GenodermatosGenodermatoses and es and

Acquired Acquired Syndromes, Syndromes,

Part IPart I

KCOM/Texas KCOM/Texas Dermatology Dermatology ConsortiumConsortiumNE Regional NE Regional

Medical CenterMedical Center

Incontinentia PigmentiIncontinentia Pigmenti

• Aka Block-Sulzberger’s diseaseAka Block-Sulzberger’s disease• X-linked, onset in girls age 4-6 weeksX-linked, onset in girls age 4-6 weeks• Whorls and sworls along Blaschko’s Whorls and sworls along Blaschko’s

lineslines• Initally VesicularInitally Vesicular• 6 weeks later – Verrucous6 weeks later – Verrucous• 6 months later – Pigmented6 months later – Pigmented• 6 years later – Hypopigmented.6 years later – Hypopigmented.• Defect in Xq28Defect in Xq28

Early vesicular stage of Incontinentia pigmenti, eosinophilic spongiosis

Incontinentia Incontinentia pigmentipigmenti

Rule out these problems, then assure parents the skin manifestations will likely begin to resolve by age 2 and be essentially clear by adulthood.

Naegeli-Franceschetti-Jadassohn Naegeli-Franceschetti-Jadassohn Synd.Synd.

• Aka Aka Chromatophore Nevus of NaegeliChromatophore Nevus of Naegeli

• Differs from IC, pattern is RETICULARDiffers from IC, pattern is RETICULAR

• MC neck, flexural, perioral, periorbitalMC neck, flexural, perioral, periorbital

• No preceding vesiculation or No preceding vesiculation or inflammationinflammation

• Vasomotor changes and hypohidrosisVasomotor changes and hypohidrosis

• Abnormal dermatoglyphics and PPK.Abnormal dermatoglyphics and PPK.

• Dental and nail abnormalitiesDental and nail abnormalities

Naegeli-Franceschetti-Naegeli-Franceschetti-Jadassohn SyndromeJadassohn Syndrome – – reticulated patternreticulated pattern

Atrophic/absent dermatoglyphics

PERIORBITAL RETICULATION

• J Invest Dermatol. 2000 Oct;115(4):694-8. J Invest Dermatol. 2000 Oct;115(4):694-8.

The gene for Naegeli-Franceschetti-The gene for Naegeli-Franceschetti-Jadassohn syndrome maps to 17q21.Jadassohn syndrome maps to 17q21.

Whittock NV, Coleman CM, McLean WH, Whittock NV, Coleman CM, McLean WH, Ashton GH, Acland KM, Eady RA, Ashton GH, Acland KM, Eady RA, McGrath JA.McGrath JA.

Hypomelanosis of ItoHypomelanosis of Ito

• ““Negative Image” of IP, whorls and Negative Image” of IP, whorls and sworls along Blaschko’s lines sworls along Blaschko’s lines hypopigmented.hypopigmented.

• First year of life, F > M First year of life, F > M

• 75% have CNS, Hair, Dental, MS or 75% have CNS, Hair, Dental, MS or internal organ abnormalitiesinternal organ abnormalities

• 50% have chromosomal mosaicism.50% have chromosomal mosaicism.

Hypomelanosis of Ito Hypomelanosis of Ito “Whorled Marble Cake”“Whorled Marble Cake”

No inflammatory or vesicular lesions.No inflammatory or vesicular lesions.No TX: eventual repigmentation is the ruleNo TX: eventual repigmentation is the rule

Linear and Whorled Nevoid Linear and Whorled Nevoid Hypomelanosis Hypomelanosis • Not IP because no vesicles.Not IP because no vesicles.• Not NFJS because no periorbital or PPKNot NFJS because no periorbital or PPK• Associated with MR, CP, Cardiac defectsAssociated with MR, CP, Cardiac defects• H&E increased prominence of basal H&E increased prominence of basal

layer melanocytes with no pigment layer melanocytes with no pigment incontinenceincontinence

• May often be misdiagnosed as IP, NFJS May often be misdiagnosed as IP, NFJS or Linear Epidermal Nevus by young or Linear Epidermal Nevus by young dermatologists looking to make a name dermatologists looking to make a name for themselves.for themselves.

Conradi Hunermann Conradi Hunermann SyndromeSyndrome• Variant of Condrodysplasia PunctataVariant of Condrodysplasia Punctata

• IchthyosisIchthyosis

• ””Whirl and swirl” hyperkeratosisWhirl and swirl” hyperkeratosis

• ““Cracked eggshell” appearance of Cracked eggshell” appearance of waxy shiny scaling skinwaxy shiny scaling skin

• As child develops, follicular As child develops, follicular atrophoderma and pseudopelade atrophoderma and pseudopelade emerge.emerge.

