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    Welcome to the Rosacea Research and Development Institute [RRDi] official web site. The RRDi is a grassroots  501 (c) 3 non profit organization for rosacea patient advocacy unlike any other rosacea non profit organization. If you suffer from rosacea you are a rosacean. Finding the cure for rosacea through research is our goal (read our mission statement for a complete list of our goals). Our website is 'everything rosacea.'   Our website is now a subscription based members only website. 95% of our website requires a donation of $12/year so we can keep this website going. Guests can only view about 5% of our website. Please register and donate $12 for a twelve month subscription (minimum is $2/donation for one month access). Thanks for your donation! We need 100 active subscribers!


    Guests vs Active Members


    Guests and Inactive members can only view about 5% of our rosacea content on this website. You can gain access to all the rosacea data on our website if you register an account. Membership is subscription based. Learn moreBeginning February 10, 2022 all inactive members will have to purchase a subscription to be active again for a minimum of $2 for one month ($1/month for three or more months). Guests will have to also purchase a subscription to view our website. We need 100 active subscribers!

    Why not read the recent activity and pick a topic that interests you? Many of the links require you purchase a subscription if you see an error message. 

    RRDi Videos • FAQs • In our menu, use FORUMS or SITE INDEX to browse our website. 

    We are rosaceans and this is a grassroots rosacea non profit organization. Read more About the RRDi.

    If you are a novice or a professional we are accepting papers on rosacea subjects to be published in the next edition of the Journal of the RRDi.

    The above question is probably the most frequently asked question on the internet about rosacea. Click here for the answer 

    Download our mobile app! • Win a free jar of the ZZ Cream?  • YouTube Videos •

    Where to Begin Your Search 
    We first of all warmly invite you to join the RRDi as an active member with just your email address. This opens up to you a huge amount of rosacea data that can help you in your search for rosacea treatment as well as gives you an opportunity to engage with other rosaceans which is part of our core mission. Guests who are not comfortable registering may post in our feedback forum, and are allowed in the following areas of our website, but are not allowed into the member forums available to active members:


    Want your own free private rosacea blog? • Open a rosacea club! (members only) • Guests can leave feedback without registering an account.

    Recommend you read our FAQs for at least a half hour. Afterwards, browse our public member forum for another half hour once you have access to our member forums. If you are concerned about your privacy when joining our non profit as a member, we have several options which are discussed below by scrolling to 'How to Join' in the third paragraph under that subheading which explains those options. We take your privacy very seriously and our privacy policy is second to none! 

    Active Members
    Once you join the RRDi you must remain an active member to continue to have access to our website in the member forums. 


    What is Rosacea?
    Rosacea is a chronic and sometimes progressive disorder of the face, characterized by some or all of the following symptoms:

    Extremely sensitive facial skin with blushing, flushing, permanent redness, burning, stinging, swelling, papules, pustules, broken red capillary veins, red gritty eyes (which can lead to visual disturbances) and in more advanced cases, a disfiguring bulbous nose. Men and women of all ages can be affected, with over 415 million estimated rosacea sufferers worldwide

    Most links below require you to subscribe. 

    "Rosacea is probably a collection of many different diseases that are lumped together inappropriately." Zoe Diana Draelos, MD. 
    Dr. Draelos is a member of the ROSIE [ROSacea International Expert] Group that says the subtype classification of rosacea is controversial. Dr. Draelos is also a member of the RRDi MAC. Just because you have a red face might mean you have another skin condition instead of or with rosacea, since other skin conditions may co-exist with rosaceamimic rosacea or you might have a rosacea variant (over a dozen variants to differentiate).  

    "Rosacea is a multifactorial, hyper-reactivity, vascular and neural based disease with a broad range of facial manifestations where normal vasodilation is greater and more persistent and involves an autoimmune component of microscopic amounts of extravasated plasma induce localized dermal inflammation that may induce repeated external triggers, vasodilation, telangiectasias, redness with eventual fibrosis and hypertrophic scarring of the dermis." Sandra Cremers, M.D., F.A.C.S., RRDi MAC Member.

    If you note, there are different definitions of what constitutes rosacea which is common. Clarity with phenotypes (see below) helps in a differential diagnosis

    In November 2016, the RRDi endorsed the phenotype classification of rosacea which was announced by the ROSCO panel as a better approach of diagnosising rosacea than using subtypes. If your dermatologist still refers to subtypes, he/she is not keeping up with the latest classification of rosacea and you should point this out to your physician. Learn more about phenotypes

    Rosacea Differential Diagnosis and Misdiagnosis
    Your physician should differentiate rosacea from a plethora of other skin conditions. If you need photos of rosacea click here.

    Sometimes rosacea is misdiagnosed.

    'There are a number of topical, oral and systemic treatments available. Yet, treatment for rosacea remains difficult." Expert Opinion Pharmacotherapy 

    “There’s no one treatment that’s going to work for everybody, but we evaluate each patient individually and try to select the treatments from our armamentarium that we think will be the simplest and safest for long-term control.” John Meisenheimer, MD, Orlando, The City's Magazine

    "Ultimately, rosacea is a subjective and entirely individual experience." Rosacea: Beyond the visable

    There are prescription, non prescription and natural or alternative treatments (check out our affiliate store) for rosacea that the RRDi keeps up with and posts on our website. Volunteer Members also contribute to the website. You will not find any other website about rosacea that has more information on rosacea than the RRDi. None. The RRDi website is a wealth of rosacea data found no where else on the internet (you can google and find rosacea information and the results will include what is categorized in appropriate places on our website). Volunteers make sure of this. You can join and continue to add to the rosacea data. Isn't that what volunteering is all about? 

