WHAT YOU SHOULD HAVE READ BUT….2010




                 atopic dermatitis
Attilio Boner
University of
Verona, Italy
• Differential Diagnosis
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363
Every screening evalu...
Diagnosis of primary immunodeficiency: Let your
   eyes do the talking.     Shah JACI 2009:124:1363

Every screening evalu...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363
Every screening evalu...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
Diagnosis of primary immunodeficiency: Let your
    eyes do the talking.     Shah JACI 2009:124:1363

Every screening eval...
• Prevalence
Global variations in prevalence of eczema symptoms
        in children from ISAAC Phase Three
            Odhiambo JACI 20...
Global variations in prevalence of eczema symptoms
           in children from ISAAC Phase Three
                   Odhiam...
Global variations in prevalence of eczema symptoms
           in children from ISAAC Phase Three
                   Odhiam...
• burden
Infant-onset eczema in relation to mental health
 problems at age 10 years: Results from a prospective
birth cohort study ...
Infant-onset eczema in relation to mental health
 problems at age 10 years: Results from a prospective
birth cohort study ...
Increased risk of serious pneumococcal disease (SPD)
 in patients with atopic conditions other than asthma
             Ju...
Increased risk of serious pneumococcal disease (SPD)
  in patients with atopic conditions other than asthma
             J...
Increased risk of serious pneumococcal disease (SPD)
  in patients with atopic conditions other than asthma
              ...
• The atopic march
Correlates of outcome for atopic dermatitis
     Horwitz Ann Allergy Asthma Immunol 2009;103:146

                        ...
Correlates of outcome for atopic dermatitis
     Horwitz Ann Allergy Asthma Immunol 2009;103:146

4.5 –   OR for Persistan...
Correlates of outcome for atopic dermatitis
     Horwitz Ann Allergy Asthma Immunol 2009;103:146

4.5 –       OR for Persi...
Early exposure to solid foods and the development
      of eczema in children up to 4 years of age
         Sariachvili Pe...
Early exposure to solid foods and the development
      of eczema in children up to 4 years of age
         Sariachvili Pe...
Early exposure to solid foods and the development
      of eczema in children up to 4 years of age
         Sariachvili Pe...
Early exposure to solid foods and the development
      of eczema in children up to 4 years of age
         Sariachvili Pe...
• protective factors
• intestinal flora
• probiotics
Probiotics during weaning reduce the incidence of eczema
            West Pediatr Allergy Immunol 2009:20:430


          ...
Probiotics during weaning reduce the incidence of eczema
            West Pediatr Allergy Immunol 2009:20:430


          ...
Probiotics during weaning reduce the incidence of eczema
            West Pediatr Allergy Immunol 2009:20:430

           ...
The effects of selected probiotic strains on the
       development of eczema (the PandA study)
                      Nier...
The effects of selected probiotic strains on the
       development of eczema (the PandA study)
                      Nier...
The effects of selected probiotic strains on the
       development of eczema (the PandA study)
                       Nie...
The effects of selected probiotic strains on the
   development of eczema (the PandA study)
             Niers Allergy 200...
The effects of selected probiotic strains on the
   development of eczema (the PandA study)
             Niers Allergy 200...
Lactobacillus Reuteri Modulates Cytokines Production in
 Exhaled Breath Condensate of Children With Atopic
      Dermatiti...
Lactic acid bacteria differ in their ability to
  induce functional regulatory T cells in humans
               de Roock C...
Lactic acid bacteria differ in their ability to
       induce functional regulatory T cells in humans
                    ...
Lactic acid bacteria differ in their ability to
       induce functional regulatory T cells in humans
                    ...
High circulating immunoglobulin A levels in infants are
   associated with intestinal toxigenic Staphylococcus
        aur...
High circulating immunoglobulin A levels in infants are
   associated with intestinal toxigenic Staphylococcus
        aur...
High circulating immunoglobulin A levels in infants are
   associated with intestinal toxigenic Staphylococcus
        aur...
High circulating immunoglobulin A levels in infants are
   associated with intestinal toxigenic Staphylococcus
        aur...
High circulating immunoglobulin A levels in infants are
  associated with intestinal toxigenic Staphylococcus
       aureu...
• Antioxidants
• Antioxidants
Antioxidant nutrient intakes and corresponding
biomarkers associated with the risk of atopic dermatitis
    in young child...
• Risk factors
Gestational diabetes, atopic dermatitis, and
        allergen sensitization in early childhood
                     Kumar ...
Gestational diabetes, atopic dermatitis, and
        allergen sensitization in early childhood
                     Kumar ...
Gestational diabetes, atopic dermatitis, and
        allergen sensitization in early childhood
                     Kumar ...
Gestational diabetes, atopic dermatitis, and
         allergen sensitization in early childhood
                   Kumar J...
Gestational diabetes, atopic dermatitis, and
           allergen sensitization in early childhood
                        ...
Risk analysis of early childhood eczema
                    Bisgaard   JACI 2009;123:1355


                              ...
Risk analysis of early childhood eczema
                    Bisgaard    JACI 2009;123:1355

                              ...
Risk analysis of early childhood eczema
                 Bisgaard       JACI 2009;123:1355

                              ...
Risk analysis of early childhood eczema
             Bisgaard   JACI 2009;123:1355


 The mechanism by which exposure to ...
Risk analysis of early childhood eczema
             Bisgaard   JACI 2009;123:1355



 Length at birth exhibited an inver...
Filaggrin mutations in the onset of eczema, sensitization,
asthma, hay fever and the interaction with cat exposure.
      ...
Filaggrin mutations in the onset of
   eczema, sensitization, asthma, hay fever and the
    interaction with cat exposure....
Meta-analysis of filaggrin polymorphisms in eczema
  and asthma: Robust risk factors in atopic disease
               Rodr...
Meta-analysis of filaggrin polymorphisms in eczema
  and asthma: Robust risk factors in atopic disease
               Rodr...
Meta-analysis of filaggrin polymorphisms in eczema
  and asthma: Robust risk factors in atopic disease
               Rodr...
Maternal Asthma, its Control and Severity in Pregnancy
 and the Incidence of Atopic Dermatitis and Allergic
  Rhinitis in ...
Maternal Asthma, its Control and Severity in Pregnancy
 and the Incidence of Atopic Dermatitis and Allergic
  Rhinitis in ...
Maternal Asthma, its Control and Severity in Pregnancy
 and the Incidence of Atopic Dermatitis and Allergic
  Rhinitis in ...
Maternal meat and fat consumption during pregnancy and
    suspected atopic eczema in Japanese infants aged
 3–4 months: T...
Maternal meat and fat consumption during pregnancy and
    suspected atopic eczema in Japanese infants aged
 3–4 months: T...
Maternal meat and fat consumption during pregnancy and
    suspected atopic eczema in Japanese infants aged
 3–4 months: T...
Maternal meat and fat consumption during pregnancy and
     suspected atopic eczema in Japanese infants aged
  3–4 months:...
Prevalence and risk factors of wheeze and eczema in
1-year-old children: the Butajira birth cohort, Ethiopia
             ...
Prevalence and risk factors of wheeze and eczema in
1-year-old children: the Butajira birth cohort, Ethiopia
             ...
Prevalence and risk factors of wheeze and eczema in
1-year-old children: the Butajira birth cohort, Ethiopia
             ...
Prevalence and risk factors of wheeze and eczema in
1-year-old children: the Butajira birth cohort, Ethiopia
             ...
Swimming pool attendance and risk of allergic
                symptoms in children
                 Font-Ribera ERJ 2009:3...
Swimming pool attendance and risk of allergic
                symptoms in children
                Font-Ribera ERJ 2009:34...
• batteri
• funghi
• virus
Expression patterns of atopic eczema (AE) and
     respiratory illnesses in a high-risk birth cohort
                     ...
Expression patterns of atopic eczema (AE) and
     respiratory illnesses in a high-risk birth cohort
                     ...
ROLE OF STAPHYLOCOCCUS AUREUS NASAL
   COLONIZATION IN ATOPIC DERMATITIS IN INFANTS
               Lebon Arch Ped Adoles M...
ROLE OF STAPHYLOCOCCUS AUREUS NASAL
   COLONIZATION IN ATOPIC DERMATITIS IN INFANTS
               Lebon Arch Ped Adoles M...
ROLE OF STAPHYLOCOCCUS AUREUS NASAL
  COLONIZATION IN ATOPIC DERMATITIS IN INFANTS
            Lebon Arch Ped Adoles Med 2...
Infected atopic dermatitis lesions contain pharmacologic
  amounts of lipoteichoic acid. Travers JACI 2010:125:146


   Ba...
Infected atopic dermatitis lesions contain pharmacologic
  amounts of lipoteichoic acid. Travers JACI 2010:125:146


 89 ...
Infected atopic dermatitis lesions contain pharmacologic
  amounts of lipoteichoic acid. Travers JACI 2010:125:146


