Laser Treatment of Pigmented Lesions

Anatomy and Physiology

For a laser of any wavelength to induce a change in a tissue, it must be absorbed by a cellular target, called a chromophore. One principle to consider when selecting a laser for medical therapy is that a laser’s depth of penetration is inversely proportionate to the wavelength – the shorter the wavelength, the farther it can travel. Regardless, a maximally effective laser will not affect all of the tissue in its path. Instead, an efficient laser will only effect change in its target tissue, also known as a chromophore.[1]

A chromophore is a cellular element that can selectively absorb a specific wavelength and was described by Anderson and Parrish in the 1980s as part of the “selective photothermolysis” principle. Primarily, when a chromophore absorbs energy from a laser, heat is generated and causes desired destruction of the target tissue, but without damage to tissues surrounding the target. Examples of chromophores include water, hemoglobin, melanin, and deoxyhemoglobin. These chromophores differ in that each has a unique wavelength. However, hemoglobin, melanin, and deoxyhemoglobin share the similarity of being visibly pigmented, although their respective colors vary.[1][2]

When lasers induce thermal effects, the chromophore within the target tissue heats to the point of protein denaturation, bond breakage, or boiling of intracellular water, depending on the temperature reached and the duration of exposure to increased heat. In considering how aggressively to treat a lesion, the target tissue’s thermal relaxation time, which is defined as the time required for the tissue to cool to half the peak temperature reached, must be taken into account. It is essential to understand that thermal relaxation time is proportionate to the size of the targeted object. For example, capillaries will take longer to cool than melanosomes.[1]

Laser-induced photomechanical effects are also related to heat, but indirectly.  When the duration of laser exposure is shorter than a tissue’s thermal relaxation time, such as in cases when a pulsed laser is being used, a thermoelastic expansion ensues, sending a shockwave through tissues. This shockwave induces mechanical destruction of the target. Keeping in mind that thermal relaxation time still applies, it would follow that a rapidly pulsing laser would be useful in targeting chromophores that are small, or that are located in smaller structures (e.g., capillaries vs. veins).[1]

One of the critical components of selective photothermolysis is the concept that an effective laser must create a maximal effect on the chromophore and the tissues immediately surrounding it, and minimal impact on the outlying tissues. In other words, inflammation and subsequent repair of the targeted area should occur without collateral damage. It is, therefore, crucial to understand how laser energy is measured and described. A working knowledge of laser measurements and terminology will help to avoid not only unnecessary and ineffective laser treatments, but also overly aggressive treatments, which could lead to iatrogenic injury. The measures to be familiar with are joules, power, watts, fluence, and irradiance.[1]

Joules – Joules are the measure of energy. They are used to describe the energy delivered by pulsed lasers.[1]

Power – Power is equivalent to the rate of energy, or “energy per second.”[1]

Watts – Watts is the measure of power. They are used to describe the energy/ power delivered by continuous lasers.[1]

Joules, power, and watts all measure the amount of energy emanating from a laser. They do not take into account the intensity of the laser energy’s effect on the skin or mucosa. To quantify this effect, the measurements of fluence and irradiance are necessary.[1]

Fluence – Fluence is used to measure the delivery of pulsed lasers, and equals joules per squared centimeter. It is another word for energy density and considers the area of skin or mucosa over which joules are delivered. In other words, it takes into account the size of the laser beam. Consider if the same number of joules is produced by a 0.5 cm laser beam vs. a laser beam with a circumference of 1 cm. The 0.5cm beam will deliver denser energy.[1]

Irradiance – Irradiance is measured in watts per squared centimeter. It is used to measure the energy delivered to the skin or mucosa by continuous laser beams.[1]

Indications

Lesions of the skin or mucosa containing highly dense collections of pigmented chromophores, including hemoglobin, melanin, and deoxyhemoglobin, are generally demarcated from the surrounding tissues through stark color contrast. Such lesions lend themselves to treatment with medical lasers, as this color contrast facilitates the delivery of selective photothermolysis. Basic knowledge of common pigmented lesions will assist the provider in recognizing appropriate indications for medical laser use.

Vascular Anomalies – Vascular anomalies are a broad category of lesions and masses that often require management by several medical specialists, and with multimodality therapies. These are divided into vascular tumors and vascular malformations. Several vascular anomalies are pigmented, the most common of which will be discussed here as they pertain to laser treatment.[3] It is essential for the treating professional to not only be able to differentiate between the different pigmented vascular anomalies, but also to have an understanding of several syndromes which may be encountered during the workup of a vascular lesion.

