JANUARY 2017

Vol. 38 No. 1
www.pedsinreview.org

Fungal Skin Infections

Gupta, MacLeod, Foley,
Gupta, Friedlander

Tube Feeding in Children

Singhal, Baker, Bojczuk, Baker

Overcoming Challenges
to Care in the Juvenile
Justice System: A Case
Study and Commentary
Savage, Reese, Wallace, Wang,
Jester, Lowe, Hyndman, Durant

ONLINE

Visual Diagnosis: A Child

with Presumed Reactive
Airway Disease, Pectus
Carinatum, and Aortic
Root Dilation
Jeewa, Morris, Dreyer, Adachi,
Denfield, McKenzie
contents

Pediatrics in Review ®
Vol. 38 No. 1 January 2017

COMMENTARY
1 Training to Teach, Teaching to Train
Joseph A. Zenel

3 Plagiarism in Review
Mark Weems

6 Then What?
Hugh D. Allen
ARTICLES
8 Fungal Skin Infections
Aditya K. Gupta, Melissa A. MacLeod, Kelly A. Foley,
Gita Gupta, Sheila Fallon Friedlander

23 Tube Feeding in Children

Sarita Singhal, Susan S. Baker, Georgina A. Bojczuk, Robert D. Baker

35 Overcoming Challenges to Care in the Juvenile Justice System:

A Case Study and Commentary
Rebekah J. Savage, Jasmine M. Reese, Stephenie Wallace, Timothy Wang,
Traci Jester, Robert Lowe, LaKeshia Hyndman, Nefertiti Durant
INDEX OF SUSPICION
44 Case 1: Poor Growth With Presence of a Pituitary Lesion in an
11-year-old Boy
Alexander S. Karageorgiadis, Charalampos Lyssikatos,
Elena Belyavskaya, Georgios Z. Papadakis, Nicholas J. Patronas,
Maya B. Lodish, Constantine A. Stratakis

46 Case 2: Fever and Back Pain in 13-year-old Girl

Reem Shawar, Pisespong Patamasucon, Shawn Rowles

48 Case 3: Recurrent Lesions on Palms of a 12-year-old Girl

Alexander K.C. Leung, Benjamin Barankin

49 Case 4: Worsening Abdominal Distention in a 2-year-old Boy

Sean Indra, Shazia Maqbool

50 Case 5: Fatigue, Polydipsia, and Nocturia in a 17-year-old Boy

S. Amara Ogbonnaya

52 Case 6: Episodic Stiffness in a 30-month-old Girl

Lisa Mitchell, William Adams, Francois Aspesberro
IN BRIEFS
54 Medication Reconciliation
Jenna Merandi, Matthew Sapko, Charline Catt, Jeffrey M Hoffman

56 CHARGE Syndrome
Alexandra Hudson, Carrie-Lee Trider, Kim Blake
ONLINE
e1 Visual Diagnosis: A Child with Presumed Reactive Airway Disease,
Pectus Carinatum, and Aortic Root Dilation
Aamir Jeewa, Shaine A. Morris, William J. Dreyer, Iki Adachi,
Susan W. Denfield, E. Dean McKenzie

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 Pediatrics in Review ®

Editor-in-Chief: Joseph A. Zenel, Sioux Falls, SD
Deputy Editor: Hugh D. Allen, Houston, TX
Associate Editor, Index of Suspicion: Philip R. Fischer, Rochester, MN
Associate Editor, Index of Suspicion: Deepak M. Kamat, Detroit, MI
Associate Editor, Visual Diagnosis: Mark F. Weems, Memphis, TN
Associate Editor, In Brief: Henry M. Adam, Bronx, NY
Associate Editor, In Brief: Janet Serwint, Baltimore, MD
Associate Editor, CME: Rani Gereige, Miami, FL
Editorial Fellow: Aamir Jeewa, Toronto, ON
Early Career Physician: Heather Campbell, Washington, DC
Editor Emeritus: Lawrence F. Nazarian, Rochester, NY
Founding Editor: Robert J. Haggerty, Canandaigua, NY
Managing Editor: Luann Zanzola
Publications Editor: Sara Strand
Medical Copyediting: Deborah K. Kuhlman, Lisa Cluver

EDITORIAL BOARD
Robert D. Baker, Buffalo, NY Neal S. LeLeiko, Providence, RI
Peter F. Belamarich, Bronx, NY Michael Macknin, Cleveland, OH
Eyal Ben-Isaac, Los Angeles, CA Susan Massengill, Charlotte, NC
Theresa Auld Bingemann, Rochester, NY Carrie A. Phillipi, Portland, OR
Stephen E. Dolgin, New Hyde Park, NY Peter Pizzutillo, Philadelphia, PA
Lynn Garfunkel, Rochester, NY Mobeen Rathore, Jacksonville, FL
Rani Gereige, Miami, FL Jennifer S. Read, Rockville, MD
Nupur Gupta, Boston, MA E. Steve Roach, Columbus, OH
Gregory A. Hale, St. Petersburg, FL Sarah E. Shea, Halifax, Nova Scotia
Thomas C. Havranek, Bronx, NY Andrew Sirotnak, Denver, CO
Jacob Hen, Bridgeport, CT Miriam Weinstein, Toronto, ON
Jeffrey D. Hord, Akron, OH

PUBLISHER: American Academy of Pediatrics

Mark Grimes, Director, Department of Publishing
Joseph Puskarz, Director, Division of Journal Publishing
Pediatrics in Review® Print Issue Editorial Board Disclosures
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of those in a position to influence and/or control CME content. All individuals in a position to influence and/or control the content of AAP CME activities are required to
disclose to the AAP and subsequently to learners that the individual either has no relevant financial relationships or any financial relationships with the manufacturer(s)
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Disclosures
• Nupur Gupta, MD, MPH, disclosed she has a financial relationship with Springer US as co-editor for MassGeneral Hospital for Children Handbook of Pediatric Global Health.
• Michael Macknin, MD, FAAP, disclosed that: he and his wife each receive a free cruise for his seven one-hour talks annually on general pediatric subjects for University at
Sea; he receives a grant from the Wendel Family Foundation to fund a randomized study comparing various diets, and one member of the Wendel Family produced the
film “Forks Over Knives,” which describes the virtues of a vegan diet.
• Janet Serwint, MD, FAAP, disclosed she has a clinical research grant from the Centers for Disease Control and Prevention for quality improvement for HPV vaccines.
• Andrew Sirotnak, MD, disclosed that he serves as an expert witness in cases of suspected child abuse.
• Miriam Weinstein, MD, has disclosed she receives research funding (through her hospital’s foundation) from LaRoche-Posay.
The journal extends special thanks to the following question writers and ancillary reviewers who contributed to this issue:
–Denise Bratcher, MD
–Melissa Held, MD
–William Walker, MD
–Courtney Wusthoff, MD
Pediatrics in Review offers 36 CME articles per year. A maximum of one AMA PRA Category 1 CreditTM is earned after achieving a 60% score on each designated quiz.
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provider via online submission of answers. Course evaluations are online.

Training to Teach, Teaching to Train
AUTHOR DISCLOSURE Dr Zenel has
disclosed no financial relationships relevant to
this commentary. This commentary does not
contain a discussion of an unapproved/
investigative use of a commercial product/
device.
Commentary
Although privileged to be Editor-in-Chief of Pediatrics in Review (PIR), I am even
more privileged to be a pediatrics residency program director. Training future
pediatricians similarly to the way pediatricians trained me is an opportunity to
instill the inquisitiveness, compassion, and dedication I witnessed in my teachers,
who I now realize wanted to impart their enjoyment, satisfaction, and sense of
purpose to pediatricians yet-to-be. My attending physicians made sure I knew my
patients and their illnesses well enough that when asked, at any time of day or
night, I could give in my own words a quick, succinct synopsis of a patient’s course
and a coherent rationale for that patient’s therapy. Each attending physician had
a different approach, some nurturing, others curt, but all strove to impress upon
an apprentice their personal interpretation of pediatrics. During my 3 years of
residency, thanks to constant faculty oversight, I grew confident in my skills
and took pride in knowing my patients, being responsible for them, and caring for
them. When I graduated and joined a rural practice, I was certain I was trained to
practice well.
What I did not know was that I also was trained to teach. Very soon in clinical
practice, I found that patients and parents frequently asked about the how and
why of disease and the how and why of treatment. Patient and parental acceptance
of my advice depended on understandable, practical explanations given with a
personal spin. Similarly, the cooperation of fellow nurses and physicians de-
pended on how well I could communicate. As I learned to teach, train, write, and
edit over the years, I found career satisfaction in being able to assess, compre-
hend, and pass on that comprehension. I too was contributing my own personal
interpretation of pediatrics. Through those many long rounds during residency,
my wise attendings had trained me to synthesize what I saw, heard, read, and
reported so I could ascribe meaning to my future patients, colleagues, and now,
residents.
Today, residency training is more standardized and formalized. The Accred-
itation Council of Graduate Medical Education (ACGME) requires residency
programs to train residents to be satisfactorily skilled in 6 competencies upon
graduation: patient care, medical knowledge, communication, professionalism,
practice-based learning and improvement, and systems-based practice. These 6
competencies define the essence of a doctor, a healer, an advocate, and a teacher.
A residency program director is expected to model these very same competen-
cies, and I find as a residency program director that these competencies are
reflected in PIR. In other words, the journal, in concert with the American Board of
Pediatrics, provides opportunities for pediatricians to maintain medical knowl-
edge and to improve good patient care by publishing professional communica-
tions that can be applied to the practice of pediatrics in all systems of care.
PIR was established by the American Academy of Pediatrics (AAP) in 1979
with the original purpose of providing useful, valuable, and up-to-date information
Vol. 38 No. 1 JANUARY 2017 1
 for pediatricians in practice. Founding Editor-in-Chief,
Dr Robert Haggerty, basically said the overriding mission of
the journal was to synthesize what pediatric experts saw, heard,
read, and reported and to publish that synthesis in practical
review articles for general pediatricians. Authors were invited
based on their national expertise. Soon, invited experts sought
permission to have their trainees serve as coauthors. Over
time, the journal became a resource for junior faculty to
author a peer-reviewed case report or review article, giving
them a chance to develop a scholarly career. Meanwhile,
thanks to a generous grant, PIR was provided free of charge
to pediatric residents throughout the country, a service that
helped residents synthesize what they saw, heard, read, and
reported. In a sense, the journal developed into a “resi-
dency” primer for pediatricians-to-be while mentoring med-
ical authors-to-be.
Recently, the Executive Board of PIR has witnessed a
trend of submitted articles containing material that has not
been properly cited, thereby creating an impression of false
authorship. PIR relies on authors to synthesize what they
see, hear, read, and have reported. Skipping the synthesis
part short circuits the personal touch that leads to effective
teaching and training. Furthermore, author submissions
that contain unacknowledged sources demean the ACGME
competencies of professionalism, communication, medical
knowledge, and systems-based practice. Because such sub-
missions may be the result of incomplete training, the PIR
Executive Board believes some mentoring is due. In accom-
panying commentaries, Deputy Editor Dr Hugh Allen and
Associate Editor Dr Mark Weems give their personal spin on
plagiarism.
In the spirit of practice-based learning and improve-
ment, PIR continues to evolve. Although continuing medical
education (CME) content is based on the American Board of
Pediatrics (ABP) list of specifications for maintenance of
certification (MOC), the ABP recently streamlined that list,
which gives PIR the opportunity to cover more subjects. One
of the Accreditation Committee on Continuing Medical Edu-
cation (ACCME) missions is to address physicians’ “gaps” in
medical knowledge and practice. Our journal has begun
publishing more review articles on subjects that our Editorial
2 Pediatrics in Review
Board and national experts believe are important for practic-
ing pediatricians but are not covered by the ABP MOC speci-
fications. Another expansion is the number of “Index of
Suspicion” cases per issue. This feature is extremely popular.
Case submissions are growing in number, as is the backlog
of cases to be published. To accommodate this backlog, PIR
will now publish 6 cases per issue.
In the spirit of systems-based practice, acknowledgements
of various teachers and trainers are in order. Dr Hugh Allen,
Deputy Editor, serves as our scholarly statesman. Associate
Editors Drs Deepak Kamat and Philip Fischer of “Index of
Suspicion” and Associate Editors Dr Henry Adam and
2016 AAP Education Award Winner Dr Janet Serwint of
“In Brief” continue to add educational variety to the
journal. Dr Mark Weems, having successfully completed
his editorial fellowship, has taken on the role of Associate
Editor for “Visual Diagnosis.” Associate Editor Dr Rani
Geriege replaces Dr Paula Algranati, who we thank for
overseeing all those edifying CME questions these past
years. The PIR Editorial Board suggests authors and topics,
reviews submissions, and advises the Executive Editorial
Board. Managing Editor Luann Zanzola and Publications
Editor Sara Strand fine-tune the journal and Director,
Division of Journal Publishing Joseph Puskarz, provides
editorial insight.
Being Editor-in-Chief of PIR helps me train as a resi-
dency program director; being a residency program direc-
tor helps me teach pediatricians as Editor-in-Chief. PIR
and residency are uniquely tied together. Although the
grant that provided the printed journal to residents ended a
few years ago, the AAP has continued offering the journal
online to residents. Thanks to residents and residency
program directors continually telling PIR of the value of
the printed journal, AAP will resume providing the printed
journal to residents, starting with this issue. As residents
read this issue, they will add 1 more experience in a long-
established and enduring process of training to teach and
teaching to train.
Joseph A. Zenel, MD
Editor-in-Chief

Plagiarism in Review
AUTHOR DISCLOSURE Dr Weems has
disclosed no financial relationships relevant to
this commentary. This commentary does not
contain a discussion of an unapproved/
investigative use of a commercial product/
device.
Commentary
For more than 35 years, the editors of Pediatrics in Review (PIR) have turned to
content experts to write review articles that can be used by pediatricians in daily
practice. We also understand that our “Index of Suspicion” and “Visual Diagnosis”
sections provide opportunities for young physicians to build their portfolios, and
we welcome case submissions by junior faculty and residents when supervised by
more experienced pediatricians. When I joined the Editorial Board 2 years ago as
the first PIR editorial fellow, I was shocked by a disturbing trend in submitted
articles: plagiarism.
Plagiarism is not unique to PIR. In fact, it is so prevalent in medical
literature that Miguel Roig’s 2013 PubMed search for “plagiarism” resulted
in 1,086 articles. (1) As of August 24, 2016, that number has risen to 1,461.
Plagiarism threatens the authority of our peer-reviewed journal and puts our
publisher, the American Academy of Pediatrics (AAP), at risk for copyright
infringement. In an effort to prevent plagiarized material from being
published, all manuscripts submitted to PIR are screened with Crossref
Similarity Check, powered by iThenticate (Crossref, Lynnfield, MA, and
Turnitin, LLC, Oakland, CA) and compared against a database containing
more than 60 billion documents. This process is described in our author
instructions, but we continue to receive plagiarized manuscripts. Therefore,
we feel it is important to share some deeper insight into the issue of
plagiarism.
Reading through a small selection of the 1,461 PubMed results, I recognize
that it is far easier to condemn plagiarism than to define it. There is general
agreement that plagiarism always involves theft or deception; that is, reusing
another’s words or ideas without properly acknowledging the original author.
(2) However, there is variation among journal editors as to exactly what is
acceptable. (1) The issue is further complicated by attempts to characterize
different types of plagiarism, depending on the context. Steven Shafer, former
Editor-in-Chief of Anesthesia & Analgesia describes 5 types of plagiarism:
“intellectual theft, intellectual sloth, plagiarism for scientific English, technical
plagiarism, and self-plagiarism.”(3)
Intellectual sloth is the most common type of plagiarism we see at PIR. This is
a function of poor copy-paste habits. I believe that many writers do not recognize
the flaw in this behavior. After all, it seems to be encouraged in so many aspects of
modern medical communication. Each traditional medical school multiple-choice
examination is, in essence, an exercise in copy-paste; the student is expected to
reproduce, verbatim, the lesson material that was presented in the textbook. In
the clinical years, bedside teaching reinforces this behavior when higher grades
are awarded to those students who can best regurgitate medical facts rather than
to those students who ask the most challenging questions. In the world of
inpatient medicine, residents become masters of the electronic medical record
Vol. 38 No. 1 JANUARY 2017 3
 copy-paste function. This ensures that all progress note data
are reproduced daily until the final note can simply be
retitled as a discharge summary.
Peer-reviewed medical literature, however, must main-
tain a higher standard; there is no role for the copy-paste
function. When an author employs copy-paste to “use of the
words of another author simply to avoid the effort of writing
new text,”(3) the author deceives the reader by empirically
claiming that the written words are those that have come
from careful review of the literature that is summarized in
the author’s language. The copying of entire paragraphs is
the most blatant example and can be easily recognized as
deception. More frequently, we find mosaic plagiarism in
which an author copies multiple sentences from another
source and stitches them together by changing 1 or 2 words.
This practice is no less deceptive and erodes the trust that
the reader places in the author. Even a small amount of copy-
paste plagiarism can cause a reader to question the authen-
ticity of an entire article or journal.
We commonly find that Wikipedia (Wikimedia Founda-
tion, Inc, San Francisco, CA) is the source for plagiarized
material in submitted manuscripts. This occurs two ways.
First, the submitting author may use Wikipedia as a source
and reference it appropriately, but the plagiarism screening
software recognizes the text as having been copied from
another source. Such plagiarism may occur without the
author’s knowledge, that is, the Wikipedia content was
copied from the original source. Second, the author may
copy Wikipedia text into the manuscript without reference,
taking advantage of Wikipedia’s open license to freely copy
and reuse material. This is an interesting phenomenon
because Wikipedia does encourage readers to use, copy,
and adapt content. Nonetheless, the license requires proper
attribution. A second stipulation of the license is that
content adapted from Wikipedia must retain the same
copyright license as the original material. This may suggest
that PIR articles containing content sourced from Wikipedia
must be licensed to the public, which could violate copyright
agreements made between the submitting author and the
AAP. Personally, I feel that Wikipedia should never be cited
as a source of medical literature. The openly editable content
is not peer-reviewed, and its reliability varies, depending on
whoever last updated the content. Citing Wikipedia puts the
credibility of PIR at risk, and the open license requirements
may put the AAP in legal jeopardy.
As previously described, PIR seeks authors who are
leaders in their field and expects that they have previously
4 Pediatrics in Review
written on the invited topic. This brings up the challenge of
self-plagiarism. Although we do not discourage an author
from reusing his or her own words, the appropriate citation
is necessary to prevent copyright violations and to acknowl-
edge the coauthors and publisher who first produced the
material.
Technical plagiarism, as described by Shafer, is the
simple omission of quotation marks when a reference
has been cited word-for-word. (3) This may be a result of
sloth or accident, but in either case, it is not acceptable and
remains a misrepresentation of one’s work. Intellectual
theft and plagiarism for scientific English rarely occur in
submissions to PIR; these are more applicable to primary
scientific literature.
Since we began plagiarism screening of all submissions,
we have come to realize that the process is much more
sensitive than specific. Nearly every submission has several
phrases identified in the review, and each is examined by a
member of the editorial staff. Common phrases such as “a
15-year-old girl” are ignored. We also see that vital signs,
laboratory values, and simple clinical descriptions are
frequently flagged; these are also generally ignored. Any
remaining large areas of flagged text are reviewed by an
editor, matched against the source, and evaluated on a
case-by-case basis.
If the editors of PIR suspect plagiarism after reviewing
the plagiarism screening report, we follow the recommen-
dations of the Committee on Publication Ethics (COPE).
Generally, this means that we may allow the author to revise
minor copying of short phrases or add quotation marks as
appropriate. More substantial plagiarism, however, results
in a rejection with possible notification to the author’s
academic institution. The AAP has a plagiarism policy that
is consistent with COPE guidelines and standardized across
all AAP publications.
I share these thoughts with you as readers and aspiring
authors. As readers, I hope you continue to trust that PIR
will offer clinically relevant peer-reviewed content to help
guide your pediatric practice. As authors, I hope that you
understand that submitting to PIR should be the culmination
of extensive literature review and meticulous manuscript
preparation. I ask that you review COPE resources available
at http://publicationethics.org/ and consider checking your
manuscript with plagiarism screening software before sub-
mission. Several screening programs are available, but you
can use Crossref Similarity Check, powered by iThenticate,
by paying a usage fee for each document at http://www.
ithenticate.com/products/crosscheck. This will protect you Mark Weems, MD
from unknowingly submitting plagiarized material and will Associate Editor
ensure that your manuscript moves quickly through plagia-
rism screening so you can share your work with PIR readers References for this article are at http://pedsinreview.aappub-
across the world. lications.org/content/38/1/3.

Vol. 38 No. 1 JANUARY 2017 5

 Commentary
Then What?
AUTHOR DISCLOSURE Dr Allen has disclosed
no financial relationships relevant to this
commentary. This commentary does not
contain a discussion of an unapproved/
investigative use of a commercial product/
device.
6 Pediatrics in Review
At all universities, a code of academic integrity is in place that defines academic
misconduct as falsification, fabrication, or plagiarism. Ours is a journal that
concentrates on review articles, interesting cases, or brief commentaries and,
thus, the falsification and fabrication legs of the 3-legged stool are generally not
applicable. Nonetheless, they can occur.
Dr Robert A. Good was a pioneering genius in the field of immunology. He
performed the world’s first bone marrow transplant for severe combined
immunodeficiency disease in 1968. (1) The patient who received that transplant
is still living and is healthy. This miracle treatment opened the pathway for
many applications that today seem commonplace. He received the Lasker award
in 1970 for his work and was in line for a Nobel Prize. His work moved to the
Sloan-Kettering Institute for Cancer Research in New York. There, one of his
fellows, William Summerlin, said he had developed a technique for trans-
planting skin from black mice to white mice and showed that melanocytes
migrated to the white mice, turning their skin to a grey color. Unfortunately,
unbeknownst to Dr Good, this fellow’s success was accomplished by painting
the mouse skin with a marker pen, true research fraud. This is falsification. It
cost Dr Good his job and reputation.
Dr John Darsee (2) was a cardiac researcher at Harvard and Emory universities
who published more than 80 papers that contained fake data. He wrote well and
often but without data to support his hypotheses. This is fabrication. His very
prominent coauthors were mortified and stained by the association.
Let us now progress to the primary problem we are encountering at Pediatrics
in Review: plagiarism. Most high schools, colleges, and universities have an honor
code that specifically prohibits copying the work of others. All medical schools have
a code of academic integrity that prohibits the same. Society expects the same, as
reflected by responses to a recent national convention speech found to contain word-
for-word passages from a previous national convention speech. As a journal, we have
the responsibility to hold a high ethical standard that does not allow copying the work
of others and claiming it to be one’s own. Dr Weems’ commentary nicely addresses
this.
If we detect plagiarism, generally through a software program and occasionally
from reviewers, we are obligated to take certain steps. First, we give the author (via
registered mail) an opportunity to respond. Next we weigh the responses. If, as
a group, the Editorial Board determines that entire paragraphs, tables, and other
items (not bibliography, individual words, standard case report style [see Weems’
commentary]) are plagiarized, the article is rejected. If other articles from the same
author are also plagiarized, they are publicly retracted. The author and his/her
institution are notified, and the author is told not to submit any work to any of the
American Academy of Pediatrics journals.
Once notified, the author’s school of medicine, which has a compliance office,
investigation committee, and due process, can review the situation, usually at the
request of the Dean, and make their own determination, he or she will be hurt. Descent into the cesspool of
which is forwarded to the Dean for determination of out- academic dishonesty might result in drowning or if the
come (which can be dismissal). This not only applies to the author and coauthors emerge from the pool, they will never
lead author but to coauthors as well. There went the Nobel smell like a rosebud.
Prize. DON’T DO IT!
This is serious business. We as editors must be account- Hugh D. Allen, MD
able to our readership. Authors are accountable to the Deputy Editor
integrity of their work. Their institution must be account-
able as well. When an author falls off the 3-legged stool of References for this article are at http://pedsinreview.aappubli-
academic integrity due to 1 or more of the legs being fake, cations.org/content/38/1/6.

Vol. 38 No. 1 JANUARY 2017 7

 Fungal Skin Infections
Aditya K. Gupta, MD, PhD, FRCP(C), FAAD,*† Melissa A. MacLeod, MSc,† Kelly A. Foley, PhD,† Gita Gupta, MD,‡
Sheila Fallon Friedlander, MDx
*Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
†
Mediprobe Research, Inc, London, Ontario, Canada
‡
Wayne State University, Detroit, MI
x
Dermatology and Pediatrics, Pediatric Dermatology Training Program, University of California at San Diego School of Medicine, Rady Children’s Hospital,
San Diego, CA

Education Gap
Most pediatricians appear to be familiar with candidal diaper dermatitis,
but there is a lack of knowledge about other, less common fungal
infections in children.

Objectives After completing this article, readers should be able to:

1. Recognize the clinical presentations of different fungal infections in

children.
2. Know the differential diagnosis of various fungal skin infections.
3. Know what diagnostic tests can be used to confirm infection.
4. Be aware of available treatment options and how to manage the
infections appropriately.
AUTHOR DISCLOSURE Dr A. Gupta has
disclosed that he is on the Speakers’ Bureaus
of Valeant, Janssen, Novartis, and Bayer; he is a
consultant for Anacor, Sandoz, and Moberg
INTRODUCTION Pharma; and he is a clinical trials investigator
for Valeant Canada, Nuvolase, Bristol Meyers
Candidal diaper dermatitis is the most common fungal infection of childhood. Squibb, Eli Lilly, Merck, Novartis, Janssen, and
This yeast infection almost always secondarily invades diaper-area skin that has Allergan. Ms MacLeod and Dr Foley have
disclosed that they are employees of
been damaged by an irritant contact dermatitis from maceration, urine, and/or Mediprobe Research, Inc, which conducts
stool. Children in the preschool-age group who no longer wear diapers are clinical trials under the supervision of Dr. A.
more likely to develop tinea infections, particularly tinea capitis. Tinea refers to Gupta. Drs G. Gupta and Fallon Friedlander
have disclosed no financial relationships
dermatophyte infections in the epidermis and areas high in keratin, such as the
relevant to this article. This commentary does
hair and nails. In prepubertal children, tinea capitis and tinea corporis are most contain a discussion of an unapproved/
common; in adolescence, tinea pedis (TP), tinea cruris, and tinea unguium investigative use of a commercial product/
device.
(onychomycosis) are more common. (1) Yeast infections other than candidal
diaper dermatitis, including pityriasis versicolor (PV) (formerly known as tinea ABBREVIATIONS
versicolor) and mucocutaneous candidiasis (MC), may also occur. Chronic MC CMC Chronic mucocutaneous candidiasis
(CMC) is a rare, usually inherited disorder. PV is a common infection in adolescents HIV Human immunodeficiency virus
and adults that usually affects the sebum-prone areas (face, chest, back). Fungal id Dermatophytid
KOH Potassium hydroxide
infections can be a substantial source of morbidity in the pediatric population,
MC Mucocutaneous candidiasis
accounting for about 15% of pediatric outpatient visits in the United States. (2) PCR Polymerase chain reaction
This article reviews the epidemiology and clinical presentations of tinea in- PV Pityriasis versicolor
fections (capitis, corporis, pedis, cruris, unguium), PV, and MC in children. The TP Tinea pedis

