Long-Term Results of Split-Skin Grafting in Combination with Excimer Laser for Stable Vitiligo:...

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Long-Term Results of Split-Skin Grafting in Combination with Excimer Laser for Stable Vitiligo NAWAF AL-MUTAIRI, MD, FRCPC, YASHPAL MANCHANDA, MD, DNB, y AZARI AL-DOUKHI, MD, z AND AHMAD AL-HADDAD, MD z BACKGROUND Some cases of focal or segmental vitiligo are refractory to medical treatment, and surgi- cal management is the treatment of choice. Postsurgical exposure to ultraviolet B rays can lead to faster and better cosmetic results. OBJECTIVE To determine the long-term results of combination therapy with split-skin-thickness graft- ing and 308-nm excimer laser for the management of stable focal or segmental vitiligo. PATIENTS AND METHODS Seventeen patients (8 female, 9 male) with stable focal or segmental vitiligo not responding to nonsurgical modalities were treated with split-skin-thickness grafting and postgraft- ing with 32 sessions of 308-nm excimer laser, beginning 2 weeks after surgery. The patients were followed up every year for evaluation of results. RESULTS All seventeen (100%) patients showed repigmentation, and overall results were graded as excellent in 12 patients and good in the other five at the end of excimer laser therapy. Final evaluation done at the end of 1 year revealed excellent results in all 17 patients. Two patients developed new vitiligo lesion on other parts of the body during follow-up. None of the patients developed depigmentation of the transplanted skin. CONCLUSION Combination treatment with split-skin-thickness grafting and postsurgical exposure to 308-nm excimer laser in patients with stable focal or segmental vitiligo can lead to fast, cosmetically good, long-lasting results. The authors have indicated no significant interest with commercial supporters. V itiligo is an idiopathic acquired pigmentary disorder clinically characterized by solitary or multiple depigmented macules that may arise in a localized, segmental, or generalized distribution. 1 It is cosmetically disfiguring, especially in dark-skinned individuals, and can cause significant psychological morbidity. Some degree of spontaneous repigmenta- tion occurs in 10% to 20% of patients, but rarely is it cosmetically acceptable, 2 often occurring in a perifollicular pattern. The duration of vitiligo and the body site of depigmented lesions seem to play an important role in the overall response rate achievable with different treatment modalities. 3 The treatment of vitiligo is challenging; although medical therapies are the primary treatments, some patients are refractory to medical treatment. In such patients, surgical therapies can be used alone or in conjunc- tion with medical therapy to achieve repigmentation, provided the disease is stable. In 1964, Behl 4 was the first to report the use of thin Thiersch’s skin grafts to treat vitiligo. Since then, various surgical techniques and modifications have been used to treat recalci- trant but stable vitiligo with permanent and almost complete regimentation. 5 Also, a combination of grafting and other nonsurgical modalities such as psoralen plus ultraviolet (UV) radiation (PUVA) 6,7 and narrow-band (NB) UV-B 8,9 have been used to achieve better and faster results. Ideally, the aim of vitiligo treatment should be to achieve complete and permanent repigmentation toward the color of the surrounding normal skin in the shortest possible time with minimal or no side effects. & 2010 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2010;36:499–505 DOI: 10.1111/j.1524-4725.2010.01477.x 499 Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait; y Departments of Dermatology and z Venereology, Farwaniya Hospital, Kuwait

Transcript of Long-Term Results of Split-Skin Grafting in Combination with Excimer Laser for Stable Vitiligo:...

Long-Term Results of Split-Skin Grafting in Combination withExcimer Laser for Stable Vitiligo

NAWAF AL-MUTAIRI, MD, FRCPC,� YASHPAL MANCHANDA, MD, DNB,y AZARI AL-DOUKHI, MD,z AND

AHMAD AL-HADDAD, MDz

BACKGROUND Some cases of focal or segmental vitiligo are refractory to medical treatment, and surgi-cal management is the treatment of choice. Postsurgical exposure to ultraviolet B rays can lead to fasterand better cosmetic results.

