Successful treatment of vitiligo with punch graft followed by outdoor topical psoralen plus ultraviolet A radiation

Abstract

Background and Objective – Punch grafting is a therapy for vitiligo but, to our knowledge, its combination with outdoor topical psoralen plus ultraviolet A radiation (PUVA) has not yet been studied. This study was designed to evaluate the efficacy of combination of punch graft and outdoor topical PUVA in recalcitrant vitiligo. Methods – The study was performed in Razi Hospital, Tehran in 2000. After obtaining informed consent, 20 patients with stable and refractory vitiligo (4 segmental, 8 focal and 8 generalized) underwent treatment with punch grafting. After 3 months, outdoor topical PUVA with 8-methoxypsoralen was instituted and continued for a maximum of 4 months. Results – After the 3 months of punch grafting, only nine patients experienced 33 – 66% repigmentation. Four months after starting topical outdoor PUVA, 13 patients experienced 90 – 100% and three patients 25 – 50% repigmentation. One focal and three generalized patients showed no response. Conclusion – The combination of punch grafting and topical PUVA may be an effective treatment in stable and intractable vitiligo, especially the segmental and localized types.

Full text

Arch Iranian Med 2003; 6 (2): 86 – 90
Archives of Iranian Medicine, Vol 6, No 2, April 2003
86
SUCCESSFUL TREATMENT OF VITILIGO WITH
PUNCH GRAFT FOLLOWED BY OUTDOOR TOPICAL
PSORALEN PLUS ULTRAVIOLET A RADIATION
Zahra Hallaji MD
•
, Maryam Daneshpazhooh MD, Samad Rezai-Khiabanloo MD
Department of Dermatology, Tehran University of Medical Sciences, Tehran, Iran
Background and Objective – Punch grafting is a therapy for vitiligo but, to our
knowledge, its combination with outdoor topical psoralen plus ultraviolet A radiation
(PUVA) has not yet been studied. This study was designed to evaluate the efficacy of
combination of punch graft and outdoor topical PUVA in recalcitrant vitiligo.
Methods – The study was performed in Razi Hospital, Tehran in 2000. After obtaining
informed consent, 20 patients with stable and refractory vitiligo (4 segmental, 8 focal and 8
generalized) underwent treatment with punch grafting. After 3 months, outdoor topical PUVA
with 8-methoxypsoralen was instituted and continued for a maximum of 4 months.
Results – After the 3 months of punch grafting, only nine patients experienced 33 – 66%
repigmentation. Four months after starting topical outdoor PUVA, 13 patients experienced
90 – 100% and three patients 25 – 50% repigmentation. One focal and three generalized
patients showed no response.
Conclusion – The combination of punch grafting and topical PUVA may be an effective
treatment in stable and intractable vitiligo, especially the segmental and localized types.
Keywords • punch grafting • topical PUVA • vitiligo
Introduction
itiligo, a common acquired disease, is
manifested by circumscribed de-
pigmented patches. Histologically there
is an absence of cutaneous melanocytes.
1
Vitiligo can be classified into several types. The
localized type includes segmental and focal
vitiligo. Vitiligo vulgaris, acrofacial and universal
vitiligo are classified as the generalized type. Ten
percent of cases are localized and 90% are
generalized.
2
Treatment for vitiligo includes the use of
topical corticosteroids, calcipotriol, topical or
systemic methoxypsoralen, and oral psoralen plus
ultraviolet A radiation (PUVA), ultraviolet B
radiation (UVB), phototherapy, pseudocatalase
plus calcium plus UVB, vitamin supplementation,
melagenina, systemic corticosteroids, other
immunomodulators, and topical L-phenylalanine in
combination with UVA (PAUVA).
1, 2
However,
such treatments usually induce incomplete
repigmentation and occasionally the outcome is
poor.
1 – 3
Vitiligo patients, resistant to medical treatment,
in exposed areas represent a therapeutic problem to
physicians and an aesthetic problem to patients,
especially those with dark skin. Several surgical
procedures for the treatment of intractable lesions
have been reported to be effective, including thin
Thiersch grafts,
2
suction-blistered epidermis,
2 – 5
minigrafting,
6 – 8
and injection of noncultured and
various cultured cell-grafting techniques.
9, 10
All
employ melanocytes from the patient's normal skin
to cover depigmented patches.
11
Cutaneous
cultured autologous melanocyte grafting has
excellent results, but this technique is expensive
and time consuming. To achieve favorable results,
up to 8 months is necessary. The minigrafting
technique is relatively simple and can be used in an
outpatient clinic with simple instruments.
However, repigmentation due to minigrafting is
usually incomplete after 3 months to 4 years.
2, 3, 6–
V
•Correspondence: Z. Hallaji MD, Department of Dermatology,
Razi Hospital, Vahdat-e-Eslami Sq, 11996, Tehran, Iran. Fax: +98-
21- 5618989, E-mail: zhallaji@yahoo.com.
O
RIGINAL
A
RTICLE
Archive of SID
www.SID.ir

