1. No category

Topical Therapy in Pediatric Atopic Dermatitis
Andrew C. Krakowski, MD,*,† and Magdalene A. Dohil, MD*,†
With a prevalence of 10% to 20% in the first decade of life, atopic dermatitis (AD) is one
of the most common skin disorders in young children. It is a chronic illness with limited
therapeutic options. Topical anti-inflammatory agents remain at the core of medical management; however, their efficacy must be balanced with safety concerns, especially as they
relate to the pediatric population. This article discusses the principles of topical AD therapy
with a detailed review of the differences between topical corticosteroids and topical
calcineurin inhibitors. It also includes specialized topical treatment strategies for AD, such
as wet wraps and diluted bleach baths, and highlights the most common challenges to
patient compliance in atopic dermatitis.
Semin Cutan Med Surg 27:161-167 © 2008 Elsevier Inc. All rights reserved.
Importance of
Recognition and Management
C
linicians should recognize that atopic dermatitis (AD) is
a skin condition that impacts an individual child’s overall physical, emotional, and social well-being.1 Pruritus, a key
feature of AD, often leads to a vicious cycle of itching and
scratching that further traumatizes an already compromised
epidermal barrier thought to be related to numerous “outside-inside-outside” factors such as reduced ceramide levels,
increased levels of endogenous proteolytic enzymes, and
downregulation of cornified envelope genes such as the filament-aggregating protein filaggrin.2-4 Barrier dysfunction results in increased transepidermal water loss, xerosis, microbial colonization, and secondary infection. Beyond these
physical changes, AD can affect a child’s psychosocial state in
a variety of ways that include disturbed sleep, decreased
school performance (marked by an inability to focus), behavioral problems, low self-esteem (compounded by teasing
from other children), decreased participation in extracurricular activities, family stress, and anxiety. In children with AD,
the impairment of their health-related quality of life (HRQL)
may at least equal that experienced in many other chronic
diseases of childhood, including diabetes and cystic fibrosis.5,6 Family dynamics may also suffer significantly at the
*University of California, San Diego, CA.
†Rady Children’s Hospital, San Diego, CA.
Andrew C. Krakowski and Magdalene A. Dohil have served as investigators
for multiple pharmaceutical-sponsored studies on atopic dermatitis, but
they have no personal or family equity interest in any company.
Address correspondence to: The Eczema Center, c/o Magdalene A. Dohil,
MD, Division of Pediatric and Adolescent Dermatology, 8010 Frost
Street, Suite 602, San Diego, CA 92123. E-mail: [email protected].
Website: www.EczemaCenter.org
1085-5629/08/$-see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.sder.2008.04.003
physical, emotional, and functional levels, as parents and
caregivers try to live with the limitations imposed by this
chronic disease.7
AD represents a huge impact on public health resources. It
affects 10% to 20% of children living in developed nations.8
Between 1997 and 2004, the disease accounted for an estimated 7.4 million office visits in the United States alone, with
national cost estimates ranging widely from $364 million to
$3.8 billion U.S. dollars per year.9,10 These figures will likely
increase in proportion to the increasing prevalence of AD,
which has risen steadily during the past several decades and
is paralleled by increases in the prevalence of asthma, allergic
rhinoconjunctivitis, and the emerging entity of eosinophilic
esophagitis.11,12 The epidemiologic linkage among AD,
asthma, and allergic rhinitis (a.k.a., the “atopic triad”) is especially evident when considered in the context of increasing
disease severity.13 Because AD is frequently the first disorder
of the atopic triad to manifest, it has been hypothesized that
infants with AD—through epicutaneous sensitization that
leads to systemic allergic responses and airway sensitization—are predisposed to developing asthma and/or allergic
rhinitis later in childhood.14-16 This progression of one disease to another is known as the “atopic march.” An ongoing,
long-term prospective study is currently investigating the hypothesis that prompt recognition and intervention of AD
early in life may improve outcomes with respect to the clinical course of AD and influence the subsequent development
of asthma and allergic rhinitis.17
Foundations for
Effective Control of AD
A comprehensive long-term strategy should be the overall
goal of AD management and, in order of importance and
161
A.C. Krakowski and M.A. Dohil
162
necessity, should consist of the following: educating patients
and their families about AD; laying the groundwork for excellent skin care; reducing signs and symptoms of the condition; preventing and decreasing the degree and frequency of
flares; modifying the overall disease course; and, possibly,
slowing the atopic march. A personalized therapeutic strategy should be tailored to the individual child’s age and needs,
extent and localization of AD at presentation, and overall
disease course (including clinical severity, disease persistence, frequency of flares, etc.). Physicians should also explain that AD has distinct phases with distinct clinical localization requiring different types of therapies during each
phase. Close monitoring for changes in disease status is critical and should support stepwise treatment that is adjusted in
tune with the clinical course to allow for transition from acute
flare treatment to chronic maintenance therapy and vice
versa. This sliding-scale treatment approach allows patients
and their families to respond appropriately and promptly to
minor disease variations so that more serious sequelae may
be avoided.
