[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

[Epidemiological description of long-term oral glucocorticoid use: Results from the French health insurance database]. / Description épidémiologique de la corticothérapie orale prolongée : résultats issus de la base de données de l'assurance maladie.

BACKGROUND: There is very little epidemiologic data available in the literature concerning long-term corticosteroid prescriptions in France. METHODS: The information was collected from a national public health-insurance database in our geographic area of Provence-Alpes-Côte-d'Azur and Corsica. We included in the analysis, patients using a daily glucocorticoid above 7,5 milligrams for a period exceeding 90 days. RESULTS: Among the patients, 4,1 million were included in the analysis. The prevalence of glucocorticoids was around 0.8% and the incidence was 2.3/1000 inhabitants/year. The mean age of the patients was 57.6±18.8 years old. The median prednisone-equivalent dose was 11.9mg/day (Interquartile range: 8.6-20.0). The average treatment duration was 206 days (CI 95% 202-210). Most prescriptions (72,0%) were started by general practitioners. CONCLUSION: Long-term corticosteroid therapy is frequent in France. Its description is close to what is already known in Europe.

Superimposition of maximal stress and necrosis areas at the top of the femoral head in hip aseptic osteonecrosis.

INTRODUCTION: Recent reports described possible mechanical factors in the development and aggravation of osteonecrosis of the femoral head (OFH), but these have yet to be confirmed on dedicated mechanical study. We therefore developed a 3D finite element model based on in-vivo data from patients with incipient OFH, with a view to determining whether the necrosis area was superimposed on the maximal stress area on the femoral head. HYPOTHESIS: The location of the necrosis area is determined by stress on the femoral head. MATERIAL AND METHOD: All patients from the rheumatology department with early stage OFH in our center were investigated. Analysis of CT scans showed stress distribution on the head by 3D finite elements models, enabling determination of necrosis volume within the maximal stress area and of the percentage intersection of necrosis within the stress area (%I n/s: necrosis volume in stress area divided by total stress area volume and multiplied by 100) and of stress within the necrosis area (%I s/n: stress volume in necrosis area divided by total necrosis area volume and multiplied by 100). RESULTS: Nineteen of the 161 patients assessed retrospectively for the period between 2006 and 2015 had incipient unilateral OFH, 10 of whom (4 right, 6 left) had CT scans of sufficient quality for inclusion. Mean age was 52 years (range, 37-81 years). Mean maximal stress was 1.63MPa, mean maximal exported stress volume was 2,236.9 mm3 and mean necrosis volume 6,291.1 mm3. Mean %I n/s was 83% and mean %I s/n 35%, with no significant differences according to gender, age, side or stress volume. There was a strong inverse correlation between necrosis volume and %I s/n (R2=-0.92) and a strong direct correlation between exported stress volume and %I s/n (R2=0.55). %I s/n was greater in small necrosis (<7,000mm3). CONCLUSION: OFH seems to develop within the maximal stress area on the femoral head. The present results need confirmation by larger-scale studies. We consider it essential to take account of these mechanical parameters to reduce failure rates in conservative treatment of OFH. LEVEL OF EVIDENCE: IV.

Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial.

AIM: To test the efficiency of tumour necrosis factor blockers (adalimumab) in patients with painful refractory (non-responders to analgesics and non-steroidal anti-inflammatory drugs (NSAIDs)) hand osteoarthritis (OA). METHODS: We performed a randomised, double-blind, placebo-controlled, parallel group, multicentre study. Patients were randomised to: 1/1 adalimumab 40 mg for two subcutaneous injections at a 15-day interval or placebo and monitored for 6 months. The primary outcome was the percentage of patients with an improvement of more than 50% in global pain (Visual Analogue Scale) between week 0 (W0) and week 6 (W6). Secondary outcomes included the number of painful joints, swollen joints, morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, and consumption of analgesics. Analysis on the mean primary outcome measure was done on patients who received at least one injection. RESULTS: 99 patients were recruited and 85 patients were randomised. Among them, 37 patients in the placebo group and 41 in the adalimumab group received at least one injection and were evaluated at W6 (n=78) on the main efficacy outcome. Mean age was 62 years, 85% were women, and mean level of pain was 62 mm at W0. At W6, 35.1% in the adalimumab group versus 27.3% in the placebo group had a pain reduction ≥50% (RR 1.12 (95% CI 0.82 to 1.54; p=0.48). There were no statistical differences for all secondary end points. The rate of adverse events was similar in the two groups. CONCLUSIONS: Adalimumab was not superior to placebo to alleviate pain in patients with hand OA not responding to analgesics and NSAIDs. TRIALS REGISTRATION NUMBER: NCT00597623.

