Atopic dermatitis exacerbations

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  • Treatment with cefuroxime axetil versus placebo results in significant reduction of S aureus colony counts from a mean of 3 cultured areas (*P = .0014). Twenty patients (11 of them female) aged 6 to 58 years (10 pediatric) completed the study. At baseline, the mean body surface area involved was 40% (CI, 28% to 51%) and the mean total clinical severity score was 11.67 (CI, 10.61-12.72). All patients were treated with a moderate-potency topical steroid that was kept constant starting at 1 week before the baseline visit. In 11 of 20 patients with atopic dermatitis treated initially for 2 weeks with cefuroxime axetil, colony counts increased during the 1-week washout period by a median count of 2 × 105 (interquartile range, 2 × 104 to 2.7 × 106; **P = .003). Treatment sequence: ▴, cefuroxime/placebo; ■, placebo/cefuroxime.
  • Treatment with cefuroxime axetil versus placebo results in significant reduction of S aureus colony counts from a mean of 3 cultured areas (*P = .0014). Twenty patients (11 of them female) aged 6 to 58 years (10 pediatric) completed the study. At baseline, the mean body surface area involved was 40% (CI, 28% to 51%) and the mean total clinical severity score was 11.67 (CI, 10.61-12.72). All patients were treated with a moderate-potency topical steroid that was kept constant starting at 1 week before the baseline visit. In 11 of 20 patients with atopic dermatitis treated initially for 2 weeks with cefuroxime axetil, colony counts increased during the 1-week washout period by a median count of 2 × 105 (interquartile range, 2 × 104 to 2.7 × 106; **P = .003). Treatment sequence: ▴, cefuroxime/placebo; ■, placebo/cefuroxime.
  • Treatment with cefuroxime axetil versus placebo results in significant reduction of S aureus colony counts from a mean of 3 cultured areas (*P = .0014). Twenty patients (11 of them female) aged 6 to 58 years (10 pediatric) completed the study. At baseline, the mean body surface area involved was 40% (CI, 28% to 51%) and the mean total clinical severity score was 11.67 (CI, 10.61-12.72). All patients were treated with a moderate-potency topical steroid that was kept constant starting at 1 week before the baseline visit. In 11 of 20 patients with atopic dermatitis treated initially for 2 weeks with cefuroxime axetil, colony counts increased during the 1-week washout period by a median count of 2 × 105 (interquartile range, 2 × 104 to 2.7 × 106; **P = .003). Treatment sequence: ▴, cefuroxime/placebo; ■, placebo/cefuroxime.
  • Atopic dermatitis exacerbations

    1. 1. Atopic Dermatitis Exacerbations <ul><li>Predisposing factors and triggers </li></ul><ul><li>Prevention & Treatment General Concepts </li></ul><ul><li>Topical Treatment </li></ul><ul><li>Systemic Treatment </li></ul><ul><li>Education </li></ul><ul><li>Conclusions </li></ul>University of Verona, Italy Attilio Boner
    2. 2. Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis Sator J Am Acad Dermatol 2003;48:352-8. Comparison of water content of stratum corneum between atopic dermatitis group and control group on right forehead. P<0.001 H 2 O H 2 O <ul><li>48 patients </li></ul><ul><li>Corneometer CM 820 </li></ul><ul><li>Sebumeter SM 810 </li></ul>
    3. 3. Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis Sator J Am Acad Dermatol 2003;48:352-8. Comparison of skin surface lipids between atopic dermatitis group and control group on left forehead. P<0.001 ceramides ceramides <ul><li>48 patients </li></ul><ul><li>Corneometer CM 820 </li></ul><ul><li>Sebumeter SM 810 </li></ul>
    4. 4. Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis Sator J Am Acad Dermatol 2003;48:352-8. <ul><li>48 patients </li></ul><ul><li>Corneometer CM 820 </li></ul><ul><li>Sebumeter SM 810 </li></ul>Comparison of skin surface lipids between atopic dermatitis group and control group on left forehead. P<0.001 the dry skin of patients with atopic dermatitis, as previously shown, is due not only due to a decrease in skin moisture but also to a reduction of skin ceramides ceramides ceramides
    5. 5. Comparison of epidermal hydration and skin surface lipids in healthy individuals and in patients with atopic dermatitis Sator J Am Acad Dermatol 2003;48:352-8. <ul><li>48 patients </li></ul><ul><li>Corneometer CM 820 </li></ul><ul><li>Sebumeter SM 810 </li></ul>Comparison of skin surface lipids between atopic dermatitis group and control group on left forehead. P<0.001 A reduced content of ceramides has been reported in the cornified envelope of both lesional and nonlesional skin in patients with AD ceramides ceramides
    6. 6. The brick wall analogy of the stratum corneum of the epidermal barrier
    7. 7. New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene–environment interactions. Cork MJ JACI 2006; 118:3 . Serin leukoprotease inhibitor - (MastCell Chymase) “ mattone” “ mattone” malta
    8. 8. Corneodesmosomes are not only broken down by endogenous proteases . Once a flare of AD has been triggered, cells within the inflammatory infiltrate produce secondary proteases , which can also break down the skin barrier. The stratum corneum is also exposed to many exogenous proteases from the environment, such as Staphylococcus aureus and house dust mites. New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene–environment interactions. Cork MJ JACI 2006; 118:3 . Serin leukoprotease inhibitor - (MastCell Chymase)
    9. 9. New insights into the mechanism and management of allergic diseases: atopic dermatitis Novak Allergy 2009;64:265 The first level of the barrier is the mechanical skin barrier represented by the stratum corneum and the upper part of the skin. The second level of the skin barrier is represented by structures of the innate immune system such as pattern recognition receptors expressed by skin cells or antimicrobial peptides. The third level of the skin barrier is represented by the cellular defense of components of the adaptive immune system.
    10. 10. FLG EXPRESSION AND PUTATIVE FUNCTIONS IN THE SKIN BARRIER. O’Regan JACI 2008;122:689
    11. 11. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 Relative significance of exacerbating factors in patients with AD from infancy to adulthood. 2°y sIgE
    12. 12. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Triggers of AD </li></ul><ul><li>Stress. mediated by neuroimmunologic factors, such as </li></ul><ul><li>neuropeptides. </li></ul><ul><li>Allergens. Food particularly before the age 3 years and inhalant </li></ul><ul><li>allergens thereafter Dermatophagoides in particular. </li></ul><ul><li>Microorganisms. S. aureus and Malassezia species. </li></ul><ul><li>Autoantigens. IgE against manganese superoxide dismutase </li></ul><ul><li>(MnSOD). </li></ul><ul><li>Irritant factors. rough or woolly clothing, and chemical irritants </li></ul><ul><li>like skin-cleansing agents or house detergents, </li></ul><ul><li>hot water. </li></ul>
    13. 13. TRIGGER FACTORS DRY SKIN IRRITANTS EMOTIONAL STRES ALLERGENS HEAT AND SWEATING INFECTIONS
    14. 14. Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice S Pavlovic J Invest Dermatol 2008;128:434 <ul><li>C57BL/6 mice: </li></ul><ul><li>Controls </li></ul><ul><li>sensitised to ovalbumin to establish AD </li></ul><ul><li>Under sound stress </li></ul>Increased nerve fiber skin density (SP) in AD and after stress.
