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Effet rétinol hyperpigmentation.

Retinol, a molecule that combats brown spots?

Although harmless, brown spots can be a source of discomfort and frustration for many people seeking an even complexion. Retinol, however, presents itself as one of the effective options for diminishing the appearance of these stubborn marks. Here, we explain how retinoids work against this dermatological condition.

What are brown spots?

Pigmentation disorders , such as post-inflammatory hyperpigmentation, actinic lentigines, or melasma, are characterized by irregular spots ranging from light brown to gray-brown, which can appear anywhere on the body but are most commonly found on the face and hands. This is the result of changes in various aspects of pigmentation, including an increased production and accumulation of melanin or irregular clumping of melanin in the epidermis or dermis .

While they can persist for months or even years, the precise cause of pigment spots remains unknown. However, intense exposure to UV rays, hormones (endogenous and exogenous), inflammatory diseases (acne, contact dermatitis, psoriasis, folliculitis, impetigo, etc.), familial predisposition, photosensitizing medications, and endocrine dysfunctions have been identified as pathophysiological factors that could be involved in the pathogenesis of this common skin condition.

Using retinol to lighten pigmentation spots?

Generally challenging to treat, retinoids topicals (tretinoin, adapalene, tazarotene, etc.) apparently constitute a favorable option for lightening hyperpigmented lesions, without reducing the normal color of the skin. Indeed, there are several pieces of evidence from clinical trials in favor of the continuous use of topical retinoids alone or in conjunction with other topical depigmenting agents (azelaic acid, hydroquinone, etc.) in the treatment of pigmentation disorders. The results of these studies have shown effectiveness on the severity of the disease, the intensity of pigmentation, and the surface area of the lesions.

ReferencesParticipantsTreatmentsResults
VOORHEES J. J. & others. (1993) -19 patients exhibiting melasma0.1% retinoic acid cream applied once daily for 40 weeks Clinical lightening of melasma in 68% of patients after 24 weeks of treatment
VOORHEES J. J. & others. (1993) -24 adults with dark phototypes exhibiting moderate to severe hyperpigmented lesions due to acne, shaving irritation, eczema, ingrown hairs, and folliculitis0.1% Tretinoin cream for 40 weeks92% of patients showed a significantly greater lightening with tretinoin than with the control starting from week 4
BULGER L. & al. (2000)800 individuals with moderate to severe photo-damaged skin0.1% Isotretinoin cream applied once daily for 36 weeksSignificant reduction in facial, forearm, and hand pigmentation after just 12 weeks of treatment, increasing throughout the 36-week treatment period
GIBSON J. R. & others. (2001) -349 subjects exhibiting facial photodamageTazarotene cream at various concentrations (0.1%, 0.05%, 0.025%, and 0.01%) for 24 weeksReduction in melanin content in the epidermis over the course of 24 weeks of treatment
GIBSON J. R. & al. (2002) -542 patients exhibiting photodamage to the faceTazarotene cream at various concentrations (0.1%, 0.05%, 0.025%, and 0.01%) applied once daily for 24 weeks, followed by a 28-week open-label extensionClinical improvement of hyperpigmentation at week 24, continuing with the ongoing treatment
PARSAD D. & al. (2002)31 Indian female patients (with skin phototype IV) diagnosed with clinical epidermal facial melasma0.05% Retinoic Acid (Tretinoin) Cream versus 0.1% Adapalene Gel over a 14-week periodA 37% reduction in the area and severity of melasma was observed in the retinoic acid group, compared to a 41% reduction in the adapalene group.
GRIFFITHS C. E. M. & et al. (2003)90 Caucasian patients aged 18 to 85 years old suffering from age spotsAdapalene gel at 0.1% or 0.3% once daily for 4 weeks, followed by twice-daily applications, if tolerated, up to 9 monthsLightening of senile lentigines was observed in 57% and 59% of patients treated with 0.1% and 0.3% adapalene, respectively, compared to patients treated with the control gel after 9 months of treatment
CALLENDER V. & et al. (2006)74 patients aged over 12 years, with skin phototypes III to VI, suffering from post-inflammatory hyperpigmentation caused by acne0.1% Tazarotene cream applied once daily for 18 weeksSignificant reduction in the overall severity of hyperpigmentation, intensity, and surface area of hyperpigmented lesions after 18 weeks
LE GALL N. & et al. (2010)180 patients over the age of 12 with post-inflammatory hyperpigmentation0.1% Tazarotene cream versus 0.3% Adapalene gel once daily for 16 weeks of treatmentSignificantly greater reduction of hyperpigmented lesions with tazarotene cream than with adapalene gel
TAYLOR S. C. & et al. (2012)33 patients, with phototypes IV to VI, aged over 12 years, suffering from post-inflammatory hyperpigmentation caused by acne1.2% Clindamycin Phosphate Gel + 0.025% Tretinoin once daily for 12 weeksImprovement in overall hyperpigmentation severity was observed in 33% of patients between the start of the study and week 12
BHATT V. & al. (2019)766 Hispanic subjects aged 11 to 50 years suffering from moderate to severe acne0.05% tretinoin lotion once a day for 12 weeksGradual reduction in the severity of hyperpigmentation with treatment
GUÉNIN E. & al. (2020) -41 black patients over the age of 9 suffering from moderate to severe post-inflammatory hyperpigmentation facial lesions0.05% tretinoin lotion once a day for 12 weeksOverall improvement in the severity of hyperpigmentation in 58.5% of subjects after 12 weeks
HARRIS S. & et al. (2020)1,614 participants suffering from moderate to severe acne0.045% Tazarotene lotion over a period of 12 weeksImprovement of hyperpigmentation sequelae associated with inflammation after 12 weeks of treatment

