Christelle Darrieutort-Laffite

IL-1β and TNFα promote monocyte viability through the induction of GM-CSF expression by rheumatoid arthritis synovial fibroblasts.

Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone (P < 0.001). This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF (P < 0.001). Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization.

Ultrasonography of the lumbar spine: Sonoanatomy and practical applications

Ultrasonography of the bones and joints has gained considerable ground in the field of rheumatology over the past decade and is now used in everyday practice both for diagnostic purposes and to guide local injections. However, the use of ultrasonography is virtually confined to the peripheral joints, whereas spinal diseases make a major contribution to rheumatology practice. Studies have established that ultrasonography of the lumbar spine is feasible. Adequate equipment and familiarity with spinal sonoanatomy are required. In this update, we suggest starting with a systematic examination of the lumbar spine to assess the various anatomic structures, from the thoracolumbar fascia superficially to the posterior part of the vertebras at the deepest level. The ligaments, erector spinae muscles, facet joints, and transverse processes can be visualized. Ultrasonography can serve to guide injections into the facet joints, about the nerve roots, and into the iliolumbar ligaments; as well as to identify relevant landmarks before epidural injection. Although diagnostic applications are more limited at present, systematic studies of abnormal ultrasonography findings will allow evaluations of the potential usefulness of ultrasonography for diagnosing spinal disorders. The depth of the spinal structures limits the ability to obtain high-resolution images. However, future technical improvements in ultrasound transducers and machines, together with the growing number of physicians trained in ultrasonography, can be expected to benefit the development of spinal ultrasonography in the near future.

Sodium 18F-sodium fluoride PET failed to predict responses to TNFα antagonist therapy in 31 patients with possible spondyloarthritis not meeting ASAS criteria

OBJECTIVES To determine whether (18)F-NaF positron-emission tomography (PET) contributes to the diagnosis of spondyloarthritis and whether observed uptakes predict the response to TNFα antagonist therapy. METHODS We studied patients who had suspected spondyloarthritis but did not meet ASAS criteria and who were referred for an assessment of eligibility for TNFα antagonist therapy. (18)F-NaF PET was offered instead of bone scintigraphy. TNFα antagonist therapy was given if the clinicians level of confidence in the diagnosis of spondyloarthritis based on (18)F-NaF PET findings was ≥50/100. RESULTS Thirty-one patients accepted to undergo (18)F-NaF PET. Their mean age was 39.9±11.7 years; 22% were HLA-B27-positive and none had evidence of sacroiliitis by magnetic resonance imaging. Of the 31 patients, 30 had abnormal (18)F-NaF PET findings. However, of the 312 high-uptake foci, only 123 (39.4%) matched sites of pain. TNFα antagonist therapy was given to 16 patients. The treated group and untreated group (n=15) were not significantly different for the mean number of high-uptake foci per patient (11.7±8.1 vs. 8.3±5.1, respectively) or for the proportion of patients with high uptake by the sacroiliac joints (13/16 [81%] vs. 8/15 [53%], respectively). In the treated group, 5 patients met ASAS response criteria after 3 months. These 5 patients were among the 9 treated patients who met Amors modified criteria (arthritis instead of asymmetrical oligoarthritis). In the 5 responders, the (18)F-NaF uptake scores were nonsignificantly lower than in the 11 nonresponders (9.0±8.5 vs. 13.0±6.4, respectively). In the patients for whom the (18)F-NaF PET findings increased the level of confidence in the diagnosis of spondyloarthritis, this effect was short-lived. DISCUSSION The positive predictive value of (18)F-NaF PET for diagnosing spondyloarthritis or predicting a response to TNFα antagonist therapy seems very low. This finding is probably ascribable to poor specificity.

Usefulness of a pre-procedure ultrasound scanning of the lumbar spine before epidural injection in patients with a presumed difficult puncture: A randomized controlled trial

UNLABELLED Ultrasound (US) is widely used in rheumatology to study and guide injection of peripheral joints. It can also provide useful information about the anatomy of the lumbar spine. Studies have shown that US examination of the spine was a useful tool to help perform epidural anaesthesia. The purpose of the study was to determine if the selection of the optimum puncture level by US may facilitate epidural steroid injection in case of presumed difficult puncture (BMI>30 kg/m(2), age>60 years or lumbar scoliosis). METHODS We performed a prospective randomized controlled study. Eighty patients were randomized in two groups: US group (n=40) which underwent a pre-procedure spinal US to determine the optimal lumbar level for injection or control group (n=40) for which the level of injection was determined by palpation. Primary endpoint was the pain during the procedure assessed using the Visual Analogue Scale (VAS). RESULTS We found a positive correlation between depth of the epidural space and BMI (P<0.001) and a negative correlation between size of the interspinous spaces and age (P<0.01). Visibility of the epidural space was not altered by obesity or age. We observed a trend toward a reduction in pain intensity during the procedure in the US group compared to the control group with a mean difference at -0.94 [-1.90; 0.02] but the difference was not significant (P=0.054). CONCLUSION US of the lumbar spine was feasible in patients with lumbar conditions even in obese and old ones and allowed the visualization of the epidural space. However, pre-procedure US examination did not reduce pain during the procedure.

