Laser and light therapy for cutaneous vascular lesions

INTRODUCTION — Lasers and intense pulsed light (IPL) are used for the treatment of multiple cutaneous vascular lesions, including telangiectasias, port wine birthmarks (PWBs; also called capillary malformations or port wine stains), and infantile hemangiomas. During treatment, the absorption of light energy by intravascular oxyhemoglobin leads to heating and coagulation of lesional blood vessels. The responses of vascular lesions to therapy are influenced by the type of light source used, the clinical characteristics of the target lesion, and patient-specific factors (eg, skin color, patient age).

Although laser and IPL therapy can result in clinical benefits, treatment is not innocuous. Cutaneous and ocular damage can occur if clinicians are not vigilant. The use of appropriate equipment settings, skin cooling mechanisms, and other safety measures minimize the occurrence of adverse events due to treatment.

The types of lasers used in the treatment of vascular lesions as well as the efficacy and clinical use of lasers for the treatment of PWBs, infantile hemangiomas, and telangiectasias will be discussed here. The general principles of medical lasers, the principles of light therapy for the treatment of skin, and laser and light therapy for lower extremity telangiectasias and veins are reviewed elsewhere. (See "Basic principles of medical lasers" and "Principles of laser and intense pulsed light for cutaneous lesions".)

PRINCIPLES OF LASER THERAPY — The theory of selective photothermolysis describes the method through which lasers or intense pulsed light (IPL) can be used to selectively destroy specific targets in the skin while minimizing damage to other cutaneous structures [1]. In concordance with this theory, light energy must be delivered in a manner that results in preferential absorption of light by light-absorbing molecules (chromophores) located within the target. The absorption of light energy by chromophores leads to heating and coagulation of the target. To limit collateral damage, the diffusion of heat to adjacent tissues must also be minimized. The principles of laser and light therapy for cutaneous lesions are reviewed in greater detail elsewhere. (See "Principles of laser and intense pulsed light for cutaneous lesions".)

The major chromophore targeted during therapy of vascular lesions is generally oxyhemoglobin, although absorption by other hemoglobin species, including deoxyhemoglobin and methemoglobin, can also occur. Significant light absorption by oxyhemoglobin occurs in the range of yellow and green light; peak absorption occurs at 418, 542, and 577 nm [1]. A lower peak of light absorption by oxyhemoglobin occurs in the near-infrared light range. Thus, lasers that emit wavelengths of light near the primary absorption peaks of oxyhemoglobin, such as the 585 or 595 nm pulsed dye and the 532 nm frequency-doubled neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers, are often favored for the treatment of vascular lesions. Infrared-range lasers (1064 nm Nd:YAG, alexandrite, or diode) can also be effective for this indication but are associated with a greater risk for tissue damage and ulceration.

The potential for light absorption by melanin, another chromophore ubiquitously present in the skin, must be considered prior to the treatment of vascular lesions. Light absorption by melanin progressively increases as wavelengths of light decrease, leading to a relatively higher risk of dyspigmentation secondary to melanin absorption with the use of shorter wavelengths of light. This is of particular concern in patients with darkly pigmented skin, in whom epidermal melanin is abundant. Epidermal skin cooling techniques and adjustments to laser settings can be used to reduce the incidence of adverse effects secondary to epidermal melanin absorption [2]. Absorption of light by epidermal melanin can also affect the efficacy of treatment through reducing the amount of light that reaches vessels in the dermis. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Skin cooling'.)

Although the absorption of light by superficial chromophores can influence the amount of light that reaches deep tissues, the wavelength of emitted light is a critical factor for determining the depth to which light penetrates the skin. Longer wavelengths of light penetrate the skin more deeply than shorter wavelengths. As an example, in a patient with Fitzpatrick skin type II (table 1), light with a 585 nm wavelength may penetrate roughly 0.65 mm into the skin, while 595 nm may reach a depth of approximately 1 mm [2]. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Wavelength'.)

Because short wavelengths of light penetrate the skin only superficially, long wavelengths (eg, those in the near-infrared range) are required to reach vessels that are deeper than the upper dermis. This feature plus a relatively high risk of light absorption by epidermal melanin are the primary reasons that lasers with wavelengths near the 418 nm peak of oxyhemoglobin light absorption are generally avoided in the treatment of vascular lesions. Since target vascular lesions often contain vessels at variable depths, using lasers of different wavelengths over the course of several treatments can be useful for achieving desired clinical effects.

Other laser settings that influence the efficacy of laser and light therapy for vascular lesions include the pulse duration, fluence (energy delivered per unit area), and spot size.

●Pulse duration – Pulse durations equal to or shorter than the vessel thermal relaxation time (time required for a target to lose accumulated heat) are often used to reduce the risk of damage to surrounding structures. Pulse durations that exceed a structure's thermal relaxation time allow the diffusion of heat to adjacent structures, increasing the risk for collateral damage in the skin. The thermal relaxation times for vessels in port wine birthmarks (PWBs; typically 10 to 300 micrometers in diameter) range from 1 to 10 ms [3,4]. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Pulse duration'.)

The pulse duration also affects clinical responses to treatment. Short pulse durations (eg, 0.45 ms) often result in rapid heating and rupture of target vessels, contributing to the appearance of post-treatment purpura, which some patients treated for telangiectasias find undesirable. In contrast, long pulse durations deliver light energy over a longer period and allow slower heating of target vessels, preventing sudden vessel rupture and reducing the risk of purpura. Long pulses may also be useful for the destruction of large vessels. Large structures lose heat slowly, and the accumulation of heat that occurs over long pulse durations may facilitate coagulation of larger vessels.

