26 replies to this topic

[LionQueen]

Time to call in the real expert!

LabGirl ... could you please explain, in your usual awesome level of detail, what goes on with people's skin during the initial 3 months on retinoids?

There has been quite a bit of discussion about this lately ... someone actually went so far as to call the initial breakout a myth. She basically said that any pimples that show up during that time were going to show up anyway. Do you think that is true?

Also, do you think the severity of the IB (assuming it isn't a myth) correlates to the severity of the acne someone had going into the treatment?

Any and all information would be much appreciated ... thanks, hun.

(I am not entirely sure this thread belongs in the Research section, but I'm reasonably certain of finding you here.)

[LabGirl81]

Waits in anticipation...

Good Morning!!!!!

I just woke up so I'm a little groggy......I'll try my best but I have way more info at work (I'm relying solely on what's in my head).

This is a really good question since many scientists still don't know exactly how retinoids work. Dr. Albert Kligman is the original patent holder on using topical retinoic acid to treat acne (he has done tons of research on this topic, and has 40 years of studies on acne, sebaceous gland function and retinoids).

Anyway. A retinoid is any molecule capable of binding to and activating a retinoid receptor. There are many types of retinoid receptors, RAR-alpha, RAR-gamma, RXR (retinoid-X receptors), and their activation does all different things (cis-13 retinoic acne or Isotretonin acts on the retinoid-X receptor, and can inhibit cellular proliferation....especially of the sebocytes, where as trans-retinoid acid stimulates the other retinoid receptors...as well as the RXR and increases the proliferation of keratinocytes.)....it's not really that simple and the retinoid receptors actually interact with eachother and form heterodimers that control various types of cellular proliferation in epithelial tissue and also in other types of tissue.........


Okay so in the first few weeks of treatment with topical retinoic acid (or other topical retinoid), the skin cells begin to proliferate rapidly. This really only takes a few days to have an effect, but you don't see the effects instantly (although you may feel them). As you already know a retinoid makes skin cells proliferate and desquamate in only 5-6 days (it usually takes a month). This may be why.......but we don't know for sure ....

Physiological and retinoid-induced proliferations of epidermis basal keratinocytes are differently controlled

Within a couple weeks the epidermis thins out. This is when you begin to see the derided initial breakout. Is it really an initial breakout? Is the skin actually purging itself???.....well yes and no.....

You may see after about 2-3 weeks of treatment a bunch of tiny bumps (whiteheads, comedoes, clogged pores, etc). As the skin cells rapidly proliferate inside the pore ducts the microcomedo swells up. At the same time the stratum corneum is becoming thinner. It's usually 8-9 cell layers thick, but by using a topical retinoid it becomes only 4-5 cell layers thick. This happens to the entire epidermis. The granular layer is also smaller and the granules contain less keratin. The proliferating skin cells don't have the chance to become hyperkeratinized as they loose their nuclei and cytoplasm, flatten out and become enclosed in the cell envelope of the corneocyte.

Since the epidermis is thinner the comedoes (which actually form in the dermis), become visible through the thin epidermis.......this also makes you more sensitive to UV radiation.....so wear a good sunscreen...

So what about the inflammatory initial breakout? Some of the comedoes may become inflamed.....if you are prone to inflammatory acne. Retinoids do cause a bit of irritation, and this can induce inflammation. Sometimes the pores are so blocked up that it takes weeks to resolve the comedo, and the bacteria and sebum trapped inside, and the irritation from the retinoid make it a perfect opportunity for a pimple to form. The reason it seems like an initial breakout is because it speeds up the rate of cellular proliferation. Those may or may not have become pimples without the retinoid. But in the worse case scenario you will get about 15 months of pimples in only 3 months.

I have another theory about the initial breakout phenenmon. Since the retinoids thin out the epidermis they cause increased transepidermal water loss. Water in the skin is important to normal desquamation. Water is necessary for the destruction of the desmosomes and tonofilaments that hold the cells of the stratum corneum together. If there isn't enough water present in the skin, the cells don't desquamate properly.....this is why you get flakes .......the cells are stuck together in clumps.......this is bad if it happens inside the pores.......Dry skin is bad for acne, since abnormal desquamation inside pore ducts can cause the formation of comedoes.

