ORIGINAL
ARTICLE
A comparative study of the mini-punch grafting and hair follicle transplantation in the treatment of refractory and stable vitiligo Mohammad Ali Mapar, MD,a Moslem Safarpour, MD,a Mokhtar Mapar, MSc,c and Mohammad Hosein Haghighizadeh, MScb Ahvaz, Iran, and G€ oteborg, Sweden Background: Some vitiligo lesions are resistant to all medical treatments. Objective: We sought to compare the efficacy of hair follicle transplantation and mini-punch grafting for the treatment of refractory vitiligo lesions. Methods: A total of 25 patients with stable and resistant vitiligo participated in the study. In each patient, a resistant vitiligo patch was divided into 2 equal parts. One part was treated with hair follicle transplantation and the other part with mini-punch grafting. Postsurgically, the recipient areas were exposed to narrowband ultraviolet B twice a week for 6 months. The diameter of the repigmentation around each graft was measured monthly. Results: At the end of the sixth month, 68% of follicle grafts, and 72% of mini-punch grafts, had repigmentation. The mean diameter of repigmentation around follicle grafts was 5 6 1.7 mm and around punch grafts was 5.3 6 1.6 mm. There was no significant difference between the 2 groups statistically (P = .18). Limitations: Small sample size and short time of follow-up are limitations. Conclusions: Because the results of the 2 methods are not statistically different and mini-punch grafting is much easier to do than follicular transplantation, we recommend mini-punch grafting to treat drug-resistant vitiligo. ( J Am Acad Dermatol 10.1016/j.jaad.2013.11.044.) Key words: Ahvaz; grafting; hair follicle; punch; resistant; transplantation; vitiligo.
itiligo is an acquired skin pigmentary disorder characterized by circumscribed white macules and patches. Affected individuals have a vast reduction of quality of life, and psychological problems.1-3 Treatment of vitiligo is often difficult and prolonged. Many treatments have been suggested. The disease is primarily treated by medical therapies but complete repigmentation is rare. Most vitiliginous lesions respond well to medication, however, a few of them may not repigment in spite
V
of long-term therapy and even with a combination of several medical therapeutic regimens. A surgical technique may be necessary to obtain an optimal result for such refractory lesions. Several surgical methods have been developed including minipunch grafting,4,5 hair follicle transplantation,6 suction blister epidermal grafting,4,7 split-thickness grafting,8 transplantation of cultured autologous melanocytes,9 and noncultured melanocytes grafting.10,11 This study was designed to compare the efficacy of 2 surgical techniques (mini-punch
From the Department of Dermatology, Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaza; Department of Biostatistics, Health School, Jundishapur University of Medical Sciences, Ahvazb; and Department of Applied Physics, Division of Biological Physics, Chalmers University of Technology, G€ oteborg.c This study was Dr Safarpour’s postgraduate thesis and supported by a grant from Jundishapur University of Medical Sciences to Dr M. A. Mapar. Conflicts of interest: None declared.