8 Pediatrics in Review
differential diagnosis and methods for confirming diagnosis
based on clinical presentation are discussed. Recommended
treatment options for each type of infection are specified
(Table 1). Of note, many recommendations are off-label, as the
safety of many agents has not been established for children.
TINEA CAPITIS
Epidemiology
Tinea capitis, a communicable fungal infection of the scalp
and hair shaft, is the most common fungal infection in
children. (3) The prevalence ranges from less than 1% in
western Europe to as much as 50% in Ethiopia where the
infection is endemic. (4) In North America, the prevalence is
estimated to range from 3% to 8% in children. It is unclear
whether it is increasing, but immigrant populations, par-
ticularly those from Africa, are at higher risk. (5) Tinea
capitis most often affects children between ages 3 and 9
years, those of African heritage, those of low socioeconomic
status, and those residing in urban settings and/or crowded
living conditions. (1)(4) Prior to the 1950s, Microsporum
TABLE 1. Summary of Treatment Recommendations for Tinea Infections
in Children*
INFECTION FIRST-LINE TREATMENT
Tinea capitis Oral antifungals: terbinafine, griseofulvin
(Microsporum canis)
Tinea corporis/ Topical antifungals: butenafine, ciclopirox,
Tinea cruris clotrimazole, miconazole, terbinafine,
tolnaftate
Tinea pedis Topical antifungals: butenafine, clotrimazole, Topical antifungals: ciclopirox
miconazole, terbinafine
Oral antifungals (resistant or recurrent
Pityriasis versicolor Zinc pyrithione, selenium sulfide, or
ketoconazole shampoos
Other topical antifungals: clotrimazole,
ketoconazole, miconazole, terbinafine
Tinea unguium Topical antifungals: ciclopirox, efinaconazole, Oral antifungals (severe infection):
(onychomycosis) tavaborole
MC – Oropharyngeal Mild: Clotrimazole troches, miconazole,
candidiasis nystatin suspension
Moderate-severe: fluconazole
MC – Esophageal Fluconazole
candidiasis/CMC
*Some agents may be used off-label usage in children or be approved for particular ages. See Table 3 for details.
CMC¼chronic mucocutaneous candidiasis, MC¼mucocutaneous candidiasis.
audouinii was the major source of tinea capitis in North
America. (6) Subsequently, epidemiology shifted and cur-
rently about 95% of tinea capitis in North America is caused
by Trichophyton species (predominantly T tonsurans). Micro-
sporum species, (7) usually transmitted by pets, causes the
remainder of the cases. However, in central and southern
Europe as well as in developing countries, M canis is the
most common causal species. (7) It is important for clini-
cians to be aware of the predominant pathogen in their
communities because this has implications for optimal
treatment choice.
Clinical Presentation
Tinea capitis may be difficult to diagnose because clinical
signs may be subtle and can vary substantially from child to
child. Symptoms may include scaling, alopecia, broken hair
shafts at the scalp, erythema, pustules, and/or large boggy
scalp masses. Patients may complain of pruritus or tender-
ness, and occipital and posterior cervical adenopathy are often
present (Fig 1). A nonspecific, eczematous, pruritic eruption
may be noted on the trunk and extremities either before or
ALTERNATIVES TERTIARY OPTIONS
Adjunctive agents: selenium sulfide Itraconazole, fluconazole
shampoo, ketoconazole shampoo
Oral antifungals (resistant or severe
infection): terbinafine, griseofulvin,
itraconazole, fluconazole
Urea cream
infection): terbinafine, itraconazole,
fluconazole
Oral antifungals (resistant, recurring, serious
infection): itraconazole, fluconazole
Itraconazole, fluconazole
terbinafine
Fluconazole-resistant infections: Amphotericin B
itraconazole, posaconazole suspension
Intravenous fluconazole, echinocandin Amphotericin B
(anidulafungin, caspofungin, micafungin)
Fluconazole-resistant infections:
itraconazole, voriconazole, amphotericin
B, or an echinocandin
Vol. 38 No. 1 JANUARY 2017 9
 during treatment; this is known as an autoeczematization or
dermatophytid (id) eruption. Tinea capitis typically presents
as 1 of 6 clinical patterns: gray type, black dot, diffuse scale,
pustular type, favus, and kerion. Gray type is characterized
by circular patches of alopecia and marked scaling with or
without erythema. (4)(8) Black dot presents with patches of
alopecia and is dotted with broken hair stubs (“black dots”).
Diffuse scale is characterized by widespread scaling and is
dandruff-like, with or without erythema. Pustular type pre-
sents as alopecia with scattered pustules, scaling, and lymph-
adenopathy. Favus has distinctive yellow cup-shaped crusting
around the hair called scutula, along with patchy alopecia
and generalized scale; this variant is extremely rare and not
usually seen in the United States. Kerion is a boggy tumor
with pustules, lymphadenopathy, erythema, and tenderness.
(4)(8) It is the most severe inflammatory response and can
be caused by either T tonsurans or M canis. (9) When chil-
dren present without distinguishing characteristics of tinea
capitis such as black dot alopecia or kerion, diagnosis may be
simplified by recognizing clusters of symptoms. Hubbard
(10) found that children with adenopathy, alopecia, pruritus,
and scaling were most likely to have a positive culture. Some
dermatologists now use scalp dermoscopy (visualization of
scalp and hair shaft with magnification and light) to increase
diagnostic accuracy; corkscrew and comma-shaped hairs are
frequently seen in fungal scalp infections. (11)
Differential Diagnosis
Because of its broad and varying symptoms, tinea capitis
has a substantial differential diagnosis. Among the possi-
bilities are alopecia areata, atopic dermatitis, bacterial scalp
abscess, seborrheic dermatitis, trichotillomania, traction alo-
pecia, psoriasis, lichen planopilaris, lupus erythematosus, syph-
ilis, and Langerhans cell histiocytosis (Table 2). (1)(3)(6)
Figure 1. Tinea capitis. Photo courtesy of Dr Avner Shemer, The Chaim
Sheba Medical Center Israel.
10 Pediatrics in Review
Diagnostic Tests
Clinical diagnosis should be confirmed via either potassium
hydroxide (KOH) microscopy or culture. Culture is prefer-
able because speciation is provided, allowing determination
of the most appropriate treatment option. Polymerase chain
reaction (PCR) evaluation of dermatophyte infections has
become much more cost effective and “kits” are now avail-
able, which is likely to lead to wider availability of this
exceedingly rapid and sensitive test in the next few years.
At this time, PCR appears more sensitive for nail and skin
infections than for hair samples. (12) Wood’s light exami-
nation causes Microsporum species to fluoresce, but most
infections in North America are caused by T tonsurans, which
does not fluoresce. (13) Pathogens that do fluoresce include
Microsporum species and Trichophyton schoenleinii. (7) Under
microscopic analysis, an infected hair can present with
mycelium (mass of fungal hyphae) on the external surface
of the hair shaft (ectothrix) or with mycelium within the hair
shaft (endothrix). (7) A favus infection presents with fungal
hyphae and characteristic airspaces within the hair shaft. (7)
Wood’s light analysis takes minutes to complete compared
with 1 to 4 weeks required for culture results, which are
accompanied by low culture-positive rates, all of which may
delay treatment and increase the spread of infection. (10)
A reasonable course is to start treating children with
typical presentations before culture confirmation, although
a culture should be attempted. Samples may be obtained
either from plucked hairs or cotton swabs that have been
premoistened and rolled over the affected site and are
inoculated into transport culture. (14)
Kerion (abscesses filled with purulent exudate) should be
treated aggressively with systemic antifungal medication
pending laboratory results because if left untreated, perma-
nent hair loss and scarring may occur. Unfortunately, the
degree of inflammation noted in a kerion is not linked to the
fungal burden, and cultures may sometimes be negative.
However, every attempt should be made to swab the kerion
area as well as other areas of the scalp with a cotton swab.
Tinea capitis infection may spread from the scalp to other
areas of the body (eg, causing tinea corporis) and secondary
bacterial infections (eg, Staphylococcus aureus) may occur. (15)
If children are unlikely to have an infection (eg, no adenop-
athy and scaling), experts recommend confirming infection
via KOH microscopy or a culture before treatment. (4)
Treatment
Systemic treatment is required to penetrate hair shafts.
Traditionally, griseofulvin was considered the treatment of
choice, (16) but a Cochrane collaborative analysis found that
terbinafine, fluconazole, and itraconazole are as effective as
TABLE 2. Differential Diagnosis of Tinea Capitis (1)(2)(6)
DISORDER DISTINGUISHING CHARACTERISTICS OF CLINICAL PRESENTATION

Alopecia areata
Atopic dermatitis
Bacterial scalp abscess
Seborrheic dermatitis
Trichotillomania
Traction alopecia
Psoriasis
Lichen planopilaris
Lupus erythematosus
Syphilis
Langerhans cell histiocytosis
Patches of hair loss; total loss of hair; fine miniature hair growth; exclamation point hairs; can involve
eyebrows, eyelashes, beards; possible nail pitting
Uncommon: scaling, crusting, inflammation (consider infection, other diagnoses)
Personal or family history of atopy, may appear on face
Uncommon: alopecia, large posterior occipital or cervical nodes, erythema of scalp usually minimal with
diffuse faint scales common
Culture should be used to distinguish from kerion
Greasy scaling, typical distribution includes nasolabial folds, hairline, eyebrows, postauricular folds, chest
Uncommon: alopecia and significant lymphadenopathy
Often involves eyelashes and eyebrows, hairs of varying lengths, scaling uncommon, large geometric
shapes of alopecia present
Hair loss in areas under tension; folliculitis may also be present
Gray or silver scaling that extends beyond scalp line, nail pitting, family history, involvement of other sites
Often affects skin, mucosa, and nails; no hair follicles seen in areas of hair loss; slowly progressive
Involves skin, especially face and sometimes connective tissue of internal organs; discoid lesions can lead
to scarring
Involves other areas of the body, not pruritic, scaling uncommon
May involve buttocks, liver problems causing jaundice, fluid in the belly, bulging eyes or eye problems

griseofulvin, with shorter periods of treatment with newer
antifungals achieving similar results to griseofulvin. (17) For
Trichophyton species, terbinafine is preferable, but this agent
is not as effective as griseofulvin for Microsporum species.
(17)(18) When a child presents with a lesion highly suspi-
cious for Microsporum species (eg, infected cat or dog at
home, and/or lesion fluoresces under Wood’s lamp), gris-
eofulvin should be used. Most experts believe that effective
treatment doses of griseofulvin should be higher than
advised in the package insert (Table 3). If griseofulvin is
not available or terbinafine is preferred, the duration of
treatment for Microsporum species may be longer compared
to the duration for Trichophyton species. The duration of
treatment for terbinafine is generally 4 to 6 weeks, and
continuing treatment for 2 weeks after symptoms resolve
may be beneficial. (8) Griseofulvin therapy is generally used
for 8 weeks, but many experts reevaluate a child after 4 to 6
weeks of therapy to consider discontinuation. Some systemic
antifungals, such as itraconazole and fluconazole, have been
successfully used for pediatric tinea capitis, but such use is
off-label, and a large multinational study investigating flu-
conazole reported cure rates below those seen with either
griseofulvin or terbinafine. (40) Nonetheless, fluconazole
has been widely used in children for candidiasis and may be
an option when other agents are either not available or not
covered by the patient’s insurance plan (Table 3).
Adjunctive therapy with either selenium sulfide sham-
poo (1% or 2.5%) (41) or ketoconazole shampoo should be
used to decrease the spread of infection. (1)(42) Because
tinea capitis is communicable, children should not at-
tend school or child care until treatment has started. Once
treatment has begun, the child may return to school but
should not share combs, brushes, helmets, or other items
that come in contact with the scalp or play contact sports for
14 days to avoid transmission. (1) Household members
should be queried and clinically examined for signs and
symptoms if possible and mycologically tested if these
exist. The use of selenium sulfide shampoo or ketoconazole
shampoo prophylactically (2 times/wk for 2-4 weeks) is
controversial, and no clear evidence-based data support
its use for this purpose, although some experts recommend
this. Some also recommend the same prophylaxis for peo-
ple outside the home in close contact with the child. (1)(4)
Close contacts include other children seen daily, such as in a
classroom or child care. Although this process may seem
daunting, families at least should be informed so that chil-
dren can be monitored for signs and symptoms and given
the option to engage in prophylactic treatment.
In some cases, patients may develop an immune re-
sponse to the fungus triggered by treatment, known as
an id reaction. It often presents as a pruritic, papular, or
vesicular rash on the face and body and may be alleviated by

Vol. 38 No. 1 JANUARY 2017 11

 TABLE 3. Antifungal Agents for Fungal Infections in Children
APPLICABLE MONITORING OTC OR
ANTIFUNGAL DOSAGE DURATION INFECTIONS NOTES GUIDELINES PRESCRIPTION

Topical:
Butenafine 1% cream, twice 1 week Tinea corporis, tinea Children 12þ years OTC
hydrochloride daily (19) pedis, tinea cruris
Ciclopirox 0.77% cream, twice 1 week Tinea corporis, tinea Safety in children <10 OTC
daily (20) pedis, tinea cruris years has not been
established
When topical
clotrimazole and
miconazole fail
8% lacquer, daily 48 weeks Onychomycosis Considered safe for 12þ Prescription
with weekly years
professional
debridement
Clotrimazole 1% cream, twice 4 weeks Tinea corporis, tinea Children 2þ years OTC
daily (21) pedis
1% cream, twice 2 weeks Tinea cruris Children 2þ years OTC
daily (21)
1% cream, twice 1-2 weeks Pityriasis versicolor Children 2þ years OTC
daily (22)
Efinaconazole 10% solution, daily 48 weeks Onychomycosis Safety and efficacy not Prescription
established
Ketoconazole 2% once (23) Once Tinea capitis To decrease spread of OTC
shampoo infection as an
adjunct therapy
Safety in children not
established
2% daily (22) 3-14 days, up to Pityriasis versicolor See above for safety OTC
4 weeks Following treatment, use
monthly for 3 months
to prevent recurrence
Miconazole 2% cream, twice 4 weeks Tinea corporis, tinea Children 2þ years OTC
daily (24) pedis
2% cream, twice 2 weeks Tinea cruris Children 2þ years OTC
daily (24)
2% cream, once or 2 weeks Pityriasis versicolor Children 2þ years OTC
twice daily (22)
Selenium 1% or 2.5% 2 times Duration of oral Tinea capitis To decrease spread of OTC for 1%
sulphide a week (25) treatment infection as an
shampoo adjunct therapy
Safety in children <12 Prescription
years has not been for 2.5%
established for 2.5%
1% (shampoo) or 1-2 weeks, up to Pityriasis versicolor See above for safety OTC
2.5% (lotion) 4 weeks Following treatment,
daily (22) use monthly for 3
months to prevent
recurrence
Tavaborole 5% solution daily 48 weeks Onychomycosis Safety and efficacy not Prescription
established
Terbinafine 1% cream twice 1-2 weeks Tinea corporis, tinea Children 12þ years OTC
daily (26) pedis, tinea cruris
When topical clotrimazole
and miconazole fail
1% cream once or 1-2 weeks Pityriasis versicolor Children 12þ years OTC
twice daily (22)
Continued

12 Pediatrics in Review
TABLE 3. (Continued )

APPLICABLE MONITORING OTC OR

ANTIFUNGAL DOSAGE DURATION INFECTIONS NOTES GUIDELINES PRESCRIPTION

Tolnaftate 1% cream twice 4 weeks Tinea corporis, tinea Children 2þ years OTC
daily (27) pedis, tinea cruris
Urea cream 39% twice daily Not available Tinea pedis Safety in children not OTC
(28) established
When topical terbinafine
and ciclopirox fail
Oral:
Clotrimazole 10 mg 5 times a 2 weeks MC Children 3þ years (need Prescription
troches day (29) to swallow them
properly)
Fluconazole 3-6 mg/kg daily (30) 2-3 weeks, Tinea capitis, For mild-to-severe MC Liver tests, Prescription
(tablet) 12 mg/kg daily for additional 2 tinea corporis, Extensive or resistant exercise
neonates (31) weeks after tinea pedis, tinea infections when caution if liver
Loading dose first symptoms tinea cruris, not tinea capitis dysfunction
day resolve MC
3-6 mg/kg weekly FN: 12 weeks Onychomycosis Not approved for See above Prescription
(32) TN: 26 weeks onychomycosis
Griseofulvin* 10 mg/kg daily (33) 6-8 weeks tinea Tinea capitis, tinea Children 2þ years Prescription
(microsize) up to 20-25 mg/kg capitis, 4-8 corporis, tinea Extensive or resistant
daily weeks tinea pedis, tinea cruris tinea infections when
pedis not tinea capitis
Itraconazole 5 mg/kg daily 4-6 weeks MC, tinea capitis, Safety not established in Liver tests, Prescription
(capsules) (1)(31) tinea corporis, children exercise
tinea pedis, For fluconazole- caution if liver
tinea cruris, resistant MC dysfunction
onychomycosis Extensive or resistant
tinea infections when
not tinea capitis
Pulse (1 week on FN: 2 pulses Efficacy and safety not See above, do Prescription
therapy, 3 weeks TN: 3 pulses established in children not use if
off) congestive
10-20 kg: 50 mg heart failure
every other day,
3x/week; 20-30 kg:
100 mg/day;
30-40 kg:
100 mg/day
alternating
200 mg/day;
40-50 kg: 200
mg/day; >50 kg:
200 mg 2x/day
(32)
Nystatin 100,000 U/mL, 4-6 48 hours after MC Prescription
suspension mL, 4 times a symptoms
day for older resolved
children, 2 mL
for younger
children (34)
Terbinafine 125 mg/day for 6 weeks Tinea capitis, tinea Children 4þ years ALT, AST, do not Prescription
(oral granules) <25 kg corporis, tinea use if liver
187.5 mg/day for pedis, tinea cruris dysfunction
25-35 kg Extensive or resistant
250 mg/day for tinea infections when
>35 kg (35) not tinea capitis
Continued

Vol. 38 No. 1 JANUARY 2017 13

 TABLE 3. (Continued )

APPLICABLE MONITORING OTC OR

ANTIFUNGAL DOSAGE DURATION INFECTIONS NOTES GUIDELINES PRESCRIPTION

Terbinafine Same dosage as FN: 6 weeks Onychomycosis Efficacy and safety not See above Prescription
(tablets) above TN: 12 weeks assessed in children
Amphotericin B 0.25-1.5 mg/kg Based on MC Safety in children not Renal, liver, Prescription
daily (36) severity established hematologic
When clotrimazole, tests, monitor
nystatin, fluconazole, electrolytes
itraconazole fail
Anidulafungin 0.75-1.5 mg/kg 2 weeks after MC Safety not established in Prescription
daily (37)(38) last positive children <16 years
culture When clotrimazole,
nystatin, fluconazole,
itraconazole fail
Caspofungin Loading dose of About 2 weeks, MC Safety not established in Prescription
70 mg/m2, followed may be more children <12 months
by 50 mg/m2 When clotrimazole,
daily nystatin, fluconazole,
itraconazole fail
Micafungin 2-3 mg/kg daily for About 2 weeks, MC Safety not established in Prescription
children £ 30 kg may be more children <4 months
2-2.25 mg/kg daily or less When clotrimazole,
for children >30 nystatin, fluconazole,
kg (39) itraconazole fail

ALT¼alanine aminotransferase, AST¼aspartate aminotransferase, FN¼fingernails, MC¼mucocutaneous candidiasis, OTC¼over-the-counter,

TN¼toenails.
*Griseofulvin is no longer available in Canada. Other than griseofulvin, all of the drugs listed have been approved and are available for use in the United
States and Canada, but they are not all indicated for use in children, as specified in the Notes column of the table.
This review is limited to the United States and Canada. Information is based on package inserts obtained from the National Institutes of Health, United
States National Library of Medicine, DailyMed; United States Food and Drug Administration Approved Drug Products Database; and Health Canada’s Drug
Product Database.
Please check the regulatory status of each drug in your jurisdiction. Check for current dosing and monitoring guidelines. Table 3 is presented as a guide only.

topical corticosteroids and systemic antihistamines. How-
ever, an id reaction does not necessarily require discontinu-
ing treatment and may occur before institution of therapy.
(13)(43) This reaction should be distinguished from a drug
reaction, but id reactions are much more common. (5)
TINEA CORPORIS
Epidemiology
Tinea corporis is a dermatophyte infection of the body, often
referred to as ringworm. It can be caused by any dermato-
phyte that infects humans. Among young children, acute
infections may be caused by M canis from contact with dog
or cat carriers. (2) However, in North America, it is most
commonly caused by Trichophyton species, especially T
tonsurans and Trichophyton rubrum. (2)(3)(4) Tinea corporis
may be spread by close body contact and has been found to
be more prevalent in warm and moist environments and
among wrestlers (tinea corporis gladiatorum), where it is
often limited to the neck and arms but may also involve the
scalp. (2)
Clinical Presentation
Tinea corporis presents as a single or multiple red, scaly
papules (sometimes follicular) that may spread and com-
bine, forming plaques that tend to be annular and clear in
the center. (2) The plaques generally are limited to a few
sites on the body and are usually unilateral (Fig 2). (2) Mild
erythema, edema, vesicles, pustules, or bulla formation can
occur, and the sites may be pruritic. (2) The presence of
pustules and inflammation tends to be more common with
infections caused by M canis whereas follicular infections
are often caused by T rubrum. (2) In addition, follicular
inflammatory reactions are more common among patients
who have used topical corticosteroids. (2) Because the use
of topical corticosteroids (eg, when atopic dermatitis is

14 Pediatrics in Review
suspected) may alter the appearance of tinea corporis (tinea
incognito), physicians should use clinical judgement in
obtaining a sample for KOH microscopy for annular scaly
skin lesions, particularly for those lesions that have an
atypical appearance. (4)
Differential Diagnosis
The differential diagnosis of tinea corporis includes gran-
uloma annulare, nummular eczema, erythema multiforme,
erythema annulare centrifugum, psoriasis, pityriasis rosea,
subacute cutaneous or discoid lupus, atopic dermatitis,
candidiasis, fixed drug eruption, early Lyme disease, and
seborrheic dermatitis. (1)(2) These conditions often have
several characteristics that distinguish them from tinea
corporis. For example, granuloma annulare is smooth; has
no scaling, vesicles, pustules, or pruritus; and is often nod-
ular (dermal with no epidermal component) and present
on the dorsum of the hands or feet. (1) Histologically the
epidermis is not affected; rather, inflammation is in the
dermis. (4) Nummular eczema is less likely to have central
clearing and has more convergent scaling while erythema
multiforme is characterized by acute-onset target lesions
(sometimes oral) without scaling. (1) For additional differen-
tiating characteristics, please refer to Ely et al (1) and Kelly. (4)
Figure 2. Tinea corporis. Photo courtesy of Dr Avner Shemer, The Chaim
Sheba Medical Center Israel.
Diagnostic Tests
Diagnosis can be confirmed with KOH microscopy or a
culture, although cultures are usually not needed.
Treatment
Topical antifungals are generally effective and should be
used for 1 additional week after symptoms resolve. (2) Some
have suggested that butenafine and terbinafine are more
effective than miconazole and clotrimazole. (3) Topical corti-
costeroids eventually worsen the infection and should not be
used. When topical treatments fail or infections recur, oral
antifungals may be needed. This is often the case for those
who have had prolonged pretreatment with topical cortico-
steroids, those who have follicular infections, and for indi-
viduals who are immunocompromised because they often
have extensive and severe infections. Because tinea corporis is
more common in warm and humid environments, the skin
should be kept cool and dry to promote healing. (2)(4)
TINEA PEDIS
Epidemiology
TP, known as athlete’s foot, is largely caused by T rubrum
and Trichophyton mentagrophytes. Athlete’s foot is most
common among adolescents and is relatively rare among
prepubertal children. Prevalence is estimated to be approx-
imately 3% to 9% in children. (44)(45)(46)(47)(48) Because
TP is uncommon among children, it is often misdiagnosed.
(49) This can be problematic because treatment with topical
corticosteroids may alter the clinical appearance, making
subsequent diagnosis difficult. (50)
Clinical Presentation
Symptoms of TP include erythema, scaling, fissures, mac-
eration, and pruritus between the toes extending to the
soles, borders, and sometimes the dorsum of the foot
(Fig 3). Onychomycosis may occur concomitantly. (1) The
3 typical presentations are intertriginous dermatitis (inter-
digital), “moccasin” pattern, and vesicular. Interdigital TP
is the most common presentation and is characterized by
scaling (usually between the fourth and fifth toes (9) because
for anatomic reasons this web space tends to be the most
occluded), maceration, pruritus, and fissuring of the lateral
toe web spaces that may spread to the soles and dorsum of
the foot. (51) This presentation often starts in the toe web
where maceration and moisture are present. (9) Moccasin
TP is typically chronic and is characterized by dry scaling
patches or hyperkeratotic plaques, erythema on the soles
and border of the foot, and possibly tenderness or pruritus.
Vol. 38 No. 1 JANUARY 2017 15

Figure 3. Tinea pedis. Photo courtesy of Dr Avner Shemer, The Chaim
Sheba Medical Center Israel.
(51) This presentation may also involve infection of the nails
(onychomycosis) and hand (tinea manuum). (9) The vesic-
ular presentation is characterized by vesicles and pustules
that are often on the anterior sole or instep but can occur on
all areas of the foot (51), often accompanied by intertriginous
infections. (9)
Differential Diagnosis
TP may appear similar to contact dermatitis, dyshidrotic
eczema, foot eczema, juvenile plantar dermatosis, and pso-
riasis, although TP is generally more likely to affect the
intertriginous areas. (3) However, Guenst (51) argues that
TP should be included as a differential diagnosis for every
child who presents with a foot rash. Contact dermatitis can
be distinguished from TP because the distribution gener-
ally matches the footwear. (1) Dyshidrotic eczema uniquely pre-
sents with vesicles on the lateral aspects of the digits and often
involves the hands. Children with foot eczema may have an
atopic history. Juvenile plantar dermatosis is characterized by
shiny, taut skin involving the great toe, ball of the foot, and
heel. Psoriasis usually involves other sites and presents with
gray or silver scale, nail pitting or other nail signs, occasionally
arthritis, and possibly a family history. (1)
Diagnostic Tests
In cases with a typical presentation, diagnosis based on
appearance may be adequate; when the presentation is
atypical, KOH microscopy or a culture is recommended. (1)
KOH microscopy may be difficult with vesicular presenta-
tions because samples should be taken from the root of the
vesicle. (9)
16 Pediatrics in Review
Treatment
Topical antifungals such as azoles or allylamines are usually
effective in treating TP, with the duration of therapy rang-
ing from 1 to 4 weeks based on the agent (Table 3). First-
line treatment is generally topical clotrimazole, miconazole,
naftifine, or terbinafine. If such therapy is unsuccessful, the
patient should be reevaluated and other topical agents can be
used, including ciclopirox (52) and butenafine hydrochlo-
ride. (3) Upon failure of other topical treatments, high-
potency urea cream is a consideration as adjunctive therapy.
This agent functions as both a keratolytic and humectant
(to keep moist) and is useful in removing scale. (28)(52)
Patients should thoroughly dry their feet before applying
topical antifungals. Wearing breathable shoes with 100%
cotton socks changed twice daily also is recommended. (51)
Adjunctive treatments such as topical antiperspirants (eg,
aluminum chloride) may be used if there is extreme sweat-
ing. (2) Cool tap water or Burow’s solution soaks may help
relieve discomfort, particularly if secondary bacterial infec-
tion is suspected. (52)
If the infection is extensive or involves the toenails, is
recalcitrant or recurrent, or presents in immunosuppressed
patients or as moccasin TP, systemic therapy (eg, terbina-
fine, fluconazole, itraconazole) may be required. (51)(52)(53)
In moccasin type TP, topical treatment is typically only
useful for reducing the spread of lesions. (9) With extensive
maceration, bacterial infection (ie, dermatophytosis com-
plex) also may occur, requiring simultaneous antibiotic
therapy. (2)(52) As with tinea capitis, an id reaction may
occur with treatment, but the hand is usually the first place
to react in TP. (9)
TINEA CRURIS
Epidemiology
Tinea cruris (jock itch) primarily affects adolescent and
young adult males; it is less common among children. Risk
factors include diabetes, obesity, crowded living conditions,
tight or wet clothing in the groin area, membership in a
sports team, and a fungal infection on another part of the
body. (54) In North America, jock itch is most often caused
by T rubrum, although Epidermophyton floccosum is also a
common pathogen. (2) It can be spread by fabric such as
clothing, towels, and sheets as well as by direct contact,
especially in warm and humid environments. (2) A person
who has tinea cruris may also have tinea pedis because they
can both be caused by T rubrum. (2) Accordingly, the feet
should always be examined in a child presenting with tinea
cruris. (54)
Clinical Presentation
Tinea cruris occurs on the upper-medial thighs with bor-
ders that generally spread outwards, possibly extending to
the buttocks and above the waistline. It usually spares the
scrotum (in contrast to candidal infections) and is charac-
terized by edema, erythema, skin-colored (hyperpigmented)
scaling, papules or plaques that can become vesicles or pus-
tules, and often maceration. (2) Compared to tinea corporis,
there is usually less central clearing and inflammation. (2)
Tinea cruris is typically very itchy, and scratching of the skin
may create lichenification as well as thickening of the scrotal
skin. This may falsely create the appearance of an infection
involving the scrotum. (2) However, the scrotum may be
involved if candidiasis is also present. Clinical presentation
can be further complicated if the use of topical medications
results in allergic contact dermatitis. (2)
Differential Diagnosis
The differential diagnosis of tinea cruris includes candidal
intertrigo, erythrasma, inverse psoriasis, and seborrheic
dermatitis. Tinea cruris is generally the only one of these
conditions that does not affect the scrotum and penis. (1)
Distinguishing features of candidal intertrigo include in-
volvement of the scrotum, satellite lesions, and uniform
redness. (1) Erythrasma is typically red-brown and does not
have a border. It can be distinguished from tinea cruris
under Wood’s light as it fluoresces coral-red. (1)(2) Inverse
psoriasis is red, clearly distinguished by boundaries, and
may involve nail pitting. Seborrheic dermatitis involves
greasy scaling in the nasolabial folds, hairline, eyebrows,
postauricular folds, and chest; lesions are generally not
annular. (1) Tinea cruris may also appear similar to contact
dermatitis, lichen simplex chronicus, pityriasis versicolor,
Darier disease, Majocchi granuloma, Langerhans cell his-
tiocytosis, and pemphigus vegetans. (54)
Diagnostic Tests
KOH microscopy of skin scrapings from the periphery of
the lesion should be used to confirm diagnosis. Hyphae in
the middle of healthy superficial stratum corneum (known
as the “sandwich sign”) as well as a deeper parakeratotic or
hyperkeratotic stratum corneum may be visible if biopsy
is performed. (54) A culture can also be used to confirm
diagnosis. PCR may be the diagnostic option of choice in
the future.
Treatment
Treatment with topical antifungals, including clotrimazole,
miconazole, tolnaftate, and butenafine, is usually adequate.
They should be applied as directed on the affected area and
2 to 3 cm beyond. (54) Oral itraconazole, terbinafine, or
fluconazole may be needed to treat extensive or resistant
infection. Griseofulvin is not recommended because it ad-
heres poorly to keratinocytes in the stratum corneum. (54)
Combined treatment with corticosteroids and oral ketocona-
zole is also not recommended. (55) Throughout treatment,
the affected area should be kept dry and patients should wear
loose-fitting clothing and use a separate towel for the groin
area after bathing. (54)
TINEA UNGUIUM (ONYCHOMYCOSIS)
Epidemiology
Tinea unguium, widely referred to as onychomycosis to
account for fungal infection due to dermatophytes, non-
dermatophyte molds, and/or yeasts, is a therapeutically
challenging condition that usually requires systemic ther-
apy. The pooled prevalence of culture-confirmed onycho-
mycosis in childhood has been estimated at 0.14%. (56) Risk
factors include concomitant TP, family members with TP
and/or onychomycosis, and frequent wearing of occlusive
footwear (as in organized sports). The most common caus-
ative organisms are the dermatophytes T rubrum and Tri-
chophyton mentagrophytes. Toenails are more commonly
affected, although fingernail onychomycosis caused by yeast
may be seen in children younger than age 6 years. (57)
Clinical Presentation
Features of tinea unguium may include thickened and
dystrophic nails, discoloration ranging from whitish to brown,
onycholysis, and/or destruction of all or part of the nail plate
(Fig 4). Distal lateral subungual onychomycosis is the most
common subtype in all groups, but superficial white ony-
chomycosis, which is characterized by white lesions, is more
common in children. Proximal subungual onychomycosis
may indicate immunocompromise. Concomitant TP, 2 or
more affected nails on the same foot, or unilateral dystrophy
of the first and fifth nails may be predictive. (58) When only
1 digit is involved, the possibility of a subungual exostosis
(bony projection) should be considered, and radiologic
evaluation should be performed, particularly if the patient
does not respond to antifungal therapy.
Differential Diagnosis
A number of conditions have similar presentations to ony-
chomycosis, including nail trauma, paronychia, psoriasis,
subungual exostosis, and contact/atopic dermatitis. Wait-
ing a short period may lead to resolution of symptoms (ie,
from trauma) because children have thinner nail plates
Vol. 38 No. 1 JANUARY 2017 17

