Histopathological Changes Induced by Malassezin: A Novel Natural Microbiome Indole for Treatment of Facial Hyperpigmentation

February 2022 | Volume 21 | Issue 2 | Original Article | 141 | Copyright © February 2022


Published online January 31, 2022

doi:10.36849/JDD.6596

Pearl E Grimes MD,a,* Jag Bhawan MD,b Michael D. Howell PhD,c Seemal R. Desai MD,d Edna Coryell DC,e Michael Einziger BS,f Ann Marie Simpson BS,f Alex Yaroshinsky PhD,g Tim Mc Craw PhDe

aVitiligo and Pigmentation Institute of Southern California, Los Angeles, CA
bBoston University, Boston, MA
cDermTech, La Jolla, CA
dInnovative Dermatology, Plano, TX; University of Texas Southwestern Medical Center, Dallas, TX
eSkin Science Advisors LLC, Pacolet, SC
fVersicolor Technologies LLC, Santa Monica, CA
gVital Systems Incorporated, Rolling Meadows, IL

Abstract
Background: Malassezin is a natural indole compound produced by the fungus Malassezia furfur and preclinical investigations have demonstrated an ability to suppress melanogenesis.
Objective: To investigate the histopathological effects of malassezin for treatment of facial hyperpigmentation.
Methods: In this proof-of-concept study, seven subjects with facial hyperpigmentation caused by melasma or photodamage applied topical malassezin twice daily for 14 weeks, followed by eight weeks of observation. At baseline, 2 mm punch biopsies were taken from hyperpigmented areas and adjacent uninvolved skin. Skin biopsies from hyperpigmented areas were repeated at 8, 14, and 22 weeks. Paraffin-embedded sections were cut and stained with H&E, Fontana Masson, and MART 1 and assessed for histopathological changes.
Results: Increased epidermal melanin and dermal melanophages were observed in all biopsies at baseline in the hyperpigmented compared to uninvolved skin of all subjects. Eight and 14 week biopsies of involved skin revealed decreased epidermal melanin in all subjects treated with malassezin. Melanocytes appeared less dendritic compared to baseline, and numbers were slightly reduced at eight weeks. Biopsies at 22 weeks showed no significant difference in epidermal melanin levels compared to baseline hyperpigmented skin, and melanocytes were comparable in number and dendricity to baseline. There was no evidence of melanocyte atypia in any of the biopsies. These features were similar in melasma and photo-damaged skin.
Conclusion: This study documents the histopathological features and ability of malassezin, a novel agent unique to the skin microbiome, to decrease epidermal pigmentation and the temporary and revisable nature of the process.

J Drugs Dermatol. 2022;21(2):141-145. doi:10.36849/JDD.6596

INTRODUCTION

Common acquired disorders of hyperpigmentation include melasma, post-inflammatory hyperpigmentation, the dyschromia of photoaging, and solar lentigines.1,2 Melasma and post-inflammatory hyperpigmentation are the most common conditions in subjects with skin of color affecting more than five million people globally.3–5 These conditions are often disfiguring, have a profoundly negative impact on quality of life, and can be therapeutically challenging.6,7

Treatment approaches currently involve a multimodality protocol incorporating photoprotective agents, antioxidant treatments, skin lighteners, exfoliants, and resurfacing procedures.6,7 Commonly used skin lighteners include hydroquinone, kojic acid, azelaic acid, vitamin C, and retinoids. However, these agents are not effective in many patients and there remains an unmet need for new efficacious and safe topical products to treat facial hyperpigmentation.

Malassezia species comprise a genus of lipophilic fungi and represent the predominant single eukaryotic commensal