Guide

May 14, 2020

Nina Dobrev, a Canadian actress and model, has rosacea. [1]

end notes

[1] Nina Dobrev Shared Her Secret for Combating Rosacea, LAUREN REARICK, TeenVogue

May 14, 2020

An American actress, producer, director, and singer, Brittany Snow, has rosacea. [1]

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End notes

[1] Brittany Snow Cleared Her Chronic Rosacea Using These 5 Products, Amanda Montell, Byrdie

May 14, 2020

The American actress and filmmaker, Brie Larson, has rosacea. [1]

End notes

[1] Instagram

Red Carpet, Red Face: Rosacea In Hollywood, NRS

May 14, 2020

The actress, Naomi Watts, is reported to have rosacea. [1]

End notes

[1] Naomi Watts Says She Suffered from 'Miserable' Rosacea While Filming Netflix's Gypsy, People

May 14, 2020

The actress, Julia Fox, is reported to have rosacea. [1]

End notes

[1] Red Carpet, Red Face: Rosacea In Hollywood, NRS

May 13, 2020

[3] Ivermectin Anti-Inflammatory Properties

"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."

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End Notes

[1] Inflammation, Wikipedia

[2] From Depression to Dementia, Inflammation Is Medicine’s New Frontier, Edward Bullmore, The Guardian, Pocket Worthy

[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.

May 13, 2020

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?

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May 13, 2020

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

May 9, 2020

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.

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May 9, 2020

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.

May 8, 2020

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

May 8, 2020

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

May 8, 2020

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
------------------------------------------------------------------------------------------------------------------------------------------------

May 6, 2020

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

May 4, 2020

(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

May 3, 2020

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.

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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

May 2, 2020

Life-on-hold reports how to Alleviate Mirvaso Rebound Flushing

May 2, 2020

There are basically two schools of thought when it comes to treating rosacea, the 'more is better' philosophy, and the 'less is more' thought.

+ = √ More is Better
Generally, the 'more is better' philosophy treatment plan is what rosaceans prefer, based upon anecdotal reports of what a typical rosacean is using to treat rosacea. This is usually because their physician recommends an oral systemic treatment, either low dose, timed released doxycycline as well as a topical ivermectin (Gold Standard). Old school dermatologists continue to prescribe a high dose oral doxycycline and a metronidazole topical. These are just two examples of multiple treatments for rosacea, and there are other examples too numerous to list. Anecdotal reports of rosaceans using over the counter products for rosacea usually range from two or more treatments at the same time. Physicians use multiple approaches in treating rosacea. For example, a patient with severe rosacea phenotype 2 and 4 was treated with multiple treatments.

Rosaceans typically will think that if this little treatment improves my rosacea then 'more is better' and while on occasion this may be the case, i.e., Carvedilol (Coreg) to treat flushing, the dosage may actually need to be increased if the physician recommends, this is not always the case, when it comes to using multiple, concurring rosacea treatments. Furthermore, when taking more than one drug for rosacea, there are drug interactions to consider (synergism).

- = + Less is More
Of course, not every decision you make about rosacea treatment means 'less is more,' but in the number of concurring treatments, this should be a chief concern. The less is more approach simply means to use just one rosacea treatment at a time to see if it improves the rosacea. If you think the treatment is working to improve your rosacea, then stop the treatment to see if the rosacea comes back or gets worse. If it does come back or gets worse, it usually indicates the treatment worked. The best way to prove it does work is then again use the one treatment again after you have stopped the treatment and see if your rosacea improves again. Voila! Eureka! This rosacea treatment has proved to work and if the treatment is stopped my rosacea returns or gets worse.

Then if you still feel you need to add another treatment along with the one that is working for you, add another or second treatment for rosacea and notice if it gets better or gets worse. If it gets worse, stop the treatment and see if you return to your baseline (how your skin was before you started the second treatment). If you return to baseline then if you want to completely convince yourself you could try it again to see the results. If the same, surely this is enough convincing. If not, then experiment.

If the second treatment improves your rosacea along with the first treatment, then wondeful! To convince yourself, remove the second treatment to see what happens? If removing the second treatment your rosacea gets worse, then you know. Try using the second treatment again and see if it improves again. Convinced?