Accepted for publication November 30, 2013. Reprint requests: Mohammad Ali Mapar, Department of Dermatology, Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaz, Iran. E-mail: mapar.m@ gmail.com. Published online January 22, 2014. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.11.044
1
2 Mapar et al
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was explained to the participants that some unwanted hairs may grow on their lesions. The nearest anatomic site of normal pigmented skin to the recipient patch was chosen as the donor for mini-punch grafting. This decision was taken to assure the highest similarity of texture and color of the donor to the recipient site. We used 1-mm punches both for donor and METHODS recipient sites. Dressing was This prospective comparaCAPSULE SUMMARY removed after 1 week, and tive trial was conducted from then the recipient areas were May 2012 to May 2013 in the Hair follicle transplantation and miniexposed to narrowband outpatient department of punch grafting are useful surgical ultraviolet B twice a week Imam Khomeini Hospital, methods for the treatment of drugfor 6 months. Patients were Ahvaz, Iran. The ethics resistant vitiligo. treated initially with an committee of Jundishapur The efficacy of the 2 techniques was not irradiation dose of 0.2 J/cm2 University of Medical significantly different but mini-punch followed by 20% increments Sciences, Ahvaz, Iran, grafting is much easier to do. at each visit if tolerated. The approved the protocol of the diameter of the repigmentastudy (eth-436, 1391.2.2). We recommend mini-punch grafting to tion around each graft was Vitiligo was considered resistreat drug-resistant vitiligo. measured monthly by a ruler tant when it had not rein millimeters. The data were sponded to standard medical analyzed using software (SPSS, Version 19.0, IBM treatments during the past 2 Corp, Armonk, NY). We used K2 and t test to years. Stable vitiligo was defined when no progression compare the data. Statistical significance was of the old lesions and no development of new lesion assumed at P less than .05. was observed in a patient during the past year. Exclusion criteria included ages younger than 12 or older than 60 years, pregnancy, lactation, hepatitis, HIV infection, history of photosensitivity or skin cancer, or a RESULTS tendency to keloid formation. All patients with vitiligo A total of 25 patients (21 women and 4 men) with who have been under treatment in previous years but nonsegmental vitiligo participated and all completed left with some resistant patches that did not respond to the study. Their mean age was 26.7 years (range, any treatment were allowed to participate in the study, 20-47 years). In all, 20% had Fitzpatrick skin type II, if they fulfilled the defined criteria and signed the 52% type III, and 28% type IV. The most common site consent form. of grafting was the wrist (40%) then the elbow (16%). Skin lesions on different anatomic regions of the In 44% of the patients, the hair color on the vitiligo body may show different response to treatments. lesions was white (Table I). A family history of Therefore, we decided to apply the treatments on the vitiligo was positive in 20% of the patients. exact same lesion, rather than trying to spot totally The transplanted hairs grew in black in all lesions symmetric lesions on the opposite sides of the body. and did not change color in the course of the In this way we made sure the conditions for both treatment. One month into the treatment, follicular methods were as similar as possible. isolation technique was more effective than miniOne resistant patch in each patient was selected punch grafting statistically, with 2 6 0.6 mm of according to the patient’s preference. The lesion was repigmentation relative to 1.6 6 0.4 mm (P \ .03). divided into 2 equal parts with a straight line passing Nevertheless, there was no statistical difference in the middle of the lesion. A random number table between the efficacies of the 2 techniques in was used to randomly assign the treatments to each the following months. At the end of the study, the half. One half of the lesion was treated with single follicular grafts in 68% of the patients and the minihair follicle transplantations and the other half with punch grafts in the 72% of the patients showed mini-punch grafts. On each side, grafts were repigmentation (Figs 1 to 4). The mean diameter of implanted 1 cm apart from each other. Follicular repigmentation was 5 6 1.7 mm around follicular isolation technique was used for follicle grafting. grafts and 5.3 6 1.6 mm around mini-punch grafts (P Hair follicle donor site was occiput. Unlike most \ .18) (Table II). No complications such as Koebner previous trials, we transplanted complete hair phenomenon, scar formation, and cobblestoning follicles and did not cut a third lower part of it. It were observed in our patients. grafting and hair follicle transplantation) in the treatment of resistant and stable vitiligo patches. To our knowledge, there is no study comparing these 2 surgical techniques simultaneously in the same patient for the treatment of refractory and stable vitiligo.
d
d
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Table I. Demographic information of the patients Case no. Sex Age, y
Treatment Hair color Extent of site of the lesion involvement, %
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Wrist Wrist Wrist Shin Elbow Forearm Ankle Elbow Foot Chest Wrist Shin Elbow Wrist Wrist Elbow Wrist Wrist Neck Thigh Hand Wrist Wrist Armpit Hand
F M F F F M F M F F F F M F F F F F F F F F F F F
47 28 27 20 20 21 22 39 25 35 24 23 42 32 22 22 20 25 27 38 24 22 24 20 20
White White White White White White Black Black Black Black White White Black White Black White Black Black Black Black White Black Black Black Black
10 10-20 10-20 30 10 20-30 10-20 10-20 10 10 10 20-30 10 10-20 10-20 20-30 10 10-20 10 10 10-20 10-20 10 10 10-20
Fig 2. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 2 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
F, Female; M, male.