Stippled Epiphyses, pathognomonic of Chondrodysplasia Punctata or Conradi Hunermann

Klinefelter’s SyndromeKlinefelter’s Syndrome

• XXXY, Hypogonadism, high XXXY, Hypogonadism, high gonadotropinsgonadotropins

• Shortening of 5Shortening of 5thth digit both hands digit both hands• Thrombophlebitis and chronic leg ulcersThrombophlebitis and chronic leg ulcers• Increase risk of cancers, male breast, Increase risk of cancers, male breast,

germ tumors, hematologic germ tumors, hematologic malignancies, sarcomas.malignancies, sarcomas.

• XXYY variant has acrocyanosis, PVD, XXYY variant has acrocyanosis, PVD, stasis dermatitisstasis dermatitis

• TX: Testosterone injections.TX: Testosterone injections.

Behavioral disturbances

None to scant body/pubic hair

Gynecomastia

Truncal obesity

Sterility

Small testes

Venous stasis with varicosities

Long lower extremities

Leg ulcers

Turner’s SyndromeTurner’s Syndrome• Aka Gonadal dysgenesisAka Gonadal dysgenesis• XO genotypeXO genotype• Triangular mouthTriangular mouth• Alopecia of frontal scalpAlopecia of frontal scalp• KoilonychiaKoilonychia• Cutis laxaCutis laxa• Increased risk of melanoma suggested Increased risk of melanoma suggested

due to plenty of melanocytic nevidue to plenty of melanocytic nevi• TX with growth hormone is TX with growth hormone is

controversialcontroversial

Redundant neck skin, low set posterior hairline

Short stature

Spatial relations deficit

Hypertelorism

Low set ears

Triangular facies

Webbed neck

Coarctation of the aorta

Nevus

Shield chest

Wide set nipples

Kidney malformations

Nails hypoplastic, hyperconvex, deep-set

Short 4th & 5th digits

Amenorrhea, infertility\

Lymphedematous legs

Noonan’s SyndromeNoonan’s Syndrome

• Mimics Turner’s except the # of Mimics Turner’s except the # of chromosomes is normal.chromosomes is normal.

• Short curly hairShort curly hair

• Tendency toward keloid formationTendency toward keloid formation

• Keratosis pilaris atrophicansKeratosis pilaris atrophicans

• Abnormal dermatoglyphicsAbnormal dermatoglyphics

Cardio-Facio-Cutaneous Cardio-Facio-Cutaneous Synd.Synd.• Variant of Noonan’s with characteristic Variant of Noonan’s with characteristic

craniofacial appearance.craniofacial appearance.• Hair is sparse, curly, fine or thick, wooly Hair is sparse, curly, fine or thick, wooly

or brittle. Skin is ichthyoticor brittle. Skin is ichthyotic• Eyebrows and eyelashes sparse or Eyebrows and eyelashes sparse or

absentabsent• Keratosis pilaris atrophicans faciei, PPKKeratosis pilaris atrophicans faciei, PPK• Café au lait, nevi, hemangiomasCafé au lait, nevi, hemangiomas• Cutis marmorata, sacral dimples.Cutis marmorata, sacral dimples.

What are the What are the Phakomatoses?Phakomatoses?• Inherited CNS disorders that have Inherited CNS disorders that have

congenital retinal tumors and congenital retinal tumors and cutaneous involvement.cutaneous involvement.

• Tuberous SclerosisTuberous Sclerosis• Neurofibromatosis (Von Neurofibromatosis (Von

Recklinghausen’s)Recklinghausen’s)• Von Hippel-Lindau’sVon Hippel-Lindau’s• Ataxia-TelangiectasiaAtaxia-Telangiectasia• Basal Cell Nevus SyndromeBasal Cell Nevus Syndrome• Nevus SebaceousNevus Sebaceous• Sturge-Weber SyndromeSturge-Weber Syndrome

Tuberous SclerosisTuberous Sclerosis• Aka Bourneville’s Dz or Epiloia, (Aka Bourneville’s Dz or Epiloia, (EpiEpi = epilepsy, = epilepsy, loi loi

= low intelligence, = low intelligence, a a = adenoma sebaceum) = = adenoma sebaceum) = triadtriad

• Other findings – seen next 3 slidesOther findings – seen next 3 slides

• 2 tumor suppressor gene mutations2 tumor suppressor gene mutations

• AD, but 50% may be spontaneous mutationsAD, but 50% may be spontaneous mutations

• TSC1=hamartin=9q34, TSC2=tuberin=16p13.3TSC1=hamartin=9q34, TSC2=tuberin=16p13.3

• Neuro: Astrocytomas, calcified subependymal Neuro: Astrocytomas, calcified subependymal nodulesnodules

• Ophtho: Retinal hamartomasOphtho: Retinal hamartomas

• Renal: multiple, may cause renal failureRenal: multiple, may cause renal failure

