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Pigmentary Disorders in the South East
Dermatol Clin 25 (2007) 431–438
Pigmentary Disorders in the South East Seung-Kyung Hann, MD, PhDa,*, Sungbin Im, MD, PhDa, Won Soon Chung, MDa, Do Young Kim, MDb a
Drs. Woo and Hann’s Skin Clinic, Department of Dermatology and Cutaneous Biology Research Institute, 15-3 Galwol-Dong, Yongsan-Gu, Seoul 120-752, Korea b Yonsei University College of Medicine, Seoul, Korea
Dermatologic diseases that commonly occur in Asians are xerosis, pruritus, nummular dermatitis, dyshidrosis, atopic dermatitis, melasma, photodermatoses, psoriasis, vitiligo, lichen amyloidosis, nevus of Ito, nevus of Ota, Mongolian spot, longitudinal pigmented band of nail, Bowen’s disease, pigmented basal cell carcinoma, and pigmented Ofuji’s disease [1]. Of utmost concern among these diseases are pigmentary disorders, which are common in Asians [1]. Pigmentary disorders account for 14.2% of all dermatologic disease of individuals of Hispanic race in the United States. Although the exact incidence of pigmentary disorders in Asians has not been determined, it is supposed to be as high as that for Hispanics. These disorders can be psychologically distressing because of their visible nature. From the review of Korean literature, two important pigmentary disorders in Asians are vitiligo and melasma, which are especially resistant to various kinds of conventional treatments and tend to have a chronic progression that makes patients doubt the results and the prognosis. This article introduces new information regarding vitiligo and melasma based on clinical studies of Korean patients and specific pigmentary disorders that occur in Asians. Geographic characteristics of South East Asia Asia can be subdivided into the following areas: South Asia, which includes the subcontinent region of Pakistan, India, and Sri Lanka;
* Corresponding author. E-mail address: [email protected] (S-K. Hann).
South East Asia, which includes the regions of Malaysia, Singapore, Philippines, Thailand, and Indonesia; and East Asia, which includes Japan, Korea, and China. In this article, East Asia and South East Asia are considered the same subdivision to provide a more comprehensive understanding of pigmentation disorders in South East Asia.
Incidence of vitiligo and melasma in South East Asia The incidence of vitiligo and melasma varies depending on nations. Several demographic studies since the early 1980s in Korea suggested that vitiligo accounted for 1.7% to 4.7% of outpatients [2–5]. The estimated prevalence of vitiligo of China was 0.19% in a survey. Vitiligo accounted for 1% of cases reported in Hong Kong and 3% of cases in Malaysia [6–8]. The incidence of vitiligo in childhood was reported to be 4.1% in Thailand [9]. The incidence of melasma in South East Asia was 0.25% to 4% of patients seen in dermatology institutes, with peak incidence at age 30 to 44 years. One survey from a dermatology clinic in Thailand suggested that the prevalence of melasma may be as high as 40% in women and 20% in men [10]. Melasma also accounted for 4% of cases reported in Malaysia and 0.98% of cases reported in Indonesia [10]. In a study of 26,766 patients who attended a dermatologic clinic in Korea, the prevalence of melasma was 3.8% [2]. Because of a selection bias, however, the actual incidence of these diseases in South East is estimated to be higher than in people of other races.
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Vitiligo Vitiligo is a pigmentary disorder of major concern in ethnic populations. The well-circumscribed depigmented macules are more visible in individuals with darker skin and cause significant cosmetic and psychological concerns in darker skinned individuals. Vitiligo affects approximately 0.5% to 2% of the population, without racial, gender, or regional differences [11,12]. Although many studies have concentrated on its pathogenesis, the hypothesis concerning the pathogenesis of vitiligo has not yet been fully elucidated. Vitiligo has various clinical features as reported by investigators, but the number of patients studied is limited and there is no uniform classification on which all clinicians agree. Understanding these characteristics can give valuable information not only regarding differentiating vitiligo from other pigmentary disorders but also in treating vitiligo with the proper modalities and predicting the prognosis of vitiligo to a certain degree. Classification Currently, a classification describing vitiligo as generalized or localized type according to the distribution of lesions is widely used (Box 1). The localized type is subdivided into focal, segmental, and mucosal subtypes, whereas the generalized type is subdivided into acrofacial, vulgaris, and universal subtypes. An overlap of various types can be classified as mixed type [13]. New classification In 1977, Koga [14] performed a sweat secretion stimulation test using physiostigmine and accordingly reclassified vitiligo into nonsegmental type (type A) and segmental type (type B). He
et al
proposed that the nonsegmental type results from immunologic mechanisms, whereas the segmental type results from dysfunction of the sympathetic nervous system in the affected skin [14]. After Koga’s report suggested that these two types differed in pathogenesis and clinical presentation, many clinicians began to take an interest in segmental vitiligo, because most of these cases did not cross the midline and were distributed along a unilateral dermatome, which meant the ability to predict the prognosis [15,16]. Segmental-type vitiligo is usually localized to one dermatome, shows relatively stable disease activity after its initial rapid spreading phase, and is associated with a significantly lower rate of autoimmune diseases than nonsegmental type (Fig. 1) [15,16]. According to these characteristics, vitiligo also can be classified into three major clinical types: segmental (unilateral), nonsegmental (bilateral), and mixed (Box 2). The segmental form generally does not cross the midline and does not have a classical dermatomal distribution but affects one segment of the integument. The segment might be composed of several or parts of several adjacent dermatomes or have no relationship to dermatomes at all or any other lines, such as Blaschko’s line or acupuncture lines. The progression is usually limited to months or a few years [16,17]. The nonsegmental form is characterized by bilateral, usually symmetrical, depigmented macules. It is further subdivided into localized type, including focal and mucosal subtypes, and generalized type, including acrofacial, vulgaris, and universal subtypes. The former type is characterized by involvement of limited small areas of the integument, and the latter type is characterized by widespread extensive depigmentation that most commonly spreads
Box 1. Classification of vitiligo according to the distribution of lesions Localized Focal Segmental Mucosal Generalized Acrofacial Vulgaris Universal Mixed Fig. 1. Segmental vitiligo on face.
