Remission in rheumatoid arthritis (RA) is an important therapeutic target that is not easy to achieve in real-life conditions. Some prognostic factors have been identified but the literature is ...variable. The objectives of this study were to evaluate the remission rate and the maintenance of remission in patients with RA over 7 years of follow-up in real-life conditions and to identify prognostic factors of long-term remission. Patients with RA seen at the Poitiers University Hospital were identified and clinical and biological data were collected. Data were analysed after 1 year and 7 years. Twice as many patients were in remission at 7 years than at 1 year of follow-up. 48.6% of patients who were not in remission at 1 year obtained remission at 7 years of follow-up. Patients achieving remission were more often receiving coprescription of csDMARDs and bDMARDs. Patients not in remission at 7 years were given more corticosteroids at higher doses. After 7 years of follow-up, low initial disease activity and use of csDMARDs and bDMARDs appeared to be independent positive predictive factors. Once obtained at one year, remission was maintained for 76% of our patients. As a conclusion, modern management of RA, whatever disease duration, leads to remission rates similar to those of early RA after 7 years of follow-up.
Abstract
Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is ...crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.
IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually ...misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection.MethodsPatients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017.Results56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP.ConclusionIn this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.
Among the different interacting molecules implicated in bone metastases, connexin43 (Cx43) may increase sensitivity of prostate cancer (PCa) cells to bone microenvironment, as suggested by our in ...silico and human tissue samples analyses that revealed increased level of Cx43 expression with PCa progression and a Cx43 specific expression in bone secondary sites. The goal of the present study was to understand how Cx43 influences PCa cells sensitivity and aggressiveness to bone microenvironment. By means of Cx43-overexpressing PCa cell lines, we revealed a Cx43-dependent promigratory effect of osteoblastic conditioned media (ObCM). This effect on directional migration relied on the presence of Cx43 at the plasma membrane and not on gap junctional intercellular communication and hemichannel functions. ObCM stimulation induced Rac1 activation and Cx43 interaction with cortactin in protrusions of migrating PCa cells. Finally, by transfecting two different truncated forms of Cx43 in LNCaP cells, we determined that the carboxy terminal (CT) part of Cx43 is crucial for the responsiveness of PCa cells to ObCM. Our study demonstrates that Cx43 level and its membrane localization modulate the phenotypic response of PCa cells to osteoblastic microenvironment and that its CT domain plays a pivotal role.
Over the past 50years, increasing experimental evidences have established that connexins (Cxs) and gap junctional intercellular communication (GJIC) ensure an important role in both the onset and ...development of cancerous processes. In the present review, we focus on the impact of Cxs and GJIC during the development of prostate cancer (PCa), from the primary growth mainly localized in acinar glands and ducts to the distant metastasis mainly concentrated in bone. As observed in several other types of solid tumours, Cxs and especially Cx43 exhibit an ambivalent role with a tumour suppressor effect in the early stages and, conversely, a rather pro-tumoural profile for most of invasion and dissemination steps to secondary sites. We report here the current knowledge on the function of Cxs during PCa cells migration, cytoskeletal dynamics, proteinases activities and the cross talk with the surrounding stromal cells in the microenvironment of the tumour and the bones. In addition, we discuss the role of Cxs in the bone tropism even if the prostate model is rarely used to study the complete sequence of cancer dissemination compared to breast cancer or melanoma. Even if not yet fully understood, these recent findings on Cxs provide new insights into their molecular mechanisms associated with progression and bone targeted behaviour of PCa. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.
•Epithelial cells of normal prostate express different connexin subtypes.•In prostate carcinoma progression, Cxs (mainly Cx43) exhibit an ambivalent role.•A tumour suppressor role of Cxs is demonstrated during primary growth.•A pro-tumourigenic function of Cx43 is shown during each steps of metastatic cascade.•Cx43 may act as facilitating metastatic cells implantation in bone.
