Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis.

Demodex blepharitis, a chronic lid margin disease, is caused by an infestation of Demodex mites, the most common ectoparasites in human skin and eyelids. Lotilaner ophthalmic solution, 0.25% (Xdemvy, Tarsus Pharmaceuticals), is the first therapy approved to treat Demodex blepharitis. This narrative review characterizes lotilaner ophthalmic solution, 0.25%, and describes its efficacy, safety, and tolerability. The safety and efficacy of lotilaner ophthalmic solution, 0.25%, for treating Demodex blepharitis was evaluated in four phase 2 and two phase 3 trials. The data of 980 patients included in these phase 2 and 3 clinical trials revealed that the proportion of eyes with a clinically meaningful reduction to 10 or fewer collarettes (the cylindrical, waxy debris found at the base of the eyelashes) ranged from 81 to 93%. The mite eradication rate confirmed by a microscopy of epilated lashes ranged from 52 to 78%. No serious treatment-related adverse events were reported in any of these clinical studies. As high as 92% of the patients receiving lotilaner eyedrops in the phase 3 trials found it to be neutral to very comfortable. Given the positive safety and efficacy outcomes, the drug is likely to become the standard of care in the treatment of Demodex blepharitis.

Dermoscopy as a clinical tool for the diagnosis of demodicosis: a retrospective intrapatient case-control study.

Dermoscopy has been used for the non-invasive diagnosis of demodicosis. Several studies have evaluated the usefulness of this tool in the diagnosis, however, there are differences in the gold standard (SSSB or KOH test) and criteria of positivity used between studies. Added to this, is the lack of controls and objective quantification of the usefulness of dermoscopic signs in clinically observable and relevant ranges. To validate the usefulness of dermoscopy for the diagnosis of demodicosis by calculating the performance indicators for the different dermoscopic signs. Retrospective intrapatient case-control study, which included adults with suspicion of demodicosis. Dermoscopic photographs and scraping of healthy and lesional skin were obtained. Samples were analyzed microscopically by trained personnel. Photographs were evaluated by determining the presence of Demodex tails (DT), dilated follicular openings (DFO) and dilated blood vessels (DBV) in pre-defined ranges. 64 patients were included (total = 256 samples); the presence of demodex on skin scraping was seen in 69%. Under dermoscopy, the presence of DT in range 11-20/field had a positive likelihood ratio (LR) of 12.10 (95%CI 6.52-22.45) and negative LR 0.32 (95%CI 0.23-0.45). Combined and dichotomized performance for at least one positive sign under dermoscopy (DT > 10/field, DFO > 10/field or DBV > 50% of the field): positive LR 7.14 (95%CI 4.80-10.62) and negative LR 0.11 (95%CI 0.06-0.22). The presence of DT, DFO or DBV has a high correlation with a positive mite test, so the diagnosis of demodicosis could be made only through dermoscopy.

Investigation of the in-vitro lethal effect of spilanthol on demodex and finding the most effective dose.

Demodex species are associated with many dermatological diseases, so an acaricidal agent that is effective against them and safe for skin applications may benefit many diseases. This study aims to investigate the anti-demodex potential of spilanthol, a product obtained from the Spilanthes Acmella plant, by determining the minimal effective dose for the first time in the literature. Demodex mites were obtained from 70 patients with standard superficial skin biopsy. Spilanthol extract was used at 1%, 2%, 3%, 4%, and 5%. Standard immersion oil was used for the negative control, and permethrin 5% was used for the positive control group. The dependent variable is the survival time of the mite. Comparisons with the negative control group, the anti-demodex effect demonstrated itself in all groups, creating a statistically significant difference (p < 0.001). The positive control group, had 3%, 4%, and 5% spilanthol rates which were very similar to the results with 5% permethrin (p > 0.05). Higher concentrations than 3% did not make any additional contribution to survival times. This is the first attempt to show the dose-dependent acaricidal effect of spilanthol on demodex mites. Even the 3% dose shows similar results to 5% permethrin, and no additional effect increase was observed at higher doses. Therefore, in vivo, studies may be planned with a 3% spilanthol dose for further studies.

Ocular and Systemic Pharmacokinetics of Lotilaner Ophthalmic Solution, 0.25%, Following a Single Dose or Repeated Doses in Dutch-Belted Rabbits.

