Gestione della dermatite atopica
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1 Gestione della dermatite atopica Peroni Diego Clinica Pediatrica di Verona
2 Pathogenesis of atopic eczema Genes Environment Abnormal TH2 immune response to environmental allergens Skin hyperresponsiveness to inflammatory stimuli Permeability barrier disfunction Phenotypic heterogeneity of disease
3
4 Atopic Dermatitis Bieber T, N Engl J Med 2008;358:1483 the typical histologic aspects of acute lesions, indicates a spongiotic area within the epidermis Perivascular infiltrate
5 Gestione della DERMATITE ATOPICA dermatite atopica Role of allergens Epidermal barrier impairment Role of infections
6 Prevalence of IgE-mediated food allergy among Children with atopic dermatitis Eigenmann Pediatrics 1998; 101: E8 % C H I L D R E N % Approximately one third of children with refractory, moderate-severe AD have IgE-mediated clinical reactivity to food proteins
7 AD TRIGGERS Jones Imm All CNA; 2002; 22: 55 food allergens (most common) 77% of (+) SPT to food milk are clinically irrivelant egg peanut soy wheat shellfish fish
8 Gestione della DERMATITE ATOPICA dermatite atopica Role of allergens Epidermal barrier impairment Role of infections
9 The brick wall analogy of the stratum corneum of the epidermal barrier If the iron rods are already weakened, an environmental agent, such as soap, can corrode them much more easily. The brick wall starts falling apart (C) and allows the penetration of allergens (D).
10 Epicutaneous aeroallergen sensitization in atopic dermatitis infants determining the role of epidermal barrier impairment. F Boralevi, Allergy 2008; 63: AD children and 30 controls aged 3 12 mo TEWL SPT, APT, sige x 7 aeroallergens The majority of AD patients (79%) had a TEWL above 15 g/m2/h, while TEWL was less than 15 g/m2/ h in 83% of controls.
11 Epicutaneous aeroallergen sensitization in atopic dermatitis infants determining the role of epidermal barrier impairment. F Boralevi, Allergy 2008; 63: 205 % of patients with positive tests At baseline At follow-up, after 2 yrs
12 Epicutaneous aeroallergen sensitization in atopic dermatitis infants determining the role of epidermal barrier impairment. F Boralevi, Allergy 2008; 63: 205 % of patients with positive tests At baseline At follow-up, after 2 yrs
13 Exposure to Dermatophagoides pteronyssinus and the occurrence of atopic dermatitis at 3 years of age Huang Ped. All. Imm. 2001; 12:11 % C H I L D R E N % p < % > 1 < 1 Der p 1 µg/g dust
14 Household peanut consumption as a risk factor for the development of peanut allergy Fox JACI 2009; 123:417 Peanut allergy among children with food allergy (n= 293) as a function of environmental exposure depending on whether child first ate peanuts by 12 months. g. peanut protein / week g. peanut protein / week
15 Household peanut consumption as a risk factor for the development of peanut allergy the strong relationship between PA (in high-risk children) and household peanut breaks down in the subgroup of children who themselves ate peanuts by 12 months Peanut allergy among children with food allergy (n= 293) as a function of environmental exposure depending on whether child first ate peanuts by 12 months. Fox JACI 2009; 123:417 g. peanut protein / week g. peanut protein / week
16 Household peanut consumption as a risk factor for the development of peanut allergy Peanut allergy among children with food allergy (n= 293) as a function of environmental exposure depending on whether child first ate peanuts by 12 months. Fox JACI 2009; 123:417 High levels of environmental exposure to peanut during infancy appear to promote sensitization, whereas low levels may be protective in atopic children g. peanut protein / week g. peanut protein / week
17 SKIN BARRIER FUNCTION AND ALLERGIC RISK Hudson Nature Genetics 2006; 38: 399 An intact epithelial barrier (a) prevents allergens from reaching antigen presenting cells (APCs) in subepithelial tissues. Damage to this barrier (b) allow allergens to penetrate into the subepidermal layer and interact with APCs, leading to allergic sensitization and, secondarily, to allergic manifestations in the host.