An initial breakout can be controlled by using a topical or oral antibiotic in the first 12 weeks of treatment. After that you shouln't need as much bacterial control, since the pores aren't easily blocked and most of the comedoes will have resolved themselves. BP just irritates the skin and increases barrier damage. Moisturizing is crucial on a retinoid, since the epidermal barrier is compromised due to the thinning of the epidermis. A good moisturizer is one that contains about 3-5% glycerin. Glycerin is a great ingredient and really improves the barrier function of the skin, by filling in the extra-cellular matrix between the corneocytes ....and it promotes healthy desquamation of skin cells by drawing water into the skin from deeper dermal tissue and it is known to activate certain genes in the keratinocytes (just don't tell the FDA).

Okay when I get to work I'll look up some more stuff.........

I didn't even mention the effects topical retinoids have on the dermis........they reduce shallow scarring and wrinkles by stimulating the fibroblasts in the dermis to produce Collagen I and III.....which fills in shallow scars and plumps up wrinkles........another reason to stick with it even if the initial breakout makes you think that "this can't be good for my skin".....eventually it will be........

[Ariventa]

Awesome post. Thanks so much.

[LionQueen]

LabGirl, you ROCK!!!! This board is so lucky to have you.

Thank you so much for taking the time to do this. I'm going to be linking to this thread all the time! And once you've added in any other information you want to, I'd like to turn this into a sticky in the Prescription Medications forum.

[abbylee]

There has been quite a bit of discussion about this lately ... someone actually went so far as to call the initial breakout a myth. She basically said that any pimples that show up during that time were going to show up anyway.

Haha, she's talking about me. Well, I did retract that..but think of it from my perspective:

I didn't even come close to experiencing breakouts the whole time I was on it. Zits just stopped immediately, not even PMS ones!

Nobody I knew personally had such a reaction, my own doctor told me the myth was "total nonsense".

But I did suggest the possibility that people with IB were probably more likely to get bacterial infections while comedones were being exposed and shed.

Labgirl's explanation makes sense, I actually like it. It would explain why certain people would get IBs but not others.

Labgirl, you sound like you're familiar with the retinoid receptors. May I ask you something I've been trying to figure out? (I have noone else to ask )

If tretinoin binds unselectively to all subtypes of RAR (alpha, beta and gamma) while tazoratene is selective towards RAR beta and gamma, does this mean that given equal concentrations of both retinoids, tazoratene is able to express RAR-beta and RAR-gamma MORE than it does to RAR-alpha when compared with tretinoin?

If so, doesn't it also mean that tretinoin has a stronger gene expression of RAR-alpha than tazoratene?

From what i've been reading, RAR-gamma is solely responsible for the comedolytic effects of retinoids. Is RAR-gamma also responsible for the anti-aging effects as well?

I guess what I'm getting at is whether a retinoid that binds specifically to RAR-gamma (ie see gamma specific retinoid (ER36009))
is not only the best possible comedolytic agent, but also the most potent in terms of anti-aging?
Is RAR-alpha not relevant at all to anti-aging or anti-acne??

Tazoratene has been shown to be a stronger comedolytic agent than tretinoin, but I haven't seen studies that compare the anti-aging effects of taz and tretinoin of equal concentrations.

So theoretically
Is taz the better anti-aging agent than tretinoin???
That is what I'm trying to figure out...

[LionQueen]

Haha, she's talking about me.

I was trying to be a little discreet. But Abby, you definitely got me wondering about it. I didn't know enough to argue with you on a scientific basis ... all I knew was that I'd read at least a couple of dozen accounts of horrible initial breakouts here on the board.

Anyway, I am really grateful for LabGirl's account because I think a few conclusions can be drawn from it that will help at least some people get thru the tough times.

Now I will shut up and let her answer your question.

