Atopic dermatitis exacerbations

Atopic Dermatitis Exacerbations Predisposing factors and triggers Prevention & Treatment General Concepts Topical Treatment Systemic Treatment Education Conclusions University of Verona, Italy Attilio Boner

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 48 patients Corneometer CM 820 Sebumeter SM 810

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 48 patients Corneometer CM 820 Sebumeter SM 810

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. 48 patients Corneometer CM 820 Sebumeter SM 810 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

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. 48 patients Corneometer CM 820 Sebumeter SM 810 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

The brick wall analogy of the stratum corneum of the epidermal barrier

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

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)

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.

FLG EXPRESSION AND PUTATIVE FUNCTIONS IN THE SKIN BARRIER. O’Regan JACI 2008;122:689

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

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 Triggers of AD Stress. mediated by neuroimmunologic factors, such as neuropeptides. Allergens. Food particularly before the age 3 years and inhalant allergens thereafter Dermatophagoides in particular. Microorganisms. S. aureus and Malassezia species. Autoantigens. IgE against manganese superoxide dismutase (MnSOD). Irritant factors. rough or woolly clothing, and chemical irritants like skin-cleansing agents or house detergents, hot water.

TRIGGER FACTORS DRY SKIN IRRITANTS EMOTIONAL STRES ALLERGENS HEAT AND SWEATING INFECTIONS

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 C57BL/6 mice: Controls sensitised to ovalbumin to establish AD Under sound stress Increased nerve fiber skin density (SP) in AD and after stress.

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

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 44 patients with atopic dermatitis affecting exposed sites (≥ 18 years). APT evaluated after 2 days to exclude irritant reaction. % PATIENTS WITH (+) APT TO MITES AFTER 4 DAYS 77% 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0

% 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 44 patients with atopic dermatitis affecting exposed sites (≥ 18 years). APT evaluated after 2 days to exclude irritant reaction.

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

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

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

Topographical and temporal diversity of the human skin microbiome. Grice EA Science. 2009;324(5931):1190-2. Human skin is a large, heterogeneous organ that protects the body from pathogens while sustaining microorganisms that influence human health and disease. 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. The complexity and stability of the microbial community are dependent on the specific characteristics of the skin site. 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.

SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 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. DNA for S. aureus was extracted from dust samples. 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

SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 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. DNA for S. aureus was extracted from dust samples. 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

SEVERE ATOPIC DERMATITIS IS ASSOCIATED WITH A HIGH BURDEN OF ENVIRONMENTAL STAPHYLOCOCCUS AUREUS Leung CEA 2008;38:789 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. DNA for S. aureus was extracted from dust samples. 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

Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1. 50 children (1-6 yrs) with AD. SCORAD. 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)

Serum IgE to staphylococcal enterotoxin (SE) A, SEB, SEC, SED, and toxic shock syndrome toxin-1. 50 children (1-6 yrs) with AD. SCORAD. 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.

Evidence for superantigen involvement in skin homing of T cells in atopic dermatitis . Strickland I, J Invest Dermatol. 1999;112:249–253 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 ). 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.

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

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

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. SEB, vehicle (PBS), and sodium lauryl sulfate (SLS) on normal skin 6 AD patients biopsy specimens N°of CD3+ T cells in AD biopsy 600 - 500 – 400 – 300 – 200 – 100 – 0 108 PBS SLS SEB 354 567 P<0.03

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.

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.

SENSITIZATION TO MALASSEZIA IN INFANTS AND CHILDREN WITH ATOPIC DERMATITIS: PREVALENCE AND CLINICAL CHARACTERISTICS. Lange Allergy 2008; 63: 486 Sensitization to three different Malassezia species in 141 of children suffering from AD (mean age 3 yrs). Immuno CAP™ system to M. sympodialis , --- M. globosa , and --- M. restricta. 5.8 % patients with (+) sIgE <1 YR 18.1% >1 YR 20 – 15 – 10 – 5 – 0 15.2% AGE

SENSITIZATION TO MALASSEZIA IN INFANTS AND CHILDREN WITH ATOPIC DERMATITIS: PREVALENCE AND CLINICAL CHARACTERISTICS. Lange Allergy 2008; 63: 486 Sensitization to three different Malassezia species in 141 of children suffering from AD (mean age 3 yrs). Immuno CAP™ system to M. sympodialis , --- M. globosa , and --- M. restricta. 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

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

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 ?

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

Hit early and hit hard in atopic dermatitis and not only in asthma Reitamo Allergy 2009; 64:503 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 . Instead, atopic dermatitis should be treated efficiently from the beginning to clear the inflammation and restore the barrier function .

Hit early and hit hard in atopic dermatitis and not only in asthma Reitamo Allergy 2009; 64:503 Instead of keeping long intervals between corticosteroid courses, treatment should be continued for a few times weekly after the acute phase is controlled. 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 . After intensive topical treatment, the dosage and dosing intervals are reduced to the levels that are able to keep control of the disease.

Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677 Atopic dermatitis is a chronic disease which must be managed rather than cured . As with other chronic diseases, adherence to treatment regimens can diminish over time , resulting in treatment failure. In addition, first-line treatment involves a variety of topical medications , sometimes several at the same time. Treatment must also be adjusted during a temporary worsening , or flare, if good control is to be maintained.

Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677 Atopic dermatitis is a chronic disease which must be managed rather than cured . As with other chronic diseases, adherence to treatment regimens can diminish over time , resulting in treatment failure. In addition, first-line treatment involves a variety of topical medications , sometimes several at the same time. Treatment must also be adjusted during a temporary worsening , or flare, if good control is to be maintained. Written action plans (WAPs) can improve adherence in pediatric atopic dermatitis

Skin barrier breakdown: a renaissance in emollient therapy. Cork MJ, Br J Nurs. 2009;18:872 Complete emollient therapy The most important treatment for all dry skin diseases, including atopic eczema, asteatotic eczema and irritant contact dermatitis, is complete emollient therapy Complete emollient therapy consists of: Emollient bath products Emollient wash products Emollient creams or ointments Everything that goes on to the skin should be emollient based. All soap and detergents should be replaced with emollient wash, bath and shower products 1 2 3

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

Written action plans: Potential for improving outcomes in children with atopic dermatitis. Chisolm SS. J Am Acad Dermatol 2008;59:677

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 .’’

Proactive therapy of atopic dermatitis – an emerging concept A. Wollenberg Allergy 2009: 64: 276–278 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. 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.

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.

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: Emollients. 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. Emollients should be applied continuously , even if no actual inflammatory skin lesions are obvious. ‘‘ Water-in-oil’’ or ‘‘oil-in-water’’ emulsions might be substituted to support the skin barrier function.

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 * * * * * * * * * *

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 .

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 Emollient therapy 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). Their direct use on inflamed skin is poorly tolerated and it is better to treat the acute flare first. Emollients containing potentially allergenic proteins such as peanut or oat should be avoided in the most vulnerable age group before the age of 2 years .

52 ch with AD (2-12 yrs). 26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). 26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). 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

52 ch with AD (2-12 yrs). 26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). 26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). 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

52 ch with AD (2-12 yrs). 26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). 26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). 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

52 ch with AD (2-12 yrs). 26 ch received a steroid cream for 2 weeks (+4 weeks follow-up with no treatment) (Group A). 26 ch received steroid cream for 2 weeks + emolients for 6 weeks (Group B). 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

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

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’’ )

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. New steroid preparations with improved risk/benefit ratios and lower atrophogenic potential , such as prednicarbate, mometasone furoate , fluticasone , and methylprednisolone aceponate. Topical steroid preparations should be applied no more than twice daily as short-term therapy for acute eczematous lesions. Only mild to moderately potent preparations should be used on genital, facial, or intertriginous skin areas. In children only mild to moderately potent steroid preparations should be used.

Retrospective case note study of 82 admissions to a children’s hospital for treatment of AD. Different topical corticosteroid ointments were applied to the two sides of the body. Side to side comparison of topical treatment in atopic dermatitis Ainley-Walker Arch Dis Child 1998;79:149–152 more potent topical corticosteroid preparations appeared more effective than weaker preparations on 25 occasions, there was no difference on 20 occasions, and on seven occasions a weaker preparation appeared more effective. incorporation of an antimicrobial agent did not appear to increase the efficacy of a preparation.

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.

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.

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%.

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

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

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

Classes of Topical Corticosteroids creams, lotions, ointments, gels 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:

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;324:1–7 174 children with mild or moderate AD 0.1% betamethasone valerate ( potent group) applied for 3 days followed by the base ointment for 4 days versus 1% hydrocortisone ( mild group) for 7 days . No differences were found between the two groups for all outcomes. 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). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life .

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).

Prevention of exacerbations with topical treatment An important concept with therapeutic implications is the recognition that normal-appearing skin in patients with AD is not immunologically normal. Hamid Q, J Clin Invest 1994;94:870-6. One approach to patients whose eczema tends to relapse in the same location is that of proactive therapy . 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. 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 .

Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for 4 weeks to stabilise their condition. 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 base (emollient alone) twice weekly to the areas that were usually affected . 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.