• Pregnant: pulmonary lymphangioleiomyomasPregnant: pulmonary lymphangioleiomyomas

ASH LEAF MACULE

SEBACEOUS ADENOMAS, histo = angiofibroma

SUBUNGUAL FIBROMAS

CONFETTI MACULES

SHAGREEN PATCH histo = connective tissue nevus

LEFT: Retinal hamartomas of tuberous sclerosis, angioid streaks

RIGHT: Cranial CT demonstrating multiple calcified subependymal nodules in a paraventricular location

Neurofibromatosis Type INeurofibromatosis Type I• 85% of cases, AD85% of cases, AD• Diagnostic criteria: 2 or more of the followingDiagnostic criteria: 2 or more of the following• 1) > 6 café au lait macules > 5mm prior to 1) > 6 café au lait macules > 5mm prior to

puberty or > 15mm after pubertypuberty or > 15mm after puberty• 2) 2 or more NFs or 1 plexiform NF.2) 2 or more NFs or 1 plexiform NF.• 3) Axillary or inguinal freckling (Crowe’s sign)3) Axillary or inguinal freckling (Crowe’s sign)• 4) 2 or more Lisch nodules4) 2 or more Lisch nodules• 5) optic glioma5) optic glioma• 6) bone lesion: sphenoid wing dysplasia, 6) bone lesion: sphenoid wing dysplasia,

thinning of long bone cortex with or without thinning of long bone cortex with or without pseudoarthrosispseudoarthrosis

• 7) first degree relative with NF-1.7) first degree relative with NF-1.

NF1 is located on chromosome 17q11.2 and encodes for the GAP-related protein NEUROFIBROMIN. One of the functions of neurofibromin is to negatively regulate the activity of RAS proteins. RAS, like other related G proteins, is dependent upon GTP binding for its full activity, and GAP proteins shut off the signal by accelerating the hydrolysis of GTP to GDP.

Café-au-lait macule and axillary freckling . An oval-shaped light-brown patch is present in the axilla of this child along with multiple small 1–2 mm lentigines.

NOTE: AXILLARY FRECKLING = CROWE’S SIGN

Cutaneous neurofibromas. Small, soft, skin-colored to pink polypoid papules that characterize NF1. They exhibit “button-holing” : they can be pressed down into the panniculus by light pressure and spring back when released

Left: Lisch nodules. Multiple yellow-brown papules on iris. These are a late finding, usually seen in older pts. Eye exam may also reveal JPSLO or Juvenile Posterior Subcapsular Lenticular Opacity

Plexiform neurofibroma . Soft tissue swelling of the left hand, note the overlying hyperpigmentation. These feel like a “bag of worms”

Neurofibromatosis Type II, Neurofibromatosis Type II, etc…etc…• NF-2 resembles NF-1 but it has Bilateral NF-2 resembles NF-1 but it has Bilateral

acoustic neuromas and the affected gene acoustic neuromas and the affected gene is MERLIN or SCHWANNOMIN, 22q11-q13is MERLIN or SCHWANNOMIN, 22q11-q13

• NF-3 (mixed) and NF-4 (variant) have NF-3 (mixed) and NF-4 (variant) have higher risk of optic neuromas, higher risk of optic neuromas, neurilemomas and meningiomasneurilemomas and meningiomas

• NF-5 segmental (dermatomal)NF-5 segmental (dermatomal)• NF-6 only café au lait, no neurofibromasNF-6 only café au lait, no neurofibromas• NF-7 late onsetNF-7 late onset

Dx/Tx for Neurofibromatosis…Dx/Tx for Neurofibromatosis…• Multidisciplinary approach is best…..Multidisciplinary approach is best…..• Neurologist: MR, dementia, epilepsy, astrocytomas, Neurologist: MR, dementia, epilepsy, astrocytomas,

meningiomas, schwannomas, neurofibrosarcomas.meningiomas, schwannomas, neurofibrosarcomas.• Ophthalmologist: lisch nodules, optic gliomas, JPSLO.Ophthalmologist: lisch nodules, optic gliomas, JPSLO.• Endocrinologist – acromegaly, cretinism, Endocrinologist – acromegaly, cretinism,

hyperparathyroidism, myxedema, hyperparathyroidism, myxedema, phaeochromocytomaphaeochromocytoma

• Orthopedist – erosive bone changes, lordosis, Orthopedist – erosive bone changes, lordosis, kyphosis, pseudoarthrosis, spina bifida, dislocations, kyphosis, pseudoarthrosis, spina bifida, dislocations, atraumatic fractures, sphenoid wing dysplasiaatraumatic fractures, sphenoid wing dysplasia

• Oncologist – NF-1 pts 4 x more likely to get CA – Oncologist – NF-1 pts 4 x more likely to get CA – myeloproliferative, Wilm’s tumor, rhabdomyosarc, GI.myeloproliferative, Wilm’s tumor, rhabdomyosarc, GI.

