21 March, 2018

The Warm Room Theory, and how being in cold air could make your flushing and skin burning worse

When my skin burns and flares and feels on fire, the most natural urge is to open all the windows and let in cold air. Or to put my head in a bucket of cold water. Or to sit right in front of a powerful air conditioning machine. The colder the better! But according to the Warm Room Theory, this is actually not the best thing to do when you have rosacea. Making your rosacea skin very cold, might cause rebound worsening in the long run, according to Colin Dahl.

He explains that it is normal for anyone with rosacea to get a rush of warmth up the cheeks when entering a warm room. Every person that gets too hot, can rely on their body to deal with the overheating, usually by stimulating the body to sweat (a way to release excess heat from the body) but also by widening the blood vessels in the skin. The wider the vessels are, the more warm blood will be closely exposed to the skin and be able to lose some of its heat that way.

When the body signals the blood vessels in our skin that the body is overheating, then the body activates nerves in the skin to dilate the blood vessels in the skin (vasodilation). The way in which the nerves do this, is by releasing certain chemicals, that message to the blood vessels to widen. And to make the effect even stronger; the more blood flows through the blood vessels, the more these blood vessels themselves release chemicals to keep this vasodilation going. This is a normal process; everyone alive experiences this, or else we humans wouldn't be able to regulate our temperature or fight off infections or have proper wound healing, for instance.

The problem occurs when our skin has too many of these flushing events. When it becomes very frequent that the skin flares red and hot. This is the moment that the blood vessels are dilated for a longer period over time, and that the vessels give off a signal that make the body create new (and thus more!) blood vessels in the skin (angiogenesis). The bodies way to create more infrastructure for this extra blood flow. This principle is also normal, but in people with healthy skin it is a limited occurrence. For people with rosacea, it is however the mechanism in which our rosacea progresses, slowly over many years, from mild to moderate, to severe. Because when you have more blood vessels and more nerves in your skin, you will have more dilation of blood vessels and more facial flushing, especially when you are in a warm room and your body goes through its normal steps and paces to cool off the body.

The good news is that this process is reversible, according to the author of the Warm Room Theory, Colin Dahl. So a person with rosacea will have more blood vessels and nerves in the skin than a person with healthy skin, and they have been made by the body to release heat. They will give a rosacea face often the distinctive red(der) cheeks and sometimes also nose and chin or forehead. The human face and head are special, in that they have more and different blood vessels and nerves than any other area of skin on the body. They have special nerves to dilate blood vessels and special blood vessels to release the heat carried in the blood.

The nerves involved in these areas are sympathetic nerves. They can act to dilate special blood vessels
(arteriovenous anastomoses), which open up and shunt blood into the blood vessels of your skin, creating the phenomenon we know as the flush. This also explains why many people have intense flushing confined to certain regions of the face. many people with rosacea flush on their cheeks, some (but far less) also flush in their neck and chest and it is very rare to find rosacea patients who flush on the rest of their body, unless they have other skin conditions that cause skin problems elsewhere. Rosacea, however, is mostly limited to the more densely vascularized face, where our skin is also thinnest, compared to other body parts. Showing the redness in our dilated blood vessels even more!

More on these nerves in the skin that are involved in skin flushing
Another important type of nerve involved in rosacea is the sensory nerve. Unlike sympathetic nerves that are triggered centrally in the brain, sensory nerves are locally handling the blood vessel dilation in the skin. When your face is exposed to sun for instance, or to a skin care product that has irritating ingredients, then it are the sensory nerves that can act immediately and signal to the blood vessels in the skin to dilate and give off a warning signal to us. They play a role in rosacea flushing, as such.

When our blood vessels in the skin dilate, after being signaled to do so by the sensory nerves, they not only become wider and let more blood through, but they also create local inflammation, which
in turn makes our nerves in the skin give off a burning pain feeling. For most people with rosacea, a deep flush is therefore painful, feeling hot, sore and like a burn almost. Due to rosacea, more nerves are created along with the new blood vessel infrastructure, but the existing nerves can also become hypersensitive. This can explain why early on, with mild rosacea, facial flushing can be fairly painless, but later on the flushing can create moderate to severe pain and hot burning sensations; the nerves in the skin have become super reactive and sensitive from the long history of being triggered by flushing attacks of the skin. As a result, some people with rosacea have such a sensitive and extensive nerve and blood vessel infrastructure, that even a small increase in blood flow will result in significant flushing episodes.

Chemicals involved in facial flushing
There are hundreds of known chemicals involved with nerves and blood vessels. But there are very specific chemicals released by our nerves and blood vessels, when we have rosacea and suffer from facial flushing, such as neurotransmitters, neuropeptides and growth factors. Neurotransmitters are chemicals that transmit a nerve signal to other nerves as well as other tissues, such as blood vessels. Neuropeptides do the same, but are stronger and act longer. Both can signal blood vessels to dilate or constrict, and nerves to feel pain or to go numb again. There is something special going on with these neuropeptides, research showed. More on this soon.
 Growth factors, released by skin cells, help to maintain existing blood vessels and nerve structures, and also make it possible for both to grow. They also play a role in the process of our nerves becoming more sensitive and easily triggered to feel burning and pain. When the nerves in our skin are activated (for instance during a flush), this in turn stimulates more growth factor release, like a waterfall-construction. They are all in place to help the body deal with overheating, but with rosacea patients this system of blood vessels and nerves and chemicals are going in overdrive, causing our increasing facial flushing and red faces.

Understanding the warm room flush
When people with rosacea step from a cold environment into a warm room, we are likely to get a flush. Why is this? When we are in a cold environment, our bodies naturally has a built-in system to conserve heat. In the cooler environment, the body will constrict
blood vessels in the skin. These blood vessels carry warm blood, and the wider the blood vessels are, the more body heat is released to the air, and thus the colder the body gets. In a cold environment, this is not wanted! So the body automatically constricts the blood vessels in the skin, giving the skin a more pale look and keeping the warm blood well inside, to contain and retain our body heat. We not only have more blood vessels in our facial skin than those with 'healthy skin', we also have more skin nerves to go with it, who can constrict all these extra blood vessels when it is cold. Normal skin builds up a small amount of inflammatory chemicals such as neuropeptides in the cold, but because we have so many more blood vessels and nerves in our rosacea skin zones, these build up a large storage of neuropeptides. Our faces feel often cold to the touch now and the same goes for our hands and feet. But when blood vessels get too cold they begin to automatically dilate, because the blood vessels lose their ability to constrict, causing redness of the skin. This is why in the cold of winter, many (northern) people have a blushed face. It rarely burns however for them.

Neuropeptide storage
In cooler environments, chemicals the body uses to dilate blood vessels are no longer getting released
much. If the person is in a cool environment for a long period of time, then these dilating chemicals such as neuropeptides, the major (inflammatory) dilating chemicals released by the body, begin to build up. Neuropeptides can only be made in small amounts by the body everyday. So the nerves have a way of storing these chemicals to use when needed. Similarly, other dilating chemicals are also building up their availability. Now research has shown that more neuropeptides are released in rosacea skin during flushes, and also that the body of a rosacea patient makes new neuropeptides faster than normal. They play a role in the warm room flush phenomenon.

So when we walk from a cold environment into a warm room, as rosacea patients, we tend to flush. Our skin has more blood vessels and nerves, and therefore our skin gets more red and warm and sooner than normal too. But because our skin has been building up inflammatory neuropeptides while we were in the cold environment for some time, our skin has been building up inflammatory chemicals such as neuropeptides. We walk into the warm room, and our internal thermostat tells our skin that we are hot. The body quickly responds by initiating the release of heat. Nerves are activated in the skin to dilate blood vessels and trigger other nerves. These nerves can now release not just a small amount of neuropeptides, but ALL of the built up neuropeptides that we accumulated while being in the cold environment. Remember that more neuropeptides are released in rosacea skin, and also that the body of a rosacea patient makes new neuropeptides faster than normal. So while we are in the warm room, the nerves release their abundant neuropeptides in a big burst. As a result, we get a lot of blood vessel dilation in the skin, and this triggers the nerves in our skin even more, with the end result; a red hot burning facial flush. The extra blood flow stresses our blood vessels out, and in turn make them release more chemicals that keep the blood vessel dilation ongoing or even worse.
If you get it bad enough, the flush can be very difficult to cool down, even when we go back into the cold outdoors again.

Then after some time, for no apparent reason, the flush abruptly goes away. The skin has worked its way through the entire storage of the neuropeptide chemical and needs now time to rebuild the storage.

Colin Dahl has an important suggestion regarding how we can avoid these extreme flushes, triggered by moving from cold to warmer environments
Colin Dahl himself had rosacea flushing, and noticed that when he stayed abroad in a country with a stable warm climate, his rosacea flushing calmed down. Back home in his home country of Australia (where he did experience seasonal temperature changes), he tried to create a summer-like environment, by using heaters to prevent his face and body from getting cool (without getting too hot). He got through the winter and saw further improvement in his skin redness and flushing. He continued the experiment in the summer, but this time the cool environment was inside due to air conditioning. The warm room was now outdoor exposure to hot weather. he again tried to continually release neuropeptides throughout the day, by not allowing his skin to get too cold. He did use air conditioning sparingly during the summer, only to reduce very warm environments like hot cars. But he did not focus cool air directly on his face (flush zones) and did not get too cool. Again he noticed a great reduction in overall flushing and his facial redness was further improved. Over time he also noticed a greater tolerance to warm environments.

When he had to go back to China, it was approaching winter there. He was spending eight hours a day in a cold lab that was only 15 degrees Celsius. After just a few days he began to experience  warm room flushing again. Only once he started working in a heated room again, did the warm room flush stop. Even short periods in below zero weather did not cause the warm room flushing to re-appear. He wondered if the build up of neuropeptides and other inflammatory chemicals cause of all his rosacea flushing? Unfortunately the answer is no. However, this build up did play a major role in warm room flushing and warm environment flushing, both very common flushing triggers.

Colin Dahl sees a correlation between cooler environments and rosacea. In tropical southern
China there is little rosacea found, but as you travel north towards areas that experience cold winters (think of Mongolia!), rosacea is much more common.

The heat regulation process in rosacea skin, as described above, may have much to do with this
‘inflammatory cycle’ of rosacea. This is likely due to the fragile balance of heat conservation and heat release systems seen in people with rosacea. Even slightly cool environments will kick off the heat conservation phase in flush zones, enabling greater stores of neuropeptides, which when released in large amounts are likely to result in a flush.

Many people with rosacea even try to stay in cool environments for long periods, trying to reduce facial flushes and redness that way. Let's face it; when your skin burns and feels and looks very hot, the natural thing to do is to find a cold area to find some relief. However, Colin Dahl states that this is counter productive in the end, because it can result in significant inflammatory neuropeptide storage. When you then eventually enter a warm environment, your skin has a build up of neuropeptides ready for release. In this situation a large flush will be difficult to prevent. he says that even slightly cool environments may cause neuropeptide storage to begin in your flush zones, as these areas begin to conserve heat very early. The impact of this neuropeptide storage may result in an increase in the number of warm room flushes and an increase in the severity in warm room flushes.