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PIGMENTARY DISORDERS IN THE SOUTH EAST
Box 2. Classification of vitiligo with emphasis on segmental vitiligo Segmental (unilateral) Nonsegmental (bilateral) Localized Focal Mucosal Generalized Acrofacial Vulgaris Universal Mixed: segmental and nonsegmental throughout the life of the individual. There is also a rare variety of generalized vitiligo that seems to be a manifestation of a systemic autoimmune disease. This disorder is manifested by vitiligo with multiple endocrine failures, such as diabetes mellitus, adrenal insufficiency, and thyroid dysfunction. All of the latter endocrine abnormalities seem to be caused by autoantibodies, but the cause of the loss of melanocytes remains unidentified. Segmental vitiligo The incidence of segmental type varies; one group of investigators reported 5%, whereas another group reported 27.9%, and previous Korean studies showed a range between 5.5% and 16.1% [16]. Vitiligo develops at all ages, but it usually occurs in young people between the ages of 10 and 40. According to an epidemiologic study reported in 1977, however, approximately half of the patients developed vitiligo after 40 years of age, which was different from other clinic-based studies. On the other hand, one group reported that onset of nonsegmental vitiligo could occur at any age, whereas segmental vitiligo generally affected young persons. In our study, segmental vitiligo developed before 30 years of age in 87% of patients, 41.3% of whom were younger than age 10 [16]. The commonly involved sites of vitiligo are exposed areas, such as the face and dorsum of the hand. In the case of segmental vitiligo, the involved sites were the face, trunk, neck, extremities, and scalp, in descending order (Table 1). Dermatomal distribution revealed that the trigeminal nerve was most frequently involved, followed by the thoracic, cervical, lumbar, and sacral nerves (Table 2).
Table 1 Site of segmental vitiligo Site
Men (%) Women (%) Total (%)
Head and neck Face Neck Scalp Trunk Chest and abdomen Back Extremities Upper extremities Lower extremities Total no. of patients
57 (62.6) 87 (65.9)
144 (64.6)
49 7 1 21 17
114 27 3 55 48
(53.8) (7.7) (1.1) (23.1) (18.7)
65 20 2 34 31
(49.2) (15.2) (1.5) (25.8) (23.5)
4 (4.4) 3 (2.3) 13 (14.3) 11 (8.3) 7 (7.7) 7 (5.3) 6 (6.6) 91
7 (3.1) 24 (10.8) 14 (6.3)
4 (3.0) 132
(51.1) (12.1) (1.4) (24.7) (21.5)
10 (4.5) 223
Hand dominancy also was appraised to determine whether there is any relation to vitiligo involving the right or left side of the body, but there was no significant relationship between these two factors. The left side was slightly more involved, regardless of the dominant hand. Poliosis, known to be associated with vitiligo in 8.9% to 45% of cases, occurred in 48.6% of patients in our study. The eyebrows and scalp hair were mostly involved (46.7%), which occurs because when vitiligo involves the face, neck, and scalp, poliosis of the eyebrows and scalp hair is also commonly present (67.4%). Most segmental vitiligo usually persists unchanged for the rest of a patient’s life after initially spreading rapidly in the affected dermatomal area. Sometimes it can progress again after several years, however. Segmental vitiligo usually spreads over the affected area, so the progression pattern can be detected and predicted easily. Lesions may spread out away from the affected site, however. This type of vitiligo is called the mixed type of segmental vitiligo. Early segmental vitiligo usually appears as a single oval-shaped white macule or a patch, which is difficult to differentiate from Table 2 Dermatomal distribution of segmental vitiligo Dermatome
Men (%)
Trigeminal Cervical Thoracic Lumbar Sacral Total
49 12 19 10 1 91
(53.9) (13.2) (20.9) (11.0) (1.1)
Women (%) 65 26 31 4 2 128
(50.8) (20.3) (24.2) (3.1) (1.6)
Total (%) 114 38 50 14 3 219
(52.1) (17.4) (22.8) (6.4) (1.4)
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focal-type vitiligo until a typical distribution of lesions has appeared. Depigmentation of hair in segmental vitiligo Melanocytes of the hair bulb are responsible for hair color. They transfer their melanosomes to the surrounding hair keratinocytes. In the hair follicles, melanin granules are mainly in the cortex, where their long axes parallel the hair surface. Involvement of hair in vitiligo macules varies, which indicates that the follicular compartment of the melanocyte organ may be spared while the vitiligo process destroys the epidermal compartment. This dissociated behavior of epidermal and follicular melanocytes is common in vitiligo. The incidence of body leukotrichia in the different series of the literature varies from 10% to more than 60%. Poliosis occurs in patients with nonsegmental or segmental vitiligo. The occurrence of leukotrichia on eyebrows, scalp, and eyelashes was estimated at 48.6% in a group of 101 patients with segmental vitiligo [16]. If the cases of body involvement of segmental vitiligo were excluded, the incidence of leukotrichia of segmental vitiligo would be higher than previous reports. It is assumed that segmental vitiligo often destroys epidermal and follicular melanocytes in the early phase of disease compared with nonsegmental vitiligo. The presence of leukotrichia has been accorded special significance. In these instances, repigmentation of hair is difficult to treat with ultraviolet (UV), medical, or topical treatment. On the other hand, transplantation of melanocytes is required for rapid and complete repigmentation.
et al
linear and may evolve into an almost starburst distribution. Most lesions of melasma are composed of a single large patch on one side of the face with or without small satellite lesions. All lesions have a symmetrical distribution pattern. Hypermelanotic lesions on the face with unilateral involvement cannot be diagnosed as melasma. Melasma only rarely shows pigmented spots in the midline of the face. The color of melasma varies from brown to gray to blue, depending on the skin type of patients and amount of melanin deposited in the skin. Most darkly pigmented patches occur over the bony prominences of the malar regions, which receive the greatest amount of sunlight. The size of patches varies, from a limited area of malar or infraorbital to a large patch covering most of the side of face. The borders are usually well demarcated from the normal skin, but the outlines are irregular. Melasma itself does not have any subjective symptoms. It does not have preceding signs of inflammation, such as itching or erythema. Melasma is not accompanied by any other systemic symptoms. No elevated lesion or changes of skin surface texture could be diagnosed as melasma. Melasma only involves the skin, and no mucosal involvementdincluding of the eye and lipdhas been reported.