• Only treatment for neurofibromas is excision.Only treatment for neurofibromas is excision.

Proteus SyndromeProteus Syndrome• Greek god Proteus (the Greek god Proteus (the

polymorphous) mimics NF.polymorphous) mimics NF.• Partial gigantism of hands, Partial gigantism of hands,

feet, hemangiomas, feet, hemangiomas, lipomas, linear epidermal lipomas, linear epidermal nevi, patchy dermal nevi, patchy dermal hypoplasia, macrocephaly, hypoplasia, macrocephaly, hyperostosis, hypertrophy hyperostosis, hypertrophy of the long bones.of the long bones.

• Skull on the right exhibits Skull on the right exhibits hyperostosis and partial hyperostosis and partial gigantismgigantism

““Elephant Man” Joseph Merrick may have had Proteus SyndromeElephant Man” Joseph Merrick may have had Proteus Syndrome

Von Hippel-Lindau Von Hippel-Lindau SyndromeSyndrome• AD, mutation in VHL tumor suppressor geneAD, mutation in VHL tumor suppressor gene

• Pancreatic cysts/microcystic adenomas (75%)Pancreatic cysts/microcystic adenomas (75%)

• Cerebellar/spinal hemangioblastomas (65%) Cerebellar/spinal hemangioblastomas (65%)

• Retinal angiomas (60%) Retinal angiomas (60%)

• Clear-cell renal carcinomas (45%) Clear-cell renal carcinomas (45%)

• Bilateral renal cysts (45%) Bilateral renal cysts (45%)

• Bilateral pheochromocytomas (26%) Bilateral pheochromocytomas (26%)

• MC skin is not involved, but a hemangioma MC skin is not involved, but a hemangioma located in the occipito-cervical region may located in the occipito-cervical region may occur.occur.

Ataxia-Telangiectasia Ataxia-Telangiectasia AKA Louis-Barr SyndromeAKA Louis-Barr Syndrome

• Mutated ATM gene 11q22.3 is responsible Mutated ATM gene 11q22.3 is responsible for DNA repair mechanismsfor DNA repair mechanisms

• Patients are hypersensitive to ionizing Patients are hypersensitive to ionizing radiation.radiation.

• Cerebellar Ataxia, Oculocutaneous Cerebellar Ataxia, Oculocutaneous Telangiectasia & Sinopulmonary Infections Telangiectasia & Sinopulmonary Infections

• Familial, first noted when child begins Familial, first noted when child begins walking, awkward swaying gait leads to walking, awkward swaying gait leads to need for wheelchair by age 10need for wheelchair by age 10

• CA: MC lymphoma, leukemia, breastCA: MC lymphoma, leukemia, breast

Telangiectasia of the neck in a 20-yo woman with ataxia telangiectasia.

By age 3 fine venous By age 3 fine venous telangiectasias seen telangiectasias seen on exposed surface of on exposed surface of ocular conjunctivaocular conjunctiva

Café au lait patches

Hypopigmented macules

Premature graying/alopecia

Chronic skin granulomas

EB EB SimplexSimplex

Keratins 5 & 14Keratins 5 & 14 Keratin Keratin tonofilamentstonofilaments

IE- lower IE- lower basalbasal

EBSSEBSS Type VII Type VII CollagenCollagen

UnknownUnknown IE- below IE- below granulargranular

EBS-MDEBS-MD PlectinPlectin HemidesmosoHemidesmosomeme

IE- lower IE- lower basalbasal

JEBJEB Laminin 5, BPA-Laminin 5, BPA-2, Type XVII Coll.2, Type XVII Coll.

Anchoring Anchoring FilamentFilament

Lamina Lamina LucidaLucida

JEB-PAJEB-PA α6ß4α6ß4 Integrin Integrin HemidesmosoHemidesmosomeme

Lamina Lamina LucidaLucida

DDEBDDEB Type VII Type VII CollagenCollagen

Anchoring FibrilAnchoring Fibril Sub Sub Lamina Lamina DensaDensa

RDEBRDEB Type VII Type VII CollagenCollagen

Anchoring FibrilAnchoring Fibril Sub Sub Lamina Lamina DensaDensa

EB Simplex (Koebner)EB Simplex (Koebner)• Keratins 5 & 14, defective intermediate keratin Keratins 5 & 14, defective intermediate keratin

filaments affected, split is @ lower basal layerfilaments affected, split is @ lower basal layer

• Generalized form, AD, onset at birthGeneralized form, AD, onset at birth

• Vesicles, bullae, milia on areas of repeated Vesicles, bullae, milia on areas of repeated trauma, ie. joints of hands, elbows, knees, feettrauma, ie. joints of hands, elbows, knees, feet

• Nikolski sign negativeNikolski sign negative

• Worse in summer, improves in winterWorse in summer, improves in winter

• Mucous membranes and nails not involvedMucous membranes and nails not involved

• TX: decompression of large blisters, treat TX: decompression of large blisters, treat infections. With time this condition improvesinfections. With time this condition improves

Weber Cockayne (EB Weber Cockayne (EB Simplex)Simplex)• Another K5 & K14 mutationAnother K5 & K14 mutation

• Localized to hands & feet w/ hyperhidrosisLocalized to hands & feet w/ hyperhidrosis• Onset varies, usually infancyOnset varies, usually infancy• Exacerbated by hot weather, prolonged walkingExacerbated by hot weather, prolonged walking• TX: Drysol BID.TX: Drysol BID.

