Demodex and skin diseases

Demodicosis, encompassing various skin conditions caused by Demodex mites, presents with a spectrum of clinical features and severity as shown in Fig. 3 [40, 141]. These features depend on mite density, the skin microenvironment, and the host's immune response. Manifestations can range from non-specific dryness and sensitivity to papules, nodules, and even granulomas [47]. There are two main clinical types: (1) Primary demodicosis involves an unexplained increase in mite colonization leading to inflammatory skin lesions that persist without treatment [40]. This type encompasses conditions like pityriasis folliculorum, nodulocystic demodicosis, and blepharitis [39, 40]; and (2) Secondary demodicosis refers to the presence of Demodex mites in individuals with pre-existing skin diseases or systemic conditions, often seen in immunosuppressed patients who may experience a wider range of symptoms than immunocompetent individuals [39, 40].

Fig. 3

Skin conditions linked to Demodex mites

Clinically, demodicosis manifests in four main categories:

Pityriasis folliculorum type: presents with dry, rough, erythematous patches on the face due to increased follicular scaling [142, 143].

Rosacea-like type: characterized by papulopustules on the face, with or without rosacea, accompanied by dryness, itching, and burning [144].

Folliculitis-like type: localized follicular pustules resembling folliculitis or acne [85, 145].

Peri-oral dermatitis-like type: papulopustules around the mouth mimicking peri-oral dermatitis [146].

Pityriasis folliculorum is the most common presentation, followed by rosacea-like and peri-oral dermatitis-like types [146]. Demodicosis can also manifest as unexplained eczema, scalp issues (pruritus, dandruff, folliculitis), seborrheic dermatitis-like lesions, Demodex abscesses, granulomatous lesions, and even involve the ears and vulva [142, 147,148,149,150,151,152,153,154]. More information on the Demodex-related skin and ocular diseases is provided below.

Rosacea and Demodex

Rosacea, a chronic inflammatory facial skin condition characterized by redness, pustules, and dilated blood vessels, has an unclear etiology [155]. Multiple factors are suspected, including abnormal blood flow in the face, dysregulated inflammatory responses, and the overgrowth of resident skin microorganisms [91]. Demodex mites have been considered the cause of facial rosacea since the 1930s due to their potential to activate these pathways and their increased abundance on rosacea patients' skin [84, 156]. According to certain theories, the pathogenic potential is correlated with an increase in mite density (above 5 mites/cm2). That is why there is a seasonal worsening of rosacea during the warmer spring and summer months when mite populations might flourish [84].

Topical antibiotics (metronidazole 0.75%) were shown to be more effective in treating rosacea than topical anti-Demodex cream (permethrin 5%), despite the fact that the latter lowered Demodex levels [157]. This suggests that bacterial involvement may also play a role in rosacea pathogenesis. The combination of Demodex mites and the Bacillus oleronius bacteria, they are connected with, may synergistically trigger inflammatory pathways in rosacea patients [158, 159]. Additionally, Staphylococcus epidermidis, another bacterium potentially associated with Demodex mites, has been found in follicular biopsies from rosacea patients [26]. These findings suggest a multifaceted interplay between Demodex mites, bacteria, and the host immune response in rosacea development. It is also important to recognize that while Demodex mites may play a role in the development of rosacea, rosacea itself may also be a sign of demodicosis. This viewpoint draws attention to the complex interactions between these factors and stresses how important it is to comprehend how they are related.

Acne and Demodex

The potential link between Demodex mite infestation and acne vulgaris is a topic of ongoing debate in dermatology. Several studies support this association [160,161,162]. A meta-analysis by Zhao et al. evaluated 63 articles from various nations on 42,130 individuals and found a significantly higher Demodex infestation rate in acne patients compared to controls [161]. The overall Demodex mite infestation rate was 54.9% in acne patients, which was 31.5% higher than in the control group, suggesting a positive correlation between Demodex and acne development. However, other studies, such as those by Okyay et al. (2006), and Paichitrojjana et al. (2024) have reported no significant association between Demodex density and acne prevalence [163, 164].

Proponents of the Demodex-acne link point to several observations. First, individuals with oily or combination skin, more prone to acne, also exhibit higher Demodex infestation rates compared to those with normal skin [160]. Second, factors like hyperandrogenism, obesity, and insulin resistance, which contribute to acne development, may also increase susceptibility to D. folliculorum infestation [165,166,167,168,169,170]. Additionally, Yarim et al. demonstrated elevated insulin-like growth factor 2 (IGF-2) levels in dogs with demodicosis, mirroring the increased levels observed in acne patients [171].