What is cool then and what is warm?
So how can you tell what is a cool environment and what is a warm environment? The answer according to Colin Dahl lies in your flush zones. If the flush zones of your face (cheeks, etc) are cool to the touch, then it is very likely that inflammatory chemicals such as neuropeptides are building up. Your flush zones don’t have to be red hot for these chemicals to be released. If you want to continually release neuropeptides gradually, then you want to have neutral to slightly warm skin (not hot and not cold). The longer you stay in a heat conservation phase (your flush zone feeling cold to the touch) then the longer the neuropeptide build up continues.

If the room you are in is warm, then your flush zones will not be building up these inflammatory chemicals. Even slightly cool environments will set your flush zones into heat conservation mode and neuropeptide build up, and slightly warm environments are enough to enable continual neuropeptide release in flush zones.

However, unless your rosacea is very mild, all this is often in itself not enough to get your rosacea back under control. If there is already an excessive flush zone and a lot of extra blood vessels have been formed over the years, then you need to reduce these blood vessel networks too. Colin Dahl  suggests IPL light therapy or laser treatments for this, to reduce the excessive amount of blood vessels in our skin. Read more about this here and here. He also stresses the importance of calming your rosacea flushing down in other ways. Avoid triggers like direct sunlight. Stop using irritating skin care products for instance, and switch to mild and neutral ones that sooth your skin (or in my own case, stop using all skin care products entirely. For the past 14 years I have only been washing my skin at night with bottled water and cotton pads and use jojoba oil around my mouth, leaving the rest of my skin alone. No wrinkles have been forming, despite the lack of anti ageing products and my skin is a lot less irritated because of it).

Anti flushing medication can also help to break the flushing cycle. This is very important according to Colin Dahl, and most dermatologists will stress the same thing; break the flushing cycle, and your skin and blood vessels get a break and a chance to normalize. If you reduce the over activity of the skin, you reduce the infrastructure required to maintain it. Less nutrients will be needed for supply, so less blood vessels are needed to get them there. Just as the body has a system to increase blood vessels and nerves in your skin to correlate with their activity, the body also has a system to reduce blood vessels and nerves in your skin when they are less active.  The body uses growth factor regulation as one method of achieving this balance. This is why reducing flushing and skin irritation is so important. Read also up about the use of vitamins and supplements for the normalization of inflammatory skin cells. Colin Dahl mentions natural compounds such as silymarin, egcg and vitamin B12.

My own experience with the Warm Room Flush suggestions

The problem I have with the warm room flush mechanism, is that it is impossible to implement for me, unless I want to stay in a controlled environment all day. It's winter here now and I had to go in and out of hot trains, buses, airports, planes and back into the cold and wind the past weeks. The same for visiting people, how do you avoid the sharp transitions from warm to cold and back again in every day life? Living in a country with not the same mild or warm temperature all year round.

It is a great theory and probably working for a lot of people. I have no doubt that in my mild/moderate rosacea days, this was very useful. But these days I have such dense vascularity in my face and such vasodilation (also from all sorts of other triggers, despite keeping neuropeptides low or not) that it is impossible to sleep in a - say- 22 degree Celsius room. Even in summer when temperatures are consistently around or above 22 degrees, sleeping in such a temperature will ensure a beet red pulsating face during the night/next day. And the day after. And the week and months after, if I keep up with sleeping in such high temperatures. Sometimes the face is such a vascular mess that I don't believe in a few transition days before the skin gets used to sleeping in such a hot room. That one probably works better for people with transient and milder flushing and not a red face continuously due to decades of rosacea flushing.

Colin Dahl suggests IPL and laser in his theory text, but they are not for everyone unfortunately. Some rosacea patients react badly to them, or have the misfortune of having hypersensitive, photosensitive skin like me. I had 2 full face IPL treatments by different doctors and a dozen of small area IPL treatments, as well as laser test patches, and it virtually all made my rosacea worse or did nothing. Unfortunately I am a poor responding patient, but both IPL and laser have helped many rosacea patients tremendously, to the point of letting them go into rosacea remission, so worth exploring as a patient (but be sure to find a good practitioner, with rosacea skin treatment experience and up to date machinery, and insist on test patches first!).

I am very happy when my skin feels cold to the touch. Because then I won't be burning and flushing. Ice cold is bad news (my skin gets very red from that sort of cold too, mainly in winter), but cool to the touch? Yayy! I take anti flushing medication and the cold feel of the facial skin is the sort of thing that anti flushing medication are aiming to achieve. To me, it feels counteractive to heat the place up to such a point that the skin feels warm again. Despite all efforts, there seem only three skin temperatures possible for me: cold to the touch, chilly to the touch, or burning hot to the touch. Like the skin lost the ability to just feel right. But when someone flushes not that often and has good periods of skin control, sticking to the warm room  flush theory might be the best non invasive thing around for now to avoid those awful temperature induced flares.

But it does help me too in other ways; I'm not making it as cold as possible anymore in the house when I flare, but a mild temperature. Same in heat of summer, not too cold with the air-conditioning, or there will be rebound once going outside in the heat. I do keep indoor temperatures higher than I used to, since understanding more about the warm room theory. It used to be 16 degrees or below in my house (yikes.... but my face was so hot and sore), and these days I do well on 17- 18 degrees celsius, and even a bit higher when it is natural warmth outside instead of central heating. I think my skin is less inflamed actually then, and it might explain why so many people with rosacea flushing and redness do better in summer than in winter..
Not everyone with rosacea has the same severity of burning and flushing, and not everyone can handle temperatures as high as 22-23 degrees I'm afraid. This is what Colin Dahl also highlighted in his writings, the need to first and foremost control the amount of flushing and excess vascularity one has.

I agree with Colin Dahls Warm Room Theory, and that being in a cold environment, or cooling the skin too much does indeed give a neuropeptide fueled flushing (rebound also) inferno when entering a substantial warmer room. But he also stresses in both the middle of his treaty as at the end, the importance of reducing the vast vascular/nerval infrastructure that rosacea skin often has. Through IPL in his view. or otherwise through trigger avoidance, skin care adaptations etc. So if someone has moderate to severe rosacea and flushing, he acknowledges himself that his avoidance of cold air is not going to cut it. And that the aim is to reduce this vascular network, first with the heavy guns if rosacea is bad enough, then through avoiding the cold to warm environment stress.

Unfortunately not everyone with rosacea has the same great experience with IPL. I had my mild rosacea sped to severe (24/7 flushing) after a botched IPL and it was literally the worst thing I have done in my entire life, probably due to the wrong practitioner and machine and also for having hyper reactive skin and being slightly photosensitive. I have only anti flushing medication now to make life bearable and curb the bad flushing. It s*cks but it is what it is.
Saying that the vascular network needs to be eradicated first is an open door and not as easy said as done for many patients. If your rosacea is mild, the warm room theory alone and trigger avoidance on top might make rosacea very manageable, but I think it is just one piece of the puzzle, as Dahl himself openly acknowledged in his piece as well.

Below is an impression of the experience from other rosaceans with the information gathered from the Warm Room Flush manual

Carly1981 wrote on November 7th, 2017: "Regarding the Warm room flush theory, I've read a little bit about it and I think I understand the concept, but how arduous is the path to improvement? I practically live in front of a small fan during the winter months because my cheeks flush so easily. If I ease up on using it, do I just have to push through the heat/flushes until they lesson?  I went to the theater over the weekend and after about an hour, I could feel my cheeks start to burn (my friends actually thought the auditorium was too cold). Of course this made me feel embarrassed, so the flushing was made worse. *ugh* I have the acne more or less under control now, but I can't seem to shake the flushing."

Rednessator wrote on November 7th, 2017: "The whole premise of this theory is that only heat causes flushes, but as we know, people have many triggers, thus keeping environment warm all the time might actually lay the bed for the other triggers."

BraceYourself wrote on November 10th, 2017: "I've been to the tropics and the weather there was at a constant 20 °C with not much humidity. My skin must've been around a constant temperature and it was fantastic. Then again there are many different factors that would've changed, since I was on vacation, so my diet, sun exposure, stress and sleep pattern were not the same as usual. So it might not just be the temperature, but an array of things. Back to the title of the thread; walking into a warm room from the cold is probably my biggest nightmare honestly, because I can't control ANYTHING at that point. Then once I go red I feel embarrassed, which causes a deep blush and that makes it even more awful."

Violetsareblue wrote on November 17th, 2017: "Flushing, I guess, is very complex. In my case it is/was a combination of a damaged lipid barrier (sun damage, seb derm etc), hormonal fluctuations (my period, estrogen), body temperature over the day and menstrual cycle, Raynaud's syndrome (overactive vessels), bad physical shape in general (diet and blood circulation), depression and passivity. I still see a logic in the warm room theory but there is def more to it.. And def things we can effect even if we don't think so.
I have managed to almost eradicate my flushing through an improved diet, skin barrier and avoidance of freezing or spending to much time in cold and dry environments, working out more (getting better blood circulation). Its winter here now and I barely have any flushing atm. I occasionally have some issues with what I believe is caused by my low blood pressure, but really, I am so so much better then I was a year ago. My rosacea also almost completely vanishes when I go to warm, humid places..

I remember the doctor used to tell me that stress was a big factor in rosacea and I didn't understand it back then because I never flushed from stress. But the fact that long term stress and depression actually constricts your blood vessels all over your body, making your whole system tense and cold makes us more prone to flushing as well.. To be continued.."

Dzed1 wrote on November 17th, 2017: "Hi, I didn't meant that there are no other factors, you are right stress is huge thing same as hormones. What I meant was specifically for cold-warm exposure. Also you said Raynaud's syndrome, see there are conditions that overlap with rosacea, that's why I managed to learn quite a bit for this condition, and trust me many different chronic diseases are the same - I stand by my theory that rosacea is associated with CVD, blood clots, and insulin resistance destroyed digestive tract (immunity) this are the primary causes imho. Many people talk about demodex, let me tell you why they are not the issue. If you got good immunity, no demodex will ever do any harm to you, when i get on better diet - and started to use the methods i explained in the other threads, suddenly no demodex.....so no, they are not the cause, they come after."

Violetsareblue wrote on January 26th, 2018: "So I just wanted to report some of my latest findings regarding warm room theory etc. since I noticed the connection cold face, nose body and then flushing etc. I have tried to keep my body warm lately. I have started to keep a little electric radiator by my side at work for example so that I don't get into freeze mode anymore. My experience so far is really positive. Most of all, my body is much more relaxed which feels good and it feels like I build up less tension overall, tension that can possibly enhance flushing later in the day. My nose is also more even temperature all day which I think is beneficial. I rarely experience cheeks flushing nowadays however, if it happens its when I talk to cute guys haha (and that might be pretty normal).
I have had continuous progress with my rosacea since I went paleo in April 2017. I have made several radical life style changes so its hard for me to say exactly what is making me better but maybe "every little helps". I know the diet was a big one, doing colon hydrotherapy in August 2017 was another and a good routine with nice skincare + metronidazole cream was yet another. The progress for me is  extremely slow, but if I look back a year, the progress is obvious. A year ago I couldn't even wear a turtle neck because it would make me over heat and flush, I had to keep my windows open all time to cool my face. If I went into a warm room my face would explode into flushing/swelling within five minutes. All of this is totally gone now and my life is back to normal. Instead I find I love the warm and do all I  can to stay warm. 

I rent a flat and it has central heating that my landlord has decided. I have a few thermometers to keep my eye on the temp and it stays pretty even at 23 degrees celcius, which is warm for Sweden. My home is comfy temp and I rarely feel cold there. A year ago I couldn't handle this temperature at all and slept just with a thin cotton sheet on me but now I am fine and can sleep with a normal duvet.