EB Herpetiformis (Dowling-EB Herpetiformis (Dowling-Meara)Meara)

• Circinate configurations, milia presentCircinate configurations, milia present

• Oral mucosa involvedOral mucosa involved

• Nails are shed, but may regrowNails are shed, but may regrow

• Palmoplantar keratodermaPalmoplantar keratoderma

• Clumped tonofilaments on EMClumped tonofilaments on EM

• Blistering lessens with ageBlistering lessens with age

• Again K5 & K14 mutationsAgain K5 & K14 mutations

Epidermolysis bullosa simplex, Dowling–Meara. Small clustered vesicles in an arcuate array on the shoulder in this child.

Epidermolysis bullosa simplex, Dowling–Meara. Diffuse keratoderma of the palm in an adult

EB Simplex w/ Muscular EB Simplex w/ Muscular DystrophyDystrophy

• AR, EBS with late onset MDAR, EBS with late onset MD

• Mutation in PLECTIN geneMutation in PLECTIN gene

• PLECTIN is absent in skin and musclesPLECTIN is absent in skin and muscles

• Widespread blistering at birth Widespread blistering at birth associated with scarring, milia, atrophy, associated with scarring, milia, atrophy, nail dystrophy, dental anomalies, nail dystrophy, dental anomalies, laryngeal webs, urethral strictures.laryngeal webs, urethral strictures.

JEB (Herlitz, EB Letalis)JEB (Herlitz, EB Letalis)• AR, Laminin 5, BPA-2, Collagen XVIIAR, Laminin 5, BPA-2, Collagen XVII• Anchoring filaments, Lamina Lucida splitAnchoring filaments, Lamina Lucida split• Anemia and Growth RetardationAnemia and Growth Retardation• Dental – enamel pits, mouth erosionsDental – enamel pits, mouth erosions• Nails- dystrophic or absent Nails- dystrophic or absent • Generalize bullae with non-healing Generalize bullae with non-healing

granulation tissue, often prone to granulation tissue, often prone to infections.infections.

• Usually fatal by age 3-4 years of age. Usually fatal by age 3-4 years of age. • Non-Herlitz variant heals with atrophic Non-Herlitz variant heals with atrophic

scarring, but remits with time – lacks scarring, but remits with time – lacks granulation tissue, anemia, growth granulation tissue, anemia, growth retardation and has normal lifespanretardation and has normal lifespan

Junctional epidermolysis bullosa, Herlitz. Blisters on the elbow and large areas of denuded skin; note the bright red color in the axilla and groin.

JEB with Pyloric AtresiaJEB with Pyloric Atresia• AR, Similar to JEB because defect is AR, Similar to JEB because defect is

at the level of the lamina lucidaat the level of the lamina lucida• Defect is Defect is α6ß4α6ß4 Integrin genes ITGA6 & Integrin genes ITGA6 &

ITGA4 Hemidesmosome is defectiveITGA4 Hemidesmosome is defective

• Severe mucocutaneous fragility and Severe mucocutaneous fragility and gastric outlet obstruction, urethral gastric outlet obstruction, urethral stricturesstrictures

• Prognosis is poor, but if they survive Prognosis is poor, but if they survive the neonatal period the blistering the neonatal period the blistering diminishesdiminishes

Generalized Atrophic Benign Generalized Atrophic Benign EB (GABEB)EB (GABEB)

• Onset at birth, Autosomal recessiveOnset at birth, Autosomal recessive• Cleavage at the lamina lucidaCleavage at the lamina lucida• Type XVII collagen = BPA-2Type XVII collagen = BPA-2• Generalized blisters, atrophy, mucosal Generalized blisters, atrophy, mucosal

involvement, thickened, dystrophic or involvement, thickened, dystrophic or absent nails, dental defectsabsent nails, dental defects

• In contrast to EB Herlitz, pts often In contrast to EB Herlitz, pts often survive to adulthoodsurvive to adulthood

Cicatricial JEBCicatricial JEB

• Blisters heal with scarringBlisters heal with scarring

• Syndactyly and contracturesSyndactyly and contractures

• Stenosis of anterior naresStenosis of anterior nares

• EM: junctional bullae with EM: junctional bullae with rudimentary hemidesmosomesrudimentary hemidesmosomes

