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CHAPTER 13 SKIN PIGMENTATION AND PIGMENTATION DISORDERS
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FIGURE 13-4 UV radiation activates p53, which stimulates the POMC gene to transcribe alpha melanocyte-stimulating hormone MSH binds the MC1-R receptor located on the melanocytes, which triggers adenylate cyclase to produce cAMP cAMP then stimulates tyrosinase to produce melanin Interestingly, when POMC transcription is stimulated, -endorphin production also increases, leading to the tanning high reported by sun seekers
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MELASMA
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Melasma, also known as chloasma or the mask of pregnancy, is a very common condition usually seen in women of childbearing age (Fig 13-5) It is a chronic disorder that can be frustrating to patients and physicians alike because it is very difficult to treat Melasma presents as irregularly shaped, but often distinctly defined, blotches of light- to dark-brown pigmentation These patches are usually seen on the upper lip, nose, cheeks, chin, forehead, and, sometimes, the neck There are three typical patterns of distribution most common is centrofacial, involving the cheeks, forehead, upper lip, nose, and chin30 The malar pattern, which affects the nose and cheeks, and mandibular pattern, are less common It is most commonly seen in areas that receive sun exposure; however, melasma has been reported on the nipples and around the external genitalia31,32
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Etiology
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Melasma is a fairly typical, physiologic occurrence seen most often during pregnancy or oral contraceptive use It can occur at any time during a woman s reproductive years, and is more common in women of darker skin types Although there have been many suggested causative factors, estrogen and UV light seem to be the most prominent culprits Melasma is so common in pregnancy that it has been dubbed the mask of pregnancy It is currently unknown how
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increased estrogen levels lead to melasma; however, recent studies have suggested that estradiols may play an important role in the etiology 17 -Estradiol, which is known to affect other cells of neural crest origin, has been shown to significantly increase the activity of tyrosinase when added to melanocyte cultures33 However, melasma also occurs in men in approximately 10% of cases, most often in those of Middle Eastern, Caribbean, or Asian descent Solar exposure is well known to exacerbate the condition and seems to be necessary for its development4,34 In fact, melasma has been reported to be less noticeable in the winter months when sun exposure is typically lower4 The other proposed causes of melasma include genetic predisposition, nutritional deficiency, and influence from hormones such as progesterone, although the exact etiology remains vague31,32 In addition, the antiepilepsy drugs Hydantoin and Dilantin have been implicated in contributing to melasma in both women and men32,35 Approximately one-third of cases in women and most cases in men are idiopathic32 Some authors have hypothesized an endocrine, causal mechanism,32 but no such mechanism has been established35 Although there have been a few familial cases reported, the evidence that melasma can be inherited is sparse35 Heat may play a role in melasma as well Many women develop melasma on the upper lip after hot wax has been used as a hair removal method Although this may represent a coincidence, it is so commonly reported
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FIGURE 13-5 Patient with diffuse melasma The patient has not improved despite multiple therapies including depigmenting agents, chemical peels, and good sun protection
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by patients that the author believes that heat may play a role in melasma as it does in erythema ab igne (Erythema ab igne is a reticulated erythematous hyperpigmented eruption that occurs after chronic exposure to heat) Several authors have noted that melasma most often appears in young women who are using oral contraceptives31,32 Melasma is also common among pregnant women and together these two conditions comprise the majority of melasma cases Menopausal and premenstrual presentations occasionally occur as well Although estrogen is thought to play a major role in the etiology of melasma, there is also a low incidence of melasma cases among postmenopausal women on estrogen replacement therapy4 Although melasma may diminish in the months following a patient s pregnancy or after the patient discontinues oral contraceptives, the condition often persists, taking up to 5 years to resolve32,35 The course of the condition varies significantly from patient to patient and within individual women, even from pregnancy to pregnancy4 Increased incidence of melasma also coincides with some ovarian disorders Unfortunately, once patients develop melasma, they have a high chance of experiencing recurrence of this difficult disorder It is always important to consider the possibility of pigmented contact dermatitis (Riehl s melanosis) in response to cosmetic products when evaluating a patient for treatment of melasma, since avoidance of the specific allergen will improve the clinical picture (see 18 for more information about contact dermatitis) As mentioned earlier, stress hormones such as ACTH and MSH are involved in skin pigmentation It has been previously shown that human keratinocytes are capable of synthesizing and secreting POMC-derived peptides such as ACTH and MSH36 Inoue et al demonstrated that pretreatment of stressed mice, exposed to UV light, with an ACTH-inhibitor reduced the numbers of dopa-positive melanocytes21 More structural studies are needed to evaluate the effect of stress in induction or aggravation of melasma in humans Another influence in melasma is the stem cell factor, which is the ligand for c-kit located on the melanocytes Stem cell factor is secreted by dermal fibroblasts and keratinocytes37 One study showed that there is increased expression of stem cell factor in the dermis and c-kit of lesional skin of patients with melasma38 The authors of this study proposed that UV light activates the
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