18 FILAGRIN LOSS-OF-FUNCTION MUTATIONS PREDISPOSE TO PHENOTYPES INVOLVED IN THE ATOPIC MARCH OR for non atopic eczema 3.94 p= Marenholz JACI 2006; 118: 866 OR for atopic eczema 3.84 OR ratio for concomitant eczema and allergic rhinitis 4.79 OR ratio for concomitant eczema and asthma 6.21 p= p= p= IN CHILDREN WITH FILAGGRIN LOSS-OF-FUNCTION MUTATION
19 Gestione della DERMATITE ATOPICA dermatite atopica Role of allergens Epidermal barrier impairment Role of infections
20 Severe atopic dermatitis is associated with a high burden of environmental Staphylococcus aureus. Leung, CEA pts aged 1-40 yrs 18 participants had mild AD; 14, moderate AD; 15, severe AD; and 15 had no AD Bed, floor, dust bag evaluation for S.A.
21 Severe atopic dermatitis is associated with a high burden of environmental Staphylococcus aureus. Leung, CEA pts aged 1-40 yrs 18 participants had mild AD; 14, moderate AD; 15, severe AD; and 15 had no AD Bed, floor, dust bag Strong association between home environmental S. aureus burden and severe AD. High environmental S. aureus burden could cause severe disease in susceptible hosts, both inflammatory and infectious.
22 Atopic eczema and indoor climate: results from the children from Lubeck allergy and environment study (KLAUS). Schafer, Allergy 2008; 63:244. Relationship between prevalence of atopic eczema and measured house dust mite allergen exposure levels
23 Atopic eczema and indoor climate: results from the children from Lubeck allergy and environment study (KLAUS). Schafer, Allergy 2008; 63:244. Relationship between prevalence of atopic eczema and measured house dust mite allergen exposure levels an unfavourable indoor climate, especially a high humidity and visible moulds, which is known to be associated with allergic sensitization and respiratory allergy, also correlates with AE. eczema prevalence in households with visible moulds was significantly higher (12.8%) than in households without moulds (7.3%) (OR 1.84)
24 HIGHER PH LEVEL, CORRESPONDING TO THAT ON THE SKIN OF PATIENTS WITH ATOPIC ECZEMA, STIMULATES THE RELEASE OF MALASSENZIA SYMPODIALIS ALLERGENS The opportunistic yeast Malassenzia is a trigger factor in atopic eczema; Salander Allergy 2006;61:1002 Express and release allergens in culture supernatants Around 30-80% of patients with AE have an IgE and/or T-cell reactivity to the yeast; MALASSEZIA MALASSEZIA The ph of the skin surface in patients with AE is higher than that of normal healthy skin. ph = 5.0 ph = 6.1 CULTURED FOR 1-15 DAYS
25 Sensitization to Malassezia in infants and children with atopic dermatitis: prevalence and clinical characteristics. Lange, Allergy 2008: 63: ch. Aged mo. SCORAD IgE to Malassezia We demonstrate a sensitization rate to Malassezia of 17% in infants and children with atopic dermatitis.
26 Vitamin D Regulation of Cathelicidin in the Skin: Toward a Renaissance of Vitamin D in Dermatology? Segaert J Invest Dermatol 2008, 128, 773 1,25-Dihydroxyvitamin D3, the active form of vitamin D, is a major regulator of the expression of the cationic antimicrobial peptide cathelicidin, not only in monocytes but also in epidermal keratinocytes.
27 Gestione della DERMATITE ATOPICA dermatite atopica Role of allergens Epidermal barrier impairment Role of infections Conclusions
28 Early predictors for developing allergic disease and asthma: examining separate steps in the allergic march Almqvist ClinExpAll 2007;37:1296 Chilhood Asthma Prevention Study In (children non-sensitized with a children, family history eczema, of but athma) not wheeze, is Children a predictor who were for non-sensitized at subsequent 18 months and had data development on of sensitization. at 5 years 1 0 In children not sensitized at 18 months OR for sensitization at age Eczema at age 18 months
29 Early predictors for developing allergic disease and asthma: examining separate steps in the allergic march Almqvist ClinExpAll 2007;37:1296 Chilhood Asthma This suggest that Prevention Study early childhood (children with a eczema may promote family history of subsequent allergen athma) sensitization and raises Children the who possibility were that non-sensitized early managment at of 18 eczema months may and reduce had data the prevalence on of sensitization in at 5 years children 1 0 In children not sensitized at 18 months OR for sensitization at age Eczema at age 18 months
30 Prevention of allergic respiratory disease in infants: current aspects and future perspectives Holt Curr Opin Allergy Clin Immunol 2007; 7: the reversibility of severe atopic diseases decreases over time after onset,
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