My body usually stays warm until around 11-12 am at work and then I need to put the radiator on as I start to get colder. I feel it in my hands and feets, nose but also pretty much my whole body. I have also changed in my office space so I have a standing desk because sitting makes me very cold, tired and enhances flushing. At around 4-6 pm I get warm again and tapper down the extra heating. I think for me the next thing to try to add is some of this old type of humidifiers to my flat.

Regarding supplements I take a few: vitamin D3, C, zink, magnesium and iron. Every other day also cod liver oil and omega3. I also take antihistamines at night. To be continued.. And all my best to all of you /V"

Whiteshadows wrote on March 20th, 2018: "Its crazy to me that the warm room flush theory doesn't have more traction on this forum, I've used it and my flushing has all went away except for alcohol (which is just from a enzyme deficiency, look up asian flush). I remember when my rosacea started when I was around 13, I would go outside in -20 degree weather, waiting for the bus, going outside for hours with nothing covering my face. I would go inside an bam intense flush. Obviously the vicious cycle starts when I started to try to stay in cold rooms all the times only making things worse without knowing it. The theory makes so much sense and its also why so many people clear up when they go to the tropics. The opposite is also true if one lives in a hot climate but are in AC all day long, they will flush when they go out its just in reverse.

Warm room flush theory should be tagged for every newcomer to see.

I live in Canada and the theory worked super well for me also. From experience its not as much that you need to keep a consistent temperature, the trick is that you must not let your face get cold. When my rosacea was at its worst I would do the opposite and try to maintain cold temperatures, but I always flushed in warmer rooms because my face was accumulating neuropeptides. Hot trains, buses, and airports are not problems IF you make sure you're face doesn't accumulate neuropeptides by being cold for long periods of times. HOT environments will only be a problem is you let your neuropeptides accumulate by being in cold environments for to long. If you put your hand on you face and feel that it is cold it means your accumulating neuropeptides. When you go outside in the cold you wear a scarf to keep your face warm (preventing it from accumulating neuropeptides). When you are home and sleeping the temps must be 22 Celsius or above, if the temperature is less than that I feel me face is cold and accumulating.

Ever noticed how in the summer 22 degrees feels cold yet in the winter it feels warm and can make you flush? That's because in the summer your neuropeptides are not accumulating (unless you work in a very air conditioned environment. You will flush the first times though but you have to go through it, for me it lasted one night I slept with the temp at 23-24 I flushed like crazy (depleted my neuropeptide reserve). But the morning after I started to keep my face warm consistently and I pretty much never flushed again.(except for alcohol, and emotions but i feel these are normal and not rosacea caused). At this point I truly believe most peoples flushes are caused by this theory and some people have more severe rosacea the longer they have been stuck in the loop of keeping face cold which is the opposite of what one has to do. Ultimately this builds more and more blood vessels which makes skin even more sensitive. The less you flush the less blood vessels your skin will have long term."

Antwantsclear wrote on March 21st, 2018: "When my ear flushing was very bad before using the medications, I could not manage a warm room to sleep in, for example. However, now I prefer a moderately warm room (e.g. 23 C). But hydroxychloroquine/mepacrine made my flushing more tolerable. I think you do need to either have mild flushing or otherwise control moderate to severe rosacea flushing sufficiently in order to get the warm room syndrome theory to work.

The other point here is that hydroxychloroquine and mepacrine are anti-parasitic drugs which I think do help control the demodex population. Demodex mites do respond to warm temperatures - in my experience they go crazy when you consistently have to deal with a temperature above about 25C-27C. There is broader evidence beyond rosacea to show that demodex mites respond to temperature in their levels of activity and breeding etc. So, I also do find that controlling the mites topically with almond oil and tea tree oil combined does help - that has to be on the hair and the face. I notice a lot less itching from the mites etc when I consistently use the oils. Again the warm room syndrome works better when the mite populations are under control - otherwise a hot room means increased demodex mite activity - flushing, burning and itching."

Whiteshadows wrote on March 21st, 2018: "Its true that for some people with too much "infrastructure'' or vascularity, like you said, the warm room flush may be hard to apply. The doctor that came up with the theory mentioned in the article that for some people they may require initial IPL or v-beam laser to reduce their infrastructure or vascularity as you said . He even says the more flushes one gets the more infrastructure ones builds and the less flushes one gets the body will reduce the infrastructure naturally.
Yes rosacea meds make it a point to make the face feel cold but most of them cause a rebound effect similar to the release of neuropeptides. Essentially they work because they do the same thing a cold room does do your vessels which is constricting them. keeping the face warm may sound counter intuitive I remember thinking that was crazy back when it was bad but it truly makes sense now since now i make it a point to mostly never let my face become cold to touch since I know that although it may feel good my face is only accumulating neuropeptides to be released down the line.

This is an original forum discussion about the Warm Room Flush research at the time it first came out, and its author Colin Dahl also chimes in, answering some questions

Artist wrote on March 2nd, 2008: "WOW David this is an amazing read! I posted some excerpts and commented here and there, but I just think everyone should read this whole thing. VERY eye-opening. Please read The Warm Room Flush!!! I'm just going through it now. This reminds me of a camping trip one year. We went camping and it was only around 60-65 degrees most of the time. During the whole trip my skin looked amazing. My vessels were completely constricted at all times. On the way home, we went into a warm restaurant and I ate. I had the biggest "warm room" flush ever. It was very sudden, and awful. Now I realize that, while my skin was cool, dilating chemicals were not being used - so they built up. So, after such a long time building up, there was an abundant amount to be released. I think this also helps explain why many of us do worse in the winter going from warm to cold rooms.. Thanks for finding this.

The author actually has rosacea. Perhaps this also explains why I do so well in tropical environments.
I think a lot of us try and do this: "Many with rosacea even try to remain in cool environments for long periods in an attempt to reduce facial flushes from occurring. However, this is counter productive because it can result in significant inflammatory neuropeptide storage. When the person eventually enters a warm environment they have a build up of neuropeptides ready for release. In this situation a large flush will be difficult to prevent." Interesting!!!! Artist"

Quiller wrote on March 23rd, 2008: "I like the neuropeptide buildup idea because it's original, and testable. It looks like one of the neuropeptides is Substance P, which always interested me because it sounds so mysterious. Here's a nifty illustration of how it interacts with Nitric Oxide.

David Pascoe wrote on March 4th, 2008: "It is certainly an interesting thought that is worth exploring further to see if we can't understand how much this might help. The author did say it wasn't the cure, but did help. It is probably too hard for all to follow this sort of temperature regulation regime, but if it does help it is worth exploring and understanding it fully."

Melissa W. wrote on March 4th, 2008: "This is probably a silly question but what about people who can stay flushed for days? Doesn't the dilating chemical (neuropeptides) get depleted and shouldn't the flush die out sooner? I remember when I was first diagnosed I was fortunate enough to get to speak with Dr. Peter Crouch and he warned me not to sleep in too cool a room as that may require me to keep in cooler and cooler temps and harder to tolerate the warm room temps. I'm not sure he knew the mechanism behind this at the time but he was right! Best wishes, Melissa"

AustralianSciences (Colin Dahl) wrote on March 4th, 2008: "Hi Melissa, Regarding your question about those who stay flushed for long periods. The booklet does advise those in this situation to reduce their excessive heat regulation infrastructure (through IPL) before attempting some of the recommendations in the booklet. I can explain the reason for this a little further for you. In this situation, the person would obviously has an excessive heat regulation infrastructure (more nerves and blood vessels). This extra skin infrastructure is also involved in the generation of neuropeptides and inflammatory chemicals. So the flush won't die out faster, in fact it will last longer because more of these chemicals are being produced and released. If you have less of this heat regulation infrastructure in your skin, you will produce less of these inflammatory chemicals. Best regards, Colin Dahl"

Rusie wrote on March 4th, 2008: "Hello all, I have many questions regarding the warm room flush. First, thank you David for posting this info. I have had rosacea for three years now and for three years have been trying to keep my face cool or cold, even at night. I constantly have fans blowing on me and keep my house at 60 degrees in the winter (where I generally do better) and 69 degrees in the summer and spring (where I generally do worse). My general problem is facial flushing, not really p&p's. After three years of constantly trying to keep my face cool, with every trick you can imagine, how do I now stop and keep it warm? Should I use a gradual process? I should also mention that I get warm and hot easily, which results in a flush. Nighttime is especially hard for me, as it is difficult for me to sleep if I am not cool. Any suggestions?? I live in the Atlanta, Georgia area so it is hot in the summer and cool, but not extremely cold (most of the time) in the winter. Thank you for any help or advise any of you can offer. Rusie"

Eric123 wrote on March 4th, 2008: "I really enjoyed this booklet and think it will prove to be of great help. I had a couple questions
1) Is there any way to release the neuropeptides, if you have stored them up, other than a flush? I noticed in Asia that topical application of L-Menthol on the back of my neck quickly resolved any flush, as did a proper neck/upper back massage.... could this be releasing or diverting the neuropeptides away from my flush zones to the neck/back areas?
2) Are there any neuropeptide inhibitors, topical or internal, which might be useful to achieve balance?
3) How does this affect how we regulate our temperature with things like hot drinks, chewing on ice chips, etc...? Chinese medicine always warns of drinking cold drinks, eating ice cream, etc... and I seemed to notice a marked decrease in my flushing episodes after I began to drink only room temperature water and other drinks."

AustralianSciences (Colin Dahl) wrote on March 7th, 2008: "Hi Rusie, I can totally relate to your situation. I kept myself in a cool environment for a few years too. It didn't help me and I can guess it is not working for you too. If you keep yourself in that cool environment you are setting yourself up for more flushes and longer flushes, which is likely to progress your rosacea even further. But what to do now? If I was you, I would find out how my body reacts to long periods of slightly warm temperatures. It doesn't really matter what happens the instant the air conditioner goes off, or when heater goes on. What matters is what is happening several days later. Don't be afraid to experience flushing during this initial period (think of this as a positive, you are reducing your build up of inflammatory chemicals in your flush zone, take advantage of this!). You are trying a medication free approach here, you really have nothing to lose and everything to gain. As the booklet states, if you just go from hot to hotter in even slightly warm environments (while restricting cool environments for a number of days) then it is possible that your heat regulation infrastructure is just too excessive to attempt this regime at this time, so IPL is recommended in the booklet. A good indication on excessive infrastructure is how much redness you have in your flush zone.

Rosacea takes many years of flushing and skin excitation to progress. If you reduce the flushing and skin activity downwards every month, you are progressing towards the reversal of rosacea. For example purposes, you don't have to go from 10 flushes a week to zero in order to begin reversing rosacea. If you do experience 10 flushes a week for an extended period of time, then the infrastructure in your skin will be in proportion to 10 flushes/week. If you go down to 9 flushes a week for an extended period of time, then the infrastructure in your skin will be in proportion to 9 flushes/week. And so on. (I left out skin activity in the example, I didn't want to make it too complicated). Maybe I can discuss it next time. Best regards, Colin Dahl"

AustralianSciences (Colin Dahl) wrote on March 8th, 2008: "I typed ROSACEA into google, because for the last few years I haven't looked at what rosacea resources were on the internet. At the top of the list is rosacea.org I read their Winter 2008 Newsletter. A feature story is about research they funded on Demodex Mites. Are we still talking about this rubbish? To spend time and money on this kind of research is an insult to people with rosacea and anyone who donated to them. Am I the only one who feels like this? The other research isn't much better.
Let me save them their research budget for the next few years with the following advice. At its most basic definition, Rosacea is an inflammatory condition. The severity of the condition is in relation to the inflammation/skin infrastructure. People with a basic understanding of rosacea should know that just about every kind of inflammatory chemical can play a role (vaso, nero, immuno). So isn't it then obvious that many of these chemicals will be elevated or over reactive in rosacea. Then why would you bother looking to see if one of these chemicals is increased or overactive? In my opinion, people with rosacea deserve much more innovative research than this! Maybe if people wrote to them and demanded better research then a positive may be achieved out of this. Best regards, Colin Dahl, Australian Sciences"

Oops.. In light of the recent research on the role of demodex in (subtype 2) rosacea, this was a little misstep perhaps from Colin.

