What 2012 atopic dermatitis

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What 2012 atopic dermatitis

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2012  atopic dermatitisAttilio BonerUniversity ofVerona, Italy
  2. 2. • Differential Diagnosis
  3. 3. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105Psoriasis (Pso) in % children with Pso were correctlychildren may be confused diagnosed by the referring doctor.clinically with atopic 10 –dermatitis (AD)and, indeed, the twoconditions may co-exist. 9.4%170 children with 50 –features of psoriasis oreczema, or both Pso (n=64), AD (n=62)or PD (n=44). 0
  4. 4. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105Psoriasis (Pso) in % children with Pso were correctlychildren may be confused diagnosed by the referring doctor.clinically with atopic 10 –dermatitis (AD)and, indeed, the twoconditions may co-exist. 9.4% Children with Pso relative to AD were170 children with 50 – more likely to have had a history offeatures of psoriasis or scaly scalp and nappy rash in infancy, a family history of psoriasis, current scalpeczema, or both and periauricular rashes, defined, patchy Pso (n=64), AD (n=62) plaque morphology and papulosquamous rashes not typical of adult psoriasisor PD (n=44). on extensor elbows and knees. 0
  5. 5. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105Psoriasis (Pso) in % children with Pso were correctlychildren may be confused diagnosed by the referring doctor.clinically with atopic 10 –dermatitis (AD)and, indeed, the twoconditions may co-exist. 9.4%170 children with 50 – •Children with PD had features of both but presented most often as typical paediatricfeatures of psoriasis or psoriasis combined with flexural eczema.eczema, or both •Both Pso and PD tended to require Pso (n=64), AD (n=62) more potent topical corticosteroidsor PD (n=44). than AD to achieve disease suppression. 0
  6. 6. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105Psoriatic plaque in a child is:1) thinner,2) paler and3) less well defined than in an adult and4) may resemble nummular discoid eczema.
  7. 7. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105 This child with typical guttate psoriasis also demonstrates periauricular rash butdoes not have xerosis and was only mildly itchy.
  8. 8. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105 Severe scalp scale in this baby was associated with afamily history of psoriasis in Typical psoriatic nappy rash. the child’s mother.
  9. 9. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105 Well-defined facial Typical plaques on this baby with a very well genital demarcated extensor psoriasis. plaque on the elbow and a family history of psoriasis.
  10. 10. A comparative study of childhood psoriasis and atopic dermatitis and greater understanding of the overlapping condition, psoriasis-dermatitis. Kapila S, Australas J Dermatol. 2012;53:98-105Papular and papulosquamous rashes were commonly found in children with classic signs of childhood psoriasis on other parts of the body.
  11. 11. Recognizing and managing eczematous Id reactions to molluscum contagiosum virus in children Netchiporouk Pediatrics 2012;129:e1072• Molluscum contagiosum (MC) is a self-limiting cutaneous viral eruption that is very common in children.• MC infection can trigger an eczematous reaction around molluscum papules known as a hypersenitivity or an id reaction.• In addition, a hypersenitivity reaction can occasionally occur at sites distant from the primary molluscum papules.• These eczematous reactions are often asymptomatic or minimally pruritic.• Id reactions represent an immunologically mediated host response to MC virus and a harbinger of regression.
  12. 12. Recognizing and managing eczematous Id reactions to molluscum contagiosum virus in children Netchiporouk Pediatrics 2012;129:e1072Pearly pink papules withcentral umbilicationare visualized on thepatient’s chests.A and B, Selected MCpapules are surroundedby scaly red/browneczematous patchesand plaques (arrows).C, Nonpruritic eczematouspatches and plaques at sitesproximal and distalto MC papules.
  13. 13. Recognizing and managing eczematous Id reactions to molluscum contagiosum virus in children Netchiporouk Pediatrics 2012;129:e1072Pearly pink papules withcentral umbilicationare visualized on the These reactions often do not require treatmentpatient’s chests.A and B, Selected MC other than emollients.papules are surrounded Topical steroids or immunomodulators may suppressby scaly red/browneczematous patches process and potentiate the spread thisand plaques (arrows). of the primary MC infection.C, Nonpruritic eczematouspatches and plaques at sitesproximal and distalto MC papules.
  14. 14. • Prevalence
  15. 15. Prevalence of eczema and food allergy is associated with latitude in Australia Osborne, JACI 2012;129:865Australia has one of the longest north-south borders in theworld, measuring approximately 4500 km from the North of 8 –Queensland to the South of Tasmania:• North region: Queensland (latitude ≅ 10° to 29°S) 7 –• Central region: New South Wales and Australian Capital Territory 6 – (latitude ≅ 29° to 35°S)• South region: Victoria and Tasmania (latitude ≅ 35° to 43°S) 5 – 4 OR for EGG ALLERGY – 3 – 2.87 3.05 2 – p<0.001 1 – 0 1 NORTH CENTRAL SOUTH REGIONS
  16. 16. Prevalence of eczema and food allergy is associated with latitude in Australia Osborne, JACI 2012;129:865Australia has one of the longest north-south borders in theworld, measuring approximately 4500 km from the North of 8 –Queensland to the South of Tasmania:• North region: Queensland (latitude ≅ 10° to 29°S) 7 –• Central region: New South Wales and Australian Capital Territory 6 – (latitude ≅ 29° to 35°S)• South region: Victoria and Tasmania (latitude ≅ 35° to 43°S) 5 – 4 OR for ECZEMA – OR for ECZEMA 3 – 2 – p<0.001 2.58 1 – 1.75 0 1 NORTH CENTRAL SOUTH REGIONS
  17. 17. Prevalence of eczema and food allergy is associated with latitude in Australia Osborne, JACI 2012;129:865Australia has one of the longest north-south borders in theworld, measuring approximately 4500 km from the North of 8 –Queensland to the South of Tasmania:• North region: Queensland (latitude ≅ 10° to 29°S) both 7 – Latitude gradient existed for• Central region: New allergy and Australian Capital Territory food South Wales and eczema 6 – (latitude ≅ 29° to 35°S)• South region: Victoria and Tasmania (latitude ≅ 35° to 43°S) 5 – 4 OR for ECZEMA – OR for ECZEMA 3 – 2 – p<0.001 2.58 1 – 1.75 0 1 NORTH CENTRAL SOUTH REGIONS
  18. 18. • The atopic march
  19. 19. Development and comorbidity of eczema, asthma andrhinitis to age 12 – data from the BAMSE birth cohort. Ballardini, Allergy 2012;67:537 % of children at 12 yrs with 100 – 90 – 80 – 70 – At 1, 2, 4, 8, 12 60 – yrs, parental questionnaires 50 – 40 – 58% on allergy-related diseases. 30 – 2916 children. 20 – 10 – 0 eczema, asthma and/or rhinitis at some time
  20. 20. Development and comorbidity of eczema, asthma andrhinitis to age 12 – data from the BAMSE birth cohort. Ballardini, Allergy 2012;67:537 % of children at 12 yrs with 25 – 90 – 20 – 70 – At 1, 2, 4, 8, 12 15 – yrs, parental 50 – questionnaires 10 – on allergy-related diseases. 30 – 2916 children. 05 – 7.5% 10 – 000 at least 2 allergy-related diseases
  21. 21. Development and comorbidity of eczema, asthma andrhinitis to age 12 – data from the BAMSE birth cohort. Ballardini, Allergy 2012;67:537 Prevalence rates of allergy-related children who… % of diseases up to 12 yrs in the BAMSE birth cohort.
