Are they a cause or simply a coincidence? Demodex mites have long been a conundrum for rosacea patients. Unlike other environmental triggers, they are unavoidable, as they are normal inhabitants of facial skin, but they do exist in greater numbers on the skin of individuals with rosacea.^1,2

In a recent study, researchers in South Korea found a link between the presence of elevated numbers of Demodex mites and several molecules that have been identified as playing a role in the inflammation of rosacea, according to a recent study in the Journal of the European Academy of Dermatology and Venereology.³

“The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments,” the investigators wrote. “The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research.”

In an in vitro study, researchers applied mineral oil to 38 rosacea patients’ skin and squeezed, collecting the oil and skin microbiome contents on glass slides. They then grouped the samples into three categories: those containing no mites (12 samples), those with 1 to 9 (16 samples) and those with more than 10 (10 samples).

An mRNA expression lab test of the samples showed that expression levels of genes related to rosacea were significantly increased in the groups with higher Demodex counts, including toll-like receptor 2 (TLR2), kallikrein-5 (KLK5) and cathelicidin LL37. The higher Demodex samples also showed increased levels of transient receptor potential vanilloid 1 (TRPV1), a neuroinflammatory molecule, as well as tropomyosin receptor kinase A (TRKA) and nerve growth factor (NGF), which play a role in pain sensation.

Next, the downstream effects of TRPV1 activation were investigated in a mouse model. The researchers generated a rosacea-like condition in lab mice by injecting them with the cathelicidin LL37, an important factor in the innate immune response thought to contribute to rosacea by inducing inflammation and promoting blood vessel growth. Then capsaicin, the chemical that gives chili peppers their heat, was applied topically to the mice’s ears. The researchers found that TRKA, TRPV1 and NGF levels increased in the rosacea-like mouse models compared with controls.

“This research offers an explanation for the skin sensitization and cutaneous neurogenic inflammation symptoms associated with rosacea, which are caused by increased LL37 in the presence of larger Demodex population counts in the skin of patients with rosacea,” the investigators wrote. They suggested that the results may provide further insight into the disease process in rosacea.

References

1. Jarmuda S, O’Reilly N, Zaba R, et al. Potential role of Demodex mites and bacteria in the induction of rosacea. J Med Microbiol 2012;61:1504-1510.
    
2. Forton FMN. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol 2012;26:19–28.
    
3. Lee SG, Kim J, Lee YI, Kim J, Choi YS, Ham S, Lee JH. Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites. J Eur Acad Dermatol Venereol 2023;00:1-12.