Lasers in dermatology: Four decades of progress

Transcription

1 CONTINUING MEDICAL EDUCATION Lasers in dermatology: Four decades of progress Elizabeth L. Tanzi, MD, a Jason R. Lupton, MD, b and Tina S. Alster, MD a Washington, DC, and San Diego, California Advances in laser technology have progressed so rapidly during the past decade that successful treatment of many cutaneous concerns and congenital defects, including vascular and pigmented lesions, tattoos, scars, and unwanted hair-can be achieved. The demand for laser surgery has increased substantially by patients and dermatologists alike as a result of the relative ease with which many of these lesions can be removed, combined with a low incidence of adverse postoperative sequelae. Refinements in laser technology and technique have provided patients and practitioners with more therapeutic choices and improved clinical results. In this review, the currently available laser systems with cutaneous applications are outlined, with primary focus placed on recent advancements and modifications in laser technology that have greatly expanded the cutaneous laser surgeon s armamentarium and improved overall treatment efficacy and safety. (J Am Acad Dermatol 2003;49:1-31.) Learning objective: At the completion of this learning activity participants should be able to identify the various types of dermatologic lasers currently available, to list their clinical indications, and to understand the possible side effects of laser treatment. LASER HISTORY The term laser is an acronym for light amplification by the stimulated emission of radiation. Although the first laser was developed by Maiman 1 in 1959 using a ruby crystal to produce red light with a 694-nm wavelength, the concept of stimulated light emission was initially introduced by Einstein 2 in Einstein 2 proposed that a photon of electromagnetic energy could stimulate the emission of another identical photon from atoms or molecules that are in an excited state. In 1963, Dr Leon Goldman pioneered the use of lasers for cutaneous applications by promoting ruby laser treatment for a variety of cutaneous pathologies. 3-5 The development of the argon and carbon dioxide (CO 2 ) lasers soon followed and served as the focus of cutaneous laser research during the next 2 decades. 6 The argon laser produced blue-green 488-/514-nm light that was primarily used to treat benign vascular birthmarks. Although most port-wine stains and hemangiomas could be effectively lightened, there was an From the Washington Institute of Dermatologic Laser Surgery a and Dermatology Associates of San Diego County. b Funding sources: None. Conflict of interest: None identified. Reprint requests: Tina S. Alster, MD, Washington Institute of Dermatologic Laser Surgery, 2311 M St NW, Suite 200, Washington, DC talster@skinlaser.com. Copyright 2003 by the American Academy of Dermatology, Inc /2003/$ doi: /mjd Abbreviations used: APTD: argon-pumped tunable dye CO 2 : carbon dioxide CW: continuous wave Er:YAG: erbium:yag FDA: Food and Drug Administration IPL: intense pulsed light KTP: potassium titanyl phosphate LP: long-pulsed Nd: neodymium PDL: pulsed dye laser PDT: photodynamic therapy QS: quality-switched YAG: yttrium-aluminum-garnet unacceptably high rate of hypertrophic scar formation. 7,8 Emitting infrared light at 10,600 nm, the CO 2 laser was used for tissue vaporization and destruction of various epidermal and dermal lesions. 9 Unfortunately, the continuous-wave (CW) CO 2 laser also yielded high rates of hypertrophic scarring and pigmentary alteration as a result of prolonged tissue exposure to laser energy resulting in excessive thermal injury to the skin. 10,11 Cutaneous laser surgery was revolutionized in the 1980s with the introduction of the theory of selective photothermolysis by Anderson and Parrish. 12 Application of their theory effects specific destruction of a target in the skin with minimal unwanted thermal injury. During the past decade, greater understanding of the complex laser-tissue interaction coupled 1

2 2 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 with extensive advances in laser technology have refined cutaneous laser surgery to the point that it is now considered a first-line treatment for many congenital and acquired cutaneous conditions. LASER PRINCIPLES The therapeutic action of laser energy is based on the unique properties of laser light itself and complex laser-tissue interactions Laser light is monochromatic-the emitted light is of a single, discrete wavelength determined by the lasing medium (eg, solid, liquid, gas) in the optical cavity of the laser through which the light passes. At certain wavelengths of light, specific absorption of laser energy can be achieved by distinct cutaneous targets or chromophores such as melanin, hemoglobin, or tattoo ink. The second property, coherence, refers to laser light traveling in phase with respect to both time and space. Lastly, collimation of laser light indicates emission of a narrow, intense beam of light in parallel fashion to achieve its propagation across long distances without light divergence. Thus, collimated light can be focused into small spot sizes allowing for precise tissue destruction. When a laser is used on the skin, the light may be absorbed, reflected, transmitted, or scattered. The first law of photobiology, the Grotthus-Draper law, states that light must be absorbed by tissue for a clinical effect to take place, whereas transmitted or reflected light has no effect. The energy absorbed is measured in joules per square centimeter and is known as the energy density or fluence. The amount of absorption is determined by the chromophore present in the skin and whether a wavelength that corresponds to the absorptive characteristics of that chromophore is used. The principle endogenous chromophores of the skin are water, melanin, and hemoglobin, whereas tattoo ink is an example of an exogenous chromophore. Once laser energy is absorbed in the skin, 3 basic effects are possible: photothermal; photochemical; or photomechanical. Photothermal effects occur when a chromophore absorbs the corresponding wavelength of energy and destruction of the target results from the conversion of absorbed energy into heat. Photochemical effects derive from native or photosensitizerrelated reactions that serve as the basis of photodynamic therapy (PDT). Extremely rapid thermal expansion can lead to acoustic waves and subsequent photomechanical destruction of the absorbing tissue. Although all 3 types of laser effects can occur, photothermal and photomechanical reactions are most commonly observed in current cutaneous laser surgery practice. The depth of penetration of laser energy into the skin is dependent upon absorption and scattering. Although scattering is minimal in the epidermis, it is greater in the dermis as a result of the presence of collagen fibers, which are responsible for the majority of tissue scatter in the skin. The amount of scattering of laser energy is inversely proportional to the wavelength of incident light. In general, the depth of penetration of laser energy increases with wavelength until the midinfrared region of the electromagnetic spectrum. Penetration of 300- to 400-nm wavelengths are limited by strong scattering of the beam whereas scattering is minimal at longer wavelengths ( nm), allowing greater penetration into the skin. However, wavelengths in the midto upper-infrared range of the electromagnetic spectrum penetrate superficially as a result of high absorption by tissue water, the principle chromophore at this range. As such, selective vaporization of water-containing tissue serves as the basis of ablative laser skin resurfacing. The world s understanding of laser-tissue interactions was greatly enhanced with Anderson and Parrish s 12 theory of selective photothermolysis. The theory describes how controlled destruction of a targeted lesion is possible without significant thermal damage to surrounding normal tissue. To achieve selective photothermolysis, a proper wavelength that is absorbed preferentially by the intended tissue target or chromophore is selected. To limit the amount of thermal energy deposited within the skin, the exposure duration of the tissue to light (pulse duration) must be shorter than the chromophore s thermal relaxation time (defined as the time required for the targeted site to cool to one half of its peak temperature immediately after laser irradiation). Finally, the energy density (fluence, measured in joules per square centimeter) delivered by the laser must be sufficient to achieve destruction of the target within the allotted time. Therefore, on the basis of these principles, laser parameters (wavelength, pulse duration, and fluence) can be tailored for specific cutaneous applications to effect maximal target destruction with minimal collateral thermal damage. There are several types of lasers used in cutaneous laser surgery. CW lasers, such as the CW CO 2 and older argon technology, emit a constant beam of light with long exposure durations that can result in nonselective tissue injury. Quasi-CW mode lasers, including the potassium-titanyl-phosphate (KTP), copper vapor, copper bromide, krypton, and argonpumped tunable dye (APTD) lasers, shutter the CW beam into short segments, producing interrupted emissions of constant laser energy. The pulsed laser systems emit high-energy laser light in ultrashort

