Clinical dermatology Original article CED

Clinical and Experimental Dermatology

Acral vitiligo and lesions over joints treated with non-cultured
epidermal cell suspension transplantation
A. P. Holla,
1
K. Sahni,
2
R. Kumar,
3
D. Parsad,
3
A. Kanwar
3
and S. D. Mehta
4
1
MelanoSite, New Delhi, Delhi, India;
2
Department of Dermatology, Lady Hardinge Medical College, New Delhi, Delhi, India;
3
Department of Dermatology,
Postgraduate Institute of Medical Education and Research, Chandigarh, India; and
4
Department of Dermatology, Government Multispecialty Hospital,
Chandigarh, India
doi:10.1111/ced.12040
Summary Background. Vitiligo is a disguring condition that can cause considerable psycho-
logical distress to patients. Vitiligo lesions on acral areas and joints are considered
difcult to treat, and they are unsuitable for surgical treatment because of their poor
response. There are few studies on the management of those lesions with non-
cultured epidermal cell suspension transplantation.
Aim. To evaluate the efcacy of a modied procedure using noncultured epidermal
cell suspension transplantation in the management of vitiligo lesions over acral
areas and joints.
Methods. We retrospectively analysed data for patients who had undergone non-
cultured epidermal cell suspension transplantation for treatment of vitiligo. In total,
36 patients with 80 lesions over acral areas and joints were reviewed: 33 patients
had generalized vitiligo, while the remaining three patients had focal vitiligo, and
they had been followed up for 618 months.
Results. Of the 80 treated lesions, 51 had regained > 75% repigmentation and 23
had regained 5075% repigmentation. The remaining six lesions, which were all no
the distal ngers or toes and the ankle joint, had a poor response.
Conclusions. Non-cultured epidermal cell suspension transplantation was success-
ful in producing some degree of repigmentation in our patients, and could be a use-
ful therapy for vitiligo lesions.
Introduction
Vitiligo affects 12% of the world population,
1
and is
one of the commonest acquired disorders of pigmenta-
tion, It is characterized by sharply dened white patches
on the skin, which are particularly noticeable in
patients with darker skin. Because of the stigma
attached to it in some countries, the condition can be
psychologically distressing to patients,
2
particularly if
lesions are on visible areas of the body. Lesions on the
wrist, hand, ankle and foot constitute acral vitiligo.
Acral lesions and lesions over joints are resistant to
medical treatment, and their response to surgical man-
agement is often disappointing.
3
Reasons for this poor
response may be movement of the affected area, which
can lead to loss of transplanted cells, the uneven sur-
faces in these areas, and practical problems with the
surgical procedure.
4
There are few reports on the man-
agement of such lesions by noncultured epidermal cell
suspension transplantation.
4,5
Methods
The study was approved by the ethics committee of
the Postgraduate Institute of Medical Education and
Research, Chandigarh, India and patients provided
Correspondence: Dr D. Parsad, Department of Dermatology, Postgraduate
Institute of Medical Education and Research, Chandigarh, 160012, India
E-mail: dprs@sify.com, parsad@me.com
Conict of interest: none declared.
Accepted for publication 6 August 2012
The Author(s)
CED 2013 British Association of Dermatologists Clinical and Experimental Dermatology, 38, 332337 332
signed informed consent before undergoing the trans-
plantation procedure.
Patients
This was a retrospective analysis study. The study
enrolled patients who had qualied for treatment with
noncultured epidermal cell suspension. Only patients
with lesions that had been stable for > 1 year and had
not responded to medical management were consid-
ered for surgery. The patients had undergone various
treatments previously, including phototherapy, sys-
temic therapies (e.g., oral mini pulse steroids, psora-
lens and methylcobalamin supplement), and topical
therapies (e.g., corticosteroids, tacrolimus).
We analysed the data for any patients who had
undergone the surgery for vitiligo lesions over their
joints and acral areas. In total, 36 patients (24
women, 12 men; mean SD age 22.6 3.4 years,
range 1647) were enrolled. Of these, 33 had general-
ized vitiligo and 3 had focal vitiligo.
Graft preparation and surgical procedure
To prepare the cell suspension, a split-thickness graft,
usually one-tenth the size of the recipient area, was
taken under local anaesthesia from the anterior or lat-
eral thighs, using a shaving blade held rmly by a
long straight artery forceps. The wound was dressed
using chlorhexidine dressing.
The skin graft was transferred to a centrifuge tube
containing a solution of 0.25% trypsin and 0.02%
EDTA, and incubated at 4 C overnight as described
previously by Gauthier et al.
5
The following day, the
graft was transferred to phosphate-buffered saline
(PBS), and the dermis was separated from the epider-
mis using sterile forceps, allowing the cells from the
suprabasal region to be released into the PBS. After
removing any pieces of epidermis or dermis, the cell
suspension was separated by centrifugation, and the
pellet was resuspended in serum, PBS or melanocyte
medium, as appropriate.
