Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma

J Dermatol Sci. 2015 Mar;77(3):146-9. doi: 10.1016/j.jdermsci.2015.02.001. Epub 2015 Feb 7.


Recently, an unexpected outbreak of patients with leukoderma occurred in Japan with the use of brightening/lightening cosmetics containing rhododendrol (RD). Patients developed leukoderma mostly on the skin sites repeatedly applied with RD, but some patients also had vitiligo-like lesions on the non-applied sites. RD is a tyrosinase-competitive inhibiting substance, thereby serving as an inhibitor of melanin synthesis. Upon inhibition of tyrosinase, RD is converted to new products such as tyrosinase-catalyzed hydroxyl-metabolite, which damage melanocytes. The melanocyte cell lysates seem to induce T-cell response. The frequencies of CD8+ T cells in both lesional skin and peripheral blood are significantly higher in the RD leukoderma as well as non-segmental vitiligo patients than in normal controls. In HLA-A*02:01 positive cases, circulating Melan-A-specific cytotoxic T cells can be detected at a high frequency. It is thus suggested that RD-induced leukoderma is induced by not only cytolysis of melanocytes but also subsequent immune reactions toward melanocytes.

Keywords: Leukoderma; Rhododendrol; Tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Butanols / adverse effects*
  • Butanols / metabolism
  • CD8-Positive T-Lymphocytes*
  • Cosmetics / adverse effects
  • Humans
  • Hypopigmentation / chemically induced*
  • Hypopigmentation / enzymology
  • Hypopigmentation / immunology
  • Melanocytes / drug effects
  • Melanocytes / immunology
  • Monophenol Monooxygenase / antagonists & inhibitors*


  • Butanols
  • Cosmetics
  • rhododendrol
  • Monophenol Monooxygenase