LASER TREATMENT OF PIGMENTED LESIONS

LASER TREATMENT OF PIGMENTED LESIONS David J. Goldberg, MD In 1958, Schawlow and Townes, working with microwaves, first proposed a technique for the generation of monochromatic radiation by stimulated emission. They produced monochromatic radiation in the infrared optical region of the electromagnetic spectrum with an alkali vapor used as the active medium. Maiman, using a ruby crystal in 1960, developed stimulated emission of a red-light beam with a wavelength of 694 nm. This was the first working laser, and it is from this prototype that today's lasers are derived. Since 1960, research and technical advances have adapted lasers to dermatology. Leon Goldman, the father of dermatologic laser surgery, published preliminary results on the effects of a ruby laser on skin diseases. Early work with the ruby laser consisted of ablation techniques. Little bleeding was noted after nonspecific damage to the superficial dermal layers, and small areas of skin could be treated with high-intensity radiation with few sequelae. Not surprisingly, the ruby laser was found to treat pigmented lesions well owing to its ability to target melanin. Today, there are numerous lasers that can specifically target pigmented lesions, including other red light lasers (ie, alexandrite, neodymium:yttriumaluminum-garnet [Nd:YAGI) and green light lasers (ie, 510-nm pulsed dye, 532-nm frequency-doubled Nd:YAG). The wide range of lasers that can be used to treat pigment is a result of the broad absorption spectrum of melanin. Even so, other less pigment-specific lasers have been used to treat pigmented lesions, including the CO Z and argon lasers. The CO Z laser exerts its effect on tissue by simple vaporization of water-containing cells. Textural skin changes and scarring may result from this nonselective destruction. A very low wattage CO Z laser appears to reduce the risk of scarring and has been used effectively to treat superficial epidermal pigmented lesions, such as solar lentigines. The green and blue light (488 and 514 nm, respectively) of the argon laser is specifically absorbed by melanin. The problem with the system is that it functions as a continuous wave laser. Thus, although this laser selectively targets the melanin chromophore, the heat produced dissipates from the absorbing melanosomes, causing thermal damage to surrounding tissue with resultant hypopigmentation and scarring. Lasers that produce pulses of light shorter than the thermal relaxation time of melanosomes are now used to selectively destroy targeted melanin. The process of removing pigmented lesions using sufficiently shorter laser pulses is called selective photothermolysis. The targeted melanosome selectively absorbs the laser light and the resultant increase in temperature induces thermal damage of

the melanosome. Because this damage occurs over a time period shorter than the melanosome's thermal relaxation time, the absorbed energy is confined to the targeted melanin-containing melanosomes within melanocytes and keratinocytes. Selective destruction of melanosomes results without damage to surrounding tissue structures. The pigmented skin of guinea pigs and human volunteers has been shown to respond to short laser pulses over a wide range of visible light wavelengths. Lasers that target pigment include the pulsed dye (510 nm), copper vapor (511 nm), krypton (520-530 nm), frequency-doubled Q-switched Nd:YAG (532 nm), 0-switched ruby (694 nm), 0 switched alexandrite (755 nm), and Qswitched Nd:YAG (1064 nm). All these wavelengths can effectively treat pigmented lesions without disrupting the normal surrounding tissue. Pigment-specific lasers can be divided into three categories: (1) green, (2) red, and (3) nearinfrared. Green light lasers are further subdivided into both pulsed and nonpulsed systems. The red and near-infrared lasers currently available are pulsed (or Q-switched) systems. Green light lasers do not penetrate as deeply into the skin as do the red and near-infrared lasers owing to their shorter wavelengths. Green light lasers are therefore effective only in the treatment of epidermal pigmented lesions. Figure 1. Solar lentigines prior to (A) and after (B) one treatment session with a green light pulsed laser.

