Guide

Sunny Beach Treatment Increases RF Irradiation in Rosacea A paper about RF irradiation may explain why short term sun can improve rosacea when you are on a vacation on a sun filled beach. When you are exposed short term on a vacation by the sun you are receiving more RF radiation in the form of radio waves along with the visible sun light due to you being on the beach. [1] This exposure may actually accentuate* your rosacea. Of course, over exposure to sun light and radio waves will trigger your rosacea, so you have to be careful to not get sun burned, which would exacerbate your rosacea. Balance is the key. A little sun can help your rosacea, not to mention reducing your stress level. "Notably, blood vessel densities in the skins of UVB-treated mice and rosacea patients were significantly decreased by RF irradiation. These results provide experimental and molecular evidence regarding the effectiveness of RF irradiation for the treatment of rosacea." [2] End Notes [1] "All of the energy from the Sun that reaches the Earth arrives as solar radiation, part of a large collection of energy called the electromagnetic radiation spectrum. Solar radiation includes visible light, ultraviolet light, infrared, radio waves, X-rays, and gamma rays." Lab Activity: Heat Transfer by Radiation, NOAA Earth System Research Laboratories (ESRL) [2] Exp Dermatol. 2020 May 20;: Radiofrequency irradiation attenuates angiogenesis and inflammation in UVB-induced rosacea in mouse skin. Son M, Park J, Oh S, Choi J, Shim M, Kang D, Byun K * "Attenuate is a verb that means to make or become weaker. The effects of aging may be attenuated by exercise — or by drinking from the fountain of youth. The versatile word attenuate denotes a weakening in amount, intensity, or value." vocabulary.com

* image "Since SARS-COV-2 pandemic began, frontline healthcare workers demonstrated to develop facial dermatoses, such as acne, rosacea and seborrheic dermatitis, secondary to prolonged use of personal protective equipment (PPE)." Clin Exp Dermatol. 2020 Jul 13;: Facial dermatoses in general population due to personal protective masks: first observations after lockdown. Giacalone S, Minuti A, Spigariolo CB, Passoni E, Nazzaro G Personal Protective Equipment (PPE) Personal Protective Equipment (PPE) includes among other items a facial mask, safety glasses, gloves, etc. Issues with PPE and Rosacea Sensitive Skin You may be concerned with how to protect your skin as well as the mucous membrane, especially if you have issues with a mask irritating your rosacea sensitive skin. One paper on this subject states, "Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier." [1] Another paper calls this 'Surgical Mask Dermatitis." [2] One paper discusses an allergic reaction to the elastic bands from certain PPE masks and noted, "Allergic contact dermatitis caused by elastic bands mask FFP2 (SIBOL, NR‐D, NUEVA SIBOL, Zamudio, Spain) was diagnosed. Complete clearance of dermatitis was achieved within 2 weeks after changing the mask to a type with cotton cloth bands." [3] At least one report of a corneal abrasion from removing a face mask. [10] "Of the people who wore face masks (three layers of surgical, cloth, respirators and half-face masks), 31.6% reported itch. Sensitive skin, atopic predisposition and facial dermatoses significantly predisposed users to the development of itch. The vast majority of subjects reported itch of moderate intensity. Itch in HCW may cause scratching and decrease the effectiveness of the necessary protection. The results indicate that face-mask-associated itch is an important problem, which should be addressed in future studies...Among the possible adverse effects of prolonged face mask use, authors frequently mention xerosis, rash, acne, facial dermatitis, pigmentation of the nasal bridge, chicks or chin and itching." [11] "15.3% (360 individuals) reported skin changes on their faces during the pandemic. 4.9% of those with skin changes believed that they were due to the usage of face masks. However, the symptoms were mild for most (87.2%) of the patients. One hundred sixty-three of the participants were healthcare workers, and among them, 78.5% were working in hospitals." [12] "Mask-related Koebner phenomenon is an important clinical sign to orient clinician's therapeutic protocols during COVID-19 pandemic, especially in patients with psoriasis." [13] "Masks appear to trigger both acne and rosacea flares." [14] "It has been reported that up to 97% of HCWs showed skin lesions (14), including acne, skin breakdown, rashes, contact and pressure urticaria, rosacea, perioral dermatitis, contact dermatitis, or aggravation of pre-existing skin disorders." [16] Treatment for Skin Irritation Resulting from Using Protection It has been recommended that, "using moisturizing products is highly recommended to achieve better protection." [1]. If you are concerned about wearing a mask, there are masks that may reduce skin irritation, i.e,, Anti-fog Full Face Shield, Anti-fog Adjustable Full Face Shield, Safety Face Shield. In using goggles, one source states, "Over‐tight using cannot enhance the protective effect but damage the skin and generate fogs instead." [1] Some prefer the disposable paper mask. "Therapeutic measures for redness and swelling include hydropathic compress with three to four layers of gauze soaked by cold water or normal saline for about 20 minutes each time every 2 to 3 hours and then applying moisturizers. Avoid washing with over‐heated water, ethanol or other irritative products." [1] The paper recommends other therapeutic treatments if you are suffering from further damage to your skin. "After 3 days of anti‐allergic treatment (oral desloratadine and topical desonide cream), the lesions almost completely disappeared. The patient switched to other masks without sponge strips which were tolerated. No recurrence was found after 3‐month follow‐up." [4] There is a report of an experience to skin reactions caused by personal protective equipment (PPE) during COVID-19 pandemic from a tertiary hospital in Granada, Spain and mentions a therapeutic approach to resolve this. [5] These ten step recommendations were made: 1. Avoid using makeup and other similar cosmetics during the working day 2. Avoid wearing jewellery and other decorative materials during the workday 3. Use cotton gloves as the first layer, and on top put the vinyl or nitrile gloves. 4. Change gloves every 30-40 minutes, whenever possible. 5. Handwashing with mild syndet soaps or oils, fragrance-free, and with the fewest preservatives possible. 6. Shower with warm water, short baths of no more than 10 minutes in length 7. Light touch drying of the skin after the shower, avoiding intense skin friction 8. Apply an emollient cream after the bath to the entire body surface. 9. Wash the scalp with mild or balancing shampoo. 10. Hands must be cared for more thoroughly. Among the care, a good rinse during hand washing is essential, and the application of emollient creams 2-3 times a day. The best time to apply it will be right after breakfast (before the workday), after eating (after the workday), and before going to bed (at this time higher fat emollients can be applied to increase the hydration of the skin). One report states, "frontline healthcare workers demonstrated to develop facial dermatoses, such as acne, rosacea and seborrheic dermatitis, secondary to prolonged use of personal protective equipment (PPE)." [7] "This study suggests that prolonged use of facemasks induces difficulty in breathing on exertion and excessive sweating around the mouth to the healthcare workers which results in poorer adherence and increased risk of susceptibility to infection." [8] “We present a case of flare-up of rosacea in a nurse working in an Intensive Care Unit for COVID-19 patients, using FFP1 type mask at work and textile or paper mask outside the hospital.” [9] Anecdotal Reports "In the past week I am wearing Full Face Shield and it is much better." Obon, post no 7 There are a couple of threads on this subject at RF. [6] Why not volunteer for the RRDi and post your experience using masks or any helpful suggestions you might have. Did you know that volunteering actually has benefits for you if your motive is to help other rosacea sufferers? Etcetera Rosacea and the Corona Virus "The World Health Organization (WHO) named the disease 2019 coronavirus disease (COVID‐19) in February 2020." [15] Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. End Notes [1] Dermatol Ther. 2020 Mar 29 : e13310. Consensus of Chinese experts on protection of skin and mucous membrane barrier for health‐care workers fighting against coronavirus disease 2019 Yicen Yan, Hui Chen, Liuqing Chen, Bo Cheng, Ping Diao, Liyun Dong [2] Contact Dermatitis. 2020 May 28. doi: 10.1111/cod.13626. Online ahead of print. Surgical Mask Dermatitis Caused by Formaldehyde (Releasers) During the COVID-19 Pandemic Olivier Aerts, Ella Dendooven, Kenn Foubert, Sofie Stappers, Michal Ulicki, Julien Lambert [3] Contact Dermatitis. 2020 Jun 1 : 10.1111/cod.13600. doi: 10.1111/cod.13600 [Epub ahead of print] Allergic contact dermatitis caused by elastic bands from FFP2 mask Francisco J. Navarro‐Triviño, Carolina Merida‐Fernández, Teresa Ródenas‐Herranz, Ricardo Ruiz‐Villaverde [4] Contact Dermatitis. 2020 May 26 : 10.1111/cod.13599. doi: 10.1111/cod.13599 Mask‐induced contact dermatitis in handling COVID‐19 outbreak Zhen Xie, Yu‐Xin Yang, Hao Zhang * image courtesy of the above source [5] Dermatol Ther. 2020 Jun 15;:e13838 PMID: 32543015 Therapeutic approach to skin reactions caused by personal protective equipment (PPE) during COVID-19 pandemic: An experience from a tertiary hospital in Granada, Spain. Navarro-Triviño FJ, Ruiz-Villaverde R The Full Text of this article is available as a PDF (1.3M). [6] How are you all coping with face masks? New Here and Anxious About Face Masks at Work [7] Clin Exp Dermatol. 2020 Jul 13 : 10.1111/ced.14376.doi: 10.1111/ced.14376 [Epub ahead of print] Facial dermatoses in general population due to personal protective masks: first observations after lockdown S. Giacalone, A. Minuti, C.B. Spigariolo, E. Passoni, G. Nazzaro [8] Indian J Otolaryngol Head Neck Surg. 2020 Sep 15 : 1–7. Effects of Prolonged Use of Facemask on Healthcare Workers in Tertiary Care Hospital During COVID-19 Pandemic P. K. Purushothaman, E. Priyangha, and Roopak Vaidhyswaran [9] Maedica (Bucur). 2020 Sep;15(3):416-417 Flare-up of Rosacea due to Face Mask in Healthcare Workers During COVID-19. Chiriac AE, Wollina U, Azoicai D [10] Vis J Emerg Med. 2020 Dec 23 : 100958. Corneal Abrasion from Removing Face Mask during the COVID-19 Pandemic Sunny, Chi Lik Au, and Callie, Ka Li Ko [11] Biology (Basel). 2020 Dec; 9(12): 451. Increased Prevalence of Face Mask—Induced Itch in Health Care Workers Piotr K. Krajewski, Łukasz Matusiak, Marta Szepietowska, Rafał Białynicki-Birula, and Jacek C. Szepietowski [12] Dermatol Res Pract. 2020; 2020: 6627472. The Prevalence and Determinants of Hand and Face Dermatitis during COVID-19 Pandemic: A Population-Based Survey Mohammed Saud Alsaidan, Aisha H. Abuyassin, Zahra H. Alsaeed, Saqer H. Alshmmari, Tariq F. Bindaaj, Alwa'ad A. Alhababi [13] Dermatol Ther. 2021 Feb 02;:e14823 Mask-Induced Koebner phenomenon and its clinical phenotypes: a multicenter, real-life study focusing on 873 dermatological consultations during COVID-19 pandemics. Damiani G, Gironi LC, Kridin K, Pacifico A, Buja A, Bragazzi NL, Spałkowska M, Pigatto PD, Santus P, Young Dermatologists Italian Network, Savoia P [14] Dermatol Ther. 2021 Feb 03;:e14848 COVID-19 related masks increase severity of both acne (Maskne) and rosacea (Mask rosacea): Multi-center, real-life, telemedical, observational prospective study. Damiani G, Gironi LC, Grada A, Kridin K, Finelli R, Buja A, Bragazzi NL, Pigatto PD, Savoia P [15] Int J Clin Pract. 2020 Dec 26 : e13948. Comparison of patients’ diagnoses in a dermatology outpatient clinic during the COVID‐19 pandemic period and pre‐pandemic period Dursun Turkmen, Nihal Altunisik, Irem Mantar, Imge Durmaz, Serpil Sener, Cemil Colak [16] Front Public Health. 2021; 9: 815415. The Dermatological Effects and Occupational Impacts of Personal Protective Equipment on a Large Sample of Healthcare Workers During the COVID-19 Pandemic Paolo Emilio Santoro, Ivan Borrelli, Maria Rosaria Gualano, Ilaria Proietti, Nevena Skroza, Maria Francesca Rossi, Carlotta Amantea, Alessandra Daniele, Walter Ricciardi, Concetta Potenza, Umberto Moscato

