Rosacea

This  is a complex subject. the article should give good insights into why your skin is red, why you flush and what you can do about it.

What is this skin condition?

Rosacea redness is the problem suffered by most rosacea patients where the facial skin being abnormally red . Flushing is when the skin colour becomes temporarily even more red often in response to triggers but sometimes with no clear trigger factors.

Why have I got it?

Rosacea redness can be explained relatively easily. Rosacea flushing is complex and is only just starting to be understood.

Rosacea redness is multifactorial and includes the following factors

  1. Skin type: most patients who get rosacea have type 1, pale white skin. Anyone with this skin type has slightly red or rosy cheeks. The lack of skin pigment means that the underlying blood vessels are easier to see. For rosacea patients it is important to remember that they have always had a reddish complexion. Research has been done studying “erythemaphobia” where patients become paranoid about their level of redness which may not always be that abnormal

 

  1. Blood vessels: The blood supply to the skin is complex. The skin has 3 layers, the epidermis, dermis and the fat. Blood vessels are found in the dermis and the fat. In the dermis there are 2 main groups of blood vessels; one nearer the surface- the superficial vascular plexus and one deeper down- the deep vascular plexus. Larger blood vessels that supply the dermis run through the fat. In rosacea 5 things can happen:-
    1. Increased faster blood flow through normal vessels
    2. Temporary Dilatation (widening) of blood vessels leading to more blood in the skin
    3. The formation of small extra blood vessels above the superficial plexus just below the epidermis- these are called telangiectasia. They are common in all sun damaged skin but can become a major problem in rosacea
    4. Permanent dilatation of telangiectatic blood vessels
    5. Permanent dilatation of blood vessels in the superficial and deep plexus is possible but less likely due to the muscular vessel walls. Telangiectasia do not have a smooth muscle layer.

 

  1. Inflammation: Rosacea patients have a skin immunity that is more sensitive than normal. Inflammation is the bodies way of destroying unwanted bacteria, viruses etc. When the immune system is activated to kill some bacteria, chemicals are released to make blood vessels wider to allow more blood to flow to the affected area and carry immune cells to target the bacteria. Experiments have shown that rosacea skin has higher levels of anti-bacterial proteins than unaffected skin ( cathelicidins are one of the antimicrobial proteins). We have evolved to have a highly efficient immune system that can recognise external organisms but tolerate our own cells and also tolerate the friendly (commensal) bacteria that live with us. In rosacea skin the skin immunity seems to over react and produce unwanted inflammation.  This inflammation can lead to an increase in molecules such as VEGF ( vascular endothelial growth factor) which promote the growth of small superficial blood vessels- telangiectasia.

 

Thousands of years ago in primitive humans there may have been a survival advantage to having a very active skin immunity although now it is more annoying. Another theory relates to vitamin D. As man migrated out of Africa it is thought that skin pigment was gradually lost to allow for more UV light production of Vitamin D. Vitamin D is needed for the skin immunity to function correctly. It is possible that in a situation of vitamin D deficiency the skin immunity evolved to be more sensitive to make up for the lower functioning due to vitamin D deficiency. This is a theory.

 

  1. Triggering factors: The full story of rosacea triggers has not been worked out although we do know a number of things learned from patient histories and from experiment. We need to set the scene with the knowledge that rosacea skin is more prone to inflammation. Factors that trigger the inflammation include:-
    1. Alcohol – a molecule known to cause inflammation in many disease. In rosacea, red wine is often reported to be a major problem possibly due to all of the impurities that give the complex flavours
    2. Heat- hot environments promote blood vessel dilatation so that the skin can cool down
    3. Irritant products- washing the skin with products that cause dryness will often worsen inflammation. Many rosacea patients develop itchy dry skin. Washing with moisturising products and regular moisturising is needed
    4. UV light. Many rosacea patients complain that bright sunlight worsens their redness although this complaint is not universal
    5. Demodex mites- these are emerging as a probably cause of rosacea in many patients. See the dedicated article here. All adults have demodex mites in their oil glands and hair follicles. Evidence has shown that many rosacea patients develop and immune response against the mites or against the bacteria that live within the mites. Ivermectin cream ( Soolantra) kills the mites and has been shown to be effective in reducing rosacea inflammation ( and papules and pustules)

 

Rosacea Flushing

This is a distinct problem that clearly overlaps with rosacea redness. All patients with rosacea will have a degree of redness but not all get the episodes of flushing. Rosacea flushing describes the intense redness that often begins at the cheeks but can go on to affect the whole face. It can be accompanied by a distressing burning sensation or pain. Sometimes clear triggers can be identified such as change in temperature- especially going from cold to hot, alcohol, certain foods or even stressful situations.

Facial flushing is a normal physiological reaction and occurs in 2 situations

  1. When we are hot our blood vessels dilate to allow us to lose more heat from the body and cool down
  2. When we are feeling stressed our bodies activate the fight or flight response. Blood vessels in skin dilate in anticipation of the need for cooling when we start to fight or run away.

