**2. Laser treatments approach in vitiligo patients**

#### **2.1 Excimer laser for immunomodulation in adult vitiligo patients**

Monochromatic excimer light was first described for the treatment of psoriasis in 1997 and 4 years later Baltás et al. reported the first case of successful use of the excimer laser for the treatment of vitiligo in 2001 [3]. In vitiligo patients, the widely use narrowband UVB (NUVB) that contains 310–313 nm wavelength has safety profile. At that wavelength arrival we can also conduct monochromatic excimer laser (MEL) with an obligation of limited skin areas to protect nonlesional apart. Mostly clinicians uses 308 nm wavelength according to obtain skin epidermal barrier to induce immunotargeted therapy. New concept of era called targeted phototherapy is usually recommended for localized forms of vitiligo affecting less than 10% of the body surface area. Although these localized modality could prevent hyperpigmentation of uninvolved skin, it could not achieve to deprive new lesion output. In the literature we do not have so much scientific verifications. In Egypt, Eldin et al. *analyzed* 30 patients with nonsegmental vitiligo with at least two symmetrical vitiliginous patches. They treated twice a week for 6 weeks with 308-nm MEL and NUVB for 6 weeks these contralateral lesions. Three punch biopsies were taken from baseline and 6 weeks later. At the MEL group statistically significant rise in the number of basal pigmented cells in the earlier period [4]. According to that, MEL would be treatment of choice rather than NUVB because of rapid onset, lower cumulative doses and lesser treatment sessions. This study is the only proof of histopathological verification for comparison of these proven treatment modalities. Narrowband UVB, excimer laser and lamp has spreaded out similar wavelength even though they have different radiation properties. Mostly articles have shown that excimer laser and lamp have similar repigmentation rate and also minimal side effects so that clinicians should decide how to treat due to cost benefit analysis.

Lopes et al. published a metanalysis, they conducted there is no difference between repigmentation rate for all three treatment options. 308 nm excimer laser has much more safety profile than narrowband UVB because it works lesser time without affecting uninvolved skin and also affect deeper skin via changeable impulse frequency and intensity. However, excimer laser is characterized by monochromatic, coherent, and high-energy light, whereas NB-UVB consists of polychromatic, incoherent light with lower intensity [5]. Yan et al. declared that lesions located on the face and neck had better repigmentation rate with excimer lamp controversially extremities have better response with NB-UVB. Le Duff et al. observed that the excimer lamp is less expensive than the laser, allowing cost/ effectiveness prolificacy however treatment period has been longer [6]. Sun et al. presented a scientifically supportive study such as seven randomized controlled trials. They declined that excimer laser has as similar as therapeutic effects with lamp and also combination of 308-nm excimer laser with 0.1% tacrolimus or with tacalcitol ointment can improve the repigmentation rate [7]. Different responses could be based on different angle of UVB-light emission to epidermis via fiber optic devices of excimer laser. Mostly, narrowband UVB treatment is used the most effective for nonsegmental vitiligo, while excimer laser treatment is commonly chosen for localized vitiligo by clinicians.

**11**

*Lasers in the Treatment of Vitiligo*

*DOI: http://dx.doi.org/10.5772/intechopen.83836*

Efficacy of the excimer laser depends the number of session in a week or total cumulative doses. Fitzpatrick skin types of III and above typically respond better than lower skin types. As usual, facial, neck and axillary regions have quick response opposed to acral parts of body. Clinicians should refer minimal erythema dose (MED) and increment arrival differs between 10 and 25%. Frequency of the laser did not play a role in pigmentation although rapid onset of treatment depends on suitable action plan. Shen et al. determined that time of repigmentation begins earlier as same as in 2.0 and 3.0 frequency period than 1.0 but also all of them have same pigmentation areas [8]. According to small spot size, these modality is not suitable for patients with vitiligo involving large body surface areas (>15%). Repigmentation differs site by site consist of perifollicular, diffuse, marginal, and

combined. The perifollicular pattern was the most common seen.

