etas_11 hair nail

11 Disorders of the Hair and Nails

Ming H. Jih, MD, PhD

C o n t e n t s

11.1 Hair Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391

11.2 Hirsutism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402

11.3 Hypertrichosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405

11.4 Nails . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405

Disorders of the Hair and Nails 389

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11.1 HAIR DISORDERSHair Anatomy

Figure 11-1. Hair Follicle Anatomy

Hair Cycle

Phase Duration Percent in Each Phase

Anagen = growth phase 2-6 years 85-90%

Catagen = transition phase 2-3 weeks <1%

Telogen = resting phase “club hair” 3 months 10-15%

Figure 11-2. Hair Mount Anatomy

Hair ColorPheomelanin Eumelanin

Blond hair, red hair Black hair

ABBREVIATIONS

AR: autosomal recessive

AD: autosomal recessive

EM: electronmicrograph

MR: mental retardation

PPK: palmoplantar keratoderma


Hair Shaft Abnormalities

Pili Torti = Hair Twisted at Intervals of 90 to 360 Degrees• Acquired,isolatedorinherited• Menke’sKinkyHairsyndrome

– X-linked recessive, ATP7A (MKN) gene – copper translocating membrane ATPase– Brittle “steel wool” hair (most common = pili torti but also can see trichorrhexis nodosa

and monilethrix)– Cupid’sbowlips,pale,laxskin– MR, seizures– Tortuous arteries

• Björnstadsyndrome

– AR mutation is BCS1L gene (S. cerevisige bsc1, protein, a component of the inner mito chondrial membrane)

– Pili torti + sensorineural deafness• Crandall’ssyndrome

– Pili torti + deafness + hypogonadism• Bazex’sFollicularAtrophoderma(Bazex-Dupre-Christolsyndrome)

– X-linked dominant– Hypotrichosis, follicular atrophoderma of dorsal hands and feet, face and extensor arms,

hypohidrosis, multiple BCCs of face

Figure 11-3. Pili Torti

Trichorrhexis Nodosa = Frayed Ends Resembling “Broom-Stick” or “Paint Brush”• Acquired:Mechanicalorchemicaldamageassociatedwithtrichoptilosis(splitend)• Argininosuccinicaciduria

– Absent argininosuccinase– Acidosis, low serum arginine, hyperammonemia– MR, red flourescence of hair

• Citrullinemia– Absent arginosuccinic acid synthetase– Perioral and diaper dermatitis, pili torti

• Menke’skinkyhairsyndrome• Trichothidystrophy(seebelow)• Netherton’ssyndrome(seebelow)

Figure 11-4. Trichorrhexis Nodosa

392 2011/2012 Dermatology In-Review lCommittedtoYourFuture

Trichoschisis = Clean Transverse Fracture of the Hair Follicle• Acquired,mechanicalorchemical• Trichothiodystrophy(Tay’s,PIBIDS=Photosensitivity, Icthyosis, Brittle hair, Intellectual

impairment, Decreased fertility, Short stature)

– Nucleotide excision repair defect in DNA repair genes ERCC2/XPD and ERCC3/XPB– Brittle hair and nails (reduced content of cysteine-rich matrix proteins), ichthyosis– Trichoschisis, trichorrhexis nodosa, “tiger tail” hair under polarized light (alternating dark

and light bands) – MR– 50% photosensitivity

• Marinesco-Sjögren,AR,mutationsinSIL1(BAP)anucleotideexchangefactorofHsp70– Cerebellar ataxia, mental retardation– Bilateral congenital cataracts– Skeletal abnormalities (kyphoscoliosis, pes planovalgus)– Hypergonadotropic hypogonadism

Figure 11-5. Trichoschisis

Trichorrhexis Invaginata = Invagination of the Distal Hair Shaft into the Cup Formed by the Proximal Hair Shaft, “Ball and Socket” or “Bamboo Hair”• Netherton’ssyndrome

– Ichthyosis linearis circumflexa, atopy, trichorrhexis nodosa

– Mutation in SPINK5: serine protease inhibitor

Figure 11-6. Trichorrhexis Invaginata

Monilethrix = Elliptical Nodes at 0.7-1 mm Intervals, Hair Fractures at Nodes

• AD,mutationsinhairkeratinshHB6andhHB1.AR,mutationsinDesmoglein4(DSG4)• Shortbrittlehair,extensorkeratosispilaris,mentalretardation,syndactyly,cataract,nail/

teeth abnormalities

Figure 11-7. Monilethrix


Pili Annulati = Alternating Light and Dark Bands Secondary to Air-space (seen in normal light versus “tiger-tail” hair of trichothiodystrophy, which is seen only under polarized light)• Pseudo-piliannulati:lightreflectionoffperiodicflatteningofthehairshaftseeninblondhair

Figure 11-8. Pili Annulati

Trichoptilosis = “Split-ends”• Chemicalorphysicaldamage,associatedwithtrichorrhexisnodosa

Hair Cast• Retentionanddesquamationofsegmentsoftheinnerrootsheath,slidesalonglength

of hair (distinguish from nits from pediculosis capitis which are attached to hair and DO NOT slide along hair)

• Younggirls(2-8yrsofage)

Figure 11-9. Hair Cast

Hair casts should be distinguished from:Piedra:Firmlyadherentgrittynodulesonhair.BlackpiedracausedbyPiedraiahortae; white piedra caused by Trichosporon beigelii.

Figure 11-10.

Pediculosis: Nits are firmly adherent to one side of the hair shaft.

Figure 11-11.

