Is Active Synovitis of Metacarpophalangeal Joints a Neuropathic Condition in Rheumatoid Arthritis Patients? Results from an Ultrasound Study of Palmar Digital Nerves.

(1) Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, primarily characterized by pain. A significant proportion of patients report symptoms suggestive of neuropathic pain. The objectives of this study were to investigate the presence of an increased cross-sectional area (CSA) of the palmar digital nerves by ultrasound in patients with active synovitis of the metacarpophalangeal joints and to identify potential predictors of such an increase. (2) Methods: An ultrasound examination of the clinically most affected hand (from the second to the fifth metacarpophalangeal joint) was performed. The presence of synovitis was scored using a 0-3 semiquantitative method for each joint. The CSA of each pair of palmar digital nerves was measured. (3) Results: A significant correlation was found between the sum of the CSAs of the nerves and the Clinical Disease Activity Index (CDAI) (r = 0.387), as well as with the ultrasonographic grading of synovitis (r = 0.381) both at the patient and the joint level. These two variables, aimed at measuring disease activity, along with male gender, are the only predictors of the CSA of the palmar digital nerves. (4) Conclusions: Synovial inflammation of the metacarpophalangeal joints is, therefore, a condition that can influence the CSA of the palmar digital nerves and may partially explain neuropathic pain in patients with RA.

Ultrasound reveals a high prevalence of CPPD in consecutive patients with knee pain.

The objective of this study is to estimate the prevalence of US findings indicative of calcium pyrophosphate deposition (CPPD) in patients with knee pain. Consecutive patients with knee pain, equally distributed among males and females in seven different age-decades (21-90 years), were enrolled in a cross-sectional study. The presence of US OMERACT-defined CPPD (medial and lateral menisci and femoral hyaline cartilage) and osteophytes (medial and lateral compartments of the tibiofemoral joint) was scored as presence/absence in both knees. Four hundred twenty participants were enrolled (210 men/210 women). Fibrocartilage and hyaline cartilage CPPDs were detected by US in 94/420 (22.4%) and 41/420 (9.8%) participants, respectively. No significant sex differences were noted. The prevalence and the extent of CPPD increased with age. Fibrocartilage and hyaline cartilage CPPDs were identified in 0/60 participants in the third decade, and in 28/60 (46.7%) and 14/60 (23.3%) participants in the ninth decade, respectively (p for trend < 0.01). While fibrocartilage and hyaline cartilage CPPD is virtually absent in subjects younger than 40 and 50 years old, their prevalence steeply increases above from these age groups. Age (aIRR, 1.03; 95% CI, 1.02-1.05), osteophyte score (aIRR, 1.40; 95% CI, 1.22-1.60), and hyaline cartilage CPPD score (aIRR, 2.68; 95% CI, 2.06-3.49) were associated with fibrocartilage CPPD score, whereas age (aIRR, 1.02; 95% CI, 1.01-1.05) and fibrocartilage CPPD score (aIRR, 2.92; 95% CI, 2.29-3.72) were associated with hyaline cartilage CPPD score in multivariable negative binomial regression analyses. In conclusion, we report the US prevalence of CPPD in patients with knee pain. Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. Key points • Fibrocartilage CPPD occurs at a younger age and is more prevalent than hyaline cartilage CPPD. • Fibrocartilage and hyaline cartilage CPPDs are virtually absent in subjects younger than 40 and 50 years old. • In subjects older than 80 years, fibrocartilage and hyaline cartilage CPPD prevalence rises up to 46.7% and 23.3%, respectively.

Diagnosis of calcium pyrophosphate crystal deposition disease by ultrasonography: how many and which sites should be scanned?