There is a negative correlation between the duration of the disease and the percentage of repigmentation which could be named as unresponsiveness. Topical corticosteroids have been a mainstay in vitiligo treatment for decades. However refractory vitiligo patients should need combination modalities. As known, topical corticosteroids have significant adverse effects such as skin atrophy, striae, erythema, acne, increased glucose level, glaucoma. According to that, topical pimecrolimus or tacrolimus ointments have been promising for the treatment of choice. Shin et al. would like to analyze combination of NUVB and excimer laser to unresponsive patients, they also determined that acral lesions are difficult part to treat but combination could be greater choice due to less adverse effect to difficult cases mainly in facial vitiligo group [9]. Latif et al. investigated two randomly selected vitiliginous patches, first group of lesions had taken combination of excimer laser and betamethasone dipropionate and calcipotriol ointment twice daily and second group had taken only excimer laser two unconsecutive days in a week for 12 weeks. They concluded that in nonsegmental vitiligo lesions treated with topical combination of vitamin D3 analogue and steroid with 308 nm MEL gave significant results rather than excimer laser alone and it could be promising option for the treatment of vitiligo [10]. All 10 patients who have bilateral symmetric vitiliginous patches received xenon chloride excimer laser three times weekly and calcipotriol ointment was applied twice Daily one side of the body. While conversely, during the 15th month follow up Goldinger et al. compared a combination of excimer laser and calcipotriol with excimer laser alone, and found no significant difference between them [11]. Passeron et al. analyzed the efficacy of combined tacrolimus (twice daily) and 380 nm excimer laser (twice a week) or difference of monotherapy. Twenty three lesions had taken excimer laser and tacrolimus combination but also 20 lesions had taken laser monotherapy and all lesions have similar repigmentation rates such as 100 versus 85%. They determined that UV-sensitive areas do not have different response rate but in UV-resistant areas combination treatment is clearly superior to laser monotherapy via synergistic effects [12]. Park et al. have shown that increment at the molecular level of tyrosinase and melanin in human melanocytes with combination of excimer laser and tacrolimus rather than each monotherapy in the first 6 month. However, this superiority was not observed in the patients who treated more than 6 months [13]. Wang et al. published an article, all patients received laser therapy twice weekly combined with tacrolimus cream twice daily for 12 weeks. Dermoscopy is a useful tool for asses the outcome of the laser. They found statistically significant induction of residual perifollicular pigmentation and perilesional hyperpigmentation in active disease rather than stable disease [14]. Topical antioxidant cream which includes superoxide dismutase and catalase activity could combine with excimer laser. Soliman et al. published an article the comparison of excimer laser alone and antioxidant cream combination via 30 patients have similar vitiliginous patches has followed up maximum 24 sessions, they found excellent cosmetic results regard minimal side effects [15] Bapur et al.

#### *Lasers in the Treatment of Vitiligo DOI: http://dx.doi.org/10.5772/intechopen.83836*

*Depigmentation*

promising results [1, 2].

treatment response. Furthermore in stable vitiligo patients, surgical methods such as full-thickness tissue graft (punch graft), split thickness graft, and suction blister graft, cellular grafts contains cultured melanocytes/keratinocytes have shown

