non syndromic and syndromic ichthyosis

1. ICHTHYOSI
PRESENTER: DR ROHINI SONI
MODERATOR: DR PASCHAL DSOUZA

2. ICHTHYOSIS
▸Derived from the Greek word ‘ichthys’, which means fish.
▸Heterogenous group of inherited disorders of epidermal
differentiation featuring excessive scaling.
▸Due to altered cell kinetics of differentiation.
▸Excessive keratin buildup due to a desquamation defect,
leading to retention of abnormally formed scale

3. TYPES OF ICHTHYOSIS
NON‐SYNDR
OMIC
ICHTHYOSIS
SYNDROMI
C
ICHTHYOSI
S
CONGENITAL ACQUIRED
1. MALIGNAN
CIES
2. METABOLIC
DISORDER
S
3. CONNECTI
VE TISSUE
DISORDER
S
4. INFECTION
S
5. DRUGS

4. 2009. J Am Acad Dermatol 2010;63:607–41

5. 2009. J Am Acad Dermatol 2010;63:607–41

6. ICHTHYOSIS VULGARIS
▸Commonest and also the mildest
form
▸Autosomal semidominant
inheritance
▸Due to filaggrin mutations (FLG)
▸Results in impaired epidermal
barrier formation and a marked
reduction of natural moisturizing
factors (NMF) which play a critical
role in hydration of the stratum
corneum

7. ▸Presents few months after birth
to early childhood (3-12 months)
▸Mild itching, Xerosis Fine, white
scales on extensor surfaces
coarser on the lower extremities
▸Flexures spared
▸Hyperlinear palms/soles
▸Improves in summers
▸A/w Atopic diathesis keratosis
pilaris

9. ‣ Laminated
orthohyperkeratosis
‣ Markedly accentuated
granular layer
‣ On electron microscopy
:scarce and crumbly
keratohyalin granules.
HISTOLOGY

10. RECESSIVE X‐LINKED ICHTHYOSIS
▸2nd most common type of
ichthyoses
▸X linked recessive
▸Involves extremities, trunk,
neck; variable
INVOLVEMENT of flexures
▸Sparing of palms/soles

11. Mother (with affected fetus): low/absent estrogen in urine/amniotic fluid → labor fails to progress → children are com

12. ▸Presents around infancy usually before
3 months of age with mild erythroderma
and large translucent scales
▸Evolves into adherent brown “DIRTY”
polygonal scales divided by wide splits
▸Associated with
Comma-shaped corneal opacities
Cryptorchidism
Carcinoma of testis (↑risk)

13. INVESTIGATIONS
▸HISTOLOGY :hyperkeratosis or parakeratosis normal or
slightly thickened granular layer
▸OTHER TESTS: serum lipoprotein electrophoresis (detects
accumulation of cholesterol sulfate)

15. AUTOSOMAL RECESSIVE
CONGENITAL ICHTHYOSIS

16. ▸Harlequin ichthyosis
▸Lamellar ichthyosis (LI)
▸Congenital ichthyosiform erythroderma (CIE)
▸Self‐healing collodion baby (SHCB)
▸Acral self‐healing collodion baby
▸Bathing suit ichthyosis (BSI)

17. HARLEQUIN ICHTHYOSIS
▸Most devastating type of ARCI .
▸Neonates are born with armour‐like
skin (truncal plates with fissuring).
▸Impaired move- ment and the ability
to drink and breath.
▸Bilateral ectropion and eclabium are
present and hyperkeratotic skin may
result in ears lacking retroaural folds.
▸Autoamputation of digits may occur.

18. RETENTION HYPERKERATOSES

19. Only 44% of children may survive. For those who survive, in later life persistent ectropion is a frequent major problem, and
often these patients have problems achieving and maintaining normal body weight despite high‐calorie supple- mentation.

20. FEATURES ON HISTOLOGY
‣ Marked hyperkeratosis
‣ Parakeratoses
‣ Hypogranulosis
Electron microscopy reveals numer-
ous abnormal lamellar bodies in the
stratum granulosum and accumulation
of extruded irregular lamellar bodies as
vesicular structures between the
epidermal cornified cells.

