40 Years of Topical Tretinoin Use in Review

June 2013 | Volume 12 | Issue 6 | Original Article | 638 | Copyright © June 2013

Hilary E. Baldwin MD,a Marge Nighland BS,b Clare Kendall MA,c David A. Mays PharmD MBA,c Rachel Grossman MD,b,c and Joan Newburger PhDc

aSUNY Downstate Medical Center, Brooklyn, NY bValeant Dermatology, a subsidiary of Valeant Pharmaceuticals North America LLC, Bridgewater, NJ cJohnson & Johnson Consumer & Personal Products Worldwide, Skillman, NJ


Results from a limited number of studies suggest that tretinoin may be used alone or in combination with minoxidil for treating alopecia.104-107 Topical tretinoin may help promote hair growth through effects on epithelial cell proliferation and differentiation, as well as vascular proliferation.108 In addition, topical tretinoin may enhance the absorption of minoxidil, which is known to stimulate hair regrowth.106,107

Warts/Nevoid Hyperkeratosis

Case studies have evaluated topical tretinoin for warts or nevoid hyperkeratosis, with equivocal findings.109-112 Topical tretinoin may be effective in the treatment of nevoid hyperkeratosis due to its ability to modulate abnormal follicular keratinization.10

Hyperkeratosis Follicularis et Parafollicularis (Kyrle’s Disease)/ Keratosis Follicularis (Darier’s Disease)

Whereas results of a case study suggest that topical tretinoin use to treat hyperkeratosis follicularis was limited due to AEs, other studies suggest that topical tretinoin may be useful for treating Darier’s disease.113-116 The effectiveness of topical tretinoin in Kyrle’s disease may be due to its effect on epidermal proliferation and keratinization.116


Three case studies suggest that topical tretinoin may benefit patients with porokeratosis.117-119 The effectiveness of topical tretinoin in treating porokeratosis may be due to its ability to modulate abnormal follicular keratinization.118


One case study showed the effectiveness of sequential application of topical tretinoin (0.3%) and a corticosteroid for treating corticosteroid- resistant plaque-type psoriasis.120 Another study showed that adding topical tretinoin to a topical corticosteroid for treating psoriasis partially ameliorates corticosteroid-induced epidermal atrophy.121 Effectiveness in psoriasis may be attributed to the ability of topical tretinoin to modulate many of the pathogenic factors thought to be responsible for psoriasis; tretinoin is antiproliferative, normalizes abnormal keratinocyte differentiation, and is antiinflammatory.

Acanthosis Nigricans

One report showed that a combination of 12% ammonium lactate cream and 0.05% tretinoin cream improved acanthosis nigricans associated with obesity. Case studies showed that daily topical tretinoin was effective in improving both clinical and histological measures of acanthosis nigricans.122,123 The action of topical tretinoin in acanthosis nigricans may be attributed to its keratolytic effects.123


Randomized, double-blind data suggest that low-dose topical tretinon may be useful for treating rosacea.124 The effects of topical tretinoin in rosacea may be due to its inhibition of skin metalloproteinases and its down-regulation of toll-like receptor 2, which is reported to be overexpressed on the epidermis of patients with rosacea.124-126

Nevus Comedonicus

Case studies of nevus comedonicus on the face, chest, and neck have demonstrated an extrusion of comedones and a reduction in lesion size in response to treatment with retinoic acid alone or topical tretinoin in combination with a 1450-nm diode laser.127,128

Keratosis Pilaris

A case report of a woman with keratosis pilaris atrophicans faciei showed that 1 month of topical tretinoin treatment was effective in decreasing erythema and follicular hyperkeratosis. 129 Effectiveness for this condition may be expected given the keratolytic effects of tretinoin.

Antilice Agent

Due to its inhibitory effects on glutathione-S-transferase, topical tretinoin has been recommended as an antilice agent to augment the effects of topical antilice agents including permethrin, pyrethrins, and dichlorodiphenyltrichloroethane (DDT).130


Combination imiquimod and topical tretinoin may be effective as a nonscarring treatment for trichoepitheliomas.131

Eruptive Milia

A case study demonstrated rapid improvement of eruptive milia with topical tretinoin treatment.132

Lichen Planus

A case study showed that application of a tretinoin and triamcinolone combination was a successful treatment for lichen planus.133 The effects of topical tretinoin on lichen planus may be due to increased epidermal proliferation and collagenesis.134

Reactive Perforating Collagenosis

One case study demonstrated the effectiveness of tretinoin cream (0.1%) for reducing the total number of reactive perforating collagenosis lesions.135

Keratinizing Dermatoses

Multicenter trial data showed that topical tretinoin (0.1%) was effective in treating keratinizing dermatoses, including lamellar ichthyosis and ichthyosis vulgaris.136 It is unclear whether the keratolytic properties of tretinoin or its ability to normalize keratinocyte differentiation was responsible for the noted improvement.

Intrinsic/Chronological Aging

One clinical trial found that tretinoin cream applied once daily for 9 months in older women (aged 68-79 years) showed marked