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Science Immunology Oct 2023Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and the interplay between inflammatory and...
Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the consequences of disrupting and its receptor in a mouse model of house dust mite (HDM)-induced allergic dermatitis. -deficient mice displayed a deficit in HDM dermatitis-associated scratching, consistent with its well-established role as a pruritogen. In contrast, deficiency increased the number and proportion of cutaneous type 2 cytokine-producing CD4 T cells and serum IgE in response to HDM. Furthermore, monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop were selectively enriched in -deficient HDM dermatitis skin. Thus, IL-31 is not strictly a proinflammatory cytokine but rather an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in skin. Our data support a model wherein IL-31 activation of IL31RA pruritoceptors triggers release of calcitonin gene-related protein (CGRP), which can mediate neurogenic inflammation, inhibit CD4 T cell proliferation, and reduce T cell production of the type 2 cytokine IL-13. Together, these results illustrate a previously unrecognized neuroimmune pathway that constrains type 2 tissue inflammation in the setting of chronic cutaneous allergen exposure and may explain paradoxical dermatitis flares in atopic patients treated with anti-IL31RA therapy.
Topics: Animals; Mice; Cytokines; Dermatitis, Atopic; Immunity; Neurogenic Inflammation; Pyroglyphidae; Skin; Interleukins
PubMed: 37831760
DOI: 10.1126/sciimmunol.abi6887 -
Eye & Contact Lens Aug 2023Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact... (Review)
Review
Demodex blepharitis is a common disease of the eyelid, affecting approximately 25 million Americans. This article reviews what is known about the mechanisms and impact of Demodex blepharitis, risk factors, signs and symptoms, diagnostic techniques, current management options, and emerging treatments. Demodex mites contribute to blepharitis in several ways: direct mechanical damage, as a vector for bacteria, and by inducing hypersensitivity and inflammation. Risk factors for Demodex blepharitis include increasing age, rosacea, and diabetes. The costs, symptom burden, and psychosocial effects of Demodex blepharitis are considerable. The presence of collarettes is pathognomonic for Demodex blepharitis. Redness, dryness, discomfort, foreign body sensation, lash anomalies, and itching are also hallmarks of the disease. Although a number of oral, topical, eyelid hygiene and device-based options have been used clinically and evaluated in studies for the management of Demodex blepharitis, none have been FDA approved to treat the disease. Recent randomized controlled clinical trials suggest that lotilaner ophthalmic solution, 0.25%, is a topical treatment with the potential to eradicate Demodex mites and eliminate collarettes and eyelid redness for an extended period.
Topics: Animals; Humans; Mite Infestations; Mites; Blepharitis; Eyelids; Inflammation; Eyelashes; Eye Infections, Parasitic
PubMed: 37272680
DOI: 10.1097/ICL.0000000000001003 -
Cell Death & Disease Jul 2023Polymerase 1 and transcript release factor (PTRF, encoding by Cavin-1) regulates interleukin 33 (IL-33) release, which is implicated in asthma development. Z-DNA binding...
Polymerase 1 and transcript release factor (PTRF, encoding by Cavin-1) regulates interleukin 33 (IL-33) release, which is implicated in asthma development. Z-DNA binding protein 1 (ZBP1)-sensing Z-RNAs induces necroptosis which causes inflammatory diseases. House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. Whether PTRF via IL-33 and ZBP1 mediates HDM-induced macrophage necroptosis and airway inflammation remains unclear. Here, we found that deficiency of PTRF could reduce lung IL-33, ZBP1, phosphor-receptor-interacting protein kinase 3 (p-RIPK3), and phosphor-mixed lineage kinase domain-like (p-MLKL) (necroptosis executioner), and airway inflammation in an HDM-induced asthma mouse model. In HDM-treated macrophages, ZBP1, p-RIPK3, and p-MLKL levels were markedly increased, and these changes were reversed by deletion of Cavin-1. Deletion of Il33 also reduced expression of ZBP1, p-RIPK3, and p-MLKL in HDM-challenged lungs. Moreover, IL-33 synergizing with HDM boosted expression of ZBP1, p-RIPK3, and p-MLKL in macrophages. In bronchial epithelial cells rather than macrophages and vascular endothelial cells, PTRF positively regulates IL-33 expression. Therefore, we conclude that PTRF mediates HDM-induced macrophage ZBP1/necroptosis and airway inflammation, and this effect could be boosted by bronchial epithelial cell-derived IL-33. Our findings suggest that PTRF-IL33-ZBP1 signaling pathway might be a promising target for dampening airway inflammation.
Topics: Animals; Mice; Interleukin-33; Pyroglyphidae; Necroptosis; Endothelial Cells; Asthma; Macrophages; Protein Kinases; Signal Transduction; Inflammation
PubMed: 37454215
DOI: 10.1038/s41419-023-05971-1 -
Ophthalmology Oct 2023To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis.
DESIGN
Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial.
PARTICIPANTS
Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25% (study group) or vehicle without lotilaner (control group).
METHODS
Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n = 203) to receive lotilaner ophthalmic solution 0.25% or to the control group (n = 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash.
MAIN OUTCOME MEASURES
Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events.
RESULTS
At day 43, the study group achieved a statistically significant (P < 0.0001) higher proportion of patients with collarette cure (56.0% vs. 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs. 33.0%), mite eradication (51.8% vs. 14.6%), erythema cure (31.1% vs. 9.0%), and composite cure (19.2% vs. 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation, 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable.