Advanced hip osteoarthritis: magnetic resonance imaging aspects and histopathology correlations.

OBJECTIVES: To correlate magnetic resonance imaging (MRI) aspects of the femoral head with histological findings in advanced hip osteoarthritis (OA), with special emphasis on bone marrow edema (BME). METHODS: MRI was performed in patients with advanced hip OA scheduled for hip arthroplasty. Coronal T1-, fat-suppressed T2-, T1 with gadolinium intravenous injection sequences were obtained on a 1.5 T MR-scanner within 1 month before surgery. Coronal MR images corresponding to the ligamentum teres plane were analyzed by two independent readers blinded to histological data. Normal bone marrow, subchondral cyst, subchondral fracture, edema-like, necrosis-like, and necrosis MR patterns were reported on a synthesis scheme. After surgery, the femoral heads specimens were cut through the ligamentum teres plane and histologically analyzed for correlations. RESULTS: Twenty-three femoral heads were analyzed (female 56.5%, mean age 64.5 years). Edema-like MR pattern was correlated with histological (H) edema (Kappa (K): 0.77). Necrosis-like MR pattern was correlated with H fibrosis (K: 0.49) and with H necrosis (K: 0.24). Cyst MR pattern was correlated with H bone cysts (K: 0.58). Necrosis MR pattern corresponded to a mixture of histological lesions. Sensitivity and specificity of MRI varied from 26% to 80% and from 86% to 95% respectively. CONCLUSION: In advanced hip OA, the so-called "BME" MR lesion corresponds to a combination of edema, fibrosis, and necrosis at histopathology. When the classical "BME" is more specifically separated into edema-like and necrosis-like MR patterns, MR Imaging and histological findings show substantial agreement, with edema-like MR pattern mainly corresponding to histological edema.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Intravenous pamidronate for pain relief in recent osteoporotic vertebral compression fracture: a randomized double-blind controlled study.

INTRODUCTION: We performed a randomized, double-blind, controlled clinical trial comparing intravenous pamidronate and placebo for pain relief in recent osteoporotic vertebral compression fractures (VCF). METHODS: Patients suffered from recent (<21 days), painful, osteoporosis-related VCF. They were randomized to receive daily intravenous infusions of either placebo or 30 mg pamidronate for three consecutive days (total pamidronate: 90 mg). The main criterion for efficacy was improvement in standing pain on a 100-mm visual analogical scale (VAS) at day 7. Secondary criteria were standing pain at days 3 and 30; supine pain at days 3, 7, and 30; patients' overall assessment of improvement; mobility index; and number of "20% responders" and "50% responders" (respectively, 20% and 50% improvement in standing pain at days 7 and 30). Statistical analysis with non-parametric tests was carried out on an intention to treat basis. RESULTS: Thirty-two patients were enrolled in the study; 16 were given placebo and 16 pamidronate. Thirty-one patients were evaluated at day 7 and 26 patients at day 30. VAS pain decreased significantly in both groups at day 7 (placebo -23 mm, pamidronate -42 mm, p<0.01). The difference in pain scores between groups was -23.25 mm (confidence interval (CI) [-42.3; -4.2], p=0.018) at day 7 and -26 mm at day 30 (p=0.03), in favor of pamidronate. At day 7, there were 4 versus 12 "50% responders," respectively, in the placebo and in the pamidronate groups (likelihood ratio: 8.372; p=0.004) and 9 versus 14 "20% responders" (likelihood ratio: 4.038; p=0.044). At day 30, there were 5 versus 10 "50% responders," respectively, in the placebo and in the pamidronate groups, and 7 versus 11 "20% responders." Patients' overall assessment of improvement at day 7 was 37+/-26 mm in the placebo group and 59+/-30 mm in the pamidronate group (p=0.019), and 42+/-26 mm and 72+/-21 mm at day 30 (p=0.07). The two groups did not differ significantly at days 7 and 30 for supine pain, Schober index, or finger-ground distance. No significant adverse reaction related to treatment occurred. CONCLUSION: Pamidronate provides rapid and sustained pain relief in patients with acute painful osteoporotic VCF and is well tolerated. Further investigations are needed to better define the place of pamidronate in the management of painful recent osteoporotic collapse.

