A.K. Gupta, MD, PhD, FRCPC1,2 and J.E. Ryder, HBSc2
1Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Science Center (Sunnybrook site) and the University of Toronto, Toronto, Canada.
2Mediprobe Laboratories Inc., Toronto, Ontario, Canada.
Hydroquinone has been successfully used to treat hyperpigmentation disorders for many years. Recently, new formulations containing hydroquinone have become available, including Lustra® and Lustra-AF® (Medicis). These products also contain glycolic acid 2%, an active antioxidant system (ascorbyl palmitate and tocopherol acetate), and moisturizers. Lustra-AF® also contains a broad-spectrum sunscreen. Alustra™ contains a stabilized, high-concentration of retinol. The above formulations inhibit melanogenesis, stimulate epidermal desquamation, inhibit free radical-mediated photodamage and restore the antioxidant reservoir. The addition of retinoids may facilitate epidermal penetration of hydroquinone and prevent its oxidation. Comparative studies have shown that these agents can be effective in reducing blotchiness, mottled hyperpigmentation, post-inflammatory hyperpigmentation, and surface roughness. In addition, these formulations have been generally well tolerated with patients rarely reporting mild-to-moderate adverse events such as dryness, redness, or peeling of the skin.
Key Words: hypopigmentation, melasma, photodamage, bleaching
Dyschromia is an abnormality in the skin, possibly due to an increase in the production of melanin resulting in various pigmentary disorders including melasma, lentigines, ephelides (freckles) and post-inflammatory hyperpigmentation (PIH). Also, mottled pigmentation may be seen in patients with photodamage. Hyperpigmentation of the skin may be associated with the use of oral contraceptives, estrogen replacement therapy and pregnancy. In addition, chronic exposure to ultraviolet light may disrupt the structural and functional components of the skin, increase melanin production, and thicken the stratum corneum.1 Long-term ultraviolet exposure may cause photodamage resulting in fine lines, coarse wrinkles, roughness, laxity, pigmentary disorders, dryness, sallowness, epidermal atrophy or dermal elastosis.2 In the past, pigmentary disorders were successfully treated with agents containing hydroquinone, a hydroxyphenolic chemical. Hydroquinone is available commercially in concentrations between 2% and 4%. As well, 6%-10% concentrations can be ordered from the pharmacist.3
Biology Of Melanocytes
The primary role of melanin is skin pigmentation. However, it also serves to protect the skin from UV radiation.4 The biosynthesis of melanin occurs within the melanosome, the metabolic unit of the melanocyte.5 Fully developed melanosomes are distributed to keratinocytes, and as they migrate towards the epidermis they degrade the melanosomes and micronize the melanin to spread the pigment throughout each keratinocyte.1
Components of Lustra , Lustra-AF and Alustra™
The active agent in these three formulations, hydroquinone cream USP 4%, effectively inhibits tyrosinase thereby preventing the synthesis of melanin. In addition, hydroquinone may also initiate the decomposition of preformed melanin.6 Other ingredients include antioxidants, glycolic acid, and moisturizers. Furthermore, Lustra-AF™ also contains an advanced broad-spectrum sunblock system including avobenzone that helps minimize ultraviolet induced hyperpigmentation and sun damage.7 Alustra™ contains retinol in place of glycolic acid.8
The antioxidant system helps reduce or eliminate the negative effects of the environment on the skin by inhibiting free radical mediated damage and restoring the antioxidant reservoir.1 Both water-soluble and lipidsoluble ascorbyl palmitate (vitamin C) and lipid-soluble tocopherol acetate (vitamin E) are present in the antioxidant system.
