Icthyoses Flashcards
What are 2 XLD icthyoses?
Conradi-Hunermann-Happle
CHILD syndrome
What does CHILD stand for?
Congenital Hemidysplasia
Ichthyosiform Erythroderma
Limb Defects
Inheritance of CHILD?
XLD, NSDHL (no show DHL, while child waiting for gift)
CHILD and Conradi-Hunermann H are defects in what?
CHILD - lipid metabolism disorder
CHH - cholesterol synthesis disorder
CH for CHolesterol/lipids
List 5 clinical features of CHILD?
congenital hemidysplasia ichthyosiform erythroderma limb defects organ hypoplasia on affected side scoliosis may have stripped epiphyses!!! - > resolve w/ time unlike CHH
Unique feature on path for CHILD?
foamy histiocytes in dermal papillae
acanthuses, parakeratosis, etc
unique tx for CHILD syndrome?
disorder of lipid metabolism:
topical 2% lovastatin or simvastatin in 2% cholesterol -> targets underlying cholesterol pathway
Inheritance and gene for Conradi Hunermann Happle?
XLD
EBP
CHH-Eck - BP
Cutaneous clinical presentation of Conradi HH?
birth - ichthyosiform erythroderma - pictures have whorls and streaks of keratosis
transitions to Blashkoid hyperkeratosis -> in older kids transitions to linear or patchy follicular atrophoderma w/ dilated follicular openings/icepick scarring
+- nail changes like onychoscizia
+- patchy scarring alopecia
Extracutaneous presentation of CHH?
- C for cataracts - unilateral
- C for chondrodysplasia punctuate - stripped epiphyseal
- asymmetric skeletal abs
Tx for Conradi Hunermann Happle?
emolients
optho needed (cataracts, unilateral)
ortho (chondrodysplasia punctata, skeletal abn)
List 4 erythrokeratodermas?
EKV, PSEK, KID, HID
What does PSEK stand for?
progressive symmetric erythrokeratoderma
what does KID stand for? HID?
Keratitis ichthyosis deafness
hystrix-like (spine like) ichthyosis deafness (keratitis less prominent)
which erythrokeratodermas are a/w with PPKs?
all (EKV, PSEK, KID/HID), as all are AD» AR connexin disorders; connexin is involved in PPKs and some PPKs are connexin related
Clinical hallmark of erythrokeratoderma variabilis? How is EKV different from PSEK?
transient +- burning erythematous patches lasting minutes to hours as well as permanent geographic/polycyclic erythrokeratoderma (aka red plaques with +++ keratosis) favouring PsO regions
PSEK has similar geographic erythrokeratoderma, but lacks transient erythematous patches
Other features of EKV?
PPK (connexin disorder)
Triggers and tx for EKV?
trauma, heat, sun
avoid triggers, keratolytics, retinoids TO/PO, camouflage makeup, avoidance of triggers
Clinical of PSEK?
slowly progressive figurate hyperkeratotic plaques
favours knees, elbows, extremities
PPK common (connexin disorder)
Tx for PSEK?
keratolytics, PO retinoids, PUVA reported
genetics of EKV and PSEK?
AD»> AR
connexin disorders: GJB3 and GJB4 in EKV
GJB4 in PSEK
cutaneous presentation of KID?
erythroderma at birth -> hyperkeratotic plaques with well demarcated borders
face = radial furrows
chelitis prominent (also a/w candida and staph)
recurrent Candidiasis
increased SCC (cutaneous and mucosal)
stripped palmoplantar keratoderma (connexin d/o)
nail, hair, dental abn
also epidermoid/pilar cysts
follicular occlusion triad (acne, dissecting cellularitis, HS)
stomatitis
extracutaneous features of KID?
congenital sensorineural hearing loss
progressive keratitis with corneal neovascularizaitno, conjunctivitis in 95%
Tx for KID?
emollients, keratolytics, TO/PO retinoids, hearing aids,
- treat infections
- regularly screen for SCCs (10-20%)
Gene and inheritance for Netherton syndrome? What does it code for?
