An ultrasonographic insight into musculoskeletal manifestation in 100 systemic lupus erythematosus patients.

OBJECTIVES: We aimed to investigate the prevalence of US findings in the hand joints and related tendons and explore clinical and laboratory associations in SLE patients of the typical lupus clinic. METHODS: One hundred consecutive SLE patients were enrolled in the study. Using B-mode and Doppler US, bilateral wrist, metacarpophalangeal and proximal interphalangeal joints were examined for synovitis and erosions, as well as for signs of hand tenosynovitis. RESULTS: US detected synovitis (grade 1-3) in 75% and erosive changes in 25% of the cohort. We found that clinical examination underestimated grade ≥2 synovitis by 13%, while US detected SH grade ≥2 in 10% of asymptomatic patients. The overall inflammatory burden, reflected by the US score, was associated with disease activity (respectively with CPR, SELENA-2K, MS-BILAG, and hypocomplementemia), as well as the presence of bone erosions. Rhupus patients had higher inflammatory markers, significantly more synovial hypertrophy, more erosions, more grade 3 tenosynovitis, and were more likely to receive methotrexate (p<0.001) than patients with SLE arthritis, while patients with Jaccoud's arthropathy were more likely to accumulate damage. The dominant hand exhibited more inflammatory changes (respectively synovial hypertrophy grade ≥2) at both the wrist and MCP joints; however, handedness was not associated with structural damage. CONCLUSIONS: In conclusion: 1. joint involvement in SLE is frequent and underacknowledged; 2. the overall inflammatory burden is associated with systemic disease activity and joint damage; (3) destructive arthritis is more likely to occur in the context of concomitant RA or within an "RA-like" subtype of SLE arthropathy; 4. hand dominance is associated with synovitis, but not structural changes; 5. US assessment may help tailor the management of joint involvement, thus preventing joint damage and disability in SLE patients.

Shear wave elastography as a new method to identify parotid lymphoma in primary Sjögren Syndrome patients: an observational study.

Parotid non-Hodgkin lymphoma (NHL) in primary Sjögren syndrome (pSS) has no specific biomarker for diagnosis. Salivary glands ultrasound (US) is largely used, but its contribution in detecting parotid NHL has not been established. The aim of our study was to determine the added value of bidimensional shear wave elastography (2D-SWE) in pSS diagnosis and to determine its accuracy in identifying parotid NHL. Grey-scale US (GSUS) and 2D-SWE of salivary glands were performed in 35 patients with pSS and 35 healthy controls. The GSUS scores were calculated and the mean of three SWE consecutive measurements was used to appreciate the gland stiffness. SWE increase the diagnostic rate at a cut-off of 6.45 kPa (from 88.6 to 94.2%, p < 0.001) only if applied in patients with insufficient GSUS criteria for pSS diagnosis. The parotid glands with NHL (8 patients, all mucosa-associated lymphoid tissue type) had hyperechoic bands in more than half of the glandular parenchyma (in 68.75% of the glands), large hypoechoic area > 20 mm (all glands), traced gland area over 5 cm2 (all glands), parotid US score greater than 13 (in 68.75% of the glands), and high stiffness (elasticity modulus 13.9 ± 4.08 vs 6.32 ± 2.24) (all p < 0.001). These findings give high sensitivity (92.3%), specificity (100%), and positive (100%) and negative predictive values (98.3%) for NHL identification. The rest of GSUS findings did not correlate with the classic risk factors for lymphoma development (all p > 0.05). 2D-SWE had added value for pSS diagnosis in cases where GSUS aspect is normal or nonspecific. The higher stiffness of parotid NHL can be used for early diagnosis, biopsy guidance, and, possible, for treatment monitoring.

Elevated Serum Levels of Sclerostin are Associated with High Disease Activity and Functional Impairment in Patients with Axial Spondyloarthritis.

