Autosomal recessive congenital ichthyoses: Lamellar ichthyosis

1. LAMELLAR
ICHTHYOSIS
Dr. K. S. Lakshmi Srividya
Final year postgraduate
Dept. of DVL
Kamineni Institute of medical
sciences, Narketpally

2. ICHTHYOSIS
INTRODUCTION:
• The term ichthyosis is derived from the Greek
word “icthys” which means fish and refers to fish
scale like appearance of skin
• Ichthyosis is a disorder of cornification where
there is abnormal differentiation and
desquamation of epidermis resulting in defective
epidermal barrier

3. ICHTHYOSES
INHERITED
NON-
SYNDROMIC
SYNDROMIC
ACQUIRED

4. • Non-syndromic type: the phenotypic expression of
underlying genetic defect is seen only in the skin
1. Ichthyosis vulgaris
2. X-linked ichthyosis
3. Harlequin ichthyosis
4. Lamellar ichthyosis
5. Congenital ichthyosiform erythroderma

5. • Syndromic type: the phenotypic expression of
underlying genetic defects is seen in skin as well as
other organs
1. IFAP syndrome (Ichthyosis follicularis, Alopecia and
Photophobia syndrome)
2. Netherton syndrome
3. Trichothiodystrophy
4. Refsum’s syndrome

6. • Acquired type:
1. Malignancy (Lymphomas, Ca. breast, lung)
2. Autoimmune and inflammatory (SLE,
Dermatomyositis, Sarcoidosis)
3. Nutritional (Malnutrition, malabsorption)
4. Endocrine (Hypothyroidism, Diabetes)
5. Infectious (Leprosy, AIDS)
6. Drugs (Hypolipidemic drugs, allopurinol,
clofazimine, nicotinic acid)
7. Miscellaneous (Renal failure, bone marrow
transplantation)
.

7. LAMELLAR
ICHTHYOSIS (LI)

8. Synonyms :
Ichthyosis Congenital Type 2
Non-erythrodermic Autosomal Recessive Lamellar Ichthyosis
 Lamellar Ichthyosis is one of the most severe forms of
ichthyosis
 Transmitted as an autosomal recessive trait

9.  Rarely autosomal dominant transmission can occur
 The manifestations are usually present at birth and
parental consanguinity is common

10. PATHOGENESIS
 Mutations in keratinocyte transglutaminase 1 (TGase1)
results in defective process of cornification and
desquamation
 Mutation in ABCA12 may cause milder phenotype of
lamellar ichthyosis

11.  Mutations in the CYP4F22 (cytochrome P450 family 4
subfamily F member 22) gene, which encodes a
cytochrome P450 enzyme causes lamellar ichthyosis with
hyper linear palms and absence of collodion membrane
 Mutations in the ALOX12B and ALOXE3 genes, and the
NIPAL 4 gene are associated with mild or intermediate LI

12. CLINICAL FEATURES
 Incidence: 1 case per 300,000 population
 Gender: It affects both genders equally
 The manifestations are usually present at birth and
persists throughout life
 The child is born encased in a collodion membrane
that sheds within 10-14 days
 As the membrane sheds, there is generalized scaling
with erythema

14.  This can lead to increased risk of infection, disturbances of
thermoregulation and hypernatremic dehydration
 With advancing age, ichthyosis becomes generalized more
commonly affecting the flexures
 Maceration of thick scales may cause malodor
 The skin dries up and develops fissures during winter season

15.  Periodic shedding of skin (molting) can occur
 The palms and soles are commonly involved and are
associated with hyperkeratosis, maceration and fissuring
 The facial skin is often dry, red, shiny and taut

17.  The scales are large, thick, quadrilateral, free at the
edges and adherent at the center
 The scales are gray brown in the dark and appear
transparent in the light.
 Erythroderma is usually mild or absent
 The scaling may be plate like or resemble fish skin

20.  Other features include ectropion (outward turning of eyelid),
eclabium (outward turning of lip), and bilateral conjunctivitis
 Ectropion causes abnormal tear flow and inability to close
eyelids leading to dryness of cornea and conjunctiva, thereby
leading to keratitis
 Pseudoscarring alopecia, small deformed ears, inflexible digits
may be present

22.  Nails grow 2-3 times the normal rate and may be
stippled, ridged, thickened or with subungual
hyperkeratosis
 Teeth are normal

24. HISTOPATHOLOGY
 Epidermis: Marked hyperkeratosis, hypergranulosis,
moderate acanthosis with prominent rete ridges
 Dermis: Mild perivascular lymphocytic infiltrate in upper
dermis

25. ELECTRON
MICROSCOPY
 Thin or absent cornified envelope
 Elongated cholesterol clefts, translucent lipid droplets in
corneocytes (stratum corneum)

26. DIFFERENTIAL
DIAGNOSIS
Major variants :-
 Harlequin Ichthyosis
 Congenital ichthyosiform erythroderma
Minor variants :-
 Self healing collodion baby (SHCB)
 Acral SCHB
 Bathing suit ichthyosis

