25. Topical Retinoids - The Cornerstone of most Treatment Regimens

Doctor Jacob here today, and this episode is talking about topical retinoids - the cornerstone of most treatment regimens.

Topical retinoids are key to the successful treatment of acne topically in almost all patients. In fact, pretty much everyone with acne, unless the patient is pregnant, should be on a topical retinoid. There a couple exceptions, for example people with really bad eczema, and we'll get to them later; also patients who are taking the oral medicine called isotretinoin, formally known as Accutane. Those patients don't need the retinoid - they're too drying, because we're already giving them a systemic retinoid. Anyway, the basic gist of it is almost everybody with acne needs a retinoid topically, assuming we're not in one of those very few special groups.

So what are retinoids? Retinoids are vitamin A and their derivatives, things in the vitamin A family. The first retinoid to be used topically for the treatment of acne was all-trans retinoic acid, which is also given the drug name tretinoin, known by its brand name as Retin-A. There are many Retin-A products available on the market today, and there are spin-offs into other drugs and other formulations, and we're going to cover all of them. But suffice it to say, these work by drying up your oil glands. They decrease the oil production from the oil glands.

So how does that work? First off the comedone, which is the salient feature of acne, the clogged pore - that can't form if there is not enough oil production going on, so that's one of the ways in which it works, decreasing oil production. Is it antibacterial? Not directly, but the bacteria feed off of the oil, so by reducing their food, in a way, it can reduce the counts of bacteria on the skin, but it's not directly an antibacterial agent.

Retinoids also work by increasing the rate of turnover of skin cells, meaning it hastens their transition from the bottom layer of the skin all the way through the top layer of the skin, at which point the skin cell is sloughed off into the environment. It just works also the same down the pores as it does on the surface of the skin, it increases the turnover of skin cells, so that actually helps unclog the pores.

With retinoids, they also carry an FDA approval and indication for minimizing the appearance of fine lines and wrinkles, so although many patients with acne aren't worried about that, a lot of people are happy to know that if they're using their retinoid long-term on a daily basis not only will it help keep their skin clear, but also minimize the appearance as we age of fine lines and wrinkles.

So what are the different types of retinoids and where can we find them? Many of them are prescription medications, but one is called retinol, which is over-the-counter. For example, there is retinol sold as ROC, which is retinol 0.1% - that's too weak for the treatment of acne. It may do something for wrinkling, but nothing for acne. To start getting into usable concentrations for acne for retinol, we want to see something like retinol 0.25% or higher. On my website you can find retinol products which are available without a prescription, over-the-counter, for sale.

In general, with most retinol treatments we want to start with a relatively low strength and work your way up to a higher strength product, otherwise there can be initial worsening of acne, as well as too much peeling if the skin is not used to the product. That can be a couple weeks before the skin kind of adjusts and gets a little bit used to the product.

If the skin is drier, the patient may not be able to tolerate a higher strength retinoid and may be stuck using the weakest strength forever, or even the weakest strength at every other night, which is fine. If the skin is already a little bit drier, it's going to be that much easier for the retinoid to work. For example, a patient with dry skin or eczema-prone skin may be satisfied and having a good result with a retinol 0.25% treatment, which is roughly equivalent to a tretinoin 0.025% treatment.

Let's talk about retinol versus tretinoin. There's about a 10x difference in effective concentrations being equivalent. For example, retinol 1% would be equal to tretinoin 0.1% gel, for example. So with that regard, tretinoin is a prescription medication, also known as Retin-A, and there's a microsphere formulation of it which enhances the penetration a little bit, makes it a little bit more tolerable, called Retin-A Micro, or tretinoin microsphere is the generic for that. Depending on the patient's insurance, the cost may be similar between the two preparations. If given the choice, I usually prefer tretinoin microsphere over plain old tretinoin gel or cream.

With the tretinoins, the cream formulation does contain isopropyl myristate, which if you go back and look at our episodes earlier in the series, you'll realize that that actually is comedogenic, meaning it can clog pores, cause acne, so I usually try to avoid for my acne patients the plain tretinoin cream formulations. That doesn't apply to the tretinoin gels or the tretinoin microspheres; just the plain tretinoin creams have the formulation with isopropyl myristate.

Next there is adapalene. Adapalene is another type of retinoid, it's a prescription medicine and it's a derivative of tretinoin, chemically related, but it is interestingly stable in combination with light and stable in combination with benzoyl peroxide, so it can be used in the day time, whereas tretinoin and retinol are usually used in the night time. With adapalene, you can certainly use it in the day time. You can even use it in combination with benzoyl peroxide applied at the same time, or formulated in a combination product. We'll talk more about these combination products later on. ***update: as of Jan 2017,
Differin (adapalene) 0.1% gel is OTC.

Finally, there is tazarotene, which is the newest retinoid to be on the market. It's also known by the brand names Tazorac gel or Tazorac cream, or Fabior foam. There actually is an indication for that drug as well for topical treatment psoriasis, because it helps increase the turnover of cells and it actually thins out psoriatic plaques or psoriasis plaques.

In any case, the best way to pick a topical retinoid is to figure out how dry or oily your skin is. If your skin is really dry, you start with a weaker strength one; if your skin is really oily, you start more in the middle or even middle to high. Also, whatever you can get your hands on in terms of cost, you can also dilute things. If you have a more concentrated one than you need, you mix it with a drop of moisturizer, 50/50 and you dilute it. With a moisturizer like daily moisturizing lotion you can easily dilute most of these retinoids and they won't be so irritating.

