Chapter 36Disturbances of PigmentationJoAnne M. LaRow. D.O.

Melanin = primary pigment producing brown colorationTyrosine tyrosinase melanin- this occurs in the melanosomes of melanocytesThen the melanosomes are transferred from the melanocyte to a group of keratinocytes called the epidermal melanin unitVariations in skin color is related to the number of melanosomes, the degree of melanization, and the distribution of the epidermal melanin unit

Pigmentary Demarcation LinesCan be divided into five categories:Group A- lines along the outer upper arms with variable extension across the chestGroup B-lines along the posteromedial aspect of the lower limbGroup C-Paired median or paramedian lines on the chest, with midline abdominal extensionGroup D-medial, over the spineGroup E-bilaterally symmetrical, obliquely oriented, hypopigmented macules on the chest

Pigmentary Demarcation LinesMore than 70% of blacks have one or more linesThese are much less common in whitesType B lines often appear for the first time during pregnancy

Normal PigmentationNormal skin pigmentation is influenced by: -the degree of vascularity -the amount & location of melanin -the presence of carotene -the thickness of the horny layer

Melanin ProductionThe amount produced is dependent on: -genetics -the amount and the wavelengths of ultraviolet light received -the amount of melanocyte-stimulating hormone(MSH) secreted - the effect of melanoccytestimulatingg chemicals like furocoumarins (psoralens)

Hemosiderin HyperpigmnetationPigmentation due to deposits of hemosiderin occurs in: -purpura -hemochromatosis -hemorrhagic diseases -stasis ulcers** difficult to distinguish from postinflammatory dermal melanosis clinically

Postinflammatory HyperpigmentationAny inflammatory condition can cause either hypopigmentation or hyperpigmentationAlso may be a complication of chemical peels, dermabrasion, laser therapy, or liposuctionHistologically, there is melanin in the upper dermis and around upper dermal vessels, located primarily in macrophages (melanophages)

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

Industrial HyperpigmentationOccurs in coal miners, anthracene workers, pitch workers, etcPigmentation of the face may occur from the incorporation in cosmetics of derivatives of coal tar, petrolatum, or picric acid, mercury, lead, bismuth, or furocoumarins (psoralens)

Systemic DiseasesSyphilis, malaria, pellagra, and diabetesAddisons disease- diffuse melanosis pronounced in the axillae and palmar creases, and nipples and genitals, and buccal mucosaDiabetes produces diffuse bronzing of the skin** patients with virilizing adrenal tumors usually develop hyperpigmentation and hypertrichosis

Systemic DiseasesNelsons syndrome (a pituitary MSH-producing tumor) PheochromocytomaHemochromatosisAmyloidosisScurvyPregnancyMenopausePorphyria cutanea tardaVitamin B12 deficiencyKwashiorkorVitamin A deficiencyPrimary biliary cirrhosis (triad= hyperpigmentation, pruritis, xanthomas)

Hemochromatosis

Characterized by:Gray-brown mucocutaneous hyperpigmentationDiabetes mellitushepatomegalyUsually are present:CirrhoisisHypogonadismLiver cirrhosis

Hemochromatosis

Skin pigmentaion is usually generalizedBut, more pronounced on face, extensor aspect of the forearms, backs of the hands, and the geniocrural areaIron is deposited in the skinIron is present as granules around blood vessels and sweat glands and within macrophagesThe actual pigmentation is caused by increased basal-layer melaninMucous memebranes are pigmented in up to 20% of patientsKoilonychia is present in 50%Localized ichthyosis in 40%Alopecia is common

HemochromatosisOccurs mostly in men in their sixtiesWomen who have genetic hemochromatosis can have full phenotypic expression Extremely rare in the youngNeonatal hemochromatosis has been associated with intrauterine infections ie cytomegalovirusAdults with hemochromatosis are susceptible to Yersinia enterocoliticaDx:Elevated plasma iron and IBPHigh serum ferritin without an obvious cause should prompt investigation for both hemochromatosis and PCTEtiology is either an inborn error of metabolism or excessive number of blood transfusionsAR gene for heredity hemochromatosis is linked to the HLA-A locus on chromosome 6p

Hemochromatosis-txPhlebotomy until satisfactory iron levels are foundExtracorporeal chelation has also been used successfullyAssociated DM requires medical txLong-term complications are cirrhosis and then hepatomas