Monochromatic excimer light was first described for the treatment of psoriasis in 1997 and 4 years later Baltás et al. reported the first case of successful use of the excimer laser for the treatment of vitiligo in 2001 [3]. In vitiligo patients, the widely use narrowband UVB (NUVB) that contains 310–313 nm wavelength has safety profile. At that wavelength arrival we can also conduct monochromatic excimer laser (MEL) with an obligation of limited skin areas to protect nonlesional apart. Mostly clinicians uses 308 nm wavelength according to obtain skin epidermal barrier to induce immunotargeted therapy. New concept of era called targeted phototherapy is usually recommended for localized forms of vitiligo affecting less than 10% of the body surface area. Although these localized modality could prevent hyperpigmentation of uninvolved skin, it could not achieve to deprive new lesion output. In the literature we do not have so much scientific verifications. In Egypt, Eldin et al. *analyzed* 30 patients with nonsegmental vitiligo with at least two symmetrical vitiliginous patches. They treated twice a week for 6 weeks with 308-nm MEL and NUVB for 6 weeks these contralateral lesions. Three punch biopsies were taken from baseline and 6 weeks later. At the MEL group statistically significant rise in the number of basal pigmented cells in the earlier period [4]. According to that, MEL would be treatment of choice rather than NUVB because of rapid onset, lower cumulative doses and lesser treatment sessions. This study is the only proof of histopathological verification for comparison of these proven treatment modalities. Narrowband UVB, excimer laser and lamp has spreaded out similar wavelength even though they have different radiation properties. Mostly articles have shown that excimer laser and lamp have similar repigmentation rate and also minimal side effects so that clinicians should decide how to treat due to cost benefit analysis. Lopes et al. published a metanalysis, they conducted there is no difference between repigmentation rate for all three treatment options. 308 nm excimer laser has much more safety profile than narrowband UVB because it works lesser time without affecting uninvolved skin and also affect deeper skin via changeable impulse frequency and intensity. However, excimer laser is characterized by monochromatic, coherent, and high-energy light, whereas NB-UVB consists of polychromatic, incoherent light with lower intensity [5]. Yan et al. declared that lesions located on the face and neck had better repigmentation rate with excimer lamp controversially extremities have better response with NB-UVB. Le Duff et al. observed that the excimer lamp is less expensive than the laser, allowing cost/ effectiveness prolificacy however treatment period has been longer [6]. Sun et al. presented a scientifically supportive study such as seven randomized controlled trials. They declined that excimer laser has as similar as therapeutic effects with lamp and also combination of 308-nm excimer laser with 0.1% tacrolimus or with tacalcitol ointment can improve the repigmentation rate [7]. Different responses could be based on different angle of UVB-light emission to epidermis via fiber optic devices of excimer laser. Mostly, narrowband UVB treatment is used the most effective for nonsegmental vitiligo, while excimer laser treatment is commonly chosen

**2. Laser treatments approach in vitiligo patients**

**2.1 Excimer laser for immunomodulation in adult vitiligo patients**

**10**

for localized vitiligo by clinicians.

Efficacy of the excimer laser depends the number of session in a week or total cumulative doses. Fitzpatrick skin types of III and above typically respond better than lower skin types. As usual, facial, neck and axillary regions have quick response opposed to acral parts of body. Clinicians should refer minimal erythema dose (MED) and increment arrival differs between 10 and 25%. Frequency of the laser did not play a role in pigmentation although rapid onset of treatment depends on suitable action plan. Shen et al. determined that time of repigmentation begins earlier as same as in 2.0 and 3.0 frequency period than 1.0 but also all of them have same pigmentation areas [8]. According to small spot size, these modality is not suitable for patients with vitiligo involving large body surface areas (>15%). Repigmentation differs site by site consist of perifollicular, diffuse, marginal, and combined. The perifollicular pattern was the most common seen.

There is a negative correlation between the duration of the disease and the percentage of repigmentation which could be named as unresponsiveness. Topical corticosteroids have been a mainstay in vitiligo treatment for decades. However refractory vitiligo patients should need combination modalities. As known, topical corticosteroids have significant adverse effects such as skin atrophy, striae, erythema, acne, increased glucose level, glaucoma. According to that, topical pimecrolimus or tacrolimus ointments have been promising for the treatment of choice. Shin et al. would like to analyze combination of NUVB and excimer laser to unresponsive patients, they also determined that acral lesions are difficult part to treat but combination could be greater choice due to less adverse effect to difficult cases mainly in facial vitiligo group [9]. Latif et al. investigated two randomly selected vitiliginous patches, first group of lesions had taken combination of excimer laser and betamethasone dipropionate and calcipotriol ointment twice daily and second group had taken only excimer laser two unconsecutive days in a week for 12 weeks. They concluded that in nonsegmental vitiligo lesions treated with topical combination of vitamin D3 analogue and steroid with 308 nm MEL gave significant results rather than excimer laser alone and it could be promising option for the treatment of vitiligo [10]. All 10 patients who have bilateral symmetric vitiliginous patches received xenon chloride excimer laser three times weekly and calcipotriol ointment was applied twice Daily one side of the body. While conversely, during the 15th month follow up Goldinger et al. compared a combination of excimer laser and calcipotriol with excimer laser alone, and found no significant difference between them [11]. Passeron et al. analyzed the efficacy of combined tacrolimus (twice daily) and 380 nm excimer laser (twice a week) or difference of monotherapy. Twenty three lesions had taken excimer laser and tacrolimus combination but also 20 lesions had taken laser monotherapy and all lesions have similar repigmentation rates such as 100 versus 85%. They determined that UV-sensitive areas do not have different response rate but in UV-resistant areas combination treatment is clearly superior to laser monotherapy via synergistic effects [12]. Park et al. have shown that increment at the molecular level of tyrosinase and melanin in human melanocytes with combination of excimer laser and tacrolimus rather than each monotherapy in the first 6 month. However, this superiority was not observed in the patients who treated more than 6 months [13]. Wang et al. published an article, all patients received laser therapy twice weekly combined with tacrolimus cream twice daily for 12 weeks. Dermoscopy is a useful tool for asses the outcome of the laser. They found statistically significant induction of residual perifollicular pigmentation and perilesional hyperpigmentation in active disease rather than stable disease [14]. Topical antioxidant cream which includes superoxide dismutase and catalase activity could combine with excimer laser. Soliman et al. published an article the comparison of excimer laser alone and antioxidant cream combination via 30 patients have similar vitiliginous patches has followed up maximum 24 sessions, they found excellent cosmetic results regard minimal side effects [15] Bapur et al.

