Tretinoin, and more on skin sensitivity (was: topical RETIN-A / RENOVA)

[Guest guest]

Yeah, Tom, I saw that study. It looked good to me. I didn't share it

here because I wasn't sure what it was about. At first I thought it

was a side-by-side comparison study, but the study design isn't the

best for that -- yet it looks like they tried to design an objective

study, you know? So what are they doing? I assume this would be

around the time that low dose isotretinoin was being introduced? If

so, that, together with the unusual study design, makes me wonder if

this was intended to demonstrate that the new-fanagled <g> low dose

isotretinoin was as effective and safe as to the standard care at the

time for recalcitrant rosacea, topical tretinoin (as opposed to which

is superior, which for us 8 years later is the more important

information). Or maybe not -- we probably need the full-text article

to know for sure. Older studies need to be read in their own time

capsule, not ours. <g>

As an aside, I find it hard to believe that 22 hard core rosaceans

could all tolerate the " inert " topical vehicle, much less tretinoin,

for eight months without any side effects or developing

sensitivities?

Alternatively -- and this is something I'm wrestling with -- I could

well be over-reacting to how sensitive rosacean skin can be,

universalizing my own experiences and those in this group and the few

things I've read. Maybe things like tretinoin and chemical peels

really are OK for many rosaceans, just not for all rosaceans. This

group gets a tremendous over-representation of certain problems

because they are drawn here, and Dr. Nase's words are so respected

here they often accepted without questioning.

I don't know the answer to this, but I have a suspicion that the

relationship between skin sensitivity and rosacea is very important

and as yet undefined.

Is retin-a or renova the aldehyde version of tretinoin? It's curious

that I'm having a hard time finding this out -- my references

describe the various formulations as a type of tretinoin, as if the

type doesn't matter pharmacologically (while the studies we're been

talking about clearly demonstrate different, no? I'm confused here.)

Aside from Ian's study proporting a vascular benefit -- which I

appreciate but am holding at bay for the moment -- what is the

proposed mechanism of action for tretinoins and rosacea? Best I can

find, it's a generalized anti-inflammatory and/or immune-mediated

involvement. Doesn't differ from low dose accutane, or does it?

Again, I'm showing my ignorance.

Marjorie

Marjorie Lazoff, MD

> Don't recall seeing this study. Kligman says tretinoin (i assume

> delivered as retin-a or renova) beneficial and well tolerated for

> cea. (Dr Nase says opposite).

>

>

> 1: Arch Dermatol 1994 Mar;130(3):319-24

>

> A comparison of the efficacy of topical tretinoin and low-dose oral

> isotretinoin

> in rosacea.

>

> Ertl GA, Levine N, Kligman AM.

>

> University of Arizona, Tucson.

>

> BACKGROUND AND DESIGN: Twenty-two patients with severe or

> recalcitrant rosacea

> were divided into three treatment groups in a randomized, double-

> blind trial

> that compared low-dose oral isotretinoin (10 mg/d), topically

applied

> tretinoin

> (0.025% cream), and the combined use of both isotretinoin and

> tretinoin. For the

> first 16 weeks of the trial, subjects received one of these three

> trial

> regimens. For the final 16 weeks, isotretinoin was withheld while

> tretinoin

> cream or a placebo cream was continued. RESULTS: Twenty subjects

> completed the

> trial. Each treatment produced therapeutic benefits with regard to

> the number of

> papules and pustules and erythema. Treatment with oral isotretinoin

> appeared to

> give a more rapid onset of improvement, but there were no

differences

> between

> the groups after 16 weeks. This level of improvement continued

during

> the

> succeeding 16 weeks of observation whether the subjects used the

> tretinoin or

> the placebo cream. Adverse events were minimal and well tolerated

in

> all groups.

> CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin cream

> therapy

> appear to be beneficial in the treatment of severe or recalcitrant

> rosacea. No

> additive benefit is noted with the combined use of these two

> modalities.

>

> Publication Types:

> Clinical Trial

> Randomized Controlled Trial

>

> PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

Yeah, Tom, I saw that study. It looked good to me. I didn't share it

here because I wasn't sure what it was about. At first I thought it

was a side-by-side comparison study, but the study design isn't the

best for that -- yet it looks like they tried to design an objective

study, you know? So what are they doing? I assume this would be

around the time that low dose isotretinoin was being introduced? If

so, that, together with the unusual study design, makes me wonder if

this was intended to demonstrate that the new-fanagled <g> low dose

isotretinoin was as effective and safe as to the standard care at the

time for recalcitrant rosacea, topical tretinoin (as opposed to which

is superior, which for us 8 years later is the more important

information). Or maybe not -- we probably need the full-text article

to know for sure. Older studies need to be read in their own time

capsule, not ours. <g>

As an aside, I find it hard to believe that 22 hard core rosaceans

could all tolerate the " inert " topical vehicle, much less tretinoin,

for eight months without any side effects or developing

sensitivities?

Alternatively -- and this is something I'm wrestling with -- I could

well be over-reacting to how sensitive rosacean skin can be,

universalizing my own experiences and those in this group and the few

things I've read. Maybe things like tretinoin and chemical peels

really are OK for many rosaceans, just not for all rosaceans. This

group gets a tremendous over-representation of certain problems

because they are drawn here, and Dr. Nase's words are so respected

here they often accepted without questioning.

I don't know the answer to this, but I have a suspicion that the

relationship between skin sensitivity and rosacea is very important

and as yet undefined.

Is retin-a or renova the aldehyde version of tretinoin? It's curious

that I'm having a hard time finding this out -- my references

describe the various formulations as a type of tretinoin, as if the

type doesn't matter pharmacologically (while the studies we're been

talking about clearly demonstrate different, no? I'm confused here.)

Aside from Ian's study proporting a vascular benefit -- which I

appreciate but am holding at bay for the moment -- what is the

proposed mechanism of action for tretinoins and rosacea? Best I can

find, it's a generalized anti-inflammatory and/or immune-mediated

involvement. Doesn't differ from low dose accutane, or does it?

Again, I'm showing my ignorance.

Marjorie

Marjorie Lazoff, MD

> Don't recall seeing this study. Kligman says tretinoin (i assume

> delivered as retin-a or renova) beneficial and well tolerated for

> cea. (Dr Nase says opposite).

>

>

> 1: Arch Dermatol 1994 Mar;130(3):319-24

>

> A comparison of the efficacy of topical tretinoin and low-dose oral

> isotretinoin

> in rosacea.

>

> Ertl GA, Levine N, Kligman AM.

>

> University of Arizona, Tucson.

>

> BACKGROUND AND DESIGN: Twenty-two patients with severe or

> recalcitrant rosacea

> were divided into three treatment groups in a randomized, double-

> blind trial

> that compared low-dose oral isotretinoin (10 mg/d), topically

applied

> tretinoin

> (0.025% cream), and the combined use of both isotretinoin and

> tretinoin. For the

> first 16 weeks of the trial, subjects received one of these three

> trial

> regimens. For the final 16 weeks, isotretinoin was withheld while

> tretinoin

> cream or a placebo cream was continued. RESULTS: Twenty subjects

> completed the

> trial. Each treatment produced therapeutic benefits with regard to

> the number of

> papules and pustules and erythema. Treatment with oral isotretinoin

> appeared to

> give a more rapid onset of improvement, but there were no

differences

> between

> the groups after 16 weeks. This level of improvement continued

during

> the

> succeeding 16 weeks of observation whether the subjects used the

> tretinoin or

> the placebo cream. Adverse events were minimal and well tolerated

in

> all groups.

> CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin cream

> therapy

> appear to be beneficial in the treatment of severe or recalcitrant

> rosacea. No

> additive benefit is noted with the combined use of these two

> modalities.

>

> Publication Types:

> Clinical Trial

> Randomized Controlled Trial

>

> PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

Dr. M

>> Is retin-a or renova the aldehyde version of tretinoin? It's

>>curious

>> that I'm having a hard time finding this out

Best I recall, tretinoin (or retinoic acid) and retin-a, and are the

same animal (chemical name / trade name), and renova is trade name

for tretinoin/retin-a formulated with emollients (and buffers

perhaps?) to lessen dryness and irritation. retin-a targeted to acne,

renova targeted to anti-aging.

Retinaldehyde, on the other hand, is an intermediate form of Vit A, a

retinoid between retinol and retinoic acid (tretinoin/retin-a). It

converts in the deeper skin layers into retinoic acid/tretinoin/retin-

a. (Why can't they just call a substance by 1 name, and leave it at

that? <g>) At the end of this message, is another study that

describes some retinaldahyde mechanics.

> my references describe the various formulations as a type of

>tretinoin, as if the

> type doesn't matter pharmacologically (while the studies we're been

> talking about clearly demonstrate different, no? I'm confused here.)

>

It appears that it is retinoic acid(tretinoin etcetcetc) in the

deeper dermal layers that imparts the anti-aging benefits. You can

deliver it as topical retinoic acid, a small portion of which makes

it to those deeper layers (the rest just irritates the top

layers<g>), or you can deliver it as topical retinaldahyde at smaller

dosage/concentration, which will then metabolize in vivo in the

deeper layers to comparable levels of retinoic acid (without all the

irritation).

>> what is the proposed mechanism of action for tretinoins and

>>rosacea?

based on recollection (don't have the studies), tretinoin has been

shown to increase collagen production and thicken the skin, reduce

wrinkles and lines, fade brown spots and surface roughness, fade

newer stretch marks, and generally convert a persons skin to a

younger version of itself in lay terms. Clinically, renova treated

skin has a " healthy glow " to it and there have been studies that

attributed this to tretinoins " angiogenic " properties (maybe angio-

normalizing?).

To go off on a tangent, since tretinoin has also been shown to reduce

or eliminate redness & telangiectasia, I'm thinking that it may also

revert the skins vascular framework to a younger version of itself,

strengtening or smartening up the endothelial lining of stubbornly

dialated blood vessels (wishful thinking?).

bottom line if the studies are to be relied upon is, retinoic acid =

good for deeper skin layers, irritative to top layers. retinaldahyde

converts in the skin to retinoic acid, and is well tolerated. I was

only able to find one company with a retinaldahyde product.

Apparantly this is already big in France:

(be sure to copy entire 2-line url)

http://www.dermaweb.com/english/dermato/avene/soins_antiage_Ystheal_me

illeur.html

---

Here's that study. It was directed at hair loss applications, but is

interesting nonetheless.

thanks

tom

Didierjean et al (p. 714) show that, in mouse skin (Tommy7ro's Note:

human studies have demonstrated same), topical retinaldehyde is

transformed in vivo into small amounts of all-trans retinoic acid

sufficient to induce biologic effects similar to those resulting from

topical application of all-trans retinoic acid itself in much higher

concentration. The same group recently proposed retinaldehyde for

topical use in humans. Retinaldehyde is a natural metabolite of beta-

carotene and retinol. As retinaldehyde does not bind to retinoic acid

receptors, its biologic activity should result from enzymatic

transformation by keratinocytes into ligands for these receptors

(i.e. all-trans and 9-cis retinoic acid). To test this possibility,

the authors used the tail skin model and analyzed by high performance

liquid chromatography the type and amounts of skin retinoids and

characterized the biological effects produced by topical

retinaldehyde and all-trans retinoic acid as comparison. They

demonstrate that murine skin in vivo transforms retinaldehyde into

all-trans retinoic acid. As the authors anticipated, retinaldehyde

applied at 0.05% was unable to load the skin with as much all-trans

retinoic acid as that resulting from topical application of 0.05% all-

trans retinoic acid; nevertheless, topical retinaldehyde induced

differentiation and proliferating (retinoid) activities similar to

those produced by all-trans retinoic acid in this model. This study

supports the concept of using precursors such as retinaldehyde to

deliver retinoid activity in the skin; it suggests that the bulk of

all-trans retinoic acid applied onto the skin does not reach

molecular targets of retinoid activities within the cell.

> > Don't recall seeing this study. Kligman says tretinoin (i assume

> > delivered as retin-a or renova) beneficial and well tolerated for

> > cea. (Dr Nase says opposite).

> >

> >

> > 1: Arch Dermatol 1994 Mar;130(3):319-24

> >

> > A comparison of the efficacy of topical tretinoin and low-dose

oral

> > isotretinoin

> > in rosacea.

> >

> > Ertl GA, Levine N, Kligman AM.

> >

> > University of Arizona, Tucson.

> >

> > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > recalcitrant rosacea

> > were divided into three treatment groups in a randomized, double-

> > blind trial

> > that compared low-dose oral isotretinoin (10 mg/d), topically

> applied

> > tretinoin

> > (0.025% cream), and the combined use of both isotretinoin and

> > tretinoin. For the

> > first 16 weeks of the trial, subjects received one of these three

> > trial

> > regimens. For the final 16 weeks, isotretinoin was withheld while

> > tretinoin

> > cream or a placebo cream was continued. RESULTS: Twenty subjects

> > completed the

> > trial. Each treatment produced therapeutic benefits with regard

to

> > the number of

> > papules and pustules and erythema. Treatment with oral

isotretinoin

> > appeared to

> > give a more rapid onset of improvement, but there were no

> differences

> > between

> > the groups after 16 weeks. This level of improvement continued

> during

> > the

> > succeeding 16 weeks of observation whether the subjects used the

> > tretinoin or

> > the placebo cream. Adverse events were minimal and well tolerated

> in

> > all groups.

> > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

cream

> > therapy

> > appear to be beneficial in the treatment of severe or

recalcitrant

> > rosacea. No

> > additive benefit is noted with the combined use of these two

> > modalities.

> >

> > Publication Types:

> > Clinical Trial

> > Randomized Controlled Trial

> >

> > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

Dr. M

>> Is retin-a or renova the aldehyde version of tretinoin? It's

>>curious

>> that I'm having a hard time finding this out

Best I recall, tretinoin (or retinoic acid) and retin-a, and are the

same animal (chemical name / trade name), and renova is trade name

for tretinoin/retin-a formulated with emollients (and buffers

perhaps?) to lessen dryness and irritation. retin-a targeted to acne,

renova targeted to anti-aging.

Retinaldehyde, on the other hand, is an intermediate form of Vit A, a

retinoid between retinol and retinoic acid (tretinoin/retin-a). It

converts in the deeper skin layers into retinoic acid/tretinoin/retin-

a. (Why can't they just call a substance by 1 name, and leave it at

that? <g>) At the end of this message, is another study that

describes some retinaldahyde mechanics.

> my references describe the various formulations as a type of

>tretinoin, as if the

> type doesn't matter pharmacologically (while the studies we're been

> talking about clearly demonstrate different, no? I'm confused here.)