Pohl Pinkus Constriction• Toxicinsult→ disruption of anagen cycle with thinning of hair shaft forming constrictions alonghair,analogoustoBeau’slinesinnails

Unruly Hair

Uncombable Hair• AD/sporadic,silveryblondhair,“spunglass”appearance• Pilitriangulietcanaliculi(triangularhairshaftwithcentrallongitudinalgroove)

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Woolly Hair• AD/AR,diffusewoollyhairormixedstraightandwoollyhair• ARformcanbecausedbymutationinP2RY5geneandisallelictoautosomalrecessive

localized hypotrichosis-3 (LAH-3)

Naxos Syndrome

• AR,mutationinplakoglobin• Woollyhair,diffusePPK,rightventriculararrhythmogeniccardiomyopathy

Autosomal Recessive Woolly Hair• MutationinP2RY5gene-Gproteincoupledreceptor,nestedgenewithinthe

retinoblastoma 1 gene• Diffusescalpwoollyhairwithvariablehypotrichosisorsparsehair

Sparse Hair/Alopecia

Rothmund-Thomson Syndrome (Poikiloderma Congenitale)

• AR,mutationinDNAhelicasegeneRECQL4• Sparsescalp,eyebrow,andeyelashhairs• Poikilodermainsun-exposedareas,dystrophicnail• Juvenilecataract• Hypogonadism• SCC,BCC,rareosteosarcoma

Anhidrotic Ectodermal Dysplasia (Christ-Siemens-Touraine Syndrome)

•X-linked:mutationinEDA=ectodysplasin-A• Hypopigmented,fine,sparsehairwithlongitudinalgroovesonEM• Hypohidrosisoranhidrosis,naildystrophy,hypodontiaoranodontia,peg/conicalteeth• Periorbitalpigmentation,frontalbossing,atopicdermatitis

Hidrotic Ectodermal Dysplasia (Clouston Syndrome)

• AD,mutationinconnexin30(gapjunctionprotein)• Normalatbirththendevelopsthin,sparseorcompletelossofhairafterpuberty• PPK,dystrophicnail,hyperconvexnails,anonychia,paronychia

KID Syndrome (Keratitis-Icthyosis-Deafness Syndrome)

• AD,mutationinconnexin26• Keratitis,ichthyosis,deafness(sensorineural),alopecia

Cronkhite-Canada Syndrome• Alopecia• Generalizedpigmentation,onychodystrophy/nailatrophy• Malabsorptionsecondarytoproteinlosingenteropathy,generalizedgastrointestinal

polyposis

Incontinentia Pigmenti (Bloch-Sulzberger Syndrome)

• X-dominant,mutationNEMO(NF-kBEssentialModulator)• Scarringalopeciain30%(usuallyvertex)• Progressesthrough4stages:vesicular→ verrucous → hyperpigmented → hypopigmented

in lines of Blaschko• Peg/conicalteeth,eye(strabismus,cataract,blindness),MR,seizure,hemiatrophy


Chondrodysplasis Punctata

• Mutations:XR(arylsulfataseE),XD(EBPgene),AR(PEX7,DHAPAT,alkyldihydro-aceto-nephosphate synthase)

• Scarringalopecia• Ichthyosis,follicularatrophoderma• Stippledepiphyses,cataract• Acquired:warfarinembryopathy

Focal Dermal Hypoplasia (GoltzSyndrome,Syndactyly,“LobsterClawDeformity”)

•X-dominant,mutationinPORCN,aregulatorofWntsignaling• Brittlealopecia• FatherniationinBlaschko’slines,congenitalabsenceofskin• Absent/dystrophicnails• Osteopathiastriata(radio-opaquelongitudinalstriationsseeninlongbones)

Tricho-rhino-phalangeal Syndrome

• AD,mutationsinTRPS1gene (putative zinc finger transcription factor)• Sparse,finehair,thinnails,looseskinininfancy• Pear-shapedbroadnose• Cone-shapedepiphyses

Hay-Wells Syndrome (AEC: Ankyloblepharon-Ectodermal Dysplasia-Clefting)

• MutationsinP63• Wiry,sparsehairoralopecia• Ankyloblepharon,PPK,partialanhidrosis,cleftlip,palate,absent,dystrophicnails

Rapp-Hodgkin Syndrome• TP73L(tumorprotein73-likegenealternativelyknownasP63)• Anhidroticectodermaldysplasia• Uncombablewiryhairwithpilicannaliculi• Cleftlipwithorwithoutcleftpalate,microosmia• VariableexpressionofsinglegenedisorderwithAECorHay-Wellssyndrome

Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC)

• MutationsinP63• Light,sparse,wiryhair–longitudinalgrooveonEM• Partialanodontia,blueirides,photophobia,cleftlip+/–cleftpalate,syndactyly,ectrodactyly• Genitourinarydefects

Trichodentoosseous Syndrome

• Mutationsinthedistal-lesshomeobox-3gene(DLX3)• Curlyhairthattendstostraightenby2ndor3rddecade• Enamelhypoplasia,dentalpits• Increasedbonedensity

Hallerman-Streiff Syndrome• Frontalscalpbaldness–characteristicalongskullsuturelines• Bird-likeface,microphthalmia,microagnathia,dystrophicteeth,malocclusion• Cataract,nystagmus,strabismus

Cartilage-Hair Hypoplasia (McKusick’sMetaphysealDysplasia)

•AR,mutationinRMRP(RNAcomponentofmitochondrialRNA-processing endoribonuclease)


• Fine,sparsehair,eyebrow,eyelashes• Decreasedcellmediatedimmunityandnaturalkillercellactivity,recurrentupper

respiratory infections, increased viral infections (especially chicken pox)• Wideirregularmetaphysis

Marie-Unna Type Hypotrichosis• Sparseorabsenthair,eyebrowandeyelashatbirthwithvariablecoarsewiryre-growthin

childhood followed by loss at puberty• EM:longitudinalridge,cuticlepeeling• Diffusefollicularhyperkeratosis

Dermatopathia Pigmentosa Reticularis (DPR)• AD,mutationinkeratin-14gene• Triadofcutaneousreticulatehyperpigmentation,noncicatricialalopecia,onychodystrophy• Keratin-14mutationissharedwithNaegeli-Franseschetti-Jadassohnsyndrome.