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.

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 Patients with moderate to severe atopic dermatitis (aged 12-65) fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks 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 base (emollient alone) twice weekly to the areas that were usually affected. Kaplan-Meier plot showing the probability of remaining free from relapse during the 16 week maintenance phase.

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.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Wollenberg Allergy2008;63:742.

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.

Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8. 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). 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 to 40 weeks (Phase II). Corticosteroid use was prohibited.

Three times weekly tacrolimus ointment reduces relapse in stabilized atopic dermatitis: a new paradigm for use. Paller AS, Pediatrics 2008;122:e1210-8.

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).

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 ).

Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis Jensen JACI 2009;123: 1124 15 patients with AD treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks. Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier. Dye penetration, a marker of the outside-inside barrier.

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.

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 calcineurin inhibitors Pimecrolimus cream (1%) and tacrolimus ointment (0.03%) are approved for the treatment of AD in children aged ≥ 2 years . The anti-inflammatory potency of 0.1% tacrolimus ointment is similar to a corticosteroid with moderate potency , whereas 1% pimecrolimus cream is less active . Thus far, no trials have been published comparing pimecrolimus 1% with a mild corticosteroid. 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.

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 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. Generalized viral infections, such as eczema herpeticum or eczema molluscatum, have been observed during TCI treatment. These drugs are recommended as second-line treatments and that their use in children younger than 2 years of age is currently not recommended. Topical treatment: Topical calcineurin inhibitors

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . Co-application of physiologic lipid mixture ( PLM ) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. Antimicrobial peptide = mBD3, CRAMP

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . Co-application of physiologic lipid mixture ( PLM ) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. Antimicrobial peptide = mBD3, CRAMP 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 .

Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function Kim Exp Dermatol 2010 in press Topical pimecrolimus and tacrolimus applied twice-daily for 5 days, delay barrier recovery . Co-application of physiologic lipid mixture ( PLM ) containing an equimolar ratio of ceramides, cholesterol and free fatty acids normalized barrier homeostasis in the face of topical TCIs. Antimicrobial peptide = mBD3, CRAMP Co-application of ceramides, cholesterol and free fatty acids was associated with a reduction in TEWL induced by Tacrolimus

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 Wet-wrap therapy. 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. Mallon E, J Dermatolog Treat 1994;5:97-8. Oranje AP, J Dermatolog Treat 1999;10:73-4. Foelster-Holst R, Dermatology2006;212:66-9. A more practical alternative approach using clothing rather than bandages has also been described in detail. Boguniewicz M, Immunol Allergy Clin North Am 2002;22:107-24.

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 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. Since then many studies have demonstrated the beneficial effect of a moist environment on wound healing . 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 . The hydration and occlusion provided by the wet wraps also increases the absorption of topical medications. old style wet wraps

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 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. Since then many studies have demonstrated the beneficial effect of a moist environment on wound healing . 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 . The hydration and occlusion provided by the wet wraps also increases the absorption of topical medications. 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

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 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 . Advice is usually given to put the bandages in lukewarm water , squeeze the water out of the bandages and then apply. 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 .

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 One layer wet wrap with ointment To avoid the undesired desiccation of the skin , a modified procedure came into use for eczematous conditions, the ‘oil wet wrap’. 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. For extensive skin affections damp pyjama cloth can be used instead of bandages. The effect is the same as with WWT, without the side-effect of drying out the skin’. However, ointment enhances the risk of folliculitis .

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 Double-layer wet wrap with ointment or cream and water 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 . 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 .

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 Diluted fluticasone propionate 0.05% cream (1 : 4, 1 : 10 and 1 : 20) is used once daily. 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. However, there is still a risk of skin atrophy. 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.

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’

A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 50 children (age 4–27 months) with moderate to severe eczema ‘‘ wet wrap’’ bandages versus conventional topically applied ointments

A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 50 children (age 4–27 months) with moderate to severe eczema ‘‘ wet wrap’’ bandages versus conventional topically applied ointments There was no significant difference between the two groups in terms of overall improvement at four weeks or in the timescale of improvements.

A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 50 children (age 4–27 months) with moderate to severe eczema ‘‘ wet wrap’’ bandages versus conventional topically applied ointments The amount of topical of topical steroid used was similar in both groups.

A randomised study of ‘‘wet wraps’’ versus conventional treatment for atopic eczema Hindley D, Arch Dis Child 2006;91:164 50 children (age 4–27 months) with moderate to severe eczema ‘‘ wet wrap’’ bandages versus conventional topically applied ointments % pts requiring antibiotics 30 – 20 – 10 – 0 0% conventional p=0.05 ‘‘ wet wrap’’ 22%

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 antimicrobial therapy. The skin of patients with AD is heavily colonized with S.aureus , even at uninvolved sites. 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 . - Breuer K, Bacterial infections and atopic dermatitis. Allergy 2001;56:1034-41. - Breuer K, Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis. Br J Dermatol 2002;147:55-61.

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 antimicrobial therapy. 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. 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. 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.

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 antimicrobial therapy. 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. 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. 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. 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 .

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 Double-blind study Daily bathing with an antibacterial soap for 9 wks 50 patients 0.025% triamcinolone acetonide cream as needed for the 6 first wks 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)

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 Double-blind study Daily bathing with an antibacterial soap for 9 wks 50 patients 0.025% triamcinolone acetonide cream as needed for the 6 first wks Mean log 10 colony-forming units

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 Double-blind study Daily bathing with an antibacterial soap for 9 wks 50 patients 0.025% triamcinolone acetonide cream as needed for the 6 first wks Mean log 10 colony-forming units Leyden Br. J. Dermatol. 1974: 90: 525 Bibel Can. J. Microbiol. 1977; 23: 1062 Affected skin of 80% to 95% of atopic patients (versus about 5% of controls) is colonized with S. aureus .

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 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. Dermatitis in the antibacterial soap group remained less severe than in the placebo group during the regression period when corticosteroid use was prohibited.

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 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. Dermatitis in the antibacterial soap group remained less severe than in the placebo group during the regression period when corticosteroid use was prohibited. 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.

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 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. Regular use of an antibacterial soap containing triclocarban (triclosan) may lead to a significant improvement in atopic dermatitis without increasing the incidence of irritation.

THE EFFECT OF ANTIBACTERIAL SOAP WITH 1.5% TRICLOCARBAN ON STAPHYLOCOCCUS AUREUS IN PATIENTS WITH ATOPIC DERMATITIS Breneman Cutis 2000; 66: 296 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. Regular use of an antibacterial soap containing triclocarban (triclosan) may lead to a significant improvement in atopic dermatitis without increasing the incidence of irritation. This type of antibacterial soap may be a useful, well-tolerated, and inexpensive addition to the clinical management of atopic dermatitis.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Other topical antibiotic therapies include topical antiseptics, such as triclosan (2,4,4-trichloro-2-hydroxydiphenyl ether) or chlorhexidine , that can be used in combination with emollients or as part of wet-wrap dressing therapy. 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. Also, bleach baths given once or twice a week are a simple and effective way to decrease colonization. One-third cup of bleach into a bathtub filled to the level of the patient’s naval .

IgE-mediated allergy to chlorhexidine. Garvey LH, J Allergy Clin Immunol. 2007;120:409–415. 22 patients with clinical history suggestive of chlorhexidine allergy were included. Skin tests with chlorhexidine Twelve patients were skin test positive and 10 were skin test negative. Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test.

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. Patients were instructed to add either 0.5 cup of 6% bleach (final concentration: 0.005%) to a full bathtub of water (~150 litres). 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. Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 Half a cup of 6% bleach (NaClO)

Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 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). All patients received orally administered cephalexin for 14 days. Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. CHANGES IN MEAN EASI SCORES OVER TIME. ECZEMA AREA AND SEVERITY INDEX (EASI). time, months

Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 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). All patients received orally administered cephalexin for 14 days. Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. CHANGES IN MEAN PROPORTIONS OF BODY SURFACE AREA AFFECTED OVER TIME. time, months

Treatment of Staphylococcus aureus Colonization in Atopic Dermatitis Decreases Disease Severity Huang Pediatrics 2009;123:e808 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). All patients received orally administered cephalexin for 14 days. Randomly intranasal mupirocin ointment and sodium hypochlorite (bleach) baths or intranasal petrolatum ointment treatment and plain water baths. 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

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

Bacterial Colonization And Infection In Ad: To Treat Or Not To Treat (With Antibiotics) Boguniewicz JACI 2010;125:4 Other approaches include silver-impregnated clothing , which has been shown: to reduce staphylococcal colonization, improve clinical parameters, and reduce topical steroid use in patients with AD. Gauger A, Dermatology 2003;207:15-21. Gauger A, J Eur Acad Dermatol Venereol 2006;20:534-41.

Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr exp dermatol 2010 in press Silver textile 37 patients with AD single-blinded in vivo study. sensitization potential was tested in a patch test in 111 panellists. Silver textiles % scavenged

Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study J W. Fluhr exp dermatol 2010 in press Silver textile 37 patients with AD single-blinded in vivo study. sensitization potential was tested in a patch test in 111 panellists. Silver textiles Superoxide scavenging for the three tested groups: All three test fibres induced significant superoxide radicals scavenging compared with Phoaslisne control. % scavenged

Silver textile 37 patients with AD single-blinded in vivo study. sensitization potential was tested in a patch test in 111 panellists. 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

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.

Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. 15 patients with AD S. aureus colonization and clinical severity of AD over a 2-week period. 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 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.

Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. 15 patients with AD S. aureus colonization and clinical severity of AD over a 2-week period. 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 7 days after cessation, S. aureus density remained significantly lower compared to baseline.

Silver-coated textiles reduce Staphylococcus aureus colonization in patients with atopic eczema. Gauger A, Dermatology. 2003;207(1):15-21. 15 patients with AD S. aureus colonization and clinical severity of AD over a 2-week period. 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 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.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. 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

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. 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.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. 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.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. 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.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. Impairment of quality of life (QOL) significant improvement at the end of study in placebo (cotton) and verum (silver) group.

Efficacy and functionality of silver-coated textiles in patients with atopic eczema. Gauger A, J Eur Acad Dermatol Venereol. 2006;20:534 –541. 68 consecutive outpatients clinically diagnosed with generalized AE with a SCORAD index of at least 20. either silver-coated (verum, 35 patients + 2 dropouts) or cotton garments (placebo, 22 patients + 9 dropouts) directly on the skin for 2 weeks. Concomitant topical steroid therapy tendency of more pronounced reduction of steroid use in the verum group (silver textiles) without statistical significance.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Topical antibiotic therapies have also been investigated and are considered effective for mild and localized forms of superinfection . Topical fusidic acid is effective against S aureus and is used in combination with topical steroids. 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 . 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 .

Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. Fusidic acid inhibits bacterial protein synthesis. 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 Topical preparations of fusidic acid and a glucocorticoid 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, leading to the recommendation that fusidic acid-glucocorticoid preparations may be the treatment of choice for this condition.

Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. 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. In hospitalised patients with chronic dermatological conditions, burns, or leg ulcers, fusidic acid resistance rates may rise up to 43% following treatment. In the UK fusidic acid resistance rates of between 11.5% and 18.5% have recently been reported, with especially high rates in children.

Fusidic acid resistance in Staphylococcus aureus . Dobie D, Arch Dis Child . 2004;89:74 –77. There is no evidence to support the general use of antibiotic therapy in atopic dermatitis 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 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.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Mupirocin ointment plus hydrocortisone butyrate vs hydrocortisone alone plus vehicle ointment was compared in a double-blind, placebo-controlled, randomized trial. No difference in benefit was noted in either group on days 14 or 28 of treatment, although the combination group demonstrated a greater improvement by day 7 in patients with more severe disease . Gong JQ, Br J Dermatol. 2006;155:680–687. 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.

The case for steroid–antibiotic combinations. Leyden JJ, Br J Dermatol. 1977;96:179 –187.

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 Eczema Area and Severity Index (EASI) scores before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation from lesional and non-lesional skin. Topical therapy with mupirocin plus hydrocortisone butyrate ointment vs vehicle ointment plus hydrocortisone butyrate . 327 patients. % 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

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 Eczema Area and Severity Index (EASI) scores before the start of the trial and on the 7th, 14th and 28th day of treatment. Swabs for bacterial isolation from lesional and non-lesional skin. Topical therapy with mupirocin plus hydrocortisone butyrate ointment vs vehicle ointment plus hydrocortisone butyrate . 327 patients. 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

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). 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 . There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). 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

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). 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 . There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). 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

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). 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 . There were no differences between the two groups on the 14th and 28th days of treatment (P> 0.05). 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

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Nasal carriage of S aureus is a well-documented risk factor for staphylococcus infections, and prophylaxis with nasal mupirocin has proven effective in preventing staphylococcus infections in high-risk patients. Ravenscroft JC, Br J Dermatol 2003;148:1010-7. Applying intranasal mupirocin twice a day for 5 to 7 days can effectively eradicate nasal carriage. Again, however, prolonged use of intranasal mupirocin has also been associated with increased resistance and should be avoided.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Nasal carriage of S aureus is a well-documented risk factor for staphylococcus infections, and prophylaxis with nasal mupirocin has proven effective in preventing staphylococcus infections in high-risk patients. Ravenscroft JC, Br J Dermatol 2003;148:1010-7. Applying intranasal mupirocin twice a day for 5 to 7 days can effectively eradicate nasal carriage. Again, however, prolonged use of intranasal mupirocin has also been associated with increased resistance and should be avoided. ?

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 One issue of concern is the marked increase of community acquired MRSA (CA-MRSA). Currently, 60% to 80% of community-acquired S aureus in the United States is methicillin resistant. Fortunately, CA-MRSA at present tends to be less resistant than its health care–associated counterpart. Overall, more than 95% of MRSA isolates are susceptible to trimethoprim-sulfamethoxazole, gentamicin, and linezolid. CA-MRSA is considered resistant to β -lactams, including all of the antistaphylococcal penicillins and cephalosporins, as well as to the macrolides.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 One issue of concern is the marked increase of community acquired MRSA (CA-MRSA). Currently, 60% to 80% of community-acquired S aureus in the United States is methicillin resistant.57 Fortunately, CA-MRSA at present tends to be less resistant than its health care–associated counterpart.58 Overall, more than 95% of MRSA isolates are susceptible to trimethoprim-sulfamethoxazole, gentamicin, and linezolid.59 CA-MRSA is considered resistant to β -lactams, including all of the antistaphylococcal penicillins and cephalosporins, as well as to the macrolides. Also, it should be kept in mind that CA-MRSA develops resistance to fluoroquinolones rapidly when these agents are used alone.

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 .

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.

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 Once S. Aureus exceeds a density of 10 6 /cm 2 on the involved skin, it aggravates the dermatitis. Superantigen (SAg)– producing S aureus can be isolated from ≥50% of patients with AD. S aureus SAgs have been shown to elicit skin inflammation in patients with AD and to contribute to the severity of the disease . Boguniewicz JACI 2001; 108:651

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 If widespread superinfection is suspected, then first- or second-generation cephalosporins or penicillinase-resistant semisynthetic (“antistaphylococcal”) penicillins for 7 to 10 days can often provide effective coverage. Macrolides tend to be less effective as illustrated by higher rates of erythromycin resistance. Clindamycin and oral fusidic acid are effective alternatives. Fusidic acid is a narrow-spectrum antibiotic used to treat S aureus .

Systemic antimicrobial treatment Systemic antibiotic treatment is indicated for widespread bacterial secondary infection, (primarily S aureus). First- or second-generation cephalosporins or semisynthetic penicillins for 7 to 10 days are usually effective. Erythromycin-resistant organisms are fairly common, making macrolides less useful alternatives. Hoeger PAI 2004;15:474 In cases of penicillin or cephalosporin allergy, clindamycin or oral fusidic acid are possible alternatives. 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.

Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis Antimicrobial susceptibility 100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % children with Staphylococcus aureus (+) culture 87%

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. 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis Antimicrobial susceptibility

Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis 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.

Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis All strains isolated were susceptible to oxacillin, amoxicillin/clavulanic acid, cefadroxil and cefuroxim. Bright bars = intermediate susceptibility , Dark bars = resistance.

Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis 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.

Antimicrobial susceptibility of skin-colonizing S. aureus strains in children with atopic dermatitis. Hoeger PH. Pediatr Allergy Immunol 2004;15:474-7 . 115 consecutive children (mean age: 2.7 yr, range: 0.2-15) with moderate to severe AD (mean SCORAD: 43.2, range: 16-77) Skin colonizing S. aureus in children with atopic dermatitis 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.

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 Of note, β -hemolytic streptococci can be isolated together with S aureus and can complicate AD. Associated lesions tend to have a beefy erythema , may be associated with fever and lymphadenopathy , and are considered a primary skin infection . If suspected, then cephalosporins , penicillinase-resistant semisynthetic penicillins, or clindamycin will generally provide adequate coverage for both group A streptococcus and staphylococcus superinfection.

296 adults with skin infection Azitrhromycin 500mg on day 1 and 250mg on 2 to 5 days or cefadroxil 500mg bid for 10 days 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%

296 adults with skin infection Azitrhromycin 500mg on day 1 and 250mg on 2 to 5 days or cefadroxil 500mg bid for 10 days 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%

Flucloxacillin in the treatment of atopic dermatitis Ewing Br J Dermatol 1998; 138:1022 50 children aged 1–16 yrs with atopic dermatitis. 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. 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 –

Flucloxacillin in the treatment of atopic dermatitis Ewing Br J Dermatol 1998; 138:1022 50 children aged 1–16 yrs with atopic dermatitis. 4 weeks treatment with oral flucloxacillin, with an 8-week follow-up period. 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 –

Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 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. S. aureus SAgs have been shown to elicit skin inflammation in patients with AD and to contribute to the severity of the disease.

Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 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. Toxin production and S aureus colony counts from involved area. 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.

