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Eczema in children

Eczema in children. Hugo Van Bever Department of Pediatrics National University Singapore. APAPARI Workshop, Hanoi, May 2008. 1 year period prevalence of 20.8% from a questionnaire cum clinical examination survey in schoolchildren (Tay YK et al Br J Dermatol 2002).

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Eczema in children

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  1. Eczema in children Hugo Van Bever Department of Pediatrics National University Singapore APAPARI Workshop, Hanoi, May 2008

  2. 1 year period prevalence of 20.8% from a questionnaire cum clinical examination survey in schoolchildren (Tay YK et al Br J Dermatol 2002) Eczema in Singapore ChildrenResults of ISAAC Questionnaire Survey Wang XS et al. Arch Dis Child. 2004, Tan TN et al., Pediatr Allergy Immunol. 2005, Asian Pac J Allergy Immunol. 2006

  3. 6/7 year-olds ISAAC Asthma Hay fever Eczema Phase 1 vs. phase 3 Asher et al, Lancet 2006

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

  5. Mechanisms of Eczema in Children = complex interplay according to pt. and age 1. ALLERGY 2. SKIN BARRIER DYSFUNCTIONS 3. CHRONIC INFECTION 4. AUTO-IMMUNITY (?)

  6. Incidence of eczema at 2 years in children given probiotics from birth IgE-mediated reactions persist ! 50% decrease… Kalliomaki M, Lancet. 2001; 357:1076

  7. AD and BMT • 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.

  8. Atopic dermatitis 1. SKIN DISORDER 2. ALLERGIC DISEASE 3. Combination ?

  9. Eczema in SE-Asia more severe

  10. The Asian Skin UK US US AD in Asians… 1. more common 2. more severe (?) • 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. • 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. • 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.

  11. Is atopic dermatitis, an allergic disease ? YES, BUT…

  12. Eczema SKIN BARRIER DYSFUNCTIONS

  13. 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 …”

  14. 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

  15. Two (of the many) new players in eczema… 1. Chymotrypsin (SCCE) 2. Filaggrin

  16. Stratum corneum, corneodesmosomes and SCEE SCCE  breakdown of corneodesmosomes Cork et al. JACI, 2006, 118, 3-21

  17. Corneodesmosomes and exogenous Proteases Desquamation Thinning of the skin ECZEMA Cork et al. JACI, 2006, 118, 3-21

  18. 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

  19. JACI 2007, 120, 1406 – 1412.

  20. FLG polymorphisms • R501X • 228del4 (= FLG null alleles) Complete loss of FLG expression ICHTHYOSIS VULGARIS

  21. - 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. J Allergy Clin Immunol, 2008, 121, 940

  22. Area of new research… Dynamics of gene expression (methylation processes) DEVELOPMENT (EPIGENETICS) Phenotype (ECZEMA) Genes Environment

  23. Impaired skin epidermal barrier allergen penetration  IgE ALLERGIC MARCH (different type of allergy?) = 2nd event… Eczema severity Asthma Rhinitis

  24. Extrinsic versus intrinsic eczema AD IgE EXT INT Altered skin barrier

  25. AD:  2 features The environment allergy Skin barrier features severe severity of AD allergy

  26. The rising prevalence of atopic eczema and environmental trauma to the skin. Cork et al. Dermat Pract 2002, 10, 22. Increased skin barrier dysfunctions

  27. Pathogenesis of AD environment ALLERGY genes SKIN BARRIER DYSFUNC TIONS genes environment

  28. HYPOTHETIC MODEL OF AD early infancy early childhood late childhood adulthood 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

  29. HYPOTHETIC MODEL OF AD early infancy early childhood late childhood adulthood 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 moisturizing allergen avoidance antiseptics > antibiotics

  30. 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

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