Disturbances of Disturbances of PigmentationPigmentation

Rick Lin, D.O.Rick Lin, D.O.

MelaninMelanin

primary pigment producing brown colorationprimary pigment producing brown coloration Tyrosine – tyrosinase –melanin- this occurs Tyrosine – tyrosinase –melanin- this occurs

in the melanosomes of melanocytesin the melanosomes of melanocytes Then the melanosomes are transferred from Then the melanosomes are transferred from

the melanocyte to a group of keratinocytes the melanocyte to a group of keratinocytes called the epidermal melanin unitcalled the epidermal melanin unit

Variations in skin color is related to the Variations in skin color is related to the number of melanosomes, the degree of number of melanosomes, the degree of melanization, and the distribution of the melanization, and the distribution of the epidermal melanin unitepidermal melanin unit

Pigmentary Demarcation LinesPigmentary Demarcation Lines Can be divided into five categories:Can be divided into five categories: Group A- lines along the outer upper arms with Group A- lines along the outer upper arms with

variable extension across the chestvariable extension across the chest Group B-lines along the posteromedial aspect Group B-lines along the posteromedial aspect

of the lower limbof the lower limb Group C-Paired median or paramedian lines on Group C-Paired median or paramedian lines on

the chest, with midline abdominal extensionthe chest, with midline abdominal extension Group D-medial, over the spineGroup D-medial, over the spine Group E-bilaterally symmetrical, obliquely Group E-bilaterally symmetrical, obliquely

oriented, hypopigmented macules on the chest oriented, hypopigmented macules on the chest

Pigmentary Demarcation LinesPigmentary Demarcation Lines

More than 70% of blacks have one or More than 70% of blacks have one or more linesmore lines

These are much less common in These are much less common in whiteswhites

Type B lines often appear for the first Type B lines often appear for the first time during pregnancytime during pregnancy

Normal PigmentationNormal Pigmentation

Normal skin pigmentation is Normal skin pigmentation is influenced by:influenced by:

-the degree of vascularity-the degree of vascularity

-the amount & location of melanin-the amount & location of melanin

-the presence of carotene-the presence of carotene

-the thickness of the horny layer-the thickness of the horny layer

Melanin ProductionMelanin Production

The amount produced is dependent on:The amount produced is dependent on:

-genetics-genetics

-the amount and the wavelengths of -the amount and the wavelengths of ultraviolet light receivedultraviolet light received

-the amount of melanocyte-stimulating -the amount of melanocyte-stimulating hormone(MSH) secretedhormone(MSH) secreted

- the effect of melanoccytestimulatingg - the effect of melanoccytestimulatingg chemicals like furocoumarins (psoralens)chemicals like furocoumarins (psoralens)

Hemosiderin Hemosiderin HyperpigmnetationHyperpigmnetation

Pigmentation due to deposits of Pigmentation due to deposits of hemosiderin occurs in:hemosiderin occurs in:

-purpura-purpura

-hemochromatosis-hemochromatosis

-hemorrhagic diseases-hemorrhagic diseases

-stasis ulcers-stasis ulcers

** difficult to distinguish from ** difficult to distinguish from postinflammatory dermal melanosis postinflammatory dermal melanosis clinicallyclinically

Postinflammatory Postinflammatory HyperpigmentationHyperpigmentation

Any inflammatory condition can cause Any inflammatory condition can cause either hypopigmentation or either hypopigmentation or hyperpigmentationhyperpigmentation

Also may be a complication of chemical Also may be a complication of chemical peels, dermabrasion, laser therapy, or peels, dermabrasion, laser therapy, or liposuctionliposuction

Histologically, there is melanin in the Histologically, there is melanin in the upper dermis and around upper dermal upper dermis and around upper dermal vessels, located primarily in macrophages vessels, located primarily in macrophages (melanophages)(melanophages)

Postinflammatory Postinflammatory hyperpigmenationhyperpigmenation

Postinflammatory Postinflammatory hyperpigmentation hyperpigmentation following resolution following resolution of lymphocytoma of lymphocytoma cutis on the cheek cutis on the cheek of a black childof a black child

Industrial HyperpigmentationIndustrial Hyperpigmentation

Occurs in coal miners, anthracene Occurs in coal miners, anthracene workers, pitch workers, etcworkers, pitch workers, etc

Pigmentation of the face may occur Pigmentation of the face may occur from the incorporation in cosmetics from the incorporation in cosmetics of derivatives of coal tar, petrolatum, of derivatives of coal tar, petrolatum, or picric acid, mercury, lead, or picric acid, mercury, lead, bismuth, or furocoumarins bismuth, or furocoumarins (psoralens)(psoralens)

Systemic DiseasesSystemic Diseases

Syphilis, malaria, pellagra, and diabetesSyphilis, malaria, pellagra, and diabetes Addison’s disease- diffuse melanosis Addison’s disease- diffuse melanosis

pronounced in the axillae and palmar pronounced in the axillae and palmar creases, and nipples and genitals, and creases, and nipples and genitals, and buccal mucosabuccal mucosa

Diabetes produces diffuse bronzing of the Diabetes produces diffuse bronzing of the skinskin

** patients with virilizing adrenal tumors ** patients with virilizing adrenal tumors usually develop hyperpigmentation and usually develop hyperpigmentation and hypertrichosishypertrichosis

Systemic DiseasesSystemic Diseases Nelson’s syndrome (a Nelson’s syndrome (a

pituitary MSH-pituitary MSH-producing tumor) producing tumor)

PheochromocytomaPheochromocytoma HemochromatosisHemochromatosis AmyloidosisAmyloidosis ScurvyScurvy PregnancyPregnancy MenopauseMenopause Porphyria cutanea Porphyria cutanea

tardatarda

Vitamin B12 Vitamin B12 deficiencydeficiency

KwashiorkorKwashiorkor Vitamin A Vitamin A

deficiencydeficiency Primary biliary Primary biliary

cirrhosis (triad= cirrhosis (triad= hyperpigmentationhyperpigmentation, pruritis, , pruritis, xanthomas) xanthomas)