  22. 22. An explorative study of low levels of allergen-specific IgE and clinical allergy symptoms during early childhood Söderström L, Allergy 2011;66:1058 % children with low levels of s-IgE to egg and/or milk at the age of 6 months 80 – Relationship between 74% low levels (0.1–0.7 kUA/l) 70 – of IgE sensitization to 60 – food and inhalant allergens. 50 – Symptoms of 40 – eczema, rhinitis, and 30 – asthma. 20 – Children (268) followed 10 – prospectively from birth 0 to 5 years of age. still sensitized to one or more allergens at age 2 years
  23. 23. An explorative study of low levels of allergen-specific IgE and clinical allergy symptoms during early childhood Söderström L, Allergy 2011;66:1058 % children with low levels of s-IgE to any of the studied allergens at 12 months of age Relationship between 100 – low levels (0.1–0.7 kUA/l) 90 – of IgE sensitization to 84% 80 – food and inhalant allergens. 70 – 60 – Symptoms of 50 – eczema, rhinitis, and 40 – asthma. 30 – 20 – Children (268) followed 10 – prospectively from birth 0 to 5 years of age. still sensitized at age 5
  24. 24. An explorative study of low levels of allergen-specific IgE and clinical allergy symptoms during early childhood Söderström L, Allergy 2011;66:1058 % children with low levels of s-IgE to any of the studied allergens at 12 months of age Relationship between low The low levels levels (0.1–0.7 kUA/l) 100 – of IgE egg and milk of sensitization to 90 – 84% 80 – food and s-IgE allergens. inhalant 70 – significantly 60 – Symptoms of eczema, increased the 50 – rhinitis, and asthma. risk for 40 – eczema at Children (268) followed 30 – 2 yrs of age prospectively from birth 20 – 10 – to 5 years of age. 0 still sensitized at age 5
  25. 25. An explorative study of low levels of allergen-specific IgE and clinical allergy symptoms during early childhood Söderström L, Allergy 2011;66:1058 % children with low levels of s-IgE to any of the studied allergens at 12 months of age Relationship between low levelsLow levelsA/l) (0.1–0.7 kU of 100 – s-IgE can be of IgE sensitization to 90 – 84% 80 – fooddetected from and inhalant allergens. 70 – the age of 60 – Symptoms of eczema, 6 months and 50 – rhinitis, and asthma. are related to 40 – further IgE Children (268) followed 30 – sensitization prospectively from birth 20 – 10 – to 5 years of age. 0 still sensitized at age 5
  26. 26. Association of microbial IgE sensitizations with asthma in young children with atopic dermatitis Ong, Ann Allergy Asthma Immunol 2012;108:206• Atopic dermatitis (AD) is considered to be a major risk factor for the development of asthma in children.• A unique clinical feature of AD patients is the colonization of their skin by: - Staphylococcus aureus - Fungi• Specific IgE against these microbial pathogens or their products has been associated with AD severity.
  27. 27. Association of microbial IgE sensitizations with asthma in young children with atopic dermatitis Ong, Ann Allergy Asthma Immunol 2012;108:206 OR for persistent asthma 53 children (1-6 yrs) 5 – with mild to moderate AD. Total serum IgE and 4 – 4.3 4.2 specific IgE for: - inhalant allergens 3 – 3.5 - common food 2- - microbial allergens (Staphylococcal 1 – enterotoxins, Aspergillus fumigatus, Cladosporium 00 herbarum, Malassezia C albicans C herbarum Malassezia species, and Candida albicans). SENSITIZATION to
  28. 28. Association of microbial IgE sensitizations with asthma in young children with atopic dermatitis Ong, Ann Allergy Asthma Immunol 2012;108:206 OR for persistent asthma 53 children (1-6 yrs) 5 – with mild to moderate AD. Total serum IgE and Persistent asthma 4 – 4.3 4.2 specific IgE for: was associated with - inhalant allergens 3 – 3.5 - common food IgE fungal 2- sensitizations. - microbial allergens (Staphylococcal 1 – enterotoxins, Aspergillus fumigatus, Cladosporium 00 herbarum, Malassezia C albicans C herbarum Malassezia species, and Candida albicans). SENSITIZATION to
  29. 29. Interaction between filaggrin null mutations and tobacco smoking in relation to asthma Berg JACI 2012;129:374 4.0 – OR for asthma in FLG null mutations 3471 adults from vs wild type. general population. 3.5 - 3.70 3.0 – Lung function 2.5 – and IgE levels to inhalant allergens. 2.0 – 1.5 – 1.96 Filaggrin 1.02 1.57 1.0 – (FLG) null mutations. 0.5 - 0.0 R501X and Never Former ≤15 g/d ≥15 g/d 2282del4. current SMOKING
  30. 30. Interaction between filaggrin null mutations and tobacco smoking in relation to asthma Berg JACI 2012;129:374 4.0 – OR for asthma in FLG null mutations A significant 3471 adults from vs wild type. interaction general population. 3.5 - 3.70 3.0 – was found Lung function 2.5 – between and IgE levels to inhalant allergens. 2.0 – FLG null 1.96 mutations Filaggrin 1.5 – 1.02 1.57 1.0 – (FLG) nulland mutations. status 0.5 - smoking (p=0.02). R501X and 0.0 Never Former ≤15 g/d ≥15 g/d 2282del4. current SMOKING
  31. 31. • protective factors
  32. 32. The role of vitamin D in the immunopathogenesisof allergic skin diseases. Benson, Allergy 2012;67:296 1) Vitamin D deficiency: serum 25(OH)D <10ng/ml; 2) Vitamin D insufficiency: serum 25(OH)D 21-29 ng/ml; 3) Low Vitamin D levels connected with: - higher cardiovascular mortality; - increased risk of cancer; - increased risk of diabetes mellitus; - increased risk of infections.
  33. 33. The role of vitamin D in the immunopathogenesisof allergic skin diseases. Benson, Allergy 2012;67:296 Metabolism of Vitamin D3
  34. 34. The role of vitamin D in the immunopathogenesisof allergic skin diseases. Benson, Allergy 2012;67:296The impact of Vitamin D3 on the immune system
  35. 35. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Benson, Allergy 2012;67:296• Conflicting data surrounding the effect that Vitamin D has on the development of allergic skin diseases: - several studies collectively support the theory that increased Vitamin D may be tied to allergic diseases, including atopic dermatitis; - several studies suggest that Vitamin D deficiency contributes to the development of atopic dermatitis; - several studies link Vitamin D supplementation with either the decreased risk or clinical improvment of atopic dermatitis.
  36. 36. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Benson, Allergy 2012;67:296Studies assessing a link between allergic skin diseases & Vitamin D
  37. 37. The role of vitamin D in the immunopathogenesis of allergic skin diseases. Benson, Allergy 2012;67:296Studies assessing a link between allergic skin diseases & Vitamin D There is increasing evidence to show that vitamin D plays a significant role in the immune system, and specifically in allergic diseases. It is difficult to completely assess the role that vitamin D plays and large and prospective studies need to be conducted. Randomized controlled trials regarding treatment with vitamin D in the context of allergic diseases may also assist in determining a definitive link.
  38. 38. Circulating levels of 25-hydroxyvitamin D and humancathelicidin in healthy adults. Bhan JACI 2011;127:1302 Cathelicidins are a class of widely conserved antimicrobial peptides produced by essentially all mammalian species as part of the innate immune system. They have broad activity against both gram-positive and gram-negative bacteria and have additional effects, including neutralizing LPS, stimulating leukocyte chemotaxis, and promoting angiogenesis. Impairment in cathelicidin or other antimicrobial peptides has been linked to increased susceptibility to and severity of infection.