You could then even add a third or fourth rosacea treatment, but do so in this systematical, one at a time approach or 'less is more.'

You can do this simple approach of 'less is more' using the above method since you can clearly know if a rosacea treatment is for you or not.

Multiple Treatments for Rosacea Can Cause Confusion
If you are taking multiple treatments for rosacea, this can create a quagmire of confusion. Lets take a typical example to show you.

Lac_77 at RF [post no 4] replied to a thread about Mirvaso rebound with the following post dated April 29, 2020 at 01:58 PM:

"I had the same reaction to you only a few weeks ago After only 5 days of using it it sent my skin crazy. I stopped using it and the symptoms persisted for about another 5 days, then returned back to how it was previously thankfully (still terrible though). I hope that is the same for you."

Lac_77 [post no 1] started a thread on the very same day (April 29 at 02:07 PM) just a few minutes after posting the initial post mentioned above about "seriously intense flushing constantly" due to his five month course of accutane. So, his experience using Mirvaso, pales into insignificance when you consider five months of accutane at 20 mg/day.

To conclude the Mirvaso for his flushing issue would be tantamount to a blatant injustice. How can anyone figure out what causes 'permanent' damage in these cases of concurring rosacea treatment which blurs into confusion. Also when someone uses photo dynamic therapy, i.e., IPL, Laser, etc., there are reports that these devices all cause skin damage as well and the difficulty of sorting through what has caused 'permanent' damage is a maze of spider webs, not to mention what are the systemic oral treatments doing to the issue as well, since most rosaceans are taking oral medication treatment at the same time, i.e., antibiotics, anti-flushing drugs, etc. and possibly other topicals all at the same time! Other factors to consider that may have a bearing on the damage is the environment, i.e., sun, chemicals, activities, heat, cold, etc., which can further aggravate the damage, since they should also be ruled out.

To conclude, multiple treatments for rosacea not only confuse but also blur treatment decisions. A 'less is more' approach would resolve this.

One Treatment at a Time - Less is More
That is why using ONE treatment at a time is so much better than taking multiple rosacea treatments since it is so difficult to figure out what is helping and what is causing damage in multiple treatments for rosacea which is common among rosaceans who figure 'more is better' rather than a simplified approach. 'Less is more' is a better approach.

The typical example above with Lac_77 who has damaged his skin with accutane treatment taking high dose for five months and then he tries Mirvaso on already damaged skin, what do you think would happen? This is an example of multiple treatments confusing the issue and how the more is better approach can really cause damage and further confusion.

Less is More in Medicine
The less is more approach in medicine is particularly advocated in homeopathic medicine. The JAMANetwork has a page dedicated to this concept. Jessica A. Otte, MD, has a website and a blog devoted to this subject. Joan Stephenson, PhD, Contributing Writer for MedPage Today, wrote an article on a movement concerning this topic stating, "Whatever changes are needed to move the less-is-more movement forward, the idea has staked its claim in the culture of medicine."

"In dermatology, doctors are opting to order the medicines they want, without the inactive ingredients they don’t, at the dosage they need, and dispensing these medicines directly to patients at the point of care. These doctors are taking control of how they are treating their patients." [1]

“It is an art of no little importance to administer medicines properly; but it is an art of much greater and more difficult acquisition to know when to suspend or altogether omit them” [2]

"In our collective enthusiasm to diagnose and treat disease, a growing body of evidence indicates that we may often be doing too much of a good thing." [3]

Rocky Bilhartz, MD wrote an article, stating, "You can always do less in medicine, but you’re amiss by thinking that less is always more. What’s good for the group is not always good for the individual." [4] So not every rosacea treatment decision warrants a 'less is more' approach.

