CME #119 - June 2004Laser Treatments in Dermatology

Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for two category 1 physician credit hours. As a reader of Skin & Aging, this course is brought to you free of charge — you aren’t required to pay a processing fee. Lasers and intense pulsed light sources now account for a necessary, vital and growing part of dermatology. Laser technology and treatment has advanced steadily for treatment of many cutaneous conditions, including a host of vascular and pigmented lesions, wrinkles, tattoos, scars and unwanted hair during the past decade. This article reviews theory, clinical applications and potential for further progress of laser surgery in dermatology. At the end of this article, you’ll find a 10-question exam. Mark your responses in the designated area and fax page 84 to HMP Communications at (610) 560-0501. We’ll also post this course on our Web site — www.skinandaging.com. I hope this CME contributes to your clinical skills. Amy McMichael, M.D. CME Editor Amy McMichael, M.D., is Associate Professor in the Department of Dermatology, Director of the Hair Disorders Clinic and Residency Program Director at Wake Forest University Medical Center in Winston-Salem, NC. Principal Faculty: Hirotaka Akita, M.D., Ph.D., and R. Rox Anderson, M.D. Method of Participation: Physicians may receive two category 1 credits by reading the article on p. 76-83 and successfully answering the questions found on p. 83-84. A score of 70% is required for passing. Fill out the last page and submit your answers and evaluation via fax or log on to www.skinandaging.com and respond electronically. Estimated time to complete the activity: 2 hours Date of original release: June 2004 Expiration Date: June 2005 This activity has been planned and produced in accordance with the ACCME essentials. Accreditation Statement: NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Designation Statement: NACCME designates this continuing medical education activity for a maximum of two category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the educational activity. Disclosure Policy: All faculty participating in Continuing Medical Education programs sponsored by The North American Center for Continuing Medical Education are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation. Faculty Disclosures: Drs. Anderson and Akita have disclosed that they have no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the contexts of the subject of his article. Learning Objectives: At the conclusion of this educational activity, the participants should be able to: • identify the major indications and uses of lasers for treatment of skin, including appropriate choices among different lasers • identify major side-effects associated with laser or filtered flashlamp treatment for vascular lesions, pigmented lesions, tattoos, hair removal and photoaged skin. Target Audience: Dermatologists, Plastic Surgeons, Internists Commercial support: None Laser technology and treatment has advanced steadily for treatment of many cutaneous conditions, including a host of vascular and pigmented lesions, wrinkles, tattoos, scars and unwanted hair during the past decade. Demand for aesthetic treatments by skin ablation (resurfacing), and more subtle non-ablative treatments, has increased. Safety and ease of using lasers and high-energy flashlamps, has improved to the point that treatment can in some settings be given by non-medical personnel. Unwanted, preventable complications and side-effects are not uncommon. This article briefly reviews theory, clinical applications and potential for further progress of laser surgery in dermatology. Light-Skin Interactions LASER is an acronym for light amplification by the stimulated emission of radiation. Lasers differ from all other light sources by emitting a combination of very intense, monochromatic (single wavelength), coherent and collimated light beams. Most lasers used in dermatology now emit high-energy pulses rather than a continuous beam. Filtered xenon flashlamps, sometimes called intense pulsed light (IPL), are an alternative to some lasers for treating vascular and pigmented lesions, fine wrinkles and for hair removal. When light enters skin, it’s absorbed and scattered. With rare exception, dermatological lasers and IPLs treat skin by mechanisms of local heating at the sites of energy absorption. Absorption of light by various structures in skin is wavelength-dependent. This allows different wavelengths to “target” different structures, and is the main reason why so many lasers and IPL wavelengths are needed to treat different conditions. Depth of light penetration is also wavelength-dependent, and depends on absorption and scattering. Over the ultraviolet and visible spectrum, penetration generally increases with increasing wavelength, from several micrometers in the ultraviolet region up to several millimeters in the red and near-infrared spectral region. Penetration depth is another major factor affecting choice of wavelength. Visible light (wavelengths 400 nm to 700 nm) absorption in skin is mainly by melanin, hemoglobin and oxyhemoglobin.1 Tattoo inks consist of sub-cellular particles implanted in the dermis that strongly absorb visible light. In the near-infrared spectrum (NIR, 700 nm to1200 nm), absorption is weakest and optical penetration depth is greatest. This combination allows for deep (full-thickness skin) treatments when high energy pulses are used. Penetration depth is also effectively greater when larger exposure spot size is used. In the mid- and far-infrared spectrum (>1200 nm), water is the dominant absorbing molecule. Non-ablative mid-infrared lasers, and ablative far-infrared lasers (erbium, CO2) are weakly or strongly absorbed by tissue water, respectively. (See “Lasers in Medicine” below, which shows the lasers used in dermatology.) Selective Photothermolysis A theory called selective photothermolysis2 (SP) is an essential concept for safe treatment using most lasers and IPLs. SP is based on two fundamental principles: • Selective absorption of light by “target” structures. • Confinement of heat to these targets, by delivery of a brief light pulse. The first of these influences appropriate choice of wavelength, while the second influences appropriate choice of pulse duration. There are additional necessary criteria, such as adequate penetration of light to the target structures, and adequate fluence (fluence equivalent to the light dose equals energy delivered per unit skin area, and is typically reported in J/cm2). Thermal relaxation time is a simple concept, defined as the time for which a target structure substantially cools by heat conduction. For pigmented targets (pigmented cells, blood vessels), the laser pulse duration should ideally be approximately equal to thermal relaxation time, which allows good heat confinement and uniform heating of the targets. A very useful approximation is that the thermal relaxation time in seconds is about equal to the square of the target’s size in millimeters. Pulses are used in SP, because heat flow from the light-absorbing targets takes