Transcript Breaking a stubborn “horse”: Challenges in treating

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
Disclosure
• I have no conflicts of interest to disclose.
Introduction:
The challenges
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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 use
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].
Pruritus
dermatlas.org
“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
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
Infection
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.
Our defenses against infection, and
how they fail in AD
3. Acquired immunity
Th2 cytokine milieu of AD leads to downregulation 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
Treating S. Aureus
• Treat the AD!
• Oral antibiotics
– Cephalexin (50 mg/kg divided BID-TID)
– Dicloxacillin
– Septra, clindamycin, doxycycline if concerned
about MRSA
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
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
Education and empowerment
• Use trained assistants to help educate families
• Use written handouts and action plans
• Close follow up after the initial visit
Chisolm SS et al.
JAAD 2008
Offer support
• NEASE
– www.nationaleczema.org
– www.easeeczema.org