ICHTHYOSES AND ICHTHYOSIFORM

SYNDROMES

Presented by

Dr. Ibrahim Md. Sharaf

HMO, Dept. of Skin & VD

Ichthyosis

Derived from the word ichthys (fish) The primary ichthyoses are a heterogenous

group of inherited disorders featuring excessive scale.

Here the homeostatic mechanism of cell kinetics of differentiation is altered.

Types of Ichthyoses

1) Ichthyosis vulgaris

2) X-linked Ichthyosis

3) Lamellar Ichthyosis

4) Epidermolytic Hyperkeratosis

Ichthyosis vulgaris Commonest form and also the mildest. Autosomal-dominantly inherited Inherited disorder of keratinization associated with

decreased conversion of profilaggrin to filaggrin that is characterized by fine scaling predominantly affecting the extensor surfaces of the extremities with sparing of the flexures and tendency towards improvement in the summer months.

Filaggrin is an epidermal protein which is needed for aggregation of keratin intermediate filament and retention of moisture in the stratum corneum.

Onset : early childhood (in between 3-12 months of age)

Ichthyosis vulgaris (Clinical features)

1. Xerosis

2. Scales : White fine scales; usually most prominent on the extensor surface of extremities with flexural sparing; although it’s frequently associated with AD which shows changes in flexural areas (antecubital and popliteal fossae). Scales are coarser on the lower extremities.

3. Hyperlinear palms/palmo-planter thickening.

Ichthyosis Vulgaris

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.

Ichthyosis vulgaris ( D/D)

Xerosis/Asteatotic eczema X-Linked ichthyosis Acquired ichthyosis Atopic dermatitis KID syndrome Netherton syndrome

Associations

• Atopic dermatitis

• Keratosis pilaris

X-Linked ichthyosis

Ichthyosis seen only in men as a result of steroid sulfatase deficiency.

X-Linked recessive inheritance. Males are affected and females are asymptomatic

carrier. Onset : usually before 3 months of age. The children are commonly born via C/S, with failure

of progression of labor owing to a placental sulfatase deficiency and low maternal urinary estrogen level.

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.

X-linked Ichthyosis

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

Difference between I.V. and X-linked Ichthyosis (clinically)Traits Ichthyosis vulgaris X-linked Ichthyosis

Severity Mild Moderate

Affected sex Both sexes Only male

Onset in between 3-12 months of age

before 3 months of age

Scales Finer Coarser and darker

Affected area Abdomen is more affected than back

Spared area Flexures and face Palms and soles

Association with KP & AD

Present Absent

Eye involvement & hypogonadism

Absent Present

Autosomal-Recessive Ichthyosis

Lamellar Ichthyosis

Present at birth or appears soon after. Usually involves the entire cutaneous area. Autosomal-Recessive inheritance. It is a severe form of Ichthyosis and also is

very uncommon. Decreased or absent transglutaminase-1

activity. Onset : Birth- collodion baby.

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.

Lamellar Ichthyosis

Lamellar Ichthyosis

Ectropion

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.

Collodion baby

Nonbullous congenital ichthyosiform erythroderma Rare severe ichthyosis presenting at birth. All three enzymes have autosomal recessive inheritance have

mutations: Tranglutaminase-1 (TGM1) at 14q11.2; also involved in lamellar

ichthyosis. Two lipoxygenases at 17p13.1 (ALOX12B and ALOXE3).

Clinical features: Frequently born as collodion baby. Fine white scales and erythroderma. Also ectropion and scarring

alopecia. Nail dystrophy, short stature, cardiac malformations.

Harlequin Fetus Evolve of the word ‘Harlequin’ : Harlequin or Arlecchino in Italian or Arlequin in 

French is the most popularly known of the comic servant characters from the Italian Commedia dell'arte and its descendant, the Harlequinade. In French passion plays Hellequin, a black-faced emissary of the devil, is said to have roamed the countryside with a group of demons chasing the damned souls of evil people to Hell.

Synonym: Ichthyosis congenita gravis. A severe disorder that affects the skin in utero, causing thick, horny,

armor-like plates covering the entire surface. Ears are rudimentary or absent, eclabium and ectopion are severe. Abnormalities of profilaggrin, K6 and K16 expression have been

reported. Recessive inheritance has been favoured and is supported by reports of

consanguinity. Usually the child is stillborn or dies soon after delivery; although there

are reports of a few survivors, with lifelong systemic retinoids.

Harlequin

Harlequin Fetus

Harlequin Fetus

Bullous Ichthyosiform Erythroderma (Borcq)

Synonym: Epidermolytic hyperkeratosis. Uncommon generalized disorder with blisters and

hyperkeratotic lesions. Autosomal-dominantly inherited. Mutations in keratin1 and 10 genes. There is altered assembly process of cornified cell

envelopes. It has been described as an incidental finding in

normal skin, skin adjacent to epidermal tumor (both benign and malignant) and normal oral mucosa.

