Definition , classification types syndrome and treatment

1. CONGENITAL
ICHTHYOSIS
By Dr. Akanksha Agarwal

2. • Keratinization is a complex process in which nucleated basal cells of
epidermis are gradually transformed into dead, anucleated horny cells with
cornified lipid envelope.

3. PROCESS OF KERATINIZATION
• As keratinocytes are transformed
from mitotically active cells in the
basal layer to fully differentiated,
enucleated squames in the cornified
layer, specific proteins are
expressed at particular locations
within the epidermis.
• Keratohyalin and lamellar
granules extrude their contents in
the granular layer
• leading to bundling of keratin
filaments and
• replacement of the plasma
membrane with the highly cross-
linked, lipid-covered cornified cell
envelope

4. ICHTHYOSIS
• Ichthyosis describes dry, rough skin with scaling.
• derived from Greek word ichthys/ikhthus which means fish.
• The ichthyoses are clinically and genetically heterogeneous group of skin
disorders, characterized by a diffuse, generally uniform and persistent
pattern of scaling of the skin.

5. Retention Hyperkeratosis
• a/w impaired corneocyte shedding
Hyperproliferative Hyperkeratosis
• a/w accelerated keratinocyte
production
The development of HK in ichthyosis is a homeostatic repair response
aimed at compensating for an abnormal epidermal barrier.
It is of two types:

7. ICHTHYOSIS VULGARIS(AD)
• least severe
• most common
• autosomal dominant trait with variable penetrance.

8. Pathogenesis
• Major component
of keratohyaline
granules .
• F binds to and
condenses the
cytoskeleton >
contributes to cell
compaction.
Degraded to
hygroscopic amino
acids
Histidine rich NMF
Skin hydration and water retention
Impaired cornification Increased trans epidermal
water loss
Increase penetration to allergens and
irritants
FILAGGRIN
FLG mutation

9. Clinical Features
• Manifests usually after 3 months of life.
• M=F
• Scales :
– white or grey, small, flaky or branny, and semi-adherent
with turned-up edges .
– most pronounced on the extensor surfaces of the arms and
lower legs.
– Smaller than RXLI
– Affected by season and humidity
• The trunk, esp. the abdominal wall, is often mildly affected and
the diaper area is spared.
• Facial scaling, generally forehead and perioral, mild dandruff and
involvement of the pinnae are seen in some patients.

10. • Flexures- spared.
• The palms and soles are usually free of scale
• palmoplantar hyperlinearity – in almost all pts
• Atopic Diathesis (35-50 %)
• Atopic eczema
• Allergic rhinitis
• Keratosis pilaris
• Dennis Morgan folds
• Hypohydrosis
Palmar hyperlinearity
ICHTHYOSIS VULGARIS:KERATOSIS PILARIS

11. COURSE & PROGNOSIS
• During dry cold weather, the skin of these patients becomes more dry and
scaly but improves in warm and sunny weather because of ambient humidity.
• The condition improves as age advances.

12. INVESTIGATIONS
HISTOPATHOLOGY
• Mild hyperkeratosis
• A diminished or absent granular layer in
the epidermis.
• The dermis is normal.
IMMUNOHISTOCHEMICAL STUDIES
• absent or markedly reduced filaggrin signal
ULTRASTRUCTURE STUDIES
• scarce and crumbly keratohyalin granules
• US defects correlate very well with no: of
FLG mutation severity

13. X-LINKED RECESSIVE ICHTHYOSIS
• Primarily affects males
– Thus h/o affected grandfather and uncles is s/o RXLI.
• Transmitted as an X-linked recessive trait
• INCIDENCE
1 in 2000-6000 males