[LabGirl81]

There has been quite a bit of discussion about this lately ... someone actually went so far as to call the initial breakout a myth. She basically said that any pimples that show up during that time were going to show up anyway.

Haha, she's talking about me. Well, I did retract that..but think of it from my perspective:

I didn't even come close to experiencing breakouts the whole time I was on it. Zits just stopped immediately, not even PMS ones!

Nobody I knew personally had such a reaction, my own doctor told me the myth was "total nonsense".

But I did suggest the possibility that people with IB were probably more likely to get bacterial infections while comedones were being exposed and shed.

Labgirl's explanation makes sense, I actually like it. It would explain why certain people would get IBs but not others.

Labgirl, you sound like you're familiar with the retinoid receptors. May I ask you something I've been trying to figure out? (I have noone else to ask )

If tretinoin binds unselectively to all subtypes of RAR (alpha, beta and gamma) while tazoratene is selective towards RAR beta and gamma, does this mean that given equal concentrations of both retinoids, tazoratene is able to express RAR-beta and RAR-gamma MORE than it does to RAR-alpha when compared with tretinoin?

If so, doesn't it also mean that tretinoin has a stronger gene expression of RAR-alpha than tazoratene?

From what i've been reading, RAR-gamma is solely responsible for the comedolytic effects of retinoids. Is RAR-gamma also responsible for the anti-aging effects as well?

I guess what I'm getting at is whether a retinoid that binds specifically to RAR-gamma (ie see gamma specific retinoid (ER36009))
is not only the best possible comedolytic agent, but also the most potent in terms of anti-aging?
Is RAR-alpha not relevant at all to anti-aging or anti-acne??

Tazoratene has been shown to be a stronger comedolytic agent than tretinoin, but I haven't seen studies that compare the anti-aging effects of taz and tretinoin of equal concentrations.

So theoretically
Is taz the better anti-aging agent than tretinoin???
That is what I'm trying to figure out...

Oh man you had to bust out the big words on me. That's a really intelligent question. And I'll try my best to answer it (this is where the lecturer says....."you should look into that in your research") There is currently so much research going on about retinoids, because we're just now beginning to understand how they work. From my understanding the cells of the epidermis have mostly RAR-gamma and RXR-alpha receptors are by far the most abundent retinoid receptors and they need to function together as a pair to mediate cellular proliferation). RARs and RXRs always exist as dimers in keratinocytes. RAR's require the formation of a heterodimer complex with RXR before DNA binding and gene expression can occur. Tazaratene is a designer retinoid, and like it's brother adapalene, it's a receptor-selective retinoid targeting RAR-beta and RAR-gamma. Adapalene and Tazaratene also have anti-inflammatory activity because they inhibit chemotactic and chemokinetic responses in human polymorphonuclear leukocytes, they inhibit 5-and 15-lipoxygenase pathways and also cyclooxygenase activity......things tretoinin can't do. Tretinoin, Tazaratene and adapalene are all RAR-agomnist, where isotretionin is actually an RXR-agonist.......And yes since tazaratene specifically targets RAR-beta and RAR-gamma, tretinoin is expresses RAR-alpha gene way better than tazaratene.....but I'm not too sure of it's signifigance since the RAR-gamma is way more prevalent on the epidermial cell's DNA.....and I'm not sure exactly of RAR-alpha's role in reversing photoaging......or acne treatment.......

