Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link

Abstract

Papulopustular rosacea (PPR) is a common facial skin disease, characterized by erythema, telangiectasia, papules and pustules. Its physiopathology is still being discussed, but recently several molecular features of its inflammatory process have been identified: an overproduction of Toll-Like receptors 2, of a serine protease, and of abnormal forms of cathelicidin. The two factors which stimulate the Toll-like receptors to induce cathelicidin expression are skin infection and cutaneous barrier disruption: these two conditions are, at least theoretically, fulfilled by Demodex, which is present in high density in PPR and creates epithelial breaches by eating cells. So, the major pathogenic mechanisms of Demodex and its role in PPR are reviewed here in the context of these recent discoveries. In this review, the inflammatory process of PPR appears to be a consequence of the proliferation of Demodex, and strongly supports the hypothesis that: (1) in the first stage a specific (innate or acquired) immune defect against Demodex allows the proliferation of the mite; (2) in the second stage, probably when some mites penetrate into the dermis, the immune system is suddenly stimulated and gives rise to an exaggerated immune response against the Demodex, resulting in the papules and the pustules of the rosacea. In this context, it would be very interesting to study the immune molecular features of this first stage, named "pityriasis folliculorum", where the Demodex proliferate profusely with no, or a low immune reaction from the host: this entity appears to be a missing link in the understanding of rosacea.

Structure and function of the human skin microbiome

“…Skin inflammation also correlates with mite density on the skin of rosacea-affected patients [62]. Thus, the mite may participate in the exacerbation of disease either by disrupting the skin barrier [14, 63], or by triggering TLR2 activation through chitin in the insect’s cuticle [64, 65]. Furthermore, it has been reported that bacteria that live in the digestive tract of Demodex are released into the surrounding skin tissues, thereby triggering further tissue degradation and inflammation [66, 67].…”

Potential role of Demodex mites and bacteria in the induction of rosacea

“…The literature offers numerous arguments supportive of the theory that rosacea is primarily connected with compromised immunity (Forton, 2012). According to this theory, on the skin of healthy, immune-competent individuals, the proliferation of Demodex mites is kept under control.…”

Ivermectin: A Review in Rosacea

“…Pharmacological agents that target inflammatory pathways associated with rosacea have historically been the focus of therapy [1,5], with topical metronidazole or azelaic acid and oral antibacterials (mainly of the tetracycline class) being widely used for this reason [5]. In addition, there is growing interest in using agents that have supplementary anti-parasitic properties, as there is potential for commensal Demodex mite overgrowth to be involved in rosacea pathophysiology [1,6]. The Demodex load of rosacea skin is increased (i.e.…”

“…The Demodex load of rosacea skin is increased (i.e. more than five mites/cm 2 ) in some individuals with rosacea [7][8][9], which may possibly exacerbate inflammation [6,10].…”