Download skin barrier dysfunctions

Eczema in children
Hugo Van Bever
Department of Pediatrics
National University Singapore
APAPARI Workshop, Hanoi, May 2008
Mechanisms of Eczema in Children
1. ALLERGY
2. SKIN BARRIER DYSFUNCTIONS
?
Incidence of eczema at 2 years in children given
probiotics from birth
IgE-mediated reactions persist !
50% decrease…
Kalliomaki M, Lancet. 2001; 357:1076
AD and BMT
1. Complete correction of the Wiskott-Aldrich syndrome by
allergenic bone-marrow transplantation. Parkman et al. NEJM
1978, 298, 921.
2. Transfer of atopy following bone marrow transplantation.
Bellou A, et al. Ann Allergy Asthma Immunol 1997, 78, 513.
Atopic dermatitis
1. SKIN DISORDER
2. ALLERGIC DISEASE
3. Combination ?
Eczema in Singapore Children
Results of ISAAC Questionnaire Survey

1 year period prevalence of 20.8% from a questionnaire cum clinical
examination survey in schoolchildren
(Tay YK et al Br J Dermatol 2002)
Wang XS et al. Arch Dis Child. 2004, Tan TN et al., Pediatr Allergy Immunol. 2005, Asian Pac J Allergy Immunol. 2006
The Asian Skin
1. Ethnic differences in the pattern of skin diseases seen in a
dermatology department – atopic dermatitis is more common among
Asian referrals in Leicestershire. Sladden et al. Clin Exp Dermatol 1991,
16, 348.
2. The effect of lifestyle on wheeze, atopy, and bronchial hyperreactivity
in Asian and white children. Carey et al. Am J Respir Crit Care Med.
1996, 154, 537.
3. Atopic dermatitis in children in the United States, 1997 – 2004: visit
trends, patient and provider characteristics, and prescribing patterns.
Horii et al. Pediatrics 2007, 120, e527.
AD in Asians…
1. more common
2. more severe (?)
Eczema
SKIN BARRIER DYSFUNCTIONS
New perspectives on epidermal barrier dysfunction
in atopic dermatitis: Gene–environment interactions.
Michael J Cork et al. J Allergy Clin Immunol 2006, 118, 3 – 21.
“… on the importance of epidermal barrier dysfunction
in genetically predisposed individuals …”
Skin barrier dysfunction in AD
1. dry skin – increased transepidermal water loss
2. reduced content of ceramides
3. changes in stratum corneum pH level
4. overexpression of chymotryptic enzyme
“ Stratum corneum chymotryptic enzyme (SCCE) “
5. altered keratinocyte cytokine profile
Two (of the many) new players in eczema…
1. Chymotrypsin (SCCE)
2. Filaggrin
Filaggrin gene
- FLG is located within “the epidermal differentiation complex
(EDC) on chromosome 1q21.
- Function: to aggregate keratin filaments  formation of
stratum corneum  maintaining the barrier function of the
skin.
- Associated with ichtyosis, AD, and psoriasis
FLG polymorphisms
 R501X
 228del4
Complete loss of FLG expression
ICHTHYOSIS VULGARIS
(= FLG null alleles)
Area of new research…
Dynamics of gene expression
(methylation processes)
DEVELOPMENT
(EPIGENETICS)
Phenotype
(ECZEMA)
Environment
Genes
Impaired skin epidermal barrier
allergen penetration 
IgE
ALLERGIC MARCH
= 2nd event…
Eczema severity
Asthma
Rhinitis
(different type of allergy?)
Extrinsic versus intrinsic eczema
AD
IgE
EXT
INT
Altered skin barrier
AD:  2 features
The environment
allergy
Skin barrier
features
severe
severity of AD
allergy
The rising prevalence of atopic eczema and
environmental trauma to the skin.
Cork et al. Dermat Pract 2002, 10, 22.
UK data
1960 - 1981
1995 - 2001
Personal use of soap -detergent
76 million £
453 million £
Water for personal washing
11 L /day
51 L/day
Increased skin barrier dysfunctions
Pathogenesis of AD
genes
environment
genes
environment
SKIN
BARRIER
DYSFUNC
TIONS
ALLERGY
ECZEMA
HYPOTHETIC MODEL OF AD
early infancy
PHASE 1: Non-allergic inflammation
- ichtyosis – pruritus
- auto-immunity (?)
early childhood
PHASE 2: Allergic inflammation
- food ( through urticaria)
- inhalants
late childhood
adulthood
PHASE 3: Infectious inflammation
- Staph colonization
- Viral colonization
HYPOTHETIC MODEL OF AD
early infancy
PHASE 1: Non-allergic inflammation
- ichtyosis – pruritus
moisturizing
- auto-immunity (?)
early childhood
PHASE 2: Allergic inflammation
- food ( through urticaria)
allergen avoidance
- inhalants
late childhood
adulthood
PHASE 3: Infectious inflammation
colonization
antiseptics- Staph
> antibiotics
- Viral colonization