time to occur. Similarly, it’s possible to selectively cool and partially protect the pigmented epidermis during laser or IPL treatment. The most sophisticated version of this is dynamic cryogen spray cooling (CSC), in which a 10 ms to 100 ms blast of -30oC liquid cryogen is sprayed on the skin surface just before arrival of a laser pulse. Cold windows held in contact with skin before and during laser or IPL exposure are also highly effective for reducing unwanted epidermal damage. Cold windows are most effective when using pulse durations that are longer than about 10 ms. Skin cooling allows safe treatment, within certain limits, of darkly-pigmented skin for vascular lesions, pigmented lesions and hair removal. Microvascular Lesions In various lesions, the target blood vessels range in size from about 20 mm (e.g. for infant port wine stains) to 2 mm (e.g. for a dilated leg vein), a 100-fold size range. The yellow pulsed dye, green KTP, near infrared Nd:YAG, diode lasers and IPLs used for treating vascular lesions range from about 0.4 ms to 200 ms pulse duration. Choosing the right combination of wavelength and pulse duration for treatment should be tailored to vessel size and depth. For treatment of superficial microvascular lesions (less than 0.3 mm target vessels, less than 2 mm deep), the green-yellow absorption bands of oxyhemoglobin are typically used. Flashlamp-pumped dye lasers operating near 585 nm, with pulse durations of 0.45 ms to about 10 ms, have become a kind of gold standard for treatment of port wine stains (PWS), ulcerated hemangiomas, scars and small telangiectases.3 A series of six to 20 treatments using fluences of 3 J/cm2 to 10 J/cm2 at 585 nm, 0.45 ms pulses, and a spot size of 2 mm to 10 mm, is necessary for removal or substantial lightening of port wine stains. Many PWS are not completely removed by this approach, a fact that may be due to depth of the lesion and/or the microanatomy of its vasculature. For increased penetration of larger or deeper vessels, spot sizes greater than 5 mm are more effective. We’ve recently begun to use 1 ms to 20 ms Nd:YAG laser (1064 nm) delivered with skin cooling at the fluence threshold for subtle, immediate darkening of the lesion based on a recent abstract report by Yang et al. This approach appears to be generally effective, but must be done with caution to avoid dermal heating and subsequent scarring. There are very strong arguments for treating PWS in early childhood.4 Hypertrophy of the lesions has not yet occurred; the lesion is much smaller in area than it will be after growth of the patient; psychosocial trauma from PWS is most limited in early childhood; the trauma of each treatment is largely forgotten before about age 1. Yellow pulsed dye lasers are often effective for verruca, angiofibromas, small telangiectases, rosacea, sebaceous hyperplasia, ulcerated hemangiomas, and to flatten and remove redness from scars and keloids.5 It is unclear whether all of these applications operate primarily by selective destruction of small vessels. Unlike the other conditions, treatment of hemangiomas and scars appears to be more effective at lower fluences (3 J/cm2 to 5 J/cm2) than at higher fluences. Pulsed dye laser (PDL) treatment often causes immediate purpura that intensifies for several days after treatment. The amount and duration of purpura from PDL have been reduced by extending pulse duration to >=10 ms, and by epidermal cooling devices.6 Treatment with green 532 nm (KTP; frequency-doubled Nd:YAG) and IPLs emitting pulses longer than about 10 ms typically causes no purpura. For this reason, other green/yellow lasers or IPLs are often preferred over PDL for treatment of vascular lesions on the face of adults, such as from rosacea. The anatomy and causes underlying dilated leg veins should be worked up prior to choice of therapy. Deep venous disease should be treated by intravenous laser therapy (IVLT), RF catheter ablation or surgery before treatment of superficial vessels is considered. Sclerotherapy and lasers are useful for treating superficial vessels that may remain after correction of deep vein reflux. Properly performed, sclerotherapy is typically more effective, less painful and has fewer side effects than laser treatment. The long-pulsed alexandrite7 or 800 nm diode laser8 is effective for small or medium sized veins at lower extremity, and the Nd:YAG laser9 is effective for leg veins as large as 3 mm in diameter. Pigmented Lesions Based on selective photothermolysis, melanosomes are ruptured with sub-microsecond laser pulses, leading to selective necrosis of pigmented cells. A wide range of short-pulsed lasers are available for this including Q-switched frequency-doubled Nd:YAG (532 nm, 10 ns, green), Q-switched ruby (694 nm, 20 ns, red), Q-switched alexandrite (755 nm, 20-50 ns, infrared) and Q-switched Nd:YAG (1064 nm, 10 ns, infrared). The same lasers are also useful for tattoo removal. Immediate whitening change of the pigmented lesion occurs after a therapeutic fluence using any of these short-pulsed lasers. This immediate whitening is thought to be due to small cavitation bubbles, and is a useful clinical sign because the whitening correlates directly with melanosome rupture and pigment cell injury.10 Q-switched ruby, alexandrite or Nd:YAG lasers are excellent for treatment of dermal melanocytic lesions such as blue nevi and nevus of Ota. Common acquired benign epidermal pigmented lesions, such as solar lentigos, labial lentigo,11 freckles and seborrheic keratosis, typically respond quite well to one or two treatments with these short-pulsed lasers. Less ideal but also effective, are a wide variety of pulsed lasers, ablative lasers and IPLs for treating common acquired epidermal pigmented lesions, as well as any other modality that superficially destroys the epidermal basal layer. In contrast, congenital epidermal lesions are typically more difficult to remove, including nevus spilus and café-au-lait macules. These have a high recurrence rate after treatment, for unknown reasons. Although melasma is a common acquired benign pigmented lesion, the efficiency of laser treatment for the dermal variant of melasma is poor, and worse hyperpigmentation often results. Despite encouraging reports,12 IPL treatment usually fails for dermal melasma also. Development of an effective, rapid treatment for dermal melasma and post-inflammatory hyperpigmentation remains a worthy challenge for future studies. For melasma, a mixture of topical bleaching agents and/or retinoid, oral vitamin C or/and tranexamic acid may be first choices for therapy. The common side effects of epidermal pigmented lesion removal by Q-switched laser are mostly transient hyper- or hypopigmentation. Hyperpigmentation occurs in about 30% to 50% of cases,13 and occasionally take about 6 months to resolve while using topical bleaching agents. The red (Q-switched ruby) and near-infrared (Q-switched alexandrite and Nd:YAG) wavelength lasers are extremely useful for treating dermal melanocytosis, such as Nevus of Ota (including Hori or Ito),14 acquired bilateral nevus of Ota-like macules,15 ectopic Mongolian