 89 ...
Infected atopic dermatitis lesions contain pharmacologic
  amounts of lipoteichoic acid. Travers JACI 2010:125:146

      ...
Infected atopic dermatitis lesions contain pharmacologic
  amounts of lipoteichoic acid. Travers JACI 2010:125:146

      ...
Secreted virulence factor comparison between methicillin-
resistant and methicillin-sensitive Staphylococcus aureus,
     ...
Phenotype of atopic dermatitis subjects with
          a history of eczema herpeticum
                Beck JACI 2009;124:2...
Phenotype of atopic dermatitis subjects with
            a history of eczema herpeticum
                   Beck JACI 2009;...
Phenotype of atopic dermatitis subjects with
            a history of eczema herpeticum
                   Beck JACI 2009;...
Phenotype of atopic dermatitis subjects with
      a history of eczema herpeticum
           Beck JACI 2009;124:260


    ...
Phenotype of atopic dermatitis subjects with
          a history of eczema herpeticum
                    Beck JACI 2009;1...
Phenotype of atopic dermatitis subjects with
      a history of eczema herpeticum
                Beck JACI 2009;124:260

...
Phenotype of atopic dermatitis subjects with
            a history of eczema herpeticum
                    Beck JACI 2009...
• atopy
• sensitization
Exploring the repertoire of IgE-binding
  self-antigens associated with atopic eczema
             Zeller JACI 2009;124:27...
Exploring the repertoire of IgE-binding
      self-antigens associated with atopic eczema
                  Zeller JACI 20...
High sensitization rate to food allergens in
       breastfed infants with atopic dermatitis
       Han Ann Allergy Asthma...
High sensitization rate to food allergens in
       breastfed infants with atopic dermatitis
       Han Ann Allergy Asthma...
High sensitization rate to food allergens in
       breastfed infants with atopic dermatitis
       Han Ann Allergy Asthma...
High sensitization rate to food allergens in
       breastfed infants with atopic dermatitis
        Han Ann Allergy Asthm...
High sensitization rate to food allergens in
       breastfed infants with atopic dermatitis
        Han Ann Allergy Asthm...
• Irritants
Temperature modulated histamine-itch in lesional
   and nonlesional skin in atopic eczema – a combined
        psychophysi...
Temperature modulated histamine-itch in lesional
   and nonlesional skin in atopic eczema – a combined
        psychophysi...
• Pathogenesis
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Ceramide biosynthesis in keratinocyte and its role in
     skin function Y Mizutani Biochimie 2009;91:784
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892


                    ...
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Epidermal Barrier Dysfunction in Atopic Dermatitis
       M J. Cork J Invest Dermatol 2009;129:1892

                     ...
Broad defects in epidermal cornification in atopic
     dermatitis identified through genomic analysis
              Guttm...
Broad defects in epidermal cornification in atopic
 dermatitis identified through genomic analysis
        Guttman-Yassky ...
Mite serine protease activates protease-activated receptor-2
    and induces cytokine release in human keratinocytes
     ...
Mite serine protease activates protease-activated receptor-2
    and induces cytokine release in human keratinocytes
     ...
Filaggrin deficiency confers a paracellular barrier abnormality
that reduces inflammatory thresholds to irritants and hapt...
Filaggrin mutations that confer risk of atopic
dermatitis confer greater risk for eczema herpeticum
             Pei-Song ...
Filaggrin mutations that confer risk of atopic
 dermatitis confer greater risk for eczema herpeticum
               Pei-So...
Filaggrin mutations that confer risk of atopic
 dermatitis confer greater risk for eczema herpeticum
               Pei-So...
• Diagnosis
• Contact dermatitis
treatment
UV-B–triggered induction of vitamin D3 metabolism
  differentially affects antimicrobial peptide expression
         in ke...
UV-B–triggered induction of vitamin D3 metabolism
 differentially affects antimicrobial peptide expression
        in kera...
UV-B–triggered induction of vitamin D3 metabolism
 differentially affects antimicrobial peptide expression
        in kera...
• Treatment
    general consideration
Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
  table meeting ...
Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
  table meeting ...
Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
  table meeting ...
Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
  table meeting ...
Bathing and cleansing in newborns from day 1 to first
year of life: recommendations from a European round
  table meeting ...
• Treatment
    exclusion diet
• Treatment
    emolients
Skin barrier breakdown: a renaissance in emollient
         therapy. Cork MJ, Br J Nurs. 2009;18:872
Within the corneocyte...
Skin barrier breakdown: a renaissance in emollient
          therapy. Cork MJ, Br J Nurs. 2009;18:872
It is important that...
Skin barrier breakdown: a renaissance in emollient
         therapy. Cork MJ, Br J Nurs. 2009;18:872
 Breakdown of the ski...
Skin barrier breakdown: a renaissance in emollient
      therapy. Cork MJ, Br J Nurs. 2009;18:872
As a result of these dec...
Skin barrier breakdown: a renaissance in emollient
      therapy. Cork MJ, Br J Nurs. 2009;18:872
   Effects of a genetic ...
Skin barrier breakdown: a renaissance in emollient
      therapy. Cork MJ, Br J Nurs. 2009;18:872
 Effects of a genetic pr...
Skin barrier breakdown: a renaissance in emollient
        therapy. Cork MJ, Br J Nurs. 2009;18:872
Complete emollient the...
Skin barrier breakdown: a renaissance in emollient
         therapy. Cork MJ, Br J Nurs. 2009;18:872
In their simplest for...
Skin barrier breakdown: a renaissance in emollient
      therapy. Cork MJ, Br J Nurs. 2009;18:872
The most important deter...
Skin barrier breakdown: a renaissance in emollient
        therapy. Cork MJ, Br J Nurs. 2009;18:872

•If a patient likes a...
Skin barrier breakdown: a renaissance in emollient
        therapy. Cork MJ, Br J Nurs. 2009;18:872

•Emollient regimens c...
• Treatment
antibiotics
Empiric Antimicrobial Therapy for Pediatric Skin and
Soft-Tissue Infections in the Era of Methicillin-Resistant
  Staphylo...
Empiric Antimicrobial Therapy for Pediatric Skin and
Soft-Tissue Infections in the Era of Methicillin-Resistant
  Staphylo...
Empiric Antimicrobial Therapy for Pediatric Skin and
 Soft-Tissue Infections in the Era of Methicillin-Resistant
   Staphy...
Atopic dermatitis
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Atopic dermatitis

