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

Adapalene, tretinoin, and isotretinoin have relatively similar mechanisms of action. Their primary interest lies in their ability to regulate the keratinization 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 stratum corneum. 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 for rosacea, retinoids are not the first line of 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's worth noting 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.

• Tretinoin, 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 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 dry skin, 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. That's why they are contraindicated in pregnant or breastfeeding women. As for women of childbearing age, they are asked 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 provided by the healthcare professional.