Stretching of roots contributes to the pathophysiology of radiculopathies

PURPOSE To perform a synthesis of articles addressing the role of stretching on roots in the pathophysiology of radiculopathy. METHODS Review of relevant articles on this topic available in the PubMed database. RESULTS An intraoperative microscopy study of patients with sciatica showed that in all patients the hernia was adherent to the dura mater of nerve roots. During the SLR (Lasègues) test, the limitation of nerve root movement occurs by periradicular adhesive tissue, and temporary ischemic changes in the nerve root induced by the root stretching cause transient conduction disturbances. Spinal roots are more frail than peripheral nerves, and other mechanical stresses than root compression can also induce radiculopathy, especially if they also impair intraradicular blood flow, or the function of the arachnoid villi intimately related to radicular veins. For instance arachnoiditis, the lack of peridural fat around the thecal sac, and epidural fibrosis following surgery, can all promote sciatica, especially in patients whose sciatic trunks also stick to piriformis or internus obturator muscles. Indeed, stretching of roots is greatly increased by adherence at two levels. CONCLUSIONS As excessive traction of nerve roots is not shown by imaging, many physicians have unlearned to think in terms of microscopic and physiologic changes, although nerve root compression in the lumbar MRI is lacking in more than 10% of patients with sciatica. It should be reminded that, while compression of a spinal nerve root implies stretching of this root, the reverse is not true: stretching of some roots can occur without any visible compression.

Calcific tendonitis of the rotator cuff: From formation to resorption

Calcific tendonitis of the rotator cuff is due to apatite deposits in the shoulder tendons. Patients affected by calcific tendonitis have chronic shoulder pain and disability. Although the disease is frequent, about 10 to 42% of painful shoulders, mechanisms leading to this pathological mineralization are still largely unknown. Research reported in the 1990s suggested that the formation of calcific deposits is linked to cells looking like chondrocytes identified around calcium deposits within a fibrocartilage area. They were considered to be derived from tenocytes but more recently, tendon stem cells, able to differentiate into chondrocytes, were isolated. The pro-mineralizing properties of these chondrocytes-like cells, especially the role of alkaline phosphatase, are not currently clarified. The calcium deposits contain poorly crystalline carbonated apatite associated with protein. Among these proteins, only osteopontin has been consistently identified as a potential regulating factor. During the disease, spontaneous resorption can occur with migration of apatite crystals into the subacromial bursa causing severe pain and restriction of movement. In in vivo and in vitro experiments, apatite crystals were able to induce an influx of leucocytes and a release of IL-1β and IL-18 through the activation of the NLRP3 inflammasome. However, mechanisms leading to spontaneous resolution of this inflammation and disappearance of the calcification still need to be elucidated.

FRI0638 Comparison of ultrasound and mri in the diagnosis of proximal and distal biceps tendon pathology

