Publications by authors named "Christelle Darrieutort-Laffite"

27 Publications

  • Page 1 of 1

Clinical characteristics and management of olecranon and prepatellar septic bursitis in a multicentre study.

J Antimicrob Chemother 2021 Jul 22. Epub 2021 Jul 22.

Rheumatology Department, CHU Nantes, Nantes, France.

Background: No current guidelines are available for managing septic bursitis (SB).

Objectives: To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres.

Methods: This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy.

Results: We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted <14 days (P = 0.02) in both surgically and medically treated patients.

Conclusions: Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of <14 days may require special attention in both groups.
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http://dx.doi.org/10.1093/jac/dkab265DOI Listing
July 2021

Contribution of mycobiota to the pathogenesis of spondyloarthritis.

Joint Bone Spine 2021 Jun 21;88(6):105245. Epub 2021 Jun 21.

Service de rhumatologie, Hôtel-Dieu, CHU de Nantes, place Alexis-Ricordeau, 44093 Nantes cedex 01, France.

This review lists current evidences for a contribution of gut mycobiota to the pathogenesis of SpA and related conditions. Gut mycobiota has a small size as compared to bacterial microbiota, but an even greater inter- and intra-individual variability. Although most fungi (brought by food or air) are only transitory present, a core mycobiota of gut resident fungi exists, and interplays with bacteria in a complex manner. A dysbiosis of this gut mycobiota has been observed in Crohn's disease and sclerosing cholangitis, with decreased proportion of Saccharomyces cerevisiae and outgrowth of more pathogenic gut fungi. Fungal-induced lower number of commensal gut bacteria can promote translocation of some bacterial/fungal antigens through mucosae, and live fungi can also cross the epithelial border in Crohn's disease. This dysbiosis also lower the ability of bacteria to metabolize tryptophan into regulatory metabolites, consequently enhancing tryptophan metabolism within human cells, which might contribute to fatigue. Translocation of mycobiotal antigens like curdlan (beta-glucan), which plays a major role in the pathogenesis of SpA in the SGK mice, has been observed in humans. This translocation of fungal antigens in human SpA might account for the anti-Saccharomyces antibodies found in this setting. Contribution of fungal antigens to psoriasis and hidradenitis suppurativa would fit with the preferential homing of fungi in the skin area most involved in those conditions. Fungal antigens also possess autoimmune uveitis-promoting function. As genes associated with SpA (CARD9 and IL23R) strongly regulate the innate immune response against fungi, further studies on fungi contribution to SpA are needed.
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http://dx.doi.org/10.1016/j.jbspin.2021.105245DOI Listing
June 2021

Pro-inflammatory effects of human apatite crystals extracted from patients suffering from calcific tendinopathy.

Arthritis Res Ther 2021 04 29;23(1):131. Epub 2021 Apr 29.

INSERM UMR1238, Bone Sarcoma and Remodeling of Calcified Tissues, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035, Nantes Cedex 1, France.

Background: Calcific tendonitis of the rotator cuff is due to carbonated apatite deposits in the shoulder tendons. During the evolution of the disease, an acute inflammatory episode may occur leading to the disappearance of the calcification. Although hydroxyapatite crystal-induced inflammation has been previously studied with synthetic crystals, no data are available with calcifications extracted from patients suffering from calcific tendinopathy. The objective of the study was to explore the inflammatory properties of human calcifications and the pathways involved.

Methods: Human calcifications and synthetic hydroxyapatite were used in vitro to stimulate human monocytes and macrophages, the human myeloid cell line THP-1, and human tenocytes. The release of IL-1β, IL-6, and IL-8 by cells was quantified by ELISA. The gene expression of pro- and anti-inflammatory cytokines was evaluated by quantitative PCR. NF-kB activation and NLRP3 involvement were assessed in THP-1 cells using a NF-kB inhibitor and a caspase-1 inhibitor. The inflammatory properties were then assessed in vivo using a mouse air pouch model.

