Vitiligo and Other Disorders of Hypopigmentation

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Vitiligo and Other Disorders of Hypopigmentation

Introduction/Definitions

• Leukoderma and hypopigmentation: areas of skin are lighter in color than uninvolved skin, due primarily to a decrease in melanin; decreased blood supply to the skin (e.g. nevus anemicus) can be another cause of leukoderma.

• Hypomelanosis: an absence or reduction of melanin in the skin that may be due to any one or a combination of the following:

1. A decrease in the number of melanocytes (e.g. vitiligo).

2. A decrease in melanin synthesis by a normal number of melanocytes (e.g. albinism).

3. A decrease in the transfer of melanin to keratinocytes (e.g. postinflammatory hypopigmentation).

• Amelanosis: total absence of melanin in the skin.

• Depigmentation: usually implies a total loss of skin color (e.g. as in vitiligo).

• Pigmentary dilution: a generalized lightening of the skin, hair, and eyes (e.g. oculocutaneous albinism); sites of melanin production include the epidermis, hair follicles, pigmented retinal epithelium, and uveal tract.

• Poliosis: a lock of scalp hair, eyebrows, or eyelashes that is white or lighter in color.

• Canities: generalized depigmentation of scalp hair.

• Wood’s lamp examination: the greater the loss of epidermal pigmentation, the more marked the contrast with uninvolved skin on Wood’s lamp examination.

• All disorders of hypopigmentation are more easily observed in darkly pigmented individuals or after a suntan.

Vitiligo

• An acquired disease, due to autoimmune destruction of melanocytes, that is characterized by circumscribed, amelanotic macules or patches of the skin and mucous membranes (Fig. 54.2); hairs within involved areas may be depigmented or pigmented; the uveal tract and retinal pigmented epithelium can also be affected.

Fig. 54.2 Vitiligo. A Complete loss of pigment of the glans penis. Note the lack of any secondary changes. B Depigmentation of the volar wrists as well as the palmar surfaces; easily recognizable in darkly pigmented individuals. Courtesy, Jean L. Bolognia, MD.

• Two major subtypes of vitiligo: generalized (most common) and localized (Fig. 54.3).

Fig. 54.3 Distribution of amelanotic skin lesions in vitiligo. Vitiligo is clinically divided into two broad categories: generalized and localized. The three distribution patterns in generalized vitiligo include vulgaris, acrofacial, and universal. In focal vitiligo, the amelanotic macules or patches are limited to one or only a few areas, but not necessarily in a segmental pattern, as in segmental vitiligo, which is also unilateral and respects the midline. Adapted with permission from Le Poole C, Boissy RE. Vitiligo. Semin. Cutan. Med. Surg. 1997;16:3–14.

• A polygenic disorder, i.e. involving multiple susceptibility genes, plus environmental factors (mostly unknown); increased incidence of other autoimmune disorders, either in the individual with vitiligo (generalized > localized) or in family members.

• 10–15% of patients with generalized vitiligo have systemic autoimmune diseases, in particular thyroid disease (Hashimoto’s thyroiditis or Grave’s disease), pernicious anemia, Addison’s disease, and AI-CTD (e.g. SLE); associated cutaneous disorders include halo melanocytic nevi, alopecia areata, and lichen sclerosus.

• Generalized vitiligo.

– Includes acrofacial, vulgaris, and universal (see Fig. 54.3); occasionally an inflammatory edge is seen (Fig. 54.4).

Fig. 54.4 Inflammatory vitiligo. There is a figurate outline to the inflammatory border, which is sometimes misdiagnosed as tinea corporis. Courtesy, Jean-Paul Ortonne, MD.

– Affects ~1% of the population worldwide; males = females; onset in ~50% before age 20 years; onset after age 50 years is unusual and prompts widening of the DDx (see below).

– The typical lesion is an asymptomatic, amelanotic macule or patch that is milk or chalk-white in color; early on the pigment loss may not be complete; margins are fairly discrete and convex.

– Course is unpredictable, but often progressive.

• Segmental vitiligo.

– Usually begins in childhood; typically presents in a unilateral, segmental pattern that respects the midline and usually remains stable in size after 1–2 years (Fig. 54.5).

Fig. 54.5 Segmental vitiligo. A Unilateral band of depigmentation on the face, the most common location for segmental vitiligo. Note the pigmented and depigmented hairs within the affected area. B Under normal light, vitiligo can be subtle in lightly pigmented individuals. The clue to the diagnosis is the poliosis of the eyelashes. A, Courtesy, Kalman Watsky MD; B, Courtesy, Jean L. Bolognia, MD.

– DDx: nevus depigmentosus (decreased but not total loss of pigment).

