Laser and light therapy for cutaneous hyperpigmentation

INTRODUCTION — Lasers and light-based modalities are used to treat a wide variety of disorders characterized by the presence of cutaneous hyperpigmentation via photothermal, photomechanical, and ablative mechanisms.

Successful and safe clinical application of lasers and light-based devices requires thorough knowledge of the principles that govern the interaction between light and skin. Selection of appropriate light-based therapy is based on knowledge of lesion type and histopathologic characteristics.

This article will review principles of laser and light-based therapy for hyperpigmented skin lesions, lasers used for this indication, and therapeutic options for select disorders of hyperpigmentation. The general principles of medical lasers and the treatment of cutaneous lesions with laser and intense pulsed light are reviewed elsewhere. (See "Basic principles of medical lasers" and "Principles of laser and intense pulsed light for cutaneous lesions".)

PRINCIPLES — The use of laser and intense pulsed light for cutaneous hyperpigmentation is based upon clinical application of the theory of selective photothermolysis, which describes the mechanism by which light can be used to exert specific effects on the skin [1]. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Selective photothermolysis'.)

The basic principles of selective photothermolysis are as follows [1]:

●The wavelength of light used is preferentially absorbed by the target molecule (also known as a chromophore).

●Light must be delivered within a period of time (pulse duration) that limits damage to the target and adjacent cutaneous structures.

●The light energy transferred to the target chromophore must be sufficient to exert the desired therapeutic effect while minimizing damage to adjacent tissue.

In the majority of cutaneous disorders of hyperpigmentation, melanin is the chromophore targeted during treatment.

Light wavelength — Strong light absorption by melanin occurs in the ultraviolet range of the electromagnetic spectrum. In general, the affinity of melanin for light decreases progressively as wavelengths rise (figure 1). One might interpret this to mean that lasers emitting ultraviolet light or short wavelengths of visible light are preferred for the treatment of hyperpigmentation. Preferential absorption of melanin, however, requires consideration of competition with hemoglobin (a different chromophore with peak light absorption between 400 and 600 nm) and limited penetration depth of shorter wavelengths.

The ideal wavelengths of light for absorption by melanin in the skin, therefore, fall between 600 and 1100 nm. The lasers and light sources most commonly used for the treatment of cutaneous hyperpigmentation, such as the quality-switched (QS) lasers, nonablative pulsed lasers, and intense pulsed light, emit wavelengths within this range. Ablative lasers and fractionated lasers, in contrast, are not as selective in treating hyperpigmented skin lesions because the target chromophore in skin is water, not melanin. Wavelengths between 1550 and 10,600 nm are strongly absorbed by water and are utilized for ablative and fractional therapy. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Wavelength'.)

Generally, the depth of light penetration into the skin increases with increasing laser wavelength. Water-targeting ablative lasers are an exception to this observation, as the strong absorption of light by water in the skin limits the amount of light transmitted to the dermis. Thus, knowledge of the site of abnormal melanin deposition within the skin is critical for device selection. Lentigines, for example, are characterized by increased melanin in the epidermis, while other skin diseases are characterized by dermal hyperpigmentation (see 'Indications' below). Usually, lasers with relatively short wavelengths (eg, 532 nm frequency-doubled QS neodymium:yttrium aluminum garnet [Nd:YAG] lasers) are well suited for the elimination of epidermal melanin, and lasers with longer wavelengths (eg, 755 nm QS alexandrite and 1064 nm QS Nd:YAG lasers) are employed for the treatment of deeper melanin deposits. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Wavelength'.)

Pulse duration — The pulse duration, or length of time over which light is delivered, is an additional factor that significantly impacts the efficacy of treatment. A photothermal effect occurs when light emitted from a laser or intense pulsed light device is absorbed by the target chromophore (eg, melanin): Light energy is converted to heat and leads to thermal damage of the target tissue. The general concept is to heat the target long enough to damage the target but not so long that the heat spreads to damage surrounding structures. Smaller objects take less time to heat than larger objects. Therefore, shorter pulse durations are used for smaller objects, and longer pulse durations are used for larger targets. Typically, the delivery of light in a time period that is shorter than a target's thermal relaxation time (defined as the time necessary for a target to cool by 50 percent) allows for the destruction of the target while limiting the transfer of heat to adjacent tissues.

Melanin, the primary pigment in skin, is synthesized and stored in melanosomes, which are very small structures, approximately 500 nm in width. The thermal relaxation time of a single melanosome varies between 10 and 500 ns; therefore, lasers with very short pulse durations are used to treat most pigmented lesions. The pulse duration of the QS lasers commonly used for the treatment of pigmented lesions are in the nanosecond and picosecond range.

Extending the pulse duration can be beneficial for the treatment of larger structures in the skin. Large structures have longer thermal relaxation times and lose heat more slowly than small structures. Long pulse durations thus lead to relatively greater accumulation of heat within large structures. In this way, larger structures (eg, a large nest of melanocytes in a nevus) are preferentially destroyed, while smaller, unintended targets that also contain melanin or other light-absorbing chromophores are spared. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Pulse duration'.)