Dermabrasion was performed on the recipient area
using a manual dermabrader under local anaesthesia,
until tiny pinpoint bleeding spots were seen, indicat-
ing that the dermoepidermal junction had been
reached. The dermabraded area was washed with PBS
and covered with gauze that had been moistened with
PBS.
The non-cultured epidermal cell suspension was
carefully transferred to a tuberculin syringe with an
18G needle attached. Using this, a few drops of
suspension were placed onto the denuded surface,
and these were then spread evenly with the help of
the needle, after which the dermabraded skin was
covered with sterile chlorhexidine gauze. Small drops
of the cell suspension were placed onto the gauze
and spread evenly as before. A piece of meshed colla-
gen was washed with normal saline and placed on
top of the gauze (plus melanocyte suspension). The
collagen sheet was then covered by a nal piece of
PBS-moistened gauze. A sterile transparent occlusive
dressing (Tegaderm; 3M Healthcare, St Paul, MN,
USA) was placed on top of the gauze, followed by a
surgical pad, and nally an elastic dressing. Plaster
casts were used to immobilize acral areas and distal
joints. The patients were asked to remain lying down
for an hour after the procedure, and were then
allowed to go home.
Post-operative care
The dressings were removed on day 8. If any areas
had not healed, they were re-dressed with chlorhexi-
dine gauze and left for a further 23 days. Patients
were reassured about the self-limiting maceration of
the surrounding skin in acral lesions. Any patients
with crusting were advised to use saline gauze com-
presses for 710 days. All patients were advised to
allow sun exposure to the treated area and use oral
methylcobalamin supplements for a minimum of
4 months. Because the lesions assessed in this analysis
had been considered difcult to treat the majority of
our patients had been already been treated with
phototherapy and methylcobalamin without any
improvement.
Assessment
Photographs were taken before the surgery and during
each follow-up visit, with the follow-up periods being
618 months. Assessment of repigmentation was per-
formed by an author who had not been involved in
treatment. Patterns of repigmentation were also noted,
especially the marginal repigmentation, and the colour
match with surrounding skin was assessed. Adverse
events, if any, were documented.
Results
Of 80 treated lesions, 51 had > 75% repigmentation
and 23 had 5075% repigmentation (Figs. 13). The
remaining six lesions had a poor response; all of these
were on the distal ngers or toes or the ankle joint.
The Author(s)
CED 2013 British Association of Dermatologists Clinical and Experimental Dermatology, 38, 332337 333
Treatment of resistant areas of vitiligo with NCES A. P. Holla et al.
Table 1 shows the details of sites treated and out-
come.
Self-limiting maceration was seen in acral areas after
dressing removal, which improved after 23 days
(Fig. 4). Marginal repigmentation (Fig. 5) was seen
around the ankle joint, and this pattern of repigmentation
seemed to delay complete repigmentation, often lead-
ing to < 75% repigmentation with a peripheral ring of
hyperpigmentation and a central pinkish red area.
Hyperpigmentation was seen mostly on the elbow,
ankle and knee joints (Fig. 6). Crusting was seen
mostly around the ankle joint, which was found to
result in hyperpigmentation (Fig. 7).
Discussion
The acral and joint areas are common sites of occur-
rence of vitiliginous lesions, because they are areas
subject to repeated trauma or irritation.
6
Because
acral lesions are more visible and cosmetically impor-
tant than lesions at many other sites, they can cause
greater psychosocial distress. Involvement of the palms
and soles is also common, but such lesions are not so
visible
7
; however, they can be bothersome for darker-
skinned people.
The site of the affected area has a considerable inu-
ence on the percentage of repigmentation after treat-
ment.
8
Acral lesions are usually more resistant to
medical management. Several reasons have been put
forward,
4
including relatively low melanocyte density;
minimal density of hair follicles, which are a melano-
cyte reservoir; and a greater chance of repeated fric-
tion or trauma, which can induce koebnerization.
Both acral and joint lesions also tend to be resistant to
surgical management,
3
and this form of management
has a number of limitations,
4
including the generally
uneven recipient areas, the technical difculties in
treating these areas and in immobilizing them during
surgery, and the likelihood of repeated friction or
trauma after surgery.
9
However, split-skin grafts,
mini-punch grafts and suction-blister epidermal grafts
have all been shown to have success rates of > 80%
on the ngers and toes, which are otherwise very dif-
cult to treat with medical therapies.
10
In such cases,
minigraft transplantation on nger lesions was found
to be more successful than split-thickness or suction-
blister grafting.
10
Previous studies have reported that
larger lesions over the dorsa of the hands and feet
showed excellent results with cultured autologous
melanocyte transplantation, whereas the dorsa of the
phalanges and joints showed only fair to poor
results.
