Search

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.

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.

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.

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.

The field of inflammatory arthritis owes much to the advances in imaging technology which have enlightened not only clinical specialists but also researchers worldwide. The most exciting developments in recent decades have centred upon rheumatoid arthritis (RA) and more specifically the ultrasound (US) and magnetic resonance imaging (MRI) findings at various stages of the natural history of this condition. Investigation of RA using the standard techniques of plain radiography (x-ray) and more sophisticated computerised tomography (CT) have now been superseded by the exponential growth of use of US and MRI and this has been born out by the profusion of scientific papers published on these subjects.This paper aims to review the array of imaging modalities available as investigative tools to the rheumatologist when presented with various clinical scenarios by patients with RA.

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.

One of the largest challenges to the field of musculoskeletal ultrasonography is attempting to accurately quantify the changes seen in chronic arthritis. With advances in ultrasound technology, researchers have been increasingly exploring ways of more accurately assessing these changes and attempting to reach consensus with agreed scoring systems. This review presents the main scoring systems developed for quantifying sonographic findings indicative of synovitis and joint damage in patients with rheumatoid arthritis. Further investigation is required to attain international consensus on such scoring systems and to evaluate their impact on therapeutic decision-making.

Data on the origin and biological function of procalcitonin, the pro-hormone of calcitonin, are scarce. Since this peptide can be induced in bacterial invasive infections, serum procalcitonin levels may be useful in differential diagnosis of systemic inflammatory response syndrome. This review will focus on the clinical significance of changes in serum procalcitonin levels in patients with connective tissue diseases and other rheumatic disorders.

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.

Objective: To determine the usefulness of plasma procalcitonin (PCT) measurement to suspect infectious etiology in febrile patients with systemic autoimmune disease. Methods: PCT C-Reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) were measured in 44 consecutive inpatients with a diagnosis of systemic autoimmune disease and fever >38°C. After careful microbiologic screening no obvious infection was demonstrated in 24 patients (Group A) while an infectious bacterial complication was diagnosed in 20 cases (Group B). Results: Median PCT levels were signficantly higher in the group B (1.11 vs 0.24 ng/ml; p = 0.0007), whereas the differences for CRP, WBC and ESR did not reach statistical significance. PCT also exhibited a good sensitivity and specificity (75%) in differentiating patients with infection from those with disease flare. With respect to positive and negative predictive values (71.4% and 78.2%), PCT markedly exceeded the other variables. By analyzing PCT values by disease we identified a false positive subgroup of patients suffering from adult onset Still's disease (AOSD), showing markedly elevated PCT levels in absence of infection. By excluding these patients, PCT showed a very good sensitivity and specificity (73.6% and 89.4%) and the area under receiver operating characteristics (ROC) curve rose from 0.801 to 0.904. Conclusion: Our data indicate that elevated PCT concentrations offer go od sensitivity and specificity for the diagnosis of systemic bacterial infection in febrile patients with systemic autoimmune diseases. However, in fever associated with AOSD PCT may be elevated even in the absence of infectious complication.

Objective. To assess the efficacy of tidal irrigation in patients with Milwaukee shoulder syndrome (MSS). Methods. Ten patients with clinical diagnosis of MSS underwent ultrasound examination and tidal irrigation followed by instillation of methylprednisolone and tranexamic acid. A single shoulder was treated in 9 cases; in one patient with bilateral shoulder involvement, both shoulders were treated at different times. Six patients had longlasting disease (Group A) unsuccessfully treated with repeated joint fluid aspirations and intraarticular corticosteroid injections. Four patients had recent-onset illness without radiologic damage but with clinical findings similar to classic MSS (Group B), not previously treated with corticosteroid injections with symptoms dating from 3 months or less. Clinical examination including evaluation of adverse events, range of motion, and pain score by a 100 mm horizontal visual analog scale was scheduled just before tidal irrigation and after 2 and 6 months following the procedure in all cases. Results. Short- and longterm safety was excellent in all patients. Group A patients experienced short-lived improvement so that tidal irrigation had to be repeated within 6 to 10 months. No further therapy was necessary in any of the Group B patients during a mean followup of 16.5 months (range 12-24) due to a persistent clinical improvement without clinically detectable joint effusion. Conclusion. Closed-needle joint irrigation is a minimally invasive procedure, which led to a significant improvement in both pain and active motion in patients with longstanding symptoms. Patients with recent-onset disease recovered completely.

In rheumatoid arthritis (RA), low-dose glucocorticoid (GC) therapy has a well-established effect on disease activity. Particularly in early RA, robust evidence demonstrates that GC treatment in association with standard disease-modifying anti-rheumatic drugs (DMARDs) is effective in inducing high remission rates, earlier and more persistently. Despite international recommendations that discourage long-term concomitant GC use, the majority of the clinical trials and observational registries on biologic agents include a high proportion (up to 80%) of patients in treatment with GC. From an analysis of the literature, a substantial lack of reliable information about the efficacy of GC in association with biologic agents emerges; in particular, the role of GC co-therapy in sustaining remission after biological therapy discontinuation remains to be clarified. Given the increasing prevalence of patients in sustained remission, a rational discontinuation strategy should include low-dose GCs in the experimental design to elucidate their role in inducing and maintaining biologic-free remission, for efficacy, safety and pharmacoeconomic considerations.