spot, drug-induced hyperpigmentation,16 and traumatic and decorative tattoos.17 Permanent hypopigmentation, especially when using the Q-switched ruby laser, is seen in about 1% of cases, and may result from either inappropriately high laser fluence or from unmasking of vitiligo. Use of the Q-switched ruby laser at a low fluence (e.g., 5 J/cm2; spot size 6.5 mm) through a series of treatments can eliminate the pigmentation of nevus of Ota without laser-induced permanent hypopigmentation.14 On the other hand, the disadvantages of 1064 nm Nd:YAG laser irradiation are pinpoint bleeding after irradiation and crusting that may continue for several weeks. Congenital pigmented nevi are difficult lesions that can be associated with melanoma when the nevus is giant. Pigmentation of these lesions respond initially to Q-switched ruby laser pulses, but much of the deeper part of these lesions consist of nests of poorly-pigmented cells that remain. The use of high-fluence, longer pulse duration (0.3 ms to 1.0 ms) ruby, alexandrite or Nd:YAG lasers, appears to allow more extensive thermal damage of the nests of cells in these lesions. Efficacy of combined treatment with long-pulsed and Q-switched lasers can be impressive, and may be decided by the depth of dermal cell nests.18 Thus far there have been no reports of malignant degeneration after laser irradiation of a pigmented lesion. However, it’s necessary to follow these patients for malignant degeneration regardless of whether a laser has been used as part of therapy. Tattoo Removal The mechanism of removing a tattoo by Q-switched laser treatments is sudden heating and fracture of the intracellular ink granules that are contained by phagocytic dermal cells. Dead cells and ink are shed in part through the epidermis, but much of the ink is transported into lymphatics and, apparently, retained in regional nodes. Color of the tattoo ink is important for selecting laser wavelength(s) for treatment.19 Red ink is far better removed by green laser pulses; green ink is far better removed by red laser pulses. Yellow ink is not removed well by any of the commercially available dermatology lasers, and would be expected to respond to blue pulses. The ink of cosmetic tattoos, which often contain ferric oxide or titanium dioxide, easily and permanently turn black when exposed to Q-switched laser pulses.20 These color changes are probably due to reduction of rust-colored ferric oxide to jet black ferrous oxide and from white Ti4+ to blue Ti3+. Further treatment often removes these tattoos, but warn patients that permanent tattoo darkening is a possibility. TiO2 content is associated with poor results. Unfortunately, it is difficult to treat many colors with a single wavelength, so more than one laser system is usually needed for multi-colored, modern artistic tattoos. The number of treatments for tattoo removal is highly variable. Amateur tattoos made with carbon (India ink, graphite) are most effectively removed by laser treatment. For most tattoos, six to eight treatments are required, however, up to 20 treatments are sometimes required, given at 4 to 8 week intervals. Occasionally, tattoo ink simply cannot be cleared, especially with TiO2 tattoos, white, yellow and some green colors. Therefore, CO2 laser vaporization, dermabrasion, excision and grafting can be considered as alternative treatments. Scarring, often hypertrophic scars or keloids, may be produced by these treatments. The risk of scarring by Q-switched laser treatment of tattoo is approximately 5% or less, and usually limited to a portion of the treated area. The more common side effects of tattoo removal by Q-switched laser are transient pigmentary and textural changes. Hyperpigmentation is usually mild and transient, and can be treated with topical bleaching agents. Hypopigmentation is also usually transient, but depigmentation occurs in about 1% of cases and is often permanent. A more serious complication of treatment involves a systemic allergic or localized granulomatous tissue reaction to tattoo ink particle antigens.21 Some patients may suffer fever, joint pain, chills, and/or myalgia after each laser treatment. In our clinical experience, treatment with oral antihistamines or corticosteroids before laser treatment is useful in these cases. Hair Removal In recent years, the use of lasers and IPLs to remove unwanted pigmented hair has generated much interest since the first clinical study using the long-pulsed ruby laser for hair removal was reported by Grossman et al.22 Before the advent of melanin-based laser hair removal, Q-switched Nd:YAG laser used after application of carbon suspension was used for temporary hair removal. The primary target for hair removal is melanin in the hair shaft, hair follicle epithelium and matrix. It’s difficult or impossible to permanently remove white hair using light. Attempts to use hair dyes or applications of melanin appear to have little benefit, probably due to lack of sufficient penetration into the hair follicle. Because light must pass through the pigmented epidermis before reaching hair follicles, laser hair removal poses a kind of “contest” between the effects of light absorption by melanin in the epidermis versus in the hair follicles. It’s generally easier, very effective and safe to remove dark coarse hair in a person with fair skin. If the patient has darkly pigmented skin, safe and effective removal of pigmented hair requires proper choice of wavelength, pulse duration, and active cooling of the epidermis by cryogen spray, cold sapphire or other methods. Fine hair is more difficult to remove permanently. The most useful wavelengths for hair removal are in the red or near-infrared because the combination of sufficient optical absorption by hair melanin and depth of penetration into dermis is best in the 600 nm to 1100 nm spectral region. A large number of specific lasers and IPL systems are sold for hair removal, with a range of safety, efficacy, versatility for different skin types, speed of treatment, cost and reliability. Thus far, the long-pulsed ruby (694 nm), long-pulsed alexandrite (755 nm),23 diode (800 nm)24 and long-pulsed Nd:YAG (1064 nm)25 lasers have been cleared by FDA for permanent hair reduction. A range of pulse duration from about 3 ms to 300 ms is available among these various lasers. IPLs filtered to emit over all or part of this spectral range are also available, and utilize the same basic mechanisms as lasers for hair removal. Clinically, the optimal choice of device, wavelength and pulse duration is governed by the patient’s hair color, hair diameter and skin color. In practice, a versatile device and approach is needed. Ruby lasers have largely been replaced by the other devices. The most popular device for laser hair removal is a pulse duration-tunable (5 ms to 100 ms) 800 nm diode laser system with contact cooling provided by a cold sapphire window. For coarse diameter hair, pulse durations as long as about 300 ms are about as effective as shorter pulses. When contact cooling is used, long pulses allow the largest available safety factor for treating dark skin. A