The selective destruction of pigment using light energy that is converted to heat is called a photothermal effect. Lasers can also remove melanin via a photomechanical effect (also referred to as a photoacoustic effect). In this setting, high-energy pulses are delivered rapidly and absorbed by melanin to create shock waves within melanosomes, resulting in melanosome rupture. The QS lasers with nanosecond and picosecond pulse widths take advantage of this mechanism. (See 'Quality-switched nanosecond lasers' below.)

Fluence — Fluence (the amount of light energy delivered per unit of space) is a key determinant for achieving a desired clinical effect. Fluence settings that are too low result in inadequate treatment. Fluence settings that are too high create excessive heat that could lead to adverse effects, such as dyspigmentation and scarring. Exceedingly high fluence settings are particularly detrimental in individuals with dark skin pigmentation and may result in hyperpigmentation or permanent hypopigmentation. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Fluence'.)

DEVICES — A broad range of light-emitting devices are available for the treatment of pigmented skin lesions. It is important to consider the wavelength and pulse duration unique to a particular device with each clinical scenario.

Quality-switched nanosecond lasers — Traditional quality-switched (QS) lasers deliver exceptionally high energy laser pulses with pulse durations in the nanosecond range. When light emitted in this fashion is absorbed by melanin, acoustic shock waves form within melanosomes to break up the melanocyte and melanosomes. QS lasers also operate via photothermal effects. (See 'Principles' above.)

QS lasers are available in a variety of wavelengths, including the 694 nm QS ruby laser, 755 nm QS alexandrite laser, 1064 QS neodymium:yttrium aluminum garnet (Nd:YAG) laser, and 532 nm frequency-doubled QS Nd:YAG laser.

Picosecond lasers — A picosecond is one-trillionth of a second or 10^-12 seconds. Picosecond lasers are able to deliver energy to tissue during a pulse duration that is less than 1 nanosecond. This extremely short pulse duration induces more of a photoacoustic than photothermal effect on targeted tissue. As a result, picosecond devices can treat smaller particles than nanosecond lasers, while using much less energy, therefore achieving better confinement of thermal damage. Picosecond lasers exist in several wavelengths, including 532 nm, 755 nm, and 1064 nm. As more studies become available and their parameters become optimized, these lasers may become preferred over their QS nanosecond counterparts [2]. Studies demonstrate greater clearance of tattoo pigment by picosecond lasers compared with nanosecond lasers, with no increase in adverse effects [3]. Picosecond lasers have also shown to be beneficial in the treatment of acne scarring, rhytids, and photoaging [3]. In addition, many picosecond laser devices are being fractionated and used to treat benign, superficial hyperpigmentation (eg, melasma, postinflammatory hyperpigmentation) [4,5].

Long-pulsed lasers — Lasers with pulse durations in the millisecond range are also useful for the treatment of pigmented lesions. The relatively slow delivery of light energy facilitates the treatment of larger targets in the skin. (See 'Principles' above and "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Large versus small structures'.)

Long-pulsed 694 nm ruby, 755 nm alexandrite, and 1064 nm Nd:YAG lasers have been used for the treatment of a wide range of pigmented lesions.

Traditional ablative lasers — Traditional ablative lasers eliminate superficial skin pigmentation in a nonselective manner through the vaporization of the epidermis and superficial dermis. The 10,600 nm carbon dioxide (CO₂), 2940 nm erbium:yttrium aluminum garnet (Er:YAG), and 2790 nm yttrium scandium gallium garnet (YSGG) lasers target the chromophore of water and can be used to ablate pigment-containing skin. (See "Ablative laser resurfacing for skin rejuvenation", section on 'Traditional ablative lasers'.)

Fractionated lasers — Nonablative fractionated lasers (eg, 1550 nm erbium-doped laser, 1927 nm thulium fiber laser) and ablative fractionated lasers (eg, 10,600 nm CO₂, 2940 nm Er:YAG, 2790 nm YSGG) create microthermal zones, which are numerous microscopic vertical columns of thermal damage extending from the epidermis to the dermis (figure 2). The subsequent wound-healing response leads to repopulation of the damaged epidermis and remodeling of the dermis, resulting in normalization of the treated tissue. The efficacy of fractional lasers in hyperpigmented skin disorders is thought to arise from the elimination of epidermal and dermal melanin through a compromised dermal-epidermal junction (the "melanin shuttle" hypothesis) [6]. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Fractionated lasers' and "Ablative laser resurfacing for skin rejuvenation", section on 'Ablative fractional lasers'.)

Intense pulsed light — Intense pulsed light sources are nonlaser devices that emit polychromatic light ranging from 515 to 1200 nm. Filters can be used to limit the range of emitted wavelengths. Wavelengths at the shorter end of this range are more readily absorbed by melanin and are favored for the treatment of cutaneous hyperpigmentation. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Intense pulsed light'.)

