Dermatol Clin 25 (2007) 373–382

Hypomelanotic Conditions of the Newbornand Infant

Ramon Ruiz-Maldonado, MDDepartment of Pediatric Dermatology, National Institute of Pediatrics,

Insurgentes Sur 3700 C, Mexico City 04530, Mexico

In this article the author refers exclusively tomelanin mediated diminution or loss of skin

pigmentation in the newborn and the infant.Congenital hypopigmented disorders are ad-dressed, even if patients are seen when they are

no longer newborns or infants. The various typesof albinismus are not included. Until there is ‘‘amore precise lexicon for pigmentation, pigmen-

tary disorders, and abnormalities of ‘‘chromatics’’[1] the author will use the terms defined in Box 1in this article. Note: all depigmented lesions are

better diagnosed if examined under Wood’s light.All of the lesions discussed in this article may

be either genetically determined or sporadic,congenital or acquired, localized, disseminated

or diffuse, measure from a few millimeters topractically all of the skin, follow Blashko lines ornot, involve skin adnexa or not, be with or

without associated alterations, be static, progres-sive or regressive, and symptomatic or asymp-tomatic (Fig. 1).

Proposal for a new classification of depigmented

nevi

In the absence of sufficient knowledge regard-ing the pathophysiology of depigmented nevi, andthe important clinical differences between small

and large lesions that are at present clumpedtogether, the author proposes to name Depig-mented nevi simplex type 1 those nevi measuring

less than 10 cm in their larger diameter, withoutassociated pathology, and name Depigmentednevi simplex type 2 those depigmented nevi mea-suring more than 10 cm, without associated

E-mail address: rrm@servidor.unam.mx

0733-8635/07/$ - see front matter � 2007 Elsevier Inc. All r

doi:10.1016/j.det.2007.05.005

pathology. Depigmented nevi measuring lessthan 10 cm with associated pathology will be

called Depigmented nevi complex type 1. Depig-mented nevi measuring more than 10 cm with as-sociated pathology, will be called Depigmented

nevi complex type 2. The choice of 10 cm to definenevi size was an arbitrary decision.

Depigmented nevi simplex type 1 (Hypochromic,hypopigmented, achromic)

Depigmented nevi simplex type 1 (DNS type 1)is the most frequently found white spot onnewborns and infants. Up to 1 in 130 otherwise

healthy newborns, have at least one DNS type 1[2], usually present at birth, more commonlyfound on the trunk, usually measuring 2 cm to 3

cm, but rarely over 10 cm in their larger diameter.These lesions are well circumscribed with irregularborders, nonprogressive, hypopigmented, lighter

than the surrounding skin, seldom white, andwithout associated pathology (Fig. 2) [3–5]. Themain differential diagnosis of DNS type 1 is nevusanemicus.

Nevus anemicusAt first sight nevus anemicus may look like

a depigmented nevus simplex type 1-a congenital

lesion, 1 cm to 3 cm in diameter, round, slightlyhypochromic with a ragged outline (Fig. 3). Ifpressure is applied with a convex glass, the nevus

disappears, and if stroked, no flare is elicited. It isin fact a circumscribed area of skin, hypersensitiveto chatecholamines: a pharmacological nevus-like

lesion.

Depigmented nevi simplex type 2

Depigmented nevi simplex type 2 (DNS type 2)are larger than 10 cm, ‘‘block like’’ or linear

ights reserved.

derm.theclinics.com

374 RUIZ-MAL

lesions, with or without whorls, following Blashkolines or not, usually present at birth, involving oneor several body segments, and without associatedpathology (Fig. 4) [6–8]. The main differential di-

agnosis is metameric or segmental vitiligo.

Dermatomal, segmental or metameric vitiligoThe dermatomal, segmental or metameric form

of vitiligo, more frequently observed in children, is

not associated with systemic abnormalities. It maybe confused with DNS type 2 because this lastcondition may be achromic and first appearduring childhood (Fig. 5).