>

It appears that it is retinoic acid(tretinoin etcetcetc) in the

deeper dermal layers that imparts the anti-aging benefits. You can

deliver it as topical retinoic acid, a small portion of which makes

it to those deeper layers (the rest just irritates the top

layers<g>), or you can deliver it as topical retinaldahyde at smaller

dosage/concentration, which will then metabolize in vivo in the

deeper layers to comparable levels of retinoic acid (without all the

irritation).

>> what is the proposed mechanism of action for tretinoins and

>>rosacea?

based on recollection (don't have the studies), tretinoin has been

shown to increase collagen production and thicken the skin, reduce

wrinkles and lines, fade brown spots and surface roughness, fade

newer stretch marks, and generally convert a persons skin to a

younger version of itself in lay terms. Clinically, renova treated

skin has a " healthy glow " to it and there have been studies that

attributed this to tretinoins " angiogenic " properties (maybe angio-

normalizing?).

To go off on a tangent, since tretinoin has also been shown to reduce

or eliminate redness & telangiectasia, I'm thinking that it may also

revert the skins vascular framework to a younger version of itself,

strengtening or smartening up the endothelial lining of stubbornly

dialated blood vessels (wishful thinking?).

bottom line if the studies are to be relied upon is, retinoic acid =

good for deeper skin layers, irritative to top layers. retinaldahyde

converts in the skin to retinoic acid, and is well tolerated. I was

only able to find one company with a retinaldahyde product.

Apparantly this is already big in France:

(be sure to copy entire 2-line url)

http://www.dermaweb.com/english/dermato/avene/soins_antiage_Ystheal_me

illeur.html

---

Here's that study. It was directed at hair loss applications, but is

interesting nonetheless.

thanks

tom

Didierjean et al (p. 714) show that, in mouse skin (Tommy7ro's Note:

human studies have demonstrated same), topical retinaldehyde is

transformed in vivo into small amounts of all-trans retinoic acid

sufficient to induce biologic effects similar to those resulting from

topical application of all-trans retinoic acid itself in much higher

concentration. The same group recently proposed retinaldehyde for

topical use in humans. Retinaldehyde is a natural metabolite of beta-

carotene and retinol. As retinaldehyde does not bind to retinoic acid

receptors, its biologic activity should result from enzymatic

transformation by keratinocytes into ligands for these receptors

(i.e. all-trans and 9-cis retinoic acid). To test this possibility,

the authors used the tail skin model and analyzed by high performance

liquid chromatography the type and amounts of skin retinoids and

characterized the biological effects produced by topical

retinaldehyde and all-trans retinoic acid as comparison. They

demonstrate that murine skin in vivo transforms retinaldehyde into

all-trans retinoic acid. As the authors anticipated, retinaldehyde

applied at 0.05% was unable to load the skin with as much all-trans

retinoic acid as that resulting from topical application of 0.05% all-

trans retinoic acid; nevertheless, topical retinaldehyde induced

differentiation and proliferating (retinoid) activities similar to

those produced by all-trans retinoic acid in this model. This study

supports the concept of using precursors such as retinaldehyde to

deliver retinoid activity in the skin; it suggests that the bulk of

all-trans retinoic acid applied onto the skin does not reach

molecular targets of retinoid activities within the cell.

> > Don't recall seeing this study. Kligman says tretinoin (i assume

> > delivered as retin-a or renova) beneficial and well tolerated for

> > cea. (Dr Nase says opposite).

> >

> >

> > 1: Arch Dermatol 1994 Mar;130(3):319-24

> >

> > A comparison of the efficacy of topical tretinoin and low-dose

oral

> > isotretinoin

> > in rosacea.

> >

> > Ertl GA, Levine N, Kligman AM.

> >

> > University of Arizona, Tucson.

> >

> > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > recalcitrant rosacea

> > were divided into three treatment groups in a randomized, double-

> > blind trial

> > that compared low-dose oral isotretinoin (10 mg/d), topically

> applied

> > tretinoin

> > (0.025% cream), and the combined use of both isotretinoin and

> > tretinoin. For the

> > first 16 weeks of the trial, subjects received one of these three

> > trial

> > regimens. For the final 16 weeks, isotretinoin was withheld while

> > tretinoin

> > cream or a placebo cream was continued. RESULTS: Twenty subjects

> > completed the

> > trial. Each treatment produced therapeutic benefits with regard

to

> > the number of

> > papules and pustules and erythema. Treatment with oral

isotretinoin

> > appeared to

> > give a more rapid onset of improvement, but there were no

> differences

> > between

> > the groups after 16 weeks. This level of improvement continued

> during

> > the

> > succeeding 16 weeks of observation whether the subjects used the

> > tretinoin or

> > the placebo cream. Adverse events were minimal and well tolerated

> in

> > all groups.

> > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

cream

> > therapy

> > appear to be beneficial in the treatment of severe or

recalcitrant

> > rosacea. No

> > additive benefit is noted with the combined use of these two

> > modalities.

> >

> > Publication Types:

> > Clinical Trial

> > Randomized Controlled Trial

> >

> > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

p.s. to longer response above, as to a hypothesized mechanism of

action(s) re tretinoin and rosacea: tretinoin, by strengthening

dermal connective tissue, may thus prevent or lessen passive

dialation of vessels.

tom

> > Don't recall seeing this study. Kligman says tretinoin (i assume

> > delivered as retin-a or renova) beneficial and well tolerated for

> > cea. (Dr Nase says opposite).

> >

> >

> > 1: Arch Dermatol 1994 Mar;130(3):319-24

> >

> > A comparison of the efficacy of topical tretinoin and low-dose

oral

> > isotretinoin

> > in rosacea.

> >

> > Ertl GA, Levine N, Kligman AM.

> >

> > University of Arizona, Tucson.

> >

> > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > recalcitrant rosacea

> > were divided into three treatment groups in a randomized, double-

> > blind trial

> > that compared low-dose oral isotretinoin (10 mg/d), topically

> applied

> > tretinoin

> > (0.025% cream), and the combined use of both isotretinoin and

> > tretinoin. For the

> > first 16 weeks of the trial, subjects received one of these three

> > trial

> > regimens. For the final 16 weeks, isotretinoin was withheld while

> > tretinoin

> > cream or a placebo cream was continued. RESULTS: Twenty subjects

> > completed the

> > trial. Each treatment produced therapeutic benefits with regard

to

> > the number of

> > papules and pustules and erythema. Treatment with oral

isotretinoin

> > appeared to

> > give a more rapid onset of improvement, but there were no

> differences

> > between

> > the groups after 16 weeks. This level of improvement continued

> during

> > the

> > succeeding 16 weeks of observation whether the subjects used the

> > tretinoin or

> > the placebo cream. Adverse events were minimal and well tolerated

> in

> > all groups.

> > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

cream

> > therapy

> > appear to be beneficial in the treatment of severe or

recalcitrant

> > rosacea. No

> > additive benefit is noted with the combined use of these two

> > modalities.

> >

> > Publication Types:

> > Clinical Trial

> > Randomized Controlled Trial

> >

> > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

p.s. to longer response above, as to a hypothesized mechanism of

action(s) re tretinoin and rosacea: tretinoin, by strengthening

dermal connective tissue, may thus prevent or lessen passive

dialation of vessels.

tom

> > Don't recall seeing this study. Kligman says tretinoin (i assume

> > delivered as retin-a or renova) beneficial and well tolerated for

> > cea. (Dr Nase says opposite).