Compliance with treatment recommendations may be
maximized by acknowledging parental anxiety about both
the disease itself (ie, its chronicity and its lack of cure) and
any real or perceived potential side effects of available treatments. One guideline that may help patients estimate the
amount of topical medication needed to cover a given area is
known as the finger tip unit (FTU), which is defined as the
amount of topical medication extending from the tip to the
first joint on the palmar aspect of the index finger. It takes
approximately 1 FTU to cover the hand or groin, 2 FTUs for
the face or foot, 3 FTUs for an arm, 6 FTUs for the leg, and 14
FTUs for the trunk.18 To help assess compliance and guide
further management, physicians should perform a careful
review of all “in-hand” over-the-counter, homeopathic,
herbal, and prescriptive products at each clinic visit. Diligent
monitoring of refills is also recommended to assess quality/
quantity of use, overall compliance, and potential medication
overuse/interactions.
Interventional Education
The education of AD patients, their families, and primary
caregivers has emerged as a new focus in AD therapy in its
own right. Paralleling strategies shown to be effective in managing asthma patients, enhanced patient care centers combine several specialty services (dermatology, allergy, infectious disease, behavioral psychology, etc.) with longer
patient appointments, extensive educational curriculums,
patient support networks, and the ability to elicit patient/
caregiver feedback as a means of providing more comprehensive care.19-21 This “education as intervention” model may
allow physicians to better impress on caregivers that AD is a
complex, chronic disorder and that management should be
equated to long-term commitment rather than short-term
“fix-up.” Results of such targeted patient care studies are
starting to be explored systematically.22-25 Further critical
evaluation to examine the best way to deliver enhanced patient education and its long-term efficacy, impact on patient/
caregiver quality of life, and cost-effectiveness should be undertaken to better establish its role in AD management.
Baseline Skin Care Principles
The foundation of AD management rests on daily skin care
and typically begins with a child’s bathing regimen. The potential benefits of bathing include skin hydration, cleansing,
improved penetration of topical therapies, and the gentle
debridement of infected eczematous skin. Use of a moisturizing cleanser is preferred, and highly fragranced soaps or
bubble baths should be avoided because of their potential to
cause irritation and sensitization. After bathing, caregivers
should gently pat the child dry instead of rubbing the skin
with a towel, which can be thought of as “scratching in disguise.” Disruption of the stratum corneum barrier during
water evaporation and the potential for skin drying may be
minimized by the timely and liberal application of a moisturizer/emollient. Although limited data exist to support the
notion that emollients and moisturizers improve atopic dermatitis directly, these products are widely used because they
improve the xerosis associated with AD.26 In general, ointments contain high concentrations of lipids and are generally
more effective than creams or lotions, which are water-based
and may therefore dry the skin on evaporation. Ceramiderich products are also useful for retaining moisture in the
skin.27 Recently, several novel barrier products have been
cleared for marketing by the Food and Drug Administration
as “510(k) medical devices” and contain ingredients that
their manufacturers claim in addition to moisturizing may
help to relieve pruritus, burning, and pain associated with
AD. Studies are underway to evaluate the utility of these new
products and their potential role in helping to manage
AD.28-32
Because compliance in large part dictates the success of
any skin care regimen, patient and parental preferences
should be carefully considered when selecting an emollient
or moisturizer. We further recommend using products that
are tailored to local weather conditions, financially-affordable, dye-free, and fragrance-free. Moisturizers/emollients
should be used at least twice a day subsequent to any topical
pharmacologic therapies to promote absorption of active
medications yet provide a good seal of the skin against moisture loss.