also has propagated topical tacrolimus or topical clobetasol-17 propionate ointment enhance the efficacy of excimer laser [16]. As a summary, there is big gap for to discuss which topical choice has better results.

In segmental vitiligo patients, excimer laser has claimed as a treatment of choice. As a proof, Bae et al. made a treatment schedule that received 20 mg of prednisolone daily for the first 3 weeks, twice a week excimer laser and twice a day tacrolimus ointment. They found more than half of the patients with segmental vitiligo showed 75% or more repigmentation with combination therapy for mean period is 1 year [17]. Jag et al. also investigate small sample size, firstly gave low-dose oral prednisolone (0.3 mg/kg/day) for 4–8 weeks, 0.1% topical tacrolimus twice daily, and excimer laser twice a week for 12 weeks. They found higher response rate rather than current therapies [18].

Bae et al. evaluated 311 Titanium-Sapphire Laser (TSL) Treatment in vitiligo that based on 14 patients with non-segmental vitiligo are treated with TSL twice a week. They determined working principle as similar as NUVB an EL by immunomodulation and melanocyte stimulation. Main advantage is not necessary to check gas charging and also penetrate deeper than 308 nm wavelength of excimer laser [19].

BinSheikan et al. suggested a surgical needling technique means 30 Gauge inserted almost parallel to the skin surface towards the dermoepidermal junction moving towards the pigmented site to depigmented skin could increase the efficacy of excimer laser [20]. Mutairi et al. reported that combination of split-skin grafting from normal skin to vitiligo part with excimer laser twice a week have long-lasting good results in stable vitiligo patients. All of them satisfied to treatment and respond excellent as well [21].

Leukotrichia also called poliosis mainstays white hair involving the scalp, eyebrows, and pubis has frequently seen together with segmental vitiligo. Kim et al. evaluated the effect of the presence of leukotrichia on the response to excimer laser therapy at the first time and they suggested that leukotrichia has poor response due to lack of melanocyte reservoir. They also did not find any difference between vitiligo types [22]. All in all, disease duration longer than 12 months, presence of leukotrichia and plurisegmental subtype were identified to be independent poor prognostic factors for excimer laser treatment.

Adverse effects of treatments are mild and acceptable which are pruritus, burning sensation, and dryness. MEL has a favorable risk-to-benefit ratio which has only minimal side effects are mainly acute and self-limited phototoxicity especially erythema does not persist longer than 24 hours. Furthermore another local site effects are tolerable that consist of blisters, itching or perilesional pigmentation but do not seen frequently.

If the patient does not improve meanly after 30 sessions twice or three times weekly, it is suggested that further treatment could provide any significant response [23].

Dermatology quality of life index (DLQI) scale could provide us convenient and important data for benefits of the treatment. It occasionally contained validated questionnaires such as symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. In some analysis reports has concluded that long duration of disease, hand and face lesions and female patient have greater impairment of life index but also Shobaili et al. has shown that excimer laser has better improvement in quality of life index [25]. Alghamdi et al. made a survey in Saudi Arabia to prove dermatologists' clinical assessment for vitiligo treatment. They found excimer laser was the most common modality used to treat focal and segmental vitiligo and occasionally used in private clinics [26].

