Human Demodicosis: Revisit and a Proposed Classification

Abstract and Introduction

Abstract

Human Demodex mites (Demodex folliculorum and Demodex brevis) hold a high rank in the evolutionary and phylogenetic hierarchy of the skin microbiome, although in most people their presence is of no consequence. While human demodicosis is a skin disease sui generis, it can mimic many other inflammatory dermatoses, such as folliculitis, rosacea and perioral dermatitis, leading to unspecific and confusing descriptions in the literature. Here, we propose to classify human demodicosis into a primary form and a secondary form, which is associated mainly with immunosuppression. The clinical manifestations of primary demodicosis may include (i) spinulate demodicosis, currently known as pityriasis folliculorum, involving sebaceous hair follicles without visible inflammation; (ii) papulopustular/nodulocystic or conglobate demodicosis with pronounced inflammation affecting most commonly the perioral and periorbital areas of the face; (iii) ocular demodicosis, inducing chronic blepharitis, chalazia or, less commonly, keratoconjunctivitis; and (iv) auricular demodicosis causing external otitis or myringitis. Secondary demodicosis is usually associated with systemic or local immunosuppression. Treatment is only weakly evidence based, and the most effective concentrations of acaricides remain to be determined. Optimization of an in vitro or ex vivo culture model is necessary for future studies. Endosymbiosis between certain bacteria and Demodex mites in the pathogenesis of demodicosis deserves more attention. Further clinical observations and experiments are needed to prove our hypothesis.

Introduction

First described as a worm by Jacob Henle in Zurich in 1841,^[1] and later correctly classified as a mite by the dermatologist Carl Gustav Theodor Simon in Berlin in 1842,^[2] human Demodex mites (Demodex folliculorum and Demodex brevis) have intrigued parasitologists, veterinarians and dermatologists for almost 170 years. With regard to taxonomic classification, it is now grouped as Arthropoda/Chelicerata/Arachnida/Acarina/Demodicidae/Demodex/Demodex folliculorum or Demodex brevis. Compared with other human skin microorganisms, such as Propionibacterium acnes, Staphylococcus epidermidis and Malassezia, Demodex mites rank higher in the hierarchy of evolution. In contrast to other human mites such as Sarcoptes scabiei hominis, Cimex lectularius or Dermatophagoides pteronyssinus/farinae, Demodex mites remain largely dormant and innocuous, rarely inducing immunological or allergic reactions.^[3,4] The diseased state 'demodicosis' in other mammals, such as dogs and cats, can be very extensive and fatal if left untreated.^[5] However, the association between Demodex mites and human diseases is much less studied and poorly defined.^[3]

This paper aims to emphasize a discrete disease entity sui generis in a primary form and, thereby, provide a clear clinical portrait of the disease to distinguish it from other mimicking inflammatory dermatoses. Furthermore, we hope to pave the way for the investigation of the pathogenesis of demodicosis and encourage basic research on the biology of Demodex mites.

Table 1. Examples of skin diseases or situations associated with secondary demodicosis
Skin diseases	Entities
Inflammatory dermatoses	Perioral dermatitis¹⁹
	Papulopustular rosacea²⁰
	Seborrhoeic dermatitis²¹
	Steroid dermatitis²²
Treatment-associated diseases	Epidermal growth factor receptor inhibitors²⁴
Treatment-associated diseases	Phototherapy²⁹
Tumours	Melanocytic naevi²⁵
	Eyelid basal cell carcinoma²⁶
	Mycosis fungoides²⁷
Systemic diseases	Chronic renal failure²⁸

Table 2. Primary human demodicosis: proposed classification and nomenclature
Current terminology and description	Proposed nomenclature	Definition and clinical manifestations
Pityriasis folliculorum	Spinulate demodicosis	Discrete fine, whitish, partly yellowish, spiky, changes involving sebaceous hair follicles, with or without faint erythema and little inflammation
Rosacea-like (rosaceiform) demodicosis, perioral/periorbital/periauricular dermatitis-like demodicosis	Papulopustular demodicosis, perioral demodicosis, periorbital demodicosis, periauricular demodicosis	Papulopustules involving mostly the face, in patients without (primary form) or with pre-existing inflammatory dermatoses such as rosacea or perioral dermatitis (secondary form). The inflammatory stages show predilection for perioral, periorbital and periauricular regions
Demodex abscess/facial abscess-like conglomerates	Nodulocystic/conglobate demodicosis	Intense immune reaction with massive follicular and perifollicular inflammatory infiltrates caused by Demodex proliferation, pus accumulation and suppurative succulent changes