• DDx of depigmented lesion(s).

– In a child: if 1–2 isolated circular or oval macules, stage 3 halo nevus; piebaldism, Waardenburg syndrome (see below).

– In an adult: chemical leukoderma, melanoma-associated leukoderma, leukoderma of scleroderma, Vogt–Koyanagi–Harada syndrome, onchocerciasis, and postinflammatory depigmentation (see below).

– With the exception of onchocerciasis, or in areas of sclerosis or inflammation, a biopsy is not particularly helpful.

• Vitiligo and ocular disease.

– Uveitis is the most significant ocular abnormality; asymptomatic depigmented areas of the ocular fundus can also be seen.

– Uveitis is a major component of the Vogt–Koyanagi–Harada syndrome, in which patients also develop aseptic meningitis, otic involvement (e.g. dysacousia), poliosis, and vitiligo, especially of the head and neck region.

– Alezzandrini syndrome is a rare disorder characterized by unilateral facial vitiligo, poliosis, and ipsilateral ocular involvement.

• Rx: primarily directed at repigmentation of patient-desired areas (Fig. 54.7).

– The efficacy of treatment depends on four variables.

1. Site: face, neck, mid extremities > acral, mucosal (i.e. sites without hairs).

2. Extent of involvement: small area > large area.

3. Stability: stable > active or progressive.

4. Pigmented hairs within the vitiligo patch: presence > absence.

– Repigmentation usually appears in a perifollicular pattern (Fig. 54.6) and/or from the periphery of lesions.

– 10–20% monobenzyl ether of hydroquinone (MBEH) is sometimes used as depigmentation therapy for widespread or treatment-resistant vitiligo, but it can be permanent and lead to loss of pigment in areas distant to the sites of application.

Fig. 54.6 Perifollicular repigmentation. Vitiligo on the elbow (A) and segmental vitiligo on the back (B) responding to PUVA and narrowband UVB therapy, respectively, with repigmentation in a prominent perifollicular pattern as well as from the periphery. The areas of repigmentation are darker in color than the uninvolved skin in (A). A, Courtesy, Jean L. Bolognia, MD; B, Courtesy, Julie V. Schaffer, MD.

Fig. 54.7 Treatment options for vitiligo. Treatment of vitiligo is directed at repigmentation of patient-desired areas. Camouflage can be offered to all patients for temporary (e.g. makeup, self-tanners) or more permanent (e.g. tattoos) cosmetic relief. Referral to a support group [e.g. National Vitiligo Foundation (www.mynvfi.org)] may also be helpful. 10–20% monobenzyl ether of hydroquinone (MBEH) is sometimes used as depigmentation therapy for widespread or treatment-resistant vitiligo, but it can be permanent and lead to loss of pigment in areas distant to the sites of application. NB-UVB, narrowband ultraviolet B; BB-UVB, broadband UVB; PUVA, psoralens plus ultraviolet A.

Hereditary Hypomelanosis

Oculocutaneous Albinism (OCA)

• A group of genetic disorders characterized by pigmentary dilution due to a partial or total absence of melanin within the skin, hair follicles, and eyes; the number of melanocytes is normal.

• Estimated frequency is 1 : 20 000, but may be 1 : 1500 in areas of Africa.

• Four subtypes of OCA (Table 54.1) exist; nearly always inherited in an autosomal recessive manner; OCA1 and OCA2 constitute ~90% of all cases of OCA.

Table 54.1

Classification of oculocutaneous albinism (OCA).

TYR, tyrosinase; OCA, oculocutaneous albinism; TYRP1, tyrosinase-related protein-1; SLC45A2, solute carrier family 45 member 2.

• The ocular manifestations are due to a decrease of melanin within eye structures (e.g. photophobia, reduced visual acuity) or the misrouting of optic nerve fibers during development (e.g. strabismus, nystagmus, lack of stereoscopic vision).

• Early ophthalmologic consultation and strict photoprotection are mandatory; the development of aggressive SCCs (Fig. 54.8A) is a significant cause of morbidity and mortality.

Fig. 54.8 Oculocutaneous albinism type 2 (OCA2). A African patient with obvious squamous cell carcinomas on the cheek as well as multiple pigmented lentigines. B African patient with hypopigmented hair and large pigmented lentigines. Courtesy, James Nordlund, MD.

Disorders of Melanocyte Development

Other

Tuberous Sclerosis (TS) (See Chapter 50)

• Hypomelanotic macules are often the first sign of TS.

• These hypomelanotic macules are typically multiple in number; polygonal is the most common shape, followed by lance-ovate or ‘ash leaf’ (Fig. 54.11); less often, the macules are ‘thumbprint’-like, guttate/confetti, or segmental (see Fig. 54.11; Table 54.2); lesions favor the trunk or extremities.