However, there are several counterarguments to this proposed relationship. Even in people without acne, Demodex mites are very common, which calls into question their causal significance [84]. Establishing a clear cause-and-effect relationship between Demodex mites and acne is difficult. While some studies have shown a higher prevalence of mites in individuals with acne, correlation does not necessarily imply causation. Acne is multifactorial, encompassing hormones, environmental factors, and genetics, making it challenging to establish causation [172]. Additionally, the specific mechanisms by which Demodex mites might contribute to acne are not fully understood. There is yet no proof that Demodex causes acne through the suggested pathways of inflammation or disturbance of the microbiota, and more research is needed to confirm these potential mechanisms. Lastly, conflicting study results call for more investigation to determine the exact connection between Demodex mites and the onset of acne.

The clinical similarity between Demodex folliculitis and acne vulgaris, with papules, pustules, and nodules, further complicates diagnosis. Dermatologists may misclassify Demodex folliculitis as acne due to the absence of comedones, a hallmark of acne but not Demodex folliculitis [85].

While the causal relationship between Demodex and acne remains unclear, considering Demodex as a potential contributing factor in some acne cases may be a prudent approach. Some advocate for Demodex testing and treatment with acaricides in acne patients who fail to respond to conventional therapies [85].

In conclusion, despite some data pointing to a potential connection between Demodex mites and acne, there are a number of considerations that refute this notion. Uncertainty around this topic is exacerbated by the mites' broad presence, the challenge of proving causation, the ambiguous mechanisms of action, and the scant and contradictory research. More research is needed to completely understand the involvement of Demodex mites in the development of acne.

Pityriasis folliculorum and Demodex

Pityriasis folliculorum, characterized by facial redness, dryness, scaling, and itching is an early manifestation of Demodex overgrowth (mite density around 60/cm2) distinct from seborrheic dermatitis and rosacea. Later presentations may include papulopustular, acneiform, or maculopapular rash without comedones or telangiectasia, potentially associated with even higher mite densities [173,174,175,176].

Androgenetic alopecia and Demodex

Demodex mites have been linked to androgenetic alopecia. While the exact relationship remains unclear, Demodex-secreted lipases may trigger inflammation around sebaceous glands. This inflammation, coupled with the follicular infiltration of immune cells, can lead to fibrosis and hair follicle loss [177, 178]. Additionally, the inflammatory response might alter local hormone metabolism, promoting sebum production and creating a more favorable environment for Demodex growth. Ultimately, chronic Demodex infestation may contribute to hair cycle disruption and hair loss [177].

Basal cell carcinoma (BCC) and Demodex

There have occasionally even been suggestions linking Demodex mites to BCC. Some studies have suggested a possible link between high Demodex mite populations and BCC [84, 179]. However, these findings are not conclusive, and further research is needed to establish a definitive causal relationship. In addition to UV radiation being the primary cause of BCC, attention is also paid to local variables such as inflammation, irritation, or chronic damage. Chronic inflammation caused by Demodex in areas like the nose and eye sockets, which are commonly affected by BCC, raises the possibility of Demodex involvement in BCC. Consequently, the significance of demodicosis as one of the mechanisms driving carcinogenesis in BCC of the eyelids in predisposed individuals is also stressed [179] because of the irritating/traumatic effect that induces persistent inflammation. Moreover, Sun et al., 2005 [180] analysis demonstrated that a high infestation rate among the malignancies under study was a defining characteristic of BCC cases. According to a recent study in 2023 [181], the inflammatory response triggered by Demodex mites in rosacea may help create an atmosphere that is favorable for the development of BCC. 46.4% individuals with BCC who had concurrently diagnosed rosacea were identified. Finally, it is critical to consider the distinction between causation and correlation. Although research may indicate a link between Demodex mites and BCC, this does not imply that the mites are the direct cause of BCC, which has a complex etiology. The potential contribution of Demodex mites is likely to be one of many contributing factors. According to a systematic review in 2023, the role of Demodex mites in the development of skin cancer remains a subject of ongoing research [84].