> >

> >

> > 1: Arch Dermatol 1994 Mar;130(3):319-24

> >

> > A comparison of the efficacy of topical tretinoin and low-dose

oral

> > isotretinoin

> > in rosacea.

> >

> > Ertl GA, Levine N, Kligman AM.

> >

> > University of Arizona, Tucson.

> >

> > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > recalcitrant rosacea

> > were divided into three treatment groups in a randomized, double-

> > blind trial

> > that compared low-dose oral isotretinoin (10 mg/d), topically

> applied

> > tretinoin

> > (0.025% cream), and the combined use of both isotretinoin and

> > tretinoin. For the

> > first 16 weeks of the trial, subjects received one of these three

> > trial

> > regimens. For the final 16 weeks, isotretinoin was withheld while

> > tretinoin

> > cream or a placebo cream was continued. RESULTS: Twenty subjects

> > completed the

> > trial. Each treatment produced therapeutic benefits with regard

to

> > the number of

> > papules and pustules and erythema. Treatment with oral

isotretinoin

> > appeared to

> > give a more rapid onset of improvement, but there were no

> differences

> > between

> > the groups after 16 weeks. This level of improvement continued

> during

> > the

> > succeeding 16 weeks of observation whether the subjects used the

> > tretinoin or

> > the placebo cream. Adverse events were minimal and well tolerated

> in

> > all groups.

> > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

cream

> > therapy

> > appear to be beneficial in the treatment of severe or

recalcitrant

> > rosacea. No

> > additive benefit is noted with the combined use of these two

> > modalities.

> >

> > Publication Types:

> > Clinical Trial

> > Randomized Controlled Trial

> >

> > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

This is great, Tom. Very clear. With all these seemingly solid

abstracts, you (and Ian) are having me rethink my initial rejection

of tretinoin. I appreciate the education.

OK, so we have the generic tretinoin (=retinoic acid), which has two

popular trademark formulations: Retin-A, tretinoin in an inactive

vehicle, used for acne control, and Renova, tretinoin in an active

vehicle, used as anti-aging, right?

Two questions, then: (1) you mentioned retinol -- what is that, and

(2) where does Differin (Adapalene) fit into all this. It looks from

my references to be a competitor of Retin-A, but is it essentially

the same medication? (It's from Galderma, and is marketed for acne.)

Do you know why retinaldehyde isn't approved in the US?

> To go off on a tangent, since tretinoin has also been shown to

> reduce or eliminate redness & telangiectasia, I'm thinking that it

> may also

> revert the skins vascular framework to a younger version of itself,

> strengtening or smartening up the endothelial lining of stubbornly

> dialated blood vessels (wishful thinking?).

Does sound like wishful thinking. The study says, " Similarly,

isolated telangiectasia responded to retinaldehyde, although to a

lesser extent and after a longer period of treatment (46% responders

after 6 months, nonsignificant). " If it's not significant it's at

best a trend towards significance. By itself it means nothing.

Ian's abstract reportedly demonstrated that retinoids inhibit skin

cells' release of VEGF (vascular endothelial growth factor) which

would theoretically decrease neoangiogenesis (which is theoretically

involved in rosacea). Theoretically, that would prevent future

vascular growth -- theoretically (very theoretically) preventing

future damage. I don't know that VEGF literally increases endothelial

cells in existing vessels, or if doing so would even reverse present

damage.

I see why you and Ian argue that tretinoin treats the vascular

component of rosacea, but even with these studies I'm not convinced.

Reversibly dilated vessels secondary to smooth muscle activity, such

as arterioles, re-constrict with proper activation, but that

activation wouldn't, I think, be lack of VEGF. And dilated

superficial veins (telangectasias) that cause cosmetic problems in

rosacea don't have a smooth muscle layer, nor would I think it

reconstricts with the absense of VEGF.

I wonder if the reduced redness in these studies is inflammatory

redness, which in rosaceans is easily confused clinically with

vascular redness. Which is good enough, if the retinaldehyde

formulation is as gentle and effective as these studies suggest, and

if tretinoin works as an anti-inflammatory drug. I would need to see

doppler studies showing decreased blood flow to the face after

tretinoin use -- the same type of study Rick recommended a year ago

to document vascular improvement after laser therapy.

Thanks for the great information and discussion!

Marjorie

Marjorie Lazoff, MD

[Guest guest]

This is great, Tom. Very clear. With all these seemingly solid

abstracts, you (and Ian) are having me rethink my initial rejection

of tretinoin. I appreciate the education.

OK, so we have the generic tretinoin (=retinoic acid), which has two

popular trademark formulations: Retin-A, tretinoin in an inactive

vehicle, used for acne control, and Renova, tretinoin in an active

vehicle, used as anti-aging, right?

Two questions, then: (1) you mentioned retinol -- what is that, and

(2) where does Differin (Adapalene) fit into all this. It looks from

my references to be a competitor of Retin-A, but is it essentially

the same medication? (It's from Galderma, and is marketed for acne.)

Do you know why retinaldehyde isn't approved in the US?

> To go off on a tangent, since tretinoin has also been shown to

> reduce or eliminate redness & telangiectasia, I'm thinking that it

> may also

> revert the skins vascular framework to a younger version of itself,

> strengtening or smartening up the endothelial lining of stubbornly

> dialated blood vessels (wishful thinking?).

Does sound like wishful thinking. The study says, " Similarly,

isolated telangiectasia responded to retinaldehyde, although to a

lesser extent and after a longer period of treatment (46% responders

after 6 months, nonsignificant). " If it's not significant it's at

best a trend towards significance. By itself it means nothing.

Ian's abstract reportedly demonstrated that retinoids inhibit skin

cells' release of VEGF (vascular endothelial growth factor) which

would theoretically decrease neoangiogenesis (which is theoretically

involved in rosacea). Theoretically, that would prevent future

vascular growth -- theoretically (very theoretically) preventing

future damage. I don't know that VEGF literally increases endothelial

cells in existing vessels, or if doing so would even reverse present

damage.

I see why you and Ian argue that tretinoin treats the vascular

component of rosacea, but even with these studies I'm not convinced.

Reversibly dilated vessels secondary to smooth muscle activity, such

as arterioles, re-constrict with proper activation, but that

activation wouldn't, I think, be lack of VEGF. And dilated

superficial veins (telangectasias) that cause cosmetic problems in

rosacea don't have a smooth muscle layer, nor would I think it

reconstricts with the absense of VEGF.

I wonder if the reduced redness in these studies is inflammatory

redness, which in rosaceans is easily confused clinically with

vascular redness. Which is good enough, if the retinaldehyde

formulation is as gentle and effective as these studies suggest, and

if tretinoin works as an anti-inflammatory drug. I would need to see

doppler studies showing decreased blood flow to the face after

tretinoin use -- the same type of study Rick recommended a year ago

to document vascular improvement after laser therapy.

Thanks for the great information and discussion!

Marjorie

Marjorie Lazoff, MD

[Guest guest]

> > > Don't recall seeing this study. Kligman says tretinoin (i

assume

> > > delivered as retin-a or renova) beneficial and well tolerated

for

> > > cea. (Dr Nase says opposite).