Melasma in forearm Areas other than the facedparticularly the forearms and the neckdalso may be involved, usually in association with facial hyperpigmentation [19]. The pigmentary changes were macular, with a confluent or speckled pattern, and, like facial melasma, often with a sharp edge. Clinical classification
Melasma Melasma is a common pigmentary disorder in Asians. It tends to occur much more frequently in Asian women than white women. Clinical manifestation Melasma is common, particularly in women of childbearing age. Melasma is a common disorder of pigmentation seen frequently in essentially healthy women between early adulthood and menopause. The incidence of male cases has been reported to be up to 10% of total cases [18]. The shape of melasma is blotchy, irregular, arcuate, or polycyclic, but the lesions may be
Melasma is classified clinically into three types according to the distribution pattern of lesions: centrofacial pattern (63%) (Fig. 2), malar pattern (21%) (Fig. 3), and mandibular pattern (16%). It became the consensus classification of melasma [20]. This classification only categorized and collected the distribution patterns of melasma simply by the judgment of authors. This classification does not have a direct correlation with age, skin types of patients, aggravation, or underlying etiologic factors of melasma, such as UV light, pregnancy, or oral contraceptive use. These clinical patterns of melasma also are not correlated with Wood’s light examination and histopathologic examination.
PIGMENTARY DISORDERS IN THE SOUTH EAST
435
Our experience of melasma is different from Sanchez’s patterns. Our data on the ratio of
Korean melasma pattern are centrofacial pattern, 52%, malar pattern, 48%, and mandibular pattern, none. Practically, it is difficult to classify melasma into these categories. Melasma always involves either the infraorbital or malar area. Basically, facial melasma lesions are located on the cheek in all cases. In this classification, the involvement of the cheeks and nose is overlapping. Melasma on the nose, lips, and other midline of face is rarely seen. The periorbital area is also rarely involved, and melasma always spares the area related to eyeball movement. Based on these findings, melasma is characterized by infrequent involvement of the periorbital areas of the face. By its definition, centrofacial types should be differentiated from acquired bilateral nevus of Ota–like macules (ABNOM) (Fig. 4) [21]. In our retrospective clinicopathologic experience, the misdiagnosis rate of ABNOM as melasma among our dermatology staff is approximately 14%, especially when the clinical color of ABNOM is close to brown. ABNOM is common in East Asians, such as Koreans, Japanese, and Chinese. It should be clinically differentiated from melasma. Personally, we prefer not to classify the clinical pattern of melasma because this classification does not correlate with the clinical or pathogenic processes of melasma.
Fig. 3. Malar pattern of melasma.
Fig. 4. Acquired bilateral nevus of Ota–like macules.
Fig. 2. Centrofacial pattern of melasma.
Clinical characteristics of Korean patients who have melasma
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Clinical classification with Wood’s light Clinical typing under Wood’s light illumination has been used to aid diagnostic clues of histologic patterns [20]. The various types are as follows: (1) epidermal type, which exhibits enhancement of color contrast between affected and normal skin when examined with Wood’s light; (2) dermal type, in which there is no enhancement of color contrast by scattering and re-emission that produces a blue or blue-gray color; (3) mixed dermal-epidermal type, in which there is enhancement of lesions in some areas and no enhancement of lesions in the other areas of the same patient; (4) indeterminate type, which appears in patients of dark complexion (skin types V and VI), in whom the lesionsdfor lack of contrastdare not discernible on Wood’s light examination, perhaps because of the increased number of melanosomes in the normal skin of black individuals. Wood’s light classification is used to predict the clinical effectiveness of treatment on epidermal type. Wood’s light is absorbed by the melanin, and the intensity of the melanin color is exaggerated by viewing with Wood’s light. This Wood’s light contrast may partly work in skin types I and II but not in brown or black skin types. However, our unpublished data on the correlation of Wood’s light findings to the histologic findings in Korean individuals failed to apply to this Wood’s light classification. From our experience, it was hard to define the color contrast between affected and normal skin. Even after we arbitrarily classified, the Wood’s light classification did not match the histologic findings. In a clinical study conducted with East Asian people, such as Koreans, most patients showed epidermal melasma, a few manifested a mixed type, and no patients exhibited solely dermal or inapparent-type melasma. This observation raised a question about the usefulness of Wood’s light and the existence of dermal-type melasma [22]. We prefer not to use the Wood’s light to examine patients who have melasma.
New classification of melasma We propose to divide melasma clinically into transient or persistent types. The transient type of melasma occurs during pregnancy or with use of the contraceptive pill, and it disappears within 1 year of cessation of stimulating hormonal influence. In this type, the melanocytes in the lesional skin are activated in a reversible way so
et al
they can be normalized after removal of stimuli. This type progresses to the persistent type with a booster stimulus, such as UV exposure. Avoidance of sun exposure in the early stage of melasma is essential. The persistent type includes melasma more than 1 year after the hormonal influence has been removed, which is believed to be caused by the persistent activation or partial transformation of melanocytes in lesional skin in response to UV rays or other factors. Direct UV effect on melanocytes or indirect stimulation of the environment could influence melanocytes. Keratinocytes and dermal components are in charge of this response.