Shared clinical features in both are adermatoglyphia, palmoplantar keratoderma and hypohidrosis. However, alopecia is only seen in DPR and dental abnormalities are seen in onlyNaegeli-Franceschetti-Jadassohnsyndrome

Costello Syndrome (FaciocutaneoskeletalSyndrome)• MutationinHRASgene• Thinanteriorhair,curlyhair• Nasolabialfacialandperianalpapillomas• Redundantandthickenedskinaroundneck,palms,andsoles• Congenitalmyopathywithexcessmusclespindles• Coarsefacies,shortstature• Cardiacanddevelopmentaldisability

Cardiofaciocutaneous Syndrome•MutationsinKRAS,BRAF,MEK1,MEK2-allpartofthecommonRAS/ERKpathway

regulating cell proliferation, differentiation and apoptosis• Sparsefriablehair,patchyhyperkeratosisormoregeneralizedicthyosis• Heartdefects(pulmonicstenosis,atrialseptaldefects)• Mentalretardationandcharacteristicfacies(highforeheadwithbitemporalconstriction,

antimongoloid slant of palpebral fissures, posteriorly angulated ears)

Hypotrichosis Simplex of Scalp• MutationinCDSNgene,encodescorneodesmosin• Normalhairatbirthwithprogressive,graduallossofscalphairbeginningatmiddleof

the first decade to almost complete loss of scalp hair by third decade. Body hair, beard, eyebrows,axillaryhair,teeth,andnailsdevelopnormally.Menandwomenareequallyaffected

Hypotrichosis, Localized, AR Type 1 (LAH 2)• Mutationindesmoglein4• Fragile,breakablehair,shortsparsescalphair• Eyebrowandeyelashmaybeinvolved• Axillary,pubic,beardlargelyspared

Hypotrichosis, Localized, AR Type 2 (LAH 2)• MutationinLIPHgene(LipaseH)• Congenitalhypotrichosisofscalphair


• Wiryandtwistedhair• Sparseeyebrow,eyelash,andbodyhair

Hypotrichosis, Localized, AR Type 3 (LAH 3)• MutationinP2RY5gene(purinergicreceptorP2Y)• Diffuseandprogressivehairlossusuallyearlychildhood• Sparseeyebrow,lash,andbodyhair

Premature GrayingProgeria (Hutchinson-Gilford)

• AR,mutationinlamininA(nuclearenvelopeprotein)• Thinhairwithprematuregraying• Bird-likeface,earlywrinkling,dyspigmentation,atrophyofskin,decreasedsubcutaneousfat• Atherosclerosis

Werner Syndrome

• MutationinDNAhelicase(RECQL2)• Thin,prematuregrayingofhair• Skin:atropy,poikiloderma,scleroderma,hyperpigmentation• Atrophyofmuscle,fat• Legulcer• Cataract• Increasedcancers:fibrosarcoma,skinCA

Low-Set Hair Line Turner Syndrome

• Chromosomaldefect:XO(non-disjunction,mosaic)• Lowposteriorhairline,short,cubitusvalgus,webbedneck,cutislaxa• Precociouspuberty• Coarctationofaorta

Noonan Syndrome

• AD,mutationinPTPN11(proteintyrosinephosphatase,nonreceptor-type11)• Low-setposteriorhairline,lowsetears,cubitusvalgus,webbedneck• Pulmonarystenosis

Cornelia de Lange Syndrome

• NIPBLgene(componentofcohesincomplex),x-linkedformcausedbymutationsinSMC1L1 (component of cohesin complex)

• Lowsethairline,trichomegaly,synophrys(unibrow),hirsutism• Cutismarmorata• SevereMR• Characteristicfacies,heartdefect

Klippel-Feil• Lowposteriorhairline,fusedcervicalvertebrae(faultymesodermsomitesegregation)• Strabismus,nystagmus,cleftpalate,bifiduvula

Poliosis (LocalizedWhitePatchofHair)Acquired• Vitiligo,alopeciaareata


Waardenburg’s Syndrome• Depigmentedpatchesonbody,whiteforelock(<50%),synophrys(70%),heterochromia

irides (25%) • Type1:AD,mutationinPAX3gene:dystopiacanthorum(DC)• Type2:AD,mutationinMITF(microphthalmiagene):NoDC,+deafness• Type3:AD,Klein-Waardenberg:mutationinPAX3gene:+axiallimbdefects• Type4:AR,Waardenberg-Shah:mutationinSOX10,endothelin-3ligand(EDN3),

endothelin 3-receptor (EDNRB): + Hirschsprung

Piebaldism

• AD,mutationsinc-KITprotooncogene(regulatesmelanoblastmigration/proliferation)• Whiteforelock• Depigmentedpatchescentralface,mid-extremities,abdomen(sparesmidlineback)• OccasionalHirschsprung,MR,deafness,heterochromicirides