In rosacea, due the changes that have occurred in the skin the flushing response is significantly heightened and flushing occurs in response to minimal triggers and to an abnormal intensity.

What is causing the abnormal flushing?

Remember that rosacea skin has more blood vessels and often has blood vessels that are more prone to vasodilation. Rosacea skin also has an over sensitive skin immunity and is more prone to releasing anti-bacterial proteins that trigger skin inflammation.

There have been a number of recent research papers on molecules called TRPV( transient receptor potential vanilloid) channels. These molecules are found on the surface of sensory nerves in the skin. Think of them as detectors for environmental change. They tell the body when the temperature has gone up and allow the body to trigger cooling mechanisms. They also detect other changes in inflammation in the skin such as that caused by UV light. In rosacea, the number of TRPV channels on skin sensory nerves increases. This may be in response to the elevated levels of cathelicidin anti-bacterial proteins.  These leads to the situation whereby the skin is far more sensitive to changes in temperature and more sensitive to other inflammatory triggers. The skin then starts to over react to triggers such as temperature change and UV light. Once the sensory nerves have been stimulated they then release chemical that signal to the blood vessels to dilate causing a flush. The role of the sensory nerves explains why some patients also report very unpleasant burning of stinging sensations in the facial skin.

This explanation is an interpretation of current data and the precise details will emerge as further research is done. Further reading and scientific references include

  1. Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea
  2. TRPV4 Moves toward Center-Fold in Rosacea Pathogenesis
  3. Management of facial erythema of rosacea: what is the role of topical α-adrenergic receptor agonist therapy?
  4. Efficacy of low dose isotretinoin in patients with treatment resistant rosacea

 

Comparing the treatment options

Self-treatment

This advice is common to all rosacea

  1. Keep the skin well moisturised and avoid any irritant products
  2. Avoid alcohol as much as possible. The chronic inflammatory effect of alcohol will increase the inflammation in the skin even if triggering after drinking is not obvious
  3. Avoid any other identifiable triggers- spicy foods, warm office environments, vigorous exercise
  4. Use a sunscreen regularly . Rosacea skin is prone to flare ups after bright sun exposure but is also prone to the development of small vessels (telangiectasia) in response to UV exposure. Over time the build up of telangiectasia will worsen redness and the severity of flushing episodes.

Help from your GP

The usual treatments for rosacea will often help to reduce rosacea inflammation and redness. This in turn may help to reduce the flushing tendency.

  1. Tetracycline antibiotics such as doxycycline and lymecycline have antibacterial and anti-inflammatory effects. By reducing inflammation they can sometimes have an impact on rosacea redness but not always

 

  1. Metronidazole cream or gel will often help reduce spots but does not often have a big impact on redness

 

  1. Soolantra cream (ivermectin). Research studies have shown that a 3 month course of soolantra cream does reduce both spots and background inflammation.

 

  1. Vasoconstricting products. Blood vessels can be made to shrink down and become temporarily smaller using creams that activate the alpha receptors. The only product available currently is called MIRVASO (brimonidine) . Mirvaso does reduce redness in some patients. Unfortunately, in some cases the redness reduction is patchy giving a blotchy appearance. This may be due to the cream having a greater effect on small superficial vessels which are not evenly spread across the face. The other problem with Mirvaso has been a rebound effect. The Mirvaso lasts for up to 12 hours and then wears off; some patient found that as the effect wears off their skin flushes to a significant degree, sometime worse than the redness was in the beginning. The rebound flushing is generally temporary but clearly unwelcome and uncomfortable. Some patients have reported more prolonged problems with worsening redness and flushing having used Mirvaso. There is a newer vasoconstrictor product that has launched in the US and will be available in Europe soon. RHOFADE (oxymetazoline) targets alpha one receptors only and is reported to cause less background flushing. Time will tell how effective and useful this product is.

 

 

  1. Beta Blockers. Non cardio-selective B Blockers such as propranolol can have a significant impact on facial redness. Blood vessels have beta receptors and are involved in the fight or flight response. Adrenaline binds to blood vessel beta receptors in the skin and causes vasodilatation. Propranolol blocks beta receptors on blood vessels and prevents blood vessel vasodilatation. The problems with propranolol are that to get an effect on facial rednes  doses of 80mg 3x per day are needed. Much smaller doses are used for anxiety eg 10mg 3x per day. Many people are unable to tolerate propranolol at high doses and many people cannot take beta blockers due to other conditions such as asthma. Long acting beta blockers such as carvedilol are sometime better tolerated. The pros and cons of beta blockers need to be explored carefully with your primary care physician.

Help from a Dermatologist

Some primary care physicians may not be familiar with all of the treatments listed above and it is important that you work through all of the available licensed treatments with your Dermatologist before moving on to unlicensed treatments. Unlicensed treatments are treatments where the drug used has been approved for one condition but is then used for another condition. This means that although the drug has gone through safety testing it will not have been proven to work in the condition that it is being used in by proper randomised clinical trials. There may be good evidence that the drug works but no drug company has spent the money to get the drug formally license for that indication. In other situations, the drug may be used on a more experimental basis. In Dermatology where there are many rare diseases drugs are often used in off license situations. Your Dermatologist should always inform you if the use of a drug is off license (also referred to as off-label).

