The diagnostic value of ultrasound in the assessment of soft tissue masses in rheumatology practice - a case series of 4 patients.

A great number of studies have proved the added value of musculoskeletal ultrasound (MSUS) in the diagnosis, assessment of disease activity and treatment response in both inflammatory and degenerative rheumatic diseases. However, it is a frequent scenario that rheumatologists should also assess patients with various soft tissue masses, referred to their practices. In such cases, MSUS could be a valuable and precise tool that helps in the evaluation and triage of these lesions. Hereafter, we describe a case series, where MSUS played a decisive role in the diagnostic process and allowed for prompt patients' management.

Endophenotypes of Primary Osteoarthritis of the Hip Joint in the Bulgarian Population over 60 Years Old.

Aim. To identify subgroups of patients with primary osteoarthritis of the hip joint (pHOA) with similar imaging and laboratory findings, disease evolution, and response to conventional therapies. Methods. We performed further statistical analyses on patient data from two published, double-blind, randomized, and placebo-controlled studies (DB-RCTs), which examined the effects of intra-articular corticosteroids (ia-CSs), hyaluronic acid (ia-HA)-KИ-109-3-0008/14.01.2014, and intravenous bisphosphonates (iv-BPs) -KИ- 109-3-0009/14.01.2014 compared to the country's standard pHOA therapy. The data span an 8-year follow-up of 700 patients with pHOA, including: 1. Clinical parameters (WOMAC-A, B, C, and T; PtGA). 2. Laboratory markers (serum calcium and phosphate levels; 25-OH-D and PTH, markers for bone sCTX-I and cartilage uCTX-II turnover). 3. Radiological indicators: X-ray stage (Kellgren-Lawrence (K/L) and model (Bombelli/OOARSI), width (mJSW), speed (JSN mm/year), and zone of maximum narrowing of the joint space (max-JSN)-determining the type of femoral head migration (FHM). 4. DXA indicators: bone geometry (HAL; NSA; and MNW); changes in regional and total bone mineral density (TH-BMD, LS-BMD, and TB-BMD). 5. Therapeutic responses (OARSI/MCII; mJSW; JSNmm/yearly) to different drug regimens (iv-BP -zoledronic acid (ZA/-5 mg/yearly for 3 years)); ia-CS 40 mg methylprednisolone acetate, twice every 6 months; and ia-HA with intermediate molecular weight (20 mg/2 mL × 3 weekly applications, two courses every 6 months) were compared to standard of care therapy (Standard of Care/SC/), namely D3-supplementation according to serum levels (20-120 ng/mL; target level of 60 ng/mL), simple analgesics (paracetamol, up to 2.0 g/24 h), and physical exercises. The abovementioned data were integrated into a non-supervised hierarchical agglomerative clustering analysis (NHACA) using Ward's linkage method and the squared Euclidean distance to identify different endophenotypes (EFs). Univariate and multivariate multinomial logistic regression analyses were performed to determine the impact of sex and FHM on clinical and radiographic regression of pHOA. Results. A baseline cluster analysis using incoming (M0) patient data identified three EFs: hypertrophic H-HOA, atrophic A-HOA, and intermediate I-HOA. These EFs had characteristics that were similar to those of patients grouped by radiographic stage and pattern ('H'-RPs, 'I'-RPs, and 'A'-RPs), p < 0.05). The repeated cluster analysis of M36 data identified four EF pHOAs: 1. Hypertrophic (slow progressors, the influence of the type of femoral head migration (FHM) outweighing the influence of sex on progression), progressing to planned total hip replacement (THR) within 5 (K/LIII) to 10 (K/LII) years. 2. Intermediate (sex is more important than the FHM type for progression) with two subgroups: 2#: male-associated (slow progressors), THR within 4 (K/LIII) to 8 years. (K/LII). 2* Female-associated (rapid progressors), THR within 3 (K/LIII) to 5 (K/LII) years. 3. Atrophic (rapid progressors; the influence of FHM type outweighs that of sex), THR within 2 (K/LIII) to 4 (K/LII) years. Each EF, in addition to the patient's individual progression rate, was also associated with a different response to the aforementioned therapies. Conclusions. Clinical endophenotyping provides guidance for a personalized approach in patients with pHOA, simultaneously assisting the creation of homogeneous patient groups necessary for conducting modern genetic and therapeutic scientific studies.