Bleach Baths
The skin of atopic dermatitis patients, partly due to an innate
deficiency of certain antimicrobial peptides (so called cathelicidins and defensins) and partly due to the local conditions
created secondary to scratching, provides a favorable environment for bacterial colonization and proliferation, especially by Staphylococcus aureus.33 AD patients can have sudden exacerbations of AD because of an overgrowth of S.
aureus that can be independent of true secondary bacterial
infection, a notion supported by the clinical response of patients with severe AD to antistaphylococcal antibiotics.34,35
Topical and/or oral antibiotic therapy, typically of short duration to avoid the development of bacterial resistance, may
Topical therapy in pediatric atopic dermatitis
be indicated when signs of overt infection are present. Skin
cultures should be considered before treatment as methicillin-resistant Staphylococcus aureus may be an important
pathogen in some patients. Diluted bleach baths are currently
being evaluated for their role as adjuvant antiinfective treatment to help break the cycle of repeated local skin infections,
to decrease the number of methicillin-resistant Staphylococcus
aureus outbreaks, and to reduce the need for systemic antibiotics in AD patients with heavily-colonized and/or superinfected skin.36 This technique consists of soaking patients
for about 10 minutes in a full tub of lukewarm water mixed
with approximately one-quarter cup of chlorine bleach-analogous to swimming in a chlorinated pool. Afterward, patients
are rinsed thoroughly with fresh water and are moisturized
immediately to prevent desiccation.
163
Patients with AD will experience a flare and require pharmacologic treatment at least intermittently even if skin care regimens and guidelines for trigger avoidance are followed judiciously. Flares of mild-to-moderate intensity are characterized
by itching, erythema, and excoriations, papules, and lichenification. More severe flares present with intense and persistent itching, substantial erythema, extensive excoriations,
oozing/crusting, and lichenification. Two primary classes of
therapeutic agents are used for the treatment of AD: topical
corticosteroids and topical calcineurin inhibitors. Both groups
of agents inhibit the associated inflammatory response but
achieve this through distinct mechanisms of action.
sias, hypopigmentation, rosacea, perioral dermatitis, acne,
cataracts, and glaucoma. These local side effects can occur
more frequently when topical corticosteroids are used under
occlusion or applied to thin, sensitive skin areas such as the
face, neck, or groin. Systemic side effects, including growth
retardation in children, reduced bone density, and hypothalamic-pituitary-adrenal axis suppression, can occur, however,
they are rare when medications are used properly.41 Other factors to consider are the risk of flare relapse after discontinuation
of treatment and steroid tachyphylaxis. To minimize “steroid
phobia,” physicians should anticipate these concerns and stress
to patients and caregivers that, despite their well-known potential side-effects, topical corticosteroids remain first-line treatment for atopic flares in the pediatric population; decades of
clinical experience and specific pediatric studies support
their sensible use (Table 1).42-58
Variation in topical corticosteroid prescribing habits (eg,
quantity, frequency, and duration of therapy) is common
even among dermatologists.59 Some clinicians start treatment
with high-potency topical corticosteroid preparations to induce remission, followed by a relatively quick tapering down
of preparation potency as the atopic dermatitis improves. Alternatively, some clinicians use short bursts of high-potency
topical corticosteroid preparations followed by moisturizer/
emollient use only until relapse occurs. Yet another treatment
regimen advocates more prolonged continuous treatment
with less-potent preparations. Drug-specific Food and Drug
Administration (FDA) indications should help guide clinicians when educating and instructing patients on topical corticosteroid usage.
Topical Corticosteroids
Topical Calcineurin Inhibitors (TCIs)
Topical corticosteroids remain the first-line pharmacologic
therapy for AD. Acting on a variety of immune cells, including T lymphocytes, monocytes, macrophages, dendritic cells,
and their precursors, topical corticosteroids suppress the release of inflammatory cytokines and provide effective flare
control through their antiinflammatory, antiproliferative, immunosuppressive, and vasoconstrictive actions.37,38
In the United States, topical corticosteroids are classified
into groups of roughly equal potency based on a vasoconstrictor assay, which does not consider other factors that
influence the therapeutic effect or unwanted side effects such
as the state of the skin barrier, the body site involved, disease
extent, the age of the patient, concomitant use of occlusion,
the amount of steroid applied, and the duration of treatment.