The studies aren't as clear cut when it comes to retinoids and aging. There is still so much that remains unknown about exactly how retinoids improve the structure and function of the dermis and reverse the effects if intrinsic aging and photoaging.....and exactly how they stimulate collagen production and preserve and repir existing collagen. It may not be an actual stimulation of collagen production by RAR-beta in the fibroblasts (RAR-beta, is found in dermal fibroblasts but not in keratinocytes), but rather an inhibition of the production of matrix metalloprotinases (MMP's), which are an inportant part of the collagen destruction process...which is important in wound healing, and amy time dermal tissue destruction is required (after a woman has a baby or after someone looses weight dermal tissue is destroyed). MMP's aren't bad, unless there are too many of them produced. As we age the MMP concentration in the dermis increases.....and guess what....UV radiation also increases the formation and activity of MMP's......The effets that retinoids have on dermal collagen are still somewhar paradoxal.....but retinoids (specifically all trans- retinoic acid) always show an increase in dermal collagen (collagen I mostly, III to a lesser degree and VII at the dermal-epidermal junction). Retinoids (mainly retinoic acid, but others have similar activity) are also well known AP-1 inhibitors, and they inhibit the activity of collagenase (which also destroys collagen) and stromelysin, and gelatinase, which also destroy collagen. Treating the skin with retinoids actually prevents the desrtuction of the RAR-gamma and RXR-alpha receptors in epidermal and dermal cells. I don't know exactly how much of the increase of collagen production is a true increase in collagen synthesis (although it undoubtledly occurs) and how much of it is because the extracellular matrix isn't degraded my MMP's and other enzymes. This isn't studied nearly as much in the synthetic retinoids like tazaratene or adapalene, and the clinical studies are conflicting, and no one ever compares 0.1% tretinoin to 0.1% tazaratene. It's always 0.025 or 0.05% tretinoin compared to 0.1% tazaratene, and most studies show that tretinoin is more effective at reducing photoaging........although one study (can't find it) found tazaratene to be more effective. Maybe it depends on the individual........who knows....

Enough of the biochemistry lecture. I think I'm done....

As for me personally I'm partial to plain old tretinoin. I guess cuz it's a natural retinoid......I had some success with adapalene, but retin-a micro was way better and I haven't tried tazorac yet.........but I'm gonna give cis-13 retinoic acid a shot.....then go back to retin-a micro as maintnence.......

I was another one who did not get an initial breakout on a retinoid. I didn't break out any more than my normal breakout pattern at the time, and within about 7 weeks I was completely clear (only to have a bad relapse of cystic acne four months later).

[willow569]

That was an interesting post (the parts I understood anyway!). Almost makes me wish I got my M.A. biochemistry instead of psychology and law!

Ok, now for a layman's question! I was wondering about the point you made about retinoids causing irritation, thus possibly leading to inflammatory breakouts. Isn't Differin (I don't know about other retinoids) supposed to be anti-inflammatory?

[LabGirl81]

That was an interesting post (the parts I understood anyway!). Almost makes me wish I got my M.A. biochemistry instead of psychology and law!

Ok, now for a layman's question! I was wondering about the point you made about retinoids causing irritation, thus possibly leading to inflammatory breakouts. Isn't Differin (I don't know about other retinoids) supposed to be anti-inflammatory?

Differin does exhibit some anti-inflammatory action, but it also acts as a retionid (stiumlates RAR-gamma and RXR-alpha...and increases cellular proliferation) and can induce inflammation (this is why you get red initially) in the process.....I'd say it's action as a retinoid outweighs it's action as an anti-inflammatory agent.

[abbylee]

Tretinoin, Tazaratene and adapalene are all RAR-agomnist, where isotretionin is actually an RXR-agonist.......

Hmm, I thought isotretinoin was also an RAR-agonist
"Drugs such as tretinoin and isotretinoin that affect both RAR and RXR receptors..."

Retinoic Acid Receptor Expression Altered by Isotretinoin Treatment

"Inhaled mid-dose isotretinoin caused up-regulation of lung tissue nuclear retinoic acid receptors (RARs) relative to vehicle-exposed mice, RARalpha (3.9-fold vehicle), RARbeta (3.3-fold), and RARgamma (3.7-fold), suggesting that these receptors may be useful biomarkers of retinoid activity in this system."
(link where this was quoted)

Abstract discussion of isotretinoin's upregulation of RARbeta

So I have been playing with this idea in my little head lately..

