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

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 effect 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 Caucasian 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 were 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 (p<0.05) and IL-8 expression was confirmed on the protein level by immunofluorescence staining. All patients improved clinically and 16 out 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.

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