MelasmaBrown patches, sharply demarcated, typically on the malar prominences and foreheadThe three clinical patterns are: centrofacial, malar, mandibularIncreased pigment may simultaneously occur around the nipples and external genitalia

Tends to affect the darker-complectedIt may also be found on the forearmsOccurs at pregnancy and at menopauseIt may also be seen in ovarian disorders and other endocrine disordersMost frequently 90% of the time seen in women, 10% in men

MelasmaStrong association with the use of birth control pills or dilantinDiscontinuing the contraceptives rarely clears the pigmentation, and it may last for years after discontinuing them.Melasma of pregnancy usually clears within a few months of deliveryTx- avoid sunlight, and a complete sun block with broad-spectrum UVA coverage should be used dailyKligmans formula (Triluma)> then 4% hydroquinone may be neededSide effects of this is ochronosis and satellite pigmentationJessners solution, glycolic acid peels,azelaic acid, kojic acid, and cystamine and buthionine sulfoximine are other options

Melasma

Melasma

Melasma

Acromelanosis ProgressivaAKA acropigmentationA progressive pigmentary disorder first described in a Japanese infantCharacterized by diffuse black pigmentation on the dorsum of all the fingers and toesPigmentation became progressively more widespread and more pigmentedBy age 4 or 5 the perineum, extremities, and areas of the head and neck were involvedEpileptiform seizures occurredHistory revealed consanguinity

Pigmented Anomalies of the ExtremitiesAcropigmentation of DohiFound to affect individuals from Europe, India, CaribbeanFirst described in Japan in 12 patientsAKA dyschromatosis symmetrica hereditaria or symmetrical dyschromatosis of the extremitiesPatients develop progressive pigmented & depigmented maculesOften mixed in is a reticulate patternMany believe this to be a variation of acropigmentation of Kitamura

Reticular Pigmented Anomaly of the FlexuresA rare pigmentary adult-onset disorderAKA Dowling-Degos disease or dark dot diseaseShould be considered whenever acanthosis nigricans is in the differential & pt is not obese and is known not to have any internal malignancyClinically it looks smoothPigmententation is reticular; at the periphery, discrete, brownish black macules surround the partly confluent central pigmented areaTypically, axillae, inframmary folds, and intercrural folds are involvedThere are frequently pits, sometimes pigmented , about the mouth

Reticular Pigmented Anomaly of the FlexuresIt begins age 20 to 30 yrs and progresses graduallyUnknown etiology AD with variable penetrance and expressivity, and delayed onset

Many authors believe it is a spectrum of reticulate acropigmentation of Kitamura Another manifestation of this disorder is familial-rocacea-like dermatitis with warty keratotic plaques on the trunk and limbsThere is no treatment

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

Reticulate Acropigmentation of KitamuraADCharacterized by linear palmar pits and pigmented macules 1-4 mm in diameter on the volar and dorsal aspects of the hands and feetOne report of a pt with bony abnormalities consisting of absence of terminal phalanges of the second, third, and fourth toesSome tx success has been reported using axelaic acid ointment

Dermatopathia Pigmentosa ReticularisConsists of a triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophyOther associations: adermatoglyphia, hypohidrosis or hyperhidrosis, palmoplantar hyperkeratosis, and nonscarring blisters on dorsa of hands and feet.An autosomal dominant inheritance pattern has been reported.

Dermatopathia Pigmentosa Reticularis

Transient Neonatal Pustular MelanosisInfants develop 2- 3mm macules, pustules, and ruptured pustules at birth, predominantly involving the facePigmentation may last for weeks or months after the pustules are healedHistologically, there are intracorneal or subcorneal aggregates of predominantly neutrophils, but eosinophils may also be foundDermal inflammation is composed of an admixture of neuts and eosDifferential dx: ETN, neonatal acne, & acropustulosis of infancy

Transient Pustular Neonatal Melanosis

Transient Neonatal Pustular Melanosis

Peutz-JeghersCharacterized by hyperpigmented macules on the lips and oral mucosa and polyposis of the small intestineDark brown or black macules appear typically on the lips, especially the lower lip, in infancy or childhoodSimilar lesions may appear on buccal mucosa, tongue, gingiva, and genital mucosa