longer wavelength is also generally safer for dark skin. Nd:YAG lasers delivered with either cryogen spray or contact cooling are generally the safest devices for treating dark skin. In contrast, fine and/or lightly pigmented hair is poorly treated with long pulses and/or long wavelengths. Permanent reduction of fine, lightly-pigmented hair can best be achieved with pulse durations of 3 ms to 20 ms, using wavelengths from about 600 nm to 800 nm. Most IPL, ruby and alexandrite laser systems currently available achieve this combination. Side Effects of Hair Removal Hazards and side-effects from laser or IPL hair removal can be severe. All of these devices are designed to destroy melanin-pigmented tissue deep within the dermis. The retina and choroids layers of the eye contain the highest concentration of melanin in the body, and can easily be permanently damaged by any of the IPLs or lasers used for hair removal. It’s possible to injure the eye when treatment is done anywhere inside the bony orbits, even when a protective eye shield is used. Permanent eye injury from laser or IPLs used for hair removal can present as immediate or delayed malformation of the pupil (pear or teardrop shape), visual impairments, or uveitis. Another potentially horrifying side effect for patients is hair growth stimulation. When this occurs, laser or IPL treatment converts fine hairs to coarse dark hairs by unknown mechanisms. Further laser or IPL treatment is sometimes effective for permanently reducing these stimulated hairs. In our experience, laser or IPL-induced hair growth stimulation occurs most frequently on the face and neck in women from Mediterranean, near east or Indian subcontinent heritage, who typically have an ill-defined hairline and pigmented vellus hairs on the face when examined closely with a hand lens. The best clinical approach is probably to counsel patients with these traits, about the high risk for hair stimulation, and to use other methods. Skin Resurfacing Controlled ablation of the epidermis and upper dermis with lasers, is called laser skin resurfacing. The lasers for skin resurfacing emit far infrared wavelengths that are strongly absorbed by water. Rapid heating and removal of a thin layer of tissue, leaving a thin layer of residual thermal damage, occurs with each “pass” during laser resurfacing. As in selective photothermolysis, a short pulse or dwell time is used (dwell time is the time of exposure at a point when a focused beam is scanned) to minimize heat conduction during the vaporarization process. CO2 lasers (10,600 nm) deposit energy in the upper 20 mm of skin, and erbium lasers (2940 nm) deposit energy in the upper 5 mm of the skin, due to strong absorption by water. After ablation, a new epidermis forms within about 4 days, but healing is typically prolonged, with erythema lasting weeks to months depending mainly on the depth of resurfacing. Vaporization of epidermis removes actinic and pigmented lesions after resurfacing. Impressive, immediate shrinkage of the dermis occurs due to thermal denaturation of collagen. Shrinkage may or may not play some role in permanent tightening of the dermis. It’s clear that a secondary, active phase of skin tightening begins about 1 week after resurfacing, when the new epidermis has formed and dermal remodeling is underway. Histologically, a thin band of fibrosis is often seen in the upper dermis after CO2 laser resurfacing, less prominently after Erbium laser resurfacing. This may be the equivalent of a very thin and uniform scar, which is not apparent clinically. Hyperpigmentation is common in darker skin patients after laser resurfacing. Even when treated with topical bleaching agents, this can persist for 6 months or more. Post-operative wound care is essential to minimize risks of dessication, infection and scarring. Delayed porcelain-like hypopigmentation is common and appears to be permanent after aggressive CO2 laser resurfacing, especially in patients with poikiloderma or chronic bronzing due to photoaging. There is debate about the value of systemic corticosteroids and antibiotics used routinely. Performing aggressive laser resurfacing at the same time as face lifting or other potentially ischemia-inducing procedures may enhance the risk of scarring, particularly along the mandible. Facial skin heals faster and often better than neck skin; fluence and number of passes should be reduced in a controlled pattern if the neck is treated. A history of keloid scarring is generally considered a contraindication for laser resurfacing. Oral anti-herpes viral drugs should be started just before and continued for at least 10 days after laser resurfacing, particularly for patients with a history of facial, labial or oral herpes simplex. Laser resurfacing is commonly done under nerve block anesthesia, sedation with analgesia, or general anesthesia. Non-Ablative “Rejuvenation” The risks, pain and sometimes drastic change in appearance after laser resurfacing led to development of various non-ablative laser and IPL treatments for photoaging, often called non-ablative rejuvenation. The epidermis is left intact or nearly intact, while dermal wound healing mechanisms are stimulated by photothermal minor injury. Non-ablative rejuvenation has the advantage of less “down time,” pain and risk than resurfacing, but is almost always much less effective. Thus far, 585/595 nm pulsed dye lasers at low fluence, IPLs, 1064 nm Nd:YAG, 1320 nm Nd:YAG and 1450 nm diode lasers delivered with cryogen spray dynamic cooling, and 1540 Er:glass lasers are used for non ablative laser rejuvenation.26-30 Extracellular matrix proteins reminiscent of wound healing increase transiently after non-ablative rejuvenation, but the correlation between cellular/molecular responses and clinical outcome is not at all well established. A new approach called “fractional resurfacing” was recently reported that uses millions of microscopic epidermal-and-dermal columns of thermal injury at a density of approximately 200-1000/cm2 on the face. Each dot of injury is too small to be seen with the unaided eye, produced by focusing a mid-infrared laser. Healing response of the epidermis is rapid. Future Direction Lasers and intense pulsed light sources now account for a necessary, vital and growing part of dermatology. The ability to selectively and substantially “remove” vascular malformations and proliferations, leg veins, nevus of Ota, benign epidermal pigmented lesions, tattoos, unwanted hair, wrinkles and a host of skin lesions is truly remarkable. Major recent advances in technology have been made that will probably fuel progress further. Small robust solid state lasers, optical fibers, digital imaging and electro-optic technologies are rapidly making their way into dermatology. Some basic concepts have promise yet to be realized. For example the technology clearly exists to make “smart” lasers that could sense the desired endpoint in target structures, potentially aiding both efficacy and safety.

