Topics Discussed Below
- Introduction
- Vascular-Based Mini-Studies
- Nerve-Based Mini-Studies
- Immune-Based Mini-Studies
- Epidermal-Based Mini-Studies
I. Introduction
Based on personal communications
with research and private practice physicians, many are willing
to perform tests on rosacea sufferers and publish their results.
The studies would involve testing oral and topical medications that
have already been approved for other inflammatory skin disorders.
In certain cases, some would be willing to test novel substances
that are theoretically beneficial and safe to use. This process
is normally used to evaluate the potential effectiveness of a drug,
treatment or medication. These small mini-trials act as a
springboard for subsequent larger trials by Universities and pharmaceutical
companies..
Below is a list of topical
and oral medications that may have important implications in the
treatment of rosacea. The information below is quite technical;
it is geared primarily towards physicians.
II. Vascular-Based
Mini-Studies
- Topical Nitric Oxide Inhibitors - Nitric oxide is a
powerful dilator substance released from within blood vessel walls.
Nitric oxide inhibitors hold the potential to constrict facial
blood vessels, normalize facial inflammation and decrease blood
flow. Mini-studies are already underway in several clinical settings.
- Topical Vascular Endothelial Growth Factor (VEGF) Receptor
Antagonists - VEGF is a potent dilator substance that stimulates
the growth and development of new blood vessels. Blocking receptors
to this substance constricts blood vessels and decreases blood
flow through facial skin. It also holds the potential to decrease
the growth of new blood vessels which is proven to play a role
in the pathogenesis of rosacea. Topical VEGF-1 and VEGF-2 receptor
antagonists are available for study. Mini-studies are already
underway utilizing indirect blockade of VEGF.
- Topical Angiogenesis Inhibitors - There are several
key steps in the development and growth of blood vessels. Currently,
there are blockers for each step of angiogenesis. Various forms
of angiogenesis inhibitors should be evaluated for the treatment
of rosacea.
- Laser Treatment followed by Topical Angiogenesis Inhibitors
- After laser treatment there are substances released from the
skin that stimulate the growth of new vessels. This may explain
why some rosacea sufferers are 'resistant' to laser treatment.
Short treatment courses (30 to 45 days) with topical angiogenesis
inhibitors could decrease or completely halt this phenomenon and
result in substantial clearance of symptoms after laser treatment.
- Topical Caffeine-Based Moisturizers - Caffeine, when
applied topically results in mild constriction of blood vessels
and subsequent decreases in blood flow. Several of the large skin
care companies specializing in the treatment of sensitive skin
are now testing topical caffeine derivatives in their products.
This could be very useful to rosacea sufferers.
- Topical Phenylephrine (0.25%) - Topical Phenylephrine
causes moderate constriction of arteriolar and venular blood vessels.
Phenylephrine at 0.25% is already being used in over the counter
preparations for certain vascular conditions. Formulation of a
topical product in a time released base such as liposomes could
result in substantial constriction of blood vessels and subsequent
reductions in blood flow without 'rebound dilation'. This needs
to be investigated.
III. Nerve-Based
Mini-Studies
- Topical Neuronal Nitric Oxide Synthase (nNOS) Inhibitors
- Nitric oxide can also be released by nerves innervating the
facial skin. It is hypothesized that neural nitric oxide is responsible
for some forms of facial flushing and burning sensations. This
will be an important topic for future investigation.
- Topical Vasoactive Intestinal Polypeptide (VIP) Blockers
- VIP is a dilator substance that has been shown to be over expressed
in the central facial areas of rosacea sufferers. Effective VIP
blockers are now being developed by pharmaceutical companies.
This surely should be a main area of future interest.
- Topical Calcitonin Gene Related Peptide (CGRP) Antagonists
- CGRP is a potent dilator released by several nerve types innervating
the face. CGRP has recently become a main focus in many inflammatory
skin disorders and there have been recent trials and patents on
topical CGRP antagonists for rosacea sufferers. The results of
these studies should be closely monitored.
- Topical Substance P Blockers - Substance P is a dilator
substance that can be released by skin cells and nerve cells in
the facial skin. Two studies on rosacea sufferers indicate higher
than usual substance P levels in the facial skin and around blood
vessels. To date, there is no acceptable topical Substance P blocker,
but this is an area of interest to Pharmaceutical companies. We
shall see.
IV. Immune System-Based
Mini-Studies
- Topical Cytokine Blockers (blockers of their production
or receptors they bind to) - Inflammatory cytokines are known
to be involved in facial and ocular rosacea. They are part of
the flushing response and long-standing inflammatory response.
There are many potential cytokines involved in this inflammatory
pathway, but mini-studies can easily be performed to determine
what types of cytokines are involved and the best blockers to
be used for rosacea.
- Oral Singulair -- Singulair is a new oral pill used
to block inflammatory leukotrienes. This medication has been beneficial
to many allergy and asthma sufferers. Anecdotal reports from several
physicians and dozens of rosacea patients being treated with singulair
indicate that singulair has significantly decreased rosacea symptoms.
Are leukotrienes involved in non-allergic rosacea patients? Would
singulair be of benefit to severe rosacea with daily flushing
and unrelenting facial inflammation? This could easily be tested
in the near future.
- Topical Metronidazole (at much higher concentrations
than currently available) -- Topical metronidazole at 0.75% and
1.0% has been shown to have beneficial actions on facial inflammation.
Physicians are currently prescribing formulations from 2% to 5%
for moderate to severe rosacea sufferers. Studies need to be conducted
to see if higher concentrations are more effective.
V. Epidermal-Based
Mini-Studies
- Topical Epidermal Growth Factors -- There are currently
several classes of topical epidermal growth factors undergoing
study for prescription and non-prescription use. It is widely
documented that a significant number of rosacea sufferers have
very thin epidermal skin which makes the blood vessels and flushing
more noticeable, and more susceptible to environmental and skincare-induced
irritation. Topical substances that double or triple the thickness
of the epidermis could be beneficial to rosacea sufferers.
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