    Cause of Rosacea
    No one really knows what causes rosacea and there are a number of theories for your consideration. Our latest article on this subject, Rosacea Theories Revisited is worth your time to consider. 

    What will the RRDi Do For Me?
    If you are a rosacea newbie read this post. You can view the list of prescription treatments prescribed for rosacea. There is a list of non prescription treatments for rosacea to consider. We have an affiliate store dedicated to rosacea books, treatments and odd and ends. You can browse our public member forum and learn about rosacea. The digital medical revolution can assist you in your search for a treatment to improve your condition. Your rosacea is an individual case and you may find what treatment will work for your rosacea and not a treatment aimed at the masses. Rosaceans can come together and share data, using collaboration tools that the RRDi offers for free. If you have the volunteer spirit and want to become part of this innovative non profit, learn how you can volunteer and be part of this digital medical revolution. You can post in our member forum if you join and register simply with an email address. If you have concerns regarding your privacy, please consider this post.

    Once you join you have a number of tools to collaborate with other members. You can create your own rosacea blog, with easy step by step directions on how to do this. Our Gallery application lets members share photos and videos with the community. One other tool you can use is setting up your own Club

    Volunteers who contribute their time and energy may receive a free G Suite account through a generous contribution of Google, one of our sponsors.  

    You may receive a free ebook, Rosacea 101: Includes the Rosacea Diet as a gift from the founder/director if you mention in your registration application that you want the free ebook (write in the volunteer box you want the free ebook). If you are already a member and want the ebook just fill out the contact form and request a copy

    You can post in our member forum about your rosacea experience. However, we want real members, not spammers, hackers or trolls. We provide a safe, secure forum for our members, so our membership registration is very secure requiring your accepting our terms for membership.

    Our 2016 Rosacea Survey is completed and available for public viewing.  You may review a list of our education grants. Finally, ask not what the RRDi can do for you, ask.....

    What Can You Do for the RRDi?
    Your joining and registering with our organization will increase our membership. All that is required to join is an email address (your email address is private and members never see your email address nor does the RRDi give your private email address out to anyone). Our goal is to reach a membership of 10,000 members. Think about that, 10,000 rosacea sufferers joined together as a non profit organization and you are member. We need you to join to help us reach this goal!

    The RRDi is a volunteeer member driven organization and invites rosacea sufferers to become involved. Volunteering is the force that drives the organization and is an integral spirit of the RRDi philosophy. The RRDi warmly invites rosacea sufferers to participate in this non profit which you can become a part of. You are not required to volunteer when you join, since we still want you to join even if you can't volunteer. If all you can do is become a member, that will increase our membership which is helpful in itself. So if you can volunteer, let us know on when you register. Or just join with an email address and let us know later you want to volunteer. Please join or public forum. Or you may prefer our new private forum

    Please carefully read the next subheading on how to join and if you have concerns about privacy. 

    How to Join
    Subscribe. To post in our Member Forum or submit articles for publication you must register to join to become a member. The RRDi no longer requires that you provide us with your contact info and mailing address to be a non voting member. However you still need to agree to our policies, rules, etc., since you become a member of the RRDi whether a voting member or not. If you want to vote, simply include all the profile contact fields. We have over 1000 members who are voting members, so we have plenty. It is your choice if you want to vote or not. 

    If you need assistance contact us. Our volunteers will be happy to assist you. 

    Your privacy is our utmost concern and we will take precautions to ensure your privacy will never be violated. Our Privacy Policy is solid. If you have concerns regarding your privacy, please consider this post.

    Once you have joined you can post in our secure members forum which will allow you to post questions to the Medical Advisory Consultants (MAC) and to fellow members or to submit articles for our journal. Yes, members may have an article published on our web site or in our journal. You may receive a free G Suite account with our organization if you have the volunteer spirit. 

    Charter and Mission Statement
    The Charter of the Corporation states the purpose and Mission Statement which clearly outlines the goals of our non profit corporation. If you are interested in the history of how and why this non profit organization was formed click here for more information

    Of course there are expenses to keep this non profit organization going. Any donation you give will assist us to continue to keep this web site going, publish our journal, and sponsor education grantsMahalo for your donation. even if it is small. Every dollar helps us keep going.  