Effects of cefuroxime axetil on S.aureus colonization and superantigen production in atopic dermatitis Boguniewicz JACI 2001; 108:651 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. Toxin production and S aureus colony counts from involved area. 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.

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 Oral cefuroxime axetil and placebo bid for 2 weeks each in a crossover fashion with a 1-week washout period Treatment sequence: , cefuroxime/placebo; ■, placebo/cefuroxime.

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 Oral cefuroxime axetil and placebo bid for 2 weeks each in a crossover fashion with a 1-week washout period Treatment sequence: , cefuroxime/placebo; ■, placebo/cefuroxime. 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.

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 Oral cefuroxime axetil and placebo bid for 2 weeks each in a crossover fashion with a 1-week washout period Treatment sequence: , cefuroxime/placebo; ■, placebo/cefuroxime. 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.

Systemic antimicrobial treatment Systemic antibiotic treatment is indicated for widespread bacterial secondary infection, (primarily S aureus). First- or second-generation cephalosporins or semisynthetic penicillins for 7 to 10 days are usually effective. Erythromycin-resistant organisms are fairly common, making macrolides less useful alternatives. Hoeger PAI 2004;15:474 In cases of penicillin or cephalosporin allergy, clindamycin or oral fusidic acid are possible alternatives. Unfortunately, recolonization after a course of antistaphylococcal therapy occurs rapidly Boguniewicz M, JACI 2001;108:651-2. Family members often serve as the source of rapid recolonization Bonness J Clin Microb 2008;46:456 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

Systemic antimicrobial treatment Systemic antibiotic treatment is indicated for widespread bacterial secondary infection, (primarily S aureus). First- or second-generation cephalosporins or semisynthetic penicillins for 7 to 10 days are usually effective. Erythromycin-resistant organisms are fairly common, making macrolides less useful alternatives. Hoeger PAI 2004;15:474 In cases of penicillin or cephalosporin allergy, clindamycin or oral fusidic acid are possible alternatives. … .but maintenance antibiotic therapy , however, should be avoided because it might result in colonization by methicillin-resistant organisms. 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

Antibiotics for the allergist La Shell Ann Allergy Asthma Immunol 2009;102:1 The use of oral antibiotics in AD without signs of superinfection, although reducing colony counts, does not provide greater clinical improvement, and patients are quickly recolonized once the use of the antibiotics is stopped. Ewing CI, Br J Dermatol. 1998;138:1022–1029. Boguniewicz M, J Allergy Clin Immunol. 2001;108:651– 652. Also, maintenance therapy with antibiotics should be avoided because this could lead to colonization with methicillin-resistant S aureus (MRSA).

Abscesses associated with MRSA generally respond to drainage , and most CA-MRSA isolates are susceptible to trimethoprim- sulfamethoxazole or tetracycline , although obtaining cultures and sensitivities is important. Rifampin has been used in combination with other antibiotics but should never be used alone to treat staphylococcal infection. Other options include vancomycin , fluoroquinolones, daptomycin, newer-generation carbapenems, and linezolid . In a study of children with cultureproved CA-MRSA, treatment with incision and drainage without adjunctive antibiotic therapy was effective management of skin and soft tissue abscesses with a diameter of less than 5 cm in immunocompetent children. Methicillin-resistant S.aureus Boguniewicz JACI 2010;125:4

Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive S.aureus, and its relevance to atopic dermatitis. Schlievert PM, JACI 2010;125:39-49. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have emerged as serious health threats in the last 15 years. They are associated with large numbers of atopic dermatitis skin and soft tissue infections, but when they originate from skin and mucous membranes , have the capacity to produce sepsis and highly fatal pulmonary infections characterized as necrotizing pneumonia , purpura fulminans , and postviral toxic shock syndrome. Virulence factor production by S aureus.

Secreted virulence factor comparison between methicillin-resistant and methicillin-sensitive S.aureus, and its relevance to atopic dermatitis. Schlievert PM, JACI 2010;125:39-49. S. Aureus superantigens , including SEA, SEB, SEC, and TSST-1. can serve as allergens , stimulating specific IgE responses in patients with AD induce corticosteroid resistance of T cells difficulty in management of AD because topical corticosteroids are the most common treatment of AD.

A child with AD with course complicated by eczema herpeticum (EH). It is important for clinicians to be aware of the possibility of HSV complicating AD, especially EH. Vesicular lesions are umbilicated, tend to occur in crops, and often become hemorrhagic and crusted. Lesions can coalesce into large denuded areas . HSV might be misdiagnosed as impetigo, although herpetic lesions can become superinfected. The presence of punched-out erosions, vesicles, and/or infected skin lesions that do not respond to oral antibiotics should prompt a search for HSV by using PCR, viral culture, or Giemsa-stained Tzanck smear of cells scraped from the base of a freshly unroofed vesicle.

Tzanck smear from these lesions revealed multinucleated giant cells along with the acantholytic cells A child with AD with course complicated by eczema herpeticum (EH).

ACANTHOLYTIC CELL: Refers to an epithelial cell that has undergone dyshesion (i.e separation from another epithelial cell) by dissolution of intercellular bridges and has consequently become round. A child with AD with course complicated by eczema herpeticum (EH).

Ophthalmologic consultation should be obtained for patients with periocular or suspected eye involvement. Lumbar puncture should be considered if meningitis is suspected, but the presence of infected lesions over the lumbar areas precludes this procedure. Antiviral prophylaxis might be necessary for patients with recurrent herpetic outbreaks. A child with AD with course complicated by eczema herpeticum (EH).

Risk factors of atopic dermatitis patients for eczema herpeticum. Peng WM, J Invest Dermatol 2007;127:1261-3. The clinical course in patients withAD can also be complicated by both localized and disseminated cutaneous viral infections , most often caused by HSV , human papilloma virus , or molluscum virus, vaccinia virus (eczema vaccinatum -smallpox) . EH is a potentially life-threatening disseminated HSV-1 or less commonly HSV-2 infection that occurs in 10% to 20% of patients with AD. Risk factors for EH include: early onset of AD, severe and untreated AD, head and neck dermatitis, previous EH or HSV infections, and increased total serum IgE levels with higher levels of specific sensitizations, especially against Malassezia and S.aureus.

Eczema Herpeticum ( Herpes Simplex Virus, type 1) is a severe herpetic simplex virus infection of the skin. This only develops when the skin is already diseased , most commonly with atopic dermatitis. If the diagnosis is overlooked and antiviral treatment is not initiated, the disease can be fatal . In a typical severe primary attack of eczema herpeticum - formerly called Kaposi’s varicelliform eruption - vesicles develop abruptly in large numbers over the area of eczematous skin . They continue to appear in crops for as long as 7-9 days. The disease is most common in areas of active or recently healed atopic dermatitis, particularly the face, but normal skin can be involved. Wide denudation of the epidermis may occur.

Eczema Herpeticum Herpes Simplex Virus, type 1. Scabs eventually form, and epithelialization occurs. High fever and adenopathy occur approximately 3 days after the onset of vesiculation. The systemic reaction varies, but temperatures of 103-105°F for 7-10 days are not uncommon. The severity of infection ranges from mild and transient to fatal. Death may result from the common complication or secondary staphylococcal infection. Complications also include profound physiologic disturbances from loss of fluid and electrolytes through the skin, and from dissemination of the virus to the brain and other organs . Children are most commonly affected.

Eczema Herpeticum Herpes Simplex Virus, type 1. Scabs eventually form, and epithelialization occurs. High fever and adenopathy occur approximately 3 days after the onset of vesiculation. The systemic reaction varies, but temperatures of 103-105°F for 7-10 days are not uncommon. The severity of infection ranges from mild and transient to fatal. Death may result from the common complication or secondary staphylococcal infection. Complications also include profound physiologic disturbances from loss of fluid and electrolytes through the skin, and from dissemination of the virus to the brain and other organs . Children are most commonly affected. croste

Eczema Herpeticum Herpes Simplex Virus, type 1. Lesions include: intact vesicles (V), a pustule (P) that originated as a vesicle, and crusted areas (C) where the vesicles have burst.

ECZEMA HERPETICUM (EH), vesiculopustular stage. A disseminated eruption of distinctly monomorphic dome-shaped blisters and secondary pustules on eczematous skin is suggestive of EH . EH is the most important disseminated viral infection because it can occur in many settings and requires immediate medical action. Clinically, patients with EH present with a disseminated, distinctly monomorphic eruption of dome-shaped vesicles accompanied by fever, malaise, and lymphadenopathy. The head, neck, and trunk are most commonly affected. Wollenberg A, JACI 2003;112:667-74.

EH, crust stage. Within 2 weeks , the blisters usually dry out, forming crusts that fill eroded pits. Characteristic,disseminated slits intense erythematous plaques might also occur. Lesions generally heal within 2 to 6 weeks. Associated complications include keratoconjunctivitis and viremia, leading to multiple organ involvement with meningitis and encephalitis . The mortality of EH was about 75% before effective antiviral treatment. Wollenberg A, JACI 2003;112:667.

