1. 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

2. Disclosure I have no conflicts of interest to disclose.

3. Introduction: The challenges Skin barrier dysfunction Pruritus Infection Patient and family support

4. Skin barrier dysfunction

5. 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

6. 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

7. 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

8. 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

9. AD severity decreased as emollient use increased Goal emollient use was 500 grams per week. Specific emollients recommended not specified.

10. 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

11. 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].

13. Pruritus dermatlas.org

14. “The price of pruritus” in AD AD affects how my child sleeps: – Sometimes (26%), often (21%), all the time (21%) My child’s AD affects how my spouse and I sleep: – Sometimes (23%), often (21%), all the time (17%) My child sleeps in my bed because of his / her AD: – Sometimes (12%), often (7%), all the time (11%) – Chamlin SL et al. Arch Pediatr Adolesc Med 2005;159:745 Poor sleep may affect mood, ability to concentrate, behavior

15. Addressing pruritus and sleep disturbance Wet dressings overnight Sedating antihistamines – 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

17. Infection

18. Our defenses against infection, and how they fail in AD 1.The epidermis is our first line of defense against infections The epidermal barrier is bad in AD 2.The innate immune system is a molecular line of defense against microbes Recognition of pathogens is faulty in AD Anti-microbial peptides are poorly expressed and have diminished function in AD Hata TR and Gallo RL. Semin Cutan Med Surg 2008;27:144.

19. Our defenses against infection, and how they fail in AD 3.Acquired immunity Th2 cytokine milieu of AD leads to down- regulation of anti-microbial peptides and reduced activation of PMNs, monocytes, macrophages, and NK cells against pathogens 90% of atopics (lesional skin) are colonized with S. Aureus Adherence of S. Aureus to skin worsens AD severity

20. Treating S. Aureus Treat the AD! Oral antibiotics – Cephalexin (50 mg/kg divided BID-TID) – Dicloxacillin – Septra, clindamycin, doxycycline if concerned about MRSA

21. Treating S. Aureus Dilute bleach – ¼ cup household bleach in half-full bathtub once to twice weekly – Dilute bleach + intranasal mupirocin improved AD severity over 3 month study period – Huang et al. Poster at SPD meeting, July, 2008 Swimming in chlorinated pool may have similar effect

23. Patient and family support Parents express dissatisfaction with education and information offered about AD – Long et al. Clin Exp Dermatol 1993;18:516. – Information insufficient – Information given too quickly – Information inaccurate – Concerns or feelings not addressed – Input not valued

24. Education and empowerment Use trained assistants to help educate families Use written handouts and action plans Close follow up after the initial visit

25. Chisolm SS et al. JAAD 2008

26. Offer support NEASE – www.nationaleczema.org – www.easeeczema.org