Figure 4. Onychomycosis. Photo courtesy of Dr Avner Shemer, The
Chaim Sheba Medical Center Israel.
and faster growing nails. Onychomycosis must be con-
firmed with mycologic testing before initiating systemic
therapy.
Diagnostic Tests
A positive KOH or periodic acid-Schiff stain and positive
fungal culture are required for diagnosis. Topical therapy
may be started before diagnosis, but identification of the
infecting organism allows for selection of the most appro-
priate systemic therapy. PCR, if available, may also be used
and provides results more quickly than culture.
Treatment
In adults, mild-to-moderate disease (£50% nail involve-
ment) with no matrix involvement allows for consideration
of the use of topical antifungals in lieu of systemic drugs.
Until recently, ciclopirox was the only topical antifungal
available in North America, prescribed off-label (amorolfine
is available in the European Union). One small clinical trial
has demonstrated the efficacy of ciclopirox in children. (59)
Efinaconazole and tavaborole received US Food and Drug
Administration approval in 2014. The safety and efficacy of
these topical antifungals have not been established in chil-
dren. However, in a child with mild-to-moderate onycho-
mycosis, particularly if there is no involvement of the nail
matrix, and perhaps even in more severe disease, the topical
solutions efinaconazole and tavaborole may be considered
(off-label use). Efinaconazole and tavaborole may also be an
attractive option for adolescents who are concerned about
the appearance of their nails as there is evidence that these
new antifungals can penetrate the nail plate in the presence
of a coat of nail polish. (60)(61) Pediatric studies using these
agents are ongoing. There is not enough information on the
18 Pediatrics in Review
efficacy of lasers in treating onychomycosis to recommend
their use.
Similar to adults, systemic antifungal medications are
recommended for children with established severe ony-
chomycosis. (62) Terbinafine, itraconazole, and flucona-
zole are prescribed off-label and are effective (Table 3). (32)
Immunocompromised patients should not be started on
systemic antifungals until their other health care clini-
cians are involved in the decision-making because the
benefits of their use for onychomycosis may not outweigh
the risks (eg, drug-drug interactions, hepatic/renal com-
plications, rare marrow effects). Topical antifungal solu-
tions and topical urea creams may be a safer option for
such patients.
Medications have varying degrees of effectiveness in
treating onychomycosis, with systemic antifungals more
effective at eliminating fungus (mycologic cure) than topical
antifungals. Concomitant TP should be treated with topical
antifungals. Treating family members for TP and/or ony-
chomycosis and advising patients and families to replace old
footwear, keep feet clean and dry, and launder socks in hot
water to kill fungal spores can help to prevent recurrent
disease.
PITYRIASIS VERSICOLOR
Epidemiology
PV (formerly tinea versicolor) is a superficial fungal infec-
tion of the skin caused by overgrowth of Malassezia species
of yeast in the stratum corneum. Malassezia globosa is the
most frequent causative organism worldwide, with Malas-
sezia sympodialis and Malassezia furfur also common. (63)
PV is not contagious because Malassezia species are part
of the normal skin flora. These yeasts are more likely to flour-
ish in hot and humid environments. PV is, therefore, more
common in the summer months or in tropical climates.
PV is more common in adolescents and young adults than
in young children because increased sebum production
may facilitate fungus growth. (64)
Clinical Presentation
PV is characterized by hyper- or hypopigmented round or
oval macules with fine scale and a flaking appearance. It is
often diagnosed based on clinical appearance. Lesions are
generally confined to the trunk, neck, and upper arms, all of
which are areas with a high density of sebaceous glands. The
face, particularly the temples, is also commonly affected
in children. Lesions are generally asymptomatic, although
some patients experience mild pruritus. (64) Fine scale
may be difficult to discern and the “evoked scale sign,” a
stretching or scraping of a lesion, produces a visible fine
scale that can aid in diagnosis. (65) Hyper- and hypopig-
mentation do not necessarily resolve with drug therapy;
many months may be required for skin to recover a normal
appearance.
Differential Diagnosis
Differential diagnoses include postinflammatory hyper
(hypo)pigmentation, pityriasis rosea, pityriasis alba, sebor-
rheic dermatitis, vitiligo, and mycosis fungoides. Only PV
and seborrheic dermatitis are fungal infections. However,
cultures may be negative in both of these disorders, and
culturing requires special agents (eg, olive oil) added to the
media to support yeast growth. Seborrheic dermatitis af-
fects the head, neck, chest, and intertriginous folds, and ery-
thematous scaling plaques are often symmetric and favor
sebum-rich areas. Pityriasis alba usually affects the face,
with mild erythema preceding hypopigmented lesions and
limited to no fine scaling. A history of inflammatory rash and
a lack of scale characterize postinflammatory pigmentation.
Pityriasis rosea usually lasts 1 to 3 months; often occurs in
the spring and fall; and presents with a pinkish, erythem-
atous, scaly herald patch followed by the appearance of
multiple other plaques, often on the trunk. (66) This is
in contrast to PV, in which lesions have finer scale and are
hyper- or hypopigmented. An absence of scale in depig-
mented macules and accentuation of the depigmentation
under Wood’s light differentiates vitiligo from PV. (67)
Mycosis fungoides, although rare, is the most common
primary cutaneous lymphoma in children and presents as
numerous scaly patches on the trunk and extremities. These
lesions are often hypopigmented, particularly in patients
of color, and a biopsy is necessary for diagnosis. (68) Diag-
nosis is often delayed when pityriasis alba, rosea, or PV is
suspected instead.
Diagnostic Tests
PV is confirmed via microscopic examination with a positive
KOH. Wood’s light examination may be clinically helpful
but not necessarily conclusive because not all Malassezia
species fluoresce bright yellow or gold. Skin scrapings
should be taken from the edge of lesions, and the trans-
parent tape method may be used if it is difficult to obtain
skin scrapings. Under the microscope, Malassezia species
appear as “spaghetti and meatballs,” a combination of short
hyphae and round budding yeast cells. A clinical diagnosis
should be microscopically confirmed before systemic treat-
ment, but topical treatment can be instituted empirically.
Treatment
A systematic review concluded that topical treatments
are effective and well tolerated, with longer durations of
treatment more likely to produce favorable outcomes. (69)
Shampoos and lotions are applied once or twice daily
for 7 to 14 days. One study using ketoconazole shampoo
documented good response with daily application for 3
consecutive days. (70) Zinc pyrithione, selenium sul-
fide shampoo/lotion, and ketoconazole shampoo are
applied to affected areas for 5 to 10 minutes and then
washed off in the shower. Selenium sulfide may be more
likely to cause dry skin. Monthly applications of ketoco-
nazole, zinc pyrithione, or selenium sulfide shampoo for
3 months may prevent recurrence. Effective topical anti-
fungal agents include clotrimazole, miconazole, ketocona-
zole, and terbinafine.
Systemic treatment with oral antifungals should only be
considered in cases of recalcitrant or recurring disease or if
large areas are affected. Itraconazole (off-label) and fluco-
nazole are appropriate, but oral terbinafine is ineffective for
PV. In adults, itraconazole 200 mg daily for 5 to 7 days
or fluconazole 300 mg weekly for 2 to 4 weeks is admin-
istered. Relapse following topical or oral treatment is com-
mon (60%-80%), and repeated or maintenance therapy
may be necessary. (71) Oral ketoconazole should no longer
be prescribed for any dermatomycosis in children or adults
due to risk of hepatotoxicity. (72)
MUCOCUTANEOUS CANDIDIASIS
Epidemiology
MC encompasses any infection of the body where mucous
membrane meets skin that involves a Candida species, often
Candida albicans. However, candidiasis may also occur in
folds of skin (intertrigo) such as the groin and corners of the
mouth. Due to pediatrician familiarity with candidal diaper
dermatitis, this condition will not be discussed further.
Relatively few children present with infections in the mouth
(oropharyngeal candidiasis) and throat (esophageal candi-
diasis), known as thrush. Thrush is most common among
babies younger than age 1 month and people with compro-
mised immune systems (73) that allow the naturally present
Candida species to multiply. An estimated 5% to 7% of
babies younger than age 1 month (73) and about 39%
of children with human immunodeficiency virus (HIV)
develop an infection. (74) Other risk factors include old
age, endocrine dysfunction, malnutrition, trauma, prema-
turity, and use of antibiotics and other medical interven-
tions. (2) Chronic mucocutaneous candidiasis (CMC) is
even rarer and may involve a genetic component that is
Vol. 38 No. 1 JANUARY 2017 19
 also associated with T-cell immunodeficiency. (75) Patients
with CMC have persistent or recurrent infections that can
involve the nails and require long-term therapy. (37)(76)
Clinical Presentation
The most common symptoms of thrush are white patches
or plaques on the mucous membranes, redness or soreness
in the infected area, difficulty swallowing, and cracking
at the corners of the mouth. (73)(77) CMC is often more
widespread, occurring in the mucous membranes, skin,
and nails (onychomycosis). (76)
Differential Diagnosis
The differential diagnosis of MC depends on the location
of infection. If the patient has oral candidiasis, the differ-
ential diagnosis includes leukoplakia, oral hairy leukoplakia,
lichen planus, bullous pemphigoid, pemphigus vulgaris,
erythema multiforme, herpes simplex, and aphthous sto-
matitis. (78) However, none of these diagnoses is commonly
found in early childhood. (2) For cases of CMC or intertrigo,
the differential diagnosis includes erythrasma, seborrheic
dermatitis, dermatitis enteropathica, syphilis, Gram-negative
folliculitis, familial benign chronic pemphigus (Hailey-
Hailey disease), and bacterial intertrigo. (78)
Diagnostic Tests
Because Candida species naturally occur in the body, myco-
logic tests are of minimal value; the presence of Candida
species does not imply that there is an infection. (2) There-
fore, diagnosis of MC is primarily based on clinical pre-
sentation. However, the presence of Candida species may be
confirmed through KOH microscopy or a culture. (77) The
presence of many pseudohyphae supports the diagnosis of
a candidal infection.
Treatment
Therapy for oropharyngeal candidiasis primarily involves
azole antifungals, either topically or systemically; systemic
antifungal therapy is required for esophageal candidiasis
and CMC. (37) The following recommendations are based
on the most up-to-date clinical practice guidelines provided
by the Infectious Diseases Society of America. (37)
Mild cases of oropharyngeal candidiasis can be treated
with clotrimazole troches (small tablet or lozenge), mico-
nazole mucoadhesive buccal tablet, or nystatin suspension.
(37) Moderate-to-severe cases should be treated with oral
fluconazole. (37) In neonates, if creatinine levels are greater
20 Pediatrics in Review
than 1.2 mg/dL (106 mmol/L) for more than 3 consecutive
doses, the dose interval may be decreased to once every 48
hours until the serum creatinine measures less than 1.2
mg/dL (106 mmol/L). (31) For fluconazole-resistant infec-
tions, itraconazole or posaconazole suspension is recom-
mended. (37)(79) Amphotericin B is recommended when
other treatment options fail. (37)
Esophageal candidiasis must always be treated system-
ically and oral fluconazole is recommended. (37) For
patients who cannot complete oral therapy, intravenous
fluconazole or an echinocandin (eg, micafungin, caspofun-
gin, anidulafungin) are options, with amphotericin B less
preferred. For fluconazole-resistant infections, itraconazole,
voriconazole, amphotericin B, or an echinocandin may be
used. (37) In recurrent infections or CMC, suppressive
therapy with fluconazole has been found to be effective.
Children who have HIV infection also should be treated
with highly active antiretroviral therapy to reduce recurrent
infections. (31) Proper treatment is important because un-
treated MC may lead to a more severe, invasive infection.
Summary
• On the basis of strong evidence, tinea capitis is the most common
fungal skin infection in children. (6)(7)
• On the basis of strong evidence, treatment for tinea capitis must
be systemic to penetrate the hair shafts. (17)
• On the basis of consensus, diagnosis of fungal skin infections
often can be confirmed through potassium hydroxide
microscopy or a culture, although cultures are of limited use
for tinea corporis, pityriasis versicolor, and mucocutaneous
candidiasis.
• On the basis of consensus, topical corticosteroids eventually
worsen tinea corporis infections and should not be used.
• On the basis of consensus, the feet should be examined for tinea
pedis and possibly onychomycosis in a child or adolescent
presenting with tinea cruris. (54)
• On the basis of evidence and consensus, waiting a short period of
time may allow resolution of symptoms resembling
onychomycosis (ie, from trauma) because children have thinner
nail plates and faster growing nails.
References for this article are at http://pedsinreview.aappublications.
org/content/38/1/8.
PIR Quiz
There are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link under the article title in the Table of Contents of any issue.
2. To access all CME articles, click “Journal CME” from Gateway’s orange main menu or go directly to: http://www.aappublications.
org/content/journal-cme.

1. A 2-year-old African-American boy presents to your office with a 1-month history of an REQUIREMENTS: Learners
enlarging lesion on his head. On physical examination, you note a 3-cm in diameter lesion can take Pediatrics in
that is boggy and has overlying pustules in the occipital area. There is some shotty Review quizzes and claim
posterior cervical and occipital lymphadenopathy that is not tender. His mother denies the credit online only at:
child having any fevers but notes that he seems uncomfortable when the area on his head http://pedsinreview.org.
is touched. You suspect a kerion. What is your next step in management?
A. Begin treatment with a systemic antifungal medication pending kerion culture To successfully complete
results. 2017 Pediatrics in Review
B. Observe the skin lesion for 1 month. articles for AMA PRA
C. Obtain a skin biopsy of the skin lesion before beginning any treatment. Category 1 CreditTM,
D. Perform a Wood’s light examination of the lesion to see if the fungus fluoresces. learners must
E. Send a skin scraping for polymerase chain reaction. demonstrate a minimum
2. You diagnose tinea capitis in a 14-year-old boy who presented to your clinic with a small performance level of 60%
area of alopecia with associated scaling and erythema. Your diagnosis is confirmed with or higher on this
potassium hydroxide microscopy and culture. You give the parents a prescription for the assessment, which
appropriate systemic antifungal medication. The parents ask about whether this condition measures achievement of
is contagious to other children. Of the following, what would the best response be? the educational purpose
A. A follow-up skin culture must be performed in 2 weeks and if it does not show and/or objectives of this
fungus, the child may then return to school. activity. If you score less
B. All children in the household plus any other children who are close contacts should than 60% on the
begin prophylactic antifungal therapy. assessment, you will be
C. Once treatment is begun, the child may return to school but should not share given additional
combs or helmets or play contact sports for 14 days to avoid transmission. opportunities to answer
D. The child should avoid contact with infants younger than age 1 year during therapy. questions until an overall
E. The child should not be allowed to return to school until treatment is complete. 60% or greater score is
achieved.
3. A father brings his 5-year-old daughter to your office with concerns about an itchy rash
that developed over her face and body a few days after beginning therapy for tinea capitis.
Her vital signs show temperature of 98.4°F (36.9°C), heart rate of 98 beats/min, respiratory This journal-based CME
rate of 26 breaths/min, and blood pressure of 100/55 mm Hg. Over her cheeks and trunk, activity is available
you note a papulovesicular rash that seems to be slightly pruritic. You also note a small area through Dec. 31, 2019,
of tinea capitis on her left temporal area. There are some broken hair shafts visible with however, credit will be
mild scaling and erythema of the skin but no discharge. Of the following, what is the most recorded in the year in
likely explanation for her new symptoms? which the learner
A. A dermatophytid reaction. completes the quiz.
B. A viral exanthem.
C. Drug reaction to the antifungal.
D. Pityriasis rosea.
E. Tinea corporis.
4. You are examining a 15-year-old boy who is a varsity wrestler at his high school. He is
complaining of pruritus and erythema in his groin area for 2 weeks. On physical
examination, his vital signs are all within normal limits. He has large areas of scaling with
scattered overlying papules and areas of maceration on his upper medial thighs bilaterally.
You are concerned about tinea cruris. Of the following, which additional condition is often
associated with tinea cruris?
A. Inverse psoriasis.
B. Nummular eczema.
C. Onychomycosis.
D. Systemic candidiasis.
E. Tinea pedis.

Vol. 38 No. 1 JANUARY 2017 21

 5. An 11-year-old girl presents to your office with a chief complaint of white patches inside
her mouth and some difficulty swallowing. Her mother reports that the child just finished 5
weeks of antibiotic therapy for osteomyelitis of her right tibia. Her vital signs are within
normal ranges. Mouth examination shows several patches of white plaques on her inner
cheeks with underlying erythema. There are similar lesions in her posterior oropharynx
extending inferiorly toward her esophagus. What is your best initial choice for treatment at
this time?
A. Amphotericin B.
B. Clotrimazole troches.
C. Fluconazole.
D. Griseofulvin.
E. Terbinafine.

Parent Resources from the AAP at HealthyChildren.org

• Tips for Treating Viruses, Fungi, and Parasites: https://www.healthychildren.org/English/health-issues/conditions/treatments/Pages/Tips-
For-Treating-Viruses-Fungi-and-Parasites.aspx
• Thrush and Other Candida Infections: https://www.healthychildren.org/English/health-issues/conditions/infections/Pages/Thrush-and-
Other-Candida-Infections.aspx
• Fungal Diseases: https://www.healthychildren.org/English/health-issues/conditions/infections/Pages/Fungal-Diseases.aspx
• Tinea Infections (Ringworm, Athlete’s Foot, Jock Itch): https://www.healthychildren.org/English/health-issues/conditions/skin/Pages/
Tinea-Infections-Ringworm-Athletes-Foot-Jock-Itch.aspx

22 Pediatrics in Review

Sarita Singhal, MD,*† Susan S. Baker, MD, PhD,*† Georgina A. Bojczuk, RD, CSP,† Robert D. Baker, MD, PhD*†
*Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY
†
Digestive Diseases and Nutrition Center, Women and Children’s Hospital of Buffalo, Kaleida Health, Buffalo, NY
AUTHOR DISCLOSURE Drs Singhal, S. Baker,
and R. Baker and Ms Bojczuk have disclosed
no financial relationships relevant to this
article. This commentary does not contain a
discussion of an unapproved/investigative use
of a commercial product/device. Dr Singhal’s
present affiliation is: Department of Pediatrics,
Division of Pediatric Gastroenterology, Baystate
Children’s Hospital, Spingfield, MA.
Tube Feeding in Children
Education Gap
Enteral tube feeding (TF) is an important part of the care of acutely ill
children as well as an essential technique to deliver nutrition to
children who have chronic conditions. However, the techniques of TF
are neither a part of medical school courses nor specifically taught in
pediatric residency programs. Thus, learning how to initiate,
monitor, moderate, and transition TF is often learned by trial and
error.
Objectives After completing this article, readers should be able to:
1. Understand the need for nutritional assessment and nutrition support.
2. Recognize indications and contraindications for tube feeding (TF).
3. Plan the evaluation of a patient who requires TF.
4. Recognize the factors that are important to make the proper selection
of enteral access for TF.
5. Plan the initiation and administration of TF.
6. Recognize the potential complications of TF and learn troubleshooting
methods.
7. Coordinate care for home nutrition support and assist in the transition
to oral feedings.
8. Understand the social needs of patients who have TF.
INTRODUCTION
Tube feeding (TF) is a mode of providing enteral nutrition when oral feeding is
not possible or not sufficient. TF is delivered through a medical device that can
be placed into the stomach, duodenum, or jejunum via either the nose, mouth, or
the percutaneous route. This review focuses on TF in children beyond the neonatal
period.
Nutritional support can be either enteral or parenteral. Enteral nutrition (EN)
refers to any method of feeding that uses the gastrointestinal (GI) tract to deliver
part or all of a child’s nutritional requirements. It can include a normal oral diet or
feeding via tube. Parenteral nutrition (PN) refers to the delivery of nutrients by
Vol. 38 No. 1 JANUARY 2017 23
 vein. Studies have shown that EN is preferred over PN be-
cause it leads to earlier gut function, fewer infections, lo- TABLE 1. Indications for Tube Feeding
wer cost, and shorter hospital stay. (1)(2)(3) In addition, EN
1. Insufficient oral intake
delivers nutrients directly to the GI tract, avoiding delete-
- Anorexia
rious changes in the normal gut physiology and the aberrant
physiology that ensues when nutrients are infused directly -Food aversion
into the systemic circulation without the benefit of the -Malabsorption (cystic fibrosis, short bowel syndrome, pancreatic
modifying functions of the GI tract and liver. (4) PN is insufficiency)

reserved for patients who have GI tract dysfunction that -Increased needs (congenital heart disease, bronchopulmonary
dysplasia)
prohibits adequate nutrient absorption.
Nutrition is important for normal growth and develop- 2. As a primary therapy
ment in children. Nutritional assessment, therefore, should -Metabolic disease
be an integral part of the care for every pediatric patient. -Intolerance to fasting
Complete nutritional assessment includes a medical his-
-Inflammatory bowel disease
tory, nutritional history that includes dietary intake, physical
examination, anthropometrics, pubertal staging, skeletal ma- 3. Oral motor dysfunction
turity staging, and biochemical tests of nutritional status. -Prematurity
(5)(6)(7)(8) Most healthy children have the ability to ingest -Neuromuscular disease
enough nutrients to meet their needs, but children with
-Neurologic disease
chronic medical conditions or prolonged illnesses may not
4. Abnormal gastrointestinal tract
be able to meet their nutritional goals. Approximately 10%
to 15% of children in the United States have special health -Congenital malformations
care needs. Most of these children are at risk for poor growth. -Esophageal stenosis
It is important for clinicians to identify these children, as- -Intestinal pseudo-obstruction
sess their nutritional needs, and provide adequate nutri-
5. Injury/critical illness
tional support for their growth and development.
-Burn
-Trauma
INDICATIONS FOR TF
-Surgery
TF is used for children who have inadequate or unsafe oral
-Sepsis
intake and a functioning GI tract (Table 1). If the GI tract is
able to absorb some but not all of the nutritional needs, Adapted with permission from: Baker SS, Baker RD, Davis AM. Pediatric
partial EN should be attempted. If the patient has normal Nutrition Support. 2007; Jones & Bartlett Learning. Burlington, MA. www.
jblearning.com. Copyright 2007.
swallowing function, oral supplements may be added to
achieve the complete nutrition intake and to maintain oral skills.
dependent on various factors, including the patient’s GI
tract anatomy and function, indication for feedings, ex-
CONTRAINDICATIONS FOR TF
pected duration of feedings (short term of weeks to months
When oral feeding is not possible or is inadequate, TF is the or long term of months to years), and the risk of aspiration.
method of choice because it is more physiologic than PN. An upper GI radiographic series should be performed to
The only absolute contraindication for TF is a nonfunction- rule out anatomic barriers to TF such as malrotation or
ing GI tract, such as GI obstruction or severe intestinal gastric outlet obstruction. A careful history can identify
ischemia. Conditions such as intestinal fistulae and severe signs and symptoms suggestive of aspiration. In some
pancreatitis are no longer considered contraindications. cases, a swallow study under fluoroscopy may be helpful to
evaluate swallowing function and the risk of aspiration. A
number of options for enteral access are available (Table 2).
CHOICE OF ENTERAL ACCESS FOR TF
Orogastric (OG) feeding is used most frequently in pre-
Once it is decided that TF is necessary, the clinician must term infants before they develop a gag reflex (34 weeks’
determine the most appropriate enteral access based on the gestation). Preterm infants are obligate nose breathers, so
individual clinical situation. The choice of enteral access is OG feeding avoids obstruction of the nares. OG feedings are

24 Pediatrics in Review
TABLE 2. Choice of Tube
DURATION OF
TYPE OF TUBE FEEDING PLACEMENT COMMENT USE

Orogastric Short-term Bedside • Used in preterm infants up • Feeding

to 34 weeks’ gestation • Medication
• Safe with basilar skull fracture • Hydration

Nasogastric Short-term Bedside • With or without stylet • Feeding

• Medication
• Hydration

Nasointestinal (including any nasal Short-term Fluoroscopic • Displaces easily • Feeding

tube that extends beyond the • Weighted or unweighted • Hydration
pylorus)
Gastrostomy Long-term Surgical • Not ready for immediate use • Feeding
• Medication
• Hydration

Percutaneous endoscopic Long-term Endoscopic or radiologic • Can be used 4 hours from • Feeding
gastrostomy (PEG) techniques placement • Medication
• Hydration

Low-profile device Long-term Initial endoscopic • More convenient and easier • Feeding
to care for than gastrostomy • Medication
tube • Hydration
Internal balloon or internal Thereafter at • Aesthetically more pleasing
“mushroom” bedside (home)
Gastrointestinal (including any gastric Long-term Endoscopic, • Possible to access both stomach • Limits reflux and
tube that extends beyond the radiologic, or both and small bowel aspiration
pylorus) gastrojejunostomy or • Easily dislodged • Feeding
percutaneous endoscopic • Hydration
jejunostomy
Jejunostomy Long-term Surgical or endoscopic • No access to stomach • Feeding
• Hydration
• Limits reflux and
aspiration
Low-profile jejunal device Long-term Endoscopic • More convenient • Feeding
Internal mushroom bolster or • Aesthetically more pleasing • Hydration
fluid-filled balloon • No access to stomach • Some medications

preferred over nasogastric (NG) feedings in the presence of
a basilar skull fracture. OG feedings are also used when the
nares are obstructed (eg, cystic fibrosis).
NG feeding is the method of choice in children with
normal gastric function and a low risk of aspiration who
require short-term nutrition support. It is the simplest, least
expensive method and requires no invasive procedures.
Frequently, it is used for patients being evaluated for more
permanent tubes to ensure tolerance for intragastric feed-
ings. NG tubes have been used for long-term nutrition
support in patients who have learned to place the tube each
night, infuse feeding slowly overnight, and remove the tube
in the morning. Even for patients at some risk for aspiration,
NG feeding is not contraindicated. Infusing feedings over a
long period of time can result in less emesis by limiting the
gastric contents at any given time. It is important to recog-
nize that TF by any method does not decrease the likelihood
of aspiration of swallowed secretions, an issue with many
neurologically impaired children. An NG tube can be placed
at the bedside, but proper position should be verified ra-
diologically or by aspiration of acidic stomach contents. Aus-
cultation over the stomach is not recommended. (9)
Gastrostomy tubes (G-tubes) are preferred for intragas-
tric feeding that is expected to last longer than 3 months.
G-tubes can be placed surgically, endoscopically, or radiolog-
ically. Surgically placed tubes have the advantage of creating
a formal attachment between the abdominal wall and the
stomach wall, thus reducing the possibility that the tube
becomes dislodged, potentially contaminating the perito-
neal cavity. For the other 2 methods of placement, 2 months
are required for an attachment to form (tract maturation).
A disadvantage of a surgically placed G-tube is that it cannot
be used immediately. Some surgeons do not use a surgically
placed tube for several days, in contrast to endoscopically or