●Fluence – The appropriate laser or IPL setting for the amount of energy delivered to the skin per unit area (fluence) is an important factor for efficacious and safe treatment of vascular lesions. The energy delivered must be sufficient for the chromophore to absorb enough heat to induce vessel coagulation but should not reach levels that induce excessive damage to the skin. Skin cooling mechanisms can be used to reduce the risk of skin damage associated with the use of high fluences [2]. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Fluence'.)

●Spot size – The term "spot size" is used to describe the size of the area through which light is delivered. Large spot sizes minimize scattering of light as it enters the skin, allowing more light to reach the target structure. Large spot sizes also facilitate the treatment of large lesions. A small spot size may be preferred for the treatment of a small, focal telangiectasia. (See "Principles of laser and intense pulsed light for cutaneous lesions", section on 'Spot size'.)

TYPES OF VASCULAR LASERS — A variety of lasers are used for the treatment of vascular lesions. Specific laser characteristics determine the most appropriate clinical settings for use.

Yellow and green light lasers — High peaks for the absorption of light by oxyhemoglobin occur within the range of yellow and green light. Thus, lasers that emit light in this range are commonly used for the treatment of vascular lesions. However, the restricted depth of penetration of light emitted from these lasers may limit their efficacy for the destruction of vessels located below the superficial dermis. Dyspigmentation is also a risk associated with the use of these lasers, given the relatively high absorption of light in this range by melanin. (See 'Principles of laser therapy' above.)

Pulsed dye lasers — The flashlamp-pumped pulsed dye laser (PDL; 585 to 600 nm) has a long history of safe and effective use for vascular lesions. Original 577 nm PDLs were commonly used with pulse durations of approximately 0.45 ms, which is much shorter than the thermal relaxation time of small, superficial vessels (1 to 10 ms). Use of short pulse durations minimizes collateral damage in the skin but also often leads to rapid heating of vessels and vessel rupture, contributing to the appearance of post-treatment temporary purpura. Longer pulse PDLs (595 to 600 nm, pulse duration ≥1.5 ms) slowly heat target vessels and can be used without the formation of purpura. However, subpurpuric protocols with long-pulse PDLs may be less effective for the treatment of telangiectasias [5,6], and clinical experience suggests similar effects in the treatment of port wine birthmarks (PWBs). (See 'Pulsed dye lasers' below.)

Frequency-doubled Nd:YAG/KTP lasers — The frequency-doubled neodymium-doped yttrium aluminum garnet/potassium titanyl phosphate (Nd:YAG/KTP) laser consists of light from an Nd:YAG laser that is passed through a KTP crystal. The wavelength of this laser is 532 nm, near the 542 nm absorption peak of oxyhemoglobin. Pulse durations of frequency-doubled Nd:YAG/KTP lasers are in the millisecond range, which allows for the treatment of vascular lesions without the formation of purpura. However, the short wavelength results in a lower depth of skin penetration compared with PDLs. Light emitted by frequency-doubled Nd:YAG/KTP lasers is also absorbed to a greater extent by melanin, augmenting the risk of dyspigmentation, particularly in patients with darkly pigmented skin.

Near-infrared lasers — A secondary, lower peak for the absorption of light by oxyhemoglobin occurs in the near-infrared range (720 to 1200 nm). There is also a small deoxyhemoglobin absorption peak between 750 to 800 nm. Alexandrite (755 nm), diode (800 to 980 nm), and long-pulsed Nd:YAG (1064 nm) lasers are used to capitalize on this absorption and can be effective for the treatment of vascular lesions [7]. The relatively long wavelengths of light emitted by these lasers penetrate the skin to greater depths than is possible with PDL or frequency-doubled Nd:YAG/KTP lasers. Thus, these lasers are generally utilized when vessels deep in the skin are targeted. Pulse durations of these near-infrared lasers are in the millisecond range, facilitating the treatment of larger vessels.

A disadvantage of near-infrared lasers is that the relatively lower absorption of light by hemoglobin species in this light range demands the use of higher fluences during the treatment of vascular lesions [8]. This leads to a greater risk of inadvertent scarring compared with PDLs.

Dual wavelength lasers — Dual wavelength lasers, including the frequency-doubled Nd:YAG/KTP laser that emits 1064 and 532 nm light simultaneously and a sequentially firing 595 and 1064 nm dual wavelength device, have been used for the treatment of resistant vascular lesions [8,9].

Intense pulsed light — Intense pulsed light (IPL) sources are nonlaser flashlamp devices that produce incoherent, broad bands of light ranging from 515 to 1200 nm. Selective light filters can be used to restrict the emitted wavelengths to a narrower range for a more specific tissue effect.

IPL devices have versatility, as they generate a wide range of light wavelengths, pulse durations, and pulse sequences. However, treatment of some types of vascular lesions with IPL can require more sessions than laser therapy to achieve the same clinical effect (see 'Other lasers and light therapies' below). Another potentially detrimental feature of IPL is the emission of wavelengths of light highly absorbed by epidermal melanin, which leads to a relatively high risk of pigmentary adverse effects. Use of skin cooling techniques during IPL therapy is essential for reducing this risk.

SAFETY MEASURES — Protective eyewear is essential for all individuals present in the treatment room. Clinical personnel must wear laser safety goggles that specifically protect against the wavelength of the laser used.

Patient protective eyewear depends on the location to be treated. If nonfacial areas are to be treated, patients may wear laser safety goggles similar to those of the clinical staff. For the treatment of the face outside of the periorbital area, protective pads specific for laser procedures or laser treatment metal goggles correctly placed can be used. Corneal shields inserted with the aid of ocular anesthetic drops and lubricant are required when the eyelid or immediate periorbital area is treated. Appropriate sizing and placement of the patient's eyewear should always be confirmed prior to starting a procedure.