A significant number of articles on the 'less is more' in medicine focuses on economic waste and reducing costs. One article is typical, "As 2017 ended, the influential writer and cardiologist Lisa Rosenbaum challenged the tenets of the less-is-more movement in the New England Journal of Medicine....Rosenbaum concluded that "Mitigating waste is imperative," but she argued that doing so means considering the nuances of complex medical decisions and that what may be perceived as a greed for dollars may reflect a hunger for information." [5]

Conclusion
Whether you choose a 'more is better' or a 'less is more' approach in your treatment decisions with your rosacea will without a doubt have consequences. There really are treatments that work with either method and you, the rosacea patient, has the decision to decide which is the best one to use for your rosacea. Always, the remember the customer (the rosacean) is always right. The customer is coming to the medical provider (the seller) for advice and counsel which the customer (the rosacean) is paying for. Whatever the customer decides is always right (including consequences, risks and benefits).

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End Notes

[1] When Less Is More in Medicine, Sep 23, 2019, Physician's Weekly

[2] Healthc Policy. 2016 Feb; 11(3): 6–7.
De-prescribing: When Less Is More in Healthcare
Jennifer Zelmer, PhD, Editor-in-chief

[3] Learning More from ‘Less is More’ Medicine
By Carla Berg | September 13, 2017, Society for Participatory Medicine

[4] The problem of “less is more” in American health care, Rocky Bilhartz, MD, KevinMD.com

[5] In Defense of Less-Is-More, John Mandrola, MD, Commentary, MedScapehttps://www.medscape.com/viewarticle/891091#vp_1

May 2, 2020

Gold Standard Treatment for Rosacea moved to here.

April 30, 2020

Folliculitis is another rosacea mimic added to the long list of skin conditions or diseases in a differential diagnosis of rosacea. DermNet NZ has a number of photos with various causes due to bacteria, yeasts (fungus), virus, parasites, immunosuppression, inflammatory skin diseases, i.e., Lichen planus, Lupus and others, and environmental causes, i.e., chemicals, drugs (steroids). One report mentions "rosacea-like folliculitis" in describing it as a rosacea mimic. [1]. A google image search shows some photos that mimic rosacea. Deep dive into folliculitis.

End Notes

[1] J Clin Med. 2020 Apr; 9(4): 1241. Published online 2020 Apr 24. doi: 10.3390/jcm9041241
Dupilumab for the Treatment of Atopic Dermatitis in an Austrian Cohort-Real-Life Data Shows Rosacea-Like Folliculitis
Tamara Quint, Patrick M. Brunner, Christoph Sinz, Irene Steiner, Robin Ristl, Kornelia Vigl, Susanne Kimeswenger, Katharina Neubauer, Detlev Pirkhammer, Martin Zikeli, Wolfram Hoetzenecker, Norbert Reider, Christine Bangert

Pruritis and Rosacea

MORE INFORMATION

April 29, 2020

Higher doses of isotretinoin, but more importantly, low dose isotretinoin, has been reported to be a successful treatment for rosacea. You should be aware of the risk/benefit ratio with this treatment if you are not aware of these facts. Are you aware of isotretinoin induced rosacea?

For more information on isotretinoin.

However, in some cases there are reports of it inducing a worsening case of rosacea inflammation, hence, the possibility of causing Isotretinoin Induced Rosacea (IIR), aka, Iatrogenic Rosacea or Rosaceiform Dermatitis [see list of differential diagnosis of rosacea to consider]. Just as long term treatment with Topical calcineurin inhibitors (TCIs) or with long term steroid treatment can result in Steroid induced rosacea, long term isotretinoin treatment can also isotretinoin induce rosacea.

For example, one report states regarding treating acne with isotretinoin, "However, isotretinoin must be used with caution, as paradoxical induction/exacerbation of acne fulminans has been reported." [1] Acne fulminans (AF) developed during use of isotretinoin in low doses. [2] "Isotretinoin treatment for acne can lead to inflammatory flare-ups or an aggravation, occasionally leading to acne fulminans." [3] One paper lists the adverse effects (AEs) of isotretinoin treatment in acne which may include, "resulting mostly from changes to the eyelids and the surface of the cornea or lacrimal abnormality that leads to dry eye. The association is documented in the literature, with case reports describing blepharoconjunctivitis, keratoconjunctivitis sicca, cutaneous photosensitivity, contact lens intolerance, refractive changes, papilledema, pseudotumor cerebri, and abnormal retinal function....abnormal meibomian gland secretion, blepharoconjunctivitis, corneal opacities, decreased dark adaptation, decreased tolerance to contact lenses, decreased vision, increased tear osmolarity, meibomian gland atrophy, myopia, ocular discomfort, ocular sicca, photophobia, pseudotumor cerebri, and keratitis." [4]

