Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

Skin Pharmacol Physiol. 2017;30(3):139-145. doi: 10.1159/000464335. Epub 2017 Apr 19.


Background: Though vitiligo is a common depigmentary disorder, it still represents a substantial therapeutic challenge. Therapeutic options are limited in part due to its uncertain etiology.

Objective: Because recent studies suggest that histamine stimulates melanogenesis in vitro, we determined here whether topical histamine stimulates repigmentation in patients with stable, nonsegmental vitiligo.

Methods: A total of 23 otherwise normal volunteers with vitiligo, including 14 males and 9 females aged 6-59 years (mean age 29.2 ± 2.8), were enrolled in this study. 1% histamine in distilled water was applied to the lesions twice daily for 5 weeks, while comparable lesions, treated with distilled water alone, served as the controls. The melanin index was measured on the uninvolved and lesional skin sites before and after 5 weeks of treatments using the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne, Germany). Changes in epidermal permeability barrier were also assessed at the same time point. To determine whether histamine-induced repigmentation is receptor-dependent, both ears of C57BL/6J mice were treated topically with 5% cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10 days. One hour after each cimetidine application, the right ear was treated topically with 10% histamine, while vehicle alone was applied to the left ear. Changes in melanin index were measured 24 h after the last application of histamine and vehicle as described in the human study.

Results: In patients with vitiligo treated with vehicle alone for 5 weeks, the melanin index remained unchanged, while topical histamine treatment increased the melanin index by 38% (p < 0.001 vs. both vehicle and pretreatment), which was paralleled by a >60% reduction in lesion surface area. Moreover, topical histamine accelerated permeability barrier recovery. No adverse events were observed following histamine applications. In mice, topical histamine significantly increased the melanin index, while topical co-applications of the H2r antagonist (cimetidine) prevented the expected histamine-induced increase in melanin index.

Conclusions: These studies indicate that topical histamine or an H2r agonist could be useful for treating nonsegmental vitiligo, but further clinical studies in large populations will be required to validate the efficacy and safety of this approach.

Keywords: Epidermal permeability barrier; Histamine; Pigmentation; Transepidermal water loss; Vitiligo.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Animals
  • Child
  • Cimetidine / pharmacology
  • Female
  • Histamine / pharmacology*
  • Histamine / therapeutic use*
  • Histamine H2 Antagonists / pharmacology
  • Humans
  • Male
  • Melanins / metabolism
  • Mice, Inbred C57BL
  • Middle Aged
  • Pigmentation / drug effects
  • Receptors, Histamine H2 / metabolism*
  • Treatment Outcome
  • Vitiligo / drug therapy*
  • Vitiligo / metabolism
  • Young Adult


  • Histamine H2 Antagonists
  • Melanins
  • Receptors, Histamine H2
  • Cimetidine
  • Histamine