Placement of intra-articular injection verified by the backflow technique.

OBJECTIVE: To develop and to assess a simple, inexpensive method for ascertaining, without any imaging procedure, the intra-articular placement of the needle in the knee for intra-articular injections. METHODS: Outpatients referred for intra-articular treatment with "dry" symptomatic knee osteoarthritis were included in this prospective study. "Dry" knee disease was defined as a knee without any clinically detectable effusion. Once intra-articular positioning of the needle considered adequate using the backflow technique, contrast solution was injected using the same needle without changing its position and immediately afterwards lateral and anterior-posterior X-rays were taken to assess the needle position. RESULTS: Of the 32 of 33 cases with obtained backflow, the needle was correctly placed in all cases. In the remaining case, the needle was extra-articularly positioned. The concordance between the two techniques using the Cohen's Kappa was 1 [CI 95%: 0.22-1]. CONCLUSION: The backflow technique allows to accurate the intra-articular placement of the needle for "dry" knee joints injection. This technique can be proposed as a learning tool as well as a daily practice technique to ascertaining intra-articular knee injections without using fluoroscopy with injection of contrast material. Further studies are needed to assess the technique for other joint injections.

Laboratory and imaging studies used by French rheumatologists to determine the cause of recent onset polyarthritis without extra-articular manifestations.

BACKGROUND: The cause of recent onset polyarthritis can be difficult to identify. OBJECTIVE: To determine which laboratory and imaging studies French rheumatologists recommend, not taking cost into account, for the diagnosis of recent onset polyarthritis without extra-articular manifestations. METHODS: From the list of the French Society for Rheumatology, a random sample of 210 rheumatologists was selected, who were asked to complete a questionnaire on the laboratory and imaging studies they would recommend in two fictional cases of recent onset polyarthritis (possible rheumatoid arthritis (RA)-case 1 and probable RA-case 2). RESULTS: In case 1, the following were recommended by over 75% of respondents: hand radiographs, rheumatoid factors (RFs), and antinuclear antibodies (ANA) (92%, 98%, and 98%, respectively). 50-74% of respondents recommended radiographs of the feet, knees, and chest (50%, 57%, and 66%, respectively); blood cell counts, erythrocyte sedimentation rate (ESR), serum assays of C reactive protein (CRP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (65%, 74%, 67%, and 62%, respectively). 25-49% recommended determination of creatinine and proteinuria, HLA-B27, antikeratin antibody, radiographs of the pelvis, and synovial fluid analysis. Several investigations were recommended less often in case 2 than in case 1. Nevertheless, some laboratory and imaging studies (radiographs of hand, feet, knees, chest x rays, blood cell counts, ANA, RF, antikeratin antibody, CRP, ESR, creatinine, AST and ALT, proteinuria, and joint aspiration) were recommended by more than 25% of respondents in both cases. CONCLUSION: Wide variations were found among rheumatologists, indicating a need for standardisation. Some laboratory and imaging studies are recommended by at least 25% of respondents in recent onset polyarthritis with or without clues suggesting RA. In contrast, many tests were considered useful by fewer than 25% of the respondents in both cases.

Biological characterization of experimental carbon samples.