We all know that oral isotretinoin is comedolytic, with the amount of receptors it activates, doesn't it also mean it at least has some anti-aging effects as well??
If so, suppose if one could take an ultra-low dose (I've seen papers that suggest 2.5 mg/day was low enough not to accumulate toxicity associated with the typical mid to high dose, i'm too lazy to find them again right now... I've read somewhere they now have the 2.5mg capsules that are meant to be a long-term maintenance dose, supposedly for rosacea or resistant acne), wouldn't this method also be an effective anti-aging as well not just for face, but for all the skin of the body??
I mean, imagine getting the benefits of retinoids on areas you couldn't just simply slather the Retin-A on everyday?

I'm just wondering what you think about this. Right now I can't find a derm who dares to give me accutane.

And yes since tazaratene specifically targets RAR-beta and RAR-gamma, tretinoin is expresses RAR-alpha gene way better than tazaratene.....but I'm not too sure of it's signifigance since the RAR-gamma is way more prevalent on the epidermial cell's DNA.....and I'm not sure exactly of RAR-alpha's role in reversing photoaging......or acne treatment.......

Well, from what I could tell RAR alpha mediates the antiangiogenic effect of retinoids.
Angiogenesis(growth of new blood vessels) is needed for cancer and tumor growth. Angiogenic inhibitors are commonly used to halt and reverse cancer growths and reduce blood vessels. A topical antiangiogenic imiquimod has been shown to be effective for extreme angiogenically induced vascular lesions like port-wine stains...

I actually have a pet theory that the antiangiogenic effect of RAR-alpha
is why retinoids seem to help post-inflammatory REDNESS (NOT to be confused with post-inflammatory HYPERPIGMENTATION which is melanin-based, they're not the same thing as melanin can only produce a brown/black color). My theory is that because RAR-alpha expression inhibits VEGF, it causes capillary regression of the extra vessels that were created during wound infliction/healing process through apoptosis and such.
This may also explain why some people here seem to think neosporin works on red marks, as neomycin is also an anti-angiogenic.

no one ever compares 0.1% tretinoin to 0.1% tazaratene. It's always 0.025 or 0.05% tretinoin compared to 0.1% tazaratene, and most studies show that tretinoin is more effective at reducing photoaging........although one study (can't find it) found tazaratene to be more effective.

Study:Tazarotene 0.1% cream versus tretinoin 0.05% emollient cream
"CONCLUSIONS: Tazarotene 0.1% cream can offer superior efficacy over tretinoin 0.05% emollient cream in the treatment of facial photodamage, particularly with respect to the speed of improvement."

Which I don't think is a fair test at all. I thought it was pretty lame comparing .05% tretinoin to .1%taz

As for me personally I'm partial to plain old tretinoin. I guess cuz it's a natural retinoid......

Given that there are so much more to be known about the function of each individual receptor, I sorta feel that going with the old-fashioned unselective retinoid is probably the best bet. I mean, who knows what benefit you may losing out on when designing a narrower-range, more selective retinoid.

Thanks so much for letting me pick your brain, I happen to think retinoids are the neatest thing since sliced bread, haha. I just haven't had anyone else to talk/ask about retinoids to this extent.

[jonny_boy]

I'm scared, does the skin eventually become thicker? After use.

[LionQueen]

Retinoid fans ... I have decided to move this into the Prescriptions forum and pin it. It's too good to lose.

Many thanks to LabGirl and abbylee!

[LabGirl81]

Tretinoin, Tazaratene and adapalene are all RAR-agomnist, where isotretionin is actually an RXR-agonist.......

Hmm, I thought isotretinoin was also an RAR-agonist
"Drugs such as tretinoin and isotretinoin that affect both RAR and RXR receptors..."

Retinoic Acid Receptor Expression Altered by Isotretinoin Treatment

"Inhaled mid-dose isotretinoin caused up-regulation of lung tissue nuclear retinoic acid receptors (RARs) relative to vehicle-exposed mice, RARalpha (3.9-fold vehicle), RARbeta (3.3-fold), and RARgamma (3.7-fold), suggesting that these receptors may be useful biomarkers of retinoid activity in this system."
(link where this was quoted)

Abstract discussion of isotretinoin's upregulation of RARbeta

I didn't mean to say that isotretinoin doesn't act as an RAR-agonist at all. What I meant was that the other retinoids like tretinoin, tazaratene, and adapalene, only stimulate the RAR's not the RXR's. Isotretinoin effects both, the RAR's (alpha beta and gamma) which is where it's comedolytic activity comes from, but it also acts as and RXR ligand (and may stimilate the RAR's through stimulation of the RXR's since they exist as herterodimers on the DNA of epidermal and dermal cells).....This is where the professor says "you should look into it in your research"..........(it really means "I don't know.....go do a study and let a PhD take the credit for it" or he takes the idea and makes his grad students research it.....I hate PhD's sometimes.....but I'm going to be one of them soon)..........

