Evidence for the Clinical Association between Demodex and Rosacea: A Review.

BACKGROUND: Rosacea is a chronic inflammatory dermatological condition in humans, and its pathogenesis remains unclear. However, the development of rosacea is suspected to be related to Demodex, a microscopic commensal organism that resides in or near hair follicles and sebaceous glands. Although Demodex is known to be a host-specific, obligate commensal organism, it is currently difficult to be cultured in vitro to parasitize and infect other animal hosts. Therefore, direct evidence for a pathogenic role of Demodex in rosacea is currently lacking. SUMMARY: As circumstantial evidence, non-invasive skin-detecting techniques have shown abnormally elevated numbers of Demodex in rosacea patients. Increased cytokine levels such as IL-10, IL-8, and IL-12p70 have been observed in human sebocytes following the Demodex challenge, and acaricides have been found to be effective in rosacea therapy, all point to a close relationship between Demodex and rosacea. Based on these findings, we conducted a comprehensive literature review to summarize the current state of knowledge, research insights, and clinical treatment recommendations for Demodex-associated rosacea, with the ultimate goal of improving patient outcomes.

Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host-Parasite Interaction.

Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.

Innate type 2 immunity controls hair follicle commensalism by Demodex mites.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

Investigation of the Prevalence of Demodex spp. in Dermatological Diseases

Objective: An increase in the counts of the Demodex mites that exist in the microbiota of healthy individuals may lead to some dermatological diseases. This study aimed to investigate the prevalence of Demodex spp. among patients diagnosed with acne vulgaris, rosacea, perioral dermatitis, seborrheic dermatitis, eczema, and pityriasis folliculorum and the relationship between the demographic and clinical data of such patients and Demodex. Methods: This study included 144 patients (70 with acne vulgaris, 6 with pityriasis folliculorum, 15 with seborrheic dermatitis, 39 with rosacea, 8 with eczema, and 6 with perioral dermatitis) and 73 healthy subjects. We evaluated Demodex positivity using the standard superficial skin biopsy method in all groups. The presence of more than five Demodex mites per square centimeter was considered positive at the diagnosis. Results: Of the 144 patients included in the study, 107 (74.3%) were female, and 37 (25.7%) were male, while 40 (54.8%) of the 73 healthy subjects were female, and 33 (45.2%) were male. Twenty-one patients (14.5%) and five of the healthy subjects (6.8%) tested positive for Demodex. We found that Demodex positivity rates in the rosacea and acne vulgaris groups were higher than in the control group. However, this level was not statistically significant (p>0.05). We found the highest positivity rate among the patient groups in the pityriasis folliculorum (4/6, 66.7%), rosacea (8/39, 20.5%), and perioral dermatitis (1/6, 16.7%) groups. Lastly, we found no statistically significant relationship between the demographic and clinical characteristics of the groups and Demodex positivity (p>0.05). Conclusion: The present study is the only study that investigated Demodex positivity in six different dermatological diseases. Based on the results, we believe that investigating Demodex spp. positivity in dermatological diseases such as acne vulgaris, rosacea, and pityriasis folliculorum would be beneficial for early diagnosis and treatment.

Myostatin mutation causing double muscling could affect increased psoroptic mange sensitivity in dual purpose Belgian Blue cattle.

Belgian Blue cattle are known for their high degree of muscling and good carcass qualities. This high degree of muscling is mainly caused by a mutation in the myostatin gene (MSTN). Although the MSTN mutation is considered as fixed in the Belgian Blue breed, segregation is occurring in a sub-population bred for dual purpose. In the latter population, we observed an association between the mutation in MSTN and susceptibility to psoroptic mange, a skin disease caused by Psoroptes ovis mites that heavily plagues Belgian Blue cattle. In total, 291 animals were sampled and screened for their susceptibility for mange lesions and their MSTN genotype. Via linear mixed modelling, we observed that homozygous mutant animals had a significant increase in the size of mange lesions (+2.51% lesion extent) compared to homozygous wild type. These findings were confirmed with zero-inflated modelling, an animal model and odds analysis. Risk ratios for developing severe mange lesions were 5.9 times as high for homozygous mutant animals. All analyses confirmed an association between the MSTN genotype and psoroptic mange lesion size.

Effect of ocular demodicosis on the stability of the tear film and the tear break up time.

