Possible Mechanisms of Hypopigmentation in Lichen Sclerosus

Abstract

Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma. To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation). The degree and extent of melanization found in LS overlapped with that in acute scars showing predominantly hypomelanized keratinocytes, with that in LP containing regions with numerous melanophages, and with that in vitiligo exhibiting focal regions of keratinocytes devoid of melanin pigment. By hematoxylin-eosin staining and immunocytochemistry for Mel-5 and Mart-1, LS had a lower mean count of melanocytes than acute scars, LP, and normal skin per 200 basal keratinocytes. In addition, a few LS cases had a significant loss of melanocytes comparable to that of vitiligo. Surprisingly, Mart-1 identified rare melanocytes in 67% of vitiligo cases and a significantly larger pool of melanocytes in LS and controls other than those labeled by Mel-5. Furthermore, LP and evolving lesions of LS contained the highest Mart-1 counts. HMB-45-immunoreactive melanocytes were found in the majority of acute scars and in LP and late-stage LS lesions at significantly lower levels than Mel-5- and Mart-1- labeled melanocytes, but they were not found in vitiligo or normal skin. We propose that several mechanisms may play a role in the production of leucoderma in LS: 1) decreased melanin production; 2) block in transfer of melanosomes to keratinocytes; and 3) melanocyte loss. The latter finding may be the pathogenic connection (lichenoid dermatitis of LS triggering an autoimmune reaction to melanocytes) that underlies the documented association of LS with vitiligo.

Hypopigmenting agents: an updated review on biological, chemical and clinical aspects

“…Melatonin receptor activation has been suggested as a peculiar biological mechanism to cause toxic melanin synthesis intermediate release and its possible involvement in vitiligo (Slominski et al, 1989). Some fungal metabolites of dermatophytes, Malessezia yeasts and lichen were found toxic to melanocytes explaining depigmented lesions on the skin (Carlson et al, 2002;De Luca et al, 1996;Podobinska et al, 2003;Thoma et al, 2005).…”

Lichen sclerosus mimicking Bowen’s disease

“…It may occur when human papillomavirus infection is present at the same time. Extragenital lesions do not develop into malignancy [5,6].…”

“…Probably the real pathogenesis is multifactorial [5]. Lichen sclerosus is often connected with vitiligo, which may trigger an autoimmune reaction to melanocytes [6].…”

Efficacy of Autogenous Dermis Graft for Wound Coverage

“…Several factors may play a role in the color mismatch of a regular skin graft. These include the amount of melanin, the degree of transfer of melanosomes to keratinocytes, and the number of melanocytes (Carlson et al, 2002;Velangi & Rees, 2001). Because the melanocytes are localized to the basal cell layer of the epidermis, the origin of the color mismatch has been assumed to be in the epidermal melanin (Tyack et al, 1997;Swope et al, 2002).…”