Exogenous and endogenous glucocorticoids in rheumatic diseases.

Charité University Medicine Berlin and Berlin-Brandenburg Center of Regenerative Therapies, Berlin, Germany.
Arthritis & Rheumatology (Impact Factor: 7.48). 10/2010; 63(1):1-9. DOI: 10.1002/art.30070
Source: PubMed
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    ABSTRACT: Introduction: Glucocorticoids are widely used as anti-inflammatory and immunosuppressive agents in many immune-mediated gastrointestinal diseases. However, a number of undesirable side effects may occur and dictate continuous surveillance and monitoring to prevent complications. Areas covered: This review of the English language literature identified on PubMed focuses on key aspects of glucocorticoid therapy in patients with gastrointestinal diseases, highlighting specific aspects of recognition and management of its secondary effects. Expert opinion: Long-term cohort studies as well as placebo- and sham-controlled trials have evaluated the clinical efficacy, safety and tolerability of glucocorticoid therapy in many gastrointestinal diseases. Other immunosuppressive and biological therapies have made glucocorticoid therapy part of a broader arsenal of therapies. Newer compounds that carry less systemic toxicity and improved tolerability are increasingly used. For several gastrointestinal diseases, the role of the mucosal immunity is currently being explored and microscopic inflammation of the intestinal mucosa may have an important pathogenetic role. Glucocorticoid therapy, particularly with newer, safer compounds, may play an important new role in patients with altered motility and visceral hypersensitivity. The interplay of the gut microbiota and the host that contributes to the development of gut-associated lymphoid tissues and gut-specific immune responses will also undoubtedly be explored.
    Expert Opinion on Drug Safety 05/2014; 13(5):563-72. · 2.74 Impact Factor
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    ABSTRACT: Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice.
    Arthritis research & therapy. 01/2014; 16 Suppl 2:S2.
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    ABSTRACT: Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression. Inspired by antibody-driven pathology, we used intact RBC membranes stabilized by biodegradable polymeric nanoparticle cores to serve as an alternative target for pathological antibodies in an antibody-induced anemia disease model. Through both in vitro and in vivo studies, we demonstrated efficacy of RBC membrane-cloaked nanoparticles to bind and neutralize anti-RBC polyclonal IgG effectively, and thus preserve circulating RBCs.
    Proceedings of the National Academy of Sciences 09/2014; · 9.81 Impact Factor

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