Fig. 54.11 Tuberous sclerosis. Two types of hypomelanotic macules, lance-ovate (ash leaf) and confetti (idiopathic guttate hypomelanosis-like). Courtesy, David Strobel, MD.

Table 54.2

Differential diagnosis of guttate leukoderma.

The size of the lesions in guttate leukoderma is smaller than in guttate psoriasis. Guttate hypopigmentation may also be seen in the setting of dyschromatoses (see Chapter 55).

^* Seen in adults.

^** Minimally elevated flat-topped papules.

^† Often papular.

Adapted from Bolognia JL, Shapiro PE. Albinism and other disorders of hypopigmentation. In Arndt KA, et al. (Eds.), Cutaneous Medicine and Surgery. Philadelphia: Saunders, 1995.

Hypopigmentation in Mosaic Patterns

• Several patterns of hypopigmentation can result from a mosaic ‘clone’ of skin cells with decreased potential for pigment production (‘pigmentary mosaicism’).

• Hypopigmented areas may be apparent at birth or become evident during childhood, especially in patients with fair skin.

Linear Nevoid Hypopigmentation

• Localized or widespread streaks and swirls of hypopigmentation that follow Blaschko’s lines, which represent pathways of epidermal cell migration during embryogenesis (Fig. 54.12; see Fig. 51.1).

Fig. 54.12 Linear nevoid hypopigmentation. Note the S-shaped pattern of the hypopigmented streaks along Blaschko’s lines.

• ~10–30% of affected individuals have associated extracutaneous abnormalities, which usually develop during infancy and most often affect the CNS (e.g. seizures, developmental delay), eyes, or musculoskeletal system; evaluation is directed by clinical findings.

• The term hypomelanosis of Ito has been used in studies focusing on linear nevoid hypopigmentation associated with systemic manifestations, and it should be reserved for this subset of patients.

• DDx: outlined in Table 54.3 (see Fig. 54.14).

Table 54.3

Differential diagnosis of linear hypopigmentation.

^* More often in a unilateral band or block-like configuration.

^** Linear streaks typically resemble Chinese characters.

Fig. 54.13 Nevus depigmentosus. Hypomelanotic patch with a decrease, but not absence, of pigmentation. Note how the lesion breaks apart into smaller macules at its periphery, resembling a ‘splash of paint.’

Fig. 54.14 Stage 4 of incontinentia pigmenti. Note the absence of hairs within the streaks on the calf.

Nevus Depigmentosus

• Present in ~1 : 50 children, generally as an isolated finding.

• Lesions are typically hypopigmented, not depigmented as implied by the name.

• Classic form: ovoid or irregular hypopigmented patch, often breaking up into smaller macules at its periphery (Fig. 54.13).

• Segmental form (hypopigmented variant of ‘segmental pigmentation disorder’): block-like hypopigmented patch with midline demarcation and less distinct lateral borders.

Phylloid Hypomelanosis

• Leaf-shaped and oblong hypopigmented macules and patches in an arrangement resembling a floral ornament, usually in the setting of mosaic trisomy 13 and associated with CNS abnormalities.

Postinflammatory Hypomelanoses

• Inflammatory skin conditions can potentially result in postinflammatory hypopigmentation or hyperpigmentation or both (see Chapter 55).

• Postinflammatory hypopigmentation is a very common skin disorder that follows a wide variety of dermatoses, most commonly atopic dermatitis, seborrheic dermatitis, and psoriasis, as well as pityriasis lichenoides chronica, lichen striatus, and lichen sclerosus (Fig. 54.15).

Fig. 54.15 Postinflammatory hypomelanosis. Hypopigmentation secondary to psoriasis (A), seborrheic dermatitis in an infant (B), pityriasis lichenoides chronica (C), lichen striatus (note the flat-topped papules) (D), and hypopigmented mycosis fungoides (E). Complete pigment loss in patients with severe atopic dermatitis (F), discoid lupus erythematosus (G), and neonatal lupus erythematosus (H). B, Courtesy, Jean L. Bolognia, MD. H, Courtesy, Julie V. Schaffer, MD.

• It typically coexists or co-localizes with the inflammatory lesions, but occasionally only hypopigmented lesions are seen; the size, shape, and distribution pattern often provide clues to the underlying inflammatory dermatosis.

• Most commonly there is a decrease in pigmentation; rarely there is an absence (e.g. severe atopic dermatitis).

• Histopathologic examination is often nonspecific, but in certain diseases (e.g. sarcoidosis and hypopigmented mycosis fungoides) can be diagnostic.