Furthermore, there are anecdotal reports of Accutane Induced Rosacea. A typical example of these reports is Dave, who posted, "I'm 6 months post accutane and still having some flushing issues but it is getting a bit better. I'd say I started to see slight improvement during months 5 and 6. I've talked to other who said it took up to a year for the flushing to resolve itself." [flying_er post no 2 30th December 2011 04:55 PM] The list of anecdotal reports keeps growing.

The treatment for Isotretinoin (Accutane) Induced Rosacea will be listed in this post for your benefit.

Treatment

(1) Obviously stop isotretinoin intake and call your dermatologist and make an appointment for further treatment.
"All abnormal findings in these studies were reversible shortly after cessation of the isotretinoin treatment." [4]

(2) Let the skin heal on its own for a few days, washing only with cool water.

(3) Take analgesic medicine for any pain

Anecdotal Treatments

Lucy says she uses mepacrine. [Lease143 post no 1]

lucy_nic87 started a thread on this subject and uses Finacea, propanolol, clonidine, mepacrine

Peter B reports he is on mepacrine and clonidine which help control the worst of the flushing.

Ray reports quinacrine helps

Plaquenil (Hydroxychloroquine)

chris123 started a thread on this treatment and reports at post no 21, "It's been about 2 months since I started the plaquenil, and the past 2 weeks or so my flushing has subsided materially. I don't flush as often, and when I do it's not quite as severe, and it doesn't last as long."

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So if you have a treatment that works for your isotretinoin induced rosacea, why not help other rosaceans with this same issue and find the reply to this topic button and post!

End Notes

[1] Indian Dermatol Online J. 2013 Apr-Jun; 4(2): 133–142.
Paradoxes in dermatology
Keshavmurthy A. Adya, Arun C. Inamadar, and Aparna Palit

[2] An Bras Dermatol. 2011 Sep-Oct;86(5):983-5.
Acne fulminans and isotretinoin: case report.
Pereira MF, Roncada EM, Oliveira CM, Monteiro R, Abreu MA, Ortigosa LC.

[3] Ann Dermatol Venereol. 2001 Mar;128(3 Pt 1):224-8.
Acne flare-up and deterioration with oral isotretinoin
Chivot M.

[4] JAMA Dermatology July 2012
Ocular Adverse Effects of Systemic Treatment With Isotretinoin
Meira Neudorfer, MD; Inbal Goldshtein, MSc; Orna Shamai-Lubovitz, MD; et al

April 29, 2020

Watch Video

The logo of the RRDi includes a butterfly because rosacea typically manifests itself in a facial butterfly formation. "Half a century ago, Edward Lorenz, SM ‘43, ScD ‘48, overthrew the idea of the clockwork universe with his ground-breaking research on chaos." [1] Lorenz created an analogy with the flapping wings of a butterfly what beautifully describes how the initial conditions may create an effect not imagined. What are the initial conditions with the result in rosacea chaos?

Victor Gabriel's Butterfly Effect in Acne and Rosacea
A paper written in 2018 by Victor Gabriel, et al., discusses the 'butterfly effect' not only in rosacea but also in acne. The concept of the butterfly effect "is associated with chaos theory, and it is a concept originated in meteorology, which represents the dependence on initial conditions." [2]

"The butterfly effect (in chaos theory) represents the sensitive dependence on initial conditions, that is, a very small change in one state of a deterministic nonlinear system is associated with large differences in a later state." [2]

Initial Conditions in Rosacea May Help Explain the Rosacea Chaos
"Acne and Rosacea are chronic inflammatory skin diseases with an increasing frequency and an important negative impact on the quality of life, which are associated with a large number of false myths regarding causes and treatment." [2]

The butterfly effect psychologically may have a profound result in finding a cure for rosacea considering the initial mental conditions (scroll below to the subheading, Butterfly Effect in Psychology).