  1. 1. WHAT YOU SHOULD HAVE READ BUT….2010  atopic dermatitis Attilio Boner University of Verona, Italy
  2. 2. • Differential Diagnosis
  3. 3. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of the patient for growth, lymphoid tissue (X-linked agammaglobulenemia), allow Lymph nodes are very small. for proper direction toward making No cervical lymph nodes and no tonsills the diagnosis of primary immunodeficiency.
  4. 4. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of the patient for telangiectasias (ataxia-telangiectasia), allow for proper direction toward making the diagnosis of primary immunodeficiency.
  5. 5. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of the patient for abnormal facies (DiGeorge syndrome), allow for proper direction toward making the diagnosis of primary immunodeficiency. no thymus
  6. 6. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of the patient for chronic eczema (Wiskott-Aldrich syndrome, Wiskott-Aldrich syndrome hyper-IgE syndrome, and immune (WAS) is a condition with dysregulation polyendocrinopathy variable expression, but enteropathy X-linked syndrome), allow commonly includes IgM deficiency and persistent for proper direction toward making the thrombocytopenia diagnosis of primary immunodeficiency.
  7. 7. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of the patient for chronic eczema (Wiskott-Aldrich syndrome, hyper-IgE syndrome, and immune dysregulation polyendocrinopathy enteropathy X-linked syndrome), allow for proper direction toward making the diagnosis of primary immunodeficiency.
  8. 8. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary a syndrome of variable autoimmune immunodeficiency must include a features including eczema, enteropathies, hemolytic anemia, and physical examination of the patient endocrinopathies (diabetes mellitus because the powers of observation and thyroid pathology), abnormal should direct the evaluation for several responses to viral infections; associated death in infancy or early types of primary immunodeficiency. childhood For example, simple inspection of the patient for chronic eczema (Wiskott-Aldrich syndrome, hyper-IgE syndrome, and immune dysregulation polyendocrinopathy enteropathy X-linked syndrome), allow for proper direction toward making the diagnosis of primary immunodeficiency.
  9. 9. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of bone marrow the patient for pale skin and smears show photophobia "giant inclusion bodies" in the (Chediak-Higashi syndrome), allow cells for proper direction toward making the diagnosis of primary It is a disease with impaired bacteriolysis due immunodeficiency. to failure of phagolysosome formation. so phagocytosed bacteria are not destroyed
  10. 10. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for primary immunodeficiency must include a physical examination of the patient because the powers of observation should direct the evaluation for several types of primary immunodeficiency. For example, simple inspection of Leukocyte adhesion deficiency (LAD) the patient for severe is a rare primary immunodeficiency.1 gingivostomatitis (leukocyte The clinical picture is characterized by marked leukocytosis and localized adhesion defect) allow for proper bacterial infections that are difficult direction toward making the to detect until they have progressed diagnosis of primary to an extensive level secondary to lack of leukocyte recruitment at the immunodeficiency. site of infection.
  11. 11. Diagnosis of primary immunodeficiency: Let your eyes do the talking. Shah JACI 2009:124:1363 Every screening evaluation for Leukocyte adhesion deficiency type I primary immunodeficiency must (LAD I) may be diagnosed prior to the onset of infections when delayed include a physical examination of umbilical cord separation (normal the patient because the powers of separation is 3-45 d, with a mean of 10 observation should direct the d) is observed with a persistently high WBC count (>20 X 109/L) in the absence evaluation for several types of of infection. Patients with leukocyte primary immunodeficiency. adhesion deficiency I typically For example, simple inspection of experience from omphalitis, perirectal and labial cellulitis, infections the patient for severe classically seen in patients with gingivostomatitis (leukocyte neutropenia, otitis media with minimal adhesion defect) allow for proper inflammation, and other indolent necrotic skin infections. Pus is not direction toward making the present, but serosanguineous fluids diagnosis of primary may be present. immunodeficiency.
  12. 12. • Prevalence
  13. 13. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three Odhiambo JACI 2009:124:1251 715,033 children from 154 centers in 56 countries. For the age group 6 to 7 years the prevalence of current eczema ranged from 0.9% in India to 22.5% in Ecuador. For the age group 13 to 14 years prevalence values ranging from 0.2% in China to 24.6% in Columbia. Current eczema was lower for boys than girls (odds ratio, 0.94 and 0.72 at ages 6 to 7 years and 13 to 14 years.
  14. 14. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three Odhiambo JACI 2009:124:1251 World maps showing prevalence of current symptoms of eczema for the age group 6 to 7 yrs. Blue squares indicate prevalence < 5%, green circles indicate prevalence of 5% to < 10%, yellow diamonds indicate prevalence of 10% to < 15%, red stars indicate prevalence ≥ 15% The prevalence of atopic dermatitis in Italy is 10% to 15%
  15. 15. Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three Odhiambo JACI 2009:124:1251 World maps showing prevalence of current symptoms of eczema for the age group 13 to 14 yrs. Blue squares indicate prevalence < 5%, green circles indicate prevalence of 5% to < 10%, yellow diamonds indicate prevalence of 10% to < 15%, red stars indicate prevalence ≥ 15% The prevalence of atopic dermatitis in Italy is 5% to 10%
  16. 16. • burden
  17. 17. Infant-onset eczema in relation to mental health problems at age 10 years: Results from a prospective birth cohort study (German Infant Nutrition Intervention plus) Schmitt JACI 2010;125:404  A birth cohort (n=2916) In children with infant-onset followed until age 10 eczema OR for years. 2.0 –  Association between 1.5 – 1.62 infant-onset eczema 1.49 1.31 (age 1-2 years) and 1.0 – mental health problems P=0.005 P<0.001 P=0.08 at age 10 years 0.5 – according to the Strengths and 0 Difficulties possible/probable emotional conduct Questionnaire. mental health symptoms problems problems
  18. 18. Infant-onset eczema in relation to mental health problems at age 10 years: Results from a prospective birth cohort study (German Infant Nutrition Intervention plus) Schmitt JACI 2010;125:404  A birth cohort (n=2916) In children with infant-onset followed until age of The strength 10 eczema OR for years. 2.0 – the association between eczema  Association between and emotional 1.5 – 1.62 infant-onset at age problems eczema 1.49 1.31 (age 1-2 years) and 1.0 – 10 years mental health problems increased with P=0.005 P<0.001 P=0.08 at age 10 years 0.5 – increasing eczema according to the persistence. Strengths and 0 Difficulties possible/probable emotional conduct Questionnaire. mental health symptoms problems problems
  19. 19. Increased risk of serious pneumococcal disease (SPD) in patients with atopic conditions other than asthma Jung JACI 2010:125:217 Background: We reported an increased risk of serious pneumococcal disease (SPD) among patients with asthma. It is not known whether this is true for patients with other atopic conditions. Objective: To determine the relationship between atopic conditions other than asthma and SPD.
  20. 20. Increased risk of serious pneumococcal disease (SPD) in patients with atopic conditions other than asthma Jung JACI 2010:125:217 2.5 – OR FOR SPD 2.13 2.0 – Between 1964 and 1983 1.5 – 174 serious P=0.04 1.0 – pneumococcal disease (SPD) cases. 0.5 – 0 ATOPIC CONDITIONS OTHER THAN ASTHMA
  21. 21. Increased risk of serious pneumococcal disease (SPD) in patients with atopic conditions other than asthma Jung JACI 2010:125:217 2.5 – OR FOR SPD Like asthma, other atopic 2.13 2.0 – conditions, particularly Between 1964 and 1983 atopic dermatitis, 1.5 – 174 SPD cases. with an P=0.04 are associated 1.0 – increased risk of SPD. 0.5 – 0 ATOPIC CONDITIONS OTHER THAN ASTHMA
  22. 22. • The atopic march
  23. 23. Correlates of outcome for atopic dermatitis Horwitz Ann Allergy Asthma Immunol 2009;103:146 % Patients with Persistent AD at Age ≥ 5 Yrs 80 – 75.1% 70 –  To identify significant correlates of 60 – persistent AD. 50 – 40 –  177 patients with AD 30 – (5-18 years.) 20 – 10 – 0
  24. 24. Correlates of outcome for atopic dermatitis Horwitz Ann Allergy Asthma Immunol 2009;103:146 4.5 – OR for Persistant Atopic Dermatitis at ≥ 5 years 4.0 – 3.5 – 4.02 3.0 – 2.5 – 2.0 – 2.93 2.71 1.5 – 1.0 – 0.5 – 0 Peanut Egg Mite ALLERGY TO
  25. 25. Correlates of outcome for atopic dermatitis Horwitz Ann Allergy Asthma Immunol 2009;103:146 4.5 – OR for Persistant Atopic Dermatitis 4.0 – 3.5 – Egg, peanut, and dust mite4.02 3.0 – allergies are significant 2.5 – 2.0 – 2.93 correlates of AD persisting 2.71 beyond school age. 1.5 – 1.0 – 0.5 – 0 Peanut Egg Mite ALLERGY TO
