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Wednesday, November 21, 2007

 

New study: "Successful Treatment of the Erythema and Flushing of Rosacea"

Interesting sounding new study:

http://www.ncbi.nlm.nih.gov/sites/entrez?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=18025359&dopt=AbstractPlus

Title:
Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective {alpha}1-Adrenergic Receptor Agonist, Oxymetazoline.

Oxymetazoline is an active ingredient used in some nasal sprays to constrict the blood vessels and reduce congestion. The Collagenex topical Col-118 (which was called Sansrosa) works on a similar principle and is actually in the pipeline, expected to enter Phase III trials in early 2008.

The struggle with such topicals is to avoid rebound dilation, whereby when the constriction effect wears off, the blood vessels dilate even more than previously, resulting in a redder face and more flushing. It is also not clear what long-term effects of topical blood vessel constriction will be (I expect this is something that Collagenex will be looking at in their Phase III trials).

I'll post updates when I get access to the full paper.

[Update1 - the study is associated with a company called Aspect Pharmaceuticals which describes itself as "a privately held biopharmaceutical start-up company working to develop new and more effective therapies to treat rosacea and other dermatologic conditions" (here).]

[Update2 - I've had a chance to read the paper in full (it can be purchased here - http://archderm.ama-assn.org/cgi/content/extract/143/11/1369). Here is my brief summary:

Please don't go applying anything on your face that is not intended to by applied there... It could be very dangerous - possibly fatal.]

[Update3 - here is the patent assigned to the authors of the above paper - "Method and therapeutic/cosmetic topical compositions for the treatment of rosacea and skin erythema using a1-adrenoceptor agonists"]

Thursday, August 23, 2007

 

SansRosa / COL-118 Phase II "highly positive"

COL-118, Collagenex's topical (i.e. "cream" based) treatment for the redness and flushing associated with rosacea has had "highly positive" results in their Phase II studies. I was recently wondering what was happening with COL-118 and had started to suspect it was not progressing so this is suprising and pleasing news to me.

They are expecting Phase III trials to begin first quarter 2008.

http://phx.corporate-ir.net/phoenix.zhtml?c=65436&p=irol-newsArticle&ID=1043043&highlight=

Some quotes

"James Leyden, M.D., Professor Emeritus, University of Pennsylvania, and lead investigator of the study, said, “Col-118 appears to be the first effective treatment for the redness (flushing and blushing) associated with rosacea. Currently, there are no effective treatments for patients who suffer from this aspect of rosacea. If future studies confirm these results, this treatment should be approved by FDA. Once approved, Col-118 will offer an important new treatment to millions of rosacea patients.” "

I have written about SansRosa (as it was originally called) / COL-118 (as it is now called) many times before.

David at the Rosacea Support Group also writes about this story.

Thursday, May 03, 2007

 

Taking accurate photos pre/post IPL treatment to measure skin redness

A new paper deals with how to accurately take before and after pictures and maintain consistant colours. Before and after photos of rosacea sufferers or those with facial redness are often of poor quality and dubious in terms of reliability, indeed sometimes it may be deliberate "marketing" in order to try and entice people to the clinic.

* Different lighting before / after
* Computer-adjustment of brightness contrast
* Taken with a flush in "before" and without "after"
* Waken with a flash/without flash

This paper is therefore a welcome addition! If a clinic is showing you before/after photos you should be naturally sceptical and ask if they intend to use the method proposed in the future. At its most basic level it involves the use of coloured plastic "tabs" that are on both before and after images, to ensure consistency. In the meantime, look at background colour of photo, hair colour, lip colour and the colour of non-rosacea areas (e.g. neck, forehead) for any change in contrast/lighting.

Abstract and paper link follow.

A new method of skin erythrosis evaluation in digital images.

In the clinical field, reproducible and comparable assessments of skin color are needed for objective evaluation of lesions and efficacy of treatments. In order to provide objective, quantitative color information in skin lesions, devices such as reflectance spectrophotometer and reflectance colorimeter have been successfully used during the past decade, though they are too expensive and technically complex to be handled in routine clinical situations. Reflectance skin color measurements require direct contact of the probe with the skin, and the compression significantly influences readings. Color measurements obtained from digitized images have been proposed as a simple and cost-effective way to evaluate skin color and promote efficacy of treatments. The disadvantage is its direct and close relation to the ambient light: even if an accurate control of subject illumination is provided, readings vary between different laboratories. We propose a standard system for computerized color image analysis of skin erythrosis modification after Intense Pulsed Light (IPL) treatments, making it possible to compare readings taken by different observers in different environmental light conditions. The goal of our study is the introduction of fixed color internal controls in digital imaging in order to calculate a normalization factor of measurements, resulting not in a method of absolute quantification of erythema or erythrosis but in a method that provides the possibility of translation and comparison of the red values between systems in different environmental conditions. Between December 2004 and May 2005 we evaluated 30 patients at the Department of Plastic and Reconstructive Surgery at the University "La Sapienza" of Rome. Three points of standard colored paper (Red Green Blue) were applied with a plastic pattern (standard intersection lines) and white point in non involved area for skin control. For every patient we took a series of pictures pre-treatment and after a standard cycle of 5/6 IPL. We evaluate the grade of reproducibility of our procedure with a careful analysis of pre-treatment digital images obtained in different environmental conditions. The statistic analysis of the standard deviation between the values of R obtained (using different light conditions), and the respective normalized valor (normalized to the referent image), did not show any significant statistical difference and allows us to achieve our goal: the reproducibility of the results.