Eye injury has been reported when long-pulsed longer wavelength (755 and 1064 nm) lasers were used within the bony orbit, even with appropriate eye protection [10]. Use of these devices in the periorbital area should be avoided or approached with extreme caution.

Lasers have been reported to cause flash fires [11]. To avoid this, flammable substances should be avoided in the treatment area. Fire extinguishers should be immediately available.

ANESTHESIA CONSIDERATIONS — Local or general anesthesia or administration of pain medications prior to laser treatment may be used as needed. Anesthesia is not generally required for small lesions.

●Topical anesthesia – Topical anesthetics can be used, although some preparations (eg, eutectic mixture of lidocaine-prilocaine [EMLA]) may blanch the vessels. This may remove the target, minimizing treatment response. Local anesthetic injections or regional nerve blocks can also be utilized; however, epinephrine (a vasoconstrictor) should be avoided to prevent vessel constriction and target removal.

●General anesthesia – General anesthesia may be helpful to ensure safe and complete treatment of large lesions (port wine birthmarks [PWBs] or infantile hemangiomas) in infants, children, and some adults. The US Food and Drug Administration (FDA) has issued a warning regarding use of general anesthetics in children under three years of age [12]. The risks and benefits of use of general anesthesia should be discussed with parents/caregivers.

The multiple treatments required and the use of protective eyewear, especially corneal shields, can be difficult for children. General anesthesia is routinely used for large lesions at the author's institution for young children over the age of three years who would benefit from treatment. Older children and adults often do not need general anesthesia, but it depends on the individual.

General anesthesia performed by experienced anesthesiologists in otherwise healthy children has been reported to be quite safe, although there are some risks. (See "General anesthesia in neonates and children: Agents and techniques".)

The risk of adverse neurodevelopmental effects of general anesthesia in children is uncertain. (See "Neurotoxic effects of anesthetics on the developing brain".)

•In an international randomized trial that included 363 infants assigned to receive awake regional anesthesia and 359 infants assigned to receive sevoflurane-based general anesthesia during inguinal herniorrhaphy, no difference was noted in neurodevelopmental outcome assessed at the ages of two and five years [13,14].

•In a cohort study of 33, 514 children, single or multiple exposure to general anesthesia before the age of four years was associated with a mild decrease in later academic performance or cognitive performance compared with nonexposed children [15].

•In another cohort study that included 350 children exposed to general anesthesia before the age of two and 700 matched, unexposed controls, exposure to multiple (but not single) anesthesia was an independent risk factor for developing later learning disability, after adjustment for health status and matching for other factors associated with learning disability [16].

CAPILLARY MALFORMATIONS (PORT WINE BIRTHMARKS) — Capillary malformations (nevus flammeus, port wine stains, port wine birthmarks [PWBs], MIM #163000) are congenital low-flow vascular malformations of dermal capillaries and postcapillary venules presenting as pink to erythematous to violaceous patches (picture 1A-C). Although the term "port wine stain" is commonly used, patients may prefer the term "port wine birthmark," as "stain" has a negative connotation [17]. Lesions may be extensive, and papular and nodular components often develop during adulthood. PWBs can lead to psychologic distress in some patients, and complications such as nodules, bleeding, pyogenic granulomas, and tissue hypertrophy can occur in mature lesions [18,19]. Isolated lesions do occur, but PWBs may be associated with several syndromes that should be considered when these patients present. (See "Capillary malformations (port wine birthmarks) and associated syndromes".)

Laser therapy is the standard of care for the treatment of PWB capillary malformations. Previously established treatments, such as cryotherapy, electrocautery, and excision, resulted in unacceptable scarring.

Pulsed dye lasers — Pulsed dye lasers (PDLs) are considered by most experts first-line treatment for PWBs [20]. (See 'Other lasers and light therapies' below.)

Timing — The ideal timing of treatment of PWBs is controversial [21], although many experts agree that early treatments can provide improved results [20]. We typically aim to begin treatment of PWBs within the first month of life.

An uncontrolled study of 89 patients with PWBs treated with PDL found no difference in the degree of improvement in patients of varying ages (0 to 31 years) [22]. However, the results of multiple studies suggest that very young children (under one year of age) may require fewer treatments for lesion clearance and may be more likely to achieve greater overall lightening [23-26].

The greater efficacy of treatment in young children may be related to a variety of factors, including increased hemoglobin concentration (in the first 6 to 12 months of life), especially hemoglobin F, and the presence of thinner skin and smaller lesional vessels in this population when compared with older individuals. PWBs often develop thickening and nodularity as patients age, and lesions with these changes may be more difficult to treat [19,27-30]. The relatively smaller size of lesions in young children may also be a factor [25,26].

Therapeutic parameters — Although PDLs are the standard of care for PWBs, a lack of studies evaluating the efficacy of specific laser parameters, the continued evolution of laser technology, and variations in patient skin color and lesion characteristics have precluded the development of standardized treatment guidelines. In general, appropriate parameters for PDL treatment of PWBs include [31]:

●Wavelength and pulse duration – The 595 nm PDL with variable pulse duration has become the laser most frequently used for the treatment of PWBs. Compared with the earlier developed 585 nm PDL, light from the 595 nm PDL penetrates the skin to a slightly greater depth. In addition, the ability to deliver pulse durations in the millisecond range (typically 1.5 to 10 ms or longer) may facilitate the destruction of larger vessels.

●Fluence – Appropriate initial PDL fluence settings vary. Factors such as patient age, skin color, lesion morphology, lesion location, average vessel size, laser type, and laser spot size determine the correct fluence setting.

