With the development of science and technology and the improvement of people's living standards, skin laser therapy has become the fastest-growing branch in the field of medical lasers. The continuous emergence of new technologies and new equipment has put forward higher requirements for dermatologists. How to master the latest laser technology, operate the equipment well, and better provide satisfactory services to patients and beauty seekers is a challenge for every dermatologist. Therefore, when performing laser treatment, we should attach great importance to the correct treatment endpoint and effectively and reasonably avoid risky treatment reactions to avoid permanent damage.

 
Dermatology often uses laser/light, electricity or energy equipment to treat benign vascular diseases, benign pigmented diseases, hirsutism, tattoos, scars, photoaging and skin relaxation. Among all surgical methods, laser is the most accurate and selective treatment method. Many devices have clear treatment "targets" and can achieve the treatment purpose through different forms of skin damage without causing serious adverse reactions. Therefore, special immediate and (or) early skin reactions or treatment endpoints will appear in various laser treatments and are closely related to the efficacy. The so-called endpoint reaction refers to the immediate or short-term reaction of the skin caused by the laser during the treatment process. This reaction between the laser and the tissue is the endpoint reaction. The endpoint reaction of clinical treatment depends on the type of laser/light and the treatment target. The photothermal effect, photomechanical effect and target characteristics of the laser/light pulse will affect the endpoint reaction. The wavelength, energy, pulse width and cooling method of the laser/light are the most important factors in producing endpoint reactions and even adverse reactions. When using laser/light for treatment, it is very important to understand its treatment endpoint reaction to effectively exert its effectiveness.

Effective endpoint response during laser/light therapy

1、 Benign pigmentary diseases

The use of laser or intense pulsed light (IPL) treatment relies on the principle of selective photothermal action to destroy melanosomes, thereby causing the pigment to be destroyed and absorbed, ultimately achieving the purpose of treatment [1]. Short-pulse lasers (nanosecond or picosecond) of 532 nm, 694 nm, and 755 nm Q-switched lasers are often used to treat freckles. The endpoint of treatment is immediate skin whitening, which lasts for 3 to 20 minutes, followed by a darkening of the color. When using 532 nm laser treatment, purpura is likely to occur because the absorption peak of hemoglobin is close to it [2]. The endpoint of long-pulse (ms) laser or IPL treatment is to slightly darken the color of freckles without affecting the surrounding normal tissues. The surrounding normal tissues will have a slight redness, but it will disappear within a few minutes. Histopathologically, this endpoint reaction of slight darkening is related to the necrosis of pigmented cells in the epidermis [3]. Ota nevus is often treated with 755nm, 1064nm, and 694nm Q-switched lasers. The immediate reaction is whitening of the treated area. After 1064nm treatment, the lesion area will have oozing, bleeding, and scabs. Excessive increase in laser energy does not increase the efficacy, but may cause unnecessary epidermal damage [4]. Zygomatic brown-blue nevus is often treated with 755nm and 694nm Q-switched lasers. The immediate reaction is whitening of the treated area. Zygomatic brown-blue nevus is often accompanied by chloasma. During treatment, it should be noted that excessive doses are not beneficial to the disappearance of skin lesions. It will not only aggravate pigmentation, but also aggravate chloasma. For tattoos, after treatment with Q-switched laser or picosecond laser, the lesions will turn white, and the lesions will immediately be slightly raised by about 1mm. Long pulse laser or IPL should not be used to treat tattoos, especially IPL, which can cause scarring.

2、Benign vascular diseases

The use of laser or IPL to treat vascular diseases also relies on the principle of selective photothermal action. The theoretical basis is that oxygenated hemoglobin and reduced hemoglobin in blood vessels can absorb laser energy of specific wavelengths [5], including 532nm potassium titanylphosphate (KTP), 585nm/595nm pulsed dye laser (PDL) or 755nm emerald laser, 810nm semiconductor laser and 1064nm Nd:YAG laser, thereby destroying vascular endothelial cells [6]. Using the correct wavelength, laser energy, spot size and pulse width can treat vascular lesions. The lesions that can be treated with laser or pulsed light energy include port wine stain (PWS) and other microvascular malformations, hemangiomas, telangiectasias, erythematotelangiectasia rosacea, spider angiomas, cherry angiomas, warts, erythematous scars, poikiloderma, etc. The ideal treatment effect can be achieved by selecting the correct wavelength, combined with the appropriate pulse width and energy. Generally speaking, the pulse width should be equal to the thermal relaxation time of the target vessel. The thermal relaxation time (s) is the same as the square of the diameter of the vessel in millimeters. For very small vessels, such as PWS in children or hemangiomas in infants, a short pulse width (0.5-3ms) is selected to match the thermal relaxation time of microvessels. For large vessels, such as telangiectasias on the face of adults, a long pulse width (6-50ms) is more suitable for matching the thermal relaxation time of these large vessels [7-9].