Severe Acro-osteolysis Mimicking Arthritis Mutilans in a Patient with Primary Hyperparathyroidism: A Case Report.

BACKGROUND: Primary hyperparathyroidism (PHPT) should be considered in the differential diagnosis of a patient with suspected secondary osteoporosis, and severe osteoporosis with multiple fractures is frequently the first clinical manifestation of the disease. CASE PRESENTATION: Mutilating arthritis (arthritis mutilans) can be part of the clinical presentation of a number of rheumatic diseases, most commonly seen in psoriatic arthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, but also in systemic lupus, systemic sclerosis, and multicentric reticulohistiocytosis. Evidence exists that subperiosteal and subchondral bone resorption, seen in PHPT, could induce the so-called 'osteogenic synovitis', which could eventually lead to the development of a secondary osteoarthritis with bone deformities. CONCLUSION: Here, we present a case report of a patient initially diagnosed with PHPT who presented with mutilating arthritis of the finger joints and discuss whether the severe acro-osteolysis is a manifestation of the endocrinopathy or whether there is a co-existing undiagnosed inflammatory joint disease.

Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria-Results from a 7-Year Study.

Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including a control group on standard-of-care therapy (SC) with simple analgesics and physical exercises, and a study group (SG) on standard-of-care therapy supplemented by vitamin D3 and intravenous administration of zoledronic acid (5 mg) yearly for 3 consecutive years. Patient groups were homogenized regarding the following: (1) radiographic grade (RG), including 75 patients with hip OA RG II according to the Kellgren-Lawrence grading system (K/L), and 75 with RG III on K/L; (2) radiographic model (RM), as each of the K/L grades was subdivided into three subgroups consisting of 25 patients of different RMs: atrophic ('A'), intermediate ('I'), and hypertrophic ('H'); (3) gender-equal ratio of men and women in each subgroup (Female/Male = 15/10). The following parameters were assessed: (1) clinical parameters (CP), pain at walking (WP-VAS 100 mm), functional ability (WOMAC-C), and time to total hip replacement (tTHR); (2) radiographic indicators(RI)-joint space width (JSW) and speed of joint space narrowing (JSN), changes in BMD (DXA), including proximal femur (PF-BMD), lumbar spine (LS-BMD), and total body (TB-BMD); (3) laboratory parameters (LP)-vitamin D3 levels and levels of BT/CT markers. RV were assessed every 12 months, whereas CV/LV were assessed every 6 months. Results: Cross-sectional analysis (CsA) at baseline showed statistically significant differences (SSD) at p < 0.05 in CP (WP, WOMAC-C); BMD of all sites and levels of CT/BT markers between the 'A' and 'H' RM groups in all patients. Longitudinal analysis (LtA) showed SSD (p < 0.05) between CG and SG in all CP (WP, WOMAC-C, tTHR) parameters of RP (mJSW, JSN), BMD of all sites, and levels of CT/BT markers for all 'A' models and in 30% of 'I'-RMs (those with elevated markers for BT/CT at baseline and during the observation period). Conclusion: The presence of SSD at baseline ('A' vs. 'H') supported the thesis that at least two different subgroups of HOA exist: one associated with 'A' and the other with 'H' models. D3 supplementation and the intravenous administration of bisphosphonate were the treatment strategies that slowed down RP and postponed tTHR by over 12 months in the 'A' and 'I' RM with elevated BT/CT markers.

A Seven-Joint Ultrasound Score for Differentiating Between Rheumatoid and Psoriatic Arthritis.

BACKGROUND: Differentiating between seronegative rheumatoid arthritis (RA) and psoriatic arthritis (PsA) presenting only with the involvement of the small joints of the hands can be challenging. Implementing musculoskeletal ultrasound (US) to reveal specific patterns of joint and tendon involvement may have an added value in the management of early arthritis. OBJECTIVE: The aim was to investigate whether a seven-joint US score was able to distinguish between patients with RA and PsA. MATERIALS AND METHODS: One hundred and forty-one patients with RA, 65 patients with PsA, and 45 healthy controls (HC) were included in the current study. US assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint was performed, and the following scores were calculated: synovitis and tenosynovitis/ paratenonitis scores on grayscale ultrasound (GSUS) and on power Doppler (PD) US, erosion score, US7 score. RESULTS: RA patients had significantly higher median scores of GS synovitis, PD synovitis, erosions, and US7 than PsA patients (p < 0.001). PsA patients had significantly higher median scores of GS tenosynovitis/paratenonitis and PD tenosynovitis/paratenonitis (p < 0.001). All US scores were significantly higher for both patient groups as compared to the HC group (p < 0.001). CONCLUSION: Sonographic evaluation by a seven-joint score can be helpful in the differentiation between rheumatoid and psoriatic arthritis.

Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. There is recent evidence that the JAK/STAT signaling pathway is markedly activated in SSc patients. To assess the efficacy and safety of tofacitinib (TOF) on skin and musculoskeletal involvement as compared to methotrexate (MTX) in systemic sclerosis (SSc). In this 52-week pilot study, 66 patients with SSc were enrolled: 33 patients received 5 mg of oral TOF twice a day; 33 received 10 mg of MTX weekly. The proportion of dcSSc and lcSSc patients was similar (dcSSc: 42% TOF group and 36% MTX group; lcSSc: 58% TOF group and 64% MTX group). The primary outcome was the change in the modified Rodnan skin score (mRSS). Secondary outcomes included ultrasound (US) skin thickness and musculoskeletal involvement (US10SSc score). Digital ulcers (DUs) and adverse events (AEs) were documented through the treatment. Both groups had similar characteristics and medians on the outcome measures at baseline. At week 52, the TOF median mRSS was significantly lower than the MTX (p < 0.001) with a mean reduction of 13 points versus MTX 2.57. The mean percent improvement in the TOF group was 44% higher than in the MTX group. TOF median US skin thickness was significantly lower than MTX (p < 0.001), with a mean reduction of 0.31 mm versus 0.075 mm in the MTX group. The US10SSc median score was significantly lower in the TOF group (p = 0.002); mean reduction of 10.21 versus 5.27 in the MTX group. Healing of DUs with no new occurrences was observed in the TOF group. There was no significant difference between the groups in the number of AEs from baseline to week 52. TOF showed greater efficacy than MTX in reducing mRSS, skin thickness and musculoskeletal involvement in SSc and a satisfactory safety profile.

Hand ultrasound patterns in rheumatoid and psoriatic arthritis: the role of ultrasound in the differential diagnosis.

Many rheumatic diseases may present with an inflammatory joint syndrome, affecting the small joints of the hands, of which rheumatoid (RA) and psoriatic arthritis (PsA) being one of the most common. The aim of this systematic review was to focus on the literature evidence regarding the added value of ultrasound (US) of the hand in the differential diagnosis between RA and PsA. Pubmed and Scopus were searched to identify original manuscripts, published in the last 20 years utilising ultrasonography to reveal specific hand US patterns. Studies were eligible if they: (1) included adults (over 18 years) with a diagnosis of RA/PsA; (2) were published in the English language; (3) were published in peer-reviewed journals; (4) included description of the US machine; (5) used US for assessment of hand joints, periarticular tissues and nails. The search yielded 322 published studies, of which 16 were deemed relevant and were included in the present study. Overall, there was heterogeneity with regard to the pathology examined. Based on the included studies analysis, hand US patterns have several basic features to be considered-location of gray scale (GS) inflammatory findings, involvement of periarticular soft tissue, distribution and extent of Doppler signal (intra- and peri-articular), bone reaction, shape and location of erosions, involvement of tendons without synovial sheath, involvement of enthesis and nail abnormalities. Future research could focus on determining the sensitivity and specificity of the different US detected hand patterns in patients with early arthritis.

Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc.

Body Mass Index Impact on Disease Activity, Clinical and Sonographic Remission Rates in Patients with Rheumatoid Arthritis.