As an example, when treating a PWB on the cheek in an older child or adult with skin phototype II (table 1), appropriate initial fluence settings for a 595 long-pulsed PDL with a 10 mm spot size and a dynamic epidermal cooling mechanism generally range from 5.5 to 7.5 J/cm². Lower initial fluences are typically used for young children, individuals with darkly pigmented skin, and lesions in areas at higher risk for cutaneous damage, such as the eyelid and nonfacial lesions. Depending on the response to treatment, fluences can be increased by 0.5 J/cm² with subsequent treatments if desired results are not achieved and no adverse effects are noted [2].

●Cooling – Adequate epidermal cooling techniques reduce the risk of epidermal damage and scarring and allow for the use of higher fluences in the hands of experienced clinicians. Epidermal cooling is particularly important in patients with darkly pigmented skin, in whom inadequate cooling is likely to result in hyperpigmentation or hypopigmentation.

●Spot size – Large spot sizes (≥7 mm) are generally preferred as they minimize light scattering and thus allow greater delivery of light energy to target structures. Large spot sizes also facilitate the treatment of large PWBs.

In a retrospective study of 160 adults and children with facial and nonfacial PWBs, a novel generation, large-spot 595 nm PDL (maximum spot size of 15 mm) achieved a 50 percent improvement in half the number of treatments compared with a previous generation PDL using smaller spot sizes (4.3 versus 8.8, respectively) [32]. The overall mean improvement at the end of treatment was similar in both groups.

●Patient positioning – Although the impact of patient positioning during treatment has not been specifically studied, we typically place the treatment site in a dependent position (eg, Trendelenburg position for facial lesions) immediately prior to treatment to increase local blood volume, which theoretically may increase the size of the vascular target.

Treatment should be performed in a methodical fashion, with care to maintain the position of the laser perpendicular to the surface of the skin (picture 2). This also ensures the proper delivery of cooling when using lasers with integrated cooling technology. Overlapping pulses by approximately 10 percent reduces the amount of untreated space [2].

Number and frequency of treatments — Multiple treatments are usually required to achieve maximum lightening of PWBs, and complete clearance is uncommon [23,33,34]. In one study of 76 patients with PWBs, an overall clinical improvement of 79 percent was achieved after an average of nine treatments [35].

The frequency with which treatments are administered varies in the literature, ranging from every two weeks to every few months. We typically administer PDL treatments every three to six weeks for facial lesions. Other clinicians have successfully used shorter intervals. In a retrospective study of 24 infants with facial PWBs (Fitzpatrick skin phototype I to III), treatment intervals of two, three, or four weeks were effective for improving PWBs and were well tolerated [36].

We may use longer intervals (six to eight weeks) for patients with darkly pigmented skin (Fitzpatrick phototype IV or higher) or with extremity lesions if there is postinflammatory hyperpigmentation. Longer time intervals between sessions allow for treatment and improvement of hyperpigmentation. Hyperpigmentation can reduce treatment efficacy. (See 'Adverse effects' below.)

Treatment can continue until lesions are clear or nearly clearly or until no further improvement is noted; typically, 3 to more than 15 sessions are required [2]. Variations in vessel size and depth within a particular lesion promote the value of utilizing more than one set of PDL parameters over the course of treatment of a PWB [37].

Retreating areas during the same treatment session (multiple pass technique) may also be beneficial for facial lesions [38]. The pulse duration or laser wavelength can also be altered with subsequent passes. Multiple passes should only be performed by clinicians experienced in laser treatment due to an increased risk for adverse effects, as heat accumulates in the skin. The risk for scarring with this technique may be higher for lesions in nonfacial locations.

Factors affecting outcomes — Factors associated with a lower likelihood for a complete response include:

●Older child or adult [23-26].

●Darkly pigmented skin – Treatment of PWBs in patients with darkly pigmented skin presents specific challenges. Absorption of laser energy by epidermal melanin inhibits light delivery to underlying PWB vessels [2]. In addition, the potential for post-treatment hypopigmentation or hyperpigmentation is more likely and, once present, is often more apparent in patients with darkly pigmented skin. Use of appropriate laser settings, which may include longer pulse durations and lower energies [20], and epidermal cooling techniques help to minimize this risk.

●Location on trunk or extremity [39].

●Location on central face (medial cheek, upper lip, nose) rather than on other facial areas [26,40,41].

●Nodular, large, or hypertrophic lesions – Nodular or very large lesions may exhibit increased resistance to PDL therapy [25,26,30,42]. Treatment with other types of lasers can be beneficial in the management of resistant, nodular, or hypertrophied lesions, where longer wavelengths may be beneficial. However, these longer wavelengths do have a higher incidence of adverse effects and should be used with caution. (See 'Other lasers and light therapies' below.)

Adverse effects — Tissue response should be watched closely with initial pulses and throughout treatment. Adverse effects of PDL therapy include:

●Purpura – Immediate purpura is often the desired tissue response during PDL treatment for PWBs (picture 3). However, when longer pulse durations (3 ms or more) are utilized to target larger blood vessels, less purpura is noted. PDL-induced purpura typically resolves within 10 to 14 days [43]. Pain medications that inhibit clotting, such as nonsteroidal anti-inflammatory agents, should be avoided.

●Gray or white discoloration – After the delivery of a laser pulse, the appearance of a gray or white color on the skin that persists after a few minutes denotes epidermal injury and should be avoided.

●Edema – Local edema and sunburn-like pain are common after treatment. Elevation, ice packs, nonprescription oral analgesics that do not affect clotting, and bland topical emollients are useful for decreasing patient discomfort [2].