Progression of melasma The natural progression of melasma can be divided into three stages: developmental stage, maintenance stage, and resolution stage. The developmental stage involves patients who develop melasma during pregnancy or while taking oral contraceptives, and the underlying causes are still persisting. The maintenance stage involves melasma that persists even after the cessation of causes or idiopathic melasma in women and men. This stage belongs to limited, constitutive tanning or prolonged, facultative tanning. The resolution stage involves melasma in the stage of disappearing or melasma that has disappeared spontaneously. This stage has a higher chance of developing melasma again during subsequent pregnancy or contraceptive pill use or while using hormone replacement therapy during menopause. To put patients into the developmental stage of melasma, female sex hormones might induce pigmentation on the face of persons who are genetically prone to hyperpigmentation. To reach the maintenance stage, however, other modifications, such as UV factors, are necessary. UV light turns the pre-excited status of melanocytes by increased female sex hormones into the activated, highly melanogenic status. These modifications in the skin environment help the pigmentation in melasma to stay for an extended time in the skin. After this specific period, melanocytes in melasma areas pass through the point of no return until the major sex hormonal factor disappears. Melasma can disappear upon destruction of these balances. ABNOM has been reported only in Japanese individuals, and it seems to be an entity of circumscribed dermal melanocytosis. Clinically, it is an acquired blue-brown macule on the face that occurs bilaterally on the forehead, temples, eyelids,
PIGMENTARY DISORDERS IN THE SOUTH EAST
cheeks, and nose. It commonly involves women in the fourth of fifth decades of life. It differs from the nevus of Ota by the lack of ocular or mucous membrane involvement. Histologically, the lesion is composed of dermal melanocytes scattered in the upper and middle portion of the dermis. Specific pigmentary disorders in Asians Mongolian spot Mongolian spot is a congenital, blue-gray, macular lesion commonly observed among Asian infants. It is generally located on the lumbosacral skin or on the buttocks. Aberrant Mongolian spots refer to lesions that are present outside of the lumbosacral area. Mongolian spot is often present at birth and usually disappears during childhood, although sometimes it may persist into adulthood. The persistence of Mongolian spots into adulthood has been reported in 4.6% of young Japanese adults. No melanomas have been reported to occur in these lesions [23]. The diagnosis is based on clinical morphology and, when in doubt, is confirmed by histopathologic examination of lesions. Histologically, Mongolian spot shows elongated melanocytes located deep in the dermis. Melanocytes are not normally present in the dermis, and researchers believe that these ectopic melanocytes represent pigment cells that have been interrupted in their migration from the neural crest to the epidermis. Nevus of Ota and nevus of Ito The nevus of Ota is most commonly seen in Asians. It is said to occur in up to 0.8% of dermatologic outpatients in Japan. It has been reported in Chinese, East Indian, black, and, rarely, white persons. Women are affected five times as frequently as men. The nevus of Ito, first described by Ito in 1954, has the same features as the nevus of Ota except that the pigmentary changes occur in the distribution of the posterior supraclavicular and lateral cutaneous brachial nerves and involve the shoulder, supraclavicular areas, sides of the neck, upper arm, and scapular and deltoid regions. It may occur alone or may be seen in conjunction with the nevus of Ota [23]. Acquired bilateral nevus of Ota–like macules ABNOM shows bilateral blue-brown macules over the forehead, temples, eyelids, malar area,
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root and alae of nose sparing ocular and mucosal membrane. When the number of dermal melanocytes is low, the color looks brown and simulates the color of melasma. In cases of ABNOM confined only to the malar area or forehead, diagnosis is difficult because it mimics the centrofacial type of melasma [21]. Without careful examination of alae on the nose, forehead, and eyelids, brown ABNOM looks just like melasma. In these instances, only the pathologic examination can differentiate both conditions. Because ABNOM is frequent in Asian individuals such as Koreans and Japanese, some dermatologists who work with different skin types (white, black) might ignore it because of lack of experience. Histologically, fusiform-elongated dendritic melanocytes are scattered among the collagen with scattered melanophages. The correct diagnosis is essential because the treatment is different: melasma is treated with topical application, ABNOM is treated with lasers.
Summary Because skin is the most visible organ, it significantly determines one’s impression. Longlasting pigmentary disorders that result in unfavorable appearances can cause psychological effects, such as shame, anxiety, and lack of confidence, especially in Asians who have vitiligo and melasma. It is critical not to dismiss the emotional distress but motivate patients to the end of treatment. To approach pigmentary disorders in persons from South East Asia, it is important to have a comprehensive understanding and information on the nature of Asian skin and the treatments and related prognostic factors of the two most noteworthy chronic and recalcitrant diseases: vitiligo and melasma.
References [1] Halder RM. Ethnic skin disorders overview. J Am Acad Dermatol 2003;48(Suppl 6):143–8. [2] Bang D, Cho CK, Lee SN. A statistical study of dermatoses during the last 5 years (1976–1980). Korean J Dermatol 1983;21(1):37–45. [3] Song DH, Kang WH, Lee SN. A statistical study of dermatoses in Wonju area during the recent 5 years (1980–1984). Korean J Dermatol 1988; 26(1):34–44. [4] Chang SN, Lee JS, Lee SH, et al. A statistical study of dermatoses in the Gangnam area of Seoul. Korean J Dermatol 1994;32(5):872–85.
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[5] Bak H, Ahn SK. A statistical study of dermatoses (2000–2004). Korean J Dermatol 2005;43(9): 1192–9. [6] Hu Z, Liu JB, Ma SS, et al. Profile of childhood vitiligo in China: an analysis of 541 patients. Pediatr Dermatol 2006;23(2):114–6. [7] Yip SY. The incidence of skin diseases in Hong Kong: a comparison with the five-year survey from Sendai. J Dermatol 1979;6(1):9–11. [8] Petit JH. Perspectives in dermatology: Malaysia. Int J Dermatol 1976;15(7):505–12. [9] Wisuthsarewong W, Viravan S. Analysis of skin diseases in a referral pediatric dermatology clinic in Thailand. J Med Assoc Thai 2000;83(9):999–1004. [10] Sivayathorn A. Melasma in orientals. Clin Drug Invest 1995;10(Suppl 2):34–40. [11] Porter JR, Beuf A, Lerner A, et al. Response to cosmetic disfigurement: patients with vitiligo. Cutis 1987;39(6):493–4. [12] Lerner AB. Vitiligo. J Invest Dermatol 1959;32(2): 285–310. [13] Ortonne JP, Mosher DB, Fitzpatrick TB. Vitiligo and other hypomelanoses of hair and skin. New York: Plenum Publishing; 1983. p. 147–8. [14] Koga M. Vitiligo: a new classification and therapy. Br J Dermatol 1977;97(3):255–61.
et al [15] Koga M, Tango T. Clinical features and course of type A and type B vitiligo. Br J Dermatol 1988; 118(2):223–8. [16] Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. J Am Acad Dermatol 1996; 35(5):671–4. [17] Barona MI, Arrunategui A, Falabella R, et al. An epidemiologic case-control study in a population with vitiligo. J Am Acad Dermatol 1995;33(4):621–5. [18] Fitzpatrick TB. Pathophysiology of hyperpigmentation. Clin Drug Invest 1995;10(Suppl 2):17–26. [19] Brein TJO, Dyall-Smith D, Hall AP. Melasma of forearms. Australas J Dermatol 1997;38(1):35–7. [20] Sanchez NP, Pathak MA, Sato S, et al. Melasma: a clinical, microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol 1981;4(6): 698–710. [21] Hori Y, Kawashima M, Oohara K, et al. Acquired, bilateral nevus of ota-like macules. J Am Acad Dermatol 1984;10(6):961–4. [22] Kauh YC, Zachian TF. Melasma. In: Mallia C, Uitto J, editors. RheumaDerm: current issues in rheumatology and dermatology. New York: Kluwer Academic/Platinum Publishers; 1999. p. 491–9. [23] Lee CS, Lim HW. Cutaneous diseases in Asians. Dermatol Clin 2003;21(4):669–77.
