White : Diseases of the Skin - Pigmentary Disorders

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Gary M. White & Neil H. Cox

Diseases of the Skin

21	Pigmentary Disorders

HYPOPIGMENTATION

Generalized hypopigmentation

This occurs in albinism (Ch.19) and in some rarer genodermatoses such as Chediak-Higashi syndrome. It may also be acquired, for example loss of skin pigment in hypopituitarism and of hair pigment in pernicious anemia or in chronic protein deficiency.

Vitiligo

Etiology and pathogenesis

Vitiligo is the complete loss of pigmentation in discrete patches. The incidence of vitiligo is about 1-2% around the world. Males and females are equally affected. Peak onset is 10-30 years of age. The cause of vitiligo is unknown, although it appears that the patient’s immune system is attacking and destroying the skin’s pigment cells (i.e. melanocytes) (Fig.21.1). Family history is positive approximately 20-30% of the time; vitiligo is more likely to be familial in patients with onset before 20 years of age. Various autoimmune conditions (e.g. thyroid disease and pernicious anemia) are associated with vitiligo, but the frequency is not sufficiently high to warrant routine screening of patients with vitiligo. Koebnerization is seen with vitiligo.

Clinical

The onset and slow progression of sharply depigmented, often symmetric patches (Figs 21.2-21.6), occurring anywhere but with preference for the face, hands, feet, and genitalia, is characteristic. A peripheral hint of erythema may be seen in some patients. Hair in involved areas may loose pigment and turn white (leukotrichia, Fig. 21.5). The use of a Wood’s light is very helpful in determining the extent of lesions, as it will accentuate their appearance. In younger patients, halo nevi are often associated (Fig. 21.3b).
A less common variant is segmental vitiligo, which tends to have its onset early in life and is asymmetric (often involving a dermatome). In the uncommon pattern called trichrome vitiligo, three shades of color-from pure white (complete depigmentation of skin) to an intermediate color to the normal skin-give the clinical appearance of three colors (Fig. 21.4b).
Those with onset over 40 years of age should have a complete skin examination to exclude coexistent melanoma.

Fig. 21.1 Vitiligo in a typical location.

Fig. 21.2 Vitiligo. (a) Note the symmetry and sharp demarcation of the edges. (b) Vitiligo with marginal hyperpigmentation in an atopic patient.

Fig. 21.3 (a) Halo nevi with vitiligo. (b) Multiple halo nevi. Multiple halo nevi where the nevi are unapparent (having been mostly removed by the body's immune attack) may mimic vitiligo. The clinical tip-off is that the lesions are all circular and of similar size.

Fig. 21.4 (a) Segmental vitiligo. In this distinct variant of vitiligo, an acquired depigmented patch of skin in a segmental or dermatomal pattern occurs. In contrast to typical vitiligo, new lesions cease after 1 year, onset is in childhood in the majority, koebnerization does not occur, halo nevi are not associated, and response to PUVA therapy is poor. (b) Trichrome vitiligo. Occasionally an intermediate color may be present, making the patient three-colored. (Courtesy of Michael O. Murphy, M.D.)

Fig. 21.5 Vitiligo with leukotrichia. Hairs within patches of vitiligo often lose their color.

Fig. 21.6 Follicular repigmentation of vitiligo. When vitiligo repigments, it often does so initially about the hair follicles.

Fig. 21.7 Chemical leukoderma. Complete depigmentation of the skin may occur when certain chemicals come in contact with the skin, in this case a phenol-containing germicide that the patient used routinely at work to disinfect items.

Differential diagnosis

This is discussed in Table 21.1. The main considerations are a chemical leukoderma from industrial exposure to hydroquinones, catechols, phenols (Fig. 21.7), or mercaptoamines (Fig. 21.8), and halo nevi.

Treatment

The most important part of therapy is to explain to the patient that vitiligo is not dangerous or contagious. It can, however, cause much psychologic stress (Fig.21.9). Note that parents of children with vitiligo often have extreme guilt. They may push for therapy when treatment is not justi?ed. If the vitiligo is not very bothersome, simple observation may be all that is indicated. Indeed, for children of relatively light skin tone, sunscreen and observation is the best course.

Table 21.1 DIFFERENTIAL DIAGNOSIS OF WHITE PATCHES (LOCALIZED LOSS OF PIGMENTATION

Pigmentation	Congenital	Acquired
Depigmented	Vitiligo Piebaldism_a	Vitiligo Chemical leukoderma Halo nevi
Hypopigmented	Tuberous sclerosis_a Nevus depigmentosus Incontinentia pigmenti achromians (hypomelanosis) of Itoa Nevus anemicus	Postinflammatory hypopigmentation Idiopathic guttate hypomelanosis Pityriasis versicolor Lichen sclerosus Morphea Discoid or subacute cutaneous lupus erythematosus (older lesions) Sarcoidosis Cutaneous T-cell lymphoma Leprosy Spirochete infections: pinta, yaws Syphilis Onchocerciasis Addison disease and thyrotoxicosis (increased pigmentation but may havevitiligo-like areas)

_aSeveral other rare genodermatoses also have localized hypopigmentation as a feature.