  39. 39. Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. Bhan JACI 2011;127:1302 Change in cathelicidin level by Plasma cathelicidin change in 25(OH)D level after levels, vitamin D status, and ergocalciferol treatment (n = 25) vitamin D supplementation. 60 healthy volunteers. Subjects with plasma 25(OH)D levels of ≤32 ng/mL were treated with ergocalciferol, 50,000 IU every other day, for 5 days. Posttreatment levels of 25(OH)D, cathelicidin 10 days after completing treatment.
  40. 40. Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Masilamani, JACI 2011;128:1242Background:Although peanut and soybean proteins share extensiveamino acid sequence homology, the incidence and severity ofallergic reactions to soy are much less than those to peanut.Soybeans are rich in anti-inflammatory isoflavones andare the most common source of isoflavones in the human food supply.Objective:We hypothesized that the active isoflavones in the gut milieuare capable of modulating immune responses to dietary antigensby regulating dendritic cell (DC) function.
  41. 41. Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Masilamani, JACI 2011;128:1242 Sensitized and challenged with peanut Fed a diet fed containing a soy-free genistein dietand daidzein• Dietary isoflavones significantly reduced the anaphylactic symptoms and mast cell degranulation in vivo after peanut challenge.• Serum peanut-specific antibodies were markedly reduced in mice fed the isoflavone diet.
  42. 42. Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Masilamani, JACI 2011;128:1242 Activated with cholera toxin in the presence of isoflavonesHuman monocyte-derived dendritic cells Isoflavones inhibited cholera toxin–induced DC maturation and subsequent DC-mediated CD4+ T-cell function in vitro.
  43. 43. Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Masilamani, JACI 2011;128:1242 Chemical structure of the soybean isoflavones:• Isoflavones belong to a class of molecules related to flavonoids.• Soybeans are the most common source of isoflavones in the human diet.• Isoflavones, such as genistein, daidzein, and glycitein, have been shown to have anti-inflammatory and antioxidant properties. Barnes, Lymphat Res Biol 2010;8:89
  44. 44. Soybean isoflavones regulate dendritic cell function and suppress allergic sensitization to peanut Masilamani, JACI 2011;128:1242• The immune-regulatory effects of isoflavones, specifically genistein, have been extensively investigated. Sakai, J Med Invest 2008;55:167• The high intake of soy-containing foods and isoflavones is associated with reduced prevalence of allergic rhinitis and better lung function in asthmatic patients. Miyake, J Allergy Clin Immunol 2005;115:1176 Smith, J Asthma 2004;41:833• Dietary soy supplementation reduced: - antigen-induced eosinophilia in the lungs in a pig model of asthma; - eosinophil leukotriene C4 synthesis and eosinophilic airway inflammation ii in asthmatic patients. Regal, Proc Soc Exp Biol Med 2000;223:372 Kalhan, Clin Exp Allergy 2008;38:103
  45. 45. Dietary docosahexaenoic acid in combination witharachidonic acid ameliorates allergen-induced dermatitis in mice. Weise Pediat Allergy Immunol 2011;22:497 Skin inflammation induced by ovalbumin A diet containing 0.015% DHA, 0.029% AA or the combination of both. Sensitized mice  Dietary DHA/AA significantly improved the severity of allergen-induced dermatitis by 36% (p = 0.005).  This was accompanied with the presence of increased regulatory T cells and IL-10 expression in lesional skin.
  46. 46. • intestinal flora• Probiotics• Prebiotics
  47. 47. Oral application of bacterial lysate in infancydecreases the risk of atopic dermatitis in children withatopic parent in a randomized, placebo-controlled trial Lau, JACI 2012;129:1040Background: Lower prevalence of atopy was found in children withcontinuous exposure to livestock and thus to microbial compounds.In animal models exposure to endotoxin (LPS) decreases allergicsensitization and airway inflammation.Objective: We sought to evaluate the effect of orally appliedbacterial lysate in infancy on the prevalence of atopic dermatitis(AD) after the treatment phase at 7 months of age.
  48. 48. Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with atopic parent in a randomized, placebo-controlled trial Lau, JACI 2012;129:1040 % children with AD by age 3 606 newborns with at least years single heredity for atopy 20 – From wk 5 to mo 19% 7, bacterial lysate (heat- killed gram (-) Escherichia coli Symbio and gram (+) 10 – Enterococcus faecalis 10% Symbio) or its placebo P<0.03 Follow-up: 3 years of age 0 ACTIVE PLACEBO
  49. 49. Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with atopic parent in a randomized, placebo-controlled trial Lau, JACI 2012;129:1040 This was more % children with AD by age 3 606 newborns with at least years single heredity forin the pronounced atopy 20 – group of infants From wk 5 to mo 19% with paternal 7, bacterial lysate (heat- heredity for killed gram (-) Escherichia atopy coli Symbio and gram (+) 10 – (11% vs Enterococcus faecalis 10% 32%, P=0.004 Symbio) or its placebo ; P<0.03 RR= 0.34) Follow-up: 3 years of age 0 ACTIVE PLACEBO
  50. 50. Oral application of bacterial lysate in infancy decreases the risk of atopic dermatitis in children with atopic parent in a randomized, placebo-controlled trial Lau, JACI 2012;129:1040 OR for AD by age 3 years 606 newborns with at least 1.0 – single heredity for atopy From wk 5 to mo 7, bacterial lysate (heat- killed gram (-) Escherichia coli Symbio and gram (+) 0.5 – 0.52 Enterococcus faecalis Symbio) or its placebo Follow-up: 3 years of age 0 ACTIVE TREATED
  51. 51. • Risk factors
  52. 52. Low diversity of the gut microbiota in infants with atopic eczema Abrahamsson JACI 2012;129:434 Background It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. Objective 1) To assess microbial diversity , 2) Characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development.
  53. 53. Low diversity of the gut microbiota in infants with atopic eczema Abrahamsson JACI 2012;129:434 Infants with IgE-associated Microbial diversity eczema had lower diversity of: analyzed with 16S rDNA 454-pyrosequencing. - The total microbiota at 1 month (p=0.004); Stool samples at 1 week, 1 month, and 12 -The bacterial phylum months. Bacteroidetes and the genus Bacteroides at 1 month 20 infants with (p=0.02 and p=0.01) ; IgE-associated eczema and 20 infants without - The phylum Proteobacteria any allergic manifestation at 12 months until 2 years of age. (p=0.02).
  54. 54. Low diversity of the gut microbiota in infants with atopic eczema Abrahamsson JACI 2012;129:434 Infants with IgE-associated Low intestinal Microbial diversity eczema had lower diversity of: analyzed microbial with 16S rDNA 454-pyrosequencing. - The total microbiota at 1 month diversity during (p=0.004); Stool samples at 1 week, the first month 1 month, and 12 months. -The bacterial phylum of life Bacteroidetes and the 20 infants with genus Bacteroides at 1 month was associated IgE-associated eczema (p=0.02 and p=0.01) ; with subsequent and 20 infants without atopic eczema. any allergic manifestation - The phylum Proteobacteria until 2 years of age. at 12 months (p=0.02).