Pigmentary Disorders in the South East Seung-Kyung Hann, MD, PhDa,*, Sungbin Im, MD, PhDa, Won Soon Chung, MDa, Do Young Kim, MDb a
Drs. Woo and Hann’s Skin Clinic, Department of Dermatology and Cutaneous Biology Research Institute, 15-3 Galwol-Dong, Yongsan-Gu, Seoul 120-752, Korea b Yonsei University College of Medicine, Seoul, Korea
Dermatologic diseases that commonly occur in Asians are xerosis, pruritus, nummular dermatitis, dyshidrosis, atopic dermatitis, melasma, photodermatoses, psoriasis, vitiligo, lichen amyloidosis, nevus of Ito, nevus of Ota, Mongolian spot, longitudinal pigmented band of nail, Bowen’s disease, pigmented basal cell carcinoma, and pigmented Ofuji’s disease [1]. Of utmost concern among these diseases are pigmentary disorders, which are common in Asians [1]. Pigmentary disorders account for 14.2% of all dermatologic disease of individuals of Hispanic race in the United States. Although the exact incidence of pigmentary disorders in Asians has not been determined, it is supposed to be as high as that for Hispanics. These disorders can be psychologically distressing because of their visible nature. From the review of Korean literature, two important pigmentary disorders in Asians are vitiligo and melasma, which are especially resistant to various kinds of conventional treatments and tend to have a chronic progression that makes patients doubt the results and the prognosis. This article introduces new information regarding vitiligo and melasma based on clinical studies of Korean patients and specific pigmentary disorders that occur in Asians. Geographic characteristics of South East Asia Asia can be subdivided into the following areas: South Asia, which includes the subcontinent region of Pakistan, India, and Sri Lanka;
* Corresponding author. E-mail address: [email protected] (S-K. Hann).
South East Asia, which includes the regions of Malaysia, Singapore, Philippines, Thailand, and Indonesia; and East Asia, which includes Japan, Korea, and China. In this article, East Asia and South East Asia are considered the same subdivision to provide a more comprehensive understanding of pigmentation disorders in South East Asia.
Incidence of vitiligo and melasma in South East Asia The incidence of vitiligo and melasma varies depending on nations. Several demographic studies since the early 1980s in Korea suggested that vitiligo accounted for 1.7% to 4.7% of outpatients [2–5]. The estimated prevalence of vitiligo of China was 0.19% in a survey. Vitiligo accounted for 1% of cases reported in Hong Kong and 3% of cases in Malaysia [6–8]. The incidence of vitiligo in childhood was reported to be 4.1% in Thailand [9]. The incidence of melasma in South East Asia was 0.25% to 4% of patients seen in dermatology institutes, with peak incidence at age 30 to 44 years. One survey from a dermatology clinic in Thailand suggested that the prevalence of melasma may be as high as 40% in women and 20% in men [10]. Melasma also accounted for 4% of cases reported in Malaysia and 0.98% of cases reported in Indonesia [10]. In a study of 26,766 patients who attended a dermatologic clinic in Korea, the prevalence of melasma was 3.8% [2]. Because of a selection bias, however, the actual incidence of these diseases in South East is estimated to be higher than in people of other races.
0733-8635/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.det.2007.04.002
derm.theclinics.com
432
HANN
Vitiligo Vitiligo is a pigmentary disorder of major concern in ethnic populations. The well-circumscribed depigmented macules are more visible in individuals with darker skin and cause significant cosmetic and psychological concerns in darker skinned individuals. Vitiligo affects approximately 0.5% to 2% of the population, without racial, gender, or regional differences [11,12]. Although many studies have concentrated on its pathogenesis, the hypothesis concerning the pathogenesis of vitiligo has not yet been fully elucidated. Vitiligo has various clinical features as reported by investigators, but the number of patients studied is limited and there is no uniform classification on which all clinicians agree. Understanding these characteristics can give valuable information not only regarding differentiating vitiligo from other pigmentary disorders but also in treating vitiligo with the proper modalities and predicting the prognosis of vitiligo to a certain degree. Classification Currently, a classification describing vitiligo as generalized or localized type according to the distribution of lesions is widely used (Box 1). The localized type is subdivided into focal, segmental, and mucosal subtypes, whereas the generalized type is subdivided into acrofacial, vulgaris, and universal subtypes. An overlap of various types can be classified as mixed type [13]. New classification In 1977, Koga [14] performed a sweat secretion stimulation test using physiostigmine and accordingly reclassified vitiligo into nonsegmental type (type A) and segmental type (type B). He
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proposed that the nonsegmental type results from immunologic mechanisms, whereas the segmental type results from dysfunction of the sympathetic nervous system in the affected skin [14]. After Koga’s report suggested that these two types differed in pathogenesis and clinical presentation, many clinicians began to take an interest in segmental vitiligo, because most of these cases did not cross the midline and were distributed along a unilateral dermatome, which meant the ability to predict the prognosis [15,16]. Segmental-type vitiligo is usually localized to one dermatome, shows relatively stable disease activity after its initial rapid spreading phase, and is associated with a significantly lower rate of autoimmune diseases than nonsegmental type (Fig. 1) [15,16]. According to these characteristics, vitiligo also can be classified into three major clinical types: segmental (unilateral), nonsegmental (bilateral), and mixed (Box 2). The segmental form generally does not cross the midline and does not have a classical dermatomal distribution but affects one segment of the integument. The segment might be composed of several or parts of several adjacent dermatomes or have no relationship to dermatomes at all or any other lines, such as Blaschko’s line or acupuncture lines. The progression is usually limited to months or a few years [16,17]. The nonsegmental form is characterized by bilateral, usually symmetrical, depigmented macules. It is further subdivided into localized type, including focal and mucosal subtypes, and generalized type, including acrofacial, vulgaris, and universal subtypes. The former type is characterized by involvement of limited small areas of the integument, and the latter type is characterized by widespread extensive depigmentation that most commonly spreads
Box 1. Classification of vitiligo according to the distribution of lesions Localized Focal Segmental Mucosal Generalized Acrofacial Vulgaris Universal Mixed Fig. 1. Segmental vitiligo on face.
