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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 -
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 -
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 -
Ugeskrift For Laeger Oct 2023Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available...
Scrub typhus is caused by the mite-borne bacterium Orientia tsutsugamushi. Imported cases have been suspected in Denmark but no diagnostic method has yet been available to confirm the diagnosis. This is a case report of a 38-year-old male admitted to hospital with high fever, severe malaise and headache after returning from Malaysia. Scrub typhus was suspected and the patient recovered after one week of doxycycline treatment. The pathogen was identified by use of microbiome 16S/18S rRNA next-generation sequencing on ethylenediamine tetraacetic acid (EDTA) blood, which in the future may serve an important role in the investigation of travel-associated infections.
Topics: Male; Humans; Adult; Orientia tsutsugamushi; Scrub Typhus; Travel; Doxycycline; Travel-Related Illness; RNA, Ribosomal, 16S
PubMed: 37873999
DOI: No ID Found