Are demodex mites the best target for rosacea treatments?
Authors: J.P. Thyssen
Journal: British Journal of Dermatology (2019)

Linked Article: Forton and De Maertelaer et al. Br J Dermatol 2019; 181:818–825. In this issue of the BJD, Forton and De Maertelaer show that the density of demodex mites in cheek skin was three- to eightfold higher in patients with erythematotelangiectatic rosacea (ETR) compared with healthy controls.1 However, the density of demodex mites in patients with ETR was about fivefold lower than in patients with papulopustular rosacea who were measured in a previous study. The authors rightfully conclude that demodex mites may play a central role in the aetiopathogenesis of ETR, but it remains unclear whether mite proliferation has a primary, secondary or even tertiary role and whether targeting these is a good strategy. Recently, a phenotype-based approach was introduced to diagnose rosacea leaving the old classification system including ETR, papulopustular, ocular and phymatous rosacea partly obsolete.2 However, the old system remains useful for clinicians and was also applied in the present study by Forton and De Maertelaer. In this classification system, ETR and papulopustular rosacea are two relatively distinct clinical subtypes, but clinicians will agree that patients with rosacea may have mixed patterns of these, and that in some people there is a change from one subtype to the other over time. At least in theory, ETR and papulopustular rosacea can be regarded as representing a disease severity continuum, which also would explain the higher densities of demodex in the latter. Demodex mites are obligate commensals rather than parasitic in normal adults. They are found in skin areas with high sebum production, and typically reside in hair follicles, but may leave these at night to find new ones. The mites feed on sebum, but will eventually burst and result in release of toxins and bacteria. This may in turn activate the innate immune response and induce or worsen rosacea. The use of topical ivermectin or another demodex-killing drug, such as permethrin, is useful to reduce symptoms of papulopustular rosacea as shown in recent trials,3, 4 but the evidence for their use in ETR is not available. The study by Forton and De Maertelaer is therefore important as it emphasizes that demodex mites exist even in ETR. However, just because the mites are present, this does not lead to the conclusion that topical ivermectin or another mite-killing drug will work to reduce disease severity in patients with ETR. However, it is possible that by targeting demodex, the progression of ETR to papulopustular rosacea could be prevented. We simply do not know. Similar to atopic dermatitis (AD), rosacea shows concomitant skin barrier impairment, inflammation and colonization with microorganisms. For AD, Staphylococcus aureus growth increases with disease severity (and loss of control), but AD only resolves intermittently by the use of antibiotics. Therefore, the use of antibiotics in AD is not a wise strategy. Instead dermatologists use barrier-enhancing and anti-inflammatory therapy with good results leading to reduction of bacterial growth. It is by all means possible that the pathogenesis of rosacea is similar, i.e. the skin inflammation and the associated skin barrier impairment are the main drivers of the disease and with demodex mites increasing in numbers as the disease progresses and disease control is lost. The primary target in rosacea should then be the inflammation as well as impaired skin barrier rather than the mites. There is a strong need for more research in rosacea pathogenesis, and in particular, we need prospective cohort studies with repeated measurements to identify the temporal development of pathogenic changes taking into consideration skin inflammation and skin barrier impairment as well demodex proliferation. In particular, we need to study immune reactivity in more detail to identify new treatment targets. While endotypes of rosacea have not yet been identified, the neuroinflammatory aspect of rosacea, especially in ETR, is being increasingly recognized. Drugs that are under development for migraine may possibly find their way into rosacea treatment as well. If, or when, this happens, we are likely to learn much more about the pathogenic role of demodex in rosacea. J.P.T. is supported by an unrestricted grant from the Lundbeck Foundation. None to declare.