Eugene J. Van Scott

Effects of α-hydroxy acids on photoaged skin: Apilot clinical, histologic, and ultrastructural study

Background : α-Hydroxy acids (AHAs) have been reported to improve aging skin. The mechanisms of action of AHAs on epidermal and dermal compartments need clarification. Objective : Our purpose was to determine the effects of AHAs on photoaged human skin by clinical and microanalytic means. Methods : Patients applied a lotion containing 25% glycolic, lactic, or citric acid to one forearmand a placebo lotion to the opposite forearm for an average of 6 months. Thickness of forearm skin was measured throughout the study. Biopsy specimens from both forearms were processed for analysis at the end of the study. Results : Treatment with AHAs caused an approximate 25% increase in skin thickness. The epidermis was thicker and papillary dermal changes included increased thickness, increased acid mucopolysaccharides, improved quality of elastic fibers, and increased density of collagen. No inflammation was evident. Conclusion : Treatment with AHAs produced significant reversal of epidermal and dermalmarkers of photoaging.

Long-term efficacy, curative potential, and carcinogenicity of topical mechlorethamine chemotherapy in cutaneous T cell lymphoma.

Complete responses lasting from 4 to 14 years were documented in 65 of 331 (20%) patients with cutaneous T cell lymphoma treated with topical mechlorethamine (HN2) between 1968 and 1982. Such long-lasting remissions occurred most often, but not invariably, in patients with patch or plaque phase mycosis fungoides without palpable lymphadenopathy (stage Ia or Ib). The likelihood of a continuous remission was enhanced by initiation of treatment before an unequivocal pathologic diagnosis. Despite the long-lasting responses in these patients, however, relapses have been documented in 11 (17%) of these patients, and all relapses occurred within 8 years of discontinuing maintenance topical chemotherapy. Thus, in our experience, a continuous remission lasting 8 or more years provides evidence that cutaneous T cell lymphoma can be eradicated by aggressive topical chemotherapy. This circumstance was observed in 35 patients, representing a cure rate of at least 11% overall. In addition, when compared with the general population of the United States, patients who received topical HN2 were at an 8.6-fold and a 1.8-fold increased risk for the development of squamous cell carcinoma and enhanced for Hodgkins disease and colon cancer but not for systemic cancers known to be induced by systemic administration of alkylating drugs. These results compare favorably with experiences with topical HN2 chemotherapy at other centers but raise questions about the risks associated with long-term administration for maintenance of remissions.

Mycosis fungoides: Natural history and aspects of its relationship to other malignant lymphomas

Abstract In this study of thirty-eight patients, it was found that mycosis fungoides almost always began as a chronic benign dermatitis. Subsequently skin tumors, characteristic of mycosis fungoides, developed in all patients. At this stage three patients died; at autopsy there was no evidence of internal malignant disease. In the remainder of the patients, lymphadenopathy often became clinically apparent and in six patients serial biopsies showed transition from benign lymphadenopathy to frank malignant lymphoma. Of the patients examined at autopsy, 82 per cent had visceral lymphomatous disease with persistence of cutaneous lesions histopathologically characteristic of mycosis fungoides. The relationship of mycosis fungoides to other malignant lymphomas is discussed.

Clinical and cosmeceutical uses of hydroxyacids

The hydroxyacids are represented by the alpha-hydroxyacids, beta-hydroxyacids, polyhydroxy acids, and bionic acids. Together, these ingredients form a class of compounds with unparalleled benefits to the skin and unprecedented usage in the cosmeceutical market in cosmetic and therapeutic formulations alike. The most commonly used hydroxyacid is glycolic acid, an alpha-hydroxyacid that has been used extensively in cosmetic antiaging formulations, moisturizers, and peels, and in treatment products to improve hyperpigmentation and acne. The newer polyhydroxy and bionic acids offer the benefits of alpha-hydroxyacids without irritation, making them suitable for use on sensitive skin, rosacea, and after cosmetic procedures. They also provide additional antioxidant/chelation, barrier strengthening, and moisturizing effects. Bionic acids inhibit matrix metalloproteinase enzymes in skin, providing a preventative antiaging benefit. The hydroxyacids as a class can be combined with therapeutically active materials and cosmetic procedures to increase therapeutic effects and improve tolerability and outcomes of medicinal agents and procedures.

Citric Acid Increases Viable Epidermal Thickness and Glycosaminoglycan Content of Sundamaged Skin

background Recently, there has been an exponential increase in the use of alpha‐hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha‐hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha‐hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha‐hydroxy acid to increase viable epidermal thickness, and derma! glycosaminoglycans. objective In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness. viable epidermal thickness, and dermal glycosaminoglycan constent. Biopsy samples were harvested after 3 months of treatment. results Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin. conclustions Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha‐hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.

