Sustained improvement with prolonged topical tretinoin (retinoic acid) for photoaged skin.

We performed a 22-month trial of topical tretinoin (retinoic acid) in the treatment of photoaging. Thirty patients participated in a 4-month, randomized, blinded, vehicle-controlled study that has been reported previously; 21 patients continued tretinoin therapy on an open-label basis, participating in the study for a total of 10 months, and 16 patients continued for 22 months. During the open-label study, the statistically significant improvement that had occurred in fine and coarse wrinkling and skin texture during our original study was sustained, despite reductions in dose or frequency of application of tretinoin. The number of discrete lentigines decreased by 71% compared with the number before therapy. Histologic findings included a statistically significant thickening of the epidermis. Side effects were limited to a cutaneous retinoid reaction that diminished as therapy proceeded.

Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils. A preliminary report.

Topical 0.1% tretinoin or vehicle control was applied daily to the forearm skin of six caucasian adults for 4 months. Two-millimeter punch biopsy specimens were obtained from treatment sites at the beginning and end of the study period for electron microscopy. Anchoring fibrils within the epidermal-dermal junction of skin treatment sites were quantitated by blinded, standardized, computer-assisted morphometry. After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites (1.34 anchoring fibrils per micron of lamina densa vs 0.65, respectively). The possible mechanisms by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibiting collagenase, a dermal enzyme that degrades anchoring fibril collagen. We speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.

Linear focal elastosis (elastotic striae).

Three patients are described who had a distinctive clinical and histologic presentation of dermal elastosis. Sunlight apparently played little role in the development of this elastotic change. To the best of our knowledge, this is the first report of this form of elastosis.

Transdermal delivery of salicylic acid in the treatment of viral papillomas.

Healthy adult (New Zealand, Dutch Belt, and Wild) rabbits were infected with rabbit papilloma virus (Shope variety). The resultant papillomas were treated with salicylic acid in a new transdermal drug delivery system utilizing a karaya gum glycol matrix. Biopsy samples of treated papillomas were taken at 1, 2, and 3 weeks after initiation of treatment and examined by electron microscopy. The observed changes during the course of treatment indicated that the karaya gum glycol matrix effectively released salicylic acid into the stratum corneum. Further, the rate of delivery of salicylic acid was such that the desired keratolytic activity was achieved with minimal inflammatory response.

Intracellular elastin in generalized granuloma annulare.

This report reviews thirteen cases of generalized granuloma annulare. The light and electron microscopic appearance of intracellular elastin particles in eleven of these cases is described. These bodies were also noted in deep granuloma annulare, elastosis perforans serpiginosa, and a small percentage of localized granuloma annulare. They were not found in necrobiosis lipoidica.

Ultrastructural changes in sebaceous glands following treatment of cystic acne with isotretinoin.

Following 20 weeks of treatment with isotretinoin, sebaceous glands in patients with cystic acne shrank in size. The cells remaining in the sebaceous lobules were mainly mature lipid-filled cells, with some undifferentiated cells still present at the periphery. The ultrastructure of the glands 8 weeks after cessation of treatment was directly related to the drug dose given each patient. The larger the dose, the slower the return to pretreatment morphology. In those patients given a lower dose, most of the glands observed 2 months after treatment was stopped were similar in size to those seen prior to treatment.

Ultrastructural changes in open comedones following treatment of cystic acne with isotretinoin.

The primary change found in cellular material expressed from open comedones of patients who had been treated with isotretinoin was disintegration of desmosomes. Consequently, there was lack of cohesion between cornified cells. A marked decrease in the quantity of sebaceous material and bacteria was also evident within the comedones.

Tubular apocrine adenoma with perineural invasion.

A tumor is reported that had remarkable pathologic changes showing with light microscopy a pattern in some portions consistent with tubular apocrine adenoma, while other areas were suggestive of syringoid eccrine carcinoma. Perineural invasion, commonly seen in syringoid eccrine carcinoma and never before reported in tubular apocrine adenoma, was found. Electron microscopy revealed the true apocrine nature of the tumor even though the tissue had been stored for 2 months in buffered formalin prior to processing.

Pigmentation of open comedones. An ultrastructural study.

