CONGENITAL ICHTHYOSIS

Dr Yugandar

The word ichthyosis comes from the Greek word for a

fish.

ichthyosis : is a group of disorders that are characterized

by a persistent, non-inflammatory scaling disorder of the

skin surface.

It is caused by abnormality in keratinization and

exfoliation of the horny cell layer.

The ichthyoses are a clinically and genetically

heterogeneous group of skin disorders,

characterized by a diffuse, generally uniform and persistent

pattern of scaling without mucosal or extracutaneous

(except in ichthyosiform syndromes) involvement.

Cutaneous features can be isolated (non syndromic ichthyosis),

or associated with extra-cutaneous (syndromic ichthyosis)

Types of Non syndromic ichthyosis

Congenital ichthyosis

Ichthyosis vulgaris

X-linked ichthyosis

Bullous congenital ichthyosiform erythroderma (BCIE)

Nonbullous congenital ichthyosiform erythroderma (NBCIE)

Lamellar ichthyosis

Acquired ichthyosis

Acquired ichthyosis

Types of syndromic ichthyosis

Sjögren-Larsson syndrome

Netherton syndrome

KID syndrome

Refsum syndrome

Rud syndrome

Congenital ichthyosis

Ichthyosis vulgaris

X-linked ichthyosis

Bullous congenital ichthyosiform erythroderma (BCIE)

Nonbullous congenital ichthyosiform erythroderma (NBCIE)

Lamellar ichthyosis

Ichthyosis vulgaris It is the common inherited disorder. inheritance is autosomal dominant

Etiology : caused by mutation in the gene coding

for filaggrin, a key protein involved in skin barrier function.

Decreased convesrion of Profilaggrin to Filaggrin.

Pathogenesis :

decrease in the production of filaggrin,defective aggregation of

Keratin intermediate filaments,

abnormal exfoliation and dryness and scaling

Keratohyalin synthesis is affected because of the filaggrin

mutation.

Filaggrin is an epidermal protein that normally functions as a

barrier molecule against environmental allergens, water loss,

and infection

Pathology :

There is thickening of the horny cell layer

reduction or loss of granular cell layer.

Histopathology:

Mild hyperkeratosis

diminished or absent granular layer in the epidermis.

The dermis is normal.

Electron microscopy reveals scanty and fragmented

keratohyaline granules in granular layer cells

Diminished or absent granular layer

Absent of filaggrin with immunostaining

Age of Onset :

early 3 – 12 months of age

Clinical features :

This is the mildest form of ichthyosis.

main symptoms are dryness and scaling of the skin (fine

scale).

Present, mostly on the extensor surfaces of extremities and

trunk.

back > abdomen ,extensor surface > flexor surface

Scaling is most prominent over the trunk, abdomen, buttocks

and legs.

The flexural areas, such as the antecubital fossa, are spared.

The symptoms subside during the summer and aggravate

during the winter

scaling may be present on the eyelid skin,punctate

epithelial keratitis and recurrent corneal erosion

Linkage analysis has identified an ichthyosis

vulgaris locus on band 1q22

An association may be present between ichthyosis vulgaris

and atopic diseases

Mutations in the coding of the filaggrin gene have been

identified in both ichthyosis vulgaris and atopic dermatitis.

Treatment : symptomatic treatement

X-Linked Recessive Icthyosis

Its uncommon type

Etiology : It is caused by loss or marked reduction of steroid

sulfatase enzyme

delayed exfoliation of the horny cell layer.

inheritance : X-linked recessively inherited,male children

Its k/a Ichthyosis nigra due to dark brown scales

Pathogenesis :

the lack of steroid sulfatase causes accumulation of

cholesterol sulfate, leading to delayed exfoliation of horny

cells and hyperkeratosis

Histopathology :

Thickening of the horny cell layer.

normal or mildly thickened granular and suprabasal cell

layers.

Compact hyperkeratosis

Accentuated granular layer

Clinical features:

ichthyosis manifests shortly after birth and does not improve

with age.

The symptoms are severer than ichthyosis vulgaris,

the scales are large and dark brown.

The scalp also scaly.

Eruptions also appear on the flexures of joints.

The whole body of newborns may be encased in a translucent

covering (collodion baby) .

Scales : Large & DARK BROWN more

Prominent over flexural areas

Complication :

Corneal opacification may occur.

White opacities in slit lamp &

blue arc

D.D:

ichthyosis vulgaris is differentiated from X-linked ichthyosis by the

decrease of steroid sulfatase in the case of the latter.

Treatment:

symptomatic and the same as those for ichthyosis vulgaris

The retinoids drugs may give good improvements, but the

side effects limit their use in infants and young children.

LAMELLAR ICTHYOSIS

Etiology :

Defect in Transglutaminase – 1 enzyme

its a calcium-dependent enzyme that is necessary for the

formation of cornified cell envelopes in keratinocytes

Age of onset : begins usually at birth

Inheritance : as an autosomal recessive trait (AR).

K/a ARCI

The transglutaminase 1 enzyme is involved in the

formation of the cornified cell envelope

The formation of the cornified cell envelope is an essential

for normal intercellular lipid layer formation in the stratum

corneum.

mutations cause defects in the intercellular lipid layers in

the stratum corneum, leading to defective barrier function

of the stratum corneum

6 genes for lamellar ichthyosis have been localized and 5 of them

TGM1 (14q11)

ABCA12 (2q34)

19p12-q12

19p13

ALOXE3-ALOX12B (17p13)

ichthyin (5q33)

The areas involved in mild cases are the antecubital,

popliteal and the neck

The palms and soles may present with mild

hyperkeratosis( PPK)

Ectropion

Hyperkeratosis ,Hypergrannulosis

Parakeratosis Prominent rete

ridgesMild perivascular infiltrate in the upper dermis and mitosis

Skin biopsies can aid in the diagnosis of lamellar ichthyosis

and detection of transglutaminase-1 expression.