Macules may also occur around the mouth, on the central face, backs of the hands, especially the fingers, and on the toes and tops of the feet.Associated polyposis involves the small intestine preferencelyBut, hamartomatous polyps of the stomach and colon may occurSymptoms of hamhartomas of the small intestine may cause repeated bouts of abdominal pain and vomiting, and intussusception

Peutz-Jeghers SyndromeCosmetic tx of labial macules has been accomplished with the use of a 694-mm ruby laser incidence of malignancy within the polyps is 2-3%Incidence of GI malignancy is low, but increased incidence of other kinds of cancer-breast, and gynecologic malignancies in womenSyndrome is inherited and transmitted as a simple mendelian dominant traitSporadic noninherited cases may occurThe gene (STK11) has been localized to 19p13.319p13.3 is believed to be a tumor suppressor gene

Peutz-Jeghers SyndromeCronkhite-Canada syndrome should be considered in dxCharacterized by melanotic macules on the fingers and gastrointestinal polyposisAlso generalized , uniform darkening of the skin, extensive alopecia, and onychodystrophyThe polys that occur are usually benign adenomas and may involve the whole GI tractA protein-losing enteropathy may develop and is associated with the degree of intestinal polyposisOnset is after age 30 yrsSporaically occurring, benign conditionHypogeusia is the dominant initial symptomDiarrhea and ectodermal changes may follow75% of cases have been reported in Japan

Peutz-Jeghers syndromeLip lentigenes in an adolescent with Peutz-Jeghers syndrome

P-J syndrome

Pathology

Reihls MelanosisPhotosensitivity, phototoxic dermatitisBegins with pruritis, erythema, and pigmentation, gradually spreads, then becomes stationaryMelanosis occurs mostly in women and develops over monthsCharacteristic feature is spotty light to dark brown pigmentationMost intense on the forehead, malar regions, behind the ears, on the sides of the neck, on other sun-exposed areasAlso circumscribed telangiectasia and temporary hyperemia

pathogenesisSun exposure following perfume or creamA photocontact dermatitisOne report of a positive patch test results to lemon oil, geraniol, and hydroxycitronellalHas been reported in patients with AIDS and Sjogrens syndromeNo good treatmentsThe cause of the sensitivity needs to be determeinedHyperkeratosis and pigmentation disappear spontaneously

Tar MelanosisAn occupational dermatosis occurring among tar handlers after years of exposureSevere, widespread itching develops, followed by reticular pigmentation, telangiectases, and a shiny appearance of the skinThere is a tendency for hyperhidrosisSmall, dark, lichenoid, follicular papules become profuse on the extremities, namely the forearmsBullae are sometimes observedRepresents a photosensitivity or phototoxicity induced by tar

Familial Progressive HyperpigmentationCharacterized by patches of hyperpigmentation, present at birth, increasing in size and number with ageHyperpigmentation appears in the conjunctivae and the buccal mucosa over timeEventually large portions of skin and mucous membranes become involvedAD inheritanceHistologically- increase in melanin in the basal cell layer, especially at the tips of the rete ridgesPigmented granules are scattered diffusely throughout the epidermal layersDifferentiated from other hyperpigmentations by presence of bizarre, sharply marginated patterns of hyperpigmented skin

Universal Acquired Melanosis(Carbon Baby)Ruiz-Maldonado reported a case of a Mexican child, born white, who progressively became blackDeveloped pigmentation of the palms, soles, mucous membranesEM showed a negroid pattern in the melanosomes of the epidermal melanocytes and keratinocytesMelanocytes were not increased in number

Zebralike HyperpigmentationAlimurung et al reported an unusual pattern of hyperpigmentation in a black male infant with congenital defects (ASD, dextrocardia, auricualr atresia, deafness. And growth retardation)Hyperpigmenation was linear and symmetrical, involving the trunk and extremitiesIncreased number of melanocytes in the bands of hyperpigmentationPigmentary anomaly fades with time spontaneouslyMay be a varient of incontinentia pigmenti

Periorbital Hyperpigmentation1.) Familial periorbital melanosis (AD)Usually involves all four eyelids, may extend to involve the eyebrows and cheeks

2.) Erythema dyschromicum perstans is a rare cause3.) Familial dark circles around the eyes, frequently seen in individuals of Mediterranean ancestry

Metallic DiscolorationsPigmentation from deposition of fine metallic particles in the skinMetal may be carried to skin from the blood stream or may permeate into it from surface applications