    15. 15. Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice S Pavlovic J Invest Dermatol 2008;128:434
    16. 16. Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice S Pavlovic J Invest Dermatol 2008;128:434
    17. 17. Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice S Pavlovic J Invest Dermatol 2008;128:434
    18. 18. Further Exploring the Brain–Skin Connection: Stress Worsens Dermatitis via Substance P-dependent Neurogenic Inflammation in Mice S Pavlovic J Invest Dermatol 2008;128:434
    19. 19. Patch testing to aeroallergens, especially house dust mite, is often positive in atopics with eczema of the face and hands . H allai JEADV 2009;23:728 <ul><li>44 patients with atopic dermatitis affecting exposed sites (≥ 18 years). </li></ul><ul><li>APT evaluated after 2 days to exclude irritant reaction. </li></ul>% PATIENTS WITH (+) APT TO MITES AFTER 4 DAYS 77% 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0
    20. 20. % PATIENTS WITH (+) APT TO MITES AFTER 4 DAYS 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 Our finding supports the contention that there may be a role for HDM in atopic dermatitis. Samochocki Z, Eur J Dermatol 2007;17: 520 77% Patch testing to aeroallergens, especially house dust mite, is often positive in atopics with eczema of the face and hands . H allai JEADV 2009;23:728 <ul><li>44 patients with atopic dermatitis affecting exposed sites (≥ 18 years). </li></ul><ul><li>APT evaluated after 2 days to exclude irritant reaction. </li></ul>
    21. 21. RECOGNITION OF PATHOGENICALLY RELEVANT HOUSE DUST MITE HYPERSENSITIVITY IN ADULTS WITH ATOPIC DERMATITIS: A NEW APPROACH? Shah JACI 2002; 109: 1012 A ) Increased dermatitis after 4-days application of Dp solution to the left cubital fossa B ) no immediate response after the first application of control solution C ) Immediate contact urticaria after the first application of Dp allergen solution Type IV Type I A B C
    22. 22. Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes Kato Allergy 2009;64:1366 Release of interleukin (IL)-8 ( A ) and granulocytemacrophage colony-stimulating factor (GM-CSF) ( B ) from primary human keratinocytes stimulated with whole mite culture (WCE) and rDer f
    23. 23. Mite serine protease activates protease-activated receptor-2 and induces cytokine release in human keratinocytes Kato Allergy 2009;64:1366 Release of interleukin (IL)-8 (A) and granulocytemacrophage colony-stimulating factor (GM-CSF) (B) from primary human keratinocytes stimulated with whole mite culture (WCE) and rDer f Protease activating receptor peptides
    24. 24. <ul><li>Topographical and temporal diversity of the human skin microbiome. Grice EA Science. 2009;324(5931):1190-2. </li></ul><ul><li>Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. </li></ul><ul><li>Our analysis of 16S ribosomal RNA gene sequences obtained from 20 distinct skin sites of healthy humans revealed that physiologically comparable sites harbor similar bacterial communities. </li></ul><ul><li>The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. </li></ul><ul><li>This topographical and temporal survey provides a baseline for studies that examine the role of bacterial communities in disease states and the microbial interdependencies required to maintain healthy skin. </li></ul>
    25. 25. SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 <ul><li>Participants with mild ( n =18), moderate ( n =14), severe ( n =15), and no AD ( n =15), collected dust from their bed and bedroom floor, and from their home vacuum cleaner bag. </li></ul><ul><li>DNA for S. aureus was extracted from dust samples. </li></ul>SEVERE S. AUREUS DNA (pg/mg dust) IN BED DUST 14.67 15 – 10 – 5 – 0 MODERATE NO MILD 0.09 1.42 0.41 p<0.001 SEVERITY OF AD
    26. 26. SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 <ul><li>Participants with mild ( n =18), moderate ( n =14), severe ( n =15), and no AD ( n =15), collected dust from their bed and bedroom floor, and from their home vacuum cleaner bag. </li></ul><ul><li>DNA for S. aureus was extracted from dust samples. </li></ul>SEVERE S. AUREUS DNA (pg/mg dust) IN BED DUST 14.67 15 – 10 – 5 – 0 MODERATE NO MILD 0.09 1.42 0.41 p<0.001 Similar patterns were observed for dust from the bedroom floors and vacuum bags. SEVERITY OF AD
    27. 27. SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 <ul><li>Participants with mild ( n =18), moderate ( n =14), severe ( n =15), and no AD ( n =15), collected dust from their bed and bedroom floor, and from their home vacuum cleaner bag. </li></ul><ul><li>DNA for S. aureus was extracted from dust samples. </li></ul>SEVERE S. AUREUS DNA (pg/mg dust) IN BED DUST 14.67 15 – 10 – 5 – 0 MODERATE NO MILD 0.09 1.42 0.41 p<0.001 In the home and especially the bedroom, higher levels of S. aureus may contribute to disease severity and persistence in AD patients. SEVERITY OF AD
    28. 28. <ul><li>Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1. </li></ul><ul><li>50 children (1-6 yrs) with AD. </li></ul><ul><li>SCORAD. </li></ul>Association of Staphylococcal Superantigen-Specific Immunoglobulin E with Mild and Moderate Atopic Dermatitis Ong, J PED 2008;153:803 % children with ( +) sIgE 70 – 60 - 50 - 40 - 30 - 20 - 10 - 0 ≤ 15 (MILD) 38% 63% SCORAD >15 but <40 (MODERATE)
    29. 29. <ul><li>Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1. </li></ul><ul><li>50 children (1-6 yrs) with AD. </li></ul><ul><li>SCORAD. </li></ul>Association of Staphylococcal Superantigen-Specific Immunoglobulin E with Mild and Moderate Atopic Dermatitis Ong, J PED 2008;153:803 % children with ( +) sIgE 70 – 60 - 50 - 40 - 30 - 20 - 10 - 0 ≤ 15 (MILD) 38% 63% SCORAD >15 but <40 (MODERATE) Sensitization to staphylococcal superantigens is common even in young children with mild to moderate AD, and such sensitization may contribute to the disease severity of these patients.
    30. 30. Evidence for superantigen involvement in skin homing of T cells in atopic dermatitis . Strickland I, J Invest Dermatol. 1999;112:249–253 <ul><li>S aureus superantigens have the capacity to activate and expand T cells expressing specific T cell receptor BV gene segments, and also to increase their skin homing capacity via upregulation of the skin homing receptor, cutaneous lymphocyte-associated antigen ( CLA ). </li></ul>Analysis of skin-homing cutaneous lymphocyte antigen–positive T cells from patients with AD reveals that they have undergone a T-cell receptor V β expansion consistent with superantigenic stimulation Expansion of SAg-reactive T cells in both CD4 and CD8 subpopulations.
    31. 31. Superantigens are molecules which short-circuit the immune system , resulting in massive activation of T-cells rather than the usual, carefully controlled response to foreign antigens. It is believed that they do this by binding to both the variable region of the beta-chain of the T-cell receptor (V-beta) and to MHC II molecules, cross-linking them in a non-specific way. This results in polyclonal T-cell activation rather than the usual situation where only the few clones of T-cells responsive to a particular antigen presented by the MHC II molecule are activated. Schlievert JACI 2010;125:39
    32. 32. Model for the activation of CD41 T cells and macrophages by the superantigen (SAg) SEB compared with antigenic peptide activation of the same cells. Schlievert JACI 2010;125:39 Superantigens stimulate T-cell proliferation by forming a cross-bridge between certain variable parts of the b-chains of T-cell receptors (Vb-TCRs) and invariant regions on either or both of the a and b–chains of MHC II molecules on antigen-presenting cells
    33. 33. Application of Staphylococcal enterotoxin B (SEB) on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism. Skov L, J Allergy Clin Immunol 2000;105:820-6. <ul><li>SEB, vehicle (PBS), and sodium lauryl sulfate (SLS) on normal skin </li></ul><ul><li>6 AD patients </li></ul><ul><li>biopsy specimens </li></ul>N°of CD3+ T cells in AD biopsy 600 - 500 – 400 – 300 – 200 – 100 – 0 108 PBS SLS SEB 354 567 P<0.03
    34. 34. Skin from SEB patch test site showing positive staining of stratum corneum (open arrow) and deeper epidermis (solid arrow) , endothelium (small arrowhead), and perivascular areas (large arrowhead), with mAb to SEB. Control skin AD + SEB Application of Staphylococcal enterotoxin B (SEB) on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism. Skov L, J Allergy Clin Immunol 2000;105:820-6.
    35. 35. SEB applied to healthy and atopic skin leads to clinical reactions and increased skinfold thickness SLS: Sodium lauryl sulfate SEB: Staphylococcal enterotoxin B Application of Staphylococcal enterotoxin B (SEB) on normal and atopic skin induces up-regulation of T cells by a superantigen-mediated mechanism. Skov L, J Allergy Clin Immunol 2000;105:820-6.
    36. 36. SENSITIZATION TO MALASSEZIA IN INFANTS AND CHILDREN WITH ATOPIC DERMATITIS: PREVALENCE AND CLINICAL CHARACTERISTICS. Lange Allergy 2008; 63: 486 <ul><li>Sensitization to three different Malassezia species in 141 of children suffering from AD (mean age 3 yrs). </li></ul><ul><li>Immuno CAP™ system to M. sympodialis , --- M. globosa , and --- M. restricta. </li></ul>5.8 % patients with (+) sIgE <1 YR 18.1% >1 YR 20 – 15 – 10 – 5 – 0 15.2% AGE
    37. 37. SENSITIZATION TO MALASSEZIA IN INFANTS AND CHILDREN WITH ATOPIC DERMATITIS: PREVALENCE AND CLINICAL CHARACTERISTICS. Lange Allergy 2008; 63: 486 <ul><li>Sensitization to three different Malassezia species in 141 of children suffering from AD (mean age 3 yrs). </li></ul><ul><li>Immuno CAP™ system to M. sympodialis , --- M. globosa , and --- M. restricta. </li></ul>5.8 % patients with (+) sIgE <1 YR 18.1% >1 YR 20 – 15 – 10 – 5 – 0 15.2% The youngest sensitized patient was 4 months old. AGE
    38. 38. Atopic Dermatitis Exacerbations <ul><li>Predisposing factors and triggers </li></ul><ul><li>Prevention & Treatment General Concepts </li></ul><ul><li>Topical Treatment </li></ul><ul><li>Systemic Treatment </li></ul><ul><li>Education </li></ul><ul><li>Conclusions </li></ul>University of Verona, Italy Attilio Boner
    39. 39. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 prevention
    40. 40. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 prevention ?
    41. 41. Differential In Situ Cytokine Gene Expression in Acute versus Chronic Atopic Dermatitis Hamid Q, J Clin Invest 1994;94:870-6. P<0.01 normal-appearing skin in patients with AD is not immunologically normal. IL-4 mRNA
    42. 42. Hit early and hit hard in atopic dermatitis and not only in asthma Reitamo Allergy 2009; 64:503 <ul><li>In the treatment of atopic dermatitis a step up approach is used far too often : patients receive mild topical corticosteroid courses of variable length and no subsequent maintenance therapy . </li></ul><ul><li>Instead, atopic dermatitis should be treated efficiently from the beginning to clear the inflammation and restore the barrier function . </li></ul>
    43. 43. Hit early and hit hard in atopic dermatitis and not only in asthma Reitamo Allergy 2009; 64:503 <ul><li>Instead of keeping long intervals between corticosteroid courses, treatment should be continued for a few times weekly after the acute phase is controlled. </li></ul><ul><li>The new idea is to hit early and hit hard by using more of a step down approach to suppress inflammation as soon as possible . </li></ul><ul><li>After intensive topical treatment, the dosage and dosing intervals are reduced to the levels that are able to keep control of the disease. </li></ul>
    44. 44. Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677 <ul><li>Atopic dermatitis is a chronic disease which must be managed rather than cured . </li></ul><ul><li>As with other chronic diseases, adherence to treatment regimens can diminish over time , resulting in treatment failure. </li></ul><ul><li>In addition, first-line treatment involves a variety of topical medications , sometimes several at the same time. </li></ul><ul><li>Treatment must also be adjusted during a temporary worsening , or flare, if good control is to be maintained. </li></ul>
    45. 45. Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677 <ul><li>Atopic dermatitis is a chronic disease which must be managed rather than cured . </li></ul><ul><li>As with other chronic diseases, adherence to treatment regimens can diminish over time , resulting in treatment failure. </li></ul><ul><li>In addition, first-line treatment involves a variety of topical medications , sometimes several at the same time. </li></ul><ul><li>Treatment must also be adjusted during a temporary worsening , or flare, if good control is to be maintained. </li></ul>Written action plans (WAPs) can improve adherence in pediatric atopic dermatitis
    46. 46. Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 <ul><li>Complete emollient therapy </li></ul><ul><li>The most important treatment for all dry skin diseases, </li></ul><ul><li>including atopic eczema, asteatotic eczema and irritant </li></ul><ul><li>contact dermatitis, is complete emollient therapy Complete emollient therapy consists of: </li></ul><ul><li>Emollient bath products </li></ul><ul><li>Emollient wash products </li></ul><ul><li>Emollient creams or ointments </li></ul><ul><li>Everything that goes on to the skin should be emollient based. All soap and detergents should be replaced with </li></ul><ul><li>emollient wash, bath and shower products </li></ul>1 2 3
    47. 47. Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677 Envisoap Envioil Envicer3 Enviplus Idrocristalli Envicon pH=5.5
    48. 48. Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677
    49. 49. WRITTEN ACTION PLANS: what is it? Bhogal S, Cochrane Database Syst Rev 2006;3:CD005306. ‘‘ . . .[a] written set of instructions given to patients/parents that: 1. was intended to stay in their hands until the next visit (thus excluding pharmacy prescriptions); 2. provided instructions for daily treatment ; 3. provided instructions for initiation/step-up treatment in the event of deterioration ; and 4. provided information regarding when to seek urgent medical consultation .’’
