Photoaging: mechanisms and repair / Photoaging: mechanisms and repair

Aging is a complex, multifactorial process resulting in several functional and esthetic changes in the skin. These changes result from intrinsic as well as extrinsic processes, such as ultraviolet radiation. Recent advances in skin biology have increased our understanding of skin homeostasis and the aging process, as well as the mechanisms by which ultraviolet radiation contributes to photoaging and cutaneous disease. These advances in skin biology have led to the development of a diversity of treatments aimed at preventing aging and rejuvenating the skin. The focus of this review is the mechanism of photoaging and the pathophysiology underlying the treatments specifically designed for its prevention and treatment. LEARNING OBJECTIVES: At the conclusion of this learning activity, participants should be familiar with the mechanism of photoaging, the treatments for photoaging, and the data that supports the use of these treatments...

Editorial.

The cosmopolitan nature of current travel practices, as well as significant immigration from endemic areas, has led to increases in the incidence of leprosy. The classic presentation of leprosy usually appears as the indeterminate form, demonstrates hypopigmented macules with a loss of sensation. However, the manifestations can sometimes be quite protean. Sadeghi et al. review the rheumatic manifestations of leprosy with an illustrating case presenting with arthritis. Rheumatic symptoms are common in leprosy patients and may be the presenting manifestations and should be considered in patients with persistent rash and unusual arthritis who have a history of exposure to endemic areas. Significant interest has developed over the past decade in inhibiting cutaneous carcinogenesis with retinoic acid. This has been used as an effective therapy in certain genetically predisposed individuals, including individuals with a DNA repair defect in xeroderma pigmentosa. The molecular mechanisms of retinoids ability to inhibit ultraviolet light induced carcinogenesis have not been determined. Li and co-workers have examined the effect of retinoic acid on ultraviolet light induced programmed cell death (apotosis) as well as expression of the tumour suppressor gene P53. Their studies suggest that retinoic acid does not work on the initiation stages of the cancer development, but may work in the promotion and progression stage. Of more immediate clinical importance, in the Point-Counterpoint section, we have two insightful articles on how physician reimbursement affects patient care. As North American health care continues to evolve, there is constant debate on what model system works best for the ultimate benefit of our patients. Physicians, politicians, and administrators are constantly comparing the United States health care delivery to that of Canada. While no one can accurately predict the future developments in these areas, I think Dr. McElgunn sums the concerns that indeed are applicable on both sides of the border: ".socialized medical system has been of great benefit to patients but the ability of its physicians to continue to carry the system is at or near the breaking point. The ramifications of the issues of access and quality of care are harbingers of a system in turmoil." While these concerns must be dealt with, strong physician input is vital to continuing the effective evolution of our health care system. A vital part of our health care delivery is the increasing use of diagnostic tests. Key treatment decisions and interventions are based on the interpretation of these tests. However, most tests are "imperfect instruments." The article by Binder and Dreiseitl concisely reviews sensitivity, specificity, prevalence, predictive values, and likelihood ratios in a highly informative manner with significant examples. This paper provides a reference with which all physicians should be familiar. Traditionally, Western medicine has focused on a model of disease whereby pathology was regarded as well defined alteration in normal physiology that should respond to appropriate pharmaceutical or surgical interventions. However, in recent years patient focused medicine has become an important aspect of our practices. The concept of health related quality of life has represented an important advance in dealing with these concerns in our treatment of disease. Drs. Price and Harding examine the concept of health related quality of life using the example of a diabetic foot ulcer complications. These types of measures are important to understand, not only in the context of this disease but in the context of any chronic dermatologic condition.