  55. 55. Low diversity of the gut microbiota in infants with atopic eczema Abrahamsson JACI 2012;129:434Relative abundance of dominant bacterial phyla in stool samples in each subject 1 week 1 month 2 months
  56. 56. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children. Peroni DG, Br J Dermatol. 2011;164:1078-82. Serum vitamin D levels in relation to different threshold values of AD severity.37 children (8 monthsand 12 years) with AD, SCORAD index,Serum levels of25-hydroxyvitamin DsIgE to S.aureus and toM. furfur
  57. 57. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children. Peroni DG, Br J Dermatol. 2011;164:1078-82. Correlation between serum vitamin D levels and individual SCORAD values.37 children (8 monthsand 12 years) with AD, SCORAD index,Serum levels of25-hydroxyvitamin DsIgE to S.aureus and toM. furfur
  58. 58. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children. Peroni DG, Br J Dermatol. 2011;164:1078-82. The prevalence of allergic sensitization to staphylococcal superantigensand to Malassezia furfur in children with mild, moderate and severe AD
  59. 59. Association between obesity and atopic dermatitis in childhood: A case-control study Silverberg JACI 2011;127:1180 Retrospective, case- OR for Atopic Dermatitis control study. 2.0 – Randomly sampled 414 children and 1.5 – 2.0 adolescents with p=0.006 atopic dermatitis. 1.0 – 828 randomly 0.5 – sampled healthy controls. 0.0 OBESITY
  60. 60. Association between obesity and atopic dermatitis in childhood: A case-control study Silverberg JACI 2011;127:1180 20 – OR for Atopic Dermatitis Retrospective, case- 15 – 15.10 control study. p=0.02 Randomly sampled 3.5 – 414 children and 3.40 3.0 – adolescents with 2.5 – 2.58 2.64 p=0.01 atopic dermatitis. 2.0 – 1.5 – p=0.01 p=0.03 1.32 828 randomly 1.0 – 0.5 – sampled healthy 0.0 ns controls. Less than 2 to >5 yrs 2.5 to >5 yrs 2 yrs of age 5 yrs 5 yrs Obesity started by When obesity was prolonged for
  61. 61. Association between obesity and atopic dermatitis in childhood: A case-control study Silverberg JACI 2011;127:1180 20 – OR for Atopic Dermatitis Retrospective, case- 15 – 15.10 control study. is Obesity p=0.02 associated with Randomly sampled 414 more severe children and 3.5 – 3.40 3.0 – atopic adolescents with 2.5 – 2.58 2.64 p=0.01 atopic dermatitis. dermatitis 2.0 – 1.5 – p=0.01 p=0.03 OR, 2.37 828 randomly 1.0 – 1.32 0.5 – sampled healthy 0.0 ns controls. Less than 2 to >5 yrs 2.5 to >5 yrs 2 yrs of age 5 yrs 5 yrs Obesity started by When obesity was prolonged for
  62. 62. Association between obesity and atopic dermatitis in childhood: A case-control study Silverberg JACI 2011;127:1180 20 – OR for Atopic Dermatitis Retrospective, case- 15 – 15.10 Prolonged obesity in control study. early childhood is a p=0.02 risk factor for atopic Randomly sampled dermatitis. 3.5 – 414 children and Weight loss might be 3.0 – 3.40 adolescents with an important approach 2.5 – 2.58 2.64 p=0.01 atopic dermatitis. for the prevention 2.0 – 1.5 – p=0.01 p=0.03 and treatment of 1.32 828 randomly atopic dermatitis in 1.0 – 0.5 – sampledchildren. healthy 0.0 ns controls. Less than 2 to >5 yrs 2.5 to >5 yrs 2 yrs of age 5 yrs 5 yrs Obesity started by When obesity was prolonged for
  63. 63. Predictive value of food sensitization and filaggrin mutations in children with eczema Pittroff, JACI 2011;128:1235 Positive diagnostic likelihood ratios for asthma onset in children with food sensitization The German Infant 6 – Nutritional Intervention (GINI) and Influence of 5 – 5.5 Lifestyle-related 4 – Factors on the Immune System and 3 – the Development of Allergies in Childhood 2 – 1.9 (LISA) 1 – birth cohorts. 0 GINI cohort LISA cohort
  64. 64. Predictive value of food sensitization and filaggrin mutations in children with eczema Pittroff, JACI 2011;128:1235 Positive diagnostic likelihood ratios for asthma onset in children with filaggrin mutation The German Infant 6 – Nutritional Intervention (GINI) 5 – and Influence of Lifestyle-related 4 – Factors on the Immune System and 3 – the Development of Allergies in Childhood 2 – 2.9 2.8 (LISA) 1 – birth cohorts. 0 GINI cohort LISA cohort
  65. 65. Predictive value of food sensitization and filaggrin mutations in children with eczema Pittroff, JACI 2011;128:1235 Positive diagnostic likelihood ratios for asthma onset in children with filaggrin mutation The German Infant 6 – Nutritional Intervention The (GINI) combination 5 – of both and Influence of Lifestyle-related parameters 4 – Factors on the did not Immune System and 3 – improve 2.9 the Development of prediction. Allergies in Childhood 2 – 2.8 (LISA) 1 – birth cohorts. 0 GINI cohort LISA cohort
  66. 66. Predictive value of food sensitization and filaggrin mutations in children with eczema Pittroff, JACI 2011;128:1235 Positive diagnostic likelihood ratios for asthma onset in children with filaggrin mutation Early The German Infant 6 – food sensitization Nutritional Intervention (GINI) the presence and 5 – and Influence of of a filaggrin Lifestyle-related mutation 4 – Factors infants with in on the Immune System and 3 – early eczema the Development of increase the risk Allergies in Childhood 2 – 2.9 2.8 for later asthma, … (LISA) 1 – birth cohorts. 0 GINI cohort LISA cohort
  67. 67. Predictive value of food sensitization and filaggrin mutations in children with eczema Pittroff, JACI 2011;128:1235 Positive diagnostic likelihood ratios for asthma onset in children with filaggrin mutation The German Infant …but the 6 – Nutritional Intervention combination of (GINI) 5 – the 2 factors and Influence of does not represent a Lifestyle-related 4 – Factors clinically on the Immune System and 3 – useful approach the Development of to reliably Allergies in Childhood 2 – 2.9 2.8 identify children (LISA) 1 – at risk birth cohorts. . 0 GINI cohort LISA cohort
  68. 68. Allergic sensitization can be induced via multiplephysiologic routes in an adjuvant-dependent manner Dunkin, JACI 2011;128:1251 Repeatedly exposed to the milk allergen α-lactalbumin (ALA), ± with or without cholera toxin (CT). Sensitization routes used were: 1) intragastric, 2) cutaneous, 3) • Sensitization to ALA as measured by allergen-specific IgE intranasal, occurred by4) sublingual. all routes of sensitization and was maximal in response to cutaneous exposure. • Sensitization was dependent on CT + and did not occur to antigen alone by any route.
  69. 69. Allergic sensitization can be induced via multiplephysiologic routes in an adjuvant-dependent manner Dunkin, JACI 2011;128:1251 Repeatedly exposed to the milk allergen α-lactalbumin (ALA), ± with or without cholera toxin (CT). Sensitization routes used were: 1) intragastric, 2) cutaneous, 3) • Sensitization to ALA as measured by allergen-specific IgE intranasal, occurred Sensitization can occur via by4) sublingual. all routes of sensitization all physiologic routes and was maximal in response to cutaneous exposure. when adjuvant is present. • Sensitization was dependent on CT + and did not occur to antigen alone by any route.
  70. 70. Cord blood T-regs with stable FOXP3 expression are influenced by prenatal environment & associated with atopic dermatitis at the age of 1 yr. Hinz, Allergy 2012;67:380 OR for atopic dermatitis during the 1°yr of life Blood samples from 2 – pregnant women (34th gestational week) & in cord blood 1.55 1 – (n=346 mother-child pairs). T-reg numbers detected 0 via DNA demethylation in the FOXP3. in children with lower T-reg numbers at birth.
