Hi Jen & All,

Interesting discussion. This stuff fascinate me too.

From what I've read though, most people consider Rosacea an
inflammatory disorder. I'm no scientist, but my understanding is that
the vascular problems we have with Rosacea are more a direct result of
the inflammation rather than the actual cause (but it is sort of a
chicken and egg thing - I'll explain why a little later).

Pulling info liberally from the following Southern Illinois University
School of Medicine abstract:

http://www.siumed.edu/~dking2/intro/inflam.htm

The triggers of acute inflammation are released by mast cells,
sensitive cells which are scattered throughout ordinary connective
tissues and which react to tissue damage or other disturbance.

The basic components of the inflammatory response are:

* Vasodilation
* Increased vascular permeability
* Emigration of white blood cells

There are a host of reactions involved in this process, but keeping it
very simple:

The vasodilation causes the redness or flushing we see with Rosacea.
Some Rosaceans flush just on their faces (which is comparatively
vascular and tends to show a flush first), while others flush
elsewhere in addtion (the neck, chest and arms are common - I acually
flush pretty much from head to toe and I've read posts from others who
mention this too).

The increased vascular permeability (along with the vasodilation) is
then meant to prepare the way for leukocytes or white blood cells
(including Neutrophils, Lymphocytes and Monocytes) to leak out of the
vessels and enter the inflammed tissue for healing.

When the Leukocytes leak out into the surrounding tissue, the fluid
build-up which follows is called edema and is visible as puffiness or
swelling and the increased metabolic activity associated with
leukocyte activity also generates heat, contributing to local warmth.
Any of this sound familar?

The Neutrophil Leukocytes seem to play one of the most important rolls
here, and they are the reason you may have heard Rosacea referred to
as Neutrophilic Dermatosis. From my understanding, these leaking
neutrophils end up causing the p&p's we see, and are also responsible
for stimulating Vascular endothelial growth factor (VEGF ) which ends
up promoting additional vascular growth (and thus our visible and
non-visible excess blood vessels):

http://archsurg.ama-assn.org/cgi/content/abstract/134/12/1325

Over time, this process builds on itself, more blood vessel growth
allows more inflammation, which only creates more blood vessel growth,
etc. Thus the chicken and egg thing. Something causes the
inflammatory response to begin with, but once it starts, the excess
blood vessels only feed more inflammation, etc.

It seems that scientist have a pretty good grip on the above mentioned
process. The real question in my mind is what causes the
inflammation which leads up to this neutrophilic dermatosis.


Backing up to the mast cell, mast cells contain receptors that when
activated, cause the mast cell to release histamine and tnf-a:

http://www.annals.org/cgi/content/full/121/9/684

This part is a little fuzzy to me, but it appears that the Tnf-a
stimulates the production of Arachidonic acid via Phospholipase A2
(note that the mast cell might also release phospholipase A2 directly
- I couldn't confirm this either way) from our cellular lipid stores.

Anyway, the Arachidonic Acid is responsible for the production of a
host of downstream leukotrienese through the 5-LOX pathway and these
leukotrienes seem to be responsible for much of the problems
associated with the inflammatory response:

http://www.annals.org/cgi/content/full/121/9/684

Arachidonic Acid is also responsible for the production of downstream
prostaglandins and thromboxanes, which also play a role in making the
blood vessels dilated and leaky:

http://www.cvphysiology.com/Blood%20Flow/BF013.htm


From what I've read, Arachidonic Acid can be obtained directly through
dietary sources, but the majority in our bodies is created from
consumption of linoleic acid found in vegetable oils such as corn,
sunflower seed, safflower, soy, sesame, and cottonseed oils. And many
researchers theorize that our current diet contains too large a
percentage of this fatty acid in comparison to the omega-3 variety,
contributing to most of the modern world's inflammatory problems
(arthritis, heart disease, alzheimers, crohn's disease, and our friend
rosacea among others). Theoretically, by decreasing your intake of
linoleic acids and increasing your intake of omega-3's, over time you
will replace the contents of your body's lipid stores with less
inflammatory ones, helping to reduce the inflammatory reaction
(although research suggests not stopping it altogether).