Benzyl Benzoate, a treatment for scabies, not available in the USA but is available in the UK, Australia and China, has been reported to be "a useful alternative treatment for rosacea as well as for demodicosis" according to a paper published in the May issue of the J Dermatolog Treat. J Dermatolog Treat. 2020 May 19;:1-28 Effectiveness of benzyl benzoate treatment on clinical symptoms and Demodex density over time in patients with rosacea and demodicosis: a real life retrospective follow-up study comparing low- and high-dose regimens. Forton FMN, De Maertelaer V Benzyl Benzoate is listed with Anti-parasitic Prescription Agents For Rosacea

October 2, 2019 Galderma to become the world’s largest independent global dermatology company after completion of CHF 10.2 billion carve-out of Nestlé Skin Health

UPDATE "President Donald Trump announced he was taking hydroxychloroquine, a drug he's repeatedly touted as a treatment for coronavirus, despite warnings about its effectiveness and safety." Coronavirus live updates, Ryan W. Miller, USA TODAY President Trump suffers from rosacea.

Thought I would continue this discussion and try to stimulate any member to weigh in on this with further thoughts on this subject. We have 1333 members as of this date and basically hardly anyone is posting anything. Only a few, and I mean a few have ever posted anything in the last few months except me. Apurva Tathe, a board member, is the second most active member on the website. I have tried to gather rosaceans together to be united in doing something about rosacea but the members are silent which is so sad to me. I have repeatedly asked members to discuss why anyone thinks that a rosacea sufferer would go through the registration process and then not even make one post. There are spammers who join but we have taken the extra precaution of approving each post before it goes live because when we allowed anyone to post a spammer posted a bunch of posts on Viagra and Twitter suspended the account and I have repeatedly tried to get Twitter to unsuspend our account with no success. Twitter is one social media account that doesn't have a good help feature and ignores pleas to activate the account. If you would like to volunteer to straighten out this mess I sure could use the help. Are you a Twitter guru? I need help. So I locked the forum and each post has to be pre-approved so we don't get spam. The last four members that joined have these user names: Buy Kamagra Uk rtstar Kamagra4U Kamagra Cheap I think you get the idea. Obviously rtstar is the only legitimate member out of the four. So we try diligently to make the RRDi Forum a safe place where you won't have to see posts about viagra, kamagra, porn or other advertisements or links asking for your money. Wish someone would actually volunteer to be a moderator who could assist in all this. We have had volunteers who said they would be a moderator but have since become inactive. Can't even reach them by emai. Most of the data on rosacea has been collected since 2004 into posts/pages and categorized in logical subjects for your benefit either in the forums or on the site index. Many of the sources for anecdotal reports or subjects show the Rosacea Forum (rosaceagroup.org) with a link to RF because many years ago the RRDi had a sister relationship due to the fact that the original owner of RF, Warren Stuart, served on the board of directors of the RRDi and was also instrumental in setting up the RRDi website with Invision Power (now called Invision Community) back in 2004. We have continued to do this since the new owner of RF, David Pasco, has graciously allowed me to not only post at RF but to also refer to posts at RF with links on the RRDi website. Hence, RF has a wealth of rosacea knowledge that should be preserved, mainly for historical reasons, but also because there is a lot one can learn at RF since it has still remained somewhat active after all these years (currently about 145 active members). To me the RF website uses basically the same interface as the RRDi website but some have told me that RF is more user friendly than the RRDi which I don't get, but obviously they do since they tell me that. So we paid for a private forum through Tapatalk who hosts rosaceans.org and we are not getting any activity over there and only a handful have joined it and never post. We will probably be dropping this by the end of 2020 since it costs $120/year to maintain it. We did this because supposedly the Tapatalk forum is the latest, state of the art 'forum' and is totally private. The list of famous rosaceans continues to grow and not one of them has joined our cause, which is one of my wish lists. Of course, my biggest wish is for a rich donor to donate enough money so we can last another year or so. At the present rate we will dissolve some time towards the end of this year. I made this post in March to no avail and sent out the latest newsletter asking for a donation. I have been writing some fairly interesting posts and spent some time working with Model Tees to offer tee shirts (please be a rosacea warrior). So, what is it that the RRDi should be doing that is not listed in this post and the previous post? What needs to be done to unite rosaceans into one rosacea grassroots non profit organization that can have an impact on the medical community to take us seriously as a rosacea patient advocacy group? Can someone with a little hutzpah please post a thought? Furthermore, I have posted a lot about comparing non profit organizations with their mission and point out how few non profits spend very little on their mission and spend most of the donations on salaries, compensation to members, or private contractors. Can you comment on why you think rosaceans don't care about any of this?

