Eczema in children

Hugo Van BeverDepartment of Pediatrics

National University Singapore

APAPARI Workshop, Hanoi, May 2008

Eczema in Singapore ChildrenResults 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

Country Inc D Same Inc D Same Inc D Same

Hong Kong * * *

Indonesia * * *

Japan * * ? ? ?

Malaysia * * *

Singapore * * *

S-Korea * * *

Taiwan * * *

Thailand * * *

Australia * * *

Asthma Hay fever Eczema

6/7 year-olds ISAAC6/7 year-olds ISAAC

Asher et al, Lancet 2006Phase 1 vs. phase 3

Prevalence of AD in 6 – 7 yr-old children (ISAAC)H. Williams et al. JACI, 121, 947, April 2008.

Mechanisms of Eczema in Children

1. ALLERGY 2. SKIN BARRIER DYSFUNCTIONS 3. CHRONIC INFECTION 4. AUTO-IMMUNITY (?)

= complex interplay according to pt. and age

Kalliomaki M, Lancet. 2001; 357:1076

Incidence of eczema at 2 years in children given probiotics from birth

50% decrease…

IgE-mediated reactions persist !

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 SE-Asia

more severe

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 common2. more severe (?)

UK

US

US

Is atopic dermatitis, an

allergic disease ?

YES, BUT…

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

1. Chymotrypsin (SCCE)

2. Filaggrin

Two (of the many) new players in eczema…

Stratum corneum, corneodesmosomes and SCEE

Cork et al. JACI, 2006, 118, 3-21

SCCE breakdown of corneodesmosomes

Corneodesmosomes and exogenous Proteases

Cork et al. JACI, 2006, 118, 3-21

DesquamationThinning of the skin

ECZEMA

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

JACI 2007, 120, 1406 – 1412.

FLG polymorphisms R501X

228del4

Complete loss of FLG expression

ICHTHYOSIS VULGARIS

(= FLG null alleles)

J Allergy Clin Immunol, 2008, 121, 940

- To investigate the role of 5 common FLG null mutations in childhood AD

- n = 811 children in UK (non-selected group)

- Prevalence of AD = 24%

- CONCLUSION: FLG mutations are significantly associated with mild-to-moderate atopic eczema in childhood, with a recessive pattern of inheritance.

Phenotype(ECZEMA)

Environment Genes

DEVELOPMENT(EPIGENETICS)

Dynamics of gene expression(methylation processes)

Area of new research…

Impaired skin epidermal barrier

allergen penetration IgE

ALLERGIC MARCH

Eczema severity AsthmaRhinitis

(different type of allergy?)

= 2nd event…

Extrinsic versus intrinsic eczema

IgE

Altered skin barrier

EXT

INT

AD

AD: 2 features

severe

allergy

severity of AD

Skin barrier features

allergy

The environment

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

SKIN BARRIER DYSFUNC

TIONS

ALLERGY

genesgenesenvironment

environment

HYPOTHETIC MODEL OF AD

PHASE 1: Non-allergic inflammation- ichtyosis – pruritus- auto-immunity (?)- other (viruses?)

PHASE 2: Allergic inflammation- food ( through urticaria)- inhalants (type IV immune reaction)

PHASE 3: Infectious inflammation- Staph colonization- Viral colonization

early infancy

early childhood

late childhoodadulthood

HYPOTHETIC MODEL OF AD

PHASE 1: Non-allergic inflammation- ichtyosis – pruritus- auto-immunity (?)

PHASE 2: Allergic inflammation- food ( through urticaria)- inhalants

PHASE 3: Infectious inflammation - Staph colonization

- Viral colonization

early infancy

early childhood

late childhoodadulthood

moisturizing

allergen avoidance

antiseptics > antibiotics

Conclusion…

1. Complex disease different types

2. Not only allergy… there is more

3. More studies on “start” of AD

4. Treatment: according to age