3 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 3 Table I. Types of lasers and their cutaneous application Laser type Wavelength Cutaneous application Argon (CW) 418/514 nm Vascular lesions Argon-pumped tunable dye (quasi-cw) 577/585 nm Vascular lesions Copper vapor/bromide (quasi-cw) 510/578 nm Pigmented lesions, vascular lesions Potassium-titanyl-phosphate 532 nm Pigmented lesions, vascular lesions Nd: YAG, frequency-doubled 532 nm Pigmented lesions, red/orange/yellow tattoos Pulsed dye 510 nm Pigmented lesions nm Vascular lesions, hypertrophic/keloid scars, striae, verrucae, nonablative dermal remodeling Ruby 694 nm QS Pigmented lesions, blue/black/green tattoos Normal mode Hair removal Alexandrite 755 nm QS Pigmented lesions, blue/black/green tattoos Normal mode Hair removal, leg veins Diode nm Hair removal, leg veins Nd:YAG 1064 nm QS Pigmented lesions, blue/black tattoos Normal mode Hair removal, leg veins, nonablative dermal remodeling Nd:YAG, long-pulsed 1320 nm Nonablative dermal remodeling Diode, long-pulsed 1450 nm Nonablative dermal remodeling, acne Erbium:glass 1540 nm Nonablative dermal remodeling Erbium:YAG (pulsed) 2490 nm Ablative skin resurfacing, epidermal lesions Carbon dioxide (CW) 10,600 nm Actinic cheilitis, verrucae, rhinophyma Carbon dioxide (pulsed) 10,600 nm Ablative skin resurfacing, epidermal/dermal lesions Intense pulsed light source nm Superficial pigmented lesions, vascular lesions, hair removal, nonablative dermal remodeling CW, Continuous-wave; Nd, neodymium; QS, quality-switched; YAG, yttrium-aluminum-garnet. pulse durations with relatively long intervening time periods (0.1-1 second) between each pulse. The laser systems may be either long-pulsed (LP), such as the pulsed dye laser (PDL) with pulse durations ranging from 450 s to 40 milliseconds, or very short-pulsed (5-100 ns), such as the quality-switched (QS) ruby, alexandrite, or neodymium (Nd):yttriumaluminum-garnet (YAG) lasers. The QS lasers have electro-optical shutters that permit release of stored energy within the laser cavity in short high-energy bursts, delivering power outputs as high as 10 9 W. Superpulsed is a term specific toco 2 lasers that are modified to produce very short pulses in a repetitive pattern to reduce the amount of thermal damage that occurs adjacent to the vaporized tissue. Pulsed and quasi-cw systems (as opposed to CW systems) are better adapted for cutaneous laser surgery on the basis of the principles of selective photothermolysis because the thermal relaxation times of most cutaneous chromophores are very short. Because cutaneous lasers have different clinical applications related to their specific wavelengths and pulse durations, the choice of laser should be on the basis of the individual absorption characteristics of the target chromophore (Table I). 17,18 VASCULAR-SPECIFIC LASERS Vascular-specific laser systems target intravascular oxyhemoglobin to effect destruction of various congenital and acquired vascular lesions. The 3 primary absorption peaks for oxyhemoglobin are within the visible range of the electromagnetic spectrum: 418, 542, and 577 nm. Lasers that have been used to treat vascular lesions include the argon ( nm), APTD (577 and 585 nm), KTP (532 nm), krypton (568 nm), copper vapor/bromide (578 nm), PDL ( nm), and Nd:YAG (532 and 1064 nm). The argon laser emits a continuous blue-green beam with wavelength peaks at 488 and 514 nm. Although it has been used in the past for a variety of vascular lesions, several histologic studies have shown that the tissue effect of the argon laser is a result of nonspecific thermal injury resulting from exposure intervals exceeding the thermal relaxation time of the vessels. 7,19-22 Consequently, the risk of scarring and dyspigmentation is increased. 23 For this reason, the argon laser is no longer commonly used to treat vascular lesions. Quasi-CW systems such as the APTD, krypton, 27 copper vapor/bromide, and KTP lasers are CW systems that can be mechanically shut-

4 4 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 Fig 1. Port-wine stain in infant before treatment (A) and resolution after nm pulsed dye laser treatments (B). tered to deliver pulses as short as 20 ns to treat facial telangiectasias. However, because of the rapid delivery and short interval between laser pulses, targeted vessels are not allowed to cool adequately, rendering the tissue reaction similar to that of a CW system. Although the APTD and copper vapor/bromide lasers have been used to treat other cutaneous vascular conditions such as rosacea, poikiloderma of Civatte, and port-wine stains, their quasi-cw nature is often associated with higher incidences of hypertrophic scarring and textural changes than is seen with pulsed laser systems The KTP laser uses a Nd:YAG crystal (1064 nm) to produce light that is passed through a KTP crystal that frequency-doubles the wavelength to 532 nm. Several investigators have reported good results after 532-nm KTP or Nd:YAG treatment of facial telangiectasias The most common side effects include mild erythema, edema, and transient crusting. Because purpura is avoided and erythema is minimized with KTP laser treatment, its use may be preferable to the PDL in patients with facial telangiectasia even though additional treatments may be needed to achieve vessel clearance. 36 Compared with longer wavelength vascular-specific lasers, potential limitations of the 532-nm wavelength include decreased tissue penetration of its shorter wavelength resulting in diminished absorption by deeper vessels. In addition, the 532-nm wavelength is more avidly absorbed by melanin than is the 585- to 595-nm wavelength of a PDL, thereby limiting its use for patients with darker skin types. The flashlamp-pumped PDL was the first laser specifically developed for treatment of vascular lesions based on the principles of selective photothermolysis. 12 Although original investigators used a 577-nm system, the wavelength was later modified to 585 nm to effect deeper tissue penetration while maintaining vascular specificity Although PDL use was initially recommended for treatment of lesions in pale skin, 55 recent reports have shown that darker skin tones can be safely and effectively treated. 56,57 In addition, dynamic cooling devices were incorporated in most pulsed dye systems to reduce intraoperative discomfort and postoperative occurrence of epidermal damage or pigmentary change With a pulse duration (450 s) shorter than the thermal relaxation time of small- to medium-sized blood vessels (1 millisecond), the PDL conforms to the principles of selective photothermolysis leading to selective vascular injury without unwanted thermal damage to the surrounding tissue. The PDL has revolutionized the treatment of many vascular lesions and is considered the laser of choice for most benign congenital and acquired vascular lesions because of its superior clinical efficacy and low risk profile. 17,18,39,61 This laser has been used to successfully treat a variety of vascular lesions such as port-wine stains, 40,42,43,45,47-60 facial telangiectases, hemangiomas, pyogenic granulomas, 72 Kaposi s sarcoma, 73 and poikiloderma of Civatte. 74,75 Other conditions successfully treated with PDL irradiation include hypertrophic and keloid scars, striae distensae, 79,80 warts, angiofibromas, 84 lymphangiomas, 85 Goltz s syndrome, 86 inflammatory linear verrucous epidermal nevus, 87 atrophoderma vermiculata, 88 multiple eccrine hidrocystoma, 89 lupus pernio, 90 lupus erythematosis, 91 morphea, 92 granuloma faciale, 93 necrobiosis lipoidica diabeticorum, 94,95 elastosis perforans serpiginosa, 96 sebaceous gland hyperplasia, 97,98 and molluscum contagiosum 99,100 (Figs 1 and 2). PDL treatments are performed with fluences ranging from 3 to 10 J/cm 2 and a spot size of 2 to 10 mm with no more than 10% pulse overlap to minimize the risk of extensive thermal injury. In general, lower fluences are used in children and delicate tissue areas (infraorbital skin) and larger spot sizes are required for increased penetration of larger caliber, deeper vessels (perinasal creases, leg veins). Areas

5 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 5 Fig 2. Facial telangiectases before (A) and after (B) improvement with 2 pulsed dye laser treatments. Fig 3. A, Poikiloderma on neck and chest before treatment. B, Improvement seen after series of intense pulsed light treatments. with a higher risk of textural change, such as the neck or anterior chest, necessitate a 10% to 20% reduction in fluence. Additional treatment sessions are generally needed for lesions in the centrofacial and V2 dermatomal areas presumably as a result of thicker skin and increased pilosebaceous units in these areas. 50 Potential disadvantages of treatment with the PDL include postoperative purpura that may last 1 to 2 weeks and transient dyspigmentation. Vesiculation, crusting, textural change, and scarring are rarely seen. 39 More recently, PDLs with longer wavelengths (585, 590, 595, and 600 nm) and extended pulse durations ( milliseconds) have been developed These laser systems are able to effect relatively deep tissue penetration using large spot sizes and fluences ranging from 5 to 15 J/cm 2 while maintaining vascular specificity. 105 Port-wine stains, hemangiomas, and facial telangiectasia respond as well as they do with the traditional PDL; however, less profound purpura is produced The intense pulsed light (IPL) source emits noncoherent light within the 500- to 1200-nm portion of the electromagnetic spectrum. It has been used to successfully treat a variety of vascular lesions including facial telangiectasias, port-wine stains, and hemangiomas (Fig 3). Filters are used to eliminate shorter wavelengths, thereby concentrating light energy so that improved dermal penetration is achieved. Light is delivered as a series of single-, double-, or triple-pulse sequences with pulse durations of 2 to 25 milliseconds and delays between pulses ranging from 10 to 500 milliseconds. Because shorter wavelength light interacts more readily with epidermal melanin, the lower cut-off filters should only be used in patients with fair complexions. With longer pulse durations, the IPL source can slowly heat more deeply located vessels, thus, improving treatment efficacy and decreasing the risk of postoperative purpura and hyperpigmentation. Larger caliber vessels respond well to these treatments because high-energy densities can be delivered by trains of pulses with relatively long delays (40-60 milliseconds) between each pulse. This has been

