Guide

Email from:

From:

Robert Brodell, MD

Subject: Re: Please take five minutes to comment

Date: July 21, 2010 10:52:08 AM HST

To: Barrows Brady

The best way to categorize acne rosacea would be into subgroups that are treated in the same manner......I like erythrotelangiectatic rosacea as a subset where infection is not a key issue and antibiotics might be less important than evolving vasoconstricting drugs, laser therapy and coverups. Papulopusular acne and many of the variants mentioned in the previous comment are related to demodex, bacterial infection, and pityrosporon yeast.....to the extent that most respond to antibiotics, I have always favored bacteria as a key part of the pathogenesis in most patients, though the antiinflammatory effects of antibiotics may explain their benefits as well. The subset that is associated with seborrheic dermatitis is best treated like rosacea, plus ketoconazole cream bid to cover the pityrosporon that induces seb derm. There will always be some controversy here, but this is the approach I would take if I were a thought leader!

Robert Brodell, MD

From: Latkany, MD Robert

Subject: RE: RRDi MAC Members Please Comment on Topic

Date: July 6, 2010 10:33:48 AM HST

To: Brady Barrows

In general I would agree. However, if dividing the type of rosacea into subtypes helps explain different etiologies then it is necessary and will be helpful to guide physicians into different treatment directions. But until we better understand why people get rosacea this is all insignificant.

Robert Latkany, MD

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This post has been promoted to an article

The RRDi has now endorsed the new phenotype classification of rosacea. 

We have received only one review of the Journal of the RRDi so far which has been a rather negative one from David Pascoe. We could use some positive ones but if you feel David is warranted in his criticism of our new journal please post your thoughts here as well. I have written my thoughts on David's review on my personal web site and also thought it would be fair to post it here as well. But please give us your reviews of our new journal in this thread. My thoughts on David's negative review can be read at this article: 

Is Rosacea a ‘Complicated Diagnosis Path’ and Mysterious Disorder?

I would hope that members of the RRDi would read the Journal of the RRDi for themselves and decide what they think of the journal and then post a review here in this thread.

Thanks

Jeffry B. Stock, Ph.D., has volunteered to serve on the RRDI MAC. Dr. Stock is on some cutting edge research for a treatment for rosacea at Signum Bioscience.

Lance Christiansen is no longer serving on the RRDi Board of Directors. We appreciate Lance's volunteering to serve the RRDi.

Welcome Nick to the RRDi.

I googled it and haven't heard of using "0.375% lidocaine applied to specific sites modifies the state of the nervous system in the place where you applied and thus acts on the entire body." I had to have google translate the page.

Have you actually tried this?

This is to announce that Begül Yağcı-Küpeli, M.D. has volunteered to serve on the RRDi MAC. Dr. Begül Yağcı-Küpeli, M.D. suffers from rosacea and is a Pediatric Oncologist. The RRDi is grateful for her volunteering.

I am pleased to announce the inaugural edition of the Journal of the Rosacea Research & Development Institute is now available from iUniverse. The proceeds of the sale of this journal will be used to further the journal's publication and lead to some novel rosacea research. This journal took over two years to develop and the RRDi had many volunteers to publish this. Joanne Whitehead, Ph.D., is the editor in chief of the Journal of the RRDi and she worked countless hours making this a reality. Thanks for your support by purchasing a copy.

Some of the MAC Members reply to questions by email to me and I then publish the answers for them. Here is a reply from Kosta Y. Mumcuoglu, PhD regarding this topic question:

BEGIN REPLY:

It is known that patients with papulopustular rosacea have a higher density of Demodex folliculorum mites on their faces than normal subjects but their role in initiating inflammation is disputed. It was reported that when the number of Demodex mites increases, there is a higher chance to develop a bacterial infection and inflammation, which could be considered as a result of the mite activity and damage caused. Selective antibiotics are effective in reducing the inflammatory changes of papulopustular rosacea, but their mode of action is unknown. Lately, a bacterium (Bacillus oleronius) was isolated from a D. folliculorum mite extracted from the face of a patient with papulopustular rosacea. To investigate whether this mite-related bacterium was capable of expressing antigens that could stimulate an inflammatory immune response in patients with rosacea, Lacey et al. (2007) investigated patients with rosacea and control subjects and found that in the presence of bacterial antigens, the proliferation of peripheral blood mononuclear cells was significantly higher in patients with rosacea than in control subject. Accordingly, it is thought that mite-related bacteria have the potential to stimulate an inflammatory response in patients with papulopustular rosacea.