    50. 50. Proactive therapy of atopic dermatitis – an emerging concept A. Wollenberg Allergy 2009: 64: 276–278 <ul><li>The proactive approach starts with an intensive topical anti-inflammatory therapy until all lesions have mostly cleared, followed by longterm, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin together with daily application of emollients to unaffected areas. </li></ul><ul><li>There is overwhelming evidence that normal-looking, nonlesional AD skin is not normal at all , but is characterized by a clinically meaningful barrier function defect and a sub-clinical eczematous skin reaction. </li></ul>
    51. 51. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 Basic treatment Basic therapy ofAD should comprise optimal skin care, addressing the skin barrier defect with regular use of emollients and skin hydration , along with identification and avoidance of specific and nonspecific trigger factors . Mild syndets with an adjusted pH value (acidified to pH 5.5-6.0 in order to protect the acid mantle of the skin) should be used for cleansing. Regular medical supervision , together with education of the patient or care providers and appropriate psychosocial support , is needed.
    52. 52. Atopic Dermatitis Exacerbations <ul><li>Predisposing factors and triggers </li></ul><ul><li>Prevention & Treatment General Concepts </li></ul><ul><li>Topical Treatment </li></ul><ul><li>Systemic Treatment </li></ul><ul><li>Education </li></ul><ul><li>Conclusions </li></ul>University of Verona, Italy Attilio Boner
    53. 53. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical treatment: Emollients. </li></ul><ul><li>The regular use of emollients is important for addressing the severe dryness of the skin caused by a dysfunction of the skin barrier with increased transepidermal water loss. </li></ul><ul><li>Emollients should be applied continuously , even if no actual inflammatory skin lesions are obvious. </li></ul><ul><li>‘‘ Water-in-oil’’ or ‘‘oil-in-water’’ emulsions might be substituted to support the skin barrier function. </li></ul>
    54. 54. Dosage: fingertip unit
    55. 55. Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse M.J.CORK, Br J Dermatol 2003; 149: 582 The mean quantity (g) of emollient cream ⁄ ointment being used per week reported at each clinic visit plotted against the mean investigator’s assessment of severity of the eczema using the six area, six sign atopic dermatitis severity score (SASSAD) at each visit. 54 g weekly 426 g weekly * * * * * * * * * *
    56. 56. Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse M.J.CORK, Br J Dermatol 2003; 149: 582 % children whose eczema was controlled (six area, six sign atopic dermatitis severity score, SASSAD <5) with emollients alone at each clinic visit. SASSAD at each clinic visit, for every patient entered into the study plotted against the amount of emollient cream ⁄ ointment (g) being used per week .
    57. 57. ETFAD⁄EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis U Darsow, C Gelmetti,for the European Task Force on Atopic Dermatitis ⁄EADV Eczema Task Force 2009 <ul><li>Emollient therapy </li></ul><ul><li>The cost of high quality allergy-safe emollient therapies often restrict their use because such therapies are considered to be non-prescription drugs and the quantities required are usually high (150–200 g per week in young children, up to 500 g in adults). </li></ul><ul><li>Their direct use on inflamed skin is poorly tolerated and it is </li></ul><ul><li>better to treat the acute flare first. </li></ul><ul><li>Emollients containing potentially allergenic proteins </li></ul><ul><li>such as peanut or oat should be avoided in the most vulnerable </li></ul><ul><li>age group before the age of 2 years . </li></ul>
    58. 58. <ul><li>52 ch with AD (2-12 yrs). </li></ul><ul><li>26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). </li></ul><ul><li>26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). </li></ul>EMOLLIENTS IMPROVE TREATMENT RESULTS WITH TOPICAL CORTICOSTEROIDS IN CHILDHOOD ATOPIC DERMATITIS: A RANDOMIZED COMPARATIVE STUDY Szczepanowska Pediatr Allergy Immunol 2008;19:614 STEROID * p=0.004 ** p=0.01 ***p<0.001 No emolient plus emolient
    59. 59. <ul><li>52 ch with AD (2-12 yrs). </li></ul><ul><li>26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). </li></ul><ul><li>26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). </li></ul>EMOLLIENTS IMPROVE TREATMENT RESULTS WITH TOPICAL CORTICOSTEROIDS IN CHILDHOOD ATOPIC DERMATITIS: A RANDOMIZED COMPARATIVE STUDY Szczepanowska Pediatr Allergy Immunol 2008;19:614 STEROID * p=0.004 ** p=0.01 ***p<0.001 No emolient plus emolient
    60. 60. <ul><li>52 ch with AD (2-12 yrs). </li></ul><ul><li>26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). </li></ul><ul><li>26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). </li></ul>EMOLLIENTS IMPROVE TREATMENT RESULTS WITH TOPICAL CORTICOSTEROIDS IN CHILDHOOD ATOPIC DERMATITIS: A RANDOMIZED COMPARATIVE STUDY Szczepanowska Pediatr Allergy Immunol 2008;19:614 STEROID Concomitant usage of emollients significantly improves xerosis and pruritus during corticosteroid treatment of atopic dermatitis and enables to maintain clinical improvement after therapy discontinuation. * p=0.004 ** p=0.01 ***p<0.001 No emolient plus emolient
    61. 61. <ul><li>52 ch with AD (2-12 yrs). </li></ul><ul><li>26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). </li></ul><ul><li>26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). </li></ul>EMOLLIENTS IMPROVE TREATMENT RESULTS WITH TOPICAL CORTICOSTEROIDS IN CHILDHOOD ATOPIC DERMATITIS: A RANDOMIZED COMPARATIVE STUDY Szczepanowska Pediatr Allergy Immunol 2008;19:614 * p=0.004 ** p=0.01 ***p<0.001 No emolient STEROID plus emolient
    62. 62. <ul><li>52 ch with AD (2-12 yrs). </li></ul><ul><li>26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). </li></ul><ul><li>26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). </li></ul>EMOLLIENTS IMPROVE TREATMENT RESULTS WITH TOPICAL CORTICOSTEROIDS IN CHILDHOOD ATOPIC DERMATITIS: A RANDOMIZED COMPARATIVE STUDY Szczepanowska Pediatr Allergy Immunol 2008;19:614 * p=0.004 ** p=0.01 ***p<0.001 No emolient STEROID EASI (Eczema Area and Severity Index) plus emolient
    63. 63. Dermal Hyaluronan Is Rapidly Reduced by Topical Treatment with Glucocorticoids C Gebhardt J Invest Dermatol 2009;129:1892 Dexamethasone reduces the dermal HA content in vivo. Immunohistochemical staining of Hyaluronan (HA) in human skin treated with 0.1% dexamethasone ointment three times daily (b) or left untreated (a) from the same individual and from a similar location. untreated 0.1% dexamethasone
    64. 64. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 Topical treatment: Topical glucocorticosteroids. To avoid steroid overuse and steroid-related side effects “… during acute flares, steroids should be used in combination with baseline emollient skin care…” ( ‘‘Water-in-oil’’ )
    65. 65. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical treatment: Topical glucocorticosteroids. </li></ul><ul><li>New steroid preparations with improved risk/benefit ratios </li></ul><ul><li>and lower atrophogenic potential , such as prednicarbate, </li></ul><ul><li>mometasone furoate , fluticasone , and methylprednisolone aceponate. </li></ul><ul><li>Topical steroid preparations should be applied no more than twice daily as short-term therapy for acute eczematous lesions. </li></ul><ul><li>Only mild to moderately potent preparations should be used on genital, facial, or intertriginous skin areas. </li></ul><ul><li>In children only mild to moderately potent steroid preparations should be used. </li></ul>
    66. 66. <ul><li>Retrospective case note study of 82 admissions to a children’s hospital for treatment of AD. </li></ul><ul><li>Different topical corticosteroid ointments were applied to the two </li></ul><ul><li>sides of the body. </li></ul>Side to side comparison of topical treatment in atopic dermatitis Ainley-Walker Arch Dis Child 1998;79:149–152 <ul><li>more potent topical corticosteroid </li></ul><ul><li>preparations appeared more effective than weaker preparations on 25 occasions, </li></ul><ul><li>there was no difference on 20 occasions, and </li></ul><ul><li>on seven occasions a weaker preparation appeared more effective. </li></ul><ul><li>incorporation of an antimicrobial agent did not appear to increase the efficacy of a preparation. </li></ul>
    67. 67. Classes of Topical Corticosteroids Class 1: Superpotent Corticosteroids: These are used in chronic inflammation of the skin where the skin is thickened ( lichenified ), pigmented and/or thick scaled. A few examples of superpotent steroids are clobetasole propionate and halobetasole propionate. Indications of superpotent steroids include neurodermatitis, thick scaled psoriasis etc. Class 2: Potent Corticosteroids: These are used in chronic inflammation where the thickness, pigmentation or scales are less than the above lesions. Examples of potent steroids are betamethasone dipropionate , halcinonide , fluocinonide . Indications of potent steroids are: lichen planus, neurodermatitis, moderately severe psoriasis vulgaris, chronic eczema etc.
