The pulsed-dye laser for treatment of cutaneous conditions.

The concept of selective photothermolysis simply states that if one heats target tissue with a laser that is selectively absorbed by that tissue, heat should last sufficiently enough to cause damage to the target tissue, but not so long for the heat to spread to the surrounding tissue. The pulsed-dye laser (PDL) was the first laser to utilize the concept of selective photothermolysis to treat dermatologic conditions. The first application of this concept was directed at treating port-wine stain birthmarks (PWSs). A myriad of conditions that were previously only marginally treated by earlier-generation PDLs could be addressed, increasing by a factor of many thousand the number of potential patients for PDL treatment. Rosacea, scars, red striae, some lower-extremity spider veins, and photodamage could now be easily treated in addition to PWSs, nevus araneuses, cherry hemangioma, and verrucae. Finally, the latest advances in PDL technology have maximized the ability to treat linear vessels such as lower-extremity spider veins, and linear facial vessels associated with rosacea, photodamage or simply heredity, as well as improving the ability to treat diffuse erythema such as the facial redness of rosacea, PWSs, scars and striae with less risk of epidermal damage and hyperpigmentation. Final advances aim to reduce side-effects of both types of vascular lasers while potentially increasing benefits by allowing the delivery of higher fluencies. Cooling the surface of the skin protects melanin pigment while allowing the delivery of light to the dermis to remove unwanted blood vessels and potentially stimulate dermal remodeling.

Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin.

BACKGROUND: Chronic solar irradiation results in both morphologic and functional changes in affected skin. alpha-hydroxy acids, such as glycolic acid, have been shown to improve photodamaged skin. OBJECTIVE: To investigate alterations in collagen gene induction and epidermal and dermal hyaluronic acid production as a result of administered glycolic acid. METHODS: In this study we compared collagen gene expression from skin biopsy specimens, and epidermal and dermal hyaluronic acid immunohistochemical staining between glycolic acid-treated and vehicle-treated skin. Forearm skin was treated with 20% glycolic acid lotion or a lotion vehicle control twice a day for 3 months. RESULTS: Epidermal and dermal hyaluronic acid and collagen gene expression were all increased in glycolic acid-treated skin as compared to vehicle-treated controls. CONCLUSION: Our data suggest that epidermal and dermal remodeling of the extracellular matrix results from glycolic acid treatment. Longer treatment intervals may result in collagen deposition as suggested by the measured increase in mRNA.

Clinical characteristics of 500 consecutive patients presenting for laser removal of lower extremity spider veins.

BACKGROUND: Laser treatment for removal of lower extremity spider veins is emerging as a modality of choice in patients with small spider veins, those who have previously undergone sclerotherapy or vein stripping, and those refusing sclerotherapy. OBJECTIVE: To determine clinical characteristics of patients presenting for laser treatment of leg veins. METHODS: The clinical characteristics of 500 patients presenting for laser treatment of spider veins were evaluated to investigate characteristics leading to their development, and to characterize the type of patients presenting for laser treatment. RESULTS: Patients presenting for treatment range widely in age and have had spider veins for an average of 14 years. Both pregnancy and previous sclerotherapy were factors that contributed to the development or exacerbation of spider veins. CONCLUSION: As laser treatment of spider veins improves, this modality will play an increasing role in the management of lower extremity telangiectasias.

The nitroxide Tempol affords protection against ultraviolet radiation in a transgenic murine fibroblast culture model of cutaneous photoaging.

The generation of reactive oxygen species is among the various mechanisms by which ultraviolet radiation damages skin. Tempol, a superoxide dismutase analogue which readily penetrates cell membranes when administered exogenously, has been shown to provide protection against some forms of oxygen-dependent damage. In this study, we measured the ability of Tempol to protect against ultraviolet A- and ultraviolet B-induced damage, using a previously described transgenic mouse model of cutaneous photoaging. The ability of Tempol to prevent ultraviolet radiation-induced elastin promoter activation was determined in vitro. Tempol provided over 50% protection against ultraviolet B and over 70% protection against ultraviolet A as measured in our in vitro system. These results demonstrate the ability of the superoxide dismutase mimic, Tempol, to protect against ultraviolet induced elastin promoter activation. This compound could be a useful pharmacological agent to prevent cutaneous photoaging.

A pilot investigation to subjectively measure treatment effect and side-effect profile of non-ablative skin remodeling using a 532 nm, 2 ms pulse-duration laser.