Tuberous Sclerosis

• Spontaneousmutation75%,AD25%,mutationinTSC1(hemartin),TSC2(tuberin)• Poliosis• Angiofibroma,hypopigmentedashleafmacules,shagreenpatch(collgenoma),periungualfibromas(Koenentumor),fibrousplaques,café-au-laitmacules

Vogt-Koyanagi-Harada (Poliosis, Uveitis, Deafness, Vitiligo)• Autoimmunereactiontouvealmelanin• Prodromeoffever,headache,meningoencephalitis• Uveitis,vitiligo,poliosis,alopecia,deafness

Abnormal Hair CyclingTelogen Effluvium • 3-5weeksafterincitingstressfuleventthereisshiftfromanagentotelogen• 2-3monthslaterreleaseoftelogen=clubhair(“clumpsofhair”fallingoutatonce)• Endocrine(post-partum,thyroiddisease)• Nutritional(kwashiorkor)• Drug(Coumadin,heparin,ACEinhibitors,betablocker,lithium,oralcontraceptives,

retinoids), SSRI, amiodarone• Stress(illness,anemia,surgery)

Anagen Effluvium = Sudden Loss of Anagen Hairs • Inhibitionorarrestofcelldivisioninthehairmatrixleadstoathin,weakenedhairthat

fractures• Radiation• Chemotherapy(anti-mitotic)• Mercury(contaminatedseafood,antiseptic,fungicide)• Boricacid(insecticides)• Thallium(2-3weekspostexposure,insomnia,irritabilitiy,CNSandPNSsigns)• Severeproteinmalnutrition

Loose Anagen• Lossofclumpsofhair+/–unrulyhair,hairpullshowsanagenhairwith“ruffledcuticle”


Alopecia: Non-Scarring (seealsosections4-10 _4-11)

Alopecia Areata• Localized,totalis(entirescalp),universalis(wholebody)• Ophiasis:Band-likelossoverperipheryofscalp• Normalscalp,exclamationpointhair(taperingofhairatproximalend),nailpits• Autoimmunedisease(thyroid,vitiligo,diabetes,SLE,myastheniagravis)• Biopsy:peribulbar,perivascularlymphohistiocyticinfiltrate,“swarmofbees”• TX:ILTAC,topicalsteroid,systemicsteroid,PUVA,topicalimmunotherapy(e.g.,anthralin,diphenylcyclopropenone,squaricaciddibutylester),minoxidil,systemic cyclosporine, photodynamic therapy, Excimer laser

• Phenomenonofhair“turningwhiteovernight”fromdiffusealopeciaareatawheremostlypigmented hairs are lost

Triangular Alopecia• Congenitalorchildhood• Completeabsenceofhairorvellushairsintriangularpatterninthetemporalarea,frequentlybilateral

Androgenetic Alopecia • AD,polygeneticwithvariablepenetrance,progressiveminiaturizationofhair,increased

telogen hairs• Males–bitemporal,vertex(Hamilton-Norwoodclassification)• Females–preservedanteriorhairline,“christmas-tree”patternwithwidenedhairpartat

vertex (Ludwig classification)• TypeII5-alphareductaseactivityindermalpapillaandouterrootsheath• TX:minoxidil,finasteride,oralcontraceptivepills,spironolactone,flutamide,cyproterone

acetate, transplant

Trichotillomania• Compulsivehairpulling,irregularbrokenhairswithinageometriclocalizedarea• Biopsy:Increasedcatagenhairs,trichomalacia,melanininfollicularcanal• TX:chlormipramine,SSRI

Traction Alopecia• Hairlosssecondarytotightbraids,hairstylewithtraction• Frontalandparietal

Woolly Hair Nevus• Isolatedpatchofwoollyhair• 50%associatedepidermal,verrucousorpigmentednevus• Eye:persistentpapillarymembraneorretinalabnormality

Acquired Progressive Kinking• Post-pubescentmalewithandrogeneticalopecia,gradualcurlinganddarkeningoffrontal,

temporal and auricular regions → progression to androgenetic alopecia• AssociatedwithAIDS,retinoids

Syphilis• Secondarysyphilis,3-7%occurrencerate• “Moth-eaten”–non-scarringwithindistinctmarginsordiffusealopecia

Papular Atrichia

• AR,mutationsinHairlessgene


• Universalalopeciadevelopingshortlyafterbirth(approximatelythreemonths)• Normaleyelash,cornifiedcystsoverfaceandneck• Fewfollicleswithabsenthairshafts

Ichthyosis Follicularis, Atrichia, Photophobia (IFAP)• Absenteyebrowsandeyelashes• Photophobia,punctatecornealscarring,keratoconjunctivalinflammation,nystagmus,

myopia

Alopecia: Scarring

Table11-1.PermanentLossofHairFollicleswithFibrosis

Table11-1a.Hereditary/Developmental/UnknownEtiology

Aplasia cutis congenita Epidermal nevi Morphea

Incontinentia pigmenti Focaldermalhypoplasia Icthyosis

Darier’s Porokeratosis Chondodysplasia punctata

DLE LPP PCT

LS & A Sarcoid Amyloid

Folliculardegeneration PseudopeladeofBrocq Dissecting cellulitis

Cicatricial pemphigoid NLD Temporal arteritis

Mastocytosis Folliculitisdecalvans Follicularmucinosis

Table 11-1b. Physical Causes

Burn Trauma Radiation

Tumors

BCC SCC Melanoma

Lymphoma Metastasis Adnexal tumors

Table 11-1c. Infections

Bacterial Fungal Leishmaniasis

HSV Mycobacterial

Pseudopelade of Brocq• Alopeciainsmallpatches“footprintsinthesnow”tolargepatches• Controversyregardingdistinctentityversusend-stageofvariousscarringalopecias• Elastinstainshowspersistentelasticfiberinmid-shaftofthefollicle