Viral infections in atopic dermatitis: pathogenic aspects and clinical management. Wollenberg A, JACI 2003;112:667-74. Antiviral chemotherapy of EH Acyclovir for herpes zoster (shingles), immunocompetent pts [<12 yo] Dose: 30 mg/kg/day or 1500 mg/m 2 /day IV div q8h x7-10 days [>12 yo] Dose: 4000 mg/day PO div 5x/day x5-7 days; Alt: 30 mg/kg/day or 1500 mg/m 2 /day IV div q8h x7-10 days

Oral aciclovir, 200mg five times a day for 5 days, was studied versus placebo in 69 patients with eczema herpeticum. An efficacy rate of 83.1% was reached in the aciclovir-treated group versus 42.9% in the placebo-treated group. For severe infections, intravenous antiviral therapy should be administered for at least 5 to 7 days, using the dosage regimens recommended for patients who are immunocompromised (aciclovir 10 mg/kg/8h). Nikkels Am J Clin Der 2002;3:457 Treatment of eczema herpeticum with oral aciclovir. Niimura M, Am J Med 1988; 85: 49-52

Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Vora S Clin Infect Dis. 2008 ;46:155. A 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the US military who had recently received smallpox vaccine.

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 antimicrobial therapy. Infection of the skin with the herpes simplex virus in the form of an eczema herpeticum ( Kaposi’s varicelliform eruption ) represents a severe and possibly life-threatening complication of AD, requiring a systemic antiviral treatment with acyclovir or other antiviral agents (eg, valacyclovir ). Wollenberg A, J Am Acad Dermatol 2003;49:198-205 .

MOLLUSCUM CONTAGIOSUM : A disseminated eruption of whitish umbilicated papules on eczematous skin shows considerable variation in size. Umbilicated, small, skin-colored papules are the diagnostic hallmark of molluscum infection . Several hundred lesions can be seen. Although Eczema molluscatum (EM) lesions resolve spontaneously, treatment speeds healing and prevents spreading by autoinoculation and heteroinoculation. We usually destroy limited numbers of lesions with small curved forceps or remove them by means of curettage . Pretreatment for 30 minutes with EMLA cream provides local anesthesia and softens the lesion for easier removal. Other destructive treatment measures include cryotherapy or carbon dioxide laser vaporization. Wollenberg A, JACI 2003;112:667-74.

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 Recent findings underline the pathogenetic importance of a fungal colonization as a trigger factor. Scheynius A, Int Arch Allergy Immunol 2002;127:161-9. Mothes N, JACI 2005;116:706-9. Schmid-Grendelmeier P, JACI 2005;115:1068-75. Contradictory data have been published about the efficacy of a systemic treatment of AD with ketoconazole, Lintu P, Allergy 2001;56:512-7. Baeck O, J Eur Acad Derm Venereol 2001;15:34-8. although selected patients with AD might benefit from a topical or systemic antimycotic therapy Nikkels AF, Dermatology 2003;206:398-400.

Framing the future of antifungals in atopic dermatitis . Nikkels AF, Dermatology 2003;206:398-400. Some fungal colonization or infection of the skin may exacerbate AD severity, particularly the so-called head and neck variant . In addition, excessive intestinal colonization by Candida albicans may represent an additional triggering factor. Hence, there is a rationale to use antifungals in selected AD patients. Early trials with topical ketoconazole in head and neck AD showed a decrease in Malassezia colonization, but no significant improvement was observed in the clinical severity. In contrast, clinical improvement and decreased serum IgE were obtained in patients with positive Malassezia radioallergosorbent tests (RASTs) who were treated by oral ketoconazole. Some preliminary data suggested that oral itraconazole treatment in AD patients reduced the need for topical corticosteroids, provided clinical improvement particularly in head and neck AD , reduced the cutaneous and intestinal fungal colonization that may trigger AD, reduced the percentage of positive Malassezia cultures and demonstrated a decrease in C. albicans and Malassezia RAST values. Furthermore, beside its antifungal action, itraconazole in part relieves pruritus and inflammation. In conclusion, oral itraconazole treatment can alleviate AD severity in selected patients.

Fungi can also play a role in the chronic inflammation seen in patients with AD. IgE antibodies against M sympodialis are found in patients with AD, most frequently in patients with a head and neck distribution of dermatitis. However, patients often respond better to topical steroids than to topical antifungal therapy, and systemic antifungal therapy might benefit patients with AD through anti-inflammatory properties.

SYSTEMIC KETOCONAZOLE IS AN EFFECTIVE TREATMENT OF ATOPIC DERMATIT I S WITH IGE-MEDIATED HYPERSENSTIVITY TO YEASTS Lintu Allergy 2001; 56: 512 Only in the ketokonazale group: 80 pts with AD and (+) IgE for P . ovale or C . alb icans Keto k onazole or placebo for 1 mo (Nizoral: 5-10 mg/Kg/die: 3) itching p<0.005 area p<0.01 dryness p<0.05

ANTI-MYCOTICS SUPPRESS IL-4 AND IL-5 PRODUCTION IN T CELLS FROM PTS WITH AD Kanda N J Invest Dermatol 200 1 ; 117 : 1635 Stimulation Anti-CD3 & Anti-CD28 T cells of AD pts Production of IL-4 IL-5 ketoconazole intraconazole miconazole inhibition by suppressing the transient increase in intracellular cAMP induced by stimulation  cAMP

ANTI-MYCOTICS SUPPRESS IL-4 AND IL-5 PRODUCTION IN T CELLS FROM PTS WITH AD Kanda N J Invest Dermatol 200 1 ; 117 : 1635 Stimulation Anti-CD3 & Anti-CD28 T cells of AD pts Production of IL-4 IL-5 ketoconazole intraconazole miconazole inhibition by suppressing the transient increase in intracellular cAMP induced by stimulation  cAMP These results stress the potential use anti-mycotics for the suppression of T helper-2 mediated allergic reactions

Human keratinocytes possess the enzymatic machinery to produce calcitriol from the precursor 7 dehydrocholesterol (7-DHC) under the influence of UV-B irradiation. UV-B irradiation (290-315 nm) rapidly generates previtamin D3 from 7-DHC in these cells, and thermal isomerization subsequently generates vitamin D3, which is sequentially hydroxylated to yield calcidiol and finally calcitriol . UV-B–triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes Peric JACI 2010;125:746

Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory atopic dermatitis. Ikezawa Z, Eur J Dermatol. 2004;14:400-6. Patients with refractory atopic dermatitis were divided into two groups: Group A; a combination of itraconazole plus a conventional lactobacillus preparation was administered for 8 weeks, followed by lactobacillus preparation alone for 8 weeks, Group B; lactobacillus preparation alone was administered for 8 weeks, followed by itraconazole plus lactobacillus for 8 weeks. In both groups, a decrease in dose or strength of concomitant topical steroids was observed at the end of the treatment course of itraconazole, and improvement of parameters such as eosinophil count, serum IgE level and specific IgE antibody titers to fungi was also observed after the administration of itraconazole. These results suggest that oral itraconazole is useful for the treatment of intractable atopic dermatitis patients who do not respond to conventional therapeutic approaches.

Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory atopic dermatitis. Ikezawa Z, Eur J Dermatol. 2004;14:400-6. 27 patients with refractory atopic dermatitis Group A ; a combination of itraconazole plus a conventional lactobacillus preparation was administered for 8 weeks, followed by lactobacillus preparation alone for 8 weeks, Group B ; lactobacillus preparation alone was administered for 8 weeks, followed by itraconazole plus lactobacillus for 8 weeks. Itraconazole 100 mg/day

Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory atopic dermatitis. Ikezawa Z, Eur J Dermatol. 2004;14:400-6. Score of AD in Group A Itraconazole period 27 patients with refractory atopic dermatitis Group A ; a combination of itraconazole plus a conventional lactobacillus preparation was administered for 8 weeks, followed by lactobacillus preparation alone for 8 weeks, Group B ; lactobacillus preparation alone was administered for 8 weeks, followed by itraconazole plus lactobacillus for 8 weeks. Itraconazole 100 mg/day

Clinical usefulness of oral itraconazole, an antimycotic drug, for refractory atopic dermatitis. Ikezawa Z, Eur J Dermatol. 2004;14:400-6. Score of AD in Group B Itraconazole period 27 patients with refractory atopic dermatitis Group A ; a combination of itraconazole plus a conventional lactobacillus preparation was administered for 8 weeks, followed by lactobacillus preparation alone for 8 weeks, Group B ; lactobacillus preparation alone was administered for 8 weeks, followed by itraconazole plus lactobacillus for 8 weeks. Itraconazole 100 mg/day

Minimum effective dosage in the treatment of chronic atopic dermatitis with itraconazole. Takechi M J Int Med Res. 2005;33:273-83. regimen 1 (single-phase treatment), 100 mg/day for 1 week with a 3-week rest, repeating; regimen 2 , 200 mg/week for 4 weeks, repeating; regimen 3 ( dual-phase treatment), 100 mg/day for 1 week (introduction phase) then 200 mg/week (maintenance phase) for 11 weeks. Three oral administration regimens with itraconazole : For regimens 1 and 2, each treatment cycle was 4 weeks, and 3 cycles were undertaken. Each regimen was completed in 12 weeks.