HemochromatosisHemochromatosis

Characterized by:Characterized by: Gray-brown Gray-brown

mucocutaneous mucocutaneous hyperpigmentatiohyperpigmentationn

Diabetes mellitusDiabetes mellitus hepatomegalyhepatomegaly

Usually are present:Usually are present: CirrhoisisCirrhoisis HypogonadismHypogonadism Liver cirrhosisLiver cirrhosis

HemochromatosisHemochromatosis

Skin pigmentaion is Skin pigmentaion is usually generalizedusually generalized

But, more pronounced But, more pronounced on face, extensor aspect on face, extensor aspect of the forearms, backs of of the forearms, backs of the hands, and the the hands, and the geniocrural areageniocrural area

Iron is deposited in the Iron is deposited in the skinskin

Iron is present as Iron is present as granules around blood granules around blood vessels and sweat glands vessels and sweat glands and within macrophagesand within macrophages

The actual The actual pigmentation is pigmentation is caused by increased caused by increased basal-layer melaninbasal-layer melanin

Mucous memebranes Mucous memebranes are pigmented in up are pigmented in up to 20% of patientsto 20% of patients

Koilonychia is present Koilonychia is present in 50%in 50%

Localized ichthyosis Localized ichthyosis in 40%in 40%

Alopecia is common Alopecia is common

Hemochromatosis-txHemochromatosis-tx Phlebotomy until Phlebotomy until

satisfactory iron levels satisfactory iron levels are foundare found

Extracorporeal Extracorporeal chelation has also chelation has also been used been used successfullysuccessfully

Associated DM Associated DM requires medical txrequires medical tx

Long-term Long-term complications are complications are cirrhosis and then cirrhosis and then hepatomashepatomas

MelasmaMelasma

Brown patches, sharply Brown patches, sharply demarcated, typically on demarcated, typically on the malar prominences the malar prominences and foreheadand forehead

The three clinical The three clinical patterns are: patterns are: centrofacial, malar, centrofacial, malar, mandibularmandibular

Increased pigment may Increased pigment may simultaneously occur simultaneously occur around the nipples and around the nipples and external genitaliaexternal genitalia

Tends to affect the Tends to affect the darker-complecteddarker-complected

It may also be found on It may also be found on the forearmsthe forearms

Occurs at pregnancy Occurs at pregnancy and at menopauseand at menopause

It may also be seen in It may also be seen in ovarian disorders and ovarian disorders and other endocrine other endocrine disordersdisorders

Most frequently 90% of Most frequently 90% of the time seen in women, the time seen in women, 10% in men10% in men

MelasmaMelasma

Strong association Strong association with the use of birth with the use of birth control pills or dilantincontrol pills or dilantin

Discontinuing the Discontinuing the contraceptives rarely contraceptives rarely clears the clears the pigmentation, and it pigmentation, and it may last for years may last for years after discontinuing after discontinuing them.them.

Melasma of pregnancy Melasma of pregnancy usually clears within a usually clears within a few months of deliveryfew months of delivery

Tx- avoid sunlight, and a Tx- avoid sunlight, and a complete sun block with complete sun block with broad-spectrum UVA broad-spectrum UVA coverage should be used coverage should be used dailydaily

Kligman’s formula (Triluma)Kligman’s formula (Triluma) > then 4% hydroquinone > then 4% hydroquinone

may be neededmay be needed Side effects of this is Side effects of this is

ochronosis and satellite ochronosis and satellite pigmentationpigmentation

Jessner’s solution, glycolic Jessner’s solution, glycolic acid peels,azelaic acid, kojic acid peels,azelaic acid, kojic acid, and cystamine and acid, and cystamine and buthionine sulfoximine are buthionine sulfoximine are other optionsother options

MelasmaMelasma

MelasmaMelasma

MelasmaMelasma

Acromelanosis ProgressivaAcromelanosis Progressiva AKA acropigmentationAKA acropigmentation A progressive A progressive

pigmentary disorder pigmentary disorder first described in a first described in a Japanese infantJapanese infant

Characterized by diffuse Characterized by diffuse black pigmentation on black pigmentation on the dorsum of all the the dorsum of all the fingers and toesfingers and toes

Pigmentation became Pigmentation became progressively more progressively more widespread and more widespread and more pigmentedpigmented

By age 4 or 5 the By age 4 or 5 the perineum, perineum, extremities, and extremities, and areas of the head areas of the head and neck were and neck were involvedinvolved

Epileptiform Epileptiform seizures occurredseizures occurred

History revealed History revealed consanguinityconsanguinity

Pigmented Anomalies of the Pigmented Anomalies of the ExtremitiesExtremities

Acropigmentation of Acropigmentation of DohiDohi

Found to affect Found to affect individuals from individuals from Europe, India, Europe, India, CaribbeanCaribbean

First described in Japan First described in Japan in 12 patientsin 12 patients

AKA AKA dyschromatosis dyschromatosis symmetrica hereditaria symmetrica hereditaria oror symmetrical symmetrical dyschromatosis of the dyschromatosis of the extremitiesextremities

Patients develop Patients develop progressive progressive pigmented & pigmented & depigmented maculesdepigmented macules

Often mixed in is a Often mixed in is a reticulate patternreticulate pattern

Many believe this to Many believe this to be a variation of be a variation of acropigmentation of acropigmentation of KitamuraKitamura

Reticular Pigmented Anomaly of Reticular Pigmented Anomaly of the Flexuresthe Flexures

It begins age 20 to It begins age 20 to 30 yrs and 30 yrs and progresses progresses graduallygradually

Unknown etiology Unknown etiology AD with variable AD with variable

penetrance and penetrance and expressivity, and expressivity, and delayed onsetdelayed onset

