Breaking a stubborn “horse”: Challenges in treating pediatric atopic dermatitis Anna L. Bruckner, M.D. Assistant Professor of Dermatology and Pediatrics Stanford University School of Medicine Director, Pediatric Dermatology Lucile Packard Children’s Hospital
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Breaking a stubborn “horse”: Challenges in treating pediatric atopic dermatitis Anna L. Bruckner, M.D. Assistant Professor of Dermatology and Pediatrics.
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Breaking a stubborn “horse”:Challenges in treating pediatric
atopic dermatitis
Anna L. Bruckner, M.D.Assistant Professor of Dermatology and Pediatrics
Stanford University School of MedicineDirector, Pediatric Dermatology
Lucile Packard Children’s Hospital
Disclosure
• I have no conflicts of interest to disclose.
Introduction:The challenges
• Skin barrier dysfunction• Pruritus• Infection• Patient and family support
Skin barrier dysfunction
Epidermal barrier dysfunction is central to pathogenesis of atopic dermatitis
• Loss of function mutations in the filaggrin gene are associated with ichthyosis vulgaris, atopic dermatitis (AD), and asthma associated with AD– 37-50% with IV have AD– 8% with AD have evidence of IV
– Smith FT et al. Nat Genet 2006;38:337 – Palmar C et al. Nat Genet 2006;38:441
Epidermal barrier dysfunction is central to pathogenesis of atopic dermatitis
• SPINK5 polymorphisms are associated with atopy and AD in some families
– Walley AJ et al. Nat Genet 2001;29:175
• Ceramides decreased in AD skin• Decreased ceramides correlate with increased
TEWL in AD– Proksch E et al. Clin Dermatol 2003;21:134
Repairing the skin barrier
• Repairing the skin barrier will:– Improve xerosis– Decrease severity of AD– Lessen dependence on prescription medications
• Moisturizers can be used as:– Primary treatment for mild disease– Preventative / maintenance therapy
Traditional moisturizers:Efficacy in atopic dermatitis
• Cork MJ et al. Br J Dermatol 2003;149:582-9.• Evaluated the effect of education and
demonstration of topical therapies by a dermatology nurse on therapy utilization and severity of AD
• 51 pediatric patients enrolled and followed for 1 year
AD severity decreased as emollient AD severity decreased as emollient use increaseduse increased
Goal emollient use was 500 grams per week. Specific emollients recommended not specified.
What about ceramides?
• In a small (24 children), uncontrolled study a ceramide dominant moisturizer (TriCeram™) improved both the xerotic and inflammatory components of AD
– Chamlin SL and Kao J et al. J Am Acad Dermatol 2002;47:198
• CeraVe™ contains ceramides– No studies comparing efficacy with other
moisturizers
Topical barrier repair “devices” for AD?• NOT cost-effective for use as daily moisturizer
• May be useful as an adjuctive therapy or as an alternative to topical steroids, TIMS
• Physiogel® A.I. (MimyX®) decreased AD symptoms in an uncontrolled study of adults and children
– Eberlein B et al. JEADV 2008;22:73
• Atopiclair® improved mild-to-moderate AD compared to vehicle
– Boguniewicz M, et al. J Pediatr 2008;152:854-9.– Patrizi A, et al. Pediatr Allergy Immunol 2008 Feb 21 [Epub].
– Diphenhydramine (1mg/kg/dose)– Hydroxyzine (1-2 mg/kg as single dose at bedtime)– Doxepin (1mg/kg as single dose at bedtime)
• Cognitive and behavioral therapy
Infection
Our defenses against infection, and how they fail in AD
1. The epidermis is our first line of defense against infectionsThe epidermal barrier is bad in AD
2. The innate immune system is a molecular line of defense against microbesRecognition of pathogens is faulty in ADAnti-microbial peptides are poorly expressed and have diminished function in AD
Hata TR and Gallo RL. Semin Cutan Med Surg 2008;27:144.
Our defenses against infection, and how they fail in AD
3. Acquired immunityTh2 cytokine milieu of AD leads to down-regulation of anti-microbial peptides and reduced activation of PMNs, monocytes, macrophages, and NK cells against pathogens90% of atopics (lesional skin) are colonized with S. AureusAdherence of S. Aureus to skin worsens AD severity