Nature reviews. Rheumatology
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Sarcoidosis is an uncommon systemic inflammatory disorder characterized by noncaseating granulomatous inflammation that most commonly affects the lungs, intrathoracic lymph nodes, eyes and skin. One-third or more of patients with sarcoidosis have chronic, unremitting inflammation with progressive organ impairment. Findings of family and genetic studies indicate a genetic susceptibility to sarcoidosis, with genes in the MHC region having a dominant role. ⋯ Corticosteroids remain the cornerstone of therapy when organ function is threatened or progressively impaired. The role of immunosuppressive drugs and anti-TNF agents in the treatment of sarcoidosis remains uncertain, and there are no FDA-approved therapies. Meaningful progress in developing clinically useful tools and new therapies will depend on further advances in understanding the pathogenesis of sarcoidosis and its disease-specific pathways.
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The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. ⋯ Several studies have highlighted the importance of the tissue-specificity of DNA methylation changes, an aspect which-in contrast with genetic analysis-must be considered when designing epigenetic studies. Here I discuss the proposed mechanisms and implications of DNA methylation changes in the pathogenesis of autoimmune rheumatic diseases, the prospects for future epigenetic studies in rheumatology, the relevance of specific DNA methylation markers and the potential use of drugs with an epigenetic effect in the clinical management of these diseases.
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Persistent and disabling pain is the hallmark of osteoarthritis, rheumatoid arthritis, fibromyalgia, and various other rheumatologic conditions. However, disease severity (as measured by 'objective' indices such as those that employ radiography or serology) is only marginally related to patients' reports of pain severity, and pain-related presentation can differ widely between individuals with ostensibly similar conditions (for example, grade 4 osteoarthritis of the knee). Increasing evidence in support of the biopsychosocial model of pain suggests that cognitive and emotional processes are crucial contributors to inter-individual differences in the perception and impact of pain. ⋯ A variety of pathways, from cognitive to behavioral to neurophysiological, seem to mediate these deleterious effects. Collectively, depression and catastrophizing are critically important variables in understanding the experience of pain in patients with rheumatologic disorders. Pain, depression, and catastrophizing might all be uniquely important therapeutic targets in the multimodal management of a range of such conditions.