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.

[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.

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.

[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.

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.

An unexpected, benign cause of increased muscular uptake at bone scintigraphy.

Bone scintigraphy was performed in a healthy 30-year-old man because of post-traumatic heel pain. The scintigraphy displayed a bilateral increased uptake of 99mTc-MDP in the pectoral muscles and triceps brachii. Further extensive investigations including muscle biopsy were normal and excluded diagnoses such as polymyositis, myositis ossificans or amyloidosis. The abnormalities were in fact explained by physical exercise performed a few hours prior to the radionuclide scan. This was confirmed by the absence of these changes on a second bone scan performed 3 months later. This case shows that muscle exercise should be kept in mind as a cause of skeletal muscle uptake of bone-seeking agents, with the view to avoid unnecessary investigations.

Pseudo Felty's syndrome. A polyclonal disease with a favorable prognosis. Report of two cases with Southern blot analysis of TCR.

The authors report two patients with large granular lymphocyte (LGL) expansion associated with rheumatoid arthritis corresponding to pseudo Felty's syndrome. These cells have natural killer and T cell surface antigen markers. LGL are a heterogeneous population and expansion of these cells is responsible for leukemia, which is generally a monoclonal proliferation. It has been suggested that Epstein-Barr virus (EBV) is a putative agent in this leukemia. No EBV DNA was found with a polymerase chain reaction analysis in the lymphocyte DNA of our two patients. Some cases of pseudo Felty's syndrome have exhibited a monoclonal pattern on Southern blot analysis of the T cell receptor. On the contrary, our two cases showed a polyclonal pattern with TCR beta chain Southern blot analysis. This fact, associated with the mild course seen in both over more than twenty years, suggest that pseudo Felty's syndrome is a disease with a good prognosis.

The intravertebral vacuum phenomenon ("vertebral osteonecrosis"). Migration of intradiscal gas in a fractured vertebral body?

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To compare the prevalence of the association between contiguous intervertebral disc and vertebral collapses with or without an intravertebral vacuum phenomenon. SUMMARY OF BACKGROUND DATA: The mechanism of occasional gas accumulation within some vertebral collapses is poorly known. The current hypothesis is that this phenomenon is indicative of bone ischemia. In fact, avascular necrosis as the main pathologic event remains speculative, and should not explain per se the presence of gas within a vertebral body. METHODS: Comparison of the prevalence of intervertebral disc vacuum phenomenon adjacent to the affected vertebral body in 23 cases of intravertebral vacuum phenomenon in 19 patients (intravertebral vacuum phenomenon group) and in 708 osteoporotic collapses without intravertebral vacuum phenomenon in 199 patients (control group). RESULTS: There were no differences in sex and age between the two groups, and all the patients in the intravertebral vacuum phenomenon group had signs of underlying osteoporosis. A vacuum phenomenon in at least one intervertebral disc adjacent to the collapses on radiographs, conventional tomography, computed tomography, or magnetic resonance imaging was found in 19 cases (83%) in the intravertebral vacuum phenomenon group, compared with 13% in the control group (P < 0.0001). Considering plain radiographs only, this association was found in 50% of the intravertebral vacuum phenomenon group and in 9.7% of the control group (P < 0.0001). The intervertebral and intravertebral gaseous collections were connected through a fractured endplate in six cases. CONCLUSIONS: The high prevalence of the association of contiguous intervertebral and intravertebral vacuum phenomenon could have implications in the pathogenesis of the intravertebral vacuum phenomenon. We hypothesize that the intravertebral vacuum phenomenon could simply be the result of migration of an intradiscal-gaseous collection through the fractured endplate of some osteoporotic collapses.

Astasia-abasia revealing a primary Sjögren's syndrome.

A 63-year-old woman presented with mild arthralgias and inability to stand and walk without other significant neuropsychiatric abnormality. Neurological explorations showed intrathecal oligoclonal immunoglobulin production in CSF and numerous bright foci at brain MRI. A primary Sjögren's syndrome was concomitantly evidenced and was thought to be the cause of the astasia-abasia symptom by multiple brain involvement. Patient's condition gradually improved with hydroxychloroquine and corticosteroid therapy. Central nervous system involvement by primary Sjögren's syndrome is discussed.

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.

[Inflammatory rheumatism flare-up after surgical treatment of Cushing's disease: two cases]. / Poussée de rhumatisme inflammatoire après cure chirurgicale d'une maladie de Cushing: deux cas.