"APOSEC is a substance obtained from white blood corpuscles." [1] It is a biologic drug in clinical trials used in heart attacks, strokes, spinal cord injuries and for healing wounds. A paper suggests that APOSEC may help treat contact dermatitis. [2] APOSEC has shown to "induce angiogenesis, vasodilation, exert anti-microbial effects, inhibit thrombus formation, enhance the release of neurotrophic factors, and much more". [3] Watch this white board animation that explains APOSEC: Since APOSEC may inhibit inflammation [2], who would sponsor any research related to rosacea on this? Could 10K members of the RRDi each donate a dollar to offer a clinician a motive to investigate this subject? APOSEC is listed as one of the Biologic Treatments for Rosacea. What is APOSEC? Answer: "Secretome of Apoptotic Peripheral Blood Cells (APOSEC)" [4] Would you like to sponsor research into this independently as a group of rosacea patient advocates in solidarity? If we could gather 10K members into the RRDi and we all agreed to sponsor research into APOSEC for rosacea and each member donated one US$ dollar we could offer this to a clinician to investigate. At the very least, can you find the reply button in this post and comment on this subject? Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Biologic drug APOSEC offers possible new treatments for dermal wounds, Medical University of Vienna, Science Daily [2] Laggner, M., et al. (2020) Therapeutic potential of lipids obtained from γ-irradiated PBMCs in dendritic cell mediated skin inflammation. EBioMedicine. doi.org/10.1016/j.ebiom.2020.102774. ]3] Explain Secretome APOSEC, Focus Wound Healing, The Healing Power from Within, aposcience [4] "Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC)..." Basic Res Cardiol. 2011 Nov;106(6):1283-97. doi: 10.1007/s00395-011-0224-6. Epub 2011 Sep 28. Secretome of Apoptotic Peripheral Blood Cells (APOSEC) Confers Cytoprotection to Cardiomyocytes and Inhibits Tissue Remodelling After Acute Myocardial Infarction: A Preclinical Study Michael Lichtenauer, Michael Mildner, Konrad Hoetzenecker, Matthias Zimmermann, Bruno Karl Podesser, Wolfgang Sipos, Ervin Berényi, Martin Dworschak, Erwin Tschachler, Mariann Gyöngyösi, Hendrik Jan Ankersmit "paracrine factors secreted from apoptotic peripheral blood mononuclear cells (APOSEC)" Basic Res Cardiol. 2012 Sep; 107(5): 292. Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation K. Hoetzenecker, A. Assinger, M. Lichtenauer, M. Mildner, T. Schweiger, P. Starlinger, A. Jakab, E. Berényi, N. Pavo, M. Zimmermann, C. Gabriel, C. Plass, M. Gyöngyösi, I. Volf, H. J. Ankersmit

RRDi Tee Shirts We are happy to announce we have made an arrangement with Model Tees to have RRDi Tee shirts available for members with some slogans that we have come up with including the RRDi butterfly logo and in choices of eight colors! In the poll above we are asking you which slogan do you vote for since Model Tees has to have an order of at least 24 tee shirts before making them. Please vote above in the poll to let us know which one you like the best and logically then if more than 24 like a certain logo we can have Model Tees offer that slogan on their website and will make them in a batch order once all 24 have paid and ordered one. Want Your Own Slogan? If you want to add another slogan to the poll use our GUEST FORUM and recommend your own slogan, or please contact us with your slogan, we could use your slogan and add it to the above list. Or if you have the volunteer spirit why not find the reply button and post your slogan in this thread! All that is required is an email address to register and post in this thread. Your slogan might be added to the list above and others can vote on your slogan as the best one. All tee shirts come in eight colors and have the RRDi butterfly logo. The two beta version RRDi Model Tees has available for ordering are shown below. Here are the choices of color below:

Sutton Foster, an American actress, singer and dancer, has rosacea. [1] end notes [1] Sutton Foster Reveals What Her ‘Younger’ Alter Ego Liza Has Taught Her About Embracing Her Age, Rachel Bowie, PureWow image courtesy of Wikimedia Commons Famous Rosaceans

Nina Dobrev, a Canadian actress and model, has rosacea. [1] end notes [1] Nina Dobrev Shared Her Secret for Combating Rosacea, LAUREN REARICK, TeenVogue Image courtesy of Wikimedia Commons Famous Rosaceans

An American actress, producer, director, and singer, Brittany Snow, has rosacea. [1] Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. Famous Rosaceans End notes [1] Brittany Snow Cleared Her Chronic Rosacea Using These 5 Products, Amanda Montell, Byrdie Image courtesy of Wikimedia Commons

The American actress and filmmaker, Brie Larson, has rosacea. [1] End notes [1] Instagram Red Carpet, Red Face: Rosacea In Hollywood, NRS Image courtesy of Wikimedia Commons Famous Rosaceans

The actress, Naomi Watts, is reported to have rosacea. [1] Famous Rosaceans End notes [1] Naomi Watts Says She Suffered from 'Miserable' Rosacea While Filming Netflix's Gypsy, People Image courtesy of Wikimedia Commons