AustralianSciences (Colin Dahl) wrote on March 8th, 2008: "I no longer suffer from rosacea. I believe the key is flush minimization and reducing skin cell activity. I will try to post some messages on this over the next few weeks. One way to is to avoid flushing triggers, but you can't avoid all flushing triggers in the real world. So, together lets think of ways to minimize flushing (that doesn't involve avoidance of triggers). If you can't think of one you get an F (because the booklet talks about some ways). Best regards, Colin Dahl, Australian Sciences"

Artist wrote on March 8th, 2008: "Colin, Here's my idea on how to minimize flushing: Move to someplace tropical, where the temperature is pretty much the same all year round (absolutely fabulous), and no one has air conditioning! I think that would work like a charm for me.  :)
I have a question. So, in your opinion, while we are down-regulating our facial skin infrastructure, should we be upset by slight pinkness from allowing our skin to be "slightly warm"? My thinking is that the deep flushes, or the ones that make you pretty red with a hot or burning feeling are the ones we need to worry about. I obsess about ALL pinkness, even if it's mild and I can only see it..not really feel it. I think "it's making my rosacea progress!" Should I stop worrying about that? I think I should, because when I see ANY pinkness, I immediately try to cool myself off. This would decrease my stress over my skin.. I'm thinking I only want to worry about decreasing the deep, hot, burning flushes I get maybe twice per week. Correct?

I think your theory really makes complete sense. It follows basic physiology, and the notion that our bodies have natural compensating abilities - like negative feedback/positive feedback, hormones, blood pressure compensation, collateral blood vessel growth, heart rate, respirations, etc..it just makes sense. I'm very interested to see how folks do over time with the suggestions. Cheers!

AustralianSciences (Colin Dahl) wrote on March 9th, 2008: "Hi Artist and Quiller,
Firstly Artist, you are correct. Concentrate on reducing the larger flushes. There's nothing wrong with being a little pink or red. Try not to obsess, you're increasing stress hormones, which cause more vasodilation and redness. Also, the deeper flushes (as you put it) tend to correspond with sympathetic nerves and the burning sensation with the more peripheral sensory nerves. They can act individually or together. But the burning component is a very troubling one. Maybe it will be easier to discuss ways of minimizing flushing and skin cell activity in real situations. Do you mind volunteering and telling us what causes your two flushes every week? Best regards, Colin Dahl Australian Sciences"

Artist wrote on March 9th, 2008: "Hi Colin: I'd say my big flushes occur for four reasons:
1) Early on many of my deep flushes were from "blushing" due to things like embarrassment, taking a test, interview, social situations, tense moments at work, etc. The beta blocker, Atenolol, has taken care of most of this problem. I still suffer from this type of "deep lasting blush" a few times a month maybe. I've considered talking to my doctor about increasing my dose of Atenolol, but I think it might lower my blood pressure too much. I do want blood going to my brain, after all ;) The Atenolol is amazing. I went from deep blushng every day, to just a few times a month or so.. Beta blockers curb the sympathetic "fight or flight" response. People often use them for "stage fright" for this very reason. They may feel anxious, but they don't appear anxious. No sweating or rapid heart rate, or blushing.. So, in my experience, beta blockers minimize sympathetic blushing.
2) Food. I flush badly to certain foods. Red wine, certain alcohols, aged cheese, most processed foods with large ingredient lists. I have to eat very basic. I had a semi-deep flush yesterday from the comination of a few drinks, lots of brie cheese, and slightly smoked chicken. We were also went on a long walk in 55 degree weather. I was talking socially with some new friends. The combination was what did it, I'm sure. So, avoiding food triggers helps prevent flushing, but it's a real pain and NO fun.
3) Skin being cool for a while, then going into a warm room, or especially eating at a warm restaurant. Last week I took my son to the park. It was about 55 degrees out. We were out for a few hours. We walked to a diner on the way home. It was probably about 75 degrees there. I didn't eat much while I was there, but I flushed big-time. It had been quite some time since that had happened. I had an IPL just a few days earlier, so my skin was still sensitive from that and I should have found someplace else to stop. Anyway, I held some cool wet napkins to my skin and the flush lasted maybe ten or fifteen minutes. When that happens, the flush does stop suddenly - just like you describe in your booklet. I wonder if attenuating that type of flush when it happens would help. Cooling the skin with a wet napkin might slow the release. Or, would it snuff out the release? Once the neuropeptide release starts, should you try to slow or stop it?
4) "Sudden Cool-Down" If I'm running around all morning, physically, while concentrating and focusing (I'm a nurse). After a morning like that, sometimes sitting in the lunch-room and eating my lunch brings on a deep flush. I think of it as the "sudden cool-down". That's been an issue for me off and on. Lately it's not bad, but there have been times when it happened every day. This will also occur if I do high-impact exercise - getting my heart rate up and sweating - something like running a few miles, etc. I don't flush during it - only afterwards while cooling down.

Of course, I flush if I get way too hot, but it has to be very hot. Maybe in the 90s and I'd have to be exerting myself at least moderately. Another one is deep concentration. I notice I breathe very shallow while concentrating deeply - reading, writing this email, etc. We know that, in general, you should avoid temperature extremes and wear a scarf on your face if the weather is cold. What we didn't know is what happens with skin infrastructure and that we may have the ability to reverse it. We didn't know that, by focusing too much on trying to stay cool all the time in order to avoid the acute trigger of "warmth", we could allow our infrastructure to build up over time. When we talk about improving rosacea long-term, the discussion centers around skin irritation. What can we do to decrease irritation and treat inflammation. Cheers! Artist"

AustralianSciences (Colin Dahl) wrote on March 12th, 2008: "Hi Artist, Thanks for your information. The flushing triggers you mentioned are all normal responses (just exaggerated in accordance with the level of your skin infrastructure). In regards to beta blockers, they can be very effective. In my own experience they initially did not give much benefit (due to my very excessive skin infrastructure). But later I was able to use them successfully when my skin infrastructure was less excessive. Apart from the dose or level of drug/neurotransmitter, I believe another reason for this comes back to how the body handles stress. The beta blocker drugs block one of the major stress induced vasodilation pathways. If your skin infrastructure is only moderately excessive then blocking this one pathway may be enough to prevent a stress related flush from occurring. However if your skin infrastructure is very excessive then blocking this one pathway may not be enough to prevent a flush. The body often has many ways of achieving important functions.
One problem I found with beta blockers is that they caused dry eyes. I eventually replaced beta blockers with biological approaches to reduce the availability of blood to the facial region, thereby reducing flushing. In meetings where I thought a flush may occur, I initially tried to have the meetings in cool rooms. This in effect was constricting blood vessels in my skin and reducing the release of inflammatory chemicals (which can be a powerful opposing force to skin vasodilation). An additional approach was to have a large meal before the meeting. Regardless of which part of your body is experiencing vasodilation or vasoconstriction, overall you still have the same amount of blood in your body. So by having a meal before a meeting I was causing vasodilation in my digestive system, which forces vasoconstriction in the rest of the body (even muscles, which is why you feel tired after a meal meal). (Note Scarlet Nat: this is not the case for everyone! Digesting a large meal can for some rosacea flushers also create heat in the body by the digestion process and flare UP flushing in fact). 
Finally I adjusted the cool room approach by staying in a slightly warm environment prior to meetings, this automatically avoids large build ups of inflammatory chemicals including neuropeptides, so no matter what trigger was around the corner, you are well positioned to handle it better. By combining all of these flush reduction approaches (as well as others involving reducing skin cell activity) I no longer need to take beta blockers to prevent stress related flushes.

Yes, it is good to cool the skin during a flush, especially early on to stop it progressing. Flushes cause changes to the skin (more blood vessels and nerves). However, I would like to make one point that is very important. Reducing flushes alone may not be enough to stop or reverse rosacea. Flushing is only one way the body uses to increase blood vessels and nerves. It has many others. For me additional factors were sunlight and skin irritation.

You asked what you can do to reduce skin irritation and inflammation, well you can do a lot. Regardless of the actives or excipients, even the most basic moisturizer needs to have preservatives, which are irritants. I don't use topicals on my face, because I know they will irritate. The only thing I do is wash with soap (if you wanted to moisturize your skin you could use a moisturizing soap like Dove). If you use a moisturizing cream on the surface of your excessive skin infrastructure, then you will still have excessive skin infrastructure, but with softer skin. Best regards, Colin Dahl
Australian Sciences"

AustralianSciences (Colin Dahl) wrote on March 12th, 2008: "Australian Sciences has done tests to block individual neuropeptides (Substance P, CGRP, VIP, etc) to see what effect that has on reducing flushing. We saw that Substance P and CGRP greatly contribute to the burning sensation and delayed sensitivity. We've even done a lot of other non-neuropeptide tests, blocking Nitric Oxide and Nitric Oxide Synthase, etc. These tests were good to get a greater biological understanding of rosacea and flushing (and how the body works). However, a few years ago I felt (and still do) that this kind of approach is attractive to a pharmaceutical company but not to someone who wants to reverse rosacea. There are many neuropeptides to stop, and many other kinds of inflammatory chemicals to stop - you can't block them all, especially when you are producing more because of your excessive skin infrastructure.
So we began to look into methods that could reverse the excessive blood vessel and nerve infrastructures, which contribute to the release of inflammatory chemicals in the skin. We tested about about two hundred growth factor inhibitors or anti-inflammatory compounds to see how well they worked against various stimuli, and did get some very good results. We also looked into blood vessel removal via IPL and further with flush minimization and reducing skin cell activity using the bodies own systems (such as heat regulation, neuropeptide storage/depletion and trigger avoidance). So I favor approaches that reduce skin infrastructure and skin activity (without specifically focusing on neuropeptide blocking drugs). I am not overly familiar with ND:Yag, I am with UV lights. But will have to talk about them next time. Best regards, Colin Dahl, Australian Sciences"

Stacey wrote on March 16th, 2008: "Hello Colin, Thanks for posting all the information. I can relate to a lot of what you wrote about. I was wondering if you would be able to answer my 2 questions: 1.I have read the post about the tingling sensation in your face/cheeks. I have this too. However, sometimes it gets even more uncomfortable than just tingling. This especially happens in cooler temperatures. The tingling is accompanied by a feeling cold sensation on my cheeks, as if you are aware of them being cold. It’s hard to describe but I hope I made sense. Is this related to the sensory nerves being overstimulated and reacting to the cold??
2. Sometimes when I lay down on the bed or couch to rest or sleep I feel my face gets flushed (resting on an incline will still make me flush) . Sometimes it happens right away, sometimes in takes a few minutes, and sometimes it doesn’t happen at all. I didn't notice any relationship with temperature or time of day, just laying down or resting. Why does the act of resting or laying down induce a flush, any ideas? Thanks, Stacey"