OBJECTIVE To determine the long-term results of combination therapy with split-skin-thickness graft-ing and 308-nm excimer laser for the management of stable focal or segmental vitiligo.

PATIENTS AND METHODS Seventeen patients (8 female, 9 male) with stable focal or segmental vitiligonot responding to nonsurgical modalities were treated with split-skin-thickness grafting and postgraft-ing with 32 sessions of 308-nm excimer laser, beginning 2 weeks after surgery. The patients werefollowed up every year for evaluation of results.

RESULTS All seventeen (100%) patients showed repigmentation, and overall results were graded asexcellent in 12 patients and good in the other five at the end of excimer laser therapy. Final evaluationdone at the end of 1 year revealed excellent results in all 17 patients. Two patients developed new vitiligolesion on other parts of the body during follow-up. None of the patients developed depigmentation ofthe transplanted skin.

CONCLUSION Combination treatment with split-skin-thickness grafting and postsurgical exposure to308-nm excimer laser in patients with stable focal or segmental vitiligo can lead to fast, cosmeticallygood, long-lasting results.

The authors have indicated no significant interest with commercial supporters.

Vitiligo is an idiopathic acquired pigmentary

disorder clinically characterized by solitary or

multiple depigmented macules that may arise in a

localized, segmental, or generalized distribution.1 It

is cosmetically disfiguring, especially in dark-skinned

individuals, and can cause significant psychological

morbidity. Some degree of spontaneous repigmenta-

tion occurs in 10% to 20% of patients, but rarely is

it cosmetically acceptable,2 often occurring in a

perifollicular pattern. The duration of vitiligo and

the body site of depigmented lesions seem to play an

important role in the overall response rate achievable

with different treatment modalities.3 The treatment

of vitiligo is challenging; although medical therapies

are the primary treatments, some patients are

refractory to medical treatment. In such patients,

surgical therapies can be used alone or in conjunc-

tion with medical therapy to achieve repigmentation,

provided the disease is stable. In 1964, Behl4 was the

first to report the use of thin Thiersch’s skin grafts to

treat vitiligo. Since then, various surgical techniques

and modifications have been used to treat recalci-

trant but stable vitiligo with permanent and almost

complete regimentation.5 Also, a combination of

grafting and other nonsurgical modalities such as

psoralen plus ultraviolet (UV) radiation (PUVA)6,7

and narrow-band (NB) UV-B8,9 have been used to

achieve better and faster results. Ideally, the aim of

vitiligo treatment should be to achieve complete and

permanent repigmentation toward the color of the

surrounding normal skin in the shortest possible time

with minimal or no side effects.

& 2010 by the American Society for Dermatologic Surgery, Inc. � Published by Wiley Periodicals, Inc. �ISSN: 1076-0512 � Dermatol Surg 2010;36:499–505 � DOI: 10.1111/j.1524-4725.2010.01477.x

4 9 9

�Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait; yDepartments of Dermatology andzVenereology, Farwaniya Hospital, Kuwait

Subjects and Methods

Seventeen patients (9 male; 8 female) aged 18 to 40

with focal, segmental, stable vitiligo seen between

2005 and 2007 were enrolled in the study (Table 1)

The duration of their disease ranged from 5 to 20

years. All the patients had received various therapies

in the past, including psoralens, NB UV-B, excimer

laser, and steroids, with minimal benefit. None of the

patients had received surgical treatment. Five

patients had a family history of vitiligo, and three

had associated systemic diseases (2 diabetes mellitus;

1 thyroid disorder). None had a history of keloidal

tendency or bleeding diathesis. Eight of the lesions

were on the head and neck, three on the hands,

five on the foot, and one on the trunk). The disease

was stable in all the patients for at least 1 year (range

1–10 years) at the time of enrollment. The follow-up

period ranged from 2 years to 4 years.

Selection criteria were clinically stable lesion for

at least 1 year and focal or segmental vitiligo.

Exclusion criteria were generalized vitiligo, presence

of koebnerization, keloidal tendency, and bleeding

diathesis.