Skin & Aging is proud to bring you this latest installment in its CME series. This series consists of regular CME activities that qualify you for two category 1 physician credit hours. As a reader of Skin & Aging, this course is brought to you free of charge — you aren’t required to pay a processing fee. Lasers and intense pulsed light sources now account for a necessary, vital and growing part of dermatology. Laser technology and treatment has advanced steadily for treatment of many cutaneous conditions, including a host of vascular and pigmented lesions, wrinkles, tattoos, scars and unwanted hair during the past decade. This article reviews theory, clinical applications and potential for further progress of laser surgery in dermatology. At the end of this article, you’ll find a 10-question exam. Mark your responses in the designated area and fax page 84 to HMP Communications at (610) 560-0501. We’ll also post this course on our Web site — www.skinandaging.com. I hope this CME contributes to your clinical skills. Amy McMichael, M.D. CME Editor Amy McMichael, M.D., is Associate Professor in the Department of Dermatology, Director of the Hair Disorders Clinic and Residency Program Director at Wake Forest University Medical Center in Winston-Salem, NC. Principal Faculty: Hirotaka Akita, M.D., Ph.D., and R. Rox Anderson, M.D. Method of Participation: Physicians may receive two category 1 credits by reading the article on p. 76-83 and successfully answering the questions found on p. 83-84. A score of 70% is required for passing. Fill out the last page and submit your answers and evaluation via fax or log on to www.skinandaging.com and respond electronically. Estimated time to complete the activity: 2 hours Date of original release: June 2004 Expiration Date: June 2005 This activity has been planned and produced in accordance with the ACCME essentials. Accreditation Statement: NACCME is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Designation Statement: NACCME designates this continuing medical education activity for a maximum of two category 1 credits toward the AMA Physician’s Recognition Award. Each physician should claim only those credits that he/she actually spent in the educational activity. Disclosure Policy: All faculty participating in Continuing Medical Education programs sponsored by The North American Center for Continuing Medical Education are expected to disclose to the meeting audience any real or apparent conflict(s) of interest related to the content of their presentation. Faculty Disclosures: Drs. Anderson and Akita have disclosed that they have no significant financial relationship with any organization that could be perceived as a real or apparent conflict of interest in the contexts of the subject of his article. Learning Objectives: At the conclusion of this educational activity, the participants should be able to: • identify the major indications and uses of lasers for treatment of skin, including appropriate choices among different lasers • identify major side-effects associated with laser or filtered flashlamp treatment for vascular lesions, pigmented lesions, tattoos, hair removal and photoaged skin. Target Audience: Dermatologists, Plastic Surgeons, Internists Commercial support: None Laser technology and treatment has advanced steadily for treatment of many cutaneous conditions, including a host of vascular and pigmented lesions, wrinkles, tattoos, scars and unwanted hair during the past decade. Demand for aesthetic treatments by skin ablation (resurfacing), and more subtle non-ablative treatments, has increased. Safety and ease of using lasers and high-energy flashlamps, has improved to the point that treatment can in some settings be given by non-medical personnel. Unwanted, preventable complications and side-effects are not uncommon. This article briefly reviews theory, clinical applications and potential for further progress of laser surgery in dermatology. Light-Skin Interactions LASER is an acronym for light amplification by the stimulated emission of radiation. Lasers differ from all other light sources by emitting a combination of very intense, monochromatic (single wavelength), coherent and collimated light beams. Most lasers used in dermatology now emit high-energy pulses rather than a continuous beam. Filtered xenon flashlamps, sometimes called intense pulsed light (IPL), are an alternative to some lasers for treating vascular and pigmented lesions, fine wrinkles and for hair removal. When light enters skin, it’s absorbed and scattered. With rare exception, dermatological lasers and IPLs treat skin by mechanisms of local heating at the sites of energy absorption. Absorption of light by various structures in skin is wavelength-dependent. This allows different wavelengths to “target” different structures, and is the main reason why so many lasers and IPL wavelengths are needed to treat different conditions. Depth of light penetration is also wavelength-dependent, and depends on absorption and scattering. Over the ultraviolet and visible spectrum, penetration generally increases with increasing wavelength, from several micrometers in the ultraviolet region up to several millimeters in the red and near-infrared spectral region. Penetration depth is another major factor affecting choice of wavelength. Visible light (wavelengths 400 nm to 700 nm) absorption in skin is mainly by melanin, hemoglobin and oxyhemoglobin.1 Tattoo inks consist of sub-cellular particles implanted in the dermis that strongly absorb visible light. In the near-infrared spectrum (NIR, 700 nm to1200 nm), absorption is weakest and optical penetration depth is greatest. This combination allows for deep (full-thickness skin) treatments when high energy pulses are used. Penetration depth is also effectively greater when larger exposure spot size is used. In the mid- and far-infrared spectrum (>1200 nm), water is the dominant absorbing molecule. Non-ablative mid-infrared lasers, and ablative far-infrared lasers (erbium, CO2) are weakly or strongly absorbed by tissue water, respectively. (See “Lasers in Medicine” below, which shows the lasers used in dermatology.) Selective Photothermolysis A theory called selective photothermolysis2 (SP) is an essential concept for safe treatment using most lasers and IPLs. SP is based on two fundamental principles: • Selective absorption of light by “target” structures. • Confinement of heat to these targets, by delivery of a brief light pulse. The first of these influences appropriate choice of wavelength, while the second influences appropriate choice of pulse duration. There are additional necessary criteria, such as adequate penetration of light to the target structures, and adequate fluence (fluence equivalent to the light dose equals energy delivered per unit skin area, and is typically reported in J/cm2). Thermal relaxation time is a simple concept, defined as the time for which a target structure substantially cools by heat conduction. For pigmented targets (pigmented cells, blood vessels), the laser pulse duration should ideally be approximately equal to thermal relaxation time, which allows good heat confinement and uniform heating of the targets. A very useful approximation is that the thermal relaxation time in seconds is