Editorial

As dermatologists, we have all been active in educating patients about sun awareness and sun protection. This is even more important for children, as childhood exposure to ultraviolet light is a significant risk for both melanoma and nonmelanoma skin cancers. The importance of an educational approach in appropriate sun awareness in childhood is further underscored by the recent findings by Rivers et al., in the Vancouver Moles Cohort study, presented at the 1999 American Academy of Dermatology meeting. In a placebo-controlled trial, the findings of Rivers et al. clearly demonstrated that the use of sunscreens can significantly decrease the formation of nevae in children, providing further evidence to support sun awareness education initiatives. The lead article by Gooderham and Guenther in the Basic and Clinical Sciences section evaluates the effectiveness of a particular sun awareness program, and gives valuable insights into how more effective approaches may be used in the future. In addition to ultraviolet light playing a causal role in cutaneous malignancies, it is known to induce a number of other skin problems. One particularly difficult group of disorders is the photosensitive dermatoses, including solar urticaria. Bissonnette et al. describe an innovative approach to the management of refractory solar urticaria with plasma exchange. In the Grand Rounds section, Strauss et al. review the case of an acute SLE and give an insightful discussion related to bullous eruptions in acutely ill children. The mechanism of ultraviolet-light-induced carcinogenesis involves UV-induced DNA damage. Over the past decade, it has become clear that tumour suppressor genes can regulate these processes. In the Review section, Tron et al. discuss the role of the suppressor gene p53, which is mutated or lost in nonmelanoma skin cancer. P53 is crucial in protecting keratinocytes from the harmful effects of ultraviolet radiation, and in their instructive article, these authors use gene-targeted mutant mice lacking p53 to further evaluate the role in UV-induced DNA damage. With the warm weather upon us, we are spending more time in the outdoors and, as a result, are exposed to a vast number of environmental onslaughts. These include such things as Rickettsial disease, summarized in our CME section Summary Notes. Furthermore, in a comprehensive review, Dr. Sasseville examines another outdoor threat as he delineates the wide spectrum of plant contact dermatitis. This represents an important and in-depth reference on phytodermatitis. Our specialty, and indeed all of medicine, is being dramatically altered by recent advances in our understanding of disease at a molecular level. This new understanding of disease has led to the potential of modifying gene expression through the use of gene therapy. This is particularly attractive in skin disease, where gene therapy can be delivered quite readily through the skin. This advancement is insightfully discussed in the article by Somani et al., "Gene Therapy and Dermatology," which is both valuable for the cognoscenti and noncognoscenti alike, and serves as an important reference work in this area.

Editorial

Remarkable advances have occurred in wound healing during the past decade in both basic wound biology, as well as applied research into novel treatments of chronic wounds. Newly developed therapies have included the use of growth factors to enhance wound epithelialization, and the use of bioengineered dressings, including skin substitutes. These advances were recently highlighted in the December 1998 JCMS supplement on Wound Care. The lead article in this current issue of JCMS focuses on potential mechanisms to establish quantifiable end points during wound healing, and speculates on the potential relevance to the development of novel therapies. Palenske and Morhenn have found that measurement of skin capacitance is a useful tool in determining endpoints in wound healing. While our ultimate goal in wound healing is to completely re-epithelialize and heal a wound, sometimes interventions are less successful. In evaluating wound healing agents in preclinical or early clinical studies, surrogate markers may be necessary. Skin capacitance may serve as such a marker. In our Point Counterpoint Section, Drs Goldhar and Gratton address the controversial issue of whether dermatologists should promote treatment products. There are strong opinions on both sides of this question, and these two practitioners have concisely addressed the respective sides of this issue. The Grand Rounds Section features an article by Bergman and co-authors in which they describe a case of crusted scabies in association with HTLV-1. Dermatologists are frequently faced with individuals with generalized pruritic eruptions, where scabies is frequently in the differential diagnosis. Indeed, scabies is quite common worldwide. However, crusted scabies, or Norwegian scabies, is much less common, and one clearly has to consider immune deficiencies. This report highlights the association of crusted scabies with immune deficiency. In our CME sections of this issue, we have two important articles. The first, by Dr. Sherri Bale, is a continuation of our Genetic Studies in skin disease research, and the article reviews the area of mapping of hereditary skin disease by focusing on the gene for pseudoxanthoma elasticum. In our day-to- day clinical practice, we frequently discuss the clinical diseases we see in terms of prognosis that is often based on our own individual experience. Evidence based prognostic modelling may provide a very important technique to more accurately assess our patients' outcomes. Drs. Kantor and Margolis review the models and enhance our understanding of these techniques. In this issue of the Journal we introduce a new section of structured book reviews. Two books, Morphologic Diagnosis of Skin Disease and Handbook of Dermatology for Primary Care are reviewed. The structured review provides a concise analysis of these books to allow readers to determine application of these publications to their needs. I hope that each and every one of our readers had a very happy holiday season and I wish you the best for the new year.