The actress, Julia Fox, is reported to have rosacea. [1] End notes [1] Red Carpet, Red Face: Rosacea In Hollywood, NRS image courtesy of Wikimedia Commons Famous Rosaceans

image courtesy of Wikimedia Commons "The five classical signs of inflammation are heat, pain, redness, swelling, and loss of function (Latin calor, dolor, rubor, tumor, and functio laesa)." [1] That distinctly describes rosacea and is one of the reasons that the inflammatory theory on rosacea is still one of the leading thoughts on its cause and why rosacea is usually described as an inflammatory skin disease condition. So what are some of the anti-inflammatory treatments for rosacea to consider? "The pharmaceutical and biotech industry is invested in testing anti-inflammatory drugs for Alzheimer’s and Parkinson’s disease. There is also interest in the role of diet, obesity, stress, gum disease, the gut microbiome and other risk factors in low-grade inflammation that could be controlled without drugs. There are now dozens of studies measuring the anti-inflammatory effects of psychological interventions, such as meditation or mindfulness, or lifestyle management programmes, diets or exercise regimes." [2] Described below are some inflammation categorized as anti-inflammatory treatments to consider for your rosacea based upon the principle stated in the paragraph above. Drugs Ivermectin is now part of the gold standard treatment for rosacea and has anti-inflammatory properties. [3] Metronidazole has been a standard treatment for rosacea for many years and has anti-inflammatory properties. Low dose timed release doxycycline is part of the gold standard treatment for rosacea and has anti-inflammatory properties. Antibiotics have been used to treat rosacea for over sixty years for its anti-inflammatory properties. [5] Nonsteroidal anti-inflammatory medications (NSAIDs) are used for rosacea, particularly aspirin for flushing avoidance. Most rosaceans find their best response from over-the-counter NSAIDs, but there are prescription NSIADs that you can ask your physician about. R.I.C.E. and a Healthy Lifestyle "A good place to start is with R.I.C.E. treatment of inflammation, which stands for: rest, ice, compression, and elevation. Other treatments which may be helpful include the foods and supplements you ingest, topical treatments to the painful area, and the activities we perform." [6] Since 'the role of diet, obesity, stress, gum disease, the gut microbiome and other risk factors in low-grade inflammation that could be controlled without drugs' [2], there are many other ways to control rosacea inflammation. For example, avoiding sugar and carbohydrate in your diet may prove helpful as it has for many rosaceans. and reduce inflammation since sugar is the rosacea fuel. [7] Eating a healthy diet (supplementing any nutritional deficiencies), getting plenty of exercise, improving your gut microbiome and pursuing a healthy lifestyle (avoiding over eating and over drinking of alcohol, reducing obesity, avoiding junk food, being a couch potato) will without a doubt reduce inflammation and improve your rosacea. Probiotics may help. Lower Stress "Women who were satisfied in their relationships also reported lower psychological stress - and these two factors were associated with lower markers for inflammation in their blood." [8] Phospholipid Therapy Two phospholipids are being researched as anti-inflammatory treatments, phosphatidylserine (PS) and phosphatidylglycerol (PG). "From a medical standpoint, both phospholipids are of interest to researchers because the body does not recognise them as foreign substances, which means fewer side effects can be expected. A U.S. study has already shown that PS is particularly effective in fighting inflammation after a heart attack." Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Inflammation, Wikipedia [2] From Depression to Dementia, Inflammation Is Medicine’s New Frontier, Edward Bullmore, The Guardian, Pocket Worthy [3] Ivermectin Anti-Inflammatory Properties [4] "Metronidazole is used to treat Crohn’s disease, abscesses, bacterial overgrowth in the intestine and pouchitis. It has antimicrobial activity (kills bacteria and parasites) as well as anti-inflammatory and immunosuppressive properties." The Washington University Inflammatory Bowel Disease Clinic Medication Information Sheet for Metronidazole (Flagyl) [5] Indian J Dermatol. 2016 Sep-Oct; 61(5): 469–481. Anti-inflammatory and Immunomodulatory Effects of Antibiotics and Their Use in Dermatology Swetalina Pradhan, Bhushan Madke, Poonam Kabra, and Adarsh Lata Singh [8] A satisfying romantic relationship predicts lower stress, inflammation in breast cancer survivors, Shrout, M.R., et al. (2020) Relationship satisfaction predicts lower stress and inflammation in breast cancer survivors: A longitudinal study of within-person and between-person effects. Psychoneuroendocrinology. doi.org/10.1016/j.psyneuen.2020.104708. [6] Front Physiol. 2017;8:93. doi:10.3389/fphys.2017.00093 Effects of Topical Icing on Inflammation, Angiogenesis, Revascularization, and Myofiber Regeneration in Skeletal Muscle Following Contusion Injury. Singh DP, Barani lonbani Z, Woodruff MA, Parker TJ, Steck R, Peake JM. [7] High Sugar Content Leads to Inflammation [8] A satisfying romantic relationship predicts lower stress, inflammation in breast cancer survivors, New Medical Net Shrout, M.R., et al. (2020) Relationship satisfaction predicts lower stress and inflammation in breast cancer survivors: A longitudinal study of within-person and between-person effects. Psychoneuroendocrinology. doi.org/10.1016/j.psyneuen.2020.104708. [9]Nature as a model: Researchers develop novel anti-inflammatory substance, ScienceDaily European Journal of Pharmaceutical Sciences, 2020; 152: 105451 DOI: 10.1016/j.ejps.2020.105451 Phosphatidylserine (PS) and phosphatidylglycerol (PG) enriched mixed micelles (MM): A new nano-drug delivery system with anti-inflammatory potential? Miriam Elisabeth Klein, Max Rieckmann, Henrike Lucas, Annette Meister, Harald Loppnow, Karsten Mäder.

IS THIS ROSACEA? This is without a doubt the most frequently asked question when searching the internet regarding rosacea than the above question, 'What is Rosacea?'. There is a difference in this question, 'Is this Rosacea?', than the previous question. You can find this FAQ on just about every social media public or private rosacean group, i.e., Reddit, Facebook, etc. and invariably the questioner, a rosacea newbie, describes their skin issue in detail, typically including photo(s), and the answer in the social media group usually is, 'that's just like my condition'. Did the questioner, who thinks he/she has rosacea, and joins a rosacea social media group, who asks this question, go to a doctor and get a diagnosis? No, because if the questioner did get a diagnosis, he/she would know what the skin issue is with a proper diagnosis, not needing to ask such a question. The reason we point out this FAQ to you is this question keeps coming up more and more where all the rosaceans have gone. Since this FAQ is without a doubt the MOST frequently asked question we want to help those who ask this question to find the answer. What is Rosacea? Answer: If you want to know what rosacea is which is a popular FAQ read this post. Asking Other Rosacea Sufferers? So first and foremost, CAN YOU GET A DIAGNOSIS ON THE INTERNET? (from a group of rosacea sufferers?), should be read first. Think about this, if you ask, 'Is this rosacea?', to a group of rosacea sufferers? Could a group of rosacea sufferers have a bias in their answer? While being in a rosacea online group with other rosacea sufferers can prove to be quite helpful, the ones in the group are not experts in diagnosis unless a member is a dermatologist, which is not likely, and even if you found such a dermatologist in an online forum or group, do you think it would be proper to diagnose in a social media group discussion? Since there are a huge number of other skin conditions that present with erythema and look so much like rosacea that the 'experts', who are all suffering from rosacea, in the rosacea social media group you are asking this question, who are absolutely sure that your description and photos look 'exactly like mine' and therefore can diagnose you quickly with rosacea, you might want, instead, to be sure you get a proper diagnosis from a dermatologist, and rule out all the other of skin conditions that look like rosacea and the list is staggering and keeps growing. Online Diagnosis from a Physician With the coronavirus epidemic, doctors are now diagnosing more frequently with online video conferencing patient sessions, so this is possible, therefore, would it not be prudent to ask a dermatologist this question rather than a group of rosacea sufferers who all have rosacea (or some other rosacea mimic) who as previously mentioned may have a bias in any comments about your description or photos. You may be able to get an online diagnosis from a dermatologist who would probably be more objective in his diagnosis of your skin condition and is more qualified than rosacea sufferers. You can learn more about an online diagnosis from a physician by clicking here and scroll down to the subheading, Internet Diagnosis From a Dermatologist (Online Virtual Diagnosis). FAQs related to this subject include: What is rosacea? (definition) Diagnosing Rosacea (What is involved?) Is Flushing Rosacea? Can rosacea be misdiagnosed? Can you self diagnose rosacea? What does rosacea look like? Can rosacea exist with other skin conditions? Is Rosacea Confusing, A Bewilderment And A Mystery? P.S. Did you know you could find the reply button and make a comment to this post? That is what volunteering is all about, helping other rosaceans. What's in it for me? Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post.

