Wednesday, April 26, 2006
LED (light emitting diode) treatment for rosacea? Part 1 of 2
This is part one of a two-part post on LED treatment for rosacea. I have asked David C, who posts regularly on rosacea forums online, to share his experiences with LED treatment for rosacea for part one. Part two, coming in a few days, will look at what if any other evidence there is to support this therapy.
Here are two photos of David (click the photo to view high-resolution version).
Photo 1: Before This is a picture of me after I was hospitalized for rosacea-related complications (because of my extreme sensitivity to heat, over a period of weeks, I drove my core body temperature down to 84 degrees F using a fan, misting water on myself, and sitting in 60-degree air conditioning--my doctor said it was the lowest core body temperature he'd seen in anyone other than patients pulled out of a frozen lake) in September of 2003. Needless to say, I was of great interest to the resident med students making their rounds in the internal medicine wing. This was about as bad as my disease ever got.
Photo 2: AfterThis is how my skin looks now, in April of 2006. This photo was taken without a flash, using sunlight for illumination, so the flash did not wash out any redness in my skin. Not all of my progress is due to red light therapy, but since I have been using red light therapy over the past year my tolerance to triggers (heat, exertion, socializing) has risen an incredible amount--it has been far more effective for flushing prevention than any other treatment modality I've tried.
This is what he says:
My Experience with Red Light Therapy
- by David C
I have been using red light therapy, regularly, for a year now. As far as I understand, the light can come from any source—fluorescent tubes, LEDs, or a monochromatic filtered incandescent bulb, so long as the light is around 660nm (the range or specific wavelengths for red light therapy are not clearly understood in the treatment of rosacea; there may be a range of wavelengths, or specific peaks into the infrared spectrum that are beneficial—we just don’t know yet). I chose an LED-based product (an Acnelamp 3-headed all-red unit) to begin with.
I used the Acnelamp gingerly (sporadically) at first, as I was concerned that it might make my condition worse. But, eventually, I began to use the Acnelamp on a regular basis. I went from using it fifteen minutes a day, then fifteen minutes twice a day, then up to twenty minutes twice a day, and then sometimes for a cumulative total of an hour a day.
One of the reasons I began to increase my exposure time was that my face was almost always paler or “calmed” after a session with the Acnelamp. Also, in the hours following a session, my face was less reactive—rather like a dose of clonidine in the action of flushing suppression/prevention. Over time, I noticed that my threshold for flushing began to rise. I was able to take walks in the summer evenings that would have been impossible to tolerate before my use of red light therapy.
After a few months using my Acnelamp regularly, I started doing research on LEDs, because I wanted to construct a custom-made LED array with more LEDs than the Acnelamp had. My first design used LEDs with a viewing angle of 15 degrees that produced light at 660nm. While this design was an improvement over my Acnelamp (it had 252 LEDs (as opposed to the Acnelamp’s 72)), the viewing angle made the light diffusion of this model awkward in that one had to sit around sixteen inches from the light source to get total coverage on the face. However, I did use this model for a few months and found that my condition only continued to get better.
However, I was unsatisfied with this first array, so I built another array, using 660nm LEDs with a viewing angle of 30 degrees, which allowed for a condensing (I could sit closer to the array and get total coverage) of the array’s set-up. This is the array I am currently using, and it has 1176 LEDs, made up of 8 arrays consisting of 147 LEDs that I have arranged into a half-moon curve. I use this set-up anywhere from 20 minutes a day to a few hours (I sometimes purposefully fall asleep in a chair in front of this array with my eye-protection goggles on). I have seen nothing but benefits from this kind of extended exposure time in front of this stronger array.
Why Does it Help Rosacea?
Though there have been no good studies on red light therapy and rosacea, from my readings on this topic, red light seems to have an anti-inflammatory action. If rosacea is, at heart, a flushing disorder that is complicated by the body’s inflammatory response—which in turn cascades and creates a vicious cycle of flushing, which causes an inflammatory response in the facial vasculature, which makes the face more sensitive and prone to more flushing, etc. with eventual extreme sensitivity and a break-out of papules and pustules—daily use of red light therapy appears to act as an anti-inflammatory on the facial vasculature and thus stops the disease from progressing, and, indeed, has reversed the disease process in my case.
Moreover, red light therapy has an added bonus of promoting collagen production, which can build up a thinned dermis, which offers added protection to vessels that were previously more exposed to environmental insults. Much like IPL (though its action is non-thermal and gradual), red light therapy can, over time, treat photo-aged skin and fill in wrinkles, too.