Follicular Degeneration Syndrome• Hairlossmostlyonvertexinblackfemales+/–historyofchemicalrelaxers• Previouslyknownashotcombalopecia–butcanoccurwithoutuseofhotcombs• Biopsy:prematuredesquamationoftheinnerrootsheathwithfibrosis

Lichen Planopilaris• Alopeciawithperifollicularerythema• Biopsy:Lymphohistiocyticinfiltratearoundtheisthmusofthefollicleassociatedwith

fibrosis and atrophy


Morphea (en coup de sabre)• Linearmorpheawithlinearscarringalopeciaofthefrontalscalp• Parry-Rombergsyndrome(linearmorphea,progressivefacialhemiatrophy,

exophthalmos)

Folliculitis Decalvans• Inflammation,boggyinduration,crust,pustulesonscalp, tufted hair • Biopsy:SuppurativefolliculitiswithPMNsandeosinophils

Dissecting Folliculitis (Perifolliculitis Capitis Abscedens et Suffodiens of Hoffman)• AfricanAmericanmales• Deepinflammatoryboggynodules+/–sinustractsontheoccipitalregion• Biopsy:Follicularplugging,mixedcellinflammatoryinfiltrate,giantcells• Follicularocclusiontetrad:acneconglobata,hidradenitis,pilonidalcyst

Acne Keloidalis Nuchae• AfricanAmericanmale• Follicularpapulesandpustules→persistentfirmpapuleorplaqueatneck/occipitalscalp

Keratosis Follicularis Spinulosa Decalvans• Scarringalopecia,generalizedkeratosispilaris

Follicular Mucinosis• Alopecia/brokenhairsonscalp,beard• Hypesthetic• Mucininouterrootsheath(cysticspaces)andsebaceousgland• PrimaryorsecondarytoCTCL

Aplasia Cutis Congenita• Focalabsenceofepidermis+/–otherlayersoftheskin• 85%scalp,70%singlelesion• Associationwithtrisomy13,Adams-Oliversyndrome

Adams-Oliver Syndrome• Aplasiacutiscongenitaoverposteriorscalp• Terminaltransversedefectsoflimbs,smalltoenails

11.2 HIRSUTISM Hirsutism is the development of androgen-dependent terminal body hair (dark course pig-

mented hair normally seen in the underarms, scalp, eyebrows and pubis) in a woman in areas where this type of hair is not normally found.

Thediagnosisofhirsutismisculturallydetermined,often.Awoman’sdefinitionofhirsutismdependsonherethnicbackground.Othercausesofhirsutism,describedbelow,mayrequireclini-cal intervention.

Androgens in Women1.) Dehydroepiandrosterone (DHEA): adrenal2.) Androstenedione: adrenal, ovary3.) Testosterone: ovary, adrenal, extraglandular conversion of androstenedione and

dehydroepiandrosterone• Adrenalandrogenregulatedbyadrenocorticotropin• Ovarianandrogenregulatedbyluteinizinghormone


• Onlytestosteroneanddihydrotestosteronebindtheandrogenreceptor,thusadrenalandrogens virilize only in so far as they serve as precursors for testosterone and dihydrotestosterone

• Eyebrows,eyelashes,andvellushairarenotandrogen-dependent,thusthereisnodifference between these areas of hair growth in men and women

• Thehairfolliclerequiresconversionoftestosteronetodihydrotestosteroneforexpression of androgen action

Drugs• Hirsutismwithoutvirilization/defeminization

– Phenytoin– Minoxidil– Diazoxide– Cyclosporine– Hexachlorobenzene

Tumors• Rapidonsetofhairgrowthwithorwithoutaccompanyingvirilization

– Adrenal adenomas and carcinomas– Arrhenoblastoma– Kruckenberg tumors of ovary

Polycystic Ovarian Disease (PCOS)• Mostcommoncauseofovarianhyperandrogenism:3-5%ofwomenofreproductiveage• Manifestations:Hirsutism,amenorrhea,virilization,obesity• Diagnosis:Chronicanovulationandhirsutism• Enlargedcysticovaries,obesity,amenorrhea(Stein-Leventhalsyndrome)neednotbe

present

Congenital Adrenal Hyperplasia (CAH)• Defectsinadrenalsteroidogenesis• Canoccuratanypointinlife,butaffectedgirlswillgenerallypresentaroundpubertywith

hirsutism and menstrual irregularity or primary amenorrhea • Excessandrogenproductionisakeyfeatureofmostformsofcongenitaladrenal

hyperplasia • TypesofCAH

1.) 21-hydroxylase deficiency (95% of cases)2.) 11 b-hydroxylase deficiency3.) 3 b-hydroxysteroid dehydrogenase isomerase deficiency

Idiopathic Hirsutism• Womenwithevidenceofandrogenexcessbutwithnormalmenses,normal-sizedovaries,

no evidence of tumors of adrenal or ovary, and normal adrenal function • Slightelevationsofplasmaandrostenedioneandtestosteronecommon


Diagnosis

Clinical History•Attentiontodrugingestion• Detailsofpubertaldevelopment• Menstrualhistory

Signs of VirilizationCorrelate with androgen overproduction from either an adrenal or ovarian source

1.) Deepening of the voice2.) Temporal balding3.) Clitoromegaly4.)Increasedmusclemassinthelimbgirdles5.) Irregular or absent menses6.) Acne