about equal to the square of the target’s size in millimeters. Pulses are used in SP, because heat flow from the light-absorbing targets takes time to occur. Similarly, it’s possible to selectively cool and partially protect the pigmented epidermis during laser or IPL treatment. The most sophisticated version of this is dynamic cryogen spray cooling (CSC), in which a 10 ms to 100 ms blast of -30oC liquid cryogen is sprayed on the skin surface just before arrival of a laser pulse. Cold windows held in contact with skin before and during laser or IPL exposure are also highly effective for reducing unwanted epidermal damage. Cold windows are most effective when using pulse durations that are longer than about 10 ms. Skin cooling allows safe treatment, within certain limits, of darkly-pigmented skin for vascular lesions, pigmented lesions and hair removal. Microvascular Lesions In various lesions, the target blood vessels range in size from about 20 mm (e.g. for infant port wine stains) to 2 mm (e.g. for a dilated leg vein), a 100-fold size range. The yellow pulsed dye, green KTP, near infrared Nd:YAG, diode lasers and IPLs used for treating vascular lesions range from about 0.4 ms to 200 ms pulse duration. Choosing the right combination of wavelength and pulse duration for treatment should be tailored to vessel size and depth. For treatment of superficial microvascular lesions (less than 0.3 mm target vessels, less than 2 mm deep), the green-yellow absorption bands of oxyhemoglobin are typically used. Flashlamp-pumped dye lasers operating near 585 nm, with pulse durations of 0.45 ms to about 10 ms, have become a kind of gold standard for treatment of port wine stains (PWS), ulcerated hemangiomas, scars and small telangiectases.3 A series of six to 20 treatments using fluences of 3 J/cm2 to 10 J/cm2 at 585 nm, 0.45 ms pulses, and a spot size of 2 mm to 10 mm, is necessary for removal or substantial lightening of port wine stains. Many PWS are not completely removed by this approach, a fact that may be due to depth of the lesion and/or the microanatomy of its vasculature. For increased penetration of larger or deeper vessels, spot sizes greater than 5 mm are more effective. We’ve recently begun to use 1 ms to 20 ms Nd:YAG laser (1064 nm) delivered with skin cooling at the fluence threshold for subtle, immediate darkening of the lesion based on a recent abstract report by Yang et al. This approach appears to be generally effective, but must be done with caution to avoid dermal heating and subsequent scarring. There are very strong arguments for treating PWS in early childhood.4 Hypertrophy of the lesions has not yet occurred; the lesion is much smaller in area than it will be after growth of the patient; psychosocial trauma from PWS is most limited in early childhood; the trauma of each treatment is largely forgotten before about age 1. Yellow pulsed dye lasers are often effective for verruca, angiofibromas, small telangiectases, rosacea, sebaceous hyperplasia, ulcerated hemangiomas, and to flatten and remove redness from scars and keloids.5 It is unclear whether all of these applications operate primarily by selective destruction of small vessels. Unlike the other conditions, treatment of hemangiomas and scars appears to be more effective at lower fluences (3 J/cm2 to 5 J/cm2) than at higher fluences. Pulsed dye laser (PDL) treatment often causes immediate purpura that intensifies for several days after treatment. The amount and duration of purpura from PDL have been reduced by extending pulse duration to >=10 ms, and by epidermal cooling devices.6 Treatment with green 532 nm (KTP; frequency-doubled Nd:YAG) and IPLs emitting pulses longer than about 10 ms typically causes no purpura. For this reason, other green/yellow lasers or IPLs are often preferred over PDL for treatment of vascular lesions on the face of adults, such as from rosacea. The anatomy and causes underlying dilated leg veins should be worked up prior to choice of therapy. Deep venous disease should be treated by intravenous laser therapy (IVLT), RF catheter ablation or surgery before treatment of superficial vessels is considered. Sclerotherapy and lasers are useful for treating superficial vessels that may remain after correction of deep vein reflux. Properly performed, sclerotherapy is typically more effective, less painful and has fewer side effects than laser treatment. The long-pulsed alexandrite7 or 800 nm diode laser8 is effective for small or medium sized veins at lower extremity, and the Nd:YAG laser9 is effective for leg veins as large as 3 mm in diameter. Pigmented Lesions Based on selective photothermolysis, melanosomes are ruptured with sub-microsecond laser pulses, leading to selective necrosis of pigmented cells. A wide range of short-pulsed lasers are available for this including Q-switched frequency-doubled Nd:YAG (532 nm, 10 ns, green), Q-switched ruby (694 nm, 20 ns, red), Q-switched alexandrite (755 nm, 20-50 ns, infrared) and Q-switched Nd:YAG (1064 nm, 10 ns, infrared). The same lasers are also useful for tattoo removal. Immediate whitening change of the pigmented lesion occurs after a therapeutic fluence using any of these short-pulsed lasers. This immediate whitening is thought to be due to small cavitation bubbles, and is a useful clinical sign because the whitening correlates directly with melanosome rupture and pigment cell injury.10 Q-switched ruby, alexandrite or Nd:YAG lasers are excellent for treatment of dermal melanocytic lesions such as blue nevi and nevus of Ota. Common acquired benign epidermal pigmented lesions, such as solar lentigos, labial lentigo,11 freckles and seborrheic keratosis, typically respond quite well to one or two treatments with these short-pulsed lasers. Less ideal but also effective, are a wide variety of pulsed lasers, ablative lasers and IPLs for treating common acquired epidermal pigmented lesions, as well as any other modality that superficially destroys the epidermal basal layer. In contrast, congenital epidermal lesions are typically more difficult to remove, including nevus spilus and café-au-lait macules. These have a high recurrence rate after treatment, for unknown reasons. Although melasma is a common acquired benign pigmented lesion, the efficiency of laser treatment for the dermal variant of melasma is poor, and worse hyperpigmentation often results. Despite encouraging reports,12 IPL treatment usually fails for dermal melasma also. Development of an effective, rapid treatment for dermal melasma and post-inflammatory hyperpigmentation remains a worthy challenge for future studies. For melasma, a mixture of topical bleaching agents and/or retinoid, oral vitamin C or/and tranexamic acid may be first choices for therapy. The common side effects of epidermal pigmented lesion removal by Q-switched laser are mostly transient hyper- or hypopigmentation. Hyperpigmentation occurs in about 30% to 50% of cases,13 and occasionally take about 6 months to resolve while using topical bleaching agents. The red (Q-switched ruby) and near-infrared (Q-switched alexandrite and Nd:YAG) wavelength lasers are extremely useful for