Z. Hallaji, M. Daneshpazhooh, S. Rezai-Khiabanloo
Archives of Iranian Medicine, Vol 6, No 2, April 2003
87
8
On the other hand, PUVA, either systemic or
topical, increases the number of melanocytes and
synthesis of melanin.
1, 4, 5
Topical outdoor PUVA is
a popular, practical and efficacious therapeutic
option for patients with limited vitiligo.
12
The
mechanism of PUVA rests on the synergistic
interaction of the two components (8-
methoxypsoralen and UVA light) in the skin.
13
We
conducted this study to evaluate the efficacy of
combining punch grafting and topical outdoor
PUVA in vitiligo patients.
Patients and Methods
Twenty Iranian patients (12 women and 8 men,
in the age renge of 13 – 40 years) with stable
vitiligo underwent minigrafting in Razi Hospital,
Tehran in 2000. The disease was segmental in four,
focal in eight and generalized in eight cases. All
subjects were otherwise healthy. They had been
resistant to systemic or topical methoxypsoralen
and topical steroid therapies for at least 1 year.
They showed neither spread of existing lesions nor
development of new lesions during the previous 6
months. Patients under 12 years of age, pregnant
and lactating women, and those with a history of
photosensitivity or skin cancer were excluded from
the study. After obtaining informed consent, one
patch was grafted in each patient without previous
minigrafting test.
The grafting site was prepared by infiltration of
1% lidocaine without epinephrine followed by
perforation of recipient holes of 1.5 mm deep and
2.5 mm apart from each other. Minigrafts were
harvested from the gluteal region for the trunk and
limb regions, and the back of the ear for the face
lesions; punches of 2 mm in size were placed
within the recipient holes. Dressings were removed
2 weeks later and all subjects observed two
sessions per month for 3 months. Repigmentation
rate was scored visually. Graft rejection was
determined as necrosis of the grafs in the recipient
holes.
All subjects applied 8-methoxypsoralen (0.1%
alcoholic solution) and received sunlight for three
sessions per week, for a maximum of 4 months.
The first exposure time was 15 seconds and was
increased by 10 seconds per session until the
appearance of a slight erythema. Treatment was
continued until complete repigmentation occurred,
or for 4 months. If no evidence of repigmentation
was observed by this time, treatment was
discontinued and repigmentation was scored. Data
are presented as mean ± standard deviation.
Results
Three months after punch grafting, only nine
(45%) patients experienced 33 – 66% repigmen-
tation (partial repigmentation). The onset of
repigmentation was between 28 and 45 days (35.3
± 7.5). Further repigmentation stopped between 45
and 75 days (61.7 ± 9.0). Four months after the
institution of topical outdoor PUVA, 13 patients
experienced 90 – 100% repigmentation (complete
Figure 1. Photograph of patient No. 8 showing a vitiligo lesion on the forehead (20 cm
2
): A) before
grafting; and B) 7 months after grafting, showing 90% repigmentation.
A
B
Archive of SID
www.SID.ir

