The combination of skin ablation and 5-Fluorouracil (5-FU) ointment was previously tried in the treatment of vitiligo, and good results were specifically reported in glabrous skin without follicular melanocyte reservoirs. Methods. This study was carried out on the skins of seven guinea pigs: three were treated with mechanical dermabrasion plus topical 5-FU in an achromic area contiguous to a pigmented area; two were treated by only dermabrasion in a similar area; and two were treated by topical 5-FU alone. Clinical, histological, and ultrastructural studies were performed over two months. Results. In guinea pigs treated with dermabrasion plus 5-FU, we observed firstly a delay of wound healing with an obvious inflammatory reaction, and, after two months, evident pigment spread from the pigmented into the achromic area. After six months, we noticed black hair regrowing in the achromic area. Pigment spread was not seen in the guinea pigs skin treated by either dermabrasion or topical 5-FU. We suggest that the inflammatory mediators and enzymes (metalloproteinases), which are locally released over a long time, could stimulate and facilitate melanocyte proliferation and migration through the enlarged intercellular spaces of the epidermis. This sequence of events may be applied to vitiligo patients treated with 5-FU on ablated lesions. 1. Introduction Vitiligo affects 1% of the world’s population and probably has a higher incidence in dark-skinned individuals. Three repigmentation patterns are usually described: perifollicular, when the predominant repigmentation is follicular; marginal, when the predominant repigmentation is from the borders of patches; and diffuse, when repigmentation occurs across the patches of vitiligo [1]. Nb-UVB phototherapy is considered to be a very important modality in vitiligo treatment. Its efficacy is mainly due to the stimulation of the perifollicular repigmentation and rarely to the repigmentation from the edges, so treatment of glabrous areas localized on the elbows, the dorsa of the hands, fingers, wrists, and feet is presently challenging. Application of 5-Fluorouracil (5-FU) after mechanical dermabrasion, as a treatment for vitiligo, was introduced by Tsuji and Hamada in 1983 [2], and its efficacy was successively confirmed by other authors [3–5]. Successful repigmentation of areas devoid of hair follicles (periungueal areas and the dorsa of the feet) was first reported by Anbar after ER: YAG laser skin ablation followed by topical application of 5-FU and Nb-UVB phototherapy [6–8]. At first sight, this effective
References
[1]
D. Parsad, R. Pandhi, S. Dogra, and B. Kumar, “Clinical study of repigmentation patterns with different treatment modalities and their correlation with speed and stability of repigmentation in 352 vitiliginous patches,” Journal of the American Academy of Dermatology, vol. 50, no. 1, pp. 63–67, 2004.
[2]
T. Tsuji and T. Hamada, “Topically administered fluorouracil in vitiligo,” Archives of Dermatology, vol. 119, no. 9, pp. 722–727, 1983.
[3]
E. Szekeres and M. Morvay, “Repigmentation of vitiligo macules treated topically with Efudix cream,” Dermatologica, vol. 171, no. 1, pp. 55–59, 1985.
[4]
B. Monk, “Topical fluorouracil in vitiligo,” Archives of Dermatology, vol. 121, no. 1, pp. 25–26, 1985.
[5]
S. Sethi, B. B. Mahajan, R. R. Gupta, and A. Ohri, “Comparative evaluation of the therapeutic efficacy of dermabrasion, dermabrasion combined with topical 5% 5-fluorouracil cream, and dermabrasion combined with topical placentrex gel in localized stable vitiligo,” International Journal of Dermatology, vol. 46, no. 8, pp. 875–879, 2007.
[6]
T. Anbar, W. Westerhof, A. Abdel-Rahman, M. El-Khayyat, and Y. El-Metwally, “Treatment of periungual vitiligo with Erbium-YAG-laser plus 5-flurouracil: a left to right comparative study,” Journal of Cosmetic Dermatology, vol. 5, no. 2, pp. 135–139, 2006.
[7]
T. S. Anbar, W. Westerhof, A. T. Abdel-Rahman, A. A. Ewis, and M. A. El-Khayyat, “Effect of one session of ER:YAG laser ablation plus topical 5Fluorouracil on the outcome of short-term NB-UVB phototherapy in the treatment of non-segmental vitiligo: a left-right comparative study,” Photodermatology Photoimmunology and Photomedicine, vol. 24, no. 6, pp. 322–329, 2008.
[8]
T. Garg, R. Chander, and A. Jain, “Combination of microdermabrasion and 5-Fluorouracil to induce repigmentation in vitiligo: an observational study,” Dermatologic Surgery, vol. 37, no. 12, pp. 1763–1766, 2011.
[9]
T. Desai, C. L. Chen, A. Desai, and W. Kirby, “Basic pharmacology of topical imiquimod, 5-Fluorouracl and diclofenac for the dermatologic surgeon,” Dermatologic Surgery, vol. 38, pp. 97–103, 2012.
[10]
D. L. Sachs, S. Kang, C. Hammerberg et al., “Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis,” Archives of Dermatology, vol. 145, no. 6, pp. 659–666, 2009.
[11]
A. Yen Moore, “Clinical applications for topical 5-fluorouracil in the treatment of dermatological disorders,” Journal of Dermatological Treatment, vol. 20, no. 6, pp. 328–335, 2009.
[12]
C. J. Dillaha, G. T. Jansen, and W. M. Honeycutt, “Selective cytotoxic effect of topical 5-Fluorouracil,” Archives of Dermatology, vol. 88, pp. 247–256, 1963.
[13]
D. S. Waldorf, M. L. Engel, and E. J. Van Scott, “Inhibition of wound epithelialization by topical 5-fluorouracil,” Archives of Dermatology, vol. 94, no. 6, pp. 786–789, 1966.