Purpose: To evaluate the ocular and systemic pharmacokinetics of lotilaner ophthalmic solution, 0.25%, following bilateral topical ocular administration of single and repeated doses in rabbits. Methods: Dutch-belted rabbits (n = 34) were administered lotilaner ophthalmic solution, 0.25%, eye drops, either in a single bilateral dose (Group 1) or twice a day bilaterally for 7 days and once on Day 8 (Group 2). The pharmacokinetics and tissue distribution levels of lotilaner were assessed following the single dose in Group 1 and the last dose in Group 2. The drug levels were examined in various ocular tissues and whole blood. The maximal concentration of the drug (Cmax), time to maximal concentration, the terminal phase elimination half-life, the area under the concentration-time curve (AUC), and total clearance of the drug were determined. Results: In the eyelid margins, lotilaner exhibited the highest observed concentrations at 0.25 hour (h), presenting a mean Cmax of 14,600 ng/mL in Group 1 and 20,100 ng/mL in Group 2. The highest AUC was in the eyelid margin at 242,000 h×ng/mL in Group 1 and 535,000 h×ng/mL in Group 2. In the eyelid margin, the observed clearance rate (0.634 mL/h in single dose, 0.288 mL/h in repeat dose) was the slowest among all ocular tissues in both groups, with the longest half-life of 152 h (∼6.3 days) observed in the repeat dose group. Conclusions: Lotilaner ophthalmic solution, 0.25%, demonstrated rapid ocular tissue absorption into the eyelid margin tissue with a long half-life of almost a week. No adverse effects were observed following topical ocular administration in Dutch-belted rabbits.

Sarcoptic Mange in a Tasmanian Devil (Sarcophilus harrisii) and Bennett's Wallaby (Notamacropus rufogriseus).

ABSTRACT: Sarcoptes scabiei mites and skin lesions consistent with severe sarcoptic mange were identified in a Tasmanian devil (Sarcophilus harrisii) and Bennett's wallaby (Notamacropus rufogriseus) from Tasmania, Australia. The devil and wallaby both had severe hyperkeratotic skin lesions. All stages of mite development were identified in the devil, suggesting parasite reproduction on the host. The devil was also affected by devil facial tumor disease and several other parasites. This expands the global host range of species susceptible to this panzootic mange disease.

Detection of demodex mites in papulopustular rosacea using microscopic examination and polymerase chain reaction: a comparative case-control study.

Demodex mite proliferation is frequently involved in the pathogenesis of rosacea. The gold standard for Demodex identification is microscopic examination on a standardized skin surface biopsy. However, this method of sampling can be distressing and painful, especially when performed on hairy sites. In this case-control study, we compared the sensitivity of PCR and microscopic examination in diagnosing a Demodex infestation. Moreover, we investigated the possible correlations between the presence of Demodex mites and clinical characteristics. In total, 20 patients affected by papulopustular rosacea and 10 controls were included. At both microscopic examination and PCR, patients with rosacea presented a greater prevalence of positive samples than controls at the scalp and at the face. Microscopy had sensitivity of 50% at the face and of 46.7% at the scalp. PCR had sensitivity of 93.75% at the face and of 86.7% at the scalp. The positivity of PCR was associated to a higher frequency of facial papules and pustules. Patients with positivity at the face had a more frequent positivity at the scalp. The scalp could represent a reservoir for the Demodex mites, and should be investigated by sensitive and painless methods. PCR performed on painlessly collected samples should be further investigated.

The photothermal effect of intense pulsed light and LipiFlow in eyelid related ocular surface diseases: Meibomian gland dysfunction, Demodex and blepharitis.

The treatment and management of ocular surface diseases have shifted towards a co-treatment approach focusing on overall ocular surface homeostasis. When treating issues related to the eye, it is essential to not only focus on the damaged or disabled areas but also consider the larger picture. Meibomian gland dysfunction (MGD), Demodex infection, and blepharitis all interact at the eyelid site and can cause damage to the ocular surface to varying degrees. Palpebral lesions disrupt the balance of ocular surface homeostasis, leading to dry eye and keratitis. Traditional treatments, such as manual physical hot compress massage, have limited effectiveness due to the structure of the eyelid. However, intense pulsed light (IPL) technology uses penetrating light energy to generate heat energy, which can eliminate inflammation of capillaries or kill Demodex. Additionally, the LipiFlow thermal effect and physical compression provide a more vital and longer-lasting therapeutic effect on MGD by excluding other primary causes of ocular surface inflammation. Therefore, personalized treatment techniques based on photothermal effects may be effective. In the future, IPL and LipiFlow may potentially dismiss immune-inflammation factors causing ocular surface disease or block the delivery of systemic immune-related diseases.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

Factors affecting meibomian gland area loss in symptomatic adults.