Vol. 38 No. 1 JANUARY 2017 25

 radiologically placed tubes, which can be used within a few
hours of insertion.
If a simultaneous antireflux procedure is planned, sur-
gical placement makes sense. However, there is no indica-
tion for a prophylactic fundoplication in a patient without a
history of reflux. Even in the presence of prior reflux, a
G-tube does not necessarily worsen reflux and, at times, may
improve it.
G-tube placement carries a risk of infection (intraabdo-
minal abscess or peritonitis) or, in endoscopically or radio-
logically placed tubes, colonic perforation. Not infrequently,
air is introduced into the peritoneal cavity during the
course of either radiologic or endoscopic G-tube placement.
This is not a substantial complication because the air re-
sorbs without treatment. However, it can be alarming if
an abdominal radiograph is obtained because the air in the
cavity mimics the radiologic findings of bowel perforation.
All G-tubes are prone to local irritation, with formation of
granulation tissue, local skin irritation, and skin infection.
After the tract has matured, the G-tube can be replaced with
a “low-profile” device, which is aesthetically more pleasing
and easier to maintain. Low-profile devices cause less irri-
tation. A kit is available that allows initial placement of a
low-profile device. The standard percutaneous endoscopic
gastrostomy (PEG) kit contains a PEG tube with an external
bolster, safety trocar cannula, safety-shielded scalpel, retrieval
snare, Y-port, and C-clamp. Low-profile devices have either a
mushroom-shaped bolster or a fluid-filled balloon that keeps
the tube in the lumen of the stomach. The advantage of the
mushroom is that it is difficult to dislodge, and the advantage
of the fluid-filled balloon is that the fluid can be removed and
the tube replaced. Accidental loss of fluid from the balloon
can result in the tube coming out unintentionally.
G-tubes should be changed periodically. Some centers
recommend changing G-tubes every 3 months. Other cen-
ters do not advocate a routine, but change the tubes when
they appear worn or become nonfunctional. Parents can be
taught to change the low-profile devices that have an internal
balloon in the stomach. Because G-tubes do not prohibit
simultaneous oral feeding, they are excellent for transition-
ing from TF to oral feeding. When TF is no longer needed,
the G-tube can simply be removed. Most often the stoma
seals and heals. Occasionally, it remains open, requiring
either endoscopic closure using internal clips or formal
surgical closure.
Nasointestinal feeding tubes can be used for the short-
term delivery of feedings beyond the stomach. These tubes
can be placed by a number of methods. A weighted or
unweighted tube can be passed into the stomach with extra
length of the tube allowed to remain in the stomach and to
26 Pediatrics in Review
pass into the duodenum and jejunum by peristalsis. Neither
erythromycin, metoclopramide, nor weighting has been asso-
ciated with any benefit in promoting passage of the tube by
peristalsis. This method is time-consuming and not always
successful. Nasointestinal tubes can be placed endoscopically
using a number of techniques. The endoscopic techniques
are invasive, require anesthesia, and are not always success-
ful. The radiologic placement of nasointestinal tubes has
proven to be the fastest and most reliable approach. Nasoin-
testinal tubes are easily dislodged and may require frequent
replacement.
A previously placed G-tube can be converted into a GJ
tube by replacing the G-tube with a device that looks similar
to the G-tube but has an extension that traverses the pylo-
rus and extends into the small intestine. The extension is
usually placed into the jejunum by a radiologist, although
there are methods to carry the extension into the jejunum
with an endoscope. Usually the tract must be mature (ie, the
G-tube must have been in place for 2 months) to make this
conversion. One commercial kit allows for a small tube to be
placed through a newly inserted G-tube and then past the
pylorus into the small intestine. The smaller tube has an
adapter that fits the tube snugly into the PEG tube, thereby
eliminating leakage.
Jejunostomy feeding tubes can be placed directly through
the skin and into the jejunum either surgically or endo-
scopically. These two techniques are not used frequently
because both methods eliminate access to the stomach,
which is often necessary for venting.
PREPYLORIC VERSUS POSTPYLORIC FEEDINGS
Prepyloric feeding is more physiologic than postpyloric
feeding because feeding into the stomach allows a more
normal digestive process. Most patients tolerate prepyloric
feeding if the stomach is functionally and structurally
normal. The stomach acts as a reservoir and can tolerate
larger volumes and higher osmotic loads than the small
intestine. Prepyloric feedings allow for the use of bolus
feeding, creating a more flexible feeding schedule that is
closer to a natural pattern of eating. Bolus feedings may lead
to better gastric contractility because they are cyclical and
associated with peaks and troughs of insulin secretion.
Prepyloric feedings also provide a protective effect against
hyperosmolar formulas because duodenal osmoreceptors
regulate gastric emptying and retain the formula in the
stomach until ingested formula is isosmotic. This decreases
the risk of dumping. Dumping syndrome is the result of
high-volume or high-osmolar fluid entering the duodenum.
This induces inappropriate gut hormone release and vasomotor
GI symptoms such as abdominal pain, bloating, and diarrhea.
One of the major concerns with the prepyloric feeding is the
potential risk of pneumonia from aspiration of formula from
the stomach. (10)(11) Therefore, clinicians should be cautious
in administering prepyloric feedings to patients with severe
gastroparesis and a history of aspiration.
Postpyloric feeding is defined as feeding beyond the
pylorus, either into the duodenum or into the jejunum
distal to the ligament of Treitz. Postpyloric feeding can
be delivered via nasoduodenal tube, gastrojejunal tube, or
surgical jejunostomy. This is useful for patients who are
at risk for aspiration pneumonia or who have intolerance to
gastric feeding, recurrent emesis, or severe gastroesopha-
geal reflux. (11)(12) Postpyloric feedings bypass the stomach,
thus decreasing but not eliminating the risk of reflux and
aspiration. Especially in neurologically impaired children
who are unable to protect their airways, postpyloric feeding
can be helpful. Patients with gastroparesis or with emesis as
a result of chemotherapy also can benefit from postpyloric
feedings. Most postpyloric tubes have a “gastric port” that
allows venting of the stomach and administration of med-
ications that need to be given into the stomach.
Postpyloric feedings bypass the digestive and antibacte-
rial functions of the stomach. Because the small intestine
cannot tolerate hyperosmolar feedings, postpyloric feed-
ings must be administered slowly over most of the day,
thus precluding bolus feedings. The major disadvantages of
postpyloric feeding are the difficulty in placement of tubes
and the risk of tube migration back into the stomach. The
tubes are long and have a small caliber, which creates the
chance of occlusion. Placement into the proximal jejunum
is preferable because it decreases the likelihood of feedings
refluxing into the stomach and esophagus, with aspiration
into the airway. Also, tubes ending in the jejunum are less
likely to become displaced, a problem with all postpyloric
tubes.
BOLUS VERSUS CONTINUOUS FEEDING
TF can be administered continuously or intermittently (bo-
luses). The 2 methods are often combined, such as contin-
uous feeding during the night and bolus feeding during the
day. This combination is useful for ambulatory patients who
require large volumes to meet their nutritional requirements.
The method of delivering nutrition is dependent on various
factors, such as the type of tube (prepyloric or postpyloric),
medical condition of the patient (age, ambulatory status,
underlying diseases), expected tolerance to feedings, nutri-
tional requirements, and other factors (availability of parental
support, acceptance, availability of equipment, cost).
Bolus feedings are given to patients who receive intra-
gastric feedings because the stomach can tolerate large vol-
umes. Once the feeding volume required for a 24-hour period
is determined, it is divided into 4 to 6 bolus feedings that can
be administered by syringe, gravity, or with a pump. Bolus
feedings are more physiologic and allow patient mobility.
They are the preferred method of delivery for ambulatory
patients. They also are less expensive and easier to administer
than continuous feedings. However, bolus feedings may not
be successfully used in patients with reflux or gastroparesis or
those who require large feeding volumes. Patients might
experience nausea, vomiting, diarrhea, or abdominal disten-
sion with bolus feeding. (8)(12)
Continuous feedings are delivered via an infusion pump.
They can be administered through jejunal, gastrostomy,
or nasointestinal tubes. Continuous feedings are admin-
istered at a constant hourly rate over an 8- to 24-hour period,
depending on the patient’s nutritional requirements. Contin-
uous feedings are beneficial for critically ill patients, mal-
nourished patients, and those who have malabsorption due
to intestinal diseases. They are also used for patients who
have intolerance to gastric bolus feedings. Nocturnal feed-
ings are useful for providing extra energy to ambulatory
patients. Continuous feedings are more expensive due to
equipment requirements and supplies and they restrict
ambulation. (8)(12)
INITIATION OF TF
After a thorough evaluation by a multidisciplinary team that
consists of variable combinations of a gastroenterologist,
nurse, dietitian, speech-language pathologist, occupational
therapist, psychologist, surgeon, and radiologist, the deci-
sion to initiate TF is taken.
Initiating and administering a TF regimen requires care-
ful assessment of the nutritional status of each patient to
ensure that the best regimen is prescribed, monitored, and
maintained. Assessment takes into account each patient’s
age, medical status, and GI tract function as well as type of
feeding tube, feeding goals, and desired feeding schedule. If
results of this assessment suggest that TF is indicated, the
first step is to select an appropriate formula (Tables 3 and 4).
Once a formula is selected, TF may be administered by
bolus, continuous, or a combination of these methods. For
most patients there is no need to dilute formula; full-
strength formula is started and volume gradually increased
as tolerance is demonstrated.
Initiation and advancement of TFs can vary greatly
among clinicians and individual medical facilities, but most
medically stable patients can tolerate fairly rapid progression
Vol. 38 No. 1 JANUARY 2017 27
 TABLE 3. Choice of Formula for Infants
MACRONUTRIENT SOURCE
FORMULA EXAMPLES/PRODUCT (VARIES BY INDIVIDUAL
CATEGORY INDICATIONS MANUFACTURER PRODUCT) COMMENTS

Human Milk Preferred nutrition source for PRO: whey-predominant, • Nonhomogenized

virtually all infants* when
mother’s milk and/or
donor milk is available
Postdischarge Posthospital discharge
Formulas for formulas for former
Prematurity preterm infants
Standard Infant Normal gastrointestinal tract Enfamil Premium,a
Formulas
Soy-based Infant Galactosemia, primary or
Formulas secondary lactose
intolerance,
families preferring vegan
formula option
Extensively Food protein intolerance,
Hydrolyzed Infant malabsorption,
Formulas steatorrhea, intractable
diarrhea
Elemental/Free Severe protein allergy, Alfamino Infant,d Elecare
Amino Acid Infant eosinophilic
Formulas gastrointestinal disorders,
malabsorptive conditions,
short bowel syndrome
whey:casein ratio varies • Special care and technique
FAT: human milk needed when feeding via
CHO: lactose tube
• 20 kcal/oz, crematocrit can
be performed to measure
kcal concentration
Enfacare Lipil,a Similac PRO: whey, casein, cow milk • Standard concentration is
NeoSureb protein 22 kcal/oz
FAT: high-oleic, soy, coconut • High in protein, vitamin D,
oils, MCT, DHA, ARA calcium, and phosphorus
CHO: corn syrup solids, • 250-310 mOsm/kg water
lactose, maltodextrin
PRO: cow milk protein, whey • Standard concentration is
Enfamil Gentlease,a protein concentrate 20 kcal/oz
Gerber Good Start (Gentlease and Good Start • Similac concentration is
Gentle,c Similac contain partially hydro- 19 kcal/oz
Advanceb lyzed protein) • 230-310 mOsm/kg water
FAT: palm olein, soy, coco-
nut, high-oleic sunflower,
DHA, ARA
CHO: lactose,
galactooligosaccharides,
polydextrose, corn syrup
solids
Enfamil Prosobee,a Gerber PRO: soy protein isolate and • Lactose-free
Good Start Soy,c Similac L-methionine • 20 kcal/oz standard
Soy Isomil FAT: palm olein, soy, coco- concentration
nut, high-oleic safflower/ • Similac concentration is
sunflower, DHA, ARA 19 kcal/oz
CHO: corn syrup solids, • 180-200 mOsm/kg water
sucrose
Similac Alimentum,b PRO: cow milk protein • Hypoallergenic
Nutramigen Lipil,a hydrolysate • Lactose-free
Pregestimila FAT: long-chain fat, variable • 20 kcal/oz standard
MCT (0%-55% of fat), DHA, concentration
ARA • 320-370 mOsm/kg water
CHO: corn syrup solids,
modified corn starch,
dextrose, sucrose
PRO: free amino acids • Hypoallergenic
Infant,b Neocate Infant,e FAT: high-oleic safflower oil, • No cow milk protein, soy,
PurAminoTMa soy, coconut, sunflower fructose, galactose, or
oil, variable MCT (33%-43% lactose
of fat), DHA, ARA • 330-350 mOsm/kg water
CHO: corn syrup solids

*Contraindicated in some instances, such as galactosemia, maternal human immunodeficiency virus/AIDS, active tuberculosis, and some inborn errors of
metabolism.
a
Mead Johnson Nutrition, Chicago, IL.
b
Abbott Laboratories, Abbott Park, IL.
c
Nestlé Infant Nutrition, Florham Park, NJ.
d
Nestlé Health Science, Florham Park, NJ.
e
Nutricia North America, Gaithersburg, MD.
ARA¼arachidonic acid, CHO¼carbohydrate, DHA¼docosahexaenoic acid, FAT¼fat, MCT¼medium-chain triglyceride, PRO¼protein.
Formula content and specifications as per product manufacturers’ websites.

28 Pediatrics in Review
TABLE 4. Choice of Formula for Children Older Than Age 1 Year
MACRONUTRIENT SOURCE
FORMULA EXAMPLES/PRODUCT (VARIES BY INDIVIDUAL
CATEGORY INDICATIONS MANUFACTURER PRODUCT) COMMENTS

Standard Pediatric Normal GI tract requiring a Boost Kid Essentials TM,a
PRO: cow milk protein con- • 1 kcal/mL, 30 cal/oz
Enteral Formulas complete or supplemental Compleat Pediatric,a centrate (Compleat con- • Lactose-free
source of energy from tube Nutren Junior,a tains food ingredients: • Meets/exceeds 100% of the
feeding PediaSure Enteral 1.0 Cal, chicken, peas, carrots, DRIs for protein, vitamins/
PediaSureb tomatoes, and cranberry minerals for children 1-8
Adolescents >13 years: juice) years, 9-13 years in 1,000 mL
Jevity 1 Cal,b Nutren FAT: high-oleic sunflower oil, and 1,500 mL, respectively
1.0,a Osmolite 1.0b • For oral or tube feeding use
soybean, safflower, canola
oil, variable MCT (0%-20% of • Fiber content varies
fat) • 300-550 mOsm/kg water
CHO: maltodextrin, sucrose,
corn syrup
Calorie-dense Normal GI tract requiring Children 1-13 years: PRO: cow milk and whey • 1.2-2.0 kcal/mL
Pediatric increased energy needs, Boost Kid EssentialsTM protein concentrate, • Lactose-free
a  b
Formulas shortened feeding 1.5, PediaSure 1.5 sodium and calcium • Nutritionally complete in
schedules, fluid restriction, Adolescents >13 years: caseinate, soy protein varying volumes/patient
 b
or have volume intolerance Isosource 1.5, Jevity 1.2, isolate age-dependent
 b 
Jevity 1.5 Cal, Nutren FAT: high-oleic sunflower/saf- • 370-780 mOsm/kg water
1.5,a Nutren 2.0,a Osmolite flower, soy oil, canola oil, • 69%-81% free water; while
1.2,b Osmolite 1.5b
variable MCT (0%-20% of fat) using these, be sure ade-
CHO: sucrose, corn syrup quate free water flushes are
solids, maltodextrin provided to meet hydration
needs of patient
Reduced-calorie Age 1-13 years with decreased Compleat Pediatric Reduced PRO: cow milk and whey • 0.6-0.63 kcal/mL
Pediatric Enteral energy needs requiring a Calorie,a PediaSure protein concentrate, soy • Lactose-free
Formulas lower-energy complete SideKicks 0.63 kal/mLa protein isolate, sodium • Beneficial to address
feeding caseinate, chicken, pea disproportionate weight
protein isolate gain often associated with
FAT: canola oil, soy oil, vari- developmental disabilities
able MCT (0%-20% of fat) • Fiber content varies
CHO: corn syrup, sucrose • 300-420 mOsm/kg water
Hydrolyzed Impaired GI tract function PediaSure Peptide 1.0,b PRO: enzymatically hydro- • 1.0-1.5 kcal/mL
Pediatric requiring peptide-based PediaSure Peptide 1.5,b lyzed whey protein, • Flavored and unflavored
Formulas complete nutrition formula; Peptamen Junior 1.0,a hydrolyzed sodium • Lactose-free
may be beneficial for use in Peptamen Junior 1.5a caseinate • Fiber content varies
malabsorption, short bowel FAT: canola oil, soy oil, vari- • 260-450 mOsm/kg water
syndrome, chronic diarrhea, able MCT (50%-60% of fat)
delayed gastric emptying, or CHO: maltodextrin, sucrose,
for previous intolerance
cornstarch
issues with intact protein
formulas

Free Amino Acid For children with impaired GI Alfamino Junior,c Elecare
Pediatric tract function requiring a
Formulas hypoallergenic, amino acid-
based formula; may be
beneficial for use in patients
with multiple food allergies,
eosinophilic GI disorders,
malabsorptive conditions,
short bowel syndrome, and
other GI tract impairments
PRO: free amino acids
Junior,b Neocate Junior,d FAT: high-oleic safflower oil,
Neocate Splash,d Vivonex soy oil, variable MCT (33%-
a
Pediatric 70% of fat)
CHO: corn syrup solids,
potato starch, modified
corn starch
• 0.8-1.0 kcal/mL
• Flavored and unflavored
• Lactose-free
• Available in powder or ready
to feed (Neocate Splash
manufactured as ready
to feed)
• 360-590 mOsm/kg water

a
Nestlé Health Science, Florham Park, NJ.
b
Abbott Laboratories, Abbott Park, IL.
c
Nestlé Health Science, Florham Park, NJ.
d
Nutricia North America, Gaithersburg, MD.
CHO¼carbohydrate, DRI¼dietary reference intake, GI¼gastrointestinal, MCT¼medium-chain triglyceride, PRO¼protein.
Formula content and specifications as per product manufacturers’ website.

Vol. 38 No. 1 JANUARY 2017 29

 to reach their established goal within 1 to 2 days of initi-
ation (Table 5). Medically fragile patients (particularly those
at risk for refeeding syndrome) or patients with compro-
mised GI tracts often require slower progression of feed-
ings. Patients should be monitored closely for the initial
3 to 5 days to ensure adequate nutrient delivery and for
potential complications. The family should be involved
in the process of designing and implementing a TF reg-
imen, especially if the patient is to be discharged on home
TF. Ultimately, the family is responsible for administering
the daily feeding, and it is imperative that the schedule
work well for all involved.
COMPLICATIONS
Fortunately, most complications associated with TF are
more of a nuisance than they are causative of morbidity.
However, serious complications can occur and can be a
manifestation of the underlying disease or the enteral
feeding itself. For example, vomiting or retching is often
seen in children with developmental delays or due to an
intervention such as a fundoplication. Complications can be
attributed to the mechanics of the TF, infections, metabolic
issues, intolerance, noncompliance, lack of patient or parent
satisfaction, and failure to reach nutritional goals.
Complications seen immediately after G-tube insertion
include misplacement, bleeding, and infection and should
be referred to the service that placed the tube: gastroenter-
ology, interventional radiology, or surgery. The proceduralist
who placed the tube usually addresses these complications.
Later problems can occur that are vexing at the least and
interfere with care at the worst. Table 6 lists some of these
complications, possible causes, and how to troubleshoot
them. Table 6 does not discuss gastric residuals because
gastric residual volumes do not correlate with risk of aspi-
ration in critically ill patients and cessation of feedings based
on gastric residual volumes underfeeds ill patients and does
not prevent aspiration.
HOME NUTRITION SUPPORT
Once the TF is established and the patient shows a clinical
response, discharge planning should begin. The important
components of discharge planning are patient/caregiver
training and arranging for supplies and necessary equip-
ment, home nursing care, and follow-up evaluations with
clinicians. Home care involves a team consisting of physician,
nurse, dietitian, case manager, discharge planner, vendor for
supplies, and home nursing services.
The patient/caregiver should be educated about the
disease process and the need for TF, handling of equipment
(using feeding pump), managing feedings (feeding reg-
imen, preparation and administration of formula), and
methods for troubleshooting common problems and mon-
itoring for complications. It is also crucial to explain to the
family when to call the health care team. The family should
be provided with both routine and emergency telephone
numbers. Arranging for supplies and services at home is
handled either by the home care team of the hospital or a
commercial home care company. The home care company
provides numerous services, including the equipment, home
nursing, and delivery of nutrient supplies.

TABLE 5. Initiation and Advancement of Tube Feeding

TYPE PATIENT AGE INITIAL INFUSION RATE ADVANCEMENT GOAL

Continuous 0-12 months 1-2 mL/kg/h 1-2 mL/kg every 8 hours 5-6 mL/kg/h
1-3 years 1 mL/kg/h 1 mL/kg every 8 hours 4-5 mL/kg/h
4-10 years 20-30 mL/h 20-30 mL every 8 hours 3-4 mL/kg/h
11-18 years 30-60 mL/h 30 mL/h every 8 hours 100-150 mL/h
Bolus 0-12 months 30-60 mL every 2-3 hours 15-60 mL/feeding 150 mL every 4-5 hours
1-3 years 30-90 mL every 2-3 hours 60 mL/feeding 180 mL every 4-5 hours
4-10 years 75-90 mL every 3 hours 60 mL/feeding 210 mL every 4-5 hours
11-18 years 90-120 mL every 3 hours 60 mL/feeding 240 mL every 4-5 hours
Cyclic 0-12 months 1-2 mL/kg/h 1-2 mL/kg/2 h 75 mL/h x 12-18 h per day
1-3 years 1 mL/kg/h 1 mL/kg/2 h 90 mL/h x 8-16 h per day
4-10 years 25 mL/h 25 mL every 2 hours 120 mL/h x 8-16 h per day
11-18 years 30 mL/h 30 mL every 2 hours 150 mL/h x 12 h per day

Adapted with permission from: Baker SS, Baker RD, Davis AM. Pediatric Nutrition Support. 2007; Jones & Bartlett Learning. Burlington, MA. www.jblearning.
com. Copyright 2007.

30 Pediatrics in Review
TABLE 6. Complications of Tube Feeding and Troubleshooting
COMPLICATION POSSIBLE CAUSE TROUBLESHOOTING

Mechanical
Tube breaks Manufacturer problem, mishandling, Replace tube or part
worn out
Cannot rotate tube, dimples skin, sometimes Tube too tight Resize and change to appropriate size; if
skin is irritated balloon present, check volume and be sure
not overfilled
Buried bumper, cannot rotate tube but feeds Tube too tight and becomes imbedded into the Contact team that placed tube to assess and
flow freely into the stomach gastric wall; caused by too small a tube or replace tube
mechanical traction on the tube
Clogged tube Failure to rinse tube after feedings, delivery of Replace tube; attempts to force fluids
“crushed” medications through tube through a clogged tube often result in
tube rupture
To prevent future clogs, change
medications to liquid form if available,
educate on proper flushing protocols
Dislodged Handling by patient Reposition
Tube hangs out onto abdominal wall Tube too long or internal balloon issue Resize and replace with appropriate-sized
tube; if balloon present, be sure it is
intact and correct volume of water
is in place
Leaking at stoma site Assess tube size; assess for infection and Place correct-sized tube, treat infection, check
underfilled balloon fluid volume in balloon
Granulation tissue Caused by repeated mechanical trauma Cauterize with silver nitrite, assess tube for size,
educate about handling of tube
Metabolic
Dehydration Too little free water, hyperosmolar or Increase free water, reassess formula
high-protein formula
Hyperglycemia Diabetic with changed insulin requirement Monitor blood glucose, reduce carbohydrate
content, adjust insulin dose
Hyperkalemia High-potassium formula, renal insufficiency, Change formula; give potassium binder,
intravenous potassium, acidosis insulin, glucose; stop or decrease
intravenous potassium; correct acidosis
Hyperphosphatemia Renal insufficiency Change formula to a renal-specific
formulation; give phosphate binder,
calcium supplements
Hypokalemia Malnutrition, diarrhea, insulin administration Monitor electrolytes, fluid and electrolyte
replacement, assess insulin dose
Hypophosphatemia Refeeding syndrome, insulin administration Phosphorus supplements; hold feedings if
phosphorus is £1.0 mg/dL (£0.32 mmol/L)
until correction begins, assess insulin dose
Hyponatremia Overhydration Adjust fluids
Acute rapid weight gain Fluid overload Adjust fluids
Rapid excessive weight gain Too many calories Reassess prescription for enteral feeding:
formula concentration, rate, length of
feeding
Inadequate weight gain Not enough calories Reassess prescription for enteral feeding:
formula concentration, rate, length of
feeding
Continued

Vol. 38 No. 1 JANUARY 2017 31

 TABLE 6. (Continued )

COMPLICATION POSSIBLE CAUSE TROUBLESHOOTING

Gastrointestinal
Diarrhea, general Osmotic load, infection, contamination of
feeding
Diarrhea, gastrointestinal tract Flat villus lesion, short bowel, pancreatic
abnormalities insufficiency
Malabsorption Define cause
Vomiting Gastrointestinal obstruction, tube
malpositioned (if using a Foley catheter,
the balloon occludes the pylorus),
medications administered with feeding,
patient positioning, delayed gastric
emptying, after a fundoplication
Constipation Inadequate fluids, inadequate fiber, inactivity,
obstruction, fecal impaction
Skin is erythematous, warm, or turning Culture
tube is painful; pus is visible
Abdominal distention Gastrointestinal obstruction, constipation,
aerophagia, bacterial overgrowth
Assess formula composition; assess method of
administration, storage, handling; review all
medications, especially liquid ones, for
osmotic load (sorbitol content); reduce rate
of nutrient delivery; assess for infection
Define gastrointestinal problem and treat
accordingly: pancreatic supplements,
bulking agents; slow rate of administration
Treat identified cause; consider increased use
of medium-chain triglycerides, elemental or
semi-elemental formula
Assess and treat accordingly; reposition or
change type of tube; do not administer
medications with feedings; reposition
patient; slow feeding rate or change to
continuous feedings; consider
erythromycin trial; if after fundoplication,
trial of nasojejunal feedings
Assess fluids, consider formula containing
fiber, disimpact as necessary, consider
osmotic stool softener
Treat with broad-spectrum antibiotic, re-
educate on proper tube care and hygiene of
tube site
Treat obstruction; treat constipation; if not
obstructed or constipated, vent gastric port
or consider a Farrell Valve Bag*

*Farrell Valve Bag System (Corpak Medsystems, Buffalo Grove, IL) is a device that allows continuous venting of tube feedings and provides reservoir for
formula.

It is important to realize and relay to families that TF is
a dynamic process that can and should be adjusted fre-
quently to best meet the needs of the child. This includes
taking into account changes in medical status (which may
affect TF tolerance), variations in activity levels or nutrient
requirements, decreases or increases in oral intake, and growth.
TRANSITION FROM TF TO ORAL FEEDINGS
The decision to start weaning the child from TF depends on
his or her nutritional status, oral motor skills, swallowing
ability, and concurrent diseases as well as the readiness of
the patient/caregivers. For most children, TF has a sub-
stantial behavioral component such as absence of sucking,
withdrawal from offered food, tongue chewing, gagging,
and food aversion with the sight or smell of food. This
makes the process more complicated and challenging.
Sensory food aversions increase the child’s sensitivity to
the sight or smell of food and leads to the fear of trying
new food. Posttraumatic feeding disorder is caused by a
traumatic oropharyngeal event such as intubation or pro-
longed tube feeding. (13) Treatment involves a multidis-
ciplinary team consisting of a physician, speech therapist,
occupational therapist, dietitian, and child psychologist.
The relationship between the child and the caregiver also
plays an important role. Behavioral treatments usually
involve positive reinforcement, modeling (observation
of other person performing goal behavior), and shaping
(goal behavior is broken down into components with the
final stage of completing the behavior). Other important
components of treatment are oral motor stimulation,
supplementation, and appetite stimulants. (8)(13)(14)(15)
(16)(17)(18)
SOCIAL CONSIDERATIONS
It is important for the health care team to understand that
initiating TF is a difficult decision for the patient and family.

