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EDITOR IAL

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Blackwell Publishing Ltd.

Surgical treatment of vitiligo: why, when and how

R

Falabella

Univeridad del Valle, Centro Medico Imbanaco, Carrera 38 A no. 5 A-100 Cali, Colombia, tel. +57 (2) 558 3771; fax +57 (2) 556 0990;

E-mail: rafalabe@emcali.net.co

Why …

A number of medical therapies with diverse molecules have

been used over the years to help vitiligo repigmentation.

Patients affected with this ailment have received the benefit

of topical and oral medications to fight depigmentation; oral

8-methoxy psoralens and sunlight exposure was initially the

only really effective treatment – described over half a century

ago – but now there is a whole gamet of therapies for treating

depigmented skin, including sophisticated equipment to

deliver ultraviolet radiation.

1

During the depigmenting process in vitiligo, the ultimate

consequence of all the pathogenic mechanisms involved in this

condition is melanocyte destruction, and therefore the final

outcome is absence of pigmentation.

2

Initially only epidermal

melanocytes are affected, but as the condition proceeds the

most important pigment cell reservoir, the hair follicle, may

also become involved and leukotrichia develops and remains as

a silent witness of leukoderma, being unable to provide new

melanocytes for repigmentation.

How and to what extent this phenomenon occurs is depend-

ent on the individual response of the affected patient and the

aggressiveness of the pathogenic process. Sometimes vitiligo is

a slow-spreading disease or is limited to a specific anatomic

area, and on other occasions it is a rapidly developing dermatosis

developing in a relatively short period of time. Fortunately

most patients have a prolongued course over many years, but

progression is the rule, especially with bilateral vitiligo.

Recently, melanocytes have been cultured

in vitro

from

depigmented skin in vitiligo patients, even after years of depig-

mentation.

3

This is not a surprise, since some melanocytes can

survive the mechanisms of cell destruction according to the

severity of the aggression. But the first question that comes to

mind is, why if pigment cells are still present in depigmented

skin, with all the effective treatments available today, is com-

plete repigmentation not possible in a good proportion of

patients? and why are repigmentation rates so poor in certain

areas, such as the acral regions? Activity of the disease may be an

answer, but concentration of surviving melanocytes per mm

2

could also be an additional parameter that may intervene

in repigmentation. In other words, if melanocytes are absent

or not present in sufficient numbers within a depigmented

defect, repigmentation will not occur, even when efficacious

and adequate therapy is delivered. In fact, when using 14 anti-

bodies to melanocytes, investigators found no pigment cells in

well-established lesions of patients with vitiligo, indicating that

they had disappeared from the affected areas.

4

On the other hand, when implanting a small graft measuring

1 mm in diameter, no more than a 5-mm repigmentation halo

is obtained from the original skin graft within non-progressive

and stable macules,

5

and therefore a large number of these

small melanocyte-bearing islands must be placed close to each

other to obtain pigment cell migration and melanin transfer to

surrounding keratinocytes for coalescence and full repigmenta-

tion. This suggests that melanocytes are some sort of ‘territorial

cells’, i.e. they can cause pigmentation in their nearby surround-

ings but are unable to proliferate continuously until the whole

achromic defect becomes repigmented as may occur in large

lesions. A future solution for this limitation could be to develop

cytokines that would act as signals to stimulate continuous cell

migration, such as those found to stimulate melanocyte chemo-

taxis during

in vitro

experiments.

6

What seems to be clear is that when leukotrichia becomes

evident as a sign of poor prognosis for repigmentation and no

melanocytes are available within a depigmented area, even

under conditions of full vitiligo stability, no repigmentation

will usually occur with medical therapy unless melanocytes

are introduced artificially by surgical methods as a new source

of pigment cells. In such cases, melanocyte grafting or

transplantation if properly carried out, may induce adequate

repigmentation.

When …

All patients with vitiligo should be initially treated with medical

methods. It is surprising to observe that even after years of

onset, many patients with vitiligo may respond to medical

therapies and achieve high percentages of repigmentation, and

it is also amazing how these figures can be increased if com-

bination therapy is used.

However, after adequate therapeutic trials some lesions

remain unchanged and do not repigment as expected. This is

often seen in patients with unilateral disease, as in segmental

vitiligo, where lesions develop rapidly over a few months, and

when becoming stable do not progress and are frequently

refractory to any type of medical therapy. A similar situation is

Editorial

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observed in bilateral vitiligo, but in this case lesions do not

always become stable and have a tendency to progress over the

years; nevertheless, in a relatively small percentage of patients

bilateral lesions may also become stabilized. If refractory to

medical treatments, patients with both forms of the disease

could benefit from new melanocytes implanted within achromic

areas, which is when surgical intervention may be indicated in

vitiligo.

