Use of Excimer in Dermatology

History of phototherapy 1903 1925 (Mayo Clinic)(Goeckerman) , 1974 Fitzpatrick PUVA 1981ParrishUVB311

Types of Phototherapy Natural sunlight phototheapy (Heliotherapy, Tomesa therapy) Broad-band UVB Narrow-band UVB PUVB UVAB PUVA UVA-1: 30 - 50 - 130 J/cm2 Excimer laser & Light

UVB

DNApyrimidinepyrimidine(6-4) pyrimidone 106 E2Arch Dermatol Res 2005; 297: 3942 ICAMICAMT T J Exp Med. 1999;189:711-8 RANTESArch Dermatol Res. 2005 Nov 12;:1-4 DNA p53

UVB 308nmUVB Bonis

ExcimerJ Drugs Dermatol. 2004 Sep-Oct;3(5):522-5.The term excimer derives from the expression excited dimer. dimer A dimer is a molecule formed by the combination of two atoms, a polymer composed only of two components.Excimers are molecules that are able to bind with other atoms only when electronically excited, such as in an unstable electron configuration. The excimer,therefore, has an extremely short lifetime (10 thousand millionths of a second). When the excitation energy decreases, the excimers emit an ultraviolet photon of extremely precise energy.

Excimer: emitted wavelength Examples of excimers molecules and theirExcimerArF KrF XeF XeCl ArO XeO

Wavelength (nm)193 248 351 308 558 558

ExcimerF2 Kr2 Xe2 KrCl KrO

Wavelength (nm)157 146 72 222 556

Major Models Company: Product, spot size, pulse duration Inpro()DEx308, ?, 8ns Dermalight: Excimer 308 , 2 cm2, 60ns Photomedex: XTRAC, 3.2 cm2, 30ns Wavelight: TALOS, 10/20/25mm, 60ns Ra Medical Systems: PHAROS, 1.8 cm x 1.8 cm sq. to 2 mm round, ?

XTRAC Laser Monochromic Excimer laser 308nm wavelenght middle of narrow band UVB (305-311 nm) range proven to be effective in treating psoriasis

site specific fiberoptic delivery system cable of high doses delivery, without involving healthy skinParrish JA, Jaenicke JS. JID 1981; 76: 359-62

UV-excimer laser for psoriasis clear as little as 1 treatment, clear > 4 months Major technologic achievement UV stable, flexible fiberoptics Designed for localized treatment

more rapid clearing 6 MED well tolerated by psoriasis plaques spare healthy surrounding skin from UVB rays decrease risk of photoaging decrease risk of skin cancer decrease in the number of treatments 6-10 with XTRAC vs 30-40 with regular phototherapy Fewer treatments due to ability to administer high doses given to plaques

Excimer laser vs Excimer lightExcimer lasers are more maintenance costs are higher. expensive and their

Laser therapy requires long treatment session times, because the power and size of the spot are small, on average. Excimer lasers must be used with gas cylinders containing a mixture of He/Xe/Cl. Chlorine is dangerous. The management and disposal of these toxic substances requires specific arrangements and precautions.

Publications about 308nm wavelength in the treatment of Psoriasis

Who are good candidates for this treatment Patients with 10-20% body coverage or mild/moderate cases patients with stable plaque type psoriasis people without a history of Koebnerization

Contraindications Photosensitivity disorders history of keloid formation history of melanoma history of invasive squamous cell carcinoma

Is the treatment painful? No anesthesia is necessary most people do not experience any sensations slight warmth may be felt by some patients slight sunburn sensation 4-10 hours after treatment

XTRAC for psoriasis low energy, no carbonization,one electron transfer instead of 2 electrons (bond breakage) start with 3MED, biw use mineral oil very sparingly to plaques for better penetration descale with Lachydrin Remove any makeup, deodorants, or lotions from skin use a decreasing agent if plaques are thick this allows laser to penetrate skin easiler apply mineral oil before treatment 80/124 complete, average 6.2 times, 75% clearance

Potential side effects of laser treatment Common side effects were tolerated quite well. These included: Temporary hyper-pigmentation blistering - similar to a sunburn erythema erosion pain unsatisfactory results

How many treatments are necessary? Important to allow 2-5 weeks for treatment regimen treatments should be 2Xs per week, minimally 48-72 hours apart on average 4-10 treatments are necessary studies have shown that 84% of the people have 75% improvement in equal to or less than 10 treatments