Mostly, retinoids are used for facial acne. If the acne is really deep, cystic acne, you may be better off putting the patient straight forward onto Accutane or isotretinoin. It won't fix the hormonal causes of acne for women who have hormonal acne, but it does help not only the acne, but also the post-inflammatory erythema and post-inflammatory hyperpigmentations or the blemishes. Not scars, but the blemishes, the color changes or redness that comes after acne - this helps them get a little bit better, especially if you're using it regularly.

Retinoids are not spot treatments, they are field treatments, so you don't treat an individual pimple, you treat the whole zone that's prone to acne. Mostly it's used on the face, but can be used on the neck, chest, shoulders or back. The thing with using it off the face is that the face tends to be more tolerant and off the face tends to be a little more sensitive, so you have to dilute it with some moisturizer or use it less frequently - every other day. That's the main message I have for my patients, especially when they're using it off the face. Start slow, dilute it, thin it out and use it every other day, or even every third day at first, for a week or two, until your skin gets used to it. As you can, know you can tolerate it without increased burning or redness or dryness, then it's okay to bump up the frequency of use and to go back to full strength of product, undiluted.

One thing that patients should be familiar with when using topical retinoids is how long it takes actually to see results. Usually I tell patients it takes about four to six weeks of use of the stuff before you see results, and in fact during the first week or two you can have an initial worsening; it's kind of bringing everything to the surface. Remember I said that the retinoids can enhance the proliferation of the cells in the skin, so that it hastens the transit from the bottom layer to the top layer of skin, and what that does is it tends to unclog the pores, bring things to the surface, and you can see there is actually an initial worsening of the acne during the first week or two. But I tell my patients to hang on, they'll get through it. It's not a horrible worsening. The same type of initial worsening is actually seen frequently during the first month with Accutane, also known as isotretinoin, which is an oral retinoid for acne; so the same thing happens topically.

As a reminder, we don't want to mix any of these retinoids, except for adapalene - which goes by the name Differin - with benzoyl peroxide, because those retinoids: tretinoin and tazarotene are easily denatured or destroyed by benzoyl peroxide, whereas adapalene (Differin) is more stable.

Finally, to wrap things up with the topical retinoids, who shouldn't use them? I mentioned pregnancy. With regards to pregnancy, they haven't been studied adequately to recommend them, even though tretinoin is all-trans retinoic acid, a form of vitamin A already found in the body. It can't be recommended yet as a drug, it hasn't been studied adequately and I'm not sure it ever will be, because of Accutane's effects on the fetus.

With regard to adapalene, we also can't recommend that in pregnancy, and tazarotene especially not, it's category X, meaning that there is evidence of fetal harm with tazarotene. With regard to breastfeeding, I'm fine with my patients using topical retinoids. Although the label doesn't recommend it, something like tretinoin or adapalene is fine with me. The problem with babies or fetuses and retinoids is that the retinoid messes with embryogenesis and organogenesis, meaning the formation of the embryo and the organs. Once the baby is delivered, the organs are formed, so a little extra vitamin A on the mother's skin is not going to hurt the baby, in my opinion.

I wouldn't recommend Tazorac or adapalene, I would stick with tretinoin, which is a naturally occurring form of vitamin A. Or with retinol, which is also a naturally occurring form of vitamin A.

The next thing to keep in mind with who else should not be using retinoids - patients on Accutane, because they get too dry. You don't want to double up on oral plus a topical retinoid. The oral, which is Accutane, will suffice.

And finally, patients with very severe atopic dermatitis (eczema) which can involve much of the body surface area, especially on the face - these patients are few and far between, but patients with really bad atopic dermatitis often can't tolerate even the lowest strength of the retinoid, unless their atopic dermatitis is better controlled. Luckily, there are many options to treat the atopic dermatitis now and they seem to be coming on the market in the future.

One final word of caution: for patients who have skin of color, so I'm talking dark skin, African descent, Latino or Latina, or dark skined patients of East-Indian descent, then we have to especially caution patients on starting at a very, very mild strength of retinoid, and working our way up the retinoid treatment ladder to a stronger strength. This is extremely important. Once in a while I see a patient who is treated by usually either a pediatrician or a primary care physician in family practice, or occasionally internal medicine, a patient of dark skin who is treated right off the bat with a very strong retinoid, without working their way up; straight to a strong retinoid. This can sometimes lead to an irritant contact dermatitis, which is almost like a chemical burn, if the patient wasn't very oily to start with. If the patient had dry skin, dark skin, and had that chemical burn phenomenon, then it can leave a lot of post-inflammatory hyperpigmentation. Those are dark blemishes which can stay behind for months and in rare cases even years before they're cleared out. So patients with dark skin - always start at the lowest strength retinoid every other day and slowly work your way up, unless you know have a ton of oil on your skin.

And finally, for our patients with lighter skin tones, while you're using a retinoid, be sure to use sunscreens if you're out for any significant period of time. Use sunscreens or hats, because you can sunburn a little bit more easily if your skin is a little bit thinner, because the retinoid, as we talked, hastens the transit time from the bottom to the top, increases proliferation of the skin cells, so your skin actually gets a tiny bit thinner, less protection, it can sunburn a bit more easily. So if you're in a sunny place, be sure to wear your sunscreen and hat.

That's it for today's episode. Be sure to check out the website for the retinoid treatment ladder, so you can see all the retinoids laid out at their relative concentrations and strengths, to see which ones are weaker, which ones are medium and which ones are stronger.

I'm doctor Jacob, we'll see you next time.