27. HI LI CIE
ONSET At birth At birth At birth
INITIAL
PRESENTATION
Chances of
stillbirth or preterm
delivery,
Armour-like
collodion
membrane, extreme
ectropion,
eclabium,
contractures,
synechiae of
auricles, extremities
are swollen due to
constriction of skin
and covered by
mitten like case
Collodion
membrane,
ectropion
and
eclabium are
present
Collodion
membrane,
ectropion and
eclabium may
be present

28. HI LI CIE
DISEASE COURSE Development
of severe
erythroderma
Mild to
moderate
erythroderma
Mild to severe
erythroderma
DISTRIBUTION Generalized Generalized,
focally
pronounced
scaling
Generalized,
focally
pronounced
scaling
SCALES •Grey to
yellow scales
•Coarse and
large scales
•Brownish or
dark
•Thick, coarse
and large
plate like
scales
•White or
grey
•Fine
powdery
scales

29. HI LI CIE
SCALING Beta
glucosidase
levels-
Normal
Butyrase
levels-
Beta
glucosidase
levels-
Butyrase
levels- Normal
PALMOPLANTAR
INVOLVEMENT
Severe, auto-
amputation
occurs at times
Less severe Less severe
HYPOHIDROSIS Severe Moderate Moderate

30. HI LI CIE
OTHER SKIN
FINDINGS
Prone to
infections
EXTRA
CUTANEOUS
INVOLVEMENT
Contractures,
failure to thrive,
short stature
Short
stature if
severe
Short stature ,
failure to
thrive
RISK OF DEATH Very high High High
OTHER TESTS None In situ monitoring of
TGase1 activity

31. DIAGNOSTIC TESTS
 In situ measurement of Transglutaminase 1 activity
 Genetic testing for mutations in TGM1 and ABCA12 ,
ALOX12B, ALOXE3 ,NIPAL4
 Prenatal diagnosis can be performed in families with
unknown mutations by Chorionic villus sampling or
Amniocentesis

32. MANAGEMENT OF
COLLODION BABY
 Collodion baby is considered a medical emergency and
requires multidisciplinary approach
 These infants have defective epidermal barrier, thereby
causing hypothermia, hypernatraemic dehydration
 They are prone to infections, ectropion, poor sucking,
restricted pulmonary ventilation, digital vascular constriction

33.  Collodion babies should be placed in high humidity
incubator with close monitoring of temperature and
fluid-electrolyte balance
 A bland ointment or water in oil emollients are applied
at least twice daily

34. GENERAL MEASURES
 Patients are advised to take bath atleast once a day
 After soaking the skin for about 20-30 minutes, the
patient is advised to use sponge, microfibre cloth or silk
glove to rub the skin
 Drying with towel and immediate application of ointment
should be done while the skin is still wet

35.  Ointments are to be applied twice daily
 Special attention needs to be given to face where less
fatty creams may be used
 Usage of a portable home humidifier is also efficacious

36.  If malodor is present, bathing in potassium permanganate
solution is preferred
 Secondary infection is treated with appropriate antibiotics
 Soap is best avoided

37. TOPICAL TREATMENT
 Topical treatments consist of topical keratolytics like 2-3%
salicylic acid, 10% urea, retinoic acid
 Topical calcipotriol, topical tazarotene 0.05% gel have been
found to be effective
 Application of tazarotene gel has been recommended for
the prevention and treatment of ectropion

38.  As percutaneous absorption is very high, substances like
urea, lactic acid are avoided in 1st year of life
 Salicylic acid is contraindicated as it causes metabolic
acidosis even in low concentrations

39. SYSTEMIC TREATMENT
 Oral retinoids like acitretin and isotretinoin are given at a
minimal dose of 0.5 mg/kg/ day
 As oral retinoids have to be given for a long duration, their
side effects like teratogenicity, hepatotoxicity, premature
epiphyseal closure are to be considered
 In women of child bearing age, isotretinoin is preferred over
acitretin

40. SPECIAL ASPECTS OF
TREATMENT
 EYE: Severe ectropion has to treated in order to avoid
further complications like corneal perforation
 Regular ophthalmological examination, lubricating eye
drops, antibiotic-steroid combination ointments and surgical
modalities are used to treat ectropion

41.  HAIR: Treatment of scalp requires special washable
preparations
 Patients are advised to apply emollient or oil to the scalp
 HYPOHYDROSIS: Oral retinoids can normalize sweat
gland function and improve the quality of life

42.  MUSCULOSKELETAL SYSTEM: In infants and children,
physiotherapy is useful eg: to treat flexural contractures
 VITAMIN D: Patients with lamellar ichthyosis have
shown deficiency of vitamin D, hence should be
supplemented

43.  ECLABIUM: Surgical repair of eclabium is required to
improve quality of life
 SUPERINFECTIONS: There is higher incidence of
dermatophytosis and secondary bacterial infections often
caused by Staphylococcus aureus, which should be treated
accordingly
 PSYCHOSOCIAL: Children and adolescents require
psychological and social support

44. THANKYOU