On July 8, 2016, Differin .1% Gel was approved by the FDA for over-the-counter sale. This is a big deal in the treatment and management of mild-to-moderate acne at home, as it is the only prescription strength retinoid available in every major drugstore (and Amazon!) in the US. Bonus: it’s cheaper than most people’s co-pays (including mine) used to be. Unfortunately, it’s still kind of a mystery on how to use it properly for your skin, as there is a ton of misinformation out there on the world wide web and the tube basically tells you to just use it every day after washing your face.
General Retinoid Tips
In my last post, I talked a bit about the different types of retinoids available as well as some brief usage tips. In short:
- Wear SPF 30-50 every day while using any topical retinoid, including Differin.
- Avoid the eye area (lid and thin undereye) as well as the lips and areas next to the nasal passages.
- Apply a pea-sized amount. Dr. Dray demonstrates this amount below. It is quite literally roughly the size of a pea.
- Apply after cleansing and moisturizing your skin, once your moisturizer has dried down. Don’t use overly occlusive moisturizers before Differin application, like heavy oils.
- Do not introduce new products right before or while using Differin. The reason for this is that if you begin to break out from the new product, it can be misinterpreted as breaking out from the Differin.
If you do best by watching videos, Dr. Dray has an excellent video on this process.
When you first start using Differin, you’ll want to ween your skin into it. While some skin is very tolerant and can withstand every night almost immediately, for more sensitive skin types this can be a bit more of a process.
- Tolerant Skin. If your skin is quite tolerant of topical therapies and rarely shows signs of irritation and peeling, feel free to begin applying a pea-sized amount of Differin once a day, at night, after cleansing and applied over your moisturizer as Dr. Dray demonstrates above. If your skin begins to feel tender or like it is burning, even after application of a bland moisturizer, cut down to usage every other day.
- Normal/Sensitive Skin. If your skin is sensitive or relatively normal, apply a pea-sized amount of Differin every other night (Monday, Wednesday, Friday, etc.), after cleansing and applied over your moisturizer, as demonstrated above. If your skin begins to feel tender, even after application of a bland moisturizer, cut down to every third night.
- Very Sensitive Skin. If your skin frequently shows signs of irritation to new products, particularly things like AHA, BHA, or vitamin C serums, or if you have rosacea, you may want to start by applying a pea-sized amount, over moisturized, clean skin every third night. This is where I started. After a few weeks, your skin should be able to tolerate every other night without excessive burning, tenderness, or peeling. If it does, cut back to every third night.
If your skin starts to feel a-okay with every third night or even every other night, try to bump up frequency. The goal is to be able to use it every night, but if your skin never feels comfortable at that point, that is okay – use it as frequently as you can. Remember that for everything, everyone’s skin is different and beautiful. Your mileage may vary.
What to Expect
- Some tenderness. My skin is more sensitive to being scratched, hot water, scruffy beards, and chemical filter sunscreens, particularly sunscreens with avobenzone.
- Micro-peels. Wearing makeup will be a challenge during the adjustment period (about two months) of using Differin. Your skin will look and feel smooth, but application of foundation will show very fine peeling all over the skin. This is okay and normal. If your skin is ever showing thick “sheets” of peeling from a retinoid, you should back down on usage. Your skin should never be shedding like a snake from a low percentage retinoid.
- Slightly more breakouts. My skin isn’t particularly prone to acne, though I do get small breakouts from time to time. Experiencing slightly more breakouts for the first few weeks is normal and fine. They should not be extremely aggressive or much worse than the breakouts you were experiencing before, particularly if your acne is mild.
- Dryness. My skin became slightly drier with the introduction of Differin. To compensate, I apply moisturizer more frequently throughout the day and on nights I am not using Differin, I apply my Rosehip oil and Jojoba oil, which I do not use on the nights I apply Differin (too occlusive).
Combining Therapies at Home
Referring back to my post I made previously once again, all retinoids (and frankly, all acne treatments) are best when used as a combination therapy all over the affected area (in this case, the face).
Benzoyl Peroxide (BP)
BP is not a new drug. First shown to be effective against acne in 1934 (though not explored as a treatment for acne until the 1960s when William Pace began to treat patients with a precipitated sulphur cream that contained BP), it is now often prescribed as a treatment for mild-to-moderate acne in conjunction with topical retinoids, particularly adapalene (Differin). The FDA has permitted use of benzoyl peroxide in OTC concentrations of 2.5-10%.