An interesting article on this subject states, "The pharmaceutical and biotech industry is invested in testing anti-inflammatory drugs for Alzheimer’s and Parkinson’s disease. There is also interest in the role of diet, obesity, stress, gum disease, the gut microbiome and other risk factors in low-grade inflammation that could be controlled without drugs. There are now dozens of studies measuring the anti-inflammatory effects of psychological interventions, such as meditation or mindfulness, or lifestyle management programmes, diets or exercise regimes." From Depression to Dementia, Inflammation Is Medicine’s New Frontier, Edward Bullmore, The Guardian, Pocket Worthy

If you appreciate all the data on rosacea that you see available on the RRDi website in your search for a way to control your rosacea and found this helpful and would like to keep this non profit organization for rosacea a viable and productive web resource, can you donate two dollars to keep the RRDi going? We rely solely on donations. No one is getting paid or receives a salary. The RRDi staff are working pro bono as volunteers who care about rosacea sufferers. Note below what Margaret Mead was asked by a student that is related to what you can do for rosacea sufferers. Do you care about rosacea sufferers? If you have rosacea, you might have a bone in your body with a tinge of caring for others. A 15,000 year old bone and the Fall 2013 issue of Reflections, Jeffrey Oak ’85 M.Div., ’96 Ph.D., Yale Divinity School RRDi Non Profit Organization You may have your idea how a non profit organization for rosacea should be run and there are other non profits for you to choose giving your support. We would hope you appreciate how different the RRDi is run and that you approve of how it is run by donating two dollars to help keep the RRDi going. In May 2020 we have over 1400 plus members. If each member donated just one dollar (minimum two or one dollar a month for twelve months) it would be enough for our non profit to remain viable for about a year! Just think of the power of one dollar with so many members. That is less than the cost of a cup of coffee. Reply to this TopicThere is a reply to this topic button somewhere on the device you are reading this post.

UPDATES "There is currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently underway with results expected soon." Acad Emerg Med. 2020 May 2. doi: 10.1111/acem.14005. [Epub ahead of print] A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19. Chowdhury MS, Rathod J, Gernsheimer J.

Updates "But trials of other treatments, including those involving hydroxychloroquine, a malaria drug touted by President Trump, have been stopped because of a lack of efficacy and concerns about toxicity." Blood thinners show promise for boosting the survival chances of the sickest covid patients May 7, 2020 at 10:30 am Updated May 7, 2020 at 2:22 pm, By Ariana Eunjung Cha, The Washington Post "There is currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently underway with results expected soon." Acad Emerg Med. 2020 May 2. doi: 10.1111/acem.14005. [Epub ahead of print] A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19. Chowdhury MS, Rathod J, Gernsheimer J. "In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death." NEJM, May 7, 2020, DOI: 10.1056/NEJMoa2012410 Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19 Joshua Geleris, M.D., Yifei Sun, Ph.D., Jonathan Platt, Ph.D., Jason Zucker, M.D., Matthew Baldwin, M.D., George Hripcsak, M.D., Angelena Labella, M.D., Daniel Manson, M.D., Christine Kubin, Pharm.D., R. Graham Barr, M.D., Dr.P.H., Magdalena E. Sobieszczyk, M.D., M.P.H., and Neil W. Schluger, M.D. "It’s been some days since I posted on the hydroxychloroquine situation versus the coronavirus epidemic, but I have been getting plenty of inquiries....So overall we have one positive report (very positive indeed, and an outlier in that respect) and two safety warnings. Make of this what you will." Hydroxychloroquine Update, Derek Lowe, May 4, Clinical Trials, In the Pipeline, AAAS "Two studies published recently medical journals found that the anti-malaria medication hydroxychloroquine failed to help hospitalized coronavirus patients." The malaria pill hydroxycholoroquine failed to help coronavirus patients in 2 big studies, Business Insider, Yahoo News

The present invention relates to a combination of ivermectin and brimonidine for use in the treatment and/or the prevention of moderate to severe rosacea, preferably by topical administration of a 1% ivermectin cream and 0.33% brimonidine gel. Google Patents Inventor Philippe Martel Nabil Kerrouche Fabien AUDIBERT WO2017085226A1

One paper discusses two cases, "a 70+ year-old man having Mohs micrographic surgery for a squamous cell carcinoma and a 90+ year-old man undergoing electrodessication and curettage of a large actinic keratosis adjacent to a seborrheic keratosis. Patients were treated with 10 g of brimonidine 0.33% gel applied under occlusion for hemostasis. Both patients experienced deterioration of mental status, respiratory depression, and somnolence. Results from cardiac testing, laboratory work-up, and imaging were negative for cardiac or neurologic etiology. Both patients improved in less than 24 hours...According to Epocrates, although no serious reactions have been reported with Rhofade, bradycardia and hypotension are listed for Mirvaso. In my experience, flushing and rebound occur with Mirvaso, so I only prescribe it rarely...Based on the current literature, I wholeheartedly concur with Shagalov et al. who 'urge against the use of topical brimonidine as a hemostatic agent until its use is further investigated.' " Published in Dermatology Expert Opinion / Commentary · August 22, 2017 Dr. Warren Heymann on Avoiding Brimonidine and Oxymetazoline as Hemostatic Agents Warren R Heymann MD --------------------------------------------------------------------------------------------------------------------------------------------- "Topical brimonidine, 0.33%, gel can result in systemic central nervous system toxic effects when used as a hemostatic agent. At present, it is not possible to define a quantity with which brimonidine can be used safely, nor can a safe wound size be defined. We, therefore, urge against the use of topical brimonidine as a hemostatic agent until its safety is further investigated." JAMA Dermatol. 2017:153:575-7. Association of central nervous system depression with topical brimonidine when used for hemostasis: A serious adverse event. Shagalov DR, Taylor D, Schleichert R, Weiss J, Weiss E. ------------------------------------------------------------------------------------------------------------------------------------------------ "The top 3 reported adverse events related to BT are erythema worse than baseline (4%), flushing (3%), and burning (2%). At least 1% of patients had an adverse reaction to the medication." J AM ACAD DERMATOL, FEBRUARY 2014, Case Letters, To the Editor Rebound Erythema and Burning Sensation from a New Topical Brimonidine Tartrate Gel 0.33% Ethan T. Routt, BA, Jacob O. Levitt, MD ------------------------------------------------------------------------------------------------------------------------------------------------

At least a tablespoon a day, more if you can, or as much as you can.

(1) Stop the brimonidine (Mirvaso) treatment and notify the physician who prescribed it since your physician may have some helpful treatment for you to consider. Sometimes physicians are helpful in situations like this. (2) Life-on-Hold's post on How to Alleviate Mirvaso Rebound Flushing (3) Raymond Peat, PhD, recommends "vitamins A, E, and K, aspirin, and caffeine might be helpful for the basic problem." Source (4) "On suspicion of brimonidine rebound/contact dermatitis, the patient was asked to discontinue brimonidine and only apply a bland emollient. She was put on doxycycline 100 mg BD for 10 days. On follow-up, the plaques and papules had reduced, and erythema had improved. She was put on isotretinoin 10 mg once daily and given two sessions of intense pulse light at 15-day interval. After 2 months of isotretinoin, she was clear of all lesions and her flushing was very well controlled." [1] (5) Might want to consider whether your 'rebound' might be an allergic reaction which means treating for atopic dermatitis or contact dermatitis (Eczema). Your physician may be in a better position to judge the difference than you are able to do this and may provide some helpful treatment. Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. If you never heard about this topic and you learned about it here first, wouldn't it be a gracious act on your part to show your appreciation for this topic by registering with just your email address and show your appreciation with a post? And if registering is too much to ask, could you post your appreciation for this topic by finding the START NEW TOPIC button in our guest forum where you don't have to register? We know how many have viewed this topic because our forum software shows the number of views. However, most rosaceans don't engage or show their appreciation for our website and the RRDi would simply ask that you show your appreciation, please, simply by a post. End Notes [1] Indian Journal of Drugs in Dermatology Year : 2017 | Volume : 3 | Issue : 2 | Page : 94-96 Brimonidine “Rebound:” Worsening of rosacea following topical application of brimonidine gel Sujata Mehta Ambalal