The use of carbon is widespread in fields as wide as aeronautics, cars, electricity or electronics. The biomedical applications of carbon are also numerous. The purpose of our work is to test four experimental carbon fibers (A, B, C and D; B being the negative control) to determine the best clinical application. Four tests of cytocompatibility are carried out (cell viability, inflammatory test, cell proliferation and cell morphology). Two different cell lines are used: the L132 cell line (epithelial embryonic pulmonary human cell) and the HaCaT line (human normal spontaneously immortalized skin keratinocytes). The results of the biological tests are compared with those of a carbon fiber sample already marketed as a bandage in the treatment of infected wounds: Actisorb "Plus (J2). The various tests show us that only two experimental samples are slightly cytotoxic (A, D). On the other hand, no sample supports cell adherence. A, B, C and D do not have an inflammatory effect. J2 appears at the same time cytotoxic and inflammatory. Consequently, being given the physical presentation and the biological properties of experimental samples (A, C and D), we intend them for an application in the field of wound healing, as a bandage. Also further experimentation is needed.

Pure ectodermal dysplasia: retrospective study of 16 cases and literature review.

OBJECTIVE: To review the possible craniomaxillofacial deformative consequences associated with ectodermal dysplasias and embryonic malformations, which include dental ageneses. SETTING: Oral and Maxillofacial Surgery Department, University Hospital, Lille, France. PATIENTS: Sixteen patients (seven boys and nine girls, aged 4 to 34 years) with pure ectodermal dysplasia (no ectodermal dysplasia syndromes). INTERVENTIONS: All patients had a clinical examination. Seven (two boys and five girls, aged 4 to 25 years) had undergone plaster casts and radiographic and Delaire's cephalometric studies before being treated. MAIN OUTCOME MEASURES: All patients had tooth ageneses (from hypodontia to anodontia), associated with cutaneous dyshidrosis and hair and nail dystrophy. Most of them had a short face, with an unusual facial concavity, a maxillary retrusion, and a relative mandibular protrusion. MANAGEMENT RESULTS AND DISCUSSION: Depending on their ages and their orthopedic abnormalities, patients underwent either dental or prosthodontic, orthodontic, orthopedic, orthognathic, or implant treatment. So as not to interfere with the growth pattern, we preferred to reserve implant and orthognathic surgery for full-grown cases. CONCLUSIONS: Oral and maxillofacial surgeons must undertake a comprehensive approach to these patients to improve their dental, masticatory, growing, and orthognathic conditions.

[Dental anomalies following anticancer chemotherapy]. / Anomalies dentaires après chimiothérapie anticancéreuse.

Chemotherapy administered during childhood may induce dental abnormalities, such as acquired amelogenesis imperfecta, microdontia, hypodontia and altered root morphology. The magnitude of the defect varies according to the cytotoxic agents, the duration of their use and the stage of tooth development at the time of chemotherapy. Patients who received high-dose chemotherapy before the age of 5 are particularly concerned. The dental supervision of these children is based upon three orthopantomograms: the first one has to be performed before starting chemotherapy and will be used as a reference; the second is done soon after the drug therapy in order to evaluate the first consequences; the third is performed after the eruption of all permanent teeth (age 12-13 in average) in order to determine the dental abnormalities. In case of hypodontia, orthodontic treatment must be considered, but it is necessary to take into account the fact that it may increase the risk of root resorption. Preventive dental care is important for these children. It involves meticulous oral hygiene and frequent dental visits to assess and maintain dental health.

[Retroperitoneal complications of Erdheim-Chester disease]. / Complications Rétropéritonéales d'une maladie de Chester-Herdeim.

Erdheim-Chester disease is a non-langerhans cell histiocytosis. It is a rare and plurifocal disease. Retroperitoneal involvement manifests as a mass associated with fibrosis, which is well visualized on CT scan and MRI. This disease is characterized by its potential to involve the whole retroperitoneum. We report a case of this disease that developed over twenty years, consisting of renal arteries stenosis, bilateral ureteral stenosis and evolutive adhesive capsulitis.

Uveitis, an under-recognized adverse effect of pamidronate. Case report and literature review.

