Breaking a stubborn “horse”: Challenges in treating pediatric atopic dermatitis

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 • The epidermis is our first line of defense against infections The epidermal barrier is bad in AD • 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 • 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