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Thursday, January 11, 2007

 

New ideas for protecting the face and nose during winter

New protective garments that I've been experimenting with recently have revolutionised what outdoor activities I can take part in during winter, especially long-distance hiking which previously I avoided like the plague during the colder months.

I wanted to share my experience for anyone else whose face and nose turn red and hurt during and after cold weather exposure.

I have learnt that you must physically protect the face from the cold and the wind with a fabric layer and that although still essential, a Zinc based skin protectant such as Linda Sy's Zinco (which I use daily) is not sufficient to fully protect the face and nose.

I recommend looking into the following.

(as per the rosacea blog manifesto – these are my own pesonal recommendations – I receive no payment for placements or links and I bought all the products with my own $$)

Polartec Balaclava. There are a number of makes of balaclava that use Polartec material. The one I've been wearing uses Polartec 100 material and is made in Canada... It doesn't list a make on it. It is made of lightweight, soft Polartec fabric; thicker versions are available using Polartec 200 although I've not tried these myself.. I first read about polartec balaclavas on the rosacea support group.

I find it very comfortable next to my skin and I've tried a number of makes of balaclava over the years. It has a good size face-hole (through which eyes and upper nose are exposed – more on protecting the nose later), so looks nothing like as threatening as those with just eye holes... Different makes have different setups - e.g. nose covered / nose exposed, etc. I don't wear the balaclava around town - just in the outdoors. I don't consider balaclavas to be suitable for town wear because they can freak people out, which is a shame!

Summary: Soft, gentle fabric protects the face and neck from moderate cold and wind. Can be teamed up with a buff or neck-warmer (below) to protect nose and cheeks further.


Neck warmer / Buff. To protect my face and nose in past I've used a scarf tied around the back of my head and pulled up over my face and nose. While this has worked reasonably well it has not been ideal, and I've struggled to find a scarf made of out material soft enough not to irritate my face.

This year I have discovered some interesting face protectors called "Buffs" – these protect the neck and can be pulled high enough to cover the entire face and nose (and just as easily pulled down again on entering a shop for example). I wear one while around town if the weather is bitter, and team it up with my Polartec balaclava if I'm out in the countryside.

These look reasonably stylish and I've seen a fair few people using them in the cold around town over the last couple of weeks too, so they're getting popular and there's no need to feel out of place wearing one! They feel much less conspicuous for town wear than balaclavas. There are a wide variety of styles and fittings. I actually tried one last winter and it was such a tight and uncomfortable fit I just gave up until I spotted one in an outdoor shop recently, so you may want to find an outdoor gear shop and try on different makes and styles rather than ordering online – or at least order a number of styles. They're not expensive and cost between £10-£25 ($15-$40).

I have tried a number of different neck warmers. The best I've found to be those by "buff", and I far prefer one that is made from thick fleecy material that I picked up in an outdoor shop called a "thermal pro combi buff" (also available in UK). This is made of soft material and has a toggle at the top that can be used to vary how tight it is. It can be adjusted to be loose fitting, which reduces irritation and any pressure points. Great piece of kit for protecting the neck and cheeks and nose. I have also noted that by protecting my neck and cheeks (i.e. without the buff fully pulled over the nose), it does still proffer benefits for the nose, presumably because the vascular system of the face is not a set of isolated components; e.g. chill affecting the neck and cheeks can show as pain and throbbing in the nose.

Summary: Neck-warmers that can be pulled up to protect the entire face and nose from the elements. Suitable for about-town wear!

I recently went on a walking weekend where temperatures hovered around 5C and wind gusts of up to 60mph were battering our faces. Wind chill must have been significant. Using the gear described above (balaclava plus wind-stopper buff pulled up over my cheeks and nose + hood up) my face was completely protected from the cold and wind. My companions weren't so lucky and I got a few envious looks and questions about what I was wearing.

Zinc Skincare protectant. I still use Linda Sy's ZincO daily on top of my favourite moisturiser. I believe that gentle cleansing, moisturising and topical Zinc usage are an essential daily routine during winter.