The aim of the study was to analyze the correlation between the presence of Demodex mites in the hair follicles of patients' eyelashes and the stability and break up time of the tear film assessed with the Non-Invasive Tear Break Up Times (NIBUT) method. 319 patients were included in the study (195 women, 124 men). The patients were divided into two groups: those with Demodex infestation and without visible symptoms of eyelid or eye surface diseases, and asymptomatic non-infested patients. The NIBUT analysis was performed with a 5 M keratograph (oculus). Non-invasive tests were performed to identify the first and mean values of the tear break up time. The first and mean tear break up time in the Demodex-infested group was lower than in the non-infested subjects. The difference was a highly statistically significant. There was a significant correlation with the age of the patients for the first break up time. The first break up time in both eyes decreased with the age of the Demodex-infested and non-infested patients. The NIBUT analyses indicate the impact of Demodex mites on the tear film stability. This may suggest possible association of demodicosis with dry eye syndrome.

Clinical characteristics of Demodex-associated recurrent hordeola: an observational, comparative study.

Our study evaluated the association between Demodex infestation and recurrent hordeola and examined the clinical features associated with these eyelid lesions. This was an observational, comparative study. We reviewed 250 patients and divided them into the recurrent hordeolum (n = 153) and control (n = 97) groups. Demodex infestation was detected by epilating eyelashes around the lesion/s and viewing them under a light microscope. Patient medical records and photographs were retrospectively analyzed to identify the clinical characteristics of Demodex-associated recurrent hordeola. Demodex was detected in 91 (59.5%) and 17 (17.5%) patients in the recurrent hordeolum and control groups (p < 0.001), respectively. In the recurrent hordeolum group, Demodex mites were found in 74 (68.5%) and 17 (37.8%) of the adult and pediatric patients (p < 0.001), respectively. Among patients with recurrent hordeola, patients in their 20s were most likely to have concomitant Demodex infestation. Patients with Demodex infestations were also more likely to develop recurrent lesions within a shorter period of time from the primary incision and curettage. The most common presentation of Demodex-associated recurrent lesions was external hordeola (67%) (p = 0.002). Demodex infestation may cause recurrent hordeola in adults and children. These mites may play a greater role in the development of lesions in adult patients. The strongest association between Demodex infestation and recurrent lesions was seen in patients in their 20s. Our results suggest that if the hordeola recur within a short period of time with the clinical characteristics of external location of eyelid, multiple numbers of lesions, or anterior blepharitis, eyelash epilation should be performed to identify the presence of Demodex mites.

Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25.

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ≥1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (≤2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 ± 0.17 to 0.28 ± 0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 ± 0.39 to 0.12 ± 0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865.

Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Atypical Knemidokoptosis in Two Dunnocks (Prunella modularis) in Southern England.

Avian knemidokoptosis, caused by knemidokoptid mites (Knemidokoptinae: Epidermoptidae), has been reported in wild and domestic birds globally. We report two cases of severe knemidokoptosis in Dunnocks (Prunella modularis) from separate sites in Great Britain, where the disease has previously been reported predominantly in finches and, less frequently, in corvids.

Case Report: A New Gain-of-Function Mutation of STAT1 Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense STAT1 mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of STAT1 with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Methods: Genetic analysis via targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including STAT1, was performed to identify an underlying genetic defect. Results: NGS identified a novel variant of STAT1, c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an in vitro luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial Demodex proliferation observed via the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of STAT1 GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. Conclusion: We describe a new STAT1 GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with STAT1 GOF mutation.

Varroa destructor: how does it harm Apis mellifera honey bees and what can be done about it?

Since its migration from the Asian honey bee (Apis cerana) to the European honey bee (Apis mellifera), the ectoparasitic mite Varroa destructor has emerged as a major issue for beekeeping worldwide. Due to a short history of coevolution, the host-parasite relationship between A. mellifera and V. destructor is unbalanced, with honey bees suffering infestation effects at the individual, colony and population levels. Several control solutions have been developed to tackle the colony and production losses due to Varroa, but the burden caused by the mite in combination with other biotic and abiotic factors continues to increase, weakening the beekeeping industry. In this synthetic review, we highlight the main advances made between 2015 and 2020 on V. destructor biology and its impact on the health of the honey bee, A. mellifera. We also describe the main control solutions that are currently available to fight the mite and place a special focus on new methodological developments, which point to integrated pest management strategies for the control of Varroa in honey bee colonies.

Case for diagnosis. Erythematous and pruritic papules on forearms.

Gamasoidosis is a poorly known and underdiagnosed mite infestation. It is characterized by the presence of erythematous and flattened papules that are quite pruritic, and can affect any region of the body, with preference for areas of folds. This article reports a case of the disease caused by mites of the species Dermanyssus gallinae. Increasingly, the agents that cause this disease are found in urban environments, increasing the incidence of people affected by the disease. This dermatosis has a self-limiting clinical picture and the treatment is done with the use of topical corticosteroids and oral antihistamines.

Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis.

BACKGROUND: Demodex mites are found on the skin of many healthy individuals. Demodex mites in high densities are considered to play a pathogenic role. OBJECTIVE: To investigate the association between Demodex infestation and the three most common facial dermatoses: acne vulgaris, rosacea and seborrheic dermatitis. METHODS: This prospective, observational case-control study included 127 patients (43 with acne vulgaris, 43 with rosacea and 41 with seborrheic dermatitis) and 77 healthy controls. The presence of demodicosis was evaluated by standardized skin surface biopsy in both the patient and control groups. RESULTS: In terms of gender and age, no significant difference was found between the patients and controls (p>0.05). Demodex infestation rates were significantly higher in patients than in controls (p=0.001). Demodex infestation rates were significantly higher in the rosacea group than acne vulgaris and seborrheic dermatitis groups and controls (p=0.001; p=0.024; p=0.001, respectively). Demodex infestation was found to be significantly higher in the acne vulgaris and seborrheic dermatitis groups than in controls (p=0.001 and p=0.001, respectively). No difference was observed between the acne vulgaris and seborrheic dermatitis groups in terms of demodicosis (p=0.294). STUDY LIMITATIONS: Small sample size is a limitation of the study. The lack of an objective scoring system in the diagnosis of Demodex infestation is another limitation. CONCLUSION: The findings of the present study emphasize that acne vulgaris, rosacea and seborrheic dermatitis are significantly associated with Demodex infestation. Standardized skin surface biopsy is a practical tool in the determination of Demodex infestation.

Case for diagnosis. Erythematous and pruritic papules on forearms

Abstract Gamasoidosis is a poorly known and underdiagnosed mite infestation. It is characterized by the presence of erythematous and flattened papules that are quite pruritic, and can affect any region of the body, with preference for areas of folds. This article reports a case of the disease caused by mites of the species Dermanyssus gallinae. Increasingly, the agents that cause this disease are found in urban environments, increasing the incidence of people affected by the disease. This dermatosis has a self-limiting clinical picture and the treatment is done with the use of topical corticosteroids and oral antihistamines.

Demodex folliculorum infestations in common facial dermatoses: acne vulgaris, rosacea, seborrheic dermatitis

Abstract Background: Demodex mites are found on the skin of many healthy individuals. Demodex mites in high densities are considered to play a pathogenic role. Objective: To investigate the association between Demodex infestation and the three most common facial dermatoses: acne vulgaris, rosacea and seborrheic dermatitis. Methods: This prospective, observational case-control study included 127 patients (43 with acne vulgaris, 43 with rosacea and 41 with seborrheic dermatitis) and 77 healthy controls. The presence of demodicosis was evaluated by standardized skin surface biopsy in both the patient and control groups. Results: In terms of gender and age, no significant difference was found between the patients and controls (p > 0.05). Demodex infestation rates were significantly higher in patients than in controls (p = 0.001). Demodex infestation rates were significantly higher in the rosacea group than acne vulgaris and seborrheic dermatitis groups and controls (p = 0.001; p = 0.024; p = 0.001, respectively). Demodex infestation was found to be significantly higher in the acne vulgaris and seborrheic dermatitis groups than in controls (p = 0.001 and p = 0.001, respectively). No difference was observed between the acne vulgaris and seborrheic dermatitis groups in terms of demodicosis (p = 0.294). Study limitations: Small sample size is a limitation of the study. The lack of an objective scoring system in the diagnosis of Demodex infestation is another limitation. Conclusion: The findings of the present study emphasize that acne vulgaris, rosacea and seborrheic dermatitis are significantly associated with Demodex infestation. Standardized skin surface biopsy is a practical tool in the determination of Demodex infestation.

Intense Pulsed Light Therapy for Patients with Meibomian Gland Dysfunction and Ocular Demodex Infestation.

