clobetasol and Skin-Diseases--Infectious

The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and beta-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Clobetasol; Disease Susceptibility; Down-Regulation; Epidermis; Female; Glucocorticoids; Humans; Lipid Metabolism; Mice; Mice, Nude; Skin Diseases, Infectious; Streptococcal Infections; Streptococcus pyogenes; Stress, Psychological

Forty-one patients with skin diseases of various origins were treated with an extempore combination of three creams containing clobetasone butyrate, sodium fusidate and ketoconazole. A mixture of the creams was applied once to 3-times daily for periods ranging from 5 to 15 days (mean 8.5 days). Assessments were made before, during and at the end of the treatment period using a symptom severity rating scale. The results showed that all symptoms regressed to a significant extent and by the end of the treatment period there had been complete disappearance or improvement with satisfactory remission in 97.6% of the patients. Local tolerance was excellent or good in all patients and there were no reports of any side-effects.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Infective Agents, Local; Antifungal Agents; Clobetasol; Drug Combinations; Female; Fusidic Acid; Humans; Ketoconazole; Male; Middle Aged; Skin Diseases, Infectious