TREATMENT WITH CORTICOSTEROIDS - 10/09/11
Résumé |
Cortisone was the first glucocorticoid steroid developed for clinical application, in the early 1950s. In the United States, the most commonly used glucocorticoid steroid is prednisone, a pro-drug hydroxylated in the liver to prednisolone. The oral bioavailability of prednisone is approximately 90%.29 All glucocorticoid steroids are metabolized in the liver and their clearance can be altered by severe liver disease.29
Glucocorticoids mediate their anti-inflammatory effects through soluble receptor proteins that act by transcriptionally regulating a small number of target genes.7, 22 In vivo binding to ligands converts the glucocorticoid receptor to a transcriptionally competent factor. The glucocorticoid receptor complex is a 300-kDa phosphoprotein complex that has been shown by immunocytochemical techniques to be located in the cytoplasm in nearly all human cells, including macrophages, lymphocytes, eosinophils, and neutrophils.7, 22 There are 2000 to 30,00 binding sites per cell. By passive diffusion, glucocorticoids enter the cell, where they bind the receptors. The structure of the receptor is modified and it translocates to the nucleus. In the nucleus, the glucocorticoid receptor interacts with other transcriptionally active molecules and binds finally to sequences of DNA in the promoter region of glucocorticoid-responsive genes, including the areas of transcription of certain pro-inflammatory peptides.7, 22
Synthetic glucocorticoids are the mainstay of treatment for sarcoidosis. The initial therapeutic decision in the patient with sarcoid is whether or not to treat. The decision process begins by recognizing subgroups with different patterns of disease progression.57 Approximately 75% of patients with sarcoidosis will have spontaneous remission or mild, stable disease not requiring steroid therapy.57 Indications for treatment in 10% will be involvement of a critical extrapulmonary organ such as the eye, brain, or heart, whereas only 15% require treatment for progressive pulmonary disease.57 This article focuses on the treatment of pulmonary and cardiac sarcoidosis.
Recognition of the patient with progressive pulmonary disease is important because it allows clinicians to avoid giving corticosteroids to a patient who ultimately would have spontaneous resolution and provide early therapy for patients destined to have chronic, progressive disease. Roentgenographic patterns, sequential pulmonary function tests, and clinical patterns of disease have all been used to predict the outcome of sarcoidosis.57 Although loose correlations exist, none of the techniques has been reliable enough to become clinical dogma. For example, patients with stage 1 roentgenographic disease have an 80% frequency of spontaneous remission within 2 years of onset; stage 2 disease has a 65% chance of spontaneous remission; and stage 3, a 30% chance.57 Erythema nodosum and acute arthritis indicate an excellent prognosis, with approximately an 85% frequency of spontaneous remission.28 At the opposite extreme, patients with hepatomegaly, central nervous system involvement, upper airway disease, lupus pernio, bone lesions, nephrocalcinosis, or cor pulmonale all have less than a 25% chance of remission within 2 years, with or without therapy.28 Severely symptomatic patients are more likely to have persistent disease. Persistence of symptoms for greater than 2 years markedly reduces the chance of spontaneous remission. Racial factors are important because black patients are more likely to develop chronic, progressive disease. Although admittedly imperfect, these clinical criteria are still the best data on which to base treatment decisions. Laboratory tests such as serum angiotensin converting enzyme, bronchoalveolar lavage (BAL) fluid cell populations, and 67gadolinium scans have not proved to add significantly to treatment decisions.56, 57
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| Address reprint requests to Richard H. Winterbauer, MD Section of Pulmonary and Critical Care Medicine Virginia Mason Medical Center PO Box 900 (C7–PUL) Seattle, WA 98101 |
Vol 18 - N° 4
P. 843-851 - décembre 1997 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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