D. folliculorum was first described by Simon in 1842, and D. brevis was first distinguished as a subspecies of D. folliculorum by Akbulutova in 1963 [3]. Later, D. brevis was redefined as a distinct species living on human skin [1]. To date, numerous epidemiological studies have been conducted to determine the prevalence of Demodex mites. In a study by Gazi et al, Demodex positivity was found in 55.6% of patients with rosacea and in 29.2% of controls [5]. In another study, 60.2% of patients with rosacea were Demodex positive [11]. In a study conducted by Kubanov et al, D. folliculorum positivity was found in 66.7% of patients with rosacea and in 2.8% of controls [12]. In another study, Demodex positivity was found in 96% of patients with rosacea [13]. In a study by Durmaz et al, Demodex positivity was found in 34.4% of rosacea patients and 17.6% of controls [14]. In another study, Demodex positivity was found in 67.6% of patients with rosacea and in 6% of controls [15]. In the study conducted by Yücel and Yılmaz, D. folliculorum positivity was found in 53.5% of patients with rosacea and D. brevis positivity in 7.1% [16]. In a study by Erbagci and Özgöztaşı, D. folliculorum positivity was found in 65.7% of patients with rosacea [17]. In a study by Georgela et al, D. folliculorum was detected in 83 (90.2%) of the 92 rosacea patients and in 11 (11.9%) of the controls [18]. In a study by Rios-Yuil et al, D. folliculorum was found in 80% of rosacea patients and only in 30% of controls [19]. In a study by Kosar et al, Demodex positivity was found in 34 (87.2%) of rosacea patients [7]. In another study by Özpinar et al, Demodex positivity was found in 49.1% of patients [20]. In a study by Aktaş-Karabay and Çerman, Demodex spp. positivity was found in 52% of patients with rosacea [21]. Considering the epidemiological studies summarized above, the prevalence of Demodex varies from 34.4–96% in patients with rosacea and from 2.8–30% in healthy controls. In our study, in agreement with other studies, Demodex positivity was found in 91% of rosacea patients (D. folliculorum only in 37%, coinfection of D. folliculorum and D. brevis in 55%) and in 20% of healthy controls (D. folliculorum only).
On the other hand, Demodex species were not defined separately in the vast majority of epidemiological studies. The parasite was either referred to as Demodex spp. or only D. folliculorum was emphasized, and not much emphasis was placed on the co-infection of D. folliculorum and D. brevis. Some authors reported that D. folliculorum clumps in hair follicles and creates a plug and tension in the follicles. In addition, microabrasions of D. folliculorum with its feet were found to cause epithelial hyperplasia and reactive hyperkeratinization on hair follicles [22, 23]. It has been reported that D. brevis blocks the orifices of meibomian glands, preventing lipid secretion and causing dysfunction in these glands [22, 24, 25]. However, some researchers reported that the association of D. folliculorum and D. brevis further aggravates the clinical picture in patients with rosacea [11, 26]. Therefore, the detection of D. folliculorum alone or the coexistence and density of D. folliculorum and D. brevis in epidemiological studies of Demodex mites will provide a better understanding of the aetiology of rosacea and a better evaluation of the clinical picture.
In our study, Demodex burden was found to be approximately 30-fold higher in rosacea patients than in healthy controls, which may be due to co-infection with D. folliculorum and D. brevis (mean Demodex burden: 179.18/cm2 in rosacea patients, 6.06/cm2 in healthy controls). Turgut-Erdemir et al, reported a Demodex load of 58.87/cm2 in rosacea patients and 3.55/cm2 in controls [27]. In another study, Demodex load was found to be 10.8/cm2 in patients with rosacea and 0.7/cm2 in controls [28]. Falay-Gür et al, reported that Demodex density was 98.3/cm2 in patients with rosacea and 41.9/cm2 in controls [29]. Erbağcı and Özgöztaşı reported that Demodex density was 6.68/cm2 in patients with rosacea and 2.86/cm2 in controls [17]. In another study, Demodex density was found to be 14.0/cm2 in rosacea patients and 0.3/cm2 in controls [30]. In another study, Demodex load was found to be 16.9/cm2 in rosacea patients and 8.12/cm2 in controls [31]. In a study by Seraslan et al, the burden of D. folliculorum + D. brevis was higher than the burden of D. folliculorum, and it was reported that coinfection with D. folliculorum + D. brevis aggravated the clinical picture [11]. On the other hand, several studies reported that acaricidal treatments reduced Demodex density in patients with rosacea and disease symptoms normalised [12, 30, 32–34]. The fact that Demodex burden was higher in rosacea patients than in healthy controls and that rosacea symptoms improved with the reduction of Demodex burden by acaricidal treatments indirectly supports the role of Demodex mites in the aetiology of rosacea.
The National Rosacea Society (NRS) Expert Committee has classified rosacea into four subtypes: ETR, PPR, phymatous, and ocular rosacea. The most common subtypes are PPR and ETR [6]. Therefore, patients with PPR and ETR were included in the study. In our study, it was found that Demodex burden was higher in patients with PPR than in patients with ETR. Several studies have reported that Demodex burden is higher in patients with PPR than in patients with ETR [7, 27, 28]. In contrast, studies have reported that Demodex burden is higher in patients with ETR than in patients with PPR [13]. Many researchers explained that Demodex mites destroy follicular and sebaceous gland epithelial cells with their piercing mouthparts and claws, disrupt the skin barrier, and form a lymphocytic infiltrate around the follicle. When they invade the dermis, the mite chitin skeleton stimulates Toll-like receptors (TLR) and causes an immune response [35–38]. However, some studies have reported that the immune response to Demodex mites may vary depending on the human leukocyte antigen (HLA) haplotype. Studies investigating the relationship between demodicosis (Demodex infestation) and HLA emphasised that the HLA A2 haplotype is protective in demodicosis and individuals with this phenotype are three times more resistant to demodicosis. It has been reported that individuals with the HLA-CW2 and HLA-CW4 haplotypes are five times more susceptible to developing demodicosis, and Demodex burden increases in these individuals due to increased lymphocyte and NK apoptosis [36–39]. The difference in Demodex burden between patients with PPR and ETR in our study and other studies might be related to the genetic characteristics of the patients and their HLA haplotypes. However, further studies on this topic are needed.
Many researchers have reported that rosacea usually begins in the 30s, peaks in the 50s, and is more common in women than in men [7, 17]. However, some authors have reported that the high prevalence of rosacea in women may be related to genetic or hormonal factors, the greater use of cosmetic products that can trigger rosacea, and the higher number of women who consult a physician for cosmetic problems. However, the fact that rosacea is more common in women may also be related to the higher prevalence and burden of Demodex in female patients. Kubanov et al, reported that 53.3% of Demodex-positive patients with rosacea were female and the average age of the patients was 51 years [12]. In another study, it was reported that 67.5% of patients with rosacea diagnosed with Demodex were female and the average age of patients was 44 years [29]. In a study by Turgut-Erdemir et al, it was reported that 73% of patients with rosacea diagnosed with Demodex were female, and the mean age of patients was 45.9 years [27]. Consistent with the literature, our study found that the prevalence and burden of Demodex was higher in female patients than in male patients, and that the prevalence and burden of Demodex increased with age.