The dermatology news sheet Dermatology Times has published an item to their web site about the emerging use of oxymetazoline to treat the redness and flushing associated with rosacea. This article draws from the Nov. 2007 paper that introduced us to the possibility of treating rosacea with oxymetazoline.

We also know from the Feb. 2008 meeting of the AAD that oxymetazoline is effective for up to 6 hours after application, and that no negative side effects have been seen after 3 months usage. Further comments here in the DT article extends the apparent `durable’ treatment period to 2 years. Note that this successful long term avoidance of rebound whilst using oxymetazoline refers to just one patient.

Dr. Shanler notes that loss of effectiveness and rebound dilation is a problem associated with the use of intranasal use of oxymetazoline.

Oxymetazoline is classified as a alpha-1 Adregenic Receptor Agonist, whereas COL-118/Sansrosa is a alpha-2 Adregenic Receptor Agonist. According to this DT article oxymetazoline is “also partially selective for the alpha 2a receptor.”

The paper’s authors are both corporate officers of Aspect Pharmaceuticals, who are now planning more formal studies to evaluate rosacea friendly formulations of oxymetazoline and other alpha-1 adrenergic agonists to treat the redness and flushing of rosacea.

From: Taking the red out of rosacea: Topical alpha-1-adrenergic receptor agonist shows promise

Limited experience in a small number of patients indicates that the erythema and flushing associated with rosacea may be safely and successfully treated with topical application of a selective alpha 1-adrenergic receptor agonist, such as oxymetazoline, researchers say.

…

"The results achieved with topical oxymetazoline are exciting, but very early, and they need to be confirmed through more rigorous studies," Dr. Shanler tells Dermatology Times.

Patient responses to topical oxymetazoline were based on direct clinical assessment and review of high-resolution digital photographs taken pretreatment at one, two to three and 24 hours post application, and then again after longer-term treatment. The evaluations showed topical oxymetazoline had a rapid effect in reducing erythema.

With continued treatment, which extended up to two years in one patient, the responses remained durable, with no evidence of tachyphylaxis, rebound or adverse events.

"Loss of efficacy due to receptor desensitization and rebound vasodilation is a problem associated with use of intranasal oxymetazoline and other imidazoline- and amine-class nasal decongestants.

"There is some laboratory evidence that the potential for receptor desensitization varies depending on the agonist’s selectivity for different alpha-adrenoreceptor subtypes and its duration of action. This may be a consideration in the development of a dermatologic medication that will provide optimal efficacy with minimal risks," Dr. Shanler says.

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In November 2006 I blogged about taking part in some research at Murdoch University investigating the relationship between stress and the flushing of rosacea.

Recently the researcher, Daphne Su, has thanked the trial participants by circulating a summary document. The research has been written up as a thesis so this summary was a short description of some the research findings. Here is what I have taken away from the summary. Three of the findings look interesting for rosacea sufferers.

1. The over activity of axon reflexes contributes to facial flushing.

   By measuring the axon reflex response with acetylcholine iontophoresis it was suggested that the neural pathways (how your nerves mediate a flush) were more important in the flushing response compared to cutaneous endothelial function (blood vessel dilation).

2. Emotional flushing in rosacea sufferers may be maintained by a combination of both cognitive and physiological factors.

   Type 2 rosacea sufferers had more facial blood flow and felt more aroused during an embarrassing task, compared to Type 1 rosacea sufferers. Taken together with Point 1, it is suggested that it is a combination of both physiological and cognitive factors causing increased facial blood flow. 
    

3. The stress and fear of blushing can be mitigated by psychological intervention such as Cognitive Behavioural Therapy and Task Concentration Training.

As it appears that both the perception of a facial flush and the physiological response are important factors, psychological intervention may also be an important part of a treatment regime. The trial participants in the final phase of the research were offered CBT and TCT to help them cope with stress and anxiety. All showed a decrease in anxiety symptoms.

Daphe Su has submitted her PhD thesis, so when it has been accepted she will become a bone fide Rosacea PhD. It is thought that this is the first PhD thesis on rosacea. Well done !! Her supervisor, Professor Peter Drummond is also interested in supervising more Rosacea students in the future.

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You may have noticed that your face flushes when you enter a warm room, but have you ever thought about how that process actually works ? Well, a nicely written article just released on the web goes into detail about how your body responds when you go from a cold room to a warm room. Colin Dahl, rosacea sufferer himself, from Australian Sciences has created this article to help rosacea sufferers understand the thermoregulatory roots of facial flushing in a simple, easy to read manner. The following couple of paragraphs from Chapter 1 give an accurate description of the contents of the booklet.

A Practical Understanding of Rosacea, Part 1: Heat Regulation and the Warm Room Flush Phenomenon, By Colin Dahl, Chief Scientist, Australian Sciences.

