A substantial area of general dermatology comprises pigmentary complaints—either too much pigmentation or too little. From lentigines (sun spots), melasma, and post-inflammatory hyperpigmentation, to pityriasis alba and vitiligo, there is a spectrum of disorders that results in dark or light areas on the skin. Some of these are addressed in other sections more directly; here we will focus exclusively on the aspect of color. While generally not possessing serious underlying medical implications, dyspigmentation can have devastating psychological effects and a significant impact on the quality of life of patients (Lieu and Pandya 2012).

From a scientific standpoint, alterations in melanocyte density, melanin concentration, or both can result in anomalies of skin pigmentation (Nicolaidou and Katsambas 2014). Some diseases of hyperpigmentation such as melasma may have an epidermal component (which often responds to topical therapies), a dermal component (which is very difficult to treat), or may be mixed (Sanchez et al. 1981).

Melasma is the representative disease in the category of hyperpigmentation, and its pathogenesis appears to be multifactorial: genetics, hormones and sun exposure all appear to play a role (Grimes 1995). Patients with melasma, sometimes called “the mask of pregnancy”, often give a history of current or previous oral contraceptive use, and the signs of melasma may continue many years after such hormonal changes have ceased.

Beyond stressing the importance of strict sun protection and avoidance, conventional treatment regimens for melasma generally involve the use of hydroquinone—a bleaching agent that appears to disrupt pigment synthesis—which may cause irritant contact dermatitis and, rarely, permanent hyperpigmentation due to the development of exogenous ochronosis (primarily seen when hydroquinone is used in higher than recommended concentrations and/or prolonged periods of time). Hydroquinone is generally considered to be safe, and there has been no evidence linking topical hydroquinone to malignancy; however, public concerns about its safety arose when the FDA classified hydroquinone as having some evidence of carcinogenicity in animal studies, and recommended further study of this medication (Nordlund et al. 2006). Continuous use of hydroquinone is not recommended for longer than 3–4 months.

The most effective treatments for melasma and for hyperpigmentation in general appear to be combinations of hydroquinone along with other agents, particularly retinoids and corticosteroids, both of which have pertinent risks as well (Rivas and Pandya 2013). Alternative therapies, therefore, play a crucial role in the treatment of melasma, either as true alternatives to hydroquinone or as treatment options during a “hydroquinone holiday.” While some of the studies mentioned in this chapter involved only melasma patients, their results may be extrapolated to include patients with other forms of hyperpigmentation such as solar lentigines and post-inflammatory hyperpigmentation, as many skin lightening agents may be effective in more than one form of hyperpigmentation.

Vitiligo represents the other end of the spectrum, with total loss of melanocytes from an area. Affecting some 1–4% of the world population, with more than 50% appearing before age 20 (Szczurko and Boon 2008), it is thought to be an autoimmune disease whereby the actual pigment-producing cells are destroyed (Speeckaert et al. 2015). However, there are other hypotheses proposed such as a cytotoxic mechanism due to increased oxidative stress, and debate continues about the actual pathophysiology, raising the question that there may exist various subtypes with distinct pathogeneses. Vitiligo is also notoriously difficult to treat (Speeckaert et al. 2015). Conventional therapy focuses on topical anti-inflammatory preparations (corticosteroids and calcineurin inhibitors) which have a number of risks, particularly when used long-term, and light-based treatments, particularly narrow-band ultraviolet B phototherapy and the very similar excimer laser (Nicolaidou and Katsambas 2014). In severe cases of widespread disease that is refractory, a powerful permanent bleaching option called monobenzyl ether or hydroquinone (essentially a more potent cousin of hydroquinone discussed above) can be used to remove the remaining pigmentation to achieve uniform color. When these are ineffective or not possible due to time, risk, or cost, alternatives become an important part of the discussion for patients who do not want to use cosmetic cover-up or “just live with it.”