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Evidence For Retinoids

Recently, I came across some very interesting peer reviewed journal articles that contained good evidence about the effectiveness of topical retinoids. This appealed to me since I am currently using isotrex which is topical form of isotretinoin for my acne. I have been on oral isotretionoin (accutane) as well in the past with great results, so when my acne came back in a milder form, I decided it would make sense to treat that with the topical version.

The key message given in these reviewed articles is that retinoids work but you have to wait for results. Give it atleast 6 months before you decide if it is not for you, because any improvements in the beginning are very, very subtle. Also, expect the early irritancy and redness as this will occur if your skin is not already adapted to retinoids. A initial breakout may also occur but this is nothing to worry about as it's part of the way the drug works, increasing the cell turnover of your skin. Also, just leave your skin alone when on this treatment. You don't need to use any other harsh creams or treatments while on retinoids as it alone will do the job nicely. Just give it time.

I will post the journal article below. I think it's important to state that any results and statements of improvement and efficiency have been cited and this is from a peer reviewed article. This means it's from a reputable journal of science where facts have been referenced thoroughly and results are backed up from actual clinical trials. So basically it's not just any crap from an amateur website.

I hope anyone who is currently on a topical retinoid will find this useful and if they are going through a purging phase, then atleast it can be some consolation to them that there is hope and they will eventually have clearer skin. smile.png

Clinical Review: Topical Retinoids

ABSTRACT : With sensible patient education, the multitude of benefits that topical retinoid therapy can provide may be enjoyed. Hopefully, retinoid therapy will heighten awareness of the detrimental effects of sun exposure and motivate future generations to become "sun smart." Evidence-based medicine, current research, and case studies can arm practitioners with the resources and guidance to effectively provide current, innovating therapies for a variety of dermatologic conditions. With the strategic use of topical retinoids, several dermatologic conditions can be addressed concurrently.

Though often effective and beneficial, administration of systemic retinoids can be associatedwith disturbing, adverse reactions such as teratogenesis, pseudotumor cerebri, hepatotoxicity, elevated triglycerides, depression, alopecia, musculoskeletal symptoms, and altered night vision (Nurse Practitioner's Prescribing Reference [NPPR], 2003). With topical retinoids, the possibility of toxicity and side effects are minimized, while still contributing to a favorable localized efficacy (Verschoore, Bouclier, Czernielewski, & Hensby, 1993).

Topical retinoids can provide an extensive spectrum of benefits, addressing multiple dermatologic issues at once. Patient support and education are essential during retinoid therapy to ensure successful clinical outcomes (Baumann, 2003).

Topical retinoids (for example, tretinoin) and retinoid analogues (for example, adapalene and tazarotene) help normalize hyperkeratinization and have demonstrated significant anti-inflammatory effects. Retinoids are potent agents that can normalize abnormal growth and differentiation in keratinocytes (American Academy of Dermatology [AAD], 2003).

Topical retinoids have the potential of indirectly reducing the risk of antibiotic resistance by controlling and maintaining remission of inflammatory and noninflammatory lesions (Rizova, Pagnoni, Stoudemayer, Poncet, & Kligman, 2001).

Retinoids and retinoid analogues exert their activities by interacting with nuclear receptors (RARs [retinoic acid receptors] or RXRs [retinoic X receptors]) on cells and by activating genes that contain RARE (retinoic acid response elements) or RXRE (retinoic X response elements) in their promoters (Michel, Jombard, & Démarchez, 1998).

Retinoids promote a reversal of comedogenesis, leading to a reduction in microcomedos, which is a precursor of both inflammatory and noninflammatory acne lesions (Leyden, 2001). Retinoic acid (tretinoin) reverses thickening of the stratum corneum and the abnormal desquamation of keratinocytes, and has been a mainstay for the treatment of acne for more than 30 years (Verschoore et al., 1993). Topical retinoids reduce hyperkeratinization and allow enhanced penetration of adjunctive topical agents (Berson, 1999).

Clinicians should consider using a topical retinoid for first-line management for acne treatment (Wolf, 2002). It reverses thickening of the stratum corneum and the abnormal desquamation of keratinocytes (Verschoore et al., 1993). Acne therapy with retinoids can be frustrating in the beginning. An exacerbation of acne often occurs in the first 2 to 4 weeks of therapy as the follicular epithelium is loosening. Fortunately, by the end of the 2nd month, a significant improvement with the acne (Prystowsky, 2001) and remission of irritation is typically noted. To enhance compliance, the patient should be aware of these expected sequelae.