Miscellaneous Demodex-associated skin conditions

Demodex mites have been implicated in various other skin conditions, including perioral dermatitis, acariciariform dermatitis, Grover's disease, eosinophilic folliculitis, and facial/scalp eruptions [182]. The inflammatory response to Demodex, along with other microorganisms like bacteria, yeasts, and fungi in hair follicles, might contribute to dissecting cellulitis of the scalp [84, 183, 184]. Additionally, some authors have proposed Demodex as a potential trigger for Lupus Miliaris Disseminatus Faciei (LMDF), but this requires further investigation [185]. Excessive makeup use has also been linked to Demodex-related issues like scabies-like sores, scalp eruptions, and dandruff [84]. Additionally, dermal nevi have shown increased Demodex colonization, suggesting that the mite prefers melanin pigment [182].

Other recent reports have shown that Demodex mites are associated with the following presentations:

Pityriasis folliculorum of the back thoracic area

A case report describes a patient presenting with multiple filiform spicules, white-yellowish keratotic follicular plugs, and small angiomas on the posterior thorax [186]. Notably, numerous non-hair-bearing follicular orifices exhibited minute, hyperkeratotic spicules, and the skin exhibited a sandpaper-like texture on palpation. Dermoscopic examination revealed filiform threads and semi-round white plugs within follicular openings. Parasitological assessment confirmed the presence of Demodex folliculorum. Based on these findings, a diagnosis of thoracic pityriasis folliculorum caused by D. folliculorum was established.

Pigmented demodicidosis

A recent report describes a distinct clinicopathological and dermoscopic presentation of facial hyperpigmentation associated with Demodex mites [187]. Nineteen patients presented with dusky brown-gray pigmentation, either localized or diffuse, often accompanied by erythema and skin roughness. The authors propose the term "pigmented demodicidosis" and advocate for its inclusion in the differential diagnosis of facial hyperpigmentation.

Relationship between Demodex and SARS-CoV-2

Some researchers hypothesize that arthropods inhabiting human skin, such as Demodex mites, may play a role in the transmission of viruses, including SARS-CoV-2 [188]. This hypothesis suggests a potential interaction between the chitinous exoskeleton of the mite and the lipid envelope of the virus, mediated by molecular attraction forces. If confirmed, this could establish arthropods like Demodex as an overlooked cofactor in viral infections, with significant implications for disease prevention and treatment strategies.

It is important to note that the strength of the evidence for Demodex involvement in these conditions varies: while some associations show promise, others require further research to establish a definite link.

Demodex and eye diseases

Demodex mites, commonly found on human skin, can also colonize the eyelids, potentially contributing to various eye diseases as shown in Fig. 4. Patients with demodicosis often have higher levels of eyelash mites compared to healthy individuals, highlighting the potential for mite migration from facial skin to the eyelids [13–70% of blepharitis cases worldwide have been linked to mite infection] [39]. Therefore, eyelash mites should be examined in all demodicosis patients to prevent potential eye complications [73].

Demodex mites have been implicated in several eye conditions, including:

Blepharitis (inflammation of the eyelid margins): Both anterior (characterized by a crusty eyelash base) and posterior (marked by symmetrical eyelid bumps) blepharitis can be associated with Demodex infestation by either D. folliculorum or D. brevis mites [2, 87, 118, 189,190,191,192,193,194,195]. Unilateral blepharitis with fine follicular scaling was reported in a patient following an 8-week course of topical steroid use. Demodex folliculorum infestation was confirmed [196]. Untreated blepharitis can lead to serious complications like corneal ulcers and permanent eyelid changes [84].

Eyebrow and eyelash loss (madarosis): Demodex mites can contribute to eyebrow and eyelash loss [189].

Meibomian gland dysfunction (MGD): Blockage of meibomian gland openings by Demodex mites, along with bacterial/fungal infections, can lead to MGD, a condition affecting the quality of tear film [84].

Bacterial and fungal infections of the eyes: Demodex infestation may create a favorable environment for bacterial and fungal eye infections (including Staphylococcus aureus, Corynebacterium spp., and Bacillus oleronius) [84].

The mechanisms by which Demodex mites contribute to eye disease are multifaceted:

Inflammation: Demodex mites can trigger inflammation through the release of cytokines and allergic reactions to their chitinous exoskeletons [84].

Bacterial/fungal co-infections: Demodex infestation might create a niche for bacterial and fungal pathogens to thrive, further worsening eye health [120, 197].

Obstruction of meibomian glands: Both Demodex species can physically block the openings of meibomian glands, hindering tear secretion [84].

Corneal damage: Chronic irritation from Demodex-related blepharitis can damage the cornea [193].

Demodex mites have also been linked to recurring chalazia and styes, dry eye syndrome, and even endophthalmitis [