OBJECTIVE: To develop the optimal US scanning protocol for the diagnosis of CPPD disease. METHODS: In this cross-sectional study, consecutive patients with a crystal-proven diagnosis of CPPD disease, and age-, sex-matched disease controls and with a negative synovial fluid analysis were prospectively enrolled in two Italian Institutions. Four rheumatologists, blinded to patients' clinical details, performed US examinations using a standardised scanning protocol including 20 joints (shoulders, elbows, wrists, metacarpophalangeal joints from 2nd to 5th fingers, hips, knees, ankles). CPPD was identified as presence/absence, according to the OMERACT definitions. Reduced US scanning protocols were developed by selecting the most informative joints to be imaged by US using the LASSO technique. Patients were randomly divided into training and validation sets. Their diagnostic accuracy was tested comparing the area under the ROC curves. RESULTS: 204 participants were enrolled: 102 with CPPD disease and 102 disease controls [age (mean±standard deviation) 71.3 ± 12.0 vs 71.1 ± 13.5 years, female: 62.8% vs 57.8%].The median number of joints with US evidence of CPPD was 5 (IQR: 4-7) and 0 (IQR: 0-1) in patients with CPPD disease and controls, respectively (p< 0 01).The detection of CPPD in ≥ 2 joints using a reduced scanning protocol (bilateral assessment of knees, wrists, and hips) showed a sensitivity of 96.7% (95%CI: 82.8-99.9) and a specificity of 100 (95%CI: 88.8-100.0) for the diagnosis of CPPD disease and had good feasibility [(mean±standard deviation) 12.5 ± 5.3 min]. CONCLUSION: Bilateral US assessment of knees, wrists, and hips had excellent accuracy and good feasibility for the diagnosis of CPPD disease.

Ultrasonography in the prediction of gout flares: a 12-month prospective observational study.

OBJECTIVES: To evaluate whether US findings indicating MSU deposits and US-detected inflammation (i.e. power Doppler signal) predict gout flares over 12 months. METHODS: Gout patients on urate-lowering therapy for at least the preceding 6 months were enrolled consecutively in this 12-month prospective, observational, single-centre study. A nested case-control analysis was performed. Cases were participants with at least one flare in the follow-up period, while controls did not self-report any gout flare. The US assessment included elbows, wrists, second MCP joints, knees, ankles, and first MTP joints. The US findings indicating MSU deposits [i.e. aggregates, double contour (DC) sign and tophi] were identified as present/absent according to the Outcome Measure in Rheumatology definitions. Power Doppler signal was scored semiquantitatively. Summated scores were calculated for each US finding. RESULTS: Eighty-one gout participants were enrolled, and 71 completed the study. Thirty (42.3%) of 71 participants experienced at least one flare over 12 months, with a median of 2.0 flares. Cases had a greater US burden of MSU deposits (6.7 ± 4.7 vs 2.9 ± 2.6, P = 0.01) and power Doppler signal (3.73 ± 3.53 vs 0.82 ± 1.44, P < 0.01) than controls, at baseline. The baseline US scores indicating MSU deposits and US-detected inflammation were significantly associated with the occurrence (total MSU score, adjusted odds ratio:1.75, 95% CI: 1.26, 2.43; power Doppler score, adjusted odds ratio: 1.63, 95% CI: 1.12, 2.40) and the number (total MSU score, adjusted incidence risk ratio: 1.17, 95% CI: 1.08, 1.26; power Doppler score, adjusted incidence risk ratio: 1.29, 95% CI: 1.19, 1.40) of flares over 12 months in multivariate analyses. CONCLUSIONS: Baseline US findings indicating MSU deposits and US-detected inflammation are independent predictors of gout flares over 12 months.

In patients with acute mono/oligoarthritis, a targeted ultrasound scanning protocol shows great accuracy for the diagnosis of gout and CPPD.