Fig 3. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 3 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
Fig 1. Vitiligo lesion on the forearm before treatment. L, Left; R, right.
DISCUSSION Vitiligo is a common disease of melanocytes characterized by white depigmented skin patches. Although it is not physically disabling, it is a progressive disfiguring disease and causes severe cosmetic distress, particularly in darkly pigmented skin. Melanocytes are not only found in the skin, mucous membranes, and hair follicles, but can also be observed in eyes, ears, and central nervous system.
Normal hair follicles and basal layer of the epidermis are 2 sites of melanocyte reservoir. Vitiligo is the result of selective destruction of melanocytes in the involved skin, mucous membranes, and hair follicles. Medical treatments of vitiligo induce normal melanocyte proliferation if there are any left in the vitiliginous skin and hair follicles. They also activate the inactive melanocytes in the outer root sheath of hair follicles and induce their migration into epidermis of the skin lesions.12,13 Some patients may not respond to treatment in spite of long-term therapy and even with a combination of several medical therapeutic regimens. In such refractory cases, lack of any response to medical treatments may indicate a complete destruction of melanocytes in the lesions. Therefore, there are not any melanocytes to proliferate and it is necessary to choose a surgical method for transplantation of normal and healthy melanocytes to the skin lesions with the hope that these melanocytes may be proliferated and induced repigmentation. In our study only 18 of 25 patients showed repigmentation
4 Mapar et al
J AM ACAD DERMATOL
Fig 4. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 6 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
Table II. Comparison of mean repigmentation sizes in millimeters for 2 surgical methods Follow-up time, mo
1 2 3 4 5 6
Follicle grafting
2.1 6 0.6 2.7 6 1 3.2 6 1.2 3.9 6 1.5 4.6 6 1.6 5 6 1.7
Punch grafting
P value
6 6 6 6 6 6
.03 .88 .62 .51 .24 .18
1.7 2.7 3.3 4.0 4.8 5.3
0.4 0.6 1.1 1.5 1.6 1.6
with mini-punch grafting. At the end of the first month, follicular isolation technique was more effective than mini-punch grafting statistically. But from the second month onward, the size of repigmentation around mini-punch grafting become larger than that of hair follicle transplantation clinically. Nevertheless there was no statistical difference between the results of these 2 techniques. Our results with punch grafting are very similar to that of Malakar and Lahiri.14 They observed repigmentation in 72% of their patients with mini-punch grafting for the treatment of lip vitiligo. In another study by Feetham et al,15 84% repigmentation was reported, which is slightly higher than our case. The punch size used in that study (1.5 mm rather than 1 mm) might have contributed to the higher repigmentation rate. In contrast to the other punch grafting studies, we chose the nearest area with healthy normal pigmented skin to the recipient site as the donor site, whereas in other studies the buttock skin serves as the donor site. No complications such as cobblestone-like appearance, Koebner phenomenon, or hyperpigmentation were observed in our patients with 1-mm punch grafting. However Fongers et al,16 noticed cobblestone-like appearance at recipient areas in 27% of their patients. This might be a result of using a larger punch size of 2 mm. This
complication may be prevented by using a smaller punch size. Fongers et al16 also found 16.4% Koebner phenomenon at the donor sites whereas no case of this phenomenon was observed in our patients. The stability of vitiligo can contribute to that. Although our patients had stable vitiligo, theirs had unstable vitiligo. To obtain a good result and decrease the complications in surgical techniques, it is very important to select patients in stable status. Currently, there is no consensus among dermatologist regarding the minimum time of the stability period. Different authors have used periods ranging from 3 months to 3 years. In our study, we chose 1 year as the minimum time of stability period. In studies by Agrawal and Agrawal17 and Arrunategui et al,18 repigmentation around follicular grafts was reported in 50% to 60% and 40%, respectively, but we had 68% success rate. This difference might be a result of the