The assay does, however, correlate well with clinical efficacy
and provides a reasonable guide to the potential for adverse
side effects.39 The difference in potency between Class I
(most potent) and Class VII (least potent) topical corticosteroids is dramatic and often misunderstood by patients. For
example, a Class I preparation like clobetasol propionate
ointment 0.05% is approximately 1800 times more potent
than a Class VII preparation like hydrocortisone ointment
1%.40
Well-known local tolerability and safety concerns of topical corticosteroids include skin atrophy, striae, telangiecta-
Tacrolimus and pimecrolimus, which work by blocking the
production and release of proinflammatory cytokines after
antigen-specific or nonspecific activation of T cells and mast
cells, are currently the only FDA-approved TCIs.60,61 In January 2006, the FDA added a boxed warning to TCI labels,
noting that the long-term safety of TCIs has not been established. The warning was added in response to widespread
off-label use in the infant population (younger than 2 years of
age) and concerns about a potential cancer risk. The risk
assessment was based on 3 observations: 1) systemic calcineurin inhibitors have a shared mechanism of action; 2)
animal toxicology studies have raised some concerns; and 3)
postmarketing reports have characterized rare cases of malignancy (skin cancer and lymphomas). None of the reported
lymphomas, however, were characteristic of the posttransplant lymphoproliferative disease type observed with systemic immunosuppression.
The safety and efficacy of tacrolimus and pimecrolimus
have to date been demonstrated in several short- (6-week)
and long-term (⬎2 years) clinical trials.62-64 Data from these
clinical trials have shown that pimecrolimus reduces the
number and severity of flares, extends the length of time
between major flares, and decreases pruritus and other cutaneous signs associated with AD.65 Likewise, long-term, intermittent (once daily, 3-times weekly) maintenance use of ta-
Pharmacologic Treatment
A.C. Krakowski and M.A. Dohil
164
Table 1 Select Topical Corticosteroids and Their Corresponding Pediatric HPA-Axis Suppression Studies
Class
Steroid
Dosage and Frequency
VII
Hydrocortisone 1%
ointment
VII
Hydrocortisone
2.5% ointment
Alclometasone
dipropionate
0.05% cream
Desonide 0.05%
hydrogel
48.7 to 223.2 mg/m2 BSA/d;
9/14 also intermittently
used moderate potency
preparations
Two times/d
VI
VI
Age Group
3.1 to 10.7
Two times/d
Two times/d
6 months to 6
years
VI
Desonide 0.05%
foam
Two times/d
6 months to
17 years
VI
Fluocinolone
acetonide 0.01%
in protein-free
peanut oil
Two times/d
Study 1: 3
months to
2 years
Study 2: 2 to
12 years
3 months to 6
years
HPA Studies
PC: No change in basal/peak plasma
levels but earlier peak seen in AD
patients vs. controls42
n ⴝ 40; open label; moderate-tosevere AD; 51% mean BSA
affected; duration of test ⴝ 4
weeks
n ⴝ 75; open label; mild-to-moderate
AD; >25% BSA treated; duration
of test ⴝ 4 weeks
Study 1: n ⴝ 24; open label;
moderate-to-severe AD; >20%
BSA affected; duration of test ⴝ 4
weeks
Study 2: n ⴝ 32; open-label;
moderate-to-severe AD; >50%
BSA affected; duration of test ⴝ 4
weeks
n ⴝ 43; open label; moderate-tosevere AD; 64% mean BSA
treated; duration of test ⴝ 3 to 4
weeks
V
Fluticasone
propionate
0.05% cream
V
Fluticasone
propionate
0.05% lotion
V
Prednicarbate
0.1% cream
Two times/d
4 months to
12 years
IV
Mometasone
furoate 0.1%
cream
Fluticasone
propionate
0.005%
ointment
Triamcinolone
acetonide 0.1%
ointment
Mometasone
furoate 0.1%
ointment
Fluocinonide 0.1%
cream
One time/d
6 to 23
months
Four times/d; average
amount of drug used per
day ⴝ 13 to 46 g/d/m2
One time/d
7 months to 8
years
n ⴝ 7; open label; severe AD;
duration of test ⴝ 6 weeks
6 to 23
months
n ⴝ 63; open label; AD (severity not