PATIENT EVALUATION — Patients must be evaluated for factors that may affect treatment selection and response, such as lesion characteristics, baseline skin color, and risk factors for adverse events:

●Lesion characteristics – Selection of the most appropriate laser device and treatment parameters requires full understanding of the skin disorder, including depth of pigmentation within the skin, origin of pigmentation (eg, melanin, hemosiderin, foreign body), and size of the target particle. Generally, longer wavelengths are used on deeper targets, and shorter pulse durations are used on smaller targets.

Depending on the cutaneous disorder, pigment can be located in the epidermis, papillary dermis, or reticular dermis. The selected laser must emit the appropriate wavelength to reach the site of pigmentation. Melasma, for example, may present with epidermal or dermal pigment deposition; therefore, examination with a Wood's lamp prior to treatment can be useful for estimating the depth of pigmentation (see "Melasma: Epidemiology, pathogenesis, clinical presentation, and diagnosis", section on 'Diagnosis'). A small (eg, 2 mm) punch biopsy can also help determine the location of pigment on histopathology but is typically avoided due to scarring.

●Patient skin color – Melanin is most often the target chromophore in the treatment of cutaneous hyperpigmentation, and as such, melanin that is normally distributed in the epidermis may be adversely affected during treatment. This risk of damage to normal melanin is greatest when epidermal melanin is in abundance, such as in individuals with baseline dark skin pigmentation (eg, Fitzpatrick skin phototype IV to VI (table 1)) and, to an even greater extent, in individuals with tanned skin.

In general, treatment with lasers targeting melanin should be avoided until a tan fades completely. Additional caution is necessary for individuals with dark baseline skin pigmentation. Treatment of a small, inconspicuous area (a test spot) prior to treatment of a larger area is recommended. Moreover, lower fluence settings and lasers with longer wavelengths (eg, 1064 nm quality-switched [QS] neodymium:yttrium aluminum garnet [Nd:YAG]) are preferred, as they minimize damage to epidermal pigment.

●Risk for adverse outcomes – The risk of treatment-induced scarring should be discussed thoroughly with all patients, particularly those with a history of postinflammatory hyperpigmentation or keloidal or hypertrophic scar formation. Though it was once widely believed that laser therapy should not be performed for at least six months after treatment with isotretinoin due to increased risk for poor wound healing, two 2017 systematic reviews found insufficient data to delay fractional ablative and nonablative laser in patients currently receiving or having recently completed isotretinoin therapy [7,8].

Patients with a history of parenteral gold therapy should not be treated with QS lasers, as localized chrysiasis, manifesting as permanent skin discoloration, may occur [9].

●Possibility for melanocytic atypia – Benign and atypical melanocytic lesions cannot always be easily distinguished on clinical examination. Lesions that exhibit any features concerning for an atypical or malignant melanocytic disorder should be biopsied prior to treatment.

Adverse effects, such as permanent hypopigmentation, hyperpigmentation, and scarring, as well as ineffective results, may occur even when laser or intense pulsed light therapy is performed appropriately. Patients should be well informed of the various potential outcomes of treatment and associated risks prior to proceeding with therapy. An informed consent document must be signed prior to any procedure. Documenting lesions with photographs prior to treatment is greatly encouraged.

INDICATIONS — Multiple disorders of cutaneous hyperpigmentation can be improved with laser or intense pulsed light therapy. A select group of disorders characterized by epidermal, dermal, and mixed epidermal and dermal pigmentation is reviewed below.

Epidermal pigmented lesions — Lentigines, café-au-lait macules (CALM), and Becker's nevus are all characterized by increased melanin in the epidermis and can be treated with light-emitting devices.

Lentigines — Lentigines are small, well-circumscribed, pigmented macules characterized by melanocyte proliferation in the basal layer of the epidermis (picture 1). Various clinical subtypes exist, including solar lentigines, lentigo simplex, and labial melanotic macules. Lentigines may also occur in association with genetic syndromes. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Lentigo'.)

Multiple lasers are effective for the treatment of lentigines [10]. Continuous wave carbon dioxide (CO₂) and argon lasers were among the initial lasers used for pigment disorders and ablate the entire epidermis. These devices are no longer used due to an unacceptably high risk for adverse effects [11]. Due to the superficial location of pigment in lentigines (epidermis), lasers with relatively short wavelengths are well suited for treatment.

Quality-switched (QS) nanosecond lasers are frequently employed for the treatment of lentigines. The 694 nm QS ruby, 755 nm QS alexandrite, and 532 nm frequency-doubled QS neodymium:yttrium aluminum garnet (Nd:YAG) lasers have yielded excellent results. Treatment with a frequency-doubled Nd:YAG laser was superior to liquid nitrogen cryotherapy in a small randomized trial [12], and benefit of QS lasers has been documented in small case series and uncontrolled studies [13-18]. Complete clearing of lesions can often be attained with two to three treatments (picture 2A-B).