Results: Human calcifications were able to induce a significant release of IL-1β when incubated with monocytes, macrophages, and THP-1 only if they were first primed with LPS (monocytes and macrophages) or PMA (THP-1). Stimulation of THP-1 by human calcifications led to similar levels of IL-1β when compared to synthetic hydroxyapatite although these levels were significantly inferior in monocytes and macrophages. The patient's crystals enhanced mRNA expression of pro-IL-1β, as well as IL-18, NF-kB, and TGFβ when IL-6 and TNFα expression were not. IL-1β production was reduced by the inhibition of caspase-1 indicating the role of NLRP3 inflammasome. In vivo, injection of human calcifications or synthetic hydroxyapatite in the air pouch led to a significant increase in membrane thickness although significant overexpression of IL-1β was only observed for synthetic hydroxyapatite.

Conclusions: As synthetic hydroxyapatite, human calcifications were able to induce an inflammatory response resulting in the production of IL-1β after NF-kB activation and through NLRP3 inflammasome. In some experiments, IL-1β induction was lower with human calcifications compared to synthetic apatite. Differences in size, shape, and protein content may explain this observation.
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http://dx.doi.org/10.1186/s13075-021-02516-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082912PMC
April 2021

Factors Associated With Clinical Improvement and the Disappearance of Calcifications After Ultrasound-Guided Percutaneous Lavage of Rotator Cuff Calcific Tendinopathy: A Post Hoc Analysis of a Randomized Controlled Trial.

Am J Sports Med 2021 03;49(4):883-891

Department of Rheumatology, CHU Nantes, Nantes, France.

Background: Calcific tendinitis of the rotator cuff is a frequent cause of shoulder pain. Ultrasound-guided percutaneous lavage (UGPL) is an effective treatment, but factors associated with good clinical and radiological outcomes still need to be identified.

Purpose: To study the clinical, procedural, and radiological characteristics associated with improved shoulder function and the disappearance of calcification on radiograph after UGPL.

Study Design: Case-control study; Level of evidence, 3.

Methods: This is a post hoc analysis of the CALCECHO trial, a double-blinded randomized controlled trial conducted on 132 patients. The trial assessed the effect of corticosteroid injections after UGPL, and patients were randomly assigned to receive either corticosteroid or saline solution in the subacromial bursa. We analyzed all patients included in the randomized controlled trial as 1 cohort. We collected the patients' clinical, procedural, and radiological characteristics at baseline and during follow-up (3, 6, and 12 months). Univariable analysis, followed by multivariable stepwise regression through forward elimination, was performed to identify the factors associated with clinical success (Disabilities of the Arm, Shoulder and Hand [DASH] score <15) or the disappearance of calcification.

Results: Good clinical outcomes at 3 months were associated with steroid injections after the procedure (odd ratio [OR], 3.143; 95% CI, 1.105-8.94). At 6 months, good clinical evolution was associated with a lower DASH score at 3 months (OR, 0.92; 95% CI, 0.890-0.956) and calcium extraction (OR, 10.7; 95% CI, 1.791-63.927). A lower DASH at 6 months was also associated with a long-term favorable outcome at 12 months (OR, 0.939; 95% CI, 0.912-0.966). Disappearance of calcification at 3 and 12 months occurred more frequently in patients in whom communication was created between the calcification and the subacromial bursa during the procedure (OR, 2.728 [95% CI, 1.194-6.234] at 3 months; OR, 9.835 [95% CI, 1.977-48.931] at 12 months). Importantly, an association between calcification resorption and good clinical outcome was found at each time point.

Conclusion: Assessing patients at 3 months seems to be an essential part of their management strategy. Calcium extraction and creating a communication between the calcific deposits and subacromial bursa are procedural characteristics associated with good clinical and radiological evolution.
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http://dx.doi.org/10.1177/0363546521992359DOI Listing
March 2021

Usefulness of real-world patient cohort follow-ups using questionnaires to assess the effect of treatments on the general population.