Editorial

Epiluminescence microscopy (dermatoscopy) is a technique that was developed to improve the diagnostic abilities of physicians examining pigmented lesions. In experienced hands, this can provide a valuable adjunct to diagnosis of melanoma, but this technique has not been applied to nonmelanocytic skin cancer. Nonmelanocytic skin cancer represents the most common form of all types of cancer, with basal cell carcinoma being the most common cutaneous malignancy. The lead article in this issue of the Journal evaluates the use of epiluminescence microscopy in basal cell carcinomas. The conclusions suggest that diagnostic clinical acumen and biopsy still remain the definitive diagnostic tool. Nonmelanoma skin cancers are a preventable form of cancer, and thus organizations such as the American Academy of Dermatology and the Canadian Dermatology Association have invested significant time and effort in educating the public on the value of sun protection strategies. Sunlight exposure is the environmental exposure most often associated with squamous cell carcinomas of the skin. The article by Bajdik and colleagues uses a case controlled analysis to determine the risk of sunlight exposure for squamous cell carcinoma of the skin of the head and neck and the protective effect, if any, associated with wearing a hat. Their results confirm those of many other studies; that there is a strong association between squamous cell carcinoma and skin type, as well as with sunburn occurring in childhood, and with sunlight exposure during adulthood. However, there was an unusual observation in this study in that there appeared to be an increased risk of squamous cell carcinoma associated with wearing a hat. The authors speculate this may be do to bias or confounding. I would refer you to the Critical Appraisal series of last issue, Volume 3, Number 1 in which Gallagher and Lee review the methods of assessing the incident rates in nonmelanoma skin cancer and highlight some of the difficulties inherent in these studies. Bajdik and coauthors finally conclude that the use of sun protection, particularly with hats, is an unproven means of protecting against squamous cell carcinoma. In spite of this study, I feel that there is sufficient biologic rationale to remain a strong proponent of sun protection including use of hats as part of overall strategies of sun safety. While prevention should be our major goal in nonmelanoma skin cancers, surgery is the mainstay of treatment of established skin cancers. Certain skin cancers, particularly more aggressive basal-cell or squamous cell carcinomas, require MOHS surgery. This surgical technique can result in extensive defects, and repair of these defects is becoming more complex. McGeorge describes a technique, the modified rhombic flap, for optimal closure of some of these defects. In the Basic Science Series, Hosoi and coworkers study whether stress can effect the cutaneous immune response. The above article clearly demonstrates that stress can affect the cutaneous immune response by altering the cell density, intensity and morphology of the major antigen presenting cells in the skin, namely the Langerhans' cells. This gives us further support to the hypothesis that stress can indeed modulate immune function. In our Grand Rounds series, Drs. Searles, Tredget and Lin describe fatal Toxic Epidermal Necrolysis (TEN) associated with vaginal suppositories. Thankfully, TEN is a rare complication; however it can be induced by a number of agents. It is crucial to recognize these changes early since aggressive management with wound care and protection are at present our only therapeutic options.