Fractionated picosecond devices (diffractive lens array) have also been used effectively in the treatment of benign epidermal pigmentation in all skin types with minimal to no significant downtime [3-5]. With a diffractive lens, 10 percent of the surface area receives 70 percent of the energy, which creates a tiny, plasma-type reaction in the epidermis or superficial dermis. This in turn induces new collagen and elastin production to improve photodamaged skin.

In the authors' experience, lentigines rarely recur after complete clearance. Partially resolved solar lentigines, however, may darken with subsequent ultraviolet light exposure. Additionally, the development of new solar lentigines in areas of actinically damaged skin is common.

We typically use the following laser settings when treating lentigines with QS lasers:

●694 nm QS ruby – 3 to 6 J/cm², 5 to 6.5 mm spot size

●755 nm QS alexandrite – 3 to5 J/cm², 4 mm spot size

●532 nm frequency-doubled QS Nd:YAG – 0.7 to 2.5 J/cm², 3 mm spot size

●755 nm picosecond with focus array lens – 0.71 J/cm², 6 mm spot size

Other options for the treatment of lentigines include intense pulsed light devices [19-22] and pulsed dye lasers used with compression handpieces [19,23-27]. Unlike QS lasers, which target individual lentigines, these devices can be utilized to treat large areas, such as an entire cosmetic unit or the entire face, and offer an excellent option for patients with diffuse lentigines of the face.

Fractionated lasers offer another excellent option for the treatment of dyschromia related to cutaneous photodamage, in which solar lentigines are often a prominent manifestation. An uncontrolled study of 50 patients with facial and nonfacial signs of photodamage (including dyspigmentation) found improvement in photodamage following three treatment sessions with a 1550 nm erbium-doped fractionated laser (six to eight passes, 8 mJ/cm², 250 microscopic treatment zones [MTZs]) [28]. The subsequently developed 1927 nm thulium fiber fractionated laser, which has a higher affinity for water than the 1550 nm fractionated laser, is an excellent option for the treatment of lentigines, particularly in patients also seeking improvement in skin texture. In an uncontrolled study of nine patients with nonfacial photodamage treated with this laser, lentigines were significantly improved [11].

A 2010 consensus panel of experts released recommendations for the use of the 1550 nm erbium-doped fractionated laser that included a protocol for the treatment of lentigines. Three to five treatments performed one month apart with energy settings between 10 to 20 mJ and treatment levels of 7 to 11 (total density of 1576 to 2704 MTZ/cm² at eight passes) were recommended for patients with skin phototype I to III (table 1) [29]. Lower energy settings of 4 to 6 were recommended for patients with darker skin pigmentation. The longevity of treatment effect after fractionated laser therapy is uncertain [28].

Cafe-au-lait macules — Café-au-lait macules (CALM) are sharply demarcated light tan to dark brown macules that may occur in the presence or absence of an associated syndrome (picture 3A-B). Histologically, lesions demonstrate increased melanin within the epidermis and giant melanosomes. An increased number of melanocytes is occasionally detected. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Café-au-lait macule'.)

The response of CALM to laser treatments is variable. Clearing of pigment is often uneven, and recurrence within months or years is frequent. Retrospective and uncontrolled studies of the use of QS ruby, QS alexandrite and QS Nd:YAG lasers have yielded inconsistent results, and complete clearance of CALM with these interventions is uncommon [14,30,31]. In one series of 22 patients with pigmented skin lesions (including 12 patients with CALM) treated with a QS ruby laser and followed for an average of 14 months, the four patients with the best responses in CALM achieved only 50 to 75 percent clearance, and 50 percent of all patients with CALM exhibited repigmentation within six months [32]. Although a prospective uncontrolled study evaluating a low-fluence 1064 nm QS Nd:YAG laser found more than 50 percent clearance in 29 of 39 CALM (74 percent) in 32 patients [33], complete clearance occurred in only 12 (31 percent). Clearance of CALM with an ablative erbium:yttrium aluminum garnet (Er:YAG) laser has been reported in one patient [34]. Given the inconsistent results and high rate of recurrence, the authors do not generally treat CALM with lasers.

Becker's nevus — Becker's nevus is an organoid hamartoma that typically presents as a unilateral, hyperpigmented, and hypertrichotic plaque on the trunk or shoulder. Histologically, there is an increased number of melanosomes in keratinocytes and a normal to slightly increased number of epidermal melanocytes. (See "Benign pigmented skin lesions other than melanocytic nevi (moles)", section on 'Becker nevus'.)

Overall, laser treatment of Becker's nevi has not been shown to predictably and reproducibly improve Becker's nevi. Given limited data and the often incomplete response, the authors generally do not treat Becker's nevi in their clinic.

Lasers that have been reported to be moderately effective for Becker's nevus include long-pulsed ruby, long-pulsed alexandrite, 2940 nm Er:YAG, and fractional lasers. Examples of efficacy data include:

●Long-pulsed ruby and long-pulsed alexandrite lasers may reduce both pigment and hair. In an uncontrolled study of 11 patients with skin phototype III to V (table 1), treatment with 2 to 12 sessions with a long-pulsed (3 ms) alexandrite laser (20 to 25 J/cm², spot size 15 to 18 mm) led to more than 75 percent improvement in pigmentation in two patients (18 percent) and more than 50 percent improvement in five patients (45 percent) [35]. Hair density was reduced in all patients in the study. Improvement in pigment and hair in a Becker's nevus after treatment with a long-pulse ruby laser also has been reported in one patient [36].