    The RRDi is registered at GuideStar



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    • Skin Appendage Disord. 2022 Nov;8(6):462-468. doi: 10.1159/000525024. Epub 2022 Jun 7. ABSTRACT INTRODUCTION: The present study aimed to obtain fundamental data, including climate conditions and Demodex mites, on rosacea and similar diseases in the situation where the wearing of face masks is mandatory due to the coronavirus disease 2019 pandemic. METHODS: We enrolled 86 Japanese patients habitually wearing face masks with rosacea and similar diseases. Disease severity was assessed using the Investigator Global Assessment. The presence of Demodex mites was examined microscopically. Treatment involved acaricidal and antibiotic agents. RESULTS: The numbers of male and female patients enrolled were 11 and 75, respectively. Among these patients, 85 (98.8%), 57 (66.3%), and 76 (88.4%) had rosacea, rosacea-like dermatitis (RLD), and demodicosis, respectively. The monthly number of patients with rosacea and demodicosis showed two peaks from May to June and in October, during which monthly mean temperature was approximately 20°C (68°F). Improvement rates in rosacea, RLD, and demodicosis were significantly higher when Demodex mites were no longer detected after treatment. CONCLUSION: The present results suggest that a season with a mean temperature of approximately 20°C is a risk factor for rosacea and similar diseases in individuals wearing face masks in Japan, and a decrease in Demodex mites is associated with the attenuation of symptoms. PMID:36407649 | PMC:PMC9672874 | DOI:10.1159/000525024 {url} = URL to article
    • J Cosmet Laser Ther. 2022 Nov 17:1-6. doi: 10.1080/14764172.2022.2147953. Online ahead of print. ABSTRACT A chemical peel is chemexfoliation, a process of application of a chemical substance to the skin that causes controlled chemical destruction of the epidermis with or without part of the dermis leading to skin regeneration and remodeling. It can be classified depending upon the depth of penetration into superficial, medium, and deep peels. Among various indications, peels can be used to enhance treatment within a variety of conditions including skin- rejuvenation, inflammatory disorders like acne, rosacea, acne scar, and pigmentary disorders like melasma, freckles, lentigens, dyschromia, and post-inflammatory pigmentation. We did a chemical peel for six patients with facial melanosis, diagnosed with Riehl melanosis. All patients had visible clinical improvement. Detailed history and informed consent were taken both for photographs and procedures from all patients. PMID:36384385 | DOI:10.1080/14764172.2022.2147953 {url} = URL to article
    • J Clin Aesthet Dermatol. 2022 Nov;15(11):69-74. ABSTRACT OBJECTIVE: Subantibiotic dose doxycycline (SDD40), formulated as a modified-release 40mg capsule administered once daily, is used to treat inflammatory lesions of rosacea. In order to investigate whether the patient's weight or lesion severity impacts clinical outcomes with using SDD40, the efficacy and safety of SDD40 in treating rosacea were evaluated in randomized controlled studies (RCTs). METHODS: Phase II, III, and IV RCTs, and a subsequent meta-analysis were described. For all studies, the primary efficacy endpoint was the change in total inflammatory lesion count (papules, pustules, and nodules) from baseline to Week 16. For one of the studies, body weights were categorized by BMI (body mass index). Secondary efficacy endpoints included the change in Investigator's Global Assessment (IGA). Safety was assessed by monitoring adverse events (AEs). RESULTS: The efficacy of SDD40 was consistent across the studies (two trials including n=72 and n=91 subjects) and meta-analysis (n=127 and n=142). SDD40 remained effective regardless of baseline disease severity and weight (with a weak correlation coefficient below 0.75); overweight or obese subjects with severe rosacea cleared at least as well if not better than those with a normal BMI and mild disease. The treatment was well tolerated with no to minimal gastrointestinal-related AEs. LIMITATIONS: Retrospective analyses have methodological limitations. CONCLUSION: Consistency between study results including the meta-analysis supports the effectiveness and safety of SDD40, irrespective of the weight of the patient or rosacea severity based on inflammatory lesion count at baseline. PMID:36381182 | PMC:PMC9651154 {url} = URL to article
    • Transl Vis Sci Technol. 2022 Nov 1;11(11):13. doi: 10.1167/tvst.11.11.13. ABSTRACT PURPOSE: Dry eye disease (DED) is a heterogeneous condition with poorly characterized subtypes. The DREAM study was a large multicenter randomized clinical trial that did not find omega-3 to be more effective than placebo in treating symptomatic DED. We performed secondary analysis of DREAM data to characterize DED subtypes and their omega-3 response. METHODS: A total of 535 patients with moderate-to-severe DED were randomized to omega-3 or placebo treatment for one year. We used latent profile analysis to identify subtypes based on baseline Ocular Surface Disease Index, tear break-up time (TBUT), anesthetized Schirmer's test, corneal and conjunctival staining, and meibomian gland dysfunction (MGD). We evaluated omega-3's effect for each subtype using generalized linear regression. RESULTS: Five clinically meaningful DED subtypes were identified. They differed significantly in sex (P < 0.001) and race (P = 0.02). Subtype 1 had the most severe DED signs yet milder symptoms and was associated with more Sjögren's syndrome (21%, P < 0.001). Subtype 2 had the mildest DED signs except MGD. Subtype 3 had the most severe symptoms, out of proportion to DED signs. Subtype 4 had relatively milder symptoms and MGD. Subtype 5 had severe MGD and TBUT and was associated with rosacea (29%, P = 0.04). Omega-3 was not significantly more beneficial than placebo for any subtype. CONCLUSIONS: Five clinically meaningful DED subtypes differed significantly in demographics, symptoms, signs, and systemic disease associations. Omega-3 was not significantly more effective than placebo for any subtype. TRANSLATIONAL RELEVANCE: T3 translational research identifying subtypes in the DREAM study can improve DED clinical classification and targeted management. PMID:36383391 | DOI:10.1167/tvst.11.11.13 {url} = URL to article