An important condition for surgical therapy, however, is the

stability of the disease. The best method known so far for

detecting stable disease, besides a 2-year period of observation

free of new lesions or enlargement of old macules, is the mini-

grafting test, which consists of a miniature repigmentation pro-

cedure, implanting 4–5 minigrafts of 1 or 1.2 mm within the

area to be treated and evaluating the repigmentation halo

around such small grafts after 3–4 months. A positive response

of this trial area indicates with a high degree of accuracy the

future outcome of further treatments when definitive pro-

cedures are carried out, and this method is recommended in all

patients that may be candidates for surgical therapy.

7

The 2-year

period of time used to confirm whether lesions are progressive

or stable has been a matter of controversy, since this is a figure

that has been established arbitrarily; however, in the absence of

a better method to detect real stability, this period of time

should be used as it has been accepted by most investigators.

During this time other methods of medical therapy may also be

tried, but if lesions are definitively refractory, surgical therapy is

indicated and may be carried out.

And how …

Diverse surgical methods have been developed over the

past three decades. Epidermal grafting, minigrafting, thin

dermoepidermal grafts, epidermal suspensions, individual hair

gafts and

in vitro

cultured melanocytes either with epidermal

membranes or with pure melanocyte suspensions, are the basic

procedures published to date,

8

although a few modifications

of some techniques have also been described. Each of these

methods has been reported with varying degrees of successful

repigmentation and also with a few side-effects.

The most frequently reported complication is lack of take or

survival of grafts followed by no repigmentation. In a number

of patients, and in spite of a good take, depigmentation of grafts

or no repigmentation may also occur, even in different depig-

mented areas of the same patient, a fact that remains unex-

plained. These difficulties arise in spite of the method used and

how carefully the technique was performed.

9

Which method is chosen is dependent on the specialized

training required and the surgeon’s experience. Grafting

methods are rather easy to perform but they usually require a

level of expertise and special instruments such as a high-quality

dermatome for thin dermoepidermal grafts, or vacuum devices

for suction epidermal grafting; both are excellent instruments,

particularly the second one, which has had its efficacy fully

tested. Single hair grafts although effective are only suitable for

small areas, as donor sites are not unlimited and microdissec-

tion of hairs is not a simple task. Epidermal suspensions

are effective, but not many successful cases have been reported

in the literature.

In vitro

culture techniques require special

laboratory facilities in regard to both equipment and tech-

nology and are indeed the best methods for treating large

depigmented defects, but they are limited to the few centres

practicing these sophisticated techniques. In time, more experi-

ence and knowledge about cells grown

in vitro

will turn these

transplantation modalities into very important methods to

treat vitiligo, provided that they are simple, safe and available as

routine therapies.

A very simple method that can be performed by anyone

interested in surgical repigmentation without much training

and requiring minimal instruments is minigrafting, but an ade-

quate technique should be followed; the ideal size for minigraft-

ing is a graft of 1 mm for facial areas and a maximum of 1.2 mm

for other regions.

10

Larger grafts harvested with 2.5–3 mm

punches may originate an unsightly effect commonly known as

‘cobblestoning’ and are not recommended; the ‘bumpy’ appear-

ance frequently induced by the slight graft protrusion above the

skin surface and also because of the appearance of the pig-

mentary changes that may be provoked by these large grafts,

may originate a noticeable and permanent cobblestone-like

surface. This has been corroborated in a large series of patients

where this effect was noted in 43% of successfully repigmented

individuals.

11

In two recent publications,

1,12

‘cobblestoning’ has

been described as a major side-effect of minigrafting, but both

publications refer to previous articles where punch grafts of

2.5–3 mm were used. The idea behind selecting larger grafts for

minigrafting may be to perform the procedure in a shorter

period of time and to facilitate graft handling, but this may be

at a high price. This side-effect may be considered by the patient

as unacceptable from the aesthetic point of view, which in turn

worsens the cosmetic problem of the previous leukoderma, par-

ticularly if partial or no repigmentation occurs.

Finally an important consideration is that depigmentation

caused by vitiligo has been labelled as an exclusively ‘cosmetic

ailment’ by most health insurance companies and no reim-

bursement is provided to patients affected by this condition.

But the implications of leukoderma in vitiligo are beyond the

limits of a cosmetic disease; patients with vitiligo often have

major difficulties trying to accomplish their role in society as

active individuals and on many occasions they are socially

rejected. They may also be affected by a low self-esteem and

sometimes may lose their jobs or opportunities for improv-

ing their status or life style. Every effort needs to be made

to improve repigmentation in the affected patients, who are

otherwise healthy, and insurance companies need to revise their

policies and change the label of ‘cosmetic ailment’ for a socially

disabling disease such as vitiligo.

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© 2003 European Academy of Dermatology and Venereology

JEADV

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17

, 518–520

References

1 Njoo MD, Spuls PI, Bos JD

et al.

Nonsurgical repigmentation

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2 Nordlund J. The loss of melanocytes from the epidermis: The

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