• Rx of underlying dermatosis is followed by gradual resolution.

Pityriasis Alba (See Chapter 10)

• A very common, asymptomatic disorder seen primarily during childhood and adolescence.

• On the malar region of the face, one to several slightly scaly, hypopigmented macules and patches are seen; the lesions are usually ill-defined and occasionally there is associated mild inflammation.

• The hypomelanosis often remains stationary and unchanged for several years; emollients, sunscreens, or low-strength topical CS (e.g. hydrocortisone 2.5%) may be helpful.

• DDx: tinea versicolor, early vitiligo, and postinflammatory hypopigmentation from seborrheic dermatitis or atopic dermatitis.

Sarcoidosis

• Sarcoidosis occurs more commonly in African-Americans, and the hypopigmented variant of cutaneous sarcoidosis may go undiagnosed; this form has no associated prognostic significance and may spontaneously repigment.

• Hypopigmented papules, plaques, or sometimes nodules are seen; range in size from 1 to several cm.

• Histopathology reveals noncaseating granulomas.

Hypopigmented Mycosis Fungoides (MF) (See Chapter 98)

• A variant of early stage MF that is most commonly observed in darkly pigmented individuals (see Fig. 54.15E); seen in adults, as well as children and adolescents.

• Atrophy often observed within the hypopigmented patches.

• Histopathology reveals typical features of MF.

• DDx: hypopigmented parapsoriasis, pityriasis lichenoides chronica (PLC).

Cutaneous Lupus Erythematosus (LE) (See Chapter 33)

• In discoid LE (DLE), hypomelanosis is often seen centrally within well-developed lesions and the lesions also have cutaneous atrophy, scarring, and a hyperpigmented rim; pigmentary changes tend to be persistent (see Fig. 54.15G).

• In subacute cutaneous LE (SCLE), hypomelanosis typically occurs within the center of annular lesions and is usually reversible.

Systemic Sclerosis (SSc or Generalized Scleroderma) (See Chapter 35)

• Patients with SSc can develop several pigmentary abnormalities, including diffuse hypermelanosis with photoaccentuation, mixed hyper- and hypopigmentation in areas of chronic sclerosis, and a characteristic leukoderma in both sclerotic and nonsclerotic skin (Fig. 54.16).

Fig. 54.16 Leukoderma of scleroderma. Uniform retention of perifollicular pigment within areas of leukoderma. Hyperpigmentation is also seen overlying a superficial vein.

• This ‘leukoderma of scleroderma’ presents as circumscribed areas of depigmentation but with perifollicular and supravenous retention of pigment (see Fig. 54.16).

• This peculiar leukoderma is rather specific for SSc as it occasionally occurs in two other clinical settings, an overlap syndrome (that includes SSc) and scleromyxedema.

• Although clinically similar to the perifollicular repigmentation seen in treatment-responsive vitiligo, it is different in that in vitiligo the perifollicular macules represent new pigmentation, whereas in SSc the macules represent old or retained pigmentation.

Lichen Sclerosus (LS) (See Chapter 36)

• Genital and extragenital lesions of LS are often hypopigmented, but in addition display cutaneous atrophy, follicular plugging (extragenital), and purpura (genital).

• Occasionally extragenital LS presents as guttate leukoderma (Fig. 54.17; see Table 54.2).

Fig. 54.17 Guttate lichen sclerosus involving the areolae.

Infectious and Parasitic Hypomelanosis

Tinea (Pityriasis) Versicolor (See Chapter 64)

• A very common superficial cutaneous mycosis caused by Malassezia spp.; although there is usually minimal inflammation, this infection can lead to both hyper- and hypopigmentation.

• Typically presents symmetrically on the upper trunk and shoulders or flexural areas (e.g. groin and inframammary) as round to oval macules or thin papules that coalesce into patches or thin plaques; the lesions vary in color from pink to light tan to brown, hence the term versicolor (Fig. 54.18).

Fig. 54.18 Tinea (pityriasis) versicolor. A Hypopigmented variant with obvious scale. B Guttate hypopigmented lesions on the cheek; note the classic scaly lesions in the posterior auricular area. B, Courtesy, Julie V. Schaffer, MD.

• Lesions often coalesce and when untreated, there is usually a subtle overlying fine scale that is more readily apparent upon scratching or stretching the skin.

• Diagnosis is easily confirmed by KOH examination of the associated scale.

• Hypomelanosis without any scaling may remain for months after treatment.

• Tuberculoid leprosy (Fig. 54.19): fewer larger hypopigmented patches with discrete, often raised, borders; favor posterolateral aspects of extremities, back, buttocks, face; associated anhidrosis, alopecia, and loss of sensation.