Ichthyoses

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Ichthyosis

Ichthyosis•Derived from the word ichthys = fish

CONGENITAL

ICHTHYOSIS

AQUIRED

ICHTHYOSIS

CONGENITAL ICHTHYOSIS

•are a heterogenous group of inherited disorders of epidermal differentiation featuring

excessive scaling•Here the homeostatic mechanism of cell kinetics of differentiation is

altered

Associated with excessive keratin buildup due to a desquamation defect, leading to retention of abnormally formed scaleUsually apparent at birth

CONGENITAL ICHTHYOSIS

CONGENITAL ICHTHYOSES

1. Ichthyosis vulgaris 2. X-linked recessive ichthyosis 3. Lamellar ichthyosis 4. Non-bullous ichthyosiform

erythroderma 5. Bullous ichthyosiform erythroderma 6. Ichthyosis bullosa of Siemens 7. Harlequin ichthyosis

Ichthyosis vulgaris

Ichthyosis Vulgaris

Ichthyosis vulgaris•Inherited disorder of keratinization

associated with ↓ conversion of profilaggrin to filaggrin that is characterized by fine scaling

predominantly affecting the extensor surfaces of the extremities with characteristic

sparing of the flexures

Ichthyosis vulgaris

•Commonest form and also the mildest

Ichthyosis vulgaris

ADDecreased/absent profilaggrin )keratohyalin granules(

Ichthyosis vulgarisPresents few months after birth to early childhood )3-12 months( Mild itching XerosisFine, white scales on extensor surfaces coarser on the lower extremitiesFlexures spared Hyperlinear palms/soles

Ichthyosis vulgaris

Tendency towards improvement in the summer months

May improve in adulthood but may recur

Ichthyosis vulgaris

ASSOCIATIONS:Atopic diathesiskeratosis pilaris

Ichthyosis vulgaris

HISTOLOGY: retention hyperkeratosisattenuated/absent granular layer

Ichthyosis vulgaris

ELECTRON MICROSCOPY:scanty, fragmented keratohyaline granules

Ichthyosis vulgaris

Acquired form of IV associated with internal disease, malignancies )Hodgkin's lymphoma ‘MC’, carcinoma of bronchus, breast and cervix(, sarcoidosis, lupus and drugs

X-Linked Ichthyosis

X-linked ichthyosis

Man with preauricular brownish scaling typical of X-linked ichthyosis

Dirty scales in X-linked ichthyosis

X-Linked Ichthyosis

XLRSteroid sulfatase defect )STS gene(

X-Linked Ichthyosis

↓Steroid sulfatase → accumulation of cholesterol sulphate in the epidermal cells

X-Linked Ichthyosis

2nd most common type of ichthyoses

X-Linked Ichthyosis

Presents around infancy usually before 3 months of age with mild erythroderma and large translucent scales

X-Linked Ichthyosis

translucent scales → evolves into adherent brown “DIRTY” polygonal scales divided by wide splits

X-Linked Ichthyosis

Sites: extremities, trunk, neck; variable INVOLVEMENT of flexures Sparing of palms/soles

X-Linked Ichthyosis

Mother )with affected fetus(: low/absent estrogen in urine/amniotic fluid → labor fails to progress → children are commonly born via C/S

X-Linked Ichthyosis

Other associations: 1. Comma-shaped corneal opacities 2. Cryptorchidism3. Carcinoma of testis )↑risk(

X-Linked Ichthyosis

HISTOLOGY: hyperkeratosis or parakeratosis normal or slightly thickened granular layer

X-Linked Ichthyosis

TESTS: serum lipoprotein electrophoresis )detects accumulation of cholesterol sulfate(

FeatureIchthyosis vulgaris

X-linked Ichthyosis

Severity Mild Moderate

Affected sex Both sexes male

Onset 3-12 months before 3 months

Scales Finer Coarser and darker

Affected areapredominantly extensor surfaces of the extremities

extremities, trunk, neck; flexures variably involved

Spared area Flexures Palms, solesAss. w/ KP & AD Present Absent

Eye involvement Absent Present

Cryptorchidism Absent Present

Granular layer Hypo or agranulosis

Normal or thickened

Lamellar Ichthyosis

Collodion baby

Collodion baby with translucent membrane of the body

4 lid ectropion due to contracture of the periocular skin

Lamellar Ichthyosis

Lamellar Ichthyosis

LI: Palmar Keratoderma

Inflexible fingers due to taut skin in a young

patient with LI

Nail dystrophy & inflammation of the nail folds

Body distribution of lamellar ichthyosis

Lamellar Ichthyosis

ARTGM1 gene mutation )↓transglutaminase( or ABCA12 mutation )ATP binding cassette A12(