21. LAMELLAR ICHTHYOSIS
▸AR
▸Presents AT BIRTH with collodion
membrane encasing the baby which
desquamates over the first 2-3 weeks
▸Usually thick large platelike dark
(grayish- brown), quadrangular free
at edges and adherent at CENTER
▸Flexural involvement
▸Tends to be largest at extremities
separated by superficial fissuring
arranged in a mosaic pattern
resembling FISH SKIN
Flexural
involvement

22. Transglutaminase‐1 critically
contributes to the the
assembly of the cornified
envelope by catalysing
calcium‐dependent cross‐
linking of proteins, such as
involucrin, loricrin and proline‐
rich proteins and by binding
Ω‐hydroxy ceramides to
proteins such as involucrin,
thus connecting the lipid
envelope with the CE

25. ASSOCIATIONS
▸NAIL ABNORMALITIES
1. dystrophy
2. nail fold inflammation
3. subungual hyperkeratosis
4. longitudinal or transverse stippling
5. grow 2-3 times the normal rate.
‣ Ectropion, eclabium, scarring alopecia, hypohidrosis, contractures heat
intolerance (heat stroke), Involvement of palm and soles: Ranges from
minimal hyper-linearity to severe PPK

26. ▸MASSIVE orthokeratotic
hyperkeratosis
▸Normal or thickened
granular layer
▸Acanthosis with
increased mitoses
▸Perivascular lymphocytic
infiltrate

27. CONGENITAL ICHTHYOSIFORM
ERYTHRODERMA (CIE)
▸Mild erythema and generalized whitish desquamation
▸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 with scarring alopecia, ectropion, nail
dystrophy (similar to LI but milder), heat intolerance,
increased susceptibility to infections

28. 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
▸The membrane is then shed, leaving either
normal skin (lamellar exfoliation of newborn) or,
more often;
▸lamellar ichthyosis
▸Congenital Ichthyosiform Erythroderma
▸Bathing suit ichthyosis
▸X-linked recessive ichthyosis
▸neutral lipid storage disease
▸Gaucher's disease

29. BATHING SUIT ICHTHYOSIS
▸Peculiar type of ARCI
▸children are born as collodion babies later
develop a lamellar type of ichthyosis that spares the
face and the extremities, and follows the distribution
pattern of bathing suits.
▸Due to peculiar missense mutations in TGM1that
render the enzyme TG1 temperature
▸Shift of optimum temperature from 37C to 31C
▸Digital thermography validated a striking correlation
between warmer body areas and the presence of
scaling in patients
▸Aggravtes in summer

30. KERATINOPATHIC
ICHTHYOSES
EPIDERMOLYTIC ICHTHYOSIS
ICHTHYOSIS BULLOSA SIEMENS
ANNULAR EPIDERMOLYTIC ICHTHYOSIS
CONGENITAL RETICULAR ICHTHYOSIFORM
ERYTHRODERMA
ICHTHYOSIS CURTH–MACKLIN

31. EPIDERMOLYTIC ICHTHYOSIS
MUTATION IN
KERATIN 1 &10
Environmental stress,
Trauma,Hyperosmotic
conditions
Keratin aggregates (clumps around
nucleus)
Losing connections with desmosomes and hemidesmosomes
EPIDERMOLYSIS
Bullae formation
due to seperation
of keratinocyte

32. ▸AD
▸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.
▸Involvement of warmer areas. Thus
flexural predominance.
▸The older child and adult patients
usually present with marked keratotic
lichenification meaning rippled
keratotic ridges

33. ▸On the knees and the lower legs, patients
sometimes present with spiny hyperkeratosis
▸KRT10: mutations, the palms and soles are
usually spared
▸KRT1: mutations usually have severe
involvement of the palms and soles which can
significantly impair walking
‣ Leads to
A. recurrent infection
B. sepsis
C. dehydration & electrolyte imbalances due to
compromised skin barrier
D. failure to thrive