small sample size of these 2 studies. The sample size in the first study was 8 cases and in the second was 10 cases. In our study, 7 patients did not respond to either surgery, and 1 patient responded only to the punch grafting. This is a significant number of nonresponding patients. It remains to be known why some lesions in some patients do not respond at all. Possibly the existence of some toxins or antibodies at the recipient site contribute to the destruction of the melanocytes. Grafting may stimulate and induce antibody production at the recipient site. The clearance of antigen (melanocytes) removes the stimulus for further antibody production, and re-entry of the antigen (melanocytes) into the environment may again stimulate antibody production that destructs or rejects the grafted melanocytes and prevents the influence of surgical treatments. As can be seen in Table II, from the second month onward, pigmentation is more rapid around mini-punch grafting compared with the hair follicle transplantation, and the P values decrease gradually in the following months. We suspect, if the phototherapy was continued more than 6 months, that the difference might have become statistically significant. Our study had some limitations, including the relatively low number of patients and a short follow-up period of 6 months. Nevertheless, to our knowledge, it is the first study that compares minipunch grafting and hair follicle transplantation simultaneously in the same patient for treating refractory and stable vitiligo. Conclusions Because the results of the 2 methods are not statistically different, and mini-punch grafting is
J AM ACAD DERMATOL
much easier than follicular transplantation, we recommend mini-punch grafting for treating drug-resistant vitiligo. REFERENCES 1. Kent G, Al’Abadie M. Psychologic effects of vitiligo: a critical incident analysis. J Am Acad Dermatol 1996;35:895-8. 2. Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes 2003;1:58. 3. Parsad D, Pandhi R, Dogra S, Kanwar AJ, Kumar B. Dermatology Life Quality Index score in vitiligo and its impact on the treatment outcome. Br J Dermatol 2003;148: 373-4. 4. Falabella R. Surgical therapies for vitiligo and other leukoderma, part 1: minigrafting and suction epidermal grafting. Dermatol Ther 2001;14:7-14. 5. Singh KG, Bajaj Ak. Autologous miniature skin punch grafting in vitiligo. Ind J Dermatol Venereol Leprol 1995; 61:77-80. 6. Malakar S, Dhar S. Repigmentation of vitiligo patches by transplantation of hair follicles. Int J Dermatol 1999;38: 237-8. 7. Ozdemir M, Cetinkale O, Wolf R, Kotogyan A, Mat C, Tuzun B, et al. Comparison of two surgical approaches for treating vitiligo: a preliminary study. Int J Dermatol 2002;41:135-8. 8. Agrawal K, Agrawal A. Repigmentation with dermabrasion and thin split-thickness skin graft. Dermatol Surg 1995;21: 295-300.
Mapar et al 5
9. Czajkowski R, Placer W, Drewa T, Kowaliszyn B, Sir J, Weiss W. Autologous cultured melanocyte in vitiligo treatment. Dermatol Surg 2007;33:1027-36. 10. Mulekar SV. Long-term follow-up study of 142 patients with vitiligo vulgaris treated by autologous, non-cultured melanocyte-keratinocyte cell transplantation. Int J Dermatol 2005;44:841-5. 11. Mulekar SV, Al Issa A, Al Eisa A. Treatment of vitiligo on difficult-to-treat sites using autologous non-cultured cellular grafting. Dermatol Surg 2009;35:66-71. 12. Cui J, Shen LY, Wang GC. Role of hair follicles in the repigmentation of vitiligo. J Invest Dermatol 1991;97:410-6. 13. Ortonne JP, MacDonald SM, Micouid A, Thivolet J. PUVA induced repigmentation of vitiligo: a histochemical (split-DOPA) and ultrastructural study. Br J Dermatol 1979;101:1-12. 14. Malakar S, Lahiri K. Punch grafting for lip leukoderma. Dermatology 2004;208:125-8. 15. Feetham HJ, Chan JL, Pandya AG. Characterization of clinical response in patients with vitiligo undergoing autologous epidermal punch grafting. Dermatol Surg 2011;38:14-9. 16. Fongers A, Wolkerstorfer A, Nieuweboer-Krobotova L, Krawczyk P, Toth GG. Long-term results of 2-mm punch grafting in patients with vitiligo vulgaris and segmental vitiligo: effect of disease activity. Br J Dermatol 2009;161:1105-11. 17. Agrawal K, Agrawal A. Vitiligo: surgical repigmentation of leukotrichia. Dermatol Surg 1995;21:711-5. 18. Arrunategui A, Arroyo C, Garcia L, Covelli C, Escobar C, Carrascal E, et al. Melanocyte reservoir in vitiligo. Int J Dermatol 1994;33:484-7.
