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TreatmentFoundationalBNF 13.6

Topical retinoids

TR · tretinoin · adapalene · tazarotene · trifarotene · isotretinoin (topical)

Topical retinoids are vitamin-A derivatives that bind nuclear retinoic-acid receptors (RAR-α, β, γ) and retinoid X receptors (RXR), modulating gene transcription for keratinisation, differentiation and inflammation. UK-licensed agents include tretinoin (Retin-A), adapalene (Differin), tazarotene (Zorac) and trifarotene (Aklief). Indications span acne vulgaris, photoaging, actinic keratosis, plaque psoriasis, hyperpigmentation and lentigo maligna adjunct. Skin-oncology relevance: field cancerisation strategy, photoaging management, post-Mohs scarring optimisation and EGFRi / chemotherapy hand-foot care.

CurrentLast reviewed 16 May 2026

Mechanism

  • Bind nuclear retinoic-acid receptors (RAR-α, β, γ) and retinoid X receptors (RXR).
  • Effects:
    • Promote epidermal cell turnover and differentiation.
    • Normalise follicular hyperkeratinisation (anti-comedonal).
    • Anti-inflammatory.
    • Stimulate collagen synthesis; reverse some photoaging.
    • Inhibit melanosome transfer → reduce hyperpigmentation.
    • Apoptosis / differentiation in dysplastic keratinocytes — rationale for AK / field cancerisation.
  • Selectivity: adapalene and trifarotene more RAR-γ-selective (skin) → better tolerated; tretinoin and tazarotene pan-RAR.

Agents

AgentReceptorUK licensed indications
Tretinoin 0.01-0.1%Pan-RARAcne, photoaging (Retin-A, Retin-A Micro).
Adapalene 0.1-0.3%RAR-β/γAcne (Differin; Epiduo with BPO).
Tazarotene 0.05-0.1%RAR-β/γPlaque psoriasis (Zorac), acne.
Trifarotene 0.005%RAR-γTruncal + facial acne (Aklief).
Topical isotretinoin 0.05%Pan-RARAcne (Isotrex, Isotrexin); UK availability limited.

Indications

  • Acne vulgaris: cornerstone topical therapy per NICE NG198.
  • Plaque psoriasis: tazarotene; localised plaques.
  • Photoaging: tretinoin for fine lines, lentigines, texture; over months-years.
  • Actinic keratosis / field cancerisation: tretinoin / adapalene as adjunct; less robust evidence than 5-FU / imiquimod / MAL-PDT / tirbanibulin.
  • Hyperpigmentation: melasma, post-inflammatory hyperpigmentation; triple combination (tretinoin + hydroquinone + fluocinolone).
  • Verrucae: adjunct.
  • Off-label: lentigo maligna adjunct, post-Mohs scarring, EGFRi / chemotherapy hand-foot care, paediatric ichthyosis.

Safety considerations

  • Local effects ("retinoid dermatitis"):
    • Erythema, scaling, dryness, burning, stinging — peak weeks 2-4.
    • "Retinoid reaction" expected and usually self-limits with continued use; ramp-up regimens reduce.
    • Photosensitivity → use at night; daily SPF 30-50.
    • Post-inflammatory hyperpigmentation in Fitzpatrick III-VI.
  • Pregnancy: contraindicated (Category C/D). Reliable contraception required throughout treatment.
  • Breastfeeding: avoid; minimal systemic absorption but precaution.
  • Combination:
    • Benzoyl peroxide may oxidise tretinoin — use sequentially (BPO morning, tretinoin night) or use micronised formulations (Epiduo: adapalene + BPO).
    • Avoid alpha-hydroxy acids in same application.
    • Caution combining with topical 5-FU or imiquimod — additive irritation.
  • Counsel: gradual introduction (alternate nights); minimise amount (pea-size); avoid eyes / mucosa; allow 2-3 months for acne / 6+ months for photoaging benefit.

Practical use

  • Start with low concentration; alternate nights → nightly use as tolerated.
  • Apply at bedtime to dry skin; pea-size for whole face.
  • Daily SPF 30-50 mineral sunscreen mandatory.
  • Counsel on retinoid reaction (transient flare in week 2-4; do not stop).
  • Pregnancy avoidance crucial; document discussion.
  • Combine with bland emollient if dryness; transition to micronised formulations if intolerant.
  • Field cancerisation: tretinoin nightly for months as maintenance after 5-FU / imiquimod / MAL-PDT clearance; adjunctive — not standalone.
  • Counsel about avoiding waxing, dermabrasion, peels, laser during retinoid use.

References

  1. Roos TC, Jugert FK, Merk HF, Bickers DR. Retinoid metabolism in the skin. Pharmacol Rev. 1998;50:315-333.
  2. Kang S. The mechanism of action of topical retinoids. Cutis. 2005;75(2 Suppl):10-13.
  3. Mukherjee S et al. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1:327-348.
  4. NICE NG198. Acne vulgaris: management. London: NICE; 2021 (last updated 30 April 2026).
  5. Tan J et al. Adapalene and benzoyl peroxide combination gel in the treatment of acne vulgaris. J Am Acad Dermatol. 2018;78:1056-1063.

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