Li et al. (2010) investigated the correlation between ocular Demodex mite infestation and sero-positivity of the patients to B. oleronius in 49 patients with facial rosacea. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography. There was a significant correlation between serum immunoreactivity (presence of the bacterium) and facial rosacea, lid margin inflammation, and ocular Demodex infestation. The Demodex count was significantly higher in patients with positive facial rosacea. The strong correlation provides a better understanding of co-morbidity between Demodex mites and their symbiotic B. oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation.

References:

Li J, O'Reilly N, Sheha H, Katz R, Raju VK, Kavanagh K, Tseng SC. Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea. Ophthalmology. 2010 Jan 14. [Epub ahead of print]

Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol. 2007 Sep;157(3):474-81.

Kosta Y. Mumcuoglu, PhD

END REPLY

This is to announce that two new MAC members have volunteered to serve on the RRDi MAC:

Craig A. Elmets, M.D., Chairman, Department of Dermatology University of Alabama School of Medicine

and

Alan B. Fleischer Jr, M.D., Professor and Chair of the Department of Dermatology at Wake Forest University

The RRDi appreciates these two physicians volunteering to help us.

Here are replies by email:

From: Robert Brodell, MD

Subject: Re: Questions for the RRDi MAC Members

Date: February 12, 2010 2:49:14 AM HST

To: Barrows Brady

Misdiagnosed Rosacea

Why do you think there are reports of misdiagnosed rosacea? The diagnosis is rosacea is easy of a patient has acne papules and pustules in association with a red face. However, some patients have a form of rosacea with mostly redness and telangiectasias. Without the acne component visible, the differential diagnosis includes chronic sun-damaged skin, flushing and blushing, acute lupus, drug induced erythema, and other conditions. In some cases, patients have a combination of several causes for their facial redness. While in most patients the diagnosis of acne rosacea is easy, some patients with facial redness due to other causes may be called rosacea, and some patients with rosacea may be missed even when physicians are smart and mean well.

Robert Brodell, MD

_____________________________________________________________

Reply from Brady Barrows to Dr. Brodell:

Here is the evidence for misdiagnosed rosacea: Click Here

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Replies sent by email:

From:

Robert Brodell,MD

Subject: Re: Questions for the RRDi MAC Members

Date: February 12, 2010 2:49:14 AM HST

To: Barrows Brady

Oracea Long Term Use

How long should Oracea be prescribed?

Oracea is a low-dose doxycycline formulated to have a slow release component so that the level of drug in a patient's system is lopw at any given time. This insures that the doxycycline is working as an anti-inflammatory drug rather than an antibiotic which minimizes side effects including stomach upset, yeast infections, and the potential for developing bacteria that are resistant to this drug. This makes it an excellent drug for rosacea. While physicians never want patients to be on any oral drug longer than they need it, some patients with rosacea require long term treatment. I have patients who have been on Oracea for years since every time I try to stop the medication their condition flares up, despite attempts to suppress their rosacea with a variety of topical medications. So, How long should Oracea be prescribed? Ans> As long as needed to keep rosacea under control....and,.... as short as possible!

Robert Brodell, MD

____________________________________________________________

Galderma after it acquired Collegenex's brand Oracea, which is described as "Capsules 40 mg are hard gelatin capsule shells filled with two types of doxycycline beads (30 mg immediate release and 10 mg delayed release) that together provide a dose of 40 mg of anhydrous doxycycline," is marketing this as a first line of treatment for rosacea and as the 'only FDA approved oral medication for rosacea."