  71. 71. Cord blood T-regs with stable FOXP3 expression areinfluenced by prenatal environment & associated with atopic dermatitis at the age of 1 yr. Hinz, Allergy 2012;67:380 % T-reg cell in cord blood1.4 - p=0.0421.2 - 1.38% p=0.0391.1 - 1.17%0.8 - 1.05% 0.85%0.6 -0.4 -0.2 -0 NEVER DAILY NO YES Usage of disinfectants Maternal smoking/environmental tobacco smoke exposure at home
  72. 72. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 Infant allergic outcomes at 1 yr of age according to maternal folic acid taken as a supplement in pregnancy. 628 women recruited in the last trimester of pregnancy. Folate status determined by: - food frequency questionnaires; - levels in maternal and cord blood serum. Infant allergic outcomes at 1 yr of age (n=484).
  73. 73. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 Cord blood folate levels and allergic outcomes. 628 women recruited in the last trimester of pregnancy. Folate status determined by: - food frequency questionnaires; - levels in maternal and cord blood serum. Infant allergic outcomes at 1 yr of age (n=484).
  74. 74. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 Cord blood folate levels and allergic There was a nonlinear outcomes. relationship between 628 women recruited in cord blood folate the last trimester and sensitization, of pregnancy. levels with folate <50 nmol/L Folate status p=0.024) (OR=3.02, determined by: and >75 nmol/L - food frequency (OR=3.59, p=0.008) questionnaires; greater associated with sensitization risk - levels in maternal and cord blood serum. 50 than levels between and 75 nmol/L. Infant allergic outcomes at 1 yr of age (n=484).
  75. 75. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 In utero folate status in infants who developed subsequent eczema 628 women recruited in vs the last trimester those who did not. of pregnancy. Folate status determined by: - food frequency (μg/d) questionnaires; - levels in maternal and cord blood serum. Infant allergic outcomes at 1 yr of age (n=484). DFE=dietary folate equivalent units
  76. 76. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 In utero folate status Although maternal in infants who developed subsequent eczema 628 women recruited in folate intake from vs the last trimester those who did not. foods was also not of pregnancy. different, folate Folate status determined derived from by: supplements was - food frequency (μg/d) higher (p=0,017) in questionnaires; children with - levels in maternal and subsequent eczema. cord blood serum. Infant allergic outcomes at 1 yr of age (n=484). DFE=dietary folate equivalent units
  77. 77. The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood. Dunstan, Allergy 2012;67:50 In utero folate status Infants exposed to in infants who developed subsequent eczema 628 >500 μg folic in women recruited vs the acid/day as a last trimester those who did not. of pregnancy. supplement in utero were more likely Folate status determined by: develop eczema to - food frequency (μg/d) than those taking questionnaires; <200 μg/day - levels in maternal and cord blood p=0.013). (OR=1.85, serum. Infant allergic outcomes at 1 yr of age (n=484). DFE=dietary folate equivalent units
  78. 78. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335Background:Pre- and postnatal stress have been related to allergy inchildren, but evidence from prospective studies is limited.Several environmental factors can influencethe salivary cortisol level, which is used as a measure of activityof the hypothalamic-pituitary-adrenal axis.Objective:The aim of this study was to assess the association betweensalivary cortisol levels at 6 months of age and allergic manifestationsduring the first 2 years of life.
  79. 79. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 Geometric mean of salivary cortisol (nmol/L) 15 – Salivary samples for cortisol level at 6 mo on 3 occasions during 1 day. 10 – 11.7 203 children. Blood samples 5.1 05 – at 6, 12, and 24 mo 2.9 for specific IgE. 0 Morning Afternoon Evening
  80. 80. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 Geometric mean of Salivary cortisol levels salivary cortisol (nmol/L) on all sampling occasions 15 – were related Salivary samples to the prevalence of for cortisol level at 6 mo on 3 occasions and eczema 10 – sensitization during 1 day. 11.7 during the first 2 yrs of 203 children. life, wit h increasing levels Blood samples leading to 5.1 05 – of cortisol at 6, 12, and 24 mo of higher prevalence 2.9 for specific IgE. and sensitization eczema. 0 Morning Afternoon Evening
  81. 81. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds at different time points of the same day. Salivary samples for cortisol level at 6 mo on 3 occasions during 1 day. 203 children. Blood samples at 6, 12, and 24 mo for specific IgE.
  82. 82. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds at different time points of the same day. An association Salivary samples and between pre- for postnatal stress mo cortisol level at 6 on 3 occasions during 1 day. and subsequent development of 203 children. allergic diseases Blood samples has previously been at 6, 12, and 24 mo indicated … for specific IgE.
  83. 83. Salivary cortisol levels and allergy in children: The ALADDIN birth cohort. Stenius, JACI 2011;128:1335 OR and 95% CI for allergic sensitization and allergy-related disease during the first 2 yrs in relation to the saliva cortisol level in 6 mo-olds … at different time points of the same day. Furthermore, Salivary samples for cortisol level been mo it has at 6 on shown thatduring 1 day. 3 occasions infants predisposed 203 children. disease to allergic Blood samples levels have higher of cortisol at 6, 12, and 24 mo prior to the for specific IgE. onset of disease.
  84. 84. • batteri• funghi• virus
  85. 85. Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin. Forbes-Blom, Clin Exp Allergy 2012;42:305 Concomitant exposure to Peanut extract (PE) staphylococcal-derived superantigenTh2 model Th2 response in the skin draining lymph nodes
  86. 86. Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin. Forbes-Blom, Clin Exp Allergy 2012;42:305 Concomitant exposure to Peanut extract (PE) staphylococcal-derived superantigen Significantly enhanced specific Th2 responses.Th2 model (+) Th2 response in the skin draining lymph nodes
  87. 87. Staphylococcal-derived superantigen enhances peanut induced Th2 responses in the skin. Forbes-Blom, Clin Exp Allergy 2012;42:305Exposure of staphylococcal enterotoxin B (SEB) when being primed to peanut extract (PE) leads to an enhanced PE-dependent CD4 Th2 response.c (a) (b) Absolute n° (a) and proportion (b) of CD4+ GFP+ T cells present in the draining auricular lymph node 24h after final intradermal boost.
  88. 88. • atopy• sensitization
  89. 89. The introduction of allergenic foods and the development of reported wheezing and eczema in childhood Tromp APAM 2011;165:933 % children wheezing 605 preschool children. 40 – Timing of introduction 30 – of cow’s milk, hen’s 31% egg, peanuts, tree 20 – nuts, soy, and gluten collected by questionnaires at 6 and 10 – 14% 12 months of age. 0 2 yrs 3-4 yrs
  90. 90. The introduction of allergenic foods and the development of reported wheezing and eczema in childhood Tromp APAM 2011;165:933 % children with eczema 605 preschool children. 40 – Timing of introduction 30 – 38% of cow’s milk, hen’s egg, peanuts, tree 20 – nuts, soy, and gluten collected by 10 – 20% 18% questionnaires at 6 and 18% 12 months of age. 0 2 3 4 age (years)
  91. 91. The introduction of allergenic foods and the development of reported wheezing and eczema in childhood Tromp APAM 2011;165:933 % children with eczema 605 preschool children. 40 – Timing of introduction 30 – 38% of cow’s milk, hen’s egg, peanuts, tree 20 – nuts, soy, and gluten collected by 10 – 20% 18% questionnaires at 6 and 18% 12 months of age. 0 2 3 4 age (years)
  92. 92. The introduction of allergenic foods and the development of reported wheezing and eczema in childhood Tromp APAM 2011;165:933 with cow’s milk introduction ≤6 mo OR for eczema at age 1.0 – 605 preschool children. 0.95 Timing of introduction 0.91 0.88 of cow’s milk, hen’s egg, peanuts, tree 0.5 – nuts, soy, and gluten collected by questionnaires at 6 and 12 months of age. 0.0 2 yrs 3 yrs 4 yrs
  93. 93. • Irritants
  94. 94. •Red-Ox
  95. 95. Markers of oxidative stress are increased in exhaled breath condensates of children with atopic dermatitis. Peroni DG, Br J Dermatol. 2012;166:839-43. Levels of 8-isoprostane and LTB4 in patients with AD vs normal controls.33 ch with AD and23 healthy controlsEBC for:-pH,-LTB4,-8-isoprostane,-H2O2 ,-malondialdehyde ,-4-hydroxynoneal.
