Role of topical calcineurin inhibitors in the treatment of seborrheic dermatitis: a review of pathophysiology, safety, and efficacy.

Seborrheic dermatitis (SD) is characterized by erythematous pruritic patches and plaques with greasy scale that occur in sebaceous areas. It is common, affecting up to 3% of the population. Past treatments have relied on a wide variety of anti-inflammatory and antifungal agents, but corticosteroids have limited use because of long-term adverse effects. Topical calcineurin inhibitors provide a safe alternative for the treatment of SD, as these drugs block the inflammatory cascade involved in the disease process and pose no risk of skin atrophy. Studies of topical pimecrolimus and tacrolimus in the treatment of SD have found that improvement occurred within 2 weeks, and if SD recurred after stopping treatment, it was significantly less severe. There have been no studies of the comparative efficacy of pimecrolimus versus tacrolimus for the treatment of SD. Common adverse effects of mild burning and irritation have been associated with the use of both of these agents. Safety profile studies are limited to studies of atopic dermatitis, which show no increase in infection rate, photocarcinogenicity, or signs of immunosuppression in patients using topical calcineurin inhibitors for long-term treatment. This article reviews the clinical trials of pimecrolimus and tacrolimus in the treatment of SD, focusing on efficacy and safety.

Stratum corneum-derived caspase-14 is catalytically active.

Caspase-14, a cysteine protease with restricted tissue distribution, is highly expressed in differentiated epidermal keratinocytes. Here, we extracted soluble proteins from stratum corneum (SC) of human epidermis and demonstrate that the extract cleaves tetrapeptide caspase substrates. The activity decreased to below 10% when caspase-14 was removed by immunodepletion showing that caspase-14 is the predominant caspase in SC. In contrast to normal SC, where caspase-14 was present exclusively in its processed form, incompletely matured SC of parakeratotic skin from psoriasis and seborrheic dermatitis contained both procaspase-14 and caspase-14 subunits. Fractionation of extract from parakeratotic SC revealed that the peak caspase activity coeluted with processed caspase-14 but not with procaspase-14. Our results suggest that during regular terminal keratinocyte differentiation, endogenous procaspase-14 is converted to caspase-14 subunits that are catalytically active in the outermost layers of normal human skin.

Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.

The fuzzy rat, a genetic mutant between hairless and hairy albino rats, expresses androgen-dependent hypersecretion of sebum and hyperplastic sebaceous glands. Using this model for human acne, we examined the effects of inhibitors of human steroid 5 alpha-reductase isozymes, type I (MK 386) and type II (finasteride), and an androgen receptor blocker (RU58841) on regression of glandular and ductal hyperplasia. The above three agents, 1% weight volume, were dissolved into the vehicle (propylene glycol, alcohol and water) and applied on the backs of peripubertal male rats for 2 months. Control and castrate groups received vehicle alone. At 8 weeks, we examined the size the sebaceous glandular lobules and ducts in split epidermal preparations as well as in frozen sections of skin stained with osmium-potassium dichromate solution. The number of bromodeoxyuridine (BrdU)-positive cells was counted in the glandular lobes in split-skin tissues stained with BrdU immunochemistry. The results revealed that the sizes of both lobes and ducts in castrates were 40-60% smaller than in controls. RU58841 induced glandular and ductal regression equivalent to that in castrates. Finasteride induced a moderate degree of lobular and ductal reduction, whereas MK386 caused only ductal regression. Reduction of BrdU-positive cells in the sebaceous lobes was found in the skin treated with finasteride and RU58841. Serum concentrations of testosterone and dihydrotestosterone showed no significant changes in all drug-treated rats. The weight of the prostatic lobes was reduced significantly in rats treated with finasteride but not by the other two agents. RU58841 effectively counteracted endogenous androgens resulting in a suppression of growth of the sebaceous glands but not the prostate. This rodent model for androgen-dependent hyperplasia of the sebaceous glands is useful for the study of many pharmacological aspects comprising the rate of percutaneous absorption, stability and affinity to target organs of the testing compounds, and selection of adequate vehicle for topical application.

Acid glycosidases in basal cell epithelioma and in seborrhoeic keratosis.

Total activities of eleven glycosidases were determined in frozen-dried tissue fragments of basal cell epithelioma, seborrhoeic keratosis and epidermis. The values found were frequently much higher than those mentioned in the literature. Most enzyme activities were higher in basal cell tumours than in the adjacent epidermis; the differences between basal cell epithelioma and seborrhoeic keratosis were significant for only two of the eleven enzymes.

Enzymes of carbohydrate metabolism in human epidermal tumors. 5.

The activities of eight enzymes were determined by fluorometric micromethods in epidermal tumors (basal and squamous cell epithelioma, verruca seborroeica and keratoacanthoma) and compared to the activities in the adjoining, apparently normal epidermis. The activities were increased in basal cell epithelioma, variable in squamous cell epithelioma and verruca seborroeica and lowered in keratoacanthoma.

[Ultrastructure of the epidermis in seborrhoic dermatitis (author's transl)]. / Zur Ultrastruktur der Epidermis bei seborrhoischem Ekzem

Electronmicroscopical investigation on 12 cutaneous biopsies of different localisation showed that the seborrhoic dermatitis is not comparable to a psoriatic tissue-reaction. Both, the cyto-morphological feature and the demonstrated localisation of the acid phosphatase are distinctly different from that of the psoriatic epidermis. The described changes are clearly more similar to the well known ultrastructural pictures of eczemateous reactions. In spite of the "eczema-like" ultrastructural picture seborrhoic dermatitis apparently can be separated from the allergic and irritant contact-dermatitis. Nevertheless, the epidermal alterations are also similar to chronic nummular eczema. They therefore are unspecific and do not allow any conclusion regarding the etiopathogenesis or nosological classification of this skin disease.

Enzymes of carbohydrate metabolism in human epidermal tumors 4. Enzymes of the pentose phosphate pathway.

The acitvities of six enzymes were determined by fluorometric micromethods in epidermal tumors (basal and squamous cell epithelioma, verruca seborrhecia and keratoacanthoma) and compared to the activities in the adjoining, apparently normal epidermis. Specific changes related to malignancy were not obvious.