07 Pediatrics in Review July20 PDF

See discussions, stats, and author profiles for this publication at: https://www.researchgate.
net/publication/44901937
Movement Disorders II: Chorea, Dystonia, Myoclonus, and Tremor
Article in Pediatrics in Review · July 2010

DOI: 10.1542/pir.31-7-287 · Source: PubMed
CITATIONS READS
2 12,458
2 authors:
Jonathan W Mink Samuel H Zinner

University of Rochester University of Washington Seattle
207 PUBLICATIONS 9,202 CITATIONS 16 PUBLICATIONS 369 CITATIONS
SEE PROFILE SEE PROFILE
All content following this page was uploaded by Jonathan W Mink on 21 May 2014.
The user has requested enhancement of the downloaded file.

Egyptian_Pediatric yahoo group Egyptian_Pediatric yahoo group
http://health.groups.yahoo.com/group/ http://health.groups.yahoo.com/group/
egyptian_pediatric/ egyptian_pediatric/
Editor-in-Chief: Lawrence F. Nazarian, Rochester, NY
Associate Editors: Tina L. Cheng, Baltimore, MD
Joseph A. Zenel, Sioux Falls, SD
Editor, In Brief: Henry M. Adam, Bronx, NY
Consulting Editor, In Brief: Janet Serwint, Baltimore, MD
contents
Editor, Index of Suspicion:
Deepak M. Kamat, Detroit, MI
Consulting Editor Online and Multimedia
PediatricsinReview姞 Vol.31 No.7 July 2010
Projects: Laura Ibsen, Portland, OR
Editor Emeritus and Founding Editor:
Robert J. Haggerty, Canandaigua, NY
Managing Editor: Luann Zanzola
Medical Copy Editor: Deborah K. Kuhlman Articles
Editorial Assistant: Sydney Sutherland
Editorial Office: Department of Pediatrics
University of Rochester
School of Medicine & Dentistry
601 Elmwood Avenue, Box 777
Rochester, NY 14642
267 Developmental Milestones:
Development
Motor
R. Jason Gerber, Timothy Wilks, Christine Erdie-Lalena

sydney_sutherland@urmc.rochester.edu
278 Atopic Dermatitis and Ichthyosis

Editorial Board
Margie Andreae, Ann Arbor, MI Hal B. Jenson, Springfield, MA
Richard Antaya, New Haven, CT Donald Lewis, Norfolk, VA
Denise Bratcher, Kansas City, MO Gregory Liptak, Syracuse, NY
David Cornfield, Stanford, CA Susan Massengill, Charlotte, NC
Joseph Croffie, Indianapolis, IN Jennifer Miller, Gainesville, FL Roselyn E. Epps
Philip Fischer, Rochester, MN Blaise Nemeth, Madison, WI
Rani Gereige, Miami, FL Renata Sanders, Baltimore, MD
Lindsey Grossman, Springfield, MA Thomas L. Sato, Milwaukee, WI
Patrician Hamilton, London, Andrew Sirotnak, Denver, CO
287 Movement Disorders II:

United Kingdom Nancy D. Spector, Philadelphia, PA
Publisher: American Academy of Pediatrics
Michael J. Held, Director, Division of Scholarly Journals and Professional Chorea, Dystonia, Myoclonus, and Tremor
Periodicals
Pediatrics in Review姞 Jonathan W. Mink, Samuel H. Zinner
(ISSN 0191-9601) is owned and controlled by the American Academy of
Pediatrics. It is published monthly by the American Academy of Pediatrics, 141
Northwest Point Blvd., Elk Grove Village, IL 60007-1098
Statements and opinions expressed in Pediatrics in Review威 are those of the
authors and not necessarily those of the American Academy of Pediatrics or its
Committees. Recommendations included in this publication do not indicate an
exclusive course of treatment or serve as a standard of medical care.
Subscription price for 2010 for print and online/online only: AAP Fellow
296 Research and Statistics: Strengths and
Limitations of Randomized, Controlled Trials
$172/$131; AAP Candidate Fellow $161/$120; Nonmember $215/$167; Erica M.S. Sibinga, Jacky M. Jennings
Allied Health or Resident $160/$108. Institutions call for pricing (866-843-
2271). For overseas delivery, add $95. Current single issue price is $10
domestic, $12 international. Replacement issues must be claimed within 6
months from the date of issue and are limited to three per calendar year.
Periodicals postage paid at ARLINGTON HEIGHTS, ILLINOIS and at
additional mailing offices.
© AMERICAN ACADEMY OF PEDIATRICS, 2010. All rights reserved.
Printed in USA. No part may be duplicated or reproduced without permission
of the American Academy of Pediatrics.
299 Visual Diagnosis: A Pimple-like Lesion
on the Cheek of a 5-year-old Girl
POSTMASTER: Send address changes to PEDIATRICS IN REVIEW威, Rayna M. Dyck, Dawn M. Davis
American Academy of Pediatrics Customer Service Center, 141 Northwest
Point Blvd., Elk Grove Village, IL 60007-1098.
Pediatrics in Review
Print Issue Editorial Board Disclosures
The American Academy of Pediatrics (AAP) Policy on Disclosure of Financial
Relationships and Resolution of Conflicts of Interest for AAP CME Activities is
designed to ensure quality, objective, balanced, and scientifically rigorous AAP
CME activities by identifying and resolving all potential conflicts of interest before
302 Pediatrics in the Community:
to Get the Advocacy Snowball Rolling
A Little PUSH
the confirmation of service of those in a position to influence and/or control CME Katherine R. Snyder
content.
Every individual in a position to influence and/or control the content of AAP
303 Index of Suspicion

CME activities is required to disclose to the AAP, and subsequently to learners
whether the individual has relevant financial relationships with manufacturers of
commercial products and/or services discussed in the CME activities.
Each of the editorial board members disclosed that the CME content he/she
edits/writes may include discussion/reference to generic pharmaceuticals, off-label
pharmaceutical use, investigational therapies, brand names, and manufacturers, if Case 1: Scott M. Pugh, Joseph F. Pasternak, Patricia A. Liszewski
applicable.
None of the editors had any relevant financial relationships to disclose, unless noted Case 2: Alexandra N. Menchise, Leslie Carroll, David M. Berman
below. The AAP has taken steps to resolve any potential conflicts of interest.
Disclosures Case 3: Gurpreet Vidwan, Winsley Rose
● Richard Antaya, MD, FAAP, disclosed that he has an Astellas Pharma, US, Inc,
research grant and participates in its speaker bureau and advisory board; and that
he is a consultant for Novartis Pharmaceuticals.
● Joseph Croffie, MD, MPH, FAAP, disclosed that he has research grants and
serves on speaker bureaus of Sucampo Pharmaceuticals (Lubiprostone), Braintree
Labs (Miralax Halflytely), Medtronics (Bravo pH Capsule), Tap pharmaceuticals
(Prevacid).
● Donald W. Lewis, MD, FAAP, disclosed that he is a consultant for and has a
Internet-Only Articles
research grant from Astra Zeneca and Merck; and that he has research grants Abstracts appear on page 298.
from Ortho McNeil, Lilly, Bristol-Myers Squibb, GlaxoSmithKline, and
Boehringer Ingelheim Pharmaceutical.
● Janet Serwint, MD, FAAP, disclosed that she receives a research grant from the
Maternal and Child Health Bureau.
e49 Ethics for the Pediatrician: The Ethics of

Complementary and Alternative Medicine
Brenda J. Mears
The composition and production of Pediatrics in Review威

is supported, in part, through an educational grant from
Abbott Nutrition, a division of Abbott Laboratories, Inc. e52 In Brief: Nonalcoholic Fatty Liver Disease
Bryan Rudolph, Yolanda Rivas
Cover: The artwork on the cover of this month’s issue is

by one of the winners of our 2009 Cover Art Contest,
6-year-old Emma Rethy of Leesburg, VA. Emma’s pe-
diatrician is Patricia Rappaport, MD.
Answer Key: 1. C; 2. C; 3. A; 4. D; 5. B; 6. B; 7. C; 8. B; 9. A;
10. C; 11. E; 12. B; 13. E
Atopic Dermatitis and Ichthyosis
Roselyn E. Epps
Pediatr. Rev. 2010;31;278-286
DOI: 10.1542/pir.31-7-278
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pedsinreview.aappublications.org/cgi/content/full/31/7/278
Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of
Pediatrics. All rights reserved. Print ISSN: 0191-9601. Online ISSN: 1526-3347.
Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Article skin

Roselyn E. Epps, MD*
Objectives After completing this article, readers should be able to:
1. Identify the characteristic features of atopic dermatitis and the factors that worsen it.
Author Disclosure 2. Understand that children who have atopic dermatitis are prone to recurrent infections,
Dr Epps has disclosed particularly with Staphylococcus aureus and herpes simplex virus.
no financial 3. Know the signs of Wiskott-Aldrich syndrome.
relationships relevant 4. Plan the appropriate treatment of atopic dermatitis (emollients, corticosteroids,
to this article. This antibiotics, and allergen elimination when appropriate).
commentary does not 5. Recognize ichthyosis vulgaris and know that ichthyosis commonly occurs in children
contain a discussion who have atopic dermatitis.
of an unapproved/ 6. List the effective therapies in the management of ichthyosis vulgaris.
investigative use of a 7. Distinguish between tinea pedis and atopic dermatitis.
commercial 8. Discuss the relationship of atopic dermatitis and food allergies and how to evaluate a
product/device. patient who has both.
9. Explain why children who have one component of atopy syndrome (allergic rhinitis,
asthma, atopic dermatitis) have a threefold greater risk of developing a second
component.
Atopic Dermatitis
Atopic dermatitis (AD) is a chronic, relapsing dermatosis that features dry skin (xerosis),
pruritus, and a personal or family history of eczema, allergic rhinitis or allergies, or asthma.
Children who have one component of the atopic triad (AD, asthma, allergic rhinitis) are
three times as likely to develop a second component. There is no sex predilection, and the
onset frequently is in infancy. Although many affected children outgrow the condition by
age 5 years, AD may persist into adolescence and adulthood. A smaller percentage of
patients experience the onset of AD as older children or in adulthood.
The incidence and prevalence of AD have increased in the United States and worldwide,
particularly in developed nations. Fewer than 10% of children were affected in the 1970s,
but recent epidemiologic studies estimate that 15% to 20% of children are diagnosed with
AD. The reason for the increased rate is unknown. The “hygiene hypothesis” proposes that
decreased exposure to infectious and biologic antigens may result in an increased response
to environmental antigens or perhaps to decreased immune suppression. Additional
research must be conducted to determine the reasons for the increased prevalence and to
address the trend.
Pathophysiology
Manifestations of AD are believed to be due to the interaction of certain genes, the
environment, and immunologic response to the environment and specific trigger factors.
Patients who have AD may be considered to have systemic changes, not just manifestations
in the skin. Susceptible individuals can react to internal and environmental triggers in
certain target organs, not only resulting in skin eruptions, but also in asthma and allergic
rhinitis. Patients may exhibit extrinsic immunoglobulin E (IgE)-mediated sensitization
due to external antigens, with allergenic signs and elevated allergen-specific IgE, or
intrinsic sensitization, without IgE-mediated sensitization.
*Chief, Division of Dermatology, Children’s National Medical Center, George Washington University School of Medicine and
Health Sciences, Washington, DC.
278 Pediatrics in Review Vol.31 No.7 July 2010

skin atopic dermatitis and ichthyosis
In acute AD lesions, T-helper 2 (TH2) cells are

present in larger numbers than normal and have in-
creased expression of specific cytokines that, in turn,
stimulate B cells to produce IgE, resulting in peripheral
eosinophilia. Cytokines and chemokines are released
from cells in the skin, attracting other inflammatory cells
and producing inflammatory mediators and reactions.
Keratinocytes, Langerhans cells, endothelial cells,
monocyte-macrophages, and eosinophils all play roles in
the acute and chronic inflammation of AD.
Clinical Manifestations
Generally, the primary lesion is a red, rough, poorly
defined dry papule or plaque. Scaling may be seen. There
is no central clearing. In children of color or deep pig-
mentation, plaques can be papular or follicular, especially
on the trunk or over the extensor areas of joints.
AD is diagnosed clinically and manifests particular
patterns at different ages. Frequently, infants present
with rough patches or plaques on the cheeks, the dorsa of
the wrists, the ankles, and the lateral extremities. The
perioral and diaper areas customarily are spared. After
infancy, children develop flexural involvement, and the
cheek areas improve. The neck, antecubital and popliteal
fossae, and gluteal folds frequently are involved (Fig. 1).
Teenagers are more likely to experience eyelid erup- Figure 1. Atopic dermatitis often involves the antecubital
tions. With age, the hands and feet also become more fossa. Lichenification and excoriations are evident in this
problematic, and AD may present as dyshidrotic erup- example.
tions. Any part of the body, from the scalp to the soles
and including the lips and genitalia, may be affected at
any age. Eruptions occur whether or not an offending may occur in other dermatologic conditions that feature
factor or trigger is identified. Exacerbations and remis- chronic scratching and pruritus.
sions are common and to be expected. Friction on the skin and scratching the skin are known
Secondary skin changes occur frequently. Oozing, to exacerbate pruritus and can initiate the “itch-scratch
weeping, and crust formation can develop, which may cycle,” in which the child scratches, itching in the in-
represent secondary infection. Hyperpigmentation as volved area increases, the child continues to scratch, and
well as hypopigmentation and depigmentation (loss of the cycle continues. Plaques, papules, and nodules can
pigmentation) can occur. Normal color of the skin usu- result because of the escalating “itch-scratch cycle.”
ally returns when the signs and symptoms of AD resolve.
Weeks to months may be required for the hyperpigmen- Secondary Infection
tation and hypopigmentation to resolve. If excoriations Patients who have AD are more likely to develop skin and
are deep or the inflammation is severe, scarring or depig- possibly systemic infections. One reason superinfection
mentation can be permanent. occurs more easily is due to altered skin barrier function,
Lichenification, a hallmark of AD, is thickening and including apparent and imperceptible excoriations, fis-
accentuation of skin markings due to chronic scratching. sures, and skin defects (Fig. 2). For patients who have
Lichenified skin on the hands and feet is more likely to AD, seemingly uninvolved skin is not normal. In addi-
fissure. Excoriations are common, and some patients tion to greater irritancy and dryness, there are immuno-
create erosions and deeper wounds by unrelenting, in- logic differences in the type of TH2 cells and an increase
tense, repeated trauma. Repeated friction and trauma in the number of TH2 cells within the skin. Staphylococ-
promote inflammation and trigger inflammatory reac- cus aureus is an important cause of superinfection. S
tions and pathways in affected skin. Lichenification also aureus colonization by age 6 months, with frequent
Pediatrics in Review Vol.31 No.7 July 2010 279

have AD. If herpesvirus infection involves the eye or

periocular area, ophthalmology consultation is essential
to manage herpes keratitis and to prevent permanent loss
of vision.
Dermatophytes and yeast also can superinfect the
skin. Patients who have AD can develop tinea capitis and
tinea pedis, and it can be difficult at times to distinguish
AD from tinea infection because both may involve pru-
ritus, scaling, and inflammation. On physical examina-
tion, unlike AD, tinea pedis frequently develops in the
toe web spaces (particularly the third and fourth). Tinea
lesions frequently feature expanding plaques with central
clearing and peripheral papules and scale. Potassium
hydroxide slide examination of a sample taken from the
skin from any affected body area, including the skin, the
Figure 2. Atopic dermatitis of this leg shows erythema,
excoriations, and scaling consistent with superinfection.
scalp, and hair, can help make the diagnosis.
Allergy and Environment

colonization during the first year after birth, is associated Allergic contact dermatitis can exacerbate AD. Common
with an increased prevalence and severity of AD. Im- contact triggers include fragrances and preservatives in
paired skin barrier function, a defective host immune personal care products such as soaps, cleansers, sham-
response, and increased synthesis of extracellular matrix poos, detergents, and certain emollients. Among other
adhesion substances promote S aureus colonization. materials and substances that commonly elicit symptoms
Exotoxins secreted by S aureus penetrate the skin of allergic contact dermatitis are wool, nickel, synthetics,
barrier and stimulate T cells and antigen-presenting dyes, and rubber.
cells, thereby exacerbating and contributing to persistent Physical and environmental factors also can play a
skin inflammation. S aureus overgrowth and superinfec- role. Temperature changes between cold and hot envi-
tion can result in flares, impetigo, folliculitis, cellulitis, ronments (as when moving from an air conditioned
abscesses, bacteremia, and sepsis. Methicillin-resistant enclosure to hot outdoor weather) or change of season
S aureus, now more common in the community, can be can be problematic. Some children prefer warm or cool
particularly problematic for patients who have AD and temperatures. Therefore, their dermatitis is milder in the
their families. The patient’s infection must be treated, summer or winter, respectively. Other environmental
and treating the family may be necessary to minimize the variables such as dust and mites, pollen, and ambient
risk of AD exacerbation in the patient. The clinician humidity can have an impact. Because sweating can
should consider culturing the atopic patient who is fe- produce pruritus and skin eruptions for some patients,
brile, is unresponsive to therapy, or shows an inadequate treatment of AD may require modifying exercise regi-
response to maximized treatment that includes antibiotic mens. Clothing tags, coarse fabrics, snug clothing, and
therapy. Other bacteria also may be cultured from the footwear can worsen symptoms in a localized distribu-
AD patient’s wounds and should be treated accordingly. tion. Emotional factors such as stress, anger, sleepiness,
Although patients who have AD develop bacterial and boredom often increase pruritus.
infections, they also may acquire viral and fungal infec- The role of foods in causing AD can be significant for
tions. Eczema herpeticum occurs when AD is superin- some children; food allergies can be present in up to 40%
fected with a herpesvirus, either herpes simplex virus or of patients who have AD. Symptoms include pruritus,
varicella-zoster virus. Vesicles develop on affected and urticaria, contact dermatitis, and exacerbation of AD as
apparently unaffected skin and can be very painful. When well as wheezing, asthma, and anaphylaxis. The symp-
disseminated, there may be associated viremia, fever, and toms can be immediate or delayed. Among the leading
lymphadenopathy, and patients can become very ill. Oc- allergenic foods are milk and dairy products, eggs, wheat,
ular involvement may occur innocuously when the pa- soy, and peanuts. Some children outgrow allergies to
tient rubs his or her eyes. Acyclovir should be adminis- particular foods, but peanuts and eggs are often the
tered intravenously in critical disseminated infections or exception. Although some foods are difficult to avoid,
orally for localized, recurrent infections in patients who the improved availability of nutritional information, di-

etary counseling, and food labeling helps families make use of emollients is a cornerstone of therapy. Even with-
proper dietary choices for children who have food aller- out visible lesions, dry skin often is pruritic. Many prod-
gies. ucts are available; no single emollient provides relief,
Allergy skin prick testing usually is more reliable after moisturizes the skin, and improves skin barrier function
age 2 years; specific radioallergosorbent testing can be for all patients. The medication vehicle (eg, cream versus
performed in infancy. The patient must not take oral ointment) and the presence of fragrance, preservatives,
antihistamines or steroid medications for several days or other additives can affect the patient’s response. Lo-
before skin prick allergy testing; AD should be controlled tions, creams, ointments, and oils are composed of vary-
as much as possible to allow proper evaluation while ing amounts of oil and water. Ointments are composed
minimizing patient discomfort. Avoidance of allergenic of more petroleum jelly, creams contain more water than
substances identified by allergy testing occasionally ben- oil, and lotions contain more water than cream. If the
efits the patient who has AD, but AD can be exacerbated skin is excoriated or fissured, stinging or pain can occur
by unrelated factors while allergies are present. Allergy from products containing more water. An optimal time
testing may be repeated and expanded if the patient does for moisturizer application is immediately after the bath
not improve after avoidance therapy. or shower. Many patients benefit from several emollient
applications per day.
Management Topical corticosteroids have been a mainstay of AD
Treatment of AD requires a coordinated plan aimed at therapy for approximately 50 years. Hydrocortisone (up
moisturizing dry skin, decreasing inflammation, treating to 1%) is available over the counter, and numerous
any infections, and avoiding irritants and other factors prescription preparations are available (Table). Oint-
associated with dermatitis flares. The regimen must be ments, creams, lotions, gels, foams, and oil preparations
discussed with the family, patient, and clinicians to en- are available. Different preparations deliver corticoste-
sure compliance. roid through the skin in varying potencies. If prepara-
Bathing is an important aspect of general skin care for tions are used sparingly and appropriately, adverse effects
patients who have AD. Baths and showers should be brief should be minimized. Adverse effects include skin atro-
and the water comfortably warm, never hot. After expo- phy, telangiectasias, striae, and systemic absorption. The
sure to water, the skin should be patted or excess water use of potent and fluorinated corticosteroids on the face
brushed off of the skin before applying medication and and intertriginous and diaper areas should be avoided
moisturizer. Some patients improve and are maintained due to increased absorption through thinner or occluded
with daily or twice-daily bathing. Other patients experi- skin. Middle-strength to more potent corticosteroid
ence drying and increased pruritus or discomfort with medications may be required for treating lichenified areas
water contact, making infrequent bathing the required or on the hands and feet due to the increased skin
approach. In addition, during flares, some patients are thickness and keratin of the skin layers.
unable to bathe or shower due to discomfort and pain. Several clinical trials of topical corticosteroid use in
Bathing may be resumed when symptoms decrease. the pediatric age group have been performed or are in
Although not necessary, a variety of commercial prod- progress; some topical corticosteroids are approved spe-
ucts, including cleansers, soaps, oils, and oatmeal pow- cifically for use in children and some infants. Many
ders, can be combined with bath water. Fragrance-free practitioners find topical corticosteroids useful to break
soaps and cleansers are preferred, but which product the itch-scratch cycle, treat acute flares, and minimize
benefits or is tolerated by each patient differs. The use of symptoms of inflammation. When signs and symptoms
bubble bath, shampoo, and dishwater detergent to improve, the frequency of topical corticosteroid applica-
cleanse the body should be avoided. For some, dilute tion should be reduced while moisturizer use is contin-
chlorine bleach baths are beneficial, particularly for chil- ued. Continuous, prolonged application of topical corti-
dren whose AD improves after swimming in chlorinated costeroids also can produce tachyphylaxis or decreased
pools. One-quarter to one-half cup of bleach in the effectiveness of the medication.
bathtub (24 gallons or a standard tub filled 4 to 6 inches) Oral corticosteroid therapy has limited use in treating
should create a sufficient concentration without bleach- AD. Although helpful for some severe flares, once ther-
ing or damaging linens. Dilute white vinegar, extra light apy is discontinued, the rebound or subsequent flare that
olive oil, and other products also have been used for may occur might be more severe than the initial exacer-
bathing. bation and more difficult to control. Some patients be-
Because the skin of patients who have AD is dry, the come oral corticosteroid-dependent in their attempt to