Joint Bone Spine 2021 07 23;88(4):105142. Epub 2021 Jan 23.

Service de Rhumatologie, Hôtel-Dieu, CHU Nantes, Place Alexis Ricordeau, 44093 Nantes cedex 01, France.

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http://dx.doi.org/10.1016/j.jbspin.2021.105142DOI Listing
July 2021

Rheumatic involvement and bone scan features in Schnitzler syndrome: initial and follow-up data from a single-center cohort of 25 patients.

Arthritis Res Ther 2020 11 18;22(1):272. Epub 2020 Nov 18.

Department of Internal Medicine Interne, CHU Nantes, Nantes, France.

Objective: To report on the characteristics and long-term course of rheumatic manifestations in Schnitzler syndrome (SchS).

Methods: A retrospective cohort study of patients with SchS followed between 2000 and 2020. Inclusion criteria included a diagnosis of SchS (Strasbourg criteria). All available bone scans were reviewed and scored according to the intensity and number of pathological sites. The scintigraphic score was compared with the clinical activity score, CRP level, and treatments.

Results: Twenty-five patients were included. Median age at diagnosis was 68 years. Eighty patients (72%) had SchS-related rheumatic pain. Most patients had a long-standing isolated rash before constitutional and/or rheumatic symptoms appeared. The monoclonal component level was usually very low (IgMκ in 22/25). Rheumatic pain predominated around the knees. Bone scans revealed abnormal tracer uptake in 15/18 (85%). The scintigraphic score correlated with clinical activity (r = 0.4, p < 0.02) and CRP level (r = 0.47, p < 0.01). The scintigraphic score was lower in patients receiving corticosteroids or IL1Ra (interleukin 1 receptor antagonist) than in untreated patients (median scores:2, 0, and 13, respectively; p < 0.05). Two patients developed Waldenström macroglobulinemia. Of the 22 surviving patients, median age at follow-up was 76 years. IL1Ra was used in 13 patients, with dramatic efficacy on both symptoms and bone scan features.

Conclusions: Rheumatic manifestations are very prevalent in SchS. However, bone pain can be misleading and contribute to misdiagnosis. Bone scan abnormalities are very prevalent and correlate with disease activity and treatments. IL1-Ra has a dramatic and durable efficacy but may not be required in every patient early on.
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http://dx.doi.org/10.1186/s13075-020-02318-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677784PMC
November 2020

Location of calcifications of rotator cuff on ultrasound in 74 patients: Near the junction between the supraspinatus and infraspinatus tendons in 96% of the cases.

Joint Bone Spine 2021 03 10;88(2):105107. Epub 2020 Nov 10.

Department of rheumatology, Nantes university hospital, 1, place Alexis-Ricordeau, 44093 Nantes cedex, France.

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http://dx.doi.org/10.1016/j.jbspin.2020.105107DOI Listing
March 2021

Molecular and Structural Effects of Percutaneous Interventions in Chronic Achilles Tendinopathy.

Int J Mol Sci 2020 Sep 23;21(19). Epub 2020 Sep 23.

Rheumatology Department, Nantes University Hospital, 44000 Nantes, France.

Achilles tendinopathy (AT) is a common problem, especially in people of working age, as well as in the elderly. Although the pathogenesis of tendinopathy is better known, therapeutic management of AT remains challenging. Various percutaneous treatments have been applied to tendon lesions: e.g., injectable treatments, platelet-rich plasma (PRP), corticosteroids, stem cells, MMP inhibitors, and anti-angiogenic agents), as well as percutaneous procedures without any injection (percutaneous soft tissue release and dry needling). In this review, we will describe and comment on data about the molecular and structural effects of these treatments obtained in vitro and in vivo and report their efficacy in clinical trials. Local treatments have some impact on neovascularization, inflammation or tissue remodeling in animal models, but evidence from clinical trials remains too weak to establish an accurate management plan, and further studies will be necessary to evaluate their value.
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http://dx.doi.org/10.3390/ijms21197000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582801PMC
September 2020

Long-term follow up after denosumab treatment for osteoporosis - rebound associated with hypercalcemia, parathyroid hyperplasia, severe bone mineral density loss, and multiple fractures: a case report.