An Addendum: Rosacea Treatment through Red Light Therapy is NOT Singular Cure
I will firmly support red light therapy as the best treatment modality I have come across in my 6 years of treating/fighting/suppressing this disease. However, PLEASE do not rely on red light therapy or a given topical skincare product. Rosacea is a complex disease and must be recognized for what it is: You most likely will need a multi-pronged approach.
I currently use clonidine, clarithromycin 500mg XL, clonazepam, and have had over two dozen thermal laser treatments.
The number of laser/IPL treatments I’ve had should make the intelligent rosacean take pause; while laser/IPL treatments can treat telangiectasias and flushing, it is most likely that one will not find this an end-all a solution. Rather, one must integrate thermal laser therapy, anti-angiogeneic drugs/supplements, and, if I may be so bold as to recommend, red light therapy. This is a complex disease, and so we must all be vigilant and constantly educating one another.
This addendum is in no way meant to undercut my experiences with red light therapy: I am a rosacea sufferer, and I believe that full disclosure is the best way help us, as a community, treat our common disease.
Here are two photos of David (click the photo to view high-resolution version).
Photo 1: Before This is a picture of me after I was hospitalized for rosacea-related complications (because of my extreme sensitivity to heat, over a period of weeks, I drove my core body temperature down to 84 degrees F using a fan, misting water on myself, and sitting in 60-degree air conditioning--my doctor said it was the lowest core body temperature he'd seen in anyone other than patients pulled out of a frozen lake) in September of 2003. Needless to say, I was of great interest to the resident med students making their rounds in the internal medicine wing. This was about as bad as my disease ever got.
Photo 2: AfterThis is how my skin looks now, in April of 2006. This photo was taken without a flash, using sunlight for illumination, so the flash did not wash out any redness in my skin. Not all of my progress is due to red light therapy, but since I have been using red light therapy over the past year my tolerance to triggers (heat, exertion, socializing) has risen an incredible amount--it has been far more effective for flushing prevention than any other treatment modality I've tried. This is what he says:
My Experience with Red Light Therapy
- by David C
I have been using red light therapy, regularly, for a year now. As far as I understand, the light can come from any source—fluorescent tubes, LEDs, or a monochromatic filtered incandescent bulb, so long as the light is around 660nm (the range or specific wavelengths for red light therapy are not clearly understood in the treatment of rosacea; there may be a range of wavelengths, or specific peaks into the infrared spectrum that are beneficial—we just don’t know yet). I chose an LED-based product (an Acnelamp 3-headed all-red unit) to begin with.
I used the Acnelamp gingerly (sporadically) at first, as I was concerned that it might make my condition worse. But, eventually, I began to use the Acnelamp on a regular basis. I went from using it fifteen minutes a day, then fifteen minutes twice a day, then up to twenty minutes twice a day, and then sometimes for a cumulative total of an hour a day.
One of the reasons I began to increase my exposure time was that my face was almost always paler or “calmed” after a session with the Acnelamp. Also, in the hours following a session, my face was less reactive—rather like a dose of clonidine in the action of flushing suppression/prevention. Over time, I noticed that my threshold for flushing began to rise. I was able to take walks in the summer evenings that would have been impossible to tolerate before my use of red light therapy.
After a few months using my Acnelamp regularly, I started doing research on LEDs, because I wanted to construct a custom-made LED array with more LEDs than the Acnelamp had. My first design used LEDs with a viewing angle of 15 degrees that produced light at 660nm. While this design was an improvement over my Acnelamp (it had 252 LEDs (as opposed to the Acnelamp’s 72)), the viewing angle made the light diffusion of this model awkward in that one had to sit around sixteen inches from the light source to get total coverage on the face. However, I did use this model for a few months and found that my condition only continued to get better.
However, I was unsatisfied with this first array, so I built another array, using 660nm LEDs with a viewing angle of 30 degrees, which allowed for a condensing (I could sit closer to the array and get total coverage) of the array’s set-up. This is the array I am currently using, and it has 1176 LEDs, made up of 8 arrays consisting of 147 LEDs that I have arranged into a half-moon curve. I use this set-up anywhere from 20 minutes a day to a few hours (I sometimes purposefully fall asleep in a chair in front of this array with my eye-protection goggles on). I have seen nothing but benefits from this kind of extended exposure time in front of this stronger array.
Why Does it Help Rosacea?