BACKGROUND AND OBJECTIVE: Carbon dioxide laser skin resurfacing has become a standard treatment for wrinkles and sun-damaged skin. This ablative treatment, however, is associated with undesirable complications and long recovery times. A growing body of evidence suggests that dermal inflammation and subsequent collagen formation can be stimulated without removal of the epidermis, raising the possibility of effective non-ablative skin remodeling for mild to moderately photodamaged skin. MATERIALS AND METHODS: This preliminary study was performed to evaluate the safety and subject satisfaction of non-ablative skin remodeling using a 532 nm, 2 ms pulse-duration, frequency-doubled Nd:YAG laser. Subjects with mild-to-deep lip wrinkles and mild-moderate acne scarring were treated one half of their lip (wrinkles) or cheek (acne scarring), leaving the other side as an untreated control. Subjects were treated at 3-6 week intervals for an average of three treatments. Subjective assessment of improvement was estimated by subject self-evaluation of the percentage improvement over baseline, and a blinded observer attempted to identify the treated side on physical examination. RESULTS: Subjective assessment revealed an average improvement of 51.4% and 53.6% for upper lip wrinkles and facial acne scarring, respectively. Side effects were limited to transient erythema that resolved over 0.25-2 hours following treatment. CONCLUSIONS: These results demonstrate that non-ablative treatment with the 532 nm, 2 ms pulse-duration Nd:YAG laser results in subjective improvement of rhytides and acne scarring, with a high safety profile.

Treatment of a resistant port-wine stain with the 1.5-msec pulse duration, tunable, pulsed dye laser.

BACKGROUND: Pulsed dye lasers (PDLs) have been developed with relatively long pulse durations in comparison to their predecessors. OBJECTIVE: To demonstrate the efficacy of the 1.5-msec PDL for treating a port-wine stain that was resistant to the 0.5-msec PDL. METHODS: A 31-year-old man with a congenital port-wine stain underwent treatment with the PDL seven times over approximately 2 years. Although it lightened, no areas demonstrated complete clearing. He recently presented for treatment with the 1.5-msec PDL. RESULTS: Initial results of treatment with a 1.5-msec PDL on this patient's port-wine stain demonstrate dramatic clearance of areas previously treated with an identical fluence using a 0.5-msec PDL. CONCLUSION: Longer pulse duration PDLs should be further investigated for the treatment of port-wine stains and may offer improved efficacy over shorter pulse durations.

Laser resurfacing for dermal photoaging.

The skin is a highly organized system composed of resident cells, extracellular matrix, blood vessels, and circulating cells that all work together to maintain cutaneous integrity. Environmental insults, particularly sunlight, act to alter the skin permanently, producing visibly undesirable effects. By wounding the skin or inducing a healing response with minimal wounding, the repair process can be activated to return the skin to a more normal condition. Owing to the complexity of the healing response, even the most well-studied and precise laser system can result in unpredicted results when used to treat photo-damaged skin. Through continued research into the normal functioning of skin, the alterations brought about by chronic photodamage, and the repair process, an integrated approach to treatment of photoaging will evolve. Agents such as alpha-hydroxy acids, retinoids, and growth factors that impact the healing response can be combined with various lasers to optimize improvement of photo-damaged skin, while minimizing the adverse consequences of treatment.

Residual thermal damage resulting from pulsed and scanned resurfacing lasers.

BACKGROUND: Laser resurfacing with rapidly scanned or pulsed carbon dioxide (CO2) lasers has evolved rapidly in recent years. These lasers vaporize small amounts of tissue, while leaving minimal residual thermal damage. OBJECTIVE: To compare the depth of residual thermal damage of two of the most commonly used CO2 laser systems. A rapidly scanned laser was compared to a short-pulse laser system. METHODS: Laser treatment was performed on abdominoplasty specimens prior to removal in four subjects. One, two, or three passes of the two most commonly used energies were administered using each laser system. RESULTS: The depth of thermal damage increased with a greater number of passes with each laser system. Higher energies resulted in greater residual thermal damage with each system after the first pass up to three passes, which was the maximum number of passes administered. Combining the second and third passes, residual thermal damage was remarkably similar when comparing the pulsed and scanned lasers. CONCLUSIONS: The most commonly used energy settings of two lasers with very different modes of action resulted in remarkably similar depths of thermal damage, suggesting that the zone of thermal damage may correlate with clinical outcome. In addition, the zone of thermal damage enlarges as the number of passes increases from one to three.

Treatment of spider veins using a 10 millisecond pulse-duration frequency-doubled neodymium YAG laser.

