Hyperkeratinization

Van Scott EJ,Yu RJ (1984) Hyperkeratinization, corneocyte cohesion, and alpha hydroxy acids. J Am Acad Dermatol 11 867-879... 

The pilosebaceous follicles are the target sites for acne. The pathophysiology of acne centers on interplay of follicular hyperkeratinization, increased sebum production, action of Propi-onibacterium acnes (P. acnes) within the follicle, and production of inflammation (Table 11.1). 

No adverse effects in 40 mg/kg BW group. High dose groups had skin damage (atrophy, acanthosis, hyperkeratinization) and testicular damage (abnormal seminiferous tubules, tubular lumens filled with degenerated sperm)... 

Tandon et al. (1975) applied daily dermal applications of 132.5 mg thorium/kg body weight/day (15 nCi/kg/day = 555 Bq/kg/day), 265 mg thorium/kg body weight/day (29 nCi/kg/day = 1073 Bq/kg/day), or 529 mg thorium/kg body weight/day (58 nCi/kg/day = 2146 Bq/kg/day) to the lateroabdominal and scrotal areas of rats for 15 days. The thorium was administered to skin (hair was clipped) as thorium nitrate, and the area remained uncovered for the duration of treatment. Mild hyperkeratinization of the lateroabdominal skin was found at all exposure levels. At the highest exposure level, mild acanthosis and thickening of the epithelial lining of the lateroabdominal skin were seen. At this level, mild acanthosis, swollen collagen fibers, and foamy dermis were found in the scrotal skin. The value of 15 nCi/kg/day is a less serious LOAEL, and the exposure level of 58 nCi/kg/day is a serious LOAEL for dermal effects in the rat. These values are reported in Table 2-3. 

Effects on the skin were observed in rats treated dermally with 40 mg nickel/kg/day as nickel sulfate for 15 or 30 days (Mathur et al. 1977). The effects included distortion of the epidermis and dermis after 15 days and hyperkeratinization, vacuolization, hydropic degeneration of the basal layer, and atrophy of the epidermis at 30 days. Biochemical changes in the skin (enzymatic changes, increased lipid peroxidation, and an increase in the content of sulfhydryl groups and amino nitrogen) were observed in... 

Nickel sensitivity has also been induced in guinea pigs by skin painting or intradermal injection (Wahlberg 1976 Zissu et al. 1987) and in mice by dermal contact (Siller and Seymour 1994). Dermal effects in animals after dermal exposure to nickel included distortion of the epidermis and dermis, hyperkeratinization, atrophy of the dermis, and biochemical changes (Mathur et al. 1977, 1988). 

Figure 16-2. Section of rat skin exposed to toxic chemicals and hyperkeratinization.

Figure 16-3. Effect of toxic chemicals on rat skin. Hyperkeratinization and thickening of the dermal layer.

AHAs were first used to treat dry skin (hyperkeratinization and xerosis) before the positive effects on photoaging skin... 

Normalize the rate of exfoliation/hyperkeratinization by enhancing elimination of dead cells and hydrating the skin properly retinyl palmitate, glycolic acid and glycyrrhetinic acid. 

Tretinoin (Retin-A, others) has been used in the treatment of acne vulgaris for almost four decades. A primary use for tretinoin is to reduce the hyperkeratinization that leads to microcomedone formation, the initial lesion in acne. Follicular comeocytes become less cohesive as a result of shedding of desmosomes, decreasing tonofila-ments and increasing keratinocyte autolysis and intracellular deposition of glycogen. 

Nystatin (mycostatin, nilstat, others) is used only for candidiasis and is supplied in preparations intended for cutaneous, vaginal, or oral administration for this purpose. Infections of the nails and hyperkeratinized or crusted skin lesions do not respond. Topical preparations include ointments, creams, and powders, each containing 100,000 units per gram. Powders are preferred for moist lesions and are applied two or three times a day. Imadazoles or triazoles are more effective agents than nystatin for vaginal candidiasis. 

TCDD are associated with alterations of cell proliferation in affected tissues. Common examples of 2,3,7,8-TCDD-mediated differentiation and proliferation in both fishes and mammals include dermal hyperkeratinization (fin necrosis in fish), teratogenicity, lymphoid involution, immunotoxicity, and carcinogenesis. Lipid peroxidation in liver, kidney, thymus, and testes is induced in rats by 2,3,7,8-TCDD in a dose- and time-dependent maimer. The enhanced lipid peroxidation by microsomes from 2,3,7,8-TCDD-treated rats may be associated with an increase in hydrogen peroxide production in conjunction with a decrease in glutathione peroxidase activity and an increase in free iron. 

Induction of chloracne in humans after exposure to dioxin and related compounds is supported by studies in laboratory animals. Rabbits, monkeys, and hairless mice have all proved useful in investigating this response. In addition, cellular systems provide a research tool in elucidating the chloracne response at the cellular level. Keratinocytes, the principal cell type in the epidermis, have been used as an in vitro model for studies of TCDD-induced hyperkeratosis, a feature of chloracne, in human- and animal-derived cell cultures. The response in these systems is analogous to the hyperkeratinization observed in vivo as a part of chloracne [181]. 

It seems probable that xerosis of the skin with hyperkeratinization, so-called toad skin or phrynoderma, also represents vitamin A deficiency in man. The relationship of vitamin A to mild skin changes such as localized areas of keratinization of the hair follicles, follicular hyperkeratosis, is less well documented. Vitamin A deficiency may be responsible for the lesions in some instances but certainly not in all. Unequivocal follicular keratotic changes have not been produced experimentally in man. ... 

Van Scott EJ 1988 The unfolding therapeutic uses of the alpha hydroxy acids. Mediguide to Dermatology 3 1-5 Van Scott EJ, Yu RJ 1984 Hyperkeratinization, comeocyte cohesion and alpha hydroxy acids. Journal of the American Academy of... 

Comprised of several genetically transmitted diseases, these disorders appear to be valid disorders of keratinization. Although categorized into several types according to genetic patterns, clinical presentation and histological features, the ichthyoses are all related by the common denominator of defective cutaneous keratinization, which appears to be an isolated epidermal phenomenon insofar as hyperkeratinization of other epithelia does not occur. 

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