So I have been playing with this idea in my little head lately..

We all know that oral isotretinoin is comedolytic, with the amount of receptors it activates, doesn't it also mean it at least has some anti-aging effects as well??
If so, suppose if one could take an ultra-low dose (I've seen papers that suggest 2.5 mg/day was low enough not to accumulate toxicity associated with the typical mid to high dose, i'm too lazy to find them again right now... I've read somewhere they now have the 2.5mg capsules that are meant to be a long-term maintenance dose, supposedly for rosacea or resistant acne), wouldn't this method also be an effective anti-aging as well not just for face, but for all the skin of the body??
I mean, imagine getting the benefits of retinoids on areas you couldn't just simply slather the Retin-A on everyday?

I'm just wondering what you think about this. Right now I can't find a derm who dares to give me accutane.

My understanding is that the retinoic acid (specifically all-trans retinoic acid) doesn't necessecarly effect aging only thorugh direct stimulation of the retinoid receptors (this may be responsible for the fibroblasts peoducing more extracellular matrix proteins), but rather a complex inhibition of enzymes that break down the collagen and elastin, like MMP's, collaganase, etc....I'm not sure if the cis form of retinoic acid can inhibit those enzymes and if they are inhibited by acting on other genes as antagonists or they directly inhibit the enzymes directly. There are some studies that demostrate that the cis-verion doesn't have the same effect on collagen production/protection, and paintens who take Accutane have an increased risk of scarring and keloid formation.....suggesting that isotretinoin actually disrupts collagen synthesis.........

As far as tretinoin goes......there may be a feedback mecanism involved between RAR/RXR stimulation and the inhibition of those enzymes.......Then fos and jun get involved as do PARA's.....I could be here typing all day...... there is so much infomation out there on the effect of retinoids on the aging process......and cis-13 retinoic acid does play a role.........but I had a rough night and my brain is a bit foggy now.........I have way more info on it at work..........So I'll add to this on Tuesday.............

And yes since tazaratene specifically targets RAR-beta and RAR-gamma, tretinoin is expresses RAR-alpha gene way better than tazaratene.....but I'm not too sure of it's signifigance since the RAR-gamma is way more prevalent on the epidermial cell's DNA.....and I'm not sure exactly of RAR-alpha's role in reversing photoaging......or acne treatment.......

Well, from what I could tell RAR alpha mediates the antiangiogenic effect of retinoids.


Angiogenesis(growth of new blood vessels) is needed for cancer and tumor growth. Angiogenic inhibitors are commonly used to halt and reverse cancer growths and reduce blood vessels. A topical antiangiogenic imiquimod has been shown to be effective for extreme angiogenically induced vascular lesions like port-wine stains...

I actually have a pet theory that the antiangiogenic effect of RAR-alpha
is why retinoids seem to help post-inflammatory REDNESS (NOT to be confused with post-inflammatory HYPERPIGMENTATION which is melanin-based, they're not the same thing as melanin can only produce a brown/black color). My theory is that because RAR-alpha expression inhibits VEGF, it causes capillary regression of the extra vessels that were created during wound infliction/healing process through apoptosis and such.
This may also explain why some people here seem to think neosporin works on red marks, as neomycin is also an anti-angiogenic.

I've heard that too.....in a some of the research about retinoids and cancer treatment (actually the original application for Accutane was actually in chemotherapy.......not acne treatment....it just so happened that skin clearing was a side effect.....it's still used to treat some cancers).......I'll look for the study.....bu tI'm not at work so It may have to wait until Tuesday........