  26. 26. Early exposure to solid foods and the development of eczema in children up to 4 years of age Sariachvili Pediatr Allergy Immunol 2010:21:74 In Children with Early Introduction  Birth cohort (within the First 4 Months) of Solid Foods OR for  252 children with 1.0 – eczema (cases) and 305 children without eczema (controls). 0.5 – 0.69 0.49 0.35  Timing of 0 introduction of ECZEMA UP TO ECZEMA IN ECZEMA IN CHILDREN WITH CHILDREN WITH NO solid foods. THE AGE 4 YRS ALLERGIC PARENTS ALLERGIC PARENTS
  27. 27. Early exposure to solid foods and the development of eczema in children up to 4 years of age Sariachvili Pediatr Allergy Immunol 2010:21:74 In Children with Early Introduction  PIPO cohort (within the First 4 Months) of Solid (Prospective Cohort The current study Foods OR for on doesInfluence of a 1.0 – the not support Perinatal Factors on delayed introduction the Occurrence offor of solid foods Asthmaprevention of 0.5 – the and Allergies). 0.69 eczema in childhood. 0.49 0.35  Timing of introduction of 0 solid foods. ECZEMA UP TO THE AGE 4 YRS ECZEMA IN ECZEMA IN CHILDREN WITH CHILDREN WITH NO ALLERGIC PARENTS ALLERGIC PARENTS
  28. 28. Early exposure to solid foods and the development of eczema in children up to 4 years of age Sariachvili Pediatr Allergy Immunol 2010:21:74 In Children with Early Introduction  PIPO cohort A possible (within the First 4 Months) of Solid (Prospective Cohort explanation for the Foods OR for on the Influence of 1.0 – 'protective' effect Perinatal Factors on of early introduction theof solids on the Occurrence of Asthma and development of Allergies). 0.5 – 0.69 eczema may be the induction of oral 0.49 0.35  Timing of tolerance for foods. 0 introduction of solid foods. ECZEMA UP TO THE AGE 4 YRS ECZEMA IN ECZEMA IN CHILDREN WITH CHILDREN WITH NO ALLERGIC PARENTS ALLERGIC PARENTS
  29. 29. Early exposure to solid foods and the development of eczema in children up to 4 years of age Sariachvili Pediatr Allergy Immunol 2010:21:74 In Children with Early Introduction  PIPO cohort (within the First 4 Months) of Solid Continuation of (Prospective Cohort Foods OR for exposure of the 1.0 – on the Influence of immune system to Perinatal Factors on certain allergenic the Occurrence of food proteins once Asthma and responsible for 0.5 – Allergies). 0.69 allergy, may help to 0.49  Timing of tolerance maintain 0.35 to this food. introduction of 0 solid foods. ECZEMA UP TO THE AGE 4 YRS ECZEMA IN ECZEMA IN CHILDREN WITH CHILDREN WITH NO ALLERGIC PARENTS ALLERGIC PARENTS
  30. 30. • protective factors
  31. 31. • intestinal flora • probiotics
  32. 32. Probiotics during weaning reduce the incidence of eczema West Pediatr Allergy Immunol 2009:20:430 THE CUMULATIVE INCIDENCE OF ECZEMA AT 13 MONTHS 25 –  Lactobacillus F19 during weaning. 22% 20 –  Incidence of eczema and 15 – p<0.05 Th1/Th2 balance.  Infants were fed cereals 10 – with (n = 89) or without 05 – 11% Lactobacillus F19 (n = 90) from 4 to 13 months of age. 0 PROBIOTICS PLACEBO
  33. 33. Probiotics during weaning reduce the incidence of eczema West Pediatr Allergy Immunol 2009:20:430 THE CUMULATIVE INCIDENCE OF ECZEMA AT 13 MONTHS 25 –  Lactobacillus F19 during weaning. 22% 20 – The number  Incidence of eczema and p<0.05 needed to Th1/Th2 balance. 15 – treat was 9.  Infants were fed cereals 10 – with (n = 89) or without 05 – 11% Lactobacillus F19 (n = 90) from 4 to 13 months of age. 0 PROBIOTICS PLACEBO
  34. 34. Probiotics during weaning reduce the incidence of eczema West Pediatr Allergy Immunol 2009:20:430 IFN-γ /IL4 mRNA ratio levels in peripheral blood mononuclear cells of 13 months old infants  Lactobacillus F19 during weaning.  Incidence of eczema and Th1/Th2 balance.  Infants were fed cereals P<0.05 with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age.
  35. 35. The effects of selected probiotic strains on the development of eczema (the PandA study) Niers Allergy 2009:64:1349  Double-blind, placebo- % children with eczema controlled trial. at age 3 month  A mixture of probiotic bacteria (Bifidobacterium bifidum, Bifidobacterium lactis, and Lactococcus lactis; p=0.035 Ecologic® Panda). p=0.021  Prenatally administered to mothers of high-risk children and to their offspring (n=156) for the first 12 months of life.
  36. 36. The effects of selected probiotic strains on the development of eczema (the PandA study) Niers Allergy 2009:64:1349  Double-blind, placebo- controlled trial.  A mixture of probiotic bacteria (Bifidobacterium bifidum, Bifidobacterium P<0.05 lactis, and Lactococcus lactis; Ecologic® Panda).  Prenatally administered to mothers of high-risk children and to their offspring (n=156) for the first 12 months of life.
  37. 37. The effects of selected probiotic strains on the development of eczema (the PandA study) Niers Allergy 2009:64:1349  Double-blind, placebo- controlled trial. This particular combination of probiotic  A mixture of probiotic bacteria shows a bacteria (Bifidobacterium preventive effect on the P<0.05 bifidum, Bifidobacterium incidence of eczema in lactis, and Lactococcus lactis; high-risk children, Ecologic® Panda). which seems to be sustained during the  Prenatally administered to first 2 years of life. mothers of high-risk children and to their offspring (n=156) for the first 12 months of life.
  38. 38. The effects of selected probiotic strains on the development of eczema (the PandA study) Niers Allergy 2009:64:1349 Real-time PCR quantification of Lactococcus lactis (A) and Bifidobacterium spp (B) in stool samples
  39. 39. The effects of selected probiotic strains on the development of eczema (the PandA study) Niers Allergy 2009:64:1349 The number of Lc. lactis is significantly (P<0.0001) higher in the probiotic group during the first year of life. Real-time PCR quantification of Lactococcus lactis (A) and Bifidobacterium spp (B) in stool samples
  40. 40. Lactobacillus Reuteri Modulates Cytokines Production in Exhaled Breath Condensate of Children With Atopic Dermatitis Miniello J Ped Gast Nut 2010;in press IL-4 and IFN-Υ concentration in children with nonatopic (lined boxes) and atopic (empty boxes) eczema after 51 patients, treatment with Lactobacillus reuteri or placebo 4 to 10 years referred due to AD L. reuteri chewable tablets or placebo for 8 weeks Breath condensate IL-4 INF-Υ
  41. 41. Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans de Roock CEA 2010; 40:103 Background: Trials with probiotic lactic acid bacteria have yielded different results, which may be due to the strains used. Lactobacilli and bifidobacteria are known to be potent modulators of the immune system. The capacity of these bacteria used as probiotics to influence both T helper type 1 (Th1)- and Th2-mediated diseases has been shown before. However, the ability of strains to induce forkhead box P3 (FOXP3+) expressing regulatory T cells has not yet been investigated.
  42. 42. Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans de Roock CEA 2010; 40:103  Human PBMC were co-cultured in vitro with either Bifidobacterium lactis W51, Lactobacillus acidophilus W55 or Lactobacillus plantarum W62 or an Escherichia coli control strain.  Percentage of FOXP3+ cells Induction of CD25+forkhead box P3 (FOXP3+) cells by bacteria in peripheral blood mononuclear cells (PBMC).
  43. 43. Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans de Roock CEA 2010; 40:103  Human PBMC were Some probiotic strains co-cultured in vitro with are potent inducers of either regulatory cells, while Bifidobacterium lactis W51, others are not. The clear Lactobacillus acidophilus differences between W55 or strains imply that an in Lactobacillus plantarum vitro characterization of W62 or an probiotic strains before Escherichia coli control application is strain. recommended.  Percentage of FOXP3+ cells Induction of CD25+forkhead box P3 (FOXP3+) cells by bacteria in peripheral blood mononuclear cells (PBMC).
  44. 44. High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema Lundell CEA 2009;39:662  IgA in plasma from infants at birth and at 4 and 18 months.  Colonization in the first 8 weeks of life by quantitative culture of stool samples. Plasma levels of IgA
  45. 45. High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema Lundell CEA 2009;39:662  IgA in plasma from P<0.05 infants at birth and at 4 and 18 months.  Colonization in the first 8 weeks of life by quantitative culture of stool samples. Intestinal colonization by toxigenic or non-toxigenic Staphylococcus aureus and levels of IgA in plasma.
  46. 46. High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema Lundell CEA 2009;39:662  IgA in plasma from infants at birth and at 4 and 18 months.  Colonization in the first 8 weeks of life by quantitative culture of stool samples.
  47. 47. High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema Lundell CEA 2009;39:662 Early intestinal  IgA in plasma from infants at birth by colonization and toxigenic S. aureus at 4 and 18 months. strains seems to promote systemic  Colonization in the IgA responses and first 8 weeks of life seem to correlate by quantitative culture negatively with of allergy samples. stool development.
  48. 48. High circulating immunoglobulin A levels in infants are associated with intestinal toxigenic Staphylococcus aureus and a lower frequency of eczema Lundell CEA 2009;39:662  IgA in plasma from infants Bacterialand at birth at 4 and 18 months. colonization trigger the  Colonization in the production first 8 weeks of life of T-reg cells. by quantitative culture of stool samples.