32 Pediatrics in Review
Studies have shown that parents’ decisions about tube inser-
tion are complex. (19) Parents might have a feeling of guilt or
see it as a failure on their part to adequately feed their child.
Brotherton et al (20) reported that the key issues based on
parents’ views about the impact of feeding on daily lives of
both the children and their families, included delayed and
disturbed sleep, restricted ability to go out, difficulties in
finding a place to feed, child care problems, negative attitudes
of others toward feeding, and family divisions.
Pederson et al (21) reported that factors associated with
the stress reported by parents of children with an enteral
feeding tube were severity of their child’s illness/disability,
the constant caretaking demands placed on the parents, and
the level of support provided by the parents’ social network.
It is, therefore, important that health care professionals
prepare the child and the family for the challenges of TF
and provide them support.
CONCLUSION
TF is a means of delivering complete nutrition to those who
would otherwise not receive it, thus supporting the best
possible growth and development. A successful TF program
requires input from many health care professionals and
Parent Resources from the AAP at HealthyChildren.org
• Caring for a Premature Baby: What Parents Need to Know: https://www.healthychildren.org/English/ages-stages/baby/preemie/Pages/
Caring-For-A-Premature-Baby.aspx
• Challenges Faced by Parents of Children with Congenital Heart Disease: https://www.healthychildren.org/English/health-issues/
conditions/heart/Pages/Challenges-Faced-by-Parents-of-Children-with-Congenital-Heart-Disease.aspx
thoughtful planning and dedication to deliver safe nutri-
tion support. A team approach is necessary. The team
should always include the patient, the patient’s family,
and caregivers.
Summary
• Based on overwhelming observational studies as well as
consensus, tube feeding (TF) is a means of delivering complete
nutrition to those who would otherwise not receive it, thus
supporting the best possible growth and development. (Evidence
quality B, C, D). (4)
• A successful TF program requires input from many clinicians and
thoughtful planning and dedication to deliver safe nutrition
support. Based primarily on consensus with some observational
and cohort studies, a team approach is necessary (Evidence
quality C and D). (19)(20)
• Based on consensus with the support of some observational
studies, the team should always include the patient, the patient’s
family, and caregivers (Evidence quality C and D). (19)(20)
References for this article are at http://pedsinreview.aappubli-
cations.org/content/38/1/23.
Vol. 38 No. 1 JANUARY 2017 33
 PIR Quiz
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REQUIREMENTS: Learners
1. An 8-month-old infant is admitted to the hospital for failure to gain weight despite home- can take Pediatrics in
based efforts to provide adequate energy orally. You discuss with the parents the feeding Review quizzes and claim
options of enteral nutrition (EN) and parenteral nutrition (PN). As compared to PN, which of credit online only at:
the following EN features makes it the preferred feeding method in this patient? http://pedsinreview.org.
A. Ability to promote earlier gut function.
B. Delivery cost is similar to PN. To successfully complete
C. Effectiveness is independent of liver function. 2017 Pediatrics in Review
D. Hospital length of stay is similar to that for PN. articles for AMA PRA
E. Infection risk is similar to that for PN. Category 1 CreditTM,
learners must
2. You are asked to lead an orientation program for new nurses at your hospital on oral feeding demonstrate a minimum
alternatives. In which of the following clinical scenarios would an orogastric tube be the performance level of 60%
preferred feeding method? or higher on this
A. Preterm infant (now 32 weeks corrected age) with persistent oxygen requirement. assessment, which
B. Term infant being treated with therapeutic cooling for hypoxic ischemic measures achievement of
encephalopathy. the educational purpose
C. Term infant with 15q11.2-q13 deletion (Angelman syndrome). and/or objectives of this
D. Toddler with a temporal skull fracture and altered mental status. activity. If you score less
E. Toddler with Pierre Robin sequence who requires long-term nutrition support. than 60% on the
assessment, you will be
given additional
3. You are placing a nasointestinal tube in an infant with severe oral aversion who has not
opportunities to answer
tolerated gastric feeding. Which of the following is the most reliable method to confirm the
questions until an overall
successful placement of the tube in this patient?
60% or greater score is
A. Aspiration of bilious stomach contents. achieved.
B. Auscultation over the abdomen.
C. Clinical impression.
D. Radiologic confirmation. This journal-based CME
E. Using a tube/body length nomogram. activity is available
through Dec. 31, 2019,
however, credit will be
4. A 4–year-old girl with dystonic cerebral palsy (Gross Motor Function Classification System V)
recorded in the year in
requires enteral nutrition support because of frequent aspiration pneumonias and poor gut
which the learner
motility. Postpyloric feeding is recommended as the preferred method of enteral feeding. Which
completes the quiz.
of the following statements represents the greatest advantage of postpyloric feeding in this child?
A. Eliminates the risk for reflux aspiration.
B. Has a lower incidence of tube occlusion.
C. Is better tolerated in patients with gastroparesis.
D. Minimizes symptoms of dumping syndrome.
E. Permits a more flexible feeding schedule.

5. You are meeting with your multidisciplinary team to implement a patient’s feeding plan.
You discuss with the team the 2 considerations of bolus feeding versus continuous feeding.
In deciding to choose between the 2 methods, which of the following factors favors bolus
feedings over continuous feedings?
A. Gastroparesis.
B. Intestinal malabsorption.
C. Patient mobility level.
D. Poor nutritional status.
E. Volume of oral intake.

34 Pediatrics in Review
 Overcoming Challenges to Care in the Juvenile
Justice System: A Case Study and Commentary
Rebekah J. Savage, MD, MPH,*† Jasmine M. Reese, MD, MPH,*‡ Stephenie Wallace, MD, MSPH,* Timothy Wang, MD,x
Traci Jester, MD, RD,{ Robert Lowe, MD, PhD,** LaKeshia Hyndman,†† Nefertiti Durant, MD, MPH*
*Department of Pediatrics, Division of General Pediatrics and Adolescent Medicine; †Department of Family and Community Medicine, Division of Student
Affairs; xDepartment of Pediatrics; {Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition; **Department of Pediatrics,
Division of Pediatric Rheumatology, University of Alabama at Birmingham, Birmingham, AL
‡
Physicians’ Primary Care of Southwest Florida, Fort Myers, FL
††
University of Alabama at Birmingham School of Medicine, Birmingham, AL

Practice Gaps
1. Vulnerable youth populations, such as those in the justice system, have
been found to have disproportionately higher unmet medical needs
that sometimes require innovative approaches to diagnosis and
management. (1)(2)
2. Pediatric clinicians require education about the social and systems-
level challenges to care and the strategies to overcome these
challenges to effectively serve as treating and advocating clinicians for
these patients. (1)

Objectives After completing this article, readers should be able to:

1. Discuss demographic and health care needs of delinquent youth in the

juvenile justice setting.
2. Recognize the role of clinician biases in delivering care to delinquent youth.
3. Discuss challenges to proper diagnosis, management, and treatment of
health conditions in a justice setting and how these factors affect
AUTHOR DISCLOSURE Drs Savage, Reese, patient adherence.
Wallace, Wang, Jester, Lowe, and Durant and
Ms Hyndman have disclosed no financial 4. Discuss how to improve adherence in a vulnerable population,
relationships relevant to this article. This
including family involvement and connection to community resources.
commentary does not contain a discussion of
an unapproved/investigative use of a 5. Recognize the social and systems-level barriers associated with caring
commercial product/device.
for youth with chronic medical conditions, including family stressors,
ABBREVIATIONS transportation, and poor communication by clinicians.
AAP American Academy of Pediatrics
ED Emergency department
EMR Electronic medical record
IBD Inflammatory bowel disease Abstract
JDO Juvenile detention officer
NCCHC National Commission on Youth in the criminal justice system commonly suffer from multiple
Correctional Health Care medical and psychological health problems. Because they likely live in
NSAID Nonsteroidal anti-inflammatory
lower socioeconomic environments, the medical care they receive
drug

Vol. 38 No. 1 JANUARY 2017 35

 through the justice system might be their only recent medical care and
can result in the discovery of health problems or chronic illnesses that
must be managed while in the system and beyond. We describe the case
of an adolescent diagnosed with a serious chronic disease during his time
in an urban detention center to illustrate how health workers and justice
staff must use a team approach in caring for this vulnerable population of
children. Barriers to appropriate care, including social and systems-level
challenges, are discussed. The lessons learned in this case can be applied
more broadly to other vulnerable youth populations, including those in
foster care and impoverished communities where the primary care
pediatrician (or other assigned pediatric specialist) is both the leader of
the medical team and an advocate for quality care.

INTRODUCTION juvenile justice health care. (1)(13) According to the NCCHC

Since the Juvenile Court Act of 1899, youth have been
separated from adults in the criminal justice system. (3)
Currently in the United States, more than 61,000 youths
younger than age 21 years are incarcerated, detained, or living
in residential homes. There are almost 200 individuals in the
juvenile justice system for every 100,000 juveniles. (4) Place-
ment options for juvenile offenders include residential facil-
ities that house incarcerated adolescents after adjudication and
detention centers where adolescents typically spend a short
period of time before adjudication or while awaiting disposi-
tion or transfer to another facility. (5) In recent years, cases
handled by juvenile courts have been decreasing, with slightly
more than 1 million cases in 2013 resulting in more than
200,000 adolescents being placed in detention centers. (6)
Poverty and race are associated with youth criminal
involvement. One out of every 5 youths younger than age 18
years in the United States lives in poverty, a factor linked to
juvenile justice involvement. (7) There are proportionately more
delinquency cases for African American youth compared to
national census data. (7) Minority status and poverty are both
associated with poor health. (8) Thus, it follows that the health
needs of the juvenile justice population are greater, with youth
in the justice system disproportionately affected by multiple
medical and mental health problems, including sexually trans-
mitted infections, dental problems, substance use disorders,
trauma histories, and suicidal ideation. (1)(2)(9)(10)(11)
To address the complexity of health concerns consis-
tently, the National Commission on Correctional Health
Care (NCCHC) has published standards of care for detained
and incarcerated youth. (12) In addition, the American
Academy of Pediatrics (AAP) and the Society for Adolescent
Health and Medicine have published policy statements on
guidelines, all youth should undergo health screening upon
arrival at a detention center. (12) The initial screening rec-
ommended by NCCHC is to assess for urgent medical
problems, contagious diseases, and behaviors such as sui-
cidal ideation. Per NCCHC guidelines, youth should also
complete a comprehensive health assessment, including a
physical examination by a physician, physician assistant, or
nurse practitioner within 7 days of admission. The goal of
the NCCHC standards is to address medical and mental
health needs at the beginning of detainment and provide
continual quality of care throughout detainment. (12)
Although urgent medical concerns are appropriately the
focus of juvenile justice health care, unmet chronic medical
and psychological needs are frequently encountered. (1)(9)
(14) In a seminal study on juvenile justice health by Hein
and colleagues, (14) almost 50% of detainees had diagnos-
able medical problems. Many of these were chronic condi-
tions not yet diagnosed for various reasons, including lack of
health care access. For example, Goodwin and colleagues
(15) found that 20% of youth in the justice system had a
diagnosable mood disorder and almost 20% had asthma
when assessed upon entrance to a detention center. In a
study by Feinstein et al, (9) at least 10% of youth in a
detention center had a medical diagnosis requiring fol-
low-up evaluation after discharge, more than 16% had been
treated for mental illness before intake, and only 33%
reported having a medical home.
Biases may exist among health workers caring for incar-
cerated or detained youth. (16)(17) Although the medical
team may not intentionally exhibit prejudice or “explicit”
bias based on race, ethnicity, or institutional status, research
shows that clinical decision-making of physicians may be

36 Pediatrics in Review
affected by implicit bias (due to race, ethnicity, gender, and
other factors). (17) For youth in the justice setting, implicit
bias may be related to suspicion for secondary gain (or a
change in a social situation that results from a certain
complaint or physical symptom). (18) Such bias is uncon-
scious or “automatic” (17) and may play a role in delaying
medical diagnosis and treatment. Of the articles written to
date on detained youth, none have addressed the possibility
of implicit or explicit clinician bias.
Quality care for the juvenile justice population is chal-
lenging due to the higher prevalence of health concerns and
social issues in the context of a constrained system of care.
To explore these challenges further, we report the case of an
adolescent detained at a juvenile detention center in an
urban southeastern United States city who was diagnosed
with a complicated chronic medical condition during incar-
ceration. We describe the challenges of meeting the health
care demands of detained youth and discuss the care of
chronic illness among vulnerable youth populations. By
sharing obstacles and lessons learned, we hope to foster a
conversation among pediatric clinicians that leads to impro-
ved care for this sometimes-overlooked patient population.
Informed consent for the sharing of deidentified informa-
tion was obtained from the patient and his mother.
CASE PRESENTATION
A 15-year-old African American adolescent presents to the
county’s youth detention facility, where an initial health
screening reveals a history of asthma and normal findings
on physical examination. After 1 to 2 weeks at the detention
facility, the patient complains of right hip pain, which is
evaluated by the physician working at the detention center.
After reassuring findings on the evaluation (negative for
trauma or history of arthritis), the physician advises rest and
nonsteroidal anti-inflammatory drugs (NSAIDs). In sub-
sequent weeks, the adolescent develops multiple other joint
complaints, including hip and jaw pain in the context of
worsening behavior and altercations with other detainees
and detention officers. NSAIDs are administered for 1 week
with no improvement in the jaw pain. Detention officers and
health care staff express concern that the patient is attend-
ing medical visits for secondary gain (ie, missing required
activities with a possibility to travel outside of the facility for
medical evaluation). The patient eventually develops difficulty
eating solid food due to jaw pain, refusing many of his meals.
He also becomes unable to ambulate due to worsening hip
pain. Because of this change in status, the physician sends the
patient to the emergency department (ED) at the local chil-
dren’s hospital. He is evaluated with radiographs of the hips,
which are read as normal. The patient is diagnosed with
muscular sprain and returned to the detention center with a
plan to continue NSAID therapy and rest.
Two days later the patient develops new left knee swell-
ing. Knee radiographs obtained as an outpatient are read as
normal. On reevaluation, the detention center physician
notes worsening of left knee swelling, with increased pain
and limited range of motion. The adolescent has no other
systemic symptoms such as fever. Results of laboratory
studies obtained by the detention center nurse are concern-
ing for inflammation or infection: elevated white blood cell
count of 12,850/µL (12.85  109/L), erythrocyte sedimen-
tation rate of 68 mm/h (normal 0-15 mm/h), and C-reactive
protein of 250 mg/L (2,381 nmol/L) (normal <10 mg/L
[95.24 nmol/L]). Due to the concern for acute infection of
the knee joint, he is transported immediately to the ED,
where he is admitted to the hospital and orthopedic surgery
is consulted. Throughout his short hospitalization, joint
fluid cultures remain negative, and parenteral antibiotics
are discontinued after 2 days. He improves without antibi-
otics and is discharged to the detention center.
Two days after discharge, the patient has a stable left
knee examination but continues to have multiple joint com-
plaints with refusal to ambulate. An appointment at the local
children’s hospital adolescent clinic is coordinated by the
detention center physician, where rheumatology is con-
sulted to assist in his evaluation. In the clinic, he complains
of worsening left knee swelling; continued jaw pain precluding
normal food intake; and new-onset pain in multiple joints,
including the left elbow, right shoulder, right wrist, and right
hand. The patient’s right hand is swollen and tender to palpation.
For the first time, the patient reports an unclear number of
episodes of nonbloody diarrhea for the past 2 weeks. Physicians
note weight loss since the previous hospitalization. Given his
deterioration, he is admitted again to the local children’s hos-
pital. Laboratory tests and imaging of the involved joints show
evidence of inflammation and arthritis of his right wrist.
After ruling out infectious causes, the patient is given
corticosteroids to address a working diagnosis of inflam-
matory arthropathy. Because of the history of diarrhea, weight
loss, a perianal skin tag, and stool studies positive for blood,
gastroenterology is consulted about possible inflammatory
bowel disease (IBD). Laboratory results to investigate IBD are
pending at the time of discharge. He is discharged with
instructions to follow up with multiple specialists, including
rheumatology, physical therapy, and gastroenterology, de-
pending on stool laboratory results. Discharge medications
included high-dose NSAIDs and corticosteroids.
Because of the complexity of his illness and specialty
needs after discharge from the hospital, the patient is
Vol. 38 No. 1 JANUARY 2017 37
 granted a conditional medical probation to be released to
home early (before adjudication). Two weeks after discharge
from the hospital, stool laboratory results suggest possible IBD.
The inpatient team’s social worker contacts both the patient’s
probation officer and his family regarding the importance of
returning to appointments to discuss these results and the
need for further evaluations. However, the patient and family
do not appear for rheumatology or gastroenterology appoint-
ments and do not return phone calls.
Because of the lack of attendance at medical appoint-
ments, the physician and inpatient social worker contact the
department of human resources to obtain family assistance.
Finally, 2 months after hospital discharge and weeks after
the return of the concerning laboratory results, the patient is
ordered by the judge to reenter the short-term detention
facility due to violation of his medical probation.
On reentry, he is evaluated medically at the detention
center and found to have problems (eg, weight gain) due to the
long-term use of high-dose corticosteroid medication. Detention
staff and physicians are unable to contact his guardians regard-
ing the immediate need for home medications as well as further
diagnostic evaluations. Because of the inability to make contact
with his guardians, the patient’s medications are obtained from
pharmacies by juvenile detention officers (JDOs) and from
nursing staff. Detention center physicians consult with gastro-
enterology and rheumatology about tapering corticosteroids
while monitoring blood pressure and symptoms closely at least
3 times per week. With the help of the courts, permission from
his guardians is finally granted to complete his diagnostic
evaluation while at the detention center.
Biopsies from gastroenterology procedures verify the
diagnosis of ileocolonic Crohn disease. The patient and
his mother discuss the diagnosis with both gastroenterology
and rheumatology physicians during a coordinated joint
clinic visit. Because of the details of his charge, the patient’s
sentencing is delayed many times, and, therefore, he re-
mains in the detention center for multiple months. He is
initially treated with methotrexate (an injectable antineo-
plastic agent) with little improvement. After a few weeks,
an injectable tumor necrosis factor-a inhibitor medication
(adalimumab) is added, although another delay in treatment
results from pharmacy and shipping confusion. At the end
of his time in short-term detention, the patient is transferred
to a youth prison facility for incarceration and receives
transportation to the same hospital for subspecialist care.
DISCUSSION
Challenges to the care of detained adolescents with complex
chronic medical conditions have been infrequently dis-
cussed in the literature on juvenile justice health. The case
presented in this article illustrates numerous challenges and
lessons learned (Table 1).
Challenge 1: Communication
Communication across systems and disciplines is key to
provision of appropriate care. Challenges to communication
occurred at several levels: 1) patient-clinician, 2) system-
system, and 3) clinician-family.
The first challenge in communication occurred between
the adolescent himself and clinicians. Health screenings and
assessments are the standard of care (12) but rely on the self-
report of the detainee and, thus, can be problematic. (9) Health
complaints during detainment were addressed quickly but were

TABLE 1. Improving Health Care for Youth in Vulnerable Settings:

Challenges and Proposed Improvements
CHALLENGE PROPOSED IMPROVEMENTS EXAMPLE ACTIVITIES FROM CASE

Communication
Clinician biases
Family and social barriers
Resource and time constraints Educate nonmedical staff on health care needs Medical staff meets with management of detention center
Assign a team coordinator
Assign a family advocate
Increase objective measures of health status
Improve awareness of bias
Involve community resources early in process
Use team approach to engagement
to reallocate resources to meet needs of patient.
Coordinator connects clinicians via email correspondence
and asks for feedback and advice regarding medical
details.
Advocate works with social and legal resources to maintain
family communication.
Clinicians document vital signs, including weight, at every
medical visit.
Detention center staff and health workers meet together for
training and communication purposes.
Team leader connects family with human resources worker.
Medical, legal, law enforcement, and community agency
staff work together to meet needs of family.

38 Pediatrics in Review
difficult to assess completely due to lack of appropriate com-
munication with the patient regarding the clinicians’ medical
concerns. In addition, patient confidentiality was restricted,
given the presence of detention officers and constant shackling
during medical visits outside of the facility, leading to a lack of
information sharing between patient and clinician.
The second communication barrier occurred between
systems of care: the justice system and the hospital-based
system. Clinicians documenting information at the deten-
tion center used only paper records, but hospital records
were electronic. Electronic medical records (EMRs) are an
essential component of the health care reforms of the
Affordable Care Act because of improved efficiency and
quality of care. (19) The AAP recommends use of EMRs by
correctional health care facilities. (1) In this case, the ED and
inpatient attending physicians could not review the patient’s
medical chart via EMR. The paper chart from the justice facil-
ity was not transported to the hospital with the patient. This led
to a delay in hospital documentation of details such as diffi-
culty eating and weight loss, which were documented only in
the paper chart. Similarly, different JDOs accompanied the
patient to each medical visit, none of whom consistently
understood his medical course. This led to miscommunication
between medical and justice system providers that affected the
patient’s timely diagnosis and treatment.
Third, communication between the medical team and the
patient’s family was limited due to several factors, including
transportation and work scheduling. During his second hospital
stay, discharge planning included subspecialty appointments
and treatment of arthritis with potentially dangerous medica-
tions. The medical social worker assisted the team in commu-
nicating with the family briefly before discharge. However, as in
many rheumatologic illnesses, diagnosis takes a prolonged
period of time. The diagnostic process and treatment plan
can be confusing to clinicians, patients, and family members.
Similarly, no clinicians phoned his documented primary care
provider to discuss his course and future care needs.
In summary, communication can be a great pitfall to
caring for chronic diseases in the juvenile justice system. In
this case, the pediatrician working in the justice system took
responsibility for the patient’s care needs, which led to
improved clinician and family communication. She made
phone calls to his parents on multiple occasions before and
after hospitalizations. When he failed to present at subspe-
cialty appointments, she coordinated the legal and social
resources necessary for him to receive care (eg, contacting
the county’s human resource department). She began an
email correspondence among all involved in his care, includ-
ing the detention center nurse who was at the center every
weekday. Coordination of care in this complicated medical
and social situation led to improvement in both communi-
cation and quality of care throughout his medical course.
Challenge 2: Provider Biases
Medical complaints in the context of poor behavior may
have led to biases by medical and detention staff. Behavior
exhibited by the patient, including altercations with other
detainees and refusal to eat solid foods, led to concerns that
some of the patient’s medical complaints may have arisen to
avoid consequences or required activities (ie, meals). These
examples display the potential dangers of health care biases,
both explicit and implicit. In the patient’s case, clinician
biases due to the patient’s detained status, gender, or race
may have negatively affected or delayed appropriate care.
Research on this important phenomenon is lacking.
Clinician awareness of implicit bias based on detention
status and behavior can decrease the disparity in care that
may result. (17) Strategies to combat such bias include
treating all patients individually without comparing them
to other detainees. (17) In this case, to overcome bias, the
medical team used objective measures of medical status (eg,
physical examination) and improved upon their documen-
tation of his observed behaviors. Through consistent mon-
itoring of agreed-upon parameters, clinicians and staff
improved clinical assessments. These assessments led to his
hospital admission and disease diagnosis. Developing stand-
ard objective clinical measures to monitor such patients may be
helpful. Clinicians and detention center staff should confront
their own implicit biases for all patients through training
programs and enhanced communication about this important
topic to increase awareness and improve care for all youth,
especially those in juvenile justice settings.
Challenge 3: Family and Social Barriers
Family engagement is essential to the care of detained
adolescents. Research indicates that 50% of parents of
detainees who required follow-up evaluation and treatment
for chronic conditions were not responsive to staff phone
calls and did not make efforts to assist in this process. (9)
Our patient was placed on probation after his second
hospitalization to allow for the family to take responsibility
for his care. His family did not adhere to medical recommen-
dations. After his return to the center, he required multiple
medication changes and was difficult to manage from an
arthritis standpoint, requiring escalation of therapy and a
prolonged corticosteroid taper. The ensuing weeks involved
coordination of specialty appointments and attempts at com-
munication with the patient’s mother. She initially did not
return phone calls. Appointments, procedures, and medication
changes were delayed because of the necessity of her involve-
ment as legal guardian.
Vol. 38 No. 1 JANUARY 2017 39
 TABLE 2. Members of the Care Team for Youth in the Justice System
TEAM MEMBER ROLE

Patient Focus of the care team

Patient’s family
Justice center physician/clinician
Justice center nursing staff
Medical or other health social worker
Subspecialty physician/clinician
Law enforcement officer (eg, juvenile detention officer)
Judicial official (eg, probation officer)
Community agency (eg, human resources worker)
Medical home physician/clinician
Advocates for patient
Provides resources to patient
Communicates resource needs
Leads and coordinates care of patient
Promotes communication among team members
Provides direct care and monitors progress
Acts as liaison among patient, family, medical staff, and nonmedical staff
Assists nursing and medical staff with patient care needs
Engages family in care
Provides specialty expertise on illness
Monitors and reports on patient’s behavior
Directs disciplinary actions to promote health and positive development
Represents and serves the patient within the legal system
Understands family dynamics and social concerns
Assesses need for assistance
Connects patient and family with needed resources
Maintains relationship with patient and family
Manages health care and quality of life over time

Despite these challenges, the detention center medical
team continued to attempt to engage the family. The center’s
nurse phoned the adolescent’s mother on a daily basis to
attempt communication of medical updates and reported
needs, including medications to be filled or brought in to the
center. Medical staff and judicial officials (eg, probation
officers) communicated frequently. Medical visits to explain
Crohn disease and arthritis were coordinated between sub-
specialty providers and the patient and his mother to edu-
cate them on the details of the diagnosis. With the help of
all members of the team and some persistence, his mother
became more engaged in his care and eventually could be
relied upon for medication refills and other needs. Im-
portantly, the detention center nurse taught the patient to
administer his own medications (injections) during his time
in detention, monitoring him with each administration and
empowering him to take responsibility in the absence of his
family.
Young men and women in the justice system are more
likely to have low social support, which hinders chronic care
management. (1) Such social barriers at baseline (eg, trans-
portation) may escalate when a chronic disease is diagnosed
during detention or incarceration. Even without chronic
disease, detained youth have poor follow-up care after release
from detention. (9) One challenge to accessing this follow-up
is that most detainees have health insurance, especially
Medicaid, suspended during imprisonment, which can cause
confusion about medical care coverage after release. (20)(21)

TABLE 3. Selected Resources for the Clinician

NAME WEBSITE

National Commission on Correctional Health Care (NCCHC) www.ncchc.org

Society for Adolescent Health and Medicine www.adolescenthealth.org
Office of Justice Programs, US Department of Justice www.ojp.gov/programs/juvjustice.htm
Substance Abuse and Mental Health Services Administration (GAINS Center for Behavioral www.samhsa.gov
Health and Justice Transformation) www.samhsa.gov/gains-center
American Academy of Pediatrics (Advocacy & Policy) www.aap.org/en-us/advocacy-and-policy
Individual state departments of public health and associated mental health divisions

40 Pediatrics in Review
 Our patient’s lack of follow-up was likely due to poor
communication with his family about his illness, leading to
poor understanding of his health care needs in the context of
broader social and economic challenges. We attempted to
overcome this challenge through involvement of multiple
team members, including detention staff, probation offi-
cers, judges, and medical providers (Table 2). Future cases
may benefit from early linkage to community agencies,
including human resources and a community primary care
provider or a “medical home” before discharge or release. In
most cases of youth involved in the justice system, the
probation officer is an appropriate starting point for pedi-
atric clinicians who need to communicate with a legal
representative to provide appropriate care.
Challenge 4: Resource and Time Constraints
Although health care standards for detained youth exist,
resources such as staffing are not always readily available. For
example, detention center staff members are required to
transport youth to specialty medical appointments, laboratory
evaluations, and other studies. With complex medical diseases,
these appointments may require a full day, using a paid staff
member for 1 detainee. In a resource-deprived setting, staff
must be educated on how to appropriately address the medical
needs of the young detainee with a complex medical illness.
A team approach assisted in delivery of care via commu-
nication among the medical staff, detention officers, and
management personnel of the center itself. For example, the
center’s director and other staff received education on the
patient’s illness and its serious nature, including the daily
medication schedule and possible complications. Resource
allocation was adjusted to meet transportation needs, such as
visits to pharmacies by the center’s nurse or the probation
officer to ensure that the patient obtained his medication in a
timely fashion. Overall, to provide the necessary resources in
a unique situation, the medical team and staff had to take an
individualized and unique approach. Clinicians may obtain
more information on the care of justice-involved and other
vulnerable youth at several online resources (Table 3).
CONCLUSION
Our patient’s story illustrates the complexity of diagnosing
and caring for chronically ill youth in a justice setting. The
lessons learned can be applied more broadly to other vulner-
able youth populations, such as those in foster care and
impoverished communities. Detained youth have vulnerabil-
ities on multiple socioecological levels, including individual
high-risk behaviors and mental health needs, as well as family
and socioeconomic factors such as poverty. Thus, many
challenges arise when a detained youth is diagnosed with
a chronic illness. Poor behavior on the part of the adolescent
can lead to clinician biases; lack of family engagement and
understanding can result in nonadherence; poor communi-
cation can exist between systems of care; and many systems
and individuals must deal with resource deprivation.
The primary care pediatrician (or other assigned pediat-
ric specialist) leads the medical team through coordination
of care, consistent communication, and patient advocacy.
With persistence in family engagement, creative resource
allocation, and awareness of biases, quality of care can
improve for all patients. Pediatric clinicians are the optimal
advocates for vulnerable youth populations such as those
in the justice system. Such public health advocates are
uniquely positioned to educate health care administration
on appropriate health care delivery. Youth health providers
and policymakers must ensure that patients receive devel-
opmentally appropriate care that is no less than care for
patients outside of the justice setting. Detained youth should
retain their insurance coverage and have equal access to
primary and specialty care. Pediatric clinicians and public
health practitioners have an opportunity to engage and edu-
cate patients, their families, and communities to improve the
care of all vulnerable youth populations, especially those
within the juvenile justice system.
Summary
• Youth involved in the juvenile justice system are a vulnerable
pediatric population who require special attention due to
disproportionate rates of undiagnosed and untreated medical
illnesses that can lead to health disparities and poor outcomes.
• Challenges to care for justice-involved youth include social
factors such as family involvement, communication with
clinicians, and transportation.
• Addressing systems-level barriers to care, such as lack of
resources in justice facilities and poor access to care for
impoverished youth, can offer opportunities for improvement
through policy changes and effective collaboration.
• Quality pediatric primary care is best implemented with a team
approach to appropriately evaluate and manage the acute and
chronic health problems encountered in this setting. This
includes linkage to community resources and a medical home
after release from the justice system.
References for this article are at http://pedsinreview.aappubli-
cations.org/content/38/1/35.
Vol. 38 No. 1 JANUARY 2017 41
 PIR Quiz
There are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link under the article title in the Table of Contents of any issue.
2. To access all CME articles, click “Journal CME” from Gateway’s orange main menu or go directly to: http://www.aappublications.
org/content/journal-cme.