BACKGROUND: Recent research suggests that biomarkers may be useful in assessing disease activity, structural damage, and response to therapy in axial spondyloarthritis (axSpA). Our study aims at evaluating the relationship between inflammation and bone remodeling markers and variables assessing disease activity and functional disability in patients with axSpA. METHODS: Serum levels of sclerostin, matrix metalloproteinase-3 (MMP-3), interleukin-17 (IL-17), and IL-23 were measured in 60 patients with axSpA and 20 healthy controls. Disease activity was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Functional status was assessed by Bath Ankylosing Spondylitis Function Index (BASFI) and measures of spinal mobility. RESULTS: Sclerostin levels were more elevated in axSpA patients with high disease activity than in those with low disease activity and in controls. They were significantly correlated with BASFI values (r = 0.29, p = 0.03) and measures of spinal mobility, but not with the classical markers of disease activity (BASDAI, ASDAS, CRP, and ESR). Although both MMP-3 and IL-17 levels were elevated in patients with active disease, they were not correlated with markers of disease activity or with functional disability. The levels of sclerostin, MMP-3, IL-17, and IL-23 were similar in axSpA patients and healthy controls. CONCLUSIONS: Elevated levels of sclerostin, MMP-3, and IL-17 were observed in axSpA patients with active disease, suggesting their potential role in assessing disease activity. In axSpA patients, sclerostin levels might be equally influenced by inflammation and level of physical activity. Further studies are required to confirm our findings in order to understand their clinical value.

How much difference does the age at onset make in early arthritis patients? Comparison between the ACR 1987 and the ACR/EULAR 2010 classification criteria for rheumatoid arthritis at the time of diagnosis.

The age at onset in early arthritis (EA) may influence the disease activity and its evolution. The aim of the current study is to identify possible differences regarding the "old" and the "new" classification criteria between patients with early-onset and late-onset early arthritis. The study included 64 patients. They were divided in two groups, according to the mean age: early-onset EA--less or equal than 45 years old (group A) and late-onset EA--over 45 years old (group B). The "old" criteria as well as the "new" ones were assessed for all patients, at the time of the first visit to the rheumatologist. The initiation of treatment with Methotrexate was used as "gold standard" to calculate the sensitivity and the specificity of both criteria. "New" criteria were fulfilled in 51% (A) and 72% of cases (B), while "old" criteria were fulfilled in 37% of patients (A) and 62% (B). Methotrexate was initiated in 82% of patients (B) and in 51% (A), p = 0.01. "New" criteria demonstrated a sensitivity of 77.7% (A) and 83.3% (B), while "old" criteria had a sensitivity of 50% (A) and 66.6% (B). Patients with late onset had significantly higher disease activity scores: 76% (B) versus 40% (A), p = 0.04. The sensitivity and the specificity of the "new" criteria for RA are comparable in patients with early-onset and late-onset EA, and the sensitivity of these criteria is increased compared to the "old" criteria. Patients with late onset fulfilling the "old" criteria had poor prognostic factors and higher disease activity at the time of diagnosis, which may have possible implications for the disease course.

Evaluating antirheumatic treatments using synovial biopsy: a recommendation for standardisation to be used in clinical trials.

Inflammation of synovium is one of the hallmarks of rheumatoid arthritis (RA). Analysis of synovial tissue has increased our understanding of RA pathogenesis, aided in identifying potential therapeutic targets and has been used in the response and mechanistic evaluation of antirheumatic treatments. In addition, studies are ongoing, aimed at the identification of diagnostic and prognostic biomarkers in the synovium. This paper outlines the currently used procedures for sampling and processing of synovial tissue, and presents a standardised recommendation to support multicentre translational research.

Shoulder impingement syndrome: correlations between clinical tests and ultrasonographic findings.

OBJECTIVES: To compare the diagnosis of shoulder impingement syndrome (SIS) established by clinical and ultrasonographic examination and to evaluate the value of clinical tests for SIS as well as for rotator cuff pathology. METHODS: One hundred patients with periathrophatia scapulohumeralis entered the study, including 64 females and 36 males aged between 20-84 years (mean 56.8 and 57.5, respectively). Clinical and ultrasonographic examinations were carried out by independent observers, a rheumatologist and a musculoskeletal-trained sonographer. Clinical tests for SIS and for each of the tendons of the rotator cuff, as well as static and dynamic ultrasonographic examinations were performed for both shoulders. Findings were compared and statistically analyzed. RESULTS: The Hawkins test (72.2%) proved to be the most sensitive clinical test for the identification of SIS and the Neer test (95.3%) was the most specific one. When four tests were simultaneously positive, the specificity for the diagnosis was 98.5% but the sensitivity decreased to 40.3%. Jobe's test indicated supraspinatus involvement with a specificity of 90% but it was not able to disclose the type of lesions. The sensitivity and specificity of the tests aiming to elicit infraspinatus tendon pathology were of low value whereas those addressing subscapularis tendon involvement were rather of moderate value. SIS was clinically correctly diagnosed in 80.5% of cases, but its characteristic stages were poorly recognized (stage I 50%, stage II 70%, and stage III 30.7%). CONCLUSIONS: Although clinical tests are insufficient for clinical diagnosis, the examination of the patient still plays an important role in rotator cuff disorders. Ultrasonography should be used for all patients suffering from painful shoulder in order to improve the diagnosis.