    • We do have a few active members now who have subscribed. We need about 100 members who subscribe to keep this website going which means keeping the RRDi going. Why we chose the subscription vs the freemium version of using our website is explained here. The active members still do not post which is not a requirement, the only requirement is to subscribe. Do you have any comment and wish to post about any of this? You can post for a minimum of a two dollar subscription or if you just donate two dollars we can make you an active member for one month so you can post for a month. You simply donate through a multitude of services listed on our donation page and then CONTACT us explaining you made a minimum two dollar donation and we can activate your membership for a month (or longer if you donate more). If you don't like subscriptions, why not post and explain how we should be operating our website. Your comment could be published in this thread, ACTIVE MEMBERS POSTING, or anywhere you want to post on our website. Maybe you have some insight into why our ACTIVE members don't post at all? Even if you are a volunteer and don't post you become inactive. Read more. 
    • Our website is now a subscription based members only website. 95% of our website requires a donation of a minimum of $2/month ($1/month for three or more months) so we can keep this website going. Guests can only view about 5% of our website. We no longer allow free membership unless you are on our volunteer staff. Please register and donate $12 for a twelve month subscription. Thanks for your donation! All members will have to purchase a subscription to be active again for at least one month or longer.  The RRDi is now showing the active members vs the inactive members in member's profiles, since the non voting and the voting members haven't been engaging in any rosacea discussion for some time now. All you do is login to your account. Look at your account profile and it shows whether you are active or inactive. If you haven't posted in the last 30 days you are automatically placed in the inactive member group. Just post in any area open to guests and you automatically become active again and have access to the member area.  Because of a relatively inactive forum 'engagement' with fellow rosaceans which is really core to our mission (view the RRDi Mission) we have attempted to encourage members to post. Members, you are our only hope! Post! Read our mission goal below:  Goal #7: To allow volunteer members to have a platform to voice their concerns about rosacea and to contribute information about rosacea. Our goal is 10K members.  Since the vast majority of our 1.5K members are not engaging in any discussion, we inform everyone whether a member is active or inactive.  The definition of an active member is one who posts a minimum of at least one post a month. If after one month a member does not post the member status is inactive. This means that access will be visible to what a 'guest' user will be able to see.  Ask not what rosaceans can do for you, but what can you do for rosaceans? Rosaceans Helping Rosaceans.  INACTIVE MEMBER Steps to Become Active Simply login to your account and donate to one of our subscription plans.  If you have forgotten your login credentials use our contact form and give us your email address you used to register your account and we will help you gain back your access.  We will be happy to restore your active status once we have verified which subscription plan you donated for.  (2) Another way to become active is donate two dollars. Contact us and explain you donated and want your inactive membership to be active again. We will need to know what email address you used to register your account and on what date you donated.  (3) Become a volunteer and we waive the subscription fee. However, if you don't post in thirty days you become inactive.  (4) Simply subscribe and you become active again. Members Posting How can inactive members post and become an active member again?  Simple. Subscribe. Find an area you would like to post something, For example, any area still open to guests allows you to START A NEW TOPIC or QUOTE button. Just be sure you are logged into your RRDi member account. Post.  If you are having issues logging into your RRDi member account use the contact form and explain your issue. Be sure to include your email address so we can resolve your login issue for you, if you want a resolution.  New Members Subscribe to one of our subscription plans.  We are trying to encourage engagement. Rosaceans helping Rosaceans.  