A future post will look at other skincare and lifestyle options for making winter more bearable for those with rosacea and ultra-sensitive facial skin! Keep checking back :-)

Tuesday, November 28, 2006

 

IPL and cancer/DNA damage - another study raises questions

New study looks at whether repeated non-ablative IPL or laser exposure causes DNA damage (which may lead to cancer) in an animal model.

No tumors were caused or any health affects noted in the mice during the 6-month study, but expression of two potential "markers" of DNA damage were increased - particularly with 1320 Nd:YAG treatments.

The authors caution that further studies are needed to consider the long-term implications of repeated IPL or laser exposure.

I've blogged about this before when a previous study was published, IPL and cancer - no link in animal experiments.

Abstract:

Lasers Surg Med. 2006 Nov 17;

An animal study of the effects on p16 and PCNA expression of repeated treatment with high-energy laser and intense pulsed light exposure.

Chan HH, Yang CH, Leung JC, Wei WI, Lai KN.

Department of Medicine, University of Hong Kong, Hong Kong.

BACKGROUND AND OBJECTIVE: Non-ablative skin rejuvenation treatments that involve the use of laser/light sources together with cooling devices have gained much popularity in recent years due to the lack of down time that is associated with them. One important but neglected issue is long-term safety. Does the repeated use of non-ablative skin rejuvenation lead to photoaging? Are we creating another sun-bed phenomenon? Recently, we performed an in vitro study to examine the effect of sub-lethal QS 755 nm lasers on the expression of p16INK4a on melanoma cell lines, and found that sub-lethal laser damage could increase DNA damage, which led to an increase in p16 expression. Our objective was to assess the cutaneous effect of repeated exposure to high-energy lasers and intense pulsed light sources on male Institute of Cancer Research (ICR) mice.

STUDY DESIGN/MATERIALS AND METHODS: Twenty-eight male ICR mice were divided into four groups. Other than the control group, all groups received either laser (585 nm pulsed dye laser or 1,320 nm Nd:YAG laser) or intense pulsed light (IPL) treatment. All four groups were anesthetized with a mixture of Hypnorm/Dormicum before treatment. The animals were irradiated twice a week for 6 months. Signs of toxicity such as mortality and weight loss were checked once a week. Skin tumor formation was evidenced by lesions of greater than 1 mm in diameter that persisted for 2 weeks. At the end of the 6 months, the expression of proliferating cell nuclear antigen (PCNA) and p16 in the mouse skin was determined by immunohistochemical staining and immunoblotting using specific monoclonal antibodies for mouse PCNA and p16. The results were expressed as mean +/- standard error of the mean (SEM). Statistical difference was assessed by multiple ANOVA. A P-value of <0.05 was considered to be significant.

RESULTS: At the end of the 6 months, none of the animals had developed any signs of toxicity such as mortality or weight lost. There was no evidence of tumor formation. There were significant elevations of p16 and PCNA in all treated groups as compared to the control group (ANOVA P < 0.05). This particularly applied to the group that was treated with the 1,320 nm Nd:YAG laser. CONCLUSION: The repeated use of high-energy laser and intense pulsed light source did not cause any toxicity in mice. The changes in p16 and PCNA imply that further studies are necessary to consider the implications of repeated exposure to longer wavelength radiation in human skin. Lasers Surg. Med. (c) 2006 Wiley-Liss, Inc.

Tuesday, October 31, 2006

 

Why permanent facial redness can be hard to treat - lessons from the paper on IPL modelling

One of the authors, Gal Shaferstein Ph.D, was kind enough to send me a copy of the paper I blogged about last week, "The effects of intense pulsed light (IPL) on blood vessels investigated by mathematical modeling"... Here are some of my observations an an interested observer (but not a doctor!)

Re-iterates what I have read previously, that haemoglobin has absorption peaks around 560nm and again at around 590nm wavelengths, and drops strongly after that. This implies in my mind that using IPL cutoff filters over 590/595 is not useful for targetting blood vessels.

Temperatures higher than 70C in the centre of the blood vessel are needed for proper coagulation. Any higher and the vessel may vapourise (bruise), any lower and coagulation will not occur.

Physical properties of smaller vessels, such as those responsible for causing the erythema in rosacea, make them MUCH harder to succesfully heat to coagulation temperatures than larger vessels (e.g. visible telangiectasia). I have seen many discussions on the rosacea forums previously speculating whether hard to treat persistant redness may be "deep" redness... This paper is leading me to conclude that in many cases, the persistant redness is caused by very small vessels close to the surface of the skin. There are physical properties of these small vessels that make them hard to treat, as the paper explains:

"... it seems very unlikely to coagulate small vessels (60 um) using the given IPL spectra at radiant exposures less than 30J/cm2"

The following reasons were stated

"probably due to the limited amount of chromophores (hemoglobin) in such small vessels"

"Effect such as hypobaric pressure or dermal blood volume fraction play a significant role."