●The effects of an Er:YAG laser are reported in a prospective comparative study of 22 patients with Becker's nevus and skin phototypes ranging from II to IV [37]. The study, which compared the efficacy of a single treatment with a 2940 nm Er:YAG laser (single pass, 28 J/cm², 3 mm spot size) to three treatment sessions with a 1064 nm QS Nd:YAG laser (10 J/cm², 3 mm spot size), found that in 6 out of 11 patients treated with the Er:YAG laser, complete clearance of hyperpigmentation persisted for at least two years after treatment. In contrast, only 1 out of 11 patients treated with the QS Nd:YAG laser had greater than 50 percent improvement in hyperpigmentation after two years. Hair growth was not affected in either group.

●A randomized, single-blind, split-lesion trial of 11 patients with Becker's nevus (skin types II to V) found significantly greater improvement in hyperpigmentation in the sides of lesions treated with one to three sessions with an ablative 10,600 nm CO₂ fractionated laser (4 passes, 10 mJ per microbeam) compared with the sides that did not receive laser therapy [38]. Treatment with a nonablative 1550 nm erbium-doped fiber fractionated laser (8 to 10 passes, 6 to 10 mJ, 250 to 254 MTZs/cm² per pass) has also been associated with more than 75 percent improvement in hyperpigmentation in two patients [39]. Improvement in hypertrichosis did not occur.

Although partial improvement in a Becker's nevus after treatment with a 694 nm QS ruby and a 532 nm QS frequency-doubled Nd:YAG laser has been reported in one patient [30], these lasers are not effective for hypertrichosis, and up to 50 percent of lesions may recur within six months [32].

Ephelides (freckles) — Ephelides (also known as freckles) are small, light brown macules that develop in areas of sun-exposed skin. Histopathologically, these lesions demonstrate increased epidermal melanin. The number of melanocytes is normal.

While the authors' experience indicates that QS alexandrite lasers, QS ruby lasers, picosecond alexandrite and potassium titanyl phosphate (KTP) lasers, and intense pulsed light devices are all effective for the treatment of ephelides, studies focused on laser therapy for ephelides are limited. In a Korean series of 197 patients treated with a QS alexandrite laser (7 J/cm², 3 mm spot size), 64 percent of patients had greater than 75 percent clearance of treated lesions after a single treatment, and 100 percent had clearance after an average of 1.5 treatments [40]. Postinflammatory dyspigmentation occurred in 10 patients and resolved within several months. Recurrences were common, occurring in 28 patients (14 percent) within one year. However, recurrent lesions responded well to retreatment.

Three to eight treatments with a quasi-continuous 532 nm frequency-doubled Nd:YAG administered every 4 to 12 weeks also was effective for ephelides in a study that included 14 patients with ephelides (skin phototype IV (table 1)) [41]. Greater than 50 percent improvement occurred in 10 out of 14 patients (71 percent). Recurrence occurred within two years in 4 out of 10 patients who achieved 50 percent improvement.

Compared with pulsed lasers, quasi-continuous lasers have an increased risk for adverse effects. Transient hypopigmentation, mild textural changes, and hyperpigmentation occurred in 25, 15, and 10 percent of patients, respectively [41].

Dermal lesions — Melanocytic nevi, nevus of Ota, and postinflammatory hyperpigmentation are characterized by excess pigment that is primarily localized in the dermis.

Melanocytic nevi — The standard of care for the removal of nevi is surgical excision. Treatment of nevi with laser therapy, however, can be considered for the cosmetic removal of benign nevi in locations in which an excisional scar is undesirable. Laser treatment of nevi is controversial due to theoretical concerns regarding the promotion of malignant transformation of melanocytes. A study of eight patients in which biopsy specimens were taken from treated sites an average of 4.75 years after treatment with a ruby laser (mean period 4.75 years) found no evidence for malignant changes in these patients [42].

Laser treatment should only be performed on nevi that lack clinical signs of atypia, and if any signs of atypia are present, a biopsy should be performed prior to treatment. In general, laser treatment of nevi should be avoided in patients with personal histories of melanoma or who have first-degree relatives with melanoma. (See "Melanoma: Epidemiology and risk factors", section on 'Personal history of melanoma'.)

Nevi that are predominantly localized to the epidermis and superficial dermis, such as junctional or slightly raised compound nevi (picture 4A-B) have been successfully treated with 694 nm QS ruby, 755 nm QS alexandrite and 1064 nm QS Nd:YAG lasers in small uncontrolled studies [43-45]. Since some nevus cells typically remain, recurrence is possible [43,45].