6 6 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 termed additive heating and accounts for the system s efficiency in treating deeper vessels within thick port-wine stains and hemangiomas. Although sclerotherapy remains the cornerstone of leg vein treatment by most practitioners, it can be associated with side effects including ulceration, allergic reactions, and telangiectatic matting. 111,112 As such, interest in the laser treatment of leg veins remains high with practitioners and patients alike. In general, the treatment of leg telangiectasia with lasers and light-based sources has not been as successful as treatment of facial telangiectasia; however, recent advances and refinements in technology have shown promise for leg vein treatment. Early attempts to eradicate leg veins with the argon, APTD, or CO 2 laser were largely unsuccessful. 113,114 Despite their ability to treat facial telangiectasia, the KTP and short-pdls are less effective in the treatment of leg veins. 36, In contrast, the longer PDLs have proven more efficacious than their short pulsed counterparts by providing pulse durations that more closely approximate the thermal relaxation time of larger leg vessels. 118,119 The IPL source has also been used successfully for the treatment of leg telangiectasia by some investigators, 120,121 whereas others failed to confirm these findings. 122 Most recently, on the basis of a small but significant absorption peak of hemoglobin in the nearinfrared portion of the electromagnetic spectrum, even longer wavelength pulsed lasers have been used to treat moderately deep, larger caliber spider and reticular veins. Because high fluences are often necessary to adequately damage the vessel, concomitant cooling systems are used to limit unwanted collateral thermal injury. Several clinical trials have demonstrated encouraging results after LP alexandrite 123,124 or 800-nm diode 125,126 laser treatment of lower extremity small- to medium-sized veins. In addition, Nd:YAG lasers with pulse durations of up to 200 milliseconds have been developed to treat leg veins as large as 3 mm in diameter Weiss and Weiss 128 reported up to 75% resolution of leg telangiectasias 3 months after 1064-nm Nd:YAG laser treatment with fluences ranging from 130 to 140 J/cm 2 and a pulse duration of 16 milliseconds. In a comparison study between LP 1064-nm Nd:YAG laser treatment and sclerotherapy of lower extremity telangiectasias, Lupton et al 129 demonstrated equivocal clinical results from the 2 treatment modalities. They concluded that although recent advances in technology have improved the results of laser leg vein treatment, sclerotherapy continues to offer superior clinical effects in the majority of patients, thereby rendering laser treatment only to those with severe needle phobia, mat telangiectasias, sclerosant allergy, or untoward side effects after prior sclerotherapy. LASER TREATMENT FOR HYPERTROPHIC SCARS, KELOIDS, AND STRIAE Hypertrophic scars and keloids develop as an abnormal response to cutaneous injury and are characterized by an overabundance of collagen. By definition, keloids project beyond the boundaries of the original injury and do not regress with time, whereas hypertrophic scars are raised, firm scars limited to the confines of the original injury and have a tendency toward spontaneous regression. 130 These types of scars are notoriously difficult to eradicate and have a high rate of recurrence after traditional treatments including surgical excision, dermabrasion, radiation, and intralesional therapy. 131,132 Progress in laser technology and refinements in technique have made laser therapy one of the most advantageous modalities for the treatment of hypertrophic scars and keloids. In the 1980s, controversy existed among laser surgeons regarding the benefits of keloid vaporization with various CW lasers (CO 2, argon, Nd:YAG). Ultimately, none of the preliminary studies with the aforementioned laser systems demonstrated an advantage over scalpel excision, as laser vaporization produced unacceptably high rates of scar recurrence and other untoward side effects including pain, atrophy, and dyspigmentation During the past decade, however, multiple studies 76-79, using a 585-nm PDL have demonstrated striking improvements in scar erythema, pliability, bulk, and dysesthesia. In 1995, Alster and Williams 77 performed the first controlled study of the response of hypertrophic scars and keloids to the PDL on median sternotomy scars. Significant improvement in scar surface texture, erythema, height, flexibility, and symptomatology were reported in all treated areas with minimal side effects and treatment discomfort. These observations in clinical improvement were substantiated by skin surface textural analyses, erythema reflectance spectrometery readings, scar height measurements, and pliability scores. Significant clinical improvement in hypertrophic scars is usually noted after 1 or 2 PDL treatments; however, a greater response may be achieved after multiple treatment sessions using lower energy densities 144 (Fig 4). Keloids and very thick or proliferative hypertrophic scars may require additional laser treatments or the simultaneous use of intralesional corticosteroid or 5-fluorouracil injections to enhance clinical results. 146,147 The most common adverse effects of treatment with the PDL include cutaneous purpura lasting several days and

7 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 7 Fig 4. Hypertrophic facial scars before (A) and after (B) improved scar color, height, and pliability after two 585-nm pulsed dye laser treatments. transient hyperpigmentation or hypopigmentation that resolves spontaneously over several weeks. Given its use and low side-effect profile, the PDL has become a first-line treatment for hypertrophic scars and keloids. Initially, the PDL was used to target the vascular component of scars to reduce or eliminate persistent erythema. Scar flattening and improved pliability proved to be an incidental finding. Currently, there is no consensus on the mechanism by which the PDL achieves these additional clinical effects. Hypotheses have included histamine effects on dermal collagen, 77 decreased cellular activity resulting from laser-induced tissue hypoxia, 143 disulfide bond disruption through tissue heating, 143 and collagenolysis by laser stimulation of cytokine stimulation. 144 Striae distensae appear as linear bands of atrophic or wrinkled skin that develop as a result of rapid weight fluctuation or during increased glucocorticoid production such as seen with Cushing s syndrome, puberty, or exogenous steroid use. 148,149 Histologically, dermal inflammation and dilated capillaries mark the initial presentation of striae. 150 As a result, striae initially appear slightly pink and become darker (reddish-purple) with time. Later in their course, striae take on scarlike characteristics, appearing hypopigmented and fibrotic. Striae represent a common problem for which satisfactory treatments are limited. On the basis of the success of the PDL in treating hypertrophic scars, several investigators 80, evaluated its use for the treatment of striae. In a paired comparison trial, McDaniel et al 80 reported improvement in skin surface appearance and increased dermal elastin in 39 striae after PDL irradiation. The optimal treatment fluence was determined to be 3 J/cm 2 using a 10-mm spot size. Others have also described significant clinical improvement of early erythematous striae using lowfluence PDL irradiation, 79 whereas only minimal to modest effects has been observed in mature striae. 152,153 PDL treatment must be used with caution in patients with more heavily pigmented skin as a result of possible epidermal melanin absorption of the 585-nm wavelength and the consequent risk of pigmentary alteration. More recently, PDLs capable of longer pulse durations enable treatment of scars with a lower risk of purpura and dyspigmentation; however, the efficacy of these systems for the treatment of striae has yet to be determined. In the future, nonablative laser systems with wavelengths within the midinfrared range of the electromagnetic spectrum may prove useful in the treatment of striae. These systems are typically used in conjunction with epidermal cooling devices to provide selective dermal heating without epidermal injury. Nonablative 1320-nm Nd:YAG and 1450-nm diode lasers have been shown to improve atrophic scars, 154 and would similarly be expected to yield positive effects on striae. Although there have been anecdotal reports of improvement in striae after nonablative laser treatment, published studies documenting clinical effect are lacking. PIGMENT-SPECIFIC LASERS Melanin-specific, high-energy, QS laser systems can successfully lighten or eradicate a variety of benign epidermal and dermal pigmented lesions and tattoos with minimal risk of untoward effects. Epidermal lesions (solar lentigines, ephelides, caféau-lait macules, and seborrheic keratoses); dermal and mixed epidermal/dermal lesions (melanocytic nevi, blue nevi, nevi of Ota/Ito, infraorbital hyperpigmentation, drug-induced hyperpigmentation, Becker s nevi, and nevus spilus); and amateur, pro-

