Complementary, Holistic, and Integrative Medicine: Autism Spectrum Disorder

and Gluten- and Casein-Free Diet

Cara Dosman, Denise Adams, Bev Wudel, Laura Vogels, Justine Turner and Sunita
Vohra
Pediatrics in Review 2013;34;e36
DOI: 10.1542/pir.34-10-e36

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Complementary, Holistic, and Integrative Medicine: Autism Spectrum Disorder
and Gluten- and Casein-Free Diet
Cara Dosman, Denise Adams, Bev Wudel, Laura Vogels, Justine Turner and Sunita
Vohra
Pediatrics in Review 2013;34;e36
DOI: 10.1542/pir.34-10-e36

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Services http://pedsinreview.aappublications.org/content/34/10/e36
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Article complementary medicine

Complementary, Holistic, and Integrative

Medicine: AutismSpectrumDisorderandGluten-andCasein-Free
Diet
Cara Dosman, MD,*
Objectives After completing this article, readers should be able to:
Denise Adams, PhD,†
Bev Wudel, MD,‡ 1. Understand current evidence for using a gluten- and casein-free diet for children with
Laura Vogels, BSc, † autism spectrum disorder.
Justine Turner, MD, PhD,x 2. Understand potential harms of the gluten- and casein-free diet.
and Sunita Vohra, MD, 3. Be aware of what nutritional monitoring should be considered while children are on
MSc† the gluten- and casein-free diet.

Author Disclosure
Drs Dosman, Adams,
Wudel, Turner, and Ms
Vogels have disclosed
no financial
relationships relevant
to this article. Dr
Vohra receives salary
support from Alberta
Innovates Health
Solutions, in
Edmonton, Alberta,
Canada, as a Health
Scholar. This
commentary does not
contain discussion of
unapproved/
investigative use of
a commercial product/
device.
Abbreviations
ASD: autism spectrum disorder
BMD: bone mineral density
gfcf-d: gluten-free and casein-free diet
RCT: randomized controlled trial
Lay Summary
Many parents of children with autism want to try a gluten-free and casein-free diet (gfcf-d)
for their child to see if it will help. Some studies have found positive results, but questions
remain unanswered. Parents should consider potential benefits and potential harms of try-
ing the diet. Potential benefits to the affected child include improved communication, so-
cial interaction, and behavioral flexibility and decreased inattention and hyperactivity.
Potential harms of the diet include nutritional deficiencies and the effort and costs associ-
ated with maintaining it.
Caution should be used when trying to decide whether to try a gfcf-d for a child who
already has nutritional deficiency, growth problems, or restricted diet due to difficulty ac-
cepting new foods. Before starting a gluten-free diet, the child should be screened for celiac
disease, especially if the child has had gastrointestinal symptoms, such as diarrhea, consti-
pation, anorexia, vomiting, abdominal pain, or weight loss. If parents want to try a gfcf-d,
they should consider seeking guidance from a therapist to help introduce the diet in a grad-
ual way and a dietitian to monitor their child’s nutritional intake while on the diet and to
recommend supplementation if necessary. Weight also needs to be monitored. Parents and
health care professionals or teachers should document behavioral improvement, ideally us-
ing validated measures.
Introduction
Autism spectrum disorder (ASD) (prevalence of approximately 1 in 100) is a neurologically
based, lifelong disability characterized by impairments in social interaction, communica-
tion, and behavioral flexibility, (1)(2) with its basis in genetic and nongenetic factors.
(1) Current treatment focuses on having the child acquire skills and decrease comorbidities
through educational services, provided through family and
health or school systems, with consultation when necessary
from speech-language, occupational, physical, and behav-
ioral therapists, psychologists, and physicians. (1)(3) Studies
suggest promising outcomes for some children from early
intensive behavioral and developmental interventions, al-
though more large-scale randomized controlled trials
(RCTs) and data on potential harms are needed. (3)(4)(5)

*Division of Developmental Pediatrics, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Alberta,
Canada.
†
CARE Program, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Alberta, Canada.
‡
Internal Medicine Resident, College of, Medicine, University of Saskatchewan, Saskatchewan, Canada.
x
Department of Pediatric Gastroenterology and Nutrition, Faculty of Medicine and Dentistry, University of Alberta, Alberta, Canada.

e36 Pediatrics in Review Vol.34 No.10 October 2013


In absence of cure, many parents search for complemen-
tary and alternative therapies, (6) especially when there are
comorbid gastrointestinal and behavioral issues. (7) One
popular approach is the gluten-free and casein-free diet
(gfcf-d), used by 15% to 38% of the ASD population (8)
(9)(10)(11) and endorsed as effective by half of responding
parents (n¼479). (9) Gluten is a protein in wheat, rye, trit-
icale, and barley. Casein is a protein in mammalian milk
products (eg, milk, cheese, yogurt, butter, processed
foods).
Investigators have reported conflicting evidence re-
garding a leaky gut hypothesis (ie, increased gut perme-
ability and uptake of inadequately digested gluten and
casein peptides due to mucosal inflammation). (12)(13)
(14)(15)(16)(17)(18)(19) In the 1980s and 1990s,
Reichelt et al reported increased urine casein peptide lev-
els in children with ASD, (20)(21) elevated serum IgA
antibody levels to gluten and casein, and social and be-
havioral benefits from a total or partial gfcf-d. (12)(21)
(22)(23)(24) This review explores current evidence for
the potential benefits and risks of using gfcf-d for children
with ASD.
Effectiveness of Gfcf-d on ASD Symptoms
Two recent systematic reviews by Mulloy et al (25) and
Rossignol et al (26) included case reports, observational
studies, and controlled clinical trials, including 2 RCTs.
(27)(28)
Mulloy et al (25) identified 14 studies, with a total of
188 participants, between the ages of 2 and 17 years. Seven
studies reported positive results, 4 negative results, 2 mixed
results, and 1 inconclusive. Methodologic concerns were
identified in all the studies. An important finding was that
studies reporting negative results used the intervention for a
much shorter duration than those with positive results, for
a mean of 5 vs 18 months.
Rossignol et al (26) identified 14 studies that included
930 participants (including one survey of 479 parents). (9)
The children ranged in age from infants to 17 years. One
study was only published as an abstract. (29) Of the re-
maining 13 studies, 8 reported positive results, 3 reported
negative results, and 2 found no significant difference.
Although both Mulloy et al and Rossignol et al in-
cluded 2 RCTs, most of their included studies were of
less rigorous designs, such as surveys, case reports, and
observational studies. Limitations included lack of con-
trol groups and heterogeneous study conditions and
interventions.
A recent Cochrane systematic review evaluated the 2
RCTs, which report conflicting results. (27)(28) The trial
complementary medicine diet and autism
by Knivsberg et al (27) was a single-phase single-blind tri-
al comparing gfcf-d to standard diet for 12 months
(n¼10 on each diet). It found improvements in commu-
nication, social interaction, and behavioral flexibility (DI-
PAB or Diagnose of Psykotisk Adfærd hosBørn [Diagnosis
of Psychotic Behavior in Children]) in the intervention
group compared with the control group; all were statis-
tically significant (p<.05). Differences in nonverbal cog-
nitive (Leiter International Performance Scale) and gross
and fine motor skills (Movement Assessment Battery for
Children) were nonsignificant.
The trial by Elder et al (28) was a double-blind cross-
over trial comparing gfcf-d to standard diet for 6 weeks
(n¼15 on each diet). Although the trial reported no sig-
nificant differences between the 2 treatment groups for
communication, social relationships, behavioral flexibility,
activity level, or intellectual ability, parents of 7 children
reported improved language, hyperactivity, and tantrums,
possibly reflecting subtle changes not detected by the out-
come measure (Childhood Autism Rating Scale). Some
parents decided to continue gfcf-d despite lack of evidence
of effect.
In a more recent single-blind RCT by Whiteley et al,
(30) children were randomized to 12 months of gfcf-d or
standard diet; both groups had essential fatty acid supple-
mentation. The authors report benefits for the gfcf-d group
in communication (Autism Diagnostic Observation Sched-
ule), social interaction (Gilliam Autism Rating Scale),
inattention, and hyperactivity (attention deficit hyperac-
tivity disorder-IV rating scale). In the gfcf-d group, 11 of
37 participants withdrew from the study despite
extensive nutritional support because of difficulty in ac-
cepting the diet, and lack of time, resources, and per-
ceived beneficial effect. Gastrointestinal disease or
concomitant treatments were not reported.
Another single-blinded RCT (31) compared gfcf-d
(n¼8) to a low-sugar diet (n¼14) for 3 months in pa-
tients with ASD. Although there was no significant dif-
ference on the receptive language domain (Mullen
Scales of Early Learning AGS Edition) in the gfcf-d
group in comparison to the control group (p¼.06),
the control group did significantly better on the Mullen
visual reception domain (p¼.04). The gfcf-d group
scored significantly better on aggression and attention
deficit hyperactivity disorder (Child Behavior Check-
list), whereas the control group scored as significantly
less withdrawn. The authors suggest that more time
may be needed before effects can be seen.
Although not yet completed, it is worth noting that an
ongoing double-blind RCT sponsored by the National
Institutes of Mental Health is examining 6 weeks of gfcf-d
Pediatrics in Review Vol.34 No.10 October 2013 e37
complementary medicine diet and autism
in preschoolers followed by placebo for 12 weeks. This
study is currently being prepared for publication; there-
fore, the results are not yet available (Susan Hyman, per-
sonal communication).
Safety of Gfcf-d in Children with ASD
Adequate short- and long-term safety data from gfcf-
d are not yet available. (30) The RCTs reviewed did
not state whether any adverse effects were seen. (27)
(28) Current evidence comparing macronutrient and mi-
cronutrient deficiencies with and without a gfcf-d in chil-
dren with ASD is limited and conflicting. In one report,
minimal effect on energy, protein, and micronutrient in-
take is attributed to gfcf-d (n¼4) compared with those
not on a gfcf-d (n¼12). (8) However, when comparing
the effects of a gfcf-d on children with autism to healthy
controls, some reports associate a gfcf-d with exacerbation
of being underweight in children with autism (n¼252)
compared with healthy controls, (32) less calcium intake
(n¼14) compared with healthy controls without gfcf-d
(n¼31), (10) decreased bone development (n¼9), (33)
and plasma essential amino acid deficiency in 6 of 10 chil-
dren. (34) A study involving a short audit of dietetic re-
cords (11 of 26 on or planning to begin a gfcf-d)
suggested the complexity of managing diet within the
context of parent-child relationships/family dynamics,
dual diagnosis, and the behavioral basis of both the dis-
order and normal feeding. (35) A gfcf-d can be expensive
and might restrict lifestyle. (36)
Adequate evidence for nutritional adequacy in chil-
dren with ASD compared with healthy children is also
lacking and conflicting, (37)(38) although findings indi-
cate a potential increased risk for nutritional deficiencies.
(37)(39)(40)(41) Small studies confirm that many chil-
dren with ASD often have food preferences restricted
(8)(42) to certain textures, colors, or packaging due to
sensory hypersensitivity and insistence on sameness; (8)
(10) as food variety decreases, the number of nutrient in-
takes falling below reference nutrient intakes increases
(n¼17). (41) There is a reported lower intake of energy,
vitamin A, vitamin C, zinc, and phosphorus in children
with ASD (n¼252) compared with those without
ASD. (32) Small studies in children with ASD found they
(n¼32) consume fewer servings of dairy compared with
healthy controls (n¼23) (10) and have below recommen-
ded intake of vitamins A, D, and K, pantothenic acid, bi-
otin, and choline (n¼24). (43) Some children with ASD
(10- to 18-year-olds) have low bone mineral density
(BMD) (4 of 26) correlating with insufficient calcium
and calorie intake; (44) although asymptomatic in these
children, low BMD increases risk of fractures and future
e38 Pediatrics in Review Vol.34 No.10 October 2013
osteoporosis. Limited studies suggest that blood nu-
trients frequently deficient in children with ASD include
essential amino acids (58% of n¼26); (34) vitamin D
(61% of a cohort of 89 children, which included controls
and ASD patients with and without casein-free diet, with
no group effect); (45) and ferritin (16% of n¼96). (46)
(47) Thus, further restrictions by gfcf-d could potentially
exacerbate risk of nutritional deficiencies, (48) especially
when introducing new foods may be challenging. Supple-
mentation with multivitamins can significantly decrease
these risks except in the rare child who refuses any mul-
tivitamin supplementation.
Another potential harm of adopting gfcf-d is over-
looking possible underlying food allergy, celiac disease,
or lactose intolerance. (13) Food allergy can be IgE- or
non–IgE-mediated wheat allergy; however, both are
rare. (49) Celiac disease is the most common autoim-
mune gastrointestinal disorder (approximately 1% of
North Americans). (50) The only treatment for it is a
life-long gluten-free diet. (51)(52) Celiac disease may
present with typical gastrointestinal symptoms of diar-
rhea, constipation, anorexia, vomiting, abdominal pain,
or failure to thrive; it may also present with atypical symp-
toms, (53) such as headache, learning difficulties, and pe-
ripheral neuropathy. (54)(55) Therefore, celiac disease
would be difficult to exclude in this population, without
a screening test before commencing a gfcf-d, especially
when behavioral changes (irritability, aggression, repeti-
tive movements) are the only manifestation of gastroin-
testinal conditions. (13)(56) Current evidence about
celiac disease risk in autism is conflicting, (57)(58) but
the availability of IgA-antitissue-transglutaminase screen-
ing test for celiac disease has improved detection rates.
No current consensus exists for recommending screening
for celiac disease in individuals considering a gfcf-d. (13)
However, these diagnoses can (at minimum) coexist at
least at population rates. Lactose intolerance, although
uncommon in young children, presents usually with flat-
ulence and diarrhea. It is possible that for children with
primary or secondary lactose intolerance a casein-free diet
would reduce irritability from gaseous distention of the
intestine.
Conclusion
Evidence to date on the effectiveness of gfcf-d for chil-
dren with ASD has been inconclusive due to methodo-
logic limitations. Preliminary data suggest there may be
a subgroup of children with ASD who respond to a
gfcf-d. However, further research is necessary before
health care professionals can recommend gfcf-d dietary

modifications for ASD symptoms. (13) If parents wish to
try a gfcf-d, in our opinion it is appropriate to educate
them on a safe approach (Table).
Future Directions
Well-conducted and adequately powered double-blind
RCTs of sufficient duration are needed (36) to determine
the outcome of a gfcf-d for children with ASD and to
evaluate for possible markers for those children likely
to benefit, (13) such as underlying gastrointestinal dis-
ease. Such studies should include assessment of long-
term nutritional adequacy.
A Clinical Approach When Parents Inquire About Gfcf-d for
Table.
Children with ASD
Physical symptoms/signs
Parent education
Medical safety on gfcf-d
Measuring treatment response
HealthyChildren.org parent resources
ASD¼autism spectrum disorder; BMI¼body mass index; gfcf-d¼gluten-free and casein-free diet.
complementary medicine diet and autism
ACKNOWLEDGMENTS. The authors gratefully acknowl-
edge Laura Rogers, Occupational Therapist, Faculty of
Nursing, University of Alberta, Susan Jardine, Registered
Dietitian, Autism Clinic, Glenrose Rehabilitation Hospital,
Edmonton, Alberta, and Dr Lonnie Zwaigenbaum, De-
partment of Pediatrics, University of Alberta, for their
comments during the manuscript preparation, Soleil Sur-
ette for help with the search strategy, and Amy Moen for
coordinating the Pediatrics in Review series for the Amer-
ican Academy of Pediatrics Section on Integrative Medi-
cine. Dr Sunita Vohra receives salary support from
Alberta Innovates Health Solutions as a Health Scholar.
• Failure to thrive, gastrointestinal, skin, respiratory symptoms / require
the same thorough workup for cause in children with ASD as in the
general population.
• Inconclusive evidence for both potential benefits (communication, social
interaction, behavioral flexibility, inattention, and hyperactivity) and
harms (underweight, decreased calcium and essential amino acid intake
and bone development) / for some parents, trying gfcf-d offers
important hope, whereas other parents may feel relieved that they are not
obligated to try it.
• Practical considerations (expense, time and effort to prepare the diet and
keep daily food records, ensuring compliance outside the home). (48)
• Improvement from educational interventions and other concomitant
treatments, natural development (maturation, skill acquisition), (9) and
day-to-day behavioral variability / may make it difficult to confirm that
gfcf-d was the cause for improvements. (13)
• Before trial, we suggest rule out celiac disease and failure to thrive.
• If limited foods in baseline diet (risk of losing foods from rapid
introduction of new ones) (42) / consider gradual diet implementation
with assistance from occupational therapist or speech language
pathologist specializing in feeding.
• Dietitian guidance on gfcf-d (13) / to ensure nutritional adequacy
(protein, energy, calcium, vitamin D, and iron status), supplementation
when necessary. (8)(13)(35)(48)(59)
• Weight and/or BMI and height/growth velocity / we suggest these be
monitored. (32)
• We suggest keeping notes of systematic observations for behavior goals
with well-defined end points, using an “N-of-1 trial” consisting of
challenge-withdrawal-rechallenge (60) / validated rating scales (61)
(62)(63)(64) completed by parents and blinded (1)(13) teachers/
therapists may increase objectivity.
• Desired trial duration unknown / we suggest 12 weeks for each stage
might be reasonable.
• English: http://www.healthychildren.org/English/healthy-living/nutrition/
Pages/Gluten-Free-Casein-Free-Diets.aspx
• Spanish: http://www.healthychildren.org/spanish/healthy-living/nutrition/
paginas/gluten-free-casein-free-diets.aspx
Pediatrics in Review Vol.34 No.10 October 2013 e39
complementary medicine diet and autism
Summary
• On the basis of review of the published literature,
limitations in current data do not support the use of
a gluten-free and casein-free diet (gfcf-d) as
a primary autism spectrum disorder (ASD) treatment.
(13)(25)(26)(36)
• On the basis of clinical opinion, given the popularity
of parents seeking a gfcf-d for their children with
ASD, clinicians should acknowledge family’s concerns
and provide appropriate information about a gfcf-d to
guide them and prevent possible harm.
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Pediatrics in Review Vol.34 No.10 October 2013 e41
 Commentary: When Doing Less Is Best
H. Stephen Williams and Joseph A. Zenel
Pediatrics in Review 2013;34;423
DOI: 10.1542/pir.34-10-423

