Albert M. Kligman’s research while affiliated with University of Pennsylvania and other places

BACKGROUND: Dry, itchy, scaly skin is a common and distressing problem for elderly people. The regression method is commonly employed to compare the efficacy of moisturizers. However, this method relies solely on clinical estimates of scale removal and provides no information on the structural and functional changes of the stratum corneum. METHODS: We compared a commercial 15% glycolic acid lotion (NeoStrata) with a traditional water in oil emulsion containing a mixture of lanolin alcohols, mineral oil, and petrolatum (Eucerin cream). These were applied twice daily for 6 weeks to the xerotic legs of elderly women. A variety of methods were used to assess the effects on the horny layer barrier. RESULTS: The time to induce burning by chloroform:methanol was decreased by NeoStrata and increased by Eucerin. Transepidermal water loss increased after NeoStrata treatment and decreased after Eucerin treatment. The stratum corneum was more resistant to NaOH erosions with Eucerin but remained unchanged with NeoStrata. Dimethyl sulfoxide whealing decreased with Eucerin but was unchanged with NeoStrata. The inflammatory reaction to sodium lauryl sulfate was diminished by Eucerin and increased by NeoStrata. CONCLUSION: Both treatments were equally effective in smoothing the surface. However, the glycolic acid lotion weakened the stratum corneum barrier in contrast with Eucerin, which enhanced it. (J Dermatol Treat (2000) 11: 241-245)

Abstract There are many causes of dry skin and there are many xerotic syndromes, but the structural and physiolgical aberrations underlying the condition remain mysteries. All efforts to understand are properly directed to the horny layer: the dead tissue where the disorder is expressed. Methods for evaluating the abnormalities of the horny layer were reviewed in presentations made during the Symposium. The findings from biochemical, bioengineering, and microscopic studies at least allow some unifying concepts to be developed now. In the opinion of the presenter, moisturizers are not cosmetics but medicaments, regardless of the legal classification by the U.S. Food and Drug Administration. Dry skin is not a single phenomenon but a family of reactions ranging in severity from dryness to scaling to cutaneous damage and infection. The causes of dry skin include winter xerosis, asteatosis, and old age. Water, in fact, is not a solution to dry skin. The change in cutaneous water content is secondary to the primary dry-skin effect of desquamation. Treatment of dry skin is best accomplished with moisturizers composed of hydrophobic oils.

Prolonged topical corticosteroid use is often associated with atrophic skin changes. This trial compared signs of skin atrophy related to 3 super-high-potency corticosteroids: fluocinonide 0.1% cream, clobetasol propionate 0.05% cream, and 0.05% foam. The test treatments were applied to the forearms 10 females twice daily for 21 days. Skin characteristics were assessed pretreatment and posttreatment for atrophic changes. Further punch biopsies obtained from 5 subjects were assessed histologically. Clobetasol foam produced mild changes in noninvasive tests, but stained skin biopsies revealed structural changes nearly comparable to clobetasol cream, which showed substantial atrophic changes. Fluocinonide cream was the least atrophogenic, producing no or only mild effects that were slightly greater than vehicle. Fluocinonide cream has a lower potential to produce atrophic changes of the skin than either clobetasol cream or clobetasol propionate foam.

Enfin l’hidradénite suppurée, une maladie décrite il y a un siècle et demi, et l’une des plus dévastatrices parmi les milliers d’entités dermatologiques, est finalement reconnue par un texte dédié uniquement à cette horrible affection.

Topical therapies are effective in managing acne vulgaris but are associated with local adverse effects such as irritation and dryness. This 4-week pilot study compared skin hydration in 36 healthy adult women randomized to treatment with 1 of 4 topical therapies: 2 different (jar and tube) clindamycin 1%/benzoyl peroxide 5% gels, sodium sulfacetamide 10% lotion, or over-the-counter (OTC) moisturizing cream. Subjects treated with OTC moisturizer or sodium sulfacetamide exhibited decreased water loss, increased water retention, similar or improved levels of skin hydration, and decreased desorption rates. In contrast, subjects treated with jar or tube clindamycin/benzoyl peroxide had increased water loss, decreased water retention, decreased hydration, and increased desorption rates. Skin dryness decreased slightly in the moisturizer group. No serious adverse events occurred. Overall, the OTC moisturizer had the best skin hydration profile. Sodium sulfacetamide demonstrated some moisturizing characteristics, and no clinically relevant differences were noted between jar and tube clindamycin/benzoyl peroxide gels.