Successful Treatment of Vitiligo with Punch Graft and PUVA
Archives of Iranian Medicine, Vol 6, No 2, April 2003
88
response) and three patients 25–50% repigmen-
tation (partial). Four patients showed no response.
The mean onset of repigmentation was at 25.6
sessions (SD, 5.9 sessions). The results are
summarized in the Table.
Nine patients who responded to punch grafting
(33–66% repigmentation) showed complete
repigmentation after PUVA. Punch grafting alone
was unsuccessful in four of the patients who
responded completely and in the three patients who
responded partially (25–50%) to the combination
of punch grafting and PUVA. Three (75%)
responders had truncal, seven (70%) facial and
three (50%) limb lesions. All subjects of segmental
type, six (25%) subjects of localized type and three
(38%) subjects of generalized type experienced
90–100% repigmentation (Figures 1 and 2).
The Kobner phenomenon was observed in three
patients (2 patients with varying shape and size of
recipient facial area and 1 in donor site).
Cobblestoning was observed in 11 patients, but
spontaneously resolved between 7 and 18 months
later. Graft rejection was observed in only 14 (3%)
out of 445 grafts.
Discussion
Falabella pioneered the use of small auto-
transplant for the treatment of four patients with
segmental vitiligo in 1983.
7, 8
In 1988, he treated 22
patients with localized vitiligo after three to five
minigraft tests by this method. Thirteen patients
obtained 90 – 100% repigmentation.
8
Westerhof et al also observed satisfactory
results using minigrafting in stable leukoderma.
6
Boersma et al evaluated autologous
minigrafting followed by UVA (10 J/cm
2
) twice a
week in stable vitiligo vulgaris and found it
effective in a selected group of patients. The
results of 19 patients were analyzed, showing 80 to
99% repigmentation in 14 lesions, 50 to 80%
repigmentation in 10 lesions, and zero to 50%
repigmentation in 12 lesions.
2
Although minigrafting can be an effective
treatment in vitiligo, failure to achieve complete
repigmentation in a high percentage of patients
remains a major drawback.
2, 3, 6 – 8
The potential of PUVA to increase the number
of melanocytes prompted us to use autologous
minigrafting followed by topical outdoor PUVA in
20 patients with stable vitiligo (segmental,
vulgaris, and focal). We did not perform a
minigraft test.
In the first phase of our study, only nine
patients showed partial repigmentation (33 – 66%)
by minigrafting. Repigmentation progressed
mainly during the first 2 months and remained
stable afterward, despite the sunny climate.
The addition of topical PUVA increased the
rate of repigmentation significantly. Repigmen-
tation reached 90 – 100% in 13 patients (including
those patients who were responding to
minigrafting). Three nonresponders to minigrafting
showed 25 – 50% repigmentation with the addition
Table.
Demographic
and results
of 20 patients
with vitiligo treated with punch graft and topical PUVA.
No. of
patient
Age/
sex
Size of
treated
lesion
(cm
2
)
Type
(disease)
Area
Repig. onset after
graft/the end of
repig. after graft
Repig.
after
graft (%)
Repig. after
PUVA (%)
Skin
type
Rejected
graft
1 16/F 75 Segmental Trunk 45/60 50 90 4 8
2 20/M 9 Generalized Face 45/60 33 99 3 —
3 16/F 6 Focal Lt foot 35/60 33 100 2 —
4 17/M 4 Generalized Face —/— — 99 3 —
5 25/F 8 Generalized Rt hand 30/75 33 99 4 1
6 15/M 4 Focal Face —/— — 99 2 —
7 23/M 6 Focal Face 30/60 66 99 3 1
8 40/F 20 Segmental Face 30/60 33 95 2 —
9 27/M 15 Focal Trunk 28/60 66 90 3 2
10 21/F 8 Segmenta Trunk —/— — 99 2 —
11 15/F 3 Focal Rt shin 45/75 75 33 3 —
12 22/M 8 Segmenta Face 30/60 66 99 4 —
13 13/F 6 Focal Face —/— — 95 2 —
14 13/F 3 Focal Trunk —/— — — 3 —
15 27/F 8 Generalized Lt wrist —/— — — 4 —
16 25/F 9 Generalized Lt wrist —/— — — 3 —
17 14/F 8 Generalized Lt hand —/— — — 3 —
18 24/F 10 Generalized Lt hand —/— — 50 3 2
19 17/M 2.25 Focal Face —/— — 50 2 —
20 19/M 7 Generalized Face —/— — 25 2 —
Lt = Left; Rt = right; Repig. = repigmentation.
Archive of SID
www.SID.ir