Many authors believe Many authors believe it is a spectrum of it is a spectrum of reticulate reticulate acropigmentation of acropigmentation of Kitamura Kitamura

Another manifestation Another manifestation of this disorder is of this disorder is familial-rocacea-like familial-rocacea-like dermatitis with warty dermatitis with warty keratotic plaques on keratotic plaques on the trunk and limbsthe trunk and limbs

There is no treatmentThere is no treatment

Reticular pigmented anomaly of the flexuresReticular pigmented anomaly of the flexures J. B. Howell and R. G. Freeman J. B. Howell and R. G. Freeman

Reticular pigmented anomaly of the flexures Reticular pigmented anomaly of the flexures (Dowling-Degos' anomaly) is a rare, benign, new (Dowling-Degos' anomaly) is a rare, benign, new genodermatosis that has recently evolved from genodermatosis that has recently evolved from independent observations and studies by several independent observations and studies by several dermatologists. Because of its favorable dermatologists. Because of its favorable prognosis, differentiation of this benign disorder prognosis, differentiation of this benign disorder from acanthosis nigricans, a cutaneous marker of from acanthosis nigricans, a cutaneous marker of possible or existing internal malignant disease, is possible or existing internal malignant disease, is highly important. Careful clinical appraisal of the highly important. Careful clinical appraisal of the eruption in correlation with the characteristic eruption in correlation with the characteristic microscopic features makes the diagnosis simple microscopic features makes the diagnosis simple and straightforward. and straightforward.

HistologyHistology

Distinctive Distinctive elongation, tufting, elongation, tufting, and deep and deep hyperpigmentation hyperpigmentation of therete ridges, of therete ridges, with protrusion of with protrusion of similar tufts even similar tufts even from the sides of from the sides of the folliclesthe follicles

Reticulate Acropigmentation of Reticulate Acropigmentation of KitamuraKitamura

ADAD Characterized by Characterized by

linear palmar pits linear palmar pits and pigmented and pigmented macules 1-4 mm in macules 1-4 mm in diameter on the diameter on the volar and dorsal volar and dorsal aspects of the aspects of the hands and feethands and feet

One report of a pt with One report of a pt with bony abnormalities bony abnormalities consisting of absence consisting of absence of terminal phalanges of terminal phalanges of the second, third, of the second, third, and fourth toesand fourth toes

Some tx success has Some tx success has been reported using been reported using axelaic acid ointmentaxelaic acid ointment

Dermatopathia Pigmentosa Dermatopathia Pigmentosa ReticularisReticularis

Consists of a triad of Consists of a triad of generalized reticulate generalized reticulate hyperpigmentation, hyperpigmentation, noncicatricial alopecia, noncicatricial alopecia, and onychodystrophyand onychodystrophy

Other associations: Other associations: adermatoglyphia, adermatoglyphia, hypohidrosis or hypohidrosis or hyperhidrosis, hyperhidrosis, palmoplantar palmoplantar hyperkeratosis, and hyperkeratosis, and nonscarring blisters on nonscarring blisters on dorsa of hands and dorsa of hands and feet.feet.

An autosomal An autosomal dominant dominant inheritance pattern inheritance pattern has been reported.has been reported.

Dermatopathia Pigmentosa Dermatopathia Pigmentosa ReticularisReticularis

Transient Neonatal Pustular Transient Neonatal Pustular MelanosisMelanosis

Infants develop 2- Infants develop 2- 3mm macules, 3mm macules, pustules, and pustules, and ruptured pustules ruptured pustules at birth, at birth, predominantly predominantly involving the faceinvolving the face

Pigmentation may Pigmentation may last for weeks or last for weeks or months after the months after the pustules are healedpustules are healed

Histologically, there are Histologically, there are intracorneal or intracorneal or subcorneal aggregates subcorneal aggregates of predominantly of predominantly neutrophils, but neutrophils, but eosinophils may also be eosinophils may also be foundfound

Dermal inflammation is Dermal inflammation is composed of an composed of an admixture of neuts and admixture of neuts and eoseos

Differential dx: ETN, Differential dx: ETN, neonatal acne, & neonatal acne, & acropustulosis of infancyacropustulosis of infancy

Transient Pustular Neonatal Transient Pustular Neonatal MelanosisMelanosis

Transient Neonatal Pustular Transient Neonatal Pustular MelanosisMelanosis

Peutz-JeghersPeutz-Jeghers

Characterized by Characterized by hyperpigmented macules hyperpigmented macules on the lips and oral on the lips and oral mucosa and polyposis of mucosa and polyposis of the small intestinethe small intestine

Dark brown or black Dark brown or black macules appear typically macules appear typically on the lips, especially the on the lips, especially the lower lip, in infancy or lower lip, in infancy or childhoodchildhood

Similar lesions may Similar lesions may appear on buccal appear on buccal mucosa, tongue, gingiva, mucosa, tongue, gingiva, and genital mucosaand genital mucosa

Associated polyposis Associated polyposis involves the small involves the small intestine preferencelyintestine preferencely

But, hamartomatous But, hamartomatous polyps of the stomach polyps of the stomach and colon may occurand colon may occur

Symptoms of Symptoms of hamhartomas of the hamhartomas of the small intestine may small intestine may cause repeated bouts of cause repeated bouts of abdominal pain and abdominal pain and vomiting, and vomiting, and intussusceptionintussusception

Peutz-Jeghers syndromePeutz-Jeghers syndrome

Lip lentigenes in an Lip lentigenes in an adolescent with adolescent with Peutz-Jeghers Peutz-Jeghers syndromesyndrome

P-J syndromeP-J syndrome

PathologyPathology

Reihl’s MelanosisReihl’s Melanosis

Photosensitivity, Photosensitivity, phototoxic dermatitisphototoxic dermatitis

Begins with pruritis, Begins with pruritis, erythema, and erythema, and pigmentation, pigmentation, gradually spreads, gradually spreads, then becomes then becomes stationarystationary