BACKGROUND: The pulsed dye laser has been the standard for treating vascular lesions. Although quite effective for treating facial vessels and port-wine stains, spider veins of the lower extremities are more difficult to treat. Recent studies have shown that lasers with longer pulse durations are more effective at treating spider veins. A new long-pulse frequency-doubled Neodymium:YAG laser has been developed with a 10-ms pulse duration and sufficient energy to enable treatment with a 3- or 4-mm diameter treatment beam. OBJECTIVE: To determine the effectiveness of the long pulse Neodymium:YAG laser for treating spider veins of the lower extremities. METHODS: Spider veins less than 0.75 mm in diameter on the legs of 15 female volunteers were treated in 1 or 2 areas. Treatments were administered through a water-cooled chill tip using the frequency-doubled Neodymium:YAG laser with a 10-ms pulse duration. A dose of 16 J/cm2 was administered, completing 3 passes over each visible vein during each session, for a total of 2 sessions administered 6 weeks apart. Photographs of treatment areas were digitally analyzed for degree of vessel clearance. RESULTS: Computer-based image analysis revealed clearing of over 75% of veins following 2 treatments with 16 J/cm2. Side effects were minimal, and the treatments were well tolerated. CONCLUSIONS: The 532 nm, 10 ms pulse duration, frequency-doubled Neodymium:YAG laser is safe and effective for treating spider veins of the lower extremities less than 0.75 mm in diameter, in patients with Fitzpatrick skin Types I-III.

Treatment of spider veins with the 595 nm pulsed-dye laser.

BACKGROUND: Previous attempts to treat spider veins with the conventional 585 nm pulsed-dye laser with a 0.5-ms pulse duration have been relatively ineffective. Recently, a new pulsed-dye laser that is tunable from 585 to 600 nm with a pulse duration 3 times longer than previously available lasers has preliminarily been shown to be effective for treatment of spider veins. OBJECTIVE: Our purpose was to evaluate the effectiveness of multiple treatments with the tunable long-pulse dye laser in treatment of spider veins of the lower extremity. METHODS: Ten female volunteers were treated in two separate areas containing blue or red linear spider veins less than 1.5 mm in diameter. Treatments were administered with the pulsed-dye laser with a 1.5-ms pulse duration and 595-nm light at fluences of 15 and 20 J/cm2, and each subject received a total of 3 treatments at each site, administered at 6-week intervals. Photographs were taken before and 6 weeks after the last treatment. RESULTS: Computer-based image analysis showed clearing of more than three fourths of veins after 3 treatments with 15 or 20 J/cm2. Side effects were minimal and the treatments were well tolerated. CONCLUSION: The 595 nm, 1.5 ms pulse duration, pulsed-dye laser is safe and effective for treating blue or red spider veins of the lower extremities less than 1.5 mm in diameter in nontanned patients with Fitzpatrick skin types I and II. Multiple treatments improve on the results obtained after a single treatment.

Molecular mechanisms of cutaneous aging: connective tissue alterations in the dermis.

Cutaneous aging is a complex biological phenomenon consisting of two distinct components, (a) the intrinsic, genetically determined degenerative aging processes and (b) extrinsic aging due to exposure to the environment, also known as "photoaging". These two processes are superimposed in the sun-exposed areas of skin, with profound effects on the biology of cellular and structural elements of the skin. This overview summarizes our current understanding of the mechanisms of innate versus extrinsic aging with emphasis on connective tissue alterations, primarily collagen and the elastic fiber network. We also introduce a novel transgenic mouse model, expressing a human elastin promoter-reporter gene construct, suitable for studies on biology and preventive pharmacology of the cutaneous aging.

A novel in vivo model for evaluating agents that protect against ultraviolet A-induced photoaging.

Increasing evidence demonstrates that ultraviolet A radiation (UVA) contributes to photoaging, which results in the accumulation of massive amounts of abnormal elastic material in the dermis of photoaged skin. To study UVA-induced photoaging in an in vivo system, we utilized a line of transgenic mice containing the human elastin promoter linked to a chloramphenicol acetyl transferase reporter gene. Our prior work demonstrates promoter activation in response to ultraviolet B radiation (UVB), UVA, and psoralen plus ultraviolet A radiation in the skin of these mice. The addition of psoralen (8-MOP) prior to administration of UVA results in substantial increases in promoter activation, as compared with UVA alone. To demonstrate the utility of these mice as a model of UVA-induced photodamage, we administered four lotions to the skin of our transgenic mice that included: a sunscreen containing octyl methoxycinnamate and benzophenone-3 with a sun protection factor (SPF) of 15, the UVA filter butyl methoxydibenzoylmethane, the SPF 15 sunscreen and the UVA filter together, and the lotion vehicle alone. Following sunscreen administration, mice received a single psoralen plus ultraviolet A radiation treatment. All sunscreens decreased chloramphenicol acetyl transferase activity with the SPF 15 sunscreen, the UVA filter, and the combination SPF 15 sunscreen and UVA filter, resulting in increasing degrees of protection against psoralen plus ultraviolet A radiation. These results demonstrate that this model functions as a rapid and sensitive model of UVA photodamage for the identification and comparison of compounds that protect against UVA-induced photoaging.