REQUIREMENTS: Learners
1. A 14-year-old boy arrives at a detention center where he will be housed while he can take Pediatrics in
awaits adjudication. He undergoes health screening upon arrival. In addition to Review quizzes and claim
assessing for urgent medical problems and behaviors such as suicidal ideation, credit online only at:
which of the following conditions must be included in the routine health http://pedsinreview.org.
screen?
A. Asthma. To successfully complete
B. Contagious diseases. 2017 Pediatrics in Review
C. Mood disorder. articles for AMA PRA
D. Rheumatologic disease. Category 1 CreditTM,
E. Weight loss. learners must
demonstrate a minimum
2. A 16-year-old boy undergoes a health screening upon arrival at a detention center. The performance level of 60%
screening reveals no urgent medical problems. In the context of this initial admission or higher on this
screening, a comprehensive health assessment including a physical examination should be assessment, which
performed within what time period from admission? measures achievement of
A. 48 hours. the educational purpose
B. 7 days. and/or objectives of this
C. 14 days. activity. If you score less
D. 30 days. than 60% on the
E. 60 days. assessment, you will be
given additional
opportunities to answer
3. A medical director of a juvenile detention center conducts monthly meetings with the
questions until an overall
detention center health care team and staff to discuss operational and training issues.
60% or greater score is
Which of the following is the most effective measure to adopt to avoid disparity in care that
achieved.
may result from implicit biases?
A. Giving context by comparing patients to other detainees.
B. Implicit bias toward secondary gain as a motivator for symptom reporting. This journal-based CME
C. Provider awareness of implicit bias based on behavior. activity is available
D. Reliance upon patient reporting of medical conditions. through Dec. 31, 2019,
E. Use of subjective measures of medical status. however, credit will be
recorded in the year in
which the learner
4. A 13-year-old girl receives a provisional diagnosis of lupus while at a detention center.
completes the quiz.
Medical follow-up is required after additional test results are received and to monitor her
response to initial therapy. The hospital clinician attempts to call the patient’s family
regarding appointments but is unable to reach a parent or guardian. What percentage of
parents of detainees requiring follow-up for chronic conditions is not responsive to staff
phone calls?
A. 15%.
B. 30%.
C. 50%.
D. 70%.
E. 85%.

5. A 17-year-old boy receives a diagnosis of epilepsy while detained. After release, the patient
fails to attend multiple pediatric and neurology appointments, with no response to multiple
phone calls. Which of the following might be the most appropriate starting point of contact
for pediatric clinicians who need to communicate with a legal representative to provide
appropriate care?

42 Pediatrics in Review
 A. Judge.
B. Juvenile detention officer.
C. Juvenile dependency lawyer.
D. Probation officer.
E. Public defender.

Parent Resources from the AAP at HealthyChildren.org

• Out-of-Control Teens: PINS Petitions & the Juvenile Justice System: https://www.healthychildren.org/English/health-issues/conditions/
emotional-problems/Pages/When-a-Teenager-is-Out-of-Control.aspx
• Foster Parents: FAQs: https://www.healthychildren.org/English/family-life/family-dynamics/adoption-and-foster-care/Pages/Foster-
Parents-FAQs.aspx

Vol. 38 No. 1 JANUARY 2017 43


EDITOR’S NOTE
We invite readers to contribute Index of
Suspicion cases through the PIR manuscript
submission system at: https://mc.
manuscriptcentral.com/pir.
AUTHOR DISCLOSURE Drs Karageorgiadis,
Lyssikatos, Belyavskaya, Papadakis, Patronas,
Lodish, and Stratakis have disclosed no
financial relationships relevant to this article.
This commentary does not contain a
discussion of an unapproved/investigative
use of a commercial product/device.
44 Pediatrics in Review
Poor Growth With Presence of a Pituitary
1 Lesion in an 11-year-old Boy
Alexander S. Karageorgiadis, MD,*† Charalampos Lyssikatos, MD,*
Elena Belyavskaya, MD,* Georgios Z. Papadakis, MD,‡
Nicholas J. Patronas, MD,‡ Maya B. Lodish, MD,*
Constantine A. Stratakis, MD, DSc*
*Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health, Bethesda, MD
†
Department of Pediatrics, Georgetown University Hospital, Washington, DC
‡
Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health,
Bethesda, MD
EDITOR’S NOTE
Beginning with our January 2017 issue, Pediatrics in Review will publish three additional
Index of Suspicion cases each month. All cases will be available in their entirety online, but
only the Presentation for each case will be published in the print edition of the journal. We
anticipate the move to online will encourage authors to use more images and video in their
case submissions.
PRESENTATION
An 11-year-old boy presents to his primary pediatrician due to poor growth. His
height was at the 25th percentile between ages 6 and 10 years and now has fallen
to the 10th percentile. He also complains of fatigue and has a 1-month history
of polyuria, polydipsia, and nocturia. Review of symptoms is negative for weight
loss, headaches, vision changes, gynecomastia, breast discharge, nausea, vomit-
ing, and cold and heat intolerance. His past medical and family histories are not
contributory and his development has been normal.
On physical examination, his temperature is 96.8°F (36ºC), blood pressure is
86/52 mm Hg, heart rate is 59 beats/min, respiratory rate is 18 breaths/min, and
oxygen saturation is 100% in room air. His standing height is 138.23 cm (10th per-
centile), weight is 31.5 kg (10th percentile), and body mass index is 16.5 (10th-50th
percentile). His neurologic examination yields unremarkable results. His pubic hair
is at Sexual Maturity Rating stage 2 and testicular volume of both testes is 10 mL.
Laboratory evaluation shows free thyroxine (T4) of 0.76 ng/dL (9.78 pmol/L)
(normal range 0.93-1.60 ng/dL [11.97-20.59 pmol/L]), total T4 of 4.3 mg/dL (55.35
nmol/L) (normal range 4.5-12 mg/dL [57.92-154.45 nmol/L]), thyrotropin (TSH)
of 1.97 mIU/L (normal range 0.45-4.5 mIU/L), and insulinlike growth factor
(IGF-1) of 103 ng/mL (13.49 nmol/L) (normal range for an 11-year-old male:
112-454 ng/mL [14.67-59.47 nmol/L]). His complete blood cell count, urinalysis
results, and electrolyte values are within normal limits, and his evaluation for
celiac disease is negative. Due to these results, the pediatrician orders mag-
netic resonance imaging (MRI) of the pituitary, which shows a lesion within the
Figure. A and B. Initial magnetic resonance
imaging of the brain showing a pituitary mass
within the sella and suprasellar cistern. C. Pituitary
mass 3 months after therapy.

sella and suprasellar cistern. The greatest vertical, anterior- The Case Discussion and Suggested Readings appear with the
posterior, and transverse diameters of this lesion measure online version of this article at http://pedsinreview.aappublica-
19, 21, and 25 mm, respectively (Fig). tions.org/content/38/1/44.

Vol. 38 No. 1 JANUARY 2017 45

DISCUSSION
The patient underwent imaging immediately after initial
results became available, without further referrals or addi-
tional laboratory evaluation. Clinicians could have consid-
ered referral to pediatric endocrinology before proceeding
with imaging to evaluate pituitary function with further
tests. However, the presence of low free T4 with normal
TSH and low IGF-1 values suggested central hypothyroid-
ism and growth hormone deficiency, which justify the
decision for pituitary imaging, especially taking into con-
sideration the patient’s symptomatology.
The patient was subsequently referred to neurosurgery for
trans-sphenoidal resection of the pituitary mass that was
suspected to be a craniopharyngioma. Before the scheduled
surgery, the patient’s family asked for a second opinion. Al-
though a prolactinoma was considered as a possibility for his
pituitary tumor, his prolactin values had never been measured.
Therefore, the biochemical evaluation was repeated, and the
prolactin measurement was added. His prolactin was found to
be substantially elevated at 996 mg/L (43,304.09 pmol/L)
(normal range 2-25 mg/L [86.96-1,086.95 pmol/L]), which
led to the diagnosis of a prolactin-secreting macroadenoma.
Differential Diagnosis
Craniopharyngiomas are the most common pituitary tumors
in children, accounting for approximately 90% of all pituitary
neoplasms and 6% to 13% of all intracranial tumors. Pituitary
adenomas are rare and account for less than 3% of all supra-
tentorial tumors, with prolactinomas being the most common
(48%-52%). Other conditions that could present with similar
symptoms and lesions on imaging studies are cystic lesions,
such as Rathke cleft cysts, teratomas, or ependymomas, and
even more rarely blastomas, germ cell tumors (50% of which
are usually germinomas), and metastases from other primary
tumor locations (a relatively common event in adult patients
with pituitary tumors but very rare in children).
Taking into consideration the fact that our patient did not
present with galactorrhea or any neuro-ophthalmologic signs,
which may occur in a boy with a prolactinoma, craniopharyn-
gioma or another cystic lesion was considered as the most li-
kely initial diagnosis. In addition, the noncontrast MRI showed
a nonhomogeneous appearance of the tumor with an enhanc-
ing spot, which is more characteristic of a craniopharyngioma.
However, most probably this was due to hemorrhage because it
completely resolved in subsequent imaging studies.
The Condition
Prolactinomas are the most common hormone-secreting
pituitary tumors and have been reported to occur at all ages.
In girls with prolactinomas, microadenomas are encoun-
tered more frequently, and their clinical presentation is
associated with galactorrhea and hypogonadotrophic hypo-
gonadism. Interestingly, males have a greater incidence of
macroadenomas, which can cause neuro-ophthalmologic
signs and symptoms. Prolactinomas in adult males have
been associated with hypopituitarism, with the most com-
mon form being growth hormone deficiency and hypogonad-
ism; hypocortisolism is less common. The diameter of the
adenoma and its prolactin secretion have been shown to affect
the degree of both hypogonadism and hypothyroidism.
Diagnosis of a prolactinoma requires both the laboratory
results of persistent hyperprolactinemia and imaging stud-
ies showing an adenoma. Prolactin values can be related
to the size of the tumor. Most patients with prolactin
concentrations greater than 150 mg/L (6,521.70 pmol/L)
(normal range 2-25 mg/L [86.96-1,086.95 pmol/L]) have a
prolactinoma, but clinicians cannot rule out prolactinoma
if the prolactin values are only moderately increased. The
abnormal expression of genes such as the pituitary tumor-
transforming gene (PTTG) and high mobility group A2 gene
(HMGA2) has been associated with the development of
pituitary tumors, including prolactinomas.
Management
Prolactinomas are treated conservatively with dopaminer-
gic agonists as the initial therapy of choice to shrink the pitui-
tary mass. Such treatment offers the best chance for normal
pubertal development, gonadal function, and future fertility.
Surgery (usually with a trans-sphenoidal approach) is only
performed in cases of drug therapy failure or for neurosurgical
emergencies such as apoplexy. Radiotherapy is very rarely used
and only after failed medication therapy and/or surgery.
Patient Course
The patient was started on 0.5 mg cabergoline, a dopamine
receptor agonist that blocks prolactin secretion from the
pituitary gland, twice a week and 25 mg levothyroxine
once daily. After 1 month of cabergoline treatment, his
prolactin concentrations had substantially decreased to
15.1 mg/L (656.52 pmol/L). During his follow-up evaluation
3 months later, the pituitary MRI showed a decrease in the
size of the adenoma (1.6  1.7 cm) (Fig 1C), the prolactin
values dropped to 5.5 mg/L (239.12 pmol/L), and his thyroid
hormones and IGF-1 values returned to normal range. He
had grown 1.2 cm during those 4 months, and his puberty
had progressed, with more pubic hair and increase in testic-
ular size. Use of cabergoline, especially long-term, has been
associated with mild-to-moderate tricuspid regurgitation
and subtle changes in cardiac valves such as calcifications,
thickening, and increased mitral tenting. Because of this con-
cern for potential cabergoline-associated valvulopathy, baseline
echocardiography was also performed and results were normal.
Lessons for the Clinician
• Patients with prolactinomas do not always present with
characteristic clinical manifestations.
• Prolactin must be measured in all patients suspected to
have a pituitary mass, even if the patient does not present
with typical clinical manifestations of prolactinoma.
• A proper diagnosis of pituitary mass lesions can avoid un-
necessary surgery and/or radiotherapy and, thus, reduce
morbidity and mortality.
Suggested Readings
Delman BN. Imaging of pediatric pituitary abnormalities. Endocrinol
Metab Clin North Am. 2009;38(4):673–698
Fideleff HL, Boquete HR, Suárez MG, Azaretzky M.
Prolactinoma in children and adolescents. Horm Res.
2009;72(4):197–205
Jagannathan J, Kanter AS, Sheehan JP, Jane JA Jr, Laws ER Jr. Benign
brain tumors: sellar/parasellar tumors. Neurol Clin. 2007;25
(4):1231–1249, xi
Kars M, Pereira AM, Bax JJ, Romijn JA. Cabergoline and cardiac valve
disease in prolactinoma patients: additional studies during
long-term treatment are required. Eur J Endocrinol. 2008;159
(4):363–367
Peng J, Qiu M, Qi S, Li D, Peng Y. Hypopituitarism patterns among
adult males with prolactinomas. Clin Neurol Neurosurg.
2016;144:112–118
Stanley T. Diagnosis of growth hormone deficiency in
childhood. Curr Opin Endocrinol Diabetes Obes. 2012;19
(1):47–52
Yamada M, Mori M. Mechanisms related to the pathophysiology and
management of central hypothyroidism. Nat Clin Pract Endocrinol
Metab. 2008;4(12):683–694
Yang I, Sughrue ME, Rutkowski MJ, et al. Craniopharyngioma: a
comparison of tumor control with various treatment strategies.
Neurosurg Focus. 2010;28(4):E5

AUTHOR DISCLOSURE Drs Shawar,
Patamasucon, and Rowles have disclosed no
financial relationships relevant to this article.
This commentary does not contain a
discussion of an unapproved/investigative
use of a commercial product/device.
46 Pediatrics in Review
2 Fever and Back Pain in 13-year-old Girl
Reem Shawar, MD,* Pisespong Patamasucon, MD,* Shawn Rowles, MD*
*Pediatrics, University of Nevada School of Medicine, Las Vegas, NV
PRESENTATION
A previously healthy 13-year-old girl who plays hockey presents with fever of 6
days’ duration accompanied by lower back pain and generalized myalgia. She
initially went to an urgent care facility, where she had normal findings on
urinalysis and a negative flu antigen test. She was diagnosed with a viral illness,
but her symptoms persisted. Today she is experiencing a severe throbbing frontal
headache and nausea. She has no history of furuncles, intravenous drug use, or
recent blunt spinal trauma. Review of symptoms is negative.
Initial vital signs show temperature of 99.2°F (37.3°C), heart rate of 130 beats/
min, and blood pressure of 126/67 mm Hg. Physical examination of the girl, who
is sitting uncomfortably in bed, reveals localized tenderness to palpation in the
lower lumbar region. A nonradiating grade 2/6 systolic ejection murmur is best
heard at the apex. There are no skin lesions or rashes. The patient is alert and
oriented to person, place, and time, with intact short- and long-term memory.
Cranial nerves II through XII are intact. Strength is 5/5 in all extremities, with
normal tone and sensations to pain, temperature, and light touch. She has normal
gait with intact finger-to-nose touch and aligned ankle-over-tibia. Her deep tendon
reflexes are 2þ throughout and Brudzinski and Kernig signs are both negative.
Laboratory evaluation reveals a white blood cell (WBC) count of 10,200/mL
(10.2  109/L) with 79.9% granulocytes, 10.7% lymphocytes, 9.1% monocytes,
0.1% eosinophils, and 0.2% basophils. Her erythrocyte sedimentation rate is 36
mm/h and C-reactive protein measures 281.5 mg/L (2,681.01 nmol/L).
Figure 1. T1-weighted magnetic resonance imaging of lumbar spine after contrast.
 During her stay in the emergency department, the pa-
tient begins to experience neck pain. A lumbar puncture
is performed after results of computed tomography scan of
the head are within normal limits, with no space-occupying
lesion. The fluid drawn from the lumbar puncture is de-
scribed as purulent and mucoid, which leads to further
evaluation with magnetic resonance imaging (MRI) of the
lumbar spine to confirm the diagnosis (Fig 1).
The Case Discussion and Suggested Readings appear with the
online version of this article at http://pedsinreview.aappublica-
tions.org/content/38/1/46.
Vol. 38 No. 1 JANUARY 2017 47
DISCUSSION clinicians placed a peripherally inserted central catheter,
which allowed her to complete her antibiotic course at
The purulent fluid drawn from the lumbar puncture was
home.
sent for Gram stain, bacterial culture, and cell count. The
Gram stain showed many WBCs and Gram-positive cocci in
The Condition
clusters, and the cell count revealed more than 10,000/mm3
An epidural abscess is a rare but serious condition that
of WBCs with undetectable protein or glucose. The Gram
requires emergent diagnosis and treatment. It is a localized
stain from the blood culture drawn on admission also
collection of pus between the dura mater and the overlying
showed many WBCs and gram-positive cocci in clusters.
skull or vertebral column that can extend longitudinally over
MRI of the lumbar spine with contrast was performed
many segments of the spinal cord because there are no
(Fig 2). The lumbar puncture results and MRI findings
resisting structures. It can occur either by contiguous spread
confirmed the diagnosis of a spinal epidural abscess with
or via hematogenous dissemination from furuncles or
paraspinal musculature abscess.
urinary tract or wound infections. It may also result as a
Upon admission of the girl to the general pediatric floor,
complication from spinal surgery or, rarely, lumbar punc-
the neurosurgeon and pediatric infectious disease specialist
ture. Minor trauma to the spine, which was a possibility for
and pediatric cardiologist were consulted. The patient was
this young hockey player, may also be a cause of epidural
given a 24-hour course of dexamethasone and treated with
abscess. Multiple studies, primarily in adult populations,
vancomycin and ceftriaxone. The neurosurgeon did not rec-
have shown that predisposing conditions include diabetes
ommend any surgical intervention because the abscess
mellitus, alcoholism, infection with human immunodefi-
was partially drained during the lumbar puncture. The
ciency virus, and any spinal abnormality or intervention.
pediatric cardiologist performed echocardiography within
The most common organism isolated is S aureus, with an
24 hours of admission, which did not show any evidence of
increasing prevalence of the methicillin-resistant strain.
endocarditis. During her hospital stay, the culture obtained
Other infecting organisms include aerobic and anaerobic
from the lumbar puncture showed heavy growth of oxacillin-
streptococci as well as aerobic gram-negative bacilli, espe-
sensitive, clindamycin-resistant coagulase-positive Staphy-
cially Escherichia coli and Pseudomonas aeruginosa.
lococcus aureus. The blood culture from admission also
Back pain, fever, and headache are the usual complaints,
showed oxacillin-sensitive, clindamycin-resistant coagulase-
although many patients have nonspecific symptoms, which
positive S aureus. The girl continued to receive oxacillin for
can delay diagnosis. The clinical presentation is usually
a total of 6 weeks to treat the spinal epidural abscess,
insidious because the abscess enlarges too slowly to produce
paraspinal musculature abscess, bacteremia, and secondary
the sudden onset of major neurologic deficits. The pre-
bacterial meningitis. Because her inflammatory markers
sentation of spinal epidural abscess can be divided into 4
continued to trend down while she was receiving oxacillin,
phases: back pain at the level of the affected spine (phase 1);
nerve root pain radiating from the affected spinal area
(phase 2); motor weakness, sensory deficit, and bladder
and bowel dysfunction (phase 3); and paralysis (phase 4).
The progression from 1 phase to another can vary from
hours to days, although after stage 3, the progression to ir-
reversible paralysis can be rapid.
The diagnosis of spinal epidural abscess is based on
clinical suspicion, elevated inflammatory markers, and neu-
rologic imaging. MRI is the imaging modality of choice in
cases of suspected spinal epidural abscess because it can
properly show the spinal cord and epidural space. It can
also identify osteomyelitis, adjacent abscesses, soft-tissue
infections, and intramedullary spinal lesions. Diagnosis
Figure 2. In the T1-weighted magnetic resonance imaging, a fluid
collection (red arrow) is seen in the dorsal epidural space with no spinal of spinal epidural abscess can only be confirmed by drain-
canal or foraminal narrowing. There are also fluid collections (white age of the purulent fluid.
arrows) adjacent to the L4 spinous process along with overlying reactive
myositis within the paraspinous musculature. These findings are highly Treatment should not be delayed once spinal epidural
suspicious for abscess centered at the L4 spinous process level with
abscess has been diagnosed because disease progression
extension into the left dorsal posterior epidural space. The abscess tracks
caudally to at least the level of the S2 vertebral level, which is not shown. can be rapid and unpredictable. Treatment consists of two
principles: decreasing the size of the mass and eradicating
the infecting organism. Broad-spectrum antibiotic treat-
ment should be initiated promptly until the infecting organ-
ism’s specificity and sensitivity is identified. Due to variable
causes, identifying the microorganism through drainage fol-
lowed by long-term intravenous antibiotics is the mainstay for
treating extra-axial central nervous system infections. Typically,
treatment should be continued for 3 to 4 weeks but should be
prolonged if the patient has osteomyelitis. It is important to
note that data about management in the pediatric population
are limited, and there is no reported consensus.
The key clinical feature in this case was recognizing that
this patient could have spinal epidural abscess, which is
a serious diagnosis that can progress rapidly. The differen-
tial diagnoses include compressive and inflammatory
processes involving the spinal cord such as transverse mye-
litis, metastatic tumor, and herniation of an intervertebral
disc. Other infectious processes that must be excluded are
bacterial meningitis, osteomyelitis, endocarditis, and disc
space infection.
Lessons for the Clinician
• Physicians should be aware of spinal epidural abscess, a
rare but serious diagnosis, to avoid delay in treatment and
permanent neurologic deficits.
• The clinical presentation of the epidural abscess can be
divided into 4 stages: spinal ache, root pain, motor and
sensory deficits, and lastly paralysis.
• Epidural abscess is managed both surgically and medi-
cally to reduce the size of the abscess and eradicate the
infecting organism.
Suggested Readings
Darouiche RO. Spinal epidural abscess. N Engl J Med. 2006;355
(19):2012–2020
Hawkins M, Bolton M. Pediatric spinal epidural abscess: a 9-year
institutional review and review of the literature. Pediatrics. 2013;132
(6):e1680–e1685
Sáez-Llorens X, Guervera JN. Parameningeal infections. In: Cherry JD,
Demmler-Harrision GJ, Kaplan SL, Hotez PJ, Steinbach WJ, eds.
Feigin and Cherry’s Textbook of Pediatric Infectious Disease. 7th ed.
Philadelphia, PA: Elsevier Saunders; 2014:462–472
 Recurrent Lesions on Palms of a 12-year-old
3 Girl

Alexander K.C. Leung, MBBS,* Benjamin Barankin, MD†

*University of Calgary, Pediatrics, Calgary, Alberta, Canada
†
AUTHOR DISCLOSURE Drs Leung and Toronto Dermatology Centre, Toronto, Ontario, Canada
Barankin have disclosed no financial
relationships relevant to this article. This
commentary does not contain a discussion
PRESENTATION
of an unapproved/investigative use of a
A 12-year-old girl presents with a 1-year history of whitish papules and plaques on
commercial product/device.
her palms after brief exposure to water, such as handwashing or taking a shower
or bath. She is greatly bothered by the appearance and texture of her hands. She
denies having similar lesions on her soles or other cutaneous areas when exposed
to water. There is no family history of similar skin disorders or cystic fibrosis.
The child has atopic dermatitis and asthma. She does not have allergic rhinitis,
abnormal scalp hair, hyperhidrosis, or other skin or systemic disease. Of partic-
ular note, she has no history of chronic lung disease or gastrointestinal disease.
She is not taking any medication and is otherwise healthy.
Physical examination of the palms reveals normal findings. However, follow-
ing immersion of the hands in water at room temperature for 5 minutes,
numerous yellowish-white, nonscaling, smooth-surfaced, flat-topped papules,
some of which have coalesced to form plaques, appear on both palms (Fig).
After drying, the skin normalizes within 30 minutes. The dorsal surfaces of the
hands and other body sites are unaffected with water immersion. The remainder
of the examination is unremarkable. On specific examination, the girl has no
sparse or thin hair.

Figure. White, smooth-surfaced, flat-topped papules and plaques appear on both palms after
immersion in room temperature water for 5 minutes.

The Case Discussion, References, and Suggested Readings appear with the online version
of this article at http://pedsinreview.aappublications.org/content/38/1/48.

48 Pediatrics in Review
DISCUSSION
Based on the history and physical findings, clinicians diag-
nose aquagenic palmar keratoderma. Genetic analysis did
not find any mutation in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene.
Aquagenic palmar keratoderma is characterized by the
transient appearance of translucent white papules or
plaques on the palms shortly after brief exposure to water
that disappear after drying within minutes to 1 hour. The
primary differential diagnosis is hereditary papulotranslu-
cent acrokeratoderma. The latter condition has an autoso-
mal dominant mode of inheritance and presents with
bilateral, symmetric, asymptomatic, yellow-white translu-
cent papules, coalescing into plaques. It appears soon after
puberty and persists throughout life. The lesions occur
primarily along the margins and pressure points of the
hands and feet. Although papules and plaques appear without
water exposure, typically the papules gain increased promi-
nence with water exposure. Hereditary papulotranslucent
acrokeratoderma is associated with fine-textured scalp hair
and an atopic diathesis. Aquagenic palmar keratoderma also
should be differentiated from punctate keratosis of palmar
creases, a condition that primarily affects African American
patients in which the lesions are confined to palmar creases.
The Condition
Clinically, aquagenic palmar keratoderma is characterized
by translucent whitish papules coalescing into plaques
and wrinkling of the edematous palms after contact with
water. The skin changes usually resolve spontaneously
within minutes to 1 hour after the affected area has been
dried. The diagnostic “hand-in-the bucket” sign refers to the
fact that the skin changes are not or barely visible until the
hand is submerged in water. Warm or hot water is more
rapidly effective than cold water in inducing the pheno-
menon. Prolongation of water exposure may intensify the
lesions. Some patients react only to tap water but not salt-
water; others react to both. The condition is typically bilateral
and symmetric. This keratoderma is usually asymptomatic,
although some patients complain of pruritus, tingling, burn-
ing, tightening sensation, or pain in the affected area.
A less common variant presents with persistent translucent
whitish papules and plaques, edema, and wrinkling of the
palms that worsens after submersion of the hands in water.
Aquagenic palmar keratoderma is an uncommon con-
dition, except in patients with homozygous and, less com-
monly, heterozygous cystic fibrosis. We suspect that the
condition is much more common than is generally ap-
preciated. In 1 study, aquagenic palmar keratoderma was
present in 31 of 54 (53.4%) patients with cystic fibrosis, 2
of 23 (8.7%) carriers, and no patients in the control group
after immersion of the hands in room temperature tap water
for 3 minutes. (1) In another study, aquagenic palmar kerato-
derma was present in 11 of 27 (41%) patients with cystic fibrosis
after immersion of the palms in water for 2 to 3 minutes. (2)
Except for patients with cystic fibrosis, the occurrence
is usually sporadic. The condition has a predilection for
adolescents and females. In most cases, the cause is not
known. Aquagenic palmar keratoderma occurs in otherwise
healthy individuals and more commonly in patients with
atopy, hyperhidrosis, and marasmus as well as patients taking
angiotensin-converting enzyme inhibitors (eg, enalapril, rami-
pril), angiotensin-receptor blockers (eg, valsartan, losartan),
selective cyclo-oxygenase inhibitors (eg, celecoxib, rofecoxib),
nonsteroidal anti-inflammatory drugs (eg, acetylsalicylic
acid), and certain antibiotics (eg, aminoglycosides).
The exact pathogenesis is not known. An abnormality
of the sweat duct with dilation of the eccrine ostia, hyper-
keratosis, barrier dysfunction of the stratum corneum, and
defective chloride channels has been implicated.
Histologic examination of a classic lesion shows hyper-
keratosis of the stratum corneum, dilation of intraepidermal
eccrine sweat ducts, dilation of eccrine sweat duct ostia
(acrosyringium), and hyperplasia of the eccrine sweat glands.
Diagnosis
The diagnosis is primarily clinical, based on the character-
istic physical findings after immersion of the hands in water.
The “hand-in-the bucket” sign is pathognomonic. Dermo-
scopy of the lesion typically shows marked enlargement of
the sweat duct puncta compared with unaffected palmar
areas. Histologic investigations are usually not necessary.
Because aquagenic palmar keratoderma can occur both in
patients with cystic fibrosis and in mutation carriers, affected
patients should undergo sweat chloride testing and CFTR
mutation analysis.
Management
If present, the underlying cause should be removed if
possible. For example, offending medications should be
discontinued. Because the condition is benign and usually
asymptomatic, treatment may not be necessary. Despite not
knowing the exact pathogenesis, the cosmetic appearance
and texture can be improved. For patients who prefer to have
treatment, topical 15% to 20% aluminum chloride hexahy-
drate in anhydrous ethyl alcohol, 5% to 20% salicylic acid
ointment, 10% urea cream or ointment, 12% ammonium
lactate cream, petroleum-based barrier creams, and 3%
formalin in anhydrous ethyl alcohol can be used alone or
in combination. Based on the fact that an abnormality of the
sweat duct with dilation of the stratum corneum has been
implicated in the pathogenesis, dermal botulinum toxin
injections and iontophoresis should be considered for cases
not responding to topical treatment, especially in those
with associated hyperhidrosis.
This patient was sufficiently bothered by the cosmetic
appearance and texture of her hands that she was embar-
rassed to shake or show her hands. Accordingly, she was
treated with nightly applications of 15% aluminum chloride
hexahydrate with a hydroalcoholic salicylic acid gel base,
which was prescribed based on previous success with this
agent by the authors and a previous literature search. She
reported satisfactory control with this treatment. Dermal
botulinum toxin injections were offered and may be con-
sidered in the future.
Lessons for the Clinician
• Aquagenic palmar keratoderma is characterized by the
transient appearance of translucent white papules or
plaques on the palms shortly after brief exposure to water.
• The skin changes usually resolve spontaneously within
minutes to 1 hour after the affected area has been dried.
• It is an uncommon condition, except in patients with homo-
zygous and, less commonly, heterozygous cystic fibrosis.
• Affected patients should undergo sweat chloride testing
and CFTR mutation analysis.
References
1. Chinazzo C, De Alessandri A, Menoni S, Romanisio G, Rebora A,
Rongioletti F. Aquagenic wrinkling of the palms and cystic fibrosis:
an Italian study with controls and genotype-phenotype correlations.
Dermatology. 2014;228(1):60–65
2. Garçon-Michel N, Roguedas-Contios AM, Rault G, et al. Frequency
of aquagenic palmoplantar keratoderma in cystic fibrosis: a new
sign of cystic fibrosis? Br J Dermatol. 2010;163(1):162–166
Suggested Readings
Ertürk-Özdemir E, Özcan D, Seҫkin D. Acquired aquagenic syringeal
acrokeratoderma: a case series of 10 patients. Australas J Dermatol.
2013;56(2):e43-e45. doi: 10.111/ajd.12122
Ibusuki C, Oka M, Fukunaga A, Kunisada M, Nishigori C. Unilateral
aquagenic wrinkling of the palms with a peculiar clinical course.
Eur J Dermatol. 2012;22(5):679–680
Kent JB, Statuta SM, Greer KE, MacKnight JM. Watersport hands. Sports
Health. 2014;6(4):360–362
Rongioletti F, Tomasini C, Crovato F, Marchesi L. Aquagenic (pseudo)
keratoderma: a clinical series with new pathological insights.
Br J Dermatol. 2012;167(3):575–582
Sezer E, Erkek E, Duman D, Sahin S, Cetin E. Dermatoscopy as an
adjunctive diagnostic tool in aquagenic syringeal acrokeratoderma.
Dermatology. 2012;225(2):97–99

