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  • 1. WHAT YOU SHOULD HAVE READ BUT….2010  atopic dermatitis Attilio Boner University of Verona, Italy
  • 2. • Differential Diagnosis
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. • Prevalence
  • 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. 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. 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. • burden
  • 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. 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. 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. 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. 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. • The atopic march
  • 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. 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. 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. 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. 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. 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. 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. • protective factors
  • 31. • intestinal flora • probiotics
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • Antioxidants
  • 50. • Antioxidants
  • 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. • Risk factors
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • batteri • funghi • virus
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Phenotype of atopic dermatitis subjects with a history of eczema herpeticum Beck JACI 2009;124:260 p<0.001 p<0.001
  • 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. 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. 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. • atopy • sensitization
  • 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. 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. 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. 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. 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. 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. 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. • Irritants
  • 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. 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. • Pathogenesis
  • 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. Ceramide biosynthesis in keratinocyte and its role in skin function Y Mizutani Biochimie 2009;91:784
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • Diagnosis
  • 129. • Contact dermatitis
  • 130. treatment
  • 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. 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. 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. • Treatment general consideration
  • 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. 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. 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. 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. 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. • Treatment exclusion diet
  • 141. • Treatment emolients
  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • Treatment antibiotics
  • 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. 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. 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
  • 157. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 A. Even in region with endemic CA-MRSA, most skin and soft-tissue infections (SSTIs), including impetigo, cellulitis, and small abscesses are treated empirically without drainage or culture and therefore rarely yield a causative organism. B. Traditionally, β-lactam agents active against group A Streptococcus (GAS) and S aureus have been the preferred first-line agents. However, β-lactams are not active against CA-MRSA. C. Current guidelines for the management of nonpurulent SSTIs emphasize streptococcal coverage. D. Diseases that might predispose patients to SSTIs are diabetes mellitus, asthma, atopic or seborrheic dermatitis, previous streptococcal infection (defined as documented streptococcal pharyngitis or scarlet fever), or any evidence of topical or mucosal fungal infection.
  • 158. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 Trends in treatment failure and empiric antibiotic choice for nondrained noncultured SSTIs from 2002 to 2007. The average rate of treatment failure was 5.7%, and the rate did not change during this period.
  • 159. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 Empiric CA-MRSA coverage with clindamycin and trimethoprim sulfamethoxazole increased dramatically, from 16.4% of all prescriptions in 2004 to 62.2% in 2007. For our overall cohort, trimethoprim-sulfamethoxazole accounted for 19% of prescriptions and was associated with treatment failure (OR: 2.47)
  • 160. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 3 - OR for treatment failure 2.53 2.35 2 - 1.73 1.68 1 - 17.6% 0 TMT/SMZ WHITE FEVER INDURATION RACE OR ABSCESS
  • 161. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 E. Clinicians have dramatically increased the use of empiric CA-MRSA coverage in response to this uncertainty. F. Our indings suggested that the increased use of empiric CA-MRSA coverage was not associated with improved clinical outcomes. G. These findings may suggest that CA-MRSA is not a prevalent cause of nondrained noncultured SSTIs even in a region with endemic CA-MRSA. H. The association between treatment failure and monotherapy with trimethoprim-sulfamethoxazole suggests that GAS may remain a more common cause of these infections.
  • 162. Empiric Antimicrobial Therapy for Pediatric Skin and Soft-Tissue Infections in the Era of Methicillin-Resistant Staphylococcus aureus DJ.Elliott, Pediatrics 2009;123:e959 E. Clinicians have dramatically increased the use of empiric CA-MRSA coverage in response to this uncertainty. F. Trimethoprim-sulfamethoxazole Our indings suggested that the increased use of empiric CA-MRSA coverage was not associated with improved is not active against GAS. clinical outcomes. G. These findings may suggest that CA-MRSA is not a prevalent cause of nondrained noncultured SSTIs even in a region with endemic CA-MRSA. H. The association between treatment failure and monotherapy with trimethoprim-sulfamethoxazole suggests that GAS may remain a more common cause of these infections.
  • 163. • Treatment calcineurine inhibitors
  • 164. Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle- controlled trial. Leung DY, Br J Dermatol. 2009;161:435-43. BACKGROUND: Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. OBJECTIVES: To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD.