> > >

> > >

> > > 1: Arch Dermatol 1994 Mar;130(3):319-24

> > >

> > > A comparison of the efficacy of topical tretinoin and low-dose

> oral

> > > isotretinoin

> > > in rosacea.

> > >

> > > Ertl GA, Levine N, Kligman AM.

> > >

> > > University of Arizona, Tucson.

> > >

> > > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > > recalcitrant rosacea

> > > were divided into three treatment groups in a randomized,

double-

> > > blind trial

> > > that compared low-dose oral isotretinoin (10 mg/d), topically

> > applied

> > > tretinoin

> > > (0.025% cream), and the combined use of both isotretinoin and

> > > tretinoin. For the

> > > first 16 weeks of the trial, subjects received one of these

three

> > > trial

> > > regimens. For the final 16 weeks, isotretinoin was withheld

while

> > > tretinoin

> > > cream or a placebo cream was continued. RESULTS: Twenty

subjects

> > > completed the

> > > trial. Each treatment produced therapeutic benefits with regard

> to

> > > the number of

> > > papules and pustules and erythema. Treatment with oral

> isotretinoin

> > > appeared to

> > > give a more rapid onset of improvement, but there were no

> > differences

> > > between

> > > the groups after 16 weeks. This level of improvement continued

> > during

> > > the

> > > succeeding 16 weeks of observation whether the subjects used

the

> > > tretinoin or

> > > the placebo cream. Adverse events were minimal and well

tolerated

> > in

> > > all groups.

> > > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

> cream

> > > therapy

> > > appear to be beneficial in the treatment of severe or

> recalcitrant

> > > rosacea. No

> > > additive benefit is noted with the combined use of these two

> > > modalities.

> > >

> > > Publication Types:

> > > Clinical Trial

> > > Randomized Controlled Trial

> > >

> > > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

> > > Don't recall seeing this study. Kligman says tretinoin (i

assume

> > > delivered as retin-a or renova) beneficial and well tolerated

for

> > > cea. (Dr Nase says opposite).

> > >

> > >

> > > 1: Arch Dermatol 1994 Mar;130(3):319-24

> > >

> > > A comparison of the efficacy of topical tretinoin and low-dose

> oral

> > > isotretinoin

> > > in rosacea.

> > >

> > > Ertl GA, Levine N, Kligman AM.

> > >

> > > University of Arizona, Tucson.

> > >

> > > BACKGROUND AND DESIGN: Twenty-two patients with severe or

> > > recalcitrant rosacea

> > > were divided into three treatment groups in a randomized,

double-

> > > blind trial

> > > that compared low-dose oral isotretinoin (10 mg/d), topically

> > applied

> > > tretinoin

> > > (0.025% cream), and the combined use of both isotretinoin and

> > > tretinoin. For the

> > > first 16 weeks of the trial, subjects received one of these

three

> > > trial

> > > regimens. For the final 16 weeks, isotretinoin was withheld

while

> > > tretinoin

> > > cream or a placebo cream was continued. RESULTS: Twenty

subjects

> > > completed the

> > > trial. Each treatment produced therapeutic benefits with regard

> to

> > > the number of

> > > papules and pustules and erythema. Treatment with oral

> isotretinoin

> > > appeared to

> > > give a more rapid onset of improvement, but there were no

> > differences

> > > between

> > > the groups after 16 weeks. This level of improvement continued

> > during

> > > the

> > > succeeding 16 weeks of observation whether the subjects used

the

> > > tretinoin or

> > > the placebo cream. Adverse events were minimal and well

tolerated

> > in

> > > all groups.

> > > CONCLUSIONS: Low-dose oral isotretinoin and topical tretinoin

> cream

> > > therapy

> > > appear to be beneficial in the treatment of severe or

> recalcitrant

> > > rosacea. No

> > > additive benefit is noted with the combined use of these two

> > > modalities.

> > >

> > > Publication Types:

> > > Clinical Trial

> > > Randomized Controlled Trial

> > >

> > > PMID: 8129410 [PubMed - indexed for MEDLINE]

[Guest guest]

Dr. Nase wrote an excellent message on this subject (collagen and

rosacea), which is worth re-posting. He starts his explanation half-

way down the post. Here is the link:

http://www.escribe.com/health/rosacea-support/m4175.html

.

<snip>

> But remember the study below, Tom -- it demonstrated that " deranged

> connective tissue " was secondary to the primary pathology, dilated

> vessels, not the other way around.

<snip>

[Guest guest]

Dr. Nase wrote an excellent message on this subject (collagen and

rosacea), which is worth re-posting. He starts his explanation half-

way down the post. Here is the link:

http://www.escribe.com/health/rosacea-support/m4175.html

.

<snip>

> But remember the study below, Tom -- it demonstrated that " deranged

> connective tissue " was secondary to the primary pathology, dilated

> vessels, not the other way around.

<snip>

[Guest guest]

> OK, so we have the generic tretinoin (=retinoic acid), which has

two

> popular trademark formulations: Retin-A, tretinoin in an inactive

> vehicle, used for acne control, and Renova, tretinoin in an active

> vehicle, used as anti-aging, right?

>

Yes, and yes. Note that there is crossover effect both ways, just

that each is " better " formulated/targeted for either acne or anti-

aging (the reason they sought/got the FDA approval for renova

antiaging use was that patients/docs using retin-a for acne were

noticing anti-aging benefits in skin)

>>(1) you mentioned retinol -- what is that

Retinol is another higher retinoid form of vitamin A, used in over-

the-counter anti-aging formulations (avon, neutrogena, etc). They

make somewhat comparable claims to renova, but these are not

supported by independent peer-reviwed science, only by the individual

companies conducting their own " tests " or surveys and making claims.

As you know, as long as they carefully word the claimed benefits, and

disclaim FDA approval or review of those claims, they can say almost

anything. On a personal note, I've used these products in the past,

and they are great for skin appearance. Use was way way before my

rosacea (if thats even what I have), so can't comment on retinol and

rosacea.

>>> (2) where does Differin (Adapalene) fit into all this.

First I heard of it, but here is a link to the package insert if

anyone interested.

http://www.differin.com/products/insertadapalenegel.shtml

>>> Thanks for the great information and discussion!

hey, it's you who does lots of heavy lifting on this board, thank you.

tom

> This is great, Tom. Very clear. With all these seemingly solid

> abstracts, you (and Ian) are having me rethink my initial rejection

> of tretinoin. I appreciate the education.

>

> OK, so we have the generic tretinoin (=retinoic acid), which has

two

> popular trademark formulations: Retin-A, tretinoin in an inactive

> vehicle, used for acne control, and Renova, tretinoin in an active

> vehicle, used as anti-aging, right?

>

> Two questions, then: (1) you mentioned retinol -- what is that, and

> (2) where does Differin (Adapalene) fit into all this. It looks

from

> my references to be a competitor of Retin-A, but is it essentially

> the same medication? (It's from Galderma, and is marketed for

acne.)

>

> Do you know why retinaldehyde isn't approved in the US?

>

> > To go off on a tangent, since tretinoin has also been shown to

> > reduce or eliminate redness & telangiectasia, I'm thinking that

it

> > may also

> > revert the skins vascular framework to a younger version of

itself,

> > strengtening or smartening up the endothelial lining of

stubbornly

> > dialated blood vessels (wishful thinking?).

>

> Does sound like wishful thinking. The study says, " Similarly,

> isolated telangiectasia responded to retinaldehyde, although to a

> lesser extent and after a longer period of treatment (46%

responders

> after 6 months, nonsignificant). " If it's not significant it's at

> best a trend towards significance. By itself it means nothing.

