Human Demodicosis: Revisit and a Proposed Classification

W. Chen; G. Plewig

Disclosures

The British Journal of Dermatology. 2014;170(6):1219-1225. 

In This Article

Pathogenesis

The pathogenesis of human demodicosis remains largely obscure. The initial stage of spinulate demodicosis and its transition from a noninflammatory to an inflammatory state is a critical point. When and how Demodex mites initiate the inflammation cascade is paradigmatic to the understanding of host–parasite immunological interactions. It is unclear whether cystic or crusted demodicosis is caused more by an overshooting host immune response or by a huge amount of Demodex mites as observed in the crusted scabies. The identification of cathelicidin LL-37 in inflammatory dermatoses and the differential expression of various cytokines/proteins involved in inflammasome activation shed light on the interaction between skin innate immunity and microbial homoeostasis.[46,47] Recent observations regarding human scabies infection may help us to understand better how mites can evade immune surveillance or suppress the immune responses.[48,49] Firstly, all three pathways of the complement system (classical, lectin and alternative) can be inhibited by 'scabies mite-inactivated serine protease paralogues' and 'serine protease inhibitors' (serpins). Secondly, in a human skin-equivalent model, genes for the expression of interleukin (IL)-1α, IL-1β, granulocyte/macrophage colony-stimulating factor and granulocyte colony-stimulating factor, as well as genes involved in epithelium development and keratinization, are significantly upregulated. Thirdly, crusted scabies show features of a nonprotective T helper (Th)2 polarized response with eosinophilia, extremely high levels of IgE (often 10–100-fold higher than normal) and a predominant CD8+ T-cell infiltrate in the dermis. In ordinary scabies, a protective Th1-oriented immune response in favour of interferon-γ is observed, with a cellular infiltrate dominated by CD4+ T cells in the skin lesions.

The symbiosis between microorganisms and higher eukaryocytes can be divided into three groups: (i) mutualistic (beneficial), (ii) commensal (neutral) and (iii) parasitic (harmful). The recent observation and hypothesis that Bacillus oleronius, originally isolated from the hindgut of a termite, may be responsible for the initiation of inflammation in papulopustular rosacea is thought provoking. However, so far the bacterium has been isolated from only one microdissected Demodex mite from one patient with papulopustular rosacea.[50] The absence of serum reactivity to Bacillus antigens in a significant portion (20%) of patients at the initial stage of rosacea, and the presence of the antibodies in 40% of the controls without visible rosacea, cast doubt on the causative role of these bacteria in the inflammatory process.[51] In another study on chronic blepharitis associated with Demodex mites, the detection of B. oleronius in eyelash cultures from five of 30 healthy individuals and from only two of 15 patients with moderate blepharitis may indicate a low pathogenicity of the strains in the development of chronic inflammation.[52] It remains to be determined whether the Bacillus species exist in all dormant Demodex mites or only in those that are active, and whether they act as an innocent bystander or a copathogen in the initiation or maintenance of the skin inflammation. In contrast to the results found in filariasis, studies looking for symbiotic pathogens failed to detect Wolbachia in Demodex mites or Sarcoptes scabiei.[53,54] It is unknown whether S. scabiei relies on obligatory endosymbionts for survival.[55]

The following are some key factors awaiting answers: (i) the life cycle and behaviour of the human Demodex mites, e.g. the male-to-female ratio in the hair follicle, and day vs. night or intrafollicular vs. interfollicular differences; (ii) the increasing prevalence rate with advancing age (permanent residence in 100% of adults); (iii) pathogenesis, relationship and interaction between D. folliculorum and D. brevis in different body regions and under diseased states; (iv) virulence factors of the mites; (v) correlation between mite densities and clinical disease activity; and (vi) immune reaction, especially the innate immunity of the healthy vs. diseased host.

A recent ophthalmological study indicated that D. brevis may play a more important role than D. folliculorum in the pathogenesis of chalazia, and recurrence was significantly more common in those with D. brevis infestation than those with D. folliculorum.[43] Studies of canine demodicosis support the fact that the size of the unique species Demodex canis can vary by at least 50% depending on the breed, body site, clinical presentation, skin depth and culture condition.[56] Moreover, genetic factors (breed predisposition) seem to play a crucial role in the pathogenesis of canine juvenile-onset generalized demodicosis.[5] Molecular studies may help to clarify the issue of whether these two human Demodex mites are genuinely different subspecies or the same species differing merely in their morphological appearance.

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