J Med Case Rep 2020 Aug 11;14(1):130. Epub 2020 Aug 11.

Rheumatology Department, Nantes University Hospital, 1 place Alexis Ricordeau, 44093, Nantes, Cedex, France.

Background: The rebound effect after stopping treatment with denosumab may be associated with rapid loss of the gains in bone mineral density achieved with treatment, high levels of bone remodeling markers, the occurrence of vertebral fractures, and even hypercalcemia.

Case Presentation: A 64-year-old osteoporotic Caucasian woman suffered from a fracture of her second lumbar vertebra in 2004. From January 2005, she was treated with denosumab for 9 years, with good densitometry results for her hip and lumbar areas, and no fractures over the last 6 years of treatment. Ten months after the treatment with denosumab was stopped, a cascade of vertebral fractures, including some in unusual locations (third thoracic vertebra), and multiple rib fractures in a context of hypercalcemia, suggested possible malignancy. A complete evaluation, including systemic, biological, and biopsy analyses, ruled out this hypothesis. The hypercalcemia was associated with normal plasma phosphate and vitamin D concentrations, and a high parathyroid hormone level, with an abnormal fixation of the lower lobe of the thyroid on sesta-methoxy-isobutyl-isonitrile scintigraphy. Histological analysis of the excised parathyroid tissue revealed hyperplasia. The associated thyroidectomy (goiter) led to the discovery of a thyroid papillary microcarcinoma.

Conclusions: We consider the consequences of this rebound effect, not only in terms of the major loss of bone density (return to basal values within 3 years) and the multiple disabling fracture episodes, but also in terms of the hypercalcemia observed in association with apparently autonomous tertiary hyperparathyroidism. Several cases of spontaneous reversion have been reported in children, but the intervention in our patient precluded any assessment of the possible natural course. The discovery of an associated thyroid neoplasm appears to be fortuitous. Better understanding of the various presentations of the rebound effect after stopping treatment with denosumab would improve diagnostic management of misleading forms, as in this case. Bisphosphonates could partially prevent this rebound effect.
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http://dx.doi.org/10.1186/s13256-020-02401-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427054PMC
August 2020

2020 French recommendations on the management of septic arthritis in an adult native joint.

Joint Bone Spine 2020 Dec 3;87(6):538-547. Epub 2020 Aug 3.

Rheumatology Department, South Hospital, Rennes University Hospital, Rennes, France; Western France Reference Centre for Complex Bone and Joint Infections (CRIOGO), Rennes, France.

Septic arthritis (SA) in an adult native joint is a rare condition but a diagnostic emergency due to the morbidity and mortality and the functional risk related to structural damage. Current management varies and the recommendations available are dated. The French Rheumatology Society (SFR) Bone and Joint Infection Working Group, together with the French Language Infectious Diseases Society (SPILF) and the French Orthopaedic and Trauma Surgery Society (SOFCOT) have worked according to the HAS methodology to devise clinical practice recommendations to diagnose and treat SA in an adult native joint. One new focus is on the importance of microbiological documentation (blood cultures and joint aspiration) before starting antibiotic treatment, looking for differential diagnoses (microcrystal detection), the relevance of a joint ultrasound to guide aspiration, and the indication to perform a reference X-ray. A cardiac ultrasound is indicated only in cases of SA involving Staphylococcus aureus, oral streptococci, Streptococcus gallolyticus or Enterococcus faecalis, or when infective endocarditis is clinically suspected. Regarding treatment, we stress the importance of medical and surgical collaboration. Antibiotic therapies (drugs and durations) are presented in the form of didactic tables according to the main bacteria in question (staphylococci, streptococci and gram-negative rods). Probabilistic antibiotic therapy should only be used for patients with serious symptoms. Lastly, non-drug treatments such as joint drainage and early physical therapy are the subject of specific recommendations.
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http://dx.doi.org/10.1016/j.jbspin.2020.07.012DOI Listing
December 2020

Inadequacies of the Lasègue test, and how the Slump and Bowstring tests are useful for the diagnosis of sciatica.