ArgyriaLocalized or widespread slate-colored pigmentation Due to silver in the skinMost noticeable in parts exposed to sunlightTissue silver may stimulate melanocytesInitially discoloration is hardly perceptible, having only a faint blue color, but a slate-gray color develops with time

Local tx with a silver-containing product may produce argyriaExamples: conjunctivae, from eye drops; a wound from sulfadiazine cream, earlobes from silver earings; and from silver acupuncture needlesCan also occur from occupational exposure, usually siversmithsIn localized exposures, the appearance may be separated by many years from the exposure

HistologySystemic and localized argria have the same featuresNormal appearing skin under low powerFine black granules in the basement zone of the sweat glands,blood vessel walls, d-e junction, and arrector pili musclesUnstained biopsy section by darkfield illumination demonstrates silver granules outlining basement membrane of the epidermis and the eccrine sweat glands

BismuthRarely associated with deposition of metallic particles in gums when used IM or orallyAlso known as the bismuth linePresence of stomatitis or peridontitis increased the risk Generalized cutaneous discoloration, in addition to oral mucous membrane and conjunctival pigmentation resembling argyria has occurred but has not be reported in the last 50 years

LeadChronic lead poisoning can produce a lead hue with lividity and pallorDeposit of lead in the gums may occur and is known as the lead line

IronIn the past, soluble iron compounds were used in the treatment of allergic contact dermatitidesIn eroded areas iron was sometimes deposited in the skin, like a tattooUse of Monsels solution can produce similar tattooing

GoldChrysiasis may be induced by parenteral administration of gold salts, usually for the treatment of rheumatoid arthritisMore commonly recognized in white patientsA mauve, blue, or slate/gray pigmentation develops initially on the eyelids, spreading to the face, dorsal hands, and other areasSeverity is related to the total dose received, rare < a dose of 20 mg/kg of elemental goldPigment is accentuated in light-exposed areas, and sun protected areas do not demonstrate goldLocalized chrysiasis has been induced by the Q-switched ruby laser tx in a patient on parental gold therapy

MercuryMercurial pigmentation in the skin is rare, especially since the use of mercurials has been strictly controlledMost common presentation is subcutaneous nodules that result from accidental implantation of elemental mercury from a thermometer into skin

CanthaxanthinOrange-red pigment canthaxanthin is present in many plants ( notably algae and mushrooms) and in bacteria. Crustaceans, sea trout, and feathersWhen ingested for the purpose of simulating a tan, its deposition in the panniculus imparts a golden orange hue to the skinStools become brick red and the plasma orange, and golden deposits appear in the retina

Dye DiscolorationBlue hands from accidental dyeing were reported by Albert in 1976A mans hands were dyed as a result of warming them in his armpits while wearing a new blue flannel shirtThe dye was insoluble in water, but soluble in sweat

RubeosisA rosy coloration of the face occurring in young people with uncontrolled diabetes mellitusMay be associated with xanthochromia to produce a peaches and cream complexion

VitiligoUsually begins in childhood or young adulthood50% of cases begin before age 20Prevalence ranges from 0.5% to 1%Females are disproportionately represented among patients seeking medical care, it is not known if it is actually more common in females or simply because they more often bring it to their physicians attention

Clinical FeaturesAn acquired pigmentary anomaly of the skinManifested by depigmented white patches surrounded by a normal or a hyperpigmented borderThere may be intermediate tan zones or lesions , halfway between the normal skin color and depigmentaton-so-called trichrome vitiligoHairs in vitiliginous areas usually become white alsoRarely, the patches may have a red, inflammatory borderPatches are of various sizes and configurations

TypesLocalized or focal(including segmental)GeneralizedUniversalAcrofacial

VitiligoGeneralized is the most commonInvolvement is symmetricalMost commonly involving the face, upper chest, dorsal aspects of the hands, axillae, and groinTendency for skin around orifices to be affected (eyes,nose, mouth, ears, nipples, umbilicus, penis, vulva, anus)Lesions also favor areas of trauma (elbows and knees)

Generalized VitiligoInvolvement of perineal and inguinal skinNote the distinct borders

Acral Vitiligo

Symmetric, Acral VitiligoLeft: pre-PUVA treatmentRight:same pt shows perifollicular pattern of repigmentation during PUVA therapy

