Steroid responsive disorders

Bile acids, in particular chenodeoxycholic acid (CDCA) and cholic acid (CA), can regulate the expression of genes involved in their synthesis, thereby, creating a feed-back loop. The elucidation of this regulatory pathway came about as a consequence of the isolation of a class of receptors called the farnesoid X receptors, FXRs . The FXRs belong to the superfamily of nuclear receptors that includes the steroid/thyroid hormone receptor family as well as the liver X receptors (LXRs) , retinoid X receptors (RXRs), and the peroxisome proliferator-activated receptors (PPARs) .

Intravenously administered glucocorticoids , such as prednisone , are the standard of care in acute GvHD [7] and chronic GVHD. [24] The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect. [ citation needed ] . Cyclosporine and tacrolimus are inhibitors of calcineurin. Both substances are structurally different but have the same mechanism of action. Cyclosporin binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase A (known as cyclophilin), while tacrolimus binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase FKBP12. These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus. [25] Standard prophylaxis involves the use of cyclosporine for six months with methotrexate. Cyclosporin levels should be maintained above 200 ng/ml. [26] Other substances that have been studied for GvHD prophylaxis include, for example: sirolimus, pentostatin and alemtuzamab. [26]

The most common side effect of topical corticosteroid use is skin atrophy. All topical steroids can induce atrophy, but higher potency steroids, occlusion, thinner skin, and older patient age increase the risk. The face, the backs of the hands, and intertriginous areas are particularly susceptible. Resolution often occurs after discontinuing use of these agents, but it may take months. Concurrent use of topical tretinoin (Retin-A) % may reduce the incidence of atrophy from chronic steroid applications. 30 Other side effects from topical steroids include permanent dermal atrophy, telangiectasia, and striae.

Steroid responsive disorders

steroid responsive disorders


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