[14]
R. M. Pujol, V. Rocamora, A. Lopez-Pousa, R. Taberner, and A. Alomar, “A rare local complication of intravenous 5-fluorouracil therapy,” Journal of the American Academy of Dermatology, vol. 39, no. 5, pp. 839–842, 1998.
[15]
R. Goyal, S. B. Chalamalaseth, K. Madan, and S. B. Paul, “5-Fluorouracil is associated with a peculiar skin reaction called “hand and foot syndrome”,” Indian Journal of Gastroenterology, vol. 26, no. 6, pp. 292–293, 2007.
[16]
R. Rao and C. Balachandran, “A rare vasculo-cutaneous effect induced by systemic 5-fluorouracil,” Indian Journal of Dermatology, Venereology and Leprology, vol. 76, no. 6, pp. 714–715, 2010.
[17]
C. C. Chan and S. J. Lin, “Serpentine supravenous hyperpigmentation,” New England Journal of Medicine, vol. 363, no. 5, article e8, 2010.
[18]
E. R. C. Geddes and P. R. Cohen, “Antineoplastic agent-associated serpentine supravenous hyperpigmentation: superficial venous system hyperpigmentation following intravenous chemotherapy,” Southern Medical Journal, vol. 103, no. 3, pp. 231–235, 2010.
[19]
G. Van Tienhoven and J. W. Wilmink, “A woman with palmar and plantar hyperpigmentation,” Nederlands Tijdschrift voor Geneeskunde, vol. 155, no. 45, p. 4100, 2011.
[20]
R. Tavares-Bello, “Capecitabine-induced hand-foot syndrome and cutaneous hyperpigmentation in an elderly vitiligo patient,” Journal of the European Academy of Dermatology and Venereology, vol. 21, no. 10, pp. 1434–1435, 2007.
[21]
T. Tsuji and M. A. Karasek, “Differential effects of 5-fluorouracil on human skin melanocytes and malignant melanoma cells in vitro,” Acta Dermato-Venereologica, vol. 66, no. 6, pp. 474–478, 1986.
[22]
T. Tsuji and M. Karasek, “A procedure for the isolation of primary cultures of melanocytes from newborn and adult human skin,” Journal of Investigative Dermatology, vol. 81, no. 2, pp. 179–180, 1983.
[23]
Y. Gauthier, “An animal model applicable to vitiligo to study the marginal repigmentation pattern,” Pigment Cell Research, vol. 20, article 442, 2007.
[24]
P. M. Cox, A. P. Dhillon, S. Howe, R. M. Pittilo, and J. Rode, “Repopulation of guinea-pig skin by melanocytes during wound healing: a morphometric study,” British Journal of Experimental Pathology, vol. 70, no. 6, pp. 679–689, 1989.
[25]
J. Dre？ler, A. Busuttil, R. Koch, and D. J. Harrison, “Sequence of melanocyte migration into human scar tissue,” International Journal of Legal Medicine, vol. 115, no. 2, pp. 61–63, 2001.
[26]
R. G. Staricco, “The melanocytes and the hair follicle,” Journal of Investigative Dermatology, vol. 35, pp. 185–194, 1960.
[27]
R. G. Staricco, “Mechanism of migration of the melanocytes from the hair follicle into the epidermis following dermabrasion,” Journal of Investigative Dermatology, vol. 39, pp. 16–34, 1962.
[28]
J. S. Pegum, “Dissociated depigmentation in vitiligo. Significance and therapeutic implication,” British Journal of Dermatology, vol. 67, pp. 348–350, 1955.
[29]
J. E. Fulton, A. D. Rahimi, S. Mansoor, P. Helton, and P. Shitabata, “The treatment of hypopigmentation after skin resurfacing,” Dermatologic Surgery, vol. 30, no. 1, pp. 95–101, 2004.
[30]
H. L. Stoll and E. Klein, “Effect of occlusive dressing on the local administration of 5-fluorouracil to superficial basal cell carcinoma,” Journal of Investigative Dermatology, vol. 52, no. 3, pp. 304–306, 1969.
[31]
J. G. Morelli, J. J. Yohn, T. Zekman, and D. A. Norris, “Melanocyte movement in vitro: role of matrix proteins and integrin receptors,” Journal of Investigative Dermatology, vol. 101, no. 4, pp. 605–608, 1993.
[32]
J. G. Morelli, J. Kincannon, J. J. Yohn, T. Zekman, W. L. Weston, and D. A. Norris, “Leukotriene C4 and TGF-alpha are stimulators of human melanocyte migration in vitro,” Journal of Investigative Dermatology, vol. 98, no. 3, pp. 290–295, 1992.
[33]
J. G. Morelli, J. J. Yohn, M. B. Lyons, R. C. Murphy, and D. A. Norris, “Leukotrienes C4 and D4 as potent mitogens for cultured human neonatal melanocytes,” Journal of Investigative Dermatology, vol. 93, no. 6, pp. 719–722, 1989.
[34]
T. C. Lei, W. D. Vieira, and V. J. Hearing, “In vitro migration of melanoblasts requires matrix metalloproteinase-2: implications to vitiligo therapy by photochemotherapy,” Pigment Cell Research, vol. 15, no. 6, pp. 426–432, 2002.
[35]
C. C. E. Lan, G. S. Chen, M. H. Chiou, C. S. Wu, C. H. Chang, and H. S. Yu, “FK506 promotes melanocyte and melanoblast growth and creates a favourable milieu for cell migration via keratinocytes: possible mechanisms of how tacrolimus ointment induces repigmentation in patients with vitiligo,” British Journal of Dermatology, vol. 153, no. 3, pp. 498–505, 2005.