"Additionally, the cooling of a vessel by heat diffusion into the dermis has a major impact on the temperature in the vessel and the thermal damage. The cooling of a vessel during and after laser irradiation depends on the volume-surface ratio of each vessel and therefore on the vessel size. The smaller the vessel diameter, the faster the cooling and the smaller is the thermal damage inside the vessel".

The paper goes on to correlate this with previous clinical studies:

"Moreover, our findings support the results of clinical studies. Using IPL, a better clearance was observed in patients treated for visible teleangiectatic vessels compared to patients with diffuse erythema composed of much smaller vessels".

Because of the physical properties of small vessels, they may respond better to shorter pulse durations - long durations (over 10ms in this model) resulted in minimal increases in temperature because heat is being lost so quickly to the surrounding tissues.

Small vessels are best targetted by shoter wavelengths (from the graphs in the paper, around 530nm looks to be the peak). The paper states "There is a major contribution of the shorter wavelengths for effective heating of smaller vessels (60um and 150 um) [...] For larger vessels (300um and 500um), there is not much difference between individual wavelengths, although the photothermal effect is slightly more pronounced for longer wavelengths". This is what we have long suspected, however it does appear to indicate that for those with persistant, difficult to treat permanent redness, if you are only being treated with the 595nm+ cutoff filters, you may not successfully target that redness.


Theoretical take home points for your own IPL treatment, to discuss with your IPL doctor

* Erythema (permanent, diffuse redness) is hard to treat and this paper now gives sound theoretical reasons why that is the case.

* Visible vessels are much easier to successfully heat and treat.

* If you have permanent redness, shallow filters (less than 590) seem likely to be more successful

* Short pulse durations would appear effective for treating small vessels because maximum temperature is reached around 10ms into the pulse.

* Energy levels higher than 30J/cm2 at 10ms duration appear to be needed to successfully treat the small vessels which cause permanent erythema.

* In my opinion, based on this paper, long, multi-pulse shots (e.g. triple shots with long durations and pulse durations) are unlikely to be of much benefit in treating permanent redness - because the small vessels do not retain sufficient heat.

For anyone interested, I recommend obtaining the full paper. I look forward to seeing if clinical studies can be performed that attempt to back up the theory in this paper, in practice, and improve outcomes of IPL treatments!


Friday, October 27, 2006

 

Effects of IPL on different size blood vessels (mathematical modelling)

An interesting study that attempts to model effects of IPL on different size blood vessels. Worth noting that small vessels were the most difficult to effectively raise the temperature of to levels for successful coagulation.


Abstract:

"Lasers Surg Med. 2006 Oct 25;

The effects of intense pulsed light (IPL) on blood vessels investigated by mathematical modeling.

Baumler W, Vural E, Landthaler M, Muzzi F, Shafirstein G.

Department of Dermatology, University of Regensburg, Regensburg, Germany.

BACKGROUND AND OBJECTIVES: Intense pulsed light (IPL) sources have been successfully used for coagulation of blood vessels in clinical practice. However, the broadband emission of IPL hampers the clinical evaluation of optimal light parameters. We describe a mathematical model in order to visualize the thermal effects of IPL on skin vessels, which was not available, so far.

STUDY DESIGN/MATERIALS AND METHODS: One IPL spectrum was shifted towards the near infrared range (near IR shifted spectrum: NIRSS) and the other was heavily shifted toward the visible range (visible shifted spectrum: VSS). The broadband emission was separated in distinct wavelengths with the respective relative light intensity. For each wavelength, the light and heat diffusion equations were simultaneously solved with the finite element method. The thermal effects of all wavelengths at the given radiant exposure (15 or 30 J/cm2) were added and the temperature in the vessels of varying diameters (60, 150, 300, 500 microm) was calculated for the entire pulse duration of 30 milliseconds.

RESULTS: VSS and NIRSS both provided homogeneous heating in the entire vessel. With the exception of the small vessels (60 microm), which showed only a moderate temperature increase, all vessels exhibited a temperature raise within the vessel sufficient for coagulation with each IPL parameter. The time interval for effective temperature raise in larger vessels (diameter >60 microm) was clearly shorter than the pulse duration. In most instances, the vessel temperature was higher for VSS when compared to NIRSS.

CONCLUSIONS: We presented a mathematical model capable of calculating the photon distribution and the thermal effects of the broadband IPL emission within cutaneous blood vessels. Lasers Surg. Med. (c) 2006 Wiley-Liss, Inc."

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