Histological evaluation of systemic isotretinoin’s effect on the skin

The presented literature review contains data on histomorphological changes in the dermis when using isotretinoin. The systematic search was conducted for the results of scientific studies published between January 1980 and January 2026. The analysis included original researches, clinical and morphological work, experimental studies and review publications on morphological changes in the skin during systemic isotretinoin therapy. The result of the relevant search turned out to be 409 articles, of which, after the initial study, 25 articles were selected for final analysis: 19 articles were devoted to the anti-acne effect, the remaining 6 articles – to the involution of signs of photoaging against the background of the use of isotretinoin. Based on the literature analysis, data were collected on histological changes in the skin during the systemic use of isotretinoin from both the sebaceous glands and the dermis.

Systemic use of isotretinoin caused a number of changes in the skin, confirmed clinically and histologically. In particular, sebaceous glands were significantly reduced (up to 90%), and sebocyte differentiation was inhibited. The structure of the glands became elongated, «cellular» with a small number of sebocytes remaining in the center, on the basal plate. The amount of cytoplasm decreased by 35% compared to the size of the nucleus. There was a noticeable decrease in the number of immature cells and there was no mitotic numbers. The number of partially differentiated cells was very small, most of the cells were mature and full of lipid droplets. Desmosome destruction and disruption of links between keratinized keratinocytes were recorded, therefore, microcomedones regressed, and sebaceous filaments significantly decreased clinically. Follicular keratinization decreased by 55-70%. The amount of sebum and bacteria in comedones decreased markedly.

In the context of the effect of isotretinoin on photoaging, the following histological changes were identified: the significant increase in epidermal thickness, the decrease in elastosis, the decrease in epidermal p53, the straightening of the papillae of the dermis, the trophism improvement, the decrease in inflammatory infiltrate and in the degree of basophil degeneration of collagen, the increase in its density and concentration. There was the decrease in the number and changes in elastic fibers: elastic fibers were more tangled and fragmented before treatment, and more fibrillar and whole after treatment.

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