Depigmented nevi complex type 1

Tuberose sclerosis

Depigmented nevi complex type 1 are presentin over 90% of newborns with tuberose sclerosis(TS), are usually lighter than in DNS type 1,

typicallydbut not alwaysdash leaf shaped andmore than three in number (Fig. 6). Multiple con-fetti-like white macules may also be part of the

syndrome. A tuft of white hairs on the scalpmay denote an underlying achromic spot. Associ-ated neurological alterations (seizures and mentalretardation) are usually present. Negative family

history is not uncommon due to a high rate ofnew mutations.

In TS patients collagenomas ‘‘chagrin patches’’

may also be present at birth. By age five, facialangiofibromas start to develop and some yearslater, periungueal fibromas. Ocular, cerebral,

cardiac and renal hamartomatose tumors maybe detected through magnetic resonance imagingexamination [9,10].

Box 1. Definitions of pigmentarydisorder terms

Hypomelanosis – diminution of the blackpigment melanin

Hypochromia and hypopigmentation –diminution of any color

Amelanosis – absence of black pigment,usually melanin

Achromia and apigmentation – absenceof color

Leukoderma – white skinDepigmented – loss of pigmentDispigmented – altered pigmentation

Depigmented nevi complex type 2

Hypomelanosis of ItoThe white spots in hypomelanosis of Ito (HI)

are extensive lesions, usually involving more than

one body segment, unilateral or bilateral, linear,squared, whorl, or whirl shaped, more often whitethan depigmented, often not present at birth,and with a tendency to disappear with age (Figs.

7 and 8). Chromosomal abnormalities (mosaicismand chimerism) are often found. Associated neu-rological and bone abnormalities are present in

up to 60% of patients. HI is not a geneticallydetermined condition [3,11].

PiebaldismPiebaldism is an autosomal dominant disease

due to a defect in migration and maturation ofmelanoblasts from the neural crest. It is clinicallycharacterized by congenital, extensive and sym-

metrically-distributed white patches on the fore-head, anterior thorax and limbs, and a tuft ofwhite hair on the forehead. Small patches ofnormally pigmented skin are characteristically

observed inside depigmented areas (Fig. 9).In stable piebaldism, cutaneous depigmentation

remains unchanged through life. It is due to

a mutation of the KIT gene, which encodesa tyrosine kinase receptor related to developmentof pigment cells, located in chromosome 4q12.

Two rare cases of progressive piebaldism wererecently reported, due to a novel mutation in theirKIT gene [12]. Treatment with cultured autologous

epithelial grafts have been reported as beingsuccessful.

Waardenburg syndrome type 1Waardenburg syndrome is inherited as an

autosomal dominant trait. It is classified intofour types; type 1 is due to mutations in thePAX3 gene, located on chromosome band 2q35.Waardenburg syndrome type 1 is clinically char-

acterized by dystopia canthorum, sensorineuralhearing loss, congenital patches of achromic skin,white forelock, broad nasal root, synophrys, and

heterochromia of irides (Fig. 10). This syndromeis responsible for 1.4% of congenital deafness inchildren. Because of the possible risk of neural

tube defects, folic acid supplementation has beenrecommended for pregnant women at risk of hav-ing a child with Waardenburg syndrome [13].

DONADO

QUIRED

HEREDITARYFACIAL

DYSMORPHIADEFNESS

WAARDENBURG

STABLE

NO

VITILIGO

LIMBS

CONGENITAL

DISSEMINATED

ASSOCIATEDANOMALIES

HEREDITARYSYMETRICACHROMIA

WITHPIGMENTATION.

WITHE FORELOCK

PIEBALDIMS

ACHROMIC

RAMON RUIZ-MALDONADO, M.D.