    • J Cosmet Dermatol. 2022 Nov 14. doi: 10.1111/jocd.15492. Online ahead of print. ABSTRACT BACKGROUND: Rosacea may contribute to the development of cardiovascular (CV) diseases by causing endothelial dysfunction (ED), which is known to be the initial step of atherosclerosis, due to its inflammatory features. OBJECTIVE: This study aimed to assess ED in rosacea patients using the flow-mediated dilatation (=dilation) (FMD) method. METHODS: Seventy-three rosacea patients and 73 age, gender-matched healthy volunteers were enrolled. Individuals with cardiac risk factors, pregnant, and lactating women were excluded. Demographic, clinical data and anthropometric measurements were recorded. FMD measurement was performed ultrasonographically by a cardiologist. Systolic and diastolic blood pressures (BP) were measured and hemogram, erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), mean platelet volume (MPV), and fasting blood glucose values were assessed. RESULTS: The FMD value was statistically lower in rosacea patients compared with healthy controls (p = 0.000). Metabolic syndrome, systolic and diastolic BPs, and plasma NLR were higher in the rosacea group (p = 0.009, p = 0.000, p = 0.000, p = 0.000, respectively). According to the multivariate linear regression analysis, rosacea type significantly predicted FMD. CONCLUSIONS: Rosacea is not only a disease limited to the skin, but it may also have systemic involvement. A significant difference was found between FMD values measured in between the case and control groups, suggesting rosacea may have an atherogenic effect. Possible cardiac risks should be considered in rosacea patients, and further evaluation could be warranted. PMID:36374628 | DOI:10.1111/jocd.15492 {url} = URL to article
    • J Eur Acad Dermatol Venereol. 2022 Nov 11. doi: 10.1111/jdv.18725. Online ahead of print. ABSTRACT BACKGROUND: Rosacea is a chronic inflammatory skin disease with increased macrophage infiltration. However, the molecular mechanism remains unclear. OBJECTIVES: To determine the significance of macrophage infiltration, and correlation between Guanylate binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation. METHODS: Here we tested hypothesis that Guanylate binding protein 5 (GBP5) aggravate rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signaling pathway. We depleted macrophage by injecting clodronate-containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea-like skin inflammation when BALB/c mice was injected GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophages polarization, THP-1 cell was treated with GBP5 siRNA. RESULTS: Macrophage depletion ameliorated rosacea-like skin inflammation in mice, implying the important role of macrophages in the rosacea. Basing on transcriptome analysis, Guanylate binding protein 5 (GBP5) was identified as hub genes that was associated with the macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with the macrophage infiltration, the immunofluorescence analysis revealed the colocalization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea-like skin inflammation in the LL-37-induced mouse model and suppressed the expression of M1 signature genes such as IL-6, iNOS, and TNF-a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF-κB signaling pathways. CONCLUSIONS: Together, our study revealed the important role of macrophages in rosacea, and identified GBP5 as a key regulator of rosacea by inducing M1 macrophages polarization via NF-κB signaling pathways. PMID:36367676 | DOI:10.1111/jdv.18725 {url} = URL to article
    • Pharmaceutics. 2022 Oct 28;14(11):2322. doi: 10.3390/pharmaceutics14112322. ABSTRACT In the present investigation, a nanoemulgel of minocycline was formulated and optimized for an improved drug delivery and longer retention time in the targeted area. Combining eucalyptus oil, Tween 20, and Transcutol HP, different o/w nanoemulsions were formulated by the oil phase titration method and optimized by pseudo-ternary phase diagrams. The morphology, droplet size, viscosity, and refractive index of the thermodynamically stable nanoemulsion were determined. Furthermore, optimized nanoemulsion was suspended in 1.0% w/v of Carbopol 940 gel to formulate the nanoemulgel, and for this, pH, viscosity, and spreadability were determined and texture analysis was performed. To compare the extent of drug penetration between nanoemulsion and nanoemulgel, ex vivo skin permeation studies were conducted with Franz diffusion cell using rat skin as the permeation membrane, and the nanoemulgel exhibited sustained-release behavior. It can be concluded that the suggested minocycline-containing naoemulgel is expected to treat acne rosacea more effectively. PMID:36365140 | DOI:10.3390/pharmaceutics14112322 {url} = URL to article
    • Front Bioeng Biotechnol. 2022 Oct 21;10:1053679. doi: 10.3389/fbioe.2022.1053679. eCollection 2022. ABSTRACT Background: Recent studies have reported that the incidence of sensitive skin is increasing. Skin sensitivity and skin barrier functions were related to many skin diseases including atopic dermatitis, psoriasis, rosacea, and so on. Mesenchymal stem cell (MSC)-derived exosomes (hMSC) might be considered as a new effective therapeutic scheme. Aims: This study aims to investigate the safety and efficacy of hMSC exosomes as a novel topical treatment for sensitive skin. Patients/Methods: Exosomes were extracted from primary hMSC via ultracentrifugation method. The morphology of hMSC exosomes was studied via transmission electron microscope. Expression of exosome specific surface marker was detected via Western blot. 22 subjects (female, aged 18-55) diagnosed with sensitive skin were enrolled. Follow-up was conducted before, 7-day, 14-day, and 28-day after hMSC exosomes use. Transepidermal water loss (TEWL), surface hydration, sebum secretion, and L*a*b* value were simultaneously tested at the same time point in an environment-controlled room. Results: Under transmission electron microscopy, the extracted hMSC exosomes were circular or elliptical with intact membrane structure, and their diameters ranged mainly from 40 to 80 nm. Western blot showed that the expression of markers CD63, CD9, and Tsg101 was positive. Brownian motion based nanoparticle trajectory analysis (NTA) showed that the main peak of particle size distribution occurred around 96 nm, the average particle size was 122 nm, and the main peak accounted for 96.7%. All this conformed to the biological characteristics of exosomes standardized by the International Society for Extracellular Vesicles. In the clinical trial, scores of objective symptoms including roughness, scales, erythema, and subjective symptoms including tension, burning, or itching, were improved after 7-, 14-, and 28- day using hMSC-exosomes. TEWL, hydration, sebum, pH, and a* values were tended to return to the level of healthy skin. Conclusion: The hMSC-exosomes, with the advantages of biocompatibility and biodegradability, could improve clinical symptoms and eruptions in sensitive skin patients, and might be as an MSC cell-free novel therapy in sensitive skin-related disease treatment. PMID:36338115 | PMC:PMC9633936 | DOI:10.3389/fbioe.2022.1053679 {url} = URL to article
