BACKGROUND:Because available treatments for vitiligo generally provide unsatisfactory results, the search for viable therapeutic alternatives continues.OBJECTIVE:Our purpose was to evaluate several transplantation procedures with cultured autologous melanocytes for their practicality in treating patients with vitiligo.METHODS:Twenty-seven patients with stable or active vitiligo were treated after superficial dermabrasion with application of suspensions of autologous cultured melanocytes, melanocyte-keratinocyte mixtures, or epidermal sheets established in vitro.RESULTS:Regardless of disease activity, use of each method resulted in repigmentation to a similar degree and without scarring in all patients. Melanocyte suspensions offer several advantages: They are easily prepared, can be applied in a controlled manner, permit coverage of large areas, and produce a homogeneous skin color that affords the best cosmetic restoration. The ultrastructure of transplant sites resembled that of uninvolved skin, with one exception: the melanocytes were located slightly higher than in uninvolved skin.CONCLUSION:Application of cultured autologous melanocytes to lightly abraded skin is an advantageous addition to the treatments available for patients with vitiligo.

We have developed a technique through which we can multiply melanocytes in culture from a small specimen of normally pigmented buttock skin and reimplant them into depigmented sites of vitiligo. To date, 90 patients have benefited in our hands from such autologous transplantation of pigment cells. Often we have an excess of cells which we would like to store for later use in the event a patient requires further treatment. We report here on 4 cases in which we have cryostored cultured melanocytes for 6-12 months, reimplanted them into vitiliginous sites of the donor after one week of reculture, and obtained optimal repigmentation. We now routinely freeze melanocytes left over after treatment.

Two unusual patients with metastatic melanoma are presented. One had generalized melanosis, and the other a rapid induction of multiple small pigmented lesions within a day of exposure to the sun. From a variety of clinical observations on these 2 patients and ones reported in the literature, and from recent advances in basic biomedical knowledge, we conclude that in both conditions the anomalous presence of growth factors that stimulate the proliferation and melanogenic differentiation of normal and malignant melanocytes played a major role in producing the clinical events.

Annals of the New York Academy of SciencesVolume 680, Issue 1 p. 1-12 The Discovery of the Melanotropins: A History of Pituitary Endocrinologya AARON B. LERNER, AARON B. LERNER Department of Dermatology Yale University School of Medicine Post Office Box 3333 New Haven, Connecticut 06510-8059Search for more papers by this author AARON B. LERNER, AARON B. LERNER Department of Dermatology Yale University School of Medicine Post Office Box 3333 New Haven, Connecticut 06510-8059Search for more papers by this author First published: May 1993 https://doi.org/10.1111/j.1749-6632.1993.tb19670.xCitations: 35 a This work was supported by United States Public Health Service grant RO1 AR39869 and by a grant from the Eleanor Naylor Dana Charitable Trust. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume680, Issue1The Melanotropic PeptidesMay 1993Pages 1-12 RelatedInformation

To study the effect of vitiligo on interference with sexual relationships, we surveyed 158 patients by questionnaire. Although a majority of patients reported a negative impact on sexual relationships, most patients felt embarrassment when showing their body or meeting strangers. The majority of patients who reported a negative impact on sexual relationships attributed the problems to their embarrassment. Those who were particularly affected were those with low self-esteem, men, those to whom appearance is important, and single persons. Dermatologists should be especially alert to the effects of disfigurement and should, attempt to assist patients with this problem.

Tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1) is a key enzyme in the synthesis of melanin. Reduced levels of tyrosinase play an important role in albinism. The data described here show differences in the expression and characteristics of tyrosinase in cutaneous murine melanocytes grown in culture from normal wild-type strains (C/C); from three albino locus mutants: himalayan (ch/ch), chinchilla (cch/cch), and albino (c/c); and from the double-mutant heterozygous pink-eyed chinchilla (cchp/cp). Our results suggest that the diminished pigmentation in all mutants is due to abnormal posttranslational modification of the enzyme: the levels of mRNA for tyrosinase in wild-type, himalayan, and pink-eyed chinchilla melanocytes are similar; the himalayan mutation confers a deficiency in N-linked glycosylation, which results in an extremely unstable enzyme that is also temperature sensitive; the chinchilla and albino mutations confer susceptibility to proteolytic cleavage; the pink-eye dilution confers a reduction in the levels of immunoprecipitable tyrosinase, and what little enzyme there is fails to be translocated from the trans-Golgi network to melanosomes. The kinetics of activation and inhibition of the enzyme by the cofactor dopa are unique for the mutants tested and differ from those of tyrosinase from wild-type melanocytes. The findings support the conclusion that the albino locus in mice encodes the structural gene of tyrosinase.

Two Lyt-1+, L3T4a+ autoreactive T cell clones specific for self-class II major histocompatibility complex (MHC) gene products were established from lymph node cells and spleen cells of C57BL/6J mice, respectively, by different methods. They were stimulated to proliferate in culture in response to I-Ab antigen-bearing syngeneic spleen cells in a class II MHC-restricted manner. This stimulation was inhibited completely by the addition of anti-L3T4a (GK1.5) or anti-I-Ab (3JP) monoclonal antibodies. The autoreactive T cell clones lysed syngeneic I-Ab+ target cells such as lipopolysaccharide (LPS) blasts. They also lysed I-A- bystander cells such as Cloudman and B16 melanoma and lymphoid tumor cells in the presence of I-Ab+ stimulator cells but not I-Ad+ cells. This bystander killing was most likely mediated by soluble factors released from the autoreactive T cells in response to I-Ab antigens, because culture supernatants from activated autoreactive T cells inhibited the proliferation of B16 melanoma cells in vitro and also had significant cytolytic activity. Both lymphotoxin and interferon-gamma were released from activated autoreactive T cells, suggesting that these cytotoxic lymphokines were responsible for autoreactive T cell-mediated cytolysis. The finding that the two clones, established independently and by different methods, show self-class II MHC antigen-restricted cytolysis, and bystander cytolysis suggests that these properties are not restricted to a unique population of autoreactive T cells. These results favor the concept that in vivo, autoreactive T cells may express not only regulatory activity in regard to antibody responses, but also anti-tumor activity via bystander cytolysis.

The vitiligo mouse C57BL/6J Ler-vit/vit is a new, murine model for vitiligo in humans. It was studied with respect to morphology and fine structure of melanocytes in hair and eyes before and during depigmentation. The coat of vitiligo mice lightens progressively with age because of an increase in the ratio of white to pigmented hairs with each molt. The bulbs of white hairs are devoid of pigment, and they lack melanocytes. In other respects the epithelium is morphologically normal as determined by light and electron microscopy. The bulbs of pigmented hairs are histologically normal. By electron microscopy, however, some of the melanocytes are shown to have undergone degenerative changes. In addition, disruption of the basement membrane underlying the melanocytes and herniation of melanocytes into dermal papillae were observed at various stages of hair growth. Papillary melanophages are prominent in pigmented as well as in white hair bulbs. Newborn vitiligo mice have no uveal pigment. Pigment appears in the iris and ciliary body by Day 4 and in the choroid by Week 3. On Day 4, along with pigmentation, conspicuous spherical amelanotic cells appear over the anterior border of the iris. These cells become numerous in the ensuing weeks and gradually acquire large melanophagosomes. They occur also in the stroma of the iris and the ciliary body, associated with necrotic melanocytes. The spherical cells are identical to the clump cells of Koganei and are far more numerous in vitiligo mice than in controls. Macroscopically, no progressive decrease in iridial pigment is apparent for the life of the vitiligo mouse. In the choroid, an amelanotic patch surrounds the optic nerve. In the pigmented areas, melanocytes show compartmentalization of melanosomes and degeneration. The retinal pigment epithelium generally appeared continuous. In older animals some epithelial cells contained large fat bodies or were devoid of melanin.