8 8 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 fessional, and traumatic tattoos have all been shown to be amenable to laser treatment Using Anderson and Parrish s 12 principles of selective photothermolysis, QS laser systems replaced earlier CW lasers as a result of their ability to induce thermal necrosis that remains largely confined to the melanosomes with limited spread of coagulative necrosis to surrounding structures Although melanin has a wide absorption spectrum, treatment efficacy decreases as the wavelength of light increases Longer wavelength (near-infrared range) laser systems are advocated for some lesions, however, as increased tissue penetration permits better treatment of deeper dermal pigment. 164 Although benign pigmented lesions are usually the result of excessive melanin deposition in melanosomes, tattoos occur from the dermal implantation of ink particles and other materials that variably respond to laser treatment depending on their color and individual absorptive characteristics. Laser systems used for eradication of benign pigmented lesions and tattoos have included not only CW and quasi-cw lasers (argon, CO 2, copper vapor, krypton, KTP), but also the 510-nm PDL and various QS systems (532- and 1064-nm Nd:YAG, 694-nm ruby, 755-nm alexandrite). LP laser systems (ruby, alexandrite, 810-nm diode, and 1064-nm Nd:YAG) have also been used to better target some dermal pigmented lesions. The continuous and quasi-cw laser systems that have been used for pigment and tattoo destruction include the 488- and 514-nm argon, nm copper vapor, nm krypton, nm KTP, 168 and 10,600-nm CO lasers. These lasers typically emit light with pulse durations longer than the thermal relaxation time of a melanosome (1 millisecond) and, therefore, may result in scarring or textural irregularities as a result of excessive thermal damage of surrounding tissue during laser irradiation. 156,160,161 Use of CW lasers is, thus, generally reserved for removal of epidermal lesions because treatment of deeper, dermal lesions is often associated with significant tissue scarring. Treatment with a CW laser removes pigment by denuding the epidermis and destruction of the dermoepidermal junction. Potential postoperative sequelae include persistent erythema, pigmentary alteration, and textural irregularities. The pigmented lesion dye laser emits light with a 510-nm wavelength and a pulse duration of 300 ns, thus enabling it to target superficially located melanosomes. Although no longer commercially available, this laser has been used to eradicate epidermal pigmented lesions such as ephelides; lentigines; café-au-lait macules; and red, yellow, and orange tattoos with great success Treatment with the pigmented lesion dye laser produces an ash-gray discoloration of the skin with occasional purpura as a result of concomitant laser absorption by tissue oxyhemoglobin. A fine crust forms over the lasertreated areas and peels off after 1 week. Pigmented lesions often require 2 or more treatments at bimonthly intervals to effect their complete removal. The first QS laser system developed was the ruby, emitting visible red light with a wavelength of 694 nm, a pulse duration of 28 to 50 ns, and a repetition rate of 1 Hz. The ruby laser can effectively target a variety of epidermal and dermal pigmented lesions and tattoos The 694-nm light wavelength is so well-absorbed by melanin that caution must be taken when using this system to treat darker-skinned individuals as permanent hypopigmentation and depigmentation have been reported after treatment. 210,212,213 The 6.5-mm spot size handpiece is used at fluences ranging from 4.0 to 6.0 J/cm 2 depending on the lesion type, patient skin color, and observed tissue reaction to irradiation. 155,157,159 The QS alexandrite laser emits light at a wavelength of 755 nm, pulse duration of 50 to 100 ns, and repetition rate of 1 to 15 Hz (spot size 2-4 mm). Its longer pulse duration accounts for the alexandrite producing less tissue splatter during laser irradiation. In addition, its longer wavelength permits deeper tissue penetration , Initial treatment fluences of 5.0 to 7.0 J/cm 2 are used depending on the spot size, patient s skin phototype, and the specific area being treated. The clinical end point of treatment is epidermal whitening without tissue splatter (Fig 5). The Nd:YAG laser emits 1064-nm light, but it can be frequency-doubled using a potassium diphosphate crystal to produce visible green light with a wavelength of 532 nm. Most QS Nd:YAG laser systems have pulse durations ranging 10 to 20 ns, spot sizes of 1.5 to 4 mm, and repetition rates of 1 to 10 Hz. The longer 1064-nm wavelength has a lower melanin absorption coefficient, but can penetrate the skin more deeply so that dermal lesions are more effectively targeted Treatment fluences of 3.0 to 6.0 J/cm 2 using a 4- to 8-mm spot size handpiece are used to effect immediate tissue whitening with occasional pinpoint bleeding. The use of smaller spot sizes increases tissue splatter and risk of crusting that may take several weeks to fully resolve. LP (millisecond range) ruby, alexandrite, diode, and Nd:YAG lasers were originally developed in an attempt to effect permanent hair removal. The millisecond-range pulse duration of these lasers were necessary to adequately heat the relatively large hair follicle; but a variety of benign pigmented lesions

9 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 9 Fig 5. Solar lentigines before (A) and after (B) improvement seen after 2 quality-switched 755-nm alexandrite laser treatments. such as congenital melanocytic nevi and Becker s nevi (especially those with terminal hair growth) have been shown to be particularly amenable to treatment with these systems Several reports document the effectiveness of an IPL source in the treatment of benign pigmented lesions including ephelides and solar lentigines with more than 75% lesional clearance after a series of treatments. 244,245 IPL therapy of lesions with evidence of deep pigment such as mixed melasma and Becker s nevi have been less successful. 246 Traditionally destructive methods of tattoo removal including surgical excision, dermabrasion, cryosurgery, and chemical peels have all produced disappointing cosmetic results with unacceptably high rates of scarring. 247 Although excitement was initially generated with the early use of CW lasers for tattoo removal, these also proved to be too destructive With the development of QS laser technology, however, tattoo removal has become much safer and more reliable For optimal pigment removal, the choice of laser is based on the absorption spectra of the ink colors present within the tattoo. 248 Black pigments absorb throughout the red and infrared spectrum and can, therefore, be treated with QS ruby (694 nm), QS alexandrite (755 nm), or QS Nd:YAG (1064 nm) lasers. Blue and green inks are targeted in the 600- to 800-nm range, thus making the ruby or alexandrite laser the most appropriate choice. Red, orange, and yellow tattoo inks are specifically destroyed by green light, rendering the 532-nm QS Nd:YAG laser or 510-nm PDL the optimal treatment for these colors (Fig 6, A and B). In general, professional tattoos are more difficult to treat than are amateur tattoos as a result of the heavy concentration of their organometallic ink particles placed deeply in the dermis. Thus, several more treatments (average 8-12) are needed to effect near-complete professional tattoo elimination, compared with the average 4 to 6 treatments typically necessary to rid the superficially and sparsely placed carbon-based inks in amateur tattoos. 217 Similar to amateur tattoos, medicinal tattoos (radiation port markings) and traumatic tattoos from chemical/gunpowder explosions or asphalt abrasions are also amenable to treatment by the QS laser systems and typically clear within a few laser treatments. 184,216,232,249 Removal of flesh-tone, white, or rust-colored cosmetic (lip liner, eyeliner) tattoos is also possible using QS laser systems. The process of cosmetic ink removal may be more difficult as a result of the risk of immediate pigment darkening on laser irradiation. 250 Most cosmetic tattoos contain iron (or titanium) oxide inks that, on QS laser irradiation, are reduced from ferric oxide to the ferrous oxide form; the latter being black and insoluble. Although this unfortunate reaction pattern can be improved with continued pigment-specific QS laser treatments or vaporization with a CO 2 laser, the darkened color may be permanent. 251,252 The most common side effect of laser-assisted tattoo removal is transient pigmentary alteration. Hypopigmentation is more frequently seen after QS ruby laser irradiation and, therefore, should not be used when treating patients with darker skin. Hyperpigmentation is usually mild and transient, and can be treated with topical bleaching agents. A more serious complication of treatment involves a systemic allergic or localized granulomatous tissue reaction to tattoo ink particle antigens. 253 Localized atrophic scars have also been reported in traumatic tattoos on laser ignition of residual explosive particles. 254 In summary, the majority of benign epidermal and dermal pigmented lesions and tattoos respond quite readily to high-energy QS red and infrared lasers. Superficially located pigment is best treated with shorter wavelength lasers (eg, 510-nm PDL, 532-nm QS Nd:YAG). For removal of deeper pigment, longer wavelength lasers that penetrate to