14. Etiopathogenesis
• The gene encoding steroid sulfatase (STS) is located in the distal portion of the short arm of the X chromosome
(Xp22.32).
• A lack of steroid sulfatase has been noted in the leukocytes, keratinocytes and fibroblasts of these patients.
• Responsible for hydrolysis of cholesterol sulfate to cholesterol in the epidermis. Accumulation of cholesterol
sulfate in the epidermis leads to barrier instability.
• The increased level of cholesterol sulfate also delays the corneodesmosome degradation, leading to corneocyte
retention, due to inhibition of proteases like kallikrein 5 and 7.
• Prototype of retention hyperkeratosis
• Increased Ca++ in the stratum corneum interstices in XLI may contribute to corneocyte retention, by increasing
corneodesmosome and interlamellar cohesion

15. Clinical features
• Onset :
– Directly after birth
• Very fine scaling or peeling of the skin
• Goes unnoticed and resolves on own
– At 2-6 months of age :
• Large thick polygonal adherent brown HK over trunk, extremities and neck
• In 30 % - light grey scales : misdiagnosed as IV
• Spares folds, palms and soles
• The posterior and lateral neck ( Dirty neck disease – dark HK), pre-auricular facial
skin are commonly affected with semi adherent, grey scale.

16. Dark brown hyperkeratotic polygonal scales
Preauricular Scaling

17. Other associations
• Cryptorchidism (testicular non-
descent)
• Testicular cancer.
• Deep stromal Corneal opacity.
• Autism (25%)
• X linked chondrodysplasia punctata.
• Attention deficit hyperactivity
syndrome (ADHD) (40%)
PERINATAL
COMPLICATION
• Placental sulphatase deficiency
leads to insufficient cervical
dilatation > prolonged delivery >
forceps / LSCS.

18. Histopathology
• Orthohyperkeratosis
• The granular layer is normal or even
thickened.
• Marked follicular plugging in 30 %. No
obvious KP.
• A perivascular infiltrate is seen in the
upper dermis.
• Electron microscopy :
– Persistent corneodesmosomes
Other Tests
• Serum lipoprotein electrophoresis (to
detect accumulation of cholesterol
sulfate)
• Biochemical measurement of STS activity
in fibroblasts or plasma

19. Icthyosis Vulgaris
• Autosomal Dominant
• Filaggrin mutation
• Onset at 3 months of age
• Palmar hyperlinearity in most cases
• No sex predeliction
• Not a/w perinatal complications
• Fine grey scales
• Flexures are spared
• HPE : orthoHK with absent or reduced
granular layer
• Ultra structure : KF; normal, KH
granules are reduced
(scanty/fragmented)
Recessive X linked Icthyosis
• X linked Recessive
• Steroid sulphatase mutation
• Onset at birth
• Palms and soles spared
• Males >> females
• a/w perinatal complications
• Thick coarse brown plate like scales
• Scaling encroaches flexures, dirty neck
• HPE : orthoHK with hypergranulosus
• Ultrastructure : KH gr =normal.
Desmosomes are more persistent.
Corneal melanosomes : more
prominent

20. Autosomal Recessive Congenital Icthyosis
• Includes all non syndromic autosomal recessive congenital forms of icthyosis
• Without a tendency towards blistering
• Includes:
– HI – Harlequin icthyosis
– BSI- bathing suit icthyosis
– LI – Lamellar icthyosis
– CIE – Congenital Ichthyosiform Erythroderma
– SICI- self improving congenital icthyosis
– Transient manifestations like collodion baby

21. LAMELLAR ICHTHYOSIS
• autosomal recessive congenital ichthyoses.
Incidence
• ≤ 1:300,000

22. Etiopathogenesis
• In one subset there is mutation in the gene encoding transglutaminase 1(TGM1), an enzyme that
catalyzes the calcium dept. cross-linking of proteins during the formation of CLE.
• Biallelic missense mutation in the gene encoding ATP-binding cassette subfamily A member 12
(ABCA 12)— found in lamellar bodies, resp. for energy dept lipid transport across membranes.
– More deleterious mutation of ABCA 12 is a/w HI.
• mutation in the gene encoding arachidonate lipoxygenase, controlling hydroperoxidase isomerase.
• Mutation in CYP4F22, encodes cyt P450 enzyme inv in W-hydroxylation of ultra long chain FA to
acylceramides ( imp for barrier function)

23. Clinical features
• Severe disorder that is
apparent at birth and persists
throughout life
• At birth, most affected infants
present as collodion babies,
and after shedding the
membrane, show generalised
large scales (plate like scales in
bark like pattern ) with a less
intense erythema than infants
with NBIE.