    68. 68. Classes of Topical Corticosteroids Class 3: Upper Mid-Strength Corticosteroids: These are used in sub acute inflammation of the skin. Examples of upper mid-strength steroids are betamethasone valerate and fluticasone propionate . Uses in sub acute dermatitis, infective eczema, psoriasis, severe seborrheic dermatitis etc. Class 4: Mid-Strength Corticosteroids: These are used in sub acute and acute inflammation of the skin. Examples of mid-strength steroids are mometasone furoate , fluocinolone acetonide 0.025% , and triamcinolone acetonide . Uses in sub acute dermatitis, infective eczema, moderately severe seborrheic dermatitis, psoriasis, atopic dermatitis, alopecia areata etc.
    69. 69. Classes of Topical Corticosteroids Class 5: Lower Mid-Strength Corticosteroids: These are used in sub acute and acute inflammation of the skin. Examples of lower mid-strength corticosteroids are hydrocortisone butyrate , fluticasone propionate . Uses in infective eczema, seborrheic dermatitis, mild psoriasis etc. Class 6: Mild Corticosteroids: These are used in acute and sub acute inflammation of the skin. Examples of mild corticosteroids are desonide , fluocinolone 0.01%, clobetasone. Uses in sub acute and acute dermatitis, mild seborrheic dermatitis etc. Class 7: Least Potent Corticosteroids: These are used in mild acute and sub acute inflammation of the skin. Steroid responsive skin diseases of the face, flexures, and napkin area have to be treated with this class of topical steroids to avoid damage to the skin. Example of least potent steroids is hydrocortisone 1%.
    70. 70. Potenza degli steroidi topici Abbreviazioni: c:crema, p=pomata, u=unguento, lp= lipocrema, l= lozione, e= emulsione, s=soluzione, sch= schiuma, g= gel STEROIDI TOPICI MOLTO POTENTI (GRADO II) Alcinonide 0,1% c. Halciderm Amcinonide 0,1% p. Amcinil Betametasone dipropionato 0,05% u c Diprosone; Betamesol; Betametasone dipropionato Diflucortolone valerato 0,3% c. p. u. Nerisona forte, Temetex forte, Cortical, Dervin Fluocinonide 0,05% p. g. l. Flu 21, Topsyn STEROIDI TOPICI SUPERPOTENTI (GRADO I) Clobetasolo propionato 0,05% p. u. s. sch. Clobesol; Olux sch
    71. 71. STEROIDI TOPICI POTENTI B (GRADO IV) Alclometasone dipropionato 0,1% c. u. l. Legederm Beclometasone dipropionato 0,025% c. Menaderm simplex; Beclometasone Doc Betametasone benzoato o,1% c. l. g. Beben Budesonide 0,025 c. u. Bidien; Preferid STEROIDI TOPICI POTENTI A (GRADO III) Betametasone dipropionato 0,05% c. u. s. Diprosone, Betamesol, Betanesone dipropionato Sandoz Betametasone valerato 0,1% c. u. e. s. Ecoval 70, Bettamousse, Betesil cerotti Desossimetasone 0,025% e. Flubason Diflucortolone valerato 0,1% c. u. s. Nerisona, Temetex, Dermaval, Cortical 0,2, Flu-cortanest Fluticasone propionato 0,05% c.; 0,005% u. Flixoderm crema e unguento Metilprednisolone aceponato 0,1% c. u .s. Advantan, Avancort Mometasone furoato 0,1% c. u .s. Altosone, Elocon
    72. 72. STEROIDI TOPICI DI POTENZA MINIMA A (GRADO VI) Clobetasone butirrato 0,05% c. Eumovate Fluocinolone acetonide 0,01% glicole Localyn glicole Fluocortin butilestere 0,02% c. p. Vaspit STEROIDI TOPICI DI POTENZA MINIMA B (GRADO VII) Idrocortisone da 0,05 a 1% c. p. Lenirit; Dermocortal; Cortidro; Dermadex c Fluocinolone acetonide 0,01% glicole Localyn glicole Fluocortin butilestere 0,02% c. p. Vaspit Desametasone 0,2% c. u. Dermadex; Soldesam Flumetasone Solo in associazione Metiprednisolone Solo in associazione STEROIDI TOPICI DI MEDIA POTENZA (GRADO V) Betametasone benzoato 0,025% c. Beben crema dermica Betametasone valeroacetato 0,05% p. u. l. Beta 21 Desonide 0,05% c. e. l. Sterades; Reticus Idrocortisone butirrato 0,1% c. p. l. e. Locoidon Fluocinolone acetonide 0,025% p.l. c. Localyn; Fluocit; Fluovitef; Omniderm; Sterolone; Ultraderm; Boniderma; Dermolin; Fluvean Triamcitolone Acetonide 0,1% c Ledercort A10
    73. 73. Classes of Topical Corticosteroids <ul><li>creams, </li></ul><ul><li>lotions, </li></ul><ul><li>ointments, </li></ul><ul><li>gels </li></ul>Ointments are greasy and preferred in chronic dermatitis and scaly diseases like psoriasis. Creams and solutions are a class below in potency than ointments. Creams can be used in acute and subacute skin inflammation. Gels and lotions are preferred in hairy areas and scalp. Topical corticosteroids come in several forms, including:
    74. 74. Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema Thomas K S BMJ 2002;324:1–7 <ul><li>174 children with mild or moderate AD </li></ul><ul><li>0.1% betamethasone valerate ( potent group) applied for 3 days followed by the base ointment for 4 days </li></ul><ul><li>versus </li></ul><ul><li>1% hydrocortisone ( mild group) for 7 days . </li></ul><ul><li>No differences were found between the two groups for all outcomes. </li></ul><ul><li>The median number of scratch­free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval - 2.0 to 4.0, P = 0.53). </li></ul><ul><li>The median number of relapses for both groups was 1.0. </li></ul><ul><li>Both groups showed clinically important improvements in disease severity and quality of life . </li></ul>
    75. 75. Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema Thomas K S BMJ 2002;324:1–7 Outcome measures of children with mild to moderate atopic eczema treated with short bursts of a potent topical corticosteroid (potent arm) or continuous use of a mild preparation (mild arm).
    76. 76. Prevention of exacerbations with topical treatment <ul><li>An important concept with therapeutic implications is the recognition that normal-appearing skin in patients with AD is not immunologically normal. </li></ul><ul><li>Hamid Q, J Clin Invest 1994;94:870-6. </li></ul><ul><li>One approach to patients whose eczema tends to relapse in the same location is that of proactive therapy . </li></ul><ul><li>After a period of stabilization, topical steroids (1,2) or calcineurin inhibitors (3-5) are applied to areas of previously involved but normal-appearing skin rather than waiting for eczema to flare. </li></ul><ul><li>1) Berth-Jones J, BMJ 2003;326:1367. 2) Peserico A, Br J Dermatol 2008;158:801. 3) Wollenberg A, Allergy 2008;63:742. 4) Breneman D, J Am Acad Dermatol 2008;58:990-9. 5) Paller AS, Pediatrics 2008;122:e1210-8 . </li></ul>
    77. 77. <ul><li>Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for 4 weeks to stabilise their condition. </li></ul><ul><li>The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo </li></ul><ul><li>base (emollient alone) twice weekly to the areas that were usually affected . </li></ul>Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. Berth-Jones J, BMJ 2003;326:1367.
    78. 78. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study. Berth-Jones J, BMJ 2003;326:1367. Kaplan-Meier plot showing the probability of remaining free from relapse during the 16 week maintenance phase.
    79. 79. Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study Berth-Jones J BMJ 2003;326:1367 <ul><li>Patients with moderate to severe atopic dermatitis (aged 12-65) </li></ul><ul><li>fluticasone propionate </li></ul><ul><li>(0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks </li></ul><ul><li>The patients whose disease was brought under control then continued into a 16 week maintenance phase , applying emollient on a daily basis with either the same formulation of fluticasone propionate or its placebo </li></ul><ul><li>base (emollient alone) twice weekly to the areas that were usually affected. </li></ul>Kaplan-Meier plot showing the probability of remaining free from relapse during the 16 week maintenance phase.
    80. 80. Reduction of relapses of atopic dermatitis with methylprednisolone aceponate cream twice weekly in addition to maintenance treatment with emollient: a multicentre, randomized, double-blind, controlled study. Peserico A, Br J Dermatol 2008;158:801-7.
    81. 81. Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Wollenberg Allergy2008;63:742.
    82. 82. Intermittent therapy for flare prevention and long-term disease control instabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle. Breneman D, J Am Acad Dermatol 2008;58:990-9.
    83. 83. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8. <ul><li>206 patients who were 2 to 15 years of age and had moderate to severe atopic dermatitis were randomly assigned to 4 days of twice-daily double-blind therapy with either alclometasone ointment 0.05% or tacrolimus ointment 0.03% (Phase I acute), followed by up to 16 weeks of twice-daily open-label tacrolimus ointment 0.03% (Phase I short-term). </li></ul><ul><li>Patients whose disease stabilized underwent new randomization to double-blind tacrolimus ointment 0.03% or vehicle applied once daily, 3 times per week to clinically normal-appearing skin for up </li></ul><ul><li>to 40 weeks (Phase II). </li></ul><ul><li>Corticosteroid use was prohibited. </li></ul>
    84. 84. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8.
    85. 85. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8. % patients who achieved clear or almost clear status (Phase I).
    86. 86. Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8. Kaplan-Meier plot of the probability of remaining free from relapse. The median time to first relapse was 116 days for tacrolimus versus 31 days for vehicle ( P=0.04 ).
    87. 87. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis Jensen JACI 2009;123: 1124 <ul><li>15 patients with AD treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks. </li></ul><ul><li>Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier. </li></ul><ul><li>Dye penetration, a marker of the outside-inside barrier. </li></ul>
    88. 88. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis Jensen JACI 2009;123: 1124 <ul><li>15 patients with AD treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks. </li></ul><ul><li>Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier. </li></ul><ul><li>Dye penetration, a marker of the outside-inside barrier. </li></ul>
    89. 89. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis Jensen JACI 2009;123: 1124 <ul><li>15 patients with AD treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks. </li></ul><ul><li>Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier. </li></ul><ul><li>Dye penetration, a marker of the outside-inside barrier. </li></ul>
    90. 90. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis Jensen JACI 2009;123: 1124 Proliferation rate and epidermal thickness.