Ultrastructural examination of expressed "black" open comedones did not disclose any single melanosomes or melanosome complexes. If there is any melanin present in comedonal plugs, the amount is minimal, and it cannot be the source of the black color.

Optical transforms of epidermal Langerhans' cell granules.

The internal structure of the epidermal Langerhans' cell granule (LCG) was studied with optical transforms of electron micrographs representing 3 planes of sectioning. Its "limiting membrane" exhibited linear discontinuity with a periodicity of about 11 nm similar to the structural repeats of the core (10.8 mm) in both the "outer" and the "internal leaflets". The average thickness of the nonvesicular part of the LCG was 55.7 nm. Disarray present in the optical diffractograms was incompatible with crystallinic or paracrystallinic orderliness of the periodic structures in the LCG. The structure appeared as an assembly of 4 sheets of roughly hexagonally packed particles: The stacked particles of 2 sheets in orthogonal contact forming the core (13.2 nm) were separated by an intermediate space (2.7 nm) from the single sheet of the outer layer and staggered by one-half the particle diameter on cross-sections. The validity of this model was inferred from the similarity of optical transforms of model structures.

Skin pigmentation secondary to minocycline therapy.

Localized brown to blue-black discoloration of the skin occurred in three patients receiving long-term minocycline hydrochloride therapy. Abundant perivascular pigmented material was present at all levels of the dermis below the upper papillary portion. Histochemical studies demonstrated reactivity with the Prussian blue stain and the Fontana-Masson silver technique. The granules were brightly refractile by dark-field illumination. Ultrastructurally, there were membrane-bound dense intracellular inclusions differing from melanin and iron but identical to those known to occur in the thyroid glands of minocycline-primed laboratory animals. The abnormal pigment most likely represents a metabolic derivative of minocycline.

Elastic tissue changes in skin following PUVA therapy.

Treatment of psoriasis with psoralens and high-intensity long-wave ultraviolet light (PUVA) produces changes in the ultrastructure of elastic tissue in skin. Early alterations consist of a loss of elastin followed by a breakdown of the microfibrils and subsequent fragmentation of the elastic fiber. Tissue examined 15 months after treatment was stopped still showed marked ultrastructural changes in the elastic fibers.

Melanocyte changes following PUVA therapy.

The effect of psoralens and long-wave ultraviolet light (PUVA) therapy on human melanocytes was studied at the ultrastructural level. The results demonstrate an increase in the number of melanocytes, a change in their location, and an increase in the size of the melanosomes. Significantly, some of the melanocytes extend in narrow columns deep into the dermis, limited by the basal lamina, while others are found free within the dermis. Other morphologic alterations in the melanocytes consist of abnormal mitochondria, a swollen and distorted endoplasmic reticulum, and large lysosomes. The aforementioned abnormalities were also present in PUVA-treated skin that was examined 15 months after the treatment had been stopped.

Giant melanosomes in multiple lentigines syndrome.

Biopsy specimens of normal skin and lentigines from an 82-year-old man with multiple lentigines syndrome were examined with light and electron microscopes. Giant melanosomes were found in dermal melanophages, melanocytes, and keratinocytes in all epidermal layers. Morphologic characteristics of these melanosomes are described, and other conditions in which they have been found are discussed.

Depressed immune function in epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is a rare disease characterized by the early onset and unremitting progression of wart-like lesions and frequent association of cutaneous carcinomas. We report two siblings with EV. Immunologic study of both patients demonstrated normal immunoglobulin levels, normal numbers of T-lymphocytes and B-lymphocytes, but markedly depressed in vitro blastogenic reactivity to mitogens and antigens. Cutaneous anergy to a variety of common skin test antigens was noted. These observations may reflect an inherited abnormality in immune function, or the depressed immune function may result from the viral infection of EV.

Effects of topical fluorouracil on normal skin.

Daily application of 1% fluorouracil cream to normal white skin results in definite morphologic alterations of the epidermis. Although clinical changes were not present, electron microscopic examination of the tissue demonstrates changes especially pronounced in the epidermal keratinocytes. These changes consist of cytoplasmic vacuoles, alterations in the mitochondria, Golgi complex, and endoplasmic reticulum, as well as widened extracellular spaces.