To observe the clinical changes of meibomian gland dysfunctipn (MGD) and ocular Demodex infestation after intense pulsed light (IPL) treatment to further examine the mechanism of IPL treating patients with MGD and ocular Demodex infestation. The medical records of 25 patients (49 eyes) with MGD treated with IPL, were retrospectively examined to determine outcomes. Associated ocular-surface parameters (ocular surface disease index, OSDI; lipid layer thickness, LLT; noninvasive first breakup time, NIF-BUT; noninvasive average breakup time, NIAvg-BUT; tear film breakup area, TBUA; Schirmer I Test, SIT; corneal fluorescein staining, CFS), eyelid margin abnormalities, meibum quality and expressibility, MG morphological parameters (macrostructure and microstructure), and the number of Demodex infestation were examined before and after treatment. The MG microstructure and the Demodex infestation were examined via in vivo confocal microscopy (IVCM). The results showed that there were statistically significant differences in associated ocular-surface parameters (all P<0.05) before and after IPL treatment, except SIT (P=0.065). Eyelid margin abnormalities, meibum quality and expressibility obviously improved in upper and lower eyelid after IPL treatment (all P<0.0001). MG macrostructure (MG dropouts) decreased in upper (P=0.002) and lower eyelid (P=0.001) after IPL treatment. The nine parameters of MG microstructure in upper and lower eyelid all distinctly improved after IPL treatment (all P<0.0001). The mean number of Demodex mites on the upper lid margin (6.59±7.16 to 3.12±3.81/9 eyelashes) and lower lid margin (2.55±2.11 to 1.29±1.53/9 eyelashes) significantly reduced after IPL treatment (all P<0.0001). The Demodex eradication rate was 20% (8/40) in upper lid margin and 34.15% (14/41) in lower lid margin. These findings indicate that IPL shows great therapeutic potential for patients of MGD and ocular Demodex infestation.

Immune mechanisms in human and canine demodicosis: A review.

Demodex mites are saprophytic parasites of the mammalian skin, mostly found in or near pilosebaceous units of hairy regions. While they can be found in healthy humans and animals without causing any clinical manifestations, they were suggested to create pathogenic symptoms when they appear in high densities under favourable conditions (ie, demodicosis). Nevertheless, their role as the primary causative agent of the pathogenic conditions in humans is debated today. Canine demodicosis, which is highly prevalent in certain dog breeds, provides a valuable tool for studying the pathogenesis of human demodicosis. Canine and human demodicosis are caused by different Demodex species, and the clinical manifestations in former could be life-threatening. Nevertheless, current literature suggests similar immune responses and immune evasion mechanisms in human and canine demodicosis; cellular immunity appeared to have a central role in protection against demodicosis, and Demodex mites were shown to influence both innate and adaptive immune response to escape immune attack. The aim of this review is to summarize the relevant literature on demodicosis obtained from studies conducted on both organisms, and draw the attention to the effect of mite-associated factors (eg, microbiota) on the different clinical manifestations displayed during human and canine demodicosis.

Demodicosis in a captive African straw-coloured fruit bat (Eidolon helvum).

Demodicosis is most frequently observed in the domestic dog (Canis familiaris), but it has rarely been reported in bats (Chiroptera). The overpopulation of Demodex spp. that causes dermatological changes is generally associated with a compromised immune system. We describe the gross and histological features of generalized demodicosis in an adult female African straw-coloured fruit bat (Eidolon helvum) drawn from a captive research colony. The histology of the lesions revealed comedones and follicular infundubular cysts harbouring numerous Demodex spp. mites, eliciting a minimal inflammatory response in the adjacent dermis. The histological examination of a full set of tissues did not reveal clear evidence of immunosuppression, although a clinical history of recent abortion and possible stressors due to captivity could be considered risk factors for the demodicosis. Attempts to determine the Demodex species using PCR on DNA extracted from the formalin fixed paraffin embedded tissue failed. This is the first clinical and histological description of demodicosis in Eidolon helvum.

An Unusual Presentation of Pyemotes ventricosus Dermatitis Presenting With Umbilicated Papules Mimicking Poxvirus Infection.

Pyemotes ventricosus mites are an uncommon cause of pruritic dermatitis seen most commonly in occupational exposure, prominently found in professionals such as farmers, landscapers, and factory workers who work with grains, wheat, dried beans, or grasses. The clinical description of the rash has typically been described as papular, erythematous, with a central vesicular lesion. We describe a case of Pyemotes dermatitis with an atypical clinical presentation. A 30-year-old man presented with pruritic, umbilicated papules, which involved his right lateral trunk and upper thigh leading to the submitted clinical impression of molloscum contagiosum. A biopsy of the skin was taken, and fragments of arthropod consistent with P. ventricosus were identified within umbilicated indentations of skin. The patient subsequently admitted to the onset of the rash immediately after carrying bales of straw while supporting each bale with his right side. The possibility of Pyemotes dermatitis mimicking a poxvirus-like eruption should be considered when encountering an unusual umbilicated papular eruption in the appropriate patient with occupational exposure.