Though there have been no good studies on red light therapy and rosacea, from my readings on this topic, red light seems to have an anti-inflammatory action. If rosacea is, at heart, a flushing disorder that is complicated by the body’s inflammatory response—which in turn cascades and creates a vicious cycle of flushing, which causes an inflammatory response in the facial vasculature, which makes the face more sensitive and prone to more flushing, etc. with eventual extreme sensitivity and a break-out of papules and pustules—daily use of red light therapy appears to act as an anti-inflammatory on the facial vasculature and thus stops the disease from progressing, and, indeed, has reversed the disease process in my case.
Moreover, red light therapy has an added bonus of promoting collagen production, which can build up a thinned dermis, which offers added protection to vessels that were previously more exposed to environmental insults. Much like IPL (though its action is non-thermal and gradual), red light therapy can, over time, treat photo-aged skin and fill in wrinkles, too.
An Addendum: Rosacea Treatment through Red Light Therapy is NOT Singular Cure
I will firmly support red light therapy as the best treatment modality I have come across in my 6 years of treating/fighting/suppressing this disease. However, PLEASE do not rely on red light therapy or a given topical skincare product. Rosacea is a complex disease and must be recognized for what it is: You most likely will need a multi-pronged approach.
I currently use clonidine, clarithromycin 500mg XL, clonazepam, and have had over two dozen thermal laser treatments.
The number of laser/IPL treatments I’ve had should make the intelligent rosacean take pause; while laser/IPL treatments can treat telangiectasias and flushing, it is most likely that one will not find this an end-all a solution. Rather, one must integrate thermal laser therapy, anti-angiogeneic drugs/supplements, and, if I may be so bold as to recommend, red light therapy. This is a complex disease, and so we must all be vigilant and constantly educating one another.
This addendum is in no way meant to undercut my experiences with red light therapy: I am a rosacea sufferer, and I believe that full disclosure is the best way help us, as a community, treat our common disease.
Tuesday, April 18, 2006
Epitan rebrands as Clinuvel, Epitan product now CU1647
Epitan, the company developing a product which prompts tanning (melanin), has rebranded as Clinuvel (a combination of "clinical" and "uv"... apparently!) and renamed the Epitan product CU1674.
Regulatory approval requires that their product is demonstrated in over 1000 patients. So far they have trialled it in 167. Their struggle is that you cannot register a medicine for "sunburn" or "tanning" so they have had to seek out disorders to which it can be applied. They have chosen immuno-compromised patients susceptible to Actinic Keratosis (Solar Keratosis) which can lead to cancer and are looking for others. More here.
Rosacean sufferers may benefit. The product could potentially thicken our facial skin, protect it from sunburn and hide the redness. However, worth noting that facial flushing has been one of the side effects reported from previous trials.
Recently their pharmaceutical manager resigned. Given the speed of development, their past struggles with funding, their seeming struggle to register the drug and the slow speed of clinical trials, I doubt we will see CU1674 anytime soon.
[update, 21 Apri 06 - this article says that clinuvel hope to have "epitan"/CU1674 "registered for use by the start of 2009"... so if anything in that schedule slips it may be 2010 or later...]
For some interesting info on Melanotan peptides, see Melatan.org. They have active forums on both CU1674 and Melanotan II peptides where people are experimenting with the peptides (with the associated risks - no one knows the long or short term dangers!). Some interesting results.
Regulatory approval requires that their product is demonstrated in over 1000 patients. So far they have trialled it in 167. Their struggle is that you cannot register a medicine for "sunburn" or "tanning" so they have had to seek out disorders to which it can be applied. They have chosen immuno-compromised patients susceptible to Actinic Keratosis (Solar Keratosis) which can lead to cancer and are looking for others. More here.
Rosacean sufferers may benefit. The product could potentially thicken our facial skin, protect it from sunburn and hide the redness. However, worth noting that facial flushing has been one of the side effects reported from previous trials.
Recently their pharmaceutical manager resigned. Given the speed of development, their past struggles with funding, their seeming struggle to register the drug and the slow speed of clinical trials, I doubt we will see CU1674 anytime soon.
[update, 21 Apri 06 - this article says that clinuvel hope to have "epitan"/CU1674 "registered for use by the start of 2009"... so if anything in that schedule slips it may be 2010 or later...]
For some interesting info on Melanotan peptides, see Melatan.org. They have active forums on both CU1674 and Melanotan II peptides where people are experimenting with the peptides (with the associated risks - no one knows the long or short term dangers!). Some interesting results.