AIM: To characterize the distribution of meibomian gland (MG) area loss (MGL) and its relationship with demographic characteristics, mites, and symptoms. METHODS: This retrospective observational study included patients who visited the Dry Eye Clinic of Shenzhen Eye Hospital between June 2020 and August 2021. General patient characteristics, ocular symptoms, Demodex test results of the eyelid edges, and the results of a comprehensive ocular surface analysis were collected. MGL was analyzed using Image J software. RESULTS: This study enrolled 1204 outpatients aged 20-80 (40.70±13.44)y, including 357 males (29.65%) and 847 females (70.35%). The patients were classified into mild (n=155; 12.87%), moderate (n=795; 66.03%), severe (n=206; 17.11%), and extremely severe (n=48; 3.99%) MGL groups. MGL was significantly larger in female than in male (P=0.006). The degree of MGL also significantly differed in age (P<0.001) and the more numbers of mites with severity (P<0.001). Multivariate disordered multinomial logistic regression analysis identified that female sex, older age, secretory symptoms, and a large number of mites were risk factors for MGL (P<0.05). CONCLUSION: Patients with MGL are more likely to be older, female, more numbers of mites, and increased secretion.

[Bacterial community diversity in human Demodex mites].

OBJECTIVE: To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. METHODS: From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. RESULTS: A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. CONCLUSIONS: There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.

Demodex folliculorum (Trombidiformes: Demodecidae) infestation in medical students with facial dermatoses and healthy groups.

Demodex folliculorum (Simon, 1842) has been associated with various dermatological conditions. This study aimed to assess the prevalence of Demodex infestation in medical students with facial dermatoses compared with healthy medical students serving as controls. A total of 250 participants were enrolled, including 150 individuals with facial dermatoses and 100 healthy controls. Sampling was performed based on the standardized skin surface biopsy method. Demographic characteristics, specifically gender and age, were not statistically different between the patient and control groups. Among the facial dermatosis patients, 25 out of 150 (16.6%) were found to have Demodex infestation, while only three out of the 100 healthy controls (3%) exhibited infestations. The only identified species was D. folliculorum. The rates of Demodex infestation were significantly higher in the patients compared to the control groups. These findings indicate a higher prevalence of Demodex infestation among medical students with facial dermatosis, particularly in those diagnosed with folliculitis, acne vulgaris, and inflammatory papule, when compared to healthy controls. A better understanding of the relationship between D. folliculorum infestation and these dermatological conditions may lead to improved diagnostic and treatment strategies in the future.

Which factors influence Demodex mite density in standardized superficial skin biopsy in patients with rosacea? A prospective cross-sectional analysis.

Rosacea is a chronic cutaneous disease that manifests with facial erythema, telangiectasia, papules and pustules on the central face. Although the pathogenesis is not well established, rosacea appears to have a close relationship with Demodex mites. The aim of the study was to elucidate the factors influencing Demodex mite density by standardized superficial skin biopsy (SSSB) in patients with rosacea. This prospective, cross-sectional study included 200 patients with rosacea. Clinical characteristics of the patients were recorded and SSSB was used to measure Demodex density (Dd). If Dd was < 5 D/cm2 in the first SSSB, SSSB was repeated 4 more times to avoid false negative results. Of 200 patients, 152 (76%) were females and 48 (24%) males with a mean age of 43.47 ± 11.87 years. Ninety-nine patients (49.5%) had erythematotelangiectatic (ETR) and 101 patients (50.5%) had papulopustular (PPR) subtype of rosacea. Among 200 patients, the ratio of cumulative positive results of the consecutive SSSBs were as follows: 1st SSSB = 125 (62.5%), 2nd SSSB = 155 (77.5%), 3rd SSSB = 170 (85%), 4th SSSB = 173 (86.5%) and 5th SSSB = 174 (87%). The ratio of detecting Demodex infestation in the first SSSB was significantly lower in patients with PPR (55/101, 54.5%) than in patients with ETR (70/99, 70.7%). Median total Demodex mite density and D. folliculorum density were significantly higher in the ETR group than in the PPR group. There was a statistically significant relationship between density of Demodex tails in dermoscopy and positive/negative results of Demodex infestation in SSSB. As a conclusion, Demodex mite density by SSSB was influenced by various factors such as subtypes of rosacea, types of Demodex species, and dermoscopic findings.