Thanks so much for letting me pick your brain, I happen to think retinoids are the neatest thing since sliced bread, haha. I just haven't had anyone else to talk/ask about retinoids to this extent.

What do you do for a living? You know a lot more about retinoids than the common acne patient.........

I have some papers and info here you could take a look at.......

This is a great one....long but great....
Therapeutic Applications for Ligands of Retinoid Receptors

Here's one that has some good info on aging, not a paper, more like a discussion of papers:

Treating Photodamage Intracellularly

And this one had a good discuassion of different retinoids in acne treatment:
Mechanisms of the comedolytic and anti-inflammatory properties of topical retinoids

I'm scared, does the skin eventually become thicker? After use.

Yes it does, but only during use. It thickens up the underlying dermis (but thins the epidermis) which helps with shallow acne scars, wrinkes and photodamage.......this is actually a good thing........

When you stop using a retinoid your skin reverts back to pre-retinoid thickness.....although the filling in of acne scars and wrinkles is usually permanent.......

[DanMan1]

ok so this bsaically all means???

i just want to know one thing, is there any way that using tazorac on existing pimples makes that pimple more likely to scar, then if you had just left it alone?

Because ive been on tazorac for about 6 weeks, i do have less breakouts, but at the same time im looking at my previous breakouts from when i was on tazorac and they seem as if they have scarred or left indents in my skin...

Is this normal?

[abbylee]

I've seen references and studies to the efficacy of topical isotretinoin in regards to photodamage, Abstract of 36-week trial of .1% isotretinoin cream
and referenced here (uses of isotretinoin, oral and topical)

Now, if topical isotretinoin has this effect on photodamage, by whichever pathways of either gene expressions, enzyme inhibitions or other unknown actions, why shouldn't oral/systemic isotretinoin produce those same effects, albeit possibly by a much smaller magnitude with greater unwanted (and unrelated) side effects?
(My layman understanding of the difference between systemic absorption and topical application is that the effects from topical application would be limited to, but more concentrated to the local area applied.)

I've heard that too.....in a some of the research about retinoids and cancer treatment (actually the original application for Accutane was actually in chemotherapy.......not acne treatment....it just so happened that skin clearing was a side effect.....it's still used to treat some cancers).......I'll look for the study.....bu tI'm not at work so It may have to wait until Tuesday........

Yep
Treatment of advanced squamous cell carcinoma of the skin with isotretinoin

Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma..

and also with actinic keratosis (which is an angiogenic lesion as well), which tretinoin and tazarotene also have shown results for. I personally feel this is due to the anti-angiogenic effects induced by way of expressing RAR-alpha, a commonnality of most retinoids and perhaps helped by the antiproliferative effects mediated through RAR beta or gamma (still trying to figure out).

What do you do for a living? You know a lot more about retinoids than the common acne patient.........

I'm just an engineer, definitely a lay person when it comes to this!
I just have a tendency to research to death about things/issues that peak my interest..

I have some papers and info here you could take a look at.......

Thanks for the links! Funny how I haven't come across the Ingenta domain at all during my search sessions.

[Mrs Neuvo Wavo]

Hey, you guys who are talking about photodamage (AKA wrinkles, fine lines).

Tazorac .1% cream has recently been approved for photodamage, but what about the gel?

Would Tazorac .1% gel not have a similar effect? It's the same amount of the same active ingredient, right?




Thanks!

[jonny_boy]

Does differin help with the acne scars? I've ehard differin is somehow gentler than other retinoins, or different in some way.

[Giannina]

Thank you so much LabGirl, I just started using retin-a and already wanted to give up because I've developed little color-less bumps all over my face, you can really see them, but I can feel them and see them in different kinds of lights.... I'm not giving up now... I hope my IB does not last too long

[kuroda emi]

I have been using retin-a micro for about 5months and my whiteheads do not come out. They just sit at the surface.... I dont want to pop them because they get infected.(they are very difficult to remove) what should I do to get them out?