Minimum effective dosage in the treatment of chronic atopic dermatitis with itraconazole. Takechi M J Int Med Res. 2005;33:273-83. regimen 1 (single-phase treatment), 100 mg/day for 1 week with a 3-week rest, repeating; regimen 2 , 200 mg/week for 4 weeks, repeating; regimen 3 ( dual-phase treatment), 100 mg/day for 1 week (introduction phase) then 200 mg/week (maintenance phase) for 11 weeks . Three oral administration regimens with itraconazole : All three regimens reduced AD symptoms, regimen 3 being the most effective and efficient therapy as evaluated by overall efficacy and low drop-out rate.

ITRACONAZOLE Peds Dosing . Dosage forms: 100 mg *infections, fungal [5 mg/kg/day PO div qd-bid] Max: 10 mg/kg/day or 600 mg/day; Alt: 100 mg PO qd; Info: dose, duration vary by indication; divide dose bid if >200 mg/day; give caps w/ food *superficial mycoses [5 mg/kg/day PO div qd-bid] Max: 10 mg/kg/day or 600 mg/day; Alt: 100 mg PO qd; Info: dose, duration vary by indication; divide dose bid if >200 mg/day; give caps w/ food renal dosing [see Adult Dosing] renal impairment: dose adjustment may be required although specific pediatric dosing adjustments not defined; see adult renal dosing for guidance hepatic dosing [not defined] hepatic impairment: caution advised

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 Systemic corticosteroids Few randomized clinical trials have been performed in patients with AD thus far. Aylett SE, Acta Derm Venereol Suppl 1992;176:123-5. It is well known that relapse after the discontinuation of oral steroids is often observed. Corticosteroids in the form of a long-term oral therapy are associated with a series of well-documented side effects (eg, disturbance of growth, osteoporosis, cataracts, and development of lymphopenia). In cases of acute flare-up, patients might benefit from a short course of systemic therapy with corticosteroids, but long-term use and use in children should be avoided.

Seven children suffering from severe atopic dermatitis, unresponsive to standard therapy, received an iv bolus dose of methylprednisolone (20 mg/kg/day) for three days. Immunological parameters were evaluated before and after treatment. At the end of bolus therapy both skin lesions and itching improved for several months in five of seven patients . No side effects were observed, but a significant and transient lymphopenic response occurred, with lower CD4+ than CD8+ lymphocyte counts. Our data suggest that this therapy may be a novel and safe therapeutic approach in severe atopic dermatitis. Methylprednisolone bolus: a novel therapy for severe atopic dermatitis. Galli E Acta Paediatr. 1994;83:315-7.

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 Cyclosporin A As with TCIs, cyclosporin A (CyA) inhibits calcineurin-dependent pathways, resulting in reduced levels of proinflammatory cytokines , such as IL-2 and IFN-g. CyA is an effective treatment for adult and childhood AD, and although relapse after discontinuation of therapy is often observed, post-treatment disease severity often does not return to baseline levels. Sowden JM, Lancet 1991;338:137-40. Berth-Jones J Am Acad Dermatol 1996;34:1016-21. Zaki I, Br J Dermatol 1996;135(suppl 48):21-4.

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 Cyclosporin A Because of the possible side effects, particularly renal toxicity , the use of CyA should be limited to patients with severe refractory disease, contraindications must be excluded, and blood pressure and laboratory parameters must be monitored closely . Treatment can be performed in the form of a short- or long-term therapy with high-dose ( 3-5 mg/kg/d ) or low-dose ( 2.5mg/kg/d ) administration. (Sandimmun neoral® cps 50 mg) Berth-Jones J, Br J Dermatol 1997;136:76-81. Akhavan A, Clin Dermatol 2003;21:225-40.

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 Cyclosporin A The principle of treatment should be to aim for the lowest effective dose and the shortest treatment period because toxicity is related to both of these factors. In children it should be considered that vaccinations might not be effective during immunosuppression .

Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis. Schmitt J, J Eur Acad Dermatol Venereol. 2007;21:606-19. 602 patients 15 studies Cyclosporin dosages (3-5 mg/kg BW) 0 – -10 – -20 – -30 – -40 – -50 – -60 – % reductions in AD severity score after 2 week-treatment -22% -40% 3 mg/Kg 4-5 mg/Kg

Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis. Schmitt J, J Eur Acad Dermatol Venereol. 2007;21:606-19. 602 patients 15 studies Cyclosporin dosages (3-5 mg/kg BW) 0 – -10 – -20 – -30 – -40 – -50 – -60 – 70 % reductions in AD severity score after 6-8 week-treatment -48% -62% 3 mg/Kg 4-5 mg/Kg

Cyclosporin in the treatment of patients with atopic eczema - a systematic review and meta-analysis. Schmitt J, J Eur Acad Dermatol Venereol. 2007;21:606-19. As graphically displayed in (fig. 4) publication bias with selective publication of small studies with high responserates appears to be present ( P = 0.013). The results should therefore be interpreted with caution

Systemic therapy of atopic dermatitis in children. Ricci G, Drugs. 2009;69:297-306. Cyclosporin is an immunosuppressant agent that acts directly on cells of the immune system, with an inhibitory effect on T cells . When AD cannot be controlled by standard topical therapies, ciclosporin significantly decreases symptom scores, disease extent, pruritus and sleep deprivation, and improves quality of life . The most frequent adverse effects associated with the use of cyclosporin are hypertension and renal dysfunction , but they are usually reversible after drug discontinuation. Ciclosporin has been found to be safely used, effective and well tolerated in children with severe AD. However, studies to assess the long-term effectiveness and safety of cyclosporin in AD are lacking.

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 Azathioprine Azathioprine is an immunosuppressive agent affecting purine nucleotide synthesis and metabolism. There is accumulating evidence for its efficacy in severe recalcitrant AD. Meggitt SJ, Clin Exp Dermatol 2001;26:369-75. Berth-Jones J, Br J Dermatol 2002;147:324-30. Lear JT, J Am Acad Dermatol 1996;35:642-3. It has a number of side effects , including myelosuppression, hepatotoxicity, gastrointestinal disturbances, increased susceptibility for infections, and possible development of skin cancer.

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 Azathioprine Because azathioprine is metabolized by the thiopurine methyltransferase , a deficiency of this enzyme should be excluded before starting oral immunosuppression with azathioprine. The recommended dosage of azathioprine for dermatologic indications is 1 to 3 mg/kg daily but should be determined based on thiopurine methyltransferase levels. Regular blood tests must be performed throughout treatment with azathioprine. The onset of action is usually slow, and benefit might not be apparent until 2 to 3 months after starting treatment.

A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Murphy LA, Br J Dermatol 2002;147: 308-15 48 children (6–16 yrs) who were affected by severe AD and had normal thiopurine methyl-transferase (TPMT) levels, azathioprine 2–3.5 mg/kg once daily.

A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Murphy LA, Br J Dermatol 2002;147: 308-15 48 children (6–16 yrs) who were affected by severe AD and had normal thiopurine methyl-transferase (TPMT) levels , azathioprine 2–3.5 mg/kg once daily. Erythrocyte TPMT levels ranged from 5.2 to 22.8 nmol/h/mL red blood cells. normal levels (8–14.5 nmol/h/ mL red blood cells, (consistent with homozygosity for TPMT H ). levels in the heterozygote (TPMT HL ) range (3–7.5 nmol/h/mL red blood cells); very low range (< 3.0 nmol/h/mL red blood cells) would indicate homozygosity for TPMT L .

A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Murphy LA, Br J Dermatol 2002;147: 308-15 48 children (6–16 yrs) who were affected by severe AD and had normal thiopurine methyl-transferase (TPMT) levels , azathioprine 2–3.5 mg/kg once daily. after 3 months of treatment % children with RESPONSE 58% (28/48) 60 - 50 - 40 - 30 – 20 – 10 – 0 27% (13/48) 15% (13/48) Excellent ≥ 90% Good 90%-60% Inadequate <60%

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 Antihistamines The therapeutic value of antihistamines seems to reside principally in their sedative properties , and they are useful as a short-term adjuvant to topical treatment during relapses associated with severe pruritus. Nonsedating antihistamines seem to have only very modest value in atopic eczema. Newer nonsedating antihistamines seem to have little or no value in atopic eczema.

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 Phototherapy In phases of acute flares, a combination with corticosteroids is often practiced. The following therapy options can be used for AD: broad-band UVB (280-320 nm), narrow-band UVB (311-313 nm), UVA (320-400 nm), UVA1 (340-400 nm), PUVA, and Balneo-PUVA. In children UV therapy should be restricted to adolescents older than 12 years , except in exceptional cases. Information about the long-term side effects of UV therapy is still not available.