Increased factor XIIIa transglutaminase expression indermal dendrocytes after treatment with α-hydroxy acids: Potential physiologic significance

BACKGROUND Topical alpha-hydroxy acids (AHAs) have been shown to improve photoaging in human skin. OBJECTIVE We studied factor XIIIa transglutaminase expression in dermal dendrocytes (DDs) and mast cell degranulation after treatment of the skin with AHAs. METHODS Skin biopsy specimens obtained from patients after 4 to 8 months of treatment with lotions containing 25% AHAs were evaluated for factor XIIIa transglutaminase expression with immunoperoxidase and electron microscopy. Immunoperoxidase-stained sections were studied by means of semiquantitative methods and image analysis. Mast cell degranulation was studied by image analysis. RESULTS Increased factor XIIIa transglutaminase expression was seen after treatment with AHAs. All treated sites had increased scores compared with control sites by semiquantitative methods. Seventy-five percent of treated sites showed an increased mean area over control sites of factor XIIIa transglutaminase positivity with image analysis. These results correlated with an increased level of mast cell degranulation in treated sites and with activation of DDs as seen by electron microscopy. CONCLUSION Treatment of the skin with AHAs leads to mast cell degranulation and increased expression of factor XIIIa transglutaminase by activated DDs. Mast cell degranulation may lead to activation of DDs and increased factor XIIIa transglutaminase expression, via the action of tumor necrosis factor-alpha. We speculate that clinical and histologic improvement in photoaged skin after treatment with AHAs may be somehow related to this process.

SARCOIDOSIS: CLINICAL STAFF CONFERENCE AT THE NATIONAL INSTITUTES OF HEALTH

Excerpt Dr. John P. Utz: When presenting a conference for our group at the National Institutes of Health, one gets caught on the horns of a dilemma. One horn is to select a subject in which we are ...

Systemic lupus erythematosus.

Lupus is a serious, potentially life-threatening disease. Its natural history is to culminate in a crescendo of autoimmunity and organ involvement. Difficulty arriving at the diagnosis may delay institution of therapy, which although helpful brings new problems. The fundamental understanding of this disease has made major strides. There is no consensus on the likely etiological agent(s), though evidence implicates Epstein-Barr virus, and the genetic approach to understanding etiology is in its infancy. Nevertheless, efficacious treatments are anticipated in the plethora of new biologics likely to have therapeutic effects in lupus, essentially a disease of immune dysregulation.This document relates to methods and materials involved in diagnosing SLE. For example, this document provides arrays for detecting polypeptides that can be used to diagnose SLE in a mammal. In addition, methods and materials for assessing SLE activity, determining the likelihood of experiencing active SLE, and detecting SLE treatment effectiveness are provided herein.

Integument|[mdash]|The Hide in Seeking1

One year ago, Dr. Irvin Blank (1), in his presidential address before this Society spoke of cutaneous barriers, the properties of the skin which protect the organism from its environment, maintain it in relative isolation, and which in consequence in many ways insulate it against outside influences. He also spoke of the intangible barriers of dermatology, properties of the specialty which tend to maintain the discipline of dermatology in relative isolation, and in consequence insulate it against outside influences. In turn, on this occasion of the presidential address, it is my intention to talk of the skin as a highly functional intercommunicating and interrelating medium which mediates an intimate relationship of the organism with its environment. I wish also to direct attention to properties of the skin which similarly may be operable to induce dermatology into greater functional identities in interdisciplinary environments.

Integument—The Hide in Seeking**Presented as the Presidential Address at the Twenty-seventh Annual Meeting of The Society for Investigative Dermatology, Inc., Chicago, Illinois, June 26, 1966.

One year ago, Dr. Irvin Blank (1), in his presidential address before this Society spoke of cutaneous barriers, the properties of the skin which protect the organism from its environment, maintain it in relative isolation, and which in consequence in many ways insulate it against outside influences. He also spoke of the intangible barriers of dermatology, properties of the specialty which tend to maintain the discipline of dermatology in relative isolation, and in consequence insulate it against outside influences. In turn, on this occasion of the presidential address, it is my intention to talk of the skin as a highly functional intercommunicating and interrelating medium which mediates an intimate relationship of the organism with its environment. I wish also to direct attention to properties of the skin which similarly may be operable to induce dermatology into greater functional identities in interdisciplinary environments.