The endpoint response after treatment with lasers of different pulse widths is also different. For PWS and other vascular malformations, pulsed dye laser (585 nm/595 nm) is the most widely used, and the occurrence of purpura is the endpoint of treatment [9-11]. KTP and IPL can also be used to treat PWS, and their treatment endpoints depend on wavelength and pulse width [12]. Under the same wavelength and energy conditions, long pulse width may not cause purpura like short pulse width. In the treatment of pediatric PWS with PDL, at the same safe treatment energy, when the pulse width is >3ms, purpura may not occur. Long-wavelength lasers can produce deeper treatments, such as the alexandrite 755nm laser, which can be used to treat adult hypertrophic PWS and sometimes can be used to treat refractory PWS in children, especially those with high blood flow [13]. Nd:YAG laser (1064 nm) can penetrate the entire epidermis into the subcutaneous tissue, so it can treat adult PWS. However, since a higher energy is required during the treatment and methemoglobin is produced during the treatment, it is more likely to damage arterial vessels than target vessels, so the risk is higher than that of PDL [14].

When hemoglobin undergoes thermal denaturation, its iron atoms are oxidized to form methemoglobin, which darkens in color after absorbing red light. Then, the blood changes from bright red to dark gray or black. Within minutes, the damaged blood vessel walls leak, causing the color to turn purple, resulting in petechiae and ecchymoses [15]. Dense purpura is associated with the clearance of PWS. If the treatment does not produce a purpuric endpoint reaction immediately, the laser energy can be adjusted and the treatment can be repeated. If purpura is still not achieved, it should be considered whether there is anemia or the skin lesion is not a port wine stain. For example, mixed lymphatic microvascular malformations with low hemoglobin can simulate port wine stains. Therefore, the skin lesions should be carefully evaluated again. Whether the treatment of port wine stains is successful or not, whether the blood is full is also a prerequisite. During treatment, there should be a necessary overlap between the spots. Too large a jump will not achieve a good effect.

For alexandrite laser or Nd:YAG laser, the treatment endpoint is different. The goal is to minimize epidermal burns. Unlike PDL, the energy of these lasers should be controlled to only produce purpura, or the purpura produced is purple-blue in color.

(1). Unlike vascular malformations, the goal of treating infantile hemangioma (IH) is not to destroy blood vessels, but to trigger a biological cascade reaction that leads to the regression of hemangioma, but the specific mechanism is unclear. PDL treatment promotes the early removal of proliferative or stable IH, which can help to clear ulcerative painful hemangiomas and quickly resolve [16,17]. Premature and overly aggressive PDL treatment may lead to ulceration or persistent pigment abnormalities, especially when cooling is not used properly [18]. In clinical treatment, the correct treatment endpoint is subpurpuric volume. Within 1 minute after treatment, a brief or transient darkening of the skin lesions will occur. Laser treatment is mainly used for patients with poor drug response or ulcers, or children who are intolerant to propranolol [19-21].

(2). Telangiectasia Regardless of the cause of telangiectasia (rosacea, spider angiomas, photoaging, CREST syndrome), two useful treatment endpoints for IPL or laser are: immediate darkening of blood vessels or immediate disappearance of blood vessels, and the occurrence of purpura is not necessarily required [22]. Compared with PWS, laser or IPL uses a long pulse delay (10-50ms) to avoid damage to normal small blood vessels and avoid purpura. Long pulse width is more suitable for facial telangiectasia and can treat blood vessels with a diameter of 200-500μm [23]. The immediate darkening of blood vessels is due to the thermal denaturation of oxygenated hemoglobin, which produces darker methemoglobin. Immediate disappearance of blood vessels requires higher energy than darkening of blood vessel color. The thermal effect is caused by thermal coagulation and collagen denaturation in the target blood vessel, which leads to vascular contraction. This laser-tissue interaction leads to vascular contraction, which empties the vascular lumen [6].

Large venous malformations require long pulse width parameters with appropriate cooling measures; small varicose veins, darkening or disappearance of the target blood vessel is the end point of treatment. For larger blood vessels, such as skin veins or venous malformations, when long pulse width treatment is used, there is often a muffled "pop" sound, or the recoil of the handpiece can be felt. This is caused by the expansion of blood bubbles in the veins. Cherry angiomas require short pulse widths, and purpura without petechiae is the end point of treatment. Venous lakes respond well to 30ms 800nm semiconductor lasers, and the darkening or disappearance of blood vessels is the end point of treatment.