AUTHOR DISCLOSURE Drs Indra and
Maqbool have disclosed no financial
relationships relevant to this article. This
commentary does not contain a discussion of
an unapproved/investigative use of a
commercial product/device.
Worsening Abdominal Distention in a
4 2-year-old Boy
Sean Indra, MD,* Shazia Maqbool, MD*
*Children’s Hospital of Michigan, Detroit, MI
PRESENTATION
A previously healthy 2-year-old boy presents to the emergency department with
a history of abdominal distention that began 1 week ago and has since been
worsening. He is toilet-trained and his family mentions that he has been having
intermittently decreased urination for the past month. Some days he only urinates
once or twice. He has had no fever, emesis, joint pain, anorexia, weight loss, or
decreased activity. The boy’s medical history and family history are unremarkable.
On physical examination, he has normal vital signs. He appears well and has
normal physical examination findings, with the exception of his gastrointestinal
evaluation. His abdomen is soft but with prominent swelling in the right upper
quadrant and epigastric regions. In the area of swelling, there is a smooth, nontender,
palpable mass without overlying erythema. A liver edge is not palpable because the
mass is overlying that area, but a spleen tip is noted at the left costal margin.
Initial laboratory results include:
• White blood cell count, 14,000/mL (14.0  109/L)
• Absolute neutrophil count, 5,100/mL (5.1  109/L)
• Absolute lymphocyte count, 7,900/mL (7.9  109/L)
• Blood smear revealing occasional anisocytosis
• Hemoglobin, 11.1 g/dL (111 g/L)
• Platelet count, 329  103/mL (329  109/L)
• Aspartate aminotransferase, 47 U/L (0.78 mkat/L) (reference range 0-37 U/L
[0-0.62 mkat/L])
• Alanine aminotransferase, 31 U/L (0.52 mkat/L) (reference range 0-78 U/L
[0-1.30 mkat/L])
• Lactate dehydrogenase, 727 U/L (reference range 100-240 U/L)
• Uric acid, 4.2 mg/dL (249.84 mmol/L) (reference range 3.5-7.2 mg/dL
[208.20-428.29 mmol/L])
• Urea nitrogen, 18 mg/dL (6.3 mmol/L)
• Creatinine, 0.28 mg/dL (24.8 mmol/L)
The remainder of the basic electrolyte panel, the coagulation profile, and
urinalysis are interpreted as normal. The patient is hospitalized and additional
evaluation leads to the diagnosis.
The Case Discussion and Suggested Readings appear with the online version of this
article at http://pedsinreview.aappublications.org/content/38/1/49.
Vol. 38 No. 1 JANUARY 2017 49
DISCUSSION
Abdominal ultrasonography revealed a large heterogeneous
mass suspected to originate from the liver. Abdominal
magnetic resonance imaging (MRI) further defined the
mass to be largely involving the left hepatic lobe (Fig).
Additional laboratory results included ferritin measuring
38 ng/mL (85.39 pmol/Lng/mL) (reference range 22-322
ng/mL [49.43-723.53 pmol/Lng/mL]) and negative urine
vanillylmandelic acid and homovanillic acid. Biopsy of the
mass established the diagnosis of an embryonal rhabdo-
myosarcoma. The patient underwent a gross total resection
of the mass and had multiple lymph node biopsies and a
bone marrow biopsy that were negative. He received 22
weeks of chemotherapy with vincristine, dactinomycin, and
cyclophosphamide. He has been off therapy for 12 months
and is doing well.
Differential Diagnosis
A palpable abdominal mass is 1 of the more common
findings of malignant solid tumors in children. Neuro-
blastoma and Wilms tumor are the 2 most common intra-
abdominal tumors. For children younger than age 2 years,
neuroblastoma is the most common extracranial malignant
tumor. Wilms tumor is the most common renal malignancy
and two-thirds of cases are diagnosed before age 5 years.
Leukemia, lymphoma, hepatoblastoma, and soft-tissue
sarcomas are more prevalent in older children.
The Condition
Sarcoma is a relatively rare malignant tumor that arises
from embryonic mesenchymal cells and has the ability to
differentiate into striated skeletal and smooth muscle, bone,
Figure. Abdominal magnetic resonance imaging shows a mass largely involving the left lobe of the liver.
cartilage, and adipose tissue. Rhabdomyosarcoma (RMS) is
the most common soft-tissue sarcoma, accounting for 3%
of all pediatric tumors. Given its origin in the embryonal
mesenchyme, this disease has the potential to arise anywhere
in the body. Most cases are sporadic. Several environmental
factors have been implicated with an increased risk for RMS,
including cigarette smoking, advanced maternal age, radia-
tion exposure in utero, and antibiotic use. Inherited familial
syndromes, such as neurofibromatosis and Li-Fraumeni syn-
drome, also have some association with RMS.
The presentation depends on the site of the tumor and
whether it involves any metastasis. The head and neck region
is the most common site, accounting for about one-third of
total cases, followed by the genitourinary (GU) tract (25%)
and extremities (20%). Sites that are involved within the
head and neck include the orbit and parameningeal sites
(middle ear, nasopharynx, paranasal sinuses) and can present
with proptosis or obstruction of the parameningeal region.
GU tract tumors can involve the bladder, prostate, or vagina
and present with hematuria, outflow obstruction, or urinary
frequency. Extremity involvement typically presents with
obvious swelling and has a higher likelihood of spreading
to regional lymph nodes.
Initial evaluation involves plain radiographs of the area
surrounding the mass, followed by computed tomography
(CT) scan and/or MRI. Laboratory evaluation includes com-
plete blood cell count with smear, electrolytes, liver function
tests, uric acid, and calcium. Definitive diagnosis requires
biopsy and special staining performed by a pediatric pathol-
ogist. If there is suspicion of metastasis based on the site of
the primary tumor, further imaging should be performed
with CT scan or radionuclide bone scan.
Management
Current treatment is based on the recommendations of
the Intergroup Rhabdomyosarcoma Study Group (IRSG),
which began in 1972. The most current protocol is the IRSG-
V, which achieves a cure rate of 70% in children with
localized disease. Complete surgical excision is recom-
mended for local disease if it is possible to achieve appro-
priate functional and cosmetic results. Tumors that are in
areas such as the orbit, vagina, or bladder may require
induction chemotherapy to decrease the tumor burden to
allow for acceptable excision. Following surgical excision,
radiation therapy enhances the treatment of residual micro-
scopic disease. All patients with RMS should subsequently
undergo chemotherapy with the gold standard regimen of
vincristine, dactinomycin, and cyclophosphamide. Patients
who relapse after the initial treatment have a poor prognos-
tic outcome.
Lessons for the Clinician
• Rhabdomyosarcoma should be in the differential diagnosis
for children with enlarging masses anywhere in the body.
• Plain films are the appropriate initial imaging study, fol-
lowed by computed tomography scan and/or magnetic
resonance imaging.
• Biopsy is required to obtain the definitive diagnosis.
• Prompt therapy should be initiated with a combination
of surgical excision, chemotherapy, and radiation therapy,
depending on the tumor size and affected area.
Suggested Readings
McCarville MB, Spunt SL, Pappo AS. Rhabdomyosarcoma in pediatric
patients: the good, the bad, and the unusual. AJR Am J Roentgenol.
2001;176(6):1563–1569
Perez EA, Kassira N, Cheung MC, Koniaris LG, Neville HL, Sola JE.
Rhabdomyosarcoma in children: a SEER population based study.
J Surg Res. 2011;170(2):e243–e251

AUTHOR DISCLOSURE Dr Ogbonnaya has
disclosed no financial relationships relevant to
this article. This commentary does not contain
a discussion of an unapproved/investigative
use of a commercial product/device.
50 Pediatrics in Review
Fatigue, Polydipsia, and Nocturia in a 17-year-
5 old Boy
S. Amara Ogbonnaya, MD*
*Internal Medicine-Pediatrics, University of California-Los Angeles Medical Center, Santa Monica, CA.
PRESENTATION
A 17-year-old boy presents with a 4-month history of increasing fatigue, increased
thirst, and nocturia 3 times per night. He complains of painful masses on his
clavicle and scalp that have gradually increased in size for 1 year. In addition, he
has been unsuccessfully treated with topical antifungal medications for a rash on
his lower back. He denies sexual activity and discloses a loss of erections for
several months. He has no pertinent findings on his past medical history and is
not taking medications.
On physical examination, the adolescent’s height, weight, and body mass
index are at the 25th, 90th, and greater than the 95th percentile, respectively.
He is afebrile and his blood pressure is 100/70 mm Hg, heart rate is 83 beats/
min, and respiratory rate is 14 breaths/min. Tender, nonerythematous,
poorly circumscribed swellings are visible on the proximal left clavicle and
right parietal areas, measuring 4 and 2 cm, respectively. The genital exam-
ination reveals normal findings with Sexual Maturity Rating 5 pubic hair.
He has a hyperpigmented 10-cm patch with ulceration in the gluteal cleft
(Fig 1).
Figure 1. Hyperpigmented lesion with ulceration in the gluteal cleft.
 Laboratory tests document the following:
• White blood cell count 3,700/mL (3.7  109/L), with
77.6% neutrophils, 9.7% lymphocytes, 8.3% mono-
cytes, 3.3% eosinophils, and 1.1% basophils
• Hemoglobin 10.6 g/dL (106 g/L)
• Mean corpuscular volume 91.8 mm3 (91.8 fL)
• Red cell distribution width 16%
• Platelet count 128  103/mL (128  109/L)
• Sodium 145 mEq/L (145 mmol/L)
• Potassium 4.3 mEq/L (4.3 mmol/L)
• Chloride 105 mEq/L (105 mmol/L)
• Carbon dioxide 29 mEq/L (29 mmol/L)
• Blood urea nitrogen 5 mg/dL (1.78 mmol/L)
• Creatinine 0.67 mg/dL (59.23 mmol/L)
• Calcium 8.6 mg/dL (2.15 mmol/L)
Computed tomography scan shows lytic lesions of the
skull (Fig 2) and left clavicle with associated soft-tissue
swelling.
Because of the patient’s substantial fatigue and obesity, Figure 2. Computed tomography scan showing lytic lesions of the skull.
thyroid studies are ordered and show thyrotropin of 0.79
mIU/L (normal range, 0.50-3.50 mIU/L) and free thyroxine
of 0.85 ng/dL (10.94 pmol/L) (normal range, 0.93-1.70
ng/dL [11.97-21.88 pmol/L]). The following day, tests are The Case Discussion and Suggested Readings appear with the
ordered to evaluate the patient’s loss of erections. Biopsies of online version of this article at http://pedsinreview.aappublica-
the left clavicle and skin lesion confirm the diagnosis. tions.org/content/38/1/50.

Vol. 38 No. 1 JANUARY 2017 51

DISCUSSION
The biopsy results are consistent with Langerhans cell
histiocytosis (LCH). Additional laboratory results include
total testosterone measuring less than 12 ng/dL (0.42 nmol/L)
(normal range, 249-835 ng/dL [8.64-28.97 nmol/L]), luteinizing
hormone of less than 0.1 mIU/mL (0.1 IU/L) (normal range,
1.7-8.6 mIU/mL [1.7-8.6 IU/L]), and follicle-stimulating
hormone of 0.6 mIU/mL (0.6 IU/L) (normal range,
1.5-12.4 mIU/mL [1.5-12.4 IU/L]) are consistent with con-
comitant panhypopituitarism. Subsequently, magnetic
resonance imaging, obtained because of the abnormal
laboratory results, shows a 1-cm enhancing mass of the
pituitary stalk.
The Condition
LCH, previously called histiocytosis X or Hand-Schüller-
Christian disease, is a disorder of histiocytes that can have
highly variable presentations. The cause is unknown, but
the disease is marked by clonal proliferation of immature
Langerhans cells. The prevalence is approximately 1 in
100,000 people, with 1,200 new cases diagnosed in the
United States annually. It occurs more commonly in chil-
dren younger than age 3 years but can affect any age group.
LCH can affect all organs, which can make the diagnosis
challenging. The areas most frequently involved are bone
(80% of patients), skin (33% of patients), and the pituitary
gland (25% of patients). Because involvement of the bone
marrow, liver, and spleen portend a poor prognosis, these
are considered “risk organs.”
Differential Diagnosis
Because of the myriad presentations, the differential diag-
nosis for LCH is broad and depends greatly on organ sys-
tems involved. When the disease is isolated to the skeletal
system, the differential diagnosis may include osteomyelitis,
primary bone malignancies, benign bone cysts, or metastatic
cancer. For a patient presenting with lymphadenopathy and
splenomegaly and/or cytopenias, lymphoma or leukemia
may be considered initially.
Diagnosis
The diagnosis is made by tissue biopsy of bone or skin
lesions, as in this patient. Positive immunohistochemical
staining for the proteins CD1a and CD207, also called
Langerin, confirm the diagnosis. Electron microscopy
shows intracellular Birbeck granules, which are also confir-
matory. No laboratory findings are specific for the diagnosis
of LCH, but results may aid in identification of involved
organs.
Clinical Presentation
LCH is classified as a single-system or multisystem disease.
In children, the disease most frequently presents as an
incidentally identified solitary lytic lesion of the skull. How-
ever, infants often present with multisystem disease involv-
ing the bone marrow, liver, spleen, and skin, which requires
aggressive treatment.
The skin lesions can vary widely in appearance from
papular to nodular. Most often children have a maculopap-
ular rash that is mistaken for eczema. Skin findings suspi-
cious for atopic dermatitis or seborrheic dermatitis that are
unresponsive to standard therapies should prompt further
evaluation, including biopsy and referral to dermatology.
Adolescents and adults may have a rash with or without
ulceration in intertriginous areas that is often mistaken for
a fungal infection.
The skeletal LCH lesions are typically lytic and may have
a surrounding soft-tissue mass. The skull is most commonly
involved, followed by the pelvis and femurs. Lytic lesions
compromise bone integrity, increasing the risk of fractures.
Patients with osseous involvement of the face and skull
bones are more likely to have disease in the central nervous
system (CNS).
For unknown reasons, LCH has a predilection for the
pituitary gland. Diabetes insipidus (DI) is the most common
manifestation of LCH of the pituitary gland. Anterior pitu-
itary dysfunction can occur and usually results in growth
hormone deficiency. Less commonly, patients may present
with panhypopituitarism, as in this case. Pituitary involve-
ment in LCH is noteworthy because it can develop years
before other manifestations of LCH, can occur simulta-
neously with other signs, or can develop years after the
initial diagnosis. Thus, patients with LCH or a history of
LCH should have growth and pubertal progression as-
sessed regularly to identify development of endocrinopa-
thies. Clinicians should also consider LCH in patients
presenting with pituitary disease without other symp-
toms. Once present, pituitary dysfunction persists despite
treatment. Extrapituitary CNS disease is less common and
can lead to neurodegenerative manifestations, including
learning difficulties, memory problems, and cerebellar
ataxia.
In addition to endocrinologic and CNS complications,
other long-term complications may occur, depending on the
organs involved. Patients with lesions of the temporal,
vertebral, or jawbones may develop hearing loss, scoliosis,
or dental deformities, respectively. Patients with LCH are at
increased risk for developing leukemia and lymphoma. In
addition, secondary malignancies may occur after treatment.
Close follow-up evaluation is needed to monitor for these
complications.
Treatment
Treatment varies substantially based on the extent of dis-
ease. Rarely, when only skin is involved, lesions may spon-
taneously regress. Patients with single-system disease and
a solitary bone lesion may be treated with curettage only.
However, systemic chemotherapy is indicated for patients
with single-system disease and diffuse lesions. Generally,
vinblastine with prednisolone is the standard initial treat-
ment. Patients with single-system disease usually have good
prognoses.
Multisystem disease always requires systemic therapy.
Involvement of risk organs portends a high mortality and
morbidity, and patients are more likely to have reactivation
of disease after treatment. LCH of the CNS is treated with
systemic therapies that cross the blood brain barrier, includ-
ing cytarabine or cladribine. However, the efficacy in pre-
venting neurodegenerative complications is unclear.
Patient Course
Our patient was diagnosed with multisystem LCH with
pituitary involvement and was admitted for oncologic and
endocrinologic evaluation and treatment. Further evalua-
tion also revealed DI, which explained his nocturia and
polydipsia. He was started on testosterone, desmopressin,
hydrocortisone, and levothyroxine for panhypopituitarism.
He is being treated with cytarabine for LCH. He reports
improved energy, resolution of nocturia, and a decrease in
the size of the clavicular and scalp lesions since starting
therapy.
Lessons for the Clinician
• Langerhans cell histiocytosis (LCH) is a difficult disease to
diagnose because of its variable presentation, particularly
in multisystem involvement.
• LCH should be considered in a patient presenting with
bone and/or skin lesions and symptoms concerning for
diabetes insipidus.
• Biopsies should be performed of any suspicious lesions
or lesions that do not respond as expected to therapy.
• Patients with LCH should be monitored for the devel-
opment of endocrinologic abnormalities.
Suggested Readings
Haupt R, Minkov M, Astigarraga I, et al; Euro Histio Network.
Langerhans cell histiocytosis (LCH): guidelines for diagnosis,
clinical work-up, and treatment for patients till the age of 18 years.
Pediatr Blood Cancer. 2013;60(2):175–184
Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the
pediatrician. Curr Opin Pediatr. 2008;20(1):23–29