Fig. 21.8 Chemical leukoderma in a man working in the manufacture of para-tertiary butyl phenol. (Courtesy of Dr. C. J. Stevenson.)

Fig. 21.9 Vitiligo, diffuse. Such diffuse loss of pigmentation can be psychologically devastating. (Courtesy of Theodore Sebastian, M.D.)

Fig. 21.10 Topical PUVA treatment of vitiligo. Limited areas of vitiligo may be treated with topical application of psoralen followed by exposure to UV light. Burning is the main risk. Repigmentation, especially at the edges, may be irregular.

    If treatment is desired, tacrolimus 0.1% ointment b.i.d. over 2-3 months combined with sun exposure has been shown to help repigment the skin, especially of the sun-exposed areas. It may be combined with narrow-band UVB therapy with added benefit. Alternatively, a topical corticosteroid in the morning (hydrocortisone 2.5% for the eyelids, mometasone furoate ointment for the body) and topical calcipotriene (capitotriol) ointment in the evening was shown to be highly effective in children, and adults would probably benefit as well. For most therapies, the face and neck respond best and children respond better than adults.
    Sun protection is important. Sunscreens should be applied to the vitiliginous areas to prevent burning and, particularly in pale-skinned patients, to the normal skin to prevent tanning (as this may produce adequate, if pale, color-matching such that no other interventions are required). Cosmetic camouflages are useful in selected patients but are not always ideal in children, as they often come off during play. Some stains have been used (e.g. Vitadye and self-tanners), but the color match is not always good and the overlap may result in hyperpigmented areas. Patients should be told that artificial tans do not provide sun protection.
    Advanced therapies include narrow-band UVB, laser, 308-nm monochromatic light, 308-nm excimer laser, oral PUVA, topical PUVA (Fig.21.10), and melanocyte transplantation. Total and permanent depigmentation with 20% monobenzylether of hydroquinone is the last resort for widespread vitiligo, recalcitrant to treatment, in an adult (Fig. 21.11).

PRACTICE POINTS

•	Applying sunscreens to the normal skin of patients with vitiligo, to prevent tanning, may produce adequate, if pale, color-matching such that no other interventions are required.
•	Artificial tans do not in themselves provide sun protection for areas of vitiligo, and those that contain added sunscreen do not normally have an adequate strength or long enough lasting agent to prevent burning of depigmented skin.
•	Relatively new treatment options for vitiligo include tacrolimus or calcipotriene (calcipotriol), with or without sunlight or phototherapy.

Postinflammatory hypopigmentation
Etiology and pathogenesis
A variety of inflammatory conditions may disrupt the pigmentary system enough to leave a hypopigmented patch. The color usually returns over several months if the inciting condition has resolved.

Clinical
A hypopigmented (not depigmented) spot remains in the site of a prior inflammatory process (Fig.21.12). In cases where the initial condition is nearly unapparent, the occurrence of the white spot may be the first thing noted by the patient or parent. This is often true in pityriasis alba (Fig. 21.13).

Differential diagnosis
This is discussed in Table 21.1.

Treatment

In contrast to postinflammatory hyperpigmentation, the process of postinflammatory hypopigmentation is always epidermal. Thus once the precipitating disease has resolved, normalization of pigmentation should soon follow (e.g. in 1-2 months). It must be emphasized, however, that any residual activity of the precipitating disease (e.g. xerosis, eczema, and psoriasis) should be sought and, if present, treated. Any dry skin should be treated with emollient cream once or twice daily. Lotions, with their high water content, are less effective. If any erythema suggesting persistent inflammation is present, a topical steroid should be prescribed. For young children with pityriasis alba of the face, hydrocortisone (1% cream) is effective (see Fig. 6.36).

Fig. 21.11 Depigmentation with monobenzylether of hydroquinone. A patient with vitiligo had permanently depigmented the exposed areas of her body providing a uniform, albeit white, color. The patient was informed and accepted the fact that depigmentation might occur at areas distant from the site of application of the monobenzylether of hydroquinone.

Fig. 21.12 Post-inflammatory hypopigmentation. (a) Post-inflammatory hypopigmentation is not uncommon after a flare of psoriasis - note that there is still some peripheral thickness of the original plaque. (b) However, a possible source of confusion is that vitiligo and psoriasis may coexist.
(c) Hypopigmentation after corticosteroid injection of a joint. Although commoner after more superficial intradermal or soft tissue injections, hypopigmentation due to corticosteroids can occur even after deeper intra-articular injections. (d) Complete depigmentation after cryotherapy. Cryotherapy should not be used in darker-skinned patients as complete depigmentation may result.

Fig. 21.13 Pityriasis alba. Pityriasis alba seems to be a variant of postinflammatory hypopigmentation. The initial event is a patch of eczema that may or may not be noticed. The child then presents with multiple, hypopigmented, ill-de?ned areas on the face or arms. Often, there is a history of atopic dermatitis (see Ch. 6).