24. • Scaling occurs within the first month of life.
• The scale - typically large, quadrilateral, dark brown or grey and firmly
adherent at centre and free at edges
• Separated by superficial or deep fissures.
• Usually involves the entire skin but Flexures are more severely affected
(unlike IV and XLRI ) resulting in flexion contractures and digital
sclerodactyly.

25. • Nail abnormalities
- dystrophy
- nail fold inflammation
- subungual hyperkeratosis
-longitudinal or transverse stippling
• Scarring alopecia due to traction, esp. at scalp periphery (alopecia icthyotica).
• Hair shafts are normal but encased by thickened SC
• Facial skin dry, shiny, taut ( ectropion, Eclabion, hypoplasia of nasal or auricular
cartilage)
• Severe ectropion can be a/w:
– Madarosis
– Conjunctivitis
– Incomplete lid closure
– keratitis
• Palms and soles – always affected

26. • Severe LI does not improve with age.
• Psychological problems resulting from the cosmetic effects,
discomfort and limited mobility can lead to isolation, depression
and poor school performance.
• Intraepidermal constriction of sweat ducts predisposes to heat
intolerance and heat shock.
• Scale accumulation in EAC – occlusion, recurrent bact. infections

29. Histopathology
• Compact ortho-hyperkeratosis with
variable mild focal parakeratosis.
• The granular layer appears normal or
increased, the lower epidermis is
normal, and overall epidermal
thickness is slightly increased.
• There may be mild papillomatosis,
extension and blunting of rete
ridges, and dilatation of dermal
capillaries reminiscent of psoriasis.

30. Other Diagnostic Tests
• Measuring TG1 activity in cultured Kc.
• Skin biopsy specimens immunostaining with anti-TG1 ab,
• Genetic testing to detect pathogenic mutations in TGM1, ABCA12,
CYP4F22, ALOX12B, ALOXE3, NIPAL4 (ICHTHYIN), SDR9C7, and LIPN
is commercially available, including multigene panels
• Molecular prenatal diagnosis can be performed in families with
known mutations from CVS or amniocentesis material obtained at
an early gestational age, this has largely replaced light and electron
microscopic examination of fetal skin

31. Differential Diagnosis
• Other icthyoses presenting with collodian membrane :
– CIE (marked erythema and small white scales)
– SICI ( self improving congenital ichthyosis
• Later in life large dark scales, ectropion and no erythroderma
readily separate it from other icthyoses.

32. NON-BULLOUS ICHTHYOSIFORM ERYTHRODERMA
• A rare autosomal recessively transmitted ichthyosis.
• also known as
– erythrodermic lamellar ichthyosis
– CIE – congenital icthyosiform erythroderma
• mutation in – ALOX E3, ALOX 12B, TGM-1, NIPAL4, ABCA12B.
• Autosomal dominant inheritance has been described in some
families.

33. Clinical features
• 90% of cases, presents at birth with a collodion baby
appearance.
• After shedding of the collodion membrane, erythroderma
becomes evident and it persists.
• The scales are thin, superficial, white or grey and semi
adherent, powdery consistency. They may be lamellar on the
legs and feathery on the face and trunk.

34. palms and soles – diffuse, fissuring keratoderma.
Pityriasis amiantacea on the scalp,
ectropion and the resultant exposure keratitis are not
uncommon.
Nails – dystrophic
Hypohidrosis can occur due to sweat duct obstruction by the
hyperkeratotic horny layer.
In most cases the skin lesions deteriorate during summer

36. Histopathology
• hyperkeratosis and variable mild parakeratosis and acanthosis.
• PAS staining of frozen sections show positivity in cell membranes of the horny
layer, granular layer and in the basement membrane; this is absent in normal
skin and in other ichthyoses.