Topical Corticosteroids Ranked Strongest

Table. prevent flares and are more likely to
develop adverse systemic effects such
(Class I) to Weakest (Class VII) as hypothalamic-pituitary axis suppres-
sion, growth retardation, and cushin-
Medication Available Formulation
goid features.
Class I Clobetasol propionate 0.05% Cream, ointment, gel, foam Chronic, high-dose, or high-
Betamethasone dipropionate Ointment potency oral corticosteroid use has
augmented 0.05%
Diflorasone diacetate 0.05% Ointment been shown to cause osteopenia or
Fluocinonide 0.01% Ointment osteoporosis in children and adults. It
Halobetasol propionate 0.05% Cream, ointment is not known whether chronic inter-
Class II Amcinonide 0.01% Ointment mittent topical corticosteroid use af-
Betamethasone dipropionate Ointment
0.05% fects the bones of children. Some phy-
Betamethasone dipropionate Cream sicians give vitamin D and calcium
augmented 0.05% supplementation to patients who have
Desoximetasone 0.25% Cream, ointment AD. Of note, the American Academy
Desoximetasone 0.05% Gel
of Pediatrics has released new recom-
Fluocinonide 0.05% Cream, ointment, gel, solution
Halcinonide 0.1% Cream, ointment, solution mendations regarding vitamin D sup-
Mometasone furoate 0.1% Ointment plementation in children; the recom-
Class III Amcinonide 0.1% Cream, lotion mended minimum dose was doubled
Betamethasone valerate 0.1% Ointment to 400 IU daily for infants and chil-
Desoximetasone 0.05% Cream
dren. Clearly, corticosteroid use in
Fluocinonide emollient 0.05% Cream
Fluticasone propionate 0.005% Ointment children who have AD, the impact of
Halcinonide 0.1% Solution therapy on bone health, and the role of
Triamcinolone acetonide 0.1% Ointment vitamin D and calcium supplementa-
Class IV Betamethasone valerate 0.12% Foam tion merit additional scientific study.
Fluocinonide acetonide 0.025% Ointment
Topical calcineurin inhibitors are
Flurandrenolide 0.05% Ointment
Fluticasone propionate 0.05% Cream newer elements of the therapeutic
Hydrocortisone valerate 0.2% Ointment armamentarium. Pimecrolimus 1%
Mometasone furoate 0.1% Cream, lotion cream is approved for mild-to-
Triamcinolone acetonide 0.1% Cream, ointment moderate AD. Tacrolimus ointment is
Class V Betamethasone dipropionate Lotion
0.05% available in 0.03% and 0.1% strengths
Betamethasone valerate 0.1% Cream and is targeted for moderate-to-severe
Clocortolone pivalate 0.1% Cream AD. Tacrolimus 0.03% and pimecroli-
Desonide 0.05% Ointment mus are approved by the United States
Fluocinolone acetonide 0.025% Cream Food and Drug Administration for
Flurandrenolide 0.05% Cream
Fluticasone propionate 0.01% Oil those ages 2 years and older; tacroli-
Fluticasone propionate 0.05% Cream mus 0.1% is intended for those ages 15
Hydrocortisone butyrate 0.1% Cream, ointment years and older. Both medications can
Hydrocortisone valerate 0.2% Cream be used on any part of the body and are
Prednicarbate 0.1% Cream particularly beneficial for the eyelids,
Triamcinolone acetonide 0.1% Lotion
Class VI Alclometasone 0.05% Cream, ointment face, and intertriginous areas.
Betamethasone valerate 0.1% Lotion The most common adverse effects
Desonide 0.05% Cream reported are burning at the site of ap-
Fluocinolone acetonide 0.01% Cream, lotion plication, headache, upper respiratory
Hydrocortisone butyrate 0.1% Solution tract symptoms, cough, and pyrexia.
Triamcinolone acetonide 0.1% Cream
Triamcinolone acetonide Cream, lotion In addition, exacerbation of viral infec-
0.025% tions, including herpesvirus infection,
Class VII Hydrocortisone acetonide, Cream, ointment, lotion verrucae, and molluscum contagio-
dexamethasone sum, may be more likely in patients
Note: Vehicle affects medication potency for several products. who use these products. A black box
warning was placed on both medica-

tions, stating that long-term safety of topical calcineurin autosomal dominant form is due to a mutation in the
inhibitors has not been established and that these medi- signal transducer and activator of the transcription 3
cations are not recommended for use in children younger (STAT3) gene. Skin eruptions appear during the new-
than age 2 years. Additional therapeutic trials in children born period, with onset of infections during the first 3
who have AD are planned and needed. postnatal months. Although the type of skin infection
Several prescription topical nonsteroidal moisturizing can vary, “cold” abscesses are typical and feature slight
creams have been approved for use in AD. Their purpose redness, no or low-grade fever, little systemic involve-
is to improve the hydrolipid layer and barrier function, ment, and minimal signs and symptoms, unlike abscesses
relieve AD symptoms, and promote wound healing. seen in patients unaffected by HIES. Paronychiae and
They may be used alone or in combination with topical candidal infections are common. Although the eczema-
corticosteroids and calcineurin inhibitors. The non- tous symptoms usually resolve, the recurrent pulmonary
steroid creams Atopiclair® Nonsteroidal Cream (Grace- infections due to S aureus and Haemophilus influenzae
way Pharmaceuticals, Bristol, Tenn.), Eletone® Cream progress to chronic lung infections and subsequent lung
(Ferndale Laboratories, Ferndale, Mich.), Epiceram威 changes. Of note, children who have AD can have very
Skin Barrier Emulsion (Promius Pharmaceuticals, high concentrations of IgE; conversely, patients who
Bridgewater, NJ), and MimyX威 Cream (Steifel Pharma- have HIES can have normal IgE concentrations.
ceuticals, Bristol, Tenn.) are approved for all ages, for use
on any area of the body, and may be used two to three
times a day. Zetania威 cream (Tiber Laboratories, Su- Ichthyosis
wanee, Ga.) is approved for children 2 years of age and Ichthyosis represents a group of disorders that involves
older. Patients allergic to any components of the creams abnormal epidermal skin barrier function, keratinization,
should avoid their use. and desquamation. Multiple types of ichthyosis have
Oral antihistamine drugs have been prescribed for been described. Initially defined descriptively, the disor-
patients who have AD. Although not statistically proven ders now can be distinguished by genetic, histologic,
to be useful for treating pruritus generally, oral anti- biochemical, and molecular methods.
histamines can be helpful for children who have an Ichthyosis vulgaris (IV) is the most common type,
urticarial component or decreased or altered sleep pat- with an incidence of 1 in 250. The onset is during infancy
terns due to pruritus. or childhood, not at birth. Inheritance can be autosomal
dominant or sporadic, so patients have a varied presen-
Wiscott-Aldrich Syndrome tation. IV usually presents as fine white scales on the skin,
Wiskott-Aldrich syndrome is one important condition sparing the antecubital and popliteal fossae. Scaling is
to consider in patients who have AD. This X-linked most obvious on the lateral lower legs (Fig. 3). Hyper-
recessive disorder features eczematous eruptions in as- linearity is noted on the palms and soles. IV can be
sociation with thrombocytopenia and recurrent infec- innocuous and appear as an isolated finding. The histo-
tions. Thrombocytopenic purpura and hemorrhagic pathology may show a thinned-to-absent granular layer
events may occur. The identified Wiskott-Aldrich syn- and a compact superficial stratum corneum. However, a
drome protein (WASP) gene codes for a cytoplasmic skin biopsy may not be diagnostic; microscopically, IV
protein that has multiple functions. The impaired hu- can look like normal skin. IV often improves with age,
moral immune response to polysaccharide antigens and manifestations in adulthood may be minimal.
seen in patients who have Wiskott-Aldrich syndrome There are many forms of ichthyosis, most of which are
makes patients susceptible to bacteria such as Streptococ- rare. Ichthyosis can be inherited in autosomal or X-linked
cus pneumoniae and Pneumocystis jiroveci and, later, to patterns or by spontaneous mutation. Although IV is
viruses. After the second decade of life, these patients are rather common, X-linked ichthyosis, lamellar ichthyosis,
at risk for developing leukemia and lymphoma. and harlequin fetus are rare, well-described forms
(Fig. 4). Several syndromes and related conditions of
Job Syndrome note include ichthyosis as part of the clinical picture. KID
Another important condition to consider is Job syn- syndrome is defined as keratitis, ichthyosis, and deafness.
drome, or hyperimmunoglobulin E syndrome (HIES), Netherton syndrome, also called ichthyosis linearis cir-
which is defined by eczematous eruptions associated with cumflexa, features congenital erythroderma as well as
IgE concentrations greater than 2,000 IU/mL and re- atopic dermatitis, hair shaft abnormalities, and high IgE
peated skin and sinopulmonary infections. The classic concentrations.

Figure 3. Ichthyosis vulgaris demonstrates fine, white scales. Figure 4. Lamellar ichthyosis features larger, platelike scales.
The mutation for IV also has been identified. Studies

Management have shown that Northern European patients who have
Treatment of IV usually involves the use of topical sali-
IV have a statistically significant increased risk for devel-
cylic acid; lactic acid; or urea in lotion, cream, or oint-
oping AD as well. Also, patients who have both IV and
ment form. These products moisturize, soften the skin,
AD have a statistically significant increased risk for devel-
and aid in desquamation. For patients who have both IV
oping asthma. Overall, there is strong evidence for a
and AD, these products are more likely to cause irrita-
genetic and molecular basis for the association of IV and
tion. The products should be used cautiously in children
AD. More studies are in progress and are necessary for
because total body application can result in systemic
absorption and serious adverse effects. Salicylic acid, in
particular, should be used in children after 1 year of age
and then with caution due to risks of salicylate toxicity.
Summary
• Based on strong research evidence and consensus, a
Research multifaceted, individualized approach to treatment
Significant research has been performed in IV, AD, and benefits patients who have atopic dermatitis and
related disorders. IV often coexists with AD, and re- includes bathing, emollients, topical anti-
inflammatory medications, allergen avoidance, and
search has shown a genetic basis for this association in
the use of antistaphylococcal antibiotics and
certain populations. Gene mutations in keratin proteins antihistamines when clinically indicated. (1)(2)
alter skin barrier function. Most important, the FLG gene • Based on strong research evidence, mutations in the
produces profilaggrin, and filaggrin is critical for AD FLG gene cause ichthyosis vulgaris, resulting in
expression. Multiple international and familial studies alterations in the skin protein filaggrin. (3)(4)
• Based on strong research evidence, atopic dermatitis
have shown that FLG mutations in patients who have AD
is associated with certain populations who have
alter normal skin formation, function, and hydration and ichthyosis vulgaris. (5)(6)(7)
result in severe AD, as well as asthma associated with AD.

elucidating the role of altered cutaneous barrier function 6. Sandilands A, Terron-Kwiatkowski A, Hull PR, et al. Compre-
in AD and IV. hensive analysis of the gene encoding filaggrin uncovers prevalent
and rare mutations in ichthyosis vulgaris and atopic eczema. Nat
Genet. 2007;39:650 – 654
7. Nomura T, Akiyama M, Sandilands A, et al. Specific filaggrin
References mutations cause ichthyosis vulgaris and are significantly associated
1. Hanifin JM, Cooper KD, Ho VC, et al. Guidelines of care for with atopic dermatitis in Japan. J Invest Dermatol. 2008;128:
atopic dermatitis, developed in accordance with the American 1436 –1441
Academy of Dermatology (AAD)/American Academy of Derma-
tology Association “Administrative Regulations for Evidence-Based
Clinical Practice Guidelines.” J Am Acad Dermatol. 2004;50:
391– 404 Suggested Reading
2. Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC.
QA. New insights into atopic dermatitis. J Clin Invest. 2004;113: Efficacy and tolerability of topical pimecrolimus and tacrolimus
651– 657 in the treatment of atopic dermatitis: meta-analysis of random-
3. Smith FJ, Irvine AD, Terron-Kwiatkowski A, et al. Loss-of- ised controlled trials. BMJ. 2005;330:516
function mutations in the gene encoding filaggrin cause ichthyosis Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic
vulgaris. Nat Genet. 2006;38:337–342 dermatitis in the pediatric population. Pediatrics. 2008;122:
4. Akiyama M, Shimizu H. An update on molecular aspects of the 812– 824
non-syndromic ichthyoses. Exp Dermatol. 2008;17:373–382 Lin YT, Yang CT, Chiang BL. Role of bacterial pathogens in atopic
5. Hoffjan S, Stemmler S. On the role of the epidermal differenti- dermatitis. Clin Rev Allergy Immunol. 2007;33:167–177
ation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. McGeady SJ. Immunocompetence and allergy. Pediatrics. 2004;
Br J Dermatol. 2007;157:441– 449 113(4 suppl):1107–1113

PIR Quiz
Quiz also available online at http://wwwpedsinreview.aappublications.org.
5. Infants who have atopic dermatitis often have clinical features that are different from those of older
affected children. Which of the following areas of the body is more likely to be affected in infants?
A. Antecubital fossae.
B. Cheeks.
C. Eyelids.
D. Genitals.
E. Neck.
6. You are evaluating a 4-year-old boy who has a history of atopic dermatitis that usually affects his feet and
popliteal fossae. He complains of itching and increased rash on his feet for several weeks. His mother feels
that his atopic dermatitis is flaring up. Which of the following features makes a diagnosis of tinea pedis
more likely than an exacerbation of atopic dermatitis?
A. Erythema.
B. Lesions in web spaces.
C. Plaques without central clearing.
D. Pruritus.
E. Scaling.
7. Which of the following treatments is recommended for all patients who have atopic dermatitis?
A. Complete avoidance of eggs and peanuts.
B. Daily prophylactic topical antibiotic cream.
C. Emollient application after a bath or shower.
D. Frequent bathing with hot water.
E. Periodic oral corticosteroid courses.
8. You are evaluating a 4-month-old boy during a health supervision visit. His mother complains that he is
“always sick,” and she is concerned about his constant “dry skin.” She describes three upper respiratory
tract infections and one episode of pneumonia that required hospitalization in the past 2 months. On
physical examination, you note numerous scaly, erythematous patches on the infant’s face and the extensor
surfaces of his arms and legs. In addition, an erythematous diaper rash with satellite lesions is visible. You
obtain a complete blood count, which reveals eosinophilia but no other abnormalities. Which of the
following is the most likely diagnosis?
A. Allergic contact dermatitis.
B. Hyper-immunoglobulin E syndrome.
C. Lamellar ichthyosis.
D. Tinea corporis.
E. Wiskott-Aldrich syndrome.

Roselyn E. Epps
Pediatr. Rev. 2010;31;278-286
DOI: 10.1542/pir.31-7-278
Updated Information including high-resolution figures, can be found at:

& Services http://pedsinreview.aappublications.org/cgi/content/full/31/7/278
Permissions & Licensing Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
http://pedsinreview.aappublications.org/misc/Permissions.shtml
Reprints Information about ordering reprints can be found online:
http://pedsinreview.aappublications.org/misc/reprints.shtml

Developmental Milestones: Motor Development
R. Jason Gerber, Timothy Wilks and Christine Erdie-Lalena
Pediatr. Rev. 2010;31;267-277
DOI: 10.1542/pir.31-7-267

Article growth & development

R. Jason Gerber, MD,*
Timothy Wilks, MD,†
Christine Erdie-Lalena, 1. Identify the milestones for gross and fine motor development.
MD ‡ 2. Recognize the child whose development falls outside of the expected range.
3. Describe the sequences involved in gross and fine motor development.
This is the first of three articles on developmental milestones; the second and third articles
Author Disclosure
will appear in the September and November 2010 issues of Pediatrics in Review, respectively.
Drs Gerber, Wilks, and
Erdie-Lalena have
disclosed no financial Introduction
relationships relevant Infancy and childhood are dynamic periods of growth and change. Neurodevelopmental
to this article. This and physical growth proceed in a sequential and predictable pattern that is intrinsically
determined. Skills progress from cephalic to caudal; from proximal to distal; and from
commentary does not
generalized, stimulus-based reflexes to specific, goal-oriented reactions that become
contain a discussion
increasingly precise. As one clinician has stated, “infants [and children] are very orderly in
of an unapproved/ their ways; they actually behave [and develop] according to laws that can be explored,
investigative use of a discovered, confirmed, reconfirmed, and celebrated.” (1) By convention, these neuro-
commercial developmental “laws” or sequences often are described in terms of the traditional devel-
product/device. opmental milestones.
Milestones provide a framework for observing and monitoring a child over time.
According to recent American Academy of Pediatrics and Bright Futures guidelines,
pediatricians should incorporate developmental surveillance at every health supervision
visit. Surveillance involves analyzing the milestones in the context of a child’s history,
growth, and physical examination findings to recognize those who may be at risk for
developmental delay. A thorough understanding of the normal or typical sequence of
development in all domains (gross motor, fine motor, problem-solving, receptive lan-
guage, expressive language, and social-emotional) allows the clinician to formulate a
correct overall impression of a child’s true developmental status. However, it must be
emphasized that even experienced pediatricians cannot rely solely on their knowledge of
the milestones to identify children who have developmental concerns. Developmental
screening using validated and standardized tools should occur at the 9-month, 18-month,
and 30-month (or 24-month) health supervision visits or whenever surveillance uncovers
a concern.
Although neurodevelopment follows a predictable course, it is important to understand
that intrinsic and extrinsic forces produce individual variation, making each child’s devel-
opmental path unique. Intrinsic influences include genetically determined attributes (eg,
physical characteristics, temperament) as well as the child’s overall state of wellness.
Extrinsic influences during infancy and childhood originate primarily from the family.
Parent and sibling personalities, the nurturing methods used by caregivers, the cultural
environment, and the family’s socioeconomic status with its effect on resources of time and
money all play a role in the development of children. Developmental theory has, itself,
developed as clinicians have tried to grapple with which influence is more predominant.
The focus of this series of articles is to help the clinician frame general concepts of
development according to the developmental streams rather than highlight developmental
*Major, USAF, Medical Corps, Developmental & Behavioral Pediatrics Fellow, Madigan Army Medical Center, Joint Base Lewis-
McChord, Wash.
†
LCDR, USN, Medical Corps; Developmental & Behavioral Pediatrics Fellow, Madigan Army Medical Center, Joint Base Lewis-
McChord, Wash.
‡
Lt Col, USAF, Medical Corps, Program Director, Developmental & Behavioral Pediatrics Fellowship, Madigan Army Medical
Center, Joint Base Lewis-McChord, Wash.