Joint Bone Spine 2021 01 16;88(1):105030. Epub 2020 Jun 16.

Service de rhumatologie, Hôtel-Dieu, CHU of Nantes, 44093, Nantes cedex 01, France.

Diagnosis of sciatica mainly relies on pain reproduction by stretching of the lumbar roots since neurological examination and medical history are usually not sufficient to guarantee diagnosis. The Lasègue test is the most popular method, which starts with the straight leg-raising test (SLR). However it is not perfect, and is not always well performed or interpreted. Passive ankle dorsiflexion at the end of the SLR (Bragard test) is more sensitive, but can also remain normal in some cases of sciatica. Other stretching tests can help to recognise lumbar root damage in patients with poorly defined pain in a lower extremity: firstly, the Christodoulides test, i.e. reproduction of L5 sciatic pain by a femoral stretch test; secondly, the Slump test, performed on a patient in a sitting position, by slowly extending their painful leg then passively bending their neck (or the opposite); and thirdly, the Bowstring test, which requires, at the end of the Lasègue test, once the knee has been slightly flexed, pressing on the course of the peroneal and/or tibial nerves in the popliteal fossea to try and reproduce the exact pain felt by the patient. The combination of all these tests takes less than 2minutes, and could improve both the sensitivity and specificity of the physical examination for the diagnosis of sciatica. This article is a review of the limitations of the Lasègue/SLR tests and of the efficacy of these other tests for stretching the lumbar roots.
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http://dx.doi.org/10.1016/j.jbspin.2020.06.004DOI Listing
January 2021

Is ultrasound-guided caudal steroid injection effective in the management of lower lumbar radicular pain? A two-center prospective observational study on 150 patients.

Joint Bone Spine 2020 07 4;87(4):364-365. Epub 2019 Dec 4.

Department of rheumatology, CHU de Rennes, 16, boulevard de Bulgarie, 35200 Rennes, France; Inserm NuMeCan UMR 1274, CIMIAD, university of Rennes, 35000 Rennes, France.

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http://dx.doi.org/10.1016/j.jbspin.2019.11.006DOI Listing
July 2020

Are painDETECT scores in musculoskeletal disorders associated with duration of daily pain and time elapsed since current pain onset?

Pain Rep 2019 May-Jun;4(3):e739. Epub 2019 Apr 9.

Rheumatology Department, Nantes University Hospital, Hôtel-Dieu, CHU Nantes, Nantes, France.

Objectives: We aimed to compare painDETECT scores in outpatients seen in a rheumatology department over a 1-month period and search for correlations between painDETECT scores and the estimated duration of daily pain and time elapsed since the onset of current pain.

Patients And Methods: A total of 529 of 738 outpatients agreed to complete a set of questionnaires, including painDETECT.

Results: The mean painDETECT score was 14.14 ± 7.59, and 31% of the patients had painDETECT scores of >18. Fibromyalgia ranked first (21.2 ± 6.0), followed by osteoarthritis of the lower limbs (17.8 ± 8.2), back pain and radiculopathies (16.1 ± 6.8), osteoarthritis of the upper limbs (15.7 ± 8.1), spondylarthrosis (15.1 ± 7.2), entrapment neuropathies (14.1 ± 2.4), rheumatoid arthritis (13.8 ± 7.1), miscellaneous conditions (13.8 ± 8.2), tendinitis (13.4 ± 7.9), connectivitis (11.5 ± 6.7), and osteoporosis (8.5 ± 6.9). The duration of daily pain was much longer in patients with painDETECT scores of >18 (12.41 ± 8.45 vs 6.53 ± 7.45 hours) ( = 0.0000), but very similar painDETECT scores were observed for patients suffering from pain for less than 1 week (13.7 ± 8.2; 38% > 18), for 1 month (14.5 ± 8.2; 25% > 18), several months (12.7 ± 7.3; 23% > 18), 1 year (13.8 ± 7.7; 29% > 18), or several years (14.7 ± 7.4; 33% > 18).