34. HISTOLOGY
▸ Massive orthokeratotic
hyperkeratosis
▸ Hypergranulosis
▸ Granular and vacuolar degeneration
of spinous and granular cell layers
(EPIDERMOLYSIS)

35. ICHTHYOSIS BULLOSA SIEMENS
▸A variant of BCIE
▸AD
▸keratin 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 feet spares palms/soles
▸Keratosis is limited to the region around the navel and on the dorsal
aspects of the hands and feet or the arm and the axillary region

36. ▸ 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

37. ANNULAR EPIDERMOLYTIC ICHTHYOSIS
▸Mild variant of EI
▸Shares a similar onset at birth, but later greatly improves
▸can feature bouts of disease activity associated with the
development of numerous annular and polycyclic
hyperkeratotic lesions especially on the trunk and
extremities.
▸On histology : epidermoysis

38. CONGENITAL RETICULAR ICHTHYOSIFORM ERYTHRODERMA
▸AD
▸KRT10 mutations
▸Initially display generalized
erythema and scaling with
subsequent localized
spontaneous healing which
manifest with small pale white
spots.
▸Ichthyosis en confettis

39. ICHTHYOSIS HYSTRIX CURTH–MACKLIN

40. ▸AD
▸KRT 1 mutation
▸Extensive spiny hyperkeratosis (‘hystrix’‐like) covering the
entire body and involving the palms and soles
▸Porcupine man

41. OTHERS: ERYTHROKERATODERMA VARIABILIS
‣ Migrating polycyclic erythematous lesions
accompanied by hyperkeratosis
‣ Mutation in GJB3 gene encoding for connexins
‣ Fixed well‐demarcated keratotic and erythematous
plaques, often bizarrely shaped, which show a
predilection for extensor surfaces, lateral trunk and
buttocks and extend and regress in area thickness
and degree of erythema
‣ Transient erythematous, polycyclic or
comma‐shaped macular lesions occurring at any site

42. SYNDROMIC
ICHTHYOSIS

43. CONRADI-HU ̈NERMANN-HAPPLE SYNDROME (CDPX2)
▸XD,only in females
▸At birth
▸Ichthyosiform erythroderma may be severe
▸CIE clears up after few months, lifelong
hyperkeratosis distributed in linear, blotchy
pattern, follicular atrophoderma
▸Discrete IV-like scaling
▸Patchy areas of cicatricial alopecia
▸Stippled calcifications of enchondral bone
formation, chondrodysplasia punctata, short
stature, asymmetric shortening of legs,
kyphoscoliosis, dysplasia of hip joints, sectorial
cataracts, asymmetric facial appearance as
result of unilateral hypoplasia, flattened nose
bridge

44. IFAP SYNDROME
▸ XR
▸ At birth
▸ Mild collodion skin, congenital atrichia
▸ Development of generalized follicular keratosis that
can be severe or improves during first year of life
▸ Whitish scales with mild erythema
▸ SCALP :Follicular keratoses, atrichia, occasionally
some sparse and thin hair may be present
▸ Severe photophobia, retarded psychomotor
development: (cerebral atrophy, temporal lobe
malformation, hypoplasia of corpus callosum), failure
to thrive, atopic manifestations, inguinal hernia,
aganglionic megacolon, testicular or renal anomalies

45. Photographs of patients with typical features of IFAP syndrome. Note: A) the atrichia, the photophobia,
the cheilitis around the mouth, B) the ichthyotic scaling and erythematous and yellowish thick scaly
hyperkeratotic plaques over the scalp, and C) the psoriasiform plaques over the buttocks.

