8-12 samples for US-guided biopsies were collected and analysed. In arthrotomic samples, the analysis of a randomly selected tissue area of 2.5 mm2 was representative of the overall value for CD68, CD3 and CD20 cells. US-guided samples allowed histological evaluation in 100% of cases, with a mean valid area of 18.56 mm2 (range 7.29-38.28 mm2). The analysis of a cumulative area of 2.5 mm2 from eight randomly selected sections (from different samples or from different cutting levels) allowed to reduce the percentage mean difference to less than 10% for CD68, CD3 and CD20 cells. In conclusion, US-guided synovial biopsy represents a reliable tool for the assessment of the histopathological features of RA patients with a mini-invasive approach.