Segmental VitiligoRapidly progressing segmental vitiligo

Segmental VitiligoSegmental vitiligo of the eyebrow and eyelashes

Segmental VitiligoSegmental vitiligo on the arm , neck, and chestNote areas of spontaneous follicular repigmentation

Left upper back with partial spontaneous repigmentation

Universal VitiligoApplies to cases where the entire body surface is depigmented

Focal VitiligoMay affect one nondermatomal siteOr asymmetrically affect a single dermatomeThis form is treatment resistant, has an earlier onset, and is frequently associated with other autoimmune phenomenaIt represents 5% of adult vitiligo and 20% of childood vitiligoTrigeminal area is most commonly affected

Acrofacial VitiligoType affecting the distal fingers and the facial orifices

VitiligoLocal loss of pigment may occur around nevi and melanomas, the so-called halo phenomenonVitiligo-like leukoderma occurs in 1% of melanoma patientsIn those previously dx with melanoma, it suggests metastatic diseaseParadoxically, patients who develop leukoderma have a better prognosis than patients without itHalo nevi are more common in patients with vitiligoLesions are hypersensitive to UV light and burn easily when exposed to the sun

Ocular abnormalities are increased in patients with vitiligoIritis and retinal pigmentary abnormalities8% of pts with idiopathic uveitis have vitiligo or poliosisMost frequent associations are with other autoimmune diseases((IDDM, pernicious anemia, Hashimotos thyroiditis, Graves disease, Addisons disease, and AA)Vitiligo occurs in 13% of pts with the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)Familial aggregation is seen- up to 30% of vitiligo pts have an affected relative-it is not inherited as AD or AR trait, but has a multifactorial genetic basis

Childhood VitiligoShows an increase in segmental presentationMore frequent autoimmune or endocrine anomaliesHigh incidence of premature graying in femalesPoor response to PUVA therapy

VitiligoCompletely depigmented oval ivory white areas with convex hyperpigmentated borders

VitiligoVitiligo with depigmentation of the lips

Henne Induced Vitiligo

Occupational VitiligoThiols, phenolic compounds, catechol, derivatives of catechol, mercaptoamines, and several quinones produce depigmentationSeen in pts who work in rubber garments or wear gloves containing an antioxidant, monobenzyl ether of hydroquinoneAll the intermediates in the biosynthesis of melanin are phenolic compounds, therefore postulated that accumulation of these within the melanocyte may damage or kill the cell.Clinical pattern may be similarto vitiligo, but lesions tend to be concentrated in areas of contact with the incriminated substance

Occupational VitiligoMany phenolic compounds can produce leukoderma, with or without antecedent dermatitisExamples: paratertiary sulfhydryls; monobenzyl ether of hydroquinoneOne source is phenolic antiseptic detergents used in hospitalsAdhesives and glues containing them may be found in shoes, wristbands, and adhesive tape, and rubber products used in brassieres, girdles, panties, or condoms may also be at faultSelf-sticking bindis (the cosmetic used by many Indian woman on the forehead) has been reported to induce leukoderma from the adhesive materialElectrocardiograph electrodes may cause similar hypopigmented spots

Chemical DepigmentationChemical depigmentation due to a germicidal detergentPts usually improve with discontinuation of the offending agent

PathogenesisThree possible mechanisms have been proposed as inducing vitiligo are autoimmunity, neurohumoral factors, and autocytotoxicityNo mechanism has been conclusively proven

Histology

There is complete loss of melanocytes Usually there is no inflammatory component

DifferentialMorpheaLichen sclerosisPityriasis albaTinea versicolor tertiary pinta

TreatmentSpontaneous repigmentation occurs in no more than 15% to 25% of casesResponse is slowPUVA may actually worsen the appearance initially by pigmenting surrounding skinCover-up strategies(topical dyes, make-up, self-tanning creams)Fair-skinned pts may manage their disease with sunblockSun protection is mandatory in all pts with vitiligo because of the loss of protection from UV radiation in the depigmented skinTopical steroids may be useful on focal or limited lesionsMid to super high-potency steroids are often required on trunk and acral lesions with the strength tapered as the lesions respond