46. Autosomal ichthyosis syndromes with prominent hair abnormalities
Netherton Syndrome
Ichthyosis Hypotrichosis Syndrome
Ichthyosis Hypotrichosis Sclerosing Cholangitis

47. NETHERTON SYNDROME
SPINK 5 MUTATION
LETKI Deficiency
(Serine protease inhibitor
controls trypsin and
chymotrypsin like enzyme
activity)
over‐desquamation of
corneocytes and
degradation of
desmosomal proteins
PAR 2 induction of PAR‐2
(protease‐activated receptor
2) related pro‐inflammatory
responses

48. ▸AR
▸At birth (or later)
▸CIE in most of cases, collodion
membrane rare, ILC, atopic
dermatitis-like lesions
▸Fine or large, double-edged scales
(ILC)
▸Short, fragile, and brittle hair;
alopecia (Trichorrhexis invaginata)
▸Failure to thrive, severe atopic
diathesis, increased IgE level and
eosinophilia, frequent skin
infections

49. IHS & IHSC
▸AR
▸At birth
▸LI, severe hypotrichosis, absent eyebrows and eyelashes Over time, scalp hair
growth and appearance/color may improve
▸Brown colored coarse scales
▸Hypotrichosis in youth, sparse, unruly hair in adolescence, recessing frontal
hairline in adults
▸Hair microscopy may reveal dysplastic hair, pili torti
▸IHSC : coarse thick hair, frontotemporal scarring alopecia; hypotrichosis,
curly/woolly hair with sclerosing cholangitis or congenital paucity of bile ductsy

50. NEURO ICHTHYOTIC SYNDROMES
REFSUM SYNDROME
SLS
MEDNIK
CEDNIK
GAUCHERS

51. REFSUM SYNDROME
▸AR
▸RD was found to be caused by inactivating mutations in
PHYH encoding a human phytanoyl‐ CoA hydroxylase which
is responsible for α oxidation of phytanic
▸Presents in late childhood.
▸Deteriorating vision due to retinitis pigmentosa and hearing,
ataxia, neuropathy and usually mild ichthyosis.

55. APPROACH TO A
PATIENT WITH
ICHTHYOSIS

58. ▸Prenatal diagnosis of congenital ichthyosis is possible
specially in Harlequin ichthyosis.
▸Amniocentesis , CVS, 3D/2D USG
▸ABCA12 gene analysis
▸USG shows abnormal protrusion on eye (ectropion), fixed
open mouth and nasal hypoplasia

59. GENERAL CARE
▸Avoidance of strong drying soaps & use creamy soaps
▸Avoidance of unnecessary exposure to cold or hot climates
potential for heat intolerance and heat stroke
▸Frequent showering (w/ immediate application of emollients)
▸Manual debridement of the collodion membrane is not
recommended.
▸X-linked Ichthyosis: consultation with ophthalmologist (for
corneal opacity) and surgeon (for cryptorchidism) is needed

60. LOCAL CARE
▸Emollients: 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
▸Humectants: (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.
▸Keratolytics: Salicylic acid and lactic acid; (salicylic acid products
are best reserved for localized resistant thicker areas)

61. ▸Topical retinoids: (retinoic acids, tazarotene)
▸Calcipotriol
▸Topical Antibiotics: applied to fissures
▸Antiseptics: can be used topically to control odor (as well as
antimicrobials)

62. SYSTEMIC
▸Systemic 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
▸Oral antibiotics: for infections

63. TREATMENT OF ASSOCIATED
SYMPTOMS
▸ECTROPION: Surgical correction
▸EARS: cleaning of external ear cannal every 4 weeks esp in
BSI
▸HYPOHYDROSIS: Oral retinoids
▸MUSCULOSKELETAL PROBLEMS Physiotherapy for
flexural contractures
▸VITAMIN D SUPPLEMENTS esp in lamellar and CIE

64. GENE THERAPY
▸In the case of dominant negative gene
mutations, such as in EHK, it is possible
to silence a mutated keratin allele by
applying RNAi technology.
▸It is hoped that some encouraging in
vitro results will soon lead to clinical
trials.
▸In the case of recessive disorders where
an enzyme or transporter protein is
missing, the principle of ex vivo gene
transfer using cultured keratinocytes that
are re-transplanted to the patient.

65. THANK YOU