10 10 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 Fig 6. Multicolored professional tattoo before (A) and after (B) lesional clearance after 9 treatments with quality-switched 755-nm alexandrite laser (blue/black inks) and 4 treatments with frequency-doubled 532-nm neodymium:yttrium-aluminum-garnet laser (yellow/red inks). greater tissue depths are needed (eg, 694-nm ruby, 755-nm alexandrite, 1064-nm QS Nd:YAG). Complete removal of unwanted cutaneous pigment and tattoos may not always be possible, however, even after multiple laser treatment sessions. Some dermal pigment may simply be too deep to reach or repigmentation of a treated area may result from stimulation of residual melanocytes in the adnexal or adjacent epithelium. The most challenging aspect regarding laser treatment of pigmented lesions is determining when a lesion has atypical features or potential for malignant transformation. This issue remains controversial and without definitive answers. Any pigmented lesion with atypical features should be biopsied to rule out the possibility of malignant degeneration before laser treatment is considered. Thus far, there have been no reports of malignant degeneration occurring within a benign pigmented lesion after laser irradiation; however, it is possible that recurrence of a laser-treated lentigo maligna can occur, thereby necessitating long-term follow-up of such patients. 255 When patients are properly selected and standard treatment parameters followed, removal of most pigmented lesions and tattoos is possible with excellent cosmetic results and minimal risk of adverse sequelae. PHOTOEPILATION Excessive hair growth in cosmetically undesirable locations may be the result of a variety of factors, ranging from hereditable causes and endocrine disease to exogenous drug therapy. Temporary hair removal methods such a shaving, tweezing, waxing, and chemical depilatories may cause irritation and are only partially effective. 256,257 Until recently, electrolysis was the only method for long-lasting hair removal; however, it is associated with as much as 50% hair regrowth and the potential for scarring and dyspigmentation. 258,259 Since the first Food and Drug Administration (FDA)-approved hair removal laser system in 1996, advancements in laser and light-based technology have effected safe long-term hair reduction. Lasers and IPL sources with wavelengths in the red or near-infrared region (600 to 1200 nm) are most often used for hair removal because they effectively target melanin within the hair shaft, hair follicle epithelium, and heavily pigmented matrix Furthermore, devices operating within this region of the electromagnetic spectrum can penetrate to the appropriate depth of the dermis because they are within an optical window in which selective absorption by melanin is coupled with deep penetration of laser energy. 264 Although follicular melanin is the primary target for photoepilation, its presence within the epidermis represents a competing site for laser energy absorption. Active cooling of the skin helps to minimize unwanted epidermal injury a critical factor when treating patients with darker skin phototypes. Ice, refrigerated gels, cryogenic sprays, or contact cooling devices built into the laser handpiece can limit

11 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 11 heat accumulation in the epidermis, thereby decreasing the discomfort associated with treatment. 265,266 Moreover, epidermal cooling permits delivery of maximal fluences to achieve effective photoepilation. In addition to wavelength, pulse duration serves as an important parameter for effective photoepilation. 267,268 Photothermal laser-tissue interactions that occur within the melanin-rich matrix and hair shaft heat the surrounding follicle. To limit the thermal damage, the pulse duration should be shorter or equal to the thermal relaxation time of the hair follicle-estimated to be approximately 10 to 100 milliseconds, depending on the diameter of the follicle. 12,262,267 Thus, most systems currently used for long-term hair reduction provide pulse durations in the millisecond domain. However, other components of the follicular unit, such as follicular stem cells, do not contain significant amounts of melanin and may be located some distance from the targeted pigmented structures. Therefore, it has been proposed that pulse durations longer than the thermal relaxation time of the shaft (which allows conduction of laser energy with subsequent thermal injury through the entire follicular unit) may be more appropriate to induce permanent hair reduction. 268 Recently, the concept of thermal damage time and an extended theory of selective photothermolysis have been proposed for nonuniformly pigmented targets, such as the hair follicle. 268,269 In contrast to the original theory of selective photothermolysis, the extended theory proposes that the target be destroyed by heat diffusion from the pigmented area to the target rather than by direct heating. Preliminary studies demonstrate superpulse heating of the follicle with a pulse duration longer than 100 milliseconds has resulted in long-term hair reduction without adverse sequelae. 270,271 It is clear that the field of laser-assisted hair removal continues to evolve and that laser-follicle interactions have yet to be fully elucidated. Ongoing research will help to define optimum treatment parameters, intervals, and outcomes. Currently, there are several laser and IPL systems that deliver energy at the appropriate wavelength and pulse duration for absorption by follicular pigment. Laser systems and IPL sources currently approved by the FDA for the reduction of hair include the LP ruby (694 nm), LP alexandrite (755 nm), pulsed diode (800 nm), QS and LP Nd:YAG (1064 nm) lasers and IPL ( nm) sources. The first controlled clinical study using the LP ruby laser for hair removal was reported by Grossman et al. 272 A total of 13 patients with dark hair were treated with a 6-mm spot size at fluences ranging from 20 to 60 J/cm 2 on the back or thighs. Biopsy specimens obtained immediately after treatment demonstrated selective thermal damage to pigmented hair follicles. All patients had delayed hair growth at 1- and 3-month follow-up evaluations. Biopsy specimens obtained 2 years after the initial treatment showed an increase in the number of miniaturized vellus-like follicles similar to the findings of androgenetic alopecia. 273 Subsequent studies 260, using technique modifications-including multiple treatment sessions, and various pulse durations, spot sizes, and fluences-have confirmed similar clinical efficacy ranging from 20% to 60% hair reduction 3 months after a single treatment and progressively less regrowth with repeated treatments. Side effects included blistering, fine epidermal crusting, purpura, and transient hyperpigmentation or hypopigmentation. Patients at highest risk of complications were those with recent sun exposure or with naturally darker skin phototypes. The 755-nm wavelength emitted by the alexandrite laser penetrates more deeply into the dermis and is less likely to be absorbed by epidermal melanin than is the 694-nm wavelength of the ruby laser, theoretically making it safer to use with patients of darker skin tones. In a 15-month clinical trial of 126 patients (skin phototype III, average fluence 25 J/cm 2 ), Finkel et al 278 reported the majority of patients had 20% to 50% hair reduction after 1 treatment depending on the treatment site. Mc- Daniel et al 279 demonstrated a 40% to 56% reduction of hair growth 6 months after a single session using the LP alexandrite laser. In a study of 36 patients, Nanni and Alster 280 demonstrated equivalent longterm hair removal with the LP alexandrite laser using pulse durations of 5, 10, and 20 milliseconds. Although the efficacy was equivalent, the 20-millisecond pulse duration resulted in fewer and less severe cases of dyspigmentation. Although a number of studies have documented the safety and efficacy of hair reduction after LP alexandrite laser treatment, conservative management is indicated for patients with darker skin phototypes. Side effects and complications including blistering and transient dyspigmentation can be unpredictable and several treatment sessions using low fluences may be required to effect satisfactory results. Semiconductor diode lasers emit energy in the 800- to 810-nm portion of the electromagnetic spectrum. This longer wavelength is sufficiently absorbed by melanin to make it effective for hair removal, yet less avidly absorbed than that of the ruby or alexandrite, thus, making it potentially safer for individuals with darker skin phototypes. Several studies have demonstrated the efficacy of the

12 12 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 Fig 7. A, Dark terminal facial hair in patient with skin phototype V. B, Decreased hair seen 6 months after third long-pulsed neodymium:yttrium-aluminum-garnet (1064 nm) laser treatment. diode laser for hair removal. In a prospective study of 50 patients (skin phototype II and III), Lou et al 287 showed hair regrowth ranging from 47% to 66% 6 months after 2 treatments. Others have demonstrated the diode laser to be an effective method of hair removal in patients with dark pigment 289,290 and for the treatment of pseudofolliculitis barbae. 291 Pigmentary alterations were not uncommon in these latter patients, with several patients experiencing temporary hyperpigmentation or hypopigmentation. The deeply penetrating 1064-nm wavelength of the Nd:YAG laser may provide certain advantages over the aforementioned laser systems for laser-assisted hair removal, particularly when treating patients with darker skin phototypes (Fig 7). Precisely because the 1064-nm wavelength is less efficiently absorbed by endogenous melanin, significantly fewer instances of purpura, blistering, crusting, and dyspigmentation occur. The QS Nd:YAG was the first hair removal laser marketed in the United States. Because the 1064-nm wavelength is not well absorbed by melanin, and the early Nd:YAG systems had ultrashort (nanosecond) pulse durations, an exogenously applied mineral oil suspension of carbon particles was typically applied to the skin preoperatively in an effort to increase follicular penetration and enhance the absorption of the QS laser energy. Although investigators 292,293 showed significant hair reduction at 12 weeks after treatment, the QS system was deemed inadequate for effecting long-term hair reduction because full regrowth was seen within 6 months as a result of its inability to cause complete disruption of the follicular unit. More recently, LP Nd:YAG laser systems have been developed that are more effective than their QS predecessors given the closer approximation of their pulse durations to the thermal relaxation time of the hair follicle. Adequate heating of the targeted follicle to effect destruction of the surrounding bulge is, thus, achieved. Several studies have demonstrated the effectiveness of the LP Nd:YAG for longterm hair reduction, particularly in patients with darker skin phototypes In addition, reduced hair and decreased papule formation in patients with pseudofolliculitis barbae has been shown to occur after treatment with a LP Nd:YAG laser. 297 IPL sources emitting wavelengths ranging from 550 to 1200 nm can also be used to effect hair reduction. By using a series of cut-off filters, a specific wavelength may be selected to suit an individual skin type and color. Early studies 298 reported approximately 50% to 60% reduction in hair counts 12 weeks after a single treatment. Multiple (3 or 4) treatment sessions have been shown to result in approximately 75% hair reduction after at least 6 months follow up Side effects and complications of IPL treatment are similar to those seen after laser-assisted hair removal, and include rare instances of blistering, crusting, and transient dyspigmentation. ABLATIVE LASER SYSTEMS Cutaneous laser resurfacing has experienced unparalleled growth in the field of aesthetic operation during the past decade. High-energy, pulsed, and scanned CO 2 and erbium:yag lasers have been in widespread use since the mid-1990s and the success of these lasers in ameliorating severely photodamaged facial skin, photoinduced facial rhytides, dyschromias, and atrophic scars has been well documented Earlier CW CO 2 systems were associated with excessive heat deposition and char formation in the skin as a result of uncontrollable delivery and absorption of energy. 10,11 The unpredictable degree of