37. COLLODION BABY
• This is a descriptive term used for a transient appearance of neonates born with some
form of congenital ichthyosis.
• The baby is born encased in a shiny, taut membrane
• NBIE is the commonest condition (60%–80%) resulting in collodion baby, followed by
lamellar ichthyosis.
• In addition to the classical AR forms, the rare AD forms of these two disorders may also
result in this disorder.
• Occasionally, some ichthyosiform syndromes like,
– Sjögren–Larsson syndrome,
– Conradi–Hunermann syndrome
– Trichothiodystrophy
may also present with a collodion membrane at birth.

38. Clinical features
• At birth, the typical collodion baby presents a striking and
characteristic clinical picture with a generalized glistening, taut,
yellowish film stretched over the skin.
• It resembles a Clingfilm wrap or sausage skin, although it may
variously be described as ‘plastic skin’, ‘parchment-like’ or ‘as if
dipped in hot wax’.
• Tethering of body orifices – ectropion and eclabium, effacement of
Normal skin markings.
• Sausage-shaped swelling of digits may result from acral extension of
the membrane and, rarely, constricting bands encircle the limbs or
digits.
• General examination is usually normal and movement is minimally
restricted.

39. • It is shed completely in the next few weeks and gradually the clinical features of specific
forms of ichthyosis become evident.
• In some patients(10%–20%), the condition is transient and the child has normal skin
subsequently, termed as ‘self-healing collodion baby’ (SHCB)

40. HARLEQUIN ICHTHYOSIS
Harlequin ichthyosis is rarest & most severe form of ichthyosis.
The first report is from diary of Oliver Hart of Charleston, South Carolina who described these
features in 1750.
iopathogenesis
Mutation in ABCA12 gene in chromosome 2 underlie the severe congenital ichthyosis. ABCA 12
gene play a critical role in the formation of lamellar granules and the discharge of lipids into
intercellular spaces and it’s mutation causes defective lipid barrier in the stratum corneum.
cidence
Very rare, 1 in 2 million.

41. Clinical features
• Baby is usually still born if not
preterm.
• Body is encased in a rigid, taut,
yellow-brown, adherent thick skin,
a hyperkeratotic ‘coat of armour’,
covering the whole body surface.
• Deep fissures occur prenatally over
the scalp and soon after birth, the
inflexible ‘cast’ splits at sites of
stress, producing further red fissures
and a skin pattern resembling a
harlequin’s costume.

42. • The head may appear microcephalic, and facial features are distorted
because of severe ectropion, conjunctival oedema, which obscures the
eyes, and eclabium.
• The scalp feels boggy, and the nose and external ears are tethered and
appear rudimentary.
• Oedematous hands and feet may either be encased in hard mitten-like
casts, or covered with a mucoid membrane, but the digits are well
formed underneath.
• Additional congenital defects have been found in some cases

43. • Movement is restricted, and respiratory insufficiency results
from limited chest expansion and sometimes coexistent
skeletal deformity.
• Absence of effective sucking causes feeding difficulties which
may lead to hypoglycaemia, dehydration and renal failure.
• Temperature instability and infection commonly supervene,
and may lead to rapid demise.

44. Histopathology
• massive hyperkeratosis
• normal granular cell layer and
• EM – numerous abnormal
lamellar bodies in stratum
granulosum
- accumulation of
extruded irregular lamellar
bodies as vesicular structure in
epidermal cornified cells.

45. After 6 months of retinoid
therapy
After 6 weeks of
retinoid therapy

46. BULLOUS ICHTYOSIFORM ERYTHRODERMA
Epidermolytic Hyperkeratosis (EHK), also known as bullous ichthyosiform
erythroderma, is a rare type of ichthyosis associated with blister
formation.
Etiopathogenesis
• EHK is caused by mutations in the epidermal keratin 1 or keratin 10
gene

47. Clinical features
• At birth – flaccid bullae with erosions.
• In 1 month – blisters resolve and hyperkeratosis develops.
• But skin fragility remains.
• So during fever, skin infection, exposure to high ambient temperature, trauma etc –
bouts of blistering can occurs.
• Periodic shedding of the scales (moulting) may occur.
• Rippled keratotic ridges in flexors.