Z. Hallaji, M. Daneshpazhooh, S. Rezai-Khiabanloo
Archives of Iranian Medicine, Vol 6, No 2, April 2003
89
of PUVA, while four patients (3 generalized, and 1
localized) showed no repigmentation despite the
addition of PUVA.
Fitzpatrick skin type IV patients responded
better than other types. Also, the response rate was
higher on the trunk, followed by the face and
extremities. Segmental vitiligo responded better
than focal type. The least responsive group was the
generalized type. Complete response to PUVA in
four nonresponders to minigrafting and partial
response in three nonresponders was an interesting
finding in our study. This can be explained by the
effect of methoxypsoralen plus UVA on the
donor’s melanocytes.
Kobner phenomenon was seen in two patients
after minigrafting at recipient sites and in another
one at the donor site. Cobblestoning was seen in
55% of patients. Repigmentation was nearly
uniform.
After 1 year of follow-up, no hyperpigmen-
tation was seen and only cosmetically acceptable
mild cobblestoning was noted in 7 patients and
resolved in others. Other possible side effects such
as infection, hypertrophic scarring, keloids,
persistent pigmentary changes and necrosis of the
grafts were not seen. The combination of punch
grafting and topical PUVA was an effective
treatment in a small group of stable and intractable
vitiligo, especially segmental and localized types.
We suggest further studies to evaluate whether
earlier institution of PUVA after minigrafting leads
to an earlier satisfactory response. Also, we
suggest comparing this method with other
techniques such as Thiersch grafting and
suctioning blister epidermis in combination with
PUVA or narrow-band UVB phototherapy in
further studies.
References
1 Grimes PE. Therapies for vitiligo. In: Millikan LE,
ed. Drug Therapy in Dermatology. 1st ed. New York:
Marcel Dekker; 2000: 339 – 57.
2 Boersma BR, Westerhof W, Bos JD. Repigmentation
in vitiligo vulgaris by autologous minigrafting: results
in nineteen patients. J Am Acad Dermatol. 1995; 33:
990 – 5.
3 Falabella R. Surgical techniques for repigmentation.
In: Robinson JK, Arndt KA, LeBoit PE, et al, eds.
Atlas of Cutaneous Surgery. 1st ed. Philadelphia: WB
Saunders; 1996: 175 – 84.
4 Suga Y, Butt KI, Takimoto R , et al. Successful
treatment of vitiligo with PUVA-pigmented
autologous epidermal grafting. Int J Dermatol. 1996;
35: 518 – 22.
5 Ai-Young L, Jeong-Hoon J. Autologous epidermal
grafting with PUVA-irradiated donor skin for the
treatment of vitiligo. Int J Dermatol. 1998; 37:
551 – 4.
6 Westerhof W, Nieuweboer-Krobotova L, Mulder PG,
et al. Left-right comparison study of the combination
of fluticasone propionate and UV-A vs either
fluticasone propionate or UV-A alone for the long-
term treatment of vitiligo. Arch Dermatol. 1999; 135:
1061 – 6.
7 Falabella R. Repigmentation of segmental vitiligo by
autologous minigrafting. J Am Acad Dermatol. 1983;
9: 514 – 21.
8 Falabella R. Treatment of localized vitiligo by
autologous minigrafting. Arch Dermatol. 1988; 124:
1649 – 55.
9 Gauthier Y, Surleve-Bazeilla JE. Autologous grafting
with noncultured melanocytes: a simplified method
for treatment of depigmented lesions. J Am Acad
Figure 2. Photograph of patient No. 1 showing a vitiligo lesion on the trunk (75 cm
2
): A) before
grafting; and B) 7 months after grafting, showing 90% repigmentation.
A
B
A
B
Archive of SID
www.SID.ir

Successful Treatment of Vitiligo with Punch Graft and PUVA
Archives of Iranian Medicine, Vol 6, No 2, April 2003
90
Dermatol. 1992; 26: 191 – 4.
10 Lerner AB. Repopulation of pigment cells in patients
with vitiligo. Arch Dermatol. 1988; 124: 1701 – 2.
11 Marwa A, Mohamed B. Efficacy of noncultured
melanocytes transplantation versus minigrafting in
vitiligo. Gulf J Dermatol Venerol. 2001; 2: 25 – 35.
12 Grimes PE. Therapeutic trends for the treatment of
vitiligo. J Cosm Dermatol. 2002; 6: 21 – 5.
13 Shephard SE, Langguth P, Panizzon RG.
Pharmacokinetic behavior of sublingually
administered 8-methoxypsoralen for PUVA therapy.
Photodermatol Photoimmunol Photomed. 2001; 17:
11 – 21.
Archive of SID
www.SID.ir