Evaluation of sunscreens with various sun protection factors in a new transgenic mouse model of cutaneous photoaging that measures elastin promoter activation.

BACKGROUND: Long-term sun exposure can cause major alterations in the papillary dermis, resulting in the deposition of massive amounts of abnormal elastic material, termed solar elastosis. Previous work has demonstrated that this type of photodamage is accompanied by an increase in elastin and fibrillin messenger RNAs and elastin promoter activity. OBJECTIVE: Our purpose was to develop a rapid and sensitive in vivo method for evaluating compounds offering protection against cutaneous photodamage. METHODS: Using a line of transgenic mice that expresses the human elastin promoter linked to a chloramphenicol acetyltransferase reporter gene, we applied sunscreens with various sun protection factors to 5-day-old mice followed by 30 minimal erythema doses of solar simulating radiation for three consecutive days. RESULTS: Solar simulating radiation alone resulted in a fivefold increase in elastin promoter activity. Sun protection factors of 2, 4, 8, and 15 yielded a reduction in promoter activity by 2.8%, 42.5%, 58.1%, and 70.3%, respectively. CONCLUSION: These results confirm the use of this system as a rapid and sensitive in vivo model for evaluating compounds that protect against photodamage.

Citric acid increases viable epidermal thickness and glycosaminoglycan content of sun-damaged 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 dermal 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 content. 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. CONCLUSIONS: 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.

Chronic sun exposure alters both the content and distribution of dermal glycosaminoglycans.

Chronic sun exposure leads to structural and functional alterations in exposed skin. Photoageing is a process distinct from the changes taking place due to chronological ageing. Unique alterations in the dermal extracellular matrix occur as a result of photoageing and are responsible for many of these physiological changes taking place in sun-damaged skin. Accompanying the deposition of abnormal elastic tissue, or solar elastosis, are significant alterations in dermal glycosaminoglycans (GAGs). Accumulation of GAGs as a result of photoageing, as demonstrated in both humans and animal models of photoageing, seems almost paradoxical in view of the large amounts of GAGs present in the skin of newborns, making their skin well hydrated and supple, in sharp contrast to the weathered appearance of photoaged skin. We investigate the relative GAG content of photoaged skin using immunoperoxidase stains specific for hyaluronic acid and chondroitin sulphate, and determine the location of these GAGs using confocal laser scanning microscopy. Our results demonstrate significant increases in GAG staining in sun-damaged vs. sun-protected skin from the same individuals, as measured by computer-based image analysis. Furthermore, confocal laser scanning microscopy reveals that the increased dermal GAGs in sun-damaged skin are deposited on the elastotic material of the superficial dermis of photodamaged skin, and not between collagen and elastic fibres as in normal skin. The abnormal location of GAGs on these fibres may explain the apparent paradoxical weathered appearance of photodamaged skin despite increased GAGs.

8-methoxypsoralen and ultraviolet a radiation activate the human elastin promoter in transgenic mice: in vivo and in vitro evidence for gene induction.

Treatment of skin diseases with the combination of 8-methoxypsoralen and ultraviolet A radiation (PUVA) results in clinical alterations in treated skin that resemble those observed in chronically photodamaged skin. The PUVA-treated patients develop nonmelanoma skin cancers, pigmentary alterations and wrinkling characteristic of sun-induced changes. The major alteration in the dermis of sun-damaged skin is the deposition of abnormal elastic fibers, termed solar elastosis. Up-regulation of elastin promoter activity in dermal fibroblasts explains the excess elastic tissue but not the reason for the aberrant morphology of the elastotic material. In order to study photoaging in an experimental system, we utilized a transgenic mouse line that expresses the human elastin promoter/chloramphenicol acetyltransferase construct in a tissue-specific and developmentally regulated manner. Although UVB radiation has been demonstrated to increase promoter activity in vitro, UVA fails to demonstrate a similar effect at the doses utilized. In this study, we demonstrate the ability of PUVA treatment to up-regulate elastin promoter activity both in vitro and in vivo. These data help to explain the development of photoaging in sun-protected PUVA-treated skin. We attribute the up-regulation of elastin promoter activity in response to PUVA to the formation of DNA photoadducts, which do not occur in response to UVA radiation alone.