ARTICLE
A comparative study of the mini-punch grafting and hair follicle transplantation in the treatment of refractory and stable vitiligo Mohammad Ali Mapar, MD,a Moslem Safarpour, MD,a Mokhtar Mapar, MSc,c and Mohammad Hosein Haghighizadeh, MScb Ahvaz, Iran, and G€ oteborg, Sweden Background: Some vitiligo lesions are resistant to all medical treatments. Objective: We sought to compare the efficacy of hair follicle transplantation and mini-punch grafting for the treatment of refractory vitiligo lesions. Methods: A total of 25 patients with stable and resistant vitiligo participated in the study. In each patient, a resistant vitiligo patch was divided into 2 equal parts. One part was treated with hair follicle transplantation and the other part with mini-punch grafting. Postsurgically, the recipient areas were exposed to narrowband ultraviolet B twice a week for 6 months. The diameter of the repigmentation around each graft was measured monthly. Results: At the end of the sixth month, 68% of follicle grafts, and 72% of mini-punch grafts, had repigmentation. The mean diameter of repigmentation around follicle grafts was 5 6 1.7 mm and around punch grafts was 5.3 6 1.6 mm. There was no significant difference between the 2 groups statistically (P = .18). Limitations: Small sample size and short time of follow-up are limitations. Conclusions: Because the results of the 2 methods are not statistically different and mini-punch grafting is much easier to do than follicular transplantation, we recommend mini-punch grafting to treat drug-resistant vitiligo. ( J Am Acad Dermatol 10.1016/j.jaad.2013.11.044.) Key words: Ahvaz; grafting; hair follicle; punch; resistant; transplantation; vitiligo.
itiligo is an acquired skin pigmentary disorder characterized by circumscribed white macules and patches. Affected individuals have a vast reduction of quality of life, and psychological problems.1-3 Treatment of vitiligo is often difficult and prolonged. Many treatments have been suggested. The disease is primarily treated by medical therapies but complete repigmentation is rare. Most vitiliginous lesions respond well to medication, however, a few of them may not repigment in spite
V
of long-term therapy and even with a combination of several medical therapeutic regimens. A surgical technique may be necessary to obtain an optimal result for such refractory lesions. Several surgical methods have been developed including minipunch grafting,4,5 hair follicle transplantation,6 suction blister epidermal grafting,4,7 split-thickness grafting,8 transplantation of cultured autologous melanocytes,9 and noncultured melanocytes grafting.10,11 This study was designed to compare the efficacy of 2 surgical techniques (mini-punch
From the Department of Dermatology, Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaza; Department of Biostatistics, Health School, Jundishapur University of Medical Sciences, Ahvazb; and Department of Applied Physics, Division of Biological Physics, Chalmers University of Technology, G€ oteborg.c This study was Dr Safarpour’s postgraduate thesis and supported by a grant from Jundishapur University of Medical Sciences to Dr M. A. Mapar. Conflicts of interest: None declared.