Melanosis occurs Melanosis occurs mostly in women and mostly in women and develops over monthsdevelops over months

Characteristic feature Characteristic feature is spotty light to dark is spotty light to dark brown pigmentationbrown pigmentation

Most intense on the Most intense on the forehead, malar forehead, malar regions, behind the regions, behind the ears, on the sides of ears, on the sides of the neck, on other the neck, on other sun-exposed areassun-exposed areas

Also circumscribed Also circumscribed telangiectasia and telangiectasia and temporary hyperemiatemporary hyperemia

Tar MelanosisTar Melanosis An occupational An occupational

dermatosis occurring dermatosis occurring among tar handlers among tar handlers after years of exposureafter years of exposure

Severe, widespread Severe, widespread itching develops, itching develops, followed by reticular followed by reticular pigmentation, pigmentation, telangiectases, and a telangiectases, and a shiny appearance of shiny appearance of the skinthe skin

There is a tendency for There is a tendency for hyperhidrosishyperhidrosis

Small, dark, lichenoid, Small, dark, lichenoid, follicular papules follicular papules become profuse on become profuse on the extremities, the extremities, namely the forearmsnamely the forearms

Bullae are sometimes Bullae are sometimes observedobserved

Represents a Represents a photosensitivity or photosensitivity or phototoxicity induced phototoxicity induced by tarby tar

Universal Acquired Universal Acquired Melanosis(Carbon Baby)Melanosis(Carbon Baby)

Ruiz-Maldonado Ruiz-Maldonado reported a case of reported a case of a Mexican child, a Mexican child, born white, who born white, who progressively progressively became blackbecame black

Developed Developed pigmentation of pigmentation of the palms, soles, the palms, soles, mucous mucous membranesmembranes

EM showed a EM showed a negroid pattern in negroid pattern in the melanosomes the melanosomes of the epidermal of the epidermal melanocytes and melanocytes and keratinocyteskeratinocytes

Melanocytes were Melanocytes were not increased in not increased in numbernumber

Periorbital HyperpigmentationPeriorbital Hyperpigmentation

1.) Familial 1.) Familial periorbital periorbital melanosis (AD)melanosis (AD)

Usually involves all Usually involves all four eyelids, may four eyelids, may extend to involve extend to involve the eyebrows and the eyebrows and cheekscheeks

2.) Erythema 2.) Erythema dyschromicum dyschromicum perstans is a rare perstans is a rare causecause

3.) Familial dark 3.) Familial dark circles around the circles around the eyes, frequently eyes, frequently seen in individuals seen in individuals of Mediterranean of Mediterranean ancestryancestry

Metallic DiscolorationsMetallic Discolorations

Pigmentation from deposition of fine Pigmentation from deposition of fine metallic particles in the skinmetallic particles in the skin

Metal may be carried to skin from the Metal may be carried to skin from the blood stream or may permeate into it blood stream or may permeate into it from surface applicationsfrom surface applications

ArgyriaArgyria Localized or widespread Localized or widespread

slate-colored slate-colored pigmentation pigmentation

Due to silver in the skinDue to silver in the skin Most noticeable in parts Most noticeable in parts

exposed to sunlightexposed to sunlight Tissue silver may Tissue silver may

stimulate melanocytesstimulate melanocytes Initially discoloration is Initially discoloration is

hardly perceptible, hardly perceptible, having only a faint blue having only a faint blue color, but a slate-gray color, but a slate-gray color develops with timecolor develops with time

Local tx with a silver-Local tx with a silver-containing product may containing product may produce argyriaproduce argyria

Examples: conjunctivae, from Examples: conjunctivae, from eye drops; a wound from eye drops; a wound from sulfadiazine cream, earlobes sulfadiazine cream, earlobes from silver earings; and from from silver earings; and from silver acupuncture needlessilver acupuncture needles

Can also occur from Can also occur from occupational exposure, occupational exposure, usually siversmithsusually siversmiths

In localized exposures, the In localized exposures, the appearance may be appearance may be separated by many years separated by many years from the exposurefrom the exposure

HistologyHistology

Systemic and localized argria have the Systemic and localized argria have the same featuressame features

Normal appearing skin under low powerNormal appearing skin under low power Fine black granules in the basement zone Fine black granules in the basement zone

of the sweat glands,blood vessel walls, d-e of the sweat glands,blood vessel walls, d-e junction, and arrector pili musclesjunction, and arrector pili muscles

Unstained biopsy section by darkfield Unstained biopsy section by darkfield illumination demonstrates silver granules illumination demonstrates silver granules outlining basement membrane of the outlining basement membrane of the epidermis and the eccrine sweat glandsepidermis and the eccrine sweat glands

BismuthBismuth

Rarely associated with deposition of Rarely associated with deposition of metallic particles in gums when used IM or metallic particles in gums when used IM or orallyorally

Also known as the Also known as the bismuth linebismuth line Presence of stomatitis or peridontitis Presence of stomatitis or peridontitis

increased the risk increased the risk Generalized cutaneous discoloration, in Generalized cutaneous discoloration, in

addition to oral mucous membrane and addition to oral mucous membrane and conjunctival pigmentation resembling conjunctival pigmentation resembling argyria has occurred but has not be argyria has occurred but has not be reported in the last 50 yearsreported in the last 50 years

LeadLead

Chronic lead poisoning can produce a Chronic lead poisoning can produce a “lead hue” with lividity and pallor“lead hue” with lividity and pallor

Deposit of lead in the gums may Deposit of lead in the gums may occur and is known as the “lead occur and is known as the “lead line”line”

IronIron

In the past, soluble iron compounds In the past, soluble iron compounds were used in the treatment of were used in the treatment of allergic contact dermatitidesallergic contact dermatitides

In eroded areas iron was sometimes In eroded areas iron was sometimes deposited in the skin, like a tattoodeposited in the skin, like a tattoo

Use of Monsel’s solution can produce Use of Monsel’s solution can produce similar tattooingsimilar tattooing