    91. 91. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical treatment: Topical calcineurin inhibitors </li></ul><ul><li>Pimecrolimus cream (1%) and tacrolimus ointment (0.03%) are approved for the treatment of AD in children aged ≥ 2 years . </li></ul><ul><li>The anti-inflammatory potency of 0.1% tacrolimus ointment is similar to a corticosteroid with moderate potency , whereas 1% pimecrolimus cream is less active . </li></ul><ul><li>Thus far, no trials have been published comparing pimecrolimus 1% with a mild corticosteroid. </li></ul><ul><li>Both agents proved to be effective, with a good safety profile for a treatment period of up to 2 years with pimecrolimus and up to 4 years with tacrolimus. </li></ul>
    92. 92. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Treatment with TCIs is no t associated with a risk of skin atrophy . Therefore they are a useful alternative for the treatment of sensitive skin areas, such as the face and intertriginous regions. </li></ul><ul><li>Generalized viral infections, such as eczema herpeticum </li></ul><ul><li>or eczema molluscatum, have been observed during TCI treatment. </li></ul><ul><li>These drugs are recommended as second-line treatments and that their use in children younger than 2 years of age is currently not recommended. </li></ul>Topical treatment: Topical calcineurin inhibitors
    93. 93. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press <ul><li>Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . </li></ul><ul><li>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 </li></ul><ul><li>TCIs. </li></ul><ul><li>Antimicrobial peptide = mBD3, CRAMP </li></ul>
    94. 94. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press <ul><li>Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . </li></ul><ul><li>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 </li></ul><ul><li>TCIs. </li></ul><ul><li>Antimicrobial peptide = mBD3, CRAMP </li></ul>Topical tacrolimus impairs barrier homeostasis and SC integrity not only by inhibiting epidermal lipid synthesis and lamellar body (LB) formation , but also by decreasing corneodesmosome (CD) density .
    95. 95. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press <ul><li>Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . </li></ul><ul><li>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 </li></ul><ul><li>TCIs. </li></ul><ul><li>Antimicrobial peptide = mBD3, CRAMP </li></ul>Co-application of ceramides, cholesterol and free fatty acids was associated with a reduction in TEWL induced by Tacrolimus
    96. 96. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Wet-wrap therapy. </li></ul><ul><li>A wet layer of cotton dressing, which is then covered with tubular bandages applied over emollients in combination with antiseptics or topical steroids, has been shown to be beneficial in cases of exacerbated AD skin lesions. </li></ul><ul><li>Mallon E, J Dermatolog Treat 1994;5:97-8. </li></ul><ul><li>Oranje AP, J Dermatolog Treat 1999;10:73-4. </li></ul><ul><li>Foelster-Holst R, Dermatology2006;212:66-9. </li></ul><ul><li>A more practical alternative approach using clothing rather than bandages has also been described in detail. </li></ul><ul><li>Boguniewicz M, Immunol Allergy Clin North Am 2002;22:107-24. </li></ul>
    97. 97. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 <ul><li>The ancient Babylonians and Egyptians observed that covered moist wounds heal more rapidly than open dry wounds , but it took until 1958 for Odland to first describe that a blister healed faster when left unbroken. </li></ul><ul><li>Since then many studies have demonstrated the beneficial effect of a moist environment on wound healing . </li></ul><ul><li>Wet dressings support the rehydration of the skin and afford cooling of the skin through evaporation . This gradual cooling has an anti-inflammatory effect and reduces itching . </li></ul><ul><li>The hydration and occlusion provided by the wet wraps also increases the absorption of topical medications. </li></ul>old style wet wraps
    98. 98. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 <ul><li>The ancient Babylonians and Egyptians observed that covered moist wounds heal more rapidly than open dry wounds , but it took until 1958 for Odland to first describe that a blister healed faster when left unbroken. </li></ul><ul><li>Since then many studies have demonstrated the beneficial effect of a moist environment on wound healing . </li></ul><ul><li>Wet dressings support the rehydration of the skin and afford cooling of the skin through evaporation . This gradual cooling has an anti-inflammatory effect and reduces itching . </li></ul><ul><li>The hydration and occlusion provided by the wet wraps also increases the absorption of topical medications. </li></ul>These dressings also act as a mechanical barrier against scratching, allowing more rapid healing of excoriated lesions and protection against external factors such as allergens and bacteria, although heavily infected eczema may be worsened by the occlusion . old style wet wraps
    99. 99. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 <ul><li>The use of wet dressings in AD generally encompasses a layer of wet tubular cotton gauze bandages, covered by a corresponding layer of dry bandaging . </li></ul><ul><li>Advice is usually given to put the bandages in lukewarm water , squeeze the water out of the bandages and then apply. </li></ul><ul><li>Water should be at body temperature . If the water is too cold vasoconstriction is soon followed by secondary vasodilation . If too hot,vasodilation occurs with increased pruritus . </li></ul>
    100. 100. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 <ul><li>One layer wet wrap with ointment </li></ul><ul><li>To avoid the undesired desiccation of the skin , a modified </li></ul><ul><li>procedure came into use for eczematous conditions, the ‘oil wet wrap’. </li></ul><ul><li>First, an ointment is spread generously onto the skin . Then a bandage, soaked in lukewarm tap water and squeezed out to leave it damp is applied over it. </li></ul><ul><li>For extensive skin affections damp pyjama cloth can be used instead of bandages. </li></ul><ul><li>The effect is the same as with WWT, without the side-effect of drying out the skin’. However, ointment enhances the risk of </li></ul><ul><li>folliculitis . </li></ul>
    101. 101. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 <ul><li>Double-layer wet wrap with ointment or cream and water </li></ul><ul><li>A damp tubular bandage is applied over the ointment layer , as in the oil-wet wrap, followed by a second layer of dry tubular bandage . </li></ul><ul><li>The second bandage layer results in a more gradual evaporation of the water from the wet bandage and therefore in a prolonged effect of moisturization and cooling . </li></ul>
    102. 102. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 Wet-wrap treatment in children with atopic dermatitis <ul><li>Diluted fluticasone propionate 0.05% cream (1 : 4, 1 : 10 and 1 : 20) is used once daily. </li></ul><ul><li>FP cream and mometasone furoate are newer potent topical corticosteroid agents, which have been shown to have an improved benefit/risk ratio with relatively low systemic absorption and may further lower the risk of steroid induced side-effects. </li></ul><ul><li>However, there is still a risk of skin atrophy. </li></ul><ul><li>Currently, the use of 1 : 20 dilutions of FP cream is advocated in children under 2 years of age and dilutions of 1 : 4 and stronger are strongly discouraged. </li></ul>
    103. 103. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature Oranje AP, JEADV 2006,20:1277 Wet-wrap treatment in children with atopic dermatitis Oranje and coworkers (unpublished data) observed an initial impressive improvement after 3 to 7 days, but after 4 weeks worsening and stabilizing of AD to mild to moderate severity was observed. We call this the ‘broken stick effect’
    104. 104. A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 <ul><li>50 children (age 4–27 months) with moderate to severe eczema </li></ul><ul><li>‘‘ wet wrap’’ </li></ul><ul><li>bandages versus conventional topically applied ointments </li></ul>
    105. 105. A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 <ul><li>50 children (age 4–27 months) with moderate to severe eczema </li></ul><ul><li>‘‘ wet wrap’’ </li></ul><ul><li>bandages versus conventional topically applied ointments </li></ul>There was no significant difference between the two groups in terms of overall improvement at four weeks or in the timescale of improvements.
    106. 106. A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 <ul><li>50 children (age 4–27 months) with moderate to severe eczema </li></ul><ul><li>‘‘ wet wrap’’ </li></ul><ul><li>bandages versus conventional topically applied ointments </li></ul>The amount of topical of topical steroid used was similar in both groups.
    107. 107. A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 <ul><li>50 children (age 4–27 months) with moderate to severe eczema </li></ul><ul><li>‘‘ wet wrap’’ </li></ul><ul><li>bandages versus conventional topically applied ointments </li></ul>% pts requiring antibiotics 30 – 20 – 10 – 0 0% conventional p=0.05 ‘‘ wet wrap’’ 22%
    108. 108. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical antimicrobial therapy. </li></ul><ul><li>The skin of patients with AD is heavily colonized with S.aureus , even at uninvolved sites. </li></ul><ul><li>Toxins secreted by the majority of S. aureus on the skin behave as superantigens and can directly influence the disease activity, although clinical signs of bacterial superinfection might be absent . </li></ul><ul><li>- Breuer K, Bacterial infections and atopic dermatitis. Allergy 2001;56:1034-41. </li></ul><ul><li>- Breuer K, Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 2002;147:55-61. </li></ul>
    109. 109. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical antimicrobial therapy. </li></ul><ul><li>Topical antiseptics, such as triclosan (2,4,4’-trichloro-2’ hydroxydiphenyl ether) or chlorhexidine , offer the advantage of a low sensitizing potential and low resistance rate. </li></ul><ul><li>They can be used in emollients or as part of an additional wet-wrap dressing therapy. Breuer K, Br J Dermatol 2002;147:55-61. </li></ul><ul><li>The topical use of triclosan has been shown to be effective in significantly reducing skin colonization with S aureus and skin symptoms. Sporik R, J Allergy Clin Immunol 1997;99:861. </li></ul>
    110. 110. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 <ul><li>Topical antimicrobial therapy. </li></ul><ul><li>Topical antiseptics, such as triclosan (2,4,4’-trichloro-2’ hydroxydiphenyl ether) or chlorhexidine , offer the advantage of a low sensitizing potential and low resistance rate. </li></ul><ul><li>They can be used in emollients or as part of an additional wet-wrap dressing therapy. Breuer K, Br J Dermatol 2002;147:55-61. </li></ul><ul><li>The topical use of triclosan has been shown to be effective in significantly reducing skin colonization with S aureus and skin symptoms. Sporik R, J Allergy Clin Immunol 1997;99:861. </li></ul>Triclosan: application and safety. Bhargava HN, Am J Infect Control 1996;24:209. Triclosan has no t an irritative , photoallergenic , phototoxic, mutagenic, or carcinogenic activity .
