Topics Discussed Below

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• Introduction
  
• Vascular-Based Mini-Studies
  
• Nerve-Based Mini-Studies
  
• Immune-Based Mini-Studies
  
• Epidermal-Based Mini-Studies

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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

1. 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.
   
   
2. 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.
   
   
3. 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.
   
   
4. 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.
   
   
5. 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.
   
   
6. 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

1. 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.
   
   
2. 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.
   
   
3. 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.
   
   
4. 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

1. 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.
   
   
2. 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.
   
   
3. 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

1. 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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