>

> Ian's abstract reportedly demonstrated that retinoids inhibit skin

> cells' release of VEGF (vascular endothelial growth factor) which

> would theoretically decrease neoangiogenesis (which is

theoretically

> involved in rosacea). Theoretically, that would prevent future

> vascular growth -- theoretically (very theoretically) preventing

> future damage. I don't know that VEGF literally increases

endothelial

> cells in existing vessels, or if doing so would even reverse

present

> damage.

>

> I see why you and Ian argue that tretinoin treats the vascular

> component of rosacea, but even with these studies I'm not

convinced.

> Reversibly dilated vessels secondary to smooth muscle activity,

such

> as arterioles, re-constrict with proper activation, but that

> activation wouldn't, I think, be lack of VEGF. And dilated

> superficial veins (telangectasias) that cause cosmetic problems in

> rosacea don't have a smooth muscle layer, nor would I think it

> reconstricts with the absense of VEGF.

>

> I wonder if the reduced redness in these studies is inflammatory

> redness, which in rosaceans is easily confused clinically with

> vascular redness. Which is good enough, if the retinaldehyde

> formulation is as gentle and effective as these studies suggest,

and

> if tretinoin works as an anti-inflammatory drug. I would need to

see

> doppler studies showing decreased blood flow to the face after

> tretinoin use -- the same type of study Rick recommended a year ago

> to document vascular improvement after laser therapy.

>

> Thanks for the great information and discussion!

>

> Marjorie

>

> Marjorie Lazoff, MD

[Guest guest]

> OK, so we have the generic tretinoin (=retinoic acid), which has

two

> popular trademark formulations: Retin-A, tretinoin in an inactive

> vehicle, used for acne control, and Renova, tretinoin in an active

> vehicle, used as anti-aging, right?

>

Yes, and yes. Note that there is crossover effect both ways, just

that each is " better " formulated/targeted for either acne or anti-

aging (the reason they sought/got the FDA approval for renova

antiaging use was that patients/docs using retin-a for acne were

noticing anti-aging benefits in skin)

>>(1) you mentioned retinol -- what is that

Retinol is another higher retinoid form of vitamin A, used in over-

the-counter anti-aging formulations (avon, neutrogena, etc). They

make somewhat comparable claims to renova, but these are not

supported by independent peer-reviwed science, only by the individual

companies conducting their own " tests " or surveys and making claims.

As you know, as long as they carefully word the claimed benefits, and

disclaim FDA approval or review of those claims, they can say almost

anything. On a personal note, I've used these products in the past,

and they are great for skin appearance. Use was way way before my

rosacea (if thats even what I have), so can't comment on retinol and

rosacea.

>>> (2) where does Differin (Adapalene) fit into all this.

First I heard of it, but here is a link to the package insert if

anyone interested.

http://www.differin.com/products/insertadapalenegel.shtml

>>> Thanks for the great information and discussion!

hey, it's you who does lots of heavy lifting on this board, thank you.

tom

> This is great, Tom. Very clear. With all these seemingly solid

> abstracts, you (and Ian) are having me rethink my initial rejection

> of tretinoin. I appreciate the education.

>

> OK, so we have the generic tretinoin (=retinoic acid), which has

two

> popular trademark formulations: Retin-A, tretinoin in an inactive

> vehicle, used for acne control, and Renova, tretinoin in an active

> vehicle, used as anti-aging, right?

>

> Two questions, then: (1) you mentioned retinol -- what is that, and

> (2) where does Differin (Adapalene) fit into all this. It looks

from

> my references to be a competitor of Retin-A, but is it essentially

> the same medication? (It's from Galderma, and is marketed for

acne.)

>

> Do you know why retinaldehyde isn't approved in the US?

>

> > To go off on a tangent, since tretinoin has also been shown to

> > reduce or eliminate redness & telangiectasia, I'm thinking that

it

> > may also

> > revert the skins vascular framework to a younger version of

itself,

> > strengtening or smartening up the endothelial lining of

stubbornly

> > dialated blood vessels (wishful thinking?).

>

> Does sound like wishful thinking. The study says, " Similarly,

> isolated telangiectasia responded to retinaldehyde, although to a

> lesser extent and after a longer period of treatment (46%

responders

> after 6 months, nonsignificant). " If it's not significant it's at

> best a trend towards significance. By itself it means nothing.

>

> Ian's abstract reportedly demonstrated that retinoids inhibit skin

> cells' release of VEGF (vascular endothelial growth factor) which

> would theoretically decrease neoangiogenesis (which is

theoretically

> involved in rosacea). Theoretically, that would prevent future

> vascular growth -- theoretically (very theoretically) preventing

> future damage. I don't know that VEGF literally increases

endothelial

> cells in existing vessels, or if doing so would even reverse

present

> damage.

>

> I see why you and Ian argue that tretinoin treats the vascular

> component of rosacea, but even with these studies I'm not

convinced.

> Reversibly dilated vessels secondary to smooth muscle activity,

such

> as arterioles, re-constrict with proper activation, but that

> activation wouldn't, I think, be lack of VEGF. And dilated

> superficial veins (telangectasias) that cause cosmetic problems in

> rosacea don't have a smooth muscle layer, nor would I think it

> reconstricts with the absense of VEGF.

>

> I wonder if the reduced redness in these studies is inflammatory

> redness, which in rosaceans is easily confused clinically with

> vascular redness. Which is good enough, if the retinaldehyde

> formulation is as gentle and effective as these studies suggest,

and

> if tretinoin works as an anti-inflammatory drug. I would need to

see

> doppler studies showing decreased blood flow to the face after

> tretinoin use -- the same type of study Rick recommended a year ago

> to document vascular improvement after laser therapy.

>

> Thanks for the great information and discussion!

>

> Marjorie

>

> Marjorie Lazoff, MD

[Guest guest]

> >>(1) you mentioned retinol -- what is that

>

> Retinol is another higher retinoid form of vitamin A, used in over-

> the-counter anti-aging formulations (avon, neutrogena, etc). They

> make somewhat comparable claims to renova, but these are not

> supported by independent peer-reviwed science, only by the

individual

> companies conducting their own " tests " or surveys and making

claims.

> As you know, as long as they carefully word the claimed benefits,

and

> disclaim FDA approval or review of those claims, they can say

almost

> anything. On a personal note, I've used these products in the

past,

> and they are great for skin appearance. Use was way way before my

> rosacea (if thats even what I have), so can't comment on retinol

and

> rosacea.

That's helpful, Tom. Sounds similiar to the debate among companies

who insist their " research " demonstrates that esterification of Vit C

is as effective as its more irritating, but effectiveness-documented

Vit C.

> >>> (2) where does Differin (Adapalene) fit into all this.

>

> First I heard of it, but here is a link to the package insert if

> anyone interested.

>

> http://www.differin.com/products/insertadapalenegel.shtml

Yeah, but it doesn't say anything other than putting adapalene in the

retinoid-like group. The mechanism of action sounds like that

theorized for tretinoin.

> >>> Thanks for the great information and discussion!

>

> hey, it's you who does lots of heavy lifting on this board, thank

you.

Me and my wimpy biceps thank you for the kind words -- but esp thank

you for pointing out that the evidence is more complicated that

appears at first blush. Trentinoin may very well not be appropriate

for rosaceans, but the facts are clearly more debatable and the

information more layered then what I originally thought.