48. • Ectropion is usually not present.
• Palms and soles
– spared (KRT 10 mutation)
– severely affected in KRT 1 mutation with significantly impaired walking.
• The palms and soles may show increased skin markings or diffuse hyperkeratosis.
• The teeth, nails and hair are normal.
• Skin colonization by staphylococci, and possibly fungi produces a distinctive body odour.
• EHK has been reported in association with
– mental retardation
– ventricular septal defect
– breast hypoplasia
– congenital clubfoot deformity.

49. Neonatal Presentation of Epidermolytic Ichthyosis

50. Histopathology
• Marked hyperkeratosis and
acanthosis.
• Granular and upper spinous layer cells
contain multiple perinuclear vacuoles
and large clumps of keratohyaline
granules.
• Intraepidermal splits are present at the
sites of bullae.
• Hyperkeratosis results from increased
epidermal cell turnover and the bullae
result from epidermal dissolution

51. ERYTHROKERATODERMA VARIABILIS
• AD
• Affects GJB3 encoding connexin 31
• Onset : infancy
• Two types of lesions
o Well demarcated, bizarre shaped, ery, HK plaques
on extensors/buttocks
o Transient ery polycyclic or comma shaped macular
lesions occurring at any site. (Migrating polycyclic
lesions a/w HK )
• Aka : Mendez da costa syndrome

52. ICHTHYOSIS HYSTRIX
⮚AD disorder characterized by spiny hyperkeratotic
scale similar to that of BIE but without blistering
⮚ D/t abnormalities in expression of keratin and
abnormal keratin associated proteins
Clinical feature:-
⮚at birth- generalized scaly erythema,
blistering is absent,
⮚ hystrix (porcupine spine) scaling-muddy brown
spiny scales over ext. of limbs, flexures, &
trunk
⮚ palmoplantar keratoderma
⮚nail dystrophy

53. Histology:-
⮚Orthokeratotic hyperkeratosis
⮚Hypergranulosis
⮚Acanthosis
⮚Church spire like papillomatosis

54. TREATMENT OF ICHTHYOSIS

55. Topical Therapy
• First line treatment
• Effect :
– Reduce scales , reduce pruritis and improve general skin appearance.
• Not very effective for scalp and palmoplantar skin
1. Emollients : hydration, lubrication and occlusion
• Recommended for all ichthyoses
• At least twice a day
• Urea containing ones are not preferred for inflamed skin, flexures or
erosions. Can lead to ACD due to increased skin permeability
• Large amount of occlusive pure ointments can impair heat tolerance,
promote maceration and infections.

56. • Keratolytics
– Superior to emollients in removing scales
– Mc agent : urea
– S/E: itching, burning and irritation
– Sites not recommended : face, flexures and areas of fissuring
– To be avoided in newborns and early infants
– SA is C/I in <2 yrs of age and limited to OD application in older
children
– Urea >10 % not before age of 1, except on palms and soles

57. • Topical Retinoids
– Adapalene for EI
– Tazarotene for ectropion
• Other Topical Agents
– Calcipotriol : weekly dose of 100g
– NAC
• Targeted Topical Therapy
– CHILD syn : cholesterol plus simvastatin
• Two major mechanisms : deficiency of cholesterol and toxic accumulation of
aberrant steroid precursors.

59. • Bathing :
– Atleast once a day
– Soak skin for 20-30 min > use silk glove/ sponge to rub the skin, for mechanical scale and
residual ointment removal > drying with towel f/b immediate oint application while the skin is
still wet.
– Use of bath additives such as baking powder ( sodium bicarbonate ) to increase the pH. Two
handfuls increase pH from 5.5 to 7.9
• For ARCI
• Mild alkalinasation of the skin raises the pH to an optimum for serine protease activity such
as KLK5 and KLK7. Reqd. for normal desquamation for dissolution of corneodesmosomes.
• Other popular bath additives : wheat corn, rice starch or bran eg in Netherton syndrome
– Antiseptics in bathing water for KPI to overcome the bad odour due to recurrent infections.
• 2-3 times a week
• Chlorhexidine (5/1000), potassium permanganate (1/10000)
• Iodine based antiseptics not preferred – risk of thyroid dysfunction
• To be rinsed to prevent irritation
– Steam bath is also a good option .

