Topical Glucocorticosteroids

Topical glucocorticosteroids are the most widely prescribed drugs for skin diseases. Like systemic glucocor-ticosteroids (Chapter 60), topical glucocorticosteroids bind to cytoplasmic receptors that transport the drug to the nucleus, where the complex binds to particular regions of DNA known as the glucocorticoid response element (GRE) and alters gene expression. Such receptors have been identified in both epidermis and dermis.

Drug absorption is enhanced by the use of agents with lipophilic side chains; by application of the drug to larger areas of skin, to inflamed areas, and/or for long periods; and by the use of occlusive dressings. Like their systemic counterparts, topical glucocorticosteroids have myriad pharmacological effects. Especially important in skin diseases are their antiinflammatory and immuno-suppressive effects and their catabolic characteristics (hence their usefulness in eczematous dermatitis and their toxicity of dermal atrophy, respectively).

Although their exact mechanism of action is unclear, they are known to inhibit the expression of various cytokines and adhesion molecules and to antagonize the activity of transcription factors, including NF-k B, NF-AT, and AP-1.

Topical corticosteroids are most useful in inflammatory dermatoses, such as eczematous dermatitis and psoriasis; they may also be helpful in other skin diseases that have a prominent inflammatory component, such as autoimmune blistering diseases (e.g., bullous pemphigoid and pemphigus vulgaris) and lupus erythematosus.

Many compounds are available in both proprietary and generic forms, and their bioequivalence is difficult to document. Nonetheless, the drugs are classified into seven categories according to their relative potencies (Table 41.1).

Systemic toxicity from topical corticosteroids can occur, particularly from the more potent agents. Cushing's syndrome, although rare, has been reported.

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