375

HYPOMELANOTIC

CONDIT

IONSOFTHENEWBORN

AND

INFANT

LIGHT SPOTS

NEVUS ANEMIC

NEUROLOGIC ALTERATIONS

DESPIGMENTED NEVUS

ACCONGENITAL

YES

FACE

ACQUIRED

OVER ONE YEAR OF AGE

UNDER ONEYEAR OF AGE

HYPOESTHETIC NORMOSTHETIC

BACILLI IN LIGHTEXPOSEDAREAS

IN ANYAREA

DISAPEARS UNDER PRESURE

WORL SHARED

YES

NEUROLOGICALTERATIONS

ITOHYPOMELANOSIS

LEPROSY

ILL-DEFINED

PREVIOUSINFLAMMATION

P. ALBAYES NO

POST-INFLAMMATORYHYPOCHROMIA

ATOPIC DERMATITISPSORIASIS

P. LICHENOIDESOTHER

MICROSCOPEEXAMEN

GRAPE SHAPEDSPORES

NEGATIVE

P. VERSICOLOR ATYPICALCELLS

MYCOSISFUNGOIDES

SINGLE

TUBEROUS SCLEROSIS

HYPOCHROMIC

Fig. 1. Algorithm for achromic and hypocromic spots.

376 RUIZ-MALDONADO

Syndromes with diffuse skin and hair

hypopigmentation (excluding oculocutaneous

albinism)

Chediak-Higashi syndrome

This autosomal recessive condition is due to

a gene defect localized in chromosome 1q. Che-diak-Higashi syndrome is clinically characterizedby lighter skin than parents and siblings in sun-protected skin areas, slate-gray hair, and periodic,

life-threatening ‘‘accelerated phace’’ of systemicinvolvement, with fever, hepatic, splenic andlymph-node enlargement. Epstein-Barr induced

malignant lymphoma is usually fatal.

Fig. 2. Depigmented nevus simplex type 1, measuring

less than 10 cm and without associated pathology.

Fig. 3. Nevus anemicus.

Fig. 4. Depigmented nevus simplex type 2, measuring

more than 10 cm and without associated pathology.

Fig. 5. Segmental vitiligo in the differential diagnosis of

depigmented nevus simplex type 2.

377HYPOMELANOTIC CONDITIONS OF THE NEWBORN AND INFANT

Severe immunodeficiency is due to a diminishednumber and altered function of NKT lympho-cytes and defective chemotaxis of granulocytes,

lymphocytes and monocytes. The diagnosis isconfirmed by the presence of characteristic giantintracellular lysosomal granules. Bone marrow

transplantation is the only effective treatment[14,15].

Griscelli and Elejalde syndromes

In 1978, Griscelli and colleagues [16] originallydescribed the association of pigment delusion of

hair (silvery hair) and skin, due to the presenceof large clumps of pigment in the hair shafts andaccumulation of melanosomes in melanocytes

(Fig. 11). Patients have severe cellular immunode-ficiency and frequently die of hemophagocyticsyndrome.

Fig. 6. Ash leaf shaped, depigmented nevi complex type

1, measuring less than 10 cm, in a patient with tuberose

sclerosis.

Fig. 7. Depigmented nevus complex type 2, measuring

more than 10 cm, in Ito’s hypomelanosis and with asso-

ciating neurological alterations.

In 1977, Elejalde and colleagues [17] first de-

scribed the same pigment delusion of skin andhair associated with severe neurological altera-tions (neuroectodermal melanolysosomal disease).

What should have been called Elejalde syndromehas now been inappropriately called Griscellisyndrome type 1 (Griscelli 1) in some publica-

tions. Elejalde syndrome (or Griscelli 1) is char-acterized by silvery hair, light-bronze skin color,and profound neurological regressive functions,

Fig. 8. Unilateral, square shaped depigmented nevus

complex type 2, in a patient with chromosomal

abnormalities.

Fig. 9. Typical depigmented lesions of piebaldism in an

infant.

378 RUIZ-MALDONADO

starting from one month to 11 years of age,with muscular hypotonia, ocular alterations,

and seizures; it does not present with an immu-nodeficiency [18]. Elejalde syndrome is due toa MYO5A mutation (Fig. 12).

Griscelli syndrome type 2 (Griscelli 2) is an

unusual condition inherited as an autosomalrecessive trait, due to a mutation in theRAB27A gene.