Accepted for publication November 30, 2013. Reprint requests: Mohammad Ali Mapar, Department of Dermatology, Imam Khomeini Hospital, Jundishapur University of Medical Sciences, Ahvaz, Iran. E-mail: mapar.m@ gmail.com. Published online January 22, 2014. 0190-9622/$36.00 Ó 2013 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2013.11.044
1
2 Mapar et al
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was explained to the participants that some unwanted hairs may grow on their lesions. The nearest anatomic site of normal pigmented skin to the recipient patch was chosen as the donor for mini-punch grafting. This decision was taken to assure the highest similarity of texture and color of the donor to the recipient site. We used 1-mm punches both for donor and METHODS recipient sites. Dressing was This prospective comparaCAPSULE SUMMARY removed after 1 week, and tive trial was conducted from then the recipient areas were May 2012 to May 2013 in the Hair follicle transplantation and miniexposed to narrowband outpatient department of punch grafting are useful surgical ultraviolet B twice a week Imam Khomeini Hospital, methods for the treatment of drugfor 6 months. Patients were Ahvaz, Iran. The ethics resistant vitiligo. treated initially with an committee of Jundishapur The efficacy of the 2 techniques was not irradiation dose of 0.2 J/cm2 University of Medical significantly different but mini-punch followed by 20% increments Sciences, Ahvaz, Iran, grafting is much easier to do. at each visit if tolerated. The approved the protocol of the diameter of the repigmentastudy (eth-436, 1391.2.2). We recommend mini-punch grafting to tion around each graft was Vitiligo was considered resistreat drug-resistant vitiligo. measured monthly by a ruler tant when it had not rein millimeters. The data were sponded to standard medical analyzed using software (SPSS, Version 19.0, IBM treatments during the past 2 Corp, Armonk, NY). We used K2 and t test to years. Stable vitiligo was defined when no progression compare the data. Statistical significance was of the old lesions and no development of new lesion assumed at P less than .05. was observed in a patient during the past year. Exclusion criteria included ages younger than 12 or older than 60 years, pregnancy, lactation, hepatitis, HIV infection, history of photosensitivity or skin cancer, or a RESULTS tendency to keloid formation. All patients with vitiligo A total of 25 patients (21 women and 4 men) with who have been under treatment in previous years but nonsegmental vitiligo participated and all completed left with some resistant patches that did not respond to the study. Their mean age was 26.7 years (range, any treatment were allowed to participate in the study, 20-47 years). In all, 20% had Fitzpatrick skin type II, if they fulfilled the defined criteria and signed the 52% type III, and 28% type IV. The most common site consent form. of grafting was the wrist (40%) then the elbow (16%). Skin lesions on different anatomic regions of the In 44% of the patients, the hair color on the vitiligo body may show different response to treatments. lesions was white (Table I). A family history of Therefore, we decided to apply the treatments on the vitiligo was positive in 20% of the patients. exact same lesion, rather than trying to spot totally The transplanted hairs grew in black in all lesions symmetric lesions on the opposite sides of the body. and did not change color in the course of the In this way we made sure the conditions for both treatment. One month into the treatment, follicular methods were as similar as possible. isolation technique was more effective than miniOne resistant patch in each patient was selected punch grafting statistically, with 2 6 0.6 mm of according to the patient’s preference. The lesion was repigmentation relative to 1.6 6 0.4 mm (P \ .03). divided into 2 equal parts with a straight line passing Nevertheless, there was no statistical difference in the middle of the lesion. A random number table between the efficacies of the 2 techniques in was used to randomly assign the treatments to each the following months. At the end of the study, the half. One half of the lesion was treated with single follicular grafts in 68% of the patients and the minihair follicle transplantations and the other half with punch grafts in the 72% of the patients showed mini-punch grafts. On each side, grafts were repigmentation (Figs 1 to 4). The mean diameter of implanted 1 cm apart from each other. Follicular repigmentation was 5 6 1.7 mm around follicular isolation technique was used for follicle grafting. grafts and 5.3 6 1.6 mm around mini-punch grafts (P Hair follicle donor site was occiput. Unlike most \ .18) (Table II). No complications such as Koebner previous trials, we transplanted complete hair phenomenon, scar formation, and cobblestoning follicles and did not cut a third lower part of it. It were observed in our patients. grafting and hair follicle transplantation) in the treatment of resistant and stable vitiligo patches. To our knowledge, there is no study comparing these 2 surgical techniques simultaneously in the same patient for the treatment of refractory and stable vitiligo.