• Basal lamina and anchoring fibrils Basal lamina and anchoring fibrils intactintact

Dominant Dystrophic EB Dominant Dystrophic EB (DDEB)(DDEB)• Bullae on extensor extremities and jointsBullae on extensor extremities and joints• Albopapuloid-Pasini (most severe) – Albopapuloid-Pasini (most severe) –

spontaneous scar-like lesions on trunkspontaneous scar-like lesions on trunk• Nails often thickened, teeth normal.Nails often thickened, teeth normal.• Nikolski sign presentNikolski sign present• Healing w/ scarring, atrophyHealing w/ scarring, atrophy• Milia present, mild oral involvement, Milia present, mild oral involvement,

typically scarring at the tip of the tongue.typically scarring at the tip of the tongue.• Cockayne-Touraine - milder, no Cockayne-Touraine - milder, no

albopapuloid lesions present.albopapuloid lesions present.• Sub-Lamina Densa, Anchoring Fibrils, Coll. Sub-Lamina Densa, Anchoring Fibrils, Coll.

VIIVII

Dominant Dystrophic Epidermolysis Bullosa

Bart’s SyndromeBart’s Syndrome

• ADAD

• Mildly scarring mechanobullous Mildly scarring mechanobullous dermatosis with nail deformities and dermatosis with nail deformities and a favorable prognosisa favorable prognosis

• Variant of DDEBVariant of DDEB

• COL7A1 gene defect encoding for COL7A1 gene defect encoding for Type VII collagenType VII collagen

Transient Bullous Dermolysis of Transient Bullous Dermolysis of the Newbornthe Newborn

• Newborns who suffer blisters from every Newborns who suffer blisters from every minor traumaminor trauma

• Separation below the basal lamina with Separation below the basal lamina with degeneration of collagen and anchoring degeneration of collagen and anchoring fibrilsfibrils

• Rapid healing at 4 months, no scarring, Rapid healing at 4 months, no scarring, no nail abnormalitiesno nail abnormalities

• Again a COL7A1 defect for Type VII Again a COL7A1 defect for Type VII collagencollagen

Acrokeratotic Poikiloderma Acrokeratotic Poikiloderma (Weary-Kindler)(Weary-Kindler)

• Acral bullaeAcral bullae• Generalized poikiloderma with Generalized poikiloderma with

prominent atrophyprominent atrophy• PhotosensitivityPhotosensitivity• Acral keratosesAcral keratoses• Absence of elastic fibers in papillary Absence of elastic fibers in papillary

dermis and fragmented ones in the dermis and fragmented ones in the mid-dermismid-dermis

Recessive Dystrophic EB Recessive Dystrophic EB (RDEB)(RDEB)(Hallopeau-Siemens = severe)(Hallopeau-Siemens = severe)AR, Generalized skin and mucosal blisteringAR, Generalized skin and mucosal blistering

Mitten deformity, SCCMitten deformity, SCC

Severe dental & esophageal complicationsSevere dental & esophageal complications

Anemia, Growth retardationAnemia, Growth retardation

Reported cases with cardiomyopathy or Reported cases with cardiomyopathy or amyloidosisamyloidosis

Tx: Autologous or allogenic split thickness Tx: Autologous or allogenic split thickness skin grafts, palliative, Dental care.skin grafts, palliative, Dental care.

RDEBMITTEN DEFORMITY

50% of pts have SCCs by age 50% of pts have SCCs by age 35.35.

ESOPHAGEL STRICTURE/STENOSIS

Hailey Hailey DiseaseHailey Hailey DiseaseFamilial Benign Chronic Familial Benign Chronic PemphigusPemphigus• Persistent recurrent bullae on the lateral Persistent recurrent bullae on the lateral

neck, axillae, flexures that rupture and neck, axillae, flexures that rupture and may resemble impetigo, may have may resemble impetigo, may have annular spreading border creating annular spreading border creating circinate and configurate patterns.circinate and configurate patterns.

• Worse in summer, onset teens to 20’s, ADWorse in summer, onset teens to 20’s, AD• Genetic defect in Calcium ATPaseGenetic defect in Calcium ATPase• TX: TS, TAbx, OA, Oral retinoids, steroids.TX: TS, TAbx, OA, Oral retinoids, steroids.

“DILAPIDATED BRICK WALL” pattern of ACANTHOLYSIS = ROUNDING UP of cells

HAILEY HAILEY

• ICHTHYOSIS VULGARIS, Profillagrin ICHTHYOSIS VULGARIS, Profillagrin synthesis defect, ADsynthesis defect, AD

• IchthysisIchthysis is Greek for fish. scales is Greek for fish. scales

• Fine, whitish adherent scale SPARING THE Fine, whitish adherent scale SPARING THE FLEXURES, but worse on extensor FLEXURES, but worse on extensor extremitiesextremities

• Atopic Dermatitis >50%, Keratosis Pilaris, Atopic Dermatitis >50%, Keratosis Pilaris, Hyperlinear palmsHyperlinear palms

• TX: Emollients. TX: Emollients.