SPINK5, AR -> encodes for LEKTI which is some sort of granule storage mediator
3 hair shaft abn of Netherton?
trichorrhexis invaginata classic
trichorrhexis nodosa
pili torti
What is the triad of Netherton syndrome?
atopy/autoimmune dysregulation + ichthyosis linearis circumflexa + trichorrhexis invaginata
What is the presentation of icthyosis linearis circumflexa?
serpiginous/polycyclic scaly plaques on trunk/extremities/scalp
DOUBLE edged scale (2 collars)
List 3 other cutaneous features of Nethertons?
AD
hair shaft abn
nail abn possible
generalized erythroderma/continuous peeling possible
increased SCC reported, along with HPV
Autoimmune dysregulation in NEthErTI7?
hyper IgE of serum - urticaria, angioedema, allergies incr
increased IL 17
Tx for Netherton?
symptomatic: ICU, calories at birth TO emollients, keratolytics, tretinoin ABx PRN antihistamines for pruritis reports of PUVA
List 6 features of Sjogren – Larsson syndrome?
congenital ichthyosis spastic plegia bone abnormalities developmental delay PPK perifoveal glistening white dots on fundus
Pathonomonic finding in Sjogren-Larsson syndrome?
perifoveal glistening white dots on fundus
MA: sjogren has dry eyes -> white dry dots on fundus
Gene for Sjogren-Larsson and inheritance?
ALDH3A2 - involved in ceramide recycling
AR (aldéhyde)
Clinical for Sjogren-Larsson?
- congenital ichthyosis
- spastic plegia
- developmental delay
erythema/hyperkeratosis/scaling -> erythema resolves, hyperkeratosis persists and becomes darker
gait issues, contractures, spasticity
white matter dz of the brain
test for Sjogren-Larsson syndrome
Fatty aldehyde dehydrogenase in fibroblasts (FALDH)
Tx for Sjogren - Larsson syndrome
derm + optho + neuro + ortho topical keratolytics, vit D, skin hydration systemic retinoids anticonvulsive agents fat reduced diets not helpful
Features of neural lipid storage dz with ichthyosis?
generalized fine scale +- erythema hearing impairment cataracts dev delay hepatomegaly (fatty degeneration)
Pathognomonic finding in Neutral lipid storage disease with ichthyosis (NLSDI)?
blood smear showing lipid vacuoles in blood cells
Trichothiodystrophy - inheritance?
ERCCC2 ERCC3
eric likes tigers
AR
What does PIBIDS stand for
P - photosensitivity I - ichthyosis B- brittle hair I - intellectual impairment D - decreased fertility Short stature
hair findings in Trichothiodystrophy?
“tiger hair” - trichoschisis - transverse hair fractures
trichorrhexis nodosa
pili torti
Tx in thrichothiodystrophy
sun protection, humectant, systemic retinoids
What is an ocular finding in Refsum dz?
REfsum -> REtinitis pigmenosa
also peripheral neuropathy, cranial nerve deafness, fine white scale
What must be reduced in Refsum (no longer featured prominently in Bologna )
phytanic acid in diet
REFSUM - REtinitis pigmentosa
Fytanic acid = phytanic acid
Two ichthyoses with increased SCC?
Kid who goes North, but ends up SSouth CIEs sunset
Netherton + KID
CIE - congenital ichthyosiform erythroderma
List 6 ddx for neonatal erythroderma?
syndromic incl hair stuff: Netherton syndrome Conradi Hunnerman Happle KID Neutral lipid storage dz with ichtyosis Thrichotiodystrophy
non-syndromic
epidermolytic ichthyosis
congenital icthyosiform erythroderma
steroid sulfatase deficiency
gene in ichthyosis vulgaris and MOI?