OBJECTIVES: To determine an US scanning protocol with the best accuracy for the diagnosis of gout and CPPD in patients with acute mono/oligo-arthritis of unknown origin. METHODS: Patients with acute mono/oligo-arthritis in whom a joint aspiration at the most clinically involved joint (target joint) was requested were consecutively enrolled. US was performed in each patient before the arthrocentesis. The accuracy of different US findings and scanning protocols for the diagnosis of gout and CPPD was calculated. RESULTS: A total of 161 subjects were included (32 gout patients, 30 CPPD patients and 99 disease-controls). US findings had a high specificity for gout (0.92-0.96) and CPPD (0.90-0.97), while the sensitivity ranged from 0.73 to 0.85 in gout (double contour sign and tophi, respectively) and from 0.60 to 0.90 in CPPD (hyaline and fibrocartilage deposits, respectively). The US assessment of two joints bilaterally (gout: knees, MTP1 joints; CPPD: knees, wrists) plus the target joint had an excellent diagnostic sensitivity (gout: 0.91, CPPD: 0.93) and specificity (gout: 0.91, CPPD: 0.89). This targeted US scanning protocol yielded to higher diagnostic accuracy compared with the US evaluation of the target joint [gout area under the curve (AUC) 0.91 vs 0.84, P = 0.03; CPPD AUC 0.93 vs 0.84, P = 0.04] unless the target joint was the knee or the MTP1 joint in gout and the knee or the wrist in CPPD. CONCLUSIONS: A targeted US scanning protocol of two joints bilaterally plus the target joint showed an excellent accuracy (>90%) for the diagnosis of crystal arthritis in patients with acute mono/oligoarthritis.

Ultrasound findings of calcium pyrophosphate deposition disease at metacarpophalangeal joints.

OBJECTIVE: To explore the spectrum of articular and peri-articular ultrasound (US) findings at metacarpophalangeal (MCP) joints in calcium pyrophosphate (CPP) deposition disease (CPPD). METHODS: Consecutive CPPD patients (chronic CPP crystal inflammatory arthritis or OA with CPPD), and age- and sex-matched controls with RA were prospectively enrolled. Patients underwent bilateral US examination of MCP joints. CPP deposits, synovial inflammation, osteophytes, cartilage damage and bone erosions were recorded. RESULTS: Sixty CPPD patients (33, 55.0% with OA with CPPD and 27, 45.0% with chronic CPP crystal inflammatory arthritis) and 40 RA patients were enrolled. CPP deposits were detected in 24 (40.0%) CPPD patients and in 3 (7.5%) RA patients (P <0.01). In CPPD patients, different types of CPP deposits were identified at MCP joints: 17 (28.3%) patients had dorsal capsuloligamentous deposits, 14 (23.3%) intra-cartilaginous deposits, 13 (21.7%) lateral capsuloligamentous deposits, 12 (20.0%) intra-articular deposits, eight (13.3%) double contour sign and five (8.3%) flexor digitorum tendons' deposits. CPPD patients with chronic CPP crystal inflammatory arthritis showed more US findings indicating synovial inflammation and CPP deposits than those with OA with CPPD. Conversely, a higher prevalence of US features indicating structural damage was noted in this latter phenotype. CPP deposits and bone erosions were the US findings with the highest value for diagnosing chronic CPP crystal inflammatory arthritis and RA, respectively. CONCLUSION: This study provides pictorial evidence of the broad spectrum of US findings indicating CPP deposits at MCP joints in CPPD. Furthermore, we reported different US patterns in different CPPD phenotypes.

Sonographic estimation of monosodium urate burden predicts the fulfillment of the 2016 remission criteria for gout: a 12-month study.