Congenital melanocytic nevi often extend into the deep reticular dermis, and repigmentation is likely to occur following laser treatment (picture 5) [46-49]. Treatment with a normal-mode ruby laser, which has a longer pulse duration than QS lasers (and, therefore, may be better suited for the treatment of the deep, large nests of melanocytes seen in congenital nevi), was effective for significantly improving the appearance of congenital nevi in a series of three patients for at least 18 to 39 months [50]. Combining therapy with a normal-mode and a QS ruby laser may offer additional benefit [51]. Ablative resurfacing with CO₂ or Er:YAG lasers has been used for the treatment of melanocytic nevi, but these procedures carry a risk for significant scarring [49,52].

A retrospective study of 67 patients with congenital melanocytic nevi treated with either laser (pigmentation and/or ablative) alone or partial excision followed by laser found that 20 of 52 patients treated with lasers alone achieved near total clearance of pigmentation [53]. However, repigmentation was common among patients who were followed for at least three years, occurring in 5 of 11 patients (46 percent) who achieved near total clearance and 11 of 23 patients (48 percent) with any level of clearance. Repigmentation occurred an average of four years from the initial laser treatment. Combining laser therapy with excision was associated with greater improvement, as assessed via the Investigator's Global Assessment score, fewer laser treatments, and shorter treatment periods.

Nevus of Ota — Nevus of Ota is a dermal melanocytic hamartoma that presents with blue-brown patches in the distribution of the first and second branches of the trigeminal nerve (picture 6). Histology shows dendritic melanocytes within the papillary and reticular dermis.

QS lasers have been the most common lasers used for the treatment of nevus of Ota. The beneficial effects of treatment have been documented in multiple case series and uncontrolled studies [10,54,55]. The response to treatment ranges from lesion lightening to complete clearance, and three or more treatment sessions are often necessary.

Data are limited on the comparative efficacy of specific QS lasers for nevus of Ota, and the relative efficacy of these lasers remains uncertain. One retrospective study of 94 patients found that estimates of the dermal melanin fraction were significantly lower after treatment with a 694 nm QS ruby laser compared with treatment with a 1064 nm QS Nd:YAG laser at similar fluence settings (7 to 10 J/cm²) [56]. In addition, a prospective split-lesion study of 40 patients found that treatment with a 1064 nm QS Nd:YAG laser (7 to 9 J/cm², 2 mm spot size, 6 ns pulse duration) was superior to a 755 nm alexandrite (6 to 9 J/cm², 2 mm spot size, 75 ns pulse duration) for lesion lightening [57]. Complication rates were not statistically different (4 with QS alexandrite versus 2 with QS Nd:YAG). However, the results of another split-lesion study suggested that treatment with the QS Nd:YAG laser may be better tolerated [58].

Picosecond devices have emerged as another treatment option for nevus of Ota, and some data suggest advantages over QS laser treatment [59,60]. A split-lesion trial in which 56 patients with nevus of Ota received treatment with a picosecond alexandrite laser on one randomly selected side of a lesion and a QS alexandrite laser on the contralateral side found that picosecond laser treatment was associated with better clearance with fewer treatment sessions, less severe pain, and a lower risk for postinflammatory hyperpigmentation and hypopigmentation compared with QS laser treatment [2].

Responses to treatment are usually maintained over time. Repigmentation occurs in occasional patients [61].

The utility of fractional lasers for nevus of Ota remains to be determined. One lesion refractory to treatment with a 1064 nm QS Nd:YAG laser resolved after two treatments with a 1440 nm fractionated Nd:YAG laser [62].

We typically treat nevus of Ota with QS ruby, QS alexandrite, or 1064 nm QS Nd:YAG lasers, and picosecond lasers.

Postinflammatory hyperpigmentation — Postinflammatory hyperpigmentation represents acquired hypermelanosis of the skin that can develop following any cutaneous injury or inflammation. This disorder occurs most commonly in individuals with moderately or deeply pigmented skin (skin phototype IV to VI (table 1)). The excess pigment may be present in both the epidermis and dermis.

Spontaneous improvement in postinflammatory hyperpigmentation may take several months or longer; therefore, accelerating the clearance of hyperpigmentation is of value. Case reports have documented improvement following treatment with a 1550 nm erbium-doped fractionated laser [63-65]. However, a three-month, uncontrolled study of six patients with postinflammatory hyperpigmentation and eight patients with erythema dyschromicum perstans treated with the same laser found a lack of improvement in postinflammatory hyperpigmentation. Moreover, laser-induced postinflammatory hyperpigmentation occurred in 3 out of 14 patients [66].

The efficacy of the 1927 nm thulium fiber fractionated laser in the treatment of postinflammatory hyperpigmentation is uncertain. A retrospective evaluation of 61 patients with postinflammatory hyperpigmentation treated with the 1927 nm thulium fractionated laser at low energy and low density settings (5 mJ energy, 150 micrometer spot size, 170 micrometer depth, 5 percent coverage) found a mean 43 percent improvement in pigmentation [67].