In patients with acne, sebum fills with pro-inflammatory lipids, creating a superb growth medium for bacteria (Millikan, 1999). Optimal therapy for inflammatory acne involves using topical retinoids or retinoid analogs combined with oral or topical antibacterials (Millikan, 2003).

Since acne can flare during the initial phase of retinoid therapy, it has been recommended that an antimicrobial agent be used for the first few months of treatment only. This strategy combines speed of resolution and maintenance of remission from inflammatory and noninflammatory lesions with minimal exposure to antibiotic agents (Rizova et al., 2001).

A 12-week double blind study was conducted to evaluate the efficacy and safety of tretinoin microsphere 0.1% gel with adapalene 0.1% gel in the treatment of acne. Both drugs demonstrated similar efficacy in the resolution of acne, but tretinoin microsphere gel may result in a faster action in reducing comedones, compared to adapalene (Nyirady et al., 2001).

Dr. Elise Olsen and associates (Olsen et al., 1997) discovered that reducing the frequency of tretinoin 0.05% cream from once daily to 3 times per week maintains, and in some cases, possibly further enhances reduction of photodamage. They also observed that cessation of tretinoin therapy for 6 months, however, resulted in some reversal of the beneficial effects seen after 48 weeks of treatment.

Though usually temporary, retinoid irritation can lead to noncompliance. Rather than resorting to using unregulated, unpredictable over-the-counter products, an alternative 0.02% low-dose, oil-in-water formulation of tretinoin is now available by prescription. A 52-week clinical trial concluded safety and efficacy of 0.02% tretinoin cream for treating photodamage. The most evident outcome, in this trial, revealed improvements in fine wrinkling. Results were maintained with long-term use. Discontinuation of therapy, however, showed a gradual beneficial loss. Mild skin irritation was common, nevertheless generally well tolerated (Nyirady, Lehmann, & Nordin, 2003).

Tazarotene was developed as an antipsoriatic drug in view of the therapeutic results of minimizing scaling and plaque thickness (Prystowsky, 2001). In psoriasis, tazarotene normalizes keratinocyte differentiation, reverses keratinocyte hyperproliferation, and has better anti-inflammatory effects compared to other topical retinoids (Guenther, 2002).

Application. Although package inserts often suggest using a pea-sized amount, our dermatology practice recommends applying 1 inch of the retinoid to the entire face on a nightly basis. This off-label application can be beneficial when addressing conditions such as acne, photodamage, intrinsic aging, actinic keratoses, lentigines, melasma, rosacea, and Darier's disease. By treating the entire face, efficacy can be enhanced, for the active ingredient works where it is placed. Spot treating should be avoided. This may reasonably decrease efficacy, and can lead to a blotchy appearance of the skin. Application should extend to the hairline and feather down along the jawline (Obagi & Bridenstine, 2000). Note: An inch is approximately the length of your distal finger (from the DIP to the tip).

The benefits of topical retinoids often outweigh the risks. It is important to educate patients about the possible risks, benefits, and reasonable expectations of retinoid therapy, and address common concerns before they fill their prescription(s). Stress the differences they will find in the package insert compared to the directions you are advising

To enhance compliance, it is important for the patient to expect a temporary irritation phase. This temporary irritation usually lasts about 6 weeks, depending on the amount of damaged skin present. A person who has extensive sun damage may peel beyond the usual 6 weeks. The peeling represents a repair of sun damage. Tingling or slight stinging upon application, temporary increased erythema, and intermittent peeling of skin is common. Acne can actually flare initially, because retinoids tend to reveal what's hiding under the surface. Reinforce that with prolonged use, acne and enlarged sebaceous glands can be minimized.

To help minimize the peeling during the day, advise patients to use the tips of their fingers in circular motions, particularly in areas of movements such as around the eyes and mouth. This works well in the shower. Advise patients to avoid picking, vigorous rubbing of the skin, or using abrasive body scrubbers or washcloths. The damaged skin will come off when ready. Pat the skin dry, rather than rubbing.