AustralianSciences (Colin Dahl) wrote on May 24th, 2008: "Hi Stacey, The inner lining of blood vessels can sense extra blood flowing through them. The blood vessels respond by releasing chemicals (such as nitric oxide) to promote the blood flow. When you lay down, extra blood can flow through your head and face. This can then cause the extra release of these vasodilating chemicals to promote the flow, and may also lead to flushing. Reducing the excessive blood vessels structure in your flush zones through IPL/Laser should assist in reducing this kind of flush. The amount of flushing you experience is related to the amount of skin infrastructure you have.
You're flushing less now because you have less of this infrastructure (especially less blood vessels after you IPL). You can continue to experience these light flushes and also continue improving your rosacea. In fact, activation of the skin infrastructure of your flush zones is normal and happens throughout the day in the form of heat regulation. So vasodilation of blood vessels in your flush zones is something that will continue to happen, whether you have rosacea or not. You may be noticing this vasodilation because your skin infrastructure is still excessive. As you reduce this skin infrastructure to normal (or close to normal) levels, the flushing/vasodilation becomes less apparent and you become unaware that vasodilation is actually happening (as with someone who doesn't have rosacea). This does take time and great effort to achieve, but it is very possible. So you can get to the stage where you no longer experience warm room flushes because your skin infrastructure has bee normalized. Or if you still have excessive infrastructure, then you can minimize warm room flush by avoiding neuropeptide & inflammatory chemicals build up. Having said that, if you continue to experience these warm room flushes, you should understand that your reversal of rosacea is likely to be slower. So try to take steps to prevent these kinds of flushes.
These inflammatory chemicals can cause a flush but they also do good things for you too.
They even make up part of our immune system. So in one way you actually need these chemicals around. But the more you build up, the more gets released (like when a small trigger causes a large flush). It's difficult to quantify their release and storage because it depends on many factors (amount of skin infrastructure is a main one). If your flush zones stay in a cool environment for long periods (several hours), this will assist in inflammatory chemical build up in your flush zones. I think what you want to know is how long will this build up remain. The simple answer is that this is likely to be a contributing factor towards flushing for several hours after.

The tingling sensation to cold (as with the extra blood flow when laying down) is a normal response, but in your case (and many others with Rosacea) it is a larger response. The response could even be described as a cool burning sensationThe reasons behind this tingling may involve the over-stimulation of sensory nerves, either directly or indirectly, or excessive sensory nerve innervation in your flush zones. Try to avoid/reduce cold environments. Generally you should try to prevent sensory nerve stimulation in your flush zones (due to cold, irritating topicals, sun, etc). By combining this approach with IPL/Laser to reduce blood vessel innervation of your flush zones, you will slowly notice a reduction in this kind of response. [..] We have had good success with natural ingredients such as Chinese Licorice Root and will soon be releasing a line of oral anti-inflammatory products to assist people with reversing Rosacea. Best regards, Colin Dahl, Australian Sciences."

Stringer1989 wrote on May 24th, 2008:
"Colin, thank you very much for your reply, it is very helpful. I have eliminated most other factors that can be bad for rosacea ( sun, foods,heavy exercise, mental side of things through propranolol etc) so the only factor of concern is really only temperature and temperature related flushing and symptoms. I am having difficulty determining whether I have too much infrastructure at the moment. I have already had 5 IPL treatments with the Lumenis one machine and I wouldn’t say that I've noticed too much improvement in my rosacea. The benefits from IPL tended to be only short term ones.
You mention an indication of too much infrastructure is permanent redness. When I am normal (ie not hot and not cold) I have some permanent redness, but I have to be pretty close to the mirror to notice this redness, a few meters away from the mirror I cannot really see any visible redness. Would you say that this is not too much infrastructure or is it too difficult to say?
The reason I used to flush every day was because I was constantly putting cold water on my face and therefore during the day my face would be REALLY cold to touch and I would then flush in the latter hours of the evening, so I don’t know whether my flushing was caused by having way to much excessive infrastructure or just by the by the fact I was keeping my face way too cold during the day and this would result in an intense flush even if I had less infrastructure.
Sometimes if I get really hot, I find that my nose and face are really hot, but it is not very red/flushed only slightly pinkish. Do you know what is happening here? Like is more blood vessels and nerves being developed and thus is it progressing my rosacea ? or should I not be worried about this?
And lastly this is related to the question above, but i was wondering whether if you are constantly a bit hot and slightly red/pink in the face 24 hours a day, if this will help to reverse your rosaacea, compared to being cold during the day and then having an hour or two of intense red flushes later in the day?? Sorry to ask so many questions, it is just my rosacea has left me very confused and i have a lot of questions. Thanks heaps and best wishes"

AustralianSciences (Colin Dahl) wrote on January 20th, 2009: "Dear Stringer, I believe if someone becomes almost persistently flushed, then this is too much skin infrastructure to go directly into flush reduction programs (it's just too hard). In this situation IPL or laser treatment should deliver some much needed reduction in skin infrastructure and flushing. After this, following flush reduction programs become more realistic. Skin redness can change too rapidly to be a good indicator of Rosacea severity. Flushing gives a good indication of the level of skin infrastructure in flush zones. You don't sound like you are persistently flushed. And 5 IPL treatments sound like you gave it a good go.
Keeping your face cold during the day could cause a flush at night even if you had slightly excessive skin infrastructure! (I'm not surprised your IPL benefits were short term). You don't need extremely excessive skin infrastructure for this to happen. You said previously that this no longer happens to you. So I would think you are well placed to continue with your flush reduction program and are on your way to slowly reversing rosacea on a daily basis, as opposed to the last few years where you were probably increasing your rosacea on a daily basis. The feeling of a flush relates directly to your skin nerves. The more they are activated, the more you FEEL the flush. The redness relates more directly to blood vessels and vasodilation. Although nerve and blood vessel activation often happen together and at similar intensity during a flush, it is not always the case.

Flushing is primarily responsible for progressing rosacea, but it's all relative to how much flushing & skin infrastructure you currently have! MORE flushing = more skin infrastructure, LESS flushing = less skin infrastructure. Sometimes it is difficult to avoid a flush. But as you gradually reduce your excessive skin infrastructure it does become easier. Don't worry whether one flush has progressed your rosacea. You have to think of reducing your overall flushing (duration and intensity). Say on a weekly basis or even a monthly basis. You don't need to go from 10 flushes a week to 0, in order for you to reverse Rosacea. But having said that, the more flushing (and inflammation) you can reduce the faster you will reverse rosacea. Also, one intense flush is not equal to a minor low intensity flush. If you could replace 10 major flushes a week with 10 minor flushes, you would be well on your way to reversing rosacea (less skin infrastructure in flush zones).
To answer the last part of your qn: YES. I believe that spacing out a flush (slightly hot, red) over a day would cause less angiogenesis than one big flush. If this were not true, then I would still be red as a tomato. Best regards, Colin Dahl, Australian Sciences"

14 March, 2018

Rosacea Bulletin Board; Latest news on rosacea treatments

March 15th 2018

New class of menopause drugs reduces severity of hot flushes in three days

A new class of experimental drugs reduces hot flushes in menopausal women by almost three-quarters in just three days. The treatment, tested by scientists at Imperial College London, also reduces the severity of hot flushes by over a third within three days of taking it. The research, funded by the Medical Research Council (MRC) and the National Institute for Health Research (NIHR), is a new in-depth analysis of data collected from a clinical trial initially published last year.

This class of new drugs may provide women with a much-needed alternative to HRT, but it could also be an interesting new treatment on the horizon for people with vascular rosacea and facial flushing. Other medication aimed at reducing the severity of hot flashes (for instance clonidine, mirtazapine, other SSRI-antidepressants and certain beta blockers) all are prescribed by various dermatologists to try to curb facial flushing, a difficult to treat rosacea symptom.

The original drug trial, which was a randomised, double-blind, placebo-controlled trial, involved 37 menopausal women aged between 40 and 62 years old – and who experienced seven or more hot flushes a day. Participants were randomly chosen to first receive either an 80mg daily dose of the drug, called MLE4901 (which was previously developed as a drug for schizophrenia) or a placebo over the course of a four-week period. They then switched to receive the other tablet for an additional four weeks. This ensured the women acted as their own controls during the study, and the effects of the drug were clear. The researchers found that the compound MLE4901 significantly reduced the average total number of flushes during the four-week treatment period, as well as their severity, compared to when the patients received the placebo for four weeks.

The new experimental compounds are thought to work by blocking the action of a brain chemical called neurokinin B (NKB). Previous animal and human trials have shown increased levels of NKB may trigger hot flushes. The drug compound is thought to prevent NKB activating temperature control areas within the brain – which appears to halt hot flushes.

The new data also revealed that the drug was as effective at improving daytime flush symptoms as it was at improving night time symptoms. Furthermore, the women reported a 82 percent decrease in the amount their hot flushes interrupted their sleep, and a 77 percent reduction in interruption to their concentration.

Dr Julia Prague, first author of the study, explained: “As NKB has many targets of action within the brain the potential for this drug class to really improve many of the symptoms of the menopause, such as hot flushes, difficulty sleeping, weight gain, and poor concentration, is huge. To see the lives of our participants change so dramatically and so quickly was so exciting, and suggests great promise for the future of this new type of treatment.”

The new analysis shows the compound has a significant effect within just three days explains
Professor Waljit Dhillo, an NIHR Research Professor from the Department of Medicine at Imperial: “We already knew this compound could be a game-changer for menopausal women, and get rid of three-quarters of their hot flushes in four weeks. But this new analysis confirms the beneficial effect is obtained very quickly – within just three days.” Professor Dhillo explains this specific compound will not be taken further in trials, due to side effects that may affect liver function. However, two very similar drugs, which also block NKB but do not appear to carry these side effects have entered larger patient trials, with one such trial launched in the US last year.

The research was funded by the Medical Research Council and the National Institute for Health Research. The study was supported by the Imperial NIHR/Wellcome Trust Clinical Research Facility.

September 12th 2017

Stanford University has started clinical trials for Secukinumab, used to treat rosacea. It is an open label study to assess the effect of Secukinumab in moderate to severe papulopustular rosacea. However hopes are that it will also address rosacea redness and inflammation. Test participants receive injections of secukinumab. First impressions from one rosacea patient who is undergoing these tests were: "Redness was almost completely gone by Saturday afternoon. [one day post injection]. The doctor says full results are shown anywhere from 12 to 16 weeks."

Update from this rosacea patient, September 29th 2017: "Secukinumab update: So this thing has really worked immensely. My redness is gone and I'm going back to Stanford medical center to get my 5th dosage. I'd recommend everyone in this group if you can get there, to do so. So you can finally rid yourself of this disease."

Secukinumab is a "human IgG1κ monoclonal antibody" that binds to the protein interleukin (IL)-17A. It is injected once weekly for four weeks (or around 5 booster shots) and then once a month for 5 months. It works a bit like methotrexate; suppressing the immune response and inflammation. Secukinumab lowers the bodies immune response and is used to treat auto immune diseases like psoriasis and related inflammation in the joints (artritis psoriatica). In psoriasis the bodies immune system goes in overdrive, and multiplies the skin cells too quickly, causing plaques of skin, inflammation and scaling and ultimately a lot of skin cell shedding. By lowering the immune system response, the skin symptoms can be calmed down too. Rosacea does not have an issue usually with increased skin cell formation, but some scientists do think that rosacea can be an auto immune disease as well, having the bodies own immune system attacking normal tissue and as such creating inflammation and redness.