Posttraumatic hip bulging mimicking an abscess in a patient with hip prosthesis: the role of ultrasonography.

A 48-yr old female patient, with stage 4 rheumatoid arthritis, who had undergone multiple joint prostheses including four arthroplasties of the left hip, presented for a sudden-onset large bulge on the left thigh, after a minor local injury. Orthopedic examination and radiography excluded fractures. Ultrasonography revealed a large mixed hypo- and hyperechoic collection,with no Doppler signal, but with comet tail artifacts. Repeated cultures from the collection were negative. Fluid analysis revealed increased quantities of titanium and cobalt. The sudden-onset deformity and fluid collection were in favor of a shear lesion (Morel-Lavallée). The new collection communicated with a previously asymptomatic periprosthetic aseptic abscess, mimicking an infection. To our knowledge, Morel-Lavallée shear lesions have not been described in patients with hip prostheses. Their presence may add to the difficulties of ruling out silent infections in such patients. Ultrasonography is a very effective method for the diagnosis and follow-up of collections in this setting.

Clinical and ultrasound findings in patients with calcium pyrophosphate dihydrate deposition disease.

AIM: To evaluate the presence and distribution of calcium pyrophosphate (CPP) deposits in joints commonly affected by CPP deposition (CPPD) disease (acromio-clavicular, gleno-humeral, wrists, hips, knees, ankles, and symphysis pubis joints) using ultrasound (US). MATERIAL AND METHODS: Thirty consecutive patients fulfilling McCarty diagnostic criteria for CPPD were consecutively enrolled in the study. The data registered using the US included the affected joints, the calcification site, and the pattern of calcification (thin hyperechoic bands, parallel to the surface of the hyaline cartilage, hyperechoic spots, and hyperechoic nodular or oval deposits). The presence of CPP crystals in knees was confirmed by polarized light microscopy examination of the synovial fluid and radiographs of the knees were performed in all patients. RESULTS: In 30 patients, 390 joints were scanned, (13 joints in every patient). The mean±standard deviation number of joints with US CPPD evidence per patient was 2.93±1.8 (range 1-9). The knee was the most common joint involved both clinically and using US examination. The second US pattern (with hyperechoic spots) was the most frequent. Fibrocartilage calcifications were more common than hyaline calcification. Using radiography as reference method, the sensitivity and specificity of US for diagnosis CPPD in knees was 79.31%, 95CI(66.65%-88.83%), and 14.29%, 95CI(1.78%-42.81%), respectively. CONCLUSIONS: The knee is the most frequent joint affected by CPPD. The second ultrasound pattern is the most common. CPPD affects the fibrocartilage to a greater extent than the hyaline cartilage.

Redundant plantar skin folds.

A 46-year-old female patient presented with photosensitivity, symmetric arthritis, episodic plantar pain and strikingly redundant plantar skin folds, likely due to lipoatrophy after recurrent episodes of plantar panniculitis. In this context, leukopenia with lymphopenia, thrombocytopenia and positive antinuclear antibodies were revelatory for systemic lupus erythematosus. However, a small cerebriform plantar collagenoma, along with discrete dysmorphic features with downslanting palpebral fissures and mild right ptosis, second and third syndactyly and a larger first right toe since childhood, and early-onset bilateral ovarian cystadenoma, suggested a minimal Proteus syndrome. Genetic confirmation could not be performed. As adipose tissue dysregulation may be a feature of Proteus syndrome, the possible mechanisms leading to localized lipoatrophy in this setting are discussed. This case enlights intriguing links between adipogenesis, inflammation and dysmorphology. From a practical point of view, finding and treating an over-imposed inflammation could help limit damage in a hamartomatous syndrome.

