Impact of gender, work, and clinical presentation on diagnostic delay in Italian patients with primary ankylosing spondylitis.

The variability of demographic, social, genetic, and clinical factors might influence the time between the onset of symptoms and the diagnosis [diagnostic delay (DD)] of ankylosing spondylitis (AS) in different geographic areas. Different clinical manifestations in men and women affected by AS might indicate a possible role of gender in DD. The aim of the present study was to investigate the influence of demographic, social, genetic, and clinical factors on DD and the differences of DD between men and women related to the presence of different demographic, social, clinical, and genetic parameters in an Italian cohort of primary AS patients. A total of 135 Italian primary AS patients (45 female and 90 male, 27.9 ± 0.89 years old at onset) were studied. The DD, gender, education and work (manual or non-manual) levels, and type of first clinical presentation (inflammatory back pain, arthritis, enthesitis) at onset, family history of AS, and HLA B27 presence were analyzed. The DD (8.744 mean ±0.6869) was significantly higher in men (p = 0.0023), in axial presentation (p = 0.0021), and in manual work (even if with low significance, p = 0.047). The lower DD in women in comparison to that in men was likely related to higher education (p = 0.0045) and work (p = 0.0186) levels, peripheral involvement (p = 0.0009), and HLA B27 positivity (p = 0.0231). DD was higher in AS patients: male, employed in manual jobs, and with axial symptoms at onset. In men, DD seemed to be negatively influenced by lower level of education and work, axial clinical presentation, and HLA B27.

Rhupus syndrome: assessment of its prevalence and its clinical and instrumental characteristics in a prospective cohort of 103 SLE patients.

The term "rhupus" is traditionally used to describe patients with coexistence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The aim of the present work was to investigate prevalence, clinical and radiological picture as well as the serological profile of a series of rhupus patients; SLE patients and RA patients from our Unit were used as disease control groups. A total of 103 consecutive SLE patients were screened; among the entire cohort, 10 patients (9.7%) were classified as "rhupus". In our rhupus patients SLE features preceded the onset of arthritis in 5 patients (50%) while in the remaining patients arthritis appeared before or simultaneously (3 and 2 patients respectively). As compared with SLE patients, rhupus patients have significantly less kidney involvement (p=0.01) while no differences were observed between neuropsychiatric, cutaneous, hematological involvement or serositis. At our physical examination, 9 (90%) rhupus patients were presenting active joint involvement; CRP positivity and ESR levels resulted significantly higher than in SLE (p=0.006) patients while no differences were observed with respect to RA patients. In all rhupus patients, at least one pathological finding was revealed by ultrasound (US) examination at wrist and/or hand joints; overall, rhupus patients presented higher scores in all the US parameters with respect to SLE patients, especially at hands; no statistically significant differences have been observed with respect to RA patients. Magnetic resonance (MR) revealed erosions in all rhupus patients with a concomitant bone edema in five patients. The cumulative erosive burden in rhupus patients was significantly higher than in SLE patients and similar to RA patients (SLE vs rhupus p=0.005); bone pathology distribution was also similar between rhupus patients and RA patients. These data suggest the importance of assessing joint involvement in SLE with advanced imaging techniques and of evaluating the presence of prognostic factors for joint disease severity in order to establish adequate disease monitoring and to institute early appropriate therapies to avoid late consequences of unrecognized concomitant rheumatoid arthritis (Amezcua-Guerra et al., 2006 [25]; Zhao et al., 2009 [26]).

The promising role of lung ultrasound in systemic sclerosis.

Ultrasound (US) has an emergent and relevant role in the assessment of systemic sclerosis (SSc) even if there are many fields and applications that still have not been sufficiently explored. In this review, we will report an update of the available data regarding the use of US in lung involvement that might cause disability and mortality in SSc patients. Lung US does not employ ionizing radiation and is more rapid and less expensive than traditional high-resolution tomography (HRCT). Furthermore, recent initial studies have demonstrated that US scores correlated to HRCT and functional respiratory test results in SSc interstitial lung disease. The research agenda for the future should include a more profound investigation of its specificity (comparison with healthy subjects and other diseases) and sensitivity to change at follow-up, to adequately disseminate its use in daily practice and clinical trials.

Ultrasound imaging for the rheumatologist XXXIX. Sonographic assessment of the hip in fibromyalgia patients.

Fibromyalgia syndrome (FMS) is a common form of non-inflammatory rheumatism within the general population with symptoms often mimicking those of arthritis or muscle disorders. Arthralgic symptoms in the region of the hip are commonly mentioned by patients with FMS and one of the diagnostic trigger points for the condition is found around the greater trochanter. To date, no formal imaging studies using ultrasound (US) have been performed in FMS. This study describes the correlation between clinical and US findings in patients presenting with primary FMS to rheumatology clinics. In the majority of the patients, no significant pathological US abnormalities were detected.