d
d
d
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Table I. Demographic information of the patients Case no. Sex Age, y
Treatment Hair color Extent of site of the lesion involvement, %
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
Wrist Wrist Wrist Shin Elbow Forearm Ankle Elbow Foot Chest Wrist Shin Elbow Wrist Wrist Elbow Wrist Wrist Neck Thigh Hand Wrist Wrist Armpit Hand
F M F F F M F M F F F F M F F F F F F F F F F F F
47 28 27 20 20 21 22 39 25 35 24 23 42 32 22 22 20 25 27 38 24 22 24 20 20
White White White White White White Black Black Black Black White White Black White Black White Black Black Black Black White Black Black Black Black
10 10-20 10-20 30 10 20-30 10-20 10-20 10 10 10 20-30 10 10-20 10-20 20-30 10 10-20 10 10 10-20 10-20 10 10 10-20
Fig 2. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 2 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
F, Female; M, male.
Fig 3. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 3 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
Fig 1. Vitiligo lesion on the forearm before treatment. L, Left; R, right.
DISCUSSION Vitiligo is a common disease of melanocytes characterized by white depigmented skin patches. Although it is not physically disabling, it is a progressive disfiguring disease and causes severe cosmetic distress, particularly in darkly pigmented skin. Melanocytes are not only found in the skin, mucous membranes, and hair follicles, but can also be observed in eyes, ears, and central nervous system.
Normal hair follicles and basal layer of the epidermis are 2 sites of melanocyte reservoir. Vitiligo is the result of selective destruction of melanocytes in the involved skin, mucous membranes, and hair follicles. Medical treatments of vitiligo induce normal melanocyte proliferation if there are any left in the vitiliginous skin and hair follicles. They also activate the inactive melanocytes in the outer root sheath of hair follicles and induce their migration into epidermis of the skin lesions.12,13 Some patients may not respond to treatment in spite of long-term therapy and even with a combination of several medical therapeutic regimens. In such refractory cases, lack of any response to medical treatments may indicate a complete destruction of melanocytes in the lesions. Therefore, there are not any melanocytes to proliferate and it is necessary to choose a surgical method for transplantation of normal and healthy melanocytes to the skin lesions with the hope that these melanocytes may be proliferated and induced repigmentation. In our study only 18 of 25 patients showed repigmentation
4 Mapar et al
J AM ACAD DERMATOL
Fig 4. Vitiligo repigmentation of the lesion on the forearm (Fig 1) 6 months after treatment. Punch grafting on the right (R); follicular grafting on the left (L).