Glycolic acid 2% (an alpha hydroxy acid) gently stimulates epidermal desquamation and the removal of existing pigmentation contained within these cells, reducing the thickness of the stratum corneum.1,9 Glycolic acid may also reduce surface roughness and fine wrinkles of UV damaged skin on the face, neck and upper chest.10
Moisturizers enhance the overall appearance of the skin by increasing surface smoothness, clarity, and tone, relieving dryness, and reducing the appearance of fine lines.11 Previous studies have shown retinol to be beneficial in the treatment of photodamaged skin.8
|Lustra® vs. Melanex® vs. Solaquin Forte®1||Lustra® showed:|
• Faster onset of activity
• A greater decrease in pigmentation
• Improvement in fine lines, smoothness, and skin clarity
|Lustra® vs. Renova® vs. Lustra® plus Renova®12||• Lustra® and Lustra® + Renova® showed significant improvement in blotchiness and mottled hyperpigmentation by week 8.|
• Renova® also showed improvement in blotchiness and mottled hyperpigmentation, but more slowly.
• All treatment groups showed significant improvement in PIH and surface roughness by week 8.
|Alustra™ vs. tretinoin 0.05% cream13||• At week 12 there was significant improvement in both treatment groups for tactile skin roughness, periocular fine lines, shallow wrinkles, overall pigmentation severity, and overall melasma severity.|
• At 4 weeks post-therapy, both treatments showed significant improvement in periocular fine lines, tactile roughness and overall pigmentation.
• The hydroquinone/retinol combination was better tolerated than the 0.05% tretinoin.
Table 1: A review of some clinical trials for hydroquinone products.
Rizer and colleagues compared the efficacy and tolerance of Lustra® to Melanex® (hydroquinone topical solution USP 3%) and Solaquin Forte® (hydroquinone cream USP 4% with sunscreens SPF 17).1 Included in this singleblind, randomized, controlled, 12-week study were 69 female subjects (35-55 years old) with relatively equal numbers of Caucasian, Asian, and African-American individuals. Lustra® had a faster onset of activity and a greater decrease in pigmentation when compared to the two other treatment arms. In addition, Lustra® showed improvement in fine lines, smoothness, and clarity compared to the other agents.1
In another study, Swinyer, et al.12 compared the efficacy and safety of Lustra®, Renova® (tretinoin emollient cream 0.05%), or Lustra® plus Renova®, applied twice daily, in the treatment of moderate-to-severe facial dyschromia and actinic photodamage. Patients were also provided with a sunscreen (SPF 25) and a moisturizer. In this investigatorblind, randomized, controlled study 42 subjects were evaluated for 12 weeks. Investigators assessed blotchiness, mottled hyperpigmentation, PIH, and surface roughness. A significant improvement in blotchiness and mottled hyperpigmentation from baseline was seen by week 8 in the Lustra® and Lustra® plus Renova® treatment groups with continued improvement at 16 weeks. The Renova® treated group also experienced improvement in blotchiness and mottled hyperpigmentation, but the response occurred more slowly. At week 8, PIH and surface roughness significantly improved from baseline in all treatment groups. In this 12 week study,12 Lustra® was more effective than Renova® in diminishing the signs and symptoms of UV-induced dyschromia. As well, Lustra® plus Renova® and Lustra® alone produced a more rapid and greater reduction in mottled hyperpigmentation compared to Renova® alone. All treatments were well tolerated with no significant increase in irritation in the combined treatment group.13
In a randomized, investigator-blinded, split-face designed trial, Trookman, et al,13 compared the efficacy and tolerance of topical 4% hydroquinone/stabilized retinol (Alustra™) and tretinoin 0.05% cream. Forty-one female subjects (30-55 years old) having Fitzpatrick skin phototype I-IV, with mild-to-moderate photodamage (Glogau classification I or II), and moderate-to-severe mottled pigmentation and/or melasma were evaluated. At week 12, compared to baseline, tactile skin roughness, periocular fine lines, shallow wrinkles, overall pigmentation severity, and overall melasma severity significantly improved in both treatment groups. At 4 weeks post-therapy, tretinoin 0.05% and 4% hydroquinone/stabilized retinol demonstrated significant improvement in periocular fine lines, tactile roughness, and overall pigmentation. As well, 4% hydroquinone/stabilized retinol also showed significant improvement in the following efficacy parameters: facial lesion pigment intensity, facial lesions area, overall melasma severity, lesion size, lesion homogeneity, total face Melasma Area and Severity Index (MASI), and improvement of overall pigmentation. Patients experienced erythema, dryness/scaling and tightness in both treatment groups; however, 4% hydroquinone/stabilized retinol was better tolerated compared to 0.05% tretinoin.13 Patients preferred the esthetic characteristics of the combined product.13
Safety and Adverse Reactions
Patients may experience a mild burning sensation and transient skin reddening. Uncommonly, cutaneous hypersensitivity may occur, in which case treatment should be discontinued.7,8,14 External ochronosis may occur, especially in black individuals, with prolonged hydroquinone use. The safety of hydroquinone during pregnancy or in children <12 years of age has not yet been established.7,8,14 Hydroquinone cream USP 4% (with and without sunscreen formulations) contains sodium metabisulfite, which may cause an allergic reaction in susceptible individuals.7,14 Those who have a prior history of hypersensitivity or allergic reaction to hydroquinone or retinoids should avoid such products, and patients taking photosensitizing drugs should not use tretinoin, because it may cause phototoxicity.