  96. 96. Markers of oxidative stress are increased in exhaledbreath condensates of children with atopic dermatitis. Peroni DG, Br J Dermatol. 2012;166:839-43. Measurements of inflammatory markers and pH values in the study population, expressed as median (range)
  97. 97. Intracellular glutathione redox status in human dendriticcells regulates IL-27 production and T-cell polarization Kamide Y, Allergy 2011;66:1183Background: Glutathione redox status, changes in intracellularreduced (GSH) or oxidized (GSSG) glutathione, plays a significantrole in various aspects of cellular function.In this study, we examined whether intracellular glutathione redoxstatus in human dendritic cells (DCs) regulates the polarization ofTh1/Th2 balance.
  98. 98. Intracellular glutathione redox status in human dendriticcells regulates IL-27 production and T-cell polarization Kamide Y, Allergy 2011;66:1183 Human monocyte-derived dendritic cells (MD-DCs) Glutathione reduced form ethyl ester treated with glutathione (GSH-OEt)-treated monocyte-derived DCs reduced form ethyl ester enhanced Th1 response and reduced Th2 (GSH-OEt) or L-buthionine- response through interleukin-12 induction (S,R)-sulfoximine (BSO). P<0.05 P<0.05 Stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines.
  99. 99. • Pathogenesis
  100. 100. Decrease in interleukin-21 in children suffering with severe atopic dermatitis Lin Pediat Allergy Immunol 2011;22:869 p<0.05 IL-21 in AD cases and controls. 39 ch. with AD and 31 controls.
  101. 101. Decrease in interleukin-21 in children suffering with severe atopic dermatitis Lin Pediat Allergy Immunol 2011;22:869 p<0.05 A significantly decreased IL-21 in AD cases was level of IL-21 andobserved in children controls. suffering with severe AD compared with 39 ch. With AD controls, suggesting that and 31 controls. play a IL-21 may protective role in AD.
  102. 102. Decrease in interleukin-21 in children suffering with severe atopic dermatitis Lin Pediat Allergy Immunol 2011;22:869 IL-21 as a new member of IL-2-family. IL-21 has a significant influence on the regulation of B-cell function in vivo and association with. In the animal model, IL-21 strongly stimulates the expression of suppressor of cytokine signaling SOCS gene. IL-21 suppress the production of IgE along with an increase in the protective anti-allergic immunoglobulin G4.
  103. 103. Exploring CCL18, eczema severity and atopy Hon Pediat Allergy Immunol 2011;22:704  Chemokine (C-C motif) ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine 108 patients with AD aged family that was previously called 20 yr or younger. pulmonary and activation-regulated chemokine (PARC). SCORAD.  CCL18 is present in skin biopsies of patients with AD. The chemokine Nocturnal scratching with binds to CLA+ T cells in peripheral a wrist motion monitor. blood of patients with AD and Concentrations of plasma induces migration of AD-derived CCL18. memory T cells.  CCL18 or PARC was found to be a significant marker of atopy in children with AD.
  104. 104. Exploring CCL18, eczema severity and atopy Hon Pediat Allergy Immunol 2011;22:704 Scatter plot of objective SCORing Atopic Dermatitis against plasma CCL18 concentrations in our patients 108 patients with AD aged (r = 0.424, p < 0.001). 20 yr or younger. SCORAD. Nocturnal scratching with a wrist motion monitor. Concentrations of plasma r=0.424 p<0.001 CCL18.
  105. 105. Exploring CCL18, eczema severity and atopy Hon Pediat Allergy Immunol 2011;22:704 Distribution of plasma CCL18 concentrations in patients with different degree of atopic dermatitis severity (p < 0.001 for trend) 108 patients with AD aged 20 yr or younger. SCORAD. Nocturnal scratching with a wrist motion monitor. Concentrations of plasma CCL18.
  106. 106. Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis. Balaji JACI 2011;128:92 Background IgE-mediated cross-reactivity between fungal antigens and human proteins has been described in patients with atopic dermatitis (AD), but it remains to be elucidated whether there is also cross-reactivity at the T-cell level.
  107. 107. Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis. Balaji JACI 2011;128:92  Mala s 13–specific T-cell To explore cross-reactivity at the T-cell level between the fungal clones (TCCs) and Mala s thioredoxin (Mala s 13) of the 13–specific TCLs and TCCs skin-colonizing yeast Malassezia from the blood and skin of sympodialis and its homologous patients with AD sensitized human thioredoxin (hTrx). to Mala s 13 and hTrx were T-cell lines (TCLs) were generated in the presence of rMala s 13 fully cross-reactive with from the peripheral blood and hTrx. from skin biopsy specimens of positive patch test reactions of patients with AD sensitized to Mala s 13 and hTrx.  Mala s 13– and hTrx– Patients with AD not sensitized specific TCCs could not be to Malassezia species, healthy generated from control subjects, served as control subjects. subjects.
  108. 108. Malassezia sympodialis thioredoxin–specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis. Balaji JACI 2011;128:92  Mala s 13–specific T-cell To explore cross-reactivity at the T-cell level between the fungal clones (TCCs) and Mala s thioredoxin (Mala s 13) of the 13–specific TCLs and TCCs skin-colonizing yeast Malassezia from the blood and skin of sympodialis majority of The and its homologous patients with AD sensitized human thioredoxin (hTrx).TCCs cross-reactive to Mala s 13 and hTrx were T-cell lines (TCLs) were generated in thewere CD4 and + fully cross-reactive with presence of rMala s 13 hTrx. coexpressed from the peripheral blood and from skin biopsy specimens of cutaneous lymphocyte positive patch test reactions of antigen (CLA). patients with AD sensitized to Mala s 13 and hTrx.  Mala s 13– and hTrx– Patients with AD not sensitized specific TCCs could not be to Malassezia species, healthy generated from control subjects, served as control subjects. subjects.
  109. 109. Autoreactive CD4+ T cells in patients with atopic dermatitis. James JACI 2011;128:100 The study by Balaji et al represents the best evidence that molecular mimicry between non-self-antigens (Malassezia species proteins) and homologous self-antigens (human thioredoxin) plays a role in AD at the T-cell level. Balaji et al observed that T cells that recognized human thioredoxin could only be detected in patients with AD with Malassezia species infection, implying that Malassezia species– specific responses are required to elicit self-reactivity. Infectious agents may act as triggering agents in autoimmunity through molecular mimicry.
  110. 110. Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis. Liang, Allergy 2012;67:424Background: Overexpression of the high-affinityreceptor for IgE on atopic monocytes & dendritic cellsis known to contribute to the pathogenesisof atopic dermatitis (AD).However, it remains unclear what is the underlyingmechanism of FcεRI deregulation.It has been speculated that epigenetic deregulation mayplay a role.
  111. 111. Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis. Liang, Allergy 2012;67:424 Reduced global DNA methylation and FCER1G methylation in monocytes of patients with AD Global DNA methylation levels using a global DNA methylation kit. Monocytes from 10 AD patients & 10 healthy controls.
