, according to a report presented at the recent European Academy of Dermatology and Venereology (EADV) 2023 Congress.
“This is the first hint that the host’s cutaneous microbiome plays a secondary role in the immunopathogenesis of rosacea,” said Bernard Homey, MD, director of the department of dermatology at University Hospital Düsseldorf in Germany.
“In rosacea, we are well aware of trigger factors such as stress, UV light, heat, cold, food, and alcohol,” he said. “We are also well aware that there is an increase in Demodex mites in the pilosebaceous unit.”
National Rosacea Society
Demodex mite
Research over the past decade has also started to look at the potential role of the skin microbiome in the disease process, but answers have remained “largely elusive,” Dr. Homey said.
Ivermectin helps, but how?
Ivermectin 1% cream (Soolantra) has been approved by the U.S. Food and Drug Administration since 2014 for the treatment of the inflammatory lesions that are characteristic of rosacea, but its mechanism of action is not clear.
Dr. Homey presented the results of a study of 61 patients designed to look at how ivermectin might be working in the treatment of people with rosacea and investigate if there was any relation to the skin microbiome and transcriptome of patients.
The trial included 41 individuals with papulopustular rosacea and 20 individuals who did not have rosacea. For all patients, surface skin biopsies were performed twice 30 days apart using cyanoacrylate glue; patients with rosacea were treated with topical ivermectin 1% between biopsies. Skin samples obtained at day 0 and day 30 were examined under the microscope, and Demodex counts (mites/cm2) of skin and RNA sequencing of the cutaneous microbiome were undertaken.
The mean age of the patients with rosacea was 54.9 years, and the mean Demodex counts before and after treatment were a respective 7.2 cm2 and 0.9 cm2.
Using the Investigator’s General Assessment to assess the severity of rosacea, Homey reported that 43.9% of patients with rosacea had a decrease in scores at day 30, indicating improvement.
In addition, topical ivermectin resulted in a marked or total decrease in Demodex mite density for 87.5% of patients (n = 24) who were identified as having the mites.
Skin microbiome changes seen
As a form of quality control, skin microbiome changes among the patients were compared with control patients using 16S rRNA sequencing.
“The taxa we find within the cutaneous niche of inflammatory lesions of rosacea patients are significantly different from healthy volunteers,” Dr. Homey said.
Cutibacterium species are predominant in healthy control persons but are not present when there is inflammation in patients with rosacea. Instead, staphylococcus species “take over the niche, similar to atopic dermatitis,” he noted.
Looking at how treatment with ivermectin influences the organisms, the decrease in C. acnes seen in patients with rosacea persisted despite treatment, and the abundance of Staphylococcus epidermidis, S. hominis, and S. capitis increased further. This suggests a possible protective or homeostatic role of C. acnes but a pathogenic role for staphylococci, explained Dr. Homey.
“Surprisingly, although inflammatory lesions decrease, patients get better, the cutaneous microbiome does not revert to homeostatic conditions during topical ivermectin treatment,” he observed.
There is, of course, variability among individuals.
Dr. Homey also reported that Snodgrassella alvi – a microorganism believed to reside in the gut of Demodex folliculorum mites – was found in the skin microbiome of patients with rosacea before but not after ivermectin treatment. This may mean that this microorganism could be partially triggering inflammation in rosacea patients.
Looking at the transcriptome of patients, Dr. Homey said that there was downregulation of distinct genes that might make for more favorable conditions for Demodex mites.
Moreover, insufficient upregulation of interleukin-17 pathways might be working together with barrier defects in the skin and metabolic changes to “pave the way” for colonization by S. epidermidis.