Ultrasonography of the metacarpophalangeal joints in healthy subjects using an 18 MHz transducer.

AIM: To evaluate the metacarpophalangeal (MCP) joints (MCP2 and 5) in healthy subjects by ultrasonography (US) using a high frequency transducer (18 MHz) and to verify the interobserver agreement. MATERIAL AND METHODS: We enrolled 50 healthy volunteers (37 women, age between 30-58 years, mean age 41.7 years, divided into 3 groups according to age: 30-39, 40-49, and 50-58 years). The subjects were successively evaluated by 4 rheumatologists: 2 experienced (team A) and 2 beginners (team B) in US. Seven dorsal and palmar longitudinal scanning positions and a supplementary scan for MCP cartilage were performed. The bone surface (erosions, osteophytes), the intra-articular content (synovial thickening and vascularization, 4 grade scale), and the aspect of the metacarpal head cartilage were analyzed. The anterior palmar recess was measured. The time for examination was recorded. RESULTS: Erosions were detected in 7% of joints by team A and 2% by team B (p<0.05, kappa agreement 0.567) in subjects over 40 years. The agreement by team A in the detection of the erosions was very good (kappa value 0.83). A moderate positive correlation was obtained between the presence of erosions and age (r= 0.401, p=0.004). Osteophytes were identified only on the dorsal scan in subjects over 50 years (in 3.5% of joints team A, 1.5% team B, p>0.05, kappa value 0.421). No grade 1 synovitis was observed by team A but 4 joints with grade 1 synovitis were identified by team B (p<0.05) from the dorsal scan. The dimensions of the palmar recess had large distribution (MCP 2 between 0.55-1.3 mm; MCP 5 between 0.6-1.2 mm). No statistical significant differences were obtained when comparing the dimensions of the two hands, the values obtained in age-groups (all p>0.05). No statistical significant correlations were obtained between the dimensions of palmar recess and the body mass index or dominant hand (all p>0.05). No pathological findings were found in the examination of the metacarpal head cartilage. Power Doppler investigation found the presence of grade 1 signal in 2.5% joints by team A and 1.5% by team B (p>0.05) only in the dorsal scans. The mean time for examination was 7.8+/-1.74 min in team A and 13.78+/-2.96 min in team B (p<0.05). CONCLUSIONS: In healthy subjects pathological findings are occasionally encountered, especially erosions and osteophytes. Using an 18 MHz transducer the aspect of grade 1 synovitis was not encountered in healthy non-inflammatory MCP joints. There is a permanent need for standardized training and examination in musculoskeletal US.

The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia.

AIM: The purpose of this study is to compare and correlate US evaluation with clinical scores of the disease activity in patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM). MATERIAL AND METHODS: Ten patients diagnosed with RA according to the 2010 ACR/EULAR classification criteria and associated FM based on the ACR 1990 classification criteria and two control groups, one with RA (10 patients) and one with FM (10 patients), were included. Clinical assessment was performed and the disease activity scores were calculated. Synovial/tenosynovial hypertrophy, fluid collections in grey scale (GS), and Power Doppler (PD) US assessed by US in the 28 joints included in the disease activity score 28 (DAS28). RESULTS: GS US score and PD US scores were correlated with DAS28 only in patients with RA (Pearson r coefficients 0.3 and 0.5). Mean DAS28 score was significantly higher in the RA/FM group, compared to RA and FM (5.6 versus 4.6 versus 4.5, respectively). Patients with RA/FM had similar median US scores to RA patients, while in FM group significantly lower median US scores were detected (16 versus 9.5 versus 0 for GS US and 3.5 versus 1.5 versus 0 for PD US, respectively). CONCLUSIONS: Disease activity scores should be interpreted with caution in patients with RA and FM. When available, US should be used to guide treatment decisions in patients with RA and FM.

Primary complement and antibody deficiencies in autoimmune rheumatologic diseases with juvenile onset: a prospective study at two centers.

BACKGROUND: Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset. METHODS: A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively. RESULTS: Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap). CONCLUSIONS: Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.

Ultrasound assessment for the rapid classification of early arthritis patients.