Lamellar Ichthyosis

TGM1 mutation → ↓transglutaminase → ↓cornified cell envelope → secondarily cause defects in the intercellular lipid layers → defective barrier function

Lamellar Ichthyosis

Presents AT BIRTH with collodion membrane encasing the baby which desquamates over the first 2-3 weeks

Lamellar Ichthyosis

collodion membrane with underlying erythroderma → evolves to thick, dark scales

COLLODION BABY

Collodion Baby•A number of forms of ichthyoses present at birth with infant

encased in a glistening tight membrane of adherent keratinocytes, which has been compared

to collodion

Collodion Baby•The membrane is then shed, leaving either normal skin

(lamellar exfoliation of newborn) or, more often ;–lamellar ichthyosis–Congenital Ichthyosiform

Erythroderma•some have trichothiodystrophy, X-linked recessive

ichthyosis, neutral lipid storage disease, or Gaucher's disease.

Collodion Baby•COMPLICATIONS:

.1renal failure

.2dehydration

.3hypothermia

.4sepsis

COLLODION BABY

Lamellar Ichthyosis

SCALES: usually thick large platelike dark )grayish-brown(, quadrangular free at edges and adherent at CENTERtend to be largest at extremities separated by superficial fissuring arranged in a mosaic pattern resembling FISH SKIN

Lamellar Ichthyosis

Usually involves the entire skin with prominent flexural involvement

Lamellar Ichthyosis

NAIL ABNORMALITIES1.dystrophy 2. nail fold inflammation 3. subungual hyperkeratosis 4. longitudinal or transverse

stippling5.grow 2-3 times the normal rate.

Lamellar IchthyosisAssociated ectropion, eclabium )dt. tautness of facial skin(, scarring alopecia, hypohidrosis, contracturesheat intolerance )heat stroke( Involvement of palm and soles: Ranges from minimal hyper-linearity to severe PPKhypernatremia

Lamellar Ichthyosis

no improvement with age

Lamellar Ichthyosis

HISTOLOGY: MASSIVE orthokeratotic hyperkeratosisnormal or thickened granular layeracanthosis with increased mitoses perivascular lymphocytic infiltrate

Congenital Ichthyosiform Erythroderma (CIE)

Mild erythema and generalized whitish desquamation

Congenital ichthyosiform erythroderma


=Nonbullous CIE (n-CIE)


•AR (some AD)

•TGM1 gene, few ALOXE3 or ALOX12B gene mutation (encode lipoxygenase 3 and 12R-lipoxygenase, respectively)


•Presents at birth with collodion membrane →

generalized erythroderma and persistent fine

white scaling•flexures involved

•PPK•no improvement with age


•associated scarring alopecia

•ectropion•nail dystrophy (similar to LI but milder)

•heat intolerance•increased susceptibility to infections

Epidermolytic Hyperkeratosis

Epidermolytic Hyperkeratosis

EHK or Bullous CIE

ADkeratin 1 and keratin 10 (KRT1 and KRT10) gene mutations → Clumped tonofilaments

Bullae form due to separation of edematous keratinocytes; keratinocytes fall apart )epidermolysis( due to lack of normal cytoplasmic keratin filament infrastructure that normally gives keratinocytes their strength

EHK or Bullous CIE

EHK or Bullous CIE

Presents at birth with initial erythroderma, bullae, denuded skin → evolves into yellowish brown verrucous hyperkeratotic plaques most prominent over joints also scalp, neck and infra-gluteal folds, flexural involvement, PPK

EHK or Bullous CIE

Distinct foul odor due to secondary bacterial colonization of thickened skin

EHK or Bullous CIE

Linear epidermolytic hyperkeratosis is associated with genetic mosaicism with absence of blistering

EHK: parakeratosis, hypergranulosis &

vacuolar degeneration of the granular & spinous

layer

EHK or Bullous CIE

HISTOLOGY: massive orthokeratotic hyperkeratosisHypergranulosis Granular and vacuolar degeneration of spinous and granular cell layers

EHK or Bullous CIE

COMPLICATIONS: 1. recurrent infection2. sepsis3. dehydration4. electrolyte imbalances due to

compromised skin barrier 5. failure to thrive

Ichthyosis Bullosa of Siemens (IBS)