  • 165. Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle- controlled trial. Leung DY, Br J Dermatol. 2009;161:435-43. Percentage change in head and neck 73 patients with Eczema Area and Severity Index AD, aged 2-49 years, (EASI) score at week 6 with a documented 0 – clinical insensitivity -10 – to topical CS -20 – -25.0% -30 – 6-week double- Vehicle -40 – blind -50 – -57.1% pimecrolimus cream p<0.05 -60 – compared with Pimecrolimus vehicle.
  • 166. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Topical pimecrolimus and tacrolimus applied twice- daily for 5 days, delay barrier recovery. Co-application of physiologic lipid mixture (PLM) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. Antimicrobial peptide = mBD3, CRAMP
  • 167. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Topical tacrolimus Topical pimecrolimus and impairs barrier tacrolimus applied twice- daily for 5 days, delay homeostasis and SC barrier recovery. Co-application of only by integrity not inhibiting epidermal physiologic lipid mixture lipid synthesis and (PLM) containing an equimolar ratio of lamellar body (LB) ceramides, cholesterol and formation, but also free fatty acids normalized barrierby decreasing homeostasis in the facecorneodesmosome of topical TCIs. (CD) Antimicrobial peptide = mBD3, CRAMP density.
  • 168. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Co-treatment with physiologic lipid mixture (PLM) Topical pimecrolimus and increases the expression of antimicrobial peptides tacrolimus applied twice- in the topical pimecrolimus-treated epidermis. daily for 5 days, delay barrier recovery. Co-application of physiologic lipid mixture (PLM) containing an equimolar ratio of c ceramides, cholesterol and e c free fatty acids normalized r e a r barrier homeostasis in the a m face of topical i m i TCIs. d d Antimicrobial peptide = i i mBD3, CRAMP
  • 169. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Co-treatment with physiologic lipid mixture (PLM) Topical pimecrolimus and This was associated increases the expression of antimicrobial peptides tacrolimus a reduction in in the topical pimecrolimus-treated epidermis. with applied twice- daily for 5 days, delay TEWL barrier recovery. Tacrolimus-induced Co-application of physiologic lipid mixture (PLM) containing an equimolar ratio of c ceramides, cholesterol and e c free fatty acids normalized r e a r barrier homeostasis in the a m face of topical i m i TCIs. d d Antimicrobial peptide = i i mBD3, CRAMP
  • 170. • Treatment steroids
  • 171. Dermal Hyaluronan Is Rapidly Reduced by Topical Treatment with Glucocorticoids C Gebhardt J Invest Dermatol 2009;129:1892 Skin atrophy is part of the normal ageing process, but is accelerated by topical glucocorticoid (GC) treatments that are widely used in dermatology. Hyaluronan (HA) is one of the most abundant components of the cutaneous extracellular matrix and is involved in tissue homeostasis, hydration, and repair processes, but little is known about the effects of GCs on HA synthesis and stability.
  • 172. Dermal Hyaluronan Is Rapidly Reduced by Topical Treatment with Glucocorticoids C Gebhardt J Invest Dermatol 2009;129:1892 Quantitative RT–PCR of HAS-2 RNA levels in keratinocyte 3, 6, 24, and 48 hours Expression of the HA after treatment with 1.5 nM, 150 nM, and 1.5 mM dexamethasone, synthesizing enzymes hyaluronan synthase (HAS)-2 HAS-2 expression was markedly suppressed by dexamethasone treatment of cultured HaCaT keratinocyte cells
  • 173. Dermal Hyaluronan Is Rapidly Reduced by Topical Treatment with Glucocorticoids C Gebhardt J Invest Dermatol 2009;129:1892 untreated Dexamethasone reduces the dermal HA content in vivo. Immunohistochemical staining of Hyaluronan (HA) in human skin treated with 0.1% dexamethasone 0.1% dexamethasone ointment three times daily (b) or left untreated (a) from the same individual and from a similar location.