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 Commentary: When Doing Less Is Best
H. Stephen Williams and Joseph A. Zenel
Pediatrics in Review 2013;34;423
DOI: 10.1542/pir.34-10-423

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Commentary
When Doing Less Is Best
Author Disclosure
Drs Zenel and Williams have disclosed
no financial relationships relevant to
this article. This commentary does not
contain discussion of unapproved/
investigative use of a commercial
product/device.
Editor’s Note: During her acceptance of
the 2012 Joseph W. St Geme Jr. Leader-
ship Award, Dr Gail McGuinness remarked
that certain elements of clinical compe-
tence require time to attain: “problem
solving, pattern recognition, judgment,
(and) capability for self-reflection.”1 At
a recent resident continuity clinic that I
attended, I observed residents counsel
parent after parent that their children
did not need an antibiotic for their colds.
By clinic’s end, the residents were visibly
fatigued, and their resolve to follow
evidence-based medicine diminished. The
following self-reflection by a seasoned
pediatrician offers encouragement for all
of us to assess critically what we do and
to pursue resolutely what is in the
best interest of our patients.
Reference
1. McGuinness GA. The transformation of
pediatric education with a focus on
the subspecialists. Pediatrics. 2013;131
(4):767-771.
Joseph A. Zenel, MD
Editor-in-Chief
Abbreviations
CBC: complete blood cell count
CRP: C-reactive protein
In anything at all, perfection is finally at-
tained not when there is no longer any-
thing to add, but when there is no longer
anything to take away, when a body has
been stripped down to its nakedness.
Antoine de Saint-Exupery
Wind, Sand and Stars
Although innovative medical treatment
of childhood cancer, rheumatologic dis-
ease, metabolic disorders, and asthma
has lengthened and improved the qual-
ity of life for many children, during the
now 34 years I have been a practicing
pediatrician, I have also seen many pre-
viously well-accepted diagnostic and
therapeutic interventions abandoned
as the result of improvements in patient
safety and resource-sparing practice, rep-
resenting retreats from accepted practice
through advances in understanding
gained from curiosity, healthful skepti-
cism, a bias toward inquiry, thoughtful
questions, and good research.
Of course, true caring for the patient
must always be present; however, I be-
lieve another reliable guide to best
practice is a palpable tension between
“Just don’t stand there, do something!”
and “Just don’t do something, stand
there!” More often than not, the right
something is done by “standing there,”
with our patients protected and our re-
sources well used.
These days, most physicians have
come to recognize that resources are fi-
nite, and to enhance value to patient
care one must provide constant quality
in patient outcomes, safety, and satis-
faction, while reducing costs by elimi-
nating wasteful although well-intended
expenditure of scarce resources on un-
necessary diagnostic tests and therapeu-
tic interventions. Good intentions often
commentary
place both patients and pocketbooks at
risk. Years ago, the orthopedist Mercer
Rang pointed out the harm that often
befalls patients when laboratory and im-
aging studies are ordered without ade-
quate reflection after careful history
taking and examination. I have too fre-
quently seen the painful effects of what
I have coined the iatrogenic injury cas-
cade visited on patients by well-meaning
physicians. Most pediatricians, including
myself, have unwittingly initiated this
process at least a few times and certainly
more times than we would wish.
How can we limit harm? We must
discard the dowsers, amulets, and
leeches we use. Evidence-based prac-
tice promises to reduce the toll if we
can overcome the inertia of our estab-
lished practice comfort zones and reg-
ularly climb out of our rut, noses in
the air, always on the hunt for more ef-
ficient diagnoses and more effective
care. Established behavior always mer-
its periodic scrutiny to see whether
the behavior is as good as it was once
thought to be or is still relevant despite
being quite sound. For example, as the
advances in effective immunization re-
shape the bacteriologic landscape (eg,
Haemophilus and pneumococcus), we
need to rise and explore. Successful
navigation of the new terrain may re-
quire readjustment of thinking, mastery
of unfamiliar concepts, and regular ap-
plication of new tools. We pediatricians
are up to the task.
Below is a list of significant changes
in practice that have occurred in my
own professional lifetime as a pediatri-
cian, advances that for me add value to
the care I provide. These changes illus-
trate that what passed as self-evident
good care often failed close scrutiny.
Pediatrics in Review Vol.34 No.10 October 2013 423
commentary
I have grouped these changes under
questions I ask myself every day, ques-
tions whose answers have shaped and
continue to reshape my own care-
giving. For each question and practice
change listed, the bolded statement
is my best paraphrase of the cited
evidence.
When Doing Less is Best
1. How can I develop even more
confidence in identifying and as-
signing clinical patterns to deter-
mine accurate diagnoses more
efficiently and choose treatment
options more effectively?
I have learned over time that most
diseases have a limited number of
different presentations and that
distinctive clinical patterns can
guide my resource use efficiently.
I believe strongly that the spec-
trum of presentations for a given
condition can be learned (by
thoughtfully considering one’s
own experience while perusing
texts and reviews written by even
more seasoned clinicians) and then
can be applied appropriately to
limit diagnostic testing and focus
treatment decisions without any
serious risk of endangering the
quality of patient care. Saint-Exupery
provides a great model for us—
strip away the unnecessary and
you will uncover value underneath.
Reference: American College
of Radiology. Choosing Wisely.
http://www.abimfoundation.org/
Initiatives/Choosing-Wisely.aspx.
Accessed January 8, 2013.
2. Which diagnostic tests will truly
help me decide what to do in
a particular situation? Is any test
really necessary now? What fol-
lows are examples of routine tests
no longer thought necessary for
common clinical conditions, yet
are still quite often performed.
424 Pediatrics in Review Vol.34 No.10 October 2013
A. Testing for group A Streptococ-
cus pharyngitis usually is not
recommended for children
with acute pharyngitis whose
clinical and epidemiologic fea-
tures strongly suggest a viral
cause (cough, rhinorrhea,
hoarseness, and oral ulcers).
Reference: Shulman ST, Bisno
AL, Clegg HW, et al. Clinical
practice guidelines for the di-
agnosis and management of
group A streptococcal pharyn-
gitis: 2012 update by the In-
fectious Diseases Society of
America. Clin Infect Dis.
2012;55(10):e86–e102.
B. Diagnostic studies for group
A Streptococcus generally are
not indicated for children
younger than 3 years.
Reference: Shulman ST, Bisno
AL, Clegg HW, et al. Clinical
practice guidelines for the di-
agnosis and management of
group A streptococcal pharyn-
gitis: 2012 update by the In-
fectious Diseases Society of
America. Clin Infect Dis.
2012;55(10):e86–e102.
C. There is no need for a com-
plete blood cell count (CBC),
C-reactive protein (CRP)
measurement, or chest radi-
ography to diagnose most
pneumonias.
Reference: Bradley JS, Byington
CL, Shah SS, et al. The manage-
ment of community-acquired
pneumonia in infants and chil-
dren older than 3 months of
age: clinical practice guidelines
by the Pediatric Infectious
Diseases Society and the In-
fectious Diseases Society of
America. Clin Infect Dis.
2011;53(7):e25–e76.
D. In most patients, bronchio-
litis is a clinical diagnosis
that does not require virologic
identification, blood studies,
or imaging either for diagnosis
or assessment of severity.
Early in the season, virologic
diagnosis may be useful from
a public health perspective, and
influenza bronchiolitis may war-
rant antiviral therapy; hence, se-
lective testing may add value in
these circumstances.
Reference: American Academy
of Pediatrics Subcommittee on
Diagnosis and Management of
Bronchiolitis. Diagnosis and
management of bronchiolitis.
Pediatrics. 2006;118(4):1774–
1793.
E. CBC and CRP measurement
do not significantly alter the
posttest probability of bac-
teremia in febrile infants
and young toddlers who
are adequately immunized.
For unimmunized or less than
fully immunized infants, espe-
cially those younger than 3
months, the Rochester crite-
ria, which include the CBC,
may still be useful. (For the fe-
brile infant without immuni-
zations against Haemophilus
influenzae type B and pneu-
mococcus or only one nonpro-
tective set of immunizations,
the Rochester criteria work
pretty well.)
References: Jaskiewicz JA,
McCarthy CA, Richardson AC,
et al. Febrile infants at low risk
for serious bacterial infection –
an appraisal of the Rochester
criteria and implications for man-
agement. Pediatrics. 1994;94
(3):390–396.
Van del Bruen A, Thompson
MJ, Haj-Hassan T, et al. Diag-
nostic value of laboratory tests
in identifying serious infections

in febrile children: systematic
review. BMJ. 2012;342:d3082.
Coburn HA. Fever without a
source in children 3 to 36 months
of age. http://www.uptodate.
com/contents/fever-without-
a-source-in-children-3-to-36-
months-of-age. Accessed Jan-
uary 2, 2013. (This review
is based on evidence-based
studies.)
F. Chest radiography is unnec-
essary in febrile but other-
wise asymptomatic infants
younger than 2 months
whose physical examination
findings are normal.
Reference: Crain EF, Bulas D,
Bijur PE, Goldman HS. Is a chest
radiograph necessary in the eval-
uation of every febrile infant less
than 8 weeks of age? Pediatrics.
1991;88(4):821–824.
G. A basic metabolic panel is
not useful for the manage-
ment of previously healthy
infants and children with
clinically diagnosed mild-
moderate dehydration.
Reference: Granado-Villar D,
Cunil-De Sautu B, Granados
A. Acute gastroenteritis. Pediatr
Rev. 2012;33:487–495. (Excel-
lent discussion in which the
authors cite the original re-
search which supports their
conclusions.)
H. There is no need for a voiding
cystourethrogram in most in-
fants and young children with
first febrile urinary tract
infections.
Reference: Subcommittee on
Urinary Tract Infection, Steer-
ing Committee on Quality Im-
provement and Management,
Roberts KB. Urinary tract infec-
tion: clinical practice guideline
for the diagnosis and man-
agement of the initial UTI
in febrile infants and children
2 to 24 months. Pediatrics.
2011;128(3):595–610.
I. Other than always performing
a careful history and physical
examination, there is no need
for further evaluation of chil-
dren who experience simple
febrile seizures.
Reference: Subcommittee on
Febrile Seizures, American
Academy of Pediatrics. Neuro-
diagnostic evaluation of the
child with a simple febrile
seizure. Pediatrics. 2011;127
(2):389–394.
J. Neuroimaging for classic mi-
graine and typical stress head-
aches is not useful.
Reference: Wilne S, Collier J,
Kennedy C, et al. Presentation
of childhood CNS tumors: a
systematic review and meta-
analysis. Lancet Oncol. 2007;8
(8):685–695.
3. What harm might I cause by or-
dering a test now? Ordering diag-
nostic tests always risks harm to
patients.
A. Diagnostic studies for group
A Streptococcus generally
are not indicated for children
younger than 3 years. You
will identify colonized indi-
viduals, confuse parents,
overuse antibiotics, and risk
unnecessary tonsillectomy.
Reference: Shulman ST, Bisno
AL, Clegg HW, et al. Clinical
practice guidelines for the di-
agnosis and management of
group A streptococcal pharyn-
gitis: 2012 update by the In-
fectious Diseases Society of
America. Clin Infect Dis. 2012;
55(10):e86–e102.
Pediatrics in Review Vol.34 No.10 October 2013 425
commentary
B. There is no need for obtaining
a CBC, CRP level, or chest ra-
diography to diagnose most
pneumonias. You will only en-
counter findings, such as atel-
ectasis, that will confuse the
situation and do not require
treatment.
Reference: Bradley JS, Byington
CL, Shah SS, et al. The manage-
ment of community-acquired
pneumonia in infants and chil-
dren older than 3 months of
age: clinical practice guidelines
by the Pediatric Infectious Dis-
eases Society and the Infectious
Diseases Society of America. Clin
Infect Dis. 2011;53(7):e25–e76.
C. A CBC and CRP measure-
ment do not alter the posttest
probability of bacteremia use-
fully in adequately immunized
febrile infants and young
toddlers. You will poke and
may treat a lot of children
unnecessarily.
Reference: Van del Bruen A,
Thompson MJ, Haj-Hassan
T, et al. Diagnostic value of
laboratory tests in identifying
serious infections in febrile
children: systematic review.
BMJ. 2012;342:d3082.
D. Neuroimaging for classic mi-
graine and typical stress head-
aches creates more harm than
good. The radiation burden
from computed tomography
is high, and with magnetic
resonance imaging you may
uncover anatomical variations,
such as simple arachnoid
cysts, that raise unnecessary
concern.
References: Wilne S, Collier J,
Kennedy C, et al. Presentation
of childhood CNS tumors: a sys-
tematic review and meta-analysis.
Lancet Oncol. 2007;8(8):685–
695.
commentary
American College of Radiology.
Choosing Wisely. http://www.
abimfoundation.org/Initiatives/
Choosing-Wisely.aspx. Accessed
January 8, 2013.
4. Is any treatment really necessary
at this time? Is what I have been
taught and doing truly correct?
What will happen if I do not treat?
What harm can I cause by pre-
scribing a treatment?
What follows are treatments
now either unnecessary or un-
common and may be harmful.
A. Cough and cold medicines
do not work and may indeed
be harmful in infants.
Reference: Fashner J, Ericson K,
Werner S. Treatment of the com-
mon cold in children and adults.
Am Fam Physician. 2012;8 (2):
153-159. www.aafp.org/afp/
2012/0715/p153.html. Ac-
cessed December 18, 2012.
Pappas DE, Hendley JO. The
common cold and deconges-
tant therapy. Pediatr Rev.
2011;32(2):47–55.
B. Probing of obstructed nasola-
crimal ducts need not be done
until after age 1 year (if at all).
Reference: MacEwen CJ, Ho
WO. Is there any evidence
for surgical intervention in
childhood epiphora? Eur Oph-
thal Rev. 2009;3(1):39–41.
C. Not treating acute otitis media
in children older than 6 months
without severe signs or symp-
toms is an acceptable option
in selected cases when tympanic
membranes are intact.
References: Subcommittee on
Management of Acute Otitis
Media. Diagnosis and manage-
ment of acute otitis media. Pe-
diatrics. 2004;113:1451–1465.
426 Pediatrics in Review Vol.34 No.10 October 2013
Lieberthal AS, Carroll AE,
Chonmaitree T, et al. The di-
agnosis and management of
acute otitis media. Pediatrics.
2013;131(3):e964–e999.
D. Antibiotic prophylaxis for
recurrent otitis media is no
longer recommended.
References: Roark R, Berman
S. Continuous twice daily or
once daily amoxicillin prophy-
laxis compared with placebo
for children with recurrent acute
otitis media. Pediatr Infect Dis.
1997;16(4):376–381.
Pichichero ME. Acute otitis
media, part II: treatment in
an era of increasing antibiotic
resistance. Am Fam Physician.
2000;61(8):2410–2416.
Lieberthal AS, Carroll AE,
Chonmaitree T, et al. The di-
agnosis and management of
acute otitis media. Pediatrics.
2013;131(3):e964–e999.
E. Tonsillectomy, once a com-
mon practice, is now per-
formed primarily to treat
severe obstructive sleep apnea.
References: Burton MJ,
Glasziou PP. Tonsillectomy
or adeno-tonsillectomy ver-
sus non-surgical treatment
for chronic/recurrent acute
tonsillitis. http://summaries.
cochrane.org/CD001802/
tonsillectomy-for-chronic-or-
recurrent-acute-tonsillitis. Ac-
cessed December 18, 2012.
Paradise JL. Tonsillectomy
and adenoidectomy in chil-
dren. http://www.uptodate.
com/contents/tonsillectomy-
and-adenoidectomy-in-children.
Accessed July 14, 2013.
F. There is no need for prophy-
laxis against subacute bacterial
endocarditis in most children
with congenital heart disease.
Reference: Wilson W, Taubert
KA, Gewitz M, et al. Preven-
tion of infective endocarditis:
guidelines from the American
Heart Association: a guideline
from the American Heart Asso-
ciation Rheumatic Fever, Endo-
carditis, and Kawasaki Disease
Committee, Council on Cardio-
vascular Disease in the Young,
and the Council on Clinical Car-
diology, Council on Cardiovas-
cular Surgery and Anesthesia,
and the Quality of Care and Out-
comes Research Interdisciplinary
Working Group. Circulation.
2007;116 (15):1736–1754.
G. There is no need for medica-
tion in most young infants
who spit up.
Reference: Vandenplas Y,
Rudolph CD, Di Lorenzo C.
Pediatric gastroesophageal re-
flux clinical practice guide-
lines: joint recommendations
of the North American Society
for Pediatric Gastroenterol-
ogy, Hepatology, and Nutri-
tion (NASPGHAN) and the
European Society for Pediatric
Gastroenterology, Hepatology,
and Nutrition (ESPGHAN).
J Pediatr Gastroenterol Nutr.
2009;49(4):498–547.
H. There is no need for special
diet to treat viral diarrhea.
Reference: American Acad-
emy of Pediatrics, Provisional
Committee on Quality Im-
provement, Subcommittee on
Acute Gastroenteritis. Practice
Parameter: The Management
of Acute Gastroenteritis in
Children. Pediatrics. 1996;97
(3):424–435.