Hydroquinone is frequently prescribed in the United States and Canada to treat various pigmentary disorders including melasma and PIH. More and more, hydroquinone is being included in photodamage therapies because of the mottled pigmentation that presents with the fine lines and wrinkles. Although previous treatments for skin discoloration have relied on monotherapy with hydroquinone, Lustra®, Lustra-AF® and Alustra™ have demonstrated that this multifactorial approach (e.g., the combination of hydroquinone with glycolic acid, antioxidants, and moisturizers) to treating skin discoloration may be more effective and have a faster onset of action when compared to some monotherapies.
- Rizer R, Sklar J, Hino P, et al. The effectiveness & safety of Lustra (hydroquinone USP 4 %) in dyschromia. Skin & Aging Suppl 1:4-8 (1999).
- Weinstein GD, Nigra TP, Pochi PE, et al. Topical tretinoin for treatment of photodamaged skin: a multicenter study. Arch Dermatol 127(5):659-65 (1991 May).
- Pandya AG, Guevara IL. Disorders of hyperpigmentation. Dermatol Clin 18(1):91-8 (2000 Jan).
- Kim NY, Pandya AG. Pigmentary Diseases. Med Clin North Am 82(5):1185-207 (1998 Sep).
- Taylor SC. The traditional uses of hydroquinones. Dyschromia Rounds 1:1- 8 (2001).
- Amer M, Metwalli M. Topical hydroquinone in the treatment of some hyperpigmentary disorders. Int J Dermatol 37(6):449-50 (1998 Jun).
- Hydroquinone cream USP 4% with sunscreens SPF 20 (Lustra-AF®), Medicis Pharmaceuticals, Phoenix, AZ, US in Physicians’ Desk Reference 54th Ed. Medical Economics Company: Montvale, NJ, pp. 1728-9 (2000).
- Hydroquinone cream USP 4% with retinol (Alustra™) Package Insert, Medicis Pharmaceuticals, AZ, US (2001 Apr).
- Gans E, Christensen M. Cutaneous absorption and clinical effect of ascorbyl palmitate and tocopherol acetate antioxidants in Lustra (hydroquinone USP 4%). Skin & Aging Suppl 1:13-17 (1999).
- Gladstone HB, Nguyen SL, Williams R, et al. Efficacy of hydroquinone cream (USP 4%) used alone or in combination with salicylic acid peels in improving photodamage on the neck and upper chest. Dermatol Surg 26(4):333-7 (2000 Apr).
- Rizer R, Sklar J, Hino P, et al. Evaluation of Lustra (hydroquinone USP 4%) on the skin?s antioxidant system. Skin & Aging Suppl. 1:9-12 (1999).
- Swinyer LJ, Wortzman M. Study of hydroquinone USP 4%, 0.05% tretinoin, and in combination in UV-induced dyschromia with actinic photodamage. Cosmetic Dermatol 13-18 (2000).
- Data on File ? Medicis Pharmaceuticals.
- Hydroquinone cream USP 4% (Lustra®), Medicis Pharmaceuticals, Phoenix, AZ, USA. In: Physicians’ Desk Reference 54th Ed. Medical Economics Company, Montvale, NJ, pp. 1728-9 (2000).