TreatmentSystemic steroids lead to temporary repigmentation, this is usually lost as the steroidal agents are taperedPUVA therapy is the most common treatment for generalized vitiligoTopical application of 8-methoxypsoralen at a concentration of 0.05% to 0.01%, followed by UVA exposureTopical PUVA is used for focal or limited lesionsInadverrtent burns with blistering are frequent during txTrioxsalen, at a dose of up to 20-40mg, is taken a few hours before natural sun exposureRisk of phototoxicity is low,so this can be done at homeOcular protection must be worn from the ingestion of the drug through the whole tx day

Most commonly, 8-methoxyporalen is usedInitially tx is QOD(because of the delayed erythema of PUVA), increased to QD once dose is defined1hr to 30 mins before UVA exposure , 8-methoxypsoralen 0.5mg/kg is ingestedInitial UVA dose is 1 or 2 J/cm squared, which is gradually increased; 5-MOP has an aefficccacy equal to that of 8-MOP and less risk of phototoxicityTwo-three txs/week are done20% of pts total repigmentation occurs;30% to 40% have partial responseAcral, periorificial, and segmental lesions respond less wellDarker-skinned pts have a better response, since they tolerate higher UV dosesRepigmentation may begin after 15-25 txs;significant improvement may take 100-300 txs

If there is no follicular repigmentation after 3-6 months or approx 50 txs PUVA should be abatedCI to PUVA: photosensitivity, porphyria, liver disease, SLESurgical txs can be applied to limited lesions if all other tx modalities have been exhaustedEpidermal grafting, autologous minigrafts, and transplantation of cultured and noncultured melanocytes Phenylalanine/UVA(PAUVA) is much less effective than PUVAUVB tx alone with 311-nm irradiation is associated with a higher rate of acute phototoxicity but may be successfulUVA plus topical steroids is superior to either agent alone, but is successful only 24-36% of the time after 9 months

If > 50% of the body surface area is affected by vitiligo, the pt can consider depigmentationThis tx is permanentMonobenzone 20% is applied BID for 3-6 months to residual pigmented areasUp to 10 months may be requiredOne in six pts will experience acute dermatitis, usually confined to the still-pigmented areas

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

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

VitiligoPermanent repigmentation after 2 years of photochemotherapy (tripsoralen followed by sunlight exposure)

Vogt-Koyanagi-Harada SyndromeCharacterized by bilateral uveitis, symmetrical vitiligo, alopecia, white scalp hair, eyelashes and brows(poliosis, and dysacousia(diminished hearing)Occurs in thirtiesInitial or meningoencephalitic phase occurs with prodromata of fever, malaise, headache, nausea, and vomitingAlso may have psychosis, paraplegia, hemiparesis, aphagia, and nuchal rididityRecovery is usually complete

VKHSSecond phase(ophthalmic-auditory stage) is characterized by uveitis, dreased visual acuity, photopobia, and decreased hearing(50%)The convalescent phase begins 3weeks to 3 months after it begins to improve

Alezzandrinis Syndrome

Extremely rare syndrome characterized by a unilateral degenerative retinitsThis is followed several months later by ipsilateral vitiligo on the face and ipsilateral poliosisDeafness may also be present

Alezzandrinis Syndrome

LeukodermaPostinflammatory leukoderma may result from inflammatory dermatoses ie:Pityriasis rosea, psoriasis, herpes zoster, secondary syphilis, and morphea, sarcoidosis, tinea versicolor, mycosis fungoides, scleroderma, and pityriasis lichenoides chronica, and leprosyOther causes: burns, scars, postdermabrasion, and intralesioal steroid injections

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

LeukodermaPostinflammatory hypopigmentation following resolution of guttate psoriasis

Pityriasis albaIll-defined hypopigmented oval patches are generally seen on the face, upper arms, neck, and shoulders of affected personsIt can be differentiated from vitiligo by its fine adherent scale, partial hypopigmentation, and distribution

Pityriasis albaWhite, slightly scaly patches with indistinct borders on a childs cheek

Postinflammatory hypopigmentation

AlbinismA partial or complete congential absence of pigment in the skin, hair, and eyes (oculocutaneous albinism), or the eyes alone (ocular albinism)Cutaneous phenotype of the various forms is broad, but the ocular phenotype is reasonably constant in most formsThe ocular phenotype includes decreased visual acuity, nystagmus, pale irides that transilluminate, hypopigmented fundi, hypoplastic foveae, and lack of stereopsis

AlbinismThis pt has light skin, yellowish white hair, and a lack of pigmentation in nevi