13 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 13 Fig 8. Periocular rhytides and dyschromia before (A) and after (B) improvement seen several months after carbon dioxide laser skin resurfacing. thermal necrosis and scarring that resulted from these CW lasers precluded their use in facial resurfacing procedures. With the subsequent development of the high-energy, pulsed, and scanned lasers, however, it became possible to safely and reliably ablate layers of skin with higher energy densities and ultrashort pulse durations (shorter than the thermal relaxation time of water-containing tissue). These newer systems were able to effect controlled tissue ablation with limited coagulative necrosis of unintended neighboring structures Because of its flexibility and low side-effect profile, the highenergy, pulsed, and scanned CO 2 laser has been considered the gold standard for facial rejuvenationthe system by which all others are compared. The CO 2 laser produces the most dramatic improvements in the clinical and histologic appearance of photodamaged or scarred facial skin. 302,365 Epidermal ablation occurs after 1 pass of the CO 2 laser at standard treatment parameters (vaporizing tissue to a depth of m), but collagen shrinkage and remodeling the 2 factors most likely responsible for the long-term clinical improvements seen after resurfacing require an additional 1 to 2 passes. 302,331,363 When dermal temperatures exceed 55 C to 62 C, there is disruption of interpeptide bonds leading to conformational changes within collagen s triple helical structure that shrink the moiety to one third of its normal length. 366,367 The mechanisms of long-term collagen remodeling and neocollagenesis after resurfacing are not fully known; however, it is believed that these effects result from thermal desiccation with concomitant collagen shrinkage. In addition, because there is increased expression of smooth muscle actin after laser treatment, the contracted area may serve as a scaffold on which new collagen is formed and deposited during wound phase remodeling. 368 Facial resurfacing with the CO 2 laser typically produces at least a 50% improvement in overall skin tone, rhytide severity, and atrophic scar depth* (Fig 8). The significant postoperative morbidity experienced by patients treated by this system, however, render it a difficult prospect for many to consider. 302,342,369 The short-pulsed 2940-nm Er:YAG laser was developed subsequent to the CO 2 laser in an attempt to emulate some of its beneficial effects while limiting its side-effect profile and morbidity. This laser effects mild improvement of photodamaged facial skin and atrophic facial scars with less intense side effects and faster recovery rates. The Er:YAG laser has a higher absorption coefficient (12,800 cm 1 ) than that of the CO 2 laser (800 cm 1 ), thus, rendering the erbium energy more efficiently absorbed by water-containing tissues (by a factor of 12-18) Because 90% of the epidermis is composed of water, most of the energy of the erbium laser is superficially absorbed. As such, forcible ejection of erbium-desiccated tissue from the skin s surface allows most of the absorbed heat to be dissipated with the production of only a narrow zone of coagulative necrosis in the remaining dermis. Thus, a large photomechanical tissue effect occurs as a result of erbium laser irradiation, whereas a photothermal tissue reaction is primarily effected by CO 2 treatment. The erbium laser can, therefore, effect fine tissue ablation, penetrating to an average depth of 2 to 5 m per J/cm 2 with zones of thermal necrosis extending another 10 to 15 m. 324,374 Because collateral thermal damage is reduced, minimal vascular coagulation is effected, leading to inefficient hemostasis during treatment. The limited thermal damage also accounts for the more modest clinical improvement typically seen after treatment. All patients undergoing an ablative (CO 2 and/or erbium) laser procedure experience at least 1 week *References , 313, , , 349, 350, 358. References 302, 312, 314, ,

14 14 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 of significant morbidity until complete reepithelialization occurs. Postoperative erythema and edema are treated with head elevation, ice application, and, in extensive cases, short courses of oral corticosteroids During the re-epithelialization process, an open or closed wound technique is prescribed. The open technique involves frequent application of thick healing ointment to the de-epithelialized skin surface; whereas semiocclusive dressings are placed on the lased skin in the closed technique. Although the open technique facilitates easy wound visualization, the closed technique may be easier for patients to use and may also decrease postoperative pain Complications from ablative laser treatment are potentially numerous as a result of variations in operative technique and disruption of the integumental barrier. In addition to the expected postoperative erythema and edema, untoward side effects include bacterial and viral infection, pigmentary alteration, ectropion, and hypertrophic scar formation Even newer trends in ablative facial resurfacing have emerged that offer modest clinical improvements in rhytides and atrophic facial scars with reduced postoperative morbidity and shorter recovery times. 332,347, ,358 Less aggressive techniques include single-pass CO 2 laser ablation and use of modulated (variable-pulsed Er:YAG or combined Er: YAG/CO 2 ) laser systems. The single-pass CO 2 laser technique involves the application of 1 set of nonoverlapping scans to the skin. The partially desiccated tissue is left intact to serve a biologic wound dressing. At standard treatment parameters, this method ablates the entire epidermis and stimulates neocollagenesis; effecting improvement in pigmentary irregularities, skin sallowness, and fine rhytides. 332 The modulated Er:YAG lasers emit light with extended pulse durations (up to 500 s) producing larger zones of thermal necrosis compared with traditional short-pulsed Er:YAG laser systems. These larger zones of collateral tissue damage result in beneficial tissue effects that approximate those of the CO 2 laser. In addition, increased thermal coagulation of dermal vessels is effected, permitting deeper tissue penetration and improved intraoperative field visualization. The use of these newer methods are associated with a shorter and less severe postoperative course compared with traditional multipass CO 2 laser skin resurfacing. 352,358 The intensity and duration of such adverse sequelae as erythema and postinflammatory hyperpigmentation are also reduced, making the single-pass CO 2 or modulated Er:YAG a potentially better choice when treating patients with darker skin tones. 51,57 Eradication of a variety of benign epidermal and dermal lesions can also be achieved with either CO 2 or Er:YAG laser ablation. Benign epidermal and dermal lesions such as seborrheic keratoses, verrucae vulgaris, xanthelasma, and sebaceous gland hyperplasia have been successfully removed, as have adnexus tumors such as syringomata or trichoepithelioma Treatment of premalignant and malignant skin lesions, including actinic cheilitis, superficial basal cell carcinoma, and squamous cell carcinoma in situ has been reported The CO 2 laser can also be used for excisional and incisional operations, including blepharoplasty or rhytidectomy. These latter surgical procedures benefit from the near-bloodless field created from the CO 2 laser-tissue interaction, effecting minimal postoperative edema or ecchymoses. Cutaneous laser resurfacing represents a major advance in the treatment of photodamaged facial skin and atrophic scarring. With recent advances in laser technology, this procedure has become widely accepted as an effective means for facial rejuvenation. Despite the prolonged recovery and side-effect profile of ablative CO 2 and Er:YAG lasers, no other treatment can yet match the clinical results they can achieve when used properly. NONABLATIVE LASER SYSTEMS One of the newest trends in dermatology has been the development of nonablative laser systems for rhytides and scars with minimal morbidity or recovery time. Most of the nonablative laser systems used today emit light within the infrared portion of the electromagnetic spectrum ( nm). At these wavelengths, absorption by superficial watercontaining tissue is relatively weak, thereby effecting deeper tissue penetration. Nonablative laser resurfacing induces collagen remodeling by creation of a dermal wound without disruption of the epidermis. Contact and dynamic cooling devices are used simultaneously with laser irradiation to ensure epidermal preservation-the absorbed heat energy largely bypassing the epidermis and being deposited in the superficial papillary dermis. Although nonablative lasers are not yet capable of results comparable with those of ablative laser systems, they have been shown to improve mild to moderate atrophic scars and rhytides with virtually no external wound. 419 Nonablative laser resurfacing is, therefore, ideal for patients with either mild cutaneous pathology, or in those who are unwilling or unable to undergo an expensive, labor-intensive procedure such as ablative laser resurfacing. Clinical studies have demonstrated the ability of 585- and 595-nm PDL to reduce mild facial rhytides with minimal side effects The most common side effects of PDL treatment include mild edema,