●Hyperpigmentation – Post-treatment sun avoidance should be recommended to reduce the risk of subsequent hyperpigmentation. For patients with skin color classified as Fitzpatrick phototype III or higher as well as patients with lighter skin who develop post-treatment hyperpigmentation (table 1), we sometimes prescribe daily application of a bleaching cream (eg, hydroquinone 4%) between treatment sessions to further decrease the risk of this adverse effect. Daily application of hydroquinone should begin immediately after the resolution of purpura and can continue until the next treatment. Because irritant dermatitis can also induce hyperpigmentation, we decrease the frequency of application or discontinue topical bleaching agents in patients who develop skin irritation secondary to these drugs.

●Other – Blistering, scarring, cutaneous atrophy, and hypopigmentation are additional potential adverse effects of PDL therapy.

Other lasers and light therapies — Other lasers and light therapies have also been used for PWBs [8,44-46]. In general, our preference is to use lasers rather than intense pulsed light (IPL) or photodynamic therapy (PDT) for the treatment of PWBs.

●Other lasers

•In a prospective study of 30 patients with PWBs resistant to PDL, lesion color improved at least 25 percent in 16 patients (53 percent) after treatment with a modulated 532 nm potassium titanyl phosphate (KTP) laser [47]. Scarring, hyperpigmentation, and prolonged time to healing occurred in six patients (20 percent).

•Near-infrared lasers, such as the alexandrite, diode, and 1064 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers, have also been used for the treatment of PWBs and may be particularly useful for violaceous or nodular lesions [8,48-52]. However, the risk of scarring is significant at the relatively high fluences required to treat vascular lesions with near-infrared lasers. In a small study of 16 patients with facial PWBs, treatment with the long-pulsed Nd:YAG 532 nm laser (12 sessions spaced by four weeks) was associated with good or excellent improvement in 13 patients (81 percent) [53]. (See 'Near-infrared lasers' above.)

●Intense pulsed light – The efficacy of PDL was compared with intense pulsed light (IPL) in a randomized, side-by-side comparison trial of 20 patients who had not been previously treated with either therapy [54]. A single treatment with a 595 nm PDL was superior to IPL for the induction of lesion clearance. However, a pilot study found that IPL may have benefit for some patients with PWBs [55]. Of 15 patients with PDL-resistant PWBs, six (40 percent) achieved more than 75 percent clearance with IPL.

●Photodynamic therapy – Photodynamic therapy (PDT) using hematoporphyrin monomethyl ether (HMME; hemoporfin) as a photosensitizer has been reported as effective for the treatment of PWBs in several studies [56,57]. PDT has been widely studied in China for PWBs, but there has been less utilization in other parts of the world due to the adverse effect potential.

A randomized trial evaluated PDT-HMME with 532 nm light in 440 adolescent and adult patients with skin types III and IV and PWBs (table 1) [58]. At eight weeks, PDT-HMME demonstrated higher rates of efficacy compared with placebo. Approximately 90 percent of patients treated with PDT-HMME showed "at least some improvement" (defined as ≥20 percent color blanching) versus 24.5 percent in the placebo group, 43.5 percent of patients treated with PDT-HMME showed "at least great improvement" (defined as ≥60 percent color blanching) versus 0.9 percent in the placebo group, and 11 percent of patients' PWBs "completely resolved" (defined as ≥90 percent color blanching) in the PDT-HMME group versus 0 percent of patients' PWBs in the placebo group. The most common adverse effects included edema and hyperpigmentation.

Combination therapies — Combined modality lasers (eg, 595 and 1064 nm) [8], combination therapy with PDL and a fractionated erbium-doped yttrium aluminum garnet (Er:YAG) laser [59], and the combination of PDL plus topical agents with antiangiogenic properties, such as timolol, imiquimod, or rapamycin, may have benefit for the treatment of PWBs [60-64].

●A small, randomized trial in which 22 children were randomly assigned to treatment with either PDL followed by topical timolol (an inhibitor of neoangiogenesis used for the treatment of infantile hemangiomas) or PDL alone found that topical timolol did not significantly improve the likelihood of treatment success [65].

●In a phase 2, randomized trial that included 23 patients with Sturge-Weber syndrome and PWBs, PDL combined with topical rapamycin was more effective than PDL alone in reducing a digital photographic image score [63].

The identification of a somatic mutation in GNAQ associated with the majority of PWBs may lead to the development of targeted treatment options [66].

INFANTILE HEMANGIOMAS — Infantile hemangioma is the most common benign vascular tumor in children. In most cases, lesions are not present at birth but become evident within the first weeks or months of life. Infantile hemangiomas may be superficial (picture 4A-B), deep (picture 5), or may have a mixture of superficial and deep components [67]. Superficial hemangiomas typically present as bright red papules, plaques, or nodules. Deep lesions appear as flesh-colored or bluish subcutaneous nodules. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Infantile hemangiomas: Evaluation and diagnosis".)

Because all true infantile hemangiomas involute spontaneously over time, treatment may not be needed in many cases [68]. Uncomplicated infantile hemangiomas can be managed conservatively, with close observation for the development of complications. (See "Infantile hemangiomas: Management", section on 'Low-risk and uncomplicated hemangiomas'.)

For high-risk hemangiomas (eg, large lesions at increased risk of scarring, disfigurement, or functional impairment), oral propranolol is the first-line therapy [69]. (See "Infantile hemangiomas: Management", section on 'High-risk and complicated hemangiomas'.)

However, there are situations where lasers can be an additional therapeutic option. (See 'Indications' below.)

Pulsed dye laser — Pulsed dye lasers (PDLs) are the most common lasers used for the treatment of infantile hemangiomas. However, study results vary on their efficacy [70-75]. Interpretation of the literature is further complicated by the natural course towards involution of the lesion, variations in laser settings among studies, and the evolution of laser technology over time [70,72].