OBJECTIVE: The present study aimed to assess the role of ultrasound (US) in the rapid classification of early rheumatoid arthritis (RA) by investigating whether the US features of inflammation and bone damage in early arthritis overlap with the actual clinical concept of classifying and identifying an aggressive disease. METHODS: Patients with recent-onset arthritis of at least 1 peripheral joint of the hands and/or the feet were consecutively included in this study. Clinical examination, laboratory tests, the Disease Activity Score 28 (DAS28), and the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA were assessed for all patients. Medication with disease-modifying antirheumatic drugs was recorded. Ultrasound assessment was performed at the following anatomical sites: wrists, metacarpophalangeal joints 2 to 5, and metatarsophalangeal joints 2 to 5 for assessing the presence/absence of synovial hypertrophy, the presence/absence of power Doppler signal, and the presence/absence of bone erosions.The US features of inflammation and bone damage were analyzed in comparison with the DAS28, with the presence/absence of rheumatoid factor and anti-cyclic citrullinated peptide, with the fulfillment of the new 2010 ACR/EULAR classification criteria, and with the initiated disease-modifying antirheumatic drug. The prescription of methotrexate was considered a marker of an aggressive disease. RESULTS: The US features of inflammation and bone damage correlated with the activity scores measured by the DAS28. The presence of US bone erosions overlapped with the presence of rheumatoid factor and anti-cyclic citrullinated antibodies. Synovial hypertrophy, intra-articular power Doppler signal, and bone erosions detected in at least 1 anatomical site were seen in patients fulfilling (77.7%) and in patients not fulfilling (72.7%) the 2010 ACR/EULAR classification criteria for RA. Synovial hypertrophy was found in at least 1 site in 83.3% and 58.8% of patients in whom methotrexate was prescribed and in whom methotrexate was not prescribed, respectively (P = 0.01). The US features were not correlated with the initiation of sulfasalazine or hydroxychloroquine. The patients presenting bone erosions received in significantly higher percentages the indication for methotrexate (50%) compared with sulfasalazine (20%), P = 0.03, or hydroxychloroquine (26%), P = 0.05. CONCLUSIONS: The US features of inflammation might be of help in classifying early arthritis patients despite the presence of the immune markers for RA. Together with the US features of bone damage, these might be used as an indicator of a more aggressive disease. The absence of correlation between the US findings of RA and the 2010 ACR/EULAR classification criteria indicates a possible independent contribution of US in the understanding of the future evolution of these patients.

A case of alkaptonuria - ultrasonographic findings.

Alkaptonuria is a rare disease with autosomal recessive inheritance and variable expression. The weight-bearing joint involvement and spondylitis-like vertebral changes occur only after the 3rd decade. Musculoskeletal ultrasonographic findings in alkaptonuria were only rarely described, consisting mainly into enthesopathy and non-synovial tendon degeneration. We present the case of a 50 years old man with alkaptonuria and discuss the ultrasonographic findings and the relationship of the disease with chondrocalcinosis. The tendinous and synovial aspect may be peculiar and it could therefore allow recognition and screening for alkaptonuria, along with clinical and radiologic data.

Ultrasound findings in AL musculoskeletal amyloidosis.

Systemic AL amyloidosis is one of the differential diagnosis of chronic musculoskeletal disease, especially when swollen and painful joints is associated with claw hands. Ultrasound evaluation is a good diagnosis tool, showing a characteristic joint and tendon involvement and assisting in guided biopsy procedure. We report a 55 year old caucasian woman, diagnosed for two years with RA without improvement under different DMARDs, admitted for fixed flexion contractures of both hands ("claw hands"), worsening pain and swelling of small joints of hands and feet, elbows and shoulders. Pad shoulder sign and bilateral anterior wrist and elbow pads, macroglossia, thickened skin of fingers and ecchymotic rashes on forearm and around eyes were observed. Ultrasound examinations showed subdeltoid and bicipitoradial bursitis, presence of inhomogeneous hypoechoic material around bicipital tendons and tenosinovitis of the extensor tendons of the hand, and synovial thickening of elbow and shoulder joints. Complete analysis of the bone marrow biopsy and biopsy specimens from subacromial bursa were positive for AL amyloidosis.