Hydroquinone is a nonvolatile chemical used in the photographic, rubber, chemical, and cosmetic industries. In the late 1930s, it was observed that a chemical used in rubber manufacture, monobenzyl ether of hydroquinone, caused depigmented skin in some workers . The efficacy of hydroquinone (1,4-dihydroxybenzene) as a skin-lightening agent has been established in both human and animal studies. The chemical structure of hydro-quinone is shown in Figure 1. Clinically, hydroquinone is applied topically in the treatment of melasma, freckles, and senile lentigines, as well as postinflammatory hyperpigmenta-tion. In the United States, hydroquinone is readily available in concentrations up to 2.0% as an over-the-counter (OTC) drug and by prescription at higher concentrations [1,2]. Thus, hydroquinone is readily applied to the skin for medical and cosmetic reasons .
Hydroquinone inhibits the conversion of dopa to melanin by inhibiting the tyrosinase enzyme [1-3]. Other proposed mechanisms are inhibition of DNA and RNA synthesis, degradation of melanosomes, and destruction of melanocytes . Electron microscopic studies of black guinea-pig skin treated with hydroquinone show the anatomic consequences of this action: (1) the melanosome structure is disturbed, resulting in decreased production or increased degradation of these organelles, or both; (2) hydroquinone exposure can ultimately lead to the degradation of the melanocyte; and (3) keratinocytes are spared, showing no apparent injury .
Arndt and Fitzpatrick , in a non-placebo-controlled study, compared the efficacy of 2% and 5% hydroquinone cream for treatment of various pigmentary disorders in 56 patients. Results showed that hydroquinone was a moderately effective depigmenting agent in 80% of cases and that there was no difference between the two concentrations in therapeutic efficacy. Two percent hydroquinone was less irritating than 5%. Fitzpatrick et al. , in a non-placebo-controlled study, evaluated the efficacy of a 2% cream of stabilized hydroquinone in 93 patients. Sixty-four percent of them showed decreasing hypermelanosis without untoward effects. Sanchez and Vazquez  treated 46 patients with melasma using two versions of a 3% hydroalcoholic solution of hydroquinone. In this non-placebo-controlled study, overall improvement was noted in 88% of the patients and moderate-to-marked improvement in 36%. Side effects were minimal. The usage of a sunscreen agent was necessary for therapeutic efficacy. The efficacy of hydroquinone may be improved when it is used in combination with other chemicals as well as tretinoin, salicylic acid, or corticosteroid [1,2]. Kligman and Willis  noted an enhanced efficacy with 5% hydroquinone, 0.1% tretinion, and 0.1% dexamethasone in hydrophilic ointment for the treatment of melasma, ephelides, and postinflammatory hyperpigmentation in a non-placebo-controlled study. In contrast, they experienced poor results with each of the aforementioned as monotherapies. However, senile lentigines were resistant to this therapy. Gano and Garcia  conducted a 10-week clinical trial in 20 women with melasma. Topical applications of 0.05% tretinoin, 0.1% betamethasone valerate, and 2% hydroqui-none were used in a non-placebo-controlled study. There was an objective improvement rate of 65% and a subjective improvement rate of 95%. Side effects were frequent but minimal. Caution is necessary when using potent fluorinated corticosteroids for prolonged periods on the face, because telangiectasia, atrophy, or acne rosacea can develop.
Pathak et al.  clinically tested the efficacy of hydroquinone in varying concentrations supplemented with corticosteroids or retinoic acid (tretinoin) in 300 Hispanic women with melasma in a non-placebo-controlled study, and concluded that cream or lotion formulations of 2% hydroquinone and 0.05 to 0.1% retinoic acid provided the most favorable results. In addition, avoidance of sun exposure and constant use of broad-spectrum sunscreens are necessary for the best therapy effects. Recently, Clarys and Barel  tested the efficacy of an ascorbate-phytohydroquinone complex in 14 patients with lentigo senile lesions in a non-placebo-controlled study. Objective skin-color changes were evaluated with a chromameter. After 1 month of treatment, a clear depigmentation of the macules was measured. None of the patients reported adverse effects.
Gellin et al.  established a reliable in vivo method to predict the depigmenting action of chemicals on mammalian melanocytes. They used black guinea pigs and black mice as animal models to screen the depigmenting capacity of several phenols, catechols, and organic antioxidants. Results showed that complete depigmentation on all test sites was achieved with monomethyl ether of hydroquinone and tertiary butyl catchall in the black guinea pig. Less-pronounced pigment loss was noted with these chemicals in black mice.
To treat some cases, higher concentrations of hydroquinone may be used. The formulations contain concentrations as high as 10% combined with nonfluorinated corticoid creams with or without the additional use of tretinoin or salicylic acid. Extemporaneously compounded preparations are often effective in patients that have failed to respond to lower concentrations of hydroquinone. With controlled use and monitoring, side effects from these preparations have proved minimal . Note, however, that hydroquinone may be quickly oxidized in such formulations.
Hydroquinone occurs in nature as the beta-glucopyranoside conjugate arbutin. Ar-butin is a safe and mild agent for treating cutaneous hyperpigmentation disorders, including melasma and UV-induced ephelides . Arbutin is an active ingredient of the crude drug Uvae Ursi Folium-traditionally used in Japan and contained in the leaves of pear tees and certain herbs. The chemical structure of arbutin is shown in Figure 1. Maeda and Fukuda  determined the arbutin's inhibitory action on the melanin synthetic enzyme and its effects on melanin intermediates and melanin production in cultured human mela-nocytes. They indicated that the depigmentation effect of arbutin works through a inhibition of the melanosomal tyrosinase activity, rather than suppression of the expression and synthesis of tyrosinase in human melanocytes. Arbutin was much less cytotoxic than hydroquinone to cultured human melanocytes.
Adverse reactions associated with hydroquinone use include acute and chronic complications. Acute reactions include irritant dermatitis, nail discoloration, and postinflam-matory hyperpigmentation . Although commonly assumed to be a common allergen, the documentation of hydroquinone allergic contact dermatitis is weak . Hydroquinone use can also induce hypopigmentation and, rarely, depigmentation of treated surrounding normal skin. However, these changes are temporary and resolve on cessation of hydroqui-none treatment, in contrast to monobenzone use, which can cause permanent depigmenta-tion . Hence, the only indication for monobenzone therapy is in the treatment of severe vitiligo.
A more recent concern regarding the use of hydroquinone is the occurrence of hydro-quinone-induced ochronosis, a chronic disfiguring condition resulting, in general, from the prolonged use of strong concentrations of hydroquinone . Hydroquinone's acute and chronic toxicity toward higher terrestrial organisms appears to be minimal in humans
[20,21]. An epidemiologic investigation in 478 photographic processors has shown no significant excess mortality, sickness absence, or cancer incidence . The reported nephropathy and cell proliferation, as evidence of carcinogenicity, observed in Fischer 344/ N rats [22,23] appear to be strain and sex specific . Hydroquinone was negative in the Ames/Salmonella and Drosophila genotoxicity assays . Others suggest that carcinogenic and teratogenic potentials have been, at present inadequately studied [20,25], and that both hydroquinone and benzoquinone produce cytotoxic effects on human and mouse bone-marrow cells . Hydroquinone readily penetrates human forehead skin in vivo following a single topical exposure in an alcoholic vehicle of 24-hour duration. Elimination was complete within 5 days . Wester et al.  determined the topical bioavailability, metabolism, and disposition of hydroquinone on humans in vivo and in vitro; dose recovery in urine was 45.3%, of which the majority was excreted in the first 24 hours.
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Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.