The Prescribing Information Sheet from Galderma says that "Efficacy beyond 16 weeks and safety beyond 9 months have not been established."

There are numerous reports that Oracea has been prescribed well over 9 months. What do you think about prescribing Oracea beyond the safety threshold described in the sheet mentioned above? Should rosaceans expect to be prescribed Oracea long term in amount such as years?

The subject of misdiagnosed rosacea usually comes up when there is a discussion or articles about rosacea. I am curious what the MAC members think about misdiagnosed rosacea and why it occurs? What would be the most obvious reason a misdiagnosis occurs? Is it because the definition of rosacea is sometimes vague? The initial history and physical exam is cursory? Or is there another reason why this occurs? If there are several reasons what might they include?

Here is list of articles and anecdotal reports of misdiagnosing rosacea.

Tanweer A. Syed (Timothy Syed Andersson) is no longer affiliated in any way with the RRDi.

This is to announce that Noah Scheinfeld, M.D. has joined our Medical Advisory Committee [MAC] as a consultant to the RRDi and you may view his photo and CV at this page. Dr. Scheinfeld has a background not only in dermatology serving on the faculty at Columbia University but also a background in law having graduated from Harvard law school. The RRDi greatly appreciates his volunteering to help us.

The following replies to this thread were sent to me by email:

From: Robert Brodell, M.D.

Subject: Re: Calcium, Vitamin D(3), And Retinoic Acid

Date: January 23, 2010 2:16:31 AM HST

To: Barrows Brady

Basic science research is important because it often points up approaches to disease treatment that would not be otherwise apparent. HOWEVER, acne rosacea is a complicated process and I would not recommend any changes to the treatment of patients without clinical evidence of efficacy.

Bob

-------------------------------------------------------

A new PubMed article abstract by Dr. Gallo concludes:

"These findings show that the expression and activity of KLK are under fine control and can be distinctly influenced by variables such as differentiation, calcium, vitamin D, and RA. Thus, these variables may further control the functions of antimicrobial peptides in the skin."

Does this mean that rosaceans should increase their intake of calcium, vitamin D and RA?

What comments do you have about this research?

A new study which Dr. Tseng participated in entitled, Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea, was just announced today on PubMed. Could Dr. Tseng or any of the other MAC members interpret what the results of this study might mean for us? It is rather scientific and needs some translation into layman's tongue with your thoughts on this study, please.

Foundations often try to have their small grants serve as "seed" money, the idea being that they fund a small project which can serve as preliminary data for a larger (often NIH) grant. This in theory can turn a $25k foundation grant into a $250k NIH infusion into research in that disease. So, the foundation medical/scientific advisory committees are not necessarily looking for grants which will result in a publication or a new treatment - they're looking for grant applications which will result in a larger grant application. NIH tends to fund things which have a very high probability of resulting in an incremental increase in basic science knowledge in a field, so that's what the foundations often seek to fund too - not new treatments, not "breakthroughs".

David Jones, MD, PhD

Thanks Dr. Jones. From what I have been learning from the MAC members is that what the public thinks about rosacea research grants is quite different from what the medical or scientific community thinks. Do you have any comments on the current published or non published rosacea research being sponsored by the NRS or the AARS?

Some of the RRDi MAC Members have replied to my question by email and here is the list:

From: Latkany, MD Robert

Subject: RE: Question for RRDi MAC Members

Date: December 24, 2009 12:52:11 AM HST

To: Barrows Brady

Not all grant recipients publish their results but the majority should. A submission of a paper should be required but not all papers are guaranteed acceptance. But if you are given money a paper should be submitted. The results should not influence additional funding as this introduces conflict of interest.