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Box 2. Classification of vitiligo with emphasis on segmental vitiligo Segmental (unilateral) Nonsegmental (bilateral) Localized Focal Mucosal Generalized Acrofacial Vulgaris Universal Mixed: segmental and nonsegmental throughout the life of the individual. There is also a rare variety of generalized vitiligo that seems to be a manifestation of a systemic autoimmune disease. This disorder is manifested by vitiligo with multiple endocrine failures, such as diabetes mellitus, adrenal insufficiency, and thyroid dysfunction. All of the latter endocrine abnormalities seem to be caused by autoantibodies, but the cause of the loss of melanocytes remains unidentified. Segmental vitiligo The incidence of segmental type varies; one group of investigators reported 5%, whereas another group reported 27.9%, and previous Korean studies showed a range between 5.5% and 16.1% [16]. Vitiligo develops at all ages, but it usually occurs in young people between the ages of 10 and 40. According to an epidemiologic study reported in 1977, however, approximately half of the patients developed vitiligo after 40 years of age, which was different from other clinic-based studies. On the other hand, one group reported that onset of nonsegmental vitiligo could occur at any age, whereas segmental vitiligo generally affected young persons. In our study, segmental vitiligo developed before 30 years of age in 87% of patients, 41.3% of whom were younger than age 10 [16]. The commonly involved sites of vitiligo are exposed areas, such as the face and dorsum of the hand. In the case of segmental vitiligo, the involved sites were the face, trunk, neck, extremities, and scalp, in descending order (Table 1). Dermatomal distribution revealed that the trigeminal nerve was most frequently involved, followed by the thoracic, cervical, lumbar, and sacral nerves (Table 2).
Table 1 Site of segmental vitiligo Site
Men (%) Women (%) Total (%)
Head and neck Face Neck Scalp Trunk Chest and abdomen Back Extremities Upper extremities Lower extremities Total no. of patients
57 (62.6) 87 (65.9)
144 (64.6)
49 7 1 21 17
114 27 3 55 48
(53.8) (7.7) (1.1) (23.1) (18.7)
65 20 2 34 31
(49.2) (15.2) (1.5) (25.8) (23.5)
4 (4.4) 3 (2.3) 13 (14.3) 11 (8.3) 7 (7.7) 7 (5.3) 6 (6.6) 91
7 (3.1) 24 (10.8) 14 (6.3)
4 (3.0) 132
(51.1) (12.1) (1.4) (24.7) (21.5)
10 (4.5) 223
Hand dominancy also was appraised to determine whether there is any relation to vitiligo involving the right or left side of the body, but there was no significant relationship between these two factors. The left side was slightly more involved, regardless of the dominant hand. Poliosis, known to be associated with vitiligo in 8.9% to 45% of cases, occurred in 48.6% of patients in our study. The eyebrows and scalp hair were mostly involved (46.7%), which occurs because when vitiligo involves the face, neck, and scalp, poliosis of the eyebrows and scalp hair is also commonly present (67.4%). Most segmental vitiligo usually persists unchanged for the rest of a patient’s life after initially spreading rapidly in the affected dermatomal area. Sometimes it can progress again after several years, however. Segmental vitiligo usually spreads over the affected area, so the progression pattern can be detected and predicted easily. Lesions may spread out away from the affected site, however. This type of vitiligo is called the mixed type of segmental vitiligo. Early segmental vitiligo usually appears as a single oval-shaped white macule or a patch, which is difficult to differentiate from Table 2 Dermatomal distribution of segmental vitiligo Dermatome
Men (%)
Trigeminal Cervical Thoracic Lumbar Sacral Total
49 12 19 10 1 91
(53.9) (13.2) (20.9) (11.0) (1.1)
Women (%) 65 26 31 4 2 128
(50.8) (20.3) (24.2) (3.1) (1.6)
Total (%) 114 38 50 14 3 219
(52.1) (17.4) (22.8) (6.4) (1.4)
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focal-type vitiligo until a typical distribution of lesions has appeared. Depigmentation of hair in segmental vitiligo Melanocytes of the hair bulb are responsible for hair color. They transfer their melanosomes to the surrounding hair keratinocytes. In the hair follicles, melanin granules are mainly in the cortex, where their long axes parallel the hair surface. Involvement of hair in vitiligo macules varies, which indicates that the follicular compartment of the melanocyte organ may be spared while the vitiligo process destroys the epidermal compartment. This dissociated behavior of epidermal and follicular melanocytes is common in vitiligo. The incidence of body leukotrichia in the different series of the literature varies from 10% to more than 60%. Poliosis occurs in patients with nonsegmental or segmental vitiligo. The occurrence of leukotrichia on eyebrows, scalp, and eyelashes was estimated at 48.6% in a group of 101 patients with segmental vitiligo [16]. If the cases of body involvement of segmental vitiligo were excluded, the incidence of leukotrichia of segmental vitiligo would be higher than previous reports. It is assumed that segmental vitiligo often destroys epidermal and follicular melanocytes in the early phase of disease compared with nonsegmental vitiligo. The presence of leukotrichia has been accorded special significance. In these instances, repigmentation of hair is difficult to treat with ultraviolet (UV), medical, or topical treatment. On the other hand, transplantation of melanocytes is required for rapid and complete repigmentation.
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linear and may evolve into an almost starburst distribution. Most lesions of melasma are composed of a single large patch on one side of the face with or without small satellite lesions. All lesions have a symmetrical distribution pattern. Hypermelanotic lesions on the face with unilateral involvement cannot be diagnosed as melasma. Melasma only rarely shows pigmented spots in the midline of the face. The color of melasma varies from brown to gray to blue, depending on the skin type of patients and amount of melanin deposited in the skin. Most darkly pigmented patches occur over the bony prominences of the malar regions, which receive the greatest amount of sunlight. The size of patches varies, from a limited area of malar or infraorbital to a large patch covering most of the side of face. The borders are usually well demarcated from the normal skin, but the outlines are irregular. Melasma itself does not have any subjective symptoms. It does not have preceding signs of inflammation, such as itching or erythema. Melasma is not accompanied by any other systemic symptoms. No elevated lesion or changes of skin surface texture could be diagnosed as melasma. Melasma only involves the skin, and no mucosal involvementdincluding of the eye and lipdhas been reported.