Watch the Video! In a significant number of cases rosacea patients have been suffering damage caused by what is termed 'rebound' or an 'allergic reaction.' This post is to help you understand the difference. Rebound rebound (verb) [ no obj. ] (rebound on/upon) (of an event or situation) have an unexpected adverse consequence for (someone, esp. the person responsible for it): Nicholas's tricks are rebounding on him. rebound (noun) • [ usu. as modifier ] the recurrence of a medical condition, esp. after withdrawal of medication: rebound hypertension. (obviously there are more definitions for rebound but I picked the pertinent ones) Found this medical dictionary that said: rebound : a spontaneous reaction; especially: a return to a previous state or condition following removal of a stimulus or cessation of treatment --withdrawal of antihypertensive medication may lead to a rebound hypertensive crisis—<Emergency Medicine> Rebound Effect "The rebound effect, or rebound phenomenon, is the emergence or re-emergence of symptoms that were either absent or controlled while taking a medication, but appear when that same medication is discontinued, or reduced in dosage. In the case of re-emergence, the severity of the symptoms is often worse than pretreatment levels." Wikipedia "Many antidepressants, including SSRIs, can cause rebound depression, panic attacks, anxiety, and insomnia when discontinued." Wikipedia There is a report that there may be rebound blood clotting when aspirin is stopped suddenly when taken over a long period. In rosacea, it is not uncommon for those who have been on long term antibiotic treatment for rosacea, i.e., doxycycline, who stop the treatment experience rebound, or a worsening of the rosacea. "Pimecrolimus and tacrolimus could be effective for rosacea. However, both of them could also induce rosacea." [13] Is this a rebound effect from the treatment, an allergic reaction to the treatment or what exactly is such a reaction called? Rosacea Rebound with Brimonidine There is one case of brimonidine rebound after two years of using it, which is the generally accepted use of the term ‘rebound.’ In another paper on this subject it is called "brimonidine rebound/contact dermatitis". “Some subjects in the clinical trials discontinued use of Mirvaso topical gel because of erythema. Some subjects in the clinical trials reported a rebound phenomenon, where erythema was reported to return worse compared to the severity at baseline” [1] "An observation noted during the clinical trials and subsequently after this agent reached the United States marketplace is that a subset of individuals (10–20%) have experienced worsening of facial erythema during the course of rosacea therapy with topical brimonidine." [1] "It has been noted over time that 10 to 20 percent of patients treated with brimonidine 0.33% gel experience reversible worsening of facial erythema, usually presenting as either paradoxical erythema shortly after application or rebound erythema after eventual loss of pharmacologic effect or drug discontinuation." [1] One paper suggests naming "dermatitis medicamentosa" for this phenomenon and reports, "Rebound erythema secondary to use of topical brimonidine in the setting of rosacea is an important, possibly significantly distressing potential side effect that may be under-reported; there is little photo-documentation in the literature to date. " [2] "For example, real-world use has shown that a percentage of patients (in our experience, approximately 10 to 20%) treated with brimonidine experience a worsening of erythema that has been called "rebound." Our routine use of this agent for >1 year has yielded strategies to set patient expectations, optimize treatment initiation, and minimize potential problems; this article details those strategies. Because we believe that the term "rebound" has been used to describe several physiologically distinct events, we have also proposed more specific terminology for such events." [7] "We report a case of facial erythema of rosacea that responded well to this medication, however, rebounded with significantly greater erythema than baseline for the patient." [8] "Rebound reactions have previously been reported with alpha adrenergic receptor agonists administered nasally and ophthalmically. Rebound is medically defined as a reversed response occurring upon withdrawal of a stimulus." [9] "We propose that this reaction constitutes rebound dilation of the capillaries caused by down-regulation of alpha-2 adrenergic receptors following use of BT. This may be similar to rhinitis medicamentosa, observed with overuse of alpha-adrenergic agonist nasal sprays (eg, oxymetazoline and xylometazoline).4 This reaction directly opposes the goal of therapy." [10] "Exaggerated rebound erythema ~12 hours after application of brimonidine topical gel has also been reported. The erythema may be worse than baseline but typically resolves within 6–12 hours." [11] "Case reports have been included to highlight several instances of contact dermatitis and rebound erythema in patients who used topical brimonidine gel, in contrast to the relatively low incidence of these adverse events in early studies." [11] (bold added) Rebound is a Possible Multifactorial Effect The two top reasons for a Mirvaso-induced rebound affect are: 1. The stimulation of Hypoxia-Inducible Factors from adjacent skin cells and from within the vascular smooth cell layer of the blood vessels - these are potent dilators that measure oxygen saturation in and around cells to ensure adequate oxygen delivery. Over constriction or hours of constriction can greatly deplete oxygen saturation and inadvertently stimulate very potent dilators. 2. Over time, alpha-1 and alpha-2 adrenoceptor stimulation increases the production of inducible nitric oxide, which is the primary inflammatory form of nitric oxide -- we see this a lot in Vascular Micro-Physiology and Pharmacology. The other problem that patients will note over time is a decreased constrictor response (different from rebound dilation): 1. This is because overstimulation of alpha adrenoceptors results in downregulation of receptors (ie. they decrease in number on the vessel surface and internalize) 2. G-Proteins uncouple from active alpha adrenoceptors which blocks the signal cascade transduction -- which in turn -- blocks the ability of vessels to constrict This is an oversimplification of a complex physiological process, but that is why it is always better to block a potent dilator than add an active constrictor. Galderma acknowledges the rebound effect with Mirvaso. "Phase III trials (Fowler et al. 2013) – 2 patients (1.6%) discontinued the study because of adverse events (severe skin irritation in one subject and “intermittent rebound erythema” in the other subject)." [12] "During clinical trials, some subjects discontinued use of brimonidine topical gel because of erythema or flushing. Onset of flushing ranged from 30 minutes to several hours after application and disappeared after discontinuation of brimonidine tartrate. For some subjects the new onset erythema was worse compared to the severity at baseline. Intermittent flushing occurred in some subjects treated with brimonidine tartrate topical gel." [12] Allergic Reaction to Medicine Any prescription or nonprescription medicine can cause an allergic reaction. Allergic reactions are common and unpredictable. The seriousness of the allergic reaction caused by a certain medicine will vary. Allergic Reaction to a Medicine - WebMD So one of my questions is how does one differentiate an allergic reaction from rebound? Isn't it possible that what everyone is calling a rebound could be an allergic reaction to a medicine? It seems logical to me that in some cases what is called a ‘rebound’ could be an allergic reaction to brimonidine since the reaction happens rather quickly. A significant number of the reports of brimonidine treatment for rosacea indicate this happens within the first few days of initial treatment. All the examples of rebound I found listed for medical rebound above involve using a drug for a long period and then stopping the drug and a rebound happens, for example, rebound headaches. Take for example those who have an allergy to penicillin. If given penicillin they react quickly with rashes, hives, itchy eyes, swollen tongue, and in severe cases anaphylactic reaction. Usually one finds out rather quickly if one has an allergy to penicillin. "Topical