CONGENITAL ICHTHYOSIS
BY: DR.KIRAN DHANNUR
CHAIRPERSON: DR.GURUPRASAD K.Y.
ICHTHYOSIS
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.
It was given by Robert willan
Greek word 'ichthys' which means fish.
It is caused by abnormality in keratinization and exfoliation of the horny cell
layer.
Brick and Mortar" theory
The "brick and mortar" model of the epidermis helps
one understand the genetic basis of the primary
ichthyoses. The stratum corneum is made up of
keratins and lipids. Mutations in keratins usually have
autosomal dominant inheritance and can be viewed as
"defective bricks." Mutations in the enzymes needed to
produce and metabolize lipids are usually autosomal
recessive, and represent "defective mortar."
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.
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
Ichthyosis vulgaris (D/D)
• Xerosis/Asteatotic eczema
• X-Linked ichthyosis
• Acquired ichthyosis
• Atopic dermatitis
• KID syndrome
• Netherton syndrome
Associations
• Atopic dermatitis
• Keratosis pilaris
Ichthyosis vulgaris (association with)
• Ichthyosis vulgaris is frequently associated with keratosis pilaris and
atopic dermatitis so their C/F are found with it, accounting keratotic lesions
on on palmer creases (keratosis punctata), Follicular hyperkeratoses on
shoulders, buttocks, thighs and upper arms as in case of KP and hay fever,
asthma, eczema or urticaria may be presented as a manifestation of AD.
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
X-Linked ichthyosis(C/F)
• Large dark polygonal scales divided by wide splits prominently on
trunk and extensor extremities. The palms and soles are nearly always
spared.
• The sides of the neck usually are involved giving rise to a unwashed
look (dirty neck)
• Ocular involvement: Corneal opacity.
• Cryptorchidism, testicular carcinoma.
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.
X-Linked ichthyosis(D/D)
Ichthyosis vulgaris
Lamellar ichthyosis
Asteatotic eczema
Atopic dermatitis
Netherton syndrome
Nonbullous congenital ichthyosiform erythroderma
Associations
• Androgenetic alopecia
• Kallmann syndrome
• Multiple sulfatase deficiency
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).
The transglutaminase I 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)
Lamellar Ichthyosis (C/F)
• H/O a collodion-like (a colourless or yellow syrupy liquid) membrane
encasing the baby at birth which desquamates over the first 2/3 weeks.
• Scales: Thick dark (grayish-brown), strikingly quadrangular, free at
edges and adherent at centre; tend to be largest at extremities where
these large plate-like scales are separated by superficial fissuring
(similar to a dry river bed)
• Involvement of palm and soles: Ranges from minimal hyper-linearity to
severe keratoderma.
• Ectropion and eclabium: Ectropion is the turning out of the eyelid so that
the inner surface is exposed.
• Eclabium is eversion of a lip.
• Tautness of facial skin is responsible for these.
• 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 ridges
Mild 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
Collodion Baby
• A number of forms of ichthyosis present at birth with infant
encased in a tight membrane of adherent keratinocytes, which
has been compared to parchment or collodion.
• Kollodes is the Greek word for glutinous or glue-like.
• The membrane is then shed, leaving either normal skin (lamellar
exfoliation of newborn) or, more often, one of the forms of
nonbullous congenital ichthyosiform erythroderma or lamellar
ichthyosis
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 pigment
• 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 anomalies
• 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
• 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 .
• Lamellar Bodies Under EM
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.
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
Investigation findings
1) Ichthyosis vulgaris: Histology reveals mild hyperkeratosis with an
reduced/absent granular layer; normal thickness of spongy layer,
normal dermis. Electron microscopy: keratohayalin granules.
2) X-linked Ichthyosis: Elevated plasma cholesterol sulfate level or
lipoprotein electrophoresis showing increasing motility of low-
density lipoproteins (LDLs).
3) Lamellar Ichthyosis: The transglutaminase-1 can be stained in
frozen sections of skin; histology shows orthokeratotic
hyperkeratosis and mild to moderate acanthosis.
4) Epidermolytic hyperkeratosis: H/E shows compact hyperkeratosis.
Granular layer is markedly thickened and contains coarse
keratohyalíne granules. Electron microscopy: Perinuclear haloes.
Treatment
• Congenital ichthyosis (neonatal intensive care)
Monitor fluid balance, electrolytes; watch for skin infections
Incubator with high humidity but somewhat lower temperature;
remember infants mmonitor temperature.
• Never bathe without relubricating, apply nonmedicated cream
thinly 6-8 times a day
• Ectropion management by ophthalmology
• Watch for flexural contractures
• Check vision and hearing; get neurologic evaluation
• Put family in touch with ichthyosis self-help group
Newborns and infants
Bathe twice daily with sodium bicarbonate
Rub lightly with soft washcloth or microfiber towel
Apply nonmedicated cream 2-3 times daily
No urea or salicylic acid
Ectropion management by ophthalmology, cleaning of extemal ear
by otorhinolaryngology
Physical therapy to avoid flexural contractures
Children
Bathe twice daily with sodium bicarbonate
Rub with soft washcloth, microfiber towel, or pumice stone
Apply 5% urea cream twice daily
Treat scalp with stronger urea cream 7%-10%
Ectropion management by ophthalmology, cleaning of extemal ear
by otorhinolaryngology
On warm summer days, measure temperature, force fluids, cool
environment, no occlusiveointments; play outside earfier or later,
not in midday
No vacations in warm climates
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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