    111. 111. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>Double-blind study </li></ul><ul><li>Daily bathing with an antibacterial soap for 9 wks </li></ul><ul><li>50 patients </li></ul><ul><li>0.025% triamcinolone acetonide cream as needed for the 6 first wks </li></ul>Mean global improvement scores throughout the 6 week treatment period and the subsequent regression period when the use of corticosteroid cream was restricted. (-5=severe worsening, 0=no change, 5= total clearning)
    112. 112. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>Double-blind study </li></ul><ul><li>Daily bathing with an antibacterial soap for 9 wks </li></ul><ul><li>50 patients </li></ul><ul><li>0.025% triamcinolone acetonide cream as needed for the 6 first wks </li></ul>Mean log 10 colony-forming units
    113. 113. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>Double-blind study </li></ul><ul><li>Daily bathing with an antibacterial soap for 9 wks </li></ul><ul><li>50 patients </li></ul><ul><li>0.025% triamcinolone acetonide cream as needed for the 6 first wks </li></ul>Mean log 10 colony-forming units <ul><li>Leyden Br. J. Dermatol. </li></ul><ul><li>1974: 90: 525 </li></ul><ul><li>Bibel Can. J. Microbiol. </li></ul><ul><li>1977; 23: 1062 </li></ul>Affected skin of 80% to 95% of atopic patients (versus about 5% of controls) is colonized with S. aureus .
    114. 114. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>The clinical improvements, including reductions in the extent and severity of atopyc dermatitis, itching, and levels of microorganisms like S. aureus , were consistently greater in the antibacterial soap regimen than in the placebo soap regimen. </li></ul><ul><li>Dermatitis in the antibacterial soap group remained less severe than in the placebo group during the regression period when corticosteroid use was prohibited. </li></ul>
    115. 115. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>The clinical improvements, including reductions in the extent and severity of atopyc dermatitis, itching, and levels of microorganisms like S. aureus , were consistently greater in the antibacterial soap regimen than in the placebo soap regimen. </li></ul><ul><li>Dermatitis in the antibacterial soap group remained less severe than in the placebo group during the regression period when corticosteroid use was prohibited. </li></ul>These differences in product efficacy were not impacted by the amount of topical corticosteroids used because the total amounts used by both groups were similar.
    116. 116. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>Patients with atopic dermatitis are frequently instructed to avoid the use of antibacterial soap; however, no significant incident of irritation or irritant contact dermatitis was reported in either group. </li></ul><ul><li>Regular use of an antibacterial soap containing triclocarban (triclosan) may lead to a significant improvement in atopic dermatitis without increasing the incidence of irritation. </li></ul>
    117. 117. THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 <ul><li>Patients with atopic dermatitis are frequently instructed to avoid the use of antibacterial soap; however, no significant incident of irritation or irritant contact dermatitis was reported in either group. </li></ul><ul><li>Regular use of an antibacterial soap containing triclocarban (triclosan) may lead to a significant improvement in atopic dermatitis without increasing the incidence of irritation. </li></ul>This type of antibacterial soap may be a useful, well-tolerated, and inexpensive addition to the clinical management of atopic dermatitis.
    118. 118. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Other topical antibiotic therapies include topical antiseptics, </li></ul><ul><li>such as triclosan (2,4,4-trichloro-2-hydroxydiphenyl </li></ul><ul><li>ether) or chlorhexidine , that can be used in combination with </li></ul><ul><li>emollients or as part of wet-wrap dressing therapy. </li></ul><ul><li>These agents have low resistance and sensitization rates, although IgE-mediated hypersensitivity to chlorhexidine has been described. Garvey LH, J Allergy Clin Immunol. 2007;120:409–415. </li></ul><ul><li>Also, bleach baths given once or twice a week are a simple and effective way to decrease colonization. </li></ul><ul><li>One-third cup of bleach into a bathtub filled to the level of the patient’s naval . </li></ul>
    119. 119. IgE-mediated allergy to chlorhexidine. Garvey LH, J Allergy Clin Immunol. 2007;120:409–415. <ul><li>22 patients with clinical history suggestive of chlorhexidine allergy were included. </li></ul><ul><li>Skin tests with chlorhexidine </li></ul><ul><li>Twelve patients were skin test positive and 10 were skin test negative. </li></ul><ul><li>Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test. </li></ul>
    120. 120. <ul><li>All patients received cephalexin (Ceporex-Kepral) at 50 mg/kg per day (maximum of 2 g/day), divided into 3 daily doses, for 2 weeks to treat their staphylococcal infections. </li></ul><ul><li>Patients were instructed to add either 0.5 cup of 6% bleach (final concentration: 0.005%) to a full bathtub of water (~150 litres). </li></ul><ul><li>Patients were instructed to bathe in the dilute bleach bath (Dilution of Amukine Med=0.05%) or placebo bath for 5 to 10 minutes twice weekly. </li></ul>Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 Half a cup of 6% bleach (NaClO)
    121. 121. Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 <ul><li>31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections (weeping, crusting, and/or pustules). </li></ul><ul><li>All patients received orally administered cephalexin for 14 days. </li></ul><ul><li>Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. </li></ul>CHANGES IN MEAN EASI SCORES OVER TIME. ECZEMA AREA AND SEVERITY INDEX (EASI). time, months
    122. 122. Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 <ul><li>31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections (weeping, crusting, and/or pustules). </li></ul><ul><li>All patients received orally administered cephalexin for 14 days. </li></ul><ul><li>Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. </li></ul>CHANGES IN MEAN PROPORTIONS OF BODY SURFACE AREA AFFECTED OVER TIME. time, months
    123. 123. Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 <ul><li>31 patients, 6 months to 17 years of age, with moderate to severe atopic dermatitis and clinical signs of secondary bacterial infections (weeping, crusting, and/or pustules). </li></ul><ul><li>All patients received orally administered cephalexin for 14 days. </li></ul><ul><li>Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. </li></ul>We observed excellent tolerability of the dilute bleach baths although some children complained early in the course, when sites of dermatitis were crusted or eroded as a result of secondary infections. CHANGES IN MEAN PROPORTIONS OF BODY SURFACE AREA AFFECTED OVER TIME. time, months
    124. 124. MgCl salt Skin barrier Skin hydration Inflammation Allantoin Hydration Skin barrier Repair Urea A Skin hydration NaCl salt urea’s effects Loden,ActaDermVen.2002;82:45 Thornfeldt,DermSurg.2005;31:873 Proksch,IntJDerm.2005;44:151 Hagstromer,SkinPhaApSkinPhy.2001;14:27 Bathing in a complementary salt solution S.aureus attachment Akiyama J Dermat Sci 1998;16:216
    125. 125. Bacterial Colonization And Infection In Ad: To Treat Or Not To Treat (With Antibiotics) Boguniewicz JACI 2010;125:4 <ul><li>Other approaches include </li></ul><ul><li>silver-impregnated clothing , </li></ul><ul><li>which has been shown: </li></ul><ul><li>to reduce staphylococcal colonization, </li></ul><ul><li>improve clinical parameters, and </li></ul><ul><li>reduce topical steroid use in patients with AD. </li></ul><ul><li>Gauger A, Dermatology 2003;207:15-21. </li></ul><ul><li>Gauger A, J Eur Acad Dermatol Venereol 2006;20:534-41. </li></ul>
    126. 126. 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 <ul><li>Silver textile </li></ul><ul><li>37 patients with AD </li></ul><ul><li>single-blinded </li></ul><ul><li>in vivo study. </li></ul><ul><li>sensitization potential was tested in a patch test in 111 panellists. </li></ul>Silver textiles % scavenged
    127. 127. 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 <ul><li>Silver textile </li></ul><ul><li>37 patients with AD </li></ul><ul><li>single-blinded </li></ul><ul><li>in vivo study. </li></ul><ul><li>sensitization potential was tested in a patch test in 111 panellists. </li></ul>Silver textiles Superoxide scavenging for the three tested groups: All three test fibres induced significant superoxide radicals scavenging compared with Phoaslisne control. % scavenged
    128. 128. <ul><li>Silver textile </li></ul><ul><li>37 patients with AD </li></ul><ul><li>single-blinded </li></ul><ul><li>in vivo study. </li></ul><ul><li>sensitization potential was tested in a patch test in 111 panellists. </li></ul>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
    129. 129. <ul><li>Silver textile </li></ul><ul><li>37 patients with AD </li></ul><ul><li>single-blinded </li></ul><ul><li>in vivo study. </li></ul><ul><li>sensitization potential was tested in a patch test in 111 panellists. </li></ul>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
    130. 130. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Silver also has antimicrobial properties, and the use of silver-coated textiles has been associated with reduced S aureus colonization and AD severity as well. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541.
    131. 131. Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. <ul><li>15 patients with AD </li></ul><ul><li>S. aureus colonization and clinical severity of AD over a 2-week period. </li></ul><ul><li>Flexures were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period </li></ul>A highly significant decrease in S. aureus colonization could be seen on the site covered by the silver-coated textile already 2 days after initiation lasting until the end of the treatment.
    132. 132. Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. <ul><li>15 patients with AD </li></ul><ul><li>S. aureus colonization and clinical severity of AD over a 2-week period. </li></ul><ul><li>Flexures were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period </li></ul>A highly significant decrease in S. aureus colonization could be seen on the site covered by the silver-coated textile already 2 days after initiation lasting until the end of the treatment.
    133. 133. Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. <ul><li>15 patients with AD </li></ul><ul><li>S. aureus colonization and clinical severity of AD over a 2-week period. </li></ul><ul><li>Flexures were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period </li></ul>7 days after cessation, S. aureus density remained significantly lower compared to baseline.
