Topical retinoids

What are topical retinoids?

Topical retinoids are medications derived from vitamin A formulated as a cream, lotion, foam, emulsion, or gel.

What are topical retinoids used for?

Topical adapalene, isotretinoin, tretinoin, trifarotene

• Acne vulgaris and its complications

Applied to the face once daily at bedtime, topical retinoids such as adapalene, isotretinoin, tretinoin (retinoic acid), and trifarotene can help mild to moderately severe acne. They are effective first-line treatment for comedonal and inflammatory acne, but are not recommended as monotherapy for severe acne, especially if there are pustules with deep nodules and cysts. It may take 12 weeks or longer before improvement is seen.

Topical retinoids may reduce the severity of existing scarring and subsequent acne scarring.

Inflammatory dermatoses including acne vulgaris may resolve with postinflammatory hyperpigmentation particularly in skin of colour. Topical retinoids are useful to treat post-inflammatory hyperpigmentation as they inhibit melanosome transfer and facilitate melanin dispersal. They are particularly recommended for the treatment of acne in skin of colour.

• Photodamage and photoageing

If used longterm (>6 months) topical tretinoin can reduce freckling, solar lentigines, fine wrinkling, solar comedones, sun-induced skin fragility, and actinic keratoses [see also Skin ageing].

• Melasma

Topical tretinoin may be combined with other active ingredients in skin bleaching cream to treat melasma.

• Darier disease and others

Topical isotretinoin, tretinoin, and adapelene have been used for localised Darier disease, reporting significant clinical improvement in symptoms. Topical retinoids may be used to treat many dermatoses - see the list of page links below (On DermNet NZ).

Other topical retinoids used in dermatology

Alitretinoin

• Kaposi sarcoma — FDA approved for localised HIV-related disease

Bexarotene

• Cutaneous T-cell lymphoma

Tazarotene

• Facial acne
• Postinflammatory hyperpigmentation in dark skin
• Chronic plaque psoriasis
• Photodamage

Trifarotene

• Congenital ichthyosis including recessive X-linked ichthyosis, epidermolytic ichthyosis, and erythrokeratoderma variabilis.
• Trifarotene is approved for the treatment of lamellar ichthyosis by the FDA in the US.

Localised Kaposi sarcoma

Photodamage and fine wrinkling

X-linked recessive ichthyosis

What are the contraindications and precautions with topical retinoids?

Contraindications

• Hypersensitivity or allergy to retinoids or excipients
• Some topical retinoids are contraindicated for use in pregnancy

Precautions

• Topical retinoids can make eczema worse because of their drying effect
• Topical retinoids can cause photosensitivity
• Percutaneous absorption of topical retinoids is limited. However, women of childbearing age must use effective contraception due to the teratogenic effects of retinoids.
• Topical retinoids are generally not recommended for use by young children - varies between countries and specific product

Tell me more about topical retinoids.

Retinoids act at a cellular level. They activate genes involved in the physiology of keratinocytes by binding to specific nuclear receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR).

Topical retinoids such as retinol and retinaldehyde are commonly added to cosmetics.

Prescribed topical retinoids include adapalene, alitretinoin, tazarotene, tretinoin, and trifarotene. They come in a variety of formulations. Gels are the least cosmetically noticeable; creams are the least irritating. Applying them at night (or just before sleep) mean they are less noticeable when treating the face. The regular application of a sunblock/moisturiser combination during the day will protect against the sun sensitivity and dryness.

Retinoids can be classified as:

• First generation
  • Isotretinoin, tretinoin, and alitretinoin are modifications of natural retinoids which do not act selectively
• Second generation
  • Acitretin is an oral retinoid in which a benzene ring is replaced by a cyclohexane ring
• Third generation
  • Adapalene, tazarotene, and bexarotene are polyaromatic retinoids with selective activity for the retinoid receptors
• Fourth generation
  • Trifarotene is highly specific for the skin retinoid (RAR-γ) receptor

What are the benefits of topical retinoids?

• Favourable safety profile and avoid the systemic side effects of oral retinoids
• Effective for mild comedonal and mild papulopustular acne
• Can be used for ongoing treatment of acne after a course of oral isotretinoin
• Can reverse some of the features of photoageing, photodamage, and improve postinflammatory hyperpigmentation
• Can enhance the efficacy of other topical medications applied such as 5-fluorouracil cream for actinic keratoses or intraepidermal carcinoma, or hydroquinone in bleaching cream.

What are the disadvantages of topical retinoids?

• Not suitable to treat large areas of the body such as extensive acne over the back or chest
• Can be irritating if applied close to the eyes or lips. Adapalene is the least irritating topical retinoid, and tretinoin the most.

What are the side effects and risks of topical retinoids?

• Retinoid dermatitis (erythema, peeling, dry skin)
• Irritant contact dermatitis
• Sun sensitivity
• Allergic contact dermatitis (rare)
• Teratogenic — potential risk in pregnancy particularly with widespread tazarotene use (pregnancy category X in US)