Excimer laser treatments respond faster recovery period and induce repigmentation rate so that clinicians use fewer treatments with less cumulative dose in order to achieve repigmentation compared with traditional phototherapy. The best result

**13**

*Lasers in the Treatment of Vitiligo*

*DOI: http://dx.doi.org/10.5772/intechopen.83836*

**2.2 Excimer laser in child vitiligo patients**

**2.3 UVA1 target laser in children**

have rarely been described.

**2.4 Fractional CO2 laser for ablation modalities**

is noticed on UV-sensitive areas and also does not affect unlesional part of the body regard as the face and neck; whose has shorter history of vitiligo. Combination with topical steroid or topical calcineurin inhibitor (tacrolimus and pimecrolimus) increases the efficacy. The excimer laser has proven to be a useful tool in the treatment of vitiligo.

NBUVB is a safe and effective, well-tolerated treatment option for childhood vitiligo as well as for vitiligo in adults declared as a treatment of choice. Besides the adult population, children who has vitiligo also treated with excimer laser that based on xenon chloride lasers has been delivering radiation of 308–310 nm, with a variable spot size. Acral regions, resistant areas, hidden places are favorable for excimer laser. Gianfaldoni et al. determined treatment schedule should consist of twice weekly among 13 weeks to achieve good response [27]. Clinicians should estimate minimal erythema dose (MED) and begin with 10% lesser than it. Occasionally, face and neck has responded well but acral lesions has repigmented slowly. Cho et al. suggested that treatment response rate has correlated with ana-

Another optional treatment modality could regard as UVA1 target laser consists of an active medium and a Neodymium-doped yttrium orthovanadate (Nd:YVO4) crystal that is "energetically pumped" by another laser with 808 nm wavelength divided sequentially second (532 nm) and third (355 nm) harmonic wavelength delivery. Laser Alba allows the treatment of limited boarded lesional skin areas so that clinician can use a more appropriate dose of energy, leading to shorter duration and less frequent treatment sessions. The treatment with Laser Alba 355 is well—tolerated and already known acute side effects, such as erythema or pruritus

Furthermore, innovative modalities consist of excimer laser, focused microphototherapy and also Laser ALBA should investigate to create new options [27, 29].

As you know, vitiligo therapy is challenging though there is no definitive cure regime. Ablation therapy has recently been coalesced into combination therapy for vitiligo. These ablation modalities contains dermabrasion, erbium-YAG resurfacing, and ablative CO2 laser treatment. Ablation modalities are not curative but they are useful to induce Koebner phenomenon to increase curative topical regimes. Fractional ablative laser has worked as a principle of photothermolysis to moderate skin resurfacing. Firstly, beneficial effect of fractional CO2 laser on vitiligo is postulated to detachment of epidermis will release of cytokines and growth factors for immune response that plays a role as mitogens for melanogenesis. Additionally, fractional CO2 laser via photothermolysis could decrease to skin surface so that absorb topical treatments and also increase efficacy of narrowband UVB treatment. Koebner's phenomenon defined as the development of isomorphic lesions at traumatized uninvolved skin due to that fractional modalities to be concluded follicular hyperpigmentation as a different addition for pathogenesis. King et al. published a metanalysis, they determined ablation modalities (ER-YAG or fractional CO2 laser) manage faster and effective repigmentation than the traditional methods that have explained via four different such as more penetration, skin remodeling, melanocyte migration and cytokine secretion [30]. Despite of that Koebner phenomenon

tomic site of the vitiligo lesion especially in localized type [28].

#### *Lasers in the Treatment of Vitiligo DOI: http://dx.doi.org/10.5772/intechopen.83836*

*Depigmentation*

laser [19].

respond excellent as well [21].

do not seen frequently.

prognostic factors for excimer laser treatment.

discuss which topical choice has better results.

also has propagated topical tacrolimus or topical clobetasol-17 propionate ointment enhance the efficacy of excimer laser [16]. As a summary, there is big gap for to

12 weeks. They found higher response rate rather than current therapies [18].