GREEN LIGHT PULSED LASERS These lasers produce energy with pulses shorter than the thermal relaxation time of melanosomes. Examples of these lasers are the flashlamp-pumped pulsed dye and frequencydoubled Q-switched Nd:YAG lasers. The flashlamp-pumped pulsed dye laser produces a 510-nm wavelength and 300-ns pulse of energy whereas the frequency-doubled Qswitched Nd:YAG laser produces a 532-nm wavelength and 5- to 10-ns pulse of energy. Both lasers produce excellent results when used to treat epidermal pigmented lesions such as solar lentigines and ephilides. Because the green wavelength of these lasers is also well absorbed by oxyhemoglobin, purpura formation may occur following laser irradiation. The purpura resolves in 1 to 2 weeks after treatment, with resolution or lightening of the clinical lesion in 4 to 8 weeks. Occasionally, purpura leads to postinflammatory hyperpigmentation. It should be noted that these lasers produce a variable response in epidermal pigmented lesions such as cafe-au-lait macules, Becker's nevi, and epidermal melasma. Because of the variability in clinical response, testing the treatment areas of the respective lesion may be prudent prior to engaging in a full treatment. Even when cafe-aulait macules and Becker's nevi show resolution after treatment, recurrences have been reported. Recurrences may occur because of the impact of these lasers on melanosomes, with little effect on the pig ment-producing melanocytes. Careful sun protection may retard, but will not prevent, recurrence. Because melasma occurs secondary to a combination of genetic, sun-induced, and hormonal factors, successful laser treatment is the exception rather than the rule in this condition. The green pulsed lasers, because of their short wavelengths, do not penetrate very deeply into the dermis and are thus ineffective for treating dermal pigmented lesions (Figs. 1 and 2). GREEN LIGHT NONPULSED (QUASICONTINUOUS WAVE) LASERS L A Nonpulsed, quasi-continuous wave green light lasers such as the copper vapor (511 nm) or krypton (520-530 nm) lasers share some characteristics with the aforementioned pulsed lasers. Because the thermal relaxation time of the melanosome is exceeded using these lasers, however, they do not produce the same consistent clinical results. Although epidermal pigmented lesions may be cleared successfully with the copper vapor and krypton lasers, more treatment sessions are usually necessary to achieve lesional clearance. There is also a theoretically higher incidence of scarring when using these systems (Fig. 3). RED LIGHT PULSED LASERS The two currently available red light pulsed lasers are the Q-switched ruby and Q- Figure 2. A, Cafe-au-lait macule prior to treatment with a green light pulsed laser. B, Early recurrence of cafe-au-lait macule observed 18 months after last laser treatment.

Figure 3. A, Solar lentigines before treatment with a green quasicontinuous wave laser. B, Partial clearing seen after two treatments. switched alexandrite lasers. The Q-switched ruby laser emits a 694-nm beam with a 20- to 50-ns pulse duration. The Q-switched alexandrite laser emits a 755-nm wavelength with a pulse duration of 50 to 100 ns. The longer wavelengths of these lasers allow deeper penetration into the dermis. Their mechanism of action on melanin-containing melanosomes and melanocytes involves selective photothermolysis, photoacoustical mechanical disruption, and chemical alteration of the target tissue. Photoacoustic mechanical disruption is caused by rapid thermal tissue expansion, creating pressure waves that fragment pigment particles in the dermis. Within the dermis, absorption of the laser energy by melanin-rich stage III and IV melanosomes causes selective pigment destruction. These lasers can also be used to treat epidermal pigmented lesions without purpura formation owing to the relative lack of hemoglobin absorption at these wavelengths (Figs. 4 and 5). The major benefit of the red light systems over green light lasers is their efficacy in the treatment of dermal pigmented lesions such as congenital nevi and nevi of Ota. Although these lasers are uniformly successful in the treatment of nevus of Ota, the response to laser treatment of congenital nevi is more variable. In both clinical entities, the lasers appear to destroy some but not all of the involved melanocytes. Darker congenital nevi in younger patients appear to show the best response; however, pigment recurrence is common. Nevi of Ota are typically very responsive to laser treatment, with rare to no

Figure 4. Solar lentigo prior to (A) and after (B) treatment with a red light pulsed laser.