False Myths and Misconceptions in Acne
"Acne represents the most common diagnosis made by dermatologists, and unfortunately, a common misconception among medical and lay communities is that acne is a self-limited teenage disease and thus, it deserves not the same attention as that paid to a chronic disease." [2] Actually, "acne occurs very frequently in adulthood." [2]

The internet is replete with rosacea false myths, one paper indicates, "A total of 385 websites were included. About 44.7% of the shared content was rated as imprecise, 20% as confusing, and 35.3% as precise." [2a]

"Misunderstanding and misinformation is associated with the beliefs that poor hygiene, hormones, diet, cosmetics, infection or stress are the factors that exacerbate acne in teenagers. Patients use ”acne treatments” (cleansers, acne pads, masks, cover-up products, acne lotions, etc.) before seeking medical attention. It was reported that 74% of such patients waited more than 1 year before medical consultation." [2]

Butterfly Effect in Rosacea
Gabriel explains the butterfly effect in rosacea is based upon the 'initial conditions' that are 'associated with a large number of false myths regarding causes and treatment.' Gabriel explains, "From the authors’ point of view, “the butterfly effect” associated with Acne and Rosacea is represented by education about these chronic inflammatory skin diseases, with emphasis on myths and skin care, because the power of false myths keep patients away from medical care; also, correct and individualized skin care is associated with a better adherence to treatment and results." [2]

Similarly, it was reported in one large survey conducted by Galderma that it took on "average, women with rosacea waited at least seven months before receiving a correct diagnosis." [3]

Male patients with telangiectasia tend to wait to seek treatment due to the false myth that the skin condition is not serious. [18]

As with false myths in acne mentioned previously, similarly it could be said about rosacea that it is a 'cosmetic' issue that doesn't deserve serious medical attention, which is also a common misconception or false myth.

Another false myth is that demodex mites on pets do not transfer to humans. [15]

An example of a 'false myth' with rosacea initial conditions is the belief that rosacea progresses in stages which has been debunked. [19]

Some rosaceans think that flushing is rosacea, a common misunderstanding that is an example of a false myth with rosacea. [16]

Rosacea social media websites are replete with 'fake news.' [17]

Butterfly Effect with Rosacea Research
This is an important butterfly effect to consider for rosaceans. A paper by Elisabeth Pearson Waugarman, PhD, [9] emphasizes the need for rosaceans to unite in a patient advocacy non profit organization group to find the cure for rosacea. Dividing off into different social media private groups or forums is counter productive. Read the RRDi Mission Statement. If we could get enough rosaceans to unite into a giant butterfly with 10K members and each donated one dollar we could sponsor our own rosacea research. That would be an incredible butterfly effect.

Butterfly Effect in Inflammation
"We hypothesize that low-grade inflammation in early life (especially an imbalance between pro- and anti-inflammatory macrophages) triggers a "butterfly effect" within the arterial wall by initiating a sequence of processes that finally leads to atherosclerotic plaque development and progression." [6]

Butterfly Effect in Healthcare Systems
“When we look at the growing diversity of the populations our healthcare systems serve, we must ask ourselves this question: “What systemic by-product of yesterday is limiting our understanding of organizational needs today, pre-empting our competitive advantage?" The report concluded that, “the underestimated importance of diversity among healthcare leaders and care providers across the industry has limited our capacity for greater success.” [8]

Butterfly Effect in Psychology
"Recently, meterologists made a startling discovery about monarch butterflies—a discovery for which they have no explanation. Monarchs migrate in a gigantic cluster that forms the shape of a butterfly. The implications of this discovery are startling. Could it be that, like small fish, the monarchs gather together to form a large group that looks like a very large, inedible, butterfly? If this is the case, like small fish, butterflies have a sense of their identity. What is the message for us? If fish and butterflies unite for safety in numbers, surely humans have the same ability; but, instead, we divide ourselves into myriad groups that take precedence over our humanity. We need to relearn that to survive, we have to be united. With the butterfly effect, we can be." [9]

Butterfly Effect in the Underrepresentation of Women
The butterfly effect may explain why "the persistent underrepresentation of women is more likely to reflect unconscious bias, unequal family responsibilities, and gender stereotypes" in the economic gender gap. [4]