Thursday, April 06, 2006
More on topical (calcium) dobesilate as a potential rosacea treatment
I blogged about topical application calcium dobesilate and rosacea in November 2005, when this study was published, and said I would write more (but didn't). This week, I received an email from a blog reader who has had experience with using this as a topical with interesting results, so I thought I would revisit!
To recap on the original study, "Theraputic Response of Rosacea to Dobesilate" (emphasis mine):
Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis.
[frustratingly the full paper does not appear to be available anywhere online for purchase – if you spot it please drop me a line at rosacea.co.uk]
What is dobesilate used for?
Calcium dobesilate is administered orally as a treatment for diabetic retinopathy. The drug is called “Doxium" and is available in tablet or capsule form. Further info here, and here.
It is believed to have the following effects when taken orally, which may have implications for rosacea:
1. Potent antioxidant, “Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation” (source)
2. Reduces microvascular permeability, as measured by “vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity” (source)
3. It is an angiogenesis inhibitor, “According to the results reported here, dobesilate remarkably reduced vessel ingrowth in aFGF-containing subcutaneous sponges in mice”. One of the investiagors in this study, “Cuevas P” (Pedro Cuevas) was the author of the rosacea paper. (source) (full paper is online)
Are there any examples of topical usage other than the one rosacea study?
Yes! Again, Pedro Cuevas has studied the effect of “Dobesilate in the treatment of plaque psoriasis” (full paper is online), where the abstract reports (emphasis mine):
"Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.”
I found a copy of the full psoriasis paper as PDF, here.
The photos are impressive and show near complete resolution (cure?) of the psoriasis. The topical used was described as follows:
“Lesions were treated with potassium dobesilate [hydroquinone monosulfonic acid potassium salt (Merck) (5 percent in a cream formulation, applied twice daily by the patient himself)]”
Interestingly, the paper describes that “after 2 weeks of treatment, the patient had almost completed clinical resolution of the lesions with no recurrence after two months of treatment withdrawal. No adverse events were observed”
Pedro Cuevas MD has a long history of studying angiogenesis and anti-angiogenesis, with hundreds of published papers. Here is more information.
Calcium dobesilate has also been investigated for topical treatment of hemorrhoids, in a study "Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids", with positive results.
[update]
Via the the rosacea news site's article on this paper, I also came across this case study, again by Pedro Cuevas MD, where topical dobesilate was used to treat basal cell carinoma topically. I quote: "a nodular BCC on the face of a 62 year old man was treated with calcium dobesilate (2.5% in a suspension forumulation, applied twice daily by the patient) for 4 weeks. After 4 weeks there was nearly complete clinical resolution of the disease..."
In summary
I think this will be an interesting one to follow. Hopefully more trials of this potentially promosing drug can be performed.
To recap on the original study, "Theraputic Response of Rosacea to Dobesilate" (emphasis mine):
Despite an incomplete understanding of the pathogenesis of rosacea, therapeutic modalities continue to expand. The principal subtype of rosacea includes erythematotelangiestatic rosacea, which is characterized by uncontrolled angiogenesis. Angiogenic growth factors such as fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF) are currently targets of intense effort to inhibit deregulated blood vessel formation in diseases such as cancer. Here we report a 33-years-old woman with erythematotelangestatic rosacea who responds to a daily treatment of topically applied dobesilate, an inhibitor of FGF, with an improvement in erythema and telangectasia after two weeks. Thus, dobesilate might be useful in the treatment of rosacea and other diseases that depend on pathologic angiogenesis.
[frustratingly the full paper does not appear to be available anywhere online for purchase – if you spot it please drop me a line at rosacea.co.uk]
What is dobesilate used for?
Calcium dobesilate is administered orally as a treatment for diabetic retinopathy. The drug is called “Doxium" and is available in tablet or capsule form. Further info here, and here.
It is believed to have the following effects when taken orally, which may have implications for rosacea:
1. Potent antioxidant, “Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation” (source)
2. Reduces microvascular permeability, as measured by “vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity” (source)
3. It is an angiogenesis inhibitor, “According to the results reported here, dobesilate remarkably reduced vessel ingrowth in aFGF-containing subcutaneous sponges in mice”. One of the investiagors in this study, “Cuevas P” (Pedro Cuevas) was the author of the rosacea paper. (source) (full paper is online)
Are there any examples of topical usage other than the one rosacea study?