Signs of Cortisol Excess1.) Plethora2.) Centripetal obesity3.) Striae4.)Dorsocervical/supraclavicularfatpads

Laboratory Exam Suggestive of Neoplasm• DHEA>8000ng/mlorserumtestosterone>2ng/ml

Other Laboratory Tests and Evaluations• Plasmatestosteronelevelsinthenormalrangearedifficulttointerpretbecausetotal

levels in women do not necessarily reflect the free or unbound levels of hormone under conditions when testosterone-binding globulin levels are either increased or decreased

• LHhypersecretioninPCOS• ProlactinemiamaybeseeninPCOS• Cushingsyndrome,ifsuspected,shouldbeevaluatedwithanovernightdexamethasone

suppression test• Polycysticovariandisease:diagnosismadefromhistoryandclinicalfeaturesinawoman

with chronic anovulation• DelayedonsetadrenalhyperplasiabytheshortACTHstimulationtestandmeasurement

of plasma 17-hydroxy-progesterone• Pelvicexam:searchforpalpableovarianmasses• Ultrasoundimagingoftheovariesandadrenalglands

Treatment

Eflornithine(Vaniqa)• Appliedtotheskinforthereductionofunwantedfacialhair• Inhibitsornithinedecarboxylaselocatedintherootofthehairfollicle

Oral Contraceptives • Combination(estrogenandprogesterone)oralcontraceptivesareindicatedforwomen

with idiopathic, familial hirsutism and PCOS• Womenwithhypertension,bleedingorclottingdisorders,migraines,smokers,orafamily

history of breast and/or uterine cancer, should not use oral contraceptives to treat hirsutism• Effectiveinthattheysuppresstheovarianproductionofandrogens


Glucophage - 0ther 0ral Hypoglycemics Used Primarily in the Treatment of Diabetes• MaydecreaseinsulinresistanceandpromoteovulationinwomenwithPCOS• NotFDA-approvedforthisindication,norappropriateforthosewhohavekidneyorliver

disease

Spironolactone • Syntheticsteroidwithanaldosterone-likestructure• Blocksandrogensfrombindingtotheirreceptorreducingtheeffectsofhirsutism• SpironolactoneisnotFDA-approvedforthetreatmentofhirsutism• Teratogenic

Finasteride (Propecia)• NotFDA-approvedforthetreatmentofhirsutism,butshowntobeeffective

Mechanical Hair Removal• Popularapproach• Shaving,plucking,waxing,electrolysis,laserhairremoval,bleaching,depilatories

11.3 HYPERTRICHOSISGeneralized Congenital Hypertrichosis Lanuginosa

• Silvery,blondandgrayhairoverentirebodyatbirthorearlyinfancy• ADwithvariablepenetrance• Dentalanomalies• Acquired:Fetalhydantoinandfetalalcoholsyndrome

Acquired Hypertrichosis Lanuginosa • Paraneoplastic2cancer(lung,colon,etc)lanugohairfaceorentirebody

Ambras Syndrome• Thicker,longerhairincreasedonface,ears,shoulder,facialdysmorphism,dentalanomalies

Congenital Generalized Hypertrichosis with Gingival Fibromatosis• AD,rareAR• Hypertrichosis(terminalhairs)onfaceandupperbody,gingivalhyperplasia/fibromatosis

Localized Congenital Hypertrichosis • Congenitalnevi,Becker’snevi• HypertrichosisCubiti

– Bilateral elbows, unknown transmission• Cervicalhypertrichosis

– Posterior: X-link recessive or AD– Anterior: AR

• Fauntaildeformity– Lumbosacral, unknown transmission

11.4 NAILSThenailiscomposedof5majoranatomicregions(seeFigure11-12aand11-12b)1.) Nail plate – actual nail made up of tightly packed onychocytes2.) Proximal nail fold–dorsalpartofdigitthatliesadjacenttonail3.) Nail matrix – epithelium which starts mid distal phalanx which generated the nail plate,

determinesthethicknessofthenailplate;keratinizeswithoutagranularlayer


4.)Nail bed –thinepitheliumimmediatelybeneathnailplate;absentgranularlayer5.) Hyponychium – epithelium that lies on the volar surface of digit

The nail plate grows distally after it emerges from the proximal nail fold. Nail matrix kerati-nizationoccursalonganobliqueandupwarddirectionsothattheproximalportionofthenailmatrix gives rise to the dorsal nail plate while the distal portion produces the ventral nail plate. The distal portion of the nail matrix is visible as the lunula.

Rates of growth: fingernail – 3 mm/mo., toenail – 1 mm/mo.

Tumors Affecting the Nail

Myxoid CystSmooth,softnodulemostcommonlyadjacenttoDIPjoint(Figure11-12a).Whenatproximalnail fold, causes longitudinal gooving in the nail plate. Contains clear yellow viscous fluid (Figure11-12b).Path:Largepoolofmucinwithnolining.

Glomus Tumor Small reddish-blue tender subungual tumors. Path: Small, uniform round cells with eosinophilic cytoplasm.

Acquired Digital Fibrokeratoma(Figure11-12)Firmexcrescenceonthefingerortoe.Path:Collagenwithnoprominentnerves.

Accessory Digit Firmexcrescenceonthefingerortoe,mostcommonlyatproximalportionof5thdigit.Path: Collagen with prominent nerve fascicles.

Figure 11-12b. Structure of the Nail


Figure 11-12a. Structure of the Nail

WartWell-definedhyperkeratoticplaquesaroundnails.Rarelyinvadebeneathnail.

Bowen’s Disease Hyperkeratoticplaquesoftenwithspreadundernailplate.