• Histo: Hyperkeratosis, absent granular layerHisto: Hyperkeratosis, absent granular layer

X-Linked X-Linked IchthyosisIchthyosis

• Xp22.32, steroid Xp22.32, steroid sulfatase sulfatase deficiencydeficiency

• Retention Retention hyperkeratosis, hyperkeratosis, brown adherent brown adherent scalescale

• SPARES SPARES FLEXURES, PALMS FLEXURES, PALMS & SOLES& SOLES

• Comma-shaped Comma-shaped corneal opacities corneal opacities

• Cryptorchidism Cryptorchidism 20%, check for 20%, check for undescended undescended testicles – testicles – Urologist Urologist

• Serum cholesterol Serum cholesterol sulfate sulfate INCREASEDINCREASED

• TX: emollientsTX: emollients

• LAMELLAR ICHTHYOSIS: TRANSGLUTAMINASE defect LAMELLAR ICHTHYOSIS: TRANSGLUTAMINASE defect Collodion membrane desquamates 3 weeksCollodion membrane desquamates 3 weeks

• 5-15mm grayish brown scales, strikingly 5-15mm grayish brown scales, strikingly quadrilateral, free at the edges, adherent in the quadrilateral, free at the edges, adherent in the center. center.

• Moderate HK of palms/soles. Moderate HK of palms/soles. • TX: AHAs, Emollients, Calcipotriol, Top/Oral TX: AHAs, Emollients, Calcipotriol, Top/Oral

RetinoidsRetinoids

Non-Bullous Congenital Non-Bullous Congenital Ichthyosiform ErythrodermaIchthyosiform Erythroderma

• Born in collodion membrane, Ectropion of Born in collodion membrane, Ectropion of eyelids – resolves in 2 weeks eyelids – resolves in 2 weeks

• Redness and scaling is generalizedRedness and scaling is generalized

• Cicatricial alopecia, nail dystrophyCicatricial alopecia, nail dystrophy

• Consider r/o Neutral Lipid Storage Disease.Consider r/o Neutral Lipid Storage Disease.

• Tx: Emollients and humid environment, Tx: Emollients and humid environment, attention to infection in fissured areas, attention to infection in fissured areas, avoid keratolytics.avoid keratolytics.

Harlequin FetusHarlequin Fetus• AR, severe, often AR, severe, often

stillborn or dies soon stillborn or dies soon after delivery, but after delivery, but aggressive systemic aggressive systemic retinoids have retinoids have allowed some have allowed some have lived 9 years.lived 9 years.

• Thick, armor-like Thick, armor-like plates covering entire plates covering entire surface, ectropion, surface, ectropion, eclabiumeclabium

• Failure to convert Failure to convert profillagrin to profillagrin to fillagrin, K6 and K16.fillagrin, K6 and K16.

Epidermolytic HyperkeratosisEpidermolytic Hyperkeratosis(Bullous Congenital (Bullous Congenital Ichthyosiform Erythroderma)Ichthyosiform Erythroderma)

• Newborn – widespread bullae, erosions, Newborn – widespread bullae, erosions, erythroderma, focal hyperkeratosiserythroderma, focal hyperkeratosis

• Infancy to adulthood – Localized to generalized Infancy to adulthood – Localized to generalized hyperkeratosis with rare focal bullae secondary hyperkeratosis with rare focal bullae secondary to bacterial infection. Warty scales with spiny to bacterial infection. Warty scales with spiny ridges. “corrugated” pattern to scales.ridges. “corrugated” pattern to scales.

• TX: Neonatal ICU for fluid, electrolyte and TX: Neonatal ICU for fluid, electrolyte and sepsis work-up, broad spectrum antibiotics until sepsis work-up, broad spectrum antibiotics until cultures are negative. Adult – oral retinoids, cultures are negative. Adult – oral retinoids, AbxAbx

EHK defects K1 and K10

Restrictive DermopathyRestrictive Dermopathy

• 24 cases24 cases

• Lethal, ARLethal, AR

• Prematurity, fixed facial expression, Prematurity, fixed facial expression, micrognathia, mouth in “O” positionmicrognathia, mouth in “O” position

• Rigid and tense skin with erosions Rigid and tense skin with erosions and denudations & multiple joint and denudations & multiple joint contracturescontractures

Ichthyosis Linearis Ichthyosis Linearis CircumflexaCircumflexa• Disorder of keratinization in which bizzare Disorder of keratinization in which bizzare

migratory annular and polycyclic patches migratory annular and polycyclic patches occur. Leave no scarring or pigmentary occur. Leave no scarring or pigmentary changes.changes.