    134. 134. Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. <ul><li>15 patients with AD </li></ul><ul><li>S. aureus colonization and clinical severity of AD over a 2-week period. </li></ul><ul><li>Flexures were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period </li></ul>In addition, significantly lower numbers of S. aureus were observed on the silver-coated textile site in comparison to cotton at the end of treatment as well as at the time point of control.
    135. 135. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>
    136. 136. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Significant improvement of SCORAD after 1 week and after 2 weeks in the verum group (silver textiles). No statistical difference in the placebo group (cotton) between the condition before, during and after the study. severity of eczema
    137. 137. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Eczema extent in the SCORAD Significant reduction of eczema extension in the first and second week in the verum group (silver textiles). Reduction of eczema extent in the placebo group (cotton) without statistical significance.
    138. 138. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Subjective symptoms in SCORAD (sleep loss, itching) Significant reduction of subjective symtoms in the placebo group (cotton) in the first week, but not at the end of the study.
    139. 139. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Subjective symptoms in SCORAD (sleep loss, itching) In the verum group (silver textiles), significant reduction of sleeploss and itching after the study when compared to baseline.
    140. 140. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Impairment of quality of life (QOL) significant improvement at the end of study in placebo (cotton) and verum (silver) group.
    141. 141. Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. <ul><li>68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. </li></ul><ul><li>either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) </li></ul><ul><li>directly on the skin for 2 weeks. </li></ul>Concomitant topical steroid therapy tendency of more pronounced reduction of steroid use in the verum group (silver textiles) without statistical significance.
    142. 142. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Topical antibiotic therapies have also been investigated and are considered effective for mild and localized forms of superinfection . </li></ul><ul><li>Topical fusidic acid is effective against S aureus and is used in combination with topical steroids. </li></ul><ul><li>Although effective, its use as topical antibiotic monotherapy is controversial and should be restricted to short periods because longer courses are associated with increased resistance . </li></ul><ul><li>Topical therapy with bacitracin or neosporin is of questionable value in the treatment of AD given these agents are known sensitizers . AAAAI Ann Allergy Asthma Immunol . 2006;97:S1–38 . </li></ul>
    143. 143. Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. <ul><li>Fusidic acid inhibits bacterial protein synthesis. </li></ul><ul><li>The action of fusidic acid is largely bacteriostatic, but at high concentrations (2 to 32-fold higher than the MIC) the effect may be bactericidal </li></ul><ul><li>Topical preparations of fusidic acid and a glucocorticoid </li></ul><ul><li>are widely used in the treatment of atopic dermatitis. Skin colonisation with S aureus is a characteristic feature of atopic dermatitis, and is believed to drive the inflammatory process, </li></ul><ul><li>leading to the recommendation that fusidic acid-glucocorticoid preparations may be the treatment of choice for this condition. </li></ul>
    144. 144. Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. <ul><li>For acute skin and soft tissue infections, 5–10 day courses of fusidic acid have been associated with a low incidence(0% – 3.9%) of fusidic acid resistance emerging at the end of treatment. </li></ul><ul><li>In hospitalised patients with chronic dermatological conditions, burns, or leg ulcers, fusidic acid resistance rates may rise up to 43% following treatment. </li></ul><ul><li>In the UK fusidic acid resistance rates of between 11.5% and 18.5% have recently been reported, with especially high rates in children. </li></ul>
    145. 145. Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. <ul><li>There is no evidence to support the general use of antibiotic therapy in atopic dermatitis </li></ul><ul><li>It is sensible to restrict use of topical fusidic acid to short courses for patients outside hospital without underlying skin conditions i.e. in children with impetigo </li></ul><ul><li>Topical antibiotics are best avoided in any chronic skin condition, because of both doubtful efficacy and the higher risk of resistance emerging during therapy, at least with fusidic acid. </li></ul>
    146. 146. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Mupirocin ointment plus hydrocortisone butyrate vs hydrocortisone alone plus vehicle ointment was compared in a double-blind, placebo-controlled, randomized trial. </li></ul><ul><li>No difference in benefit was noted in either group on days 14 or 28 of treatment, although the combination group demonstrated a </li></ul><ul><li>greater improvement by day 7 in patients with more severe </li></ul><ul><li>disease . Gong JQ, Br J Dermatol. 2006;155:680–687. </li></ul><ul><li>These findings are consistent with a prior investigation that observed patients with higher numbers of S aureus (10 6 CFU/cm2) had a greater benefit from combination treatment than patients with low numbers of S aureus (mean, 150,000 CFU/cm2) who had equal benefit from combination treatment or steroids alone. Leyden JJ, Br J Dermatol. 1977;96:179 –187. </li></ul>
    147. 147. The case for steroid–antibiotic combinations. Leyden JJ, Br J Dermatol. 1977;96:179 –187.
    148. 148. Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial Gong Br J Dermatol 2006;155:680 <ul><li>Eczema Area and Severity Index (EASI) scores before the start of the trial and on the 7th, 14th and 28th day of treatment. </li></ul><ul><li>Swabs for bacterial isolation from lesional and non-lesional skin. </li></ul><ul><li>Topical therapy with mupirocin plus hydrocortisone butyrate ointment vs vehicle ointment plus hydrocortisone butyrate . </li></ul><ul><li>327 patients. </li></ul>% PATIENTS WITH (+) CULTURES FOR S. AUREUS 75% LESIONAL SKIN 34% NON LESIONAL SKIN 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 P<0.05 ATOPIC DERMATITIS
    149. 149. Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial Gong Br J Dermatol 2006;155:680 <ul><li>Eczema Area and Severity Index (EASI) scores before the start of the trial and on the 7th, 14th and 28th day of treatment. </li></ul><ul><li>Swabs for bacterial isolation from lesional and non-lesional skin. </li></ul><ul><li>Topical therapy with mupirocin plus hydrocortisone butyrate ointment vs vehicle ointment plus hydrocortisone butyrate . </li></ul><ul><li>327 patients. </li></ul>Positive rates of bacteria and scores of patients with atopic dermatitis before and on the 7th day of treatment (mean ± SD). mupirocin plus hydrocortisone hydrocortisone alone
    150. 150. <ul><li>Good therapeutic effects were obtained in both the combination experimental groups and the control groups (P< 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P> 0.05). </li></ul><ul><li>However, in patients with eczema with a clinical score of >8 or in patients with AD with a clinical score of >7, the therapeutic effect in the experimental groups was superior to that in the control groups (P< 0.05) on the 7th day of treatment . </li></ul><ul><li>There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). </li></ul>Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial Gong Br J Dermatol 2006;155:680
    151. 151. <ul><li>Good therapeutic effects were obtained in both the combination experimental groups and the control groups (P< 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P> 0.05). </li></ul><ul><li>However, in patients with eczema with a clinical score of >8 or in patients with AD with a clinical score of >7, the therapeutic effect in the experimental groups was superior to that in the control groups (P< 0.05) on the 7th day of treatment . </li></ul><ul><li>There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). </li></ul>Early combined topical therapy is beneficial to patients with moderate to severe eczema and AD, and it is unnecessary to use antibiotics at later stages of disease or in mild eczema or AD. Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial Gong Br J Dermatol 2006;155:680
    152. 152. <ul><li>Good therapeutic effects were obtained in both the combination experimental groups and the control groups (P< 0.01), and there were no differences in the global therapeutic effect between the two groups in patients with eczema and with AD (P> 0.05). </li></ul><ul><li>However, in patients with eczema with a clinical score of >8 or in patients with AD with a clinical score of >7, the therapeutic effect in the experimental groups was superior to that in the control groups (P< 0.05) on the 7th day of treatment . </li></ul><ul><li>There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). </li></ul>Mupirocin resistance is a well-described phenomenon with S aureus, and thus, if used at all, its use in AD should only be for brief periods (less than 1 week). Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial Gong Br J Dermatol 2006;155:680
    153. 153. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Nasal carriage of S aureus is a well-documented risk factor </li></ul><ul><li>for staphylococcus infections, and prophylaxis with nasal </li></ul><ul><li>mupirocin has proven effective in preventing staphylococcus </li></ul><ul><li>infections in high-risk patients. Ravenscroft JC, Br J Dermatol 2003;148:1010-7. </li></ul><ul><li>Applying intranasal mupirocin twice a day for 5 to 7 days can effectively eradicate nasal carriage. </li></ul><ul><li>Again, however, prolonged use of intranasal mupirocin has also been associated with increased resistance and should be avoided. </li></ul>
    154. 154. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Nasal carriage of S aureus is a well-documented risk factor </li></ul><ul><li>for staphylococcus infections, and prophylaxis with nasal </li></ul><ul><li>mupirocin has proven effective in preventing staphylococcus </li></ul><ul><li>infections in high-risk patients. Ravenscroft JC, Br J Dermatol 2003;148:1010-7. </li></ul><ul><li>Applying intranasal mupirocin twice a day for 5 to 7 days can effectively eradicate nasal carriage. </li></ul><ul><li>Again, however, prolonged use of intranasal mupirocin has also been associated with increased resistance and should be avoided. </li></ul>?
    155. 155. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>One issue of concern is the marked increase of community acquired MRSA (CA-MRSA). </li></ul><ul><li>Currently, 60% to 80% of community-acquired S aureus in the United States is methicillin resistant. </li></ul><ul><li>Fortunately, CA-MRSA at present tends to be less resistant than its health care–associated counterpart. </li></ul><ul><li>Overall, more than 95% of MRSA isolates are susceptible to </li></ul><ul><li>trimethoprim-sulfamethoxazole, gentamicin, and linezolid. </li></ul><ul><li>CA-MRSA is considered resistant to β -lactams, including all </li></ul><ul><li>of the antistaphylococcal penicillins and cephalosporins, as </li></ul><ul><li>well as to the macrolides. </li></ul>
    156. 156. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>One issue of concern is the marked increase of community acquired MRSA (CA-MRSA). </li></ul><ul><li>Currently, 60% to 80% of community-acquired S aureus in the United States is methicillin resistant.57 </li></ul><ul><li>Fortunately, CA-MRSA at present tends to be less resistant than its health care–associated counterpart.58 </li></ul><ul><li>Overall, more than 95% of MRSA isolates are susceptible to </li></ul><ul><li>trimethoprim-sulfamethoxazole, gentamicin, and linezolid.59 </li></ul><ul><li>CA-MRSA is considered resistant to β -lactams, including all </li></ul><ul><li>of the antistaphylococcal penicillins and cephalosporins, as </li></ul><ul><li>well as to the macrolides. </li></ul>Also, it should be kept in mind that CA-MRSA develops resistance to fluoroquinolones rapidly when these agents are used alone.