Oculocutaneous Albinism 1OCA 1 results from mutations in the tyrosinase gene Affected pts are homozygous for the mutant gene or are compound heterozygotes for different mutations in the tyrosinase geneARTwo forms: 1) OCA 1A & OCA 1B (indistinguishable at birth)OCA 1 is most severe with complete absence of tyrosinase activity and complete absence of melanin in the skin and eyesVisual acuity is decreased to 20/400OVA 1B tyrosinase activity is reduced but not absent. Pts may show increase in skin,hair, eye color with age and can tan

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

Top:albinism with white hair, pale skin, and translucent iridesBottom:ophthalmoscopic view of a pt with albinism demonstrates a pale fundus, poor macular development, and prominent choroidal vasculature

Oculocutaneous Albinism 2Prevalence of 1:15,000Pts were named tyrosinase-positive albinosAR and mutations occur in the P geneP gene codes a membrane transport protein that is present in the melanosome membraneCutaneous phenotype of OCA 2 pts is broad, ranging from nearly normal pigmentation to virtually no pigmentationPigmentation increases with age, and visual acuity improves with agePrader-Willi and Angelman syndromes are caused by deletions in the P gene; 1% of pts with these syndromes also have OCA 2

Oculocutaneous Albinism 3AR-caused by mutations in the tyrosine-related protein 1 (TRP-1), located on chromosome 9OCA 3 has been described only in black pts and is characterized by light brown hair, light brown skin, blue/brown irrides, nystagmus, and decreased visual activityBrown rather than black melanin is formed

Ocular AlbinismThere are multiple forms of ocular albinismOA 1 may be present with lighter than expected skinIt is X-linkedFemale carriers have mud-splattered fundiMacromelanosomes are found in the skin, so skin bx may be a helpful toolMany cases of AR ocular albinism have been reclassified as OCA 1 or OCA 2

Syndromes Associated with AlbinismChediak-Higashsi SyndromeHermansky-Pudlak SyndromeGriscelli Syndrome(partial albinism with immunodeficiency)Elejalde SyndromeCross-McKusick-Breen SyndromeCuna Moon Children

Classification of Oculocutaneous Albinism

Selenium DeficiencySelenium deficiency in the setting of total parental nutrition can lead to pseudoalbinismSkin and hair pigmentation return to normal with supplementation

Waardenburgs SyndromeFour genotypic variants exist:Types 1 & 3 are caused by mutations in the PAX gene on chromosome 2Type 2 is caused by mutations in the MITF gene on chromosome 3, and type 4 due to mutations in the ENDRB gene on chromosome 13Pts have features of piebaldism, with white forelock, hypopigmentation, premature graying, synophrys, congenital deafness, a broad nasal root, and ocular changes including heterochromia iridesApparently, melanoblasts fail to reach the target sites during embryogenesis

PiebaldismRare, AD with variable phenotype, presenting at birthWhite forelock, patchy absence of skin pigmenationDepigmented lesions are static and occur on the anterior and posteroir trunk, mid upper arm to wrist, mid-thigh to mid-calf, and shinsA characteristic feature is the presence of hyperpigmented macules within the areas of lack of pigmentation and on normal skin

Piebaldism

PiebaldismSegmental white patch on the neck with a tuft of white hair present from birth

PiebaldismWhite forelock and patch of unpigmented skin in a young girl with piebaldism

PiebladismThe white forelock arises from a triangular or diamond-shaped midline white macule on the frontal scalp or foreheadThe medial portions of the eyebrows, and eyelashes may be whiteHistologically, melanocytes are completely absent in the white maculesEtiology is a mutation in the c-kit protooncogenePhenotypic differences seen in families is caused by different locations of mutations in the geneThe white lesions may respond to surgical excision

Idiopathic Guttate HypomelanosisAKA leukopathica symmetrica progressivaVery common aquired disorder affecting women more frequently than menUsually occurs after age 40Lesions occur on the shins and forearms; are small (6 or 8mm), rarely become very numerous ( a dozen or two at most), and never occur on the face or trunkLesions are irregularly shaped and very sharply defined, like depigmented ephelides, and are only of cosmetic significance

Idiopathic Guttate Hypomelanosis

Find histology LeverLook for image of industrial hyperpigmentationExamples of bronze diabetes & addisons diseaesHistology image needed