Background Disorders of the long head of the biceps brachii tendon (LHBt) are commonly recognized as a source of shoulder pain. Ultrasound (US) is thought to be of limited value in the diagnosis of partial-thickness tear and non-tear abnormalities of the LHBt because of the difficulty to assess its intra-articular proximal portion. Brasseur recently described that placing the arm in extension/external rotation increased LHBt intra-articular portion visibility. Objectives The goal of this study was to determine if the systematic assessment of the intra-articular portion of the tendon, from the rotator interval to its glenoid insertion, with the arm placed in extension/external rotation could increase US sensitivity. Methods This was a cross-sectional study. All patients referred for the treatment of a rotator cuff disease (rupture, tendinopathy, calcific deposit) with an available MRI were included. US was performed blinded from the results of the clinical or MRI using a Sonosite Edge with a 6–13 MHz probe. LHBt was studied at different level: in the bicipital groove, at the rotator interval, over the upper pole of the humerus head to its insertion on the superior glenoid tubercule. To increase the visibility of the proximal portion, we placed the arm in extension/external rotation as described by Brasseur [1]. Diagnosis of tendinopathy were tendon enlargement, hypoechogenicity and an increase in the interfibrillar distance. Subluxation or dislocation of the LHBt was defined as a partial or total loss of contact between the tendon and its groove. Tearing of tendon was defined as discontinuity or absence of tendon fibers. Fluid collection was defined as an anechoic ring around the tendon >2 mm. Abnormalities of the LBHt on MRI was retrieved from the report. LBHt abnormalities detected on arthroscopy were used as the gold standard. Results We included 129 patients, 57 female (44%), and mean age 54 years (33–73). Seventy-five (58%) had a rotator cuff tear and 54 (42%) a tendinopathy. Arthroscopy found LHBt pathological changes in 39% of the case. The summary of the findings obtained with MRI, US (distal and proximal) and arthroscopy are summarised in table 1.Table 1 LHB MRI US distal US proximal Arthroscopy Normal 99 90 111 78 Subluxation 15 6 9 Effusion 12 30 Tear 3 3 6 6 Flattened 12 2 Thickening 30 Nodular 1 Inflammatory 3 We calculated the sensitivity/specificity of MRI and US (at the proximal and distal level) in the detection of LHBt changes using arthroscopy as gold standard (Table 2).Table 2 Sensitivity Specificity PPV PNV MRI 52% 96% 90% 73% US proximal 59% 88% 77% 77% US distal 29% 96% 83% 67% Conclusions US has a good specificity but a poor sensitivity in the detection of LHB tendon changes even when a systematic and carreful study of the proximal part of the tendon is undertaken. If detection of distal changes of the tendon in the inter-tubercular groove seems feasible with US, the involvement of the more proximal, intra-articular part of the tendon remains challenging. MRI sensitivity remains also poor. Overall, arthroscopy still remains the gold standard to detect LHB tendon intra-articular pathology. References Brasseur, The biceps tendons: from the top and from the bottom. Journal of ultrasound (2012) 15, 29–38. Disclosure of Interest None declared

Detection of a lumbar foraminal venous varix by Color Doppler Ultrasound

Ultrasonography is currently widely used in the rheumatology practice. Although mainly performed to study peripheral joint, several articles have underlined its interest to study spinal anatomy. However, its ability to provide diagnostic features is unknown. We studied the case of a 25-year-old woman having low back pain. Three different imaging modalities (Computed Tomography [CT], Magnetic Resonance Imaging [MRI] and Ultrasound) were used to explore it. CT and MRI showed a foraminal dilation of the lombo-ovarian vein at the L3-L4 level with a scalloping of the lateral edge of L3. We were able to detect it with Color Doppler Ultrasound and a malformation of the inferior vena cava was also found. We showed for the first time that Color Doppler Ultrasound can detect venous malformation of the spine. This imaging modality could help us in the diagnosis of atypical lesions of the spine to confirm their vascular origin.

THU0335 Identification of the Optimum Puncture Level by A Lumbar Spine Ultrasonography Decreases the Pain during the Epidural Injection Procedure in Patients with A Presumed Difficult Puncture

Background Ultrasound (US) is widely used in rheumatology to study and guide infiltration of peripheral joints. This imaging modality can also provide useful information about the anatomy of the lumbar spine. Studies have shown that US examination of the spine was an useful tool to help perform epidural anesthesia [1]. Objectives To determine if the identification of the optimum puncture level by a pre-puncture US examination of the lumbar spine may facilitate epidural corticosteroid injection in patients with a presumed difficult puncture. Methods We performed a prospective randomized single-blind controlled study (NCT01832844). All patients referred to our unit for the treatment of sciatica due to lumbar disc herniation were evaluated. Inclusion criteria were a BMI >30 kg/m2 and/or age >60 years and/or lumbar scoliosis (Cobb angle >10°). Patients were randomized to a US (n=40) or a control (n=40) group. The US group underwent a pre-procedure spinal US (Esaote Mylab 70; 3-11 MHz probe). Interspinous spaces and depth of the epidural space were measured. Visibility and accessibility of the epidural space was thus rated as “poor”, “moderate” or “good”. The best lumbar level to perform the injection was selected according these results. Patients of the control group underwent a fake US examination to remain blind to the group allocation and the level of injection was selected using the traditional landmark technique. An interspinous injection of 5 ml of Hydrocortisone was thus performed. Primary endpoint was the pain during the procedure assessed using the Visual Analogue Scale (VAS). Each redirection of the needle was counted. Data are presented as the mean (±SD). A Student t-test and a Pearson correlation test were used for the statistical analysis. Results Mean age was 62,5 (±16) and 33% were men. 47/80 (58%) patients were over 60 years, 41/80 (51%) had a BMI>30 kg/m2 and 14/80 (17%) had a lumbar scoliosis. Among the 80 patients, 21 (26%) had 2 or more criteria of presumed difficult puncture. Mean epidural space depth was 49.2 mm (±13.8) and mean interspinous distance was 14.22 mm (±5.1). We found a positive correlation between epidural space depth and BMI (p<0,001) and a negative correlation between interspinous spaces and age (p<0,01). A reduction of the intensity of pain during the procedure was observed in the US group compared to the control group (mean VAS 2,01±1,6 versus 2,95±2,5 respectively; p=0,05). The difference was even greater in patients over 60 years (mean VAS 1,86±0,4 versus 3,50±0,4; p=0,08). Finally, 22/40 (55%) injections were performed without any redirection in the US group compared with 16/40 (40%) in the control group (p=NS). Conclusions US evaluation of the interspinous space and epidural depth is feasible even in obese or old patients. Identification of the optimum puncture level by a pre-puncture US decreased the pain during the epidural injection procedure. This benefit was greater in patients over 60 years. US of the lumbar spine represents an additional technique at the rheumatologists disposal to help guiding lumbar spine injections. References Grau T, Leipold RW, Conradi R, et al. Efficacy of ultrasound imaging in obstetric epidural anesthesia. J Clin Anesth. 2002;14:169-75. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3841