15 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 15 Fig 9. Atrophic facial scars before (A) and after (B) improvement 6 months after third 1450-nm laser treatment. purpura, and transient postinflammatory hyperpigmentation. Although increased extracellular matrix proteins, and types I and III collagen and procollagen have been detected after PDL treatment, the exact mechanism whereby wrinkle improvement is effected is not currently known. One theory is that vascular endothelial cells damaged by the yellow laser light release mediators that stimulate fibroblasts to produce new collagen fibers. 422 The infrared systems that have been used for nonablative dermal remodeling include the 1064-nm Nd:YAG, 1320-nm Nd:YAG, 1450-nm diode, and 1540-nm Er:glass lasers. The QS 1064-nm Nd:YAG laser has been used successfully to effect nonablative dermal remodeling, despite its pigment specificity and relative lack of absorption by watercontaining tissue. Its relatively long wavelength is able to penetrate tissue depths sufficient for papillary dermal wounding and its brief (nanosecond) pulse duration limits thermal diffusion. Side effects of laser treatment include pinpoint bleeding, transient erythema, edema, and postinflammatory hyperpigmentation. Patients with prolonged erythema have been shown to experience the best overall improvement in rhytides. 423 The 1320-nm Nd:YAG laser was the first system developed and marketed solely for nonablative skin remodeling. The system s laser handpiece contains 3 basic features: the laser beam itself, a thermal feedback sensor, and a cryogen spray cooling device. The choice of treatment fluences is based on the skin s surface temperature. When skin temperatures are maintained at 40 to 45 C during laser irradiation, dermal temperatures of 60 to 65 C are reached, and collagen contraction and stimulation of neocollagenesis are effected. Epidermal temperatures must be kept below 50 C to prevent vesiculation or scarring. Several studies have documented improvement of mild to moderate facial rhytides after a series of monthly 1320-nm Nd:YAG laser treatments Similar to the 1320-nm Nd:YAG laser, the 1450-nm diode laser is used in a series of monthly treatments to effect significant improvement of facial rhytides, transverse neck lines, and atrophic facial scars (Fig 9). Side effects of treatment are mild and limited to transient edema, erythema, and postinflammatory hyperpigmentation. 434 Mild tissue erythema and edema are observed as the end point of treatment. Final clinical and histologic results typically require 6 months to appreciate. The relatively longer 1540-nm wavelength of the Er:glass laser is absorbed least by tissue melanin compared with the other nonablative infrared laser systems, thereby providing an advantage when treating darker-skinned individuals. Increased dermal fibroplasia and improvement in rhytides have been demonstrated in well-designed studies involving a series of 3 monthly Er:glass treatments with prolonged postoperative follow up Periorbital rhytides appear to be more clinically responsive than perioral rhytides. 438 Nonablative laser skin remodeling is in its infancy and, although several systems have been shown to effect improvement in rhytides and atrophic scars, they still do not approximate the improvement typically seen after ablative laser treatment. In addition, none of these laser systems has yet emerged as being clearly superior. With further technologic refinements, coupled with the relative lack of recovery and minimal morbidity, nonablative dermal remodeling will continue to be a popular treatment choice for patients seeking noninvasive rejuvenation.

16 16 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 LASER PHOTOTHERAPY UV phototherapy has long been a mainstay in the treatment of psoriasis. In 1981, Parrish and Jaenicke 442 demonstrated that the most efficient therapeutic wavelengths for the treatment of psoriasis were within the UVB spectrum. During the past decade, 311-nm narrow-band UVB has become popularized for the treatment of psoriasis, with results comparable with psoralen-uva; however, both modalities require phototherapy sessions several times a week to achieve a therapeutic response. 443 Recently, a 308-nm xenon chloride excimer laser has demonstrated clearing of psoriatic plaques with fewer treatments than traditional narrow-band UVB therapy The laser only targets the affected areas of the skin, thus sparing the surrounding tissue from unnecessary radiation exposure. Bonis et al 444 demonstrated clearance of psoriatic plaques with a 308-nm excimer laser in 7 to 11 treatments. Asawanonda et al 445 reported clearance after 1 treatment using high fluences. More recently, 84% of patients treated in a multicenter study reached improvement of 75% or better after 10 or fewer treatments. 446 Common side effects included blistering, erythema, and hyperpigmentation that were generally well tolerated. Complete clearance has also been reported in a patient with inverse psoriasis. 447 Potential limitations of laser therapy for psoriasis include relative cost of treatment, time constraints when treating a large surface area, and the unknown risk of carcinogenicity. Although additional studies are warranted to determine optimal dosing and administration, the 308-nm excimer laser holds great promise as a useful tool in the treatment of stable, localized psoriasis. The 308-nm excimer laser has also been used to treat problems of dyspigmentation. In a pilot study, Spencer et al 449 demonstrated slight to complete repigmentation in 57% of 23 patches of vitiligo that received at least 6 treatments during 2 to 4 weeks. These results are encouraging because conventional phototherapy often requires months of treatment before improvement is seen. However, the permanance of these results is still unknown, therefore, larger prospective studies are warranted to delineate the long-term benefits of this novel therapeutic intervention for vitiligo. Friedman and Geronemus 450 demonstrated improvement of postresurfacing leukoderma in 2 patients treated with a 308-nm excimer laser. Larger, prospective clinical trials are currently being performed to evaluate the efficacy of this laser system on postresurfacing leukoderma and hypopigmented scars and striae. Acne vulgaris is another cutaneous condition amenable to phototherapy. Investigators have reported a decrease in acne lesions after exposure to blue, red, violet, or UV light The mechanism of action by which blue light is thought to be effective is its absorption by endogenous porphyrins produced by Propionibacterium acnes with subsequent phototoxic effects. 451 More recently, diode lasers have been used to target sebaceous glands in the treatment of acne. 455,456 Investigators demonstrated significant reduction of acne lesions on the back after 4 treatments with a 1450-nm diode laser. 455 Others have used an exogenous indocyanine green chromophore followed by treatment with a LP 810-nm diode laser to reduce acne lesions for up to 10 months. 456 Although these preliminary reports seem promising, future clinical trials are ongoing to determine the actual efficacy, longevity, and costeffectiveness of treatment. PDT is based on the principle that certain compounds can be activated by particular wavelengths of light to induce cytotoxic effects in the tissue where they are located. 457 PDT has been used in dermatology to treat a variety of skin cancers, nonmalignant lesions, inflammatory diseases, and disorders of the adnexa, including hirsutism There are many types of light sources and delivery systems that have been used including nonlaser devices such as tungsten filament, xenon arc, metal halide, and fluorescent lamps. Lasers used for PDT include the APTD, gold vapor, copper vapor, PDL, Nd:YAG, and diode. 461,462 Because both lasers and noncoherent light sources have been used effectively for cutaneous PDT and the superiority of one source over the other has not been demonstrated, the use of a laser versus a nonlaser light source depends on the specific application. 463 Because the scope and practice of PDT is rapidly expanding, a thorough review of the topic is too extensive to be included in this discussion. OPTICAL IMAGING Diagnostic, noninvasive imaging is one of the most exciting developments in laser technology. Confocal scanning laser microscopy allows real-time imaging of tissue in vivo and can provide rapid, high-resolution imaging of skin cytology including the epidermis, microvascular blood flow, and inflammatory cells Using a tightly focused, lowpower, near-infrared light source, the confocal microscope illuminates a small spot in the specimen that is subsequently imaged onto a detector through a small pinhole aperture. By collecting only the light that is emitted from that spot, light outside of the thin plane is rejected, thus allowing imaging of thin slices of tissue. 469 With the same resolution as conventional histology, potential clinical applications