Fig. 10. Waardenburg syndrome with anisochromia iri-

dis, dystopia cantorum, synophrys, wide nasal root, and

achromic patch.

Fig. 11. Hair of a patient with Elejalde syndrome. No-

tice the large, irregular clumps of melanine inside the

hair shaft.

Griscelli syndrome type 3 presents hair andskin hypomelanosis only, with no neurological or

immune alterations. It may be caused by muta-tions in the melanophilin or MYO5A genes.

Phenylketonuria PK (Phenylalaninemia syndrome)

Phenylalaninemia syndrome (PK) is a rareautosomal recessive metabolic syndrome (350

cases per million live births) caused by a deficiencyof the enzyme phenylalanine hydroxylase, withthe resulting accumulation of phenylalanine in the

plasma and excretion of phenylpyruvic and phe-nylacetic acids in the urine.

Because of the impairment of melanin synthe-sis, patients with PK have fair skin and hair, and

atopic dermatitis-like lesions. If left untreated,nearly all cases will develop mental retardation;half of them will develop epilepsy and extra-

pyramidal signs. Treatment consists of a lowphenylalanine diet from diagnosis through life.Screening of at-risk families is mandatory and

at-risk mothers should begin treatment before orduring pregnancy [19].

Ziprkowski-Margolis syndrome

Ziprkowski-Margolis syndrome presents witha total absence of skin and hair pigmentation,

heterochromia of the irises, and deaf-mutism [20].With normal eyes, this syndrome is called Tietzsyndrome. It is a result of gene alteration in X

chromosome XQ 26.3-q27.

Cross syndrome

Cross syndrome, or oculocerebral syndromewith hypopigmentation, presents with a total

Fig. 12. Elejalde syndrome, presenting with generalized

skin pigment delusion and severe neurological

alterations.

379HYPOMELANOTIC CONDITIONS OF THE NEWBORN AND INFANT

absence of skin, hair and eye pigmentation.Spasticity is also an effect of this syndrome [21].

Prader-Willi and Angelman syndromes

Although independently described, Prader-Willi and Angelman syndromes are in fact the

same syndrome characterized by neurologicalalterations, mental retardation, peculiar faciesand oculocutaneous depigmentation [22].

Acquired hypopigmentations

Acquired cutaneous hypopigmentations are

extremely common and, because of diverse etio-logic factors, those affecting newborns and infantsrepresent only a small proportion of thispathology.

Pityriasis alba

There are two types of pityriasis alba (PA):endemic PA, affecting infants and children of lowsocioeconomic conditions in developing countries,

present in over 90% of the child population; andatopic dermatitis related PA, which is betterunderstood as a postinflammatory hypopigmen-

tation, more frequently observed in atopic derma-titis treated with topical anti-inflammatorymedications.

Endemic PA is clinically characterized by

round, ill-defined, finely scaling, asymptomatic,hypochromic macules in sun-exposed areas,mainly on the face (Fig. 13). Etiologic factors in-

volved may be skin dryness, bacteria (dry im-petigo), and sun exposure. Treatment withhydrating creams, mild topical antimicrobials

(Vioform), and sunscreen is usually effective in 2to 3 months. Topical corticosteroids and calci-neurin inhibitors worsen hypopigmentation.

Lichen striatus

In non white-skinned individuals lichen stria-

tus is usually characterized by a linear, finelypapular, hypochromic, asymptomatic lesion,more frequently located in the extremities follow-

ing the lines of Blashko. Lichen striatus sponta-neously disappears in 1 to 2 years, leaving behindhypopigmentation that slowly regresses. It is

relatively common in children and adolescentsbut rare in infants. It has been etiologically relatedto a virus (Fig. 14) [23].

Lichen sclerosus

Lichen sclerosus is rare in infants but mayoccur, particularly in perivulvar and peri-anallocations, more frequently in females. The lesions

are chalk white and often excoriated because ofpruritus. The possibility of child abuse should betaken into consideration in some patients

(Fig. 15). The main differential diagnosis is withvitiligo. Treatment possibilities are topical high- or

Fig. 13. Pityriasis alba, presenting with ill-defined,

hypochromic, finely scaling facial lesions.