Evaluation of the relationship between Demodex infestation and obesity in rosacea patients.

BACKGROUND: The changes in the skin caused by obesity may predispose patients with rosacea to Demodex infestation (DI). Besides, identifying predisposing factors in these patients is important for initial treatment plan. AIMS: The main purpose of this study is to determine the relationship between DI and obesity in patients with rosacea. METHODS: Sociodemographic characteristics, body mass index, and clinical features of 130 rosacea patients were recorded. Demodex density was measured by noninvasive standard skin biopsy, and a determination of ≥5/cm2 mites was regarded as positive for DI. Patients with a BMI of 30 and above were categorized as the obese group, and those with a BMI below 30 were classified as the nonobese group. Moreover, patients were divided according to DI into positive and negative. These groups were compared with each other. RESULTS: Upon comparing the patients with and without obesity, it was noted that the obese patients had significantly higher rates of erythematotelangiectatic type rosacea, rosacea severity, and flushing complaints. Furthermore, results show that the DI was significantly more common in obese patients. The most determinant factors for predicting DI in rosacea patients were papulopustular type rosacea, obesity, and rosacea severity, respectively. CONCLUSIONS: In this study, DI was found to be more common in obese patients with rosacea. Besides, obesity was found to be one of the most determining factors in detecting DI in patients with rosacea.

Efficacy of Treatments in Reducing Inflammatory Lesion Count in Rosacea: A Systematic Review.

INTRODUCTION: Rosacea is a chronic inflammatory skin condition affecting approximately 5.5% of the global population. Patients present heterogeneously with a mix of features in the central facial region, of which papules and pustules are considered to be a major feature. The identification of effective treatments for reducing inflammatory lesions in rosacea can alleviate the psychosocial burden that many rosacea patients experience, including reduced self-esteem, anxiety, and social withdrawal. The objective of this systematic review is to determine the effectiveness of topical and systemic therapies in reducing lesion count in rosacea patients. METHODS/RESULTS: Medline, Embase, and Cochrane CENTRAL databases were searched, resulting in the inclusion of 43 clinical trials reporting on a total of 18,347 rosacea patients. The most well-studied treatments include ivermectin, metronidazole, azelaic acid, minocycline, and doxycycline. Oral isotretinoin was the most effective treatment in reducing inflammatory lesions and may be recommended for severe recalcitrant cases of rosacea. CONCLUSIONS: Several topical and systemic therapies have demonstrated efficacy in reducing inflammatory lesion count in rosacea patients, with mechanisms of action centred around suppressing inflammation and killing Demodex folliculorum mites. Additional research is required to determine effective combination therapies in rosacea.

Successful treatment of non-pruritus, excessive hair shedding and scales in a cat due to Demodex gatoi with fluralaner topical spot-on.

Case summary: A 1-year-old female intact Scottish Fold cat was presented with a 1-month history of excessive hair shedding with white scales on the coat without pruritus. The cat lived mostly indoors and had no history of any systemic disease. Dermatological examinations were performed step by step. Several Demodex gatoi were identified from cellophane tape impressions from the scales and examined under a low-power objective (10×) microscope. Skin cytology showed keratinocytes without any microorganisms. Based on the findings, fluralaner (Bravecto for cats; MSD) spot-on was used once every 12 weeks for ectoparasiticidal control. An essential fatty acid supplement was recommended to repair and restore the coat and skin barrier. After 4 weeks of treatment, the cat showed substantial improvement, with a normal coat and no scales. Re-examination using a cellophane tape impression for mites was negative. Ectoparasitic control is highly recommended regularly for the treatment and prevention of ectoparasites. Relevance and novel information: Feline demodicosis is an uncommon parasitic dermatosis with primary clinical signs that may cause generalised or localised dermatitis with frequent pruritus, erythema and alopecia. The aims of this study were to report on dermatological lesions with excessive hair shedding and scales in a cat that were caused by demodicosis, without presenting the main clinical sign of pruritus or overgrooming. In addition, to the authors' knowledge, this is the first report of the successful treatment of demodicosis due to D gatoi infestation with fluralaner single spot-on in an off-label use that was safe and easy to apply clinically.