Robert Latkany, MD

___________________________________________________________________________________________

From: Robert Brodell

Subject: Re: Question for RRDi MAC Members

Date: December 24, 2009 2:38:30 AM HST

To: Barrows Brady

Picking a winner is as difficult in funding research as it is in horse racing. Several approaches can be taken. The most common approach is to have a committee of experts review grant applications and choose grantees that 1) have a proven track record in previous research in the area; 2) Have a solid plan that is feasible; 3) will provide important basic science information that can, hopefully, be translated into clinical treatments. However, this is by no means the only approach to funding research. The American Cancer Society saw a problem with research funding 50 years ago. Young researchers could not get their first grant to get started because it would be impossible for them to have a track record. Therefore, they began funding young researchers for their first grant...only requiring that they perform research applicable to the cancer problem. This approach has led to the initial funding of 43 investigators who have won the Nobel Prize in Science! My conclusion, develop a thoughtful system utilizing stakeholders with rosacea and noted clinicians and scientists. Stick to your guns and don’t put pressure on anyone to do anything BUT, make an effort to publish their research. Recognize that research that does not pan out is harder to get into the literature than research that identifies positive findings. Therefore, it is not the fault of the investigator if their reseach does not get published...they must, however, make a good faith effort.

Robert Brodell, MD

__________________________________________________________________________________________

From: raymond peat

Subject: Re: Question for RRDi MAC Members

Date: December 31, 2009 7:14:51 PM HST

To: Barrows Brady

It's good to be able to consult experts when judging the applications, but I think it's important to have some judges who aren't dermatologists. The existence of a large group of interested people communicating through the website could itself make a considerable contribution to productive research.

Raymond Peat, Ph.D.

______________________________________________________________________________

From: Peter Drummond

Subject: RE: update on the Journal of the RRDi

Date: January 2, 2010 4:36:47 PM HST

To: Barrows Brady

I have thought a little bit about the questions you posted on the forum about supporting rosacea research. I agree that one of the primary criteria for supporting research grant applications should be the track record of the applicants (whether publications have arisin from previous support, number of PhD students supervised, presentations at conferences etc). Of course the ultimate aim is to advance treatments for rosacea, but as progress has to depend on insights into pathophysiology it would be important to support fundamental as well as applied research.

Regards,

Peter Drummond, Ph.D.

_______________________________________________________________________________________________________________________________________________________________________________

This is an open question to the RRDi MAC members about grant writing since we hope someday that the RRDi will be sponsoring our own grants and would like to know more about the process of grant writing and how it works. We hope the MAC members will give us some insight into what kinds of grants we should sponsor and thoughts on the following questions:

There are now two non profit organizations taking the lead in sponsoring rosacea research grants:

National Rosacea Society

American Acne & Rosacea Society

The NRS has the lead in sponsoring rosacea research by spending over the past 12 years a reported $962,696 on 45 reported grants. The AARS has spent $30,000 on three grants.

My questions are the following:

Of the total of 45 grants sponsored by the NRS only nine have been published. The three grants by the AARS haven't been published yet. Shouldn't the sponsors of grants look for awarding grants to those who get published, or does this matter?

Secondly, of the nine grants that were published (or for that matter all the grants sponsored), shouldn't the results of new treatments be one of the criteria for judging whether or not to continue sponsoring further research on a subject? I haven't heard of any new treatments as the result of any of the grants sponsored by the NRS or the AARS. Are there any new treatments resulting from any of the sponsored research so far?

Here is a breakdown of the published results of completed NRS sponsored research:

(1) The role of vascular endothelial growth factor in rosacea

Dr. Mina Yaar, professor of Dermatology, Boston University School of Medicine.

Publication of results: Kosmadaki MG, Yaar M, Arble BL, Gilchrest BA. UV induces VEGF through a TNF-alpha independent pathway. Federation of American Societies for Experimental Biology Journal 2003;17:446-448.

(2) Influence of skin temperature on bacteria in rosacea

Dr. Mark V. Dahl, chairman of Dermatology, Mayo Clinic Scottsdale, and Dr. Patrick M. Schlievert, professor of Microbiology, University of Minnesota Medical School.