calcineurin inhibitors, pimecrolimus and tacrolimus, can be used to treat rosacea. However, they can also induce rosacea-like eruptions." [13] Are the 'rosacea-like eruptions' an allergic reaction or a rebound effect? It seems logical that some of the 242 anecdotal reports using brimonidine may indicate that what everyone is calling 'rebound' might instead be an allergic reaction. Allergic Reaction to Brimonidine "MIRVASO topical gel is contratindicated in patients who have experienced a hypersensitivity reaction to any component. Reactions have included angioedema, urticaria, and contact dermatitis" "Allergic contact dermatitis was reported in the clinical trials for MIRVASO topical gel" "Events reported post marketing with the use of MIRVASO topical gel include angioedema, throat tightening, tongue swelling, and urticaria," "Systemic Adverse Reactions of Alpha-2 Adrenergic Agonists" "Local Vasomotor Adverse Reactions" The above quotes are taken from Hypersensitivity and Adverse Reactions from the Mirvaso Package Insert "Allergic contact dermatitis, although reported on occasion, appears to be a relatively uncommon adverse event associated with use of brimonidine 0.33% gel for rosacea." [1] "However, there have been reports of cutaneous adverse reactions at the site of brimonidine application. These include flushing, worsening erythema, burning sensation, and contact dermatitis, most of which present immediately or early in the course of therapy." [3] "Topical application causes vasoconstriction of superficial vessels at the site of application, allowing for the reduction of erythema. We hypothesize that the reaction seen in our patient represents a compensatory vasodilation of vessels in the surrounding skin due to chronic vasoconstriction at the site of long-term brimonidine use. Findings from history, physical examination, laboratory testing, and histopathologic examination ruled out several other etiologies, including photosensitivity and autoimmune conditions. We therefore conclude that this is a probable adverse drug reaction to brimonidine." [3] The authors of this paper avoid the term rebound and refer to a patient who "after 7 months of brimonidine treatment, showing compensatory vasodilatation and flushing in untreated areas of right lateral cheek, neck, and chest." "Physical examination revealed marked bright erythema diffusely covering areas of the lateral cheeks, neck, and upper chest. Interestingly, there was clear sparing of the sites of brimonidine application on the central face." The authors describe this event as "a probable adverse drug reaction to brimonidine." [3] Cookson et al describes an allergic contact dermatitis caused by Mirvaso. [4] Bangsgaard et al describe two cases of "Sensitization to and allergic contact dermatitis caused by Mirvaso." [5] In a letter to the editor, Ashray Rajagopalan and Bishakha Rajagopalan describe "Allergic contact dermatitis to topical brimonidine." [6] "Early studies reported low incidence of contact dermatitis and rebound erythema with topical brimonidine tartrate, but recent case studies suggest that these are potentially significant reactions. Contact dermatitis to either vehicle ingredients or brimonidine occurred in multiple patients." [11] "Case reports have been included to highlight several instances of contact dermatitis and rebound erythema in patients who used topical brimonidine gel, in contrast to the relatively low incidence of these adverse events in early studies." [11] (bold added) "Allergic Contact Dermatitis – occurred in about 1% of subjects across clinical trials. Patch testing of 2 subjects revealed sensitivity to brimonidine tartrate in one subject and sensitivity to the preservative phenoxyethanol in the other subject." [12] RRDi MAC Members Comments Note: I sent emails to all the MAC members about this question and a few responded by email to me the following - note Post #7 by Dr. Anna Holmes😞 The source for all these replies below can be found here (scroll through all the posts in the thread all the way down). The replies are listed below for your convenience: Reply from Raymond Peat, Ph.D. "I don't think either allergy or rebound would be the best description for the direct promotion of the secretion of inflammatory cytokines by a vasoconstrictor drug or its excipients. Since nitric oxide, prostaglandins, and inflammatory cytokines probably contribute to the problem, non-toxic inhibitors of those, such as vitamins A, E, and K, aspirin, and caffeine might be helpful for the basic problem." Dr. Peat gave the following references: J Neurosci Res. 2002 Jan 15;67(2):264-74. Tumor necrosis factor expressed by primary hippocampal neurons and SH-SY5Y cells is regulated by alpha(2)-adrenergic receptor activation. Renauld AE, Spengler RN. Department of Pathology, School of Medicine and Biomedical Sciences, Buffalo, New York, USA. Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA) differentiated SH-SY5Y cells were examined. Intracellular levels of TNFmRNA accumulation, as well as TNF protein and that released into the supernatant were quantified by in situ hybridization, immunocytochemistry and bioanalysis, respectively. Both neuron cultures demonstrated constitutive production of TNF. Activation of the alpha(2)-adrenergic receptor increased intracellular levels of TNF mRNA and protein in SH-SY5Y cells after addition of graded concentrations of the selective agonist, Brimonidine (UK-14304) to parallel cultures. Intracellular levels of mRNA were increased in a concentration-dependent fashion within 15 min of UK-14304 addition and were sustained during 24 hr of receptor activation. In addition, the levels of TNF in the supernatant were increased in both types of neuron cultures within 15 min of alpha(2)-adrenergic receptor activation. Furthermore, levels of TNF significantly increased in the supernatants of both neuron cultures after potassium-induced depolarization. A reduction in this depolarization-induced release occurred in hippocampal neuron cultures after exposure to the sympathomimetic tyramine with media replacement to deplete endogenous catecholamines. This finding reveals a role for endogenous catecholamines in the regulation of TNF production. Potassium-induced depolarization resulted in the release of TNF in hippocampal neuron cultures within 15 min but not until 24 hr in SH-SY5Y cultures demonstrating a temporally mediated event dependent upon cell type. Neuron expression of TNF, regulated by alpha(2)-adrenergic receptor activation demonstrates not only how a neuron controls its own production of this pleiotropic cytokine, but also displays a normal role for neurons in directing the many functions of TNF. Copyright 2002 Wiley-Liss, Inc. Br J Ophthalmol. 2007 Jan;91(1):29-32. Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs. Malvitte L, Montange T, Vejux A, Baudouin C, Bron AM, Creuzot-Garcher C, Lizard G. CHU Dijon, Service d'Ophtalmologie, 3 rue du Faubourg Raines, 21000 Dijon, France. laure.malvitte@wanadoo.fr AIM: To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis. METHODS: Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays. RESULTS: In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group. CONCLUSION: This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H231-8. Brimonidine evokes heterogeneous vasomotor response of retinal arterioles: diminished nitric oxide-mediated vasodilation when size goes small. Rosa RH Jr, Hein TW, Yuan Z, Xu W, Pechal MI, Geraets RL, Newman JM, Kuo L. Department of Opthamology and Surgery, Scott and White Eye Institute, Texas A & M University System Health Science Center, Temple, TX 76508, USA. rrosa@swmail.sw.org Brimonidine, an alpha2-adrenergic receptor (AR) agonist, has been employed in the treatment of glaucoma due to its beneficial effects on intraocular pressure reduction and neuroprotection. In addition, some studies have implicated that brimonidine might influence ocular blood flow; however, its effect on the retinal microcirculation has not been documented. Herein, we examined the vasomotor action of brimonidine on different branching orders of retinal arterioles in vitro and determined the contribution of the alpha2-AR subtype and the role of endothelium-derived nitric oxide (NO) in this vasomotor response. First- and second-order retinal arterioles of pigs were isolated, cannulated, and pressurized for functional studies. Videomicroscopic techniques were employed to record diameter changes in