Fig. 14. Lichen striatus, presenting with a linear, finely

papular, hypochromic lesion.

380 RUIZ-MALD

medium-strength corticoids and calcineurininhibitors.

Follicular mucinosis

Follicular mucinosis in infants is a rare butpossible event. It is characterized by a round,

1-cm to 3-cm, well-demarcated, follicular, hypo-chromic and asyntomatic lesion. The clinicaldiagnosis is confirmed by the presence of abun-

dant mucin at the follicular level. Treatment withtopical corticosteroids is usually effective.

Perinevic achromia (Sutton nevus)

The development of an achromic halo arounda pigmented nevomelanocytic lesion is known as

Sutton phenomenon or Sutton nevus. It can beseen in nevocellular nevi, in caffe au lait spots, andin melanoma. It may or may not precede or follow

vitiligo lesions. The nevus progressively disap-pears and, in some cases, the normal skin color isrestored. The histopathology shows lymphocytic

Fig. 15. Lichen sclerosus et atrophicus presenting with

a white, erythematose, pruritic vulvar lesion.

Fig. 16. Sutton nevi or perinevic achromia.

infiltration compatible with an immune reaction

against melanocytic cells (Fig. 16).

Large pigmented nevi

Rarely, congenital, large, pigmented nevome-lanocytic nevi may undergo total or quasi-totaldepigmentation, probably immunologically medi-

ated, in a way similar to that observed in Sutton’snevus [24].

Pityriasis versicolor

Pityriasis versicolor (PV) is caused by the yeastMalassezia, a normal dweller of the skin. PV is

common in children and has been reported inneonates. Pediatric patients often have facial

Fig. 17. Pityriasis versicolor lesions in the forehead of

a 3-month-old infant.

Fig. 18. Hypochromia in the popliteal fossae after

atopic dermatitis lesions.

ONADO

381HYPOMELANOTIC CONDITIONS OF THE NEWBORN AND INFANT

lesions, which are rare after puberty. PV isclinically characterized by round, finely scaling,

usually hypochromic, rarely dark, asymptomaticlesions, which are at times coalescent (Fig. 17).Treatment consists of daily nighttime applications

of 2.5% selenium sulphyde, washing in the morn-ing; hypopigmentation can take several weeks torepigment. Relapses are frequent, especially inhot and humid climates.

Fig. 19. Figurated achromia left behind by erythema

multiforme lesions: A Koebner phenomenon.

Fig. 20. Pityriasis lichenoides chronica papular lesions

always leave behind hypochromia in dark skinned

individuals.

Postinflammatory hypopigmentation

Many acute or chronic cutaneous inflamma-tory lesions, regardless of their etiology, may beleft after healing hypopigmentation or hyperpig-

mentation. The shape of the dyschromia left issimilar to that of the original lesion [25]. In thissection we will describe a few examples of postin-

flammatory hypopigmentation (PIHP), more evi-dent in nonwhite individuals than in caucasians.

Atopic dermatitis

Inflammatory lesions of atopic dermatitis are

often left behind. It presents with hypopigmenta-tion, more frequent and intense if treated withpotent topical corticosteroids (Fig. 18). In sun-

exposed areas (face and upper limbs) this formof PIHP is identical with pityriasis alba.

Vitiligo-like lesions left behind by erythema

multiforme

This unique Kobner phenomenon reproducedin white color, presents lesions of erythema multi-forme (Fig. 19).

Pityriasis lichenoides chronica

In a high proportion of infants and childrenwith pityriasis lichenoides chronica, gutate hypo-pigmentation is an important clinical feature

(Fig. 20).

Epidermolysis bullosa

A good example of achromia left by small and

large bullous lesions can be seen in the infantshown in Fig. 21, exhibiting dystrophic epider-molysis bullosa.

Fig. 21. Extensive achromic lesions, presenting as se-

quela of dystrophic epidermolysis bullosa in an infant.

382 RUIZ-MALDONADO

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