FLG (filaggrin), loss of cunction
AD semidominant
what does filagrin do?
profilaggrin - major component of keratohyalin granules in granular layer
profilagrin -> filagrin -> aggregate keratin intermediate filaments which get cross-linked in cornfield envelope -> impaired cornification, TEWL, penetration of allergens and irritants
what is ichthyosis vulgarism a/w (4 conditions)
atopic derm
hand eczema
nickel contact
irritant derm
also KP, asthma, hayfever (connect in your mind to AD)
clinical presentation of ichthyosis vulgaris
fine scales at extensors (dry parts of body)
sparing of flexures and groin (moist)
may have larger scale on lower legs
palmar hyperlinearity
prognosis of ichthyosis vulgaris?
improves w/ age, 1 in 100-250/ppl
% of kids with ichthyosis vulgaris who have AD?
25-50%
ultrastructural/path findings in ichthyosis vulgaris?
decreased granular layer (disorder of keratohyaline granules)
decreased/absent filagrin immunostaining
mild orthokeratosis and hyperkeratosis
tx for ichthyosis vulgaris?
emollients esp ceramides
humectants (keep water in the skin)
moisturizing cleansers, humidifiers
glycolic, sal acid -> careful about toxicity
TO retinoids vit D -> irritation, ineffective
PO retinoids -> rarely needed
Gene and inheritance pattern in steroid sulfatase deficiency?
STS, XLR
cutaneous features of steroid sulfatase deficiency?
large dark scale
++ scale on neck and lateral face (“dirty neck” dz)
neonatal - mild erythroderma
non-cutaneous features of steroid sulfatase deficiency?
in moms: failure of labour to progress
corneal opacities (10-50%)
cryptorchidism, hypogonadism, incr. testicular maldescent and incr testicular Ca
Tx for steroid sulfatase deficiency?
humectants, keratolytics, retinoids (to> po)
Name 3 non-syndromic AR congenital ichthyoses?
HI LIe CIE (hello sky)
harlequin ichthyosis
lamellar ichthyosis
congenital icthyosiform erythroderma
Gene and inheritance in lamellar ichthyosis?
TGM1, ar (the same one in collodion baby)
|»_space; ABCA12, others
Clinical presentation of lamellar ichthyosis? how is it different from ichthyosis vulgaris?
Lamellar ichthyosis: collodion baby -> large plate-like brown scales
Ichthyosis vulgaris: no collodion -> fine, thin scale
other features of lamellar ichthyosis:
bathing suit ichthyosis possible
collodion presentation: ectropion, eclabium, alopecia, hypoplasia of nasal/ear cartilage
macaronis, conjunctivitis, incomplete lid closure
note lamellar ichthyosis -> collodion -> scale; no erythroderma
Tx for lamellar ichthyosis?
collodion baby care PO retinoids keratolytics ophthalmology if ectropion patient advocacy
inheritance of congenital ichthyosiform erythroderma?
TGM1 #1 (AR), ABCA12, ALOXE3, etc (same as lamellar ichthyosis
clinical of congenital ichthyosiform erythroderma?
collodion baby -> generalized erythroderma and scaling for life
has palm/sole involvement with fissuring and hyper linearity
ectropium, scarring alopecia possible
obstruction of sweat ducts -> hypohidrosis/heat intolerance
2’ nail dystrophy, onychomycosis, flexion contractions
increased risk of SCC and BCC
ichthyosis vulgaris = no collodion, mild scale
lamellar ichthyosis = collodion, plate like scale no erythroderma
congenital ichthyosiform erythroderma = collodion, erythroderma AND scale
Inheritance of harlequin ichthyosis?
ABCA12, ar
Clinical of harlequin ichthyosis?
very thick arbor-like stratum corneum (unlike collodion which is much thinner) -> cracks into yellow grown plates with rhomboid scale -> deep bright red fissures -> dehydration, electrolyte imbalance, T instability, infections
ectropion, eclabium, ear nasal cartilage deformity
survivors - CIE like phenotype
Extracutaneous features of harlequin ichthyosis?
premature delivery
frequent neonatal dealth due to sepsis or respiratory insufficiency
microcephaly from tautness
1/2 survive beyond neonates -> severe ichyosiform erythroderma, PPK, heat intolerance, ocular problems, joint contracture
Tx for harlequin ichthyosis?