The study protocol conformed to the ethical guide-

lines of the 1975 Declaration of Helsinki, and the

institutional ethics committee approved the study.

All participants provided signed informed consent.

Stable disease was defined as no new lesions or

expansion of the preexisting lesions in the previous

1 year. All patients had a baseline photograph taken.

Information about each patient’s name, age, sex,

occupation, and contact details were noted on a

form. A detailed history regarding the disease, such

as duration, site, progression, type, distribution, and

stability of the lesions, was recorded. Any previous

history of systemic disease, endocrinological distur-

bances, keloidal or bleeding tendency, or herpes

labialis (especially in the patients with facial lesions)

was noted. A detailed history of past treatments was

also obtained. A general physical examination and

systemic evaluation was then performed in all

the patients to exclude any other concomitant

dermatological or medical disorders. A baseline

examination, including complete blood count,

differential count, coagulation profile, liver function

tests, and renal function tests, was performed on all

patients.

Procedure

Split-Skin-Thickness Grafting

Preparation of Donor Site. The site used was the

lateral aspect of thigh. After shaving off the hairs and

proper cleansing with povidone iodine and 70%

ethanol, the area was anaesthetized with 1%

xylocaine without adrenalin. The area was then

stretched, and thin epidermal grafts were taken

using a sterilized platinum razor blade. The blade

was held in a medium-sized straight artery forceps.

The length of the cutting edge of the blade and the

angle at which the blade was held were adjusted to

obtain a uniformly thin graft. The adjusted artery

forceps were then slid against the stretched donor

skin at an appropriate angle, and normal saline was

used if necessary to reduce friction between the blade

and skin. The grafts obtained were transferred to a

petri dish containing normal saline. The area of

the recipient site determined the number of grafts

taken.

Preparation of Recipient Site. After proper cleansing

with povidone iodine and 70% ethanol, the area was

abraded using an electrical dermabrader fitted with a

diamond fraise. The recipient site was abraded until

pinpoint hemorrhages were seen uniformly all over

the lesion. The area was then cleaned with normal

sterile saline and covered with a gauze piece soaked

in normal saline. The grafts obtained were then

spread upside down on the sterile glass slides. Iris

forceps were used to spread the graft. The slide was

placed on the recipient area and pressed against the

skin. The graft was adjusted according to the shape

of the recipient site. Any blood or exudates between

the graft and recipient area were evacuated by firmly

pressing the positioned graft with the help of wet

gauze, without displacing the graft. After properly

covering the recipient site with the grafts, the area

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was dressed with paraffin-based antiseptic dressing

followed by wet gauzes and adhesive tape and then

bandaged to secure the site. A pressure bandage was

used at the recipient site to ensure immobilization.

Postoperative Care. Patients were advised to avoid

excessive movement of the grafted area and to follow

up after 1 week for a change of dressing. All

patients were prescribed prophylactic antibiotics for

1 week and a pain killer if required. Patients

with facial lesions were also given prophylactic

acyclovir to prevent the reactivation of herpes

labialis. The dressing was changed after 1 week,

and redressing was done using the same method.

Two weeks after surgery, the dressing was removed,

and patients were asked to apply topical antibiotic

cream twice daily.

Phototherapy

Method. The grafted area was then treated with

excimer laser twice a week with a fluence starting

from 100 J/cm2. The fluence was raised at every

session until a persistent erythema was noted,

after which the laser was used at the same fluence

until 16 weeks (32 sessions).

Machine. The laser used was a 308-nm excimer laser

(Talos, Wavelight Laser Technology AG, Erlangen,

Germany). The Talos excimer laser is a xenon chlo-

ride (XeCl) gas laser. Talos always operates at the

same pulse repetition frequency of 200 Hz. The

energy per pulse also remains constant in operating

mode. The laser device offers an assortment of three

different hand pieces with diameters of 15, 20, and

25 mm that encompass treatment zones of 1.8, 3.1,

and 4.9 cm2. The pulse length of the Talos excimer

laser is 60 ns, with a repetition frequency of 200 Hz

and an energy-per-pulse emission of 4.6 mJ. The

average output density is 200 mW/cm2.