growth & development motor development
abnormalities. The milestones cited are, on average, During the first postnatal year, an infant thus moves
those at the 50th percentile for age. By understanding from lying prone, to rolling over, to getting to hands and
what is “normal” or typical, the clinician can appreciate knees, and ultimately to coming to a seated position or
more keenly what is abnormal or delayed. This article pulling to stand (Fig. 6). Within the framework of Back
concentrates on normal motor development, with a brief to Sleep guidelines, infants must have age-appropriate
mention about specific “red flags” that should alert cli- and safe opportunities for “tummy time” to promote the
nicians to potential motor developmental problems. The development of these important prone-specific mile-
second article in the series discusses cognitive and lan- stones. It is important to note that crawling is not a
guage development. The final article addresses the devel- prerequisite to walking; pulling to stand is the skill infants
opment of social-emotional skills. An all-inclusive table must develop before they take their first steps. The
of milestones is provided in this first article as a reference ultimate goal of this timeframe is to develop skills that
(Table 1) both in print and online; Table 1 appears allow for independent movement and freedom to use the
online only in the September and November articles. hands to explore, manipulate, and learn from the envi-
ronment.
Gross Motor Milestones Gross motor development in subsequent years con-
The ultimate goal of gross motor development is to gain sists of refinements in balance, coordination, speed, and
independent and volitional movement. During gesta- strength. The wide-based, slightly crouched, staccato
tion, primitive reflexes develop and persist for several gait of a 12-month-old evolves into a smooth, upright,
months after birth to prepare the infant for the acquisi- and narrow-based style. The arms change from being
tion of specific skills. These brainstem and spinal reflexes held abducted and slightly elevated for balance to swing-
are stereotypic movements generated in response to spe- ing in a reciprocal fashion as the gait reaches an adult
cific sensory stimuli. Examples include the Moro (Fig. 1), pattern by age 3 years. Similarly, running develops soon
asymmetric tonic neck (ATNR) (Fig. 2), and positive after walking, starting as a stiff-legged approximation and
support reflexes (Fig. 3). As the central nervous system changing into a well-coordinated movement that in-
matures, the reflexes are inhibited to allow the infant to cludes rapid change of direction and speed by 18 months
make purposeful movements. For example, during the of age.
time when the ATNR persists, an infant is unable to roll Simultaneous use of both arms or legs occurs after
from back to front, bring the hands to midline, or reach successful use of each limb independently. At age 2 years,
for objects. This reflex disappears between 4 and 6 a child can kick a ball, jump with two feet off the floor,
months of age, the same time that these skills begin to and throw a big ball overhand. Milestones for succeeding
emerge. The Moro reflex interferes with head control ages reflect progress in the length of time, number of
and sitting equilibrium. As this reflex lessens and disap- repetitions, or the distance each task can be performed
pears by 6 months of age, the infant gains progressive successfully. By the time a child starts school, he or she is
stability in a seated position (Fig. 4). able to perform multiple complex gross motor tasks
In addition to primitive reflexes, postural reactions, simultaneously (such as pedaling, maintaining balance,
such as righting and protection responses, also begin to and steering while on a bicycle).
develop after birth. These reactions, mediated at the
midbrain level, interact with each other and work toward Fine Motor Milestones
the establishment of normal head and body relationship Fine motor skills relate to the use of the upper extremities
in space. Protective extension, for example, allows the to engage and manipulate the environment. They are
infant to catch him- or herself when falling forward, necessary for a person to perform self-help tasks, to play,
sideways, or backwards (Fig. 5). These reactions develop and to accomplish work. Like all developmental streams,
between 6 and 9 months, the same time that an infant fine motor milestones do not proceed in isolation but
learns to move into a seated position and then to hands depend on other areas of development, including gross
and knees. Soon afterward, higher cortical centers medi- motor, cognitive, and visual perceptual skills. At first, the
ate the development of equilibrium responses and permit upper extremities play an important role in balance and
the infant to pull to stand by 9 months of age and begin mobility. Hands are used for support, first in the prone
walking by 12 months. Additional equilibrium responses position and then in sitting. Arms help with rolling over,
develop during the second year after birth to allow for then crawling, then pulling to stand. Infants begin to use
more complex bipedal movements, such as moving back- their hands to explore, even when in the supine position.
ward, running, and jumping. When gross motor skills have developed such that the

Table 1. Developmental Milestones

Age Gross Motor Fine Motor Self-Help Problem-solving Social/Emotional Receptive Language Expressive Language
1 month ● Chin up in ● Hands fisted ● Sucks well ● Gazes at black- ● Discriminates ● Startles to voice/ ● Throaty noises
prone position near face white objects mother’s voice sound
● Turns head in ● Follows face ● Cries out of
supine position distress
2 months ● Chest up in ● Hands unfisted ● Opens mouth ● Visual threat ● Reciprocal ● Alerts to voice/ ● Coos
prone position 50% at sight of present smiling: sound ● Social smile
● Head bobs when ● Retains rattle breast or ● Follows large, responds to (6 weeks)
held in sitting if placed in bottle highly adult voice and ● Vowel-like noises
position hand contrasting smile
● Holds hands objects
together ● Recognizes
mother
3 months ● Props on ● Hands unfisted ● Brings hands ● Reaches for ● Expression of ● Regards speaker ● Chuckles
forearms in 50% to mouth face disgust (sour ● Vocalizes when
prone position ● Inspects ● Follows objects taste, loud talked to
● Rolls to side fingers in circle (in sound)
● Bats at objects supine ● Visually follows
position) person who is
● Regards toys moving across a
room
4 months ● Sits with trunk ● Hands held ● Briefly holds ● Mouths objects ● Smiles ● Orients head in ● Laughs out loud
support predominately onto breast ● Stares longer spontaneously direction of a ● Vocalizes when
● No head lag open or bottle at novel faces at pleasurable voice alone
when pulled to ● Clutches at than familiar sight/sound ● Stops crying to
sit clothes ● Shakes rattle ● Stops crying at soothing voice
● Props on wrists ● Reaches ● Reaches for parent voice
● Rolls front to persistently ring/rattle ● To and fro
back ● Plays with alternating
rattle vocalizations
5 months ● Sits with pelvic ● Palmar grasps ● Gums/ ● Turns head to ● Recognizes ● Begins to ● Says “Ah-goo”
support cube mouths look for caregiver respond to ● Razzes, squeals
● Rolls back to ● Transfers pureed food dropped spoon visually name ● Expresses anger
front objects: hand- ● Regards pellet ● Forms with sounds
● Anterior mouth-hand or small attachment other than crying
protection ● Holds hands cracker relationship to
● Sits with arms together caregiver
supporting ● Reaches/grasps
trunk dangling ring
6 months ● Sits ● Transfers ● Feeds self ● Touches ● Stranger anxiety ● Stops ● Reduplicative
momentarily hand-hand crackers reflection and (familiar versus momentarily to babble with
propped on ● Rakes pellet ● Places hands vocalizes unfamiliar “no” consonants
hands ● Takes second on bottle ● Removes cloth people) ● Gestures for “up” ● Listens, then
● Pivots in prone cube and holds on face vocalizes when
● In prone on to first ● Bangs and adult stops
position, bears ● Reaches with shakes toys ● Smiles/vocalizes
weight on 1 one hand to mirror
hand
7 months ● Bounces when ● Radial-palmar ● Refuses ● Explores ● Looks from ● Looks toward ● Increasing variety
held grasp excess food different object to parent familiar object of syllables
● Sits without aspects of toy and back when when named
support steadily ● Observes cube wanting help ● Attends to music
● Lateral in each hand (eg, with a
protection ● Finds partially wind-up toy)
● Puts arms out hidden object
to sides for
balance
8 months ● Gets into sitting ● Bangs spoon ● Holds own ● Seeks object ● Lets parents ● Responds to ● Says “Dada”
position after bottle after it falls know when “Come here” (nonspecific)
● Commando demonstration ● Finger feeds silently to the happy versus ● Looks for family ● Echolalia (8 to 30
crawls ● Scissor grasp Cheerios® or floor upset members, months)
● Pulls to sitting/ of cube string beans ● Engages in gaze “Where’s ● Shakes head for
kneeling ● Takes cube out monitoring: mama?”. . . etc “no”
position of cup adult looks
● Pulls out large away and child
peg follows adult
glance with own
eyes
(continued)

Table 1. Developmental Milestones—continued

9 months ● “Stands” on feet ● Radial-digital ● Bites, chews ● Inspects bell ● Uses sounds to ● Enjoys gesture ● Says “Mama”
and hands grasp of cube cookie ● Rings bell get attention games (nonspecific)
● Begins creeping ● Bangs two ● Pulls string to ● Separation ● Orients to name ● Nonreduplicative
● Pulls to stand cubes together obtain ring anxiety well babble
● Bear walks (all ● Follows a point, ● Orients to bell ● Imitates sounds
four limbs “Oh look at . . .”
straight) ● Recognizes
familiar people
visually
10 months ● Creeps well ● Clumsy release ● Drinks from ● Uncovers toy ● Experiences fear ● Enjoys peek-a- ● Says “Dada”
● Cruises around of cube cup held for under cloth ● Looks boo (specific)
furniture using ● Inferior pincer child ● Pokes at pellet preferentially ● Waves “bye-bye” ● Waves “bye-bye”
two hands grasp of pellet in bottle when name is back
● Stands with one ● Isolates index ● Tries to put called
hand held finger and cube in cup,
● Walks with two pokes but may not be
hands held able to let go
11 months ● Pivots in sitting ● Throws objects ● Cooperates ● Finds toy under ● Gives objects to ● Stops activity ● Says first word
position ● Stirs with with dressing cup adult for action when told “no” ● Vocalizes to songs
● Cruises furniture spoon ● Looks at after ● Bounces to music
using one hand pictures in demonstration
● Stands for a book (lets adult know
few seconds he or she needs
● Walks with one help)
hand held
12 months ● Stands well ● Scribbles after ● Finger feeds ● Rattles spoon ● Shows objects ● Follows one-step ● Points to get
with arms high, demonstration part of meal in cup to parent to command with desired object
legs splayed ● Fine pincer ● Takes off hat ● Lifts box lid to share interest gesture (proto-imperative
● Posterior grasp of pellet find toy ● Points to get ● Recognizes pointing)
protection ● Holds crayon desired object names of two ● Uses several
● Independent ● Attempts (proto- objects and looks gestures with
steps tower of two imperative when named vocalizing (eg,
cubes pointing) waving, reaching)
13 months ● Walks with ● Attempts to ● Drinks from ● Dangles ring by ● Shows desire to ● Looks ● Uses three words
arms high and release pellet cup with string please caregiver appropriately ● Immature
out (high in bottle some spilling ● Reaches around ● Solitary play when asked, jargoning:
guard) clear barrier to ● Functional play “Where’s the inflection without
obtain object ball?” real words
● Unwraps toy in
cloth
14 months ● Stands without ● Imitates back ● Removes ● Dumps pellet ● Points at object ● Follows one-step ● Names one object
pulling up and forth socks/shoes out of bottle to express command ● Points at object
● Falls by collapse scribble ● Chews well after interest (proto- without gesture to express
● Walks well ● Adds third ● Puts spoon in demonstration declarative interest (proto-
cube to a two- mouth (turns pointing) declarative
cube tower over) ● Purposeful pointing)
● Puts round peg exploration of
in and out of toys through
hole trial and error
15 months ● Stoops to pick ● Builds three- ● Uses spoon ● Turns pages in ● Shows empathy ● Points to one ● Uses three to five
up toy to four-cube with some book (someone else body part words
● Creeps up stairs tower spilling ● Places circle in cries, child looks ● Points to one ● Mature jargoning
● Runs stiff- ● Places 10 ● Attempts to single-shape sad) object of three with real words
legged cubes in cup brush own puzzle ● Hugs adult in when named
● Walks carrying ● Releases pellet hair reciprocation ● Gets object from
toy into bottle ● Fusses to be ● Recognizes another room
● Climbs on changed without a upon demand
furniture demonstration
that a toy
requires
activation;
hands it to
adult if can’t
operate
16 months ● Stands on one ● Puts several ● Picks up and ● Dumps pellet ● Kisses by touch- ● Understands ● Uses 5 to 10
foot with slight round pegs in drinks from out without ing lips to skin simple words
support board with cup demonstration ● Periodically commands,
● Walks urging ● Fetches and ● Finds toy visually relocates “Bring to
backwards ● Scribbles carries observed to be caregiver mommy”
● Walks up stairs spontaneously objects (same hidden under ● Self-conscious; ● Points to one
with one hand room) layers of covers embarrassed picture when
held ● Places circle in when aware of named
form board people observing
(continued)


18 months ● Creeps down ● Makes four- ● Removes ● Matches pairs ● Passes M-CHAT ● Points to two of ● Uses 10 to 25
stairs cube tower garment of objects ● Engages in three objects words
● Runs well ● Crudely ● Gets onto ● Replaces circle pretend play when named ● Uses giant words
● Seats self in imitates adult chair in form board with other ● Points to three (all gone, stop
small chair vertical stroke unaided after it has people (eg, tea body parts that)
● Throws ball ● Moves about been turned party, birthday ● Points to self ● Imitates
while standing house around (usually party) ● Understands environmental
without with trial and ● Begins to show “mine” sounds (eg,
adult error) shame (when ● Points to familiar animals)
does wrong) people when ● Names one picture
and named on demand
possessiveness
20 months ● Squats in play ● Completes ● Places only ● Deduces ● Begins to have ● Points to three ● Holophrases
● Carries large round peg edibles in location of thoughts about pictures (“Mommy?” and
object board without mouth hidden object feelings ● Begins to points to keys,
● Walks urging ● Feeds self ● Places square ● Engages in tea understand meaning: “These
downstairs with ● Makes five- to with spoon in form board party with her/him/me are Mommy’s
one hand held six-cube tower entire meal stuffed animals keys.”)
● Completes ● Kisses with ● Two-word
square peg pucker combinations
board ● Answers requests
with “no”
22 months ● Walks up stairs ● Closes box ● Uses spoon ● Completes ● Watches other ● Points to four ● Uses 25 to 50
holding rail, with lid well form board children to five pictures words
putting both ● Imitates ● Drinks from intensely when named ● Asks for more
feet on each vertical line cup well ● Begins to show ● Points to five to ● Adds one to two
step ● Imitates ● Unzips defiant behavior six body parts words/week
● Kicks ball with circular zippers ● Points to four
demonstration scribble ● Puts shoes pieces of
● Walks with one on partway clothing when
foot on walking named
board
24 months ● Walks down ● Makes a ● Opens door ● Sorts objects ● Parallel play ● Follows two- ● Two-word sentence
stairs holding single-line using knob ● Matches ● Begins to mask step command (noun ⴙ verb)
rail, both feet “train” of ● Sucks objects to emotions for ● Understands ● Telegraphic speech
on each step cubes through a pictures social etiquette me/you ● Uses 50ⴙ words
● Kicks ball ● Imitates circle straw ● Shows use of ● Points to 5 to ● 50% intelligibility
without ● Imitates ● Takes off familiar objects 10 pictures ● Refers to self by
demonstration horizontal line clothes name
● Throws without ● Names three
overhand buttons pictures
● Pulls off
pants
28 months ● Jumps from ● Strings large ● Holds self ● Matches ● Reduction in ● Understands ● Repeats two digits
bottom step beads and shapes separation “just one” ● Begins to use
with one foot awkwardly verbalizes ● Matches colors anxiety pronouns
leading ● Unscrews jar toilet needs (I, me, you)
● Walks on toes lid ● Pulls pants ● Names 10 to 15
after ● Turns paper up with pictures
demonstration pages (often assistance
● Walks backward several at
10 steps once)
30 months ● Walks up stairs ● Makes eight- ● Washes ● Replaces circle ● Imitates adult ● Follows two ● Echolalia and
with rail, cube tower hands in form board activities (eg, prepositions: jargoning gone
alternating feet ● Makes a ● Puts things after it has sweeping, “put block ● Names objects by
● Jumps in place “train” of away been turned talking on in . . . on box” use
● Stands with cubes and ● Brushes teeth around (little phone) ● Understands ● Refers to self with
both feet on includes a with or no trial and actions words: correct pronoun
balance beam stack assistance error) “playing . . . ● Recites parts of
● Walks with one ● Points to small washing . . . well-known story/
foot on balance details in blowing” fills in words
beam pictures
33 months ● Walks swinging ● Makes 9- to ● Toilet trained ● Points to self ● Begins to take ● Understands ● Gives first and last
arms opposite 10-cube tower ● Puts on coat in photos turns three name
of legs ● Puts six square unassisted ● Points to body ● Tries to help prepositions ● Counts to 3
(synchronous pegs in parts based on with household ● Understands ● Begins to use past
gait) pegboard function tasks dirty, wet tense
● Imitates cross (“What do you ● Points to objects ● Enjoys being read
hear with?”) by use: “ride to (short books)
in . . . put on
feet . . . write
with”
(continued)


3 years ● Balances on one ● Copies circle ● Independent ● Draws a two- to ● Starts to share ● Points to parts ● Uses 200ⴙ words
foot for 3 ● Cuts with scissors: eating three-part person with/without of pictures (nose ● Three-word sentences
seconds side-to-side ● Pours liquid from ● Understands long/ prompt of cow, door of ● Uses pronouns
● Goes up stairs, (awkwardly) one container to short, big/small, ● Fears imaginary car) correctly
alternating feet, ● Strings small another more/less things ● Names body ● 75% intelligibility
no rail beads well ● Puts on shoes ● Knows own gender ● Imaginative play parts with ● Uses plurals
● Pedals tricycle ● Imitates bridge of without laces ● Knows own age ● Uses words to function ● Names body parts by
● Walks heel cubes ● Unbuttons ● Matches letters/ describe what ● Understands use
to toe numerals someone else is negatives ● Asks to be read to
● Catches ball thinking (“Mom ● Groups objects
with stiff arms thought I was (foods, toys)
asleep”)
4 years ● Balances on one ● Copies square ● Goes to toilet ● Draws a four- to ● Deception: ● Follows three- ● Uses 300 to 1,000
foot 4 to 8 ● Ties single knot alone six-part person interested in step commands words
seconds ● Cuts 5-inch circle ● Wipes after bowel ● Can give amounts “tricking” others ● Points to things ● Tells stories
● Hops on one ● Uses tongs to movement (usually less than 5) and concerned that are the ● 100% intelligibility
foot two to transfer ● Washes face/ correctly about being same versus ● Uses “feeling” words
three times ● Writes part of hands ● Simple analogies: tricked by others different ● Uses words that tell
● Standing broad first name ● Brushes teeth - dad/boy: ● Has a preferred ● Names things about time
jump: 1 to ● Imitates gate alone mother/??? friend when actions are
2 feet with cubes ● Buttons - ice/cold: fire/ ● Labels happiness, described (eg,
● Gallops ● Uses fork well ??? sadness, fear, swims in water,
● Throws ball - ceiling/up: and anger in self you cut with it,
overhand floor/??? ● Group play it’s something
10 feet ● Points to five to six you read, it tells
● Catches colors time . . .)
bounced ball ● Points to letters/ ● Understands
(41⁄2 yrs) numerals when adjectives: bushy,
named long, thin,
● Rote counts to 4 pointed
● “Reads” several
common signs/
store names
5 years ● Walks down ● Copies triangle ● Spreads with ● Draws an 8- to ● Has group of ● Knows right and ● Repeats six- to
stairs with rail, ● Puts paper clip knife 10-part person friends left on self eight-word sentence
alternating feet on paper ● Independent ● Gives amounts ● Apologizes for ● Points to ● Defines simple words
● Balances on ● Can use clothes- dressing (<10) mistakes different one in ● Uses 2,000 words
one foot >8 pins to transfer ● Bathes ● Identifies coins ● Responds a series ● Knows telephone
seconds small objects independently ● Names letters/ verbally to good ● Understands “er” number
● Hops on one ● Cuts with scissors numerals out of fortune of others endings (eg, ● Responds to “why”
foot 15 times ● Writes first name order batter, skater) questions
● Skips ● Builds stairs from ● Rote counts to 10 ● Understands ● Retells story with
● Running broad model ● Names 10 colors adjectives: busy, clear beginning,
jump 2 to 3 ● Uses letter names as long, thin, middle, end
feet sounds to invent pointed
● Walks backward spelling ● Enjoys rhyming
heel-toe ● Knows sounds of words and
● Jumps backward consonants and alliterations
short vowels by end ● Produces words
of kindergarten that rhyme
● Reads 25 words ● Points correctly
to “side,”
“middle,”
“corner”
6 years ● Tandem walks ● Builds stairs from ● Ties shoes ● Draws a 12- to ● Has best friend ● Asks what un- ● Repeats 8- to 10-
memory ● Combs hair 14-part person of same sex familiar words word sentences
● Draws diamond ● Looks both ways ● Number concepts ● Plays board mean ● Describes events in
● Writes first and at street to 20 games ● Can tell which order
last name ● Remembers to ● Simple addition/ ● Distinguishes words do not ● Knows days of the
● Creates and writes bring belongings subtraction fantasy from belong in a week
short sentences ● Understands seasons reality group ● 10,000 word
● Forms letters with ● Sounds out ● Wants to be like vocabulary
down-going and regularly spelled friends and
counterclockwise words please them
strokes ● Reads 250 words by ● Enjoys school
● Copies flag end of first grade
Copyright 2007 by Chris Johnson, MD, AAP Council on Children with Disabilities. Adapted by the authors with permission and contributions from Frances
Page Glascoe, PhD, and Nicholas Robertshaw, authors of PEDS:Developmental Milestones; Franklin Trimm, MD, Vice Chair of Pediatrics, USA/APA
Education Committee; the Centers for Disease Control and Prevention “Act Early” initiative; the National Institute for Literacy/Reach Out and Read; and
the Inventory of Early Development by Albert Brigance published by Curriculum Associates, Inc. Permission is granted to reproduce these pages on the
condition that they are only used as a guide to typical development and not as a substitute for standardized validated screening for developmental problems.