Progressive macular hypomelanosis

Periodically, a patient will present with patchy hypopigmentation on the trunk that resembles pityriasis versicolor but that lacks erythema and scale, and is resistant to antifungal treatment (Fig.21.14). Recently, Westerhof and colleagues noted that these lesions show red fluorescence in a follicular pattern only in lesional skin. Furthermore, they were able to culture Propionibacterium acnes from the follicles. They proposed that the P. acnes secretes a factor that interferes with melanogenesis. If true, treatment with tetracyclines might improve this disorder. One of us (GW) treated a patient whose condition cleared on minocycline 100 mg b.i.d. for 3 months.

Nevus depigmentosus (achromic nevus)

This is a congenital, stable, hypopigmented lesion (Fig. 21.15) that may be located randomly, segmentally, linearly, or in a whorled fashion (the last resembling hypomelanosis of Ito). Melanocytes are present histologically but do not produce the usual amount of melanin. Wood’s light accentuates the lesion. Because some pigment is present, perhaps a more accurate name is nevus hypopigmentosus.

Idiopathic guttate hypomelanosis

Complete loss of pigment in tiny macules occurs in idiopathic guttate hypomelanosis. Multiple white macules, usually 1-4mm in diameter, symmetrically distributed on the outer forearms or extensor legs, are characteristic (Fig. 21.16). Women are more commonly affected than men, as are those over 40 years of age. These lesions are benign and no treatment is necessary. Cryotherapy or intralesional triamcinolone has been used.

Hypopigmented and depigmented lesions discussed elsewhere

Lichen sclerosus lesions are characteristically white; this condition is discussed in Chapters 20 (genital lichen sclerosus) and 22 (Fig.21.17). Similarly, lesions of morphea (Ch.13) are typically pale in color, as are many older lesions of discoid or subacute cutaneous lupus erythematosus (Ch. 13).Several pediatric or inherited disorders are characterized at least in part by generalized pigment loss (albinism) or by localized pale or white lesions. The ash leaf spot of tuberous sclerosis is one of the most important (see Fig.19.41) but others, such as hypomelanosis of Ito, also have implications for investigation.Halo nevi are a common disorder and are discussed in Chapter 31.
Pityriasis versicolor (Ch.26) is a common cause of spotty hypopigmentation, usually on the trunk in young adults and often noticed after tanning on holiday. Other infections, such as leprosy or pinta (Ch. 24), may cause localized pigment loss, as may several dermatoses (see Table 21.1).
Not all hypopigmentation is due to loss of melanin pigment: nevus anemicus is actually a vascular disorder caused by localized vasoconstriction (Ch. 15).

Fig. 21.14 (a,b) Progressive macular hypomelanosis. Patchy hypopigmentation of the trunk without erythema or scale is characteristic. Wood’s light examination shows a follicular red fluorescence.

Fig. 21.15 (a) Nevus depigmentosus. (b) Segmental nevus depigmentosus. A congenital white spot in a segmental distribution is typical. (c) A pigmented macule or macules may occasionally develop in the nevus depigmentosus.

Fig. 21.16 Idiopathic guttate hypomelanosis. The cause is unknown.

PRACTICE POINTS

•	Postinflammatory hypopigmentation is commonly of greater concern to the patient than the preceding inflammation, especially in those with darker skins, but strong reassurance can be given for recovery.
•	Pityriasis alba is by far the commonest cause of hypopigmented patches on the face of a child but is often erroneously considered to be vitiligo; the latter is white rather than pale, and lacks the fine scale of pityriasis alba (see Ch. 6 for discussion of this condition).
•	Pityriasis versicolor is by far the commonest cause of hypopigmented patches on the trunk of a young adult; look carefully for scaling, accentuate this by gently scraping lesions with a scalpel, and perform microscopy to prove the diagnosis (Ch. 26). This will also determine whether pityriasis versicolor has been adequately treated: repigmentation may be slow but the scaling resolves with successful treatment.

Fig. 21.17 Lichen sclerosus. (a) Lichen sclerosus et atrophicus in a young child. (b) Submammary lichen sclerosus. The multiple follicular keratoses are a tip-off to the correct diagnosis. (c) Balanitis xerotica obliterans. (Panel b courtesy of Michael O. Murphy, M.D.)

Table 21.2 SOME SYSTEMIC DISORDERS THAT MAY CAUSE HYPERPIGMENTATION

Type of disorder	Examples
Endocrine	Addison disease, Cushing syndrome, Nelson syndrome, pregnancy, oral contraceptives (the last usually causes melasma rather than widespread pigmentation; see text, this chapter); POEMS (polyneuropathy, organomegaly, endocrine disorder, M protein, skin changes) syndrome
Metabolic	Chronic renal failure, hemochromatosis, chronic hepatic cirrhosis (especially primary biliary cirrhosis), carcinoid syndrome, Wilson disease, vitamin B12 deficiency, pellagra, malabsorption, severe malnourishment
Neoplasia	Any advanced lesion causing cachexia, also cutaneous lymphomas, (rarely) diffuse melanosis due to melanoma
Rheumatologic	Still disease, rheumatoid arthritis and Felty syndrome, morphea
Systemic drugs	Especially cytotoxic agents, antimalarials; see Chapter 18