OBJECTIVE: To investigate whether baseline monosodium urate (MSU) burden estimated by ultrasound (US) predicts the achievement of the 2016 remission criteria for gout after 12 months. METHODS: In this 12-month prospective, observational and single-center study, patients with gout fulfilling all the domains of the 2016 preliminary remission criteria for gout at baseline and on urate-lowering therapy (ULT) for at least the preceding 6 months were consecutively enrolled. The US findings indicative of MSU deposits [aggregates, double contour (DC) sign, and/or tophi] were identified according to the Outcome Measure in Rheumatology US Working Group definitions. The US MSU burden was estimated by evaluating elbows, wrists, 2nd metacarpophalangeal joints, knees, ankles, and 1st metatarsophalangeal joints. RESULTS: Remission criteria were fulfilled in 21 (42.0%) out of 50 patients at 12 months. The baseline US MSU burden was significantly lower in patients who achieved remission than in those who did not fulfill the remission criteria at 12 months (1.9±1.8 vs 5.1±3.1, p<0.01). US scores and ongoing flare prophylaxis were the only significant predictors of remission with an odds ratio of 10.83 [(95%CI=1.14-102.59), p=0.04] for the absence of MSU deposits, 5.53 [(95%CI=1.34-22.76), p<0.01] for the absence of aggregates, 7.33 [(95%CI=1.71-31.44), p<0.01] for the absence of DC sign, 3.88 [(95%CI=1.08-13.92), p=0.04] for the absence of tophi, and 0.23 [(95%CI=0.07-0.75), p=0.02] for ongoing flare prophylaxis. CONCLUSION: In gout, baseline US estimation of MSU burden is an independent predictor of the achievement of the remission criteria at 12 months.

The sonographic identification of cortical bone interruptions in rheumatoid arthritis: a morphological approach.

Bone erosions are the hallmark of structural damage in rheumatoid arthritis (RA). Among imaging techniques, ultrasonography (US) has emerged as an accurate, reliable, repeatable, low-cost and non-invasive imaging modality to detect erosive changes in RA. However, small interruptions of the cortical bone detectable by last generation US equipment do not necessarily represent bone erosions. According to the available data, in addition to cortical bone interruption itself, only a few morphological US findings have been proposed to define RA bone erosions. However, other additional features may be considered to facilitate the interpretation of US cortical bone interruptions in RA. These could be summarised using the following four domains: size, site, shape and scenery. This hypothesis article provides a critical literature review of US features characteristic of RA bone erosions and pictorial evidence supporting the potential role of a morphological analysis in the US identification of bone erosions in RA patients. PLAIN LANGUAGE SUMMARY: The ultrasonographic morphology of cortical interruptions is helpful for the identification of bone erosions in rheumatoid arthritis: the "four Ss" approach Bone erosions are characteristic features of rheumatoid arthritis. They are associated with a more aggressive disease and with irreversible physical disability. In recent years, ultrasonography has emerged as an accurate and reliable technique for the detection of bone erosions, that appear as interruptions of the cortical bone with variable size. However, cortical bone interruptions do not necessarily represent bone erosions. Since bone erosions represent the earliest evidence of the destructive behaviour of RA, their identification is crucial.Besides the cortical interruption itself, only a few morphological ultrasonographic features were proposed to characterise bone erosions in rheumatoid arthritis.We believe that a morphological approach, including size, site, shape and scenery, may be considered to facilitate the interpretation of ultrasonographic cortical bone interruptions in rheumatoid arthritis.In this hypothesis article we carried out a critical review of the scientific literature and provided extensive pictorial evidence of the ultrasonographic spectrum of cortical interruptions supporting the potential role of considering the "four Ss" for the ultrasonographic identification of bone erosions in rheumatoid arthritis.

Ultrasound-Guided Procedures in Rheumatology Daily Practice: Feasibility, Accuracy, and Safety Issues.

BACKGROUND/OBJECTIVE: The aims of this study were to describe in detail the ultrasound (US)-guided procedures in our daily rheumatology practice, to evaluate the feasibility and accuracy of US-guided procedures, and to test the efficacy of our disinfection protocol in preventing infectious complications. METHODS: This was a cross-sectional and monocentric study. Information regarding patients' age, sex, body mass index, rheumatic disease, US pathological findings, aspirated and/or injected anatomical site, US equipment (ie, probe type and frequency), and needle type was consecutively collected for each US-guided procedure in a third-level rheumatology center. RESULTS: A total of 643 US-guided procedures were performed, with a mean of 5.2 procedures per working-day. In 94.2% of the patients, only one procedure was carried out, whereas in 5.8%, more than one. The mean time was 7 ± 2.5 minutes. Ultrasound-guided procedures were highly accurate (accuracy rate higher than 95%) and safe (adverse events were reported in 0.8%). Our disinfection protocol was effective in preventing infectious complications. Probes with frequency values between 8 to 13 MHz and 20-, 21-, and 22-gauge needles were the most frequently used at shoulder, knee, wrist, elbow, and ankle level. High-frequency linear probes (ranging between 18 and 22 MHz) and 23- and 25-gauge needles were used for injecting small joints of the hands and feet. Convex low-frequency probe (2-7 MHz) and 18- and 20-gauge needles were the most used for performing hip joint aspirations and/or injections. CONCLUSIONS: This study reports useful information for setting up a service providing US-guided procedures in rheumatology and supports the feasibility, accuracy, and safety of US-guided procedures.