Yes! Again, Pedro Cuevas has studied the effect of “Dobesilate in the treatment of plaque psoriasis” (full paper is online), where the abstract reports (emphasis mine):
"Fibroblast growth factor (FGF)-mediated pathways participate in many of the cellular events implicated in the pathogenesis of psoriasis. Thus, targeting FGF signals may be potentially therapeutic in the treatment of psoriasis. We report for the first time on a 43-year-old man with chronic-type plaque psoriasis with a daily topical treatment of dobesilate, a new FGF inhibitor. As early as at day 14, the patient had cleared or achieved excellent improvement of psoriatic skin lesions. Topical dobesilate offers the potential for treatment of plaque psoriasis without atrophy or other local side effects associated with the use of topical corticosteroids.”
I found a copy of the full psoriasis paper as PDF, here.
The photos are impressive and show near complete resolution (cure?) of the psoriasis. The topical used was described as follows:
“Lesions were treated with potassium dobesilate [hydroquinone monosulfonic acid potassium salt (Merck) (5 percent in a cream formulation, applied twice daily by the patient himself)]”
Interestingly, the paper describes that “after 2 weeks of treatment, the patient had almost completed clinical resolution of the lesions with no recurrence after two months of treatment withdrawal. No adverse events were observed”
Pedro Cuevas MD has a long history of studying angiogenesis and anti-angiogenesis, with hundreds of published papers. Here is more information.
Calcium dobesilate has also been investigated for topical treatment of hemorrhoids, in a study "Effectiveness and innocuousness of the association of calcium dobesilate, dexamethasone acetate and lidocaine versus prednisolone capronate with dibucaine clorohydrate in the treatment of hemorrhoids", with positive results.
[update]
Via the the rosacea news site's article on this paper, I also came across this case study, again by Pedro Cuevas MD, where topical dobesilate was used to treat basal cell carinoma topically. I quote: "a nodular BCC on the face of a 62 year old man was treated with calcium dobesilate (2.5% in a suspension forumulation, applied twice daily by the patient) for 4 weeks. After 4 weeks there was nearly complete clinical resolution of the disease..."
In summary
I think this will be an interesting one to follow. Hopefully more trials of this potentially promosing drug can be performed.
Wednesday, April 05, 2006
SansRosa Phase I clinical trial
(via Perry on rosacea support),
Sanrosa, AKA SR-01 (I thought it was SR-101), recently renamed to COL-118, is undergoing a Phase I clinical trial at the Mayo Clinic in Scottsdale, Arizona. Principal investigator is Mark V. Dahl MD, who has published before on rosacea including "Topical Metronidazole Maintains Remissions of Rosacea"
They are looking for patients with red cheeks and the clinical outcome will be reduction of redness. If anyone decides to go, do drop us a line. we are happy to report any comments
anonymously!
Full details here:
http://clinicaltrials.gov/ct/show/NCT00279890?order=2
From Perry on rosacea-support:
"Forgive me if this is old news, but the Mayo Clinic is now recruiting patients (approximately 14 more are needed) for the SR-01 product trials.I just spoke with Ms. Jan Light (her link is provided), and she informed me that these Phase 1 trials require 5 trips to the Scottsdale Arizona compound, in a 28 day period. She stressed that since these are phase 1 trials (safety, safety,safety), the patients would have to remain in the area for the duration of the 28 day study."
Previous post on SansRosa:
http://www.rosacea.co.uk/blog/2006/03/sansrosa-now-aka-col-118.html
Sanrosa, AKA SR-01 (I thought it was SR-101), recently renamed to COL-118, is undergoing a Phase I clinical trial at the Mayo Clinic in Scottsdale, Arizona. Principal investigator is Mark V. Dahl MD, who has published before on rosacea including "Topical Metronidazole Maintains Remissions of Rosacea"
They are looking for patients with red cheeks and the clinical outcome will be reduction of redness. If anyone decides to go, do drop us a line. we are happy to report any comments
anonymously!
Full details here:
http://clinicaltrials.gov/ct/show/NCT00279890?order=2
From Perry on rosacea-support:
"Forgive me if this is old news, but the Mayo Clinic is now recruiting patients (approximately 14 more are needed) for the SR-01 product trials.I just spoke with Ms. Jan Light (her link is provided), and she informed me that these Phase 1 trials require 5 trips to the Scottsdale Arizona compound, in a 28 day period. She stressed that since these are phase 1 trials (safety, safety,safety), the patients would have to remain in the area for the duration of the 28 day study."
Previous post on SansRosa:
http://www.rosacea.co.uk/blog/2006/03/sansrosa-now-aka-col-118.html