Figure 1. Moro reflex. This reflex occurs spontaneously to

loud noises or by simply holding the supine infant’s hand and
releasing the hand suddenly. Classically, the reflex is elicited
while holding the infant supine, with the head dropped
slightly backward. This produces sudden extension and abduc-
tion of the upper extremities with hands open, followed by
flexion of the upper extremities to midline (the “startle reflex”).
infant is more stable in upright positions and can move

into them easily, the hands are free for more purposeful
exploration.
At birth, infants do not have any apparent voluntary Figure 2. Asymmetric tonic neck reflex (ATNR). The sensory
use of their hands. They open and close them in response limb of the ATNR involves proprioceptors in the cervical
to touch and other stimuli, but movement otherwise is vertebrae. With active or passive head rotation, the baby
dominated by a primitive grasp reflex. Because of this, extends the arm and leg on the face side and flexes the
infants spend the first 3 months after birth “contacting” extremities on the contralateral side (the “fencer posture”).
objects with their eyes rather than their hands, fixating on There also is some subtle trunk curvature on the contralateral
faces and objects and then visually tracking objects. side produced by mild paraspinous muscle contraction.
Gradually, they start to reach clumsily and bring their
hands together. As the primitive reflexes decrease, infants 9 months. A pincer grasp emerges as the ulnar fingers are
begin to prehend objects voluntarily, first using the en- inhibited while slightly extending and supinating the
tire palm toward the ulnar side (5 months) and then wrist. Voluntary release is awkward at first, with all fin-
predominantly using the radial aspect of the palm gers extended. By 10 months of age, infants can release a
(7 months). At the same time, infants learn to release cube into a container or drop things onto the floor.
objects voluntarily. In the presence of a strong grasp Object permanence reinforces the desire to practice this
reflex, objects must be removed forcibly from an infant’s skill over and over. Intrinsic muscle control develops to
grasp or drop involuntarily from the hand. Voluntary allow the isolation of the index finger, and infants will
release is seen as the infant learns to transfer objects from poke their fingers into small holes for exploration. By 12
one hand to the other, first using the mouth as an months of age, most infants enjoy putting things into
intermediate stage (5 months) and then directly hand- containers and dumping them out repeatedly. They also
to-hand (6 months). can pick up small pieces of food with a mature pincer
Between 6 months and 12 months of age, the grasp grasp and bring them to their mouths.
evolves to allow for prehension of objects of different As infants move into their second year, their mastery
shapes and sizes (Fig. 7). The thumb becomes more of the reach, grasp, and release allows them to start using
involved to grasp objects, using all four fingers against objects as tools. Fine motor development becomes more
the thumb (a “scissors” grasp) at 8 months, and eventu- closely associated with cognitive and adaptive develop-
ally to just two fingers and thumb (radial digital grasp) at ment, with the infant knowing both what he or she wants to

Figure 4. The declining intensity of primitive reflexes and the

increasing role of postural reactions represent at least permis-
sive, and possibly necessary, conditions for the development of
definitive motor reactions. Reproduced with permission from
Johnson CP, Blasco PA. Infant growth and development.
Pediatr Rev. 1997;18:225–242.
Figure 3. Positive support reflex. With support around the

trunk, the infant is suspended, then lowered to touch the feet
gently on a flat surface. This produces reflex extension at the
hips, knees, and ankles so the infant stands up, completely or
partially bearing weight. Mature weight-bearing lacks the
rigid quality of this primitive reflex.
do and how he or she can accomplish it. Intrinsic muscle

refinement allows for holding flat objects, such as crackers
or cookies. By 15 months of age, voluntary release has
developed further to enable stacking of three to four blocks
and releasing small objects into containers. The child starts
to adjust objects after grasping to use them properly, such as
picking up a crayon and adjusting it to scribble spontane-
ously (18 months of age) and adjusting a spoon to use it
consistently for eating (20 months of age).
In subsequent years, fine motor skills are refined fur-
ther to draw, explore, problem-solve, create, and perform Figure 5. Lateral protection. In the seated position, the child
self-help tasks. By age 2 years, children can create a six- is pushed gently but rapidly to one side. The reaction is present
block tower, feed themselves with a spoon and fork, re- if the child puts out his or her hand to prevent a fall.

flexion. Their grasp and in-hand ma-

nipulation skills allow them to string
small beads and unbutton clothes.
At age 4 years, a palmar tripod
grasp allows for finer control of pencil
movements, and the child can copy a
cross, a square, and some letters and
numerals and can draw a figure of a
person (the head and a few other
body parts). Scissor skills have pro-
gressed to permit the cutting of a
circle. When a child reaches the age
of 5 years, he or she can dress and un-
dress independently, brush the teeth
well, and spread with a knife. More
precise in-hand manipulation skills
enable the child to cut a square with
mature scissor movements (indepen-
Figure 6. Chronologic progression of gross motor development during the first 12 dent finger use) and to print his or
postnatal months. Reproduced with permission from Johnson CP, Blasco PA. Infant her own name and copy a triangle
growth and development. Pediatr Rev. 1997;18:224 –242. using a mature tripod pencil grasp
(using the fingers to move the pencil
rather than the forearm and wrist).
Developmental Red Flags

As the clinician performs develop-
mental surveillance, the absence of
certain key milestones in a patient
should raise the level of concern.
Figure 7. Development of pincer grasp. Illustrations from the Erhardt developmental Table 2 lists the developmental red
prehension. In Erhardt RP. Developmental Hand Dysfunction: Theory Assessment, Treat- flags specific to the motor domain. If
ment. 2nd ed. San Antonio, Tex: Therapy Skill Builders; 1994. Reprinted with permission. one of these red flags is discovered, a
medical and more thorough devel-
opmental evaluation is warranted.
Table 2. Motor Red Flags Although reported in this article in isolation, motor
skills development overlaps significantly with the other
Age Red Flag
streams of development.
4 months Lack of steady head control
while sitting
9 months Inability to sit
18 months Inability to walk independently
Summary
• The development of motor skills is critical for a child
move clothing, and grasp and turn a door knob. They to move independently and to interact with his or her
environment meaningfully and usefully. Skills develop
have sufficient control of a crayon to imitate both ver-
in a cephalic-to-caudal progression and from proximal
tical and horizontal lines. In-hand manipulation skills to distal. Thus, consistent head support occurs before
permit them to rotate objects, such as unscrewing a voluntary control of arms and legs, and large muscle
small bottle cap or reorienting a puzzle piece before control of the upper arms occurs before small, intrinsic
putting it in place. They are able to wash and dry their muscle control in the hands.
• Skills also progress from generalized responses to
hands. By 36 months of age, they can draw a circle, put
stimuli (primitive reflexes) to goal-oriented, purposeful
on shoes, and stack 10 blocks. They make snips with actions with ever-increasing precision and dexterity.
scissors by alternating between full-finger extension and

References sleeping environment and sleep position. Pediatrics. 2000;105:

1. Lipsitt LP. Learning and emotion in infants. Pediatrics. 1998; 650 – 656
102:1262–1267 Case-Smith J, Allen AS, Pratt PN, eds. Occupational Therapy for
Children. St. Louis, Mo: Mosby Year-Book, Inc; 1996
Suggested Reading Fiorentino MR. Reflex Testing Methods for Evaluating CNS Devel-
American Academy of Pediatrics Committee on Children with opment. Springfield, Ill: Charles C Thomas; 1973
Disabilities, Section on Developmental Behavioral Pediatrics; Hagan JF, Shaw J, Ducan PM, eds. Bright Futures: Guidelines for
Bright Futures Steering Committee; Medical Home Initiatives Health Supervision of Infants, Children, and Adolescents. 3rd
for Children with Special Needs Project Advisory Committee. edition. Elk Grove Village, Ill: American Academy of Pediatrics;
Identifying infants and young children with developmental dis- 2008
orders in the medical home: an algorithm for developmental Johnson CP, Blasco PA. Infant growth and development. Pediatr
surveillance and screening. Pediatrics. 2006;118:405– 420 Rev. 1997;18:224 –242
AAP Task Force on Infant Positioning and SIDS. Changing con- Sturner RA, Howard BJ. Preschool development 1: communicative
cepts of sudden infant death syndrome: implications for infant and motor aspects. Pediatr Rev. 1997;18:291–301

PIR Quiz
Quiz also available online at http://pedsinreview.aappublications.org.
1. An 18-month-old girl is seen for a health supervision visit. Her mother has no concerns regarding her
daughter’s development. Her growth parameters are at the 25th percentile. She walks well, climbs onto her
mother’s lap, and whispers a few words to her mother. The best next step in the evaluation of this child’s
development is:
A. Full developmental surveillance.
B. Further evaluation of language skills.
C. Implementation of a developmental screening tool.
D. Review of developmental milestones with the mother.
E. Scheduling of a visit for full developmental assessment.
2. A 6-month-old infant is unable to roll from back to front or bring hands to midline. The most likely cause
of this infant’s difficulty is:
A. Absence of lateral protection postural reaction.
B. Absence of protective extension reaction.
C. Persistence of asymmetric tonic neck reflex.
D. Persistence of Moro reflex.
E. Persistence of positive support reflex.
3. A 15-month-old typically developing girl is able to release cubes into a cup and has a mature fine pincer
grasp. She most likely also is able to:
A. Build a tower of three blocks.
B. Copy a vertical line.
C. Feed herself with a spoon and fork.
D. Put on her shoes.
E. Turn a doorknob.
4. An 18-month-old typically developing boy can walk well and run. He most likely also is able to:
A. Jump with two feet off the ground.
B. Kick a ball.
C. Pedal a tricycle.
D. Stoop and pick up a toy.
E. Toe-walk.

R. Jason Gerber, Timothy Wilks and Christine Erdie-Lalena
Pediatr. Rev. 2010;31;267-277
DOI: 10.1542/pir.31-7-267


Jonathan W. Mink and Samuel H. Zinner
Pediatr. Rev. 2010;31;287-295
DOI: 10.1542/pir.31-7-287

Article neurology
Movement Disorders II:

Chorea, Dystonia, Myoclonus, and Tremor
Jonathan W. Mink, MD,
PhD,* Samuel H. Zinner,
MD† 1. Identify the important distinguishing features of chorea, dystonia, myoclonus, and
tremor.
2. Recognize important causes of chorea, dystonia, myoclonus, and tremor.
Author Disclosure 3. Describe treatment approaches for chorea, dystonia, myoclonus, and tremor.
Drs Mink and Zinner 4. Discuss common drug-induced movement disorders and their treatments.
have disclosed no
financial relationships
relevant to this
Introduction
In a previous article, (1) we considered the two most common movement disorders in
article. This
children: tics and stereotypies. Although less common, chorea, dystonia, myoclonus, and
commentary does not tremor are not rare in children. Therefore, it is important for the pediatric clinician to be
contain a discussion able to recognize and distinguish these movement disorders. The first step in diagnosis and
of an unapproved/ treatment is to identify and classify the disorders. In this article, we review these and
investigative use of a drug-induced movement disorders. Drug-induced movement disorders fall into the same
phenomenologic categories (chorea, dystonia, myoclonus, and tremor) but often are
commercial product/
considered as a separate entity because of their specific causes and treatments.
device.
Chorea
Definitions
Chorea is characterized by frequent, brief, unpredictable, purposeless movements that
tend to flow from body part to body part chaotically and unpredictably. The movements
are less sustained than those of dystonia but are more sustained and less “shocklike” than
myoclonus. Low-amplitude chorea may cause an individual to appear fidgety. Large-
amplitude chorea, sometimes termed “ballismus,” can occur as dramatic flinging limb
movements. Choreic movements (ie, characterized by chorea) can be sudden and jerky or
can be more continuous and flowing. In the latter case, the term choreoathetosis is used.
The term “choreiform” often is used to describe the minimal
twitching or “piano playing” movements seen in many other-
wise healthy young children when their arms are extended
Abbreviations during the neurologic examination. The difference between
ARF: acute rheumatic fever “choreic” and “choreiform” in clinical usage is based on am-
ASO: antistreptolysin O plitude differences only and not on other characteristics of the
CSF: cerebrospinal fluid movements. We prefer not to use the term “choreiform” but
DRD: dopa-responsive dystonia rather the more inclusive term “minimal chorea.” (For exam-
GABHS: group A beta-hemolytic Streptococcus ples of chorea, view the first three video segments in the data
GTPCH: guanosine 5⬘-triphosphate cyclohydrolase supplement.)
MERRF: myoclonic epilepsy and ragged-red fiber
disease Causes
NMS: neuroleptic malignant syndrome Chorea can be classified by cause into primary and secondary
SC: Sydenham chorea disorders. Primary chorea is uncommon in childhood. Primary
SLE: systemic lupus erythematosus causes include benign familial (hereditary) chorea and Hun-
TD: tardive dyskinesia tington disease. However, Huntington disease rarely presents
TH: tyrosine hydroxylase in childhood with chorea; juvenile-onset Huntington disease
usually is characterized by parkinsonism and dystonia. Most
*Professor of Neurology, Neurobiology & Anatomy, Brain & Cognitive Sciences, and Pediatrics; Chief, Child Neurology,
University of Rochester School of Medicine and Dentistry and Golisano Children’s Hospital at Strong, Rochester, NY.
†
Associate Professor of Pediatrics, University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, Wash.

neurology movement disorders
chorea in childhood is due to other disorders. More than

100 causes of secondary chorea have been identified, but Causes of Secondary
Table 1.
in most of those disorders, chorea is not the only sign or
symptom. The most common cause of secondary chorea
Chorea
in childhood is acute rheumatic fever (ARF). Other Metabolic
important causes include systemic lupus erythematosus
● Hypo/hypernatremia
(SLE), cardiac surgery (“post-pump chorea”), and peri- ● Hypo/hyperglycemia
natal hypoxia-ischemia. A more extensive list of causes is ● Hypocalcemia
shown in Table 1. A diagnostic strategy based on the ● Hyperthyroidism
more likely causes, with an emphasis on treatable causes, ● Wilson disease
is shown in Table 2. Perinatal Hypoxia-Ischemia
Sydenham Chorea (Rheumatic Chorea) Paraneoplastic

Chorea is one of the major Jones criteria for the diagnosis
Infectious/Postinfectious
of ARF. The presence of chorea without any other crite-
● Epstein-Barr virus infection
ria is sufficient to make the diagnosis of ARF. Although it
● Human immunodeficiency virus infection
is widely accepted that chorea can follow group A beta- ● Acute rheumatic fever
hemolytic Streptococcus (GABHS) infection, it often is ● Viral encephalitis
hard to demonstrate the antecedent infection. Depend-
Chorea gravidarum
ing on the series, 10% to 40% of children who have ARF
have chorea. Sydenham chorea (SC) is most common in Cardiac Surgery (“post-pump chorea”)
children 5 to 15 years old. There is a 2:1 female predom-
inance after age 10 years. SC begins several weeks to Psychogenic
several months after a GABHS infection. The onset of
Vascular
symptoms usually is insidious, with gradually progressive
clumsiness and behavior change, usually including emo- ● Antiphospholipid antibody syndrome
● Stroke
tional lability. After a week or more, choreic movements
● Global hypoxia
become more obvious and typically become generalized. ● Moyamoya syndrome
The chorea usually is asymmetric and, in rare cases, can ● Systemic lupus erythematosus
be unilateral. The chorea commonly is accompanied by
Toxins
hypotonia and dysarthria. Classically described findings
● Manganese
also include the “spooning sign” caused by hyperexten-
● Methanol
sion at the metacarpophalangeal joints; the “milkmaid’s ● Carbon monoxide
grasp,” a sign of chorea that is detected by having the
patient squeeze the examiner’s fingers in a sustained Heredodegenerative disease
manner, due to choreic intrusions and motor impersis- ● Ataxia telangiectasia
● Niemann-Pick disease type C
tence (ie, inability to maintain a posture), which are felt
● Gangliosidoses
by the examiner as continuous fluctuation of the grasp; ● Lesch-Nyhan disease
and the “darting tongue,” due to choreic movements of
the tongue and motor impersistence. Some children also
display “hung-up” tendon jerk reflexes (ie, brisk reflex
followed by a slowed return to the neutral position). The diagnosis of SC is based on clinical history and
Behavioral changes may be striking and include im- physical examination findings but can be supported by
pulsivity, aggression, and obsessive-compulsive behav- laboratory data. However, laboratory data should not be
iors. The natural history of SC is weeks to months of a viewed as confirmatory. Most children who have SC have
waxing and waning course, with ultimate resolution of positive serology (antistreptolysin O [ASO] and anti-
the chorea. Some individuals have behavioral changes DNase B antibodies) for GABHS, but more than 25% are
that persist for months. Chorea relapse can occur with or serologically negative. Conversely, ASO titers can be
without subsequent GABHS infection, and increased elevated in children who do not have ARF. There is no
risk of relapse is associated with pregnancy (chorea gravi- correlation between titers and the severity of the chorea.
darum) and oral contraceptives. Most children who develop SC have negative throat

effects than phenothiazines or butyrophenones. Benzo-

Diagnostic Testing in
Table 2. diazepines also may be beneficial. Symptomatic treat-
ment for 2 to 4 months generally is sufficient. There have
Chorea been no controlled studies of long-term outcomes of
● Throat culture these treatments compared with placebo.
● Antistreptolysin O titer (ASO) Based on the pathophysiology of SC, it is reasonable
● AntiDNase B titer to consider using immune-modulating therapies to
● Electrocardiography shorten the course of illness. According to one random-
● Echocardiography
ized, blinded, placebo-controlled study, (3) a 4-week
● Thyroid function tests
● Complete blood count course of oral prednisone (2 mg/kg daily) followed by a
● Antinuclear antibody taper reduced the duration of chorea and accelerated the
● Erythrocyte sedimentation rate reduction in symptoms. Weight gain was substantial by
● Magnetic resonance imaging of brain the end of 2 months, and long-term outcome, including
● Serum ceruloplasmin concentration
recurrence rates, was not different between groups.
● Antiphospholipid/anticardiolipin antibodies
● Urine drug screen Other studies have been less conclusive. Because long-
● Urine human chorionic gonadotropin concentration term outcome appears to be no different whether or not
Other testing for rare diseases is based on the presence of other
patients are treated with steroid medications, this treat-
symptoms and clinical suspicion. If results of the listed tests are normal, ment should be reserved for those who have severe
referral to a neurologist is recommended.
chorea unresponsive to symptomatic treatment.
Chorea in Systemic Lupus Erythematosus

cultures for GABHS, but a positive culture result requires Chorea is an uncommon manifestation of SLE but can be
acute treatment. Magnetic resonance imaging scans may the presenting symptom. When chorea is the sole mani-
show signal abnormalities in the basal ganglia, but no festation of SLE, it can remain so for years. Although
sensitive or specific diagnostic tests for SC exist. The fewer than 10% of children who have SLE have chorea,
presence of carditis or other manifestations of ARF sup- about 50% of individuals who have chorea due to SLE are
ports the diagnosis of SC. Every child believed to have younger than 16 years of age. The presence of neurologic
SC should have an evaluation for rheumatic heart disease. manifestations such as chorea in SLE conveys a less
Depending on the series, 40% to 75% of children who favorable prognosis. The diagnosis and treatment of SLE
develop SC have carditis. Arthritis is less common. is beyond the scope of this review. When chorea is due to
Treatment of SC consists of secondary prevention, SLE, treatment of the underlying SLE is indicated. Ad-
symptomatic treatment of chorea, and immune modula- ditional symptomatic treatment of the chorea may be
tion. All children diagnosed as having SC, even in cases of indicated if it is bothersome. Haloperidol has been re-
isolated chorea, should be treated with penicillin, accord- ported to be effective for SLE chorea, but the other
ing to American Academy of Pediatrics guidelines. (2) previously described treatments described for SC also
An appropriate alternative may be selected for children may be effective.
who have penicillin allergies. Penicillin or an acceptable
alternative is effective as secondary prevention of recur- Dystonia
rent chorea but more importantly, reduces the likelihood Definitions
that future GABHS infections will cause carditis and Dystonia is a syndrome of sustained muscle contractions,
permanent valvular damage. Current recommendations frequently causing twisting and repetitive movements or
in the United States are for treatment until age 21 years, abnormal postures. There are several classification
regardless of the age of onset of the chorea. schemes for dystonia, based on age of onset, cause, or
Symptomatic treatment of SC depends on the impair- body part affected (Table 3). Primary dystonias are those
ment or disability associated with the chorea. In many disorders in which dystonia is either the only feature or
cases, the chorea causes only mild disability, and symp- the primary feature, and the cause either is a specific
tomatic treatment is not required because SC usually is genetic mutation or is unknown. Secondary dystonias are
self-limited. When symptomatic treatment is desired, those disorders in which the dystonia is due to another
referral to a neurologist is recommended. Antiepileptic identifiable cause.
medications such as carbamazepine or valproate can be Focal dystonia occurs when only a single body part is
effective and usually are associated with fewer adverse affected. Almost any part of the body can be affected.