3、Hair Removal

The goal of hair removal treatment is to cause irreversible damage to pigmented hair follicles without damaging the epidermis containing pigment. The wavelength of hair removal is 600-1000nm, and the pulse width ranges from 1 to 200ms. Ruby laser (694nm), alexandrite laser (755nm), semiconductor laser (810nm), Nd:YAG laser (1064nm) and IPL mainly target melanin in hair follicles [24-26]. Nd:YAG laser is relatively safe for treating dark hair in dark skin. Compared with short wavelengths, melanin absorbs less 1064nm, so it causes relatively less damage to the epidermis [26]. Skin cooling is necessary, especially for people with dark skin. It should be emphasized that no laser or IPL can treat white hair.

The endpoint reaction of laser or IPL hair removal is the appearance of erythema or edema around the hair follicles within minutes after treatment. This endpoint reaction is an inflammatory reaction of eosinophils, which is related to the damage of hair follicles. In patients with dark skin, erythema is sometimes difficult to appear. Lateral observation can reveal edematous papules around the hair follicles. Although the visible hair shaft will be vaporized or burned, there will be no eschar, blisters, scabs or ulcers. Long-pulsed semiconductor lasers have contact cooling and can burn hair. These eschars should be carefully removed from the laser probe, otherwise it will cause skin burns. Before hair removal laser treatment, the skin should be fully prepared, otherwise it is easy to cause adverse reactions.

4、Lasers without clear endpoint reactions

Fractional lasers and non-ablative mid-infrared lasers have no special treatment endpoint reactions. White or black dotted scabs will appear after fractional laser treatment. Any immediate reaction to non-ablative mid-infrared and lasers means necrosis of the dermis. It is very important to pay attention to the correct cooling method and avoid pulse overlap during non-ablative fractional treatment to avoid burns. Non-ablative fractional lasers may or may not produce white dots associated with thermal damage. Post-treatment edema or mild erythema is beneficial. Small black dots or darker freckles and pigmented lesions may appear within minutes or hours, especially with the 1927nm thulium fractional laser [27]. Histologically, there is thermal damage to the epidermis and dermis, but there is almost no inflammation immediately after treatment.

(1). Ablative fractional lasers. Ablative fractional lasers may cause punctate hemorrhages, but this is not the end point of treatment. Er:YAG is generally more likely to bleed than CO2 fractional lasers. Bleeding is affected by the skin condition (such as normal skin, mature scars or new scars) and the treatment pulse width. Longer pulse widths can produce more thermal coagulation and cause less bleeding. The depth of the laser often exceeds the dermal papilla, and exudation will occur within minutes after treatment [28].

(2). Non-ablative mid-infrared laser Nd:YAG 1320nm laser, semiconductor laser 1450~1550nm, the ideal interaction of these lasers is to produce an upside-down first-degree skin burn, and specific thermal damage will occur in the superficial and middle layers of the dermis [29]. These devices have no therapeutic endpoints. If the laser energy is high enough, it can also produce a visible immediate effect, that is, the formation of white papules, which are caused by coagulation and necrosis of the dermis. The laser energy setting should be lower than the dose that can produce any visible therapeutic response. A slight redness after treatment is a relatively good therapeutic response [29-31].

Warning endpoint reactions are endpoint reactions that can be seen immediately, or manifestations that indicate tissue damage after laser irradiation. These reactions are sometimes therapeutic reactions, and sometimes have warning effects. They can be mainly divided into the following types.

1、Nikolsky sign reaction

Necrotic keratinocytes will cause Nikolsky sign within 5 minutes. When the blister is gently pressed from the side with a finger, the epidermis and dermis will peel off. Nikolsky sign is mainly caused by the loss of adhesion between keratinocytes and the dermis. This phenomenon indicates epidermal necrosis, which may be followed by blisters, erosions or ulcers, which will increase the risk of infection, pigment changes or scar formation [32].

Therefore, during the treatment process, it is necessary to carefully observe whether Nikolsky sign occurs, especially when the patient feels particularly painful during the treatment. If the patient has a history of sun exposure before treatment or has a dark skin color, Nikolsky sign is more likely to occur. Any non-ablative laser using high energy or excessive spot overlap (rapidly and repeatedly overlapping at a certain location), as well as untimely cooling during treatment, can lead to Nikolsky sign. Because the entire area will be edematous or erythematous after laser /IPL treatment, it is difficult to evaluate the signs of skin burns. When using laser or light for treatment, a test spot should be treated and observed for 5 minutes to determine whether Nikolsky's sign occurs, and then determine whether the treatment parameters are feasible.