Indications — Based on the available data, beneficial effects of laser therapy are most likely to occur in patients with small, superficial, or ulcerated lesions [70,76]. For larger lesions, combination of PDL treatment with oral beta blockers may provide additional benefit [77,78].

Superficial lesions — Superficial hemangiomas are more likely to respond completely to laser therapy than deeper lesions [70,75], an observation that is consistent with the known limits of penetration of PDL light into the skin. Superficial lesions may also respond more favorably to the slightly more deeply penetrating 595 long-pulse PDL.

●In a prospective study of 165 children with 225 infantile hemangiomas, complete clearance of lesions followed 585 nm PDL therapy in 52 out of 153 superficial hemangiomas (34 percent; mean number of treatments for complete response = 1.6±1.1) [74]. In contrast, none of 54 mixed (cutaneous and subcutaneous) hemangiomas exhibited complete clearance.

●Another prospective study of 548 children with infantile hemangiomas also found higher rates of complete responses to 585 nm PDL therapy in superficial lesions [75]. Complete remissions occurred most frequently in small superficial hemangiomas (43 percent). Larger superficial lesions, cutaneous nodular, and mixed (cutaneous and subcutaneous) lesions resolved in 19, 15, and 7 percent of cases, respectively.

●A retrospective study of 90 patients with 105 superficial or deep hemangiomas treated with the 595 nm long-pulse PDL with dynamic epidermal cooling every two to eight weeks found that ≥75 percent improvements in color occurred in similar proportions of patients with superficial or mixed lesions (approximately 80 percent) [70]. However, a ≥75 percent reduction in lesion thickness was observed in more superficial lesions than mixed lesions (78 and 40 percent, respectively).

Ulcerated lesions — Since fewer infantile hemangiomas are treated with laser due to the use of beta blockers, treatment of ulcerated lesions (picture 6A-B) may be the most common utilization of lasers for infantile hemangioma management. As little as one treatment may be required to induce healing [79,80]. (See "Infantile hemangiomas: Management", section on 'Pulsed dye laser'.)

However, PDL therapy has occasionally been associated with the development of ulceration in infantile hemangiomas [73]. (See 'Adverse effects' below.)

The efficacy of PDL for the treatment of ulcerated infantile hemangioma is supported by a few observational studies [76,79-81]. In a study of 78 children with ulcerated infantile hemangioma, 71 (91 percent) responded to therapy with 585 nm PDL [76]. An earlier retrospective study found less dramatic results, with 11 of 22 treated children exhibiting definite improvement [81].

Pain reduction is another potential benefit of PDL treatment. In a series of nine infants with ulcerated hemangiomas, pain appeared to improve in all patients after one treatment with a 585 nm PDL [79]. In another study, treatment with 595 nm PDL at 4 to 5 J/cm² with a pulse width of 0.5 ms induced a rapid decrease in pain and ulceration healing within two weeks of the first treatment in 20 of 22 infants with ulcerated infantile hemangiomas [82].

Involuting and resolved lesions — Hemangiomas in the involutional phase may benefit from treatment with PDL to hasten resolution of residual redness [74].

Timing — The ideal timing of PDL therapy in infantile hemangiomas remains uncertain. There is insufficient evidence to conclude that early treatment influences the risk for the development of deep components.

Beneficial effects of early PDL therapy are supported by the results of a prospective study of 165 children treated with a 585 nm PDL [74]. In this study, involuting hemangiomas were more likely to lighten in color than actively proliferating lesions and required fewer treatments to achieve improvement. Some authors have suggested that early treatment of infantile hemangiomas (prior to the proliferative stage) may also inhibit the proliferation of deeper components [31]. However, studies conflict on the validity of this theory [73-75,83]. (See "Infantile hemangiomas: Management".)

Although patient age often loosely correlates with lesion stage, age may not be an independent determining factor for the efficacy of treatment. In a prospective study of 548 children (age 3 to 36 months) with 692 proliferating hemangiomas who were treated with a 585 nm PDL, mean scores for response to treatment did not differ according to patient age [75].

Superficial involuting lesions may respond best to treatment, indicating that when desired, PDL may be useful for accelerating clinical resolution of actively involuting lesions [74]. (See 'Involuting and resolved lesions' above.)

Therapeutic parameters — Commonly used parameters for PDL in the treatment of infantile hemangiomas are as follows:

●Wavelength – 585 to 595 nm

●Fluence – 5 to 7.5 J/cm² (settings outside of this range are appropriate in some clinical settings)

●Pulse duration – 0.45 to 6 ms

●Spot size – 5 to 12 mm

We typically use a 595 nm PDL and select laser settings based upon multiple factors, including lesion stage (proliferating versus involuting), lesion location, and patient skin type. Low fluences (around 5 J/cm²) should be used for proliferating lesions to minimize risk of ulceration. The initial fluence setting should also be reduced for patients with darkly pigmented skin and lesions in areas with thin skin (eg, eyelid).

The often undulating surface of infantile hemangiomas requires the clinician to play close attention to the correct positioning of the laser in relation to the skin (picture 2). Integrated skin cooling mechanisms are required and should be utilized to minimize the risk of epidermal damage during treatment.

Treatments can be performed at two- to four-week intervals in rapidly proliferating or ulcerated lesions. Stable or involuting lesions may be treated less frequently every four to six weeks. Treatment is often performed without anesthesia. However, in occasional cases, local or general anesthesia may be necessary for safe and effective treatment. (See 'Anesthesia considerations' above.)