  49. 49. • Antioxidants
  50. 50. • Antioxidants
  51. 51. Antioxidant nutrient intakes and corresponding biomarkers associated with the risk of atopic dermatitis in young children. Oh SY, Eur J Clin Nutr. 2010;64:245. 180 AD children OR for Eczema in Children with the (mean age 5.3 yrs) highest (vs lowest) quintile 1.0 – 242 non-AD (mean age 5.2 yrs) children. 0.5 – Diet assessed using a validated 0.44 0.33 0.37 semi-quantitative 0 food frequency questionnaire Β-carotene Vitamin E Folic Acid
  52. 52. • Risk factors
  53. 53. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood Kumar JACI 2009;124:1031 % MOTHERS 5 –  680 children from the Boston 4 – 4.9% Birth Cohort. 3 –  Followed to a 2 – mean age of 1 – 3.2 ± 2.3 years. 0 GESTATIONAL DIABETES (GDM)
  54. 54. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood Kumar JACI 2009;124:1031 OR in Term Children Born from 10 – Mothers with Gestational Diabetes 9 –  680 children 8 – from the Boston 7 – 8.3 6 – 7.7 Birth Cohort. 5 – 4 – 5.7  Followed to a 3 – mean age of 2 – 3.2 ± 2.3 years. 1 – 0 ATOPIC ALLERGEN FOOD DERMATITIS SENSITIZATION SENSITIZATION
  55. 55. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood Kumar JACI 2009;124:1031 OR in Term Children Born from 10 – Mothers with Gestational Diabetes 9 –  680 children 8 – fromThe above the Boston 7 – 8.3 6 – 7.7 Birth Cohort.were associations 5 – not observed in 4 – 5.7  Followed to a preterm births. 3 – mean age of 2 – 3.2 ± 2.3 years. 1 – 0 ATOPIC ALLERGEN FOOD DERMATITIS SENSITIZATION SENSITIZATION
  56. 56. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood Kumar JACI 2009;124:1031 OR in Term Children Born from These data 10 – Mothers with Gestational Diabetes suggest that, at 9 –  680least in term children 8 – fromThe above infants, Boston the prenatal 7 – 8.3 associations risk metabolic 6 – 7.7 Birth Cohort.were 5 – factors increase not observed in 4 – 5.7  Followed of allergic the risk to a preterm births. 3 – disease and mean age of 2 – sensitization in 3.2 ± early life. 2.3 years. 1 – 0 ATOPIC ALLERGEN FOOD DERMATITIS SENSITIZATION SENSITIZATION
  57. 57. Gestational diabetes, atopic dermatitis, and allergen sensitization in early childhood Kumar JACI 2009;124:1031 Mothers with GDM have higher levels of TNF-α, leptin, and visfatin, as well as lower levels of adiponectin. Adiponectin attenuates allergic inflammation in murine models. Thus it is possible that altered levels of adipokines associated with GDM might have some effect on immunologic development in infancy. Krzyzanowska K. Clin Sci (Lond) 2006;110:605–609 Lewandowski KC. Diabetologia 2007;50:1033–1037 Gao XL. Chin Med J (Engl) 2008;121:701–705 Shore SA . J Allergy Clin Immunol 2008;121:1087–1095
  58. 58. Risk analysis of early childhood eczema Bisgaard JACI 2009;123:1355 % INFANTS  Copenhagen Study 45 – on Asthma in 40 – Childhood 35 – 43.5%  A birth cohort 30 – (411 children born 25 – of mothers with 20 – asthma). 15 – 10 –  Follow-up 3 yrs 5 – of life. 0 Developing Eczema
  59. 59. Risk analysis of early childhood eczema Bisgaard JACI 2009;123:1355 OR FOR ONSET OF ECZEMA 3.5 – IN CHILDREN  Copenhagen Study 3.0 – on Asthma in 3.2 Childhood 2.5 – P=0.004 2.8  A birth cohort 2.0 – P<0.0001 (411 children born of mothers with 1.5 – 1.91 P=0.02 asthma). 1.0 – 0.5 –  Follow-up 3 yrs of life. 0 FILLAGRIN MOTHER FATHER WITH MUTATIONS WITH ALLERGIC ECZEMA RHINITIS
  60. 60. Risk analysis of early childhood eczema Bisgaard JACI 2009;123:1355 OR FOR ONSET OF ECZEMA 3.5 – IN CHILDREN  Copenhagen Study Risk of eczema 3.0 – on Asthma in was significantly 3.2 Childhood by birth reduced 2.5 – P=0.004 2.8  A birthlength cohort 2.0 – P<0.0001 (411 (OR per born children cm ofincrease, with mothers 0.87; 1.5 – 1.91 P=0.02 P = 0.02) asthma). and dog 1.0 – living in the home 0.5 –  Follow-up 3 yrs (OR, 0.44; of life. = 0.02) P 0 FILLAGRIN MOTHER FATHER WITH MUTATIONS WITH ALLERGIC ECZEMA RHINITIS
  61. 61. Risk analysis of early childhood eczema Bisgaard JACI 2009;123:1355  The mechanism by which exposure to dogs around birth protects against eczema is unknown.  We speculate that the particular microbiology carried by pets may be mediating their effect on disease expression. Alternatively, having dog is a surrogate measure of other particular lifestyle factors, which needs to be explored in future studies.
  62. 62. Risk analysis of early childhood eczema Bisgaard JACI 2009;123:1355  Length at birth exhibited an inverse association to risk of eczema after confounder adjustment.  Our observation suggests an association between intrauterine growth and eczema, and lends support to the theory of intrauterine programming as a determinant of the risk of eczema.
  63. 63. Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Schuttelaar Allergy 2009:64:1758 OR IN FLG MUTATIONS 4.0 –  FLG mutations R501X, 3.7 3.5 – 2282del4 and R2447X. 3.0 –  Prevention and Incidence 2.5 – of Asthma and Mite Allergy 2.0 – birth cohort (n = 934). 1.5 – 1.0 – 2.0  For up to 8 years 0.5 – 0 ECZEMA ASTHMA
  64. 64. Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Schuttelaar Allergy 2009:64:1758 10 – OR IN FLG MUTATIONS 9 – 8 –  FLG mutations R501X, 2282del4 and R2447X. 7 – 8.2 6 – 5 –  Prevention and Incidence of Asthma and Mite Allergy 4 – 5.4 3 – birth cohort (n = 934). 2 – 1 –  For up to 8 years 0 ECZEMA AT ECZEMA AT AGE 1 YR AGE 8 YRS IN CAT EXPOSED SUBJECTS
  65. 65. Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease Rodríguez JACI 2009;123:1361  24 studies on FLG OR FOR ECZEMA 3.5 – mutations and 3.12 3.0 – eczema involving. 2.5 –  5,791 cases, 26,454 2.0 – control subjects. 1.5 –  17 studies on asthma 1.0 – involving 3,138 cases, 17,164 control 0.5 – subjects 0 IN FLG HAPLOINSUFFICIENCY
  66. 66. Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease Rodríguez JACI 2009;123:1361  24 studies on FLG OR FOR ASTHMA 2.0 – mutations and eczema involving. 1.5 –  5,791 cases, 26,454 control subjects. 1.0 – 1.48  17 studies on asthma involving 3,138 cases, 0.5 – 17,164 control subjects 0 IN FLG HAPLOINSUFFICIENCY
  67. 67. Meta-analysis of filaggrin polymorphisms in eczema and asthma: Robust risk factors in atopic disease Rodríguez JACI 2009;123:1361  24 studies on FLG OR FOR ECZEMA 3.5 – & ASTHMA mutations and 3.29 3.0 – eczema involving. 2.5 –  5,791 cases, 26,454 2.0 – control subjects. 1.5 –  17 studies on asthma 1.0 – involving 3,138 cases, 17,164 control 0.5 – subjects 0 IN FLG HAPLOINSUFFICIENCY
  68. 68. Maternal Asthma, its Control and Severity in Pregnancy and the Incidence of Atopic Dermatitis and Allergic Rhinitis in the Offspring M Martel, J Ped 2009;155:707 HR in children 2 – atopic dermatitis allergic  26.265 singletons rhinitis born to mothers with 1 – and without asthma 1.11 1.04 0 Maternal asthma during pregnancy
  69. 69. Maternal Asthma, its Control and Severity in Pregnancy and the Incidence of Atopic Dermatitis and Allergic Rhinitis in the Offspring M Martel, J Ped 2009;155:707 HR in children Maternal AR and intranasal 2 – corticosteroid atopic dermatitis allergic  26.265during use singletons rhinitis pregnancy born to mothers with 1 – increased the and without asthma 1.11 1.04 risk of childhood AR by 70% and 45% 0 Maternal asthma during pregnancy
  70. 70. Maternal Asthma, its Control and Severity in Pregnancy and the Incidence of Atopic Dermatitis and Allergic Rhinitis in the Offspring M Martel, J Ped 2009;155:707 Children of HR in children mothers with asthma or AR 2 – atopic during pregnancy allergic  26.265 singletons dermatitis should be closely rhinitis bornmonitored to with to mothers 1 – diagnose and without asthma 1.11 1.04 and treat AD and AR as early as 0 possible Maternal asthma during pregnancy
  71. 71. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 % Infants With Atopic Dermatitis at 3-4 771 mother–child pairs. 10 – Months 9 – Maternal dietary intake 8 – during pregnancy. Questionnaire 7 6 – – 8.4% 5 – completed by mothers 4 – 3–4 months postpartum. 3 – 2 – 1 – 0
  72. 72. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 OR for Doctor Diagnosis of 4.0 – Atopic Eczema in Infants 771 mother–child pairs. 3.5 – Maternal dietary intake 3.0 – 2.5 – 3.53 during pregnancy. 2.0 – p=0.02 Questionnaire 1.5 – completed by mothers 1.0 – 3–4 months postpartum. 0.5 – 0 HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY
  73. 73. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 OR for Doctor Diagnosis of 4.0 – Atopic Eczema in Infants 771 mother–child pairs. Certain components of 3.5 – meat may affect Maternal dietary intake 3.0 – 3.53 foetal immune 2.5 – during pregnancy. responses. 2.0 – p=0.02 Questionnaireprimary Meat is a 1.5 – completed of saturated source by mothers 1.0 – 3–4 months postpartum. fatty acids. 0.5 – 0 HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY
  74. 74. Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3–4 months: The Osaka Maternal and Child Health Study Saito Pediatr Allergy Immunol 2010:21:38 OR for Doctor Diagnosis of 4.0 – Atopic Eczema in Infants 771 mother–child pairs. The formation of 3.5 – heterocyclic amines Maternal dietary intake 3.0 – 3.53 during cooking and 2.5 – during pregnancy. in nitroso compounds 2.0 – p=0.02 Questionnaire processed meat are 1.5 – indicated as plausible completed by mothers 1.0 – mechanisms. 3–4 months postpartum. 0.5 – 0 HIGHEST VS LOWEST QUARTILE OF MEAT CONSUMPTION DURING PREGNANCY