2 、Severe pain accompanied by skin tissue changes

When using laser, IPL or other devices for skin treatment, if severe pain occurs, it often indicates that adverse reactions may occur. After IPL treatment with too high energy, the skin may turn white temporarily, followed by redness, swelling, and even blisters [33]. Deep-penetrating monopolar radiofrequency or ultrasound treatments can cause fat damage, which manifests as small depressions in the overlying epidermis. When photoelectric treatment causes second-degree or third-degree burns, the following symptoms may occur: severe pain, dense erythema, local edema, blisters, epidermal spatter (or epidermal flaking or epidermal adhesion to the handpiece), epidermal loss or ulceration. These iatrogenic injuries may cause erosion and/or ulceration, scabs, pigmentary changes, secondary infection and scar formation [33].

When laser/IPL is used for hair removal, when the burnt hair adheres to the contact surface of the handpiece, the energy will be greatly absorbed by the burnt tissue, which will cause "stamp"-like burns in the subsequent treatment. Cleaning the treatment handpiece in time before and during treatment can effectively avoid adverse reactions.

When using a dynamic cooling device (DCD), skin frostbite may also occur if the setting is improper. If there is a deviation between liquid nitrogen cold spray and laser emission, it will cause arched or crescent-shaped skin damage. In addition, if the laser handpiece is not completely perpendicular to the skin surface, crescent-shaped skin damage may also occur. The warning endpoint reaction is a bright white frosting on the skin that lasts for a few seconds. This situation can be completely avoided if more attention is paid during the treatment.

3、Skin contraction

Type I collagen is the most abundant protein in the dermis. When the temperature rises to 70°C, type I collagen undergoes a helical twisting conformation change, which can cause immediate skin shrinkage. This endpoint reaction can clearly indicate dermal thermal damage [34]. For some indications, immediate moderate skin contraction is a very useful treatment endpoint (especially ablative laser skin rejuvenation or the last treatment of high-intensity ablative fractional laser). However, any treatment is undesirable to cause dermal damage, and seeing this reaction should stop and re-evaluate the treatment status. For example, immediate skin contraction should not be seen with any selective photothermal laser (such as vascular lesions, pigmented lesions, tattoos, or hair removal). This warning sign also occurs during IPL, radiofrequency (RF), ultrasound or plasma treatments. Another typical clinical sign is the "Pucker" sign, which is the appearance of radiating lines around the spot. More subtle signs of dermal shrinkage are that the skin is slightly lifted and feels firm to the touch [32]. Therefore, during treatment, especially during the first treatment or when adjusting the parameters, it is necessary to observe for 3 to 5 minutes after emitting a pulse and adjust the treatment parameters according to the skin reaction to avoid risks.

4、Burning

When most of the water in the tissue is removed, if the energy is continued to be increased, tissue burning may occur. A thin layer of black or dark brown material will appear on the epidermis and adhere to the skin surface. Skin burning means excessive thermal damage and may leave permanent scars.

During the treatment process using light, sound, and electricity, specific and observable treatment reactions can reflect the effectiveness of treatment or unexpected skin damage and adverse reactions. Each operator should be familiar with the treatment endpoints of each type of photoelectric device. Although the endpoint reaction does not necessarily guarantee clinical efficacy, it is the most important reference for setting laser or pulsed light treatment parameters. Careful observation of the treatment endpoint reaction (especially when the warning endpoint reaction has not yet been reached) is more reliable than the parameters recommended by the literature or operating guidelines and the preset parameters of the device. Generally speaking, the safest and most effective way is to use the lowest possible energy to achieve the treatment endpoint without a warning endpoint reaction. If the endpoint reaction is not reached, it is necessary to adjust the energy, wavelength, pulse width, or even re-evaluate the patient's skin lesion condition. Each treating physician should be familiar with the characteristics and properties of the equipment he operates, give the patient the correct recommendation, and provide individualized treatment. At the same time, he should pay attention to the comprehensive collection of relevant medical history. Before treatment, the patient's treatment history, medication history, allergy history, and light exposure history must be fully evaluated. The endpoint response to treatment may be different in patients with different skin colors, and the doctor must carefully judge the skin type and skin condition of the treatment area. Reducing the risk of adverse reactions depends on choosing the right laser to treat the corresponding patient. Choosing the right wavelength, dose, pulse width and skin cooling measures for each color base is the key to successful phototherapy.