Response Assessment. The patient and the physician

evaluated the response twice. The first evaluation

was done at the end of the treatment (after 32 ses-

sions with the 308-nm excimer laser), and the second

evaluation was done 1 year after surgery. After that,

Figure 1. Complete repigmentation of localized vitiligo lesion on left medial malleolus. (A) Preoperative localized vitiligo.(B) One week postoperative photo showing well-placed graft. (C) Four-year postoperative photo showing complete repig-mentation.

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the patients were followed at least once a year, but

there was no change in the evaluation.

Results

The maximum area treated in one operative session

was 55 cm2, and the minimum was 2 cm2. The total

area transplanted in 17 patients was 441 cm2, with

an average of 26 cm2.

Response Assessment

Patient Response Assessment. All patients were

asked to grade their response after completion of 32

sessions of excimer laser treatment using a visual

analogue scale, with responses of excellent, good,

fair, and poor. At the first evaluation, 12 (70.5%)

patients rated their response as excellent, and the

remaining five (29.4%) as good. The five patients

with a response of good at the initial evaluation

graded their response as excellent at the time of final

evaluation 1 year after the surgery. Thus, at the

final evaluation, all 17 (100%) patients graded their

response as excellent.

Physician Response Assessment. We evaluated the

results using the scoring system suggested by Gupta

and colleagues10 for the evaluation of autologous

transplants. The scoring was done once at the end of

32 exposures of 308-nm excimer laser and again 1

year after surgery. At the first evaluation, 12 of the

Figure 2. Complete repigmentation of segmental vitiligo (face). (A) Preoperative segmental vitiligo. (B) One-month post-operative photo showing well-placed grafts, with perigraft and intergraft achromic fissures. Also seen is mild thickening ofthe nasal graft. (C) Four-year postoperative photo showing complete repigmentation.

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17 patients had excellent results, and the other five

had good results. At the second evaluation, 1 year

after surgery, all 17 patients had excellent results.

Two patients developed new vitiligo lesions in an

unaffected area, whereas the transplanted areas

retained the pigment. None of the patients developed

depigmentation of the transplanted skin during the

maximum follow-up period of 4 years.

Side Effects. Except for the mild hyperpigmentation

at the donor site visible on closer look, none of the

complications seen during the initial few months

persisted at the time of final evaluation (1 year after

surgery).

Discussion

Surgical treatment11–15 for vitiligo includes tissue

grafts (full- and split-thickness grafts, suction

blister grafts) and cellular grafts (noncultured kera-

tinocytes and melanocytes, cultured melanocytes,

autologous cultured epidermal cells), which basically

consist of transferring the autologous melanocytes

from normally pigmented donor skin to

depigmented skin. The use of surgical techniques

is restricted to the cases of stable, localized or

segmental vitiligo. A systematic review by Njoo

and colleagues16 on autologous transplantation

methods involving 63 studies (16 on punch

grafting, 13 on split-thickness grafting, 15 on

suction blister grafting, 17 on grafting of cultured

melanocytes) showed that the highest mean

success rates are achieved using split-thickness

skin grafting (87%). Khandpur and colleagues17

compared the results of split-thickness skin

grafting and minipunch grafting and had found

split-thickness skin grafting to be superior. After 1 to

2 weeks, the dressings are removed, and it might be

then combined with PUVA or psoralen with

solar ultraviolet light or NB UV-B treatment. The

success of this procedure reported by Gupta and

colleagues10 was 67% of patches with more than

75% repigmentation.

Figure 3. Complete repigmentation of localized vitiligo lesion on forehead. (A) Preoperative localized vitiligo. (B) One-weekpostoperative photo showing well-placed grafts, with a small area of hematoma beneath the graft. Single achromic fissureon the superior and medial aspect of the lesion because of possible side-wise shift of the supralateral graft. Six-monthspostoperative photo showing hypopigmented halo and small areas of graft thickening (C). One-year postoperative photoshowing complete repigmentation and no evidence of graft thickening (D).