17 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 17 include noninvasive skin imaging, detection of tumor margins, and diagnosis of lesions without biopsy. Langley et al 470 reported preliminary data that suggests confocal microscopy may be a useful adjunct to noninvasively discriminate benign and malignant lesions in vivo. Another promising new method for the noninvasive investigation of skin morphology includes optical coherence tomography The technique uses low-coherence interferometry to provide 2-dimensional images of optical scattering within the tissue. With a penetration of up to 1.5 mm, architectural changes in the epidermis and papillary dermis can be visualized; however, individual cells cannot be evaluated. Potential clinical applications of optical coherence tomography include the noninvasive diagnosis of skin tumors and bullous disease. 473 LASER SAFETY Laser safety has become a more complex issue as more cutaneous laser systems have become available for treatment. Of paramount importance is the general safety of both the patient and the operating room personnel during laser irradiation. Although most lasers are now used in private offices and smaller surgical suites, adherence to strict safety guidelines is essential to prevent intraoperative injury or serious complications during the postoperative period. Key laser safety issues include flammability, ocular safety, electric hazards, laser plume and infectious agents, and controlled access to the laser suite. 474,475 Accidental fires are a potential complication of laser use, particularly in the presence of circulating oxygen; ignition of surgical tubing, sponges, drop cloths, or drapes is possible To minimize these risks, oxygen, if present, should be minimized; saline-soaked drapes or cloths should be used intraoperatively; exposed hair-bearing areas should be kept moist; and alcohol-based skin preparations should be strictly avoided. In addition, lasers should be kept in the standby mode when not in use to avoid inadvertent firing. Eye protection is necessary for both patients and operating personnel whenever a laser treatment is performed. Permanent visual loss can result from even minor direct retinal exposure to laser light. All operating room personnel must wear appropriate eyewear glasses or goggles that filter out the specific wavelength of light depending on which laser is being used. The patient s eyes must also be protected using either glasses or goggles for nonfacial and/or noninvasive procedures or sandblasted metal contact lenses for complete corneal protection when periorbital laser treatment is performed. 479,480 Electrical hazards can largely be eliminated by dedicating a specific electric outlet for each laser and by avoiding the use of extension cords. A smoke evacuator with clean filters and tubing are also essential to contain aerosolized particles and fumes during treatment. This is especially important during QS laser tattoo ablation and CO 2 or Er:YAG laser skin resurfacing in which significant amounts of smoke and desiccated tissue splatter are typically ejected from the surgical field during the procedure. Some of these aerosolized fragments have been reported to contain human papillomavirus, HIV p24 antigens, other viruses, and cellular materials ANESTHESIA Most dermatologic laser procedures can be performed without any form of anesthesia. PDLs and LP lasers typically produce minimal discomfort (analogous to a rubber band snapping on the skin). When concomitant epidermal cooling is applied, only a slight stinging sensation is experienced. Thus, PDL or LP laser irradiation can usually be tolerated by patients without anesthesia, particularly when small areas are being treated. The QS lasers are also used without anesthesia for small treatment areas, but topical or intralesional anesthesia may be necessary to thwart the sharp needlelike pricking sensation when larger lesions or delicate tissue areas (eg, periocular) are involved. Ablative laser skin resurfacing typically requires local and/or intravenous sedation as a result of the pain involved with epidermal vaporization. The most commonly used topical anesthetic compounds for cutaneous laser procedures (particularly in children) are EMLA cream (Astra Pharmaceuticals, Westborough, Mass)-a eutectic mixture of lidocaine 2.5% and prilocaine 2.5% within an oil-in-water emulsion-and Ela-Max (Ferndale Laboratories, Ferndale, Mich)-a lidocaine-containing cream The creams are often applied under occlusion for 30 to 90 minutes before laser irradiation. A novel topical anesthetic formulation (S-Caine peel, Zars Corp, Salt Lake City, Utah) that is composed of lidocaine and tetracaine, is applied to the skin as a cream 30 minutes before the laser procedure, drying to a thin flexible film that can easily be peeled away. Two recent studies have demonstrated the superior efficacy of this unique preparation in providing anesthesia before PDL and even ablative laser treatment. 500,501 Tumescent anesthesia using the subcutaneous infiltration of large volumes of dilute lidocaine and epinephrine may also be used as a form of local anesthesia. 502 This method is particularly useful with extensive ablative laser skin resurfacing procedures

18 18 Tanzi, Lupton, and Alster JAM ACAD DERMATOL JULY 2003 (eg, CO 2 or Er:YAG), as it not only provides good surgical analgesia, but also contributes to postoperative analgesia. Regional nerve blockade of the head and neck is another effective method of providing anesthesia sufficient for surgical procedures on the superficial structures of the face. 503 Local infiltration of 1% or 2% lidocaine with or without epinephrine is generally used. Sensory blockade of the midface can be accomplished through regional nerve blocks of several superficial branches of the trigeminal nerve. Infiltration around the area of the supratrochear and supraorbital, infraorbital, and mental nerves will anesthetize the central forehead, medial cheek, and upper lip, and chin and lower lip, respectively. Complications of regional nerve blockade include hematoma formation, pain at the site of injection, and persistent paresthesia from nerve injury. Injections, therefore, should be in proximity to, but not directly into, the nerve branch. In addition, mild sedatives can be prescribed to reduce patient anxiety before invasive or perceptually painful laser procedures. The alpha-2 agonist clonidine is given at dosages of 0.1 to 0.2 mg several minutes before treatment. Clonidine acts by decreasing sympathetic nervous system outflow from the central nervous system to the peripheral tissues, thereby decreasing blood pressure, heart rate, and cardiac output. 504 In addition, clonidine produces a unique type of sedation that allows patients to be more easily aroused and communicative during their procedure, while reducing the consumption of other anesthetics. 505 Side effects of clonidine administration include orthostatic hypotension and nausea. Oral diazepam (2-10 mg) is another anxiolytic that may be given to patients preoperatively. For extensive (full-face) ablative laser skin resurfacing procedures, a combination of small intravenous doses of propofol, midazolam, ketamine, and fentanyl can provide effective short-term anesthesia and amnesia Treatment and emergency protocols must be in place whenever these medications are administered because of the risk of cardiovascular or respiratory depression. General anesthesia is not usually necessary when performing any type of cutaneous laser operation except in situations when intravenous anesthesia has been deemed inadequate (eg, uncooperative or combative children requiring extensive pulsed laser treatments, or with concomitant surgical lifting and laser procedures). 489,497 SIDE EFFECTS AND COMPLICATIONS Because of the varied side effects and complications possible after cutaneous laser therapy, it is essential that each patient receive consultation and counseling before treatment to assess his or her specific risk of adverse sequelae. It is also important that patients understand the importance of good wound care after a laser procedure. Preoperative laser evaluation should include a basic medical history including documentation of medications and allergies. A history of abnormal scarring, excessive sun exposure, allergic or inflammatory conditions, herpes simplex virus outbreaks, immune disorders, or previous cosmetic procedures within the involved area should also be ascertained. Proper pretreatment education and close physician follow up, in addition to a carefully executed postoperative wound care regimen, helps to reduce morbidity and allows for potential problems to be recognized and addressed early. PDL treatment of port-wine stains, hemangiomas, telangiectases, and vascular ectasias typically result in a variable degree of short-term purpura formation. 39, Complications of PDL treatment can be seen with use of excessive fluences, overlapping laser spots, or in treatment of darker skin tones and include vesiculation, crusting, hyperpigmentation or hypopigmentation, and scarring With the development of PDL systems with extended pulse durations and epidermal cooling devices, the incidence of purpura has been reduced. Safer treatment of darker complexions has also become possible because the refinements help protect the overlying epidermis during treatment and reduce the risk of pigmentary alteration. Other vascular laser systems such as the KTP, copper vapor, and krypton lasers are usually associated with erythema and fine crusting after treatment. The risk of incomplete lesion removal and unwanted pigmentary or textural change is higher with these systems as a result of their decreased hemoglobin absorption capabilities and their crossover specificity for melanin. 512 Pigmented lesions may lighten, darken, or recur after QS laser irradiation. Transient pigmentary alteration is the most common postoperative side effect and may last for several months after treatment. 512 Café-au-lait macules, Becker s nevi, and nevus spilus are notoriously difficult to eradicate and have a greater risk of recurrence for unclear reasons. Permanent depigmentation and scarring are rare sequelae of pigment-specific laser irradiation when conservative fluences are used and UV light exposure is minimized. Laser treatment of decorative and traumatic tattoos can also be associated with transient pigmentary alterations, scarring, darkening of cosmetic tattoos (containing iron oxide or titanium dioxide), or allergic reactions to the liberated pigments. 250,252,253,517

19 J AM ACAD DERMATOL VOLUME 49, NUMBER 1 Tanzi, Lupton, and Alster 19 Complications of laser-assisted hair removal using LP lasers are usually minor and transient. The most common adverse reactions include pain during treatment, erythema, and perifollicular edema; however, blister formation, pigmentary alteration, and scarring have also been reported. 281 Most of the latter complications have occurred in persons who are either tan or have the darkest skin phototypes and can now be avoided with the use of an LP Nd:YAG (1064 nm) laser. 294 Although complication rates reported in association with ablative laser skin resurfacing are relatively low compared with other destructive treatments, many potential side effects are possible during the re-epithelialization process. 302,357,377, Poor intraoperative technique (eg, overlapping laser spots or scans) and failure to adhere to a strict postoperative recovery regimen can also increase the development of adverse sequelae. 379,512 Side effects and complications range from mild and transient to severe and permanent. Postoperative erythema, edema, acne and milia formation, contact dermatitis, and pruritus are relatively common, but temporaryresolving either spontaneously or with appropriate topical therapy Bacterial and viral (herpes simplex) infections and pigmentary alteration (hyperpigmentation or hypopigmentation) can occur and are largely treatable with a variety of topical and/or oral treatments The most severe complications of hypertrophic scar formation and ectropion often require further laser or surgical intervention. 527,528 Fortunately, these latter reactions are very rare when proper surgical technique and postoperative care is applied. CONCLUSION Although lasers capable of cutaneous application have been available for more than 4 decades, it has been only within the past several years that their use gained widespread acceptance within the medical field. 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