I know of some severe rosacea sufferers who were given methotrexate and who had their skin issues (redness, flushing) calm down significantly. Side effects can be significant however, increased risk of infections (viral infections, nose and throat infections, sinus infections and other infections) and it even raises the risk of certain cancers. That is generally the downside of methotrexate. Luckily Secukinumab does not seem to come with an increased risk of cancer. Several studies show that secukinumab demonstrates "a highly favorable safety profile, especially compared with commonly used psoriasis treatments such as methotrexate and TNF-α blockers. More specifically, secukinumab carries no increased risks for end-organ toxicities, serious infection, multiple sclerosis, reactivation of latent tuberculosis or hepatitis B, leukemia/lymphoma, and nonmelanoma skin cancer."

So despite of secukinumab being somewhat comparable to methotrexate, a drug that lowers (auto)immune response and inflammation as well, it comes with far less severe side effect risks. On January 21, 2015, the FDA announced that it had approved secukinumab to treat adults with moderate-to-severe plaque psoriasis, followed later with the approval for the treatment of ankylosing spondylitis, and psoriatic arthritis. A 2016 study also showed that secukinumab seems to be effective in the treatment of multiple sclerosis.

I am a bit hopeful for this new trial! I know that my dermatologist treated some very severe rosacea patients with methotrexate for a little while, and their skin really cleared up (also through suppressed immune response and inflammation), but that the increased risk of infections was too tricky. Since secukinumab does not have that side effect profile as much, it seems a great alternative.

Open Label Study to Assess the Effect of Secukinumab in Moderate to Severe 
Papulopustular Rosacea 
This study is currently recruiting participants.

Verified July 2017 by Anne Chang, Stanford University
Information provided by (Responsible Party):
Anne Chang, Stanford University
ClinicalTrials.gov Identifier:
First received: March 9, 2017
Last updated: July 11, 2017
Last verified: July 2017

This is a study to determine whether secukinumab is a potential therapy for those with papulopustular rosacea. We will observe whether this drug decreases the size and/or amount and severity of the pustules of those who suffer from rosacea.

Papulopustular RosaceaDrug: SecukinumabPhase 1Phase 2

Study Type:Interventional
Study Design:Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title:An Open Label Phase 1b Study of Secukinumab in Patients With Moderate to Severe Papulopustular Rosacea

Further study details as provided by Anne Chang, Stanford University:

Primary Outcome Measures:
  • number of papules/pustules on rosacea patients at week 16 vs 0 [ Time Frame: 16 weeks ]
    Comparison of number of papules/pustules at 16 weeks compared to 0 weeks

Secondary Outcome Measures:
  • reduction in the number of papules and/or pustules in moderate to severe papulopustular rosacea at week 12 vs 0 [ Time Frame: 12 weeks ]
    Compare number of papules/pustules at 12 weeks compared to 0 weeks
  • reduction of the overall severity of rosacea by global assessment [ Time Frame: 16 weeks ]
    comparing week 16 and 0, includes clinical and patient reported symptoms
  • reduction of erythema in patients with moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]
    comparing week 16 to 0
  • improved quality of life measures in patients with moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]
    by patient questionnaire
  • assess adverse events ≥ grade 3 in patients taking secukinumab for moderate to severe papulopustular rosacea [ Time Frame: 16 weeks ]
    frequency and severity of adverse events will be recorded throughout the study by CTCAE version 4.0
  • changes in immune infiltrate in papulopustular rosacea lesions after secukinumab use [ Time Frame: 16 weeks ]
    assess by immunohistochemistry at 16 weeks versus 0 weeks

Estimated Enrollment:24
Anticipated Study Start Date:July 14, 2017
Estimated Study Completion Date:January 1, 2019
Estimated Primary Completion Date:July 1, 2018 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Experimental: secukinumab arm
This is an open label study without placebo and it is a single arm study
Drug: Secukinumab
We will be giving secukinumab to patients with papulopustular rosacea

Detailed Description:
Rosacea is a common inflammatory skin disease affecting up to 10% of adults. Despite this, the etiology of rosacea is unclear, although there may be a genetic predisposition (Chang et al., 2015). Currently, there is no cure. Rosacea can lead to scarring, itching, burning, and is associated with anxiety and depression (Moustafa et al., 2015), significantly affecting quality of life.
Secukinumab is an antibody that binds to a protein (interleukin (IL)-17A) that is involved in inflammation. When IL-17A is bound to secukinumab, it cannot bind to its receptor, thereby inhibiting its ability to feed the inflammatory response. In clinical trials, secukinumab has been effective for moderate to severe psoriasis (Blauvelt et al., 2015). Recently, human data from all types of rosacea have shown Th1/Th17 polarization profile of the T-cell response, suggesting that anti-IL-17 therapy may be beneficial for rosacea (Buhl et al., 2015). Hence, secukinumab could be effective against rosacea. This proposal is a proof-of-concept study to use secukinumab in open label design for moderate to severe papulopustular rosacea.

Ages Eligible for Study:  18 Years and older   (Adult, Senior)
Sexes Eligible for Study:  All
Accepts Healthy Volunteers:  No
Inclusion Criteria:
  • 1) moderate to severe papulopustular rosacea defined clinically using the grading system of Wilkin et al. (2004) as having at least ten lesions (either papules or pustules) on face at time of enrollment 2) age 18 years or greater willing and able to understand and sign informed consent form
Exclusion Criteria:
  • 1) known hypersensitivity to secukinumab 2) topical or oral anti-rosacea medication usage for 28 days prior to enrollment 3) active Crohn's disease, as secukinumab may exacerbate this disease 4) active infection including tuberculosis, hepatitis B or C, human immunodeficiency virus 5) participants with latent tuberculosis will need to have treatment initiated prior to starting study drug 6) pregnant or lactating 7) active and/or uncontrolled medical conditions that may interfere with study procedures or obscure rosacea assessment such as cutaneous lupus 8) use of retinoids within past 3 months of enrollment 9) use of antibiotics within 4 weeks of enrollment 10) use of light based or laser treatment to face within 8 weeks of enrollment 11) use of topical or systemic steroids within 4 weeks of enrollment 12) acne conglobate, acne fulminans, chloracne, severe acne requiring systemic treatment
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03079531

Contact: Anne S Chang, MD650 721-7151alschang@stanford.edu
Contact: Michaella Montana, BS650 721 7195mmontana@stanford.edu

United States, California
Stanford DermatologyRecruiting
Redwood City, CaliforniaUnited States, 94603
Contact: Anne Chang, MD    650-721-7151    alschang@stanford.edu   
Contact: Michaella Montana, BS    650 721 7159    mmontana@stanford.edu   
Sponsors and Collaborators
Anne Chang
Principal Investigator:Anne Chang, MDStanford University
Additional relevant MeSH terms:
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 11, 2017

Anti-CGRP migraine drugs for rosacea treatment 

I've read recently that several companies are busy with clinical trials for a new migraine treatment with anti CGRP drugs, with positive results. These drugs are geared for migraine, but the way in which they work (their aim is to constrict blood vessels), makes them also exciting and possible future treatment options for rosacea.

From Science magazine: "Four pharmaceutical companies are racing to complete advanced clinical trials of antibodies that either neutralize CGRP by binding to it, or block its receptor. So far, the data suggest the drugs work faster, for longer, and better than anything currently available. Most striking, is a subset of “superresponders,” whose attacks appear to cease entirely for 6 months after a single injection of a CGRP-blocking antibody."

CGRP is a 37–amino acid (neuro)peptide that is released by the nervous system and is a very potent blood vessel dilator. When released from the trigeminovascular nerves, CGRP is a powerful vasodilator of the blood vessels of the brain.

Medication that was designed to block CGRP’s receptor turned out to have too many side effects. Then researchers focused on antibodies to block CGRP, because they can last a long time in the body and can be exceptionally specific, reducing the frequency with which people need injections. many colleagues didn't think it was worth a shot, because antibodies are generally too large to pass through the blood-brain barrier, and it was thought to be necessary for migraine meds to target migraines actually in the brain. However, to their surprise, the CGRP peptide-blocking antibody "TEV-48125" managed to just do this; treating migraines from outside the brain, by blocking CGRP only in the peripheral nervous system. Trials show significant reductions in number of headache days over placebo, even for the most severe cases. This type of drug also lowers the risk of the side effects often provoked by drugs that act in the brain. Although there are still worries too, because of CGRP’s natural role in dilating arteries and maintaining blood supply to the heart and brain. “Theoretically, if you block CGRP you could translate a minor stroke or cardiac ischemia … into a full blown stroke or heart attack.” So far, the companies say they haven’t seen that or other significant side effects in the several thousand people who have completed phase I and II trials, but the drugs have only been administered for up to 6 months—not long enough to judge long-term effects.

CGRP-blocking drugs are also tested now for fibromyalgia, a condition that is somewhat overlapping in some symptoms with rosacea. And scientists have also discovered that CGRP plays a role in rosacea flushing and skin redness. Interestingly, migraine medication has so far been helping some people with rosacea. Drugs like propranolol, imitrex/sumatriptan and even botox have all been helpful for rosacea. Someone on the Rosacea Forum is successfully using the migraine med Maxalt/Rizatriptan for her severe type 1 rosacea/erythromelalgia.

Stress, rosacea flares and CGRP
CGRP is also part of the puzzle as to why stress can make rosacea flare so badly. Apart from stress raising blood pressure and inflammatory substances, experiments in rats now showed that corticotropin-releasing hormone, which the body releases in response to stress, also increases neuronal production of CGRP. More CGRP means much more blood vessel dilation, which causes our rosacea flares (for those with burning, flushing and redness). Strikingly, many migraine medications also boost CGRP in animal models, possibly explaining why people who use drugs like triptans too frequently end up with more severe migraines.

CGRP antagonistic treatment options for Rosacea

I hope that we can soon benefit from injections of this CGRP peptide-blocking antibody "TEV-48125". Those medications are in the making now, from what I read, so it might take a bit more time before they come on the market. In the meantime, scientists are also working on a topical cream that works in a similar way, blocking CGRP. patent is created for a special cream for rosacea patients to do just that. 'Therapeutic/cosmetic compositions comprising CGRP antagonists for treating skin redness/rosacea/discreet erythema.'

But they are not just focusing on a CGRP blocker: "Skin redness, rosacea and/or discreet erythema afflicting a mammalian, notably human patient, are therapeutically treated by administrating to such patient a therapeutically/cosmetically effective amount of at least one CGRP antagonist, advantageously in combinatory immixture with at least one antagonist of a neuropeptide other than CGRP, e.g., a substance P antagonist, and/or at least one inflammation mediator antagonist."

So this patent for a new cream will focus on three different things;
*blocking CGRP (and thus blocking one factor that leads to blood vessel dilation in our faces)
*blocking P antagonist
*blocking an inflammation mediator in the skin

CGRP is a polypeptide chemical species that is produced and released by nerve endings. CGRP dilates blood vessels and is involved in lung issues and inflammatory diseases, in allergic diseases and in certain skin diseases such as eczema and prurigo. It is a new concept to treat skin redness with a CGRP antagonist. But developers now think that CGRP blocking substances can not only treat skin redness, but also prevent it from occurring.