Table II. Comparison of mean repigmentation sizes in millimeters for 2 surgical methods Follow-up time, mo
1 2 3 4 5 6
Follicle grafting
2.1 6 0.6 2.7 6 1 3.2 6 1.2 3.9 6 1.5 4.6 6 1.6 5 6 1.7
Punch grafting
P value
6 6 6 6 6 6
.03 .88 .62 .51 .24 .18
1.7 2.7 3.3 4.0 4.8 5.3
0.4 0.6 1.1 1.5 1.6 1.6
with mini-punch grafting. At the end of the first month, follicular isolation technique was more effective than mini-punch grafting statistically. But from the second month onward, the size of repigmentation around mini-punch grafting become larger than that of hair follicle transplantation clinically. Nevertheless there was no statistical difference between the results of these 2 techniques. Our results with punch grafting are very similar to that of Malakar and Lahiri.14 They observed repigmentation in 72% of their patients with mini-punch grafting for the treatment of lip vitiligo. In another study by Feetham et al,15 84% repigmentation was reported, which is slightly higher than our case. The punch size used in that study (1.5 mm rather than 1 mm) might have contributed to the higher repigmentation rate. In contrast to the other punch grafting studies, we chose the nearest area with healthy normal pigmented skin to the recipient site as the donor site, whereas in other studies the buttock skin serves as the donor site. No complications such as cobblestone-like appearance, Koebner phenomenon, or hyperpigmentation were observed in our patients with 1-mm punch grafting. However Fongers et al,16 noticed cobblestone-like appearance at recipient areas in 27% of their patients. This might be a result of using a larger punch size of 2 mm. This
complication may be prevented by using a smaller punch size. Fongers et al16 also found 16.4% Koebner phenomenon at the donor sites whereas no case of this phenomenon was observed in our patients. The stability of vitiligo can contribute to that. Although our patients had stable vitiligo, theirs had unstable vitiligo. To obtain a good result and decrease the complications in surgical techniques, it is very important to select patients in stable status. Currently, there is no consensus among dermatologist regarding the minimum time of the stability period. Different authors have used periods ranging from 3 months to 3 years. In our study, we chose 1 year as the minimum time of stability period. In studies by Agrawal and Agrawal17 and Arrunategui et al,18 repigmentation around follicular grafts was reported in 50% to 60% and 40%, respectively, but we had 68% success rate. This difference might be a result of the small sample size of these 2 studies. The sample size in the first study was 8 cases and in the second was 10 cases. In our study, 7 patients did not respond to either surgery, and 1 patient responded only to the punch grafting. This is a significant number of nonresponding patients. It remains to be known why some lesions in some patients do not respond at all. Possibly the existence of some toxins or antibodies at the recipient site contribute to the destruction of the melanocytes. Grafting may stimulate and induce antibody production at the recipient site. The clearance of antigen (melanocytes) removes the stimulus for further antibody production, and re-entry of the antigen (melanocytes) into the environment may again stimulate antibody production that destructs or rejects the grafted melanocytes and prevents the influence of surgical treatments. As can be seen in Table II, from the second month onward, pigmentation is more rapid around mini-punch grafting compared with the hair follicle transplantation, and the P values decrease gradually in the following months. We suspect, if the phototherapy was continued more than 6 months, that the difference might have become statistically significant. Our study had some limitations, including the relatively low number of patients and a short follow-up period of 6 months. Nevertheless, to our knowledge, it is the first study that compares minipunch grafting and hair follicle transplantation simultaneously in the same patient for treating refractory and stable vitiligo. Conclusions Because the results of the 2 methods are not statistically different, and mini-punch grafting is
J AM ACAD DERMATOL
much easier than follicular transplantation, we recommend mini-punch grafting for treating drug-resistant vitiligo. REFERENCES 1. Kent G, Al’Abadie M. Psychologic effects of vitiligo: a critical incident analysis. J Am Acad Dermatol 1996;35:895-8. 2. Parsad D, Dogra S, Kanwar AJ. Quality of life in patients with vitiligo. Health Qual Life Outcomes 2003;1:58. 3. Parsad D, Pandhi R, Dogra S, Kanwar AJ, Kumar B. Dermatology Life Quality Index score in vitiligo and its impact on the treatment outcome. Br J Dermatol 2003;148: 373-4. 4. Falabella R. Surgical therapies for vitiligo and other leukoderma, part 1: minigrafting and suction epidermal grafting. Dermatol Ther 2001;14:7-14. 5. Singh KG, Bajaj Ak. Autologous miniature skin punch grafting in vitiligo. Ind J Dermatol Venereol Leprol 1995; 61:77-80. 6. Malakar S, Dhar S. Repigmentation of vitiligo patches by transplantation of hair follicles. Int J Dermatol 1999;38: 237-8. 7. Ozdemir M, Cetinkale O, Wolf R, Kotogyan A, Mat C, Tuzun B, et al. Comparison of two surgical approaches for treating vitiligo: a preliminary study. Int J Dermatol 2002;41:135-8. 8. Agrawal K, Agrawal A. Repigmentation with dermabrasion and thin split-thickness skin graft. Dermatol Surg 1995;21: 295-300.
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