60. • Scalp treatment
– Layer of keratolytic or emollient for a few hours or overnight
– Plastic occlusion may enhance efficacy
– Remove scales gently with comb post shampooing
– Hair steamer can be used to remove adherent scales
• PPK treatment
– SA upto 25 %
– Urea upto 40 %
– Protection of fissuring and surrounding areas with petroleum jelly
– In milder forms : topical tazarotene

61. Systemic Therapy
• Oral Retinoids
– Anti keratolytic effect
– Isotretinoin, Alitretinoin, etretinate and acitretin
• Ciclosporin

62. • Acitretin
– DOC, only one approved by European Medical Agency (EMA)
– Improves scaling, hyperkeratosis, hypohydrosis, hair regrowth, ectropion,
eclabion, hearing
– Esp relevant for thick scales of LI, HI, severe RXLI
– In EI, better in case of KRT10>KRT1 (may get deteriorated)
– Dosage : 0.5-1.0 mg/kg/day, max dose for EI by EMA – 75mg
– Treat with caution in case of erythroderma (EI/NS), r/o blistering and
irritation.
– After achieving desired effects taper dosage to lowest effective dose.
– Effects persist only for a short time post discontinuation.

63. Specific Situation of Children
• No minimum age for the use of retinoids
• Since acitretin is light sensitive, capsules should be opened
away from daylight or added to breast milk in a bottle
protected by an aluminium foil.
• Reserved for those with severe phenotype and functional
impairment.

64. • Alitretinoin
– More rapid clearance than acitretin
– Effective in reducing erythema
– S/E : headache, hypothyroidism, benign intracranial hypertension
• Isotretinoin
– Less safer than acitretin
– S/E : ICH, myalgia, muscle stiffness and tenderness
– Main concern : skeletal toxicity
– Exacerbates corneal neovascularisation in KID syndrome.
• In case of female patients considering a future pregnancy or in case of H/S
to aromatic retinoids, alitretinoin or isotretinoin should be preferred.

65. PSYCHO SOCIAL MANAGEMENT/GENETIC
COUNSELLING
• Factors influencing QOL : cutaneous pain >scaling > gender (F)
• Pts economic resources get constrained by ichthyosis
• Difficult situation for parents as it’s a rare, not so well known disease whose
consequences are often underestimated by the medical profession and the general
public
• Psychosocial mng should be offered ASAP and then throughout life for children and
families
• Imp for child to recognise itself as <me> and to develop its <skin ego>
• Not to make siblings feel abandoned
• Educational interventions (ichthyosis schools) for treatment adherence.
• Role of clinical geneticist to calculate the risk for other family members or the
expected child to be affected or not. Also to answer questions concerning prenatal
testing or preimplantation diagnosis.

75. Management of Collodion Babies
• HI + CB = highly disturbed Epidermal barrier.
• Placed in high humidity incubator with close temp monitoring
– To start with humidity settings in the range of 60-80 % and decrease every 3-4 days in
order to reach normal humidity to allow transfer to open crib. Optimal temperature is 32-
34 C
• Use of bland emollients is enough, 2-4 times a day. The application technique
should avoid contamination (latex-free gloves, single use packets).
• Avoid urea and lactic acid in first few yrs of life
• SA is C/I - may lead to Metb Acidosis
- death within 72 hrs even when used at 3% conc.
• Close monitoring of body temperature, input output, calorie intake, weight gain.
• Nutritional assessment and support through an oro- or nasogastric tube is often
necessary because of poor sucking due to eclabium and increased metabolic
demands.