treating dermal melanocytosis, such as Nevus of Ota (including Hori or Ito),14 acquired bilateral nevus of Ota-like macules,15 ectopic Mongolian spot, drug-induced hyperpigmentation,16 and traumatic and decorative tattoos.17 Permanent hypopigmentation, especially when using the Q-switched ruby laser, is seen in about 1% of cases, and may result from either inappropriately high laser fluence or from unmasking of vitiligo. Use of the Q-switched ruby laser at a low fluence (e.g., 5 J/cm2; spot size 6.5 mm) through a series of treatments can eliminate the pigmentation of nevus of Ota without laser-induced permanent hypopigmentation.14 On the other hand, the disadvantages of 1064 nm Nd:YAG laser irradiation are pinpoint bleeding after irradiation and crusting that may continue for several weeks. Congenital pigmented nevi are difficult lesions that can be associated with melanoma when the nevus is giant. Pigmentation of these lesions respond initially to Q-switched ruby laser pulses, but much of the deeper part of these lesions consist of nests of poorly-pigmented cells that remain. The use of high-fluence, longer pulse duration (0.3 ms to 1.0 ms) ruby, alexandrite or Nd:YAG lasers, appears to allow more extensive thermal damage of the nests of cells in these lesions. Efficacy of combined treatment with long-pulsed and Q-switched lasers can be impressive, and may be decided by the depth of dermal cell nests.18 Thus far there have been no reports of malignant degeneration after laser irradiation of a pigmented lesion. However, it’s necessary to follow these patients for malignant degeneration regardless of whether a laser has been used as part of therapy. Tattoo Removal The mechanism of removing a tattoo by Q-switched laser treatments is sudden heating and fracture of the intracellular ink granules that are contained by phagocytic dermal cells. Dead cells and ink are shed in part through the epidermis, but much of the ink is transported into lymphatics and, apparently, retained in regional nodes. Color of the tattoo ink is important for selecting laser wavelength(s) for treatment.19 Red ink is far better removed by green laser pulses; green ink is far better removed by red laser pulses. Yellow ink is not removed well by any of the commercially available dermatology lasers, and would be expected to respond to blue pulses. The ink of cosmetic tattoos, which often contain ferric oxide or titanium dioxide, easily and permanently turn black when exposed to Q-switched laser pulses.20 These color changes are probably due to reduction of rust-colored ferric oxide to jet black ferrous oxide and from white Ti4+ to blue Ti3+. Further treatment often removes these tattoos, but warn patients that permanent tattoo darkening is a possibility. TiO2 content is associated with poor results. Unfortunately, it is difficult to treat many colors with a single wavelength, so more than one laser system is usually needed for multi-colored, modern artistic tattoos. The number of treatments for tattoo removal is highly variable. Amateur tattoos made with carbon (India ink, graphite) are most effectively removed by laser treatment. For most tattoos, six to eight treatments are required, however, up to 20 treatments are sometimes required, given at 4 to 8 week intervals. Occasionally, tattoo ink simply cannot be cleared, especially with TiO2 tattoos, white, yellow and some green colors. Therefore, CO2 laser vaporization, dermabrasion, excision and grafting can be considered as alternative treatments. Scarring, often hypertrophic scars or keloids, may be produced by these treatments. The risk of scarring by Q-switched laser treatment of tattoo is approximately 5% or less, and usually limited to a portion of the treated area. The more common side effects of tattoo removal by Q-switched laser are transient pigmentary and textural changes. Hyperpigmentation is usually mild and transient, and can be treated with topical bleaching agents. Hypopigmentation is also usually transient, but depigmentation occurs in about 1% of cases and is often permanent. A more serious complication of treatment involves a systemic allergic or localized granulomatous tissue reaction to tattoo ink particle antigens.21 Some patients may suffer fever, joint pain, chills, and/or myalgia after each laser treatment. In our clinical experience, treatment with oral antihistamines or corticosteroids before laser treatment is useful in these cases. Hair Removal In recent years, the use of lasers and IPLs to remove unwanted pigmented hair has generated much interest since the first clinical study using the long-pulsed ruby laser for hair removal was reported by Grossman et al.22 Before the advent of melanin-based laser hair removal, Q-switched Nd:YAG laser used after application of carbon suspension was used for temporary hair removal. The primary target for hair removal is melanin in the hair shaft, hair follicle epithelium and matrix. It’s difficult or impossible to permanently remove white hair using light. Attempts to use hair dyes or applications of melanin appear to have little benefit, probably due to lack of sufficient penetration into the hair follicle. Because light must pass through the pigmented epidermis before reaching hair follicles, laser hair removal poses a kind of “contest” between the effects of light absorption by melanin in the epidermis versus in the hair follicles. It’s generally easier, very effective and safe to remove dark coarse hair in a person with fair skin. If the patient has darkly pigmented skin, safe and effective removal of pigmented hair requires proper choice of wavelength, pulse duration, and active cooling of the epidermis by cryogen spray, cold sapphire or other methods. Fine hair is more difficult to remove permanently. The most useful wavelengths for hair removal are in the red or near-infrared because the combination of sufficient optical absorption by hair melanin and depth of penetration into dermis is best in the 600 nm to 1100 nm spectral region. A large number of specific lasers and IPL systems are sold for hair removal, with a range of safety, efficacy, versatility for different skin types, speed of treatment, cost and reliability. Thus far, the long-pulsed ruby (694 nm), long-pulsed alexandrite (755 nm),23 diode (800 nm)24 and long-pulsed Nd:YAG (1064 nm)25 lasers have been cleared by FDA for permanent hair reduction. A range of pulse duration from about 3 ms to 300 ms is available among these various lasers. IPLs filtered to emit over all or part of this spectral range are also available, and utilize the same basic mechanisms as lasers for hair removal. Clinically, the optimal choice of device, wavelength and pulse duration is governed by the patient’s hair color, hair diameter and skin color. In practice, a versatile device and approach is needed. Ruby lasers have largely been replaced by the other devices. The most popular device for laser hair removal is a pulse duration-tunable (5 ms to 100 ms) 800 nm diode laser system with contact cooling provided by a cold sapphire window. For coarse diameter hair, pulse durations as long as about 300 ms are about as