CONCLUSIONS
Twice-daily treatment with lotilaner ophthalmic solution 0.25% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Animals; Humans; Mite Infestations; Prospective Studies; Ophthalmic Solutions; Blepharitis; Mites; Eyelashes; Erythema; Eye Infections, Parasitic
PubMed: 37285925
DOI: 10.1016/j.ophtha.2023.05.030 -
The British Journal of Dermatology Aug 2023
Topics: Animals; Humans; Vitiligo; Pyroglyphidae; Keratinocytes; Skin; Hypopigmentation; Melanocytes
PubMed: 37405425
DOI: 10.1093/bjd/ljad200 -
MMW Fortschritte Der Medizin Aug 2023
Topics: Humans; Animals; Asthma; Pyroglyphidae
PubMed: 37537441
DOI: 10.1007/s15006-023-2830-2 -
Parasitology Research Mar 2024Scabies is an itchy skin disease caused by the burrowing mite Sarcoptes scabiei. During their lifespan, the female mites invade the stratum corneum and create tunnels,... (Review)
Review
Scabies is an itchy skin disease caused by the burrowing mite Sarcoptes scabiei. During their lifespan, the female mites invade the stratum corneum and create tunnels, in which they reside, move, feed, deposit fecal pellets, and lay eggs. Recently, scabies was included in the World Health Organization roadmap for neglected tropical diseases 2021-2030. This review attempts to summarize our knowledge about the mite's biology and the disease pathogenesis, pathological changes, and complications. Generally, the host-parasite interaction in scabies is highly complex and involves different mechanisms, some of which are yet largely unknown. Elucidation of the nature of such interaction as well as the underlying mechanisms could allow a better understanding of the mite's biology and the development of novel diagnostic and therapeutic options for scabies control programs. Moreover, identification of the molecular basis of such interaction could unveil novel targets for acaricidal agents and vaccines.
Topics: Female; Animals; Scabies; Sarcoptes scabiei; Acaricides; Eggs; Epidermis
PubMed: 38433167
DOI: 10.1007/s00436-024-08173-6 -
La Tunisie Medicale Feb 2024Chronic blepharitis is a common cause of eye irritation and dryness. They are often treated without regard to causal factors such as parasites which are rarely mentioned.
INTRODUCTION
Chronic blepharitis is a common cause of eye irritation and dryness. They are often treated without regard to causal factors such as parasites which are rarely mentioned.
AIM
To describe the role of Demodex in the pathogenesis of chronic blepharitis, to analyze the epidemiological, clinical, diagnostic and therapeutic particularities.
METHODS
This is a prospective, case-control study conducted in the mycology parasitology department at the Habib Bourguiba university hospital in Sfax covering 100 cases with chronic blepharitis and 87 control cases. Clinical examination and eyelash removal were performed with direct examination for qualitative and quantitative analysis, before and after treatment.
RESULTS
Demodex was significantly more found in patients than in controls (48% vs 13.8%). The quantitative analysis showed a significant difference between the two groups with 52.1% of Demodex (+++) for patients versus 8.3% for controls. Demodex blepharitis were treated with yellow oxid mercure ophthalmic ointment with a good outcome in 81,3%.
CONCLUSION
Although it is admitted to be a saprophyte of the skin, a large number of arguments argues for the incrimination of Demodex in the etiopathogenesis of chronic blepharitis, hence the interest of eyelashes examination and a parasitic research in front of any chronic blepharitis resistant to usual treatments. In case of positive research, a specific treatment should be prescribed. Its effectiveness is another argument for the etiological diagnosis.
Topics: Animals; Humans; Prospective Studies; Mites; Mite Infestations; Tunisia; Case-Control Studies; Blepharitis; Chronic Disease
PubMed: 38567474
DOI: 10.62438/tunismed.v102i2.4449 -
Experimental Dermatology Nov 2023The latest generation ultraviolet (UV) dermatoscopes, which emit UV light at a wavelength of 365 nm and enlarge lesions, are practical devices that can facilitate the...
The latest generation ultraviolet (UV) dermatoscopes, which emit UV light at a wavelength of 365 nm and enlarge lesions, are practical devices that can facilitate the diagnosis and follow-up of some dermatological diseases with fluorescence that can be observed in skin lesions. In 305 patients, 468 tunnels were evaluated: first in polarized mode and later in UV mode. The recorded samples were compared one-to-one by the same dermatologist. Due to the study's design, images were examined in three stages: tunnel borders, tunnel content and mite appearance. In UV mode, the entire body of mites gives a bright reflex along with an oval-shaped diagnostic clue well beyond the delta sign. The borders of the tunnel reflect brightly in UV mode, with borders that are more sharply visible than in polarized mode. Although the tunnel content cannot be clearly distinguished in polarized mode, especially in people with hyperkeratotic palms, or 'working hands' (e.g. farmers, mechanics and construction workers), with the bright reflex, the tunnel borders in UV mode give a bright reflection and provide a clear view of tunnels. Tunnel content gives a bright reflection in UV mode. Our results show that UV dermatoscopes provide more effective and clearer images than polarized dermatoscopes in the diagnosis of scabies.
Topics: Animals; Humans; Scabies; Sarcoptes scabiei; Dermoscopy
PubMed: 37702268
DOI: 10.1111/exd.14930 -
MMW Fortschritte Der Medizin Mar 2024