GoldGold

Chrysiasis may be induced by parenteral Chrysiasis may be induced by parenteral administration of gold salts, usually for the administration of gold salts, usually for the treatment of rheumatoid arthritistreatment of rheumatoid arthritis

More commonly recognized in white patientsMore commonly recognized in white patients A mauve, blue, or slate/gray pigmentation A mauve, blue, or slate/gray pigmentation

develops initially on the eyelids, spreading to develops initially on the eyelids, spreading to the face, dorsal hands, and other areasthe face, dorsal hands, and other areas

Severity is related to the total dose received, Severity is related to the total dose received, rare < a dose of 20 mg/kg of elemental goldrare < a dose of 20 mg/kg of elemental gold

MercuryMercury

Mercurial pigmentation in the skin is Mercurial pigmentation in the skin is rare, especially since the use of rare, especially since the use of mercurials has been strictly mercurials has been strictly controlledcontrolled

Most common presentation is Most common presentation is subcutaneous nodules that result subcutaneous nodules that result from accidental implantation of from accidental implantation of elemental mercury from a elemental mercury from a thermometer into skinthermometer into skin

CanthaxanthinCanthaxanthin

Orange-red pigment canthaxanthin is Orange-red pigment canthaxanthin is present in many plants ( notably algae and present in many plants ( notably algae and mushrooms) and in bacteria. Crustaceans, mushrooms) and in bacteria. Crustaceans, sea trout, and featherssea trout, and feathers

When ingested for the purpose of When ingested for the purpose of simulating a tan, its deposition in the simulating a tan, its deposition in the panniculus imparts a golden orange hue to panniculus imparts a golden orange hue to the skinthe skin

Stools become brick red and the plasma Stools become brick red and the plasma orange, and golden deposits appear in the orange, and golden deposits appear in the retinaretina

Dye DiscolorationDye Discoloration

Blue hands from accidental dyeing Blue hands from accidental dyeing were reported by Albert in 1976were reported by Albert in 1976

A man’s hands were dyed as a result A man’s hands were dyed as a result of warming them in his armpits while of warming them in his armpits while wearing a new blue flannel shirtwearing a new blue flannel shirt

The dye was insoluble in water, but The dye was insoluble in water, but soluble in sweatsoluble in sweat

RubeosisRubeosis

A rosy coloration of the face A rosy coloration of the face occurring in young people with occurring in young people with uncontrolled diabetes mellitusuncontrolled diabetes mellitus

May be associated with May be associated with xanthochromia to produce a xanthochromia to produce a “peaches and cream” complexion“peaches and cream” complexion

VitiligoVitiligo

Usually begins in childhood or young Usually begins in childhood or young adulthoodadulthood

50% of cases begin before age 2050% of cases begin before age 20 Prevalence ranges from 0.5% to 1%Prevalence ranges from 0.5% to 1% Females are disproportionately Females are disproportionately

represented among patients seeking represented among patients seeking medical care, it is not known if it is medical care, it is not known if it is actually more common in females or actually more common in females or simply because they more often bring it to simply because they more often bring it to their physicians attentiontheir physicians attention

Clinical FeaturesClinical Features An acquired pigmentary anomaly of the An acquired pigmentary anomaly of the

skinskin Manifested by depigmented white patches Manifested by depigmented white patches

surrounded by a normal or a surrounded by a normal or a hyperpigmented borderhyperpigmented border

There may be intermediate tan zones or There may be intermediate tan zones or lesions , halfway between the normal skin lesions , halfway between the normal skin color and depigmentaton-so-called color and depigmentaton-so-called trichrome vitiligotrichrome vitiligo

Hairs in vitiliginous areas usually become Hairs in vitiliginous areas usually become white alsowhite also

TypesTypes

Localized or focal(including Localized or focal(including segmental)segmental)

GeneralizedGeneralized UniversalUniversal AcrofacialAcrofacial

VitiligoVitiligo

Generalized is the most commonGeneralized is the most common Involvement is symmetricalInvolvement is symmetrical Most commonly involving the face, upper Most commonly involving the face, upper

chest, dorsal aspects of the hands, axillae, chest, dorsal aspects of the hands, axillae, and groinand groin

Tendency for skin around orifices to be Tendency for skin around orifices to be affected (eyes,nose, mouth, ears, nipples, affected (eyes,nose, mouth, ears, nipples, umbilicus, penis, vulva, anus)umbilicus, penis, vulva, anus)

Lesions also favor areas of trauma (elbows Lesions also favor areas of trauma (elbows and knees)and knees)

Generalized VitiligoGeneralized Vitiligo

Involvement of Involvement of perineal and perineal and inguinal skininguinal skin

Note the distinct Note the distinct bordersborders

Acral VitiligoAcral Vitiligo

Symmetric, Acral VitiligoSymmetric, Acral Vitiligo

Left: pre-PUVA treatmentLeft: pre-PUVA treatment Right:same pt shows perifollicular Right:same pt shows perifollicular

pattern of repigmentation during pattern of repigmentation during PUVA therapyPUVA therapy

Segmental VitiligoSegmental Vitiligo

Rapidly progressing Rapidly progressing segmental vitiligosegmental vitiligo

Segmental VitiligoSegmental Vitiligo

Segmental vitiligo Segmental vitiligo of the eyebrow and of the eyebrow and eyelasheseyelashes

Segmental VitiligoSegmental Vitiligo

Segmental vitiligo on Segmental vitiligo on the arm , neck, and the arm , neck, and chestchest

Note areas of Note areas of spontaneous follicular spontaneous follicular repigmentationrepigmentation

Left upper back with Left upper back with partial spontaneous partial spontaneous repigmentationrepigmentation

Universal VitiligoUniversal Vitiligo

Applies to cases Applies to cases where the entire where the entire body surface is body surface is depigmenteddepigmented