Blocking CGRP in the skin of our faces, through a cream, should help combat skin redness and flushing. This will be tested on test persons with rosacea, by first inducing a flush (with a substance called capsaicin), and then applying the cream and seeing if the redness can be toned down by it. They will test if the levels of CGRP that is released (and that cause blood vessel dilation), will be reduced upon measuring. Secondly, P antagonist will have to be another type of antagonist of a neuropeptide used, reinforcing the CGRP antagonist. A third ingredient will have to reduce inflammation in the skin (and they will select it from a group consisting of histamine antagonists, interleukin 1 antagonists, and tumor necrosis factor alpha antagonists, and the inflammation mediator antagonist is supposed to be a diethylenediamine, aminopropane or phenothiazine compound, selected from a group consisting of cinnarizine, cyclizine, dexchlorpheniramine, triprolidine, alimemazine, promethazine, auranofin, lisophyline, A802715, sulfasalazine, cetirizine hydrochloride, loratidine, esbatine, and setastine hydrochloride).

The patent described rosacea as follows:  
"Rosacea is a skin affliction characterized by erythema (redness) of the face, predominantly on the cheeks, the forehead and the nose, hyperseborrhoea (thickened skin) of the face on the forehead, the nose and the cheeks, and an infectious component manifesting acneiform pustules (skin outbreaks and bumps). Moreover, these indications are associated with a neurogenic component, namely, a cutaneous hyperreactivity of the skin of the face and of the neck (nerve burning), characterized by the appearance of redness and subjective sensations of the itching or pruritus type (skin itching), sensations of burning or of heating, sensations of stinging, tingling, discomfort, tightness, etc.

These signs of hyperreactivity may be triggered by very varied factors such as the intake of food or of hot or alcoholic drinks, by rapid temperature variations, by heat and in particular exposure to ultraviolet or to infrared irradiation, by a low relative humidity (dry air), by exposure of the skin to strong winds or to currents of air (conditioned air, fans and blowing machines), by the application of surfactants (soaps, washing detergents), irritant dermatological topical agents (retinoids, benzoyl peroxide, alpha-hydroxy acids, etc.), or the use of certain cosmetics, even when these are themselves not recognized as being particularly irritating.

Hitherto, the mechanism for triggering these indications was very poorly understood and rosacea was treated with active agents such as anti-seborrhoeic agents and anti-infection agents, for example benzoyl peroxide, retinoic acid, metronidazole or cyclins, which act on infection and hyperseborrhoea but do not permit the neurogenic component of this affliction, and in particular hyperreactivity of the skin and redness, to be treated.
Similarly, hitherto no treatment existed for the redness which develops in discreet erythema. This latter affliction occurs at times of emotion and is characterized by redness of the face and neckline, which possibly may be accompanied by pruritus (itching). This condition is very irritating for individuals suffering therefrom, and to date it could only be treated by beta-blockers, powerful drugs used for treating hypertension and exhibiting many contraindications.
Thus, serious need continues to exist in this art for an effective treatment of skin redness and of the state of hyperreactivity of skin affected by rosacea or discreet erythema."

The patent acknowledges that their invention does not necessarily have to be applied through a cream on top of the skin: it is also possible to inject the CGRP antagonist into the skin, or even to take pills to achieve the same effect. They aim for a acceptable cream carrier, but the problem with most creams is that they contain alcohols (they help the active ingredient to penetrate deeper into the skin) and preservatives (parabens for instance, which are skin irritants). And some companies even put propylene glycol and plastic elements into their creams, which make them pretty much unusable for those with hyper reactive, intolerant rosacea skin. In the examples for cream ingredients that are mentioned in the patent itself, the list seems fairly OK to be honest, the only ingredients I wouldn't tolerate myself (but my skin is sickly reactive) are sunflower oil (12%), stearic acid, fragrance (if they are smart they leave that one out!) and preservatives.

CGRP and Rosacea

Rosacea is a common skin disorder that is not yet fully understood. It has been suggested that it is linked to interactions between nerves and blood vessels, which release inflammatory substances, but also specific neuropeptides, which cause the blood vessels in our skin to dilate. This is probably especially the case in rosacea subtype 1, with flushing, redness of the skin and burning (and less in subtype 2 with pimples and skin outbreaks). These specific neurotransmitters are easily triggered to be released, for instance by stress, ultra-violet light or microbial antigens. And when they are released, they trigger flushing and redness for us.

When you flush from heat or temperature changes, it are primary sensory neurons that stimulate the blood vessels to dilate and to release inflammatory neuropeptides. These neuropeptides play a very important role in rosacea. For example, flushing has been suggested to be controlled by two vasodilatory mechanisms including humoral substances and neuronal stimuli (Wilkin, 1988), but the exact mechanism of action is unknown. Although scientists learn increasingly more over time about how sensory nerve endings are activated to release vasoactive neuropeptides during flushing, which also triggers the inflammatory process in different stages of rosacea. Specific TRP Channels are involved in this.

Capsaicin receptor
This newly discovered TRP channel receptor family is currently composed of 28 channels with seven subfamilies. They sit on neuronal and non-neuronal tissues all over the body. One in particular is interesting for rosacea, as it is singe handedly capable to cause a lot of blood vessel dilation. It is called vanilloid 1 (TRPV1), also known as the “capsaicin receptor”. It has many functions, including as a censor in cells, signalling pain sensations and inflammation. This receptor responds to a lot of triggers, including heat, cold temperatures, touch and changes in the cell membrane.
The image left shows the structure and activators "capsaicin receptor" (TRPV1), as well as ankyrin 1 (TRPA1) receptors in primary sensory neurons with a link to rosacea. Both receptors have a similar structure and can be activated by temperature increases or for instance by spicy food. TRPA1 can be activated by reactive oxygen species (ROS; they are chemically reactive chemical species containing oxygen. They are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cells. But during times of environmental stress, for instance when exposed to UV radiation or heat, ROS levels can increase dramatically). And when activated, TRPA1 will signal for signal blood vessel widening. When this happens, mediators, such as proteases, are released, and they create inflammation. It is thought that these two, TRPV1 and TRPA1, have an interaction with each other, that regulates their activity.

TRP Channels as Thermosensors in Rosacea?
Both TRPA1 and TRPV1 channels are triggered by heat and temperature increase. It is no surprise probably that 53% of rosacea patients stated in polls that hot and cold weather are triggers for their rosacea. Very cold temperatures can also directly activate TRPA1 channels. Perhaps TRPA1 is a “cold sensor” channel. Another TRP channel (melastin) TRPM8 is also activated at temperatures below ∼23 °C. So when you are hypersensitive for the cold, it is most likely this TRPA1 channel deep in your body cells, that is responsible! (Just so you know how to blame haha). Anyway, the cold can also cause inflammation in rosacea skin.

But heat is just as much a trigger for rosacea. Heat, sun, hot baths; they all dilate out blood vessels as our body temperature rises. And rosacea skin already is a little bit warmer than 'normal' skin temperature. When the temperature rises quickly, even in healthy people, our cells produce TRPV1
Therefore TRPV1 channels have an essential role in temperature hypersensitivity when it comes to inflammation. And on top of all this, rosacea facial skin has shown to have a significantly lower heat pain threshold compared to the rest of our skin. Our faces notice heat quicker and develop painful skin much quicker (tingling, burning, prickling, blushing, pain) when we are in a warm surrounding than the rest of our bodies skin. I think everyone had detected that for him or herself already anyway :) And again, our little friend TRPV1 seems to be involved in this. The same goes for flushing after eating spices TRPV1 is dubbed the "capsaicin receptor", because it is directly activated when someone eats capsaicin, which is the chemical that makes chilli peppers so hot. The same happened in trials with mice; capsaicin also stimulates an increase in mouse skin blood flow, which shows that this blood flow increase is triggered ultimately by TRPA1 stimulation.
TRPA1 is triggered by cinnamaldehyde, the main ingredient of cinnamon, which also leads to intense and acute painful burning sensation. This is even the case by those who do not have rosacea, and the burning they can feel from this is probably similar to that observed in rosacea.
These findings highlight that TRPA1 and TRPV1 may be activated by the triggers of rosacea, such as cold or hot temperatures and spices, to mediate flushing or burning sensation episodes of rosacea.

Another aspect that makes rosacea skin burn and flush, is blood flow. Flushing longer than 10 minutes is indicative for rosacea (and therefore 'not normal' for normal skin). The smallest systems of blood vessels in our body are dilated in rosacea patients. TRPA1 is also here a factor. It sits in the basal layer of the epidermis, in the dermis, and in the epithelium of the hair follicle, so basically all throughout our skin. And when this TRPA1 is activated (for instance through heat, cold, stress, spices), a substance called "proinflammatory cytokine IL-1" is released, which is a key contributor to skin inflammation. Our skin actually recovers from such a TRPA1 triggered rosacea attack, by exposing our skin to cold air.

Apart from more blood flow in the skin, rosacea patients in studies also showed heightened sympathetic nerve activity compared to those without rosacea. The sympathetic nervous system is a part of the body’s autonomic nervous system that controls involuntary functions such as heart rate, digestion, breathing and perspiration. This portion of the autonomic nervous system functions largely below the level of consciousness and has been shown to respond to emotion.

Substance P and CGRP in Rosacea
So, studies have shown that activation of TRPV1 (by capsaicin) and TRPA1 (by mustard oil) caused the release of neuropeptides. Normal human skin that was rubbed in with a cream containing capsaicin, showed a big red flare. But, this flare could then controlled again by a specific TRPV1 antagonist, SB705498.

And there is also a new oral CGRP antagonist, telcagepant, which also managed to bring down a capsaicin-induced flushed skin reaction.
Ultimately, what makes our skin flare, is not TRPV1, but another chemical, that is triggered by TRPV1: called CGRP. CGRP is one of the strongest blood vessel dilators in the skin. And to make matters worse, it makes sure that your skin also has increased inflammatory substances as a result of all this extra blood flow going around. The neuropeptide SP is elevated in rosacea skin. They linger around the dilated blood vessels. Research showed that laser treatment reduced facial sensitivity, sensory nerve marker, and SP-positive nerve fibers in the skin of 31 rosacea patients. And there is also evidence that SP can also induce skin redness. When rosacea patients have an inflammatory flare, and biopsies are taken from their skin, scientists tend to find widely dilated blood vessels in the skin. SP might play a role in all this, as SP can stimulate mast cells to release histamine and 5-hydroxytryptamine. These mediators bind to histamine H1 receptors and serotonin 5-hydroxytryptamine-1 receptors, and as such they cause blood vessel dilation through the nerves of the skin. CGRP can make matters worse then, by forming skin redness. It is therefore a whole cluster of substances that work together to fire up a flare for us: CGRP creates blood vessel dilation and SP triggers skin redness, histamine release and inflammation, and they even strengthen each others powers by blocking degradation of each other by the body.

Proteases in Rosacea
It is also known that protease activity is higher in the facial skin of rosacea patients, and that antibiotics such as tetracyclines can indirectly inhibit (control) these proteases. Proteases also degrade elastin and collagen, which means your skin becomes less firm and strong and is not beneficial for the lymphatic system in your skin. They also indirectly increase inflammation in the skin, by stimulating the release of SP and CGRP.