  • 174. Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis M Demerjian Exp Dermatol 2009;18:643 Co-application of clofibrate (PPAR ligand) PPAR = peroxisome (1 mM) with clobetasol normalizes the proliferator-activated expression of filaggrin (FIL), involucrin receptor; (INV) and loricrin (LOR) activators of PPAR: 1) regulate keratinocyte proliferation and differentiation and improve permeability barrier homeostasis 2) prevent the GC-induced decrease in involucrin, filaggrin and loricrin expression
  • 175. Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis M Demerjian Exp Dermatol 2009;18:643 Co-application of clofibrate (PPAR ligand) PPAR = peroxisome Sunflower seed oil has been (1 mM) with clobetasol normalizes the has been shown to increase proliferator-activated the epidermal key lipid expression of filaggrin (FIL), involucrin receptor; and to reduce synthesis (INV) and loricrin (LOR) inflammation of PPAR: activators in vitro and in animal models. It has also 1) regulate keratinocyte been shown to activate proliferation and peroxisome proliferative- differentiation and activated receptor-alpha (PPAR-alpha), to stimulate improve permeability keratinocyte differentiation, barrier barrier function, and improve homeostasis 2)enhance lipid metabolism in prevent the GC-induced the skin. it has been decrease in involucrin, demonstrated that SOD filaggrin andefficacious in might also be loricrin expression atopic dermatitis (AD).
  • 176. Wet dressings used with topical corticosteroids for pruritic dermatoses: A retrospective study. Bingham LG J Am Acad Dermatol. 2009;60:792-800. BACKGROUND: Wet dressings are a mainstay for initial management of pruritic adult dermatoses at Mayo Clinic, yet few recent reports describe their effectiveness for pruritic conditions other than atopic dermatitis in children. OBJECTIVE: To examine the effectiveness of wet dressings for pruritic dermatoses.
  • 177. Wet dressings used with topical corticosteroids for pruritic dermatoses: A retrospective study. Bingham LG J Am Acad Dermatol. 2009;60:792-800. % patients reporting improvment 100 – 331 patients with 94% 90 – pruritus treated with wet 80 – dressings and topical 70 – corticosteroids. 60 – Improvement 50 – Wet dressings evaluated 1 day 40 – effectively alleviate after 30 – recalcitrant pruritic 20 – dermatoses within 10 – 1 day 0
  • 178. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Silver textile 37 patients with AD single-blinded in vivo study.  sensitization potential was tested in a patch test in 111 panellists. Silver textiles
  • 179. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Superoxide Silver textile for the scavenging 37 patients with AD three tested groups: single-blinded All three test fibres in vivo study. induced significant  sensitization superoxide potential was tested in a patch test in radicals scavenging 111 panellists. compared with Phoaslisne control. Silver textiles
  • 180. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Silver textile 37 patients with AD single-blinded in vivo study.  sensitization potential was tested in a patch test in 111 panellists.
  • 181. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Silver textile 37 patients with AD single-blinded in vivo study.  sensitization potential was tested in a patch test in 111 panellists.
  • 182. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Staphyloccocus Silver textile aureus was 37 patients with AD reduced but single-blinded not significant in vivo study. changes were  sensitization observed potential was tested in a patch test in for 111 panellists. apathogenic bacteria.
  • 183. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press
  • 184. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Stratum corneum hydration measured by Corneometry
  • 185. Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr Exp Dermatol 2010 in press Stratum corneum hydration measured by Corneometry Stratum corneum hydration measured by capacitance- based Corneometry revealed a slight, but not significant increase of stratum hydration in the second part of the study, more prominent in severely involved skin (b) in the silver group compared with cotton.
  • 186. Silver textile •No sensitization against all the tested textiles was detected 37 patients with AD with patch testing in the 111 single-blinded panellists. in vivo study.  sensitization potential was tested •The tested silver-loaded seaweed fibre can be regarded as safe and in a patch test in seams to be suited for application in 111 panellists. bio-active textiles in atopic dermatitis
  • 187. • Treatment probiotics
  • 188. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117  Randomized-  Data from 5 of these controlled trials trials showed that there (RCTs) for the was no significant treatment of reduction in eczema eczema. symptoms.  12 trials  Data from 7 trials showed no significant (781 participants) difference in investigator were identified. rated eczema severity.