  75. 75. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun CEA 2010; 40:619 15 – % Children at 1 Year with  1065 pregnant 10 – 11.5% women. 8.6% 05 –  At 1 year of age, data on wheeze and eczema in 0 the children. Wheeze Eczema
  76. 76. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun CEA 2010; 40:619 OR for Eczema 4.0 – 3.68 3.5 – 3.0 –  1065 pregnant 2.5 – women. 2.0 – 2.6 1.5 –  At 1 year of age, 1.0 – data on wheeze 0.5 – and eczema in 0 the children. Maternal allergic Paracetamol use history by the child
  77. 77. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun CEA 2010; 40:619 OR for Wheeze OR for Eczema 11 – 10 – 11.0 4.0 – 3.68 9 – 3.5 – 8 – 3.0 – 7 – 2.5 – 6 – 5 – 2.0 – 2.6 4 – 1.5 – 3 – 2 – 3.0 1.0 – 0.5 – 1 – 0 0 Maternal allergic Paracetamol use Maternal allergic Paracetamol use history by the child history by the child
  78. 78. Prevalence and risk factors of wheeze and eczema in 1-year-old children: the Butajira birth cohort, Ethiopia Belyhun CEA 2010; 40:619 OR for Eczema 1.5 – 1.48 1.0 –  1065 pregnant 1.0 women. 0.5 –  At 1 year of age, 0.42 data on wheeze 0 and eczema in Bed Floor Grass Matting the children. Child’s Sleeping Place
  79. 79. Swimming pool attendance and risk of allergic symptoms in children Font-Ribera ERJ 2009:34:1304 OR for eczema in those  3,223 9–12-yr-old children attending swimming pool in Sabadell (Spain). >5 yrs versus 0 yrs 2 –  Questionnaire on lifetime frequency of pool attendance and symptoms 1.71 in the last 12 months 1 – (wheezing, asthma medication, rhinitis and allergic rhinitis).  eczema 0
  80. 80. Swimming pool attendance and risk of allergic symptoms in children Font-Ribera ERJ 2009:34:1304 OR for eczema in those  3,223 9–12-yr-old children attending swimming pool An increased >5 yrs versus 0 yrs in Sabadell (Spain). prevalence of eczema 2 –  Questionnaire on with was associated duration of lifetime lifetime frequency of pool pool attendance attendance and symptoms 1.71 in(OR 1.71, for >5 yrs the last 12 months versus 0 yrs). 1 – (wheezing, asthma medication, rhinitis and allergic rhinitis).  eczema 0
  81. 81. • batteri • funghi • virus
  82. 82. Expression patterns of atopic eczema (AE) and respiratory illnesses in a high-risk birth cohort Singh JACI 2010;125:491 70 – % children  Natural history of AE 60 – in children (n=287) 62% enrolled in the 50 – Childhood Origin of 40 – ASThma (COAST) study, a high-risk 30 – birth cohort composed 20 – of children with 24% parental histories of 10 – 14% asthma and/or 0 allergies never had AE or had a transient course little or no disease in the first 3 years of life, and early and persistent skin manifestations then developed AE in years throughout the period 4 to 6 (late-onset AE) of observation.
  83. 83. Expression patterns of atopic eczema (AE) and respiratory illnesses in a high-risk birth cohort Singh JACI 2010;125:491 70 – % children  Natural history of AE Contrary 60 – in childrenhygiene to the (n=287) 62% hypothesis children enrolled in the 50 – with early/recurrent Childhood Origin of AE had more ASThma (COAST) 40 – moderate-to severe study, a high-risk 30 – viral respiratory birth cohort composed illnesses in the first 20 – year of life with of children compared 24% parental histories of with the healthy/ 10 – 14% asthma and/or transient group 0 allergies .02) (P=0 never had AE or had a transient course little or no disease in the first 3 years of life, and early and persistent skin manifestations then developed AE in years throughout the period 4 to 6 (late-onset AE) of observation.
  84. 84. ROLE OF STAPHYLOCOCCUS AUREUS NASAL COLONIZATION IN ATOPIC DERMATITIS IN INFANTS Lebon Arch Ped Adoles Med 2009;163:745 In children colonized with S.Aureus at 6 mo OR for Atopic Dermatitis 3 –  1079 children  Nasal swabs for 2 – 2.88 S. aureus cultivation were 2.13 taken at ages 1.5, 1 – 6, and 14 months 0 1st year 2nd year of life
  85. 85. ROLE OF STAPHYLOCOCCUS AUREUS NASAL COLONIZATION IN ATOPIC DERMATITIS IN INFANTS Lebon Arch Ped Adoles Med 2009;163:745 OR for Atopic dermatitis during 5 – the second year  1079 children 4 –  Nasal swabs for S. aureus 3 – 4.29 cultivation were 2 – taken at ages 1.5, 6, and 14 months 1 – 0 in children with frequent colonization in the first year of life (≥2 times)
  86. 86. ROLE OF STAPHYLOCOCCUS AUREUS NASAL COLONIZATION IN ATOPIC DERMATITIS IN INFANTS Lebon Arch Ped Adoles Med 2009;163:745 OR for Atopic dermatitis during 5 – the second year Nasal colonization –  1079 children 4 of S Aureus is a  Nasal swabs for S. aureus factor risk 3 that – 4.29 cultivation were precedes 2 – taken at ages 1.5, 6, Atopic Dermatitis – and 14 months 1 in infants 0 in children with frequent colonization in the first year of life (≥2 times)
  87. 87. Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. Travers JACI 2010:125:146 Background: Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown. Objective: We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions.
  88. 88. Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. Travers JACI 2010:125:146  89 children with impetiginized AD were enrolled in this study.  Eczema Area and Severity Index (EASI). Typical subject with clinically impetiginized  Wash fluid obtained AD lesion at first visit, and second visit from the lesion. 2 weeks later after treatment with topical corticosteroid and oral antibiotic.
  89. 89. Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. Travers JACI 2010:125:146  89 children with impetiginized AD were enrolled in this study.  Eczema Area and Severity Index (EASI).  Wash fluid obtained from the lesion.
  90. 90. Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. Travers JACI 2010:125:146 r=0.27 p=0.01  89 children with r=0.28 p=0.01 impetiginized AD were enrolled in this study.  Eczema Area and Severity Index (EASI).  Wash fluid obtained from the lesion. Wash fluid obtained at first visits (red circle) and follow-up visits (blue triangle)
  91. 91. Infected atopic dermatitis lesions contain pharmacologic amounts of lipoteichoic acid. Travers JACI 2010:125:146 r=0.27 p=0.01  89 children with r=0.28 p=0.01 Approximately impetiginized AD 30% of clinically were enrolled in this impetiginized AD study. lesions contained  Eczema Area and 1 greater than Severity Index μg/mL LTA, (EASI).amounts that  Wash fluideffects on exert obtained from the lesion. types various cell in vitro. Wash fluid obtained at first visits (red circle) and follow-up visits (blue triangle)
  92. 92. Secreted virulence factor comparison between methicillin- resistant and methicillin-sensitive Staphylococcus aureus, and its relevance to atopic dermatitis Schlievert JACI 2010:125:39  Staphylococcus aureus is a gram-positive bacterium that produces a remarkable array of cell-surface and secreted virulence factors to facilitate disease causation, and rapidly develops antimicrobial resistance almost as quickly as new therapeutic agents are developed.  The cell-surface MSCRAMMs (matrix molecules) typically are produced during exponential phase of growth. Virulence factor production by S aureus
  93. 93. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 Background: A subset of subjects with atopic dermatitis (AD) are susceptible to serious infections with herpes simplex virus, called eczema herpeticum, or vaccina virus, called eczema vaccinatum.
  94. 94. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 p<0.001  Subjects with AD with and without a history of eczema herpeticum [ADEH+ (134) and ADEH− (419)] and healthy control (348).  Eczema Area and Severity Index (EASI)
  95. 95. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 p<0.001  Subjects with AD with and without a history of eczema herpeticum ADEH+ subjects [ADEH+ (134) and had more ADEH− (419)] and severe disease. healthy control (348).  Eczema Area and Severity Index (EASI)
  96. 96. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 p<0.001 p<0.001
  97. 97. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 Subjects with AD in whom eczema herpeticum develops have more severe TH2-polarized disease with greater allergen sensitization and more commonly have a history of food allergy, asthma, or both. p<0.001 p<0.001
  98. 98. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 Percentage of subjects with AD or caregivers who self-report a history of, or current food allergy (A) or asthma (B).
  99. 99. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 Percentage of subjects (ADEH+, ADEH-, and CTL subjects) who self-report a history of ocular infections with HSV (A), or skin infections with S aureus (B), human papilloma virus (HPV) (C), or molluscum contagiosum virus (MCV) (D).
  100. 100. • atopy • sensitization
  101. 101. Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema Zeller JACI 2009;124:278 Background: Atopic eczema (AE) is the most common chronic inflammatory skin disease. Recent data demonstrate the presence of autoreactive serum IgE antibodies correlating with the severity of the disease.
  102. 102. Exploring the repertoire of IgE-binding self-antigens associated with atopic eczema Zeller JACI 2009;124:278  140 sequences encoding  Phage surface–displayed potential IgE-binding human cDNA libraries self-antigens associated were enriched for clones with AE were identified. binding to serum IgE  By binding IgE antibodies from patients with AE or activating specific and screened by using T cells, they might high-throughput promote, perpetuate, technology. or both existing skin inflammation.