Minimal erythema dose test Patients will come in the day before treatment for a skin test six different levels of power will be tested on healthy skin patients need to return 24 hours later to have test read to determine doe to start treatment of plaques

Determine Fitzpatrick skin type Type I - fair, always burns type II - burns easily, tans minimally type III - burns moderately, tan gradually type IV - burns minimally Type V - rarely burns, tans to dark Type VI - never burns

MED [Minimal Erythema Dose]Before starting with the treatment it is necessary to determine the MEDMEL@308nm. This value depends on the phototype of the patient:

PHOTOTYPE I 4 s = 200 mJ/cm2 PHOTOTYPE II 5 s = 250 mJ/cm2 PHOTOTYPE III 6/7 s = 300/350 mJ/cm2 PHOTOTYPE IV 7/8 s = 350/400 mJ/cm2

Minimal Eythema Dose (MED) Radiation source Dose increment Field size Nature of skin pigmentation, previous exposure, site

Definition of erythema Time of reading Ambient illumination

308-nm excimer laser for the treatment of psoriasis: induration-based dosimetryArch Dermatol. 2003 Jun;139(6):759-64

Each plaque was treated 2 times a week, with an initial dose based solely on the induration component of the modified Psoriasis Area and Severity Index score for that lesion. Subsequent treatments were twice a week with dosage increments up to 50%, based on the change in induration. Four final consolidation doses were given once the induration score was reduced to zero. RESULTS: Eighteen subjects were treated. There were 4 dropouts because of various scheduling problems. In the remaining 14 subjects, 44 plaques received a mean of 10 treatments (range, 4-14). Treatments were quick and well tolerated. The mean cumulative dose was 8.8 J/cm2 (range, 2.2-22.8 J/cm2). Compared with controls, treated plaques showed significant improvement (P95% (mean: 21 treatments; range: 652) and 16/35 (45%) cleared 5095%. Phototoxicity in the form of erythema and blistering occurred in all patients, particularly around the ears and nape of neck.

A 308-nm excimer laser for the treatment of scalp psoriasis. Lasers Surg Med. 2004;34(2):136-40. Adult subjects with scalp psoriasis unresponsive to class I topical steroids used in conjunction with medicated shampoos were treated with 308-nm excimer laser pulses in conjunction with a hair blower that parted the obstructing hair twice a week for up to 15 weeks. Half of the scalp served as a control. Starting doses were based on standard minimal erythema dose (MED)'s with subsequent increments of up to 20%. Thirteen subjects completed the study without adverse events. Two were dropped due to lack of compliance. At the end of the investigation, the difference in the mean modified PASI scores between the control and treated sites was 4.0 ( 005) comparing 308-nm laser therapy, 308-nm lamp therapy and 311-nm narrowband therapy after 10 weeks in the first regime. The mean number of treatments to achieve clearance was 24. With the accelerated scheme, clearance could be achieved with fewer treatments and with half the cumulative dose of the first regime. Nevertheless, the side-effects such as blistering and crusting were also increased.

A 308-nm monochromatic excimer light in the treatment of palmoplantar psoriasis JEADV 20;523, 2006 Methods Fifty-four patients (29 male and 25 female) affected by PP were treated with MEL every 714 days. A mean number of 10 sessions was performed with an increase of the dose depending on patient's skin type and response. Results All 54 patients completed the treatment. After 4 months of MEL we observed a complete remission in 31 patients, a partial remission in 13 patients, and a moderate improvement in 10 patients. Conclusions These results suggest that MEL can be considered as a valid therapeutic option for treatment of selected forms of PP.

B (narrow-band UVB)

Wu, Ching-Shuang, Yu, Chia-Li, Wu, Chieh-Shan, Lan, Cheng-Che E. & Yu, Hsin-Su (2004) Narrow-band ultraviolet-B stimulates proliferation and migration of cultured melanocytes. Experimental Dermatology 13 (12), 755-763.

B

Experimental Dermatology 2004; 13 : 755-763.

BbFGF ET-1 bFGF (basic fibroblast growth factor) mitogen

ET-1 (endothelin-1) DNA synthesis

Experimental Dermatology 2004; 13 : 755-763.

B phosphorylated FAK (p125FAK) adhesion kinase (FAK)

MMP-2 MMP-2 : Matrix metalloproteinase-2 MMP-2Experimental Dermatology 2004; 13 : 755-763.