At birth, electron microscopy can be used to differentiate a

severe collodion baby affected by lamellar ichthyosis from a

baby affected by harlequin ichthyosis by demonstrating the

absence of the marginal band

Bathing suit ichthyosis:

unique clinical form of autosomal recessive congenital

ichthyosis

characterized by marked scaling on the bathing suit

areas but sparing of the extremities and the central face.

caused by transglutaminase-1 deficiency

it is a temperature-sensitive phenotype

Shedding of membrane

Ichthyosiform

Erythroderms

Bullous congenital ichthyosiform erythroderma (BCIE)

it is rare disorder

autosomal dominantly inherited

sometimes born as collodion babies

Diffuse flushing and blistering recur for several weeks after

birth

Pathogenesis

intermediate filament of suprabasal cells composed of

keratin 1 and keratin 10.

Because of mutation in the keratin 1 or keratin 10 gene

abnormal keratin fiber formation & cytoskeleton distortion

epidermal blistering occur, leading to secondary thickening

of the horny cell layer

The horny and suprabasal cell layers thicken.

Vacuolar Degeneration of the granular cell layer

Clinical features

At birth child looks as Burned with widespread blisters &

erosions

May have verrucous,dirty,firm, hyperkeratotic (hystrix)

spines over erythematous background often in flexural

creases

blisters

may have erythroderma

palmar/plantar keratoderma

Frequent skin infections

characteristic pungent odor due to super infection

by mixed flora

D.D :

epidermolysis bullosa

incontinentia pigmenti

impetigo contagiosa

Treatment : oral retinoid and application of

moisturizer

Nonbullous congenital ichthyosiform

It is rare autosomal recessively inherited

Most of the patients are born as collodion babies.

The affected sites include the flexures of joints.

Defects in enzymes Trans glutaminase ,Two

Lipoxygenases

Pathogenesis

Six or more genes are thought to be associated with

occurrence of NBCIE.

the mechanism of NBCIE is known to be a

marked decrease in physical and functional

strength of keratin

Clinical features

Born as Collodion babes

Covered by fine white scales, 2-3 days after birth, the

collodion covering exfoliates,

leaving the whole body surface

with diffuse flushing and scaling

Scarring alopecia,short stature,

Cardiac anomolies

Erythroderma,

ectropion

NBCIE progresses until the age of 10,at which point it stops

and subsides.

Oral retinoid (a vitamin A derivative) is effective.

The skin should be kept clean to prevent secondary infection.

HARLEQUIN ICHTHYOSIS

very rare condition

autosomal recessively inherited

There is abnormality of the lamellar granules in harlequin

ichthyosis

Abnormalities of Profilaggrin & K 6,K16

Ichthyosis Congenita Gravis

In Italy,Comic servants characters from Italian commedia dell’arte

In french ,Black faced emissary of devil ,chasing damned souls of evil people to hell

Baby skin affected in Utero

patient is covered with an extremely thick stratum corneum

at birth causing thick, horny, armor-like plates that cover the

entire skin surface.

Cracks in the skin

ectropion of eyelids

eclabium,Ears absent

difficulty of opening the mouth are so severe that most patients die within 2 weeks after birth,still birth

Abnormal Lamellar Bodies

Under EM

Neonate after retinoid theraphy after 6 months

Ultrasound findings:

Head: cracked skin; open eyes, due to severe eversion of the

eyelids (ectropion); wide lips, (eclabium)

Skin: thickened with multiple fissures

Extremities: deformation, hypoplasia of fingers and toes

3D ultrasound helps to make the diagnosis.

thickened, Harlequin lips cracked skin on the fetal face

Transverse view of the fetal abdomen on

the image shows a thickened skin

with a crack indicated by arrow.

the foot with hypoplastic toes,

Differential diagnosis

Sjögren-Larsson syndrome

Netherton syndrome

Gaucher disease

Keratitis-ichthyosis-deafness syndrome

Trichothiodystrophy ("sulfur-deficient hair")

Chanarin-Dorfman syndrome

Conradi-Hünermann syndrome (X-linked dominant

chondrodysplasia punctata)

Hypohidrotic ectodermal dysplasia

Bullous autosomal dominant ichthyoses

 

Treatment

Prevention

In congenital ichthyosis syndromes, excessive intra-amniotic

debris and polyhydramnios on ultrasonography scanning in

utero may be the first indication of disease

Using USG in utero, fetal foot length may be an important &

first marker, seen in the second trimester, for the diagnosis of

harlequin ichthyosis

Other findings may include a persistently open mouth, dense

amniotic fluid, and fixed flexion of the extremities.

low maternal serum unconjugated estriol during pregnancy

screening may be a good indication of placental STS deficiency

and X-linked recessive ichthyosis

Microdeletion of STS gene can be confirmed by fluorescence in

situ hybridization (FISH) analysis of cultured amniotic fluid in X-

linked ichthyosis

Prenatal diagnosis of lamellar Ichthyosis can be made by direct

mutational analysis of the keratinocyte transglutaminase gene

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