  103. 103. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332 Total IgE Ku/L  143 infants with AD 110 – p=0.004 who younger than 100 – 107 6 months. 90 – 80 – p=0.07  3 groups : 70 – 60 – 69 - breastfed, 50 – - mixed feeding, and 40 – - formula fed. 30 – 20 – 10 – 25  All infants had never 0 been fed egg or soy. BF MF FF Groups
  104. 104. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332  143 infants with AD Specific IgE to Cow’s Milk Ku/L who younger than 3.0 – ns 6 months. 2.5 – 2.75  3 groups : 2.0 – - breastfed, 1.5 – ns - mixed feeding, and 1.34 1.0 – - formula fed. 0.5 – 0.57  All infants had never 0 been fed egg or soy. BF MF FF Groups
  105. 105. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332  143 infants with AD sIgE to Egg withe Ku/L 10 – who younger than 9 – p=0.002 6 months. 8 – 8.43 p=0.0002 7 –  3 groups : 6 – 7.97 - breastfed, 5 – - mixed feeding, and 4 – 3 – - formula fed. 2 – 1 –  All infants had never 0 0.09 been fed egg or soy. BF MF FF Groups
  106. 106. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332  143 infants with AD sIgE to Egg withe Ku/L 10 – who younger than 9 – p=0.002 6 months. Our results suggest 8 – 8.43 p=0.0002 that breastfeeding 7 –  3 groups not always be might : 6 – 7.97 - breastfed, in allergy beneficial 5 – - mixed feeding,some prevention in and 4 – high-risk infants. 3 – - formula fed. 2 – 1 –  All infants had never 0 0.09 been fed egg or soy. BF MF FF Groups
  107. 107. High sensitization rate to food allergens in breastfed infants with atopic dermatitis Han Ann Allergy Asthma Immunol 2009;103:332  One limitation of our study is that the FF group was smaller than the other groups.  In the present study, the 3 groups (BF, MF, and FF) were not randomly divided but were determined according to parental preferences.  The number of infants in the FF group was small.  In conclusion, our results showed that BF patients with AD had a higher rate of sensitization to egg white during early infancy, which suggests that BF might not always be beneficial in allergy prevention in some high-risk infants (ie, maternal AD).
  108. 108. • Irritants
  109. 109. Temperature modulated histamine-itch in lesional and nonlesional skin in atopic eczema – a combined psychophysical and neuroimaging study. Pfab Allergy 2010:65:84  10 patients with AD. VAS Itch Intensity  9 healthy controls. | | | | | | | | 0 10 20 30 40 50 60 70 80 90 100 | | |  Thermal modulation from 32°C (warm) COLD 55.2 to 25°C (cold).  VAS itch intensity. p<0.0001 WARM 36.0
  110. 110. Temperature modulated histamine-itch in lesional and nonlesional skin in atopic eczema – a combined psychophysical and neuroimaging study. Pfab Allergy 2010:65:84  10 patients with AD. VAS Itch Intensity Mean VAS itch  9 healthy controls. intensity was | | | | | | | | 0 10 20 30 40 50 60 70 80 90 100 | | |  Thermal modulation significantly from 32°C (warm) (P < 0.0001) higher COLD 55.2 to 25°C (cold). during the relative VAS itch intensity. cold [55.2 ± 8.3% p<0.0001 WARM 36.0 (LS); 48.6 ± 8.2% (NLS)] compared to the relative warm blocks
  111. 111. • Pathogenesis
  112. 112. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 The structure of the epidermal barrier located in the lower part of the stratum corneum (SC). Highly differentiated flattened keratinocytes, referred to as corneocytes (beige rectangles), are the building blocks of the epidermal barrier. They contain natural moisturizing factor (NMF), derived from pro-filaggrin, a mix of hygroscopic compounds, which help maintain skin hydration. A water resistant layer of lipid lamellae (pink) encases the corneocytes preventing water loss and impeding barrier permeability. The corneocytes are held together by corneodesmosomes (purple spheres), the integrity of which is dependent on a cocktail of proteases and protease inhibitors.
  113. 113. Ceramide biosynthesis in keratinocyte and its role in skin function Y Mizutani Biochimie 2009;91:784
  114. 114. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 The structure of the epidermal barrier located in the lower part of the stratum corneum (SC). The balance between the expression and activity of proteases, such as KLK7 (SCCE), and protease inhibitors, such as LEKTI and cystatin A, determines the rate of desquamation (corneocytes shedding) and thereby the thickness of the barrier. Under normal conditions, the barrier is only degraded in the upper layers of the SC providing a resilient permeability barrier that prevents the penetration of allergens.
  115. 115. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 A defective epidermal barrier is a poor permeability barrier, which permits the entry of allergens and the loss of moisture. Changes in the FLG gene encoding pro-filaggrin result in reduced, or absent, expression of filaggrin thereby adversely affecting the structure of the corneocytes (beige)—the ‗‗bricks‘‘. The levels of natural moisturizing factor (NMF), derived from filaggrin, are also adversely affected, resulting in a decreased ability of the corneocytes to hold water and a concomitant elevation of pH.
  116. 116. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 A defective epidermal barrier is a poor permeability barrier, which permits the entry of allergens and the loss of moisture. Elevated pH favors serine protease activity and inhibits enzymes involved in the synthesis of lipid lamellae (pink)—the ‗‗mortar‘‘. Genetic changes in the genes encoding SCCE (KLK7), LEKTI (SPINK5), and cystatin A (CSTA) all lead to elevated protease activity involved in desquamation— cleavage of the corneodesmosome junctions (purple spheres) between the corneocytes analogous to ‗‗rusting‘‘ of the ‗‗iron rods‘‘.
  117. 117. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 There is a defective epidermal barrier in individuals with atopic dermatitis. The epidermal barrier is found in the lower layers of the stratum corneum, and is composed of differentiated keratinocytes, termed corneocytes (beige rectangles), held together with corneodesmosomes (purple spheres). The hyperactivity of degradatory proteases (red hexagons) found within the epidermis, and contributed to by exogenous proteases (red hexagons), from house dust mites and Staphylococcus aureus, for example, facilitate the cleavage of the corneodesmosome junctions.
  118. 118. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 There is a defective epidermal barrier in individuals with atopic dermatitis. The epidermal barrier is found in the lower layers of the stratum corneum, and is composed of differentiated keratinocytes, termed corneocytes (beige rectangles), held together with corneodesmosomes (purple spheres). The hyperactivity of degradatory proteases (red hexagons) found within the epidermis, and contributed to by exogenous proteases (red hexagons), from house dust mites and Staphylococcus aureus, for example, facilitate the cleavage of the corneodesmosome junctions. .
  119. 119. Epidermal Barrier Dysfunction in Atopic Dermatitis M J. Cork J Invest Dermatol 2009;129:1892 There is a defective epidermal barrier in individuals with atopic dermatitis. This is just one event in the breakdown of the epidermal barrier that permits the penetration of allergens. Dendritic cells (DC) (green) found in the dermis take up and present these allergens (red stars) to helper T (TH) cells and recruit CD4þ T cells (blue). Activated DC and IL-4, expressed by CD4þ T cells, promote TH1 to TH2 switching with the subsequent release of pro-inflammatory cytokines and elevation of IgE levels The clinical outcome of this type of response is atopy and asthma.
  120. 120. Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis Guttman-Yassky JACI 2009:124:1235  Both psoriasis and AD skin  Cutaneous biopsy. lesions displayed regenerative epidermal  Genomic profiling of hyperplasia. mRNA in chronic psoriasis (n = 15)  In AD, we found selective defects in expression of and AD (n = 18) multiple genes encoding the skin lesions compared cornified envelope, with the with normal human largest alteration in loricrin skin (n = 15) (expressed at 2% of the level of normal skin).
  121. 121. Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis Guttman-Yassky JACI 2009:124:1235 Real-time PCR analysis showing significant downregulation of LCE1, LCE2, CDS N, and SPRR2C in AD;.
  122. 122. Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes Kato Allergy 2009:64:1366 Serine protease-rich extract of whole mite culture Release of IL-8 and granulocyte-macrophage colony-stimulating factor. HUMAN KERATINOCYTES Stimulated intracellular Ca2+ mobilization.
  123. 123. Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes Kato Allergy 2009:64:1366 Serine protease-rich extract Mite-derived of whole mite culture serine protease activity may contribute to the pathogenesis of atopic Release of IL-8 and dermatitis by granulocyte-macrophage activating colony-stimulating factor. HUMAN KERATINOCYTES keratinocytes. Stimulated intracellular Ca2+ mobilization.
  124. 124. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens Scharschmidt JACI 2009;124:496 Topical irritants and aptens • Reduced inflammatory thresholds when exposed repeatedly to topical haptens at doses that produce no inflammation in wild-type mice, • FLG deficient mice experience a severe AD-like dermatosis with a further deterioration in FLG deficient barrier function and features mouse of a TH2 immunophenotype