I. Umbilical herniorrhaphy is
unnecessary before age 4
years in most children.
Reference: Disorders of the
umbilicus in infants and chil-
dren: a consensus statement of
the Canadian Association of Pae-
diatric Surgeons. Paediatr Child
Health. 2001;6(6):312–313.
J. Antibiotic prophylaxis proba-
bly does not improve outcomes
in children with recurrent uri-
nary tract infections, even if
vesicoureteral reflux is present.
Reference: Subcommittee on
Urinary Tract Infection, Steer-
ing Committee on Quality Im-
provement and Management,
Roberts KB. Urinary tract infec-
tion: clinical practice guideline
for the diagnosis and manage-
ment of the initial UTI in
febrile infants and children 2
to 24 months. Pediatrics.
2011;128(3):595–610.
K. There is no need to treat in-
toeing or out-toeing in most
infants and children (no spe-
cial shoes or twister cables).
Reference: In toeing Gait.
http://www.orthoinfo.org/
topic.cfm?topic¼A00055. Ac-
cessed December 18, 2012.
(This review is based upon
evidence-based studies.)
5. Do I trim my practice behavior as
L. There is no need to attempt
to prevent recurrent sim-
ple febrile seizures. Risk
exceeds benefit.
Reference: Steering Commit-
tee on Quality Improvement
and Management, Subcom-
mittee on Febrile Seizures,
American Academy of Pediat-
rics. Febrile seizures: clinical
practice guideline for the
long-term management of
the child with simple febrile
seizures. Pediatrics. 2008; 121
(6):1281–1286.
M. There is no need to treat
most first afebrile seizures.
References: Camfield P,
Camfield C, Smith S, Dooley
J, Smith E. Long-term out-
come is unchanged by antiep-
ileptic drug treatment after
a first seizure: a 15-year
follow-up from a randomized
trial in childhood. Epilepsia.
2002;43(6):662–663.
Musicco M, Beghi E, Solari
A, Viani F, First Seizure
Trial Group (FIRST Group).
Treatment of first tonic-clonic
seizure does not improve the
prognosis of epilepsy. Neurol-
ogy. 1997;49(4):991–998.
N. Most children who have fever
do not require treatment. This
recommendation includes the
period before and after immu-
nizations. Acetaminophen and
ibuprofen are best thought of
as comfort medicines, not fe-
ver medicines.
Reference: Section on Clinical
Pharmacology and Therapeu-
tics, Committee on Drugs,
Farrar HC, Sullivan JE. Fever
and antipyretic use in chil-
dren. Pediatrics. 2011;127
(3):580–587.
new evidence comes to light? Can
I accomplish more with less?
A. Acute otitis media may be
treated for 7 days (rather than
10) in children age 2 to 5
years and 5 to 7 days (rather
than 10) in children older
than 6 years if the tympanic
membranes are unperforated.
Reference: Klassen TP, Kozyrskyj
AL, Moffatt M, Harvey K.
Short-course antibiotics for acute
commentary
otitis media. http://www.
thecochranelibrary.com/details/
browseReviews/577779/Otitis-
media-acute.html. Accessed
December 18, 2012.
Lieberthal AS, Carroll AE,
Chonmaitree T, et al. The di-
agnosis and management of
acute otitis media. Pediatrics.
2013;131(3):e964–e999.
B. There is no need for early
follow-up of most children
with uncomplicated otitis
media. Sterile fluid persists
for up to 3 months in 10%
of children with acute otitis
media. Early rechecks invite
inappropriate antibiotic use.
References: Subcommittee on
Management of Acute Otitis
Media. Diagnosis and manage-
ment of acute otitis media. Pedi-
atrics. 2004;113:1451–1465.
Lieberthal AS, Carroll AE,
Chonmaitree T, et al. The di-
agnosis and management of
acute otitis media. Pediatrics.
2013;131(3):e964–e999.
Your own list of questions and per-
sonal answers may be longer. As pedia-
tricians becoming more skeptical of
the value we provide, we find good
company. The Choosing Wisely initia-
tive of the American Board of Medicine
Foundation and Consumer Reports has
gathered more and more specialties and
subspecialties together to search for
well-intended but questionable tests,
treatments, and procedures whose worth
we should be discussing with our patients.
I have long believed physicians need
to reframe how we think about health
and the teaching and provision of med-
icine, given limited resources and po-
tentially boundless need. Identifying
and discussing more widely what we
do not need to do or should not do is
a very promising step forward.
Pediatrics in Review Vol.34 No.10 October 2013 427
commentary
In the absence of emergency, not
doing something but rather standing
there and thinking hard about using re-
sources wisely has served my own pa-
tients well during the past 3 decades.
If all of us let our curiosity and skepti-
cism rekindle, I am certain that the above
list of unnecessary tests and treatments
will increase during the next 3 decades.
Our patients will be the better for it.
H. Stephen Williams, MD, MPH,
Department of Pediatrics,
College of Osteopathic Medicine,
Michigan State University,
East Lansing, MI
Additional Supporting
References
Auerbach AD, Landefeld CS, Shojania KG.
The tension between needing to
improve care and knowing how to do
it. N Engl J Med. 2007;357(6):
608–613
Community Acquired Pneumonia
Guideline Team, Cincinnati Children’s
Hospital Medical Center. Community
428 Pediatrics in Review Vol.34 No.10 October 2013
Acquired Pneumonia in Children 60
Days Through 17 Years of Age. www.
cincinnatichildrens.org/workarea/linkit.
aspx?linkidentifier=id&itemid=87957
&libid=87645. Accessed December 18,
2012.
Cortese DA, Korsmo JO. Putting U.S.
health care on the right track. N Engl J
Med. 2009;361(14):1326–1327
Croskerry P. The importance of cognitive
errors in diagnosis and strategies to
minimize them. Acad Med. 2003;78
(8):775–780
Finkelstein JA, Huang SS, Kleinman K,
et al. Impact of a 16-community trial
to promote judicious antibiotic use in
Massachusetts. Pediatrics. 2008;121
(1):e15–e23
Fred HL. Hyposkillia: deficiency of clinical
skills. Tex Heart Inst J. 2005;32(3):
255–257
Fuchs VR. Three “inconvenient truths”
about health care. N Engl J Med.
2008;359(17):1749–1751
Gawande A. The cost conundrum. New
Yorker. June 2009:1
Groopman J. How Doctors Think. Boston,
MA: Houghton Mifflin; 2007
Mathews B, Shah S, Cleveland RH, Lee EY,
Bachur RG, Neuman MI. Clinical
predictors of pneumonia among
children with wheezing. Pediatrics.
2009;124(1):e29–e36
O’Brien KL, Dowell SF, Schwartz B, et al.
Cough illness/bronchitis—principles
of judicious use of antimicrobial
agents. Pediatrics. 1998;101(Suppl):
178–181
Rang M. The Ulysses syndrome. Can Med
Assoc J. 1972;106(2):122–123
Relman AS. Doctors as the key to health
care reform. N Engl J Med. 2009;361
(13):1225–1227
Sutherland JM, Fisher ES, Skinner JS.
Getting past denial—the high cost
of health care in the United States.
N Engl J Med. 2009;361(13):
1227–1230
Wenzel RP, Fowler AA III. Clinical
practice: acute bronchitis. N Engl J
Med. 2006;355(20):2125–2130
Williams HS. Toward consistent evidence-
based pediatric practice: developing
a reliable process for narrowing
variation. Pediatr Rev. 2006;27(10):
e66–e70

Acute Bacterial Sinusitis in Children
Gregory DeMuri, MD,*
Ellen R. Wald, MD†
Author Disclosure
Drs DeMuri and Wald
have disclosed no
financial relationships
relevant to this article.
This commentary does
contain discussion of
unapproved/
investigative use of
a commercial product/
device.
Abbreviations
AOM: acute otitis media
PCV-7: 7-valent pneumococcal conjugate vaccine
URI: upper respiratory tract infection
Article infectious diseases
Practice Gaps
1. Acute bacterial sinusitis should be diagnosed in a child who has an acute upper
respiratory tract infection with persistent illness (ie, nasal discharge or daytime cough
or both) lasting more than 10 days; worsening cough, worsening or new nasal
discharge, or daytime cough or fever after initial improvement; or severe onset of
fever and purulent nasal discharge for at least 3 consecutive days.
2. The clinician should prescribe antibiotics for acute bacterial sinusitis in children with
severe onset or worsening course. Children with persistent illness should be either
prescribed antibiotic therapy or offered additional observation for 3 days.
Objectives After completing this article, readers should be able to:
1. Understand the mechanisms that lead to bacterial sinusitis.
2. Be able to distinguish the child who has bacterial sinusitis from the one who has only
a viral upper respiratory infection or allergic congestion.
3. Be aware of the usefulness of nasal cultures, sinus, aspirate cultures, and findings on
imaging in diagnosing bacterial sinusitis.
4. Know the current treatment of bacterial sinusitis, taking into consideration changes in
the characteristics of infecting organisms.
The viral upper respiratory tract infection (URI) is the most common illness for
which children present to the primary care pediatrician. Approximately 5% to 10% of
viral URIs are complicated by acute bacterial sinusitis. Sinusitis results in more than
$5.8 billion in health care expenditures in the United States annually, of which $1.8
billion is spent on children younger than 13 years. (1) The diagnosis and treatment
of acute bacterial sinusitis present unique challenges to the primary care physician in
the acute care setting.
Anatomy and Pathogenesis
The ethmoid and maxillary sinuses develop in the third month of gestation and, although
small, are present at birth. The frontal sinuses develop from an anterior ethmoidal air cell
and are pneumatized by age 5 or 6 years. The sphenoid sinus starts to become aerated at age
5 years and expands in size into the second or third decade of life.
The outflow tract of the maxillary sinus is located at the most superior portion of the me-
dial wall of the sinus (Fig 1). This unfortunate positioning makes gravitational drainage dif-
ficult. The clearance of secretions of the sinus is thus dependent on the mucociliary elevator of
the mucosa. The maxillary sinus empties via the ostium into the middle meatus of the nasal
cavity at a location known as the osteomeatal complex. The
maxillary sinus ostia are small, tubular structures with a diam-
eter of only 2.5 mm and a length of 6 mm. The anterior eth-
moid and frontal sinuses also empty into the osteomeatal
complex in the middle meatus. The posterior ethmoid air cells
and the sphenoid sinus drain into the superior meatus.
A key concept in understanding the pathogenesis of acute
bacterial sinusitis is that the mucosa of the nose and
*Associate Professor, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
†
Professor and Chair, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Pediatrics in Review Vol.34 No.10 October 2013 429
infectious diseases acute bacterial sinusitis
Figure 1. Coronal (A) and sagittal (B and C) sections of the
nose and paranasal sinuses.
nasopharynx is continuous with the mucosa of the para-
nasal sinuses. This pseudostratified columnar epithelium
clears mucus and other material from the sinus by ciliary
action. Any process that affects the nasal mucosa also
430 Pediatrics in Review Vol.34 No.10 October 2013
may affect the sinus mucosa. Unlike the nasal mucosa,
which is heavily colonized with bacteria, the paranasal si-
nuses normally are sterile.
The pathogenesis of sinusitis involves 3 key factors: ob-
struction of the sinus ostia, dysfunction of the ciliary appa-
ratus, and thickening of sinus secretions. The narrow
diameter of the sinus ostia allows for easy obstruction.
The factors that predispose the ostia to obstruction may
be divided into those that result in mucosal swelling and
those that result in a direct mechanical effect (Table 1).
Viral URI is the most common cause of ostial obstruc-
tion in children and frequently precedes the development
of sinusitis. Obstruction of the ostia results in a transient
increase in pressure in the sinus cavity. As oxygen is de-
pleted, the pressure in the sinus becomes negative relative
to the atmosphere. This negative pressure allows for the
introduction of bacteria from the nose and nasopharynx
into the sinus. When the ostia are obstructed, mucous pro-
duction by the mucosa continues, resulting in the accumu-
lation of fluid in the sinus cavity and the multiplication of
bacteria and the initiation of an inflammatory reaction.
In addition to ostial obstruction, dysfunction of the
mucociliary apparatus also contributes to the development
of sinusitis. During a viral URI, progressive loss of ciliated
cells may be observed in the respiratory mucosa.
Lastly, the quality and character of sinus secretions
play an important role in the pathogenesis of acute bac-
terial sinusitis. Cilia can beat only in a liquid media, and
diseases such as cystic fibrosis result in very thick, viscous
secretions that diminish ciliary clearance of fluid and de-
bris from the sinus. Infection of the sinus results in thick-
ening of secretions, compounding this process.
The result of a viral URI is that all 3 of these factors are
present: ostial obstruction, ciliary dysfunction, and thick-
ening of sinus secretions. The viral URI is the most com-
mon predisposing factor to the development of bacterial
sinusitis in childhood and accounts for approximately
80% of cases. Allergic inflammation underlies the remain-
ing 20% of cases of acute bacterial sinusitis in children.
Microbiology
Sinus Aspiration Studies
Knowledge of the microbiology of acute sinusitis has
been derived from studies of sinus aspiration. The diffi-
culty in obtaining any sample for culture is that the si-
nuses are a closed space accessible only through a highly
contaminated mucous membrane. Maxillary sinus aspira-
tion in children is a time-consuming procedure that should
be performed only by a skilled pediatric otolaryngologist.
In this procedure, the nasal mucosa is anesthetized and dis-
infected with a solution of 10% cocaine. A trocar is passed