Infantile Hemangiomas – Infantile hemangiomas, also known as strawberry or cherry angiomas, are vascular tumors. They are the most common benign vascular tumors of childhood, affecting 4.5% of infants. They are more common in females than males, and approximately two-thirds of them are located in the head and neck. They appear as red or reddish-purple raised plaques on the skin, and display rapid endothelial cell turnover. Most infantile hemangiomas are superficial, but there are also deep infantile hemangiomas, which delve into the subcutaneous tissues, or compound hemangiomas, which have both superficial and deep components. Infantile hemangiomas can be focal, multifocal, segmental, or indeterminate. Specific subtypes of hemangiomas are more challenging to treat than others, depending on their extent and location.[4]

Unlike vascular malformations, infantile hemangiomas do not grow and progress as patients grow and age. Instead, they begin as small, flat, hypopigmented, or red spots at birth, which shortly after that begin rapidly proliferating and growing. Hemangiomas reach their peak growth rate around six months of age, and then to enter a natural quiescent phase by one year of age.[4] After the dormant period, infantile hemangiomas begin to shrink and involute over years. Involution is characterized by de-differentiation in fat cells and can leave red staining on the skin once resolved. While observation for uncomplicated infantile hemangiomas until the natural regression phase has been completed is often appropriate, intervention and treatment should be instituted if a proliferating hemangioma begins to threaten or cause cosmetic or functional compromise. In such cases, hemangiomas may bleed and ulcerate, block vital structures such as the eye or airway, or compress, distend, and disfigure skin and cartilage.

Syndromes Associated with Hemangiomas - If a patient is encountered with a facial segmental hemangioma, a workup for cardiac abnormalities, posterior fossa and cerebral vascular anomalies, and ocular irregularities may be necessary to rule out PHACE syndrome.[4]

Capillary Malformations – Also known as port-wine stains, capillary malformations are congenital lesions that are present at birth, at an equal distribution between males and females. They are the result of abnormal low-flow connections of dermal capillaries and appear red and lacy. While they are flat at first, they can become raised and nodular if left untreated, darkening to purple with age.[5] Like other vascular anomalies, capillary malformations are often present in the face and neck.[5]

Syndromes Associated with Capillary Malformations - When they are located in the upper face, along with the distribution of V1, V2, or V3, they can be associated with Sturge-Weber syndrome. This is a sporadic disease that affects the vasculature of the eye and brain and can lead to seizures and developmental delay.[6][6] Patients with significant capillary malformations in the distribution of the upper face have up to a 25% chance of having Sturge-Weber syndrome. They should, therefore, be evaluated for ocular and intracranial findings.[6]

Venous Malformations – Venous malformations are the most common vascular malformation. They result from inappropriately connected, slow-flowing venous vessels, which dilate easily and tend to grow into the tissues where they are located. They commonly present in combination with lymphatic malformations. On physical examination, they are soft, compressible, and blue-tinged. Venous malformations are usually present at birth, although they are often small and not noticed in infancy. They have a special predilection for skin/ mucosa and muscle, with almost half of them are located in the head and neck. They can be present in isolation, as localized or diffuse lesions, or as part of a syndrome.[7] As venous malformations grow and become more extensive, they become difficult to treat with surgical excision subsequent cosmetic and functional loss afterward. It is, therefore, preferable to control them with conservative measures. Lasers can be such a treatment option.

Syndromes Associated with Venous Malformations - The most common syndrome associated with venous malformations is Klippel-Trenaunay syndrome, which should be on the differential if a patient has concomitant capillary malformations, lymphatic malformations, and limb overgrowth.[7]

Arteriovenous Malformations – Arteriovenous malformations are aggressive vascular malformations that can infiltrate and affect multiple tissues and organs. They are high-flow lesions that aberrantly connected arteries and veins, leading to shunting that is locally destructive. These lesions can become severely disfiguring as well as life-threatening if left untreated.[3] They present as a soft mass that is warm to the touch, with a palpable thrill. They can be red or purple. When they are not quiescent, they can bleed, ulcerate, or become ischemic and infected without early intervention. The laser can assist in pathologic control, as full excision is often not feasible, due to extreme vascularity and invasion of local tissues.[8]

Syndromes Associated with Arteriovenous Malformations - Parkes Weber syndrome is similar to Klippel-Trenaunay syndrome, in that capillary malformations and limb overgrowth are present, but the distinguishing factor is the presence arteriovenous malformations, rather than venous malformations.[9]

Pyogenic Granuloma – Also known as lobular capillary hemangioma, a pyogenic granuloma is a benign, often rapidly growing, fibrovascular lesion associated with endothelial proliferation. Pyogenic granulomas often arise from the mucosal surfaces of the head and neck. Hormones frequently aggravate them during pregnancy, and in such cases, are called granuloma gravidarum. Pyogenic granulomas can cause problematic bleeding if left untreated.[10]