review. The two most important types of primary dysto-

Table 3. Classification of Dystonia nia in children are dopa-responsive dystonia (DRD) and
idiopathic torsion dystonia associated with the DYT1
Age of Onset mutation. Other important causes of secondary dystonia
● Childhood in children are listed in Table 4.
● Adulthood
Cause Dopa-responsive Dystonia
● Primary (Idiopathic)
DRD is a syndrome characterized by childhood onset
● Secondary and progressive dystonia that has a sustained dramatic
response to low doses of levodopa. DRD also is known
Somatic Distribution
as hereditary progressive dystonia with diurnal fluctua-
● Segmental tions or Segawa syndrome. DRD typically presents with
● Multifocal
a gait disturbance due to foot dystonia starting be-
● Hemi
● Generalized tween 1 and 12 years of age. In untreated older chil-
dren, diurnal fluctuation develops, with worsening of
symptoms toward the end of the day and marked im-
Examples of focal dystonia include torticollis and writer’s provement in the morning. Such diurnal fluctuation
cramp. Segmental dystonia refers to involvement of two usually is not apparent in younger children. In late ado-
or more adjacent body parts; multifocal dystonia de- lescence or early adulthood, features of parkinsonism can
scribes involvement of multiple nonadjacent body parts. develop.
Hemidystonia affects only one side of the body, and There are two major forms of DRD: a more common
generalized dystonia involves the entire body. Note that autosomal dominant form due to deficiency of guano-
these classification schemes overlap. Childhood onset sine 5⬘-triphosphate (GTP) cyclohydrolase (GTPCH)
of primary generalized dystonia typically starts in an
extremity and commonly progresses to generalized in-
volvement with involuntary twisting of nearly all parts of
the body. Causes of Secondary
Table 4.
Clinical Features
Dystonia in Children
Dystonia has several characteristic clinical features. Dys- Heredodegenerative Disorders
tonia commonly is triggered or exacerbated by at- ● Ataxia telangiectasia
tempted voluntary movement and may fluctuate in oc- ● Gangliosidoses
currence and severity over time. Dystonic contractions ● Glutaric aciduria
resolve during sleep. The dystonic posturing may occur ● Huntington disease
● Lesch-Nyhan disease
only with selected movements and paradoxically not with
● Metachromatic leukodystrophy
others that may use the same muscles. For example, ● Methylmalonic acidemia
walking forward may elicit severe lower extremity and ● Mitochondrial disorders
truncal twisting, yet walking backward, running, or ● Niemann-Pick disease type C
swimming may be completely normal. Individuals who ● Pantothenate kinase-associated neurodegeneration
have dystonia often find that touching one part of the (PKAN)*
● Wilson disease
body may relieve the dystonic spasms; this phenomenon
is called a sensory trick or geste antagoniste. For example, Drugs/Toxins (see Table 6)
rubbing the back of the hand may diminish hand dysto-
Psychogenic
nia. (For an example of a patient who demonstrates
dystonia, view the fourth segment of the video in the data Structural Brain Lesions
supplement.)
● Acute disseminated encephalomyelitis
● Perinatal hypoxia-ischemia
Causes ● Stroke
Historically, dystonia has been divided into primary ● Tumor
(idiopathic) and secondary causes. A full discussion of the *Also known as Hallervorden-Spatz syndrome.
many causes of dystonia is beyond the scope of this

and a relatively uncommon autosomal recessive form anticholinergic medication trihexyphenidyl has been
caused by a deficiency in tyrosine hydroxylase (TH). used with success in some patients who have dystonia.
Both forms produce dopamine deficiency without loss of Some patients who were believed to have idiopathic
nigrostriatal dopamine neurons. A few clinical differ- torsion dystonia and had a dramatic response to anti-
ences may help distinguish TH deficiency from GTPCH cholinergic medication have been shown to have DRD
deficiency, but these are neither sensitive nor specific. due to GTPCH deficiency. Thus, dramatic response
DRD due to TH deficiency can be distinguished from to trihexyphenidyl should suggest the possibility of DRD.
DRD due to GTPCH deficiency by measuring cerebro- If benefit is inadequate from levodopa or trihexy-
spinal fluid (CSF) catecholamines, their metabolites, and phenidyl, baclofen alone or in combination with trihexy-
pterins. In practice, diagnosing DRD by its exquisite phenidyl may be beneficial. Intrathecal baclofen has been
response to levodopa typically is sufficient. In some cases, found to be effective in treating dystonia due to cerebral
a specific diagnosis is required, either for the purpose of palsy, but adverse effects are frequent and can be serious.
genetic counseling or, in atypical cases, warranting CSF For that reason, we recommend an adequate trial of oral
investigations or genetic testing. baclofen before considering intrathecal baclofen. Benzo-
It is important to recognize the entity of DRD be- diazepines also may be beneficial, but often the benefit is
cause it responds dramatically to low doses of levo- limited by adverse effects or tolerance.
dopa. DRD has been misdiagnosed as cerebral palsy, If oral medications are ineffective, botulinum toxin
particularly spastic diplegia. Therefore, it is important injections may be highly effective, especially if im-
to develop suspicion for DRD in children who have pairment or disability is attributable to a few muscle
motor impairment, prominent dystonia, and a slowly groups. Deep brain stimulation of the medial globus
progressive rather than static course. With appropriate pallidus has been used with increasing success for a select
diagnosis and treatment, affected children can lead group of patients who have dystonia and may be the most
normal lives. effective treatment for dystonia due to the DYT1 muta-
tion. Because of the broad differential diagnosis of dys-
Idiopathic Generalized Torsion Dystonia (DYT1) tonia and the complexities of treatment, we recommend
Childhood-onset idiopathic torsion dystonia, formerly that any patient who has dystonia be evaluated by a
known as dystonia musculorum deformans, is an auto- neurologist.
somal dominant condition with incomplete (30%) pen-
etrance. Genetic studies have found that a GAG de- Myoclonus
letion at the DYT1 locus on chromosome 9 causes most Myoclonus is characterized by brief, abrupt, involuntary,
cases of autosomal dominant, early-onset, primary gen- nonsuppressible, jerky contractions involving a single
eralized dystonia affecting Ashkenazi Jewish families muscle or muscle group. The rapidity of the movements
(90%) and non-Jews (50% to 60%). In childhood-onset warrants the descriptor “shocklike” or “lightning-fast,”
idiopathic torsion dystonia, symptoms usually begin in as if an electrical shock had just been applied to the
a limb at a mean age of 12.5 years. Onset typically is peripheral nerve innervating the muscle. Myoclonus can
before 28 years of age but seldom before age 6 years. The be rhythmic, in which case it often appears tremor-like.
legs generally are affected before the arms, and symp- However, in true tremor, the movement oscillates with
toms usually become generalized within 5 years. Diag- near-equal amplitude around a midpoint; in myoclonus,
nosis is based on identifying a GAG deletion in the DYT1 the movement has a more “sawtooth” character. In some
gene; genetic testing is available commercially. cases, myoclonus can be elicited by a sensory stimulus
(reflex myoclonus, with the most famous example being
Treatment the acoustic startle response in infancy) or volitional
Treatment of most types of dystonia can be difficult, movement (action myoclonus). Myoclonus can be focal,
and often the response is incomplete. The clear excep- multifocal, segmental, or generalized. Occasional myo-
tion is DRD, which responds dramatically to low doses clonus is seen as a sudden muscle relaxation rather than
of levodopa. For this reason, a trial of levodopa with active contraction. In the case of sudden relaxation caus-
carbidopa is recommended for all children who have ing a visible jerk, the term “negative myoclonus” has
primary dystonia. Because some secondary dystonias also been used. (For an example of a baby who demonstrates
may respond to levodopa, a trial of levodopa is recom- myoclonus, view the fifth segment of the video in the
mended for any child in whom dystonia is a prominent data supplement.)
component of his or her neurologic syndrome. The The causes of myoclonus are numerous. A first step in

classifying myoclonic disorders is to determine if the anticonvulsant medications such as valproate, levetira-
myoclonus is epileptic. Electroencephalography is the most cetam, or clonazepam. Given the complex differential
useful tool in making this distinction. Myoclonus can be the diagnosis associated with myoclonus, we recommend
manifestation of epileptic neurodegenerative diseases such that any affected pediatric patient be evaluated by a
as progressive myoclonic epilepsy, Lafora body disease, and pediatric neurologist.
neuronal ceroid lipofuscinosis, as well as mitochondrial
diseases such as myoclonic epilepsy and ragged-red fiber Tremor
disease (MERRF). A full discussion of epileptic myoclonus Tremor is a rhythmic oscillation about a central point or
is beyond the scope of this review. position involving one or more body parts. Tremor in
Important causes of nonepileptic myoclonus are listed childhood is not rare, but few epidemiologic data are
in Table 5. The location and quality of myoclonic move- available to indicate the incidence or prevalence. Tremor
ments can be helpful in determining cause. For example, is classified by when it occurs: with rest, intention, or action.
segmental myoclonus of thoracic muscles suggests spinal Rest tremor is defined as tremor involving a body part that
cord pathology, whereas segmental myoclonus of palatal is inactive and supported against gravity. Rest tremor is
muscles suggests a brainstem lesion or Whipple disease. associated most commonly with other signs of parkinson-
Asterixis, a form of negative myoclonus, suggests meta- ism but may occur in isolation. In children, the most com-
bolic encephalopathy. Myoclonus in the setting of opso- mon cause of rest tremor is antipsychotic (neuroleptic)
clonus or ataxia suggests paraneoplastic syndrome (eg, medications. Intention tremor occurs as a moving body
neuroblastoma) or a peri-infectious autoimmune pro- part approaches a target. Intention tremor usually is associ-
cess. Alternatively, myoclonus can be a manifestation of ated with other signs of cerebellar dysfunction. Action
neurodegenerative processes such as lysosomal storage tremor occurs during maintained posture, voluntary move-
diseases, Wilson disease, or Huntington disease. Diffuse ment, or both. In evaluating the child who has tremor,
central nervous system injury from virtually any cause attention should be paid to possible other neurologic signs
(toxic, infectious, metabolic, hypoxic) can result in or symptoms. When present, such features usually direct the
myoclonus. Essential myoclonus (ie, myoclonus of un- diagnostic evaluation. When tremor is the only abnormal-
determined cause) typically is a diagnosis of exclusion. ity, it is important to identify potential tremor-enhancing
Myoclonus, even nonepileptic forms, may respond to medications. The primary laboratory tests to be considered
are thyroid function tests.
The most important childhood tremors are action trem-
ors and include physiologic tremor and essential (familial)
Causes of Nonepileptic
Table 5. tremor. Physiologic tremor is a normal phenomenon, con-
Myoclonus sisting of a 6 to 12-Hz oscillation that usually is noticed by
the individual or other observers only under certain condi-
Physiologic tions. A few individuals have a more easily noticed physio-
● Hiccups logic tremor that is termed “enhanced physiologic tremor.”
● Hypnic jerks (sleep starts) Such individuals otherwise are indistinguishable from those
● Nocturnal myoclonus who have no enhanced physiologic tremor. Physiologic
Essential tremor may increase with anxiety, excitement, fear, or cer-
tain medications. These medications include sodium val-
Developmental proate, theophylline, beta-agonists, corticosteroids, and
stimulants. The tremor of hyperthyroidism is an enhanced
Psychogenic
physiologic tremor.
Symptomatic Essential tremor often is considered a disorder of adults
but can begin in infancy or childhood. Essential tremor is
● Storage diseases
● Basal ganglia degenerations the most common movement disorder in adults, but it
● Dementias appears to be less common in children. Essential tremor is
● Infections present with posture and with action but usually is greatest
● Metabolic conditions with maintained posture. The tremor typically involves the
● Toxic
upper extremities but may involve the head and neck, voice,
● Hypoxia
● Focal damage and legs. By definition, essential tremor is unaccompanied
by other neurologic abnormalities, although individuals

may have slight clumsiness. Essential tremor is “familial” common in childhood. The dyskinesia can manifest as
(autosomal dominant) in about 60% of cases. There have any of the hyperkinetic movement disorders. TD typi-
been no studies of treating essential tremor in children, but cally manifests as an oro-buccal-lingual stereotypy, but it
experience has shown that children respond to the same can involve other body parts. The risk of TD increases
medications that are effective in adults. The most effective with total dose and treatment duration of antipsychotic
medications are propranolol (or other beta blockers) and medication and with age of the patient. There is some
primidone. Clonazepam may be effective in some cases. evidence that children who have suffered previous brain
Children should be referred to a neurologist for diagnosis injuries are more likely to develop TD.
and treatment of essential tremor. Extrapyramidal effects such as acute dystonic reaction,
parkinsonism, and TD are substantially more likely to
Drug-induced Movement Disorders occur with the older, so-called “typical” neuroleptic
The phenomenologic classification of drug-induced medications such as haloperidol and pimozide and other
movement disorders is the same as for nondrug-induced dopamine-blocking agents such as metoclopramide and
disorders. However, because medications are a relatively prochlorperazine. Atypical neuroleptic medications, such
common cause of movement disorders in children, they as risperidone, quetiapine, olanzapine, and ziprasidone,
deserve special consideration. Perhaps the best known have a demonstrably lower incidence of such extra-
drug-induced movement disorders are those associated pyramidal effects, but such adverse effects can occur.
with antipsychotic (neuroleptic) treatment. These med- Treatment of TD can be difficult and requires referral to
ications are dopamine receptor antagonists and cause a neurologist or psychiatrist experienced in its treatment.
both acute and tardive (ie, “late”) syndromes. The acute Prevention of TD requires care in avoiding indiscrimi-
adverse effects of dopamine antagonists include parkin- nate use of antipsychotic medications, limiting duration
sonism and acute dystonic reactions. Acute dystonic re- of treatment, and minimizing total daily dose.
actions can occur even after a single dose of a dopamine Many other medications have been associated with
antagonist. The typical acute dystonic reaction involves movement disorders. The more common ones are sum-
involuntary gaze deviation (oculogyric crisis), torticollis, marized in Table 6. The treatment of drug-induced
and appendicular twisting postures associated with axial movement disorders is to eliminate the offending agent
more than appendicular muscles. The reaction can last whenever possible. In most cases, it does not make sense
for hours but is readily treated with
anticholinergic medications such as Table 6. Common Drug-induced Movement
diphenhydramine (1 mg/kg per
dose every 6 hours) or benztropine Disorders
(0.5 to 2 mg daily or twice a day).
Medications* Reaction
The most severe reaction to do-
pamine antagonists is the neuro- Dopamine antagonists (antipsychotics) Acute dystonic reaction
leptic malignant syndrome (NMS), ● Haloperidol Tardive dyskinesia
● Pimozide Withdrawal dyskinesia
which is characterized by hyperther-
● Chlorpromazine Parkinsonism
mia, hypertonia, dystonic postur- ● Metoclopramide Neuroleptic malignant syndrome
ing, tremor, and autonomic insta- ● Prochlorperazine
bility. NMS can be fatal. Children ● Risperidone
suspected of having NMS should Antiepileptic agents Chorea
● Phenytoin Dystonia
be evaluated promptly by a neu-
● Carbamazepine Tremor
rologist. Treatment primarily is ● Sodium valproate
supportive and consists of control- Beta-adrenergic agonists Tremor
ling fever and correcting metabolic ● Albuterol
abnormalities. Dantrolene should ● Metaproterenol
Amphetamines Chorea
be given to diminish excessive mus-
Tremor
cle contraction. Dopamine agonists Cocaine Chorea
such as bromocriptine may be ef- Lithium Chorea
fective. Neuroleptic medications Tremor
should be discontinued. *Common examples are listed, but the list is not intended to be comprehensive.
Tardive dyskinesia (TD) is un-

to administer another medication to treat adverse effects References

from the drug causing a movement disorder. 1. Zinner SH, Mink JW. Movement disorders, Part I: tics and
stereotypies. Pediatr Rev. 2010;31:223–233
2. American Academy of Pediatrics. Group A streptococcal infec-
Summary tions. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds.
Red Book: 2009 Report of the Committee on Infectious Diseases. 28th
• Movement disorders in children can be complex. ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2009:
Identification of the specific type of abnormal 616 – 628
movement based on the spatial-temporal features is 3. Paz JA, Silva CA, Marques-Dias MJ. Randomized double-blind
the essential first step toward diagnosis. study with prednisone in Sydenham’s chorea. Pediatr Neurol. 2006;
• Specific diagnosis of these disorders usually requires 34:264 –269
evaluation and treatment by a neurologist.
• In most cases, treatment is symptomatic and
depends on the specific movement disorder.
• Most treatment recommendations for the pediatric
movement disorders discussed in this review are Suggested Reading
based on expert consensus and extrapolation from Fahn S, Jankovic J. Principles and Practice of Movement Disorders.
studies in adults who have comparable movement New York, NY: Churchill Livingston; 2007
disorders. Fernandez-Alvarez E, Aicardi J. Movement Disorders in Children.
London, United Kingdom: MacKeith Press; 2001

PIR Quiz
Quiz also available online at http://pedsinreview.aappublications.org.
9. You are evaluating a 10-year-old girl who had a group A beta-hemolytic streptococcal infection 1 month
ago. Among the following, the finding most consistent with a diagnosis of Sydenham chorea is:
A. Asymmetric chaotic-appearing involuntary movements.
B. Catatonia.
C. Diminished deep tendon reflexes.
D. Hypertonia and dysphagia.
E. Muscle fasciculations
10. You are asked to evaluate a 12-year-old boy who has an acute dystonic reaction. He has a longstanding
history of gastroesophageal reflux disease. Among the following, the drug most likely to cause his
dystonia is:
A. Aluminum-magnesium hydroxide.
B. Famotidine.
C. Metoclopramide.
D. Omeprazole.
E. Sucralfate.
11. A father brings his 9-year-old son to your clinic for evaluation of a bilateral tremor. The child has a
history of epilepsy. Among the following, the drug most likely to be responsible for the tremor is:
A. Carbamazepine.
B. Clonazepam.
C. Levetiracetam.
D. Primidone.
E. Valproate.
12. A mother brings her 16-year-old daughter to you because every morning upon waking the girl
unexpectedly tosses her toothbrush or a teacup. You worry that these shocklike movements represent
myoclonus. Of the following, the most appropriate first step to evaluate this girl is:
A. Antistreptolysin O titer.
B. Electroencephalography.
C. Psychiatry consultation.
D. Serum lactate measurement.
E. Urine toxicology screen.
13. A mother brings her 13-year-old son to your clinic because he refuses to handwrite his high school
assignments, insisting upon using a computer. He complains that his hand goes into a twisted, abnormal
posture when he writes. There are no abnormal movements in other parts of his body. Among the
following, the most likely diagnosis is:
A. Attention-deficit/hyperactivity disorder.
B. Dopa-responsive dystonia.
C. Learning disability.
D. Physiologic tremor.
E. Writer’s cramp.