Factors Predisposing
Table 1.
Patients to Obstruction of the
Sinus Ostia
Mucosal Swelling Mechanical Obstruction
Systemic factors Tumor
Viral upper respiratory Foreign body
tract infection Nasal polyps
Allergic rhinitis Choanal atresia
Tobacco smoke Ethmoid bullae
Immotile cilia syndromes Deviated septum
Immune disorders
Cystic fibrosis
Local insults
Trauma
Nasal intubation
Swimming/diving
Nasal decongestant
overuse
just below the inferior nasal turbinate across the lateral na-
sal wall. Aspirated material is sent for Gram stain and quan-
titative aerobic and anaerobic bacterial culture. The
recovery of bacteria in a density of 104 Cfu/mL or more
is considered significant growth. A Gram stain finding of at
least one organism per high-power field correlates with the
isolation of bacteria from nasal secretions in a density of
105 Cfu/mL.
Several sinus aspiration studies performed in the 1980s
in children with 10 to 30 days of sinus symptoms have
provided insight into the microbiology of acute bacterial
sinusitis. (2,3) In these studies Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella catarrhalis were
responsible for most episodes of sinusitis. S pneumoniae
was the most frequently isolated organism, accounting
for 40% of isolates, with H influenza and M catarrhalis
each accounting for approximately 20% of cases. Less
commonly isolated organisms include group A streptococ-
cus, group C Streptococcus, Peptostreptococcus spp, Eikenella
corrodens, and Moraxella spp. Anaerobic bacteria are not
isolated commonly in patients with acute sinusitis.
Because of the invasive nature of sinus aspiration,
there has been interest in obtaining specimens for culture
from a more accessible site that reflects the microbiology
of the sinus. Nasopharyngeal swabs have been studied
but unfortunately correlate poorly with sinus aspirate cul-
tures. (2) Endoscopically obtained samples of secretions
from the middle meatus near the osteomeatal complex
also have been studied. In children, these specimens have
poor correlation with sinus aspirates, likely because of the
infectious diseases acute bacterial sinusitis
narrow caliber of the nasal passages and the potential for
contamination with nasal flora. (4)
No sinus puncture studies have been performed since
1984 in children who have acute sinusitis, and yet the mi-
crobiology of the nasopharyngeal flora of children has un-
dergone important changes in the past decade. Because
the pathogenesis of acute otitis media (AOM) and acute
bacterial sinusitis is similar, it is possible to use data de-
rived from studies of tympanocentesis performed in chil-
dren who have AOM as a surrogate for sinusitis. The
middle ear cavity is, in fact, a paranasal sinus.
Since the introduction of the 7-valent pneumococcal
conjugate vaccine (PCV-7), there has been a significant
shift in the pathogens responsible for AOM. In a rural
Kentucky clinic, Block et al performed tympanocentesis
and culture of middle ear fluid on 381 children ages 7
to 24 months who had AOM in the period before and
after the introduction of PCV-7. (5) The proportion of
cases of AOM caused by S pneumoniae had decreased sig-
nificantly from 56% to 41%, whereas that caused by H in-
fluenzae had increased from 38% to 57%. The rate of
isolation of M catarrhalis remained constant at approxi-
mately 10%. Studies performed since the introduction of
the 13-valent pneumococcal conjugate vaccine have sug-
gested an even greater decrease in the proportion of
AOM cases due to S pneumoniae. (6)
In addition to the increase in the rate of isolation of H
influenzae in children with AOM, there has been a shift
in the susceptibility patterns of this organism. The mech-
anism by which isolates of H influenzae are resistant to
penicillins such as amoxicillin is by the production of
b-lactamases. Historically, approximately 20% to 30%
of isolates of H influenzae causing sinusitis and AOM
in children have produced b-lactamase. Recently, mid-
dle ear and nasopharyngeal cultures taken from children
in Rochester, New York, have demonstrated beta-
lactamase rates as high as 50%. (7) This increase in the
rate of resistance has important implications for antibiotic
selection because empirical choices will need to include
a b-lactamase stable drug.
There has been recent controversy in the medical liter-
ature over the role of Staphylococcus aureus (including
methicillin-resistant strains) in acute sinusitis. Some authors
have stated that this pathogen should be considered an im-
portant cause of acute bacterial sinusitis. (8) However, these
studies have serious methodologic flaws. (9) Most were
performed by obtaining cultures from the middle meatus
via an endoscope. The middle meatus in healthy children
is colonized with S aureus as frequently as 65% of the time.
Those authors who performed direct sinus aspirate did not
verify decontamination of the puncture site. The isolation
Pediatrics in Review Vol.34 No.10 October 2013 431
infectious diseases acute bacterial sinusitis
of S aureus in these studies likely represents contamination
from a colonized nasal mucosa. It is notable also that in the
original sinus aspirate studies performed in children, S aureus
was not isolated in any of the 50 children enrolled in the
study. It is doubtful then that this agent is a significant path-
ogen in acute bacterial sinusitis. However, S aureus plays an
important role in some of the complications of sinusitis.
Clinical Presentation
Viral URI
A major task for the clinician who is evaluating a child with
respiratory symptoms is to distinguish those who have un-
complicated viral URI from those who have acute bacterial
sinusitis. This distinction allows for the identification of
children who will benefit from an antimicrobial drug.
The clinical course of a viral URI is depicted in Figure 2
and usually begins with a sore or scratchy throat. Children
are more likely to have fever with a URI than adults, and
when fever occurs, it presents early in the illness and re-
solves within 1 to 2 days. Fever may be accompanied by
constitutional symptoms, such as headache and myalgia.
Symptoms of nasal obstruction and discharge predom-
inate during a URI and follow a predictable pattern. The
nasal discharge starts as clear and watery, becomes thicker
and mucoid, and then is colored and opaque (purulent)
for several days. This pattern then reverses, with the nasal
discharge becoming watery again or simply drying. Cough
and hoarseness also may be prominent in viral URIs. Most
uncomplicated URIs last 5 to 10 days, and resolution of
symptoms occurs without antimicrobial therapy. Although
not all children have complete resolution by day 10, the
symptoms usually have peaked in intensity on days 3 to
5 of illness and are improving.
Figure 2. Schematic representation of an uncomplicated viral
upper respiratory infection.
432 Pediatrics in Review Vol.34 No.10 October 2013
Acute Bacterial Sinusitis
The presentation of acute bacterial sinusitis conforms to 1
of 3 predictable patterns (Table 2). The first and most
common presentation in children is that of persistent respi-
ratory symptoms. These patients have nasal congestion or
nasal discharge, with or without cough, for more than 10
but fewer than 30 days without improvement. The key in
distinguishing this presentation from an uncomplicated
URI is the lack of improvement of their respiratory symp-
toms after 10 days. Although patients with uncomplicated
viral URI may have residual respiratory symptoms at 10
days, almost always these symptoms are improving.
The rhinorrhea may be of any color or character: clear
and watery, mucoid, or purulent (thick, colored, and opa-
que). The cough may be wet or dry in character. When
cough is a symptom of acute bacterial sinusitis, it must
be present during the day but often is reported to be worse
at night. Face pain and headache are rare, although pain-
less morning eye swelling occurs on occasion. Parents of
preschool children often will report malodorous breath.
The child who has this presentation usually appears only
mildly ill, and fever, if it is present, is low grade.
The second presentation of acute bacterial sinusitis is
that of the onset of severe illness. These patients present
with temperatures of at least 38.5°C accompanied by
a particular type of nasal discharge, a purulent nasal dis-
charge, for a period of 3 to 4 days. Older children and
adults may experience focal face pain, tooth pain, fever,
and purulent nasal discharge. The presence of fever for
longer than 48 hours distinguishes this presentation from
that of an uncomplicated viral URI.
The third presentation is one of biphasic or worsening
symptoms. In the Scandinavian literature, this is referred
to as “double sickening.” These patients have initial
symptoms of an uncomplicated viral URI that begins
Clinical Presentation and
Table 2.
Criteria for the Diagnosis of
Acute Bacterial Sinusitis
Persistent symptoms
• Nasal discharge/congestion and/or cough for ‡10 days
without improvement
Severe symptoms
• Temperature ‡38.5oC with purulent rhinorrhea for at
least 3 days
Worsening symptoms
• Worsening of nasal congestion or rhinorrhea, cough, and
fever after a 3- to 4-day period of improved symptoms

to improve. Then after several days there is a substantial
worsening of symptoms with exacerbation of cough or
nasal discharge or congestion. A new fever may be pres-
ent, or fever may recur if it was present at the onset.
The physical findings in children who have sinusitis
may demonstrate mucopurulent material on the nasal
mucosa or in the posterior pharynx. The nasal mucosa it-
self may be erythematous or boggy and pale, and the oro-
pharynx may be injected. Malodorous breath may be
present with sinusitis in the absence of a nasal foreign
body or dental disease. Examination of the tympanic
membranes may reveal evidence of concomitant AOM
or otitis media with effusion. Swelling and discoloration
of the eyelids are observed sometimes, and occasionally
facial tenderness over the maxillary or frontal sinuses is
present. Overall, the physical examination is of limited
use in making a specific diagnosis because none of these
physical findings distinguishes a viral URI from acute
bacterial sinusitis.
Diagnosis
Clinical Criteria
The diagnosis of acute bacterial sinusitis is almost always a
clinical one. Strict application of the clinical criteria (Table 2)
that define persistent, severe, and worsening symptoms will
distinguish those children with sinusitis from those with viral
URI and thus identify a cohort of patients most likely to
benefit from an antimicrobial agent. The use of these clinical
criteria results in a diagnosis of acute bacterial sinusitis in 6%
to 7% of children presenting in a primary care setting with
upper respiratory tract symptoms. (10)
Imaging
Although various imaging modalities have been used to
assess the paranasal sinuses, imaging is not necessary to
confirm the diagnosis of uncomplicated acute bacterial si-
nusitis. Abnormal findings on imaging studies include
complete sinus opacification, mucosal thickening of at
least 4 mm, or an air-fluid level. The continuity of the na-
sal mucosa with the sinus mucosa limits the usefulness of
imaging in the diagnosis of sinusitis. It has been demon-
strated that both adults and children have significant ab-
normalities on imaging studies that are performed during
an uncomplicated URI.
A classic study by Gwaltney et al reported on an expe-
rience in adults who had uncomplicated colds. (11)
Computed tomographic scans performed within 48 to
96 hours of the onset of symptoms demonstrated abnor-
malities of the sinuses in more than 80% of patients. In
children with viral URI, more than half will have abnor-
mal sinuses on plain radiograph. (12) Accordingly, no
infectious diseases acute bacterial sinusitis
imaging study is able to distinguish the inflammation of
the sinus mucosa caused by viruses from that due to bacteria.
Although imaging studies are not recommended rou-
tinely in the diagnosis of sinusitis, a negative radiograph
effectively eliminates the diagnosis. Computed tomogra-
phy and magnetic resonance imaging of the sinuses may
be useful when complications of sinusitis are suspected.
In this situation, fluid collections that may require surgi-
cal drainage may be identified.
Sinus Aspiration
A skilled pediatric otolaryngologist may perform maxil-
lary sinus aspiration in an outpatient setting. Indications
for this procedure include sinusitis unresponsive to mul-
tiple courses of antibiotics, orbital or intracranial compli-
cations, severe facial pain, and suspected sinusitis in an
immunocompromised host in whom unusual pathogens
such as fungi may be present.
Complications
Complications of sinusitis may be divided into those in-
volving the orbit, the central nervous system, or the bone
(Table 3). The frontal and ethmoid sinuses are the most
common sinuses from which complications arise. The
delicate and thin walls of the ethmoid sinuses, called lamina
papyracea , allow for spread of infection into the orbit. Or-
bital complications are the most common and include sub-
periosteal abscess, orbital cellulitis, and orbital abscess. Signs
of orbital infection include eyelid swelling, proptosis, and
impairment of extraocular muscle movement. This compli-
cation may result from spread of infection through the
Major Complications of
Table 3.
Sinusitis
Intracranial
Meningitis
Subdural empyema
Epidural empyema
Brain abscess
Venous sinus thrombosis
Orbital
Optic neuritis
Orbital cellulitis
Orbital abscess
Subperiosteal abscess
Inflammatory edema (periorbital cellulitis)
Osteitis
Maxillary
Frontal (Pott puffy tumor)
Pediatrics in Review Vol.34 No.10 October 2013 433
infectious diseases acute bacterial sinusitis

natural dehiscences between the bones that comprise the Antimicrobial Agents for
Table 4.
medial wall of the orbit (which is also the lateral wall of
the ethmoid sinus) or from the development of a subperios- the Treatment of Sinusitis in
teal abscess of the ethmoid bone. Children
The frontal sinuses share venous drainage with intracra-
nial structures, allowing for infection to develop within the Drug Dosage
brain and surrounding structures. Intracranial infection Oral
may present with headache, seizures, focal neurologic Amoxicillin 40-90 mg/kg/d divided
signs, or meningeal signs and can include subdural and epi- twice daily
dural empyema and brain abscess. Parenteral antibiotics are Amoxicillin- 90 mg/kg/d (amoxicillin)
necessary for treatment, and surgery is indicated when clavulanate divided twice daily
Cefdinir 14 mg/kg/d divided once
a drainable fluid collection is present. The bony complica- or twice daily
tion of acute frontal sinusitis is Pott puffy tumor, which is Cefixime 8 mg/kg/d once a day
a subperiosteal abscess of the frontal bone. Cefpodoxime 10 mg/kg/d divided twice daily
Cefuroxime 30 mg/kg/d divided twice daily
axetil
Treatment Linezolid 20-30 mg/kg/d divided
Controlled Trials (with cefixime) 2-3 times daily
Levofloxacin 16 mg/kg/d divided
The necessity of treating sinusitis with antibiotics has every 12 hours
been controversial. There have been several randomized Parenteral
trials of placebo vs antimicrobial therapy in the treatment Cefotaxime 150-200 mg/kg/d divided
of sinusitis in children that have produced conflicting re- every 6-8 hours
sults. Lack of efficacy in 2 of these studies may be ex- Ceftriaxone 50-100 mg/kg/d divided
every 12-24 hours
plained by underdosing of antibiotics and lack of clear Clindamycin 20-40 mg/kg/d divided
definition of the population of patients included in the every 8 hours
studies. (13,14) Two other trials have found consistent Vancomycin 40-60 mg/kg/d divided
benefit to antibiotic treatment when strict clinical criteria every 6-8 hours
are used to select patients with sinusitis. (10,15)
In the most recent trial, high-dose amoxicillin-clavulanate
was compared with placebo. (10) This study included 58 provides an advantage over amoxicillin alone. Using 90
children ages 1 to 10 years who met stringent criteria for si- mg/kg/d of the amoxicillin component provides better
nusitis based on persistent, worsening, or severe symptoms. coverage for penicillin nonsusceptible S pneumoniae. Al-
A standardized symptom score was used to evaluate treat- though gastrointestinal adverse events are more common
ment effect. Of those children who received antibiotic, with amoxicillin-clavulanate than placebo, most are mild
64% were cured or improved vs 32% in the placebo arm. and self-limited. Amoxicillin alone is an acceptable sec-
In addition, treatment failure was noted in 68% of those re- ond-line agent but should be used at a high dose (90
ceiving placebo vs 14% in the antibiotic arm of the study mg/kg/) in those children at risk for resistant pneumococci,
(P<.01). This study demonstrates that antibiotic treatment for example, those younger than 2 years, attending child
is beneficial when children in an office setting are diagnosed care, or having recently (<30 days) received antibiotics.
as having sinusitis using stringent clinical criteria. The choice of a second-line agent for treating sinus-
itis in children is problematic. Cephalosporins, such as
Antimicrobial Recommendations cefpodoxime, cefuroxime axetil, or cefdinir, are alterna-
The antibiotics used to treat acute bacterial sinusitis in tive antibiotics that may be used to treat sinusitis in chil-
children are listed in Tables 4 and 5. dren, although they are less active against S pneumoniae
High-dose amoxicillin-clavulanate (90 mg/kg/d) should than amoxicillin-clavulanate. As discussed, the microbiology
be considered as a first-line agent for the treatment of si- of respiratory tract infections in children is dynamic and
nusitis because it has the most comprehensive in vitro has demonstrated significant shifts since the introduction
activity against sinus pathogens. Because the proportion of the pneumococcal conjugate vaccine. If S pneumoniae,
of cases caused by H influenzae is likely increasing and the particularly penicillin-nonsusceptible strains, continues to
rate of b-lactamase production by this organism is also in- decrease in prevalence, the cephalosporins may be more
creasing, the addition of clavulanic acid to amoxicillin effective in the treatment of sinusitis.

434 Pediatrics in Review Vol.34 No.10 October 2013

 infectious diseases acute bacterial sinusitis

Table 5. Formulations and Dosing of Amoxicillin-Clavulanate

Strength/concentration (amoxicillin- Ratio (amoxicillin: Dosage per dose (mg/kg of Dosing
clavulanate), mg clavulanate) amoxicillin)a frequency (h)
Liquid per 5 mL
125-31 4:1 13.3 8
250-62.5 4:1 13.3 8
200-28.5 7:1 22.5 12
400-57 7:1 22.5 12
600-42.9 14:1 45 12
Chewable tablets, mg
250-62.5 4:1 13.3 8
200-28.5 7:1 22.5 12
400-57 7:1 22.5 12
Tablets, mg
250-125 2:1 250 8
500-125 4:1 500 8 or 12
875-125 7:1 875 12
1000-62.5b 16:1 1000-2000 12
a
Maximum daily dose of amoxicillin is 4 g.
b
Food and Drug Administration approved for children and adults 16 years and older.