  • 189. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117  Randomized-  Data from 5 of these controlled trials trials showed that there Probiotics (RCTs) for the was no significant cannot be treatment of reduction in eczema recommended eczema. symptoms. for treating  12 trials  Data from 7 trials eczema. showed no significant (781 participants) difference in investigator were identified. rated eczema severity.
  • 190. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117 SCORAD Subgroup analysis by age of participants
  • 191. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117 SCORAD Subgroup analysis by severity of eczema
  • 192. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117 SCORAD Subgroup analysis by probiotic strain
  • 193. Probiotics for the treatment of eczema: a systematic review. Boyle CEA 2010;39:1117  In summary, we conclude that probiotics are not an effective treatment for eczema.  The heterogeneity between different studies including those using different probiotic strains means that beneficial effects cannot be excluded for specific probiotic strains.  Probiotics should not be used for treating eczema except in the context of research studies.
  • 194. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants Shibata Clinical & Experimental Allergy 2009;39:1397 Background: Oligosaccharides may have beneficial properties of the prevention of atopic dermatitis (AD). Kestose, a fructo-oligosaccharide, stimulates the activity of bifidobacteria. Objective: To assess the clinical effect of kestose on the treatment of AD in infants.
  • 195. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants Shibata Clinical & Experimental Allergy 2009;39:1397 Medians of SCORAD 40 – at week 6 35 –  15 infants with AD kestose. 30 – 36.4 25 –  15 infants with AD placebo. 20 – 25.3  1 to 2 g kestose 15 – administered everyday for p=0.004 10 – 12 weeks. 05 – 0 KESTOSE PLACEBO
  • 196. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants Shibata Clinical & Experimental Allergy 2009;39:1397 Medians of SCORAD 40 – at week 12 35 –  15 infants with AD kestose. 30 – 37.5 25 –  15 infants with AD placebo. 20 –  1 to 2 g kestose 15 – 19.5 administered everyday for 10 – 12 weeks. p<0.001 05 – 0 KESTOSE PLACEBO
  • 197. Clinical effects of kestose, a prebiotic oligosaccharide, on the treatment of atopic dermatitis in infants Shibata Clinical & Experimental Allergy 2009;39:1397 Medians of SCORAD 40 – at week 12 1. No significant correlation 35 – was found between the  15 infants with AD kestose. 37.5 improvement of the 30 – SCORAD score and the 25 –  15 infants bifidobacteria. count of with AD placebo. 20 –  12. The g kestose how does to 2 mechanism 15 – 19.5 kestose improve the administered everyday for symptoms of AD remains 10 – 12 weeks. to be elucidated. p<0.001 05 – 0 KESTOSE PLACEBO
  • 198. • Treatment immunotherapy
  • 199. •In Italia la prevalenza di DA va dal 5% al 15%, •Se la malattia persiste il bambino è a rischio di disturbi emotivo-comportamentali, •La sensibilità agli acari è il fattore di rischio più importante per la persistenza della malattia, •L‘introduzione precoce dei cibi semisolidi può ridurre il rischio di comparsa di DA in particolare se durante il divezzamento si Take aggiungono probiotici, home •Una dieta ricca in sostanze antiossidanti ha un effetto preventivo sulla comparsa di DA, •Il difetto di filagrina è un importante fattore di rischio che viene aumentato dalla contemporanea esposizione ad allergeni perenni nell‘ambiente domestico, •La colonizzazione precoce con S aureus, favorisce lo sviluppo di DA,
  • 200. •Anche il freddo può stimolare il prurito, •Gli enzimi proteolitici degli acari attivano i cheratinociti a produrre IL-8 e GMC-SF, •È importante una terapia emoliente di mantenimento completa: 1° lavare il bambino in modo corretto e 2° pochi minuti dopo il bagno ungerlo con Take emolienti accetabili dal punto di vista cosmetico home ed economico, •Gli inibitori della calcineurina possono essere utili nei pazienti che hanno sviluppato resistenza ai corticosteroidi, •Quando si usano corticosteroidi topici o inibitori della calcineurina è opportuno applicare contemporaneamente creme emolienti contenenti NMF in versione ―magra‖ (olio in acqua), •Nei pazienti più impegnativi si può ricorrere al ―wet dressing‖, •I tessuti con fibra d‘argento possono essere utili.