Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea

J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1907-1911. doi: 10.1111/jdv.14437. Epub 2017 Aug 29.

Abstract

Background: Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo.

Aim: To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea.

Methods: A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining.

Results: The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1.

Conclusion: Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin.

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antiparasitic Agents / administration & dosage
  • Antiparasitic Agents / pharmacology
  • Antiparasitic Agents / therapeutic use*
  • Female
  • Humans
  • Ivermectin / administration & dosage
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use*
  • Male
  • Middle Aged
  • Mites / drug effects
  • Pilot Projects
  • Rosacea / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • Antiparasitic Agents
  • Ivermectin