Acrofacial VitiligoAcrofacial Vitiligo

Type affecting the Type affecting the distal fingers and distal fingers and the facial orificesthe facial orifices

Childhood VitiligoChildhood Vitiligo

Shows an increase Shows an increase in segmental in segmental presentationpresentation

More frequent More frequent autoimmune or autoimmune or endocrine endocrine anomaliesanomalies

High incidence of High incidence of premature graying premature graying in femalesin females

Poor response to Poor response to PUVA therapyPUVA therapy

VitiligoVitiligo

Completely Completely depigmented oval depigmented oval ivory white areas ivory white areas with convex with convex hyperpigmentated hyperpigmentated bordersborders

VitiligoVitiligo

Vitiligo with Vitiligo with depigmentation of depigmentation of the lipsthe lips

Chemical DepigmentationChemical Depigmentation

Chemical Chemical depigmentation depigmentation due to a germicidal due to a germicidal detergentdetergent

Pts usually improve Pts usually improve with with discontinuation of discontinuation of the offending the offending agentagent

PathogenesisPathogenesis

Three possible mechanisms have Three possible mechanisms have been proposed as inducing vitiligo been proposed as inducing vitiligo are autoimmunity, neurohumoral are autoimmunity, neurohumoral factors, and autocytotoxicityfactors, and autocytotoxicity

No mechanism has been conclusively No mechanism has been conclusively provenproven

HistologyHistology

There is complete There is complete loss of loss of melanocytes melanocytes

Usually there is no Usually there is no inflammatory inflammatory componentcomponent

DifferentialDifferential

MorpheaMorphea Lichen sclerosisLichen sclerosis Pityriasis albaPityriasis alba Tinea versicolor tertiary pintaTinea versicolor tertiary pinta

TreatmentTreatment Spontaneous Spontaneous

repigmentation occurs repigmentation occurs in no more than 15% to in no more than 15% to 25% of cases25% of cases

Response is slowResponse is slow PUVA may actually PUVA may actually

worsen the appearance worsen the appearance initially by pigmenting initially by pigmenting surrounding skinsurrounding skin

Cover-up Cover-up strategies(topical dyes, strategies(topical dyes, make-up, self-tanning make-up, self-tanning creams)creams)

Fair-skinned pts may Fair-skinned pts may manage their disease with manage their disease with sunblocksunblock

Sun protection is mandatory Sun protection is mandatory in all pts with vitiligo in all pts with vitiligo because of the loss of because of the loss of protection from UV radiation protection from UV radiation in the depigmented skinin the depigmented skin

Topical steroids may be Topical steroids may be useful on focal or limited useful on focal or limited lesionslesions

Mid to super high-potency Mid to super high-potency steroids are often required steroids are often required on trunk and acral lesions on trunk and acral lesions with the strength tapered as with the strength tapered as the lesions respondthe lesions respond

If > 50% of the body surface area is If > 50% of the body surface area is affected by vitiligo, the pt can consider affected by vitiligo, the pt can consider depigmentationdepigmentation

This tx is permanentThis tx is permanent Monobenzone 20% is applied BID for 3-6 Monobenzone 20% is applied BID for 3-6

months to residual pigmented areasmonths to residual pigmented areas Up to 10 months may be requiredUp to 10 months may be required One in six pts will experience acute One in six pts will experience acute

dermatitis, usually confined to the still-dermatitis, usually confined to the still-pigmented areaspigmented areas

VitiligoVitiligo

Partial Partial repigmentation of repigmentation of lesions of vitiligo lesions of vitiligo on the leg of a 14-on the leg of a 14-year-old child at year-old child at the end of the the end of the summer of sun summer of sun exposureexposure

VitiligoVitiligo

Partial Partial repigmenation of repigmenation of vitiligo following vitiligo following psorralen-psorralen-ultraviolet light ultraviolet light (PUVA) therapy(PUVA) therapy

VitiligoVitiligo

Permanent Permanent repigmentation repigmentation after 2 years of after 2 years of photochemotherapphotochemotherapy (tripsoralen y (tripsoralen followed by followed by sunlight exposure)sunlight exposure)

Vogt-Koyanagi-Harada Vogt-Koyanagi-Harada SyndromeSyndrome

Characterized by bilateral uveitis, Characterized by bilateral uveitis, symmetrical vitiligo, alopecia, white scalp symmetrical vitiligo, alopecia, white scalp hair, eyelashes and brows(poliosis, and hair, eyelashes and brows(poliosis, and dysacousia(diminished hearing)dysacousia(diminished hearing)

Occurs in thirtiesOccurs in thirties Initial or meningoencephalitic phase Initial or meningoencephalitic phase

occurs with prodromata of fever, malaise, occurs with prodromata of fever, malaise, headache, nausea, and vomitingheadache, nausea, and vomiting

Also may have psychosis, paraplegia, Also may have psychosis, paraplegia, hemiparesis, aphagia, and nuchal rididityhemiparesis, aphagia, and nuchal rididity

Recovery is usually completeRecovery is usually complete

VKHSVKHS

Second phase(ophthalmic-auditory Second phase(ophthalmic-auditory stage) is characterized by uveitis, stage) is characterized by uveitis, dreased visual acuity, photopobia, dreased visual acuity, photopobia, and decreased hearing(50%)and decreased hearing(50%)

The convalescent phase begins The convalescent phase begins 3weeks to 3 months after it begins to 3weeks to 3 months after it begins to improveimprove

Alezzandrini’s SyndromeAlezzandrini’s Syndrome

Extremely rare syndrome Extremely rare syndrome characterized by a unilateral characterized by a unilateral degenerative retinitsdegenerative retinits

This is followed several months later This is followed several months later by ipsilateral vitiligo on the face and by ipsilateral vitiligo on the face and ipsilateral poliosisipsilateral poliosis

Deafness may also be presentDeafness may also be present

Alezzandrini’s SyndromeAlezzandrini’s Syndrome

LeukodermaLeukoderma

Postinflammatory leukoderma may result Postinflammatory leukoderma may result from inflammatory dermatoses ie:from inflammatory dermatoses ie:

Pityriasis rosea, psoriasis, herpes zoster, Pityriasis rosea, psoriasis, herpes zoster, secondary syphilis, and morphea, secondary syphilis, and morphea, sarcoidosis, tinea versicolor, mycosis sarcoidosis, tinea versicolor, mycosis fungoides, scleroderma, and pityriasis fungoides, scleroderma, and pityriasis lichenoides chronica, and leprosylichenoides chronica, and leprosy

Other causes: burns, scars, Other causes: burns, scars, postdermabrasion, and intralesioal steroid postdermabrasion, and intralesioal steroid injectionsinjections

LeukodermaLeukoderma

Postinflammatory Postinflammatory hypopigmentation hypopigmentation in a 4-month-old in a 4-month-old black child with black child with atopic dermatitisatopic dermatitis

LeukodermaLeukoderma

Postinflammatory Postinflammatory hypopigmentation hypopigmentation following resolution following resolution of guttate psoriasisof guttate psoriasis

Pityriasis albaPityriasis alba Ill-defined Ill-defined

hypopigmented oval hypopigmented oval patches are generally patches are generally seen on the face, seen on the face, upper arms, neck, and upper arms, neck, and shoulders of affected shoulders of affected personspersons

It can be differentiated It can be differentiated from vitiligo by its fine from vitiligo by its fine adherent scale, partial adherent scale, partial hypopigmentation, hypopigmentation, and distributionand distribution

Pityriasis albaPityriasis alba

White, slightly White, slightly scaly patches with scaly patches with indistinct borders indistinct borders on a child’s cheekon a child’s cheek

Postinflammatory Postinflammatory hypopigmentationhypopigmentation

AlbinismAlbinism

A partial or complete congential absence A partial or complete congential absence of pigment in the skin, hair, and eyes of pigment in the skin, hair, and eyes (oculocutaneous albinism), or the eyes (oculocutaneous albinism), or the eyes alone (ocular albinism)alone (ocular albinism)

Cutaneous phenotype of the various forms Cutaneous phenotype of the various forms is broad, but the ocular phenotype is is broad, but the ocular phenotype is reasonably constant in most formsreasonably constant in most forms

The ocular phenotype includes decreased The ocular phenotype includes decreased visual acuity, nystagmus, pale irides that visual acuity, nystagmus, pale irides that transilluminate, hypopigmented fundi, transilluminate, hypopigmented fundi, hypoplastic foveae, and lack of stereopsishypoplastic foveae, and lack of stereopsis

AlbinismAlbinism

This pt has light This pt has light skin, yellowish skin, yellowish white hair, and a white hair, and a lack of lack of pigmentation in pigmentation in nevinevi

Oculocutaneous Albinism 1Oculocutaneous Albinism 1

OCA 1 results from mutations in the tyrosinase gene OCA 1 results from mutations in the tyrosinase gene Affected pts are homozygous for the mutant gene or are Affected pts are homozygous for the mutant gene or are

compound heterozygotes for different mutations in the compound heterozygotes for different mutations in the tyrosinase genetyrosinase gene

ARAR Two forms: 1) OCA 1A & OCA 1B (indistinguishable at Two forms: 1) OCA 1A & OCA 1B (indistinguishable at

birth)birth) OCA 1 is most severe with complete absence of OCA 1 is most severe with complete absence of

tyrosinase activity and complete absence of melanin in tyrosinase activity and complete absence of melanin in the skin and eyesthe skin and eyes

Visual acuity is decreased to 20/400Visual acuity is decreased to 20/400 OVA 1B tyrosinase activity is reduced but not absent. Pts OVA 1B tyrosinase activity is reduced but not absent. Pts

may show increase in skin,hair, eye color with age and may show increase in skin,hair, eye color with age and can tancan tan

OCA 1OCA 1

OCA 1B was originally called “yellow OCA 1B was originally called “yellow mutant” albinismmutant” albinism

Temperature sensitive OCA (OCA 1-TS) Temperature sensitive OCA (OCA 1-TS) results from mutations in the tyrosinase results from mutations in the tyrosinase gene that produce an enzyme with limited gene that produce an enzyme with limited activity < 35 degrees C and no activity activity < 35 degrees C and no activity below this temp. pts have white hair, skin, below this temp. pts have white hair, skin, andeyes at birth, at puberty dark hair andeyes at birth, at puberty dark hair develops in cooler acral areasdevelops in cooler acral areas

Top:albinism with Top:albinism with white hair, pale skin, white hair, pale skin, and translucent iridesand translucent irides

Bottom:ophthalmoscoBottom:ophthalmoscopic view of a pt with pic view of a pt with albinism demonstrates albinism demonstrates a pale fundus, poor a pale fundus, poor macular development, macular development, and prominent and prominent choroidal vasculaturechoroidal vasculature

Oculocutaneous Albinism 2Oculocutaneous Albinism 2 Prevalence of 1:15,000Prevalence of 1:15,000 Pts were named “tyrosinase-positive” albinosPts were named “tyrosinase-positive” albinos AR and mutations occur in the P geneAR and mutations occur in the P gene P gene codes a membrane transport protein that is P gene codes a membrane transport protein that is

present in the melanosome membranepresent in the melanosome membrane Cutaneous phenotype of OCA 2 pts is broad, ranging Cutaneous phenotype of OCA 2 pts is broad, ranging

from nearly normal pigmentation to virtually no from nearly normal pigmentation to virtually no pigmentationpigmentation

Pigmentation increases with age, and visual acuity Pigmentation increases with age, and visual acuity improves with ageimproves with age

Prader-Willi and Angelman syndromes are caused by Prader-Willi and Angelman syndromes are caused by deletions in the P gene; 1% of pts with these deletions in the P gene; 1% of pts with these syndromes also have OCA 2syndromes also have OCA 2