It has keratolytic, moderate comedolytic, and antibacterial properties, “which include the reduction of P. acnes and Staphylococcus aureus on skin.”¹ It is a largely vehicle-dependent drug, meaning that the formulation matters. One journal notes this: “Many formulations incorporate BP crystals that vary in size and do not necessarily fully dissolve completely or at the same rate. Larger crystals that are not capable of settling into the follicular ostia due to their size may randomly rest on the skin surface for more prolongued periods of time, thus producing scattered foci of ‘hot spots’ that may present as patches of cutaneous irritation.”¹
In addition, in three double-blind studies 2.5% BP gel was been found to be just as effective as 5% and 10% preparations with fewer side effects due to the lower concentration of the drug.
To combine with Differin at home, I recommend finding it in a wash, such as PanOxyl, or Differin’s brand “Daily Deep” Cleanser, which contains 5% Benzoyl Peroxide. Feel free to use BP in this form twice a week or every other night – whichever you and your skin are most comfortable with. This is a form of short-contact therapy (an effective way to use benzoyl peroxide with less side effects) that can also be done with gels or creams as well, especially if cleansers are too drying for your skin. In one study on short-contact therapy:
Short contact therapy utilizing a 2 minute skin contact time with BP 9.8% emollient foam used once daily over a 2 week duration was highly effective in reducing the quantity of P acnes organisms on the back and provided comparable colony count reduction to “leave on” therapy using BP 5.3% emollient foam. (Source)
For gels or creams, I sound like a broken record about this brand, but I do genuinely love Paula’s Choice BPO formulations. I have a small, travel-sized tube of their 5% formulation (which is not more efficacious than their 2.5%, but I had to test it!) and I love it. Unlike most BP formulations that crust up and sit as a film on the skin, the PC BP spreads easily and sinks in. Acne.org also has a pretty wonderful formulation of 2.5% BP that I used many years ago.
An additional note about BP is that is must be used all over to be effective as a combination treatment. While it is frequently billed a spot treatment product, BP really shines when it is allowed to treat acne before it becomes a problem, by blasting P. acnes and unseen microcomedones. This is why infrequent short-contact therapy is ideal, as the whole face can become quite sensitized when you’re new to Differin.
To use a cream or gel as short contact therapy, use it over your moisturizer, before washing your face. If this bothers you, wash your face very gently first, removing any makeup or sunscreen, and patting dry with a towel. Apply a thin layer all over, let sit for two minutes, and rinse away. Apply your moisturizer while skin is still damp to prevent TEWL (trans-epidermal water loss) and let dry completely before applying a thin layer of Differin (about 20 minutes, if you are using it on the same day you use Differin).
To use a benzoyl peroxide cleanser, follow the instructions on the bottle, after removing any sunscreen and makeup with an oil-cleanser. Apply your moisturizer immediately after, while skin is still damp, to prevent TEWL and let dry completely before applying a thin layer of Differin.
If your skin feels particularly raw or chapped from the introduction of BP, cut down on frequency, use it on the “rest” day that you aren’t using Differin, or remove it all together to let your skin heal before re-introducing. Please note that these instructions are not for use with Duac, a prescription topical combining clindamycin and benzoyl peroxide.
Salicylic Acid (BHA)
Salicylic acid (SA) is in a class of ingredients known as hydroxy acids, which I’ve referenced before on this blog. SA is a lipophilic (oil-friendly, meaning it is ideal for oilier skin types or in conjunction with oily products) compound and found in a plethora of products. While frequently considered as the oil-friendly version of AHA, it differs from AHAs in how it exfoliates the skin (desquamation, keratolytic) as well as it’s ability to prevent the formation of comedones (comedolytic). To quote a journal that overviews the many OTC treatments for acne:
[On AHA] At lower concentrations, AHA functions as an exfoliant, interrupting corneocyte adhesion in the upper SC by interfering with formation of ionic bonds. As a result, AHAs promote individual corneocyte desquamation and decrease corneocyte clumping, both of which lead to smoother skin texture and decreased visible scaling and flaking; a decrease in follicular hyperkeratois promotes resolution and prevents formation of AV lesions, especially comedones.