stated); 39% mean BSA affected;
duration of test ⴝ 3 weeks
n ⴝ 126; open label; moderate-tosevere AD; mean BSA affected
ranged from 34% (Cohort 1, BID)
to 43% (Cohort 4, QD); duration of
test ⴝ 2 weeks
III
III
II
I
Two times/d; average
amount of drug used per
day ⴝ 3.8 g for ages 3 to
35 months, 7.7 g for ages
36 to 70 months
Two times/d
Design
n ⴝ 14; moderate or severe AD; 58%
median BSA affected; duration of
test ⴝ 3 to 10 years (median 6.5
years)
n ⴝ 20; open label, parallel; duration
of test ⴝ 4 weeks
n ⴝ 39; open label; duration of
test ⴝ 3 to 4 weeks
One or two times/d
3 months to 6
years
Cohort 1: 12
to < 18
years
n ⴝ 42; open label; moderate to
severe AD; 65% mean BSA
treated; duration of test ⴝ 3 to 4
weeks
n ⴝ 55; open label; mostly moderate
to severe AD disease (1 “mild”
enrolled); 46.7% mean BSA
affected; duration of test ⴝ 3
weeks
n ⴝ 97; open label; AD (severity not
stated); 41% mean BSA affected;
duration of test ⴝ 3 weeks
n ⴝ 35; AD (severity not stated);
>35% BSA affected; duration of
test ⴝ 3 to 4 weeks
Cohort 2: 6 to
< 12 years
Cohort 3: 2 to
< 6 years
I
Clobetasol
propionate
0.05% lotion
Two times/d
Cohort 4: 3
months to
< 2 years
12 to 17
years
n ⴝ 14; moderate-to-severe AD;
>20% BSA affected; duration of
test ⴝ 2 weeks
CST: All normal43
PC (am): All normal44
CST: Normal in all pts without
protocol violations; 1/3 abnormal
in patients with protocol
deviations45
CST: 3/75 patients with abnormal
tests (normalized 4 weeks after
treatment)46
CST: All normal47,48
CST: 2/43 patients with abnormal
tests; 1 pt with 95% BSA affected
normalized 12 days after last
study dose; 1 pt with 35% BSA
was lost to follow-up49
CST: All normal50
CST: All normal51
CST: 16% of pts with abnormal tests
(4/5 tested pts normalized 2 to 4
weeks after treatment)52
CST: 4 pts with abnormal tests53
PC (am/pm): “No substantial
difference” 24-HUC: “No notable
depression”54
CST: 27% of pts with abnormal tests
(5/8 tested pts normalized 2 to 4
weeks after treatment)55
CST:
Cohort 1: 1/15 pts in BID group with
abnormal test (normalized 2 weeks
after treatment)
Cohort 2: 2/16 pts in BID group with
abnormal tests (1 normalized 8
days after treatment; 1 normalized
2 weeks after treatment)
Cohort 3: 1/15 pts in BID group with
abnormal test (suspected
collection error; not suppressed)56
9/14 pts with adrenal suppression
(assessment method not stated)57
HPA, hypothalamic–pituitary–adrenal; BSA, body surface area; PC, plasma cortisol; 24-HUC, 24-hour urinary cortisol; CST, cosyntropin stimulation test.
Topical therapy in pediatric atopic dermatitis
crolimus ointment in patients with stabilized AD has been
shown to significantly increase time between disease exacerbation and total number of disease-free days versus vehicle.66
The incidence of side effects is generally low and includes,
most commonly, transient application-site stinging.67,68 The
currently available data do not suggest that the use of TCIs is
associated with systemic immunosuppression, impacts the
delayed-type hypersensitivity response, or has an increased
association with skin cancer.69-71
Consequently, the FDA has not requested that ongoing
studies with TCIs in pediatric patients be halted. Official
indications for use were changed, however, to “second-line
therapy for the short-term and noncontinuous chronic treatment of moderate-to-severe atopic dermatitis in nonimmunocompromised adults and children who have failed to respond adequately to other topical prescription treatments for
atopic dermatitis, or when those treatments are not advisable” in children 2 years of age and older.72,73 Patients with
AD in whom the clinical course is marked by steroid tachyphylaxis, disease persistence, and/or frequent flares, which
would otherwise result in an almost continuous need for
topical corticosteroid treatment, may find TCIs very helpful.