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 (

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 evaluate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria for rheumatoid arthritis (RA) with a systematic literature review and a meta-analysis. Methods: PubMed, Embase, Cochrane Library and the abstracts of the ACR and EULAR meetings (2010-2012) were searched for original articles or abstracts with the following inclusion criteria: 1) recent onset arthritis, with at least one swollen joint and no alternative diagnosis; 2) the ACR/EULAR 2010 criteria as index test; 3) the prescription of methotrexate (MTX) or disease modifying antirheumatic drugs (DMARDs) at any time during follow-up as reference standard. Data were pooled using the bivariate model. Three meta-analyses were performed with MTX (primary analysis), DMARDs or their combination (secondary analyses) as reference standard. Heterogeneity was formally tested and explored performing an influence analysis. Results: The search identified 1,277 references. Six full papers and 4 abstracts met the inclusion criteria. With MTX as reference standard, sensitivity (95% confidence interval, CI) was 0.80 (0.74,0.85), specificity 0.61 (0.56,0.67), positive likelihood ratio (LR) 2.11 (1.92,2.32), negative LR 0.31 (0.25,0.38) and the diagnostic odds ratio (DOR) was 6.74 (5.49,8.28). Using DMARDs as reference standard, sensitivity was 0.73 (0.64,0.80), specificity was 0.74 (0.68,0.79), LR+2.85 (2.53,3.22), LR- 0.35 (0.27,0.45) and DOR 8.03 (6.4,10.09). Using the combination of MTX and DMARDs as reference standard, intermediate results were obtained. The influence analysis detected one potentially influential study. However, its exclusion from the meta-analysis did not have a clinically relevant impact on the results. Conclusions: The new classification criteria have good sensitivity, lower specificity and an overall moderate diagnostic accuracy. These results confirm that the criteria have classificative and not diagnostic function. © 2013 Sakellariou et al.

Objective. To make an inventory of quality and content of currently available and published sets of health care quality indicators (HCQIs) for RA and OA.Methods. A systematic review was performed for documents on the development and/or a description of HCQIs for the management of patients with RA and/or OA, using the PubMed, EMBASE, Web of Science, Cochrane and CINAHL databases up to 1 December 2010 and official websites of arthritis organizations. The following data were extracted: general characteristics, contents and quality of developmental process (six aspects related to the definition of target, target group and stakeholders, patient involvement, description of development and test of validity).Results. The search yielded 498 potentially eligible references and two websites, with ultimately six original HCQI sets for RA and/or OA being identified (one for RA and OA, two for OA and three for RA). The number of HCQI ranged from 7 to 27, with the majority being process indicators. No conflicting indicators between the HCQI sets for one condition were seen. Concerning the quality of the developmental process, all six sets lacked patient involvement.Conclusion. Only a limited number of HCQI sets for the management of OA and RA are available, mainly including process indicators. The developmental process was methodologically suboptimal in all cases. As improvement of health care quality is an ongoing process, there is a need for development of HCQIs covering different aspects of health care quality (structure, process and outcome) and using appropriate methodology. © The Author 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.

Objective: To test the predictive ability of remission in terms of long-term disability in patients with recent-onset inflammatory polyarthritis (IP). Methods: Consecutive patients with early IP, recruited between 1990 and 1994 (first cohort) and 2000 and 2004 (second cohort), were included in this study. Remission was defined as the absence of clinically detectable joint inflammation on a 51-joint count. In additional analyses, less stringent definitions of remission were used based on the 40-and 28-joint counts. Remission was assessed at 1, 2, and 3 years after inclusion. A 5-year Health Assessment Questionnaire score ≥1 (moderate disability) was chosen as the primary outcome measure. Results: A total of 841 and 498 patients from the first and second cohorts, respectively, completed 5 years of followup. In the first cohort, patients with at least 1 episode of remission had lower odds of 5-year disability (odds ratio [OR] 0.26, 95% confidence interval [95% CI] 0.17-0.41). The number of times in remission correlated with the odds of disability, with a mean decrease in the probability of disability of ∼64% for each additional time point in remission (OR 0.38, 95% CI 0.28-0.52). The time until first remission was not associated with functional disability. Remission according to less stringent criteria showed a weaker protection against future disability. Similar results were found in the second cohort. Conclusion: Patients with IP achieving a state of sustained remission early are less likely to show long-term deterioration of function compared with patients who do not achieve remission. The most persistent remission under the most stringent definition of remission has the lowest probability of long-term disability. © 2011, American College of Rheumatology.

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

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.

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.