Nail Biopsy Techniques

Nail Plate Biopsy Snipping of nail plate by scissors or nail clippers. Central portions of the nail plate can bebiopsiedwithapunch.Foronychomycosisshouldalsoincludeshaveorscrapeofsubungual hyperkeratosis from as proximal as possible. PAS stain is most sensitive test for onychomycosis.

Nail Avulsion Digital block or ring block around the nail. Nail is either twisted off with a hemostat or dissected off the nail bed using a nail elevator.

Nailbed Tumor Punch biopsy through the nail plate into the nail bed or nail avulsion plus a punch biopsy or excision. Small nailbed defects are generally allowed to heal by secondary intention.

Lateral Nail Fold Biopsy Shave or punch biopsy. A partial avulsion may be necessary for a growth that extends under the nail (e.g., SCC).

Nail Matrix Biopsy Most commonly performed for longitudinal melanonychia. The proximal nail fold is anesthetized, and two deep lateral incisions are made from the lateral cuticle to the distal PIP. TheU-Shapedskinisliftedoff,allowingtheentireproximalnailandmatrixtobevisualized.The point at which pigment arises is biopsied using punch biopsies or an excision extending down to the periosteum to include the entire matrix. Matrix is allowed to heal by secondary intention. Elevated skin flap is sewn back down.

Table 11-2. Nail DisordersProblem Features/Definition Diseases/Causes

Absent lunula Multiple myelomaYellow nail syndrome

Anonychia Absence of nail Nail-patella syndrome Congenital Onychodysplasia of theIndexfinger(COIF)Coffin-Siris syndromeDeafness, Congenital, Onychodystrophy, Recessive form (DOOR)

Beau’slines(seeFigure11-13) Transverse indented furrow from growth arrest of nail matrix

Occurs weeks after any stressful event/illness that temporarily interrupted nail formation. The lines progress distally with normal nail growth and eventually disappear at the free edge

Black nail Proteus mirabilis infection, hematoma


Problem Features/Definition Diseases/Causes

Blue lunula Matrix Defect Wilson’s,argyria,busulfan,herediatry acrolabial telangiectasia, paronychia (pseudomonas),quinacrine,topical bichloride or mercury followed by sunlight, AZT, antimalarials, minocin, silver nitrate, hemochromatosis, ochronosis, phenolphthalein, PUVA,5FU,blacks(normalvariant)

Brachyonychia(seeFigure11-15) Shortnails(width>length) Congenital: Rubenstein-Taybi (mutation in CREB-binding protein, broad thumbs and toes, beaked nose, mental retardation), micronychia with trisomy 21, congenital malalignment of great toes.Acquired:nailbiting,hyperparathyroidism, psoriatic

Clubbing(seeFigure11-16) Plate/matrix defect Hypertrophic pulmonary osteoarthropathy (hypertrophic OA + peripheral neuropathy + PVD + burning bone pain + muscle weakness)Risk of pulmonary cancerPachydermoperiostosis

Darier’sdisease(seeFigure11-17) Alternating red and white longitudinal bands, V-shaped distal nicking, subungual hyperkeratosis

Mutation in SERCA2, calcium ATPase. Skin findings of hyperkeratotic papules in a seborrheic distribution

Dolichonychia(seeFigure11-15) Longnails(Length/width>1) Ehlers-Danlos syndrome Marfan’sEununchoidHypopituitarismHED

Elkonyxis Large 2-3 mm pits

Greennail Pseudomonas (pyocyanin: darkgreen, fluorescein: yellow-green)

Habittic(seeFigure11-18) Horizontal parallel ridges oftenaccompanied by absent cuticle

Trauma to cuticle

Heller’smediancanaliformdystrophy(seeFigure11-18)

Longitudinal fissures with obliquelines(Christmastreepattern), h size of lunula

Trauma to proximal nail

Hapalonychia Soft nails, defect in matrix

Heloma Corn

Hematoma, subungual Treatment:if<25%trephinate;if>25%,removenailtoevacuatehematoma

Koenen tumor (periungual fibromas)

Smooth round tumors that grow out from the nail folds

Hereditary: 50% of tuberous sclerosis.Acquired

Table 11-2. Nail Disorders (cont.)



Koilonychia Spooning of nailDefect in plate/matrix

Hereditary: LEOPARD syndrome, ectodermal dysplasia, trichothiodystrophy, nail-patella syndrome.Acquired:faultyironmetabolism, Plummer– Vinson syndrome, hemochromatosisNeonatal (physiologic)

Leukonychia Whitenail(frommatrix) Usuallyinsignificant,hereditaryAcquired:trauma,drugs,infection, anemia, iCa, heart/renal disease

Lindsay’snails(half&half)(seeFigure11-20)

Distal nail normal, proximal nail white (=nailbed edema)

Chronic renal failure

Macronychia Large (wide) nails Neurofibromatosis ITuberous sclerosisProteus syndrome

Mee’slines Transverse white lines that affect ALL nails, grows out with nail growth. Defect in nail plate

Arsenic poisoning, rheumatic fever, congenital heart failure, leprosy, any systemic disease

Melanonychia striata Longitudinal dark streaks in nail 2° trauma, nevus/melanoma,AIDS/AZT, normal variant in blacks

Micronychia Small nails Congenital Onychodysplasia of theIndexfinger(COIF)

Muehrcke’slines Double white transverse lines from abnormal vascular bed. Disappearwithsqueezingofnail