Lower leg of a 12 month infant with Ichthyosis bullosa of Siemens

bullae with neighbouring skin showing mauserung appearance

Ichthyosis Bullosa of Siemens

A variant of BCIE


ADkeratin 2e )K2( gene defect


Presents at birth with mild erythroderma and mild superficial blistering → evolves into brown hyperkeratotic plaques over joints, flexures, abdomen, dorsal hands and feetspares palms/soles


A distinctive characteristic of IBS which is not present in other forms of ichthyosis is called the "Mauserung phenomenon" )Mauserung is German for "moulting" and was first described by H.W.Siemens(. These are small patches of bare, apparently normal peeled skin


HISTOLOGY:Epidermolytic hyperkeratosis

Harlequin Ichthyosis


HI after shedding of the armour of scales covering the body at birth )note the malformed fingers & ear(


ARABCA12 mutation

)ATP binding cassette A12(


Presents at birth with encasement of hard, thickened armor-like plates of restrictive stratum corneum covering the entire surface with deep fissuresSevere ectropion, eclabium, ears maybe rudimentary or absent, mitten-like hands and feet


Stillborn or death within few days of birth due to respiratory difficulties and sepsisOral retinoid may prolong survival

Algorithm for the diagnosis of congenital ichthyosis

TREATMENT OF ICHTHYOSES

I. GENERAL CARE II. LOCAL CARE III.SYSTEMIC CARE

GENERAL CARE

GENERAL CARE .1Avoidance of strong drying soaps & use creamy soaps.2Avoidance of unnecessary exposure to cold or hot climates

potential for heat intolerance and heat stroke .3Frequent showering (w/ immediate application of emollients).4Manual debridement of the collodion membrane is not

recommended

GENERAL CARE .5X-linked Ichthyosis: consultation with ophthalmologist (for

corneal opacity) and surgeon (for cryptorchidism) is needed

LOCAL CARE

LOCAL CARE .1Emollients: Maintaining hydration–creams and ointments

(Vaseline, liquid paraffin, glycerin, olive oil). These agents should be applied immediately after washing with water,

without allowing skin to dry.2Humectants: (10-30%) Topical urea, 40% to 60% solution of

propylene glycol in water (usually under an occlusive suits)–Drawbacks: renal failure and cardiac toxicity when given

systemically..3Keratolytics: Salicylic acid and lactic acid; here should be

mentioned that salicylic acid products are best reserved for localized resistant thicker areas

LOCAL CARE .4Topical retinoids: (retinoic acids, tazarotene) .5Calcipotriol .6Topical Antibiotics: applied to fissures.7Antiseptics: can be used topically to control odor (as well

as antimicrobials)

SYSTEMIC CARE

SYSTEMIC CARE

.1Systemic retinoids:–(Isotretinoin or Acitretin ) reserved for severe disease

that is refractory to conventional therapy –Lamellae Ichthyosis and Nonbullous congenital ichthyosiform

erythroderma: Systemic retinoids may be helpful, but long-term use problematic

–Epidermolytic Hyperkeratosis: Systemic retinoids help with keratoses but may increase tendency to blister

.2Oral antibiotics: for infections

Effects of systemic retinoid therapy in lamellar ichthyosis. Before (a) and after (b) one month of acitretin 1 mg/kg/day

Gene therapy novel futuristic therapeutic approach to ichthyosis

SYNDROMES ASSOCIATED WITH ICHTHYOSIS

ICHTHYOSIFORM SYNDROMES

1. Netherton’s syndrome 2. Sjogren Larson Syndrome 3. Refsum’s disease 4. Neutral lipid storage disease 5. IBIDS syndrome 6. KID syndrome 7. CHILD syndrome

Netherton syndrome.1Ichthyosiform skin changes.2Trichorrhexis invaginata (bamboo hair).3Atopic dermatitis

Refsum Syndrome.1Atypical retinitis pigmentosa.2Peripheral neuropathy.3Cerebellar ataxia.4Nerve deafness.5ECG changes

KID Syndrome.1Keratitis.2Ichthyosis.3Deafness

CHILD Syndrome.1Congenital hemidysplasia .2Ichthyosiform erythroderma .3Limb defects

ReferencesPresentation by Dr. Ibrahim Md. Sharaf HMO, Dept. of Skin & VDDermatology Illustrated Study Guide & Comprehensive Board Review 2012pathologyoutlines.comGoogle imagesfirstskinfoundation.org

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Ichthyoses