AUTHOR DISCLOSURE Drs Mitchell, Adams,
and Aspesberro have disclosed no financial
relationships relevant to this article. This
commentary does not contain a discussion of
an unapproved/investigative use of a
commercial product/device.
52 Pediatrics in Review
6 Episodic Stiffness in a 30-month-old Girl
Lisa Mitchell, DO,* William Adams, MD,* Francois Aspesberro, MD†
*Madigan Army Medical Center, Tacoma WA.
†
Seattle Children’s Hospital, Seattle, WA.
PRESENTATION
A previously healthy 30-month-old girl presents a third time to the emergency
department (ED) with a 3-day history of cough, increased fussiness, neck stiffness,
clumsiness, and unwillingness to open her mouth. She continues to drink well
but refuses to eat. She has had several brief episodes of screaming followed by
paroxysmal stiffness, during which she has difficulty drawing breath and has
roving eye movements, but she seems awake and alert. A normal breathing
pattern resumes quickly after the episodes resolve. Episodes have been worsening
in frequency, duration, and apparent intensity of pain, and today she had an
episode at home that lasted 60 seconds and was accompanied by perioral
cyanosis. She takes no medications, has had no immunizations, and has no
travel history or sick contacts, and her parents deny known ingestions or trauma.
Two days ago, the patient developed a cough, listlessness, and vocal raspiness.
Her parents noticed that she was drinking liquids well but had difficulty chew-
ing and opening her mouth, and her neck seemed stiff. On the second day of ill-
ness, she presented to another ED after 2 brief episodes of stiffening during which
she had noisy, shallow breathing, followed by a gasp, and then resumption of
a normal breathing pattern. Apart from erythematous tympanic membranes,
her examination results were normal, and she was diagnosed with acute otitis
media and sent home with ibuprofen and azithromycin. Early the next morning,
she had a more prolonged episode in which she cried out in pain, stiffened, and
then tried to breathe but seemed unable to do so. This lasted longer than before
and was accompanied by cyanosis but no loss of consciousness. She, therefore,
returned to the same ED on the third day of illness, where she was observed
for 2 hours with no return of symptoms and was sent home with analgesic otic
drops.
After discharge, she had multiple episodes of crying, stiffening, and airway
obstruction that progressively worsened in intensity, pain, and duration as well as
periods of inconsolable crying and screaming, so her parents brought her to our
institution for further evaluation. In the ED, her vital signs and tympanic membranes
are normal. Physical examination reveals an alert, afebrile, irritable child with con-
gestion, hoarse voice, and neck stiffness who is holding her head tilted right with
limited range of motion in flexion. There is no tenderness or swelling over her mas-
toids and no drooling. She cannot open her mouth wide and actively resists attempts to
pry it open with a tongue depressor. Her abdomen is soft and lungs are clear to
auscultation bilaterally. There is no evidence of phlegmon, abscess, trauma, or airway
compromise on soft-tissue lateral neck films, chest radiogra-
phy, or computed tomography scans of her head and neck.
She is hospitalized initially in the general medicine ser-
vice for observation because of concern for seizures but is
transferred to the pediatric intensive care unit after another
stiffening and obstructing episode that resolves after 2 doses
of lorazepam. In the unit, she is noted to be hyperreflexive
throughout, with diffuse clonus in both ankles, upgoing
Babinski sign, and intermittent spasms in the lower ex-
tremities bilaterally. She is also observed to arch backwards
intermittently. Her oxygen saturations drop to 70% because
of spasms and airway obstructions and she is intubated.
Laboratory evaluation includes an extended urine toxi-
cology screen; cultures of cerebrospinal fluid (CSF), blood,
and urine; and viral polymerase chain reaction assays on the
CSF for Ebstein-Barr virus, cytomegalovirus, varicella, her-
pes simplex, and enterovirus, all of which are negative.
Ionized calcium and serum electrolytes, CSF analysis, and
C-reactive protein results are normal.
She has had no fever or mental status changes. Clinicians
note that her jaw did not relax, even under propofol sedation
for lumbar puncture. Despite extensive laboratory and ra-
diologic evaluation, her diagnosis is established based on
her clinical presentation.
The Case Discussion and Suggested Readings appear with the
online version of this article at http://pedsinreview.aappublica-
tions.org/content/38/1/52.
Vol. 38 No. 1 JANUARY 2017 53
DISCUSSION
Tetanus was diagnosed on the basis of her classic constella-
tion of symptoms coupled with a lack of immunizations and
absence of historical or laboratory data supporting other diag-
noses. The entry point for inoculation was never identified.
The patient received intramuscular human tetanus
immune globulin (3,000 units) and a 14-day course of
metronidazole (14 mg/kg per day divided every 6 hours).
Tracheostomy was performed early in her course to ensure
airway patency during spasms. She initially showed signs of
autonomic instability, including sinus tachycardia, widened
pulse pressure, sweating, and a fluctuating body tempera-
ture, so a magnesium sulfate drip was started with a target
serum level of 4 mg/dL. She also required norepinephrine
for arterial hypotension. Her sedation package included
midazolam, morphine, and vecuronium drips initially, with
dexmedetomidine hydrochloride added later. She was main-
tained in as low a stimulation environment as possible to
avoid provoking further spasms. She was weaned off ven-
tilation 15 days after intubation, and the tracheostomy was
capped 13 days after it was placed. She was transferred to the
general medicine service for continued rehabilitation.
Condition
Tetanus is caused by Clostridium tetani, a ubiquitous obligate
anaerobe found in soil and the mammalian gastrointestinal
tract. Humans become inoculated through tissue damage,
classically through penetrating injury (eg, stepping on a
rusty nail). In most of those infected, an antecedent injury is
identifiable, but in a small percentage of cases the diagnosis
must be based solely on clinical presentation.
After entering the body, the spore transforms into a
vegetative state and produces tetanospasmin. This neuro-
toxin is taken up from peripheral nerve terminals into the
central nervous system and binds to gangliosides at the
presynaptic inhibitory motor nerve endings. Here it blocks
the release of inhibitory neurotransmitters; the classic gen-
eralized muscular spasms of tetanus result from unchecked
motor nerve impulses. This phenomenon also impairs
neural control over the adrenal cortex, leading to a hyper-
sympathetic state due to catecholamine release, with the
potential for widespread autonomic instability. The classic
presentation includes trismus (in >50% of cases), stiff neck,
opisthotonus, risus sardonicus, a boardlike rigid abdomen,
periods of upper airway obstruction due to thoracic muscle
contraction or glottic/pharyngeal contractions, and dyspha-
gia. Untreated patients frequently die of sequelae of airway
obstruction and dysautonomia. Although common in many
developing parts of the world, tetanus is now extremely rare
in more developed nations due to widespread vaccination.
The number of cases in the United States has declined 95%
since it first became a reportable disease in 1947, and the
Centers for Disease Control and Prevention reported only
20 cases in 2014.
Diagnosis
The diagnosis of tetanus is clinical, but several other causes
of symptoms should be considered. The differential diag-
nosis for such symptoms as tetany, trismus, and muscular
rigidity includes strychnine poisoning (rat poison inges-
tion), encephalopathy, meningitis, stiff person syndrome (a
rare autoimmune disorder characterized by progressive trun-
cal and proximal limb rigidity and stiffness that worsens with
painful spasms), drug ingestion (leading to drug-induced
dystonia or malignant neuroleptic syndrome), tetanic spasms,
and retropharyngeal abscess or trismus from dental infec-
tion. There is no definitive laboratory test to diagnose
tetanus, and the bacterium can only be isolated from an
infected wound in a minority of cases. The serum tetanus
immunoglobulin (Ig)G antibody assay is approved only to
confirm vaccine response in immunized individuals and was
unlikely to be helpful in this case because the initial response
is IgM-mediated. There is currently no tetanus IgM assay
available. In addition, the IgG response to primary tetanus
infection is weak, which explains why infection with tetanus
does not confer adequate immunity and infected individuals
still require vaccination after infection resolution.
Management
Tetanus toxin binding within the central nervous system is
irreversible, so treatment is primarily supportive and tar-
geted at preventing airway compromise and dysautonomia
until new axonal nerve terminals can grow. Patients require
intensive support for several weeks before complete recov-
ery can be achieved. If a wound can be found, treatment
starts with wound debridement. Patients should receive
metronidazole for 10 to 14 days to stop bacterial proliferation
at the wound site. Intramuscular injection of human tetanus
immune globulin (3,000-6,000 units), preferably infiltrated
near the wound, is recommended to neutralize any as yet
unbound toxin. We initially used a magnesium sulfate drip
for autonomic instability in our patient, as discussed in
some international studies. Other options include cloni-
dine, morphine, and labetalol. Muscle spasms have been
successfully managed with benzodiazepine drips, intra-
thecal baclofen, dantrolene, and neuromuscular blocking
agents such as vecuronium. Control of stimuli such as light
and noise around these patients is helpful to avoid provoking
spasms.
Lessons for the Clinician
• Tetanus should be considered in unimmunized patients with
intermittent airway obstruction, trismus, and/or muscle ri-
gidity, even without antecedent history or evidence of injury.
The vaccine is highly effective, so the likelihood of infection in
a properly immunized individual is extremely small.
• Tetanus occurs frequently in the developing world but
may still be seen in underimmunized populations in
more developed nations. Because few clinicians in the
more developed world have ever seen this disease, the
diagnosis may not be considered until clinical manifes-
tations are obvious, thus delaying treatment. Correct
diagnosis is crucial because most patients recover with
access to modern supportive care.
Suggested Readings
American Academy of Pediatrics. Tetanus (lockjaw). In: Kimberlin DW,
Long SS, Brady MT, Jackson MA, eds. Red Book: 2015 Report of the
Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2015:773–778
Govindaraj GM, Riyaz A. Current practice in the management of
tetanus. Crit Care. 2014;18(3):145
Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of
tetanus: an evidence-based review. Crit Care. 2014;18(2):217
 Brief
in
Medication Reconciliation
Jenna Merandi, PharmD, MS,* Matthew Sapko, PharmD, MS,* Charline Catt, RN, MS,* Jeffrey M Hoffman, MD*
*Nationwide Children’s Hospital, Columbus, OH
AUTHOR DISCLOSURE Drs Merandi, Sapko,
and Hoffman and Ms Catt have disclosed no
financial relationships relevant to this article.
This commentary does not contain a
discussion of an unapproved/investigative
use of a commercial product/device.
National Patient Safety Goals Effective
January 1, 2015. Oak Brook, IL: Hospital
Accreditation Program. The Joint Commission;
2015. Available at: http://www.jointcommission.
org/assets/1/6/2015_NPSG_HAP.pdf. Accessed
January 27, 2015
Establishment and Evaluation of Pharmacist-
Managed Admission Medication History and
Reconciliation Process for Pediatric Patients.
Provine AD, Simmons EM, Bhagat PH. J Pediatr
Pharmacol Ther. 2014;19(2):98–102
Value of the Student Pharmacist to
Experiential Practice Sites: A Review of the
Literature. Mersfelder TL, Bouthiller MJ. Ann
Pharmacother. 2012;46(4):541–548
How to Implement EHRs: Step 5: Achieve
Meaningful Use Stage 2: Medication
Reconciliation. HealthIT.gov.2015. Available
at: https://www.healthit.gov/providers-
professionals/achieve-meaningful-use/core-
measures-2/medication-reconciliation.
Accessed October 14, 2016
54 Pediatrics in Review
A young boy presents to the emergency department (ED) for a leg laceration
suffered during a skateboarding accident. The fast-paced ED triages the patient,
sutures the wound, and discharges him. Almost immediately, the boy returns to the
ED after having a seizure in the parking garage and sustaining a head injury that
requires an admission. Why? It turns out that his skateboarding accident was related
to adherence issues with his antiepileptic medication. Unfortunately, his complete
medication history was not available to the ED staff. This type of event happens all
too frequently across our health systems, but it is one that we must be committed
to eliminating through improvements in our medication reconciliation process.
Medication reconciliation is a complex, continuous process of creating and
maintaining an accurate list of new and current medications for a patient. The
ultimate goal of the medication reconciliation process is to prevent adverse drug
events, provide education to patients and caregivers, and prevent hospital admis-
sions or readmissions.
According to Joint Commission guidelines, medication reconciliation in the
hospital setting must occur at admission, each transition of care, and discharge.
Thus, all members of an interdisciplinary team must participate in the medica-
tion reconciliation process to achieve success. It is essential that documentation
is correct and communication is clear between the health care team and patients
or caregivers during these transitions. Gathering information such as medica-
tion name, dosage form, route, and frequency and evaluating for appropriate-
ness of the therapy are all components of the medication reconciliation process.
Nurses, physicians, pharmacists, and other allied health care personnel all play
integral roles in keeping patients safe and preventing medication errors. A com-
parable process is appropriate in all health care environments.
As part of every health care system’s goal to eliminate all preventable patient
harm, medication reconciliation should be targeted as a focus area for improve-
ment. To achieve that goal, many interventions can be implemented related to medi-
cation reconciliation, including changes to the electronic medical record (EMR),
increased involvement from pharmacists, and improved patient instructions.
The EMR is one of the first areas of focus that can improve medication
reconciliation. To standardize the medication reconciliation process, a workflow
can be created that allows the clinician to view all medications at once, both
recently ordered and those used long-term. Those that have not been reviewed
should be highlighted for increased visibility, and only after all medications have
been evaluated should clinicians be permitted to move onto the next step in the
medical encounter process.
Other visual indicators can serve as a safety net, such as a red banner that re-
minds clinicians that 1 or more medications still need reconciliation; the banner
turns green only after review, helping guarantee that all medications have been
reconciled. Clinicians should then be instructed to verify all medications to be
prescribed, check for duplicates, and preview the patient
instructions to ensure that the full list of medications,
including their instructions for use, appears correctly.
As part of the reconciliation process, random audits can be
conducted on discharge instructions at the end of a hospi-
tal admission or any medical encounter. Typical problems
that may be identified include duplicate medications and
conflicting usage information, often resulting from medica-
tion information being entered into the free text portions
of discharge instructions. By avoiding free text fields and
documenting medication instructions only in the medication
section of the discharge summary, clinicians give patients
and their caregivers information that is both clearer and less
likely to lead to errors.
Increased auditing as part of the medication reconcilia-
tion process also allows for direct feedback to clinicians
when errors are identified. This enables prescribers to
correct the errors before a patient is discharged either from
an admission or an outpatient encounter.
Pharmacists can be crucial resources in the process of
medication reconciliation. As medication experts, they are
integral team members involved not only in direct patient
care but also during the process of admission, unit-to-unit
transfers, and at the time of discharge. By providing custom-
ized education for patients and caregivers, pharmacists can
help to substantially reduce medication errors and im-
prove patient satisfaction. Hospital pharmacists should rou-
tinely review every patient’s medication list to determine
the accuracy of all prescribed medications. As part of the
medical team, a pharmacist should be available to counsel
every patient or caregiver, providing another opportunity for
patients and their families to learn about their medications.
Another helpful intervention in the hospital setting is to
have prescriptions/discharge medications delivered directly
to patients at the bedside before discharge from inpatient
units, perioperative areas, and the ED. This gives pharmacists
the opportunity to provide counseling and education about
prescribed medicines as well as to review the medication
reconciliation details contained on the discharge instructions.
Another important role for pharmacists (or student phar-
macists, if available) is to complete medication histories for
patients admitted from the ED. They can review current and
past medications to ensure that correct information is present
in each patient’s profile and enter notes and suggestions for the
inpatient care team about perceived issues and follow-up needs.
Of course, most of a patient’s medication behaviors occur
at home. Leveraging relationships within the community
for enhanced sharing and collaboration among outpatient
practices, community pharmacies, and where relevant,
hospital-based services should be a focus. The goal is to have
more complete and up-to-date information readily available
by strengthening communication throughout the network of
health care providers for each patient. In addition, patients
and their families should be empowered to share information
about their medications to improve medication reconciliation
efforts further.
The time invested today in medication reconciliation
pays dividends far into the future. By establishing effective
medication reconciliation workflows throughout each patient’s
network of care, from the community to the hospital setting,
and promoting collaboration among physicians, nurses, and
pharmacists, we give our patients the best chance to be cared
for safely.
COMMENT: Why medication reconciliation? In the United
States today, preventable medical errors are responsible for
about 400,000 deaths per year, third only to heart disease and
cancer, as well as for something like 10 times as many serious
complications not resulting in death. The cost of preventable
errors in terms of human suffering, not to mention dollars, is
enormous. Of course, not all preventable errors are adverse
drug events, but enough are to make this an issue we need to
take very seriously in our offices as well as in our hospitals.
– Henry M. Adam, MD
Associate Editor, In Brief
Vol. 38 No. 1 JANUARY 2017 55
 Brief
in
CHARGE Syndrome
Alexandra Hudson, HBSc,* Carrie-Lee Trider, MD,† Kim Blake, MB, FRCPC*‡
*Dalhousie University School of Medicine, Halifax, Nova Scotia, Canada.
†
Queen’s University School of Medicine, Kingston, Ontario, Canada.
‡
IWK Health Centre, Nova Scotia, Canada.
AUTHOR DISCLOSURE Ms Hudson, Dr Trider,
and Dr Blake have disclosed no financial
relationships relevant to this article. This
commentary does not contain a discussion
of an unapproved/investigative use of a
commercial product/device.
Clinical Utility Gene Card for CHARGE
Syndrome - Update 2015. van Ravenswaaij-
Arts CMA, Blake K, Hoefsloot L, Verloes A. Eur
J Hum Genet. 2015;23(11)
CHARGE Syndrome: A Review. Hsu P, Ma A,
Wilson M, et al. J Paediatr Child Health. 2014;50
(7):504–511
CHARGE Syndrome. Blake KD, Prasad C.
Orphanet J Rare Dis. 2006;7(1):34
Postoperative Airway Events of Individuals
with CHARGE Syndrome. Blake K, MacCuspie
J, Hartshorne TS, Roy M, Davenport SL,
Corsten G. Int J Pediatr Otorhinolaryngol.
2009;73(2):219–226
Quality of Life in Adolescents and Adults
with CHARGE Syndrome. Hartshorne N,
Hudson A, MacCuspie J, et al. Am J Med Genet
A. 2016;170(8):2012–2021
56 Pediatrics in Review
CHARGE syndrome (CS) is an autosomal dominant genetic condition caused
by a mutation in the CHD7 gene. The incidence is approximately 1 in 10,000 to
15,000 live births. Most cases result from de novo mutations on the q12 arm of
chromosome 8, which interfere with neural crest cell migration and embryo-
genesis. The parent of a child with a de novo mutation causing CS has a
recurrence risk of approximately 1% to 3% for future pregnancies. However, if
the disease-causing mutation of the proband is found in a parent, depending upon
whether in a mosaic or nonmosaic form, the recurrence risk may be increased up
to 50%, and subsequent pregnancies can be screened genetically and with fetal
ultrasonography and/or magnetic resonance imaging.
CS remains a predominantly clinical diagnosis that can be confirmed with
genetic testing. Physical features are highly variable and include those repre-
sented by the CHARGE mnemonic: Coloboma ocular, Heart defects, Atresia or
stenosis of the choanae, Retardation of growth and/or development, Genito-
urinary anomalies, and Ear abnormalities. However, the mnemonic does not
include all of the major diagnostic criteria. Central nervous system find-
ings are important clues to the diagnosis, with more than 90% of affected
individuals having cranial nerve (CN) dysfunction. Many individuals have
more than 1 dysfunctional cranial nerve, manifesting as an absent or reduced
sense of smell (CN I), weak chewing/swallowing (CN V), facial palsy (CN VII)
(Fig 1), sensorineural hearing loss (CN VIII), balance vestibular problems (CN
VIII), and swallowing problems (CN IX, X). Visual and hearing impairments
as well as intellectual disabilities are prevalent and can range from mild to
severe.
Because CS is the most common syndrome associated with choanal atresia or
stenosis, it should be considered in the differential diagnosis of any infant
presenting with this defect. The characteristic outer ear malformation seen in
CS is another important diagnostic clue (Fig 2). The diagnosis is also informed by
imaging of the inner ears (for cochlear/vestibular anomalies and absent olfac-
tory bulbs). A thorough clinical evaluation of an individual suspected to have CS
should include echocardiography, renal ultrasonography, cranial computed
tomography scan, cerebral magnetic resonance imaging, audiometry testing,
CN testing, a swallowing study, nasal endoscopy, and funduscopy.
An early diagnosis is important to establish a multidisciplinary care team to
manage developmental concerns. CS is one of the most common causes of
combined deafness-blindness and should be considered in all infants who have
both of these sensory deficits.
Communication can be challenging for individuals with CS. They are best
supported using multiple methods, including verbal, sign language, picture

Figure 1. Facial palsy is a common manifestation of cranial nerve
dysfunction in CHARGE syndrome.
exchange, and gestures. Cochlear implants are an option if
there is an intact vestibular nerve (Fig 3). Bone-anchored
hearing aids are also an option for hearing impairment. Pain
can be an underdetected symptom in genetic disorders
in which individuals have difficulty communicating. For
children who are nonverbal, the “Multidimensional Pain
Assessment for Individuals with CHARGE Syndrome”
Figure 2. The characteristic outer ear appearance in CHARGE syndrome
is a short, wide, cup-shaped ear with decreased cartilage and a triangular
concha. The ears are often asymmetric.
has been developed to better evaluate pain. Aside from
hearing and vision impairment, the senses of touch, body
position, balance, smell, and taste are often dysfunctional.
Balance and vestibular problems can cause difficulties with
mobility, creating the need for a walker early in life to allow
the child to walk in an upright position. Affected children
should undergo a mobility and sensory integration assess-
ment by an occupational and physical therapist so that
adaptations for sensory impairments can be provided early
in life and into school.
Long-term and complex feeding issues can contribute
to morbidity and mortality. Feeding difficulties are highly
prevalent, mostly present from birth, but can start at any
point across the lifespan. Gastrostomy/jejunal tube feed-
ing may be necessary and can continue for many years. CN
dysfunction is hypothesized as the primary clinical anomaly
adversely affecting feeding development. The most com-
mon upper gastrointestinal tract problems are weak suck-
ing/chewing, dysphagia, severe gastroesophageal reflux
(GER), and aspiration. Problematic feeding behaviors, such
as overstuffing of the mouth or pocketing of food in the
cheeks, are also encountered. Constipation and bowel dys-
regulation are common, believed to result from vagus nerve
dysfunction affecting gut motility. Every patient who has CS
and feeding difficulties should be assessed by a multidisci-
plinary team, including an occupational therapist, physical
therapist, and speech-language pathologist to evaluate swal-
lowing and CN function. A scale specifically designed for CS
is currently being developed to help parents and therapists
assess and monitor feeding difficulties over time.
Patients with CS often require numerous surgeries and
face a substantial risk of postoperative airway events with
anesthesia. Where possible, multiple surgical procedures
should be combined under one anesthetic to reduce the risk
of intubation and postoperative complications. In child-
hood, sleep apnea may warrant the removal of tonsils and
adenoids and should be investigated by an otolaryngologist.
Excessive salivary secretions, which can lead to aspiration
and related complications, are also a common problem;
injections of onabotulinumtoxinA into the salivary glands
can be effective and may avert the need for a tracheostomy.
Although infant mortality is high in CS, life expectancy
has improved for patients who survive beyond the first
postnatal year. Death in the neonatal period is associated
with combinations of major cardiovascular malforma-
tions, bilateral choanal atresia, esophageal atresia, severe
T-cell deficiencies, and central nervous system anomalies.
Vol. 38 No. 1 JANUARY 2017 57

Figure 3. A cochlear implant used to ameliorate hearing loss from
common middle and inner ear malformations in CHARGE syndrome.
Mortality in the postnatal period is attributed primarily to
CN dysfunction, specifically to difficulties with swallowing,
GER disease, respiratory aspiration, and postoperative air-
way events. Early management of CS often involves repair
of the malformations (cardiac, choanal atresia, esophageal
atresia) and treatment of feeding difficulties and GER (tube
feeding and antireflux and motility medications).
An endocrinologist should follow affected children as
they move into preadolescence because of the risk of delayed
puberty. Hormone replacement therapy is often indicated,
especially when there were signs of hypogonadotropic hy-
pogonadism at birth. Growth hormone deficiency may also
be a problem, although it is less prevalent. Poor bone health
is common with CS. Contributing risk factors include
dietary restrictions, inactivity, and hypogonadism. Patients
often fail to meet the recommended nutritional intake of
calcium and vitamin D and are at risk for osteoporosis.
Failure to thrive is common in childhood, but obesity
becomes prevalent later in life. In addition to input from
58 Pediatrics in Review
an endocrinologist, consultation with a nutritional therapist
can be helpful.
New issues that appear in adolescence/adulthood include
scoliosis, sleep apnea, gallstones, seizures, ophthalmo-
logic complications (eg, retinal detachment), and the onset
of problematic feeding behaviors (eg, food pocketing in
cheeks). Parents should be advised that acute behavioral
changes warrant prompt clinical evaluation. Adolescents
and adults with CS continue to need care in a variety of
subspecialties (ophthalmology, otolaryngology, endocrinol-
ogy, and cardiology) as well as ongoing coordination of their
care by their primary care physician.
A newly developed and easy-to-use comprehensive clin-
ical checklist is available to clinicians and parents to facilitate
coordinating the complex medical needs faced by patients
with CS across their lifespans. The checklist tracks all the
medical specialties involved in the care of the particular
individual and alerts caregivers to the timing of common
medical issues that may affect the person with CS.
A book titled CHARGE Syndrome by Hartshorne et al was
published in 2010, describing the sensory, physical, and
behavioral findings in CS. Individuals and parents can also
learn more about CS through www.chargesyndrome.org, a
website created by The International CHARGE Syndrome
Foundation. SENSE, a national charity in the United King-
dom for people with deafness and blindness, has created
a “CHARGE Information Pack for Practitioners” consisting
of 28 factsheets summarizing all aspects (medical and
educational) of living with CS.
Lastly, individuals and their parents with CS can join the
International CHARGE Syndrome Foundation to become
connected to the larger global community affected by this
genetic disorder. The International Foundation, the United
Kingdom, and Australasia (Australia and New Zealand) all have
well-established Facebook groups where parents can post ques-
tions to other parents of children with CS. Family support groups
that exist around the world are the CHARGE Family Support
Group UK, Texas CHARGE Group, CHARGE Syndrome Asso-
ciation of Australasia, Association CHARGE (France), Dutch
CHARGE Syndrome Network, Belgian CHARGE Syndrome,
CHARGE Syndrome Canada, CHARGE Syndrome German,
Asociacion Espanona Sindrome de CHARGE (Spain), and
National Family Association for Deaf-Blind (USA). This is
not an exhaustive list and does not list all of the available
family support groups for CS around the world.
COMMENT: First described in 1979 in a report of 17
children with choanal atresia, CHARGE was coined as an
acronym in 1981. Initially it was termed the CHARGE as-
sociation, not syndrome. A syndrome in genetics denotes
a set of signs and/or symptoms appearing together that re-
sults from an identified cause. In 1981, the CHD7 gene on
chromosome 8 was not known to be the site of mutation(s)
underlying the condition, so all that could be claimed was
that an association had been recognized, indicating that
this group of anomalies appeared together more often
than would happen purely by chance. With dramatic
advances in genetic technology over the past few decades,
other acronymic associations have had their underlying
causes identified (WAGR and LEOPARD are examples),
but some (like VACTERL) have not yet graduated from
association to syndrome. If by chance you don’t remem-
ber what these acronyms represent, have fun looking
them up. I do almost every time I come across one of
them!
– Henry M. Adam, MD
Associate Editor, In Brief
Vol. 38 No. 1 JANUARY 2017 59
 A Child with Presumed Reactive Airway
Disease, Pectus Carinatum, and Aortic
Root Dilation
Aamir Jeewa, MD,* Shaine A. Morris, MD, MPH,* William J. Dreyer, MD,*
Iki Adachi, MD,† Susan W. Denfield, MD,* E. Dean McKenzie, MD†
*Lillie Frank Abercrombie Section of Cardiology, Department of Pediatrics;
†
Michael E. DeBakey Department of Surgery, Division of Congenital Heart Surgery, Baylor College of
Medicine, Houston, TX.

PRESENTATION

A 6-year-old girl of South Asian descent has a history of reactive airway disease
that has been treated with bronchodilators from age 3 years. She is referred to
a pulmonologist for refractory wheezing after multiple antibiotic courses and
treatments with levalbuterol and corticosteroids, both oral and inhaled. Her
parents had noted an increase in wheezing and upper respiratory tract infections
during the winter months. She has no history of recurrent pneumonias or
other hospitalizations. Prior chest radiographs had not shown any signifi-
cant pulmonary pathology but incidentally did show evidence of scoliosis.
The patient’s parents had noticed a chest deformity since the age of 4 years.
Allergy testing shows she is allergic to mold, eggs, grass, and peanuts. The
patient’s perinatal history is unremarkable. The family history is notable for
a maternal grandfather who died suddenly after developing chest pain at 45
years of age.

AUTHOR DISCLOSURE Drs Jeewa, Morris,

Dreyer, Denfield, and McKenzie have
disclosed no financial relationships relevant to
this article. Dr Adachi has disclosed that he is a
consultant for New England Research
Institute’s (NERI) PumpKin trial with the Jarvik
ventricular assist device, for which his
employing institution receives salary support;
he also serves as a consultant for Heartware,
Inc, and Sony-Olympus, Inc. This commentary
does not contain a discussion of an
unapproved/investigative use of a Figure 1. Preoperative computed tomography angiography (sagittal [A] and short axis [B] views)
commercial product/device. showing the dilated aortic root.

Vol. 38 No. 1 JANUARY 2017 e1


Figure 2. Transesophageal echocardiography with color Doppler
demonstrating severe aortic insufficiency (arrows).
The patient’s initial physical examination reveals a Sex-
ual Maturity Rating 1 girl with a thin build (84th percentile
for height and 27th percentile for weight), frontal bossing,
mild bilateral tonsillar hypertrophy, pectus carinatum, and
a hyperdynamic precordium. Further evaluation demon-
strates a wide uvula with a prominent raphe, hypertelorism,
downward-slanting palpebral fissures, mild thoracic sco-
liosis, and a grade II/VI systolic ejection murmur that is
Figure 3. Intraoperative photograph of the massively dilated aortic root
and ascending aorta. The root is rotated such that the noncoronary sinus
lies more anterior than usual and the right coronary artery origin is
displaced leftward, with the right coronary artery stretched over the
dilated root. rt¼right.
e2 Pediatrics in Review
TABLE. Major Systems Involved in Loeys-Dietz
Syndrome
Vascular
• Aortic complications include dissection or dilation; aortic root
dilation is common and seen in >95% of probands
• Other arterial aneurysms and tortuosity are common, with 50% of
the aneurysms detected away from the aortic root
• Atrial septal defect and patent ductus arteriosus are frequently
seen
• Bicuspid aortic valve may be associated
• Mitral valve prolapse is common
Musculoskeletal
• Pectus deformities: either excavatum or carinatum
• Spinal curvature disorder: scoliosis
• Joint hypermobility (most often involving the fingers)
• Arachnodactyly
• “Club foot” or talipes equinovarus
• Craniosynostosis: most commonly dolichocephaly, brachycephaly,
and/or trigonocephaly
Craniofacial
• Widely spaced eyes or hypertelorism
• Presence of a cleft palate or a bifid/wide uvula
• Premature fusion
Cutaneous
• Translucent skin
• Easy bruising
• Dystrophic scars
Other (by systems)
• Allergy and Immunology: Environmental and food allergies
• Gastrointestinal: Malabsorption, chronic diarrhea, abdominal pain,
and/or gastrointestinal bleeding and inflammation; possible
rupture of the spleen or bowel
• Genitourinary: Potential for rupture of the uterus during pregnancy
loudest at the right upper sternal border with continuation
into diastole.
DIAGNOSIS
Based on the abnormal cardiac findings and the long-
standing history of reactive airway disease, computed
tomography (CT) angiography of the chest was performed
that showed massive dilation of the aortic root (6.5 cm),
moderate dilation of the ascending aorta and transverse

Figure 4. Three-dimensional reconstruction from computed
tomography angiography performed after valve-sparing aortic root
replacement with graft replacement of the aortic arch and innominate
artery.
arch, a patent ductus arteriosus, and significant left
ventricular dilation (Fig 1). Transthoracic echocardiogra-
phy revealed severe aortic insufficiency and moderately
depressed left ventricular function (Fig 2). Genetic test-
ing confirmed the suspected diagnosis of a connective
Figure 5. A. Three-dimensional reconstruction from magnetic resonance angiography 6 months after cardiac transplantation with replacement of
entire arch with donor arch except for the left carotid and subclavian artery origins, which were incorporated using a beveled anastomosis with the
donor aorta. B: Magnetic resonance angiography 1.5 years after transplantation documenting progressive dilation localized to the native tissue around
the left carotid and subclavian arteries.
tissue disorder (CTD). During intraoperative inspection
for aortic root replacement, a massively dilated aortic root
measuring 6.5 cm was noted (Fig 3).
Discussion
Loeys-Dietz syndrome (LDS) belongs in the category of
CTDs and is primarily due to mutations in TGFBR1
or TGFBR2. (1) This syndrome is characterized by involve-
ment in four major systems (Table) (2). A key distinction
compared to Marfan syndrome is that patients with LDS
appear to have a higher overall risk of dissection and of
early mortality, even though they have similar incidences
of aortic dilation.
The inheritance pattern is primarily autosomal dominant
with most cases (w75%) due to a de novo mutation. In this
case, genetic testing documented c.797 A>G transition in
exon 4 of the TGFBR1 gene that results in conversion of a
codon for aspartic acid to a codon for glycine in the serine-
threonine kinase domain of TGFBR1. Outcome data for the
rare patient with CTD requiring orthotopic heart transplan-
tation (OHT) are limited and conflicting. (3)(4) For LDS in
particular, a single case report exists of a 44-year-old man
with systolic failure who underwent emergent OHT before
obtaining the genetic diagnosis. (5)
Patient Course
The patient underwent aortic root replacement with a 21-
mm HP St. Jude mechanical composite graft, graft replace-
ment of the entire aortic arch and innominate artery, and
ligation and division of the patent ductus arteriosus (Fig 4).
Vol. 38 No. 1 JANUARY 2017 e3

Figure 6. Three-dimensional reconstruction of computed tomography
angiography documenting significant arterial tortuosity, most evident in
the vertebral arteries (see arrows). Vertebral artery tortuosity index is
severely elevated at 179.
Pathology of the aorta at the time of repair showed a vari-
ably thickened aortic wall with diffusely increased acid
mucopolysaccharides and markedly decreased elastic tissue
and smooth muscle fibers. Postoperatively, the girl devel-
oped severely depressed left ventricular function. She was
ultimately discharged but returned to the hospital later with
seizures and chorealike movements. Neuroimaging at the
time ruled out any evidence of a stroke. Her heart failure
worsened such that she required mechanical ventilation and
inotropic support. After extensive evaluation and literature
review for OHT in CTD, she was listed for cardiac trans-
plant. She received the transplant 17 days after listing, and
e4 Pediatrics in Review
the donor arch was used to replace the entire arch graft. A
beveled anastomosis was created to incorporate the left
carotid and subclavian arteries. After lengthy rehabilita-
tion, she was discharged 1.5 months later and is now more
than 3 years post-OHT.
She is currently followed by the pediatric cardiac trans-
plant team and the cardiovascular genetics team. In addition
to her immunosuppression regimen, she is receiving com-
bination therapy of a b-blocker and angiotensin receptor
blocker and undergoes serial echocardiography and mag-
netic resonance angiography. Although her cardiac function
has been normal, the aortic arch has progressively dilated.
This increase in diameter appears to be limited to the area of
native aortic tissue remaining in the arch surrounding the
origins of the head and neck vessels (Fig 5).
Of note, the arterial tortuosity in this patient, as mea-
sured by the vertebral artery tortuosity index (VTI) on
magnetic resonance angiography, is severely increased,
with a measurement of 179 (Fig 6). In a study by Morris
et al, (6) patients with a VTI greater than 50 (defining severe,
with normal measured as <10) had a median age at first sur-
gery of 11.2 years, had an average of 0.8 surgeries per decade,
and were at the highest risk of experiencing an aortic dis-
section. In this study, 6 patients had VTIs equal to or greater
than 100, with 4 dying at ages ranging from 5 months to 26
years and 2 surviving at ages 11 and 21 years.
Summary
• Vascular, skeletal, craniofacial, and cutaneous findings on
physical examination should raise suspicion for the diagnosis of a
connective tissue disorder (CTD).
• Multimodality imaging techniques (such as chest radiography,
echocardiography, computed tomography scan, and magnetic
resonance angiography) are often required for complete
assessment of the cardiac and vascular abnormalities that can
occur in children with Loeys-Dietz syndrome (LDS).
• To our knowledge, this is the first successful case of heart
transplantation in a pediatric patient with LDS.
• Close long-term follow-up evaluation is crucial in this very high-
risk patient to try to prevent the occurrence of CTD-related
complications.
References
1. Loeys BL, Chen J, Neptune ER, et al. A syndrome of altered
cardiovascular, craniofacial, neurocognitive and skeletal development
caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005;
37(3):275–281
2. Loeys BL, Dietz HC. Loeys-Dietz syndrome. GeneReviews. Seattle,
WA: 2013. Available at: https://www.ncbi.nlm.nih.gov/books/
NBK1133/. Accessed October 24, 2016
3. Kesler KA, Hanosh JJ, O’Donnell J, et al. Heart transplantation in
patients with Marfan’s syndrome: a survey of attitudes and results.
J Heart Lung Transplant. 1994;13(5):899–904
4. Knosalla C, Weng YG, Hammerschmidt R, et al. Orthotopic heart
transplantation in patients with Marfan syndrome. Ann Thorac Surg.
2007;83(5):1691–1695
5. Eckman PM, Hsich E, Rodriguez ER, Gonzalez-Stawinski GV,
Moran R, Taylor DO. Impaired systolic function in Loeys-Dietz
syndrome: a novel cardiomyopathy? Circ Heart Fail. 2009;
2(6):707–708
6. Morris SA, Orbach DB, Geva T, Singh MN, Gauvreau K,
Lacro RV. Increased vertebral artery tortuosity index is associated
with adverse outcomes in children and young adults with
connective tissue disorders. Circulation. 2011;124(4):
388–396
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