Nephrotic syndrome, low albumin, liver disease, malnutrition

Oil spots Brownish macules beneath the nail plate. Defect in nailbed

Psoriasis

Onychalgia Painful nails

Onychauxis Simple hypertrophy without anydystrophy

Onychia Inflammation in nail unit

Onychoatrophy Retinoids, paronychiaSJS/TENEpidermolysis bullosaAmyloidIdiopathic childhoodPsoriatic

Onychoclavus Subungual corn

Onychocyrptosis Ingrown nail ± exuberant granulation tissue

1st toe

Onychogryphosis(seeFigure11-21)

Rams nail (long, curving) Neglect, trauma

Onychoheterotopia Abnormally placed nail

Onycholysis Distal separation In psoriasis Systemic disease, trauma, drugs(chemotherapeutics, retinoids, TCN), contact dermatitis




Onychomadesis = defluvium unguium

Periodic shedding of nail beginning with separation proximally

Systemic disease-arrest PCN allergy, syphilis, psoriasis, TEN, SJS,pemphigus,radiation,drugs(chemotherapeutic agents,carbamazepine, lithium)

Onychophagia Nail biting

Onychophosis Local or diffuse hyperkeratotic tissue that develops on the lateral or proximal nail folds

Traumafrequentlyon1stand5th toe

Onychoptosis Nail loss

Onychorrhexis Longitudinal striations Older patients

Onychoschizia Distal horizontal splitting Repeated wetting of nail, enamelremovals

Pachyonychia Thickened, hypertrophied nail plates

Pachyonychia congenita: subungual hyperkeratosis, pincer nail, paronychiaTypeI:Jadassohn-Lewandowsky:Keratin 6 & 16 mutation, focal PPK, follicular hyperkeratosis, oral leukokeratoses (not premalignant)TypeII:Jackson-Sertole:Keratin6b,17mutation;steatocystomamultiplex, natal teeth, noleukokeratosisType III: Shafer-Brunauer: Type I + corneal leukokeratosisType IV: I/II/III + laryngeal lesions, MR, alopeciaType IV: pachyonychia congenita tarda: hyperpigmentation of flexures, amyloid deposition

Paronychia, acute Staph (most common), Strep, E Coli

Paronychia, chronic Candida, molds (Scytalidium),syphilis, TB, leprosy

Parrotbeaknails(seeFigure11-19)

Freenailcurvesdownward(disappears with soaking)

Pitting Psoriasis, alopecia areata, eczema, paronychia. Defective keratinization on proximal matrix

Pigmentation Actinomycin, antimalarials,bleomycin, cytoxan, doxorubicin,5-FU,melphalan,MTX,minocycline, nitrogen mustard,AZT,Addison’s,hemochromatosis, Peutz- Jeghers,B12deficiency

Pincernails(seeFigure11-22) Transverse excessive curvature from widened base of terminal phalanx

Hereditary or from shoes, usually1sttoenails;subungualexostoses, osteoarthritis, psoriasis




Platyonychia h nail curvature in the long axis

Plicaturednails(seeFigure11-22) Flattransverselywithverticallateral drops

Plummer’snails Onycholysis from hypothyroidism

Dorsalpterygium(seeFigure11-23)

Scarring of proximal nail fold Lichen planus, acrosclerosis, onychotillomania, Lesch-Nyhan syndrome,chronicGVHD,SJS/TEN,cicatricial pemphigoid

Ventral pterygium: pterygium inversum unguis

Adherence of ventral surface of distal nail plate to the hyponychium

Systemic sclerosis, congenital

Red lunulae Matrix Alopecia areata, psoriasis, prednisone for connective tissue diseases, carbon monoxide poisoning, cardiac failure,SLE, RA, COPD, CO2, cirrhosis,azathioprine, radiation

Samitz sign Cuticle Cuticular fraying fromdermatomyositis

Shiny nails Fromchronicrubbingorscratching

Splinter hemorrhage Nail bed Endocarditis, vasculitis, trichinosis, trauma, psoriasis

Spotted red lunulae Alopecia areata, psoriasis, SLE,LP, RA

Terry’snails(seeFigure11-20) All but distal 2mm evenly whiteDefect in nail bed

Cirrhosis, congenital heart failure, diabetes

Trachyonychia Rough nails 20 nail dystrophy – may resolve with age

Transverse white bands Affects 1-2 nails Trauma of matrix

Triangular lunulae Nail-patella syndrome: mutationin LMX1b, triangular or absentlunulae, hypoplastic or absentpatella, nephropathy

Unguisincartus Ingrown nails

Yellow nail syndrome Absent cuticles/lunulae, slow growth, dystrophic shape, transverse ridging

Lower extremity lymphedema + bronchiectasis/pleural effusion (TB, asthma, cancer). Associated with D-penicillamine and bucillamine use in patients withrheumatoid arthritis



Table 11-3. Infections of the Nail

Onychomycosis Most Common Organism Other Organisms

Distal subungual Trichophyton rubrum T mentag, E floc

Whitesuperficial/Proximalwhite subugal

T rubrum (kids, HIV patients) Fusariumoxysporum,Scopulariopsis brevicalis, Acremonium, Aspergillus,Candida

Superficial onychomycosis T mentag Fusarium,Acremonium,(toenailsonly), Aspergillus

Lateral invasion + paronychia Hendersonula toruloidea,Scatylidium hyalinum

Figure 11-13.

Figure 11-14. Beau’s Lines Figure 11-15.


Figure 11-16. Clubbing

Figure 11-17. Darier’s Disease

Figure 11-18. Figure 11-19.

Figure 11-20. Figure 11-21. Onychogryphosis

Figure 11-22. Figure 11-23.


NOTES


NOTES

416 2011/2012DermatologyIn-ReviewlCommittedtoYourFuture

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