If burning, discomfort, itching, or excessive bothersome peeling occurs, recommend taking 1 to 2 nights off of the retinoid. Moisturize during the break and then resume the retinoid with only a broad-spectrum sunscreen (with a physical block such as zinc oxide or titanium dioxide as the key ingredient) serving as the moisturizer. Patients should avoid missing more than 2 days of the retinoid, to minimize the duration of the irritation phase. This irritation phase can be prolonged if using additional moisturizers (other than a sunscreen) or if more than 2 nights are missed

Sensitivity and pruritus can occur quickly. If patients find the prescribed regimen to be intolerable, encourage them to be patient and review the numerous benefits. Decreasing the frequency to every other day or even 3 times a week can be helpful. The strength can also be temporarily decreased until they can tolerate the addition of a retinoid. A gradual increase in the strength and frequency can then be achieved.

At most, topical retinoids, including tretinoin, adapalene, and tazarotene, deliver minuscule amounts of active ingredient into the circulation. Definitive links to systemic toxicity in humans are practically nonexistent.

With sensible patient education, the multitude of benefits that topical retinoid therapy can provide may be enjoyed. Evidence-based medicine, current research, and case studies can arm practitioners with the resources and guidance to effectively provide current, innovating therapies for a variety of dermatologic conditions. With the strategic use of topical retinoids, several dermatologic conditions can be addressed concurrently.

Topical retinoids represent a mainstay of acne treatment because they expel mature comedones, reduce microcomedone formation, and exert anti-inflammatory effects. The first-generation retinoid tretinoin (all-trans retinoic acid) and the synthetic third-generation polyaromatics adapalene and tazarotene are approved for acne treatment by the US FDA, whereas topical tretinoin, isotretinoin (13-cis retinoic acid), and adapalene are accredited in Canada and Europe.

Topical retinoids have a favorable safety profile distinct from the toxicity of their systemic counterparts. Local adverse effects, including erythema, dryness, itching, and stinging, occur frequently during the early treatment phase. Their impact varies with the vehicle formation, skin type, frequency and mode of application, use of moisturizers, and environmental factors such as sun exposure or temperature. The broad anti-acne activity and safety profile of topical retinoids justifies their use as first-line treatment in most types of non-inflammatory and inflammatory acne. They are also suitable as long-term medications, with no risk of inducing bacterial resistance, for maintenance of remission after cessation of initial combination therapy.

Hypercornification is an early feature of acne and precedes inflammation. It is associated with ductal hyperproliferation and there are many controlling factors such as androgens, retinoids and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself.


Rolewski, S. L. (2003). Clinical review: topical retinoids. Dermatology nursing/Dermatology Nurses' Association, 15(5), 447.

Thielitz, A., & Gollnick, H. (2008). Topical retinoids in acne vulgaris. American journal of clinical dermatology, 9(6), 369-381.

Cunliffe, W. J., Holland, D. B., Clark, S. M., & Stables, G. I. (2000). Comedogenesis: some new aetiological, clinical and therapeutic strategies. British Journal of Dermatology, 142(6), 1084-1091.


Recommended Comments

Wow. I feel so relieved that my use of tretinoin really is working. I love the science behind it. I love learning about how medications work and how to defeat acne. I have been using retin-a for 20 years with great results. I use benzaclin too and I take antibiotics, so, right now I have zero acne. But I plan to continue all my medications to remain pimple free. Awesome article though I have to admit I got lost a few times in the scientific vernacular. lol good show!

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Hey thank you,

Yep the article is very scientific, but the information is very encouraging and interesting for us all who use retinoids. It definitely opened my eyes as I wanted to know how it was helping me and some kind of proof to be honest. I suffered for years with acne believing there is nothing I can do to control it, but by educating myself about the pathogenesis of acne and treatments, I have managed to control it.

It's really good to hear the retin-a has worked for you and you have been able to use it in the long term. This means you haven't just got the acne under control but you will continue to reap other benefits like smoother and softer skin in the long term.

In the actual article there was actually information on more uses for retinoids such as fighting psoriasis, getting rid of melasma, actinic keratosis and even reversing signs of aging and sun damage. I cut these bits out of the article as it would of been ten times more longer lol, but it just goes to show there are so many other benefits of topical retinoids.

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