The simplified biological mechanics of rosacea have been explained in the booklet. Minimal medical terms have been used and may be further referenced online. I believe that a basic understanding of how the body deals with heat regulation and dilation of blood vessels is needed if you want to begin reversing this and other forms of facial flushing associated with rosacea.

It is not the intention of this booklet to name or deal with specific chemicals. The reason for this is simple, once you have excessive blood vessels and nerves in your skin, you will have an excess of numerous inflammatory chemicals. It is the intention of this booklet to highlight the systems involved, so that these systems can be used in your favor.

Often we see terms like nerve-mediated vasodilation, cutaneous nerves, angiogenesis (and a new one axonogenesis), sympathetic nerves, neurotransmitters, neuropeptides, nerve growth factors etc. thrown around. Finally here is a document that puts them together in context. Whatsmore, it is a pleasure to read.

I like that the document doesn’t suggest that IPL is the end-game for treating flushing. See the document for Mr. Dahl’s thoughts on how to enhance the effectiveness of IPL therapy.

If you go to the Products section of the web site you will also see that Australian Sciences have products related to rosacea in the development pipeline. From the PDF;

Australian Sciences is developing a range of effective products aimed at assisting in the reduction of excessive skin cell activity due to environmental factors such as sun exposure. Australian Sciences has conducted extensive research into the normalization of inflammatory skin cells with natural compounds such as silymarin, egcg, vitamin B12 and many others. Independent research has also showed these compounds to be effective for other inflammatory skin disorders such as atopic dermatitis and psoriasis. We believe these products can help normalize skin cells and assist in the long-term reversal of excessive skin infrastructure.

Further benefits can be achieved through reducing the exposure of skin cells to environmental factors. A major contributor to excessive skin cell activity is sunlight. Not only is the ultraviolet radiation a major contributor, but the excessive heat energy delivered to skin cells is enough on its own to cause problems for those with rosacea.

Stay tuned for further information.

Read the document here: Australian Sciences Rosacea Page.

What do you think about this document ? Leave a comment below or discuss it online at the Blushing and Flushing Forum at the Rosacea Support Forum.

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PubMed pushed out an interesting abstract in the last couple of days. A bit of digging reveals what looks to be a running mate for COL-118/Sansrosa. COL-118 and Oxymetazoline appear to be promoted by separate groups of researchers.

This is good news for rosacea sufferers as it means there may well be a choice between 2 topicals that can help address the redness and flushing of rosacea.

With the publishing of this new paper, Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective {alpha}1-Adrenergic Receptor Agonist, Oxymetazoline, a new, but similar to COL-118/Sansrosa topical, has become more public.

Oxymetazoline is classified as a alpha-1 Adregenic Receptor Agonist, whereas COL-118/Sansrosa is a alpha-2 Adregenic Receptor Agonist.

Whilst COL-118 is further along the development path towards general availability, this paper raises the hope that oxymetazoline may also become available `on-label’ for rosacea treatment.

It is worthwhile listing some similarities and differences between these 2 redness reducing relatives.

The Sansrosa patent also has references to oxymetazoline, so there appears to be some overlap in at least some of their invention claims.

I would urge rosacea sufferers to use caution when using OTC or prescription drugs off label. It is a far safer option to wait for the FDA to approve any possible new topical redness treatments. Please be very wary until these drugs have been proven safe and effective in treating the redness and flushing of rosacea.

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Alluding to a link between rosacea and migraines, Dr. Joseph Bikowski says that aspirin should be the first line of defense against rosacea flushing. A recent article in Dermatology Times highlights the potential benefits (and risks) of taking low doses of aspirin long term for rosacea swelling and flushing.

From: Miracle-worker aspirin represses rosacea flushing

An informal study with his rosacea patients who took a daily aspirin (81mg) reported less flushing and shorter episodes of erythema.

Dr. Bikowski argues, “Aspirin therapy is safe. It’s great for the heart. It’s great for the colon. Why not the skin?” He further notes that there are few contraindications for aspirin use, it’s inexpensive and it can be taken in combination with most drugs.

The NRS also recommends aspirin: Tripwires – Foods and Beverages

Taking an antihistamine about two hours before a meal may counter the effects of histamine, while aspirin may reduce the effects of niacin-containing foods in sufferers affected by these substances.

And finally, Asprin forms part of Dr. Linda Sy’s rosacea swelling relief regimen.

At bedtime: Take 1 baby aspirin; 1 chlor-trimeton(4 mg) and 1 tab of Tums (Calcium Carbonate , an antacid to offset the gastric irritating effect of the aspirin.

In the AM: Take a B Complex vitamin that contains 50 mg. of B-6. Avoid
one w/ Niacin (Niacinamide is fine) and 1 Tagamet (200 mg). During bouts of flushing, apply a cool (not cold) compress on face. Do deep breathing 10 times slowly.