Alkyl ester quaternary ammonium compounds (ester quats) are used extensively in fabric rinse conditioners. It is important to document in the literature the outcome of historical studies that were performed to assess the risk of adverse skin effects associated with their use. (1) To document the outcomes of historical studies performed to evaluate the skin sensitizing potential of two ester quats (the di-[hardened tallow fatty acid] ester of 2,3-dihydroxypropyl-trimethyl ammonium chloride [HEQ] and the dialkyl ester of triethanol ammonium methyl sulfate [TEA-Quat]) and (2) to demonstrate that these ester quats lack marked skin-sensitizing potential in humans, such that they do not present a risk of contact allergy for consumers who use fabric rinse conditioners. Each material was assessed in the human maximization test in a panel of 25 volunteers. Diagnostic patch testing was also performed with each material in a population of 239 patients undergoing routine patch testing for suspected allergic contact dermatitis. These data are also considered in the context of an exposure-based quantitative risk assessment. Neither HEQ nor TEA-Quat was found to cause skin sensitization under the conditions of the human maximization test. No evidence of contact allergy to the materials was found among the relatively small population assessed by diagnostic patch testing. This study provides evidence that HEQ and TEA-Quat lack substantial skin-sensitizing potential in humans. Taken together with similar data for other ester quats, it suggests that compounds in this class are unlikely to be significant human contact allergens.

Background: In the USA, Europe and Japan 40 to 50% of women report that they have sensitive skin, defined as abnormal sub‐clinical sensory responses to drugs, cosmetics and toiletries in the absence of visible signs of irritation. Itching, burning, stinging and tightness are the commonest complaints, which mainly afflict women. Manufacturers of skin care products have made available a large variety of products which are designed for persons with sensitive skin. Such products are not required by regulatory agencies to submit evidence of safety and efficacy, allowing marketers to make claims that are often exaggerated, irrational and even preposterous. The consumer with self‐assessed sensitive skin has no way of judging which products are likely to be most beneficial and least harmful. The marketplace is awash with products for which there is no evidence that the rosy claims have been substantiated by appropriate testing procedures. There is no internationally accepted consensus regarding the criteria which define sensitive skin. Many papers have been published in the last 15 years, mainly originating from industry, which express widely differing views regarding what constitutes sensitive skin. For some, any adverse reaction to a product topically applied to sensitive skin, including breakouts, redness, scaling etc., a panoply of adverse reactions which is virtually meaningless. Others include environmental factors as causative, including cold, dry wind, heat and high humidity, solar radiation, etc., which add to the manifest complexities of the subject. Methods: This is the first paper in a series which provides a comprehensive review of the subject, emphasizing the all too many controversies and confusions arising from the lack of a consensus regarding the identification, classification, epidemiology, prevalence and pathogenesis of sensitive skin. Sensitive skin is a biologic reality and not a psychological, fashionable fantasy on the part of impressionable women. Result/Conclusion: There is an urgent necessity to establish rigorous methodologies for estimating the quality and severity of sensitive skin, a heterogeneous condition involving multi‐factorial factors. Subsequent papers in this series will describe in detail the experimental approach our group has used to bring some clarity and credibility to this querulous, but important subject.

Ten healthy women with moderate signs of facial photodamage (fine lines, wrinkles, dyspigmentations, hyperkeratotic prominent pores, and poor skin texture) applied imiquimod 5% cream once daily for 5 days each week for 4 weeks. None of the subjects had actinic keratoses or had received previous treatment for basal or squamous cell cancers. Histology, hydration, coloration, and imaging assessments were conducted before and after treatment to determine the effects of imiquimod therapy. Global assessments of the improvement in skin appearance were evaluated by subjects and a dermatologist. Histologic analysis revealed that the structurally regressive changes of the epidermis - atrophy, atypia, hyperchromatic nuclei, disorderly differentiation, and loss of polarity - were completely reversed after imiquimod treatment. The dermal matrix was unaffected by imiquimod therapy. Global assessments of skin appearance revealed that imiquimod treatment yielded appreciable reductions in wrinkles, dyspigmentations, and hyperkeratotic pores. Clinical improvements in skin appearance were confirmed by imaging, coloration, and hydration assessments that demonstrated a smoother surface, more uniform color, improved texture, and elimination of hyperkeratotic pores. The correction of epidermal dysplasia, a characteristic feature of photoaged skin in which epithelial tumors arise, suggests that imiquimod exerts a prophylactic action in the prevention of cutaneous tumors. Imiquimod provides an alternative to topical retinoids in reversing the clinical and histologically regressive changes of photoaged facial skin.