For those children in whom amoxicillin-clavulanate or
second- or third-generation cephalosporins fail, a combi-
nation of cefixime (or cefdinir) and linezolid may be used.
Despite the increased complexity and expense of this reg-
imen, it is an alternative to the use of parenteral antimi-
crobial agents in these children.
Levofloxacin, a quinolone antimicrobial, is also an ef-
fective agent for children in whom amoxicillin-clavulanate
therapy fails or in the severely (type 1 hypersensitivity) pen-
icillin allergic patient. It is not approved by the Food and
Drug Administration for this indication, however. The rate
of musculoskeletal adverse events, such as tendinopathy,
arthritis, or arthralgia, is slightly higher in patients receiv-
ing levofloxacin than other antibiotics. However, the drug
usually is well tolerated in children, and the American
Academy of Pediatrics has issued a policy statement on
the use of fluoroquinolones in children. It was concluded
that their use may be justified where there is no safe and
effective alternative. (16)
Patients with evidence of systemic toxic effects, compli-
cations of sinusitis, or an inability to take antibiotics orally
should be hospitalized for parenteral therapy. For uncom-
plicated sinusitis, ceftriaxone or cefotaxime should be used
as single agents. If complications are suspected, the ceph-
alosporin should be combined with vancomycin until the
results of culture and susceptibilities are known.
Response to therapy is prompt in children who have si-
nusitis and are adherent to therapy with an appropriate an-
timicrobial agent. Fever, if present at onset, resolves, and
a rapid decrease in cough and nasal symptoms occurs
within 48 hours. If symptoms are not improved within this
time frame, then clinical reevaluation is warranted. If the
diagnosis is unchanged, a second-line antimicrobial should
be prescribed. Alternatively, sinus aspiration may be con-
sidered for precise identification of the causative organism.
The appropriate duration of antimicrobial therapy has
not been studied systematically. For patients who have
a rapid response to the initiation of antimicrobial, 10 days
of therapy usually is adequate. For those who respond at
a slower rate, treating until the patient is symptom free
plus an additional 7 days is reasonable.
Adjunctive Therapies
Adjunctive therapies, such as antihistamines and decon-
gestants, have not been found consistently to provide
benefit in children with sinusitis and may be associated
with toxic effects. Intranasal corticosteroids have too
modest a benefit to be recommended routinely.
Recurrent Sinusitis
Some children experience frequent recurrences of sinus
symptoms. The most common cause of such symptoms
is recurrent viral URI, especially in those children at-
tending child care. Other conditions, such as allergic
rhinitis, exposure to tobacco smoke, gastroesophageal
reflux, anatomical abnormalities, cystic fibrosis, an
immunodeficiency disorder, or ciliary dyskinesia, may
predispose patients to recurrent symptoms. The evalua-
tion of a child with recurrent sinusitis should include

Pediatrics in Review Vol.34 No.10 October 2013 435

infectious diseases acute bacterial sinusitis
consultation with an allergist, measurement of serum
quantitative immunoglobulins and CH50, a test for cystic
fibrosis, and a biopsy of nasal mucosa to assess ciliary
structure and function. If sinusitis does not respond to
medical therapy, surgical intervention may be indicated.
Chronic sinusitis in children is less common in adults
and occurs often in children who have the above predis-
posing conditions. Children with chronic sinusitis have
more of an inflammatory disease, although bacteria may
cause acute exacerbations.
Summary
• On the basis of strong research evidence, the
pathogenesis of sinusitis involves 3 key factors: sinus
ostia obstruction, ciliary dysfunction, and thickening
of sinus secretions.
• On the basis of studies of the microbiology of otitis
media, H influenzae is playing an increasingly
important role in the etiology of sinusitis, exceeding
that of S pneumoniae in some areas, and b-lactamase
production by H influenzae is increasing in respiratory
isolates in the United States.
• On the basis of some research evidence and consensus,
the presentation of acute bacterial sinusitis conforms
to 1 of 3 predicable patterns; persistent, severe, and
worsening symptoms.
• On the basis of some research evidence and consensus,
the diagnosis of sinusitis should be made by applying
strict clinical criteria. This approach will select
children with upper respiratory infection symptoms
who are most likely to benefit from an antibiotic.
• On the basis of some research evidence and consensus,
imaging is not indicated routinely in the diagnosis of
sinusitis. Computed tomography or magnetic
resonance imaging provides useful information when
complications of sinusitis are suspected.
• On the basis of some research evidence and consensus,
amoxicillin-clavulanate should be considered as
a first-line agent for the treatment of sinusitis.
References
1. Anand VK. Epidemiology and economic impact of rhinosinusi-
tis. Ann Otol Rhinol Laryngol Suppl. 2004;193:3–5
Parent Resources From the AAP at HealthyChildren.org
• English only: http://www.healthychildren.org/English/health-issues/conditions/ear-nose-throat/Pages/The-Difference-Between-
Sinusitis-and-a-Cold.aspx
• English: http://www.healthychildren.org/English/news/Pages/AAP-Issues-Guideline-on-Treating-Acute-Bacterial-Sinusitis-in-
Children.aspx
• Spanish: http://www.healthychildren.org/spanish/news/paginas/aap-issues-guideline-on-treating-acute-bacterial-sinusitis-in-
children.aspx
436 Pediatrics in Review Vol.34 No.10 October 2013
2. Wald ER, Milmoe GJ, Bowen A, Ledesma-Medina J, Salamon
N, Bluestone CD. Acute maxillary sinusitis in children. N Engl J
Med. 1981;304(13):749–754
3. Wald ER, Reilly JS, Casselbrant M, et al. Treatment of acute
maxillary sinusitis in childhood: a comparative study of amoxicillin
and cefaclor. J Pediatr. 1984;104(2):297–302
4. Hsin CH, Tsao CH, Su MC, Chou MC, Liu CM. Comparison
of maxillary sinus puncture with endoscopic middle meatal culture
in pediatric rhinosinusitis. Am J Rhinol. 2008;22(3):280–284
5. Block SL, Hedrick J, Harrison CJ, et al. Community-wide
vaccination with the heptavalent pneumococcal conjugate signifi-
cantly alters the microbiology of acute otitis media. Pediatr Infect
Dis J. 2004;23(9):829–833
6 Pichichero M, Casey J, Center K, et al. Efficacy of PCV13 in
prevention of AOM and NP colonization in children: first year of data
from the US. Paper presented at the Eighth International Symposium
of Pneumococci and Pneumococcal Diseases; Iguacu Falls, Brazil; 2012
7. Casey JR, Adlowitz DG, Pichichero ME. New patterns in the
otopathogens causing acute otitis media six to eight years after
introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis
J. 2010;29(4):304–309
8. Payne SC, Benninger MS. Staphylococcus aureus is a major path-
ogen in acute bacterial rhinosinusitis: a meta-analysis. Clin Infect Dis.
2007;45(10):e121–e127
9. Wald ER. Staphylococcus aureus: is it a pathogen of acute bacterial
sinusitis in children and adults? Clin Infect Dis. 2012;54(6):826–831
10. Wald ER, Nash D, Eickhoff J. Effectiveness of amoxicillin/
clavulanate potassium in the treatment of acute bacterial sinusitis in
children. Pediatrics. 2009;124(1):9–15
11. Gwaltney JM Jr, Phillips CD, Miller RD, Riker DK. Computed
tomographic study of the common cold. N Engl J Med. 1994;330(1):25–30
12. Kovatch AL, Wald ER, Ledesma-Medina J, Chiponis DM,
Bedingfield B. Maxillary sinus radiographs in children with non-
respiratory complaints. Pediatrics. 1984;73(3):306–308
13. Garbutt JM, Goldstein M, Gellman E, Shannon W, Littenberg
B. A randomized, placebo-controlled trial of antimicrobial treat-
ment for children with clinically diagnosed acute sinusitis. Pediat-
rics. 2001;107(4):619–625
14. Kristo A, Uhari M, Luotonen J, Ilkko E, Koivunen P, Alho OP.
Cefuroxime axetil versus placebo for children with acute respiratory
infection and imaging evidence of sinusitis: a randomized, controlled
trial. Acta Paediatr. 2005;94(9):1208–1213
15. Wald ER, Chiponis D, Ledesma-Medina J. Comparative
effectiveness of amoxicillin and amoxicillin-clavulanate potassium
in acute paranasal sinus infections in children: a double-blind,
placebo-controlled trial. Pediatrics. 1986;77(6):795–800
16. Bradley JS, Jackson MA; Committee on Infectious Diseases;
American Academy of Pediatrics. The use of systemic and topical
fluoroquinolones. Pediatrics. 2011;128(4):e1034–e1045
 infectious diseases acute bacterial sinusitis

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1. Which of the following mechanisms can potentially lead to bacterial sinusitis?

A. Dysfunction of mucociliary apparatus.
B. Increase in bacterial load in the nasal mucosa.
C. Increase in positive sinus pressure relative to the atmosphere.
D. Prolonged fever during upper respiratory tract infection.
E. Thinning of sinus secretions.

2. A 5-year-old boy comes to the office with 3 days of a low-grade fever (maximum temperature, 38.3 C),
a cough that is described as wet, clear rhinorrhea, and decreased oral intake. The child has not had a headache
˚
or facial pain, and his urine output has been adequate. The next step in management is:
A. Amoxicillin-clavulanate (50 mg/kg/d).
B. Close observation and follow-up.
C. Maxillary sinus aspiration by an otolaryngologist.
D. Obtain a nasopharyngeal swab for bacterial culture.
E. Plain radiographs of the sinuses.

3. Since the introduction of the 7-valent pneumococcal conjugate vaccine, the most common organism isolated
in bacterial sinusitis is:
A. Anaerobic bacteria.
B. Haemophilus influenzae.
C. Moraxella catarrhalis.
D. Streptococcus pneumoniae.
E. Streptococcus pyogenes.

4. A 15-year-old girl comes to see you with acute onset of fever, facial pain, headache, and purulent nasal
discharge. You diagnose her with bacterial sinusitis. Which of the following antibiotics should be prescribed at
this time?
A. Amoxicillin (40-50 mg/kg/d).
B. Amoxicillin-clavulanate (90 mg/kg/d).
C. Clindamycin (30-40 mg/kg/d).
D. Cephalexin (40 mg/kg/d).
E. Ciprofloxacin (30 mg/kg/d).

5. The most common complication seen in children who have bacterial sinusitis is:
A. Brain abscess.
B. Meningitis.
C. Orbital cellulitis.
D. Osteomyelitis of maxillary bone.
E. Venous sinus thrombosis.

Pediatrics in Review Vol.34 No.10 October 2013 437

Article infectious diseases

Pneumonia
Rani S. Gereige, MD, MPH,*
Practice Gap
Pablo Marcelo Laufer, MD†
The epidemiology of pneumonia is changing; chest radiographs and routine laboratory
testing are unnecessary for routine diagnosis of community-acquired pneumonia in chil-
Author Disclosure dren who are candidates for outpatient treatment.
Drs Gereige and Laufer
have disclosed no Objectives The readers of this article are expected to:
financial relationships
1. Know the cause, clinical manifestations, differential diagnosis, and general approach
relevant to this article.
to the diagnosis, treatment, and prevention strategies of the different types of
This commentary does
pneumonia in children of various age groups.
not contain discussion
2. Be aware of the challenges that face the clinician in making an accurate diagnosis of
of unapproved/
pneumonia due to the inaccuracies and shortcomings of the various laboratory and
investigative use of
imaging studies.
a commercial product/
3. Know the complications of pneumonia in children and their appropriate diagnostic
device.
and therapeutic strategies.

Introduction
Pneumonia is commonly encountered by emergency department and primary care clini-
cians. Childhood pneumonia remains a significant cause of morbidity and mortality in de-
veloping countries, whereas mortality rates in the developed world have decreased
secondary to new vaccines, antimicrobials, and advances in diagnostic and monitoring tech-
niques. (1) This review focuses on pneumonia in children: its causes in various age groups,
clinical manifestations, indications for hospitalization, and the challenges that clinicians face
in making an accurate diagnosis despite the new and emerging diagnostic tests.

Epidemiology
The incidence of pneumonia varies by age groups and between
developing and developed countries. Worldwide, the overall
Abbreviations annual incidence of pneumonia in children younger than 5
BAL: bronchoalveolar lavage years is 150 million to 156 million cases, (2)(3) leading to
CAP: community-acquired pneumonia an estimated 2 million deaths per year, most of which occur
CA-MRSA: community-associated methicillin-resistant in developing countries. (4) Forty percent of cases require hos-
Staphylococcus aureus pitalization. (5) In developed countries, the annual incidence of
ELISA: enzyme-linked immunosorbent assay pneumonia is estimated at 33 per 10,000 in children younger
HIV: human immunodeficiency virus than 5 years and 14.5 per 10,000 in children ages 0 to 16 years.
hMPV: human metapneumovirus In the United States, pneumonia is estimated to occur in 2.6%
IGRA: interferon gamma release assay of children younger than 17 years. Fortunately, the mortality
LRTI: lower respiratory tract infection rate in developed countries is less than 1 per 1000 per year. (3)
MRSA: methicillin-resistant Staphylococcus aureus According to the World Health Organization (WHO),
MSSA: methicillin-sensitive Staphylococcus aureus pneumonia is the single largest cause of death in children
PCR: polymerase chain reaction worldwide, leading to an annual death of an estimated 1.2 mil-
RSV: respiratory syncytial virus lion children younger than 5 years. This accounts for 18% of all
VATS: video-assisted thoracoscopic surgery deaths of children younger than 5 years worldwide. (6)
WHO: World Health Organization Cases of pneumonia occur throughout the year; however,
the incidence is increased during the colder months in

*Editorial Board. Department of Medical Education, Miami Children’s Hospital, Miami, FL.
†
Division of Pediatric Infectious Diseases, Miami Children’s Hospital, Miami, FL.