• Inheritance AR, patients are born Inheritance AR, patients are born erythrodermic and 1/3 can have fatal erythrodermic and 1/3 can have fatal complications.complications.

• Most also have trichorrhexis invaginata Most also have trichorrhexis invaginata and AD – Netherton’s Syndromeand AD – Netherton’s Syndrome

• May clear completely in summertimeMay clear completely in summertime

BALL IN SOCKET DEFECT

TWISTING DEFECT

ILC

Chanarin-Dorfman Syndrome Chanarin-Dorfman Syndrome Neutral Lipid Storage DiseaseNeutral Lipid Storage Disease

• Ichthyosis, Myopathy Ichthyosis, Myopathy and lipid vacuoles ->and lipid vacuoles ->

• Impaired degradation Impaired degradation of triacylglycerol-of triacylglycerol-derived diacylglycerolderived diacylglycerol

• Dietary modulation of Dietary modulation of fats aids in controlling fats aids in controlling the diseasethe disease

Lipid vacuoles in granulocytes and monocytes but not lymphocytes or erythrocytes. -- ML Williams, M.D.

Ichthyosis Follicularis Ichthyosis Follicularis (IFAP Syndrome)(IFAP Syndrome)

• IFAP = Ichthyosis Follicularis, IFAP = Ichthyosis Follicularis, Alopecia, PhotophobiaAlopecia, Photophobia

• Generalized spiny follicular lesions Generalized spiny follicular lesions with xerosis of non-follicular skin, with xerosis of non-follicular skin, striking alopecia.striking alopecia.

• M>F 5:1M>F 5:1

• X-linked recessive and AD forms X-linked recessive and AD forms reportedreported

Sjogren-Larsson SyndromeSjogren-Larsson Syndrome• Fatty alcohol oxidoreductase deficiencyFatty alcohol oxidoreductase deficiency• Infancy: generalized erythroderma, Infancy: generalized erythroderma,

ichthyosis, fine to large lamellar scalingichthyosis, fine to large lamellar scaling• After Infancy: generalized darker scale After Infancy: generalized darker scale

without erythema accentuated in flexures without erythema accentuated in flexures and lower abdomen; spares central face.and lower abdomen; spares central face.

• CNS: MR, spastic diplegia with scissor gaitCNS: MR, spastic diplegia with scissor gait• Eyes: atypical retinitis pigmentosa Eyes: atypical retinitis pigmentosa

“glistening dots” pattern on slit lamp “glistening dots” pattern on slit lamp exam.exam.

• Dental dysplasiaDental dysplasia• Tx: Low fat diet with MCT oil anecdotal, Tx: Low fat diet with MCT oil anecdotal,

but worth trying.but worth trying.

•SJOGREN LARSSON SJOGREN LARSSON SYNDROME - atypical SYNDROME - atypical retinitis pigmentosa retinitis pigmentosa “glistening dots” pattern “glistening dots” pattern on slit lamp exam.on slit lamp exam.

Refsum’s SyndromeRefsum’s Syndrome• Phytanol-CoA hydroxylase deficiency Phytanol-CoA hydroxylase deficiency

• Leads to phytanic acid deposition in…Leads to phytanic acid deposition in…

• Skin (ichthyosis)Skin (ichthyosis)

• CNS (ataxia, peripheral neuropathy)CNS (ataxia, peripheral neuropathy)

• Eyes (retininitis pigmentosa “salt & Eyes (retininitis pigmentosa “salt & pepper”)pepper”)

• Ears (deafness)Ears (deafness)

• Cardiac (arrhythmias, block, CHF)Cardiac (arrhythmias, block, CHF)

• Musculoskeletal (wasting, skeletal Musculoskeletal (wasting, skeletal anomalies)anomalies)

• TX: dietary restriction of phytanic acid.TX: dietary restriction of phytanic acid.

Rud’s SyndromeRud’s Syndrome

• AR or X-linkedAR or X-linked

• IchthyosisIchthyosis

• HypogonadismHypogonadism

• Small statureSmall stature

• MF, EpilepsyMF, Epilepsy

• Macrocytic anemiaMacrocytic anemia

• Rule out Steroid sulfatase deficiency, Rule out Steroid sulfatase deficiency, Refsum’s Syndrome or Sjogren-Larsson Refsum’s Syndrome or Sjogren-Larsson SyndromeSyndrome

KID KID SyndroSyndromeme

• KeratitisKeratitis

• IchthyosisIchthyosis

• DeafnessDeafness

DISTINCTIVE LEATHERY VERRUCOID PLAQUES

AVOID ISOTRETINOIN, IT WORSENS THE KERATITiS!!!

THE THE END….END….