Efficacy

●Pulsed dye laser alone – Although a beneficial effect of PDL therapy has been reported in a meta-analysis of 13 observational studies [84], the results of a randomized trial raised controversy on the use of PDL for this indication [73]. In this trial, 121 infants aged 1 to 14 weeks with early infantile hemangiomas were assigned to PDL treatment or observation and followed up to the age of one year. At one year, the proportion of children who achieved complete clearance or minimal residual signs was similar in both groups (42 versus 44 percent, respectively). Infants treated with PDL were more likely to have skin atrophy (28 versus 8 percent) and hypopigmentation (45 versus 15 percent).

It should be noted that a 585 nm PDL without epidermal cooling technology (fluence 6 to 7.5 J/cm², spot size 3 to 5 mm, pulse duration 0.45 ms) was used in the trial summarized above. Modern lasers use integrated cooling techniques that allow for the safe use of higher and potentially more effective fluences. Several observational studies support the use of these lasers:

•In a randomized trial of 121 infants with hemangiomas, a 595 nm PDL with cryogen spray cooling technology (fluence 9 to 15 J/cm², spot size 7 mm, pulse duration 10 to 20 ms) was compared with a 585 nm PDL without cooling technology (fluence 5.5 to 7 J/cm², spot size 7 mm, pulse duration 0.45 ms) [85]. Although similar numbers of patients achieved complete or near complete lesion clearance at one year (approximately 60 percent), patients treated with the 595 nm laser were found to have shorter periods of maximum lesion proliferation (106 versus 177 days) and a lower risk for laser-induced hypopigmentation, hyperpigmentation, and textural skin changes.

•In a retrospective study of 90 patients with 105 superficial or superficial and deep hemangiomas treated with a 595 nm PDL with a dynamic spray cooling device (fluence 6.2 to 14 J/cm², spot size 7 or 10 mm, pulse duration 0.45 or 1.5 ms), 85 percent exhibited near complete or complete clearance of lesion color, and 64 percent exhibited near complete or complete resolution of lesion thickness after an average of seven treatments [70].

●Propranolol plus pulsed dye laser combination – PDL may provide added benefit to treatment with propranolol:

•In a small, retrospective study of 17 children with large or segmental facial infantile hemangiomas treated with concurrent propranolol and PDL (n = 12), propranolol followed by PDL (n = 5), or propranolol alone (n = 8), infantile hemangiomas treated concurrently with propranolol and PDL achieved complete clearance more often than when PDL followed propranolol or when propranolol was used alone [77]. In addition, combined treatment achieved near complete clearance after fewer days of propranolol (92 days for concurrent treatment versus 288 days for propranolol alone). The cumulative propranolol dose until near complete clearance was lower in the concurrent treatment group than in the propranolol alone group (149 versus 401 mg/kg).

•In another study of 27 infants with 29 infantile hemangiomas (average tumor area 11 cm²) treated with oral propranolol and an average of 10 PDL sessions, 15 patients (60 percent) achieved lesion resolution without sequelae [78]. In 12 patients, sequelae included skin bulging, scarring, pigmentation, alopecia, and telangiectasias.

Adverse effects — Temporary local swelling is a common adverse effect [31]. Application of ice packs and elevation of the affected area may reduce symptoms. However, infants may be upset by the cold sensation of ice. Hyperpigmentation or hypopigmentation are other potential consequences of PDL treatment. Severe pain, scarring, and life-threatening hemorrhage have rarely been reported [86].

PDL treatment occasionally induces ulceration [86]. The use of large spot sizes with low fluences and epidermal cooling mechanisms may help to minimize the risk of ulceration. Patients with diffuse segmental hemangiomas may be at increased risk for ulceration [86,87].

Other lasers — Frequency-doubled lasers have been used for the treatment of hemangiomas. However, in a retrospective study in which 50 infants with 62 superficial infantile hemangiomas were treated with a 585 nm PDL or a frequency-doubled neodymium-doped yttrium aluminum garnet/potassium titanyl phosphate (Nd:YAG/KTP) laser (532 nm), treatment with the PDL was more effective [88]. Successful treatment of deep infantile hemangiomas with intralesional KTP bare fibers has been reported [89,90].

Some authors have suggested the cautious use of 1064 nm Nd:YAG laser for thicker infantile hemangiomas [31]. In one uncontrolled study of a sequential laser system that delivered 595 nm PDL and 1064 nm Nd:YAG light, excellent improvement occurred in 18 out of 25 hemangiomas (72 percent) involving the skin and mucous membranes of the head and neck [91]. However, the relatively high risk of scarring associated with the 1064 Nd:YAG laser and the risk of eye injury when this device is used in the periorbital area must be seriously considered prior to attempting treatment with this laser [31]. Infantile hemangiomas with a deep component are generally best treated with beta blockers [69]. (See "Infantile hemangiomas: Management", section on 'First-line therapy'.)

Fractionated lasers may be effective for improving fibrofatty residua that remain after involution of hemangiomas [92,93]. Fractional laser therapy appeared to be beneficial in a series of five children with involuted hemangioma residua who were treated with an ablative fractional carbon dioxide (CO₂) laser [93]. In addition, in an 18-year-old female patient with residual fibrofatty tissue and redundant skin at the site of a previous facial hemangioma, treatment with a nonablative 1440 nm fractionated laser led to marked clinical improvement [92].

TELANGIECTASIAS AND THE RED FACE — Telangiectasias are common lesions that present as vascular dilatations (0.1 to 1 mm in diameter) that are visible on the skin (picture 7). Telangiectasias occur spontaneously or arise in the setting of other conditions, such as cutaneous photodamage, rosacea, connective tissue or liver disease, radiation, hereditary hemorrhagic telangiectasia, and long-term topical corticosteroid therapy [94]. Patients with numerous telangiectasias on the face frequently present with a complaint of facial redness.