Conclusion: PainDETECT scores differed little depending on the musculoskeletal condition, strongly correlated with the duration of daily pain, and appeared to be as high in patients with recent pain as in those suffering for years.
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http://dx.doi.org/10.1097/PR9.0000000000000739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749904PMC
April 2019

Rotator Cuff Tenocytes Differentiate into Hypertrophic Chondrocyte-Like Cells to Produce Calcium Deposits in an Alkaline Phosphatase-Dependent Manner.

J Clin Med 2019 Sep 26;8(10). Epub 2019 Sep 26.

INSERM UMR1238, Bone Sarcoma and remodeling of calcified tissues, Nantes University, 44093 Nantes, France.

Calcific tendonitis is a frequent cause of chronic shoulder pain. Its cause is currently poorly known. The objectives of this study were to better characterize the cells and mechanisms involved in depositing apatite crystals in human tendons. Histologic sections of cadaveric calcified tendons were analyzed, and human calcific deposits from patients undergoing lavage of their calcification were obtained to perform infrared spectroscopy and mass spectrometry-based proteomic characterizations. In vitro, the mineralization ability of human rotator cuff cells from osteoarthritis donors was assessed by alizarin red or Von Kossa staining. Calcifications were amorphous areas surrounded by a fibrocartilaginous metaplasia containing hypertrophic chondrocyte-like cells that expressed tissue non-specific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which are two key enzymes of the mineralization process. Calcific deposits were composed of apatite crystals associated with proteins involved in bone and cartilage development and endochondral bone growth. In vitro, tenocyte-like cells extracted from the rotator cuff were able to mineralize in osteogenic cultures, and expressed , , and , which are hypertrophic chondrocytes markers. The use of a TNAP inhibitor significantly prevented mineral deposits. We provide evidence that tenocytes have a propensity to differentiate into hypertrophic chondrocyte-like cells to produce TNAP-dependent calcium deposits. We believe that these results may pave the way to identifying regulating factors that might represent valuable targets in calcific tendonitis.
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http://dx.doi.org/10.3390/jcm8101544DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833470PMC
September 2019

Is it currently reasonable to offer short, 14-day antibiotic therapies after a surgical synovectomy in native joint septic arthritis?

Ann Rheum Dis 2020 11 5;79(11):e146. Epub 2019 Jul 5.

Osteoarticular Infections Working Group of the French Society of Rheumatology, Paris, France.

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http://dx.doi.org/10.1136/annrheumdis-2019-215887DOI Listing
November 2020

Are corticosteroid injections needed after needling and lavage of calcific tendinitis? Randomised, double-blind, non-inferiority trial.

Ann Rheum Dis 2019 06 11;78(6):837-843. Epub 2019 Apr 11.

Department of Rheumatology, CHU Nantes, Nantes, France

Objective: Steroid injections are common after an ultrasound-guided puncture and lavage (UGPL) of calcific tendonitis of the rotator cuff. However, steroids may prevent calcification resorption and negatively affect tendon healing. Our study was designed to determine whether saline solution was non-inferior to steroids in the prevention of acute pain reactions in the week following UGPL.

Methods: This was a randomised, double-blinded, controlled non-inferiority trial with 12-month follow-up. We included 132 patients (66 in each group) with symptomatic calcification measuring more than 5 mm. Patients received 1 mL of saline or steroid (methylprednisolone 40 mg) in the subacromial bursa at the end of UGPL. Primary outcome was the maximal pain during the week following the procedure with a prespecified non-inferiority margin of 10 mm (0-100 visual analogue scale). Secondary outcomes included pain at rest and during activity, function (disabilities of the arm, shoulder and hand score) and radiological evolution of the calcification over the 12-month follow-up.