response to brimonidine. RT-PCR was performed for detection of alpha-AR and endothelial NO synthase (eNOS) mRNA in retinal arterioles. All first-order arterioles (82 +/- 2 microm ID) dilated dose dependently to brimonidine (0.1 nM to 10 microM) with 10% dilation at the highest concentration. Second-order arterioles (50 +/- 1 microm ID) responded heterogeneously with either dilation or constriction. The incidence and magnitude of vasoconstriction were increased with increasing brimonidine concentration. Administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester abolished the brimonidine-induced vasodilation in first- and second-order arterioles. Regardless of vessel size, vasomotor responses (i.e., vasodilation and vasoconstriction) of retinal arterioles were sensitive to the alpha2-AR antagonist rauwolscine. Consistent with the functional data, alpha2A-AR and eNOS mRNAs were detected in retinal arterioles. Collectively, our data demonstrate that brimonidine at clinical doses evokes a consistent NO-dependent vasodilation in first-order retinal arterioles but a heterogeneous response in second-order arterioles. These vasomotor responses are mediated by the activation of alpha2-AR. It appears that brimonidine, depending on the concentration and vessel size, may alter local retinal blood flow. ------------------------------------------------------------------------------------------------------------------------ Reply from Anna Holmes, PhD Allergic sensitization was measured by patch testing patients across the Mirvaso clinical development program with suspected allergic contact dermatitis. The overall incidence of confirmed sensitization was less than 1%. Sensitization can occur, but the incidence is low. Reply from Robert Latkany, M.D. "Mirvaso is 0.33% brimonidine gel. Brimonidine has been used to lower intraocular pressure on the eyes for glaucoma for years. It typically is not a first line agent and has had several modifications over the years. The most recent formulation is Alphagan P 0.1% by Allergan. This concentration appears to cause less redness and irritation than the higher concentration bottles. In fact, I often use this drop to decrease the redness in some patients with fairly prominent vessels that are disfiguring. I am pretty sure there is an ophthalmologist seeking a patent on the use of brimonidine to address "red eyes". So all that said, there is probably a role here for facial erythema. But further studies will need to be done on what concentration is most appropriate and what frequency is needed. My guess is it should be given in 4 week cycles in a diluted concentration but a study should easily determine the most successful approach." Reply from Husein Husein El-Ahmed, MD Allergic reaction is a immune-mediated process which requires a previous contact of antigen presenting cells to the drug. This first contact shows no symptoms in the person, and it is known as sensibilization. Once one person is sensibilized, the second contact to the drug leads to a rapid reaction including rash, itchy eyes, swollen tongue, and even, anaphylactic reaction. Rebound is a NON-immune-mediated process in which the symptoms are caused for the effect or the lack of effect (discontinuation) of a drug. This reaction is rather quickly, but no immune cells are implicated, in overall terms. Since Mirvaso was lanched in my country (Spain), I have observed poor impact on my clinical practice: This drug is targeted to reduce erythema on rosácea (Flushing) with many researches supporting its efectivity. However, most of my patients suffering from rosacea do not complain on flushing, but permanent redness for which brimonidine gel is not indicated. This reduces dramatically the prescription of this drug on my daily clinical practice. I have discussed this matter with my local colleages and they have found the same limitation in this way. Reply from Joseph Fowler, MD In the clinical trials that I am aware of, there were few if any reports of this "rebound" phenomenon occurring. Also, in the many patients that I have prescribed the drug for, I have had a few who felt Mirvaso did not work as well as they wished. But I have had only 1 patient have worsening of redness as the drug effect wears off. So while I'm sure there are some patients who don't like Mirvaso, the majority in my experience have had beneficial effects. As I am sure you are aware, it is much more likely for someone to send in negative comments than to report in when they are satisfied with a product. Perhaps those who are experiencing unwanted effects haven't been initially counseled by the prescribing doc about appropriate usage and application techniques? perhaps other diagnoses instead of or in addition to rosacea are in the mix? Perhaps there are other reasons for less than optimal success being reported. At any rate, since the effect of topical brimo is very transient, I can't imagine any serious adverse effects and any "reaction" lasting more than a few days probably suggests something else is going on in the patient's skin. It is unfortunate that not all patients respond perfectly to this or any other drug, but from what I have seen it is a very valuable agent to combat erythema of rosacea. Conclusion It is very clear from the package insert that comes with each prescription for Mirvaso that an allergic reaction was found in the clinical trials in some cases and that happens post marketing. It is also conclusive that Galderma acknowledges the rebound issue with Mirvaso. Whether you experience an allergic reaction or rebound depends on who describes the event and the history. Reply to this Topic There is a reply to this topic button somewhere on the device you are reading this post. End Notes [1] J Clin Aesthet Dermatol. 2017 Jul; 10(7): 28–32. Topical a-Agonist Therapy for Persistent Facial Erythema of Rosacea and the Addition of Oxmetazoline to the Treatment Armamentarium: Where Are We Now? James Q. Del Rosso, DO, FAOCD, FAAD [2] Dermatol Online J. 2015 Jan 1;21(3). pii: 13030/qt93n0n7pp. Dermatitis medicamentosa: severe rebound erythema secondary to topical brimonidine in rosacea. Werner K, Kobayashi TT. [3] JAMA Dermatol. 2015 Oct;151(10):1136-7. doi: 10.1001/jamadermatol.2015.1252. Full Text Erythema in Skin Adjacent to Area of Long-term Brimonidine Treatment for Rosacea: A Novel Adverse Reaction. Gillihan R, Nguyen T, Fischer R, Rajpara A, Aires D. [4] Contact Dermatitis. 2015 Dec;73(6):366-7. doi: 10.1111/cod.12476. Allergic contact dermatitis caused by Mirvaso®, brimonidine tartrate gel 0.33%, a new topical treatment for rosaceal erythema. Cookson H, McFadden J, White J, White IR. [5] Contact Dermatitis. 2016 Jun;74(6):378-9. doi: 10.1111/cod.12547. Sensitization to and allergic contact dermatitis caused by Mirvaso(®) (brimonidine tartrate) for treatment of rosacea - 2 cases. Bangsgaard N, Fischer LA, Zachariae C. [6] Australasian Journal of Dermatology, LETTER TO THE EDITOR, https://doi.org/10.1111/ajd.12299 Allergic contact dermatitis to topical brimonidine Ashray Rajagopalan, Bishakha Rajagopalan [7] J Drugs Dermatol. 2015 Jan;14(1):33-40. Optimizing the use of topical brimonidine in rosacea management: panel recommendations. Tanghetti EA, Jackson JM, Belasco KT, Friedrichs A, Hougier F, Johnson SM, Kerdel FA, Palceski D, Hong HC, Hinek A, Cadena MJ. [8] J Am Acad Dermatol. 2014 May;70(5):e109-10. doi: 10.1016/j.jaad.2014.01.853. Full Text Brimonidine effective but may lead to significant rebound erythema. Ilkovitch D, Pomerantz RG. [9] J Clin Aesthet Dermatol. 2015 Aug;8(8):29-35. Dermatological Adverse Events Associated with Topical Brimonidine Gel 0.33% in Subjects with Erythema of Rosacea: A Retrospective Review of Clinical Studies. Holmes AD, Waite KA, Chen MC, Palaniswamy K, Wiser TH, Draelos ZD, Rafal ES, Werschler WP, Harvey AE. [10] J Am Acad Dermatol. 2014 Feb;70(2):e37-8. doi: 10.1016/j.jaad.2013.10.054. Full Text Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%. Routt ET, Levitt JO. [11] Patient Prefer Adherence. 2017; 11: 1143–1150. Spotlight on brimonidine topical gel 0.33% for facial erythema of rosacea: safety, efficacy, and patient acceptability Michael S Anderson, Anish Nadkarni, Leah A Cardwell, Hossein Alinia, and Steven R Feldman [12] National Drug Monograph, March 2015 Brimonidine Topical Gel (MIRVASO) VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives [13] Topical calcineurin inhibitors as a double-edged sword in rosacea: a systematic review