Blocking the downstream leukotrienes through 5-lox inhibitors and/or
the the downstream prostaglandins and thromboxanes through cox
inhibitors like aspirins should theoretically help too.

By the way, studies seem to suggest that women's hormonal cycles seems
to influence this inflammatory cycle as well. And I've also read
something about high glucose levels being involved in this cycle, but
I'll have to provide more on that later...

The real unanswered question though, is what sets off this
inflammatory event for us in the first place. Could it be some
bacterial, viral, or fungal pathogen? Is it genetics where we might
have the potential for more 5-LOX and/or COX production? Or could it
be more of a self purpetuating cycle where frequent flushing from
allergies, heat, hot flashes, etc causes irritation (tissue damage)
which then causes inflammatory response which continually leads to
more inflammation, and if so, could replacing the the body's lipid
stores with less inflammatory lipds finally break this cycle?

For those of us who have other problems such as IBS, arthritis,
asthma, even seb derm, etc, I tend to think it is more likely due to
some pathogen, but I may be wrong of course. Interestingly though,
some studies seem to suggest that the pathogens themselves are even
responsible for some of the arachidonic acid production:

http://iai.asm.org/cgi/content/full/70/1/400

Interesting how our old friend Candida keeps popping up...

Hope you find this interesting. Forgive me if I've gotten any of
this wrong, as I am really no scientist. I do believe that most of
this pretty fairly represents current studies however...

Take care,
Dan






--- In rosacea-support@yahoogroups.com, "Jen-Bear" <rothco@b...> wrote:
>
> Sharon wrote:
> "I once read that the Chinese believe people with skin disorders
> actually have really strong immune systems. The symptoms you
> experience are a result of your immune system trying to fight off
> inflammation. I don't know if this is true, but I've read it in
> several articles on the net."
>
> KHM wrote:
> "For some of us an overactive immune system certainly seems to be a
> factor (not merely strong - way over sensitive too)
>
> Many of the things that help us are immune system modifiers - e.g.
> interfere with one of the outputs of inflammation, usually caused by
> your immune system believing something needs to be attacked.
>
> This would include Singulair, Eledil, Protipic, Boswellia, Cox 2
> inhibitors, and probably simple things like asprin.
>
> …my immune system is hypervigilant."
>
> Laurie wrote:
> "That sounds like allergies. True allergic responses are your body
> fighting against normal and healthy things that it thinks are not
> good for your body. Some people with allergies think they need
> to "strengthen their immune systems" but really they already have
> an over-active immune system."
>
> ..............................................
>
> Now this is from me… :o)
>
> I find Chinese Medicine really fascinating – yet at the same time –
> I find it a little intimidating! I guess it is the fear of the
> unknown? Whilst I understand that most ingredients are sourced from
> nature, some are kinda weird to me. Having said that, Chinese
> Medicine has been around for far longer than western medicine and
> one should at least give it the benefit of the doubt. I must do some
> more research into it and over come my fear! LOL
>
> So, if people with skin disorders have a stronger/over
> sensitive/over-active immune system, I don't understand why the skin
> is not fixed quickly from our internal repair mechanism ie. the
> immune system. Think I am getting myself into a bit of a spin over
> this one! LOL
>
> On the other hand, I have read that Rosacea is considered to be a
> vascular disorder as opposed to a skin disorder. What we see on our
> faces is the reaction (the symptoms) to the cause. Which brings me
> full circle – what is the root cause – the common thread?!
>
> If Rosacea is a vascular disorder, then it may be possible that our
> immune systems are not working to full capacity to fix the problems
> that appear on our faces?! If Rosacea is a skin disorder, then our
> stronger immune system should fix the problem?! Theoretically, that
> is!
>
> So if we boost our immune system with vitamins and the like, is this
> a good thing or bad thing? If we weaken our immune system by taking
> long-term antibiotics, is this a good thing or bad thing? I guess it
> depends on what type of disorder one terms Rosacea to be?!.
>
> If our bodies are reacting to an allergen, why does it come out on
> our faces? What makes us different from non-Rosaceans? Again, back
> to the Common Thread/Root Cause thing.
>
> Guess I'm just throwing it back out there again to see what other
> people believe.
>
> Jen :o)
>