6 GOLDBERG Figure 5. Cafe-au-lait macule on the right cheek before (A) and after (B) treatment with a red light pulsed laser. Lesion showed no evidence of recurrence 1 year after final treatment. recurrences seen (Figs. 6 and 7). The responses of dermal melasma are quite variable, with repigmentation or pigmentary worsening a common occurrence. Recently, long-pulsed ruby lasers (300-700 µs pulses) have been shown to be effective in the treatment of Q-switched ruby laserresistant congenital nevi. These lasers may also be of use in laser-assisted hair removal (see the article by Dr. Wheeland elsewhere in this issue). LASER TREATMENT PROTOCOL Green Light Lasers Pulsed Dye (510 nm) Laser Treatments are usually initiated at 2.0 to 3.0 J/cm 2 using nonoverlapping 5-mm laser spots. An immediate ash-white tissue response should occur. Repeat treatments are delivered at 6- to 8- week intervals. Solar lentigines typically require one to two laser treatments, whereas cafe-au-lait macules may require 2 to 12 treatment sessions. NEAR-INFRARED PULSED LASERS The Q-switched Nd:YAG laser produces a 1064-nm wavelength beam with a pulse duration of 10 ns. Despite less absorption of this wavelength by melanin compared with the green and red light lasers, its advantage lies in its ability to penetrate more deeply in the skin. In addition, it may prove to be more useful in the treatment of lesions in individuals with darker skin tones. Like the Qswitched ruby and alexandrite lasers, the Q- switched Nd:YAG laser is highly effective in clearing of nevus of Ota. When used in combination with a carbon-containing topical suspension, the Nd:YAG laser may also effectively remove unwanted hair (Fig. 8). Because carboncoated hair, rather than the melanin of pigmented hairs, is the absorbing chromophore, both pigmented and nonpigmented hairs may be treated (see the article by Wheeland). Frequency-Doubled Nd: YAG (532 nm) Laser Solar lentigines and cafe-au-lait macules are typically treated at fluences of 2.0 to 2.5 J/cm 2 using 1- to 3-mm spots at 10 Hz. Like the pulsed dye laser, only a couple of laser sessions are needed to treat lentigines. The response of cafe-aulait macules is variable. Quasi-Continuous Wave Copper Vapor (511 nm) and Krypton (520-530 nm) Lasers The copper vapor laser is used at 0.16 to 0.25 W using a 150-µm spot at 0.2-second intervals. The krypton laser is operated at 700 mw with a 0.2- second pulse and 1-mm spot. These lasers can be used to treat solar lentigines, but their use in cafe-au-lait macules has

Figure 6. Nevus of Ota prior to (A) and after (B) treatment with a red light pulsed laser.

Figure 7. Congenital pigmented nevus prior to (A) and after (B) several treatment sessions with the Q-switched ruby laser.

Figure 8. Terminal hairs prior to (A) and 8 weeks after (B) treatment with a topical carbon-containing suspension and Q- switched Nd:YAG laser irradiation. No hair regrowth is seen. commonly led to textural changes following treatment. Red and Infrared Light Lasers Q-Switched Ruby Laser (694 nm) Fluences of 5.0 to 6.0 J/cm 2 are used to treat epidermal and dermal pigmented lesions. One or two treatments effectively clear lentigines whereas cafe-au-lait macules and nevi of Ota require four or more treatments at bimonthly intervals. Significant lightening of infraorbital hyperpigmentation can be achieved within two laser sessions. Q-Switched Alexandrite Laser (755 nm) Fluences of 6.0 to 7.0 J/cm 2 are used to treat nevi of Ota, melanocytic nevi, and infraorbital hyperpigmentation. Treatment sessions are scheduled at 6- to 8-week intervals with an average of five treatments required to effect clearance of nevus of Ota. Three treatments produce significant clearing of melanocytic nevi, whereas two sessions can significantly lighten infraorbital hyperpigmentation. Q-Switched Nd: YAG Laser (1064 nm) Energy densities averaging 8.0 J/cm 2 using a 3- mm spot size are required to treat nevus of Ota. Similar parameters are used to treat benign melanocytic nevi; however, lower fluences are used for infraorbital hyperpigmentation. SUMMARY Several pigment-specific lasers can effectively treat epidermal and dermal pigmented