438 Pediatrics in Review Vol.34 No.10 October 2013


temperate climates for unknown reasons. It is presumed
that person-to-person transmission of respiratory drop-
lets enhanced by indoor crowding, impaired mucociliary
clearance, and the peak of viral infections that led to viral
pneumonias with secondary bacterial pneumonias are the
cause of this peak. In tropical climates, peaks of respira-
tory infections are seen sporadically throughout the year.
(4) Table 1 highlights the risk factors of pneumonia in
neonates and older children and teens.
Definitions
Before further discussion of this topic, it is important to dis-
cuss the definitions of the various terms related to pneumonia.
Pneumonia
Pneumonia still remains a condition that is challenging to
accurately diagnose. Therefore, no single definition that
accurately describes childhood pneumonia currently ex-
ists. Pneumonia is defined as a lower respiratory tract in-
fection (LRTI) typically associated with fever, respiratory
symptoms, and evidence of parenchymal involvement by
either physical examination or the presence of infiltrates
on chest radiography. Pathologically, it represents an
Table 1. Risk Factors of Pneumonia (4)(29)(30)
Risk factor for pneumonia in children
• Sex: M:F [ 1.25:1–2:1
• Socioeconomic/environmental factors:
B Lower socioeconomic status (family size, crowding)
B Low maternal educational level
B Poor access to care
B Indoor air pollution
B Malnutrition
B Lack of breastfeeding
B Cigarette smoke (active and passive smoke exposure)
B Alcohol, drugs, and cigarettes use (increased risk of
aspiration) in teens
• Underlying cardiopulmonary disorders and medical
conditions:
B Congenital heart disease
B Bronchopulmonary dysplasia and chronic lung disease
B Diabetes mellitus
B Cystic fibrosis
B Asthma
B Sickle cell disease
B Neuromuscular disorders (especially those associated
with altered mental status)
B Some gastrointestinal disorders (eg, gastroesophageal
reflux, tracheoesophageal fistula)
B Congenital and acquired immunodeficiency disorders
infectious diseases pneumonia
inflammatory process of the lungs, including airways, al-
veoli, connective tissue, visceral pleura, and vascular
structures. Radiologically, pneumonia is defined as an in-
filtrate on chest radiograph in a child with symptoms of
an acute respiratory illness. (1)(7)
Walking Pneumonia
Walking pneumonia is a term typically used in school-aged
children and young adults with clinical and radiographic ev-
idence of pneumonia but with mild symptoms in which the
respiratory symptoms do not interfere with normal activity.
Typically, Mycoplasma pneumoniae has been implicated as
the organism presumably responsible for walking pneumonia.
Community-Acquired Pneumonia
Community-acquired pneumonia (CAP) refers to an acute
pulmonary infection in a previously healthy individual ac-
quired in the community (as opposed to hospital-acquired
or nosocomial pneumonia)(8)
Hospital-Acquired Pneumonia
A pneumonia that develops in a hospitalized child within
48 hours after admission is considered hospital-associated
Risk factor for pneumonia in neonates
Early-onset
• Prolonged rupture of the fetal membranes (>18 hours)
• Maternal amnionitis
• Premature delivery
• Fetal tachycardia
• Maternal intrapartum fever
Late-onset
• Assisted ventilation (4 times higher in intubated than
in nonintubated)
• Anomalies of the airway (eg, choanal atresia,
tracheoesophageal fistula, and cystic adenomatoid
malformations)
• Severe underlying disease
• Prolonged hospitalization
• Neurologic impairment resulting in aspiration of
gastrointestinal contents
• Nosocomial infections due to poor hand washing or
overcrowding
Pediatrics in Review Vol.34 No.10 October 2013 439
infectious diseases pneumonia
pneumonia. (9) Pneumonia that affects those individuals
living in chronic care facilities and those who were re-
cently hospitalized fall in this category as well.
Etiology
A large number of microorganisms cause pneumonia,
ranging from viruses to bacteria and fungi (Table 2).
The etiologic agents of pneumonia depend on the pa-
tient’s age. In neonates (0-3 months of age), maternal
flora, such as group B streptococcus and gram-negative bac-
teria, are common causes that are vertically transmitted.
Overall, Streptococcus pneumoniae remains the most com-
mon bacterial cause of pneumonia in children older than 1
week, whereas viruses account for 14% to 35% of cases. (7)
(10) In children ages 3 months to 5 years, 50% to 60% of
cases are associated with viral respiratory infections. (11) In
school-aged children (>5 years), atypical organisms, such
as M pneumoniae and Chlamydophila (previously known
as Chlamydia) pneumoniae, are more common. (12)
Mycoplasma pneumoniae remains the leading cause of
pneumonia in school-age children and young adults.
New vaccines and emerging antibiotic resistance led to
a change in the pathogens implicated in pneumonia. The
first vaccine that affected the epidemiology of pneumonia
in the United States was the conjugated Haemophilus in-
fluenzae type b vaccine (1990). It drastically reduced in-
vasive disease by this organism. In 2000, the
pneumococcal conjugated 7-valent vaccine not only de-
creased the rates of invasive disease significantly (98.7
cases per 10,000 in 1998–1999 vs 23.4 cases per
10,000 in 2005) but also decreased the incidence of
pneumonia that required hospitalization and ambulatory
visits in children younger than 2 years. (10)(12)(13) The
rates for children ages 1 to 18 years, however, remained
stable. Conjugated vaccines reduce nasopharyngeal colo-
nization. This effect benefited nonimmunized adults
older than 65 years through herd immunity. As expected,
the pneumococcal conjugated 7-valent vaccine led to
a shift of the most common serotypes that cause disease
in children, and the 13-valent pneumococcal conjugate
vaccine introduced in 2010 provides additional coverage
against common pneumococcal serotypes 1, 3, 5, 6A, 7F,
and 19A, further decreasing the incidence of pneumonia
that requires hospitalization. (10)(12)(13)
Community-associated methicillin-resistant Staphylococcus
aureus (CA-MRSA) should be considered in cases of
complicated pneumonia with empyema and necrosis.
The latter can be severe when associated with influenza
infection. In the last few years, clinicians have encoun-
tered severe secondary bacterial infections after influenza
440 Pediatrics in Review Vol.34 No.10 October 2013
infection. This mechanism is still not clear, but animal
models suggest that influenza A enhances transmission
of bacteria such as S aureus. (13)
New viruses emerged in the past few years. The hu-
man metapneumovirus (hMPV) was described in 2001.
Often considered to be a pathogen associated with bron-
chiolitis, it is described in association with pneumonia.
Children younger than 5 years are susceptible to hMPV
infection, and infants younger than 2 years with primary
infection are particularly at risk of severe infection.
Seroepidemiologic studies indicate that virtually all chil-
dren are infected with hMPV by 5 to 10 years of age.
In one series, hMPV was isolated in 8.3% (second only
to respiratory syncytial virus [RSV]) of cases of radio-
logically diagnosed CAP. Children with hMPV were
older than those with RSV (mean age of 19 vs 9 months)
and had a higher incidence of gastrointestinal symptoms
and wheeze. Indicators of severity (such as saturations
on admission, respiratory rate, and duration of stay) were
no different in hMPV compared with other viruses. (13)
(14)
The human bocavirus is in the parvovirus family. Al-
though it has not been cultured yet, it can be identified
by electron microscopy. Initially, its role in pneumonia
was unclear. Preliminary evidence suggests that nearly
all children have produced antibodies to human bocavirus
by school age, and most newborns receive antibodies from
their mothers. (13)(14)
Clinical Manifestations
Pneumonia in children is a challenging diagnosis because
the presenting signs and symptoms are nonspecific, might
be subtle (particularly in infants and young children), and
vary, depending on the patient’s age, responsible patho-
gen, and severity of the infection. (1)(4)(7)(13)
In all age groups, fever and cough are the hallmark of
pneumonia. (4) Other findings, such as tachypnea, in-
creased work of breathing (eg, nasal flaring in infants),
and hypoxia, may precede the cough. The WHO uses ta-
chypnea and retractions to effectively diagnose pneumo-
nia in children younger than 5 years but tachypnea
becomes less sensitive and specific as age increases (in
children >5 years). (4) Most of the clinical signs and
symptoms have a low sensitivity and specificity except
for cough, crackles (rales), retractions, rhonchi, and nasal
flaring (in young infants), which are highly specific but
not sensitive, meaning that their absence might help rule
out the disease. (1) The rate of diagnosed pneumonia in
patients with fever but no cough or tachypnea is 0.28%.
Upper lobe pneumonias may present with a clinical pic-
ture suggestive of meningitis due to radiating neck pain.
 Table 2. Cause by Age Groups
Pathogens Neonates
Viruses Herpes simplex virus
Enteroviruses
Adenovirus
Mumps
Congenital rubella
Cytomegalovirus
Bacteria Group B streptococci
Gram-negative enteric
bacteria
Ureaplasma urealyticum
Listeria monocytogenes
Chlamydia trachomatis
Streptococcus pneumonia
Group D Streptococcus
Anaerobes
Fungi Candida species
• Rate of colonization of
gastrointestinal and
respiratory tract of very
low-birth-weight infants
is 25% (during labor and
delivery)
• Pneumonia in 70% of
infants with systemic
candidiasis
Other Congenital toxoplasmosis
Syphilis
• Early-onset pneumonia
Pediatrics in Review Vol.34 No.10 October 2013 441
(7)(21)(30)
Infants
Cytomegalovirus (CMV)**
Respiratory syncytial virus
Parainfluenza
Influenza
Adenovirus
Metapneumovirus
Streptococcus pneumoniae
Haemophilus influenzae
Mycoplasma pneumoniae
Mycobacterium tuberculosis
Chlamydia trachomatis**
Mycoplasma hominis**
Ureaplasma urealyticum**
Bordetella pertussis
Children <5 years
Respiratory syncytial virus
Influenza A and B
Parainfluenza viruses,
usually type 3
Adenovirus serotypes
(1, 2, 3, 4, 5, 7, 14, 21,
and 35)
Human metapneumovirus
Rhinovirus
Coronaviruses (including
the severe acute
respiratory syndrome
virus and the New Haven
coronavirus)
Human bocavirus
Human parechovirus types
1, 2, and 3
Streptococcus pneumoniae
H influenzae type b
Nontypable H influenzae
Moraxella catarrhalis
Staphylococcus aureus
(including CA-MRSA)
Streptococcus pyogenes
Mycobacterium tuberculosis
Children > 5 years
• Respiratory viruses
• Rare causes of
pneumonia:
B Coronavirus
B Varicella-zoster
B Epstein-Barr virus
B Mumps
Streptococcus pneumoniae
Mycoplasma pneumoniae
Chlamydia pneumoniae
Mycobacterium tuberculosis
Chlamydia psittaci
Coxiella burnetti
Klebsiella pneumoniae
Legionella
Streptococcus pyogenes
Brucella abortus
Coccidioides immitis
Histoplasma capsulatum
Blastomyces dermatitidis
infectious diseases
Continued
pneumonia
infectious diseases pneumonia

Lower lobe pneumonias may present as vague abdominal

pain mimicking appendicitis.
In neonates, pneumonia can occur as early or late on-
set. (1) Early-onset pneumonia typically presents in the
Children > 5 years

first 3 days of life. The infection is acquired from the

mother either hematogenously through the placenta or
through aspiration of infected amniotic fluid in utero
or during or after birth. It commonly presents with respi-
ratory distress beginning at or soon after birth. Newborns
may also present with nonspecific symptoms, such as leth-
argy, apnea, tachycardia, and poor perfusion, occasionally
progressing to septic shock or pulmonary hypertension.
Causes pneumonia complicated

Other signs include temperature instability, metabolic aci-

associated with severe and

by necrosis and empyema.

influenza and chickenpox

Frequently are seen after

dosis, and abdominal distension. (2) Late-onset pneumonia

Adenovirus serotypes 3, 7,

complicated pneumonia

occurs after birth during hospitalization or after discharge

and 21 have been

and is either nosocomial acquired or due to colonization

Children <5 years

or contaminated equipment. Late-onset pneumonia typi-

cally presents with nonspecific signs of apnea, tachypnea,
poor feeding, abdominal distention, jaundice, emesis, respi-
ratory distress, and circulatory collapse. Ventilator-dependent
infants may have increased oxygen and ventilator require-
ments and/or purulent tracheal secretions.
It is virtually impossible to clinically differentiate bac-
terial from viral pneumonia except that bacterial pneu-
monia might have a more abrupt and severe onset after
• With or without conjunctivitis
3-4 months. Symptoms include:

days of symptoms of an upper respiratory tract infection.

seen between age 2 weeks to

• Diffuse inspiratory crackles

The patient may be ill appearing and sometimes experi-

rhinorrhea and tachypnea

ence toxic effects, with moderate to severe respiratory dis-

pneumonia of infancy”

tress and localized chest pain. Finally, complications are

• Insidious onset of

more likely to occur in bacterial pneumonia. (13)

**Causes of “afebrile

• Staccato cough

Pneumococcal pneumonia is typically a lobar pneu-

monia that presents with fever, nonproductive cough, ta-
CA-MRSA¼community-acquired methicillin-resistant Staphylococcus aureus.

chypnea, and decreased breath sounds over the affected

lobe. (10)(12)
Infants

Atypical bacterial pneumonia caused by M pneumoniae

or C pneumoniae usually presents with abrupt onset of
fever, malaise, myalgia, headache, photophobia, sore
throat, and gradually worsening prolonged nonproductive
agent to cause early-

cough. Atypical bacterial pneumonia may be difficult to

disseminated herpes
B From the mother at
B Most common viral

simplex virus fatal

• Herpes simplex virus

despite treatment
onset pneumonia

differentiate from viral pneumonia. Hoarseness is more fre-

quently seen with C pneumoniae infection compared with
B 33%-55% of
time of birth

a viral origin. Wheezing in a child older than 5 years might

be associated with atypical bacterial (Mycoplasma or Chla-
Neonates

mydia) and viral pneumonias and is unlikely to be due to

(Continued)

other bacterial causes. (13) Mycoplasma pneumoniae may

be asymptomatic or may present with minimal physical ex-
amination findings. In one review, 75% to 100% of patients
Comments
Pathogens

with M pneumoniae infection have an intractable, nonpro-

ductive cough, whereas only 3% to 10% developed pneu-
Table 2.

monia. M pneumoniae is self-limited. A Cochran review

found that there is still insufficient evidence that antibiotics

442 Pediatrics in Review Vol.34 No.10 October 2013


are effective against LRTI caused by Mycoplasma in chil-
dren. (15) Mycoplasma pneumoniae may be also associated
with a variety of extrapulmonary manifestations (Table 3).
Chlamydia pneumoniae is indistinguishable from pneu-
monia caused by other factors. Extrapulmonary manifes-
tations of C pneumoniae infections may include the
following:
• Meningoencephalitis
• Guillain-Barré syndrome
• Reactive arthritis
• Myocarditis
Viral pneumonia has a gradual insidious onset. The pa-
tient usually experiences nontoxic effects, with upper re-
spiratory tract symptoms, and auscultatory findings are
more likely to be diffuse. Wheezing is more frequent in
viral than bacterial pneumonia.
General Approach
History and Physical Examination
The approach to the child with suspected pneumonia be-
gins with a detailed history and careful physical examination.
History is more likely to reveal fever, with associated respi-
ratory symptoms, including cough and tachypnea. On phys-
ical examination, the clinician must pay special attention to
the general appearance of the patient and assess for hypoxia
Clinical Manifestations of
Table 3.
Mycoplasma pneumoniae
Infections (7)
Respiratory tract disease
• Intractable nonproductive to mild cough (75%-100%)
• Pneumonia (3%-10%)
• Chills
• With or without wheezing and dyspnea
• Pharyngitis (6%-59%)
• Rhinorrhea (2%-40%)
• Ear pain (2%-35%)
• Severe earache secondary to bullous myringitis (5%)
• Sinusitis
Extrapulmonary disease
• Hemolytic anemia
• Rash (erythematous maculopapular rash, urticaria,
Stevens-Johnson syndrome)
• Joint involvement (polyarthritis)
• Gastrointestinal (pancreatitis, hepatitis)
• Central nervous system
• Cardiac disease (pericarditis, myocarditis)
infectious diseases pneumonia
and cyanosis. Young infants may present with lethargy, poor
feeding, or irritability. Although the presence of fever is not
specific for pneumonia, it may be the only sign in occult
pneumonia. In a systematic review, tachypnea was twice
as frequent in children with vs without radiographic pneu-
monia, and its absence was the most valuable sign for ruling
out the diagnosis, making it the most sensitive sign. Other
signs of respiratory distress include increased work of
breathing (intercostal, subcostal, or suprasternal retractions;
nasal flaring; grunting, head bobbing; use of accessory
muscles), apnea, and altered mental status. Signs of respira-
tory distress are more specific than fever or cough for LRTI
but not as sensitive.
Lung examination is a key part of the assessment. Aus-
cultation of all lung fields should be performed, listening
for crackles (rales) or crepitations, the presence of which
correlates with pneumonia. The absence of these findings
does not rule out pneumonia. Other findings consistent
with consolidated lung parenchyma might include de-
creased breath sounds, egophony, bronchophony, tactile
fremitus, or dullness to percussion. Again, wheezing is
more likely in viral or atypical pneumonia, but when
wheezing is only heard unilaterally and is associated with
fever, bronchial obstruction (intrinsic or extrinsic) and
associated bacterial infection should be suspected.
Splinting, dullness to percussion, distant breath sounds,
and friction rub are suggestive of pleural effusion and
must be confirmed by imaging. It is important to men-
tion that many patients clinically suspected of having
pneumonia are treated empirically with no need for im-
aging or laboratory workup except for severely ill chil-
dren with hypoxia, respiratory distress, and inability to
eat or drink.
Diagnostic Testing and Evaluation
RADIOGRAPHIC IMAGING. In a child with mild lower
respiratory symptoms consistent with CAP who is a can-
didate for outpatient treatment, chest radiographs are not
routinely needed to make the diagnosis. (7)(8)(16) The
presence of infiltrates on chest radiograph in a child with
fever and respiratory distress confirms the diagnosis of
pneumonia; however, the absence of chest x-ray findings
does not rule out pneumonia if there is high clinical sus-
picion. This is due to several factors: the radiographic
findings may lag behind the clinical picture, dehydrated
children may not have an infiltrate initially, and it is im-
possible to differentiate atelectasis from pneumonia on
a single chest radiograph (an infiltrate that resolves in less
than 48-72 hours is more likely atelectasis than pneumonia).
An initial chest radiograph may be indicated in the fol-
lowing situations (16):
Pediatrics in Review Vol.34 No.10 October 2013 443
infectious diseases pneumonia
1. Severe disease, hypoxemia, or significant respiratory
distress that requires hospitalization.
2. Inconclusive clinical findings.
3. To rule out other causes of respiratory distress (eg,
foreign body, heart disease, underlying cardiopulmo-
nary conditions).
4. Prolonged fever and worsening symptoms despite ad-
equate antibiotic coverage to rule out complications
(parapneumonic effusion, pneumothorax).
5. As part of the workup of a young infant with fever
without a source and leukocytosis.
Follow-up chest radiographs are not routinely indi-
cated in children who are adequately treated and recov-
ered. Follow-up radiographs are indicated in complicated
pneumonias that are clinically unstable, in patients receiv-
ing adequate antibiotic coverage for 48 to 72 hours with
poor clinical improvement or worsening, and in recurrent
pneumonias that involve the same lobe to rule out a sus-
pected anomaly, chest mass, or foreign body. Children
with complicated pneumonia treated with chest tube
placement or video-assisted thoracoscopic surgery (VATS)
do not require routine daily chest radiography if they are
clinically stable and improving.
When indicated, chest radiographs should be obtained
in the posteroanterior upright position in children younger
than 4 years and in the supine anteroposterior position in
younger children. A lateral view is preferred, and a lateral
decubitus view (with affected side down) should be ob-
tained when a pleural effusion is suspected.
Bedside ultrasonography of the chest was studied and
compared with chest radiographs. In one prospective cohort
study of 200 patients, ultrasonography had an overall sensi-
tivity of 86% (95% CI, 71%-94%) and a specificity of 89%
(95% CI, 83%-93%). Specificity increased to 97% in children
with consolidation greater than 1 cm by chest radiographs.
The authors concluded that bedside ultrasonography was
found to be a highly specific, noninvasive, radiation-free test
that can be used by clinicians to diagnose pneumonia. (17)
Laboratory Testing
Routine laboratory testing is not indicated to diagnose pneu-
monia, particularly in children who are stable, are nonhy-
poxic, and have suspected CAP and are candidates for
outpatient treatment. Patients with hypoxemia, severe respi-
ratory distress, possible complicated pneumonia, or associ-
ated comorbid conditions may need further workup.
Blood Tests
A complete blood cell count with differential does not
allow differentiation among bacterial, atypical, or viral
444 Pediatrics in Review Vol.34 No.10 October 2013
origins or dictate management, particularly in the out-
patient setting. (7)(8) A complete blood cell count with
differential is typically performed in children who are
candidates for hospitalization (Table 4). Peripheral eo-
sinophilia suggests Chlamydia trachomatis in infants
with afebrile pneumonia of infancy. Acute phase reac-
tants, such as erythrocyte sedimentation rate, C-reactive
protein, and serum procalcitonin, should not be routinely
measured in fully immunized children with mild disease
but may be useful in monitoring response to treatment
in children hospitalized with severe or complicated pneu-
monia. (11)(16) Other blood tests might include serum
electrolytes to assess for degree of dehydration and to rule
out hyponatremia secondary to syndrome of inappropriate
antidiuretic hormone secretion.
Microbiologic Tests
BLOOD CULTURES
• Not routinely indicated in the outpatient setting in
children who have nontoxic effects and fully immu-
nized due to low yield (only positive in 10%-12% of
children). (8)
• In patients with parapneumonic effusion or empyema
the yield increases to 30% to 40%.
• Should be obtained in children hospitalized with se-
vere disease, who fail to demonstrate response despite
adequate antibiotic coverage, or in children with com-
plicated pneumonia. (16)
• Follow-up blood cultures are not necessary in patients
with clear improvement.
NASOPHARYNGEAL SAMPLES. Nasopharyngeal cul-
tures do not provide useful information because the bac-
teria recovered are usually normal upper respiratory tract
flora and do not necessarily correlate with the cause of
pneumonia. Polymerase chain reaction (PCR) is now
available for the detection of several pathogens in naso-
pharyngeal samples as discussed below. The identification
of bacteria by PCR in nasopharyngeal samples is not as
useful for the same reason expressed above.
SPUTUM CULTURES
• Difficult to obtain and induce in young children (<5
years) and in outpatient setting.
• Should be obtained in older hospitalized children,
children who are in intensive care, those who have
complicated pneumonia, or those who do not respond
to empiric therapy; good-quality sputum samples can be
obtained.
• An adequate sputum specimen for examination is one
with:

Indications for
Table 4.
Hospitalization (8)(16)
• Hypoxia (oxygen saturations <90%-92%)
• Infants <3-6 months with suspected bacterial
infection (unless a viral cause or Chlamydia
trachomatis is suspected and they are normoxemic and
relatively asymptomatic)
• Tachypnea:
B Infants <12 months of age: respiratory rate >70
breaths/min
B Children: respiratory rate >50 breaths/min
• Respiratory distress: apnea, grunting, difficulty
breathing, and poor feeding
• Signs of dehydration
• Inability to maintain hydration or oral intake
• Capillary refill time >2 seconds
• Infants and children with toxic appearance or
suspected or confirmed to have infection with
a virulent organism (CA-MRSA or group A
Streptococcus)
• Underlying conditions comorbidities that:
B May predispose patients to a more serious course
(eg, cardiopulmonary disease, genetic syndromes,
neurocognitive disorders)
B May be worsened by pneumonia (eg, metabolic
disorder)
B May adversely affect response to treatment (eg,
immunocompromised host, sickle cell disease)
• Complications (eg, effusion/empyema)
• Failure of outpatient therapy (48-72 hours with no
response)
• Caretaker unable to provide appropriate observation or
to comply with prescribed home therapy
Indications for intensive care admission include:
• Severe respiratory distress or impending respiratory
failure requiring
B Intubation and mechanical ventilation
B Positive pressure ventilation
• Recurrent apnea or slow irregular respirations
• Cardiopulmonary monitoring due to cardiovascular
compromise secondary to:
B Sustained tachycardia
B Inadequate blood pressure
B Requires pharmacologic support of blood pressure or
perfusion
B Altered mental status due to hypercarbia or hypoxemia
• Pediatric Early Warning Score >6
CA-MRSA¼community-acquired methicillin-resistant Staphylococcus
aureus.
B 10 or fewer epithelial cells
B And 25 or more polymorphonuclear leukocytes
under low power (100).
B A predominant microorganism and/or intracellu-
lar organisms suggest the etiologic agent.
infectious diseases pneumonia
PLEURAL FLUID
• When pleural fluid is more than minimal in amount, it
should be obtained through a diagnostic (and possi-
bly therapeutic) thoracentesis and sent for Gram
stain and culture ideally before administration of
antibiotics.
• Because most children have already received antibiotics
by the time the pleural fluid is sampled, thereby signif-
icantly reducing the yield of conventional cultures, an-
tigen testing and PCR may be helpful in identifying the
causative agent.
• Studies such as pH, glucose, protein, and lactate
dehydrogenase rarely change management and are
not recommended, except for white blood cell
count with differential to differentiate bacterial
from mycobacterial causes and from malignancy.
(16) Table 5 highlights the laboratory findings in
empyema.
Rapid Tests
Nasopharyngeal swab specimen for rapid testing by PCR
or immunofluorescence may be useful. (8) A positive
rapid test result for viruses in inpatient and outpatient set-
tings might decrease the need for further testing or for
starting antibiotic therapy; it may also give the opportu-
nity for starting antiviral therapy early. (16) Rapid tests
exist for the following microorganisms:
• RSV
• Influenza viruses
• Parainfluenza viruses
• Adenovirus
• Mycoplasma pneumoniae
• Chlamydophila pneumonia
• Coronaviruses
• Bordetella pertussis
• Picornavirus (rhinovirus and enterovirus)
• hMPV (can only be identified by PCR)
The PCR tests for pneumococcus in sputum and
blood are not recommended because their sensitivity
and specificity in children have not been conclusively
established.
Antigen Detection and Serologic Testing
Urinary antigen detection tests have low sensitivity and
high false-positive rates. (8)(16) Hence, they are not rec-
ommended for the diagnosis of pneumococcal pneumo-
nia in children. (16)
Pleural fluid antigen detection: In children with para-
pneumonic effusion or empyema whose pleural fluid
Pediatrics in Review Vol.34 No.10 October 2013 445
infectious diseases pneumonia
Laboratory Findings in
Table 5.
Empyema (2)(4)(16)
Studies Empyema
pH <7.1
Glucose <40 mg/dL
Lactate dehydrogenase >1000 IU/mL
Gram stain and culture with or Bacteria
without polymerase chain reaction
Gross appearance Purulent
culture was obtained after antibiotic therapy, a positive
pneumococcal antigen in the pleural fluid can be helpful
in confirming the cause.
Routine serologic testing for specific pathogens (eg,
S pneumoniae, M pneumoniae, C pneumoniae) is not in-
dicated because results do not usually influence manage-
ment. Viral serologic testing is not practical because acute
and convalescent specimens are needed. Serologic testing
for Chlamydophila species is not readily available.
Mycoplasma pneumoniae, when suspected in an older
child, is often treated empirically. However, serologic and
PCR testing can be helpful in evaluating the younger
child or in establishing the diagnosis in patients with ex-
trapulmonary (particularly central nervous system) man-
ifestations. The most widely used serodiagnostic test is
enzyme-linked immunosorbent assay (ELISA); however,
the complement fixation test has better specificity. It
measures early IgM (predominantly) and IgG antibodies
(to a lesser extent) to M pneumoniae. A positive result is
defined as follows:
• A 4-fold or greater increase in titer in paired sera OR
• A single titer of greater than or equal to 1:32
Antibody titers rise 7 to 9 days after infection and peak
at 3 to 4 weeks. A 4-fold decline in titer also is diagnostic
if late samples are obtained. The presence of antibodies
either by enzyme immunoassay or complement fixation
is highly sensitive for the detection of M pneumoniae
infection. A major disadvantage of these tests is their
false-positive results, particularly during inflammatory re-
actions, such as neurologic syndromes, bacterial meningitis,
and acute pancreatitis.
Less commonly used diagnostic tests are as follows:
1. Tuberculin skin testing or Quantiferon gold (children
>5 years old): If pulmonary tuberculosis is suspected,
either tuberculin skin testing (purified protein deriva-
tive) or interferon gamma release assays (IGRAs) can
be used. There are 2 available IGRAs:
446 Pediatrics in Review Vol.34 No.10 October 2013
a. Quantiferon Gold: Measures interferon gamma
produced by lymphocytes
b. ELISA spot: Measures the number of lymphocytes
producing interferon gamma both in response to
specific M tuberculosis antigens.
IGRAs measure response to antigens not present in
BCG or Mycobacterium avium; therefore, it has better
specificity than tuberculin skin testing, especially in
children who had received BCG vaccine in whom fre-
quent purified protein derivatives can cause a boosting
effect.
2. Urine antigen testing for legionellosis due to serogroup 1.
3. Serum and urine antigen testing for histoplasmosis.
4. Histoplasmosis serologic testing (immunodiffusion
and complement fixation).
5. Cryptococcus antigen detection in serum.
6. The following tests can be used as part of the workup
of the immunocompromised patient with suspected
pneumonia:
a. b-D-Glucan levels: b-D-Glucan is part of the cell wall
of yeast and fungi and even Pneumocystis jirovecci
and can be elevated in fungal pneumonias. (18)
b. Galactomannan levels: Galactomannan is part of the
cell wall of molds, such as aspergillus. Antigen levels
in bronchoalveolar lavage (BAL) or serum are pos-
itive in suspected pneumonia due to aspergillus.
(19)
The clinician must be aware that certain antibiotics,
such as piperacillin-tazobactam or transfusion with blood
or blood-derived products such as intravenous immuno-
globulin, may induce false-positive test results. (20)
Invasive Studies
Invasive studies to establish the cause of pneumonia in
children are reserved for the critically ill child or the child
with significant comorbidity whose initial diagnostic
workup is inconclusive and in whom the risk of establish-
ing the diagnosis outweighs the risk of the invasive pro-
cedure. (16) Invasive studies are rarely needed. Invasive
studies include the following:
• Bronchoscopy with BAL - Quantitative culture techni-
ques differentiate true infection from upper airway
contamination.
• Morning gastric lavage through a nasogastric tube for
acid fast bacilli stain and culture is used in the diagnosis
of tuberculosis.
• The BAL technique for obtaining cultures in intubated
patients uses a catheter inside a catheter, avoiding

sampling the upper airway and directly obtaining cul-
tures from the alveoli. Because of the anatomy of the
lungs, samples are obtained from the right lower lobe.
• Computed tomography or ultrasonography-guided
percutaneous needle aspiration of the affected lung
tissue.
• Lung biopsy either by a thoracoscopic or thoracotomy
approach is rarely used in United States, but open bi-
opsy yields diagnostic information that may affect
medical management in up to 90% of patients. In
one study, open lung biopsy confirmed the infectious
cause in 10 of 33 patients, 8 of whom had a prior non-
diagnostic BAL. Lung biopsy is commonly used in im-
munocompromised patients.
Differential Diagnosis
When the clinician is faced with a child presenting with fe-
ver, tachypnea, cough, respiratory distress, and infiltrates
on chest radiograph, the diagnosis of pneumonia is highly
likely. (7) Other diagnoses, however, must be considered.
In a neonate with respiratory distress, congenital anatom-
ical cardiopulmonary anomalies must be ruled out, such as
tracheoesophageal fistula, congenital heart disease, and
sepsis. In infants and young children, foreign body aspira-
tion (even if no history of any witnessed aspiration), bron-
chiolitis, heart failure, sepsis, and metabolic acidosis may all
cause tachypnea. In these cases, a careful history and phys-
ical examination and a supportive imaging study can dis-
tinguish pneumonia from other conditions.
In adolescents and young adults, Lemierre syndrome
(jugular vein suppurative thrombophlebitis) must be
considered. Lemierre syndrome is typically caused by
Fusobacterium species that infect the carotid sheath and
spread to lungs and mediastinum.
Children who present with respiratory distress and
wheezing may have CAP; however, first-time wheezing
of asthma with or without bronchiolitis can be the true
diagnosis. A patient with asthma or bronchiolitis may
have a radiographic picture that is normal or has infiltrates
that could potentially be due to atelectasis.
Other entities that may mimic pneumonia on clinical
examination or on radiographs in children are listed in
Table 6
Treatment
Treatment of pneumonia varies between inpatient and
outpatient settings. In either setting, supportive care in-
cludes the use of antipyretics, suctioning, and hydration
when needed. Mucolytics and cough suppressants have
infectious diseases pneumonia
no role in the treatment of pneumonia. (21)(22) Zinc sup-
plementation has been studied and found to be an effective
adjunct to decreasing the incidence and prevalence of
pneumonia in children 2 to 59 months. (23)(24) In most
cases of CAP, the chances of having a specific etiologic di-
agnosis are low, leading the clinician to treat empirically.
The Figure gives highlights of the decision tree of the ap-
proach to the child with suspected pneumonia.
Outpatient Management
EMPIRIC THERAPY. Antimicrobial therapy is not rou-
tinely recommended in preschool children with pneumonia
(viruses are more common). (21) Because S pneumoniae
remains the most commonly implicated pathogen, amoxi-
cillin or amoxicillin-clavulanate remains the most appropri-
ate first-line antimicrobial agent used empirically for CAP in
fully immunized, healthy, young preschool children with
mild to moderate symptoms. (25) Clavulanate adds the
benefit of action against b-lactamase–producing organ-
isms (H influenza and Moraxella catarrhalis). S pneu-
moniae resistance to penicillin is due to a penicillin-
binding protein (PBP2x) that has decreased affinity
to b-lactams. Increasing the dose of amoxicillin (90-
100 mg/kg daily) may overcome this mechanism of re-
sistance and should be prescribed if the clinician suspects
resistance (eg, children in day care or siblings in day
care, history of frequent infections). Amoxicillin-clavu-
lanate is dispensed in 2 different amoxicillin-clavulanate
ratios: 7:1 and 14:1. The 14:1 ratio should be used when
high-dose amoxicillin is required to reduce the possibility
of antibiotic-associated diarrhea.
In school-aged children and teens with a clinical pic-
ture compatible with atypical CAP, coverage using a mac-
rolide (azithromycin or clarithromycin) should be
considered. A systematic review of studies in developing
countries found no significant difference in the treatment
failures or relapse rates between 3- and 5-day courses of
antibiotics in children ages 2 to 59 months with outpa-
tient management of CAP. (26)
In children with moderate to severe CAP suspected of
having influenza infection and because early antiviral
therapy provides the maximum benefit, treatment with
antiviral therapy should not be delayed until confirmation
of a positive influenza test result. It is also worth noting
that treatment after 48 hours of symptoms might still
provide clinical benefits in severe cases of influenza. (16)
Inpatient Management
Table 4 highlights the indications for hospitalizations and
intensive care admission.
Pediatrics in Review Vol.34 No.10 October 2013 447
infectious diseases pneumonia