Ultrasound imaging for the rheumatologist XXXVII. Sonographic assessment of the hip in ankylosing spondylitis patients.

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.

Ultrasound imaging for the rheumatologist XXXIV. Sonographic assessment of the painful foot.

The foot is increasingly the 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 (US) findings in patients presenting with a variety of rheumatic disorders linked with foot pain. Poor correlation was found between conventional clinical examination and US in cases with joint inflammation, tendonitis and, more particularly, those cases with enthesopathy.

Ultrasound imaging for the rheumatologist XXXIII. Sonographic assessment of the foot in early arthritis patients.

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.

Ultrasound imaging for the rheumatologist. XXXII. Sonographic assessment of the foot in patients with psoriatic arthritis.

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.

Ultrasound imaging for the rheumatologist XXIX. Sonographic assessment of the knee in patients with osteoarthritis.

OBJECTIVES: 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<0.0001). CONCLUSIONS: This US study showed both inflammatory abnormalities and structural damage lesions in knee OA. Interestingly, statistically significant correlations were demonstrated between US inflammatory findings and the main clinical tests for OA, confirming that sonography has a relevant role in the global evaluation of patients with knee OA.

Ultrasound imaging for the rheumatologist. XXVIII. Impact of sonographic knee joint involvement in recent-onset inflammatory polyarthritis.

OBJECTIVES: 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<0.001). This difference was still clinically and statistically significant even after controllino for disease extension and pattern of joint involvement. US shoulder involvement was also significantly and independently associated with higher mean HAQ scores. CONCLUSIONS: US knee involvement is associated with higher disability in IP at first presentation. US is a good tool to help in the differentiation of patients with recent-onset IP with different disease severity.

Ultrasound imaging for the rheumatologist XXVI. Sonographic assessment of the knee in patients with psoriatic arthritis.

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.

Ultrasound imaging for the rheumatologist. XXV. Sonographic assessment of the knee in patients with gout and calcium pyrophosphate deposition disease.

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.

Ultrasound imaging for the rheumatologist XXX. Sonographic assessment of the painful knee.

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.

Ultrasound imaging for the rheumatologist. XXIII. Sonographic evaluation of hand joint involvement in primary Sjögren's syndrome.

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.

Ultrasound imaging for the rheumatologist. XXII. Achilles tendon involvement in spondyloarthritis. A multi-centre study using high frequency volumetric probe.

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.

Ultrasound imaging for the rheumatologist. XXI. Role of ultrasound imaging in early arthritis.

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.

Ultrasound imaging for the rheumatologist. XX. Sonographic assessment of hand and wrist joint involvement in rheumatoid arthritis: comparison between two- and three-dimensional ultrasonography.

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.

Ultrasound imaging for the rheumatologist XIX. Imaging modalities in rheumatoid arthritis.

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.

High values of Th1 (CXCL10) and Th2 (CCL2) chemokines in patients with psoriatic arthtritis.

OBJECTIVE: To evaluate serum levels of CXCL10 and CCL2 in a large series of PsA patients, and to relate chemokines levels to the clinical phenotype of these patients. METHODS: Serum levels of CXCL10 and CCL2 were measured in 68 PsA patients, and in gender- and age-matched (1:1) controls drawn from the general population. RESULTS: PsA patients showed significantly (p<0.001) higher mean CXCL10 serum levels than controls (p<0.0001), (269+/-234 vs. 92+/-53 pg/ml; respectively). By defining a high CXCL10 level as a value at least 2 SD above the mean value of the control group (>198 pg/ml), 49% of patients with PsA and 5% of the control subjects had high CXCL10 (p<0.0001; chi-square). A significant inverse correlation was observed between CXCL10 serum levels and disease duration (r= 0.374, p=0.002).Patients with PsA showed significantly higher mean CCL2 serum levels than controls (p<0.001), (512+/-309 vs. 386+/-172, pg/ml; respectively). By defining a high CCL2 level as a value at least 2 SD above the mean value of the control group (>730 pg/ml), 19% of patients with PsA, 2% of the control subjects had high CCL2 (p<0.001; chi-square=22.02). CONCLUSION: In conclusion, high circulating levels of CXCL10 and CCL2 have been found in PsA patients, with a Th1 immune predominance in the early phase of the disease. A decline of CXCL10 levels has been observed in long lasting PsA, with a significant increase of the CCL2/CXCL10 ratio, suggesting a shift from Th1 to Th2 immune response in long duration PsA.