Tattoos – Of the lesions discussed in this review, tattoos are the only ones not native to patient skin. Through various methods, tattoo pigment is placed in the dermis. There, dermal fibroblasts engulf the pigments and trap them in the superficial dermal layer. While many tattoos today are electively placed as forms of body art and personal expression, not all tattoos are strictly elective. There are incidents of traumatic tattooing from substances such as gunpowder or dust that can become accidentally embedded in the skin. Providers may also tattoo the skin for medical purposes, such as radiation therapy. Regardless, some patients seek the removal of their tattoos.[11][12][13]

Pigmented Nevi – Benign nevi are melanin-rich, slow-growing, soft, pigmented growths of the skin, which can be congenital or acquired.[14] They vary in location and depth and can carry malignant potential.[15] Excision is possible at times but can be disfiguring with extensive nevi. Topical treatments, dermabrasion, chemical peels, cryosurgery, and other modalities are also used for melanocytic nevi, but carry the risk of scarring and unwanted pigmentary changes.[14][15]

Contraindications

Pregnancy – Pregnancy is not a contraindication to cutaneous laser therapy. In the past, cutaneous or mucosal laser treatments during pregnancy were frequently postponed until after delivery, out of concern for maternal or fetal risk. However, a recent systematic review demonstrated that laser therapy in the treatment of gravid patients had not been proven as a significant risk to human fetuses in any trimester of pregnancy.[16]

Dark Complexions - Darkly pigmented skin is not an absolute contraindication to laser therapy but can be a risk for worsened scarring, given the increased risk for pigmentation changes and scarring in this population. Special considerations are discussed in the "Complications" section.[17]

Suspicion of Malignancy in Cases of Pigmented Nevi -  There is some controversy in treating nevi with lasers as a whole, as the disappearance of the pigment makes a nevus harder to follow in cases of unknown malignant potential. No lesion that is suspicious for malignancy should be treated with laser, and all patients with pigmented nevi should receive long-term follow up.[18]

Equipment

Laser Housing - The utility of lasers lies in their organization and manipulation of electron excitation through a powerful and constant energy source. This energy source is located external to a chamber, within which photons of energy are reflected off of mirrors, stimulating further emissions that occur in a uniform wavelength along an axis. The mirrors within the chamber are constructed so that one of them is partially reflective. This allows for the escape of an organized, monochromatic column of energy, known as the laser beam. A laser beam is collimated, which means that it has a low tendency to diverge, despite traveling long distances. Collimation helps with focusing and aiming the laser beam towards a specific target. Not only can a laser's energy be aimed with specificity, but its delivery can also be manipulated as either a continuous beam or a beam with multiple, successive bursts, called pulses.[1]

Laser Accessories - Several tools have been invented which assist in the delivery of the laser energy. Lasers that are not within the visible spectrum are termed aiming beams. When shone on tissues, these beams guide the laser operator to the laser's location. The beam can also be manipulated by directing it through a fiber optic cable. These fiber optic cables allow for localized laser therapy in hard-to-reach areas.[19]

Cryogen/Coolant – Cooling devices have been shown to protect the epidermis during laser treatments by reducing pain and erythema and helping to prevent blistering, scarring, and pigment changes.[20][21] Cooling can occur before (pre-cooling), during (parallel cooling), and after (post-cooling) contact with a laser beam, and can occur in contact or non-contact manner. Contact cooling involves conducting heat away from the skin to the coolant. It can be active, such as when laser tips of cooled copper are used, or it can be passive, such as when ice or gels are used. Active contact cooling removes heat transmitted to the device by thermoelectric components or liquid cooling agents. Passive contact cooling removes heat from the skin by energy transfer to a cold cooling agent that has been heated. When heat is removed from the skin by evaporation or convection, such as when a cryogen is sprayed, or cold air is blown on the skin, it is referred to as non-contact cooling.[20]

Personnel

Laser Team – Besides the provider who is delivering laser treatment to patients, various individuals comprise a laser team. Each individual should know about laser science and safety protocols.[22]

Laser Operator – Providers who employ the use of lasers should take a certified laser safety course.[23]

Laser Safety Officer – The role of a laser safety officer (LSO) as an individual who maintains laser registration and is well-versed in laser safety emerged in the late 1990s. The LSO is responsible for the management of laser risk and is in touch with personnel in the hospital, who will be involved with laser usage.[23][24]