ICU to monitor temp, lytes, fluids, infections, resp humidified incubator hepful do not peel scale optho care systemic retinoids at 1mg/kg/d
ddx for collodion baby - give 7?
SuCCuLENTS (waxy like collodion) Sjogren-Larson Congenital Ichthyosiform erythroderma Conradi-Hunermann-Happle Lamellar Ichthyosis Ectodermal dysplasias Netherton Trichothiodystrophy Self-improving collodion ichthyosis (SICI)
Clinical of collodion baby?
taught shiny transparent membrane from thickened stratum corneum, “plastic-wrap” like
ectropion, eclabium, hypoplasia of nasal and auricular cartilage
gradually cracks and dries -> impaired transepidermal barrier -> TEWL, infections, late imbalance, sepsis -> circular bands can lead to vascular constriction and edema
MC cause of collodion baby?
congenital ichthyosiform erythroderma or lamellar icthyosis
self-improving collodion ichthyosis also possible with normal skin underneath
Tx for collodion baby?
ICU at birth for thermostability, hypernatremic dehydration, sepsis, infection, lung function
humidified incubator helps
do not remove skin manually due to infection
Which ichthyosis has congenital absence of hair?
ichthyosis follicular with atricia and photophobia
name 3 ichthyoses with hearing impairments?
KID* neural lipid storage dz with icthyosis Refsum Conradi CHILD*
name 3 icthyoses w/ ocular abn?
KID CHH NLSD with icthyosis trichotiodystrophy Refsum Sjogren alrson
Name 4 keratinopathic icthyoses?
epidermolytic icthyosis superficial epidermolytic ichthyosis ichthyosis hystrix Curth Macklin Icthyosis Hystrix - descriptive term Ichthyosis en confetti
keratin mutation in epidermolytic ichthyosis?
KRT 1, KRT 10 , AD
KRT 1 in PP skin -> PPK
KRT 10 mutated only -> no PPK due to compensation
clinical of epidermolytic ichthyosis?
erythroderma, blistering at birth -> cobblestone pattern hyperkeratosis over joints, ridging along skin lines at flexures, palmoplantar involvement +- pseudoainhum and blistering/fragility
path of epidermolytic ichthyosis?
epidermolytic hyperkeratosis -> unique vs other icthyoses:
dense orthokeratotic hyperkeratosis
acanthosis
hypergranulosis
cytolysis of supra basal/granular layer - > intraepidermal blisters
mild perivasc infiltrate
Tx for epidermolytic ichthyosis?
neonatal - > ICU (dehydration, hates, padded bed, Abx, lubricants ) - > erosions heal
than keratolytics, to retinoids, emollients, antiseptics, PO retinoids, preventing trauma
Mutation/inheritance in superficial epidermolytic ichthyosis?
KRT 2, AD
Clinical of superficial epidermolytic ichthyosis?
spares palms and soles (no keratin 1 mutation)
normal at birth or mild blistering
colarette like borders with molding due to superficial blistering - looks like tight shoes
KRT mutation in ichthyosis hysterix Curth Macklin?
KRT 1, AD
Clinical of ichthyosis hystrix Curth Macklin
like epidermolytic ichthyosis but no skin fragility
mild to severe, from severe mutilating PPK to localized hyperkeratosis
PSEUDOAINHUM, starfish like keratoses, knuckle pads, digital flexion contractors, 2’ bacterial infections
*hystrix - porcupine
Clinical of Icthyosis Hystrix?
descriptive term for ++ hyperkeratosis
mutation in Icthyossi en confetti?
KRT10, AD
ichthyosiform erytrhoderma + PPK
clinical of ichthyosis en confetti?
100-1000s of confetti “islands of normal skin”
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