The 1064 nm QS Nd:YAG laser may have benefit for postinflammatory hyperpigmentation. In a nonrandomized comparison study of 40 Korean patients with acne and postinflammatory hyperpigmentation, 11 out of 20 patients given five weekly treatments with a 1064 nm Nd:YAG laser (5 to 10 passes, 3.3 to 5.8 J/cm²) had more than 50 percent improvement in hyperpigmentation, while no patients who were excluded from laser therapy achieved similar results [68]. The QS ruby laser was poorly effective for postinflammatory hyperpigmentation in a small case series [69].

The 1064 nm picosecond laser may also improve the hyperpigmented component of scars. In an Israeli case series, 16 patients with skin types II to VI received three to eight treatments with low energy settings (1.7 to 2.5 mJ/microbeam) spaced three to six weeks apart [70]. All patients were noted to have improvement on the global assessment scale and a decrease in melanin scar content as measured by a narrowband simple reflectance meter [70].

Melasma — Melasma is a common, acquired disorder that usually presents with symmetric hyperpigmented patches on the face (picture 7A-B). Multiple laser modalities have been used for melasma, but treatment results are highly variable and recurrence after treatment is common. Worsening of hyperpigmentation or mottled hypopigmentation may also occur as a result of laser therapy. (See "Melasma: Management".)

Treatment with a low-fluence 1064 nm QS Nd:YAG laser can be effective [71-73]. In a retrospective study of 25 women with melasma, 11 out of 25 patients had marked improvement with this treatment [71]. In another study of 27 women with refractory, mixed-type melasma, a series of monthly treatments with a low-fluence 1064 nm ND:YAG laser (1.6 to 2 J/cm², 5 to 6 mm spot size) administered immediately after microdermabrasion was associated with >75 percent clearance in 81 percent of patients [74].

The long-term efficacy of fractional lasers for melasma is uncertain [75-79]. Although small case series and an open-label study have reported improvement with a 1550 nm erbium-doped fractional laser [75], worsening of hyperpigmentation following laser treatment was noted in 9 out of 29 patients in a split-faced, randomized trial [76]. A single treatment with an ablative fractionated CO₂ laser used in combination with topical therapy appeared to be beneficial for lengthening the duration of response in one prospective study [80].

Treatment with a nonablative 1927 nm diode laser may be beneficial. In a single-center, uncontrolled study that included 23 patients with facial photodamage, melasma, or postinflammatory hyperpigmentation, treatment with a low energy, low density, nonablative fractional 1927 nm diode laser led to visible improvement in melasma without exacerbation of existing pigmentation [81,82].

Picosecond lasers have an emerging role in the treatment of melasma. A Korean, prospective, split-face study with 39 patients with melasma that compared hydroquinone 2% cream with hydroquinone 2% cream plus picosecond laser at dual 595 nm and 1064 nm wavelengths found greater efficacy in areas treated with combination therapy [83]. Similarly, a split-face study with 10 patients with melasma that compared treatment with a topical skin-lightening cream with a topical skin-lightening cream combined with 1064 nm picosecond laser found a greater likelihood of improvement with combination therapy [84].

Additional treatment options include intense pulsed light [85-88] and ablative laser resurfacing with traditional Er:YAG or CO₂ lasers [89-91]. Traditional ablative laser therapy of melasma is often complicated by postinflammatory hyperpigmentation.

Daily use of broad-spectrum sunscreens after laser therapy is typically recommended to minimize the risk of recurrence after laser therapy [92].

Drug-induced hyperpigmentation — Multiple drugs may cause hyperpigmentation of the skin. While discontinuation of the inciting drug leads to improvement in some cases, dyspigmentation can be persistent. Pigment deposits related to drug therapy may consist of melanin, iron, or other substances:

●Minocycline – Different variants of minocycline-induced pigmentation have been described [93,94]. Type I pigmentation is seen in sites of previous inflammation, trauma or scarring, is blue-black in color, and histologic assessment shows pigment within dermal macrophages that stains positively for iron. Type II pigmentation presents with blue-black discoloration on the extensor surfaces, especially the shins, with characteristic staining for both iron and melanin in the dermis (picture 8). Type III pigmentation is often very persistent and presents as a muddy-brown discoloration in sun-exposed areas. Histologic examination of type III pigmentation reveals increased epidermal and superficial dermal pigment that stains only for melanin.

The 694 nm QS ruby, 755 nm QS alexandrite, 1064 nm QS Nd:YAG, and 532 nm frequency-doubled QS Nd:YAG lasers have been used successfully for the treatment of minocycline-associated pigmentation [95-102]. Treatment with a 1550 nm fractionated laser has also been effective in a patient [103].

●Imipramine – Imipramine hyperpigmentation has responded to QS ruby or QS alexandrite lasers in individual patients [104,105]. Of note, paradoxical darkening of hyperpigmentation has occurred in a patient following treatment with a 1064 nm QS Nd:YAG and QS ruby laser [106].