Preparation

Safety Goggles – The eye is an organ that is at particular risk during laser treatment. Therefore, ocular protection during laser use is critically important for the patient and all members of a laser team. Safety goggles should be specific to the wavelength of the laser in use and should fit snugly and comfortably.[21]

Eye Shields – In addition to safety goggles, patients undergoing laser therapy in the vicinity of the face or eye should also be provided with corneal shields. Corneal shields can be made of metal or plastic and should be lubricated before insertion. While ocular injury has occurred during the use of corneal shields, the incident of damage is higher when the shields have not been worn.[21]

Local Anesthesia - Heat generation and tissue destruction, both hallmarks of laser therapy, can be painful.[25] One of the benefits of laser therapy for skin lesions is that their minimally invasive qualities allow for treatment to be done without general anesthesia. This opens up the possibility of in-office procedures and saves a trip to the operating room. In such cases, local anesthetics can be very useful, especially when children are being treated. Topical solutions such as EMLA cream (eutectic mixture of local anesthetics) and LMX (lidocaine 4% topical in lisosomal formula) can be used. Local nerve blocks may also be administered.[25][26]

General Anesthesia - At times, local anesthetics are insufficient for pain control in cutaneous laser therapy. This situation is encountered more frequently in the pediatric population, as it can be traumatic to require a child to stay still during a prolonged and painful procedure. In such cases, general anesthesia exposure should be discussed with patients and their parents, as well as anesthesia colleagues.[25]

Coolant – Cooling of the treated surface may be achieved through a connected device, or immediately postoperatively by placing ice or ice packs over the treated area.[20]

Technique or Treatment

Treatment of Red Lesions (Infantile Hemangiomas, Capillary Malformations, Arteriovenous Malformations, Pyogenic Granulomas) -

The flash pulsed/ pump dye laser (FPDL) has become a mainstay in treating red lesions, including infantile hemangiomas, arteriovenous malformations, capillary malformations, and pyogenic granulomas. Its 595nm wavelength targets the red chromophore, oxyhemoglobin. The FPDL is most useful for superficial lesions, as its depth of penetration is only 1.2mm.[4] Spot size, which is the area over which the laser beam is delivered, can be varied. Fluence can also be varied, depending on the desired effect and the patient's response. In general, a lower fluence is used for a larger spot size. For example, varying the fluence between 9.5 joules per centimeter squared and 15 joules per centimeter squared would be appropriate for a 7mm spot size. In contrast, a fluence between 8 joules per centimeter squared and 10 joules per centimeter squared would be more desirable for a spot size of 10mm. Slight overlapping of the edges of the spots is beneficial when using the FPDL.[27][5]

Multiple treatments may be necessary to fade the red pigment in a lesion sufficiently.[5] The target tissue should also be protected from overheating, which could induce damage to melanocytes and keratinocytes, resulting in blistering, scarring, and pigmentary changes. Coolants, such as a cryogen spray that can be sprayed during treatment sessions, should be employed during FPDL use.[27]

Treatment of Blue Lesions (Venous Malformations, Arteriovenous Malformations)

The most commonly used laser in the treatment of venous malformations is the Neodymium: yttrium aluminum garnet (Nd: YAG) laser. The Nd: YAG laser, having a wavelength of 1064, targets deoxyhemoglobin as its chromophore. Deoxyhemoglobin, which is blue, is prevalent in venous blood.[28] The Nd: YAG laser can penetrate 5-6 mm, and has coagulative properties.[29]

If the skin is being treated, then the Gentle YAG laser can be used. The Gentle YAG laser is an Nd: YAG laser which delivers a cryogen spray as a coolant for the epidermis, which is susceptible to heat-induced injury. Settings for the Gentle YAG laser can be varied, as the laser power can be delivered over various spot sizes and duration, but generally range from 130 – 200 joules per centimeter squared.[30]

In mucosal treatments, a cryogen is not used. The laser is delivered on a fiber that is placed approximately 0.5 cm above the target tissue, and power is delivered for variable durations, generally from 0.5 to 1.5 seconds. The visible shrinking of the tissue involved in the malformation can be noted immediately upon treatment. The treated areas will develop small, white spots, which should not overlap. Separating the spots will help to prevent the sloughing of the mucosa. Different mucosal lesions can handle different laser power; oral lesions should be treated with 25 W to 30 W, while laryngotracheal lesions should be treated with lower settings between 18 W to 20 W. It should be kept in mind that venous malformations, as other pigmented lesions, generally require repeated treatments.[30]

