Adapalene, Tretinoin, Isotretinoin: What is the significance of retinoids in the treatment of rosacea?

Commonly used to treat acne, adapalene, tretinoin, and isotretinoin are part of the retinoid family, derivatives of vitamin A. Adapalene and tretinoin are topical retinoids : they come in the form of creams or gels to be applied directly to the skin. According to a study conducted by KATSAMBAS and his team, these two retinoids have similar efficacy on acne lesions. This was evaluated on 80 patients who applied a 0.1% adapalene gel or a 0.05% isotretinoin gel once a day for 12 weeks. Both treatments have shown to be effective in reducing papules and pustules, and the observed differences between them were not significant, although adapalene was slightly better tolerated.

To date, relatively few studies have been conducted on the effect of these retinoids on rosacea. However, research by ESTURK and his team has shown that adapalene may have some relevance in the case of papulopustular rosacea. Over a period of 55 days, 27 patients with papulopustular rosacea applied a 0.1% adapalene gel twice daily. At the end of the treatment, the volunteers saw their number of papules decrease from 6.89 ± 1.57 to 1.22 ± 0.97 and their number of pustules drop from 5.22 ± 0.97 to 0.78 ± 0.11. However, no effect was observed on erythema and telangiectasia. These results could explain why the use of topical retinoids in cases of papulopustular rosacea is not common: these treatments can only act on one aspect of the disease.

With regards to isotretinoin, it is an active substance consumed in the form of capsules. Highly effective in cases of acne, it also appears to have potential against papulopustular rosacea. This is at least what a study involving 28 patients with moderate papulopustular rosacea and 24 patients with a more severe form suggests. The former group received 20 mg of isotretinoin per week, while the latter took 40 mg per week. After four months, an improvement of more than 50% was observed in 60.7% of the individuals in the first group, while an improvement of more than 90% was noted in 62.5% of the patients in the second group. Furthermore, the researchers noted a general decrease in the patients' skin inflammation. It thus appears that low-dose isotretinoin could be a genuine aid in cases of papulopustular rosacea.

Adapalene, tretinoin, and isotretinoin have relatively similar mechanisms of action. Their primary interest lies in their ability to regulate the keratinisation process. To do this, retinoids interact with the nuclear receptors of retinoic acid (RAR) and the retinoid X receptor (RXR). This binding results in the formation of an activated RAR/RXR heterodimeric complex that behaves like a transcription factor capable of modulating cellular differentiation. Moreover, retinoids promote the removal of dead cells by decreasing the cohesion between the cells of the horny layer. By stimulating cellular renewal, retinoids thus accelerate the elimination of papules and pustules. Retinoids also have comedolytic properties, meaning they are capable of inducing the lysis of comedones, or their destruction.

Other interesting properties, this time specific to isotretinoin: this active ingredient can reduce the amount of matrix metalloproteinases in sebum, enzymes involved in the hyperproliferation of keratinocytes and in inflammation, and act at the level of the sebaceous glands. Indeed, isotretinoin can suppress the activity of the sebaceous glands and decrease their size, which reduces sebum synthesis. As a reminder, an overproduction of sebum increases the risk of skin pore obstruction and the occurrence of blemishes, particularly of the papule or pustule type.

Even though some of their properties are beneficial in the case of rosacea, retinoids are not prescribed as a first-line treatment, unlike metronidazole, an antibiotic. However, this does not mean they are never used. The dosage of these treatments depends on the severity of papulopustular rosacea. It should be noted that adapalene, tretinoin and isotretinoin are all prescription-only:

• Adapalene is presented in the form of a 0.1% gel to be applied once or twice daily on clean, dry skin.

• The retinoid, often measured at 0.025% usually comes in the form of a cream. It is also applied once or twice a day.

• Isotretinoin is administered in relatively low doses compared to its use as an anti-acne treatment. : 10 to 20 mg per day. It is generally reserved for severe or recurring forms of rosacea. Isotretinoin is often prescribed for a period of three months with regular reassessment.

As with any medication, the use of retinoids can be associated with side effects. Thus, adapalene, tretinoin, and isotretinoin can cause skin dryness, dermatitis, itching, peeling, and irritation. These substances can also increase the skin's sensitivity to the sun. Additional adverse effects are associated with isotretinoin, such as eye irritation. This results from a decrease in the production of meibum by the Meibomian glands, the equivalent of sebum for the skin. Some patients on isotretinoin also complain of joint and muscle pain.

Furthermore, oral retinoids can have a teratogenic effect. This is why they are contraindicated in pregnant or breastfeeding women. As for women of childbearing age, they are advised to use oral contraception, an intrauterine device or a progestin implant. Adapalene and tretinoin are also contraindicated in pregnant or breastfeeding women as it is not ruled out that they may cross the skin barrier and reach the bloodstream. However, they do not require strict contraception.

The prevention of various side effects of retinoids is achieved through a strict adherence to the instructions given by the healthcare professional.

• KATSAMBAS A. & al. Topical adapalene gel 0.1% vs. isotretinoin gel 0.05% in the treatment of acne vulgaris: a randomised open-label clinical trial. British Journal of Dermatology (2002).

• ESTURK E. & al. Adapalene vs. metronidazole gel for the treatment of rosacea. International Journal of Dermatology (2005).

• VIDAL: Active Ingredient: Tretinoin (2013).

• VIDAL: Active Ingredient: Adapalene (2013).

• VIDAL: Active Ingredient: Isotretinoin (2015).

• GALILI E. & al. Low-dose isotretinoin versus minocycline in the treatment of rosacea. Dermatologic therapy. (2021).