Epidermolytic hyperkeratosis (C/F)

At birth, widespread blisters and erosions; child looks as if burned.

Then development of distinctive dirty, spiny, hyperkeratotic lesions, often scattered on an erythematosus background; most often in flexures.

Palmoplantar keratoderma common. Epidermolytic hyperkeratosis skin is usually has a

characteristic pungent odor, thought to be related to super-infection by mixed flora.

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 keratohyaline granules. Electron microscopy : Perinuclear haloes.

Treatment modalities in general Maintaining hydration – Emollients (Vaseline, liquid

paraffin, glycerin, olive oil). These agents should be applied immediately after washing with water, without allowing skin to dry.

Topical urea (10-30%) acts as humectants-holds water. Salicylic acid and lactic acid-as keratolytics; here should

be mentioned that salicylic acid products are best reserved for localized thicker areas, when 40% urea has failed.

40% to 60% solution of propylene glycol in water (usually under an occlusive suits) – Drawbacks: renal failure and cardiac toxicity when given systemically.

Topical calcipotriene. Avoidance of strong soaps.

Specific management Ichthyosis vulgaris : general modality. X-linked Ichthyosis : as like IV but a consultation

with ophthalmologist (for corneal opacity) and surgeon (for cryptorchidism) is needed.

Lamellae Ichthyosis and Nonbullous congenital ichthyosiform erythroderma : Systemic retinoids may be helpful, but long-term use problematic; otherwise, as for ichthyosis vulgaris. Management of ectropion.

Epidermolytic Hyperkeratosis : Systemic retinoids help with keratoses but may increase tendency to blister; watch for infections (antibiotics); otherwise, same as ichthyosis vulgaris.

Features of different types of Ichthyosis

Features IV X-linked Ichthyosis

Lamellar Ichthyosis

EK

Inheritance AD X-linked AR AD

Severity Mild Moderate Severe Becomes less severe with age

Defect Flaggrin protein Steroid sulphatase enzyme

Transglutaminase 1

Abnormal distribution of keratinocytes

Distribution All over body All over body

Only men

All over body, very severe, involves flexure, neck, face, scalp, scaly palms and sole

All over body, bullae and hyperkeratotic lesions over knee, elbows; keratoderma

Features of different types of Ichthyosis (contd.)

Features IV X-linked Ichthyosis

Lamellar Ichthyosis

EK

Onset 3-12 months of age

Before 3 months of age

Birth- collodion baby

Birth- bullae, erythroderma.

Spared areas Flexures and face

Palms and soles

None None

Other features Fine scales, improves in summer

Scales are black and brown, eye involvement, cryptorchidism

Scales are large and quadrangular, ectropion and eclabium

Erythroderma

Treatment Emollients Emollients Retinoids- acitretin

Systemic and oral retinois + antibiotics

Prognosis Good Good Causes serious disability

Tends to become less severe with age

“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.”

Ichthyosis Linearis Circumflexa

Inherited autosomal-recessive disorder. Migratory annular and polycyclic patches

occur. May first appear as generalized exfoliative

erythroderma; later lesions predominate on trunk and extrimities, appear as polycyclic patches characterized by constantly changing patterns.

Syndromes associated with Ichthyosis

Netherton syndrome

Ichthyosiform skin changes Trichorrhexis invaginata (bamboo hair) Atopic dermatitis.

Difficult to manage; keratolytics for ichthyotic lesions; topical tacrolimus, acitretin.

Refsum Syndrome

Autosomal recessive inherited ichthyosis, resembling ichthyosis vulgaris.

Atypical retinitis pigmentosa. Peripheral neuropathy. Cerebellar ataxia. Nerve deafness. ECG changes.

KID Syndrome

Keratitis-Ichthyosis-Deafness syndrome. Other name : Senter syndrome. Vascularization of cornea, deafness, hyperkeratotic

palms and soles, hypotrichosis, partial anhydrosis, nail dystrophy and tight heel cords are the characteristic features.

Treatment with acitretin (isotretinoin exacerbate corneal vascularization), cyclosporin A eye drop.

CHILD Syndrome

Congenital hemidysplasia with ichthyosiform erythroderma and limd defects.

Unilateral inflammatory nevi and ipsilateral limb defect.

X-linked dominant and lethal in hemizygous male.

H/E : presence of foamy macrophages in dermal papillae.

Acquired Ichthyosis Vitamin deficiency: Vitamin A, vitamin B6, and nicotinic

acid deficiency. Infections: Leprosy, tuberculosis, syphilis. Medications: nicotinic acid (most common), triparanol,

clofazemine. Systemic diseases : Sarcoidosis, hypothyroidism, lupus

erythromatosus, AIDS. Malignancy : lymphoma specially Hodgkin’s lymphoma;

also occurs in NHL, mycosis fungoids, multiple myeloma. Caution: Whenever ichthyosis appears in adult life for the first time, exclude an underlying malignancy.

Severe xerosis in the elderly.