See Also:

• RSRP: Aspirin

How about you ? have you take aspirin specifically for rosacea swelling or flushing ? did it help any ?

FDA Issues Warning Letter to Melanocorp, Inc. For Illegal Sale of Melanotan II

Melanocorp, Inc. advertises the product Melanotan II on its Web site as an injectable tanning product, with additional claims that it is effective in protecting against skin cancer and rosacea (a flushing and redness of the skin). These claims cause Melanotan II to be classified as a drug under the Federal Food, Drug and Cosmetic Act, as well as a new drug because there is no evidence that it is generally recognized as safe and effective for its labeled uses.

I’m still of the impression that it is too early to be getting excited about Melanotan and rosacea. There seems to be too many unanswered questions about efficacy and side effects. So here we can see the FDA stepping and saying that it is too early for it to be generally available.

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See Dr. Dummond’s Publication History for more information about his area of research interest.

You can find his interview in so-called RSRP – Rosacea Support Resource Pages

• Rosacea and the SNS

The Support group would like to express our deepest thanks to Professor Drummond for kindly taking the time to answer a few questions relating to some of these possibilities.

See Also other RSRP interviews:

• Ocular Rosacea: Dr. Eric Jones, MD
• Ocular Rosacea: Dr. Mark J. Mannis, MD
• Rosacea Highlights: ETS comments and warnings

This paper explores the different problems that may be causing flushing. The list of possible reasons other than rosacea is extensive. It is worth consider what other conditions may be causing your red face before embarking on any treatment regime. Treatments that are good for some of the conditions listed here may make your rosacea worse, so read as widely as you can.

The author was kind enough provide a full copy of this paper, so contact me if you’d like to read it.

If you would like some ideas about about how to treat a red face, see another popular article I wrote titled how to treat a red face

The flushing patient: Differential diagnosis, workup, and treatment, Journal of the American Academy of Dermatology, Volume 55, Issue 2 , August 2006, Pages 193-208. Leonid Izikson MD, Joseph C. English III MD and Matthew J. Zirwas MD, Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Abstract: Cutaneous flushing—a common presenting complaint to dermatologists, allergists, internists, and family practitioners—results from changes in cutaneous blood flow triggered by multiple conditions. Most cases are caused by very common, benign diseases, such as rosacea or climacterum, that are readily apparent after a thorough taking of history and physical examination. However, in some cases, accurate diagnosis requires further laboratory, radiologic, or histopathologic studies to differentiate several important clinicopathologic entities. In particular, the serious diagnoses of carcinoid syndrome, pheochromocytoma, mastocytosis, and anaphylaxis need to be excluded by laboratory studies. If this work-up is unrevealing, rare causes, such as medullary carcinoma of the thyroid, pancreatic cell tumor, renal carcinoma, and others, should be considered.

Learning objective: At the completion of this learning activity, participants should be familiar with the mechanisms of flushing, its clinical differential diagnosis, the approach to establish a definitive diagnosis, and management of various conditions that produce flushing.

Abbreviations: CS, carcinoid syndrome; 5-HIAA, 5-hydroxyindoleoacetic acid; 5-HT, 5-hydroxytryptamine; MCT, medullary carcinoma of the thyroid; NSAID, nonsteroidal anti-inflammatory drug; TMEP, telangiectasia macularis eruptiva perstans; VIP, vasoactive intestinal polypeptide

…
When evaluating patients with rosacea, it is important to exclude the diagnoses of polycythemia vera, photosensitive eruption, lupus erythematosus, mixed connective tissue disease, carcinoid syndrome, systemic mastocytosis, or side effects from long-termfacial application of topical steroids. Since rosacea is typically limited to the face, extra facial erythema is generally an exclusionary sign. Rosacea flushing is associated with burning or stinging but not sweating, lightheadedness, or palpitations. Erythematotelangiectatic rosacea, while considered by many to represent a separate entity, may in fact be difficult to distinguish from simple benign cutaneous flushing and sun-damaged skin. In attempting this distinction, it may be useful to assess the extent of baseline facial telangiectasia and the overall degree of poikiloderma. However, since these 3 conditions are all common, they may coexist in many patients. Also, since erythematotelangiectatic rosacea and benign cutaneous flushing may have common triggers for flushing, it may be reasonable to consider these 2 entities as different points on a single continuum, making distinction of academic value only.
…
Table II
Differential diagnosis of flushing

Common Causes

Benign cutaneous flushing

Emotion
Temperature
Food or beverage

Rosacea
Climacteric flushing
Fever
Alcohol

Uncommon, serious causes

Carcinoid
Pheochromocytoma
Mastocytosis
Anaphylaxis

Other causes

Medullary thyroid carcinoma
Pancreatic cell tumor (VIP tumor)
Renal cell carcinoma
Fish ingestion
Histamine
Ciguatera

