SUMMARY:In situ immune infiltrates in lesional, perilesional, and nonlesional skin biopsies from patients with vitiligo were analyzed by immunohistochemistry and compared with immune infiltrates found in the skin of normal healthy donors and relevant disease controls. An increased influx of activated skin-homing T cells and macrophages were seen in the perilesional biopsies. The overall percentages of cutaneous leukocyte-associated antigen-positive (CLA ϩ ) T cells were similar to those found in normal healthy donors. This is compatible with the similar expression of E-selectin. Most strikingly, however, the CLA ϩ T cells in perilesional skin were mainly clustered in the vicinity of disappearing melanocytes, and 60% to 66% of these interacting T cells expressed perforin and granzyme-B. The perforin ϩ /granzyme-B ϩ cells were not seen in locations different from that of disappearing melanocytes. Interestingly, the majority of the infiltrating T cells were HLA-DR/CD8 ϩ . Another hallmark of the present study is the focal expression of intercellular adhesion molecule (ICAM)-1 and HLA-DR in the epidermis at the site of interaction between the immune infiltrates and the disappearing melanocytes. The data presented in this study are consistent with a major role for skin-homing T cells in the death of melanocytes seen in vitiligo. (Lab Invest 2000, 80:1299-1309.
The appearance of depigmentation during the course of malignant melanoma has been considered a good prognostic sign. Is it only a side-effect, informative of the immune system's response to the treatment, or does it act as a necessary amplifier of these clinically important anti-tumor responses? The current review will attempt to tackle this question by reviewing the current literature, as well as by posing some novel hypotheses. Understanding the nature of humoral and cellular immune responses directed against normal melanocytes and their malignant counterparts may lead to the design of improved therapeutic strategies relevant to both vitiligo and melanoma.
Vitiligo involves a progressive loss of melanocytes from the epidermis and hair follicles. Milky-white patches appear resulting in cosmetic disfiguration that is most apparent in dark-skinned individuals. The disease is further classified according to distribution pattern and extent of depigmentation. The presence of several clinical subtypes may reflect the diversity in causative factors. To select appropriate therapeutic measures it is important to distinguish vitiligo from other disorders that affect melanocyte function. Although vitiligo has a characteristic clinical appearance and histological features, the presence of early or atypical lesions often requires the exclusion of other disorders such as postinflammatory hypopigmentation and piebaldism. Multiple hypotheses have been put forward to explain vitiligo. An inherited tendency to develop depigmentation may involve the inherent aberrancies that have been observed in nonlesional vitiligo melanocytes in vivo as well as in vitro. These abnormalities potentially render vitiliginous melanocytes more vulnerable to assaults from extracellular factors. Such factors include keratinocyte physiology, extracellular matrix composition, humoral and cellular immunity, and environmental agents. Therapies aimed at repopulation of lesional skin include phototherapy, application of topical corticosteroids, and transplantation of skin or skin cells. Moreover, micropigmentation or camouflage can be used to restore a pigmented appearance to lesional skin. In patients in which vitiligo affects extensive areas of the body, depigmentation may be the treatment of choice. In all, this acquired pigmentary disorder can be treated in a variety of ways and should not be regarded as an untreatable affliction.
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