[On BHA/SA] Due to its desmolytic properties, salicylic acid promotes individual corneocyte desquamation, thus simulating natural exfoliation, and exerts moderate comedolytic activity. The desmolytic and comedolytic properties of salicylic acid are concentration-dependent. In fact, salicylic acid is not keratolytic. Rather, it exerts its effect on SC desquamation by breaking the bonds created by corneodesmosomes, also called the “rivets” or “staples” of the SC, which sustain the adherence between contiguous corneocytes. … The “physiological” desquamation provided by salicylic acid provides smoother texture and appearance to the skin and can give the illusion of decreased pore sizes.
The journal goes on to add: “Unfortunately, lower concentrations of salicylic acid may provide only a modest desmolytic [the process of breaking down carbon-to-carbon double bonds, such as between skin cells] activity, thus producing minimal therapeutic effects.” In shorter terms, your mileage may vary.
Over the counter formulations can appear in 0.05% to 5%, while higher concentrations of SA are reserved for prescriptions and chemical peels.
These features make it less ideal (and much less studied) than BP for combination therapy with Differin, especially in lower percentages or untested formulations, but for some it may prove useful or even better than BP.
To use it with Differin, look for unscented washes or leave-on applications and use on clean, moisturized skin, before applying Differin or every-other-night, when not using Differin. Many people like Stridex pads due to their wide availability, but the formulation can be irritating to some. My personal favorite is (again – I swear I am not sponsored, I just really love their active ingredients) Paula’s Choice 2% BHA Liquid (Extra Strength, if using her acne line). CosRX also has a couple products, if you prefer Asian beauty products.
For cleansers, there are fewer options. Clinique has one that is fairly pricey and Dr. Dray loves the classic orange, oil-free Neutrogena cleanser in the pump (not the bar!). Use after removing makeup, following the directions on the bottle, and immediately apply your moisturizer to prevent TEWL. Once dry, apply a thin layer of Differin.
The risks with BHA combination therapy are largely the same as BP – redness, dryness, tenderness. If you begin to feel any of these effects, cut down on the frequency of usage of BHA before cutting back on Differin. If needed, remove the BHA entirely until your skin heals.
Glycolic Acid, Lactic Acid, Mandelic Acid (AHAs)
AHAs or Alpha Hydroxy Acids are a group of products that include glycolic, lactic, mandelic, and fruit acids. While the exact mechanism of these ingredients is rather poorly understood, it is known that they exert some effect by thinning the stratum corneum (SC) – the upper most layer of the epidermis – as well as dispersing basal layer melanin and increasing collagen synthesis in higher concentrations.
As mentioned above, AHAs can be helpful for some conditions of hyperkeratinization where the epidermal thickening impairs the SC permeability, resulting in skin fissures (microfissuring and macrofissuring). The most extreme examples of macrofissuring is usually seen on hands or feet, where the skin may split or “fissure.” At low concentrations (below 8%), AHAs disrupt the corneocyte adhesion. To re-iterate from above:
At lower concentrations, AHA functions as an exfoliant, interrupting corneocyte adhesion in the upper SC by interfering with formation of ionic bonds. As a result, AHAs promote individual corneocyte desquamation and decrease corneocyte clumping, both of which lead to smoother skin texture and decreased visible scaling and flaking; a decrease in follicular hyperkeratois promotes resolution and prevents formation of AV lesions, especially comedones. Higher concentrations of AHAs (8-10%) can lead to both epidermolysis and thickening of the dermis.
For some, this action can prove helpful when used in conjunction with retinoids, which most frequently cause peeling and dryness.
To use with Differin, look for low percentages to start with (4-8%) and in leave-on products. Glycolic, while the most effective form of AHA, is quite irritating to some skin types due to it’s ability to work quickly. Mandelic and lactic acid are especially gentle forms of AHAs due to their larger molecules that penetrate slower and may allow some people to use AHAs when they otherwise wouldn’t be able to.
To start, add them to your routine on your off-nights and work up tolerability from there. Some people also find value in using short-contact therapy with AHAs – particularly glycolic – though this limits their efficacy, particularly with forms that penetrate much slower, such as mandelic acid.