Melasma in forearm Areas other than the facedparticularly the forearms and the neckdalso may be involved, usually in association with facial hyperpigmentation [19]. The pigmentary changes were macular, with a confluent or speckled pattern, and, like facial melasma, often with a sharp edge. Clinical classification
Melasma Melasma is a common pigmentary disorder in Asians. It tends to occur much more frequently in Asian women than white women. Clinical manifestation Melasma is common, particularly in women of childbearing age. Melasma is a common disorder of pigmentation seen frequently in essentially healthy women between early adulthood and menopause. The incidence of male cases has been reported to be up to 10% of total cases [18]. The shape of melasma is blotchy, irregular, arcuate, or polycyclic, but the lesions may be
Melasma is classified clinically into three types according to the distribution pattern of lesions: centrofacial pattern (63%) (Fig. 2), malar pattern (21%) (Fig. 3), and mandibular pattern (16%). It became the consensus classification of melasma [20]. This classification only categorized and collected the distribution patterns of melasma simply by the judgment of authors. This classification does not have a direct correlation with age, skin types of patients, aggravation, or underlying etiologic factors of melasma, such as UV light, pregnancy, or oral contraceptive use. These clinical patterns of melasma also are not correlated with Wood’s light examination and histopathologic examination.
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Our experience of melasma is different from Sanchez’s patterns. Our data on the ratio of
Korean melasma pattern are centrofacial pattern, 52%, malar pattern, 48%, and mandibular pattern, none. Practically, it is difficult to classify melasma into these categories. Melasma always involves either the infraorbital or malar area. Basically, facial melasma lesions are located on the cheek in all cases. In this classification, the involvement of the cheeks and nose is overlapping. Melasma on the nose, lips, and other midline of face is rarely seen. The periorbital area is also rarely involved, and melasma always spares the area related to eyeball movement. Based on these findings, melasma is characterized by infrequent involvement of the periorbital areas of the face. By its definition, centrofacial types should be differentiated from acquired bilateral nevus of Ota–like macules (ABNOM) (Fig. 4) [21]. In our retrospective clinicopathologic experience, the misdiagnosis rate of ABNOM as melasma among our dermatology staff is approximately 14%, especially when the clinical color of ABNOM is close to brown. ABNOM is common in East Asians, such as Koreans, Japanese, and Chinese. It should be clinically differentiated from melasma. Personally, we prefer not to classify the clinical pattern of melasma because this classification does not correlate with the clinical or pathogenic processes of melasma.
Fig. 3. Malar pattern of melasma.
Fig. 4. Acquired bilateral nevus of Ota–like macules.
Fig. 2. Centrofacial pattern of melasma.
Clinical characteristics of Korean patients who have melasma
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Clinical classification with Wood’s light Clinical typing under Wood’s light illumination has been used to aid diagnostic clues of histologic patterns [20]. The various types are as follows: (1) epidermal type, which exhibits enhancement of color contrast between affected and normal skin when examined with Wood’s light; (2) dermal type, in which there is no enhancement of color contrast by scattering and re-emission that produces a blue or blue-gray color; (3) mixed dermal-epidermal type, in which there is enhancement of lesions in some areas and no enhancement of lesions in the other areas of the same patient; (4) indeterminate type, which appears in patients of dark complexion (skin types V and VI), in whom the lesionsdfor lack of contrastdare not discernible on Wood’s light examination, perhaps because of the increased number of melanosomes in the normal skin of black individuals. Wood’s light classification is used to predict the clinical effectiveness of treatment on epidermal type. Wood’s light is absorbed by the melanin, and the intensity of the melanin color is exaggerated by viewing with Wood’s light. This Wood’s light contrast may partly work in skin types I and II but not in brown or black skin types. However, our unpublished data on the correlation of Wood’s light findings to the histologic findings in Korean individuals failed to apply to this Wood’s light classification. From our experience, it was hard to define the color contrast between affected and normal skin. Even after we arbitrarily classified, the Wood’s light classification did not match the histologic findings. In a clinical study conducted with East Asian people, such as Koreans, most patients showed epidermal melasma, a few manifested a mixed type, and no patients exhibited solely dermal or inapparent-type melasma. This observation raised a question about the usefulness of Wood’s light and the existence of dermal-type melasma [22]. We prefer not to use the Wood’s light to examine patients who have melasma.
New classification of melasma We propose to divide melasma clinically into transient or persistent types. The transient type of melasma occurs during pregnancy or with use of the contraceptive pill, and it disappears within 1 year of cessation of stimulating hormonal influence. In this type, the melanocytes in the lesional skin are activated in a reversible way so
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they can be normalized after removal of stimuli. This type progresses to the persistent type with a booster stimulus, such as UV exposure. Avoidance of sun exposure in the early stage of melasma is essential. The persistent type includes melasma more than 1 year after the hormonal influence has been removed, which is believed to be caused by the persistent activation or partial transformation of melanocytes in lesional skin in response to UV rays or other factors. Direct UV effect on melanocytes or indirect stimulation of the environment could influence melanocytes. Keratinocytes and dermal components are in charge of this response.