    • Front Med (Lausanne). 2022 Oct 20;9:1026447. doi: 10.3389/fmed.2022.1026447. eCollection 2022. ABSTRACT BACKGROUND: An overlap between the skin disease rosacea and the headache disease migraine has been established; however, the magnitude of this overlap and the distribution between subtypes/phenotypes remains unclear. OBJECTIVE: The aim was to determine the magnitude of the overlap between rosacea and migraine, and to determine which subtypes/phenotypes were present in patients with concomitant rosacea and migraine. METHODS: In this cross-sectional study, 604 patients with a diagnosis of either rosacea or migraine were phenotyped through a face-to-face interview with clinical examination, to determine prevalence and phenotype of rosacea, and prevalence and subtype of migraine. RESULTS: We found a prevalence of migraine of 54% in patients with rosacea, and a prevalence of rosacea of 65% in patients with migraine. Concomitant migraine was significantly associated with the rosacea features flushing (odds ratio = 2.6, 95% confidence interval = 1.4-4.7, p = 0.002), ocular symptoms (odds ratio = 2.4, 95% confidence interval = 1.5-3.9, p < 0.001), and burning (odds ratio = 2.1, 95% confidence interval = 1.3-3.4, p = 0.002), whereas papules/pustules were inversely related with concomitant migraine (odds ratio = 0.5, 95% confidence interval = 0.3-0.8, p = 0.006). No association was found between concomitant migraine and centrofacial erythema, rhinophyma, telangiectasia, edema, or dryness. Concomitant rosacea was not associated with any specific migraine subtype in patients with migraine. CONCLUSION: This study highlights a substantial overlap between rosacea and migraine, particularly in patients with certain rosacea features. Individuals with rosacea should be asked about concomitant migraine, and comorbidities should be considered when choosing between treatments. PMID:36341245 | PMC:PMC9635264 | DOI:10.3389/fmed.2022.1026447 {url} = URL to article
    • Inflamm Res. 2022 Nov 3. doi: 10.1007/s00011-022-01635-6. Online ahead of print. ABSTRACT BACKGROUND: Rosacea, a chronic inflammatory disorder of the facial skin, is effectively treated by intense pulsed light (IPL). OBJECTIVE: To explore the potential molecular mechanism underlying the photobiomodulation effect of IPL for rosacea treatment. METHODS: Skin samples from patients with rosacea were subjected to histological and immunohistological staining. Ten patients were followed up after IPL treatment using the VISIA® skin analysis system, and the severity was assessed. In vivo, skin changes in mice with rosacea-like inflammation induced by intradermal injection of 320 μM LL-37 with or without IPL treatment were evaluated using L*a*b colorimetry as well as histological and immunological staining. In vitro, LL-37-stimulated mast cells (MCs) with or without IPL treatment were evaluated for protein expression of matrix metalloproteinase (MMP)-9, kallikrein-related peptidase 5 (KLK5), and cathelicidin using western blotting and qRT-PCR. RESULTS: Profound infiltration of inflammatory cells and evident MC degranulation were found in rosacea skin lesions. The expression of rosacea-related biomarkers and inflammatory cytokines was higher in lesional areas than in non-lesional areas, as demonstrated via immunochemical staining. In all patients, rosacea severity reduced after IPL therapy. In vivo, IPL alleviated inflammation in mice with rosacea-like inflammation, as demonstrated by the significantly decreased MMP-9, KLK5, and cathelicidin expression and reduced percentage of degranulating MCs. In vitro, IPL decreased MMP-9, KLK5, and cathelicidin expression in P815 cells, reducing the release of inflammatory cytokines and inhibiting rosacea-like inflammatory reactions. CONCLUSION: The photobiomodulation effect of IPL for rosacea treatment may inhibit MC degranulation and alleviate inflammatory reactions. PMID:36329130 | DOI:10.1007/s00011-022-01635-6 {url} = URL to article
    • Expert Opin Pharmacother. 2022 Nov 5:1-10. doi: 10.1080/14656566.2022.2142907. Online ahead of print. ABSTRACT INTRODUCTION: Rosacea is a chronic and relapsing facial dermatosis that encompasses a wide spectrum of clinical phenotypes (transient/persistent erythema, telangiectasias, papules/pustules, edema, phymatous changes, and ocular symptoms) often with uncomfortable symptoms such as flushing, pain, burning, edema, and dryness. Current pharmacological treatment includes topical agents, spanning from several conventional (azelaic acid, metronidazole, sodium sulfacetamide) to new ones (brimonidine, oxymetazoline, ivermectine, minocycline), and systemic agents (doxycycline 40 mg modified-release), all Food and Drug Administration approved. AREAS COVERED: The aim of our article is to review the state of art of pharmacological treatment, either as monotherapy or in combination therapy, tailored to the most common rosacea phenotypes (persistent erythema, inflammatory papules/pustules). Other off-label topical or systemic drugs and several adjuvant phytotherapeutic agents are considered. EXPERT OPINION: Combined therapies to target different phenotypes, when present in the same patient, represent one of the major achievements in the management of vascular and inflammatory papules and pustules of rosacea. Future investigations should be addressed to early inflammatory phyma or ocular rosacea, which have actually been neglected. Finally, there is still an ongoing need for therapeutic interventions able to relieve symptoms and social burden, all factors that greatly contribute to improve rosacea quality of life. PMID:36330970 | DOI:10.1080/14656566.2022.2142907 {url} = URL to article