  112. 112. Demethylation of the FCER1G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis. Liang, Allergy 2012;67:4241) CD14+ monocytes from patients with AD were globally hypomethylated relative to healthy controls.2) When methylation is reduced, the FcεRI expression increased.3) Together, these results suggest that the demethylation of specific regulatory elements contributes to FcεRI overexpression on monocytes from patients with AD, which in turn leads to hyperallergic responses.
  113. 113. • Diagnosis• Evaluation of severity
  114. 114. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Stalder J, Allergy 2011;66:1114 The Patient-Oriented SCORing Atopic Dermatitis Patient-Oriented SCORing Atopic (PO-SCORAD) index is a Dermatitis (PO-SCORAD) and SCORing self-assessment score. Atopic Dermatitis (SCORAD) scores at day 0 471 (185 adults, 286 children). R=0.67 p< 0.0001 The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 days later (D28).
  115. 115. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Stalder J, Allergy 2011;66:1114 The Patient-Oriented SCORing Atopic Dermatitis Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a (PO-SCORAD) and SCORing Atopic self-assessment score. Dermatitis (SCORAD) scores at day 28 471 (185 adults, 286 children). R=0.79 p< 0.0001 The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 days later (D28).
  116. 116. EASI, (objective) SCORAD and POEM for atopic eczema:responsiveness and minimal clinically important difference Schram, Allergy 2012;67:99 1. Until now, 20 clinical outcome measures have been inaugurated to measure the severity of AE. 2. However, a recently published systematic review indicated that only three of these measures have shown adequate validity and reliability: the Eczema Area and Severity Index (EASI), the Severity Scoring of Atopic Dermatitis (SCORAD), of which there is a variant called the objective SCORAD, and the Patient-Oriented Eczema Measure (POEM). Schmitt, JACI 2007;120:1389; SCORAD index. European Task Force on Atopic Dermatitis. Dermatology 1993;186:23; Charman, Arch Dermatol 2004;140:1513; Tofte, J Eur Acad Dermatol Venereol 1998;11:S197.
  117. 117. EASI, (objective) SCORAD and POEM for atopic eczema:responsiveness and minimal clinically important difference Schram, Allergy 2012;67:99 Minimal clinically important difference (MCID). Severity Scoring of Atopic Dermatitis The MCID was: (SCORAD). - 8.7 points for the SCORAD; - 8.2 for the objective SCORAD; Objective SCORAD. - 6.6 for the EASI; - 3.4 for the POEM. Eczema Area and Severity Index (EASI) Patient-Oriented Eczema Measure (POEM).
  118. 118. • Contact dermatitis
  119. 119. Pulpitis as clinical presentation of photoallergic contact dermatitis due to chlorpromazine Monteagudo-Paz, Allergy 2011;66:1494Chlorpromazine (CPZ) is a phenotiazine (Largactil);Photoallergic contact dermatitis has been described in health workers who become sensitized by manipulating this drug.
  120. 120. Pulpitis as clinical presentation of photoallergic contact dermatitis due to chlorpromazine Monteagudo-Paz, Allergy 2011;66:1494 We present three patients presenting eczematous pulpitis as the only manifestation of photoallergic contact dermatitis because of CPZ…
  121. 121. Burden
  122. 122. Depression, anxiety and dermatologic quality of life in adolescents with atopic dermatitis Slattery JACI 2011;128:668 % children with anxiety 30 – disorders 36 adolescents, mean age 20 – 26% 14.7 yrs with AD. Social SCORAD index. anxiety 10 – Children’s Depression disordes was 6% most common Inventory and the 3% (14%) Multidimensional Anxiety 0 Scale for Children. AD Community estimates
  123. 123. Depression, anxiety and dermatologic quality of life in adolescents with atopic dermatitis Slattery JACI 2011;128:668 % children with current depressive disorders 10 – 36 adolescents, mean age 14.7 yrs with AD. 9% 6% 05 – SCORAD index. Children’s Depression Inventory and the Multidimensional Anxiety 0 Scale for Children. AD Community estimates
  124. 124. Depression, anxiety and dermatologic quality of life in adolescents with atopic dermatitis Slattery JACI 2011;128:668 % children with current depressive disorders Subjective report 10 – of sleep loss was the 36 adolescents,severity only AD mean age 14.7 yrs with AD. 9% measure found 05 6% – SCORAD index. to be associated with symptoms Children’s Depression Inventorydepression. of and the Multidimensional Anxiety 0 Scale for Children. AD Community estimates
  125. 125. Allergy is associated with suicide completion with apossible mediating role of mood disorder-a population- based study Qin, Allergy 2011;66:658 % subjects with a history of hospital contact for allergy 2 – 27 096 completedsuicides.467 571 live controls. 1 – 1.17 % 0.79 % 0 Suicide Controls
  126. 126. Allergy is associated with suicide completion with apossible mediating role of mood disorder-a population- based study Qin, Allergy 2011;66:658 % subjects with a history of hospital contact for allergy 2 – We observed a 27nonsignificantly 096 completed stronger effectsuicides. in women than in men and a467 571 live controls. 1 – 1.17 % stronger effect 0.79 % for individuals at high ages 0 Suicide Controls
  127. 127. Allergy is associated with suicide completion with apossible mediating role of mood disorder-a population- based study Qin, Allergy 2011;66:658 OR for suicide 2 – 27 096 completedsuicides. 1.59467 571 live controls. 1 – 0 Allergy that led to inpatient treatment
  128. 128. Allergy is associated with suicide completion with apossible mediating role of mood disorder-a population- based study Qin, Allergy 2011;66:658 OR for suicide Allergy increased 2 – suicide risk only in 27persons with no 096 completedsuicides. history of mood 1.59 disorder,467 571 live controls. whereas 1 – it eliminated suicide risk in those with a history of mood 0 disorder. Allergy that led to inpatient treatment
  129. 129. treatment
  130. 130. Sticker Charts: A Method for Improving Adherence to Treatment of Chronic Diseases in Children. Luersen K, Pediatr Dermatol. 2012 [Epub ahead of print]Medline and PsycINFO Adherence to medicalsearches were conducted treatments in children can beusing the key words "positive increased using sticker chartsreinforcement OR behavior or other positivetherapy" and "adherence OR reinforcement techniques.patient compliance" and"child." Example of a sticker chart.
  131. 131. • Treatment general consideration
  132. 132. Delayed Acyclovir and Outcomes of Children Hospitalized With Eczema Herpeticum Aronson Pediatrics 2011;128:1161 % children who received acyclovir on the first day of admission. 70 – Retrospective 67.1% study. 60 - 50 - 1331 children aged 40 - 2 months to 17 years with 30 – eczema herpeticum. 20 – 10 – 0
  133. 133. Delayed Acyclovir and Outcomes of Children Hospitalized With Eczema Herpeticum Aronson Pediatrics 2011;128:1161 Lenght of Hospital Stay according to day of acyclovir initiation. Retrospective study. 1331 children aged 2 months to 17 years with eczema herpeticum. LOS; length of stay.
  134. 134. Delayed Acyclovir and Outcomes of Children Hospitalized With Eczema Herpeticum Aronson Pediatrics 2011;128:1161 Lenght of Hospital Stay according to day of acyclovir initiation. Delay of acyclovir initiation by 1 day was Retrospective an 11% associated with study. increased length of stay (p=0.008), increased by 1331 children aged on 41% when started 2 months day 3 (p<0.001) and to 17 years with by 98% when started on eczema to 7 (p<0.001). day 4 herpeticum. LOS; length of stay.