11,12
Olsson and Juhlin
13
carried out 19 trans-
plantation procedures on the dorsa of the hands;
excellent results were seen in 10 patients, and fair to
poor results were seen in the other nine patients, who
all had involvement of the phalanges and knuckles. In
the same study, 24 cases involved the feet; the result
were rated as excellent for 11, good for 10 and fair for
(a)
(b)
(c)
Figure 1 Patients ngers (a) before transplantation; (b) after
4 weeks; (c) after 6 months.
The Author(s)
CED 2013 British Association of Dermatologists Clinical and Experimental Dermatology, 38, 332337 334
Treatment of resistant areas of vitiligo with NCES A. P. Holla et al.
3 patients. There is also a case report of successful
management with minigraft transplantation of a lesion
on the palm, for which punch grafts were taken from
the sole.
12
In a recent article on difcult areas treated
with autologous melanocyte keratinocyte suspension
transplantation, 13 patients with lesions on the ngers
or toes were treated, with 8 achieving excellent and 6
achieving good results, while for 6 patients with
lesions on the palms, 2 had excellent and 3 had good
results.
14
By contrast, of 43 treated lesions over joints,
only 27 had an excellent or good outcome. It has been
suggested that acral connective tissue is less capable of
supporting the uptake of melanocytes in grafts;
8
how-
ever, the results of our study and that of the previous
study, both using noncultured epidermal cell suspen-
sion transplantation, disproves this notion. Patients in
our study generally had a good to excellent outcome
for lesions on the dorsa of the hands and feet, and on
the wrist, elbow and knee joints. Two of the poor out-
comes in lesions on the ankle joint were attributed to
the marginal repigmentation pattern, which is charac-
terized by a hyperpigmented ring at the periphery and
a central pinkish-red area. The hyperpigmented ring
might prevent further repigmentation of the central
area and thus result in an overall poor outcome. We
also saw a good to excellent response in patients with
lesions on the proximal ngers or toes; however, the
distal areas were more resistant. Overall, most of the
treated lesions gave satisfactory results considering
their difcult nature, with 74 of the 80 lesions being
rated as either good or excellent. This may be due in
part to the fact that we followed a strict immobiliza-
tion procedure for the treated areas, and encouraged
post-operative phototherapy in the form of sun expo-
sure. However, in the literature, controversy exists
about the use of immobilization and phototherapy.
14
The hyperpigmentation seen in some lesions, especially
over joints, may not be due to phototherapy alone, as
we believe that certain sites are more prone to hyper-
pigmentation with or without phototherapy, and this
may be especially the case in darker-skinned popula-
(a) (b)
Figure 2 Patients foot (a) before trans-
plantation; (b) after 6 months.
(a) (b)
Figure 3 Patients right elbow joint
(a) before transplantation; (b) after
6 months.
Table 1 Details of sites treated and outcome.
Site
Total
number
Excellent (>75%
repigmentation)
Good (75
50%)
Poor
(<50%)
Fingers 14 6 5 3
Dorsum
of hand
10 8 2 0
Palm 2 1 1 0
Toes 5 2 2 1
Dorsum
of foot
16 13 3 0
Wrist joint 3 2 1 0
Elbow
joint
8 6 2 0
Ankle
joint
14 8 4 2
Knee joint 8 5 3 0
The Author(s)
CED 2013 British Association of Dermatologists Clinical and Experimental Dermatology, 38, 332337 335
Treatment of resistant areas of vitiligo with NCES A. P. Holla et al.
(a) (b)
Figure 7 (a) Visible crusting at 2 weeks
after surgery; (b) hyperpigmentation at
4 months after surgery.
(a) (b)
Figure 6 Patients left knee (a) before
transplantation; (b) after 4 months,
showing hyperpigmentation.
(a) (b)
Figure 4 Appearance of treated area
(a) immediately after dressing removal;
(b) 4 days later.
(a) (b)
Figure 5 Patients ankle (a) before trans-
plantation; (b) after 5 months, showing
marginal pigmentation.
The Author(s)
CED 2013 British Association of Dermatologists Clinical and Experimental Dermatology, 38, 332337 336
Treatment of resistant areas of vitiligo with NCES A. P. Holla et al.
tions such as in India. Other sites such as the face and
trunk were not affected, even though they had greater
sun exposure. This hyperpigmentation on acral areas
may be a type of frictional melanosis.
There are some limitations to the study. It was is a
retrospective study and the longest follow-up period
was 18 months, with some patients being followed up
for a considerably shorter time. There is a need for a
prospective study on surgical management of such
vitiligo lesions with a larger number of patients and
a longer follow-up period.
Conclusion
Vitiligo lesions on acral and joint areas are cosmetically
disguring, and may have severe psychological
consequences. They are classically considered as dif-
cult to treat, as they are resistant to medical manage-
ment; however, with detailed patient selection criteria
and the correct procedure, these lesions can be man-
ageable. More new therapies are needed to treat such
areas successfully and to achieve long-term pigment
retention.
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Treatment of resistant areas of vitiligo with NCES A. P. Holla et al.