    157. 157. Atopic Dermatitis Exacerbations <ul><li>Predisposing factors and triggers </li></ul><ul><li>Prevention & Treatment General Concepts </li></ul><ul><li>Topical Treatment </li></ul><ul><li>Systemic Treatment </li></ul><ul><li>Education </li></ul><ul><li>Conclusions </li></ul>University of Verona, Italy Attilio Boner
    158. 158. A child with AD superinfected with toxin-secreting Staphylococcus aureus. Colonization by toxin-secreting S aureus can induce secretion of IL-31 and exacerbate pruritus and inflammation .
    159. 159. Nearly all patients with AD may be colonized with S aureus . This is likely the result of a combination of host factors including skin barrier dysfunction as well as impaired host immune responses in AD.
    160. 160. ANTIMICROBIAL THERAPY FOR SKIN INFECTIONS JV Hirschmann: Cutis 2007(79): 26-38 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 85% 60% Presence of S. Aureus among people with eczema 60% nares affected skin uninvolved skin <ul><li>Once S. Aureus exceeds </li></ul><ul><li>a density of 10 6 /cm 2 on the </li></ul><ul><li>involved skin, it aggravates the </li></ul><ul><li>dermatitis. </li></ul><ul><li>Superantigen (SAg)– </li></ul><ul><li>producing S aureus can be </li></ul><ul><li>isolated from ≥50% of patients </li></ul><ul><li>with AD. </li></ul><ul><li>S aureus SAgs have been </li></ul><ul><li>shown to elicit skin </li></ul><ul><li>inflammation in patients with </li></ul><ul><li>AD and to contribute to the </li></ul><ul><li>severity of the disease . </li></ul><ul><li>Boguniewicz JACI 2001; 108:651 </li></ul>
    161. 161. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>If widespread superinfection is suspected, then first- or </li></ul><ul><li>second-generation cephalosporins or penicillinase-resistant </li></ul><ul><li>semisynthetic (“antistaphylococcal”) penicillins for 7 to 10 </li></ul><ul><li>days can often provide effective coverage. </li></ul><ul><li>Macrolides tend to be less effective as illustrated by higher rates of erythromycin resistance. </li></ul><ul><li>Clindamycin and oral fusidic acid are effective alternatives. Fusidic acid is a narrow-spectrum antibiotic used to treat S aureus . </li></ul>
    162. 162. <ul><li>Systemic antimicrobial treatment </li></ul><ul><li>Systemic antibiotic treatment is indicated for widespread bacterial secondary infection, (primarily S aureus). </li></ul><ul><li>First- or second-generation cephalosporins or semisynthetic </li></ul><ul><li>penicillins for 7 to 10 days are usually effective. </li></ul><ul><li>Erythromycin-resistant organisms are fairly common, making macrolides less useful alternatives. Hoeger PAI 2004;15:474 </li></ul><ul><li>In cases of penicillin or cephalosporin allergy, clindamycin or oral </li></ul><ul><li>fusidic acid are possible alternatives. </li></ul>Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/ American Academy of Allergy, Asthma and Immunology/ PRACTALL Consensus Report JACI 2006;118:152 nummular eczema lesion impetiginized with Staphylococcus aureus.
    163. 163. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul><ul><li>Antimicrobial susceptibility </li></ul>100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % children with Staphylococcus aureus (+) culture 87%
    164. 164. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . Bright bars = intermediate susceptibility , Dark bars = resistance. <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul><ul><li>Antimicrobial susceptibility </li></ul>
    165. 165. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul>Antimicrobial susceptibility testing revealed resistance against erythromycin in 18% and against roxithromycin in 19%, respectively. 6% of the strains were resistant or only intermediately susceptible to fusidic acid , 13% to amoxicillin and 1% to clindamycin . Bright bars = intermediate susceptibility , Dark bars = resistance.
    166. 166. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul><ul><li>All strains isolated were susceptible to </li></ul><ul><li>oxacillin, </li></ul><ul><li>amoxicillin/clavulanic acid, </li></ul><ul><li>cefadroxil and </li></ul><ul><li>cefuroxim. </li></ul>Bright bars = intermediate susceptibility , Dark bars = resistance.
    167. 167. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul>The high rate of primary resistance to macrolides should be born in mind when starting antibiotic therapy in children with AD. Bright bars = intermediate susceptibility , Dark bars = resistance.
    168. 168. Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . <ul><li>115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) </li></ul><ul><li>Skin colonizing S. aureus in children with atopic dermatitis </li></ul>First generation cephalosporins such as cefadroxil, whose antimicrobial spectrum is basically restricted to Gram-positive bacteria , would appear to be the ideal first-line antibiotics for the treatment of bacterial superinfections Bright bars = intermediate susceptibility , Dark bars = resistance.
    169. 169. Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 <ul><li>Of note, β -hemolytic streptococci can be isolated together with S aureus and can complicate AD. </li></ul><ul><li>Associated lesions tend to have a beefy erythema , may be associated with fever and lymphadenopathy , and are considered a primary skin infection . </li></ul><ul><li>If suspected, then cephalosporins , penicillinase-resistant semisynthetic penicillins, or clindamycin will generally provide adequate coverage for both group A streptococcus and staphylococcus superinfection. </li></ul>
    170. 170. <ul><li>296 adults with skin infection </li></ul><ul><li>Azitrhromycin 500mg on day 1 and 250mg on 2 to 5 days </li></ul><ul><li>or cefadroxil 500mg bid for 10 days </li></ul>100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % pts with eradication of S.aureus between days 10 and 13 C0MPARISON OF AZITHROMICIN AND CEFADROXIL FOR THE TREATMENT OF SKIN INFECTIONS Jennings Cutis 2003;72:240 94% 86%
    171. 171. <ul><li>296 adults with skin infection </li></ul><ul><li>Azitrhromycin 500mg on day 1 and 250mg on 2 to 5 days </li></ul><ul><li>or cefadroxil 500mg bid for 10 days </li></ul>100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % pts with eradication of S.aureus between days 28 and 33 C0MPARISON OF AZITHROMICIN AND CEFADROXIL FOR THE TREATMENT OF SKIN INFECTIONS Jennings Cutis 2003;72:240 100% 89%
    172. 172. Flucloxacillin in the treatment of atopic dermatitis Ewing Br J Dermatol 1998; 138:1022 <ul><li>50 children aged 1–16 yrs with atopic dermatitis. </li></ul><ul><li>4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. </li></ul>0 100% 28 84 42 flucloxacillin follow-up % CHILDREN WITH S AUREUS POSITIVE CULTURE DURING 4 WEEK TREATMENT WITH FLUCLOXACILLIN AND FOLLOW-UP 68% 91% 95% DAYS 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 100 –
    173. 173. Flucloxacillin in the treatment of atopic dermatitis Ewing Br J Dermatol 1998; 138:1022 <ul><li>50 children aged 1–16 yrs with atopic dermatitis. </li></ul><ul><li>4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. </li></ul>0 100% 28 84 42 flucloxacillin follow-up % CHILDREN WITH S AUREUS POSITIVE CULTURE DURING 4 WEEK TREATMENT WITH FLUCLOXACILLIN AND FOLLOW-UP 68% 91% 95% Flucloxacillin did not improve the symptoms or clinical appearance of atopic dermatitis and only temporarily changed skin colonization by S. aureus . DAYS 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 100 –
    174. 174. Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 <ul><li>S. aureus can be cultured from the skin of >90% of patients with AD (versus only 5% of normal subjects). In addition, superantigen (SAg)–producing S. aureus can be isolated from ≥50% of patients with AD. </li></ul><ul><li>S. aureus SAgs have been shown to elicit skin inflammation in patients with AD and to contribute to the severity of the disease. </li></ul>
    175. 175. Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 <ul><li>20 subjects without overt skin infection colonized by cefuroxime-sensitive S aureus were treated twice daily with oral cefuroxime axetil (Glaxo Wellcome Pharmaceuticals) and placebo for 2 weeks each in a crossover fashion with a 1-week washout period between treatments. </li></ul><ul><li>Toxin production and S aureus colony counts from involved area. </li></ul>The addition of an antibiotic in the management of patients with AD who are colonized yet not overtly infected with S aureus results in a significant reduction in colony counts but that patients are quickly recolonized when the antibiotic is discontinued.
    176. 176. Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 <ul><li>20 subjects without overt skin infection colonized by cefuroxime-sensitive S aureus were treated twice daily with oral cefuroxime axetil (Glaxo Wellcome Pharmaceuticals) and placebo for 2 weeks each in a crossover fashion with a 1-week washout period between treatments. </li></ul><ul><li>Toxin production and S aureus colony counts from involved area. </li></ul>The addition of an antibiotic in the management of patients with AD who are colonized yet not overtly infected with S aureus results in a significant reduction in colony counts but that patients are quickly recolonized when the antibiotic is discontinued. Of note, bathing and treatment with topical corticosteroids can reduce S aureus colonization.
    177. 177. Fig. 1 Source: Journal of Allergy and Clinical Immunology 2001; 108:651-652 Copyright © 2001 Mosby, Inc. Terms and Conditions Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 <ul><li>Oral cefuroxime axetil and placebo bid for 2 weeks each in a crossover fashion with a 1-week washout period </li></ul>Treatment sequence: , cefuroxime/placebo; ■, placebo/cefuroxime.
    178. 178. Fig. 1 Source: Journal of Allergy and Clinical Immunology 2001; 108:651-652 Copyright © 2001 Mosby, Inc. Terms and Conditions Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 <ul><li>Oral cefuroxime axetil and placebo bid for 2 weeks each in a crossover fashion with a 1-week washout period </li></ul>Treatment sequence: , cefuroxime/placebo;

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