Results: The estimated mean difference in the first week's maximal pain between these two groups was 11.76 (95% CI 3.78 to 19.75). Steroids significantly improved VAS pain at rest and during activities, as well as function at 7 days and 6 weeks. They did not change the rate of calcification resorption, which occurred in 83% and 74% of patients at 12 months in the saline and steroid groups.

Conclusion: Non-inferiority of saline when compared with steroids could not be established. However, steroid injection improved pain in the 6 weeks following the procedure, and function in the 3 months after, with no significant effect on calcification resorption.

Trial Registration Number: NTC02403856.
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http://dx.doi.org/10.1136/annrheumdis-2018-214971DOI Listing
June 2019

Calcific tendonitis of the rotator cuff: From formation to resorption.

Joint Bone Spine 2018 12 28;85(6):687-692. Epub 2017 Nov 28.

Department of Rheumatology, Nantes University Hospital, 44093 Nantes cedex 1, France; Inserm U1238, PHY-Os, Bone Sarcomas and remodeling of calcified tissues, University of Nantes School of Medicine, 44093 Nantes, France.

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.
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http://dx.doi.org/10.1016/j.jbspin.2017.10.004DOI Listing
December 2018

Multiple Vertebral Osteonecroses (Kümmell's Disease) After 10 Years on Denosumab: Is Osteocyte Apoptosis to Blame?

Calcif Tissue Int 2018 03 4;102(3):368-372. Epub 2017 Nov 4.

Rheumatology Department, Nantes University Hospital, 1 Place Alexis Ricordeau, 44093, Nantes Cedex, France.

We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell's disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways. The vertebral osteonecrosis in our case may, therefore, have resulted from osteocyte apoptosis, decompensated by the sudden reactivation of bone remodeling after the cessation of denosumab treatment.
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http://dx.doi.org/10.1007/s00223-017-0357-1DOI Listing
March 2018

Efficacy of local glucocorticoid after local anesthetic in low back pain with lumbosacral transitional vertebra: A randomized placebo-controlled double-blind trial.

Joint Bone Spine 2018 05 8;85(3):359-363. Epub 2017 May 8.

Service de rhumatologie, CHD Vendée, boulevard S.-Moreau, 85925 La Roche-sur-Yon cedex 9, France.

Objective: The primary objective of this study was to compare the efficacy of local injection of a local anesthetic with a glucocorticoid versus a local anesthetic with saline to treat low back pain due to lumbosacral transitional vertebras (LSTV) with a pseudoarticulation.

Methods: A randomized placebo-controlled double-blind study was conducted in patients with unilateral low back pain ascribed clinically to LSTV. Patients were randomized to lidocaine plus saline (LS group) or lidocaine plus cortivazol (LC group) injected locally under computed tomography guidance. The primary outcome measure was the 24-hour mean visual analog scale (VAS) score for low back pain 4 weeks after the injection.

Results: Of 16 randomized patients, 15 were included in the analysis, 8 in the LS group and 7 in the LC group. The mean VAS pain score at week 4 was not significantly different between the two groups. In the two groups pooled, the mean VAS pain score decreased significantly from baseline to week 4, from 5.52±0.99 to 3.86±2.55 (P≤0.05). The difference remained significant at week 12. Significant improvements occurred in the EIFEL disability index and items of the Dallas Pain Questionnaire. No adverse events were recorded.

Conclusion: In patients with chronic low back pain consistent with a symptomatic LSTV type II or IV in the Castellvi classification, a local injection of lidocaine with or without cortivazol may provide sustained improvements in pain and function. The underlying mechanism is unclear.
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http://dx.doi.org/10.1016/j.jbspin.2017.05.003DOI Listing
May 2018

Stretching of roots contributes to the pathophysiology of radiculopathies.

Joint Bone Spine 2018 01 20;85(1):41-45. Epub 2017 Jan 20.

Rheumatology Unit, Nantes University Hospital, CHU de Nantes, 1, place Alexis-Ricordeau, 44093 Nantes cedex 01, France.