Cutaneous lymphocyte-associated antigen ( CLA ) is a surface glycoprotein expressed by skin-homing T cells; Vitamin A (retinoic acid RA) and 1,25 dihydroxyvitamin D3 ; Cultured human T cells with 1,25D(3) and RA. Both RA and 1,25D(3) completely eliminated the human T-cell skin-homing marker CLA at physiologically attainable levels, whereas inactive/precursor forms of vitamin A and vitamin D had little inhibitory action. VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148 Cutaneous lymphocyte-associated antigen (CLA) is a surface glycoprotein expressed by skin-homing T cells; Vitamin A (retinoic acid RA) and 1,25 dihydroxyvitamin D3; Cultured human T cells with 1,25D(3) and RA. Both RA and 1,25D(3) completely eliminated the human T-cell skin-homing marker CLA at physiologically attainable levels, whereas inactive/precursor forms of vitamin A and vitamin D had little inhibitory action. 1,25D(3) can selevtively downregulate CLA expression without influencing lymphocyte migration patterns to other tissues

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148 NORMAL T CELLS WERE CULTURED WITH VITAMIN D OR VITAMIN A CLA expression levels were reduced with 1nM 1,25D(3) whereas cholecalciferol, an inactive precursor of vitamin D, had no effect CLA expression levels were also decreased with 100 pM RA, 1 nM retinal and 1µM retinol. * P<0.05

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148 NORMAL T CELLS WERE CULTURED WITH VITAMIN D CLA expression levels were reduced with 1nM 1,25D(3) whereas cholecalciferol, an inactive precursor of vitamin D, had no effect

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148 NORMAL T CELLS WERE CULTURED WITH VITAMIN D OR VITAMIN A CLA expression levels were reduced with 1nM 1,25D(3) whereas cholecalciferol, an inactive precursor of vitamin D, had no effect CLA expression levels were also decreased with 100 pM RA, 1 nM retinal and 1µM retinol. * P<0.05 Vitamin D(3) (cholecalciferol) is produced in the skin after exposure to sunlight and is converted to its biologically active metabolite, 1,25 dihydroxyvitamin D(3) in the liver and kidney

VITAMINS A AND D ARE POTENT INHIBITORS OF CUTANEOUS LYMPHOCYTE-ASSOCIATED ANTIGEN EXPRESSION Yamanaka JACI 2008;121:148 NORMAL T CELLS WERE CULTURED WITH VITAMIN D OR VITAMIN A CLA expression levels were reduced with 1nM 1,25D(3) whereas cholecalciferol, an inactive precursor of vitamin D, had no effect CLA expression levels were also decreased with 100 pM RA, 1 nM retinal and 1µM retinol. * P<0.05 Retinoic acid (RA) synthesis is accomplished by 2 sequential oxidation steps in which retinol is oxidized to retinal and retinal is oxidized to RA

RANDOMIZED CONTROLLED TRIAL OF VITAMIN D SUPPLEMENTATION FOR WINTER-RELATED ATOPIC DERMATITIS IN BOSTON: A PILOT STUDY Sidbury Br J Dermatol 2008;159:245 11 children with AD with winter-time onset or exacerbation of AD. Median age of 7 years (range 2–13). Ergocalciferol 1000 IU or an identical-looking placebo once daily for 1 month . Change in I nvestigator's G lobal A ssessment ( IGA ) score in a randomized, double-blind, placebo-controlled trial ( P = 0·04)

RANDOMIZED CONTROLLED TRIAL OF VITAMIN D SUPPLEMENTATION FOR WINTER-RELATED ATOPIC DERMATITIS IN BOSTON: A PILOT STUDY Sidbury Br J Dermatol 2008;159:245 11 children with AD with winter-time onset or exacerbation of AD. Median age of 7 years (range 2–13). Ergocalciferol 1000 IU or an identical-looking placebo once daily for 1 month . Change in I nvestigator's G lobal A ssessment ( IGA ) score in a randomized, double-blind, placebo-controlled trial ( P = 0·04) The active form of vitamin D 1,25-dihydroxyvitamin D3 induces expression of antimicrobial peptides that help prevent skin infection. Schauber J Clin Invest 2007;117:803

La vitamina D è un gruppo di pro-ormoni liposolubili; il Gruppo si presenta sotto due forme principali dall'attività biologica molto simile: il colecalciferolo (D3), derivante dal colesterolo e sintetizzato negli organismi animali, e l' ergocalciferolo (D2), di provenienza vegetale (ergosterolo). In vari tessuti il colecalciferolo subisce una reazione di idrossilazione con formazione di 25-idrossicolecalciferolo[25(OH)D] il quale passa nella circolazione generale e si lega ad una proteina trasportatrice specifica (vitamin D binding protein, DBP). Arrivato nel rene, il 25 (OH)D può subire due diverse reazioni di idrossilazione, catalizate da differenti idrossilasi (la 1-idrossilasi e la 24-idrossilasi), che danno origine, rispettivamente, all'1,25-diidrossicolecalciferolo [1,25(OH)D] ( calcitriolo ), la componente attiva, ed al 24,25-diidrossicolecalciferolo [24,25(OH)D], una forma inattiva. A livello della cute si forma l’altra forma attiva della vitamina D, l'ergocalciferolo, tramite trasformazione dell’ergosterolo.

ADMINISTRATION OF ORAL VITAMIN D INDUCES CATHELICIDIN PRODUCTION IN ATOPIC INDIVIDUALS Hata JACI 2008;122:829 UNITS OF RNA FOR CATHELICIDIN EXPRESSION IN SKIN LESION (BIOPSY) 23.91 Individuals with atopic dermatitis are at an increased risk for cutaneous infections with Staphylococcus aureus . Defects in the production of antimicrobial peptides like cathelicidin, may account for this increase in infections. Supplementation with oral vitamin D3 (cholecalciferol) at 4000 IU per day was given for 21 days . 3.53 AFTER BEFORE 25 – 20 – 15 – 10 – 5 – 0 SUPPLEMENTATION

Individuals with atopic dermatitis are at an increased risk for cutaneous infections with Staphylococcus aureus . Defects in the production of antimicrobial peptides like cathelicidin, may account for this increase in infections. Supplementation with oral vitamin D3 (cholecalciferol) at 4000 IU per day was given for 21 days . ADMINISTRATION OF ORAL VITAMIN D INDUCES CATHELICIDIN PRODUCTION IN ATOPIC INDIVIDUALS Hata JACI 2008;122:829 UNITS OF RNA FOR CATHELICIDIN EXPRESSION IN SKIN LESION (BIOPSY) 23.91 3.53 AFTER BEFORE 25 – 20 – 15 – 10 – 5 – 0 4000 IU of vitamin D 3 has been well documented to effectively increase 25-hydroxyvitamin D levels while maintaining normal serum calcium levels , suggesting that the current recommendation for vitamin D supplementation may be too conservative . SUPPLEMENTATION

UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo . Gläser JACI 2009;123: 1117 Antimicrobial peptide expression by normal human keratinocytes was measured by real-time PCR. Biopsies taken from human volunteers and skin explants studied with immunohistochemistry. Normal human keratinocytes were UV- irradiated (0, 150, 350 J/m2). RNA was extracted 24 hours later.

UV radiation induces antimicrobial peptides in vivo. Six healthy volunteers were irradiated on 3 consecutive days with 1 MED UV-B on their buttocks. Punch biopsies were taken from these areas before and 1 day and 6 days after UV exposure. Biopsies of unirradiated skin serves as controls (Co). UV radiation induces antimicrobial peptides in skin explants. UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo . Gläser JACI 2009;123: 1117

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 EDUCATION The goal of the patients’ education should be living with atopic dermatitis by means of an empowered patient or, in the case of infants and young children, a caregiver who can work as a partner with the doctor in selfmanaging their own or their children’s disease. Education to enhance disease knowledge, psychologic improvement in disease perception, and scratch control behavior modification, together with regular daily treatment , will lead to better skin care.

THE IMPACT OF ATOPIC DERMATITIS Mothers’ of atopic eczema children who lack information and confidence in their treatment will feel more helpless, develop feelings of guilt, be prone to depression and become overprotective of their children, and then develop cognitive avoidance* of the actual problem of managing the disease ( RUMINATION ). The family unit becomes dysfunctional as these children develop “dominant child” behaviour with narcisism and stigmatisation, while in turn the mother become increasingly submissive . *Evitare di prendere cosienza

% OF PTS USING UNCONVENTIONAL THERAPIES 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 Evaluation of a parental training program for the management of childhood atopic dermatitis Staab Ped All Immunol 2002;13:84 204 families of children (5mo-12y) with moderate-severe AD (SCORAD>20) 93 partecipated to the education program , 111 served as controls Follow-up 1 y 56% 26% 64% 51% P=0.003 EDUCATION CONTROLS

% PTS USING DIETS WITHOUT PROVEN ALLERGY 50 – 40 – 30 – 20 – 10 – 0 204 families of children (5mo-12y) with moderate-severe AD (SCORAD>20) 93 partecipated to the education program , 111 served as controls Follow-up 1 y Evaluation of a parental training program for the management of childhood atopic dermatitis Staab Ped All Immunol 2002;13:84 19% 7% 33% 27% P=0.001 EDUCATION CONTROLS