●Topical hydroquinone – Exogenous ochronosis due to topical hydroquinone presents on histology with yellow-brown, banana-shaped deposits in the papillary dermis. Reports have documented successful treatment with QS ruby lasers, QS alexandrite lasers, and 1064 nm/532 nm picosecond lasers [107-109].

●Amiodarone – Amiodarone-induced hyperpigmentation can be associated with granular, yellow-brown pigment deposits in the cytoplasm of dermal histiocytes. QS ruby laser treatment has induced clearing of pigmentation in a single treatment session [110,111].

SAFETY — The implementation of practices focused on safety is of paramount importance for the administration of laser therapy:

●Eye protection – Lasers used to treat pigmentary disorders can induce severe retinal injury and blindness. All individuals in the treatment room, including both clinical personnel and patients, must wear protective eyewear. Safety goggles are specific to the laser wavelength, and selection of the correct goggles should be confirmed prior to the start of treatment. In addition, application of metal eye shields to the eyes of patients is recommended during the treatment of periocular areas.

●Fire prevention – To prevent accidental fires, complete removal of flammable products (makeup, creams, and topical anesthetics) should be performed prior to treatment. The treatment site must be free of alcohol residue. Care should be taken to remove any drapes, towels, plastics, or clothing from the treatment area to prevent accidental ignition.

ANESTHESIA — The vast majority of patients treated with lasers for pigmented lesions in limited areas do not require anesthesia. The level of discomfort during treatment with quality-switched (QS) lasers is often likened to a rubber band snapping against the skin surface.

Factors that can determine the need for anesthesia include the size of the lesion, anatomical location, depth of pigment, type of laser device, and the patient's pain threshold. Children, patients with lesions characterized by a large amount of dermal pigment (eg, Nevus of Ota), and patients treated with fractionated laser devices often require some form of anesthesia.

Topical anesthesia with agents, such as topical lidocaine 5% cream (LMX-5), are the most commonly used anesthetic agents in laser therapy. Occasionally, infiltrative anesthesia, regional nerve blocks, and oral or intramuscular sedation are used. The need for general anesthesia is primarily limited to children.

POSTOPERATIVE CARE AND COMPLICATIONS — Expected side effects of treatment vary with treatment type. It is not uncommon to experience a sensation of pain or stinging immediately after laser treatment. Postoperative use of ice packs, cool compresses, and occlusive dressings can reduce these symptoms.

The appropriate treatment endpoint with the use of quality-switched (QS) lasers is immediate skin whitening, which typically fades within 20 to 30 minutes (picture 9). Treated lesions subsequently become darker and form superficial crusts that fall off in 7 to 10 days.

In some patients, urticarial reactions can develop following QS and picosecond laser treatment, presenting with edema, itching, and stinging. If these symptoms do not subside within an hour, oral antihistamines may be administered.

The healing process is optimized with gentle cleansing of treated areas with soap and water and daily application of occlusive ointments to allow crusts to slough on their own.

Blistering, bruising, dyspigmentation, and scarring are complications that may occur as a result of treatment with lasers or intense pulsed light. Greater detail on the adverse effects of treatment with pulsed and ablative fractional lasers is reviewed separately. (See "Ablative laser resurfacing for skin rejuvenation", section on 'Traditional ablative lasers' and "Ablative laser resurfacing for skin rejuvenation", section on 'Ablative fractional lasers' and "Laser and light therapy for cutaneous vascular lesions", section on 'Adverse effects'.)

Treatment-induced hyperpigmentation is a risk of laser and intense pulsed light therapy; therefore, patients should be instructed to engage in sun-protective practices, including the daily use of sunscreen after treatment.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Melasma and hyperpigmentation disorders".)

SUMMARY AND RECOMMENDATIONS

●Laser and intense pulsed light therapy can be effective for the treatment of a wide variety of hyperpigmented skin lesions. A thorough understanding of laser principles and the characteristics of the lesion to be treated is essential for the effective and safe use of light-based therapies. (See 'Principles' above and 'Indications' above.)

●Different classes of light-emitting devices, including quality-switched (QS) nanosecond lasers, picosecond lasers, long-pulsed lasers, traditional ablative lasers, fractionated lasers, and intense pulsed light, are used for the treatment of pigmented lesions. The wavelength, pulse duration, energy setting, and mode of light delivery determine the effects of a device on tissue. (See 'Devices' above.)

●Patients should be carefully evaluated prior to laser or intense pulsed light therapy for hyperpigmented skin lesions. Factors that influence the efficacy and safety of treatment, such as specific lesion characteristics, patient skin color, and risk factors for adverse events, should be assessed. In addition, patients should be well informed of the possible treatment outcomes and potential adverse effects. (See 'Patient evaluation' above and 'Postoperative care and complications' above.)

●Prevention of eye injury and accidental fire is an important component of the safe administration of laser therapy. All individuals in the treatment room must wear protective eyewear and flammable substances or products should be removed from the treatment site. (See 'Safety' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Andrei Metelitsa, MD, FRCPC, who contributed to an earlier version of this topic review.