Tattoo Removal - The most common lasers used today in tattoo removal are the Q-switched (denoting fast-pulsed) 694-nm ruby laser, the Q-switched 755-nm alexandrite laser, the 1,064-nm Nd: YAG laser, and the 532-nm Nd: YAG laser. The different lasers used when removing tattoos can target different colors that have been deposited in the skin.[31] Although the exact mechanism of action of tattoo fading by laser treatment is unknown, it is assumed that the pigments are fractured by photothermal, photochemical, or photoacoustic effects, thereby altering the optical properties of the pigment.[31]

Treatment of Pigmented Nevi - Lasers commonly used in nevus removal can be either specific or nonspecific. Pigment nonspecific lasers target water as their chromophore and resurface the entire epidermis. They are outside the scope of this summary.[18] Specific lasers target melanosomes in the dermis, presumably lysing them photomechanically. Such lasers include the Q-switched ruby laser, the Q-switched alexandrite laser, and the Nd: YAG laser.  During the treatment of pigmented nevi with these lasers, the pulses must be shorter than the melanosomes' thermal relaxation time for lysis to occur.[14] Spot size and fluence can be varied, as with laser treatment of vascular anomalies. In general, deeper lesions are treated with larger spot sizes and higher fluence, as these settings improve penetration.[14]

Complications

Ocular - The Nd: YAG laser, with its ability to be absorbed by the melanin-rich pigment of the retina, can cause retinal hemorrhage, vitreous hemorrhage, retinopathy, preretinal membrane formation, and scarring. Other lasers can damage the lens and the cornea, especially if the beam of the laser is invisible or in the near-visible spectrum. Studies that have published untoward outcomes emphasize the importance of eye shields and safety goggles.[21][32]

Unwanted Skin Changes – Temporary erythema and purpura are normal after many forms of laser treatment, but blistering, scarring, and pigmentary changes should not be expected. All such complications have been reported after laser therapy, as a result of thermal injury. It is critical to test a small area of skin for responsiveness in any patient receiving laser therapy, regardless of skin color, before treating the entire affected area. Additionally, patients should be advised about what skin changes are normal after surgery. For example, when the QSRL is used, patients should be counseled that several color changes will occur. Initially, the lesion may turn white, but this generally fades within minutes. Erythema and edema should be expected, followed by crusting and flaking of the skin within approximately 7 to 10 days.[17]

Darker Complected Patients – Given the wide absorption spectrum of melanin (250 nm to 1,200 nm) patients with darker skin, which at a cellular level contains copious melanin, can experience a nonspecific thermal injury. The competitive absorption that melanin deposits in the basal layer predispose patients with deeper skin tones to not only have a higher incidence of untoward effects but also can decrease the overall efficacy of laser treatments targeted towards pigment. Patients with intensely pigmented skin, including patients with Fitzpatrick phototype VI skin, can still receive laser treatments, but special considerations must be taken into account. First, it is essential to understand that the absorption of laser energy by melanin decreases as wavelength increases. Therefore, longer wavelengths can penetrate more deeply into the skin while being less absorbed by endogenous melanin. In light of this, lasers with longer wavelengths should be used whenever possible on patients with darker complexions.[17]

Clinical Significance

Laser therapy can be a minimally invasive method to treat pigmented lesions of the skin and mucosa. In the case of vascular anomalies, lasers have been shown to control the growth of lesions that would otherwise cause disfigurement or functional impairment. Lasers have also been effectively used to treat other pigmented lesions, that while they may not be growing or progressing, can still cause patients aesthetic concern. For any provider who follows patients with pigmented lesions, lasers are a tool essential to the treatment armamentarium.

Enhancing Healthcare Team Outcomes

All staff members who will encounter lasers must be well-versed in laser safety protocol. Clear communication is essential when verifying that the following measures are in place before firing the laser.

Laser Safety – As lasers are necessarily heat generators, great care must be taken in their use. Collateral damage to not only laser patients’ eyes and skin have been reported, but also damage to the eyes and skin of personnel who are in the room during laser operation. Besides, lasers can start airway and fabric fires. The American National Standards Institute (ANSI) and the Occupational Safety and Health Administration (OSHA) have come up with accessible guidelines to protect both patients and personnel involved in medical laser use.[24]

Fire Safety – Since flammability is a potential laser hazard, safeguards must be in place in case of an open flame. An open basin of water should be available in case of laser fire. A fire extinguisher should be present in the room. Patient skin near the laser treatment area should be washed free of cosmetic products that might contain alcohol.[22]

Laser Sign – The ANSI recommends placement of a laser sign on the outside of each door in which a laser is being used, warning those outside that goggles must be worn, and precautions are being taken.[24]

Window Covers – These should be implemented to reduce the accidental escape of a laser beam outside of the laser treatment room.[22]