In segmental vitiligo patients, excimer laser has claimed as a treatment of choice. As a proof, Bae et al. made a treatment schedule that received 20 mg of prednisolone daily for the first 3 weeks, twice a week excimer laser and twice a day tacrolimus ointment. They found more than half of the patients with segmental vitiligo showed 75% or more repigmentation with combination therapy for mean period is 1 year [17]. Jag et al. also investigate small sample size, firstly gave low-dose oral prednisolone (0.3 mg/kg/day) for 4–8 weeks, 0.1% topical tacrolimus twice daily, and excimer laser twice a week for

Bae et al. evaluated 311 Titanium-Sapphire Laser (TSL) Treatment in vitiligo that based on 14 patients with non-segmental vitiligo are treated with TSL twice a week. They determined working principle as similar as NUVB an EL by immunomodulation and melanocyte stimulation. Main advantage is not necessary to check gas charging and also penetrate deeper than 308 nm wavelength of excimer

BinSheikan et al. suggested a surgical needling technique means 30 Gauge inserted almost parallel to the skin surface towards the dermoepidermal junction moving towards the pigmented site to depigmented skin could increase the efficacy of excimer laser [20]. Mutairi et al. reported that combination of split-skin grafting from normal skin to vitiligo part with excimer laser twice a week have long-lasting good results in stable vitiligo patients. All of them satisfied to treatment and

Leukotrichia also called poliosis mainstays white hair involving the scalp, eyebrows, and pubis has frequently seen together with segmental vitiligo. Kim et al. evaluated the effect of the presence of leukotrichia on the response to excimer laser therapy at the first time and they suggested that leukotrichia has poor response due to lack of melanocyte reservoir. They also did not find any difference between vitiligo types [22]. All in all, disease duration longer than 12 months, presence of leukotrichia and plurisegmental subtype were identified to be independent poor

Adverse effects of treatments are mild and acceptable which are pruritus, burning sensation, and dryness. MEL has a favorable risk-to-benefit ratio which has only minimal side effects are mainly acute and self-limited phototoxicity especially erythema does not persist longer than 24 hours. Furthermore another local site effects are tolerable that consist of blisters, itching or perilesional pigmentation but

it is suggested that further treatment could provide any significant response [23].

segmental vitiligo and occasionally used in private clinics [26].

If the patient does not improve meanly after 30 sessions twice or three times weekly,

Dermatology quality of life index (DLQI) scale could provide us convenient and important data for benefits of the treatment. It occasionally contained validated questionnaires such as symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. In some analysis reports has concluded that long duration of disease, hand and face lesions and female patient have greater impairment of life index but also Shobaili et al. has shown that excimer laser has better improvement in quality of life index [25]. Alghamdi et al. made a survey in Saudi Arabia to prove dermatologists' clinical assessment for vitiligo treatment. They found excimer laser was the most common modality used to treat focal and

Excimer laser treatments respond faster recovery period and induce repigmentation rate so that clinicians use fewer treatments with less cumulative dose in order to achieve repigmentation compared with traditional phototherapy. The best result

**12**

is noticed on UV-sensitive areas and also does not affect unlesional part of the body regard as the face and neck; whose has shorter history of vitiligo. Combination with topical steroid or topical calcineurin inhibitor (tacrolimus and pimecrolimus) increases the efficacy. The excimer laser has proven to be a useful tool in the treatment of vitiligo.

## **2.2 Excimer laser in child vitiligo patients**

NBUVB is a safe and effective, well-tolerated treatment option for childhood vitiligo as well as for vitiligo in adults declared as a treatment of choice. Besides the adult population, children who has vitiligo also treated with excimer laser that based on xenon chloride lasers has been delivering radiation of 308–310 nm, with a variable spot size. Acral regions, resistant areas, hidden places are favorable for excimer laser. Gianfaldoni et al. determined treatment schedule should consist of twice weekly among 13 weeks to achieve good response [27]. Clinicians should estimate minimal erythema dose (MED) and begin with 10% lesser than it. Occasionally, face and neck has responded well but acral lesions has repigmented slowly. Cho et al. suggested that treatment response rate has correlated with anatomic site of the vitiligo lesion especially in localized type [28].