And then in the last place, there is Reactive Oxygen Species (ROS), which also seems to play a role in rosacea. Substance P can cause their release. There is evidence in the literature suggesting that inflammation in the early stage of rosacea may be linked with ROS such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, which are released by inflammatory cells such as neutrophils. The level of ROS was significantly higher in the facial skin of patients with rosacea compared with healthy control subjects, OR of the same rosacea patients after being treated with the antibiotic azithromycin. ROS is involved in microbicidal activity. Studies have shown that cathelicidin, a potent inflammatory peptide, is upregulated in rosacea. Cathelicidin can stimulate ROS, which plays a role in inflammation. And ROS is in turn again linked to TRPV1 receptor activation, which dilates our blood vessels and increases blood flow in the skin. It is a rosacea avalanche, in other words, when all working and activating each other together. And this is another reason why rosacea should be treated as soon as possible and controlled.

So in summary, TRPV1 and TRPA1 may contribute to the development of rosacea. The high skin reactivity of rosacea skin can be blamed on TRPA1 and TRPV1 receptors. When they are activated, they create blood vessel dilating substances such as CGRP and SP, as well as inflammation, which may further aggravate the symptoms of rosacea. They work together and strengthen each others actions.
All the more reason to be very excited about this new treatment option; blocking of the neuropeptide-driven inflammatory processes resulting from activation of TRPV1 and TRPA1 receptors. This could become a completely new therapeutic approach to treating rosacea.

 August 2017

My dermatologist told about a cream that really seems promising for rosacea skin. Some patients reported very good success with a mix of 0,5% ketamine with 1% amitriptyline in a cream base.. You use it topically and it apparently pales the skin. It also helps (more officially) with erythromelalgia, a health condition that also involves a deep red flushing and burned red skin of the legs, arms, chest etc. The cream has to be made by a compounding pharmacist. My doctor is looking for one right now, willing to make it, as it's not a commercial cream yet.

Here is some more information on this cream:

Deansm wrote on December 2nd, 2016: "Cleared up my type 1 Rosacea (flushing red nose).
I have had flushing and swelling (caused by the flushing) on my nose for around 7 years (no pustules or pastules). Tried antibiotics, Soolantra, metrogel etc, nothing worked, every treatment has had absolutely zero effect. Two months ago the GP I am seeing prescribed me an ointment containing Ketamine 0.5% and Amitriptyline 1%. Withing 3 days of using it twice a day the flushing disappeared and my skin is white, the same as it was before Rosacea. It has been the same ever since for the last two months. I can eat, exercise, go out in the sun and nothing will bring on a flush. If anyone has this subtype and nothing has worked have a look into this, I have no side affects(the GP said it is very safe as the amount of active ingredients is too low and it's not absorbed systemically). I am not sure which or if both of the ingredients are working. I have since learned that topical Ketamine behaves as an anti-inflammatory by acting on Toll-like receptor (TLRs), which leads to down regulation of pro-inflammatory gene expression."


"The packaging has no branding, it was made in a compounding pharmacy. He said he has found it helpful going back years for patients with Erythromelalgia and it was worth trying for my Rosacea as nothing else worked."

Hg24 wrote on December 3rd, 2016: "This is really interesting, Dean. I googled and found reference to a study about this topical for erythromelalgia. The ointment seems to be for the pain (versus redness). I have type 1 rosacea, too. Flushing and permanent redness. Dean, you mentioned that your skin color is back to normal (pre-rosacea). So did you also have permanent redness? Or just the redness that comes on temporarily when you flushed?  I guess I'm wondering if the ointment returned your vessels to normal - constricted them back. I wonder if the ingredients work because they address nerve pain. Nerves can stimulate our flushing. Eg, nerves release acetylcholine, a chemical that tells our vessels to dialate."

Deansm wrote on December 3rd, 2016: "I'm from Wales, I don't see any reason why it could not be prescribed in the other UK countries (The only problem I can think of is Scotland/Wales/England having separate devolved NHS bodies and rules etc). It probably is completely up to the GP, how many treatments you have already tried etc. He told me the ointment reduced redness and flushing on patients with Erythromelalgia(no idea what this was). I never expected this to work as every other treatment he presvribed (Soolantra, Antibiotics, Metrogel) has either done nothing or even made my Rosacea worse.
My Rosacea started (I was 24) as a sudden huge flareup (huge flushing episode) on my nose when I went to bed one night. I had never blushed or flushed on my nose before that first flareup.
Ever since every night without fail I would have a flareup when I went to bed. Through the day I had one or two flareups and my nose was sensitive to flushing but not as bad as in the night. After each flare up it would take around 2-3 hours for my skin to return normalish in colour but there was always a slight pink hue on my nose. The worse symptom of all is the nose swelling for around 7 hours when I sleep and waking up every morning with a swollen nose. The flushing has stopped now and that stopped the swelling. My nose still looks a bit swollen but it's slowly going down now(2 months so far)."

Fiugs wrote on December 4th, 2016: "There is a topical with the brand name Epicept, although I think the compund's percentages are different than you describe, Deansm. 
https://www3.rcsb.org/ligand/NP1. Did your GP indicate if s/he thought this would be a short or long term solution? Just wondering because I got the impression that some topical analgesics lose their effectiveness after a while.... I say that only based on what my local pharmacist told me in relation to a lidocaine based gel I was inquiring about; he said it would stop working after a while. I will certainly ask my GP about this! Thanks Deansm and all the best. I also found this article, referring to a compound using the same percentages as Deansm has been given http://jamanetwork.com/journals/jamadermatology/fullarticle/403191

Deansm wrote on December 4th, 2016: "From looking at the link EpiCept Cream is much stronger (2% ketamine / 4% amitriptyline), The cream I am on is 1%ami and 0.5%ket and it stops the flushing (the lower dose it works the better). Since my doctor said he had success with the ointement on patients with Erythromelalgia I have been reading a lot on Erythromelalgia forums about the safety of this cream (it seems very safe at low dose). I am not sure which ingredient (or a combination of both) is stopping the flushing, but this is something I found about topical ketamine.
Also from reading various Erythromelalgia forum posts, the vasodilation, flushing, redness are very similar to Rosacea, only it happens on the feet and hands and sometimes the face in Erythromelalgia. The only real difference over type 1 Rosacea as far as symptoms is the addition of more pain, stinging. It is interesting hearing about the other treatments they use on those forums to stop flushing that might also work for flushing on people with Rosacea."

Brady Barrows wrote on December 4th, 2016: "What a wonderful find to substantiate this thread. Note what the article says: "Erythromelalgia is a clinical syndrome characterized by attacks in which the affected limbs become bright red, hot, and excruciatingly painful. The common trigger is heat exposure induced by exercise or increased ambient temperature. As the condition progresses, the limbs become permanently red, hot, and painful. The pain of erythromelalgia, commonly described as hot and burning in quality, is frequently disabling, and patients obtain relief by lowering skin temperature, for example, by applying cold objects to the affected area, exposing the affected extremities to cold surfaces, immersing the limb in ice water, or by elevating the affected extremity. Frequently, these measures damage the skin, further exacerbating the pain, and occasionally cause maceration.
Pain associated with erythromelalgia may be difficult to treat. Because erythromelalgia is not a single disease but a syndrome, the response to various treatments may differ depending on the underlying condition and pathophysiology. Furthermore, treatment of the pain symptoms may have little if any effect on the other manifestations (ie, the redness and increased temperature of the affected limbs). According to various theories, erythromelalgia is a vascular disorder or neuropathic condition. In previous studies, we have shown that both systems are involved, but we do not know which one is affected first. It is plausible that the vascular and neuropathic components differ in each subject depending on the underlying cause."
Hopefully in the future we will know more if this treatment for erythromelalgia will be a standard treatment for rosacea."

arsenalista wrote on December 5th, 2016: "Looks like another guy has also great results with this stuff.. https://www.reddit.com/r/SkincareAddiction/comments/5ggpha/beforeafter_dealing_with_rosaceaerythromelalgia/ I was read about Erythromelalgia (first time hear about it) and it looks like something very similar to rosacea but more painful. One of my worst symptoms is a chronic burning feeling at all my face. Damn, have to get the prescription."

wrote on December 6th, 2016: "A very interesting find! I'm very curious if more people with facial (rosacea) flushing and burning will find relief from this cream. It's also a big bonus if your pharmacist can just add the powdered medication to your regular moisturizer. It's a fascinating distinction between facial erythromelalgia and rosacea. I'm not completely sure how you can detect one from the other, (apart from EM typically at the least affecting the hands and feet - but people with rosacea can get Raynauds (me too), which mimic these symptoms a lot), as these cases mentioned here look and sound pretty much like rosacea.

"A 53-year-old man presented to an outside dermatologist with an erythematous
facial eruption of 4 years' duration. The eruption was associated with burning and swelling,
which the patient reported worsened with sun exposure. These symptoms were debilitating,
preventing the patient from working and maintaining daily activities. Initially, the eruption was
thought to be rosacea and actinic damage; however, it was unresponsive to standard therapies."

"Upon further questioning, the patient reported skin burning not only with sun exposure, but also 
with heat exposure. Furthermore, he reported attempting cooling measures, such as the frequent 
use of ice packs, to relieve his symptoms. With these additional details, a clinical diagnosis of facial 
and auricular erythromelalgia was established. Further workup excluded potential causes of secondary erythromelalgia. Given that erythromelalgia is thought to involve both small fiber neuropathy as well as vasculopathy, we initiated therapy with aspirin, pentoxifylline, and
gabapentin.1 Subsequently, nifedipine was added to this treatment regimen. At 5 months' follow-
up, the patient reported 80% improvement (Fig 2, B) and was able to return to work and enjoy
normal daily activities

With a picture:

Curious if aspirin, pentoxifylline and gabapentin together could help some of us too.  And this woman seems to have serious rosacea, and she wonders whether or not she has erythromelalgia or rosacea;

With pictures:

Someone with fybro emailed me that her rosacea disappeared once she started to take guaifenesin tablets (a decongestant). Anyway, shows how complex these skin conditions are, there might be a lot of overlap and different factors at play. So curious to hear who else here might have benefit from this cream that is suggested." 

RaymondS wrote on April 18th, 2017: "Didn't harm me but didn't help either. And it was a hell of a process to get the stuff. Just proves what works for one doesn't always work for another. 
I will keep it and just use in one area to make sure that over time it works or doesn't. 
But unfortunately it did not cure me."

Fiugs replied on April 18th, 2017: "Sorry to hear it didn't work for you either. I gave up on mine quite some time ago as it really aggravated my skin. It seems that only one person on our forum - the original poster - got marked results with this. It's truly weird, isn't it, that our skins are all so different! Every day I grow more of the opinion that there is no such single condition as Rosacea, but rather it's a blanket term for a red, irritated and sensitive flushy face, that may or may not include P&Ps, the unique cure of which is probably only going to be determined by the cause(s)."

Vice wrote on February 23rd, 2017: "Nobody should be worried about ketmamine having an effect. I take ketamine in powedered form recreationally and in my eyes 'medicinally'. It has an anti depressant effect and is currently being reviewed and researched as a breakthrough anti depressant for treatment resistant patients. It's a wonder drug really. The hallucinations are more distortions and only occur with high doses. - I personally love them myself. I am also trying to get the cream ointment and am in the middle of the process to getting it in uk now but it's difficult. Obviously I know it won't have any effect on my mind but it's still crazy that a drug I used systemically to get high might also be a good treatment for Rosacea! Who'd have thought!"