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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 (<1 year) who were randomized to receive (P) or not (non-P) low-dose prednisone in association with step-up disease-modifying antirheumatic drug therapy over 2 years. Prevalence and duration of clinical remission were evaluated in the first and second year. Each treatment group included 105 patients; no significant differences were found at baseline. During the first year, P patients achieved higher rates of clinical remission with a time-averaged odds ratio (OR) of 1.965 (CI 95% 1.214-3.182, P= 0.006). Moreover, they showed a higher probability of sustained remission during the second year (OR 4.480, CI 95% 1.354-14.817, P= 0.014). In conclusion, we found as in early RA low-dose prednisone comedication is associated with higher rate of clinical remission, earlier disease activity control and more stable remission over time.

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 soft 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.

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.

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.

Identification of early indicators of diagnosis and prognosis together with tight control of disease activity are the current goals of management of early arthritis. Several studies in the literature to date suggest that musculoskeletal ultrasonography (US) may have a role in this setting. US is a valid and reliable tool for the assessment of inflammatory arthritis - either as an ultra-sensitive measure of inflammation or joint damage. US is also useful in the differential diagnosis of early arthritis, both identifying disease specific findings and integrating clinical findings into structured diagnostic algorithms. Grey scale and power Doppler US are sensitive disease activity and severity markers, identifying subgroups of patients with poorer clinical and radiological outcomes, even once clinical remission has been achieved. The present review provides an update of the available data and discusses research issues of ultrasound imaging in early arthritis.

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 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.

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.

The use of Doppler ultrasound in rheumatology has grown in recent years. This is partly due to the increasing number of rheumatologists who perform US in their daily clinical practise and also to the technological advances of US systems. Both colour Doppler and power Doppler are used to evaluate the degree of intra- and peri-articular soft tissue inflammation. Moreover, Doppler US has been found to be of help in the assessment of vascular pathologies such as the vasculitides. In this review we provide an update of the data regarding the use of colour Doppler and power Doppler in rheumatology.

Ultrasonography (US) has proved to be a useful tool for the clinical evaluation of patients with rheumatic diseases. It is also recognised as a useful imaging technique in interventional radiology. In the last few years, a number of rheumatologists have also described and advocated the use of US guidance in joint and soft tissue aspiration and injection technique in clinical practice. Moreover, US-guided synovial biopsy methods have been proposed as an interesting and reliable method for the histopathological assessment of small and large joint sinovium. The present review provides an update of the available data regarding the use of US in interventional procedures in clinical rheumatology.

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.

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 masculine 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 significantly 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 good 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 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 > or = 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.

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.