AIM: To investigate the impact of body mass index (BMI) on clinical disease activity indices and clinical and sonographic remission rates in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: Sixty-three patients with RA were categorized according to BMI score into three groups: normal (BMI<25), overweight (BMI 25-30) and obese (BMI≥30). Thirty-three of them were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and 30 with biologic DMARDs (bDMARDs). Patients underwent clinical and laboratory assessment and musculoskeletal ultrasound examination (MSUS) at baseline and at 6 months after initiation of therapy. We evaluated the rate of clinical and sonographic remission (defined as Power Doppler score (PD) = 0) and its correlation with BMI score. RESULTS: In the csDMARDs group, 60% of the normal weight patients reached DAS28 remission; 33.3% of the overweight; and 0% of the obese patients. In the bDMARDs group, the percentage of remission was as follows: 60% in the normal weight subgroup, 33.3% in the overweight; and 15.8% in the obese. Within the csDMARDs treatment group, two significant correlations were found: BMI score-DAS 28 at 6th month, rs = .372, p = .033; BMI score-DAS 28 categories, rs = .447, p = .014. Within the bDMARDs group, three significant correlations were identified: BMI score-PDUS at sixth month, rs = .506, p =.004; BMI score-DAS 28, rs = .511, p = .004; BMI score-DAS 28 categories, rs = .592, p = .001. Sonographic remission rates at 6 months were significantly higher in the normal BMI category in both treatment groups. CONCLUSION: BMI influences the treatment response, clinical disease activity indices and the rates of clinical and sonographic remission in patients with RA. Obesity and overweight are associated with lower remission rates regardless of the type of treatment.

Musculoskeletal ultrasound as a biomarker of remission - results from a one-year prospective study in patients with rheumatoid arthritis.

AIMS: To assess the role of musculoskeletal ultrasound (MSUS) as a biomarker of remission and to compare the rates of clinical and imaging remission in patients with rheumatoid arthritis (RA) on different types of treatment. MATERIAL AND METHODS: One hundred and forty-one patients underwent physical and ultrasound examination at 5 visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joints, and the second and fifth metatarsophalangeal joints was performed on gray scale ultrasound (GSUS) and on power Doppler ultrasound (PDUS) (German US7-score). The rate of imaging and clinical remission (DAS28, SDAI, CDAI, and Boolean) was established. The percentage of patients in clinical remission with persistent PD signal was assessed. RESULTS: In the sDMARDs group at month twelve, 43.6% of the patients achieved DAS28 remission, 5.1% - SDAI, 3.8% - CDAI, and 3.8% - Boolean remission. In the bDMARDs group 49.2% achieved DAS28 remission, 6.3% - SDAI, 4.8% - CDAI, and 4.8% - Boolean remission. Irrespective of which clinical index was applied, all patients in clinical remission had persistent synovial hypertrophy on GSUS. Synovial PD signal (PDUS score≥1) was detected in 77% and 71% of patients in DAS28 remission in the sDMARDs and bDMARDs group, respectively. Patients in SDAI, CDAI and Boolean remission in both treatment groups did not have а positive PD signal. CONCLUSIONS: There is persistence of synovitis both in patients on sDMARDs and bDMARDs in DAS28 clinical remission. This fact points to a discordance between DAS28 clinical remission and the imaging remission assessed by MSUS irrespective of the type of treatment. MSUS may be a feasible imaging method for the assessment of residual inflammation in daily rheumatology practice.

Musculoskeletal ultrasound for predicting remission in patients with rheumatoid arthritis: results from a 1-year prospective study.

To assess the role of musculoskeletal ultrasound as a predictor for the achievement of DAS28 remission in patients with rheumatoid arthritis (RA). One hundred and forty-one patients underwent physical and ultrasound examination at five visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint (the German US7 score) was performed on gray scale (GS) and on power Doppler ultrasound (PDUS). The rate of clinical remission and clinical and sonographic predictors for the achievement of DAS28 remission at month 12 were assessed. In the sDMARDs group at month 12, 43.6% of the patients achieved DAS28 remission, 5.1%-SDAI, 3.8%-CDAI, and 3.8%-Boolean remission. In the bDMARDs group, 49.2% achieved DAS28 remission, 6.3%-SDAI, 4.8%-CDAI, and 4.8%-Boolean remission. Predictors for DAS28 clinical remission in the sDMARDs group were low baseline DAS28 (p = 0.002), short disease duration (p = 0.007) and lower baseline PDUS score (p = 0.038). In the bDMARDs group low baseline DAS28 (p < 0.001) and PDUS score (p = 0.035) predicted DAS28 remission. Shorter disease duration, lower baseline DAS28 and PDUS scores are associated with a higher probability of achieving DAS28 remission at month 12 in patients with RA. Musculoskeletal ultrasound and in particular the German US7-scoring system may be used as a predictor for the achievement of clinical remission in RA patients.