effective as shorter pulses. When contact cooling is used, long pulses allow the largest available safety factor for treating dark skin. A longer wavelength is also generally safer for dark skin. Nd:YAG lasers delivered with either cryogen spray or contact cooling are generally the safest devices for treating dark skin. In contrast, fine and/or lightly pigmented hair is poorly treated with long pulses and/or long wavelengths. Permanent reduction of fine, lightly-pigmented hair can best be achieved with pulse durations of 3 ms to 20 ms, using wavelengths from about 600 nm to 800 nm. Most IPL, ruby and alexandrite laser systems currently available achieve this combination. Side Effects of Hair Removal Hazards and side-effects from laser or IPL hair removal can be severe. All of these devices are designed to destroy melanin-pigmented tissue deep within the dermis. The retina and choroids layers of the eye contain the highest concentration of melanin in the body, and can easily be permanently damaged by any of the IPLs or lasers used for hair removal. It’s possible to injure the eye when treatment is done anywhere inside the bony orbits, even when a protective eye shield is used. Permanent eye injury from laser or IPLs used for hair removal can present as immediate or delayed malformation of the pupil (pear or teardrop shape), visual impairments, or uveitis. Another potentially horrifying side effect for patients is hair growth stimulation. When this occurs, laser or IPL treatment converts fine hairs to coarse dark hairs by unknown mechanisms. Further laser or IPL treatment is sometimes effective for permanently reducing these stimulated hairs. In our experience, laser or IPL-induced hair growth stimulation occurs most frequently on the face and neck in women from Mediterranean, near east or Indian subcontinent heritage, who typically have an ill-defined hairline and pigmented vellus hairs on the face when examined closely with a hand lens. The best clinical approach is probably to counsel patients with these traits, about the high risk for hair stimulation, and to use other methods. Skin Resurfacing Controlled ablation of the epidermis and upper dermis with lasers, is called laser skin resurfacing. The lasers for skin resurfacing emit far infrared wavelengths that are strongly absorbed by water. Rapid heating and removal of a thin layer of tissue, leaving a thin layer of residual thermal damage, occurs with each “pass” during laser resurfacing. As in selective photothermolysis, a short pulse or dwell time is used (dwell time is the time of exposure at a point when a focused beam is scanned) to minimize heat conduction during the vaporarization process. CO2 lasers (10,600 nm) deposit energy in the upper 20 mm of skin, and erbium lasers (2940 nm) deposit energy in the upper 5 mm of the skin, due to strong absorption by water. After ablation, a new epidermis forms within about 4 days, but healing is typically prolonged, with erythema lasting weeks to months depending mainly on the depth of resurfacing. Vaporization of epidermis removes actinic and pigmented lesions after resurfacing. Impressive, immediate shrinkage of the dermis occurs due to thermal denaturation of collagen. Shrinkage may or may not play some role in permanent tightening of the dermis. It’s clear that a secondary, active phase of skin tightening begins about 1 week after resurfacing, when the new epidermis has formed and dermal remodeling is underway. Histologically, a thin band of fibrosis is often seen in the upper dermis after CO2 laser resurfacing, less prominently after Erbium laser resurfacing. This may be the equivalent of a very thin and uniform scar, which is not apparent clinically. Hyperpigmentation is common in darker skin patients after laser resurfacing. Even when treated with topical bleaching agents, this can persist for 6 months or more. Post-operative wound care is essential to minimize risks of dessication, infection and scarring. Delayed porcelain-like hypopigmentation is common and appears to be permanent after aggressive CO2 laser resurfacing, especially in patients with poikiloderma or chronic bronzing due to photoaging. There is debate about the value of systemic corticosteroids and antibiotics used routinely. Performing aggressive laser resurfacing at the same time as face lifting or other potentially ischemia-inducing procedures may enhance the risk of scarring, particularly along the mandible. Facial skin heals faster and often better than neck skin; fluence and number of passes should be reduced in a controlled pattern if the neck is treated. A history of keloid scarring is generally considered a contraindication for laser resurfacing. Oral anti-herpes viral drugs should be started just before and continued for at least 10 days after laser resurfacing, particularly for patients with a history of facial, labial or oral herpes simplex. Laser resurfacing is commonly done under nerve block anesthesia, sedation with analgesia, or general anesthesia. Non-Ablative “Rejuvenation” The risks, pain and sometimes drastic change in appearance after laser resurfacing led to development of various non-ablative laser and IPL treatments for photoaging, often called non-ablative rejuvenation. The epidermis is left intact or nearly intact, while dermal wound healing mechanisms are stimulated by photothermal minor injury. Non-ablative rejuvenation has the advantage of less “down time,” pain and risk than resurfacing, but is almost always much less effective. Thus far, 585/595 nm pulsed dye lasers at low fluence, IPLs, 1064 nm Nd:YAG, 1320 nm Nd:YAG and 1450 nm diode lasers delivered with cryogen spray dynamic cooling, and 1540 Er:glass lasers are used for non ablative laser rejuvenation.26-30 Extracellular matrix proteins reminiscent of wound healing increase transiently after non-ablative rejuvenation, but the correlation between cellular/molecular responses and clinical outcome is not at all well established. A new approach called “fractional resurfacing” was recently reported that uses millions of microscopic epidermal-and-dermal columns of thermal injury at a density of approximately 200-1000/cm2 on the face. Each dot of injury is too small to be seen with the unaided eye, produced by focusing a mid-infrared laser. Healing response of the epidermis is rapid. Future Direction Lasers and intense pulsed light sources now account for a necessary, vital and growing part of dermatology. The ability to selectively and substantially “remove” vascular malformations and proliferations, leg veins, nevus of Ota, benign epidermal pigmented lesions, tattoos, unwanted hair, wrinkles and a host of skin lesions is truly remarkable. Major recent advances in technology have been made that will probably fuel progress further. Small robust solid state lasers, optical fibers, digital imaging and electro-optic technologies are rapidly making their way into dermatology. Some basic concepts have promise yet to be realized. For example the technology clearly exists to make “smart” lasers that could sense the desired endpoint in target structures, potentially aiding both efficacy and safety.