Ultrasound measurement of muscle thickness at the anterior thigh level in rheumatology setting: a reliability study.

Ultrasound (US) is a promising tool for assessing sarcopenia. We aimed to test in the rheumatology setting two US scanning protocols to measure muscle thickness (MT) at the anterior thigh level and to assess their feasibility and reliability. In the first phase of the study, three rheumatologists performed a US examination on 19 consecutive patients adopting two scanning protocols, namely the anterior superior iliac spine (ASIS) and the greater trochanter techniques. After consensus was obtained on the easiest scanning protocol to perform, two rheumatologists adopted only the ASIS technique in 40 consecutive patients. MT measurements were recorded as well as the time needed to complete each scanning protocol bilaterally. The median time needed to complete the US examination was under 5 minutes for each of the two techniques, with no significant difference between them (p = 0.64). In the first phase, we found an excellent inter-observer reliability of the proposed scanning protocols, with a higher but nonstatistically significant intraclass correlation coefficient (ICC) for the ASIS technique compared with the greater trochanter technique (ICC 0.97 vs. ICC 0.92, p = 0.05). The ASIS technique had a significantly higher intra-observer reliability (ICC 0.97 vs. ICC 0.92, p < 0.01). In the second phase, the ASIS technique confirmed on a larger sample its excellent inter-observer reliability, with an ICC of 0.96. The present study presents a novel tool for assessing sarcopenia and provides evidence in favor of feasibility and reliability of US measurement of MT at the anterior thigh level in rheumatology setting. Key Points • This study demonstrates that ultrasound (US) measurement of muscle thickness at the anterior thigh level is highly reliable, especially for the "anterior superior iliac spine (ASIS)" technique. • The short time needed to complete the US assessment highlights the feasibility of the proposed scanning protocols. • The simplicity and conciseness of the proposed techniques will allow other researchers and clinicians to use it for a fast assessment of sarcopenia.

Association of Silicone Breast Implants, Breast Cancer and Anti-RNA Polymerase III Autoantibodies in Systemic Sclerosis: Case-Based Review.

Some case reports and small case series of patients with silicone breast implant (SBI) have reported the development of systemic sclerosis (SSc) many years later, despite conflicting evidence of this association in the literature. Recently, patients with SSc and anti-RNA polymerase III antibodies positivity have been associated with previous silicone implants and/or breast cancer, showing clinical features that differ from the classic SSc, such as rapid and diffuse cutaneous involvement and scleroderma renal crisis (SRC). The specific autoimmune reaction is not yet fully understood, although knowledge in this regard is increasing. We describe a case that can support these previous observations, strengthening this association which must be taken into account. Clinicians should be aware of this new clinical entity, given the widespread use of silicone implants.

Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review.

The main aim of this systematic literature review (SLR) was to summarise the evidence in the use of biological therapies in calcium pyrophosphate deposition disease (CPPD). We performed a SLR using PubMed, Embase and Cochrane databases. Only studies reporting the efficacy of biologics in CPPD were selected. The search resulted in 83 articles; 11 were further evaluated in the SLR. Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments (23.0%). Clinical response to anakinra was observed in 80.6% of patients with acute and 42.9% of those with chronic CPPD. Short-term treatment was well tolerated and adverse events were reported in 4.1% of the cases. This review provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.