Parry-Romberg syndrome (PRS) is a variant of morphea usually characterized by a slowly progressive course. Clinical and radiological involvement of the central nervous system may be observed in PRS. ...We describe 2 patients with PRS and neurological symptoms (one with trigeminal neuralgia associated with deafness, and the second with hemifacial pain associated with migraine without aura) in conjunction with abnormal cerebral MRI including white matter T2 hyperintensities and enhancement with gadolinium. Despite the absence of specific immunosuppressive treatments, both patients have presented stable imaging during follow-up without any clinical neurologic progression. We have performed a large review of the medical literature on patients with PRS and neurological involvement (total of 129 patients). Central nervous system involvement is frequent among PRS patients and is inconsistently associated with clinical abnormalities. These various neurological manifestations include seizures, headaches, movement disorders, neuropsychological symptoms, and focal symptoms. Cerebral MRI may reveal frequent abnormalities, which can be bilateral or more often homolateral to the skin lesions, localized or so widespread so as to involve the whole hemisphere: T2 hyperintensities, mostly in the subcortical white matter, gadolinium enhancement, brain atrophy, and calcifications. These radiological lesions do not usually progress over time. Steroids or immunosuppressive treatments are controversial since it remains unclear to what extent they are beneficial and there is often no neurological progression.
Ces dernières années, de nouveaux traitements ont permis une amélioration du pronostic du myélome multiple, mais l’atteinte osseuse reste une préoccupation chez ces patients. L’atteinte osseuse du ...myélome multiple est caractérisée par une augmentation de la résorption osseuse et une diminution de la formation osseuse. Les lésions osseuses au cours de cette affection sont des lésions lytiques, souvent associées avec des douleurs, des fractures pathologiques, une hypercalcémie, une compression médullaire et une augmentation de la mortalité. Leur prise en charge nécessite une approche multidisciplinaire. Elle comporte l’association du traitement antitumoral à un traitement inhibiteur de la résorption, et si nécessaire à un traitement local des atteintes osseuses. Les bisphosphonates sont recommandés pour diminuer les complications de ces lésions osseuses. La radiothérapie ou la chirurgie peuvent être nécessaires en cas de douleur mal contrôlée, de fractures pathologiques ou de compression médullaire. Une vertébroplastie ou une cyphoplastie peuvent être envisagées en cas de fractures vertébrales symptomatiques. D’autres traitements ciblant notamment dickkopf-1, activin-A ou BAFF sont en cours d’étude.
Recent advances in the treatment of multiple myeloma have resulted in improved prognosis, but bone lesions remain a major concern in these patients. Multiple myeloma bone disease is characterized by increased bone resorption and decreased bone formation. Myeloma bone lesions are osteolytic and are often associated with pain, pathologic fractures, hypercalcemia, spinal cord compression and increased mortality. A multidisciplinary approach is needed to manage multiple myeloma bone lesions. Current management of multiple myeloma bone disease involves the combination of anti-myeloma therapy, anti-resorptive therapy, and if necessary a local treatment of skeletal lesions. Bisphosphonates are the current standard of care for reduction in skeletal-related events. Radiotherapy or surgery can be used for specific conditions such as uncontrolled pain, pathologic fractures or spinal cord compression. Vertebroplasty or kyphoplasty should be considered in case of symptomatic vertebral fractures. Other treatments targeting dickkopf-1, activin-A, and BAFF are under development.
Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We ...investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease.
We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease.
Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases.
Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.
•Tropheryma whipplei infections often present with inflammatory joint symptoms.•These symptoms may lead to misdiagnosis of inflammatory rheumatic diseases.•T. whipplei infection should be considered in patients with extra-articular manifestations, elevated CRP or hypoalbuminemia.•T. whipplei infection should be considered in patients with an inadequate response to disease-modifying antirheumatic drugs.•Antibiotic treatment of T. whipplei is associated with rapid remission of misdiagnosed inflammatory rheumatic diseases.
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