TCIs may also be specifically indicated in sensitive thin skin
areas, such as around the eye, face, neck, and genital area,
where local safety concerns and systemic absorption are of
special concern. Long-term prospective studies investigating
the clinical use of TCIs in a pediatric population are currently
underway and will hopefully help to clarify these safety concerns.74,75
Combining Topical Therapies
Appreciating the risk-benefit profile of both topical corticosteroids and TCIs allows for individualized and optimized
patient care. Treatment should be readily adjusted along a
sliding scale that takes “best-use” advantage of available ther-
165
apeutic agents. For children with rapid flares, this may mean
using short-term bursts of mid- to high-potency topical steroids, typically applied twice daily for about 7 to 10 days (vs
the long-term use of less-potent agents) followed by close
reexamination of the patient at regular intervals (eg, evaluations at 2, 6, and 12 weeks) to evaluate the efficacy and
tolerability of local and systemic therapies. Once control of a
flare is achieved, therapy should shift to a less intense treatment with a focus on maintenance and proper skin care at its
core. A topical corticosteroid that has been used to treat a
flare can now be tapered to a lower-potency agent and from
daily to intermittent (eg, thrice- or twice-weekly) application.
Transition to TCI therapy for patients with a history of flare
recurrence on discontinuation or tapering of topical corticosteroids may be a good choice at this point. The use of TCI
monotherapy to control flare recurrence while limiting patients’ extended exposure to corticosteroids is supported by
some physicians.76
Wet Wraps
Developed more than 20 years ago, wet wraps afford a relatively safe and effective treatment option for patients with
severe AD or disease refractory to standard topical treatment
(Table 2).77 Wet wraps act as an occlusive barrier that promotes the penetration of topical medications into the skin.
They can also increase skin hydration and serve as an effective mechanical barrier to scratching. A recent review of the
literature found wet wraps with once-daily application of
topical corticosteroids to be an efficacious and safe shortterm intervention in children with severe and/or refractory
AD; temporary systemic bioactivity of the corticosteroids was
the only reported serious side-effect.78 Wet wraps have been
criticized by caregivers for being time-consuming and may
cause maceration of the skin and secondary infections if overused or used incorrectly. Paradoxically, they may promote
skin dryness if sufficient emollients are not part of the regi-
Table 2 Wet Wraps Primer
1. Gather supplies.
Topical steroid as prescribed by the physician
Emollient of choice (eg, petroleum jelly)
Wraps consisting of a bottom, wet layer and a top, dry layer. Gauze wraps such as Kerlex or cotton sleepers, pajamas, or
long johns may be used. It is necessary to have two sets of the chosen material on hand.
Warm water in a sink or a basin.
2. Apply topical steroid directly to affected areas of child’s skin. Use a tongue depressor to apply medication in order to
avoid contamination of the medication supply, to cover large areas quickly and evenly, and to prevent caregivers from
being unnecessarily exposed to topical corticosteroids.
3. Apply emollient (eg, petroleum jelly) to affected areas of child’s skin.
4. Soak a single layer of wrap in warm water.
5. Wring out excess water so that the wrap is only slightly damp.
6. Wrap affected area of skin with damp layer of material, making sure not to wrap too tightly.
7. Immediately wrap a dry layer of material over the damp layer.
8. Keep child in a warm, humid environment to ensure that the child does not grow cold as the evaporation process
occurs.
9. Leave wraps in place overnight.
10. Change wraps once daily for 3 to 5 days in a row or as instructed by physician.
11. Maintain close contact with physician while using wet wraps technique. Report any suspected side effects or concerns
immediately.
166
men.79 Patients should therefore be closely supervised by a
physician with experience in the use of wet wraps.
Summary
Atopic dermatitis in childhood is common and often appears
early in life. It is not merely a chronic skin condition, but may
adversely affect a child’s overall physical health and psychosocial development. Management should take into consideration the role that the compromised epidermal barrier plays
in AD. AD’s chronic and unpredictable course requires that
caregivers be educated about the nature of flares and proper
use of the primary anti-inflammatory agents, topical corticosteroids, and TCIs in its management. Because atopic dermatitis is a multifactorial disease, treatment needs to be teamoriented with a focus on parent and patient education
creating disease perspective and a long-term plan for AD
control.
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