Telangiectasias and secondary facial redness do not require treatment, but lesions that are cosmetically distressing for patients can be removed with electrocautery or lasers. Lasers provide quick and effective therapy, particularly for multiple telangiectasias, large areas with telangiectasias, or lesions that have failed to resolve after electrocautery.

Pulsed dye lasers — Pulsed dye lasers (PDLs) are commonly used for the treatment of telangiectasias. Laser spot sizes and, in some cases, the spot shape (round versus elliptical) can be adjusted to conform to the size or shape of the target vessel.

PDL therapy can result in temporary purpura, which is viewed as unfavorable by many patients (picture 3). Purpura can be minimized or eliminated by use of longer pulse durations (≥6 ms) [95]. However, treatment with subpurpuric laser settings may be less efficacious, contributing to the need for additional treatment sessions [5].

The efficacy of purpura-inducing versus subpurpuric PDL settings was investigated in the following studies:

●In a split-face comparison study of nine patients with facial telangiectasias and erythema treated with a 595 nm long-pulse (6 ms) PDL, purpuric fluences were more effective at reducing vessel diameter and arborization of telangiectasias than multiple passes with subpurpuric laser settings [5]. Subpurpuric fluences were more effective for the reduction of background erythema.

●In a split-face, nonblinded, randomized trial in which patients were treated with a 595 nm PDL (10 ms pulse duration) at either purpuric or subpurpuric fluences, purpura-inducing treatments were more effective [6]. The greatest benefit of treatment was observed in thick, dense telangiectasias.

Multiple passes or judicious pulse stacking can be used to improve treatment response when longer pulse durations are utilized [38,96]. Pulse stacking involves the immediate delivery of repeated pulses (usually two to three) to the same treatment area to increase cumulative heating of the target vessels, while allowing sufficient time for epidermal cooling between pulses. Multiple passes and pulse stacking techniques should only be used cautiously. Cutaneous damage may occur if incorrect settings are used or if the skin response to treatment is not properly monitored.

Other lasers — Frequency-doubled neodymium-doped yttrium aluminum garnet/potassium titanyl phosphate (Nd:YAG/KTP) lasers and intense pulsed light (IPL) are also effective for the treatment of telangiectasias. Lasers with longer wavelengths (eg, the alexandrite, diode, and Nd:YAG) are useful for targeting larger vessels that are located deeper in the skin. Millisecond pulsed 532 nm frequency-doubled Nd:YAG/KTP lasers and IPL can also be used to treat facial telangiectasias with minimal to no purpura [97].

Adverse effects — As in other settings, the risks of laser therapy for telangiectasias include pigmentary alteration, blistering, ulceration, and scarring. Risks of ulceration and scarring are higher with long wavelength lasers, such as the 1064 nm Nd:YAG and 755 nm alexandrite lasers.

ROSACEA-ASSOCIATED ERYTHEMA — Rosacea-associated telangiectasias are managed similarly to other telangiectasias. Laser and light sources are also commonly used for facial erythema secondary to rosacea, and based upon our clinical experiences, treatment can also provide relief from accompanying symptoms of burning and stinging.

Multiple light-based treatments are generally required to achieve the desired clinical response. Intermittent therapy is often necessary to maintain improvement after the completion of a successful treatment course. Although some patients require retreatment every three months, others maintain disease control with treatments separated by several years. (See "Management of rosacea", section on 'Laser and intense pulsed light'.)

SUMMARY AND RECOMMENDATIONS

●Principles of laser therapy – The efficacy of lasers and intense pulsed light (IPL) for vascular lesions stems from the absorption of light by oxyhemoglobin and other hemoglobin species (deoxyhemoglobin and methemoglobin) in lesional vessels. Yellow and green light and, to a lesser extent, near-infrared light are preferentially absorbed by hemoglobin species. Light sources that emit light in these ranges are generally used for the treatment of vascular lesions. Pulsed dye lasers (PDLs) are most commonly used for the treatment of vascular lesions. (See 'Principles of laser therapy' above and 'Types of vascular lasers' above.)

●Port wine birthmarks – PDL therapy is considered the standard of care for the treatment of port wine birthmarks (PWBs) in children and young patients who desire treatment (see "Capillary malformations (port wine birthmarks) and associated syndromes"). We typically utilize a 595 nm PDL with pulse duration of 0.45 ms or greater and an integrated mechanism to cool the epidermis. Multiple treatments are required to achieve clinically significant improvement. (See 'Pulsed dye lasers' above.)

Millisecond pulsed near-infrared lasers such as the 755 nm alexandrite or 1064 neodymium-doped yttrium aluminum garnet (Nd:YAG) laser may be useful for the treatment of thick or nodular PWBs. However, the risk of scarring with long wavelength lasers exceeds the risk with PDL, and the use of these lasers for PWBs should be restricted to experienced clinicians.

Other treatment options for PWBs include the 532 nm frequency-doubled Nd:YAG/potassium titanyl phosphate (KTP) laser, diode laser, IPL, and photodynamic therapy (PDT). (See 'Other lasers and light therapies' above.)

●Infantile hemangiomas – Because of the self-regressing nature of most infantile hemangiomas and the availability of effective medical treatment for large or at-risk lesions, the use of laser therapy is limited to small superficial lesions or ulcerated lesions. (See 'Infantile hemangiomas' above and "Infantile hemangiomas: Management".)

●Facial telangiectasias – Telangiectasias are common benign vascular lesions that are amenable to laser therapy. PDL and other vascular lasers can be effective for these lesions. (See 'Telangiectasias and the red face' above.)