SAT0411 Visualization of the Lumbar Epidural Space by Ultrasonography

Background Epidural steroid injections are a common method used for the treatment of patients with sciatica. They are usually performed without imaging guidance using anatomical landmarks. However, injections are sometimes challenging resulting in prolonged procedure times, multiple needle passes and significant pain. Ultrasonography (US) is mainly used by rheumatologist for the guidance of peripheral joint injections. However, some studies have shown that US examination of the spine was useful before epidural anesthesia to predict which patients were at risk for a difficult procedure (1). Objectives The aim of our study was to evaluate the feasibility of a pre-procedure ultrasound examination of the spine before epidural steroid injections. Methods US examination of the lumbar spine was performed in 21 patients referred to our unit for the treatment of sciatica due to lumbar disc herniation. The scanning was performed with an Esaote My lab 70 unit using a curved-array, low-frequency (1–8 MHz) probe on a patient seated. L5-S1 intervertebral space was first located on a sagittal view, and the probe was then moved cranially. At each intervertebral level, we recorded our ability to depict the epidural space. We rated the visibility as ‘absent’, ‘poor’, ‘moderate’, ‘good’ with assigned numerical values of 0, 1, 2 and 3, respectively. We measured distance between spinous processes and depth of the epidural space in L3-L4, L4-L5 and L5-S1. Each measurement was performed 3 times and the mean was used for statistical analysis. Data are given as the median (+/- interquartile range). Differences between measurements at each lumbar levels was assessed with a Friedman’s Test and correlations between age, gender and Body mass index (BMI) and epidural visibility with a Pearson’s test. Results 21 patients (11 men and 10 women), mean age 46 years (38-60.5) were included in our study. Median weight was 73 kg (59-85) and median BMI 24.8 (20.85-27.05). Median depth of the epidural space was 44.5 mm (41.60-48.45) in L3-L4, 43.80 mm (41.35-45.85) in L4-L5 and 40.8 mm (39.2-46.9) in L5-S1. Median distance between spinous processes was 17.9 mm (12.95-20.75), 15.9 mm (13.15-17.8) and 16.4 mm (15.30-17.7) in L3-L4, L4-L5 and L5-S1, respectively. Visibility of the epidural space was significantly lower in L5-S1 (p<0.01). We found a negative correlation between age and the distance between spinous processes and visibility of the epidural space at all levels (p<0.01). No significant correlation was found between the visibility of the epidural space and the BMI. Conclusions We accurately identified each intervertebral level, estimated depth to the epidural space, and located the most appropriate interspinous space for needle insertion. As expected, the distance between spinous processes and epidural accessibility was reduced in older patients. US might help us to predict which patients are at risk for a difficult epidural injection and help the physician to identify the optimal site of injection. Overall, US of the lumbar spine represents a new imaging modality available for the rheumatology to treat patients with lumbar conditions. References Weed JT, Taenzer AH, Finkel KJ, Sites BD. Evaluation of pre-procedure ultrasound examination as a screening tool for difficult spinal anaesthesia. Anaesthesia. 2011 Oct;66(10):925-30. Disclosure of Interest None Declared