The basic principles of redness and flushing reduction are

  1. Physical – reduce the number of excess blood vessels and prevent more from re-forming
  2. Pharmacological- reduce the tendency of blood vessels to vasodilate by reducing the general inflammation or by directly targeting the blood vessels themselves.

 

  1. Lasers and IPL (Intense pulsed light)

Most patients with rosacea develop a degree of excess superficial blood vessels. These clearly contribute to facial redness and removing them will help to reduce the appearance of redness. Many different lasers and IPL systems can be effective in reducing these vessels. The most important thing for a patient is to choose an experienced laser practitioner who knows how to operate the equipment.

Some basic principles for rosacea laser treatments include

  1. IPL targets relatively superficial vessels. It cannot be used on darker skin types as the energy can be taken up by the pigment. It can be slightly uncomfortable and will cause some redness, the degree depending on the energy used. However, patients can sometimes return to work after treatment and it is unusual to have residual problems the following day. IPL will not affect deeper vessels and does not have much impact on what is often called background redness
  2. Long pulse ND-Yag. These lasers can deliver high energies to small areas and are excellent for treating larger telangiectasia that do not respond to IPL. Bruising can occur but is unusual and patients are normally fine to go to work the following day.
  3. Pulse Dye Lasers (such as the V-beam) can target larger and deeper blood vessels. These lasers are powerful and are used for a wide variety of skin vascular problems including port wine stains. Following treatment there will often be bruising which can last for days.

A combination of different lasers is sometimes needed to get the best results. After an initial course repeated top up treatments are often needed.

  1. Low dose isotretinoin

Isotretinoin is a retinoid drug which is licensed to treat acne. Any use in rosacea is off label. Skincompare has an article dedicated to low dose isotretinoin for rosacea. Clinical trial data has shown that low dose isotretinoin is highly effective for rosacea spots but also has an impact on redness. Reports from patients suggest that the dose of isotretinoin used is critical. If the dose is too high, isotretinoin can make the skin more red, as it always does when used in high doses to treat acne. The therapeutic window for reducing redness in rosacea seems to be at around 10mg OD although it can be lower in some patients. The precise mechanism of action is unknown. Retinoids are known to stimulate TRPV receptors (see above) but chronic low dose stimulation may lead to downregulation of the TRPV receptors with a subsequent reduction in facial redness and a reduced flushing tendency.

  1. Anti-histamines

Mast cells contain histamine. Release of histamine causes increased blood vessel dilation and blood vessel wall leaking. Skin becomes red, swollen and itchy. Rosacea skin contains significantly more mast cells than un-affected skin. Mast cells are thought to be an important source of inflammation in rosacea. Although there are no formal clinical trials some patients do find that regular anti-histamines can be helpful. Long acting ones such as fexofenadine 180mg in the morning can be tried. Short acting anti-histamines such as cetirizine need to be taken more regularly.

      4. Clonidine

This drug is mainly used to treat high blood pressure. Treatment will start with very low doses and can be increased. There is not much published evidence to support a benefit for rosacea redness and flushing although isolate reports have claimed good effects. Many patients develop side effects. Gradual withdrawal is needed to prevent side effects

  1. Anti-depressants.

A number of anti-depressant drugs have been reported to reduce facial redness. These include mirtazapine and sertraline. These drugs can have quite wide ranging side effects. Careful consideration and discussion with your Doctor is needed before trying them or rosacea.

 

SUMMARY

Rosacea redness and flushing are more difficult to treat than rosacea papules and pustules and are generally a cause of great frustration and distress for patients. It is important to remember the following

  1. Rosacea is a life-long condition. You will always be prone to it. Cure is not possible and the aim is good control
  2. You will not always look as red as you feel. Having a red face is one end of a spectrum of facial colours. Many red faced people are not bothered. Try not to let your rosacea impact too heavily on other more positive parts of your life
  3. Do the basics. Moisturiser, sun protection, alcohol and other trigger avoidance. Some Dermatologists would add a 3 month course of Soolantra, possibly repeated to this list.
  4. Laser treatments. If you have visible telangiectasia then some form of laser or IPL treatment will almost certainly be helpful. If you have smooth redness then the problem is with the deeper vessels and any laser treatment will need to be more powerful such as pulse dye laser. The outcomes when using lasers to treat background redness as opposed to telangiectasia are less certain but worth pursuing in some situations. Choose your laser provider carefully.
  5. Non-licensed medications for rosacea may take time to work. The size of benefit you will get will NOT be cure or 100% better. You need to set your targets at reasonable levels. A 50% improvement in redness or  frequency of flushing is often a good outcome. Combinations of medication may often be needed. Side effects are common and you will need to weigh them up against the benefits.
  6. The precise molecular science of rosacea has not yet been worked out. Different Doctors will have different ideas and experiences. You may well have to work through a number of different treatments and combination before finding an effective regime.