Ophthalmologic adverse effects of bisphosphonate therapy are infrequent and of unclear pathogenesis. The most common has been anterior uveitis, of which 18 cases have been reported. Onset was within 24 to 48 hours after infusion initiation, and both eyes were affected in most patients. The outcome was favorable within a few days after bisphosphonate discontinuation and topical glucocorticoid therapy, although rechallenge was frequently followed by a recurrence. Bisphosphonates are being used successfully in an increasingly broad range of disorders. We report a case of pamidronate-induced anterior uveitis and present a review of the relevant literature.

[Differential diagnosis of infective spondylodiscitis and erosive degenerative disk disease]. / Diagnostic différentiel entre spondylodiscite infectieuse et discopathie dégénérative erosive.

PURPOSE: To assess the value of imaging in the differential diagnosis of erosive intervertebral osteochondrosis (EIVO) versus infectious discitis (ID). MATERIALS AND METHODS: Twelve cases of EIVO and 30 cases of ID were reviewed to define the usefull signs for differential diagnosis on plain films, CT, and MR. RESULTS: No single sign is sufficient, but the association of several signs is suggestive of EIVO: discal vacuum phenomenom, well-defined sclerosis and erosions of vertebral endplates, high signal strip surrounding low signal of vertebral endplates on T1-weighted images. CONCLUSION: Imaging is helpful in difficult differential diagnosis of EIVO versus ID.

Painful swelling of the thigh in a diabetic patient: diabetic muscle infarction.

A 44-year-old woman with a 5-year history of poorly controlled Type 1 diabetes mellitus presented with a painful, firm and warm swelling in her right thigh. Pain was severe but the patient was not febrile, and had no history of trauma or abnormal exercise. Laboratory tests showed ketoacidosis, major inflammation (erythrocyte sedimentation rate (ESR) = 83 mm/h), normal white blood cell count and normal creatine kinase level. Plain radiographs were normal, and there were no signs of thrombophlebitis at Doppler ultrasound. Magnetic resonance imaging (MRI) showed diffuse enlargement and an oedematous pattern of the adductors, vastus medialis, vastus intermedius and sartorius of the right thigh. The patient's symptoms improved dramatically, making biopsy unnecessary, and a diagnosis of diabetic muscular infarction was reached. Idiopathic muscular infarction is a rare and specific complication of diabetes mellitus, typically presenting as a severely painful mass in a lower limb, with high ESR. The diabetes involved is generally poorly controlled longstanding Type 1 diabetes with established microangiopathy. Differential diagnoses include deep vein thrombosis, acute exertional compartment syndrome, muscle rupture, soft tissue abscess, haematoma, sarcoma, inflammatory or calcifying myositis and pyomyositis. In fact, physician awareness should allow early diagnosis on the basis of clinical presentation, routine laboratory tests and MRI, thereby avoiding biopsy and its potential complications as well as unnecessary investigations. Rest, symptomatic pain relief and adequate control of diabetes usually ensure progressive total recovery within a few weeks. Recurrences may occur in the same or contralateral limb.

Fibrous dysplasia with intramuscular myxoma (Mazabraud's syndrome). Report of a case and review of the literature.

About 30 cases of fibrous dysplasia associated with one or more myxomas (Mazabraud's syndrome) have been reported since 1926. We report a new case in a woman with polyostotic fibrous dysplasia and a myxoma in the left femoral muscle. She also had a history of precocious sexual development and café au lait spots, two manifestations whose association with polyostotic fibrous dysplasia defines McCune-Albright syndrome.

Anteroposterior atlantoaxial subluxation in cervical spine osteoarthritis: case reports and review of the literature.

Nontraumatic anteroposterior atlantoaxial subluxation (AAS) has been described in several rheumatic or inherited disorders, especially rheumatoid arthritis and to a lesser extent the inflammatory spondyloarthropathies. We describe AAS secondary to osteoarthritis (OA) of the cervical spine in a 76-year-old man and a 73-year-old woman with severe cervical OA, symptomatic C1-C2 facet joints, and signs of generalized OA. Only 6 similar cases exist in the literature. OA should be added to the causes of AAS, and conversely AAS should be assessed in cases with severe OA of the upper cervical spine.