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Breaking a stubborn

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Epidermal barrier dysfunction is central to pathogenesis of atopic dermatitis ... Cephalexin (50 mg/kg divided BID-TID) Dicloxacillin ... – PowerPoint PPT presentation

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Title: Breaking a stubborn


1
Breaking a stubborn horseChallenges 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 Childrens Hospital

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

3
IntroductionThe 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 200638337
  • Palmar C et al. Nat Genet 200638441

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 200129175
  • Ceramides decreased in AD skin
  • Decreased ceramides correlate with increased TEWL
    in AD
  • Proksch E et al. Clin Dermatol 200321134

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 moisturizersEfficacy in atopic
dermatitis
  • Cork MJ et al. Br J Dermatol 2003149582-9.
  • 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
    200247198
  • 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 20082273
  • Atopiclair improved mild-to-moderate AD compared
    to vehicle
  • Boguniewicz M, et al. J Pediatr 2008152854-9.
  • Patrizi A, et al. Pediatr Allergy Immunol 2008
    Feb 21 Epub.

12
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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 childs 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
    2005159745
  • 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

16
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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
    200827144.

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

22
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23
Patient and family support
  • Parents express dissatisfaction with education
    and information offered about AD
  • Long et al. Clin Exp Dermatol 199318516.
  • 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
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