Jonathan W. Mink and Samuel H. Zinner
Pediatr. Rev. 2010;31;287-295
DOI: 10.1542/pir.31-7-287


Research and Statistics: Strengths and Limitations of Randomized, Controlled
Trials
Erica M.S. Sibinga and Jacky M. Jennings
Pediatr. Rev. 2010;31;296-297
DOI: 10.1542/pir.31-7-296

research and statistics
Strengths and Limitations of

Randomized, Controlled Trials
Erica M.S. Sibinga, MD, MHS,* Jacky M. Jennings, PhD, MPH*
Case Study results are widely viewed as the stron-

The father of a 3-year-old boy, who has gest form of research evidence. The
just started preschool, brings the boy to strength of this study design comes
your office for “his fourth cold in a from: 1) the study participants being
row.” The boy was back to his baseline randomly assigned to the study con-
last week but now has congestion and dition (experimental or control) and
rhinorrhea. On physical examination, 2) a control arm being present,
he is afebrile and has no signs of otitis against which to compare the effects
media or lower respiratory tract in- seen in the experimental arm. RCTs
volvement. His father expresses frus- are used most often to compare new
tration with these frequent illnesses treatments or approaches (in this
Author Disclosure
and asks if there is something else he case, probiotics) with current treat-
Drs Sibinga and Jennings have can do. As a general pediatrician, you ment (in this case, approximated by
disclosed no financial relationships often are confronted with this clinical placebo). In an RCT, the study pop-
relevant to this article. This scenario. You recall a recent study of ulation is carefully determined before
commentary does not contain a probiotics for the prevention of colds beginning the study (in this case,
discussion of an unapproved/ and influenza-like illnesses and re- healthy children 3 to 5 years of age in
view it more carefully. a child care center in China), study
investigative use of a commercial
Leyer and associates (1) conducted participants are assigned randomly to
product/device. a prospective, randomized, double- either the experimental group(s) or
blind, placebo-controlled study of 326 the control group (probiotic I, pro-
children, in which 3- to 5-year-old biotic II, or placebo), and partici-
children received one of three products pants receive either the experimental
for 6 months. Probiotic I consisted of or control treatment according to
one strain of probiotic, probiotic II group assignment during the study
consisted of two strains of probiotic, period.
and a placebo preparation contained Unlike other study designs, par-
no probiotics. The investigators found ticipants from a single subject pool
that compared with placebo, both pro- are assigned randomly to their study
biotic groups had reductions in fever, condition, which should lead to a
coughing, rhinorrhea, antibiotic use, balance of baseline confounders
and missed school days due to illness. (known and unknown subject differ-
You are excited to tell this frustrated ences relevant to the outcome of in-
father about probiotics but pause to terest) across the experimental and
reflect on how best to apply the results of control arms. If randomization is
this study specifically to his son. successful and the groups are bal-
anced at baseline, the researcher can
Randomized, Controlled Trials conclude that differences between
Randomized, controlled trials (RCTs) the experimental and control groups
are considered the “gold standard” at the end of the study are due to the
among research designs, and their experimental treatment itself. In the
case of the Leyer study, the random-
ization was not entirely balanced; the
*Assistant Professor of Pediatrics, Division of
General Pediatrics & Adolescent Medicine, Johns placebo group had an older average
Hopkins University, Baltimore, Md. age, which may have been the result

research and statistics
of the modest sample size. To ac- ence). For example, the probiotics intervention/control, those collect-
count for the age imbalance between study was conducted in China, and it ing data, data analysts), primary and
groups at baseline, age was adjusted is important to consider if the loca- secondary outcomes, and numbers
for in subsequent analyses. Such is- tion introduced relevant systematic analyzed. As seen in the Leyer study,
sues highlight the complexity of con- biases. the broad use of the CONSORT
ducting RCTs, despite high levels of Finally, what element of the in- guidelines can facilitate readers’ abil-
rigor. Compared with other study tervention is controlled for by the ity to interpret RCT results appropri-
designs, RCTs tend to be more time- control group? Ideally, the control ately for their needs.
consuming and expensive. group experiences what are believed
to be the nonspecific aspects of the
Interpreting Results intervention (eg, the benefits of Conclusion
Despite the strengths of the RCT getting a placebo), and the experi- After careful consideration of the
design, a few important consider- mental group experiences the non- Leyer study with these issues in mind,
ations should be kept in mind when specific (eg, the benefits of the pla- you feel comfortable assessing the
interpreting results from or design- cebo) plus the specific aspects (the strengths and weaknesses of RCT and
ing RCTs. First, not all research benefits of the active ingredient). If discussing the use of probiotics for the
questions can be answered with an the control group effectively controls prevention of upper respiratory tract
RCT. For example, recruiting par- for the nonspecific effects, differ- symptoms with this father.
ticipants for an RCT may not be ences between groups can be attrib-
possible when studying very personal uted to the specific effect.
choices (eg, breastfeeding, corporal In an attempt to improve the
punishment, educational choices). transparency related to the reporting References
Further, unless both study arms are and interpretation of RCTs, the 1. Leyer GJ, Li S, Mubasher ME, Reifer C,
Ouwehand AC. Probiotic effects on cold
understood to be clinically equivalent CONSORT (Consolidated Standards
and influenza-like symptom incidence and
(state of equipoise), it may not be eth- of Reporting Trials) statement now is duration in children. Pediatrics. 2009;124:
ical to randomize treatments. (2) used widely to guide the publication e172– e179
Another important factor is how of RCTs. (3)(4) The central issues 2. Gordis L. Epidemiology. Philadelphia,
the study population compares with addressed by the CONSORT guide- Pa: Elsevier Saunders; 2004:140
the general population or with a par- lines include the requirement for 3. Altman DG, Schulz KF, Moher D, et al;
CONSORT GROUP (Consolidated Stan-
ticular population of interest. It is clear descriptions of: the study pop- dards of Reporting Trials). The revised
important to consider how restrictive ulation (inclusion and exclusion cri- CONSORT statement for reporting ran-
the eligibility criteria are, how the teria), participant flow (a diagram domized trials: explanation and elaboration.
study procedures themselves might tracking all participants is sug- Ann Intern Med. 2001;134:663– 694
exert a bias (are the study conditions gested), group treatment (for ex- 4. Altman DG; CONSORT Group. En-
dorsement of the CONSORT statement
unusually burdensome?), and how perimental and control groups), by high impact medical journals: survey of
participants move through the study randomization procedures, blinding instructions for authors. BMJ. 2005;330:
(eg, rates of dropout, nonadher- (participants, those administering 1056 –1057

Research and Statistics: Strengths and Limitations of Randomized, Controlled
Trials
Erica M.S. Sibinga and Jacky M. Jennings
Pediatr. Rev. 2010;31;296-297
DOI: 10.1542/pir.31-7-296


Visual Diagnosis: A Pimple-like Lesion on the Cheek of a 5-year-old Girl
Rayna M. Dyck and Dawn M. Davis
Pediatr. Rev. 2010;31;299-301
DOI: 10.1542/pir.31-7-299

visual diagnosis
A Pimple-like Lesion on the Cheek

of a 5-year-old Girl
Rayna M. Dyck,* Dawn M. Davis, MD†
Presentation
A healthy-appearing 5-year-old girl comes to the derma-
tology clinic for evaluation of a lesion on her face that has
been present for at least 3 years. The lesion started as a
pimple-like growth on her left superior cheek near the
lower eyelid, subsequently grew in size, but has been
stable in size for the past 1 to 2 years. The lesion is only
occasionally tender when bumped, but the patient and
parents report no precipitating trauma to the area. The
lesion previously was believed to be a wart and was
Figure 1. Clinical presentation of 6-mm pimple-like lesion
below the left eye. treated with imiquimod (a topical immune response
modifier used to treat superficial basal cell carcinoma,
actinic keratosis, and external genital and perianal warts),
but no significant change was seen after approximately
2 weeks of use. Later, a primary care physician applied
liquid nitrogen cryotherapy to the lesion, resulting in
only some superficial sloughing. The patient was seen by
another dermatologist, who again prescribed imiquimod
for the presumed wart, but the parents chose to get
another opinion.
The patient’s past medical and surgical history in-
cludes prior eustachian tube dysfunction requiring
pressure-equalization tubes and a severe reaction to
chickenpox requiring hospitalization. Her perinatal his-
tory is unremarkable. She is taking no medications.
Figure 2. Closer view of the raised, erythematous lesion. On physical examination, the lesion is a 6-mm, raised,
erythematous papule that is semifirm to palpation
(Figs. 1 and 2). No underlying dermal component is
appreciated; under epiluminescence microscopy (also
known as dermoscopy), the lesion appears to have prom-
Author Disclosure
inent vascularity. No other lesions are noted on the face,
neck, and scalp.
Ms Dyck and Dr Davis have disclosed no financial
Because of the location of the lesion on the face, the
relationships relevant to this case. This commentary does
patient is referred to the plastic surgery department for
not contain a discussion of an unapproved/investigative removal. The lesion is excised, and on the basis of patho-
use of a commercial product/device. logic findings, a diagnosis is suspected.
*Student, Mayo Medical School, Rochester, Minn.

†
Department of Dermatology, Mayo Clinic, Rochester, Minn.

visual diagnosis
Diagnosis: Malignant Melanoma Melan-A (also known as MART-1) is a protein antigen

(Spitzoid and Nodular Type) found on melanocytes, and although it is a useful marker
Histopathologic analysis showed a malignant melanoma for melanocytic tumors, it also can be found in benign
without ulceration, spitzoid type, and nodular type (Figs. nevi.
3 and 4). The tumor was Clark level IV and 2.6 mm in The tumor also was found to involve the lateral inked
Breslow thickness (T classification: T3a). Immunohisto- margins of the biopsy specimen. Therefore, a complete
chemical studies showed tumor cells that were S-100 re-excision of the lesion with clinically appropriate mar-
positive and weakly Melan-A-positive. An HMB-45 im- gins was recommended. Subsequently, the patient un-
munostain highlighted focal deep nodules of tumor cells, derwent whole body positron emission tomography,
and an MIB-1 immunostain highlighted increased pro- which showed no evidence of metastases. A wide local
liferative activity throughout the dermis within the ture-excision was performed as well as a sentinel lymph
mor cells. S-100 normally is found in cells derived from node biopsy. Pathologic and immunohistochemical anal-
the neural crest, such as melanocytes. HMB-45 is a ysis showed no residual melanoma and documented the
monoclonal antibody against an antigen present in mela- sentinel node to be negative for Melan-A, S-100 protein,
nocytic tumors. S-100 is highly sensitive for melanomas, and tyrosinase. Additional biopsies showed multiple
and HMB-45 is highly specific for these tumors. lymph nodes to be negative for tumor.
Discussion
The American Cancer Society reports that 59,940 new
cases of melanoma were reported in 2007, along with
8,110 deaths attributable to the disease. The Centers for
Disease Control and Prevention estimated the occur-
rence of 506 new cases of melanoma in the United States
in 2004 in persons ages 19 years and younger and 55 new
cases in children younger than 10 years of age (1).
Although pediatric melanoma may be rare, its incidence
has been reported to be increasing. In the United States,
the incidence of pediatric melanoma increased 46% per
Figure 3. Histopathologic sample of the lesion (hematoxylin- year of age and 2.9% per year from 1973 to 2001. (2)
eosin, original magnification ⴛ4), showing atypical melano- As in adult melanoma, most pediatric melanomas are
cytic nests. cutaneous, but they present differently in the pediatric
population. In 2005, one study showed that compared
with adult melanoma, pediatric melanomas have a higher
frequency of atypical features, thicker lesions at diagno-
sis, a higher proportion of the nodular histotype, and a
higher frequency of developing in particular sites. (3) In
children, as opposed to adults, there is a disproportionate
number of amelanocytic melanomas. Many childhood
melanomas have features of both nodular and amelano-
cytic melanomas. Many melanomas in children are mis-
diagnosed as pyogenic granulomas.
Risk factors for pediatric melanoma include white
race, female sex, increasing age, and environmental ultra-
violet (UV) exposure. Because the only modifiable risk
factor is UV exposure, it is important to educate parents
and younger patients about the importance of sun pro-
tection very early in life. Case-control studies of adults
Figure 4. Histopathologic sample of the lesion (hematoxylin- have shown that increased UV exposure (ie, blistering
eosin, original magnification ⴛ4), showing atypical melano- sunburns) confers a two- to fivefold increased risk of
cytic nests. Arrows point to blue-elled nodule, which is a melanoma.
nodular focus of the melanoma. Pediatric melanoma is difficult to diagnose, and diag-

visual diagnosis
nostic concordance is variable, even among dermato- Patient Course

pathologists. In this case of a patient who has a nodular The patient has fared well since excision of the mela-
melanoma, the differential diagnosis could include pig- noma, with no recurrence. A genetics evaluation deter-
mented lesions such as the common nevus, blue nevus, mined that although the family history is notable for a
pigmented Spitz nevus, and pigmented basal cell carci- melanoma in her paternal grandfather and Burkitt lym-
noma. The differential diagnosis also includes amelanotic phoma in her father, her tumor most likely was sporadic.
lesions such as basal cell carcinoma, hemangioma, pyo- She is being followed by the departments of dermatology
genic granuloma, and Merkel cell carcinoma. If the diag- and pediatric hematology/oncology via serial positron
nosis is questionable, a biopsy must be obtained. emission tomography scans.
When diagnosing pediatric melanoma, clinicians should
evaluate the lesion, employing the commonly used
ABCDE (asymmetry, border, color, diameter, and evo-
lution) criteria, just as in the adult population. Key
Summary
features are asymmetry of the lesion, irregularity of its • Although melanoma is rare in the pediatric
borders, and irregular distribution of color (or pigmen- population and its diagnosis remains difficult, the
tation) within the lesion. The size of the lesion also is possibility of this tumor cannot be ignored.
important. Although Spitz and other benign nevi tend Clinicians treating pediatric patients must recognize
when a skin lesion warrants biopsy instead of simply
to be regular-appearing and less than 1 cm in diameter, considering the questionable lesion to be refractory
melanomas tend to be larger and less uniform in clinical to treatment and deferring additional investigation.
appearance. It should be noted, however, that many • Future studies must address whether a more
melanomas may be small, so if other clinical character- specialized diagnostic and treatment approach to
istics of the lesion are of concern, melanoma should stay melanoma is necessary in the pediatric population.
• As in the adult population, early diagnosis is key,
in the differential diagnosis. The final key features are with the overall 5-year observed survival being
changes to any long-standing lesion. These changes strongly associated with initial summary stage.
could include an increase in size, a change in color or in
distribution of color, bleeding, inflammation, swelling,
or ulceration. When evaluating a suspicious lesion, clini- References
cians always should palpate for underlying masses and 1. U.S. Cancer Statistics Working Group. United States Cancer
examine for regional lymphadenopathy. Statistics: 2004 Incidence and Mortality. Atlanta, Ga: U.S. Depart-
Existing studies of pediatric melanoma have been few. ment of Health and Human Services, Centers for Disease Control
and Prevention and National Cancer Institute; 2007
Currently, the diagnosis and treatment of these tumors is
2. Strouse JJ, Fears TR, Tucker MA, Wayne AS. Pediatric mela-
the same as for adults. Surgery continues to be the noma: risk factor and survival analysis of the surveillance, epidemi-
mainstay of initial treatment, with sentinel lymph node ology and end results database. J Clin Oncol. 2005;23:4735– 4741
biopsy for lesions thicker than 1 mm. Positive sentinel 3. Ferrari A, Bono A, Baldi M, et al. Does melanoma behave
lymph nodes are found more often in patients younger differently in younger children than in adults? A retrospective study
of 33 cases of childhood melanoma from a single institution.
than 35 years of age, and that finding supports the
Pediatrics. 2005;115:649 – 654
recommendation that sentinel lymph node biopsy be
performed in patients in this age group, even if the tumor
is less than 1 mm thick. Sentinel lymph node biopsy is Suggested Reading
performed for purposes of prognostication; the proce- Barnhill RL, Flotte TJ, Fleischli M, Perez-Atayde A. Cutaneous
dure does not seem to offer any survival benefit, and it melanoma and atypical Spitz tumors in childhood. Cancer.
1995;76:1833–1845
remains a controversial technique. Adjuvant therapy
Ceballos PI, Ruiz-Maldonado R, Mihm MC Jr. Melanoma in
commonly is not used for those who have localized children. N Engl J Med. 1995;332:656 – 662
invasive or only regionally metastatic melanoma. The Lange JR, Palis BE, Chang DC, Soong SJ, Balch CM. Melanoma in
chemotherapeutic agents used to treat melanoma in- children and teenagers: an analysis of patients from the National
clude dacarbazine, cisplatin, vinblastine, carmustine, in- Cancer Data Base. J Clin Oncol. 2007;25:1363–1368
Paek SC, Sober AJ, Tsao H, Mihm MC Jr, Johnson TM. Cutaneous
terferon alpha, and tamoxifen. Chemotherapy rarely, if
melanoma. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA,
ever, results in a cure. Therefore, the best help for pa- Paller AS, Leffell DJ, eds. Fitzpatrick’s Dermatology in General
tients is prevention, early detection, and removal at an Medicine. 7th ed. Vol. 1. New York, NY: McGraw Hill; 2008:
early stage. 1134 –1157

Visual Diagnosis: A Pimple-like Lesion on the Cheek of a 5-year-old Girl
Rayna M. Dyck and Dawn M. Davis
Pediatr. Rev. 2010;31;299-301
DOI: 10.1542/pir.31-7-299


Pediatrics in the Community: A Little PUSH to Get the Advocacy Snowball
Rolling
Katherine R. Snyder
Pediatr. Rev. 2010;31;302
DOI: 10.1542/pir.31-7-302

pediatrics in the community
A Little PUSH to Get the Advocacy

Snowball Rolling
Pediatricians Urging Safety & Health impact of the project. This resident
(PUSH) is an advocacy group cre- went from being not so active to
ated in 2006 by Dr Josh Honaker, a being a dynamo in 1 year’s time after
former resident in pediatrics at the the encouragement from peers and
University of Louisville (http:// advisors.
Author Disclosure pushkentucky.org/home). Among Every residency class, at its incep-
Drs Snyder and Aligne have disclosed its successes, PUSH has helped to pass tion, has that handful of people who
no financial relationships relevant to the Graduated Driver License Bill, are natural champions for a cause.
this article. This commentary does Booster Seat Bill, and Shaken Baby Bill Focusing on the development and
not contain a discussion of an
in the state legislature while also work- success of those people creates mo-
ing at a community level. PUSH has mentum, which brings others into
unapproved/investigative use of a
sparked interest in advocacy among the group naturally. They see the
commercial product/device. residents, faculty, and the community. successes of other residents and start
Phone calls or emails are common to believe that they can make a differ-
from these groups for information on ence, too. Once residents are in-
topics, state law, or how to be an advo- volved, they can’t stop.
cate and start their own projects. We all entered pediatrics to make
Two thirds of Louisville’s pediat- a difference for children and their
ric residents participate in this elec- families: to advocate for them. We do
tive activity. Currently, PUSH is fo- it every day at an individual level in
cusing on child abuse and obesity, the clinic or hospital. Once residents
although the specific topics high- realize that they can have a more
lighted at any given time are not as global effect, they start to pay atten-
important as the underlying process tion to hospital committees as well as
of engaging residents in child advo- to local and national legislative agen-
cacy. The energy and excitement of das and begin to develop their own
the group has instigated multiple project ideas.
projects outside of the focus areas. Residents administer PUSH with
For example, one recent resident support from the Kentucky Chapter
who was interested in smoking cessa- of the AAP, faculty advisors, the pro-
tion submitted an application for an gram director, the department chair
American Academy of Pediatrics and staff, and several community-
(AAP) CATCH grant. Although he based organizations. Each new class
did not get the grant, he obtained a re-evaluates organizational structure
better prize—the experience of the and priorities and makes any neces-
SECTION EDITOR’S NOTE: One of process. He was forced to think sary changes. A mission statement
the difficulties in implementing through the intricacies of the project keeps them focused and centered on
the AAP policy to train residents and realize that there was more work their goal of improving the health
in community health and advocacy is to do before this project could come and safety of Kentucky’s children.
the lack of experienced faculty to fruition. Months later, together PUSH’s model follows that of the
in this area. The PUSH experi- with another resident, he presented Olympics: “It’s not the triumph, but
ence indicates that creating an en- an improved plan to the Chairman of the struggle.” The “struggle” is the
couraging environment for residency the Department of Pediatrics and the goal. This is how we teach; this is
advocacy projects can start a positive PUSH leadership committee, who how we learn. (Katherine R. Snyder,
feedback loop of seeing, doing, and stayed late after the meeting, ener- MD, MPH, University of Louisville,
teaching.—C. Andrew Aligne, MD gized about the possibly far-reaching Louisville, Ky.)