  135. 135. • Treatment exclusion diet
  136. 136. • Treatment emollients
  137. 137. Emollients, education and quality of life: the RCPCH care pathway for children with eczema Cox Arch dis Child 2011;96:i19The Royal College of Paediatrics andChild Health (RCPCH)• Effective eczema management is holistic and encompasses: - assessment of severity and impact on quality of life, - treatment of the inflamed epidermal skin barrier, - recognition and treatment of infection, - assessment and management of environmental and allergy trigger.• Patient and family education which seeks to maximise understanding and concordance with treatment is also important in all children with eczema.
  138. 138. Emollients, education and quality of life: the RCPCH care pathway for children with eczema Cox Arch dis Child 2011;96:i19Stepped approach to treatment
  139. 139. Emollients, education and quality of life: the RCPCH care pathway for children with eczema Cox Arch dis Child 2011;96:i19NICE holistic assessment
  140. 140. Emollients, education and quality of life: the RCPCH care pathway for children with eczema Cox Arch dis Child 2011;96:i19NICE holistic assessment
  141. 141. Emollients, education and quality of life: the RCPCH care pathway for children with eczema Cox Arch dis Child 2011;96:i19NICE holistic assessment There is not necessarily a direct relationship between the severity of the atopic eczema and the impact of the atopic eczema on quality of life.
  142. 142. Effect of moisturizers on epidermal barrier function. Lodén M. Clin Dermatol. 2012;30:286-96. Time to outbreak of eczema in patients with controlledA daily moisturizing atopic eczema being treated with a barrier-improvingroutine is a vital part moisturizer, being untreated or a being treated with aof the management of potentially barrier deteriorating moisturizerpatients with atopic (vaseline suggested to promote relapse of eczema).dermatitis and otherdry skin conditions.The composition ofthe moisturizerdetermines whetherthe treatmentstrengthens ordeteriorates the skinbarrierfunction, which mayhave consequences forthe outcome of thedermatitis.
  143. 143. Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1% hydrocortisone ointment in thetreatment of childhood atopic dermatitis: a pilot study. Udompataikul M, J Drugs Dermatol. 2012;11:366-74. The effectiveness of 5% DT26 ch treated topically ointment is equal to that of 1%with 5% DT ointment on HC ointment.the right side of the bodyand 1% HC ointment on DT ointment may be used asthe other side twice daily alternative treatment in mildfor 4 weeks. to moderate childhood AD therapy.
  144. 144. Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Chan, Allergy 2012;67:336Background: It is unclear whether the initial route of allergenexposure in early life could influence the subsequent developmentof allergy, with cutaneous sensitization leading to peanut allergy,and tolerance induced by oral exposure.The skin- and gastrointestinal (GI)-homing markers, cutaneouslymphocyte antigen (CLA) (skin) and α4β7 integrin(gastrointestinal), are used to determine whether the state ofpeanut allergy correlates with peanut-specific CLA responses, withtolerance associated with predominant α4β7 responses.
  145. 145. Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Chan, Allergy 2012;67:336 Stimulation indices to increasing peanut antigen concentration in the CLA+ & α4β7+ subsets of peanut allergic&non-allergic participants. Proliferation of CLA+ and α4β7+ memory T-cells isolated and cultured with peanut extract. p=0.008 Stimulation indices compared in peanut allergic & non-allergic (NA) groups.
  146. 146. Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Chan, Allergy 2012;67:336 Stimulation indices to increasing peanut antigen concentration in the CLA+ & α4β7+ subsets of The predominance of peanut allergic&non-allergic participants. Proliferation+ of CLA+ the CLA response andto peanut in peanut α4β7+ memory T-cells isolated and allergic patients cultured with peanut is consistent with extract. the hypothesis that p=0.008 Stimulationsensitization allergic indices occurs through compared in peanut the skin. allergic & non-allergic (NA) groups.
  147. 147. Cutaneous lymphocyte antigen and α4β7 T-lymphocyte responses are associated with peanut allergy and tolerance in children. Chan, Allergy 2012;67:336 Stimulation indices to increasing peanut antigen concentration in the CLA+ & α4β7+ subsets of peanut allergic&non-allergic participants. The predominant α4β7 Proliferation of CLA+ + and response in peanut α4β7+ memory tolerant groups T-cells isolated and suggests that allergen cultured with peanut exposure through the extract. p=0.008 GI tract induces Stimulation indices tolerance. compared in peanut allergic & non-allergic (NA) groups.
  148. 148. • Treatmentantibiotics
  149. 149. • Treatment calcineurine inhibitors
  150. 150. • Treatment steroids
  151. 151. • Treatment severe diseaseUVBCiclosporin,methotrexate,azathioprin
  152. 152. Reversal of atopic dermatitis with narrow-band UVBphototherapy and biomarkers for therapeutic response Tintle JACI 2011;128:583BackgroundAtopic dermatitis (AD)is a common inflammatory skin diseaseexhibiting a predominantly TH2/‘‘T22’’ immune activationand a defective epidermal barrier.Narrow-band UVB (NB-UVB) is considered an efficienttreatment for moderate-to severe AD.In patients with psoriasis, NB-UVB has been foundto suppress TH1/TH17 polarization, with subsequent reversalof epidermal hyperplasia.The immunomodulatory effects of thistreatment are largely unknown in patients with AD.
  153. 153. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response Tintle JACI 2011;128:583 Mean % reduction in SCORAD post Narrow Band-UVB 0 – Effects of NB-UVB on immune and barrier abnormalities in -10 – patients with AD. 12 patients with -20 – moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly -30 – for up to 12 weeks. at least 50% Lesional and nonlesional -40 - skin biopsy. Gene expression and -50 – immunohistochemistry.
  154. 154. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response Tintle JACI 2011;128:583 Genomic Effects of NB-UVB on immune difference and barrier abnormalities in s patients with AD. in patients 12 patients with moderate-to-severe with AD chronic AD received NB-UVB before and phototherapy 3 times weekly after NB- for up to 12 weeks. UVB Lesional and nonlesional photothera skin biopsy. Gene expression and py. immunohistochemistry. ANL; Non
  155. 155. Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response Tintle JACI 2011;128:583 Scatterplot of gene expression values in pre-NB-UVB (x-axis) and post-NB-UVB (y-axis) samples shows the substantial reduction (78%) in the AD disease phenotype with NB-UVB. Effects of NB-UVB on immune and barrier abnormalities in patients with AD. 12 patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy. Gene expression and immunohistochemistry.
  156. 156. Reversal of atopic dermatitis with narrow-band UVBphototherapy and biomarkers for therapeutic response Tintle JACI 2011;128:583 Scatterplot of gene expression values in pre-NB-UVB (x-axis) and post-NB-UVB (y-axis) samples shows the substantial reduction (78%) in the AD disease phenotype with NB-UVB. Effects of NB-UVB on immune The resolution of clinical and barrier abnormalities in patients with AD. patients disease in 12 patients with with chronic AD moderate-to-severe chronic AD accompained is received NB-UVB by reversal of both phototherapy 3 times weekly for the epidermal defects up to 12 weeks. Lesional and nonlesional and the underlying skin biopsy. immune activation. Gene expression and immunohistochemistry.
  157. 157. A randomized trial of methotrexate versus azathioprine for severe atopic eczema Schram JACI 2011;128:353BackgroundPatients with severe atopic eczema frequently requiresystemic treatment to control their disease.Methotrexate and azathioprine are proposed as off-labeltreatment options, but direct comparisons are lacking.ObjectivesWe sought to compare theefficacy and safety of methotrexate versus azathioprinein adults with severe atopic eczema.

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