Publication of results: Dahl MV, Ross AJ, Schlievert PM. Temperature regulates bacterial protein production: possible role in rosacea. Journal of the American Academy of Dermatology 2004;50:266-272.

(3) Immune system may trigger onset of rosacea symptoms

Dr. Richard Gallo, associate professor of dermatology and pediatrics at the University of California - San Diego and Dr. Masamoto Murakami, postdoctoral scientist, Veterans Medical Research Center.

Publication of results: Yamasaki K, Barden A, Taylor K, Wong C, Ohtake T, Murakami M, Gallo RL. Expression and potential pathological role of cathelicidin expression in rosacea [abstract]. The Journal of Investigative Dermatology 2004;122:A51. Abstract 301.

(4) The role of bacterial antigen(s) in the etiology and persistence of papulopustular bacteria.

Dr. Kevin Kavanagh, Department of Biology, National University of Ireland - Maynooth, and Dr. Frank Powell, consultant dermatologist, Mater Misericordiae Hospital, Dublin.

Publication of results: Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. British Journal of Dermatology 2007;157:474-481.

(5) Perceptions of self in persons with rosacea.

Karol Burkhart Lindow, RN, C, CNS, assistant professor of nursing; Deb Shelestak, RN, MSN; Joan Lappin, RN, MSN, Kent State University.

Publication of results: Lindow KB, Shelestak D, Lappin J. Perceptions of self in persons with rosacea. Dermatology Nursing 2005;17(4):249-254,3

(6) Glycomics analyses of tear fluid for the diagnostic detection of ocular rosacea.

Dr. Mark J. Mannis, Department of Ophthalmology, University of California - Davis.

Publication of results: An HJ, Ninonuevo M, Aguilan J, Liu H, Lebrilla CB, Alvarenga LS, Mannis MJ. Glycomics analyses of tear fluid for the diagnostic detection of ocular rosacea. Journal of Proteomic Research 2005 Nov-Dec;4(6):1981-7.

(7) Allergy-like reaction may trigger inflammation in rosacea

Dr. Richard L. Gallo, associate professor of dermatology and pediatrics at the University of California - San Diego, and Dr. Kenshi Yamasaki, Veterans Medical Research Center

Publication of results: Yamasaki K, DiNardo A, Bardan A, et al. Increased serine protease activity and cathelicidins promotes skin inflammation in rosacea. Nature Medicine 2007;13:975-980.

(8) Cell biologic effects of ATP on endothelial cells

Dr. Richard Granstein, chairman, Department of Dermatology, Cornell University.

Publication of results: Seiffert K, Ding W, Wagner JA, Granstein RD. ATPγS enhances the production of inflammatory mediators by a human dermal endothelial cell line via purinergic receptor signaling. Journal of Investigative Dermatology 2006;126:1017-1027

(9) Mite-related bacteria may induce rosacea inflammation

Dr. Kevin Kavanagh, Department of biology, National University of Ireland, Maynooth, and Dr. Frank Powell, Consultant Dermatologist, Mater Misericordiae Hospital, Dublin.

Publication of results: Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. British Journal of Dermatology 2007;157:474-481.

Source of the above published results

________________________________

Do you have any comments on any of the sponsored published rosacea research that would enlighten us on what the RRDi should be looking at to sponsor?

It is with sorrow that we just learned that Karl Rebert passed away October 9, 2009 at the age of 29. Karl joined the RRDi April 5, 2008. He had a background in pharmaceutical chemistry and was quite knowledgeable about rosacea treatment. He volunteered to help edit the new journal and I asked him if he would volunteer also to serve on the board of directors which he gladly did. He worked many hours of volunteer service to the RRDi editing and proof reading the journal. Karl will be missed.

Dr. Tseng,

Could you answer a couple of questions about the following report:

Study finds cause of rosacea

Can you explain if you feel that the cause of rosacea has really been found as the article above suggests?

What can you tell us about this study and is there an abstract available on this study with PubMed?

Thanks.