Immunotherapy-induced Leukoderma from Treatment of Melanoma with IL-2: A Case Report and a Review of the Literature

Abstract

Melanoma-associated leukoderma (MAL) is a relatively uncommon phenomenon in the literature that can present (1) before melanoma detection, (2) after detection and before treatment, and (3) after treatment with immunotherapeutic agents. We report a case of MAL in an 83-year-old man after treatment with high dose IL-2 for metastatic melanoma and further describe the literature of the underlying mechanisms behind it that involve the immune system. Cytotoxic CD8+ T cells are thought the mediate the process at a cellular level. Self-antigens (e.g. MART-1/2, gp100, tyrosinase) have been presented on the surface of both normal and malignant melanocytes and mediate the development of MAL after cytotoxic CD8+ T cells attack both cell types. Autoimmune manifestations have a positive effect on tumor immunity, with patients at stage III and stage IV melanoma showing a better prognosis after leukoderma development. In addition, immunotherapy induced leukoderma has been associated with a higher therapeutic response rate. Recently, newer immuno-therapeutic drugs, such as vemurafenib and ipilimumab, have been associated with leukoderma as a side effect.

Immunomodulatory Activity of Polysaccharide–Protein Complex from the Mushroom Sclerotia of Polyporus rhinocerus in Murine Macrophages

“…Recently, research on immunotherapy that is focused on the naturally occurring substances which exhibit beneficial therapeutic properties through stimulating the immune response mechanism of the host is increasing. − Among the bioactive substances targeted in these studies, polysaccharides and polysaccharide–protein complexes derived from edible and medicinal fungi/mushrooms have attracted the most attention as immunomodulators because of their high potency and nontoxicity. The most used mushroom polysaccharides or polysaccharide–protein complexes are derived from Trametes versicolor , Lentinus edodes , and Agaricus brasiliensis , which are rich in β-glucans .…”

Sneaky side effects and ineffectiveness of an immunotherapy with ipilimumab in a case of metastatic melanoma

“…There are reports that the development of leukoderma or vitiligo was associated with a better prognosis. 17 and that immune-related adverse events such as vitiligo and autoimmune thyreoiditis were associated with responses to ipilimumab, at the cost of considerable toxicity. 18,19 However, there are other studies that report that development of autoimmune diseases whether they were tumor-associated or drug-induced was not associated with a better prognosis.…”

Low frequency of skin cancers in vitiligo patients

“…Although the efficiency of this antitumour response may not be sufficient for complete eradication of melanoma, longer survival has been observed in MAL patients on different antitumor therapies [22,23]. Studies by Quaglino et al [24] and Phan et al [25] showed a higher response to high-dose interleukin 2 (IL-2) therapy in patients who developed MAL.…”