Editorial

As clinical dermatologists, we are all striving to achieve the highest possible accuracy in our clinical acumen and diagnostic skills. Over the past decade, one relatively simple advance, epiluminescence microscopy with the use of the dermatoscope, has significantly contributed to our diagnostic skills in the detection of benign versus pigmented lesions. In the paper by Kawabata and Tamaki, these authors delineate distinctive dermatoscopic features of acral lentiginous melanoma in situ, and contrast this with melanocytic nevi. The restructuring of healthcare delivery systems by third party payers and governmental programs is impacting on the pattern of our medical practices. In Canada, this has limited access to widespread use of techniques such as Mohs' micrographic surgery. The article by Arlette and colleagues has further supported the well-established studies indicating that Mohs' micrographic surgery for high-risk skin cancers has a dramatic benefit. Healthcare restructuring has also led to a decreased number of trainees in a number of subspecialties, including dermatology. This decrease in manpower has been an impetus to look at alternative forms of care for underserviced areas. Telemedicine, the use of telecommunications technology to provide healthcare services over a distance, has been examined as one attempt at solving this problem. In the Point-Counterpoint articles, we have two distinct views on the future of telemedicine as it applies to dermatology. Over the past decade, there have been dramatic advances in our understanding at a molecular nature of various disease processes. This rapid development has translated into a large number of therapies. Regulatory agencies such as the Food and Drug Administration in the United States, or the Health Protection Branch in Canada, are caught between demands to bring effective therapies to the market in an expedited fashion, and yet establish efficacy and maintain safety of new therapeutic entities. This occurs by a multistaged approval process. During the early phases, exposure is limited in order to accumulate preliminary data on pharmacology and toxicity. In the Critical Appraisal CME series, Muglia and DiGiovanna describe early testing processes in Phase 1 clinical trials. Calciphylaxis is a severe disease associated with calcification of the skin, subcutaneous tissue and potentially, internal organs. While the disease itself is relatively uncommon, the manifestations are quite distinctive. In this issue of the Journal, we have a review of calciphylaxis from Richard Worth, as well as a preamble by Dr. Goodall and a case report by Kalaaji et al. illustrating the consequences of this rare but distinctive entity.

Editorial

I am delighted to inform our readership that we have been accepted for inclusion in EMBASE and MEDLINE, the indexing databases of Excerpta Medica and Index Medicus. You are now able to obtain journal article citations commencing with this issue, by searching EMBASE, and in the near future, by searching MEDLINE. Both databases are also accessible through Silver Platter. With continued concern over the increasing incidence of melanoma, this issue of the Journal focuses on a number of important areas related to this subject. In our our Point-Counterpoint editorials, Drs. Frans Rampen and Martin Weinstock evaluate the pros and cons of mass screening programs in a cogent fashion. An ongoing controversy in the treatment of melanoma has been the margin required for optimal excision of the primary lesion. Over the past several decades, there has been a steady reduction in the extent of the resection of the primary tumour. Drs. Beasley and Cartotto retrospectively analyzed over 100 primary melanomas. Two local recurrences were seen in melanomas less than 2 mm thick, despite a margin of 1.7 and 2.4 cm. While larger studies are needed, this analysis stimulates some question on the true safety of currently accepted margins for 1 to 2 mm thick melanomas. Continuing with the theme of melanoma, our Grand Rounds from the University of British Columbia discusses a patient with melanoma and unilateral vascular tumours. In their article on familial melanomas, Hogg et al. review the area of the genetics of melanoma, with particular reference to the role of cyclin dependent kinase inhibitor gene CDKN2A, on chromosome 9p21 and its potential predictive role in identifying at risk individuals for melanoma. I am pleased to have Dr. Robert Jackson introduce a new section in the Journal, Classics in Dermatology. This series provides a historical perspective on dermatologic disease. While the above article on melanoma illustrates how advances in molecular biology have dramatic impacts on our diagnostic skills, as dermatologists we still greatly value accurate clinical skills. The Classics in Dermatology focuses, from a historical perspective, on the importance of clinical acumen. Advances in dermatologic surgery have dramatically transformed our specialty. Hair transplantation was one of the initial areas of dermatologic surgery and dermatologists have been at the forefront of this field since the landmark studies by Dr. Orentreich in 1959. Since that time there have been major changes in the technique of hair transplantation that have greatly enhanced the outcomes. Drs. Bertucci, Berg, and Pollack update us on current techniques in this field.