    • J Eur Acad Dermatol Venereol. 2022 Nov 4. doi: 10.1111/jdv.18721. Online ahead of print. ABSTRACT BACKGROUND: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. OBJECTIVES: To validate RASI against the IGA and to assess the inter- and intraobserver reliability for RASI. METHODS: Sixteen dermatologists evaluated photos of 60 adult patients with rosacea (3 photos pr patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least one week interval. RESULTS: The IGA and RASI correlated well (Spearman Correlation Coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72 - 0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate-to-strong intraobserver agreement both for IGA and RASI. CONCLUSIONS: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies. PMID:36331365 | DOI:10.1111/jdv.18721 {url} = URL to article
    • J Fr Ophtalmol. 2022 Oct 29:S0181-5512(22)00131-0. doi: 10.1016/j.jfo.2022.01.003. Online ahead of print. ABSTRACT BACKGROUND: Ocular rosacea is a chronic inflammatory disorder with periods of exacerbation and remission, often underdiagnosed in children. When diagnosed, its management is challenging because of a lack of effective long-term treatment options. OBJECTIVE: To report our experience in cases of pediatric ocular rosacea treated with moist heat therapy and topical azithromycin 1.5%. METHODS: The medical records of six children diagnosed with ocular rosacea based on a careful medical history and slit-lamp examination of the eyelids and ocular surface were reviewed. Previous treatments were discontinued, and children/parents were instructed to use the eyelid-warming device for 1 or 2 sessions of 10minutes each day, followed by eyelid massage and cleansing, in combination with azithromycin 1.5% eye drops. RESULTS: The diagnosis of ocular rosacea in these children was delayed for several months or years from the first identifiable clinical sign or symptom. All the children presented with corneal sequelae and decreased vision. Ocular manifestations included meibomian gland disease, recurrent chalazia, and phlyctenular keratoconjunctivitis. Cutaneous signs were not always associated with the condition. Ocular rosacea was usually resistant to initial treatments with antibiotics and topical corticosteroids. Treatment with the eyelid-warming device in combination with azithromycin 1.5% led to a rapid improvement in the clinical signs and was well tolerated by all patients. CONCLUSIONS: Childhood ocular rosacea is potentially sight threatening. Practitioners should consider this condition in order to minimise diagnostic delay and subsequent complications. Combined therapy of eyelid hygiene (including an eyelid warming device) and azithromycin 1.5% eye drops was effective in treating ocular rosacea in children. PMID:36319524 | DOI:10.1016/j.jfo.2022.01.003 {url} = URL to article
    • Acta Derm Venereol. 2022 Nov 1. doi: 10.2340/actadv.v102.4391. Online ahead of print. NO ABSTRACT PMID:36317858 | DOI:10.2340/actadv.v102.4391 {url} = URL to article
    • Dermatology. 2022 Oct 28:1-20. doi: 10.1159/000526296. Online ahead of print. ABSTRACT BACKGROUND: Demodex mites are related to some inflammatory diseases such as rosacea and blepharitis and could be harmful in patients with immunodeficiency or immunosuppression, especially notable in patients using biologic like dupilumab. In order to have an objective observation of different anti-Demodex strategies, we conducted this study, based on interventional clinical evidence with quantified Demodex mite data. METHODS: We used the PubMed, Embase, ClinicalTrials.gov, Medline, and International Clinical Trials Registry Platform (ICTRP) as databases. To assess the risk of bias, the RoB2 and ROBINS-I tools were used. The certainty of evidence was assessed following the GRADE guideline. Furthermore, the effect sizes (ESs) of different strategies were compared in different time periods (0-1, 1-2, 2-3, >3 months), as well as Demodex decrease rates. RESULTS: 1,618 studies were identified in the databases, with 21 of which included in the final quantitative synthesis. Interventions in these studies included ivermectin, tea tree oil (TTO), permethrin, crotamiton, metronidazole, light therapies, combined therapies, and other therapies. During 0-1 month, the ES varied from 0.07 (cleanser) to 1.95 (systemic ivermectin-metronidazole). During 1-2 months, the ES varied from 0.88 (topical permethrin) to 4.40 (topical ivermectin). During 2-3 months, the ES varied from 0.79 (topical permethrin) to 8.37 (topical ivermectin). During the time of 3 months, the ES varied from 0.59 (topical permethrin) to 2.25 (intense pulsed light [IPL]). In terms of Demodex decrease rates, topical ivermectin, TTO, permethrin, IPL, and baby shampoo had achieved a nearly 100% decrease. The reported adverse events were mostly mild, without severe adverse events reported in any of the studies. CONCLUSIONS: We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-Demodex interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control Demodex mite infestation. PMID:36310014 | DOI:10.1159/000526296 {url} = URL to article
    • Innov Pharm. 2022 Apr 2;13(1):10.24926/iip.v13i1.4493. doi: 10.24926/iip.v13i1.4493. eCollection 2022. ABSTRACT Isolated pigmentation of the nails induced by minocycline therapy is an uncommon occurrence that has only been reported in a handful of cases. In the reported cases of isolated nail discoloration, it has been suggested that nail discoloration may occur preceding other sites of pigmentary changes. As certain types of minocycline-induced pigmentation can be permanent, it is important for clinicians to be aware of this association and discontinue therapy as soon as pigmentary changes are noticed. In this report, we present a case of isolated nail discoloration in the setting of prolonged minocycline therapy for the treatment of rosacea. PMID:36304674 | PMC:PMC9598967 | DOI:10.24926/iip.v13i1.4493 {url} = URL to article
