, a narrative review proposes.
According to the author, Fabienne Forton, MD, PhD, a dermatologist based in Brussels, recent studies suggest that Demodex induces two opposite actions on host immunity: A defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favoring its own proliferation. “Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor (VEGF), which may also explain the favorable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation,” she wrote in the review, which was published in JEADV, the Journal of the European Academy of Dermatology and Venereology.
Courtesy National Rosacea Society
A higher density of Demodex mites on the skin may play a role in the development of papules and pustules associated with rosacea, mounting evidence suggests.
She presented several arguments for and against a causal role of Demodex in rosacea. Three on the “for” side are:
High Demodex densities (Dds) are observed in almost all cases of rosacea with papulopustules (PPR). Dr. Forton pointed out that Demodex proliferation presents in as many as 98.6% of cases of PPR when two consecutive standardized skin surface biopsies (SSSBs) are performed (Acta Derm Venereol. 2017;97:242-8). “Dds in patients with PPR are as high as those in patients with demodicosis, much higher than in healthy skin and other facial dermatoses (except when these are associated with demodicosis [as is often the case with seborrheic dermatitis and acne vulgaris]),” she wrote.
The Demodex mite has the elements necessary to stimulate the host’s innate and adaptative immune system. Dr. Forton characterized Demodex as “the only microorganism found in abundance in almost all subjects with PPR, which can, in addition, alter the skin barrier. To feed and move around, Demodex mites attack the epidermal wall of the pilosebaceous follicles mechanically (via their stylets, mouth palps and motor palps) and chemically (through enzymes secreted from salivary glands for pre-oral digestion).”
The Demodex mite stimulates the immune system (which ultimately results in phymatous changes). A healthy immune system, including T helper 17 cells, seems necessary to adequately control mite proliferation. Dr. Forton noted that researchers have observed a perivascular and perifollicular infiltrate in people with rosacea, “which invades the epidermis and is often associated with the presence of Demodex. The lympho-histiocytic perifollicular infiltrate is correlated with the presence and the numbers of mites inside the follicles, and giant cell granulomas can be seen around intradermal Demodex mites, which attempt to phagocytize the mites.”
The three arguments that she presented against a causal role of Demodex in rosacea are the following:
No relationship with the mite was observed in two early histological studies. Rosacea biopsies conducted in these two analyses, published in 1969 and 1988, showed only mild infiltrate, with few parasites and no inflammation around the infested follicles.
However, she countered, “these data are now obsolete, because it has since been clearly demonstrated that the perifollicular infiltrate is a characteristic of rosacea, that this infiltrate is statistically related to the presence and the number of Demodex mites, and that high Dds are observed in almost all subjects with PPR.”
Demodex is not always associated with inflammatory symptoms. This argument holds that Demodex is present in all individuals and can be observed in very high densities without causing significant symptoms. Studies that support this viewpoint include the following: J Eur Acad Dermatol Venereol. 2001;15:441–4 and J Zhejiang Univ Sci B. 2011;12:998-1007.
However, Dr. Forton pointed out that the normal, low-density presence of Demodex in the skin “does not contradict a pathogenic effect when it proliferates excessively or penetrates into the dermis. The absence of intense inflammatory symptoms when the Dd is very high does not negate its potential pathogenicity.”
Demodex proliferation could be a consequence rather than a cause. Dr. Forton cited a study, suggesting that inflammation could be responsible for alteration of the skin barrier, “which, secondarily, would favor proliferation of the parasites, as with skin affected by atopic dermatitis that becomes superinfected by Staphylococcus aureus”. On the other hand, she argued, “unlike S. aureus, Demodex does not require alteration of the skin barrier to implant or proliferate. It also does not require an inflammatory background.” She added that if mite proliferation was a consequence of clinical lesions, “the Demodex mite should logically proliferate in other inflammatory facial skin conditions, which is not the case.”
A Sept. 14 National Rosacea Society (NRS) press release featured the paper by Dr. Forton, titled, “Which Comes First, The Rosacea Blemish or The Mite?” In the release, Richard Gallo, MD, PhD, who chaired the NRS Expert Committee that updated the standard classification of rosacea in 2018, said that “growing knowledge of rosacea’s pathophysiology has established that a consistent multivariate disease process underlies its potential manifestations, and the clinical significance of each of these elements is increasing as more is understood.”
While the potential role of Demodex in rosacea has been controversial in the past, “these new insights suggest where it may play a role as a meaningful cofactor in the development of the disorder,” added Dr. Gallo, chair of the department of dermatology at the University of California, San Diego.
Dr. Forton reported having no financial disclosures.