Joint, bone, spine : revue du rhumatisme
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Review Historical Article
Advances in the treatment of systemic lupus erythematosus: From back to the future, to the future and beyond.
There have been many advances in the diagnosis and therapeutic management of systemic lupus erythematosus (SLE) over the past decades. Following more than eleven centuries of therapeutic uncertainty, the discovery of the therapeutic properties of glucocorticoids is without any doubt one of the most significant advance in the field of autoimmune diseases. The many progresses made by rapidly growing chemical industry of the 19th century chemistry have allowed the identification of valuable therapeutic compounds such as anti-malarials, cyclophosphamide, azathioprine, cyclosporine and later mycophenolate mofetil, which have all profoundly changed the face of the disease. ⋯ With the approval of belimumab in 2011 and 74 targeted therapies in clinical development, we may expect great changes in the therapeutic management of SLE. Those molecules target inflammatory cytokines or chemokines and their receptors, B cells or plasma cells, intracellular signalling pathways, B/T cells co-stimulation molecules, interferons, plasmacytoid dendritic cells, as well as various other targets of interest. Current challenges are now slowly shifting from whether some new drugs will be available to how to select the most adequate drug (or drug combination) at the patient-level.
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Histone deacetylation, DNA methylation, and micro-RNAs (miRNAs) are the three main epigenetic mechanisms that regulate gene expression. All the physiological processes involved in bone remodeling are tightly regulated by epigenetic factors. This review discusses the main epigenetic modifications seen in tumoral and non-tumoral bone diseases, with emphasis on miRNAs. ⋯ Advances in the understanding of epigenetic regulation shed new light on the pathophysiology of other non-tumoral bone diseases, including genetic conditions inherited on a Mendelian basis. Finally, in the area of primary and metastatic bone tumors, the last few years have witnessed considerable progress in elucidating the epigenetic regulation of oncogenesis and its local interactions with bone tissue. These new data may allow the development of epigenetic outcome predictors, which are in very high demand, and of innovative therapeutic agents acting via miRNA modulation.
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Small fiber neuropathy, which affects the sensory Aδ and C fibers, is now a major diagnostic and therapeutic challenge. Nearly 7% of the general population have chronic neuropathic pain responsible for severe quality-of-life impairments. Awareness must therefore be raised among clinicians of the somatosensory and autonomic symptoms that can reveal small fiber neuropathy, appropriate diagnostic investigations, most common causes, and best treatment options for each patient profile. To help achieve this goal, the present review article discusses the clinical presentation of neuropathic pain and paresthesia and/or autonomic dysfunction due to involvement of nerves supplying exocrine glands and smooth muscle; normal findings from standard electrophysiological investigations; most informative diagnostic tests (epidermal nerve fiber density in a skin biopsy, laser-evoked potentials, heat- and cold-detection thresholds, electrochemical skin conductance); main causes, which consist chiefly of metabolic diseases (diabetes mellitus, glucose intolerance), dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy), and genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases); and the available symptomatic and etiological treatments.
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Greater accuracy in clinical descriptions combined with advances in muscle histology and immunology have established that inflammatory myopathies (IMs), similarly to inflammatory rheumatic diseases, constitute a highly heterogeneous group of conditions. The topographic distribution, severity, and tempo of onset of the myopathy vary widely, and the histological findings distinguish at least five different profiles, which may reflect different pathophysiological processes. Most IMs are connective tissue diseases that can affect multiple organs, among which the most common targets are the skin, joints, and lungs. ⋯ These subgroups are also characterized by specific genetic and environmental factors. The advances made in the nosology of IMs have benefited the diagnosis, personalization of treatment strategies, and understanding of pathophysiological mechanisms. They can be expected to assist in the development of specific treatments.
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Nutcracker syndrome (NCS) is symptomatic unilateral renal venous hypertension due to compression of the left renal vein between the superior mesenteric artery and aorta (anterior NCS) or between the aorta and spine (posterior NCS). The left ovarian or spermatic vein empties into the left renal vein and is an additional site of venostasis in about half the cases of NCS. The presenting symptom of NCS in about half the cases is atypical left flank pain suggesting a disorder of the lower ribs or thoracolumbar spinal junction, particularly as the pain worsens with standing and increased lumbar lordosis. ⋯ Narrowing of the left renal vein on imaging studies is required but far from sufficient to establish the diagnosis. Several converging clinical findings and a marked pressure gradient between the left renal vein and inferior vena cava must be present also. Urological procedures and vascular surgery are being superseded by endovascular stenting with or without simultaneous treatment of the acquired gonadal vein insufficiency by embolization.