    • Biomedicines. 2022 Oct 9;10(10):2523. doi: 10.3390/biomedicines10102523. ABSTRACT The skin harbors a huge number of different microorganisms such as bacteria, fungi and viruses, and it acts as a protective shield to prevent the invasion of pathogens and to maintain the health of the commensal microbiota. Several studies, in fact, have shown the importance of the skin microbiota for healthy skin. However, this balance can be altered by intrinsic and extrinsic factors, leading to the development of skin disease, such as acne vulgaris (AV), atopic dermatitis (AD) and rosacea(RS). Although these diseases are widespread and affect both adolescents and adults, the scientific correlation between these disorders and the skin microbiota and physiological parameters (TEWL, hydration and lipid composition) is still unclear. This review aims to investigate the current literature regarding the correlation between the skin microbiota and its imbalance underlying microbiological aspects, how the skin microbiota changes over the course of the disease and the current possible treatments. The following reported studies show a general imbalance of the bacterial flora. For this reason, more in-depth studies are necessary to explore the different subspecies and strains involved in all three diseases. PMID:36289784 | PMC:PMC9599554 | DOI:10.3390/biomedicines10102523 {url} = URL to article
    • Eur J Dermatol. 2022 Jul 1;32(4):505-515. doi: 10.1684/ejd.2022.4301. ABSTRACT BACKGROUND: Ocular rosacea is a common skin condition leading to dry eye that is difficult to manage. OBJECTIVES: To estimate the efficacy and safety of a new intense pulsed light device, Thermaeye Plus, for meibomian gland dysfunction and blepharitis due to ocular rosacea. MATERIALS & METHODS: This prospective, longitudinal study included 74 eyes of 37 consecutive patients with ocular rosacea, with mean age of 45.6±11.7 years. Four consecutive sessions were undertaken, including14 flashes with 10 J/cm² on the periocular area and facial cheeks on Day 1, 14, 28, and 49. Clinical evaluation was based on: ocular surface disease index (OSDI) and symptom score questionnaires, quality of live and facial severity degree, non-invasive tear meniscus height, non-invasive tear break up time, corneal fluorescein staining and eyelid margin and meibomian gland assessment. Adverse effects on the eye and periocular area, and systemic complications were evaluated. RESULTS: The OSDI questionnaire showed a decrease in symptoms, achieving normal values in 91.9% of patients. The symptom score showed amelioration, with the most significant changes relating to dryness, foreign body sensation, light sensitivity, and pain. Longitudinal analysis showed the most significant improvement between baseline at Day 1 and 49. All eyelid signs improved, most significantly for telangiectasia/vascularity and blepharitis, leading to a 78% clearance of facial rosacea and 81.1% reduction of flushing. In total, 100% of the patients reported an improvement in their quality of life after treatment and 94.6% a very significant improvement (p<0.001). CONCLUSION: These results demonstrate that Thermaeye Plus is an effective and safe treatment for ocular rosacea. PMID:36301756 | DOI:10.1684/ejd.2022.4301 {url} = URL to article
    • JAMA Dermatol. 2022 Oct 26. doi: 10.1001/jamadermatol.2022.3911. Online ahead of print. ABSTRACT IMPORTANCE: Acne and rosacea have substantial implications for quality of life, and it is therefore important to ensure the patient's voice is being captured in pivotal randomized clinical trials (RCTs). Although patient-reported outcome measures (PROMs) are a valuable tool to capture the patient perspective, little is known about use of PROMs in RCTs on acne and rosacea. OBJECTIVE: To characterize the use of PROMs in RCTs on acne and rosacea. EVIDENCE REVIEW: A systematic literature search was conducted using the search terms acne vulgaris and rosacea in the following databases: MEDLINE through PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. A modified search hedge for RCTs from the McGill Library was applied. All phase 2, 3, and 4 RCTs published between December 31, 2011, through December 31, 2021, that evaluated the efficacy and safety of therapies for acne and rosacea vs any comparator were eligible for inclusion. FINDINGS: A total of 2461 publications describing RCTs were identified, of which 206 RCTs met the inclusion criteria (163 trials [79%] on acne and 43 [21%] on rosacea). At least 1 PROM was used in 53% of trials (110) included; PROM use was more common in rosacea RCTs (67% [n = 29]) compared with acne RCTs (50% [n = 81]). At least 1 dermatology-specific (13% [n = 27]) or disease-specific (14% [n = 28]) PROM was included in the RCTs analyzed. Only 7% of trials (14) included a PROM as a primary outcome measure. There was no statistically significant increase in PROM inclusion over the study period (11 of 21 trials in 2011 vs 5 of 12 trials in 2021). CONCLUSIONS AND RELEVANCE: In this systematic review, PROMs were included in approximately one-half of acne and rosacea RCTs performed over the study period. In addition, PROMs were rarely used as a primary outcome measure, and inclusion of PROMs has not increased substantially over the past 10 years. Increasing use of PROMs in RCTs can ensure that the patient's perspective is captured during the development of new treatments for acne and rosacea. PMID:36287541 | DOI:10.1001/jamadermatol.2022.3911 {url} = URL to article
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