Oculocutaneous Albinism 3Oculocutaneous Albinism 3

AR-caused by mutations in the tyrosine-AR-caused by mutations in the tyrosine-related protein 1 (TRP-1), located on related protein 1 (TRP-1), located on chromosome 9chromosome 9

OCA 3 has been described only in black OCA 3 has been described only in black pts and is characterized by light brown pts and is characterized by light brown hair, light brown skin, blue/brown irrides, hair, light brown skin, blue/brown irrides, nystagmus, and decreased visual activitynystagmus, and decreased visual activity

Brown rather than black melanin is formedBrown rather than black melanin is formed

Ocular AlbinismOcular Albinism

There are multiple forms of ocular albinismThere are multiple forms of ocular albinism OA 1 may be present with lighter than OA 1 may be present with lighter than

expected skinexpected skin It is X-linkedIt is X-linked Female carriers have “mud-splattered” Female carriers have “mud-splattered”

fundifundi Macromelanosomes are found in the skin, Macromelanosomes are found in the skin,

so skin bx may be a helpful toolso skin bx may be a helpful tool Many cases of AR ocular albinism have Many cases of AR ocular albinism have

been reclassified as OCA 1 or OCA 2been reclassified as OCA 1 or OCA 2

Syndromes Associated with Syndromes Associated with AlbinismAlbinism

Chediak-Higashsi SyndromeChediak-Higashsi Syndrome Hermansky-Pudlak SyndromeHermansky-Pudlak Syndrome Griscelli Syndrome(partial albinism Griscelli Syndrome(partial albinism

with immunodeficiency)with immunodeficiency) Elejalde SyndromeElejalde Syndrome Cross-McKusick-Breen SyndromeCross-McKusick-Breen Syndrome Cuna Moon ChildrenCuna Moon Children

Classification of Classification of Oculocutaneous AlbinismOculocutaneous Albinism

Selenium DeficiencySelenium Deficiency

Selenium deficiency in the setting of Selenium deficiency in the setting of total parental nutrition can lead to total parental nutrition can lead to pseudoalbinismpseudoalbinism

Skin and hair pigmentation return to Skin and hair pigmentation return to normal with supplementationnormal with supplementation

Waardenburg’s SyndromeWaardenburg’s Syndrome

Four genotypic variants Four genotypic variants exist:exist:

Types 1 & 3 are caused Types 1 & 3 are caused by mutations in the PAX by mutations in the PAX gene on chromosome 2gene on chromosome 2

Type 2 is caused by Type 2 is caused by mutations in the MITF mutations in the MITF gene on chromosome gene on chromosome 3, and type 4 due to 3, and type 4 due to mutations in the ENDRB mutations in the ENDRB gene on chromosome gene on chromosome 1313

Pts have features of Pts have features of piebaldism, with white piebaldism, with white forelock, forelock, hypopigmentation, hypopigmentation, premature graying, premature graying, synophrys, congenital synophrys, congenital deafness, a broad deafness, a broad nasal root, and ocular nasal root, and ocular changes including changes including heterochromia iridesheterochromia irides

Apparently, Apparently, melanoblasts fail to melanoblasts fail to reach the target sites reach the target sites during embryogenesisduring embryogenesis

PiebaldismPiebaldism Rare, AD with variable Rare, AD with variable

phenotype, presenting at phenotype, presenting at birthbirth

White forelock, patchy White forelock, patchy absence of skin pigmenationabsence of skin pigmenation

Depigmented lesions are Depigmented lesions are static and occur on the static and occur on the anterior and posteroir trunk, anterior and posteroir trunk, mid upper arm to wrist, mid-mid upper arm to wrist, mid-thigh to mid-calf, and shinsthigh to mid-calf, and shins

A characteristic feature is A characteristic feature is the presence of the presence of hyperpigmented macules hyperpigmented macules within the areas of lack of within the areas of lack of pigmentation and on normal pigmentation and on normal skinskin

PiebaldismPiebaldism

PiebaldismPiebaldism

Segmental white Segmental white patch on the neck patch on the neck with a tuft of white with a tuft of white hair present from hair present from birthbirth

PiebaldismPiebaldism

White forelock and White forelock and patch of patch of unpigmented skin unpigmented skin in a young girl with in a young girl with piebaldismpiebaldism

PiebladismPiebladism The white forelock arises from a triangular or The white forelock arises from a triangular or

diamond-shaped midline white macule on the diamond-shaped midline white macule on the frontal scalp or foreheadfrontal scalp or forehead

The medial portions of the eyebrows, and The medial portions of the eyebrows, and eyelashes may be whiteeyelashes may be white

Histologically, melanocytes are completely absent Histologically, melanocytes are completely absent in the white maculesin the white macules

Etiology is a mutation in the c-kit protooncogeneEtiology is a mutation in the c-kit protooncogene Phenotypic differences seen in families is caused Phenotypic differences seen in families is caused

by different locations of mutations in the geneby different locations of mutations in the gene The white lesions may respond to surgical The white lesions may respond to surgical

excisionexcision

Idiopathic Guttate Idiopathic Guttate HypomelanosisHypomelanosis

AKA leukopathica symmetrica progressivaAKA leukopathica symmetrica progressiva Very common aquired disorder affecting Very common aquired disorder affecting

women more frequently than menwomen more frequently than men Usually occurs after age 40Usually occurs after age 40 Lesions occur on the shins and forearms; are Lesions occur on the shins and forearms; are

small (6 or 8mm), rarely become very small (6 or 8mm), rarely become very numerous ( a dozen or two at most), and numerous ( a dozen or two at most), and never occur on the face or trunknever occur on the face or trunk

Lesions are irregularly shaped and very Lesions are irregularly shaped and very sharply defined, like depigmented ephelides, sharply defined, like depigmented ephelides, and are only of cosmetic significance and are only of cosmetic significance

Idiopathic Guttate Idiopathic Guttate HypomelanosisHypomelanosis