VitiligoPhototherapy with peak emission at 311-313 nm is recent and it was initially used for psoriasis. Since then, this light source has also been found useful in the treatment of vitiligo. A recent report on a trial using the 308 nm excimer laser in vitiligo has been published by Spencer and coll.(1). The authors conclude that the degree of repigmentation in a period of 2 to 4 weeks is much higher than that achieved with any other current vitiligo therapy and that the xenon-chloride excimer laser may represent a new treatment modality for the management of stable vitiligo.

Spencer JM, Nossa R, Ajmeri J. Treatment of vitiligo with the 308-nm excimer laser: a pilot study. J Am Acad Dermatol 2002; 46:727-31

(1):

Treatment of Vitiligo with 308-nm xenon-chloride excimer laser: therapeutic efficacy of different initial doses according to treatment areas. J Dermatol. 2004 Apr;31(4):284-92. We evaluated the clinical efficacy of the 308-nm excimer laser treatment for various body areas, using different initial UV doses. One hundred forty vitiligo patches from 69 patients were assigned to 4 groups; face and neck, trunk, extremities, and acral and joint areas. They were then treated twice a week, using different initial UV doses. The rate of repigmentation continued to increase with the number of treatments up to 20 sessions, and then showed plateaus between 20 to 30 sessions. On the other hand, the lesions in acral and joint areas showed the worst responses throughout the treatment sessions. Our findings extend previous observations that the 308-nm excimer laser is an effective treatment option for patients with vitiligo. However, further studies will be needed to determine the optimal dosing and administration method, especially for acral and joint areas.

Publication about MEL@308nm in the treatment of VitiligoG Leone, P Iacovelli, A Paro Vidolin, M Picardo.

Monochromatic Excimer Light 308 nm (MEL) in the treatment of vitiligo: a pilot study.J Eur Acad Dermatol Venereol 2003 Sep; 17(5): 531-7

Optimal weekly frequency of 308-nm excimer laser treatment in vitiligo patients. METHODS: In this prospective, university-based hospital study over 12 weeks we enrolled 14 patients. Each had at least three stable vitiligo lesions in the same body area. The three stable vitiligo lesions in each subject were randomly assigned to receive excimer laser treatment once (1 x), twice (2 x) and three times (3 x) weekly, respectively. The initial ultraviolet (UV) dose was 50 mJ cm(-2) less than the 308nm minimal erythematous dose in vitiligo skin. The UV dose was increased at each treatment session according to the erythematous response to the previous treatment. RESULTS: Thirteen subjects were treated for at least 6 weeks; seven were treated for all 12 weeks. At 6 weeks, the repigmentation rates for treated lesions were 8% (1/13) after 1 x weekly treatment, 23% (3/13) after 2 x weekly treatment and 62% (8/13) after 3 x weekly treatment (P = 0.0134; 3 x vs. 1 x weekly); at 12 weeks, these rates were 46% (6/13), 62% (8/13) and 69% (9/13), respectively (P = NS; 3 x vs. 1 x weekly). Repigmentation initiation correlated with treatment number, regardless of frequency (P = NS). Repigmentation occurred earliest in the most frequently treated lesions (P = 0.0336). At 12 weeks, the projected repigmentation rates for 1 x, 2 x and 3 x weekly treatment approached each other (60%, 79% and 82%, respectively); the mean repigmentation grades (on a scale of 0-5) for 1 x, 2 x and 3 x weekly treatment were 1.7, 2.4 and 3.3, respectively (P = 0.018; 3 x vs. 1 x weekly).

Br J Dermatol. 2005 ;152(5):981-5.

Treatment of atopic dermatitis with the xenon chloride excimer laser. J Eur Acad Dermatol Venereol. 2006 Jul;20(6):657-60. BACKGROUND: Narrow-band ultraviolet B phototherapy is an effictive and safe treatment for atopic dermatitis. We have previously found that the 308 nm xenon chloride excimer laser was more effective than the narrow-band ultraviolet B light for the treatment of psoriasis, suggesting that ultraviolet B laser might offer advantages over narrow-band ultraviolet B. OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy of the 308 nm excimer laser in atopic dermatitis. PATIENTS AND METHODS: Fifteen patients with atopic dermatitis (less than 20% body area involvement) were treated with a xenon chloride excimer laser (XTRAC laser, Photomedex Inc.) twice weekly. The severity of the atopic dermatitis was assessed via (i) a clinical score characterizing the intensity of erythema, infiltration, lichenification and excoriation; (ii) the quality of life, determined by means of a questionnaire; and (iii) a visual linear analogue scale, with which the patients scored the severity of their pruritus. RESULTS: After 1 month of laser therapy, the clinical scores were significantly lower than the initial values. Similar decreases were observed for the quality of life and pruritus scores. No serious or unpleasant side-effects were observed. CONCLUSION: These results suggest that the xenon chloride excimer laser is an effective and well-tolerated treatment for localized atopic dermatitis.

Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses. British Journal of Dermatology 152 (1), 99-103.Alopecia areata. (a) One week after 308-nm monochromatic excimer light treatment with 7 minimal erythema doses (MED), showing intense erythema and peeling. (b) After an additional 6 MED weekly for 6 weeks, complete regrowth was observed and was still present at the 6month follow-up visit.

Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses. British Journal of Dermatology 152 (1), 99-103.Figure 5. Length of remission after treatment with 308-nm monochromatic excimer light. PPPP, palmoplantar pustular psoriasis; P, plaque-type psoriasis; Atopic, chronic atopic dermatitis of the palms; Nonatopic, chronic nonatopic dermatitis of the hands; AA, alopecia areata. *P < 005 vs. the maximal percentage improvement observed after treatment.

Efficacy of 308-nm monochromatic excimer light in different dermatosesDermatosis Mean number of MED per treatment 13 118 Mean number Mean of treatments improveme nt (%) 53 53 73 125 47% 79% 54% 46%

Plaque-type psoriasis (n = 7) Palmoplantar pustular psoriasis (n = 17)

Chronic atopic dermatitis 13 of the palms (n = 8) Chronic nonatopic dermatitis of the hands (n = 10) Alopecia areata (n = 8) 84

91

31

475%

MED, minimal erythema dose. Improvement was calculated as: 1 (posttreatment score/baseline score).

Low-dose excimer 308-nm laser for the treatment of oral lichen planus. Arch Dermatol. 2004 Apr;140(4):415-20. A single-center, before-after trial in nine patients with symptomatic, biopsy-proven OLP, unresponsive to conventional therapies in MGH Eight participants completed the entire study, and 1, despite early improvement, did not complete the study because of hospitalization for an unrelated reason.Intervention an initial dose of 100 mJ/cm(2) once a week. Five patients demonstrated overall excellent clinical and subjective improvement after 7 treatments. Two participants with nonerosive OLP were deemed fair responders. The only poor responder in the study also had chronic active hepatitis C infection. for the responders, remission times ranged from 2 to 17 months. Treatments were painless and well tolerated

Treatment of erosive oral lichen planus by the 308 nm excimer laser. Lasers Surg Med. 2004;34(3):205. Treatment of oral lichen planus with the 308-nm UVB excimer laser--early preliminary results in eight patients. Lasers Surg Med. 2003;33(3):158-60.

The safety and efficacy of the 308-nm excimer laser for pigment correction of hypopigmented scars and striae alba. Arch Dermatol. 2004 Aug;140(8):955-60. Histologic and ultrastructural analysis of ultraviolet B laser and light source treatment of leukoderma in striae distensae. Dermatol Surg. 2005 Apr;31(4):385-7. 308-nm Excimer laser treatment of mature hypopigmented striae. Dermatol Surg. 2003 Jun;29(6):596-8; discussion 598-9.

Mycosis fungoides & Lymphomatoid papulosis 308-nm excimer laser for the treatment of lymphomatoid papulosis and stage IA mycosis fungoides. Photodermatol Photoimmunol Photomed. 2006 Jun;22(3):168-71 Efficacy of the 308-nm excimer laser in the treatment of mycosis fungoides. Arch Dermatol. 2004 Oct;140(10):1291-3 Efficacy of monochromatic excimer laser radiation (308 nm) in the treatment of early stage mycosis fungoides. Br J Dermatol. 2004 Oct;151(4):877-9. Monochromatic excimer light (308 nm) in patch-stage IA mycosis fungoides. J Am Acad Dermatol. 2004 Jun;50(6):943-5.

The excimer laser in dermatology and esthetic medicine Hautarzt. 2004 Jan;55(1):48-57 Mycosid fungoides Lymphomatoid papulosis Oral lichen planus Prurigo nodularis Stria distnesae Alopecia areata psoriasis vulgaris vitiligo atopic eczema light-sensitive dermatoses post-operative hypopigmentation parapsoriasis en plaque Chronic palmar atopic dermatitis palmoplantar pustular psoriasis

Summary Photo and systemic treatments effective but costly and risky UVB is the least painful laser in cosmetic field Useful in patients with limited disease