% pts using antiseptics for weeping wounds 30 – 20 – 10 – 0 Evaluation of a parental training program for the management of childhood atopic dermatitis Staab Ped All Immunol 2002;13:84 10% 204 families of children (5mo-12y) with moderate-severe AD (SCORAD>20) 93 partecipated to the education program , 111 served as controls Follow-up 1 y 19% 19% 7% P=0.025 EDUCATION CONTROLS

% pts using antiseptics for weeping wounds 30 – 20 – 10 – 0 Evaluation of a parental training program for the management of childhood atopic dermatitis Staab Ped All Immunol 2002;13:84 10% 204 families of children (5mo-12y) with moderate-severe AD (SCORAD>20) 93 partecipated to the education program , 111 served as controls Follow-up 1 y 19% 19% 7% P=0.025 OR for the use in the program group versus control group of: Emollients = 2.25 Antiseptics = 3.94 EDUCATION CONTROLS

100 – 90 – 80 – 70 – 60 – 50 – 40 – 30 – 20 – 10 – 0 % pts regularly using skin care products 82% 204 families of children (5mo-12y) with moderate-severe AD (SCORAD>20) 93 partecipated to the education program , 111 served as controls Follow-up 1 y Evaluation of a parental training program for the management of childhood atopic dermatitis Staab Ped All Immunol 2002;13:84 67% P=0.041 EDUCATION CONTROLS

PRE-LESIONAL PHASE Previously involved Never involved ACUTE PHASE (Flare) INFLAMED First signs or symptoms Degree of inflammation Conventional approach Gaining long-term control – treat at very first signs or symptoms Early intervention Early intervention

0 – -10 – -20 – -30 – -40 – -50 – -60 – -70 – -80 – -90 – -100- % REDUCTION IN SEVERITY SCORE AFTER EDUCATION -89% Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 51 ch with AD Follow-up 1 y Severity od AD evaluated using the six area, six sign atopic dermatitis severity score (SASSAD) Instruction in topical treatment

51 ch with AD Follow-up 1 y Severity od AD evaluated using the six area, six sign atopic dermatitis severity score (SASSAD) Instruction in topical treatment 0 – -10 – -20 – -30 – -40 – -50 – -60 – -70 – -80 – -90 – -100- % REDUCTION IN SEVERITY SCORE AFTER EDUCATION -89% Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 THIS WAS ACHIEVED THROGHOUT AN 800% INCREASE IN THE USE OF EMOLIENTS (CREAMS/OINTMENTS) FROM A MEAN USE OF 54 g WEEKLY TO 426 g WEEKLY

51 ch with AD Follow-up 1 y Severity od AD evaluated using the six area, six sign atopic dermatitis severity score (SASSAD) Instruction in topical treatment 0 – -10 – -20 – -30 – -40 – -50 – -60 – -70 – -80 – -90 – -100- % REDUCTION IN SEVERITY SCORE AFTER EDUCATION -89% Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 THIS WAS ACHIEVED THROGHOUT AN 800% INCREASE IN THE USE OF EMOLIENTS (CREAMS/OINTMENTS) FROM A MEAN USE OF 54 g WEEKLY TO 426 g WEEKLY WITHOUT AN INCREASE IN TOPICAL STEROIDS USE

Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 51 ch with AD Follow-up 1 y Severity od AD evaluated using the six area, six sign atopic dermatitis severity score (SASSAD) Instruction in topical treatment 54 g/weekly 426 g/weekly

Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 Best practice management of atopic eczema 1 The key to the successful management of atopic eczema is to spend time to listen and to explain the nature of the disease and how to use topical therapies and dressings. 2 In addition to explanation, practical demonstrations of how to apply topical products and dressings should be given. 3 Emollients should be prescribed in adequate amounts and these should be used liberally and frequently, e.g. for emollient cream ⁄ ointment a minimum of 500 g per week . Emollient bath oils and soap substitutes should also be used.

Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 Best practice management of atopic eczema 4 Topical steroids should be prescribed, considering the age of the patient, site to be treated and extent of the disease. These considerations guide the potency, quantity of steroid and duration of therapy. The fingertip unit is a simple method to demonstrate the correct quantity to apply. 5 Patients ⁄ parents should be given written instructions and information to reinforce the therapies which have been explained and demonstrated.

Comparison of parent knoledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specilist dermatology nurse Cork Br J Dermatol 2003;149:582 Best practice management of atopic eczema 6 Deterioration in previously stable eczema may be due to secondary bacterial or viral infection or to the development of contact dermatitis. Prompt diagnosis and treatment are important to prevent exacerbations. 7 Treatments that suit one child may not suit another. Treatments should be individualized to suit each child and their parents.

0 – -10 – -20 – -30 – -40 - -50 – Use of an emolient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children Lucky Pediatr Dermatol 1997;4:321 25 ch with AD (3-15 years) Application of hydrocortisone 2.5% cream alone or in association with a water-in-oil cream 3 weeks treatment % REDUCTION IN CORTICOSTEROID WITH THE USE OF THE EMOLLIENT -50%

% reduction in erythema, dryness, and pruritus at week 1 and 3 0 – -10 – -20 – -30 - Effects of a low-potency corticosteroid lotion plus a moisturizing regimen in the treatment of atopic dermatitis Hanifin Cur Ther Res 1998;59:227 80 patients with AD A 3week study Investigator masked Desonide lotion 0.05% alone bid vs plus moisturizing cream tid 23% p<0.05 With the use of the moisturizing cream

To investigate what quantity of topical preparations is applied by outpatients in daily routine treatment over a 26 week period To what extent this consumption is related to the course of the severity of patients’ skin conditions ATOPIC DERMATITIS TOPICAL THERAPY: DO PATIENTS APPLY MUCH TOO LITTLE? Niemeier J Dermatollog Treat 2005; 16: 95 Only patients who applied the correct amount preparations to the areas of affected skin showed a significant improvement in SCORAD indices.

To investigate what quantity of topical preparations is applied by outpatients in daily routine treatment over a 26 week period To what extent this consumption is related to the course of the severity of patients’ skin conditions ATOPIC DERMATITIS TOPICAL THERAPY: DO PATIENTS APPLY MUCH TOO LITTLE? Niemeier J Dermatollog Treat 2005; 16: 95 Only patients who applied the correct amount preparations to the areas of affected skin showed a significant improvement in SCORAD indices. “ It is not unusual for an adult to require a 500 g tub emolient per week and a child to require a 500 g tub every 2 weeks”. Prodigy Guidance Eczema Atopic .

Bathing in a magnesium-rich Sea salt solution improves skin barrier function, enhances skin hydratation, and reduces inflammation in atopic dry skin. Proksch Int J Dermatol 2005;44:151 Patients witha atopic dry skin submerged one forearm for 15 min in a bain solution containing 5% DeadSea salt solution vs tap water. At time 0, 1 and 6 weeks later TEWL was evaluated. Skin hydratation was enhanced in the forearm treated with Sea salt solution. TEWL was significantly reduced. Skin roughness and redness were significantly reduced.

Bathing in a magnesium-rich Sea salt solution improves skin barrier function, enhances skin hydratation, and reduces inflammation in atopic dry skin. Proksch Int J Dermatol 2005;44:151 Patients witha atopic dry skin submerged one forearm for 15 min in a bain solution containing 5% DeadSea salt solution vs tap water. At time 0, 1 and 6 weeks later TEWL was evaluated. Skin hydratation was enhanced in the forearm treated with Sea salt solution. TEWL was significantly reduced. Skin roughness and redness were significantly reduced. The benefic effect is due to the high content in magnesium salt. Magnesium salts are known: - to bind water, - to influence epidermal p proliferation, - to enhance permeability b barrier repair

Conclusions ITCH-SCRATCH CYCLE Wahlgren J Dermatol 1999;26:770 Scratch Itch Damaged skin RED, DRY SKIN Inflammation

Bacterial Colonization And Infection In Ad: To Treat Or Not To Treat (With Antibiotics) Boguniewicz JACI 2010;125:4 Given the complex pathophysiology of AD, a Multipronged approach directed at healing or protecting the skin barrier and addressing the immune dysregulation will improve the likelihood of successful outcomes. This includes: proper skin hydration , identification and elimination of flare factors , such as irritants, allergens, infectious agents, and emotional stressors, addressing the itch-scratch cycle, as well as 3) pharmacologic therapy. Conclusions

Furthermore, it is important to recognize the unique propensity for patients with AD to be colonized or infected by microbes, especially toxin-secreting S aureus, including MRSA, as well as HSV. Management needs to be directed at basic skin care, including repair and protection of the skin barrier with proper hydration and topical therapy, which includes both moisturizers and anti-inflammatory medications. Conclusions

If the iron rods are already weakened, an environmental agent, such as soap, can corrode them much more easily. The brick wall starts falling apart (C) and allows the penetration of allergens (D). The brick wall analogy of the stratum corneum of the epidermal barrier

Clinicians caring for patients with AD need to understand the important relationship between skin barrier abnormalities and immune dysregulation in this common but complex disease. They need to appreciate the strong association between FLG mutations and early-onset, persistent severe AD and the association with allergic sensitization and asthma. Conclusions

Atopic dermatitis exacerbations

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