76. Gene Therapy
• LI : KB105, a replication-incompetent, non-integrating HSV-1
vector expressing human transglutaminase 1 (TGM1)
formulated as a topical gel
• Other Name: HSV1-TGM1

77. • Lamellar Ichthyosis (LI)
• In an effort to correct the disease phenotype, LI patient keratinocytes were
transduced with a retroviral vector engineered to express transglutaminase 1.
Corrected keratinocytes were grafted on to immunodeficient mice, displaying
normal phenotypes.
• Harlequin Ichthyosis (HI)
• Corrective gene transfer was performed on keratinocytes from HI patients using a
cytomegalovirus-based vector in vitro, which restored lamellar granule lipid
secretion
• Sjögren-Larsson Syndrome (SLS)
• Mutations in ALDH3A2 result in ichthyosis as well as mental retardation and
spasticity (which can lead to quadraplegia). Using a recombinant AAV2 vector,
FALDH was transduced into SLS keratinocytes. Corrected keratinocytes appeared
phenotypically normal with normal FALDH expression

78. • LIAROZOL :
– For moderate and severe LI
– Retinoic acid metabolism blocking agent
– Good clinical improvement and tolerated well
• Ketoconazole
– 14 alpha demethylase inhibitor
– Useful in CHILD syndrome

79. ICHTHYOSIFORM DISORDER

80. NETHERTON’S SYNDROME
⮚ It is the AR & commonest ichthyosiform syndrome
⮚ with characterstic skin & hair abnormality & features of atopy
Aetiopathology:-
⮚ Mutations in SPINK-5 gene - encoding LEKTI (lympho-epithelial
Kazal-type related inhibitor).
Clinical features:-
⮚ Skin shows congenital erythroderma and ichthyosis linearis
circumflexa (ILC)- erythematous scaly annular or polycyclic flat
plaque with advancing double edge of peeling scale, migrating
cephalocaudally, and pustular lesions may superimpose.

81. ⮚ HAIR-
⮚ hair shaft defect or trichorrhexis invaginata
⮚ scalp, eyebrow & body hair remains sparse
⮚ slow growing, lustreless and brittle,
⮚ patchy traumatic alopecia occurs in child (improves with
age)
⮚ ATOPIC FEATURES –
⮚ Recurrent urticaria or facial angio-oedema triggered by
certain food like nuts and fish
⮚ NAIL-
⮚ Dystrophy, ranging from thickening to pterygium
.
Trichorrhexis Invaginata

82. • Diagnosis : triad of
– congenital ichthyosis
– Hair shaft anomalies
– Severe atopic diathesis
• D/d :- In infancy-erythrodermic atopic or seborrhoeic eczema, NBIE,
• Histology:-
– parakeratotic Hyperkeratosis,
– reduced or absent granular layer,
– acanthosis
– Eosinophilic material may collect in corneal and granular layer.
– papillomatosis And
– with mixed inflammatory infiltrate
• Acute erythroderma –shows pronounced inflammatory changes with spongiosis,
exocytosis, intraepidermal microabscess & supracorneal split

83. SJÖGREN–LARSSON SYNDROME
• An AR neurocutaneous disorder.
• Mutations in the ALDH3A2 gene located on chromosome 17p11.2.
• This gene encodes fatty aldehyde dehydrogenase (FALDH)
Clinical features
• SLS is characterized by generalized ichthyosis, mental retardation, spastic paralysis
and degenerative retinitis.
• The ichthyosis is generalized with flexural accentuation and involves the palms and
soles.

84. • There is no ectropion and the hair and nails are normal.
• Mental deficiency is severe and is present in almost all cases.
• By the age of 2 to 3 years, the features of spastic paresis
develops.
• Grand mal type of seizures may occur.
• Degenerative changes of the foveal region of the retina and
teeth abnormalities may be observed in some children

85. • Histopathology
– hyperkeratosis and acanthosis with normal thickness of the granular layer.
– The diagnosis is possible by measurement of fatty aldehyde dehydrogenase in
cultured fibroblasts from skin biopsies, and
– by identifying known mutations by allele-specific PCR.
Treatment
– Reduction of total fatty intake (to 30% of total calorie intake) with essential
fatty acid supplements results in improvement in the cutaneous and
neurological features.
– Oral retinoids may relieve scaling and lichenification.
– Ophthalmologic and neurologic consultation.
– Therapeutic approaches to target specific metabolic defects associated with
FALDH deficiency or to correct the genetic defect by gene transfer are under
development.