The anti-inflammatory effect of natural glucocorticoids is often overlooked, as shown by these two cases of inflammatory rheumatism flare-up which occurred after surgical treatment of Cushing's syndrome. The disorder in the first case was exacerbation of a probable rheumatoid arthritis; in the second case an unlabelled inflammatory rheumatism appeared in a context of postoperative corticotropic deficiency. In both cases a purely substitutive hydrocortisone therapy resulted in dramatic regression of the articular symptoms. It is well known that rheumatismal manifestations may occur in patients with slow adrenal failure. The determinant factor seems to be a glucocorticoid deficiency, either isolated or associated with others, since cortisol exerts and anti-inflammatory activity. In patients with corticotropic deficiency following surgical treatment of Cushing's disease, the endogenous corticosteroid therapy of hypercortisolism is interrupted, allowing the aggravation or emergence of inflammatory rheumatism.

[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.

[Algodystrophy of the femoral head. Contribution of new imaging methods]. / L'algodystrophie de la tête fémorale. Apport des nouvelles méthodes d'imagerie.

Results are reported of the use of new imaging methods, CT scan and magnetic resonance imaging, in 12 patients with algodystrophy of femoral head. During the early stages a CT scan can detect partial demineralizations, observed on MR images in sagittal sections. When the disease is installed the CT scan images show global demineralization, but the MR images with coupled T1-T2 study appear to be more pathognomonic (hyposignal extended in T1 with hypersignal in T2, associated with a more marked subchondral hyposignal in T1 as in T2) particularly in relation to the osteonecrosis of femoral head.

[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.

[Post-traumatic psoriatic arthritis. 2 cases]. / Rhumatisme psoriasique post-traumatique. Deux observations.

Physical trauma is generally accepted as a possible factor in the pathogenesis of rheumatoid arthritis. In the last ten years, there have been a few rare case reports of physical trauma precipitating psoriasic arthritis. We observed two such cases following an occupational accident discovered one and a half year and two and a half year after onset of the first clinical manifestations. In the first case, a 43-year-old man had a fracture of the right calcaneus in March 1991. He was treated with nailing and also required emergency surgery of the posterior tibial artery. The tibiotarsal joint was normal radiologically. Pain persisted after treatment and in 1993 he presented with psoriasis of the scalp and several other localizations together with Hallopeau's acrodermatitis continua of the ankle, pathognomonic for psoriasic arthritis. Salazosufapyridin was given. The second case was a 50-year-old man who had major pain in both wrists immediately after falling on the palm of his hands in 1992. Bilateral carpal tunnel syndrome developed which did not respond well to surgery. In 1993, he developed inflammatory synovitis and also had psoriasis mainly located at the elbows. Immunological tests were negative. Cortisone and salazosulfapyridin were not particularly effective and the patient later developed arthritis of the hip and ankle joints. Physicians should be aware of physical trauma as a causative factor in psoriasic arthritis due to the potential legal implications. Criteria for imputability are: single major physical trauma, absence of clinical signs prior to the trauma, continuous clinical course, first signs occurring then predominating at the joint exposed to trauma. The pathophysiology of this type of arthritis is not well understood. Deep Koebner's phenomena could be involved. Activation of substance P has also been hypothesized.

[Treatment of idiopathic thrombocytopenic purpura and thrombocytopenia associated with the HIV virus using anti-Rhesus immunoglobulins]. / Traitement du purpura thrombocytopénique idiopathique et des thrombocytopénies liées au VIH par les immunoglobulines anti-Rhésus.

Fourteen Rhesus-positive patients with idiopathic thrombocytopenic purpura or thrombocytopenia associated with human immunodeficiency virus (HIV) infection were treated with intravenous Rhesus antibodies. The mean total dose was 6,800 micrograms administered over a 3 to 6 days' period. A significant rise in platelet count was observed in 13 of the 14 Rhesus-positive patients, but not in 3 Rhesus-negative patients used as controls. This rise was usually transient, lasting less than 3 weeks, but it persisted for more than 3 months in 2 cases. Treatment was well tolerated; transient signs of haemolysis appeared in 11 patients who did not require transfusion. Rhesus antibodies are quick-acting, the number of platelets being doubled as early as the second day of treatment. Interaction between antibody-coated red blood cells and macrophages is a possible mode of action and a feasible therapeutic approach in selected patients with autoimmune of HIV-mediated thrombocytopenia.

[Disclosing muscular metastases. Their peculiarities apropos of 3 cases]. / Métastases musculaires révélatrices. Leurs particularités à propos de trois observations.

Three cases of muscular metastasis as the first manifestation of malignancy are reported. These patients had no previous history of malignancy. All three were male. One had a single metastasis in the gluteus minimus muscle, and the other two had multiple metastases which were located in the adductor compartment of the thigh in one case and in the biceps brachii, quadriceps femori, and paraspinal muscles in the other. These metastases first manifested as a painful mass. The various imaging techniques (ultrasonography, computed tomography, and magnetic resonance imaging) determined the location and extension of the masses, although the images were nonspecific. The metastatic nature of the tumors was confirmed only upon histological studies. With reference to these three cases, features of muscular metastases are reviewed. The development of muscular metastases is an infrequent occurrence during the course of a cancer. The mechanisms which may explain the low incidence of muscular metastases are discussed.