Marjorie

Marjorie Lazoff, MD

> In rosacea-support@y..., " emarjency " <emarjency@s...> wrote:

> > This is great, Tom. Very clear. With all these seemingly solid

> > abstracts, you (and Ian) are having me rethink my initial

rejection

> > of tretinoin. I appreciate the education.

> >

> > OK, so we have the generic tretinoin (=retinoic acid), which has

> two

> > popular trademark formulations: Retin-A, tretinoin in an inactive

> > vehicle, used for acne control, and Renova, tretinoin in an

active

> > vehicle, used as anti-aging, right?

> >

> > Two questions, then: (1) you mentioned retinol -- what is that,

and

> > (2) where does Differin (Adapalene) fit into all this. It looks

> from

> > my references to be a competitor of Retin-A, but is it

essentially

> > the same medication? (It's from Galderma, and is marketed for

> acne.)

> >

> > Do you know why retinaldehyde isn't approved in the US?

> >

> > > To go off on a tangent, since tretinoin has also been shown to

> > > reduce or eliminate redness & telangiectasia, I'm thinking that

> it

> > > may also

> > > revert the skins vascular framework to a younger version of

> itself,

> > > strengtening or smartening up the endothelial lining of

> stubbornly

> > > dialated blood vessels (wishful thinking?).

> >

> > Does sound like wishful thinking. The study says, " Similarly,

> > isolated telangiectasia responded to retinaldehyde, although to a

> > lesser extent and after a longer period of treatment (46%

> responders

> > after 6 months, nonsignificant). " If it's not significant it's at

> > best a trend towards significance. By itself it means nothing.

> >

> > Ian's abstract reportedly demonstrated that retinoids inhibit

skin

> > cells' release of VEGF (vascular endothelial growth factor) which

> > would theoretically decrease neoangiogenesis (which is

> theoretically

> > involved in rosacea). Theoretically, that would prevent future

> > vascular growth -- theoretically (very theoretically) preventing

> > future damage. I don't know that VEGF literally increases

> endothelial

> > cells in existing vessels, or if doing so would even reverse

> present

> > damage.

> >

> > I see why you and Ian argue that tretinoin treats the vascular

> > component of rosacea, but even with these studies I'm not

> convinced.

> > Reversibly dilated vessels secondary to smooth muscle activity,

> such

> > as arterioles, re-constrict with proper activation, but that

> > activation wouldn't, I think, be lack of VEGF. And dilated

> > superficial veins (telangectasias) that cause cosmetic problems

in

> > rosacea don't have a smooth muscle layer, nor would I think it

> > reconstricts with the absense of VEGF.

> >

> > I wonder if the reduced redness in these studies is inflammatory

> > redness, which in rosaceans is easily confused clinically with

> > vascular redness. Which is good enough, if the retinaldehyde

> > formulation is as gentle and effective as these studies suggest,

> and

> > if tretinoin works as an anti-inflammatory drug. I would need to

> see

> > doppler studies showing decreased blood flow to the face after

> > tretinoin use -- the same type of study Rick recommended a year

ago

> > to document vascular improvement after laser therapy.

> >

> > Thanks for the great information and discussion!

> >

> > Marjorie

> >

> > Marjorie Lazoff, MD

[Guest guest]

> >>(1) you mentioned retinol -- what is that

>

> Retinol is another higher retinoid form of vitamin A, used in over-

> the-counter anti-aging formulations (avon, neutrogena, etc). They

> make somewhat comparable claims to renova, but these are not

> supported by independent peer-reviwed science, only by the

individual

> companies conducting their own " tests " or surveys and making

claims.

> As you know, as long as they carefully word the claimed benefits,

and

> disclaim FDA approval or review of those claims, they can say

almost

> anything. On a personal note, I've used these products in the

past,

> and they are great for skin appearance. Use was way way before my

> rosacea (if thats even what I have), so can't comment on retinol

and

> rosacea.

That's helpful, Tom. Sounds similiar to the debate among companies

who insist their " research " demonstrates that esterification of Vit C

is as effective as its more irritating, but effectiveness-documented

Vit C.

> >>> (2) where does Differin (Adapalene) fit into all this.

>

> First I heard of it, but here is a link to the package insert if

> anyone interested.

>

> http://www.differin.com/products/insertadapalenegel.shtml

Yeah, but it doesn't say anything other than putting adapalene in the

retinoid-like group. The mechanism of action sounds like that

theorized for tretinoin.

> >>> Thanks for the great information and discussion!

>

> hey, it's you who does lots of heavy lifting on this board, thank

you.

Me and my wimpy biceps thank you for the kind words -- but esp thank

you for pointing out that the evidence is more complicated that

appears at first blush. Trentinoin may very well not be appropriate

for rosaceans, but the facts are clearly more debatable and the

information more layered then what I originally thought.

Marjorie

Marjorie Lazoff, MD

> In rosacea-support@y..., " emarjency " <emarjency@s...> wrote:

> > This is great, Tom. Very clear. With all these seemingly solid

> > abstracts, you (and Ian) are having me rethink my initial

rejection

> > of tretinoin. I appreciate the education.

> >

> > OK, so we have the generic tretinoin (=retinoic acid), which has

> two

> > popular trademark formulations: Retin-A, tretinoin in an inactive

> > vehicle, used for acne control, and Renova, tretinoin in an

active

> > vehicle, used as anti-aging, right?

> >

> > Two questions, then: (1) you mentioned retinol -- what is that,

and

> > (2) where does Differin (Adapalene) fit into all this. It looks

> from

> > my references to be a competitor of Retin-A, but is it

essentially

> > the same medication? (It's from Galderma, and is marketed for

> acne.)

> >

> > Do you know why retinaldehyde isn't approved in the US?

> >

> > > To go off on a tangent, since tretinoin has also been shown to

> > > reduce or eliminate redness & telangiectasia, I'm thinking that

> it

> > > may also

> > > revert the skins vascular framework to a younger version of

> itself,

> > > strengtening or smartening up the endothelial lining of

> stubbornly

> > > dialated blood vessels (wishful thinking?).

> >

> > Does sound like wishful thinking. The study says, " Similarly,

> > isolated telangiectasia responded to retinaldehyde, although to a

> > lesser extent and after a longer period of treatment (46%

> responders

> > after 6 months, nonsignificant). " If it's not significant it's at

> > best a trend towards significance. By itself it means nothing.

> >

> > Ian's abstract reportedly demonstrated that retinoids inhibit

skin

> > cells' release of VEGF (vascular endothelial growth factor) which

> > would theoretically decrease neoangiogenesis (which is

> theoretically

> > involved in rosacea). Theoretically, that would prevent future

> > vascular growth -- theoretically (very theoretically) preventing

> > future damage. I don't know that VEGF literally increases

> endothelial

> > cells in existing vessels, or if doing so would even reverse

> present

> > damage.

> >

> > I see why you and Ian argue that tretinoin treats the vascular

> > component of rosacea, but even with these studies I'm not

> convinced.

> > Reversibly dilated vessels secondary to smooth muscle activity,

> such

> > as arterioles, re-constrict with proper activation, but that

> > activation wouldn't, I think, be lack of VEGF. And dilated

> > superficial veins (telangectasias) that cause cosmetic problems

in

> > rosacea don't have a smooth muscle layer, nor would I think it

> > reconstricts with the absense of VEGF.