Pediatrics in the Community: A Little PUSH to Get the Advocacy Snowball
Rolling
Katherine R. Snyder
Pediatr. Rev. 2010;31;302
DOI: 10.1542/pir.31-7-302


Index of Suspicion
Scott M. Pugh, Joseph F. Pasternak, Patricia A. Liszewski, Alexandra N. Menchise,
Leslie Carroll, David M. Berman, Gurpreet Vidwan and Winsley Rose
Pediatr. Rev. 2010;31;303-307
DOI: 10.1542/pir.31-7-303

index of suspicion
Case 1 Presentation The fair-skinned girl weighs

A 10-year-old girl presents with left 12.5 kg (25th to 50th percentile),
eye pain 1 day after being hit in the has a temperature of 37.5°C, and has
face with a palm tree leaf that sprang other vital signs within normal range
back at her while playing. She imme- for age. She has blonde hair and
diately complained of eye pain, tear- bluish-gray eyes. There is full passive
ing, and blurry vision following the range of motion of her extremities.
incident. Her pain is improving to- Her gait is abnormal. She favors her
day, but the tearing and blurred vi- right leg, with her left foot externally
sion remain, and the eye still looks rotated and left hip abducted. There
The reader is encouraged to write red. She has no fever or headache, is no erythema or tenderness in any
possible diagnoses for each case before and she does not wear glasses or con- extremity. The remaining physical
turning to the discussion. We invite tact lenses. Her past medical history findings are normal.
readers to contribute case presentations is unremarkable. The MRSA-positive blood culture
and discussions. Please inquire first by
contacting Dr. Deepak Kamat at Physical examination reveals a well- from the transferring hospital shows
dkamat@med.wayne.edu. appearing girl in no acute distress, resistance to clindamycin and suscep-
who prefers to keep her left eye tibility to vancomycin, rifampin, and
closed. Vital signs are normal and trimethoprim-sulfamethoxazole. Her
visual acuity is 20/15 in the right eye antibiotics are changed to IV vanco-
Author Disclosure and 20/200 in the left eye. She has mycin and rifampin. Her initial CBC
Drs Pugh, Pasternak, Liszewski, no signs of head or facial trauma. shows a WBC count of 6.8⫻103/mcL
Menchise, Carroll, Berman, Vidwan, She has moderate photophobia, in- (6.8⫻109/L), with 10% neutrophils,
and Rose have disclosed no financial creased tear production, and signifi- 77% lymphocytes, and 13% mono-
relationships relevant to these cases. cant conjunctival injection in the left cytes; Hgb of 9.9 g/dL (99 g/L); Hct
This commentary does not contain a eye. Extraocular movements are nor- of 31.1% (0.311); mean corpuscular
discussion of an unapproved/ mal. There is no anisocoria, subcon- volume of 67.2 fL; mean corpuscular
investigative use of a commercial junctival hemorrhage, or chemosis. hemoglobin of 21.4 pg; and platelet
product/device. Fluorescein is placed in the left eye, count of 232⫻103/mcL (232⫻109/
and examination under a Woods L). Comprehensive metabolic panel
lamp does not reveal any obvious up- results are unremarkable. C-reactive
take of dye on the cornea or conjunc- protein measures 2.5 mg/dL. Repeat
tiva. The child is taken for urgent blood culture shows no growth. MRI
Frequently Used Abbreviations consultation with the ophthalmolo- and radiograph of the femur show nor-
ALT: alanine aminotransferase gist, who makes the diagnosis. mal results. Spine MRI shows evidence
AST: aspartate aminotransferase of osteomyelitis involving the left S1
BUN: blood urea nitrogen segment of the sacrum.
CBC: complete blood count Case 2 Presentation
CNS: central nervous system A 21⁄2-year-old girl presents to a com-
CSF: cerebrospinal fluid munity hospital with fever and Case 3 Presentation
CT: computed tomography a limp. Her blood culture grows A 12-year-old girl is admitted to the
ECG: electrocardiography methicillin-resistant Staphylococcus au- hospital after her first seizure. Her
ED: emergency department reus (MRSA), and she is treated em- friends noticed that she “passed out”
EEG: electroencephalography pirically with 3 days of intravenous on the school bus the morning of ad-
ESR: erythrocyte sedimentation rate (IV) clindamycin but remains febrile. mission and then experienced 2 min-
GI: gastrointestinal She is transferred for additional man- utes of both arm and leg jerking move-
GU: genitourinary agement. Significant findings on her ments. She was unresponsive and had
Hct: hematocrit past medical history include a MRSA urinary incontinence during the epi-
Hgb: hemoglobin skin abscess on the left knee treated sode. The movements resolved spon-
MRI: magnetic resonance imaging 3 months ago with trimethoprim- taneously, and she was acting normally
WBC: white blood cell sulfamethoxazole, speech delay, pneu- by the time paramedics arrived to
monia, and asthma. transport her to the hospital. She had

index of suspicion
been complaining of intermittent healing (cellular infiltrate) or infec-

headache for 1 week before the sei- tion (endophthalmitis).
zure. She denies fever, visual changes,
vomiting, recent illness, or recent Differential Diagnosis
travel. She is not taking any medicines. A corneal abrasion is disruption of
Her parents emigrated from Guate- the epithelial covering that protects
mala, and her father works as a farm the cornea. It is caused frequently
laborer. by trauma or foreign body but also
On physical examination, the girl is can result from infection. Patients
alert, oriented, and in no apparent dis- usually experience immediate severe
Figure 2. Egress of aqueous humor
tress. Her vital signs are normal. She pain, photophobia, and tearing. Of-
through full-thickness traumatic lacer-
has completely normal neurologic ten they experience the sensation of
ation.
and musculoskeletal examination find- a foreign body. The area of exposed
ings. Her complete metabolic profile, corneal tissue should take up fluor-
CBC, urinalysis, urine drug screen, Initial attempts to seal the leak with escein dye and be apparent under
and C-reactive protein value are nor- a bandage contact lens and pressure Woods lamp examination. Care must
mal. Her clinical history and imaging patch did not succeed. Eventually, the be taken to rule out a corneal foreign
studies lead to the diagnosis. girl required sedation and suturing of body, ulcer, or infiltrate. The abra-
the cornea as an ambulatory proce- sion heals when surrounding tissue
dure. She also received topical fluoro- regenerates the epithelial defect, a
Case 1 Discussion quinolone and oral ciprofloxacin for process that typically requires a few
This child easily could have had a heal- 72 hours. One day after closure, the days, depending on the size of the
ing corneal abrasion diagnosed and anterior chamber had reformed, and initial wound.
been sent home. However, her sig- she showed no signs of intraocular in-
nificantly impaired visual acuity de- fection. The suture was removed after Management
spite improvement in pain combined 2 weeks, and her vision returned to If a globe rupture is suspected, the
with the absence of fluorescein uptake 20/20 in the affected eye. examination should stop and a sim-
was concerning for a more serious oc- ple protective eye shield should be
ular injury. A central corneal abrasion The Condition placed. Immediate referral to an oph-
might account for some decreased A ruptured globe is defined as any thalmologist, potentially in a tertiary
visual acuity, but improvement would perforation of the anterior or pos- care center, is critical because surgical
be expected after 24 hours. Under terior segment of the eye. Perfora- closure often is required. It is impor-
slitlamp examination by the ophthal- tion can occur at any location from tant to avoid any manipulation (such
mologist, the anterior chamber of the sharp penetrating objects; blunt as patching) that could increase in-
left eye appeared shallow (Fig. 1) and a force more commonly causes rup- traocular pressure and possibly cause
leak was evident through a perforated ture at the limbus or behind the extrusion of intraocular contents.
cornea (Fig. 2). Handheld penlight ex- rectus muscle insertions where the Broad-spectrum parenteral or oral
amination did not demonstrate these sclera is weakest. Signs of globe rup- antibiotics should be administered
features. ture include subconjunctival hemor- early in the course to reduce the risk
rhage, chemosis, pupillary defects, of endophthalmitis, which can have
vitreous hemorrhage, or retained for- devastating effects.
eign bodies and may be associated Simple corneal abrasions (⬍10 mm)
with visual impairment out of pro- can be treated with topical antibi-
portion to the injury. As aqueous otics. Occasionally, an ophthalmo-
humor leaks through the defect, it plegic agent may be used to relieve
can wash away fluorescein dye, mak- pain associated with ciliary spasm.
ing it difficult to detect the tear. A suspected corneal abrasion in a
Globe rupture and laceration fre- contact lens wearer warrants immedi-
quently lead to permanent visual im- ate referral to ophthalmology to rule
Figure 1. Shallow anterior chamber pairment either through direct dam- out a corneal ulcer.
from central perforation of the cornea. age to the eye or through aberrant Retained foreign bodies in the

index of suspicion
scleral or palpebral conjunctiva often ous albinism, recurrent pyogenic in-

can be removed in the primary care fections, progressive neurologic prob-
setting. After instilling the topical an- lems, and mild coagulation defects. It
esthetic, the object may be brushed presents in infancy or childhood. This
away by using a cotton-tipped swab. patient had oculocutaneous albinism
This removal should be followed by and recurrent pyogenic infections
copious irrigation and treatment of without neurologic insult.
any underlying corneal abrasion. Affected patients usually have fair
Lessons for the Clinician Figure 4. Hair analysis shows silver hair skin. The hair typically is blonde, gray,
without medullary core pigmentation. or white and has a metallic sheen. The
● Corneal abrasions are common,
but when the history or examina- eyes usually are light. Strabismus,
tion results are not consistent with results were normal. Epstein-Barr vi- photophobia, and progressive visual
the expected course, globe rupture rus (EBV) antibody titers revealed loss are common. Morbidity and mor-
should be considered. past EBV infection. DNA analysis tality are increased by pyogenic in-
● Visual acuity testing is an impor- showed CHS-1 mutation, confirm- fections, most commonly from Staph-
tant part of the physical examina- ing the diagnosis of CHS. ylococcus aureus and Streptococcus
tion that must not be overlooked Although anemia can be associ- pyogenes. Infections include cellulitis,
when patients have perceived vis- ated with CHS, this patient’s micro- abscesses, superficial pyoderma, peri-
ual impairment or other eye com- cytic anemia can be explained by iron odontal disease, and enterocolitis. The
plaints. deficiency from increased cow milk clinical presentation for CNS involve-
● Early closure and prevention of en- ingestion. In addition, this girl had ment includes seizures, peripheral
dophthalmitis are paramount in neutropenia (absolute neutrophil neuropathy, weakness, ataxia, tremors,
preserving vision. count of 0.680⫻103/mcL [0.680⫻ and cognitive decline.
109/L]), which is a feature of CHS. Severe immunodeficiency and mas-
(Scott M. Pugh, MD, Joseph F. Pas- Once she improved clinically, her sive lymphohistiocytic infiltration of
ternak, MD, Patricia A. Liszewski, IV antibiotics were discontinued and organ systems occurs in most patients.
MD, United States Naval Hospital, she was started on oral trimethoprim- This occurrence is described as the
Naples, Italy) sulfamethoxazole. She did well clini- accelerated phase of CHS and is
The views expressed in this case are cally. Subsequently, she underwent a characterized by hepatosplenomegaly,
those of the authors and do not neces- matched unrelated donor bone mar- pancytopenia, lymphadenopathy, and
sarily reflect the official policy or posi- row transplant for her CHS and is bleeding diathesis. It has been hypoth-
tion of the Department of the Navy, doing well at this time. esized that the accelerated phase may
the Department of Defense, or the be an expression of the familial form of
United States government. The Condition hemophagocytic lymphohistiocytosis
CHS is a rare autosomal recessive dis- that may be triggered by viral infec-
order, with fewer than 500 cases re- tions such as EBV.
Case 2 Discussion ported worldwide in the past 20 years.
Based on a peripheral blood smear It is characterized by oculocutane- Pathogenesis
showing giant cytoplasmic granules Mutations in the lysosomal traffick-
within neutrophils (Fig. 3) and hair ing regulator gene (CHS1/LYS) are
analysis revealing silver hair without the underlying defect in CHS. These
medullary core pigmentation (Fig. 4), mutations can result in absent or
Chediak-Higashi syndrome (CHS) abnormal CHS1/LYST proteins. It
was diagnosed. is hypothesized that such defective
Immune evaluation included T- proteins lead to abnormal protein
and B-lymphocyte enumeration; lym- trafficking and fusion of vesicles as
phocyte transformation to antigen well as failure to transport lysosomes
and mitogen stimulation; quantita- to the designated sites of action.
tive immunoglobulins; and anti- Figure 3. Peripheral blood smear shows All cell types are affected in CHS.
diphtheria, anti-tetanus, and anti- giant cytoplasmic granules within neu- Cytotoxic T cells and neutrophils
pneumococcal antibody titers. Test trophils. have abnormal granules that do not

index of suspicion
function when exposed to patho- Treatment man, DO, All Children’s Hospital,
gens, resulting in severe infection. The gold standard treatment is he- St. Petersburg, Fla.)
In melanocytes, the melanosomes are matopoietic stem cell transplantation
not transferred to epithelial cells or (HSCT) from a human leukocyte
keratinocytes, resulting in albinism. A antigen-matched donor. Transplan- Case 3 Discussion
reduction in platelet-dense bodies can tation should occur before the accel- Brain MRI revealed a solitary 9-mm
result in mild coagulation defects. erated phase or during remission. ring-enhancing lesion in the left supe-
Successful HSCT improves progno- rior parietal lobe (Fig. 5). The lesion
sis, reduces risk of infection, and pre- raised concern primarily for an abscess
Diagnosis vents development of the accelerated due to Mycobacterium tuberculosis, No-
Giant azurophilic cytoplasmic gran- phase. HSCT does not prevent neu- cardia, Actinomyces, or Aspergillus in-
ules in granule-containing cells are rologic sequelae or albinism. With- fection or neurocysticercosis (NCC).
pathognomonic for CHS. Diagnosis out transplantation, most patients Other causes for this type of lesion
can be confirmed by genetic testing die from infection in childhood. include a low-grade glioma, infarction,
for CHS1/LYST gene mutations. As with other immunodeficiency contusion, demyelinating process, or
Light microscopy of the hair shaft syndromes, prophylactic antimicro- resolving hematoma.
reveals accumulation of irregularly bial drugs and aggressive therapy for This patient’s history of first-time
distributed pigmentation that ap- infection is the mainstay of ther- seizure, her parents’ history of emi-
pears bright and polychromatic un- apy. Various case reports document grating from Central America, the
der polarized light microscopy. The success with granulocyte colony- girl’s normal physical findings, and
diagnosis can be made prenatally by stimulating factor and interferon- the brain MRI images led to the
sampling fetal blood, fetal hair, or gamma in reducing the risk of infec- strong suspicion of NCC. Her EEG
amniotic and chorionic villus cells. tion. For patients in the accelerated tracing was normal. Serology for Toxo-
Neutropenia and hypergamma- phase, glucocorticoids, splenectomy, plasma, cytomegalovirus, and human
globulinemia, with preserved B-cell antiviral therapy, chemotherapy, and immunodeficiency virus was negative.
function, are common findings. intravenous gamma globulin have A tuberculosis skin test was negative.
Platelet aggregation and bleeding been used with variable success. Empiric antihelminthic therapy was
time can be abnormal. In the accel- begun pending Cysticercus titers. This
erated phase of CHS, thrombocyto- Lessons for the Clinician patient’s enzyme-linked immunosor-
penia can occur. bent assay (ELISA) titers were in the
● Although rare, patients present-
equivocal range. A probable diagnosis
ing with oculocutaneous albinism
and recurrent pyogenic infections
Differential Diagnosis
should be evaluated for CHS.
Differential diagnosis for a patient
● Diagnosis is made by identifying
who has oculocutaneous albinism and
cytoplasmic granules on a periph-
immunodeficiency includes Griscelli
eral blood smear and genetic mu-
syndrome, a rare autosomal recessive
tation testing.
disorder. The lack of intracellular ● Infection is the most common
granules within cells and polarized
cause of mortality.
light microscopy examination of the ● Prognosis is poor, even with suc-
hair shaft revealing a uniformly white
cessful stem cell transplantation,
appearance distinguishes it from CHS.
because patients endure debilitat-
Hermansky-Pudlak syndrome is an-
ing neurologic sequelae in adult-
other rare autosomal recessive disorder
hood.
characterized by partial oculocutane- ● Medical and social care is provided
ous albinism and platelet storage pool
best by a coordinated team of spe-
deficiency caused by a different genetic
cialists due to the complexity of
mutation from CHS. Waardenburg
this syndrome.
syndrome, Prader-Willi syndrome, and Figure 5. Brain MRI shows a solitary
Angelman syndrome also should be (Alexandra N. Menchise, MD, 9-mm ring-enhancing lesion in the left
considered. Leslie Carroll, MD, David M. Ber- superior parietal lobe.

index of suspicion
of NCC was made based on the clinical ity. The seizures typically respond to Albendazole (15 mg/kg) in two
presentation, highly suggestive neuro- antiepileptic therapy. daily doses for 14 days is the recom-
imaging results, and contact with en- In addition to seizures, headaches mended therapy for patients who
demic hosts. are very common and may be the have active lesions. Systemic cortico-
initial presenting symptom. An extra- steroids may be used before starting
The Condition parenchymal granuloma may ob- albendazole to ameliorate the ad-
The pork tapeworm (Taenia solium) struct CSF flow, causing increased verse effects of cysticidal therapy.
is responsible for a great burden of intracranial pressure and hydroceph- The addition of systemic corticoste-
disease in the developing world and alus. Parenchymal involvement may roids in patients who do not have
is being seen with greater frequency produce changes in school perfor- hydrocephalus has been shown to
in the United States. Human infec- mance, mood, or personality. decrease the inflammatory response
tion occurs following ingestion of following antihelminthic treatment,
Diagnosis
eggs from a tapeworm-infected host thereby limiting emergent complica-
NCC usually is suspected when there
via the fecal-oral route. Cysticerco- tions such as seizures or increased
is a history of seizures and identifica-
sis occurs when the larval form of intracranial pressure. Patients who
tion of a ring-enhancing lesion or
T solium, known as Cysticercus cellu- have single enhancing lesions have a
lesions on neuroimaging studies.
losae, invades human tissue. Once in 15% recurrence rate of seizures fol-
Serologic tests for cysticercosis have
the GI tract, the eggs hatch and re- lowing antihelminthic therapy at 5
been limited in the past due to
lease oncospheres into the vascular years. Patients who have extraparen-
poor sensitivity. Patients who have
system and lymphatics that spread to chymal lesions have an increased risk
solitary or inactive calcified lesions
other tissues. for developing hydrocephalus and,
may not demonstrate elevated titers
NCC refers specifically to infec- therefore, a less favorable prognosis.
by ELISA. This patient’s titers by
tion of the CNS. Once passing the
ELISA were in the equivocal range. Lessons for the Clinician
blood-brain barrier, the oncospheres
Electroimmunotransfer blot assay ● NCC is the most common cause
reach adult size within a few weeks.
has shown superiority to ELISA (sen- for unprovoked seizures in the de-
However, full neurologic symptoms
sitivity 86%, specificity 92%). CSF veloping world.
may not present for years. In the
studies are not required for diagnosis. ● NCC should be suspected in an
brain, the parasite gradually may be-
come inactive and calcify from a local Treatment and Prognosis otherwise healthy older child pre-
inflammatory response or remain ac- Treatment of NCC remains contro- senting with a first unprovoked sei-
tive, with continued cyst production. versial. Factors to be considered in- zure and a ring-enhancing lesion.
● A history of pork ingestion or ex-
NCC is the leading cause of ac- clude the location, number, and size
quired epilepsy worldwide, account- of cysts as well as the degree of cyst posure is not required for diagno-
ing for up to 70% of all new-onset activity. Until recently, very few con- sis, although epidemiologic risk
seizures in the developing world. trolled studies have investigated the factors should be ascertained on
A recent outbreak among New York efficacy of different treatments. Fore- admission.
● Active NCC lesions should be
orthodox Jews demonstrated that in- most, seizures should be controlled
gestion of pork or recent travel to with antiepileptic drug therapy. Typ- treated with albendazole and corti-
endemic areas is not required for ically, such drugs may be discontin- costeroids; inactive lesions do not
NCC infection. ued after the patient has been free of require treatment. Generally, chil-
seizures for 1 year and lesions are dren who have single solitary le-
Clinical Features resolving on neuroimaging studies. sions from NCC have a favorable
Children who have NCC present with Hydrocephalus and increased in- prognosis.
seizures of variable type, depending on tracranial pressure require neurosur- (Gurpreet Vidwan, MD, Levine
the location of the Cysticercus granu- gical management. Children’s Hospital, Charlotte, NC,
loma. The most common manifesta- The treatment of a solitary CNS Winsley Rose, MD, Christian Medical
tion is a partial seizure, with or without lesion remains controversial. Recent College, Vellore, India)
secondary generalization, due to local evidence suggests that inactive cal- To view Suggested Reading lists for
tissue inflammation associated with a cified lesions do not require anti- these cases, visit http://pedsinreview.
solitary enhancing lesion. EEG may helminthic treatment because viable aappublications.org and click on In-
show focal signs of epileptiform activ- cysts are not present. dex of Suspicion.