406 GOLDBERG lesions without complications using the basic principles of selective photothermolysis. Although such pigmented lesions as solar lentigines and nevi of Ota are relatively easy to treat using pigment-specific laser technology, cafe-au-lait macules and melasma show variable responses to treatment. New, longpulsed pigment-specific lasers may prove to further enhance the clinical results obtained in resistant pigmented lesions and other conditions. References 1. Alster TS: Complete elimination of large cafe-aulait birthmarks by the 510 nm pulsed dye laser. Plast Reconstr Surg 96:1660-1664, 1995 2. Alster TS: Cafe-au-lait macule in type V skin: Successful treatment with a 510 nm pulsed dye laser. J Am Acad Dermatol 33:1042-1043, 1995 3. Alster TS, Williams CM: Treatment of nevus of Ota by the Q-switched alexandrite laser. Dermatol Surg 21:592-596, 1995 4. Alster TS: Manual of Cutaneous Laser Techniques. Philadelphia, Lippincott-Raven, 1997 5. Anderson R, Margolis RJ, Watanabe S, et al: Selective photothermolysis of cutaneous pigmentation by Qswitched Nd:YAG laser pulses at 1064, 532, and 355 nm. J Invest Dermatol 93:28-32, 1989 6. Anderson RR, Parrish JA: Selective photothermolysis: Precise microsurgery by selective absorption of pulsed irradiation. Science 22:524-527, 1983 7. Apfelberg DB, Maser MR, Lash H, et al: The argon laser for cutaneous lesions. JAMA 245:2073, 1981 8. Ara G, Anderson RR, Mandel KG, et al: Irradiation of pigmented melanoma cells with high intensity pulsed radiation generates acoustic waves and kills cells. Lasers Surg Med 10:52, 1990 9. Ashinoff RA, Geronemus RG: Q-switched ruby laser treatment of labial lentigos. J Am Acad Dermatol 27:809-811, 1992 10. DePadova-Elder SM, Milgraum SS: Q-switched ruby laser treatment of labial lentigines in Peutz-Jeghers syndrome. J Dermatol Surg Oncol 20:830-832, 1994 11. 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LASER TREATMENT OF PIGMENTED LESIONS 407 of wavelength on cutaneous pigment using pulsed irradiation. J Invest Dermatol 92:717, 1989 37. Tan OT, Morelli JG, Kurban AK: Pulsed dye laser treatment of benign cutaneous pigmented lesions. Lasers Surg Med 12:538, 1992 38. Taylor CR, Anderson RR: Treatment of benign pigmented epidermal lesions by Q-switched ruby laser. Int J Dermatol 32:908-912, 1993 39. Taylor CR, Anderson RR: Ineffective treatment of refractory melasma and postinflammatory hyperpigmentation by Q-switched ruby laser. J Dermatol Surg Oncol 20:592-597, 1994 40. Taylor CR, Flotte TJ, Gange RW, et al: Treatment of nevus of Ota by Q-switched ruby laser. J Am Acad Dermatol 30:743-751, 1994 41. Watanabe S, Anderson R, Brorson S, et al: Comparative studies of femtosecond to microsecond laser pulses on selective pigmented cell injury in skin. Phototest Photobiol 757-762, 1991 L A 42. Watanabe S, Takahashi H: Treatment of nevus of Ota with the Q-switched ruby laser. N Engl J Med 331:1745-1750, 1994 43. Yasuda Y, Tan OT, Kurban AK, et al: Electron microscopic study on black pig skin irradiated with pulsed dye laser (504 nm). Proc SPIE: Lasers Derm Tissue Welding 1422:19-26, 1991 Address reprint requests to David J. Goldberg, MD 390 Old Hook Road Westwood, NJ 07675