Demodex and rosacea revisited
Introduction
The skin is home to a vast array of biologic life forms. These reside both on the skin surface and within the various skin appendages, such as hair follicles and sebaceous and sweat glands. The physical barrier of the stratum corneum, the various epidermal and specialized appendageal cells, and the immune cells dynamically interact with the various microorganisms to maintain the homeostasis of the skin.1 Recent research relating to the innate immune system has focused on the cutaneous bacterial community. The presence and potential role of Demodex mites in normal and disordered human skin has been largely overlooked.
The widely varied biogeography of the cutaneous surface suggests that organisms may play specific roles in particular biologic niches.2 Demodex mites are complex organisms that are ubiquitously present on adult human skin, particularly in the pilosebaceous units of the face. We review the possible role of these mites in the orchestration of the immune response within the facial pilosebaceous unit. Topical ivermectin, an antiparasitic agent, has recently been approved for the treatment of papulopustular rosacea.2 Similar to other rosacea treatments, the exact mechanism by which it improves the clinical signs of rosacea is unclear; however, the compound has been shown to display a broad range of activities: antimicrobial, antiparasitic, antibacterial, and anti-inflammatory.3 The advent of ivermectin as a major treatment for rosacea has stimulated renewed interest in the possible role of Demodex mites in the pathogenesis of this disorder and the capacity of Demodex mites to interact with the host immune system.
Section snippets
Demodex and healthy skin
Mites are microscopic arthropods closely related to ticks that belong to the class Arachnida subclass Acari. They are considered to be one of the most diverse and successful of all the invertebrate groups with more than 48,000 species described. They inhabit a vast range of ecologic niches.4 Two species of Demodex mite are known to inhabit the human pilosebaceous unit: Demodex folliculorum and Demodex brevis. D folliculorum resides within the hair follicle, whereas D brevis is found
Demodex mites and skin disorders
Only a few mite species cause dermatologic issues in humans. These include the scabies, food, house dust, poultry, murine, and harvest mites. Demodex mites differ in that they have not been proven to cause disease in humans.
The causal role of Demodex mites in the generation of diseases, such as mange in dogs, is well established.[7], [16] In humans an increased mite density of greater than 5 mites on 1 cm2 of skin has been associated with rosacea and associated blepharitis.[7], [10] Patients
Evasion of the innate immune response by Demodex: Clues from the scabies mite
Arthropods, such as mites and ticks, have evolved various mechanisms that modulate or circumvent host immune responses to survive within the host.
Scabies mites secrete molecules that down regulate the human complement system and macrophage function. Complement inhibitors secreted by scabies mites are also hypothesized to support the promotion of a microenvironment in which noncommensal pathogenic bacteria could flourish. These molecules also show homology to allergens of house dust mites.[29],
Identification of Demodex by the immune system and implications for disease pathogenesis
In veterinary medicine, the pathogenic role of Demodex in causing mange is well established, although the exact mechanisms involved are unclear.[4], [44] In human skin, Demodex are generally considered symbiotic inhabitants, and their role in mediating dermatologic conditions is still under debate.[19], [50], [51]
In rosacea, increased numbers of mites could contribute to its pathogenesis in a number of ways (Figure 3). An overabundance of mites may lead to a blockage of the hair follicles and
Demodex mites as vectors of disease
Recent studies suggest that mites from patients with rosacea harbor pathogenic bacteria and other microorganisms on their surface that drive inflammatory skin responses,[59], [60], [61], [62], [63] and typically nonpathogenic bacteria display an altered functional profile in patients with rosacea in comparison to normal controls64 (Figure 2). Interestingly, the microbiome profile may be specific to rosacea disease subtype62; furthermore, serum immunoreactivity against the bacterium Bacillus
Genetically susceptible individuals
A number of studies indicate a genetic component to rosacea. The condition is more common in fair-skinned individuals of European descent. A number of MHC class II HLA alleles have been associated with rosacea, all of which have been associated with autoimmune diseases, such as multiple sclerosis, type 1 diabetes, and retinopathy.71 Gene polymorphisms in HLA-DRA and butyrophilin-like 2 have also been associated with rosacea.72 Such variations in these molecules have been previously linked to
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