What are the mechanisms that underlie these effects?

To induce skin depigmentation, retinoids trigger numerous structural modifications and histological changes. The depigmenting effects of topical retinoids involve theacceleration of epidermal cell renewal, meaning that keratinocytes differentiate more quickly from the basal layer to the horny layer, which leads to a rapid loss of melanin pigment through epidermopoiesis. However, by modifying the horny layer, retinoids also facilitate the penetration of other depigmenting agents into the epidermis, when they are used in combination to optimize the depigmenting potential.

Another theory suggests that retinoids could induce a uniform dispersion/distribution of melanin granules within keratinocytes. It has also been demonstrated that topical retinoids directly affect melanogenesis through the inhibition of the expression of the melanin-forming enzyme tyrosinase, as well as TRP-1 and TRP-2 proteins, thereby interrupting melanin synthesis. It has also been suggested that they could modulate the epidermal melanin content through an indirect action on keratinocytes. However, the fundamental mechanisms underlying the lightening effect of retinoids are not fully understood.

In the skin, the various retinoids are converted into retinoic acid, which is the active form.

Hyperpigmented Marks: How to Use Retinoids?

Thus, we can anticipate improvements in hyperpigmentation. However, it is crucial to apply retinoids as prescribed to further minimize side effects (irritation, skin dryness, exacerbation of existing brown spots, flaking, etc.), to avoid any application during pregnancy and breastfeeding, to use a sunscreen daily, to use a pH-balanced cleanser and a non-comedogenic moisturizer after the retinoids, to start retinoid treatment as early as possible unless contraindicated or there are tolerance issues, and to apply a moisturizer before the retinoid for those with sensitive skin without affecting its percutaneous absorption.

Sources

  • PAWELEK J. M. & others. Retinoic acid is a powerful inhibitor of inducible pigmentation in murine and hamster melanoma cell lines. Journal of Investigative Dermatology (1990).

  • GRIFFITHS C. E. M. & al. Cellular, immunological, and biochemical characterization of human skin treated with topical retinoic acid. Journal of Investigative Dermatology (1991).

  • VOORHEES J. J. & others. An in vivo experimental model for the effects of topical retinoic acid on human skin. British Journal of Dermatology (1993).

  • VOORHEES J. J. & others. Topical tretinoin (retinoic acid) treatment for hyperpigmented lesions caused by skin inflammation in black patients. New England Journal of Medicine (1993).

  • BULGER L. & al. Isotretinoin enhances the appearance of photo-damaged skin: findings from a 36-week, multicenter, double-blind, placebo-controlled study. Journal of the American Academy of Dermatology (2000).

  • GIBSON J. R. & others. Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator-masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Archives of Dermatology (2001).

  • GIBSON J. R. & al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial. Archives of Dermatology (2002).

  • PARSAD D. & al. Adapalene in the treatment of melasma: a preliminary report. Journal of Dermatology (2002).

  • GRIFFITHS C. E. M. et al. Evaluation of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. Journal of the American Academy of Dermatology (2003).

  • CALLENDER V. & al. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis (2006).

  • ORTONNE J-P. Retinoid treatment for pigmentation disorders. Dermatologic Therapy (2006).

  • LE GALL N. & al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. Journal of Drugs in Dermatology (2010).

  • TAYLOR S. C. & others. Efficacy and safety of clindamycin phosphate 1.2% and tretinoin 0.025% gel for the treatment of acne and acne-induced post-inflammatory hyperpigmentation in patients with skin of color. Journal of Clinical and Aesthetic Dermatology (2012).

  • BHATT V. & al. Novel tretinoin 0.05% lotion for once-daily treatment of moderate-to-severe acne vulgaris in a Hispanic population. Journal of Drugs in Dermatology (2019).

  • GUENIN E. & al. Tolerability of Tretinoin Lotion 0.05% for Moderate to Severe Acne Vulgaris: A Post Hoc Analysis in a Black Population. Cutis (2020).

  • HARRIS S. & al. Novel polymeric tazarotene 0.045% lotion for moderate-to-severe acne: Pooled phase 3 analysis by race/ethnicity. Journal of Drugs in Dermatology (2020).

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