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 (Lasègue's) 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.
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http://dx.doi.org/10.1016/j.jbspin.2017.01.004DOI Listing
January 2018

Detection of a lumbar foraminal venous varix by Color Doppler Ultrasound.

Joint Bone Spine 2016 Jul 7;83(4):451-2. Epub 2016 Apr 7.

Rheumatology unit, Nantes University Hospital, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France.

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.
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http://dx.doi.org/10.1016/j.jbspin.2015.09.009DOI Listing
July 2016

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

Joint Bone Spine 2015 Dec 1;82(6):411-6. Epub 2015 Oct 1.

Service de rhumatologie, Hôtel-Dieu, CHU de Nantes, 1, place Alexis-Ricordeau, 44093 Nantes cedex 01, France. Electronic address:

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 clinician's 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 Amor's 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.
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http://dx.doi.org/10.1016/j.jbspin.2015.08.012DOI Listing
December 2015

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.

Joint Bone Spine 2015 Oct 9;82(5):356-61. Epub 2015 Mar 9.

Rheumatology unit, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France.

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.
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http://dx.doi.org/10.1016/j.jbspin.2015.02.001DOI Listing
October 2015

Sjögren's syndrome complicated by interstitial cystitis: A case series and literature review.

Joint Bone Spine 2015 Jul 10;82(4):245-50. Epub 2015 Feb 10.

National Referral Center for Rare Systemic Autoimmune Diseases, Department of Internal Medicine, hôpital Cochin, université Paris Descartes, Assistance publique-Hôpitaux de Paris, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Inserm U1016, CNRS UMR 8104, institut Cochin, 75014 Paris, France. Electronic address:

Objectives: To characterize the interstitial cystitis (IC) associated with Sjögren's syndrome (SS).

Methods: Report of three new cases. Only cases fulfilling the American-European consensus criteria for SS and the European Society for the Study of Interstitial Cystitis criteria with positive histological findings for IC were included.

Results: Thirteen cases of SS and IC have been reported in women, including the three reported here, with a mean age of 54 years. SS appeared first in 77% (n=10) of cases, a mean of 6.6 years before IC. The symptoms of IC included pollakiuria (n=11), lower abdominal pain (n=8), urinary urgency (n=5), painful micturition (n=6), hematuria (n=3) and dysuria (n=3). Urinary dilatation occurred in three cases, leading to acute renal failure in two patients. The diagnosis of IC was confirmed by anatomical evidence of cystitis inflammation on bladder biopsy in all (n=13) patients. Treatment was reported for nine patients, seven of whom (78%) received corticosteroid treatment, which was partially or completely effective in six cases. Immunosuppressive treatment was added in three cases (cyclosporine, n=2; azathioprine, n=1; cyclophosphamide, n=1). Local bladder treatments were performed, with hydraulic distension in five cases and DMSO instillation in one patient. A urinary catheter was inserted in the two cases of acute obstructive renal failure.

Conclusions: Urinary symptoms without infection should lead the physician to consider a diagnosis of IC in SS patients. Urinary dilatation may occur, leading to acute obstructive renal failure. Corticosteroid treatment may be effective and local treatments have been tried.
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http://dx.doi.org/10.1016/j.jbspin.2014.12.007DOI Listing
July 2015

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

Mediators Inflamm 2014 17;2014:241840. Epub 2014 Nov 17.

INSERM, UMR 957, 44035 Nantes, France ; Rheumatology Unit, Nantes University Hospital, 44093 Nantes, France ; Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Faculté de Médecine, 44035 Nantes, France.

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.
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http://dx.doi.org/10.1155/2014/241840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251793PMC
July 2015

Ultrasonography of the lumbar spine: sonoanatomy and practical applications.

Joint Bone Spine 2014 Mar 4;81(2):130-6. Epub 2014 Mar 4.

Service de rhumatologie, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex, France. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jbspin.2013.10.009DOI Listing
March 2014
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