Some popular brands of AHAs are Paula’s Choice (8% Glycolic Gel), Pixi Glow Tonic (note: this contains several plant extracts, which can be very irritating), Nip + Fab pads (also contain fragrance and plant extracts), The Ordinary (7% Glycolic Solution as well as 10% Lactic), Stratia (10% Mandelic), and as CosRX (Glycolic Acid).
It is not advised to use an AHA in a cleanser, as it is often not on the skin long enough to create noticeable differences.
Azelaic Acid (AzA)
A natural component of everyone’s skin, azelaic acid (AzA) is also a viable combination therapy, and there are increasingly more products available over-the-counter that contain this ingredient. While AzA is not frequently prescribed for acne, it can be very helpful for some skin types, particularly those that are very sensitive.
Unfortunately, there are no good studies around AzA when used with Differin, but there are studies around AzA in comparison to clindamycin and BP. Specifically, one study showed it to be as effective as 5% BP as well as 1% clindamycin in a randomized controlled study with 351 patients (BP gel) and 229 patients (clindamycin).
Azelaic acid 15% gel proved to be as effective as BPO and clindamycin with median % reduction of the inflamed lesion (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was well-tolerated, the side effects (local burning and irritation) were distinctly less than with BPO but more pronounced than with clindamycin. Despite these side effects, the treatment was well-accepted by the majority of patients. (Abstract, source)
AzA is also bacteriostatic, meaning that it can suppress the ability for bacteria to reproduce, which can help inflammation. It also suppresses hyper-proliferation of keratin, which is a factor in acne.
Unfortunately, it does take time to work and the side-effects when initially starting off can be aggravating. The most common side-effects are itching and stinging as well as mild dryness or peeling. This tends to resolve within 4 weeks. This can be difficult to push through. As someone who uses AzA, I can say that the initial itching upon application canfeel very intense and aggravating to deal with, though icing my skin helped me push through the worst days. Your mileage may vary.
To use AzA with Differin, I recommend trying to use it in your “off” nights, when not using Differin. If your skin tolerates this fine, feel free to use it every night.
There are a few trustworthy AzA topicals available over-the-counter in the US. Paula’s Choice makes one that contains 10% AzA and 2% BHA, which I reviewed. The Ordinary also makes a 10% AzA, though it feels quite powdery and silicone-y, which some people dislike. Garden of Wisdom is another option, especially for people sensitive to many ingredients. Their product is an 8% serum that receives a lot of love, though I have never used it myself.
Another option is Melazepam Cream (20% AzA). However, I want to mention that this formula contains two oils, which may inhibit some of it’s efficacy. Specifically, in a study involving 15% AzA, waiting until after moisturizing seemed to result in greater penetration of AzA in all moisturizers tested except for one, which contained an oil (macadamia nut oil). It was surmised that this was due to the occlusivity of the oil. Another potential issue is that Melazepam is made in Israel – something that may concern some consumers.
Topical sulfur is another option, though hard to find and frequently found in masks and other short-contact products. Sulfur exhibits antimicrobial properties and has been used for hundreds of years to treat AV as well as seborrheic dermatitis. It is frequently found in formulas up to 10% in combination with other products, particularly resorcinol, which is thought to be antibacterial, antifungal, and keratolytic.
Unfortunately, topical sulfur frequently causes mild irritation and sensitization, and has limited popularity.
Queen Helene’s Mint Julep Mask is a popular product with sulfur, as well as the ProActiv mask. I would advise anyone using the Mint Julep Mask in particular with Differin to be cautious, as the clay (kaolin) can be very drying to skin that is already dry and peeling, and the fragrance content is fairly high, making it a potentially extremely irritating choice of treatment.
Whatever you decide, it is important to be consistent and not treat either the Differin or the combination product as a spot treatment. While this is a popular way to avoid irritation and sensitization, it only treats the symptom, not the disease, which is to say that it is only treating the comedone once it has surfaced as a larger issue rather than treating the root of the problem: the formation of microcomedones.
Differin takes roughly twelve weeks to see full results, and products like AzA can take even longer. Whatever you decide, stick with it and listen to your skin by backomg off when it feels a bit more sensitive and moving up slowly in application when you feel you’re adjusting.