What Are the Needs for Transplantation Treatment in Vitiligo, and How Good Is It?

Patchy loss of skin pigmentation can have significant consequences for affected individuals, who often experience difficulty functioning as socially active individuals and may not achieve the lifestyle they desire simply because they have white spots on their skin. In some countries with a predominantly dark-skinned population, leukoderma (white skin) can result in social stigmatization, leading to major difficulties in getting married and obtaining work.¹ I have worked in India on several occasions and observed some of the social problems that this type of skin disorder can cause. In addition, the white areas, which lack melanin pigmentation, are very sensitive to sun exposure; in the summer, affected individuals must wear protective clothing and sunscreens.

Several etiologically distinct disorders or unrelated side effects of different physical or chemical treatments result in leukoderma, but in most cases we do not understand the biological mechanisms that underlie these disorders.

The most common disorder that results in depigmented patches of skin is generalized vitiligo (vitiligo vulgaris). The white areas of generalized vitiligo, which affects about 0.5% to 1% of individuals in most populations, are usually distributed in a symmetric bilateral fashion. Generalized vitiligo is a polygenic, multifactorial disorder whose etiology is not easy to understand, treat, or predict, but many studies indicate autoimmune involvement in its pathogenesis. Although the primary triggers of the disease are unknown, most researchers and clinicians in the field agree that therapies affecting/suppressing the local skin immunoenvironment are of importance and have proved beneficial in many cases.

Several genetically distinct pathways may confer susceptibility to generalized vitiligo in different populations and even in different individuals within a given population. The epidemiology of vitiligo in probands and their families has been well studied² ; in a genomewide screening, susceptibility loci on chromosome 1 and other chromosomes have been detected in some families with multiple cases of vitiligo.³ Nevertheless, most patients with vitiligo have sporadic nonfamilial occurrence of disease, which may involve different pathogenic mechanisms not following the genetic pattern seen in the families with multiple cases. It thus seems unlikely that there will be a single cure or a single prevention protocol for this complex disease. Accordingly, a battery of different therapies has been and likely will continue to be used for the treatment of vitiligo, which includes surgical therapy.

Surgical therapies can attack the loss of pigment cells (melanocytes) in the skin, but it is important to know how and when they are applicable and to know their limitations. Most published reports only cover short-term results (3-12 months), but the clinician must know about the long-term results before recommending surgical treatment to a patient. How much of the repigmentation is left after 10 years? Has the treatment in any way affected the progression of the disease?

We have more than 12 years of experience using technically different surgical methods in the treatment of different kinds of leukoderma, and many of our patients have been evaluated frequently in a long-term follow-up study.⁴ This study compared 3 surgical methods for several parameters, and compared results for different types of leukoderma as well as anatomical locations, age at disease onset, disease duration, age at the time of surgery, habits regarding sun exposure, sex, and leukoderma-associated diseases. This experience may offer guidance regarding the numerous choices and questions confronting the clinician when considering whether or not to offer transplantation treatment.

In piebaldism and stable types of vitiligo (such as segmental unilateral vitiligo) the outcome of transplantation therapy is usually excellent; in some cases, transplantation may indeed be the only effective treatment.

However, the long-term experience with both surgical and medical treatment of generalized vitiligo that we have acquired in Uppsala has made us very conservative regarding patient selection, and we now most often decline requests for transplantation therapy in patients with generalized vitiligo.

Unfortunately, as yet there is no reliable test to predict the activity and outcome of melanocyte transplantation treatment in patients with generalized vitiligo. Minigrafts (small punch grafts) have been used prior to more extensive treatments as an approach to predict stability. However, vitiligo can be active in one skin area and inactive or even in regression in another at the same time. Thus, it can be difficult to draw conclusions from the test spot.

Until we have a blood test to analyze vitiligo-specific markers predictors of the activity of the disease, we are very much dependent on a careful anamnesis. But we have to keep in mind that many patients are willing to try almost anything, and might also believe that surgical treatment can stop the progression of their disease. Sometimes, when patients know our selection criteria, their strong desire to undergo a transplantation treatment can lead them to adjust their history, which, in turn, can bias our decision. We must carefully explain how important it is to make the right treatment selection; we must also explain that we do not treat the underlying disease, merely symptoms in the affected areas of the skin!

With a medical treatment controlling the underlying causes of melanocyte destruction, the usefulness and outcome from transplantation treatment would increase tremendously.

Questions sometimes arise about whether there are any risks in performing autotransplantation in vitiligo and other indications, and it is our responsibility to try to answer these questions, which I partially discuss below.

Even though there is no scientific proof, we must consider that there might be, at least theoretically, a chance of activating and/or exacerbating generalized vitiligo by implanting mechanically damaged, enzyme-damaged, autoantigen-exposed melanocytes to the recipient wound bed. Both melanocyte-specific cytotoxic T lymphocytes^{5 - 6} and autoantibodies against melanocytic proteins have been detected in some patients with vitiligo.^{7 - 10} More research on the involvement of the immune system in the pathogenesis of generalized vitiligo must therefore be conducted.

For about 2 decades, many burn care centers around the world have prepared and cultured autologous skin cells as part of their regular treatment arsenal. Clinical use of skin-derived cells that have been chemically and mechanically prepared and/or cultured before transplantation have resulted in few or no specific reports of harmful effects. Nevertheless, this does not prove that there are no risks to this approach.

To justify the use of transplantation treatment in leukoderma we must take every possible precaution to reduce all risks of undesirable effects.

For cell preparation it is important to use a medium containing a minimum of foreign proteins, eg, pituitary extract or bovine serum. If foreign proteins must be used, they should derive from the safest possible source. Several investigators have stressed the need to develop an easy-to-use, completely traceable delivery system free of phorbolesters and foreign proteins, and some progress has been made toward such a product.¹¹ If growth factors are added, they should be from a recombinant source and produced in accordance with international good manufacturing practices standards.

Today there exist melanocyte media free of phorbolesters, pituitary extract, and serum, but these products, like all other such products, are manufactured for in vitro cell culture. Whether these products are to be used in the treatment of patients is a risk/benefit decision that has to be made by the responsible clinician and discussed with the local human ethical committee, and, in some countries, also approved by a government agency.

To neutralize the action of trypsin, soy bean extract can be used instead of bovine serum. Soy bean–derived trypsin inhibitor can be found in powder or liquid form. All these precautionary measures are taken to reduce the risk, even theoretical, of carrying slow viruses, prions, and similar agents to the recipient site. Even the bandage should be from a safe source. In our practice we currently only use an inert silicone mesh to retain cells in place before covering with occlusive plastic dressing.

It must be stressed that it is important to help patients with leukoderma, as they often suffer severely from their skin disorder. However, we must know that there exists no treatment totally free from possible adverse effects. Although the medical alternatives offered to these patients, such as different kinds of UV therapies and corticosteroid treatments, are not totally free from undesirable side effects, they still serve as important segments in the circle of alternatives. And if used for the appropriate indications and in the right circumstances, surgical treatments represent an important strategy to restore pigmentation in skin that has lost its melanocytes, and it will most likely continue to serve this purpose for many more years.

Correspondence: Dr Olsson, Department of Medical Sciences, Division of Dermatology and Venereology, Uppsala University, SE-751 85 Uppsala, Sweden (mats.olsson@medsci.uu.se).

The author has no relevant financial interest in this article.