  125. 125. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum Pei-Song Gao JACI 2009;124:507 Background Loss-of-function null mutations R501X and 2282del4 in the skin barrier gene, filaggrin (FLG), represent the most replicated genetic risk factors for atopic dermatitis (AD). Atopic dermatitis eczema herpeticum (ADEH) is a rare but serious complication of AD resulting from disseminated cutaneous herpes simplex virus infections.
  126. 126. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum Pei-Song Gao JACI 2009;124:507 % SUBJECTS WITH R501X MUTATION  Loss-of-function 25 – mutations plus 9 FLG polymorphisms . 20 – 25% 15 – OR=3.4 P=0002  278 patients with AD, of whom 112 had Atopic 10 – Dermatitis Eczema Herpeticum (ADEH), 5 – 9% and 157 nonatopic 0 controls. ADEH AD
  127. 127. Filaggrin mutations that confer risk of atopic dermatitis confer greater risk for eczema herpeticum Pei-Song Gao JACI 2009;124:507 % SUBJECTS WITH R501X MUTATION  Loss-of-function 25 – mutations plus 9 FLG R501X mutation in polymorphisms . the gene encoding 20 – 25% OR=3.4 P=0002  278 patients confers filaggrin, 15 – with AD, an even greater of whom 112 had Atopic 10 – risk for ADEH. Dermatitis Eczema Herpeticum (ADEH), 5 – 9% and 157 nonatopic 0 controls. ADEH AD
  128. 128. • Diagnosis
  129. 129. • Contact dermatitis
  130. 130. treatment
  131. 131. UV-B–triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes Peric JACI 2010;125:746  Human keratinocytes possess the enzymatic machinery to produce calcitriol from the precursor 7 dehydrocholesterol (7-DHC) under the influence of UV-B irradiation.  UV-B irradiation (290-315 nm) rapidly generates previtamin D3 from 7-DHC in these cells, and thermal isomerization subsequently generates vitamin D3, which is sequentially hydroxylated to yield calcidiol and finally calcitriol.
  132. 132. UV-B–triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes Peric JACI 2010;125:746  Keratinocytes were treated with 7-DHC and/or inhibitor ketoconazole and irradiated with UV-B.
  133. 133. UV-B–triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes Peric JACI 2010;125:746  Keratinocytes of Hydroxylation were treated to vitamin D3 formactive calcitriol with 7-DHC was and/or inhibitor blocked by the CYP ketoconazole and inhibitor irradiated with ketoconazole. UV-B.
  134. 134. • Treatment general consideration
  135. 135. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting Blume-Peytavi JEADV 2009,23,751/759 : routine bathing of infants
  136. 136. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting Blume-Peytavi JEADV 2009,23,751/759 : safety while bathing infants
  137. 137. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting Blume-Peytavi JEADV 2009,23,751/759 : procedures after bathing •Bathing can be a fun experience for the infant, providing tactile stimulation and bonding with parents and other caregivers, •Bathing can be a calming, soothing experience for the infant.
  138. 138. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting Blume-Peytavi JEADV 2009,23,751/759 : use of liquid cleansers in bathing
  139. 139. Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting Blume-Peytavi JEADV 2009,23,751/759 : use of liquid cleansers in bathing
  140. 140. • Treatment exclusion diet
  141. 141. • Treatment emolients
  142. 142. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Within the corneocytes, in a normal skin barrier, are high levels of a substance called natural moisturising factor (NMF). NMF is a humectant, which means that it attracts water to itself
  143. 143. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 It is important that the actions of proteases are held in check by protease inhibitors, such as LEKTI. It is important to prevent excessive protease activity because this will lead to a thinning of the stratum corneum, causing it to become vulnerable to the penetration of irritants and allergens.
  144. 144. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Breakdown of the skin barrier, producing dry, itchy skin, is an extremely common problem in babies and children. Up to 25% of babies and children are affected by atopic eczema. As we grow older we will all develop drier skin, particularly on our legs and arms, which can be manifest as asteatotic eczema. Breakdown of the skin barrier is commonest at the extremes of age.
  145. 145. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 As a result of these decreased NMF levels, the amount of water that can be held within the corneocytes is reduced. The lipid lamellae are also defective in eczematous skin – this is analogous tobroken, crumbly mortar in an old brick wall. Breakdown of the skin barrier is commonest at the extremes of age.
  146. 146. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Effects of a genetic predisposition to atopic eczema.
  147. 147. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Effects of a genetic predisposition plus environmental factors on the skin barrier.
  148. 148. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Complete emollient therapy The most important treatment for all dry skin diseases, including atopic eczema, asteatotic eczema and irritant 1 contact dermatitis, is complete emollient therapy Complete emollient therapy consists of: 2 1) Emollient bath products 2) Emollient wash products 3) Emollient creams or ointments 3 Everything that goes on to the skin should be emollient based. All soap and detergents should be replaced with emollient wash, bath and shower products
  149. 149. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 In their simplest form, emollient products provide an occlusive layer of oil (such as petrolatum) over the surface of the stratum corneum However, such ‘heavy’ emollient ointments are extremely greasy and therefore are cosmetically unacceptable to the majority of patients
  150. 150. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 The most important determinant in choosing an emollient is cosmetic acceptability Emollient formulations containing low concentrations of humectants are therefore much more likely to be cosmetically acceptable to patients
  151. 151. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 •If a patient likes a particular emollient formulation, they will use it regularly and it will be effective. •If a patient does not like an emollient formulation, they will not use it; therefore it can have no effect. •It is important to use sufficient quantities of emollients to achieve the optimum repair of the skin barrier. •For a leave-on emollient cream for a child with atopic eczema, this should be between 250 and 500 grams per week. •In order to produce the optimum repair of the skin barrier in AD a complete emollient therapy regimen should be used
  152. 152. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 •Emollient regimens can be complex and their combination with treatments for flares such as topical corticosteroids and topical calcineurin inhibitors even more complicated. •It is essential that all topical treatments are demonstrated and explained in detail to patients to ensure they are effective. Cork MJ, Br J Dermatol 2003;149:582–9 Staab D, Br Med J 2006;332: 933–8
  153. 153. • Treatment antibiotics
  154. 154. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959  Effectiveness of monotherapy with β-lactams, clindamycin, or 10 – trimethoprim-sulfamethoxazole 9 – in the outpatient management % of children with 8 – of nondrained noncultured skin and treatment failure soft-tissue infections (SSTIs), 7 – 7.7% in a methicillin-resistant 6 – Staphylococcus aureus 5 – (MRSA)-endemic region. 5.0% 4 –  Treatment failure 3 – (a drainage procedure, hospitalization, 2 – change in antibiotic, or second 1 – antibiotic prescription within 28 days). 0  2096 children
  155. 155. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959  Effectiveness of monotherapy Compared with with β-lactams, clindamycin, or 10 – trimethoprim-sulfamethoxazole β-lactam therapy, in the outpatient management 9 – % of children with clindamycin was of nondrained noncultured skin and 8 – treatment failure equally effective but soft-tissue infections (SSTIs), 7 – 7.7% in a methicillin-resistant 6 – trimethoprim- Staphylococcus aureus 5 – sulfamethoxazole (MRSA)-endemic region. 5.0% 4 – was associated  Treatment failure with 3 – an increased risk (a drainage procedure, hospitalization, 2 – change in antibiotic, or second of failure. antibiotic prescription within 28 days). 1 – 0  2096 children
  156. 156. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959  Effectiveness of monotherapy with β-lactams,regions with Even in clindamycin, or 10 – trimethoprim-sulfamethoxazole endemic 9 – % of children with in the outpatient management community-acquired of nondrained noncultured skin and 8 – treatment failure MRSA, β-lactams soft-tissue infections (SSTIs), 7 – 7.7% may still be in a methicillin-resistant 6 – Staphylococcus aureus appropriate, 5 – (MRSA)-endemic region. 5.0% first-line, 4 – empiric therapy for  Treatment failure 3 – children presenting (a drainage procedure, hospitalization, 2 – change in antibiotic, or second with these infections. 1 – antibiotic prescription within 28 days). 0  2096 children

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