Psychiatric or anxiety disorders
Idiopathic flushing
Neurologic

Parkinson’s
Migraine
Multiple sclerosis
Trigeminal nerve damage
Horner syndrome
Frey syndrome
Autonomic epilepsy
Autonomic hyperreflexia
Orthostatic hypotension
Streeten syndrome

Medications

Very rare causes

Sarcoid, mitral stenosis, dumping syndrome, male androgen deficiency, arsenic intoxication,
POEMS syndrome, basophilic granulocytic leukemia, bronchogenic carcinoma, malignant histiocytoma, malignant neuroblastoma, malignant, ganglioneuroma, peri-aortic surgery,
Leigh syndrome, Rovsing syndrome

Summary: The differential diagnosis of cutaneous flushing is extensive and encompasses a variety of benign and malignant entities. Most flushing reactions result from benign causes. However, since flushing may be the presenting sign or symptom of several life-threatening conditions, it should prompt a thorough investigation to exclude such possibilities as anaphylaxis, systemic mastocytosis, carcinoid syndrome and other malignant tumors, pheochromocytoma, and autonomic epilepsy after more common benign causes have been ruled out and if there is no response to treatment. In the absence of an identifiable benign organic cause of flushing, psychiatric illness must be suspected and the patient should undergo appropriate evaluation. History and physical examination are critical in the evaluation of the cause of flushing and should be supplemented with laboratory and other investigations based on the clinical suspicion of an underlying cause. The most common causes of flushing – fever, emotional flushing, climacterium, and rosacea are obvious to most physicians and thus are likely to be promptly recognized and treated appropriately. Dermatologists have a unique role in the management of patients with flushing, as referred patients may be unresponsive to conventional therapy and are more likely to have a serious or life-threatening underlying cause. Accordingly, proper workup, recognition, and management of conditions that cause cutaneous flushing may have a significant impact on the patients’ morbidity and mortality.

• Abstract Online
• PubMed Extract

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Some extracts from the article ;

On the other hand, flushing associated with rosacea commonly fails to respond to standard therapies for rosacea. Idiopathic flushing rends to occur in women and the symptoms persist for a long duration. Treatment of flushing is difficult primarily because it has been assoicated with multiple etiologies. Improvement in transient flushing is also difficult ot quantitate, although attempts to provoke flushing and to measure the responses to medications have been performed. Even so, only small series and case reports are found in the literature.
…
Beta-blocker therapy should be monitored for side effects. Fatigue, somnolence, and dizziness and reported by approximately 10% of patients.
…
Symptomatic idiopathic flushing and flushing associated with rosacea deserve separate treatment, since the flushing does not respond to conventionial rosacea treatment. Although the perceived improvement of flushing and its sumptoms in 8 of our 9 patients treated with propranolol is encouraging, prospective randomized studies with control subjects and standardized quality of life date are necessary to better determine the efficacy of propranolol therapy.

Symptomatic treatment of idiopathic and rosacea-associated cutaneous flushing with propranolol

Journal of the American Academy of Dermatology, Volume 53, Issue 5 , November 2005, Pages 881-884.

Helen Craige MD and Jack B. Cohen DO,

Department of Dermatology, University of Texas Southwestern Medical School
Dallas, Texas. Available online 20 October 2005.

Flushing has been associated with medications, rosacea, menopause, carcinoid syndrome, pheochromocytoma, polycythemia, and mastocytosis, although it can occur without known cause. There are no known specific treatments available, but ???-blockers have suppressed flushing reactions in some patients, particularly when associated with anxiety. The medical histories and clinical characteristics of 9 patients with either idiopathic flushing or flushing associated with rosacea were reviewed. Eight patients experienced subjective improvement with propranolol therapy.

• Abstract Online Full Article available from author.
• PubMed Extract
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Botulinum Toxin for the Treatment of Facial Flushing, Dermatologic Surgery, Volume 30, Number 1, January 2004, pp. 102-104, Melanie Yuraitis, MS, and Carolyn I. Jacob, MD

Background: Facial flushing is a common problem that is encountered by fair-skinned patients of Celtic and Northern European descent. Although usually transient in nature, some patients display a persistent reddened skin tone, with periods of increased erythema. Treatment of this condition is limited.

Objective: To describe a novel method for the treatment of persistent facial flushing.

Method: We report a case of persistent facial flushing that was resistant to multiple pulsed dye laser treatments and was successfully treated with botulinum toxin A.

Results: The post treatment appearance was dramatic, and the patient was highly satisfied with the cosmetic outcome.

Conclusion: Botulinum toxin A can be used in small quantities to decrease persistent facial flushing temporarily.

• Abstract Online #1
• Abstract Online #2
• PubMed Abstract

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