Progression of melasma The natural progression of melasma can be divided into three stages: developmental stage, maintenance stage, and resolution stage. The developmental stage involves patients who develop melasma during pregnancy or while taking oral contraceptives, and the underlying causes are still persisting. The maintenance stage involves melasma that persists even after the cessation of causes or idiopathic melasma in women and men. This stage belongs to limited, constitutive tanning or prolonged, facultative tanning. The resolution stage involves melasma in the stage of disappearing or melasma that has disappeared spontaneously. This stage has a higher chance of developing melasma again during subsequent pregnancy or contraceptive pill use or while using hormone replacement therapy during menopause. To put patients into the developmental stage of melasma, female sex hormones might induce pigmentation on the face of persons who are genetically prone to hyperpigmentation. To reach the maintenance stage, however, other modifications, such as UV factors, are necessary. UV light turns the pre-excited status of melanocytes by increased female sex hormones into the activated, highly melanogenic status. These modifications in the skin environment help the pigmentation in melasma to stay for an extended time in the skin. After this specific period, melanocytes in melasma areas pass through the point of no return until the major sex hormonal factor disappears. Melasma can disappear upon destruction of these balances. ABNOM has been reported only in Japanese individuals, and it seems to be an entity of circumscribed dermal melanocytosis. Clinically, it is an acquired blue-brown macule on the face that occurs bilaterally on the forehead, temples, eyelids,
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cheeks, and nose. It commonly involves women in the fourth of fifth decades of life. It differs from the nevus of Ota by the lack of ocular or mucous membrane involvement. Histologically, the lesion is composed of dermal melanocytes scattered in the upper and middle portion of the dermis. Specific pigmentary disorders in Asians Mongolian spot Mongolian spot is a congenital, blue-gray, macular lesion commonly observed among Asian infants. It is generally located on the lumbosacral skin or on the buttocks. Aberrant Mongolian spots refer to lesions that are present outside of the lumbosacral area. Mongolian spot is often present at birth and usually disappears during childhood, although sometimes it may persist into adulthood. The persistence of Mongolian spots into adulthood has been reported in 4.6% of young Japanese adults. No melanomas have been reported to occur in these lesions [23]. The diagnosis is based on clinical morphology and, when in doubt, is confirmed by histopathologic examination of lesions. Histologically, Mongolian spot shows elongated melanocytes located deep in the dermis. Melanocytes are not normally present in the dermis, and researchers believe that these ectopic melanocytes represent pigment cells that have been interrupted in their migration from the neural crest to the epidermis. Nevus of Ota and nevus of Ito The nevus of Ota is most commonly seen in Asians. It is said to occur in up to 0.8% of dermatologic outpatients in Japan. It has been reported in Chinese, East Indian, black, and, rarely, white persons. Women are affected five times as frequently as men. The nevus of Ito, first described by Ito in 1954, has the same features as the nevus of Ota except that the pigmentary changes occur in the distribution of the posterior supraclavicular and lateral cutaneous brachial nerves and involve the shoulder, supraclavicular areas, sides of the neck, upper arm, and scapular and deltoid regions. It may occur alone or may be seen in conjunction with the nevus of Ota [23]. Acquired bilateral nevus of Ota–like macules ABNOM shows bilateral blue-brown macules over the forehead, temples, eyelids, malar area,
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root and alae of nose sparing ocular and mucosal membrane. When the number of dermal melanocytes is low, the color looks brown and simulates the color of melasma. In cases of ABNOM confined only to the malar area or forehead, diagnosis is difficult because it mimics the centrofacial type of melasma [21]. Without careful examination of alae on the nose, forehead, and eyelids, brown ABNOM looks just like melasma. In these instances, only the pathologic examination can differentiate both conditions. Because ABNOM is frequent in Asian individuals such as Koreans and Japanese, some dermatologists who work with different skin types (white, black) might ignore it because of lack of experience. Histologically, fusiform-elongated dendritic melanocytes are scattered among the collagen with scattered melanophages. The correct diagnosis is essential because the treatment is different: melasma is treated with topical application, ABNOM is treated with lasers.
Summary Because skin is the most visible organ, it significantly determines one’s impression. Longlasting pigmentary disorders that result in unfavorable appearances can cause psychological effects, such as shame, anxiety, and lack of confidence, especially in Asians who have vitiligo and melasma. It is critical not to dismiss the emotional distress but motivate patients to the end of treatment. To approach pigmentary disorders in persons from South East Asia, it is important to have a comprehensive understanding and information on the nature of Asian skin and the treatments and related prognostic factors of the two most noteworthy chronic and recalcitrant diseases: vitiligo and melasma.
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[5] Bak H, Ahn SK. A statistical study of dermatoses (2000–2004). Korean J Dermatol 2005;43(9): 1192–9. [6] Hu Z, Liu JB, Ma SS, et al. Profile of childhood vitiligo in China: an analysis of 541 patients. Pediatr Dermatol 2006;23(2):114–6. [7] Yip SY. The incidence of skin diseases in Hong Kong: a comparison with the five-year survey from Sendai. J Dermatol 1979;6(1):9–11. [8] Petit JH. Perspectives in dermatology: Malaysia. Int J Dermatol 1976;15(7):505–12. [9] Wisuthsarewong W, Viravan S. Analysis of skin diseases in a referral pediatric dermatology clinic in Thailand. J Med Assoc Thai 2000;83(9):999–1004. [10] Sivayathorn A. Melasma in orientals. Clin Drug Invest 1995;10(Suppl 2):34–40. [11] Porter JR, Beuf A, Lerner A, et al. Response to cosmetic disfigurement: patients with vitiligo. Cutis 1987;39(6):493–4. [12] Lerner AB. Vitiligo. J Invest Dermatol 1959;32(2): 285–310. [13] Ortonne JP, Mosher DB, Fitzpatrick TB. Vitiligo and other hypomelanoses of hair and skin. New York: Plenum Publishing; 1983. p. 147–8. [14] Koga M. Vitiligo: a new classification and therapy. Br J Dermatol 1977;97(3):255–61.
et al [15] Koga M, Tango T. Clinical features and course of type A and type B vitiligo. Br J Dermatol 1988; 118(2):223–8. [16] Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208 patients. J Am Acad Dermatol 1996; 35(5):671–4. [17] Barona MI, Arrunategui A, Falabella R, et al. An epidemiologic case-control study in a population with vitiligo. J Am Acad Dermatol 1995;33(4):621–5. [18] Fitzpatrick TB. Pathophysiology of hyperpigmentation. Clin Drug Invest 1995;10(Suppl 2):17–26. [19] Brein TJO, Dyall-Smith D, Hall AP. Melasma of forearms. Australas J Dermatol 1997;38(1):35–7. [20] Sanchez NP, Pathak MA, Sato S, et al. Melasma: a clinical, microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol 1981;4(6): 698–710. [21] Hori Y, Kawashima M, Oohara K, et al. Acquired, bilateral nevus of ota-like macules. J Am Acad Dermatol 1984;10(6):961–4. [22] Kauh YC, Zachian TF. Melasma. In: Mallia C, Uitto J, editors. RheumaDerm: current issues in rheumatology and dermatology. New York: Kluwer Academic/Platinum Publishers; 1999. p. 491–9. [23] Lee CS, Lim HW. Cutaneous diseases in Asians. Dermatol Clin 2003;21(4):669–77.