> >

> > I wonder if the reduced redness in these studies is inflammatory

> > redness, which in rosaceans is easily confused clinically with

> > vascular redness. Which is good enough, if the retinaldehyde

> > formulation is as gentle and effective as these studies suggest,

> and

> > if tretinoin works as an anti-inflammatory drug. I would need to

> see

> > doppler studies showing decreased blood flow to the face after

> > tretinoin use -- the same type of study Rick recommended a year

ago

> > to document vascular improvement after laser therapy.

> >

> > Thanks for the great information and discussion!

> >

> > Marjorie

> >

> > Marjorie Lazoff, MD

[Guest guest]

Thanks, . I assume you're referring to this 1999 post quote

from Dr. Nase:

" First, he [dermatologist Albert Kligman, MD] is correct that retin A

is an anti-inflammatory in the skin -- however, retin A is also a

powerful inflammatory stimuli directly on blood vessels (irritates

blood vessels causing increase blood flow to the area of trauma) --

this is bad for us. Second, and most importantly, although retin A

does indeed enhance collagen synthesis in the superficial dermis, it

does not lend support for damaged blood vessels. 85% of the strength

of the blood vessel comes from within its muscular walls and not from

the surrounding skin. For example, I could take the damaged facial

blood vessels out of a rosacean and put them in a 13 year old teen

with perfect skin and collagen -- she would develop rosacea very very

quickly. Conversely, I could take perfectly strong blood vessels

from a 14 year old boy and put them into the facial skin of a 98

year old (with extensive collagen damage to the dermis) and she would

probably never develop one rosacea symptom. The key is the blood

vessel itself. If you are getting rid of inflammation within the

dermis with azelex, and retin A, while you are aggravating the blood

vessels (the real beast), then it is extremely hard to ever break

through this disease. Concerning Retin A, if one were to do further

research, one would find that Wilkin, a rosacea expert (now in

the FDA) strongly recommends against retin A use in several key

articles. He states that a physician should " first do no harm' when

it comes to the treatment of rosacea-sensitive skin.

Sun damage can play a role in rosacea (UV induced damage to vascular

smooth muscle contractile proteins, endothelial cells and DNA

modification of cellular 'cement' in blood vessel), however, it is

never the sole cause of rosacea. "

I agree with his second point regarding the independence of collagen

synthesis and blood vessel strength, but Dr. Nase has not explained

his first point: how trentinoin is a direct irritant/inflammatory

stimulus to blood vessels. I can't find the key articles from Dr.

Wilkin published on the topic within the past years; one article from

1999 is available online:

http://archderm.ama-assn.org/issues/v135n1/ffull/ded8021.html

....which discusses the Use of Topical Products for Maintaining

Remission in cea. Although mostly on topical metronidazole, he

does mention other agents once: " Carefully select the topical drug

product to achieve remission maintenance. In 1994 I discussed topical

metronidazole that was " the only topically applied agent currently

approved to be marketed for rosacea. " Now, of course, there are other

agents and multiple products. The clinician should find that product

which the individual patient with rosacea tolerates best.

Occasionally, but fortunately not so often today because of the

multiple approved choices, this may require extemporaneous

compounding. "

To me, that sounds like he's open to other topicals as long as they

are tolerated by the patient, but obviously I don't know.

I will do a more indepth Medline and Web search on this topic, and

get back to the group.

Thanks again, .

Marjorie

Marjorie Lazoff, MD

> <snip>

> > But remember the study below, Tom -- it demonstrated

that " deranged

> > connective tissue " was secondary to the primary pathology,

dilated

> > vessels, not the other way around.

> <snip>

[Guest guest]

Thanks, . I assume you're referring to this 1999 post quote

from Dr. Nase:

" First, he [dermatologist Albert Kligman, MD] is correct that retin A

is an anti-inflammatory in the skin -- however, retin A is also a

powerful inflammatory stimuli directly on blood vessels (irritates

blood vessels causing increase blood flow to the area of trauma) --

this is bad for us. Second, and most importantly, although retin A

does indeed enhance collagen synthesis in the superficial dermis, it

does not lend support for damaged blood vessels. 85% of the strength

of the blood vessel comes from within its muscular walls and not from

the surrounding skin. For example, I could take the damaged facial

blood vessels out of a rosacean and put them in a 13 year old teen

with perfect skin and collagen -- she would develop rosacea very very

quickly. Conversely, I could take perfectly strong blood vessels

from a 14 year old boy and put them into the facial skin of a 98

year old (with extensive collagen damage to the dermis) and she would

probably never develop one rosacea symptom. The key is the blood

vessel itself. If you are getting rid of inflammation within the

dermis with azelex, and retin A, while you are aggravating the blood

vessels (the real beast), then it is extremely hard to ever break

through this disease. Concerning Retin A, if one were to do further

research, one would find that Wilkin, a rosacea expert (now in

the FDA) strongly recommends against retin A use in several key

articles. He states that a physician should " first do no harm' when

it comes to the treatment of rosacea-sensitive skin.

Sun damage can play a role in rosacea (UV induced damage to vascular

smooth muscle contractile proteins, endothelial cells and DNA

modification of cellular 'cement' in blood vessel), however, it is

never the sole cause of rosacea. "

I agree with his second point regarding the independence of collagen

synthesis and blood vessel strength, but Dr. Nase has not explained

his first point: how trentinoin is a direct irritant/inflammatory

stimulus to blood vessels. I can't find the key articles from Dr.

Wilkin published on the topic within the past years; one article from

1999 is available online:

http://archderm.ama-assn.org/issues/v135n1/ffull/ded8021.html

....which discusses the Use of Topical Products for Maintaining

Remission in cea. Although mostly on topical metronidazole, he

does mention other agents once: " Carefully select the topical drug

product to achieve remission maintenance. In 1994 I discussed topical

metronidazole that was " the only topically applied agent currently

approved to be marketed for rosacea. " Now, of course, there are other

agents and multiple products. The clinician should find that product

which the individual patient with rosacea tolerates best.

Occasionally, but fortunately not so often today because of the

multiple approved choices, this may require extemporaneous

compounding. "

To me, that sounds like he's open to other topicals as long as they

are tolerated by the patient, but obviously I don't know.

I will do a more indepth Medline and Web search on this topic, and

get back to the group.

Thanks again, .

Marjorie

Marjorie Lazoff, MD

> <snip>

> > But remember the study below, Tom -- it demonstrated

that " deranged

> > connective tissue " was secondary to the primary pathology,

dilated

> > vessels, not the other way around.

> <snip>

[Guest guest]

FWIW - when I was having problems with the pustule stage of my

rosacea I was prescribed tretinoin. I was warned that it would take

time to work and that things would get worse before they got better.

It did take time and it did get worse but I hung in there and after

about four to six weeks I had great results. I still keep a tube

around " just in case " ! I might add that I do have very sensitive

skin. It was quite drying but I just used a good moisturizer and

didn't have any problems.

Sue

[Guest guest]

FWIW - when I was having problems with the pustule stage of my

rosacea I was prescribed tretinoin. I was warned that it would take

time to work and that things would get worse before they got better.

It did take time and it did get worse but I hung in there and after

about four to six weeks I had great results. I still keep a tube

around " just in case " ! I might add that I do have very sensitive

skin. It was quite drying but I just used a good moisturizer and

didn't have any problems.

Sue