Biologic therapy increases Demodex density in psoriasis patients.

BACKGROUND: Demodex density is known to increase in various immunosuppressive conditions. The relationship between biologic therapy and Demodex density remains unknown. We aimed to investigate whether the density of Demodex mites is higher in psoriasis patients treated with biologic agents compared to treatment-naive or topically treated patients. METHODS: A cross-sectional study was conducted, comparing psoriasis patients receiving biologic therapy (n = 34) with controls (n = 33). Demodex density was assessed using the standardized skin surface biopsy technique (SSSB). Statistical analysis was performed to compare the densities and prevalence of demodicosis between the two groups. RESULTS: Demodex density was significantly higher in the biologic therapy group compared to the control group on the right cheek (7.29 vs. 0.12/cm2; P = 0.001), left cheek (8.15 vs. 0.24/cm2; P = 0.002), and whole face (average of all four regions: 5.50 vs. 0.80/cm2; P = 0.001). The prevalence of demodicosis was significantly higher in the biologic therapy group on the forehead (35.3% vs. 12.1%; P = 0.043), right cheek (41.2% vs. 0%; P < 0.001), and left cheek (44.1% vs. 0%; P < 0.001). The frequency of cases with demodicosis in at least one localization was higher in the biological therapy group compared to the control group (61.8% vs. 15.2%; P < 0.001). CONCLUSIONS: Psoriasis patients receiving biologic therapy had a higher Demodex density and prevalence of demodicosis compared to controls. Biologics may lead to an increase in Demodex density by blocking specific cytokines, such as interleukin-17 and tumor necrosis factor-α, which play a role in immunity against Demodex. Further research is needed to explore the impact of different biological agents on Demodex density.

The Nevus Lipomatosus Superficialis of Face: A Case Report and Literature Review.

Nevus lipomatosus superficialis (NLS) is a hamartoma of adipose tissue, rarely reported in the past 100 years. We treated one case, and we conducted a systematic review of the literature. A 41-year-old man presented with a cutaneous multinodular lesion in the posterior region near the right auricle. The lesion was excised and examined histopathologically. To review the literature, we searched PubMed with the keyword "NLS." The search was limited to articles written in English and whose full text was available. We analyzed the following data: year of report, nation of corresponding author, sex of patient, age at onset, duration of disease, location of lesion, type of lesion, associated symptoms, pathological findings, and treatment. Of 158 relevant articles in PubMed, 112 fulfilled our inclusion criteria; these referred to a total of 149 cases (cases with insufficient clinical information were excluded). In rare cases, the diagnosis of NLS was confirmed when the lesion coexisted with sebaceous trichofolliculoma and Demodex infestation. Clinical awareness for NLS has increased recently. NLS is an indolent and asymptomatic benign neoplasm that may exhibit malignant behavior in terms of huge lesion size and specific anatomical location. Early detection and curative treatment should be promoted.

Follicular scales, scalp and ocular involvement in patients with papulopustular rosacea: prevalence and association with Demodex mite proliferation.

Facial follicular scales, dandruff, scalp itching and ocular alterations are lesser-known signs of rosacea and demodicosis. The aim of this prospective original study was to investigate the presence of these signs and symptoms in patients with almost-clear, mild and moderate papulopustular rosacea (PPR) and to study the differences between Demodex-positive (D+) and Demodex-negative (D-) rosacea. Twenty-seven out of 60 patients (45%) presented follicular scales, 24 (40%) ocular involvement and 22 (36.67%) scalp involvement. Follicular scales were more frequently observed in mild and moderate than in almost-clear rosacea (P<0.001). Itching of the scalp was more frequently reported in patients with moderate rosacea than in those with mild disease (P=0.05). Follicular scales (P=0.002) and scalp itching (P=0.05) were more frequently reported in D+ than in D- patients. Among D+ patients, scalp itching was more frequently reported in mild than in almost clear rosacea (P=0.01) and ocular symptoms associated to scalp itching were more frequently reported in moderate than in almost-clear rosacea (P=0.05). We suggest looking for these signs and symptoms in all patients with PPR, because they can be a sign of a more severe form of rosacea or of demod-icosis.