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The literature on successful use of the 308-nm

excimer laser dates to 2001. The 308-nm excimer laser

emits a monochromatic light of 308nm and induces

photobiological effects similar to NB UV-B, thus stimu-

lating adjacent melanocytes in the outer root sheath of

hair follicles and on the margins of lesions to migrate

and repopulate the vitiliginous areas. Several studies18–20

have shown the response of vitiligo patches to excimer

laser, and U.S. Food and Drug Administration has

approved it for the treatment of vitiligo and psoriasis.

Excimer laser permits the selective treatment of only

lesional skin in a small number of treatment sessions

over a short period of time and ensures no unnecessary

treatment of healthy skin. Thus the patient receives less

radiation, reducing the risk of skin aging and carcino-

genesis. Furthermore, the unsightly tanning of all

perilesional skin is avoided. Targeted phototherapy with

the 308-nm excimer laser can also reach areas inacces-

sible to conventional phototherapeutic modalities.

Combination treatment with grafting and postsur-

gical PUVA and NB UV-B therapy has been used in

the past. NB UV-B therapy has an advantage

over PUVA because no drugs are required for the

treatment, and the effect of photo-carcinogenesis

and photo-aging are probably reduced. However, the

use of NB UV-B leads to radiation of noninvolved

skin. With most of the suitable candidates for

surgery being cases of localized or segmental vitiligo,

we decided to combine split-thickness skin grafting

with the 308-nm excimer laser therapy postsurgi-

cally because our team has long experience in the

technique, and all of the patients selected in our

study had stable localized or segmental vitiligo

so we thought it was unnecessary to expose our

patients to excessive radiation. Hence, we used a

more targeted 308-nm excimer laser in our patients.

Conclusion

Split-skin grafting is a quick and effective modality

for the treatment of resistant cases of localized

vitiligo. The use of excimer laser after grafting min-

imizes the chances of developing perigraft halo or

achromic fissures, which is a common complication

of the surgery, particularly in a situation in which

TABLE 1. Patient Characteristics

Patient

Age/

Sex Site

Type of

Vitiligo

Duration

(Years)

Area

(cm2)

Grafts

Used, n

Physician Response

Assessment

Follow-Up

(Years)

Initial

Score

Final

Score

1 (Figure 1) 40/M Leg Focal 15 8 4 19 21 4

2 (Figure 3) 36/F Face Focal 20 38 8 18 21 2

3 30/M Leg Focal 10 2 2 13 18 2

4 28/M Face Segmental 15 55 9 18 21 3

5 18/F Neck Focal 5 30 6 18 21 3

6 30/F Hand Focal 8 20 5 13 18 2

7 18/M Trunk Segmental 6 42 7 19 21 2

8 18/M Face Segmental 4 36 11 18 18 4

9 22/M Hand Focal 10 15 8 19 21 3

10 20/F Face Segmental 8 10 6 13 21 3

11 (Figure 2) 40/F Face Segmental 15 5 3 19 21 4

12 19/M Leg Segmental 5 50 14 18 21 2

13 30/F Hand Focal 10 35 10 13 18 4

14 29/M Face Segmental 12 25 8 18 21 3

15 38/M Neck Focal 15 8 5 18 18 4

16 21/F Leg Focal 5 40 7 13 18 4

17 20/F Leg Focal 3 22 6 19 21 2

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some of the grafts fail to survive for any reason.

Routine use of postgrafting excimer laser may lead

to fast, uniform, complete repigmentation of the

recipient area.

Our study shows that permanent cure of a stable,

localized vitiligo is achievable provided that patients

are selected judiciously, proper precautions are taken

during surgery and more importantly for the initial 2

weeks after surgery, and the surgeon has expertise in

the technique.

References

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Address correspondence and reprint requests to: NawafAl-Mutairi, MD, P.O. Box: 280, Farwaniya 80000,Kuwait, or e-mail: [email protected]

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