86. REFSUM’S DISEASE
• It is very rare AR neuro-cutaneous disorder caused by defective fatty acid metabolism
Etiopathogenesis
– D/t mutation in PAHX gene located on ch.10p13
– defective metabolism of phytanic acid→ increased level in serum and lipid rich
tissue→ it replaces other FA and binds to sterols → resulting in lipid vacuoles
accumulation in basal epidermis→ interferes with membrane struct. & function.
Clinical feature
– Ichthyosis in form of mild white scales over the trunk & limbs,
– coincides with neurological manifestations at early adult life like cerebellar ataxia
– Ocular : night blindness, retinitis pigmentosa, cataract
– Ear : SN deafness, tinitus, anosmia,
– Neural : polyneuropathy & foot drop,
– peripheral hypertrophic nerves, cardiac conduction defect.

87. IBIDS SYNDROME /
TRICHOTHIODYSTROPHY/TAY SYNDROME
• DEFINITION :- it is a AR disorder characterized by association of
– Ichthyosis
– Britle hair
– Intellectual impairment
– Decreased fertility
– Short stature
• D/t ↓ level of sulphur & sulphur containing Aminoacids in hair & defective DNA synthesis in UV light
Clinical feature:-
-Newborns may present as collodion baby or CIE
-ranging from fine,translucent scaling to large, dark yellow-brown hyperkeratosis.
-nails – dystrophic may be associated with palmoplantar keratoderma,
-LBW, lack of subcutaneous fat (progeria-like facies),
short stature,and delayed psychomotor development are seen.
-cryptorchidism in males and impaired sexual maturation in females.
-Hair is sparse and under microscope shows trichoschisis (transverse fracturing),
trichorrhexis nodosa (transverse, frayed fractures), and undulating contour of shaft
-under polarization, it has a pattern of alternating bright & dark-banding (tiger-tail)

88. KID SYNDROME
⮚ KID syndrome is a rare AD disorder characterized by Keratitis,
Ichthyosis, and Deafness
Clinical features:-
• Characterised by discrete erythematous plaques with mild, generalized
hyperkeratosis
• plaques –have discrete border, verrucous appearance with crusting
• may be figurate and symmetric on the face,and spiny keratotic papules
on flexures
• Scalp shows scarring alopecia(prominent follicular hyperkeratosis )
• Nails -dystrophic
• Neurosensory hearing defect ,
• Eye - keratitis (corneal opacification)
• Teeth - small.
• ↑susceptibility to bact.fungal & viral infections, and dev. of SCC of skin &
tongue.

89. ⮚ Mutations in GJB2, the gene encoding
connexin. Leading to disruption of intercellular
communication through defect in gap junction,
is resp. in pathogenesis.
⮚ In contrast to many other ichthyotic conditions,
treatment with oral retinoids has been reported
to be of little benefit and possibly exacerbate
the corneal neovascularization.

90. CHILD SYNDROME
• Congenital hemi dysplasia, Ichthyosiform
erythroderma, and Limb defects
• It is a rare X linked dominant disorder found almost
exclusively in females(28:1)
• skin abnormality, distinguished by a sharp midline
demarcation of the ichthyosis,
• frequently on Rt.side with minimal linear /segmental
contralateral involvement.
• Limb defects occur ipsilaterally (range fm digital
hypoplasia – agenesis of limb)
• There may be punctate calcification of cartilage.

91. • Unilateral hypoplasia can involve the central nervous system and cardiovascular,
pulmonary, renal, endocrine and genitourinary systems
• occurs b/c of mutation in NSDHL gene which is responsible for cholesterol
biosynthesis

92. Thank You