Index of Suspicion
Scott M. Pugh, Joseph F. Pasternak, Patricia A. Liszewski, Alexandra N. Menchise,
Leslie Carroll, David M. Berman, Gurpreet Vidwan and Winsley Rose
Pediatr. Rev. 2010;31;303-307
DOI: 10.1542/pir.31-7-303

Supplementary Material Supplementary material can be found at:

/DC1

Ethics for the Pediatrician: The Ethics of Complementary and Alternative
Medicine
Brenda J. Mears
Pediatr. Rev. 2010;31;e49-e51
DOI: 10.1542/pir.31-7-e49
http://pedsinreview.aappublications.org/cgi/content/full/31/7/e49

ethics for the pediatrician
The Ethics of Complementary and

Alternative Medicine
Brenda J. Mears, MD*
Introduction such as herbs, vitamins, and nutritional

Complementary and alternative med- therapy; manipulative and body-based
icine (CAM) is being used by a sig- practices such as chiropractic or mas-
nificant segment of society. To aid sage; and energy medicine such as
families who are using or consider- biofield and bioelectromagnetic thera-
ing CAM, pediatricians need to edu- pies has been considered CAM by
cate themselves about the available some people. (6)
modalities and make this information When families use alternative
available to these families. (1)(2) medicine, these therapies are used in-
The 2007 National Health Inter- stead of conventional medicine. Com-
Author Disclosure view Survey from the Centers for Dis- plementary medicine uses these thera-
Dr Mears has disclosed no financial ease Control and Prevention’s Na- pies as well as conventional medicine.
relationships relevant to this article. tional Center for Health Statistics Integrative medicine blends conven-
This commentary does not contain a estimated that 38.2% of adults and tional medicine and complementary
11.8% of children had used some type therapies for which there is evidence of
discussion of an unapproved/
of CAM in the preceding 12 months. safety and effectiveness. The bound-
investigative use of a commercial
(3) The rates may range as high as 70% aries may blur, and some therapies
product/device. in some groups. (4) In one survey, once believed to be CAM, such as cog-
87% of pediatricians had been asked nitive behavior therapy or prebiotic
by patients or parents about CAM, and probiotic use, now are considered
although as many as 66% may not by many to be conventional. (6)
tell their physicians when they do use Conventional medicine is in-
CAM. (4)(5) Some of the cost of this tended to be based on knowledge of
care may be covered by insurance or safety and efficacy obtained from ran-
government programs, but much is domized, controlled trials and at-
paid directly by families. tempts to avoid treatments that are
not supported by such evidence;
Types of CAM CAM therapies may have fewer sup-
The National Center for Comple- porting data. In practice, many activ-
mentary and Alternative Medicine ities in both conventional medicine
(NCCAM) of the National Institutes and CAM lack rigorous evaluations.
of Health defines CAM as “a group This is not a reason to exempt either
of diverse medical and health care CAM or conventional medicine from
systems, practices, and products that attempts to improve the evidence
are not generally considered part of supporting the care given to patients.
conventional medicine.” Everything NCCAM funds and conducts many
from whole medical systems such as of the increasing number of scientific
homeopathy or naturopathy; mind- studies of CAM. (6)(7)
body medicine such as meditation, Concerns about using CAM in-
prayer, yoga, biofeedback, hypnosis, clude the risk that it will be used by
guided imagery, and art or music someone who has a serious disease in
therapy; biologically based practices place of a beneficial, well-studied
treatment whose risks and benefits
*Department of Pediatrics, University of Texas at are known. If families do not tell
Southwestern Medical School, Dallas, Tex. clinicians that they are using CAM,
Pediatrics in Review Vol.31 No.7 July 2010 e49

clinicians are unable to monitor for disease, promotion of health, relief of Before any diagnostic or thera-
possible problems. The CAM practi- symptoms, improved quality of life, peutic procedures are performed, in-
tioner may or may not be trained and and health promotion, families may formed consent must be given. An
licensed. Specific CAM remedies, feel that their own goals are not be- adequate informed consent requires
such as some herbs, are toxic (mistle- ing met by conventional medical the decision-maker to have all rele-
toe and skullcap). St John’s wort and practitioners. Some families are dis- vant information about the risks and
garlic may affect the P450 system. satisfied with the complex technol- benefits of possible management op-
Even therapies believed to be non- ogy and adverse effects of conven- tions, including treatment and non-
toxic may have poor quality control tional medicine. They may perceive a treatment, with both conventional
in their production. Vitamin over- “natural” treatment as being safer. and relevant CAM modalities. This
dose, chemical burns, lead toxicity, Conventional medical practitioners disclosure should include the rare
and vertebral artery thrombosis after recognize the necessity of physician- and serious as well as the common
chiropractic manipulation all have patient relationships for successful and mild problems. Some families
been reported. (8)(9) treatment, but families may see the want much more information, in-
emphasis on studies in conventional cluding that which may not be avail-
Legal Questions medicine as undervaluing relation- able. For pediatric patients, informed
Legal questions about CAM fall in- ships and may want care that is more consent normally is obtained from
to several categories: reporting of empowering and patient-centered. the parents, and assent is obtained
abuse and neglect, malpractice lia- from the child, when appropriate.
In cases of chronic or terminal illness,
bility, disciplinary issues of state li- Withholding available information
they may believe that any approach is
censing, and possibly, issues of fraud. undermines the trust among the fam-
worth a trial.
Caregivers who use CAM are not ily, patient, and doctor and interferes
When a pediatrician needs to of-
relieved of their duty to seek neces- with the adequacy of the informed
fer an ethical response to concerns
sary medical care for the children in consent. (11)
about the use of CAM, a number of
their care. It may, at times, be unclear
factors must be considered, includ-
if reliance on CAM is abuse or ne- Beneficience
ing the patient, the illness, the con-
glect, but if parents are using alter- Beneficence is the duty to promote
ventional treatments being used, the
native therapies for life-threatening good and act in the best interest of
proposed CAM treatment, and prac-
illnesses for which effective conven- the patient. This principle implies an
tional therapies are available, physi- titioner and family understanding. obligation to protect and defend the
cians must notify child protective The four principles of Beauchamp rights of others by our actions. Clini-
services. Generally, courts allow pa- and Childress—autonomy, nonmal- cians have an obligation to help pa-
rental choice and are reluctant to eficence, beneficence, and justice— tients achieve the goals of medicine,
overrule parents unless the situation provide an approach to organizing such as promoting health and reliev-
is life-threatening. Although the use this decision-making, even when ing suffering, even when the patient
or provision of CAM is not neces- multiple principles apply and may be and medical practitioner differ in the
sarily negligent, the same rules of in conflict in a single situation. (10) prioritization of these goals and the
negligence apply to both CAM and preferred methods of achieving such
conventional medicine. If the pati- goals. The principle of beneficence
ent is injured and the practitioner has Autonomy requires clinicians to promote under-
not conformed to an appropriate Personal autonomy is the right of a standing and respect for patients’ re-
standard of care, these can be competent patient to make deci- ligious, cultural, and health-related
grounds for either a civil lawsuit or sions about personal medical care beliefs and values.
professional discipline. (8) consistent with personal values. This
right includes the ability to choose Nonmaleficence
Ethical Considerations or refuse treatment that may be Nonmaleficence is the duty to pro-
Why would families choose to use conventional, nonconventional, ex- tect and to not harm patients. Al-
therapies that may be unproven, perimental, dangerous, or ineffec- though many procedures, whether
risky, and expensive? Although the tive. Rules for truth telling, disclo- conventional or nonconventional,
goals of both conventional medicine sure, and informed consent derive cause pain, clinicians should cause no
and CAM may include prevention of from our ideas about autonomy. more discomfort than necessary, cause
e50 Pediatrics in Review Vol.31 No.7 July 2010

no offense, and avoid causing harm whether conventional, alternative, on Ethical and Judicial Affairs. Code of Med-
through negligence or carelessness. complementary, or integrated. Fam- ical Ethics. 2001. Accessed December 2009
at http://www.ama-assn.org/ama/pub/
ily goals may lead to choices that
physician-resources/medical-ethics/code-
Justice differ from those who provide the medical-ethics/principles-medical-ethics.
Justice is fairness. Social benefits and health care, but if the assumption is shtml
burdens should be distributed fairly, made that there is no negligence or 3. Barnes PM, Bloom B, Nahin RL. Com-
abuse involved in their choices, any plementary and alternative medicine use
with “access to medical care for all
treatment should be directed at among adults and children: United States,
people.” If some CAM therapies are 2007. National Health Statistics Reports.
safe, effective, and appropriate, pa- meeting those goals. All discussions
2008;12:1–24
tients should have access to them. If and consents need to be as informed 4. Kemper KJ, Vohra S, Walls R. The use
others are not helpful, resources used as possible and documented clearly, of complementary and alternative medi-
for them are not available for other, whether advice has been accepted or cine in pediatrics. Pediatrics. 2008;122:
rejected by the family. All responses 1374 –1386
more beneficial management. Clini- 5. Kemper KJ, O’Connor KG. Pediatri-
cians should consider and act fairly of all patients to the chosen therapies
cians’ recommendations for complementary
when the interests of various individ- of any type should be monitored. If a and alternative medical (CAM) therapies.
uals are in conflict. (2) family chooses a treatment outside Ambul Pediatr. 2004;4:482– 487
the clinician’s scope of practice, he or 6. National Center for Complementary and
she still can evaluate responses, even Alternative Medicine. What is CAM? 2007.
Conclusion if unable to refer or provide treat-
Accessed December 2009 at: http://nccam.
In visits with patients and families, nih.gov/health/whatiscam/overview.htm
ment. If the physician and family are 7. Hansen K, Kappel K. The proper role
clinicians should obtain histories,
unable to agree on management, but of evidence in complementary/alternative
perform physical examinations, and
the involvement of child protective medicine. J Med Philos. 2009. Accessed
secure documentation, including ask- December 2009 at: http://jmp.oxford
services is not appropriate, transfer of
ing about the use of various CAM journals.org/cgi/content/full/jhp059v1
the family to another pediatrician
therapies. This knowledge is essen- 8. Cohen MH, Kemper KJ. Complemen-
may be necessary. tary therapies in pediatrics: a legal perspec-
tial to evaluating and counseling
tive. Pediatrics. 2005;115:774 –780
families about their children’s health. 9. Zimmerman AW, Kumar AJ, Gadoth N,
Clinicians never should dismiss the References Hodges FJ. Traumatic vertebrobasilar oc-
concerns of the family about man- 1. American Academy of Pediatrics. Com- clusive disease in childhood. Neurology.
agement options and should avoid mittee on Children with Disabilities. Coun- 1978;28:185
defensive reactions. Pediatricians must seling families who choose complementary 10. Beauchamp T, Childress J. Principles of
and alternative medicine for their child with Biomedical Ethics. 5th ed. New York, NY:
educate themselves and their families chronic illness or disability. Pediatrics. Oxford University Press; 2001
about the risks and benefits of vari- 2001;107:598 – 601 11. Ernst E. The ethics of complementary
ous treatments being considered, 2. American Medical Association. Council medicine. J Med Ethics. 1996;22:197–198

Ethics for the Pediatrician: The Ethics of Complementary and Alternative
Medicine
Brenda J. Mears
DOI: 10.1542/pir.31-7-e49

& Services http://pedsinreview.aappublications.org/cgi/content/full/31/7/e49

In Brief: Nonalcoholic Fatty Liver Disease
Bryan Rudolph and Yolanda Rivas
DOI: 10.1542/pir.31-7-e52
http://pedsinreview.aappublications.org/cgi/content/full/31/7/e52

in brief
In Brief
Nonalcoholic Fatty Liver Disease
Bryan Rudolph, MD and insulin resistance and, by defini- lipids within the liver and is linked
Yolanda Rivas, MD tion, occur in the absence of alcohol closely to the hyperinsulinism and de-
Children’s Hospital at Montefiore consumption. creased insulin sensitivity associated
Bronx, NY First described in the pediatric liter- with obesity. Insulin resistance causes a
ature just over 25 years ago, NAFLD total body increase in lipolysis; the
today is recognized as an increasingly circulating free fatty acids produced are
Author Disclosure significant cause of liver disease. Esti- ultimately taken up by hepatocytes.
Drs Rudolph and Rivas have disclosed mates of the overall prevalence of Hyperinsulinism, on the other hand,
no financial relationships relevant to NAFLD vary, based on the method of contributes to steatosis via two routes:
this In Brief. This commentary does detection, but it likely is present in increasing fatty acid synthesis through
approximately 9% of all children and increased glycolysis and decreasing
not contain a discussion of an
in up to 80% of obese children. With hepatic production of apolipoprotein
unapproved/investigative use of a
the obesity epidemic and increased B-100, the principal protein responsible
commercial product/device. physician awareness, these figures are for fatty acid exportation. With excess
almost sure to increase. production and decreased exportation,
Currently, the average age at diag- excessive fat accumulates within hepa-
Nonalcoholic Fatty Liver Disease. nosis is 12 years, with the earliest tocytes.
Schwimmer J. In: Suchy F, Sokol RJ, reported cases at about 2 years of age. Although the exact pathogenesis of
Balisteri WF, eds. Liver Disease in Evidence also suggests that children are NASH is unclear, a “two-hit” mecha-
Children. 3rd ed. New York, NY: developing more advanced stages of nism seems likely. Fat accumulation
Cambridge University Press; NAFLD at earlier ages. In 2006, for within hepatocytes, as described pre-
2007:830 – 839
example, it was estimated that 25% of viously, is the first “hit.” Steatosis ren-
AGA Technical Review on Nonalcoholic
Fatty Liver Disease. Sanyal AJ. Gas-
children who had NASH were younger ders hepatocytes more susceptible to
troenterology. 2002;123:1705–1725 than 10 years of age. Several recent injury and is a prerequisite for develop-
Non-alcoholic Steatohepatitis in case reports have described toddlers ing the inflammation and fibrosis found
Children. Roberts E. Clin Liver Dis. who have NASH and even have linked in NASH.
2007;11:155–172 NASH to the formation of cirrhosis in In response to steatosis, hepatocytes
Nonalcoholic Fatty Liver Disease. children younger than 10 years. have two primary mechanisms to dis-
Alfie ME, Treem WR. Pediatr Ann. Boys are approximately 40% more pose of excess lipids: mitochondrial
2006;35:290 –294, 297–299 likely than girls to have steatosis, even beta oxidation converts fatty acids into
after controlling for confounding fac- adenosine triphosphate and ketone bod-
Nonalcoholic fatty liver disease (NAFLD) tors such as body mass index (BMI) and ies and triglycerides are secreted via apo-
is a generic term encompassing a spec- ethnicity. NAFLD is more common in lipoprotein B-100 into the bloodstream
trum of disorders defined by their his- certain ethnic groups, with the highest as very low-density lipoprotein. However,
topathology. On one end of the contin- prevalence seen among Hispanic chil- in NAFLD, apolipoprotein B-100 concen-
uum is simple macrovesicular steatosis, dren. Hispanic adolescents specifically trations are decreased and the triglyc-
which is defined by large fat droplets are more likely to develop significant eride load to the liver is increased
within hepatocytes. Over time, how- liver fibrosis. Surprisingly, despite hav- dramatically. As such, lipid metabolism
ever, simple steatosis may progress. ing higher rates of risk factors such as is shunted toward mitochondrial beta
When inflammation is present, with or insulin resistance and obesity, African oxidation, which can produce a high
without fibrosis, the condition is known American children have the lowest burden of free radicals. The oxidative
as nonalcoholic steatohepatitis (NASH). prevalence of fatty liver disease. Asian stress from beta oxidation and other
The far end of the spectrum is frank and white children have intermediate pathways is the likely second “hit” in
cirrhosis. All of the entities constitut- prevalences. the pathogenesis of NASH.
ing NAFLD are associated with obesity NAFLD results from accumulation of Patients who develop NAFLD often
e52 Pediatrics in Review Vol.31 No.7 July 2010

in brief
are asymptomatic, although about one homogeneous, increased liver echoge- frequently children advance from sim-
third complain of vague right upper nicity. This finding can be associated ple steatosis to steatohepatitis and,
quadrant pain. On initial diagnosis, ac- with fatty infiltration, inflammation, or ultimately, to cirrhosis. The severity of
anthosis nigricans is found in up to fibrosis, making this imaging modality baseline liver histology, however, likely
50% of affected children, and hepato- an insensitive test. Yet, when coupled is predictive. A disheartening statistic
megaly, although often difficult to with an increased serum, ALT concen- is that 5% to 10% of patients present
appreciate, is present in 40% to 50%. tration in the correct clinical picture, with advanced fibrosis at the time of
Other metabolic abnormalities such as ultrasonography may be highly sugges- pathologic diagnosis.
hyperinsulinemia and dyslipidemia (spe- tive of, but not definitive for, NAFLD. Very few treatments are available
cifically high triglyceride values) are Serum transaminases, with or without for NAFLD. Lifestyle changes, particu-
especially common. Although 90% of ultrasonography, therefore, should be
larly diet and exercise, are the most
children who have NAFLD are obese assessed as part of the evaluation of an
widely recommended interventions but
(as defined by a BMI ⱖ95th percentile), obese child or if fatty liver disease is
should be undertaken relatively slowly
10% have the disease from other suspected. Other noninvasive imaging
because rapid weight loss can worsen
causes. Thus, patients who have normal modalities such as computed tomogra-
liver disease acutely. In small studies, a
BMIs still may have NAFLD. phy scan and magnetic resonance im-
mere 10% decrease in excessive body
The diagnostic approach to NAFLD aging have not yet been validated
weight normalized serum transaminase
varies among pediatric gastroenterolo- against liver histology and are largely
values. Even so, it is unclear whether a
gists. Liver histology obtained from a nonspecific.
biopsy is the gold standard in diagnosis, Particularly in the setting of obesity, decrease in transaminase concentra-
but the procedure can be associated practitioners must be wary of assuming tions is associated directly with im-
with significant morbidity and even a diagnosis of NAFLD based solely on provement in pathology or disease pro-
mortality. Therefore, the decision to an elevated serum ALT value, sugges- gression.
obtain a biopsy should not be made tive ultrasonography, or a combination The use of medications for NAFLD is
lightly, and the procedure should be of the two. Other causes of liver dis- an area of ongoing research. In partic-
undertaken only when clinically justi- ease, including infectious, metabolic, ular, metformin appears to hold
fied and necessary. nutritional, immunologic, or pharmaco- promise, having been shown to im-
Several screening tests for NAFLD logic, must be excluded. As a general prove transaminase concentrations,
are available. An elevated serum ala- rule, any child who has persistently decrease hepatic fat quantities, and
nine aminotransferase (ALT) value is the elevated transaminase values should be improve insulin resistance in a small
most helpful and, when elevated, often referred to a pediatric gastroenterolo- cohort of children. However, there
is two to three times the upper limit of gist for additional evaluation. currently is not enough evidence to
normal. However, children can have he- Children can develop cirrhosis from justify the use of metformin specifi-
patic steatosis or even NASH with normal NAFLD and may develop hepatocellular cally for pediatric NAFLD. Other med-
or only mildly elevated ALT values. carcinoma in adulthood. Fatty liver dis- ications studied show no significant
Ultrasonography is another common ease also has necessitated transplanta- efficacy. Additional research is
screening tool. Approximately 50% of tion as early as adolescence. Neverthe- needed regarding disease pathogene-
abdominal ultrasonography performed less, data on disease progression are sis, noninvasive diagnostic modalities,
in obese patients demonstrates diffuse, limited. It is unclear, for example, how and pharmacotherapy.

In Brief: Nonalcoholic Fatty Liver Disease
Bryan Rudolph and Yolanda Rivas
DOI: 10.1542/pir.31-7-e52

& Services http://pedsinreview.aappublications.org/cgi/content/full/31/7/e52
View publication stats

07 Pediatrics in Review July20 PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

07 Pediatrics in Review July20 PDF

Uploaded by

Copyright:

Available Formats

See discussions, stats, and author profiles for this publication at: https://www.researchgate.

Movement Disorders II: Chorea, Dystonia, Myoclonus, and Tremor

Article in Pediatrics in Review · July 2010

Jonathan W Mink Samuel H Zinner

SEE PROFILE SEE PROFILE

The user has requested enhancement of the downloaded file.

R. Jason Gerber, Timothy Wilks, Christine Erdie-Lalena

278 Atopic Dermatitis and Ichthyosis

287 Movement Disorders II:

303 Index of Suspicion

e49 Ethics for the Pediatrician: The Ethics of

The composition and production of Pediatrics in Review威

Cover: The artwork on the cover of this month’s issue is

Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Atopic Dermatitis and Ichthyosis

278 Pediatrics in Review Vol.31 No.7 July 2010

In acute AD lesions, T-helper 2 (TH2) cells are

Pediatrics in Review Vol.31 No.7 July 2010 279

have AD. If herpesvirus infection involves the eye or

Allergy and Environment

280 Pediatrics in Review Vol.31 No.7 July 2010

Pediatrics in Review Vol.31 No.7 July 2010 281

Topical Corticosteroids Ranked Strongest

282 Pediatrics in Review Vol.31 No.7 July 2010

Pediatrics in Review Vol.31 No.7 July 2010 283

The mutation for IV also has been identified. Studies

284 Pediatrics in Review Vol.31 No.7 July 2010

Pediatrics in Review Vol.31 No.7 July 2010 285

286 Pediatrics in Review Vol.31 No.7 July 2010

Updated Information including high-resolution figures, can be found at:

Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Developmental Milestones: Motor Development

Pediatrics in Review Vol.31 No.7 July 2010 267

268 Pediatrics in Review Vol.31 No.7 July 2010

Table 1. Developmental Milestones

Pediatrics in Review Vol.31 No.7 July 2010 269

Table 1. Developmental Milestones—continued

270 Pediatrics in Review Vol.31 No.7 July 2010

Table 1. Developmental Milestones—continued

Pediatrics in Review Vol.31 No.7 July 2010 271

Table 1. Developmental Milestones—continued

272 Pediatrics in Review Vol.31 No.7 July 2010

Figure 1. Moro reflex. This reflex occurs spontaneously to

infant is more stable in upright positions and can move

Pediatrics in Review Vol.31 No.7 July 2010 273

Figure 4. The declining intensity of primitive reflexes and the

Figure 3. Positive support reflex. With support around the

do and how he or she can accomplish it. Intrinsic muscle

274 Pediatrics in Review Vol.31 No.7 July 2010

flexion. Their grasp and in-hand ma-

Developmental Red Flags

Pediatrics in Review Vol.31 No.7 July 2010 275

References sleeping environment and sleep position. Pediatrics. 2000;105:

276 Pediatrics in Review Vol.31 No.7 July 2010

Pediatrics in Review Vol.31 No.7 July 2010 277

Updated Information including high-resolution figures, can be found at:

Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Downloaded from http://pedsinreview.aappublications.org. Provided by Health Internetwork on July 1, 2010

Movement Disorders II:

Pediatrics in Review Vol.31 No.7 July 2010 287

chorea in childhood is due to other disorders. More than

Sydenham Chorea (Rheumatic Chorea) Paraneoplastic