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Autologous in vitro reconstituted epidermis in the treatment of a large nevus depigmentosus

2006; Elsevier BV; Volume: 54; Issue: 5 Linguagem: Inglês

10.1016/j.jaad.2005.08.013

1097-6787

Desanka Raskovic, Sergio Bondanza, Tommaso Gobello, A. Luci, Giovanna Zambruno, Rudolf Happle, Liliana Guerra,

Hedgehog Signaling Pathway Studies

To the Editor: Nevus depigmentosus is a circumscribed hypopigmentation recognized either at birth or during early childhood.1Jimbow K. Fitzpatrick T.B. Szabo G. Hori Y. Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.J Invest Dermatol. 1975; 64: 50-62Crossref PubMed Scopus (128) Google Scholar Histopathologic examination shows a normal or decreased number of melanocytes, but melanosome synthesis and transfer into keratinocytes appears to be decreased.1Jimbow K. Fitzpatrick T.B. Szabo G. Hori Y. Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.J Invest Dermatol. 1975; 64: 50-62Crossref PubMed Scopus (128) Google Scholar We report an unusual case of systematized nevus depigmentosus in which we evaluated the effectiveness of cultured epidermal autografts bearing melanocytes to restore the physiologic photoprotection by normal amounts of melanin.A 29-year-old man had a large congenital hypopigmented lesion on the right side of his abdomen, with a segmental arrangement. Normally pigmented and hyperpigmented macules were present within the hypopigmented area (Fig 1, A). Similar lesions were also noted on the patient's feet. Although the lesions were uniformly hypochromic at birth, normally pigmented and hyperpigmented macules progressively appeared within the hypochromic areas from the age of 18 months to the age of 10 years. There were neither associated systemic abnormalities nor a family history of similar cutaneous findings. The transmission electron microscopic examination of the hypopigmented skin showed that melanocytes were regularly distributed above the basal lamina, but contained very few melanosomes (Fig 1, B). The amount of melanosomes was likewise markedly reduced in the surrounding keratinocytes. We established a diagnosis of systematized nevus depigmentosus with lentiginosis, as already described in two patients by Bolognia et al.2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google ScholarOnce the patient's informed consent had been obtained, a skin biopsy specimen was taken from an unaffected area and cell cultures were performed as previously reported.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar For transplantation procedures a pretreatment with EMLA cream under 2-hour occlusion was carried out and the hypochromic epidermis of the abdomen was removed by means of a pulsed erbium:yttrium-aluminum-garnet laser (Laser Smart 2940, DEKA MELA srl, Firenze, Italy), with a 2-mm spot-sized hand piece at an energy setting of 400 mJ and a fluence of 12.73 J/cm2.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar Cultured autografts were then applied onto the receiving bed. Although uneven, repigmentation was almost complete at the 6-month follow-up visit (Fig 1, C), and it remained stable during the following 30 months. Electron microscopic examination of the transplanted skin, 16 months after autografting, showed a normal population of melanocytes above the basal lamina, with melanosomes in several stages of melanization (Fig 1, D). Numerous melanosomes were visible in the keratinocytes of the basal (Fig 1, D) and first suprabasal layer.Nevus depigmentosus is usually a stable hypomelanosis. However, some modifications within the nevus have been described, such as multiple lentigines2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google Scholar and multiple agminated Spitz nevi.5Menni S. Betti R. Boccardi D. Gualandri L. Both unilateral naevus achromicus and congenital agminated Spitz naevi in a checkerboard mosaic pattern.Br J Dermatol. 2001; 144: 187-188Crossref PubMed Scopus (12) Google Scholar Whatever pathogenetic mechanism may have caused melanocyte modifications within the nevus depigmentosus in these cases,2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google Scholar, 5Menni S. Betti R. Boccardi D. Gualandri L. Both unilateral naevus achromicus and congenital agminated Spitz naevi in a checkerboard mosaic pattern.Br J Dermatol. 2001; 144: 187-188Crossref PubMed Scopus (12) Google Scholar UV damage could have played an important role. Properly functioning epidermal melanocytes, in fact, are a prerequisite for protecting the skin from UV-induced damage, especially through the synthesis and transfer of melanin-containing melanosomes from melanocytes to keratinocytes.In the last few years, we have reported that it is possible to achieve very high levels of repigmentation in stable vitiligo and piebaldism, by means of autologous cultured epidermal sheets.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar The results obtained in the current case indicate that cultured autografts can also be used for the treatment of nevus depigmentosus, allowing to restore a physiologic photoprotection by normal amounts of melanin within melanocytes of hypochromic skin areas. However, the success rate and the limits of this technology in the surgical therapy of nevus depigmentosus need to be further evaluated by treating additional patients. To the Editor: Nevus depigmentosus is a circumscribed hypopigmentation recognized either at birth or during early childhood.1Jimbow K. Fitzpatrick T.B. Szabo G. Hori Y. Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.J Invest Dermatol. 1975; 64: 50-62Crossref PubMed Scopus (128) Google Scholar Histopathologic examination shows a normal or decreased number of melanocytes, but melanosome synthesis and transfer into keratinocytes appears to be decreased.1Jimbow K. Fitzpatrick T.B. Szabo G. Hori Y. Congenital circumscribed hypomelanosis: a characterization based on electron microscopic study of tuberous sclerosis, nevus depigmentosus, and piebaldism.J Invest Dermatol. 1975; 64: 50-62Crossref PubMed Scopus (128) Google Scholar We report an unusual case of systematized nevus depigmentosus in which we evaluated the effectiveness of cultured epidermal autografts bearing melanocytes to restore the physiologic photoprotection by normal amounts of melanin. A 29-year-old man had a large congenital hypopigmented lesion on the right side of his abdomen, with a segmental arrangement. Normally pigmented and hyperpigmented macules were present within the hypopigmented area (Fig 1, A). Similar lesions were also noted on the patient's feet. Although the lesions were uniformly hypochromic at birth, normally pigmented and hyperpigmented macules progressively appeared within the hypochromic areas from the age of 18 months to the age of 10 years. There were neither associated systemic abnormalities nor a family history of similar cutaneous findings. The transmission electron microscopic examination of the hypopigmented skin showed that melanocytes were regularly distributed above the basal lamina, but contained very few melanosomes (Fig 1, B). The amount of melanosomes was likewise markedly reduced in the surrounding keratinocytes. We established a diagnosis of systematized nevus depigmentosus with lentiginosis, as already described in two patients by Bolognia et al.2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google Scholar Once the patient's informed consent had been obtained, a skin biopsy specimen was taken from an unaffected area and cell cultures were performed as previously reported.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar For transplantation procedures a pretreatment with EMLA cream under 2-hour occlusion was carried out and the hypochromic epidermis of the abdomen was removed by means of a pulsed erbium:yttrium-aluminum-garnet laser (Laser Smart 2940, DEKA MELA srl, Firenze, Italy), with a 2-mm spot-sized hand piece at an energy setting of 400 mJ and a fluence of 12.73 J/cm2.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar Cultured autografts were then applied onto the receiving bed. Although uneven, repigmentation was almost complete at the 6-month follow-up visit (Fig 1, C), and it remained stable during the following 30 months. Electron microscopic examination of the transplanted skin, 16 months after autografting, showed a normal population of melanocytes above the basal lamina, with melanosomes in several stages of melanization (Fig 1, D). Numerous melanosomes were visible in the keratinocytes of the basal (Fig 1, D) and first suprabasal layer. Nevus depigmentosus is usually a stable hypomelanosis. However, some modifications within the nevus have been described, such as multiple lentigines2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google Scholar and multiple agminated Spitz nevi.5Menni S. Betti R. Boccardi D. Gualandri L. Both unilateral naevus achromicus and congenital agminated Spitz naevi in a checkerboard mosaic pattern.Br J Dermatol. 2001; 144: 187-188Crossref PubMed Scopus (12) Google Scholar Whatever pathogenetic mechanism may have caused melanocyte modifications within the nevus depigmentosus in these cases,2Bolognia J.L. Lazova R. Watsky K. The development of lentigines within segmental achromic nevi.J Am Acad Dermatol. 1998; 39: 330-333Abstract Full Text Full Text PDF PubMed Google Scholar, 5Menni S. Betti R. Boccardi D. Gualandri L. Both unilateral naevus achromicus and congenital agminated Spitz naevi in a checkerboard mosaic pattern.Br J Dermatol. 2001; 144: 187-188Crossref PubMed Scopus (12) Google Scholar UV damage could have played an important role. Properly functioning epidermal melanocytes, in fact, are a prerequisite for protecting the skin from UV-induced damage, especially through the synthesis and transfer of melanin-containing melanosomes from melanocytes to keratinocytes. In the last few years, we have reported that it is possible to achieve very high levels of repigmentation in stable vitiligo and piebaldism, by means of autologous cultured epidermal sheets.3Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.Arch Dermatol. 2003; 139: 1303-1310Crossref PubMed Scopus (60) Google Scholar, 4Guerra L. Primavera G. Raskovic D. Pellegrini G. Golisano O. Bondanza S. et al.Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.Br J Dermatol. 2004; 150: 715-772Crossref PubMed Scopus (31) Google Scholar The results obtained in the current case indicate that cultured autografts can also be used for the treatment of nevus depigmentosus, allowing to restore a physiologic photoprotection by normal amounts of melanin within melanocytes of hypochromic skin areas. However, the success rate and the limits of this technology in the surgical therapy of nevus depigmentosus need to be further evaluated by treating additional patients.