EMPIRIC THERAPY. It is helpful for the clinician to be

Mimickers of Pneumonia
Table 6. familiar with the antibiograms of the local community
hospitals when deciding on empiric therapy. Fully immu-
in Children nized infants or school-aged children hospitalized with
Anatomical considerations
CAP must be empirically prescribed an antibiotic regi-
• Prominent thymus
men that provides coverage for S pneumoniae using am-
• Breast shadows picillin or penicillin G (if no significant local resistant
• Bronchogenic cyst strains in community data). Ampicillin-sulbactam
• Vascular ring provides additional coverage against H influenzae,
• Pulmonary sequestration M catarrhalis, or methicillin-sensitive S aureus (MSSA).
• Congenital lobar emphysema
• Atelectasis (due to a foreign body or mucous plug)
The currently available intravenous formulations of
ampicillin-sulbactam do not permit high-dose ampicillin
Aspiration of gastric contents secondary to (300-400 mg/kg daily) when pneumococci with high
• Gastroesophageal reflux
• Tracheoesophageal fistula
ampicillin mean inhibitory concentration is suspected.
• Cleft palate If this dose is desired, a combination of ampicillin-
• Neuromuscular disorders sulbactam at 300 mg/kg daily (dosing ampicillin at
Chronic pulmonary disorders 200 mg/kg daily) and regular ampicillin at 100 to 00
• Asthma mg/kg daily is a recommended regimen. The alternative
• Bronchiectasis is third-generation cephalosporin (ceftriaxone at 100 mg/kg
• Bronchopulmonary dysplasia daily or cefotaxime at 200 mg/kg daily) used in infants
• Cystic fibrosis and children who are not fully immunized, in regions with
• Pulmonary fibrosis
• a1-Antitrypsin deficiency
high rates of invasive penicillin-resistant pneumococcal
• Pulmonary hemosiderosis strains, and in infants and children with severe life-threatening
• Alveolar proteinosis infections and/or pneumonia complications, such as em-
• Desquamative interstitial pneumonitis pyema. In patients with suspected M pneumoniae or C
• Sarcoidosis pneumoniae, the addition of an oral or parenteral macro-
• Histiocytosis X
lide to empiric cephalosporin or b-lactam antibiotic
Drugs and chemicals should be considered. In hospitalized patients with other
• Nitrofurantoin comorbidities or clinical or radiographic findings sugges-
• Bleomycin
• Cytotoxic drugs
tive of S aureus, vancomycin, linezolid, or clindamycin
• Opiates should be added to the regimen (Table 7). (16) Ceftaro-
• Radiation therapy line, a fifth-generation cephalosporin, may provide an at-
• Smoke inhalation tractive alternative in those patients with complicated
• Lipoid pneumonia pneumonia. Ceftaroline does not yet have an indication
Vasculitis in pediatrics hence, data on dosing is limited. Ceftaroline
• Systemic lupus erythematosus is the first cephalosporin with proven efficacy against S au-
• Granulomatosis with polyangiitis (Wegener) reus expressing the penicillin-binding protein PBP2a and
• Juvenile idiopathic arthritis
pneumococci expressing PBP2x. Even though ceftaroline
Others is indicated for use, it has not been approved for treating
• Hypersensitivity pneumonitis lung infections due to MRSA, but it is indicated for MSSA.
• Neoplasm
• Pulmonary edema due to heart failure There is no evidence that chest physiotherapy plays a ben-
• Pulmonary infarction eficial role in the management of pneumonia or leads to
• Acute respiratory distress syndrome a decrease in the length of stay or a change in the outcome.
• Graft-vs-host disease (27)
• Poor inspiratory film Complicated pneumonia (eg, parapneumonic effusion,
• Near drowning
• Underpenetrated film
lung abscess) is an indication for hospitalization. The an-
tibiotic choice in these patients must provide a broader
Adapted from Barson WJ. Clinical Features and Diagnosis of
Community-Acquired Pneumonia in Children. UpToDateÒ. June 2012.
coverage for b-lactam resistant bacteria and CA-MRSA.
In addition, coverage for anaerobes must be provided in
children with lung abscess or aspiration pneumonia until
a specific etiologic agent is identified.

448 Pediatrics in Review Vol.34 No.10 October 2013

 infectious diseases pneumonia

SPECIFIC THERAPY. When a bac-

terial pathogen is identified on
blood or pleural fluid cultures, sus-
ceptibility testing should guide the
antibiotic choice (Table 8).
The treatment regimen for un-
complicated cases must be contin-
ued for a total of 7 to 10 days
(parenteral and oral therapy). In
hospitalized cases whose baseline
inflammatory markers are checked,
some centers recommend continu-
ing antibiotics until the erythrocyte
sedimentation rate falls below 20
mm/h. Longer antibiotic regimen
is recommended in complicated
cases, starting parenterally and con-
tinuing orally. Suggested antibiotic
courses are 4 weeks total or 2 weeks
after defervescence and clinical
improvement.
Children receiving adequate an-
Figure. General approach to childhood pneumonia.
tibiotic coverage for 48 to 72 hours
without clinical improvement or
with deterioration of clinical picture should undergo length of stay. Prolonged or persistent fever or worsening
further investigation to rule out alternative diagnosis (for- of symptoms despite adequate antibiotic coverage in
eign body), antibiotic resistance, or complicated pneu- a child is suspect for complications. Table 9 lists the com-
monia. (16) plications of pneumonias
Children with allergy to b-lactams become a therapeu- Necrotizing pneumonia is suspected when a translu-
tic challenge. History is essential in this situation because cent lesion is seen on chest radiography in a child with
many children whose parents report penicillin allergy are prolonged fever or septic appearance. Diagnosis is con-
not necessarily truly allergic. If real allergy is suspected, firmed with contrast-enhanced computed tomography.
options are carbapenems (meropenem, 20-40 mg/kg Most necrotizing pneumoniae in pediatrics are caused by
per dose every 8 hours), which rarely cross react with
penicillins or cephalosporins, or clindamycin (even in
hospitals with reported clindamycin resistance >30% Table 7. Empiric Antibiotic Regimen
on antibiograms), or combination of antibiotics, such
(4)(7)
as vancomycin or linezolid plus aztreonam. Quinolones
such as levofloxacin will cover most respiratory patho- Outpatient Inpatient
gens that cause pyogenic and walking pneumonia.
First line First line
• Young children • Ampicillin
B Amoxicillin • Cephalosporin
Complications and Sequelae • Adolescent: D
B Azithromycin • Azithromycin
Children with pneumonia might experience several com-
plications. (7)(13)The complications are more likely Second line (adolescent) Second line
• Macrolide or doxycycline • Vancomycin
due to bacterial pneumonias than atypical or viral pneu-
• Fluoroquinolones (eg, levofloxacin, • Clindamycin
monias. The rate of complications in hospitalized chil- moxifloxacin) – Also used for • Linezolid
dren with pneumococcal pneumonia is estimated at adolescent or older child with
40% to 50%. type 1 hypersensitivity to
Patients with chronic illness or comorbid conditions b-lactam antibiotics
are more subject to complications that result in increased

Pediatrics in Review Vol.34 No.10 October 2013 449

infectious diseases pneumonia

Table 8. Specific Antibiotic Regimen (7)(31)

Pathogen Antibiotic(s) Comments
Streptococcus pneumoniae
• Penicillin susceptible • Penicillin or ampicillin 50-90 mg/kg daily
(drug of choice)
• Cefuroxime For patients allergic to b-lactam antibiotics
• Cefotaxime
• Ceftriaxone
• Clindamycin (oral or
intravenous)
• Intermediate and resistant • Cefotaxime Most active oral cephalosporin in vitro against
strains • Ceftriaxone penicillin-resistant strains
• Linezolid and
• Clindamycin
• Cefdinir

B Pneumococcal serotype • Vancomycin, linezolid, or Multidrug resistant to penicillin, macrolides,

19A levofloxacin clindamycin, and trimethoprim-sulfamethoxazole
Mycoplasma pneumoniae • Azithromycin • 10 mg/kg in 1 dose on the first day and 5 mg/kg in
1 dose for 4 days
• Clarithromycin • 15 mg/kg per day in 2 divided doses for 10 days
• Erythromycin • 30 to 40 mg/kg per day in 4 divided doses for 10
days
• Tetracycline • 20 to 50 mg/kg per day in 4 divided doses for 10
days (maximum daily dose 1 to 2 g)
• Doxycycline • 2 to 4 mg/kg per day in 1 or 2 divided doses for 10
days (maximum daily dose 100 to 200 mg)
• Doxycycline or a • In children age ‡8 years
fluoroquinolone
• If macrolide resistance is suspected or documented,
particularly if the child is severely ill
Chlamydia pneumoniae
• Children age ‡8 years • Doxycycline • 2 to 4 mg/kg per day divided into 2 doses
and adults (maximum daily dose, 200 mg) for 10 to 14 days
• Children age <8 years • Erythromycin • 30 to 40 mg/kg per day divided into 4 doses for 10
to 14 days

S aureus and pneumococci. Pneumatoceles are frequently Treatment of Complications

encountered, and radiologic cure lags behind clinical cure.
Lung abscess presents with nonspecific clinical signs
and symptoms similar to those of pneumonia. It has an
indolent course and is often associated with a parapneu-
monic effusion. Lung abscesses may occur in healthy chil-
dren or may be secondary to a congenital (cystic
malformation) or acquired (cystic fibrosis, immunodefi-
ciency) lung anomaly. (25) Up to 90% of cases might
be adequately treated with a prolonged course of intrave-
nous antibiotics.
Parapneumonic effusion can be in the form of pleural
effusion or empyema. The pleural fluid analysis allows dif-
ferentiating one from the other (Table 5). Empyema
is a pleural effusion that has become purulent or
semipurulent.
PARAPNEUMONIC EFFUSION. The effectiveness of
treating pleural effusion and empyema in children and
teens is unknown because there is a lack of well-designed
controlled studies. Traditionally, pleural fluid is obtained
by needle aspiration for culture, and antibiotic therapy is
started. Further chest tube drainage is resorted to if there
is no improvement or the patient’s condition worsens. In
severe cases, surgical intervention may be necessary. (4)
The management of parapneumonic effusion depends
on the size of the effusion and the child’s degree of respi-
ratory compromise. (16)
• A small, uncomplicated effusion (<10 mm on lateral
radiograph or opacification less than one-fourth of
the hemithorax) can be empirically treated without

450 Pediatrics in Review Vol.34 No.10 October 2013


need for needle aspiration or
chest tube drainage (with or
without fibrinolysis) or VATS.
• A moderate-sized effusion (>10
mm rim of fluid with less than
half the hemithorax opacified)
in a child with respiratory com-
promise or empyema requires
chest tube drainage with fibrino-
lytics or VATS (regardless of cul-
ture results).
• A large effusion (opacifies >50%
of hemithorax) consistent with
empyema (positive culture) re-
quires chest tube drainage with
fibrinolytics or VATS. (Both have
been found to be equally effective
and associated with decreased
morbidity.) The choice of drain-
age procedure depends on lo-
cal expertise. Either VATS or
open chest debridement with
decortication is indicated in a pa-
tient who continues to have
moderate to large effusions and
respiratory compromise despite
2 to 3 days of chest tube and fi-
brinolysis. Decortication is asso-
ciated with higher morbidity
rates. A chest tube that demon-
strates lack of intrathoracic air
leak and less than 1 ml/kg daily
during the past 12 hour drainage
can be clamped or removed.
Fibrinolytics are used along with
chest tube placement for moderate
to large effusions. The initial dose
of fibrinolytics is administered at
the time of chest tube placement
with a “dwell” time, during which
the chest tube is clamped, before
applying suction to the tube. In var-
ious studies, the dwell time varied
between 1 and 4 hours with a repeat
administration of fibrinolytics any-
where from every 8, 12, or 24 hours
later. On the basis of the currently
available data, both chest tube
with fibrinolysis and VATS are con-
sidered equally acceptable initial
infectious diseases pneumonia
Table 9. Pneumonia Complications (2)(4)(13)(21)
Complications Comments
Respiratory complications
Pleural effusion • Associated with hypoalbuminemia
Empyema • Affects 1:150 children with pneumonia
• Staphylococcus aureus, Streptococcus
pneumoniae, Haemophilus influenzae
• 3 Stages:
B Exudative phase
B Fibrinopurulent phase
B Organizing phase
• Associated with hypoalbuminemia
• 3% of all pediatric hospitalizations
• One-third of admissions for pneumococcal
pneumonia
Pneumatocele • Classically associated with S aureus
• May occur with a variety of organisms
• Frequently associated with empyema
• Many involute spontaneously without treatment
• Surgery for refractory cases
• Occasionally lead to pneumothorax
Necrotizing pneumonia • Seen in:
B S pneumonia (especially serotype 3 and
serogroup 19)
B S aureus
B Group A Streptococcus
B Mycoplasma pneumoniae
B Legionella
B Aspergillus
• Prolonged fever
• Septic appearance
• Diagnosis:
B Chest radiography – radiolucent lesion
B Confirmed with contrast enhanced computed
tomography
• Rare
Lung abscess • Predisposing factors:
B Aspiration (1-2 weeks after event)
B Airway obstruction
B Congenital lung anomaly
B Acquired lung anomaly
• S aureus is the most frequently involved
organism. Other organisms include anaerobes,
Klebsiella, and streptococcal species
• Should be suspected when:
B Unusually persistent consolidation
B Persistent round pneumonia
B Increased volume of involved lobe (bulging
fissure)
• Complications:
B Intracavitary hemorrhage
B Empyema
B Bronchopleural fistula
B Septicemia
B Cerebral abscess
B Inappropriate secretion of antidiuretic hormone
Continued
Pediatrics in Review Vol.34 No.10 October 2013 451
infectious diseases pneumonia

Table 9. (Continued) • Stable and/or baseline mental

and cardiorespiratory status.
Complications Comments • Ability to tolerate their home
Bronchopleural fistula antiinfective regimen, and the
Pneumothorax caretaker at home has the ability
Other complications to administer therapy.
Hyponatremia • 45% of children with community-acquired • Ability to maintain adequate
pneumonia fluid and nutrition orally.
• One-third of children hospitalized with
community-acquired pneumonia In addition, children hospitalized
• Increase length of stay, complications and with pneumonia eligible for discharge:
mortality (in severe cases)
• Secondary to syndrome of inappropriate • Who have had a chest tube and
antidiuretic hormone secretion meet the requirements listed
Sepsis or systemic
inflammatory response
above, the chest tube must have
system, meningitis, been discontinued 12 to 24
pericarditis, endocarditis, hours before discharge with no
osteomyelitis, septic clinical evidence of deterioration
arthritis, central nervous since chest tube removal
system abscess, and
atypical hemolytic-uremic
• Must have a follow-up plan prior
syndrome to discharge.

drainage strategies, and either measure is found to be su- Follow-up

perior to chest tube alone. (16)
Additional imaging and further investigation to assess
effusion progression are indicated for the child not re-
sponding to broad-spectrum therapy after 48 to 72 hours
to assess progression of the effusion. For children receiv-
ing mechanical ventilatory support with no improvement,
BAL or a percutaneous lung aspirate should be performed
for culture to determine antibiotic resistance. An open lung
biopsy for a Gram stain and culture should be obtained in
the persistently and critically ill child receiving mechanical
ventilatory support in whom previous investigations have
not yielded a microbiologic diagnosis. (16)
Lung Abscess
Up to 90% of patients with a lung abscess may be ade-
quately treated with intravenous antibiotics alone or with
combination of intravenous antibiotics transitioning to oral
antibiotics without requiring drainage of the abscess. (2)
Discharge Criteria
Children hospitalized with pneumonia are eligible for dis-
charge when they demonstrate any of the following (Ta-
ble 10) (15):
• Clinical improvement in level of activity and appetite,
with a decreased fever for at least 12 to 24 hours.
• Sustained pulse oximetry measurements greater than
90% in room air for at least 12 to 24 hours.
Children hospitalized with pneumonia must follow up
with their primary care physician soon after discharge
to ensure continued improvement and adherence with
the antibiotic regimen prescribed. It is important to dis-
cuss with caretakers that cough may persist for several
weeks to 4 months after a CAP and 3 to 4 months after
viral pneumonia or pertussis. Recovering children may
continue to have moderate dyspnea on exertion for 2
to 3 months.
Special Considerations
Immunodeficiency
Children and young adults who are immunocompro-
mised secondary to congenital or acquired immunodefi-
ciency require special considerations in their treatment
regimen in addition to coverage for the typical pathogens
discussed in the normal host (2):
• Gram-negative bacilli (including Pseudomonas aerugi-
nosa) and S aureus are common causes in neutropenic
patients or in patients with white blood cell defects.
• History of exposure to an aquatic reservoir of Legionella
pneumophila, such as a river, lake, air-conditioning tower,
or water distribution system, places the patient at risk for
legionellosis.
• Opportunistic fungi, such as Aspergillus and Candida,
are the most common fungal pathogens in immuno-
compromised patients. Aspergillus affects the lungs
through spore inhalation.

452 Pediatrics in Review Vol.34 No.10 October 2013


Pneumonia Discharge
Table 10.
Criteria (15)
• Clinical improvement (activity level, appetite)
• Afebrile for 12-24 hours
• Sustained pulse oximetry >90% on room air for 12-24
hours
• Baseline and stable cardiorespiratory and mental status
• Ability to tolerate oral anti-infective therapy and
ability of caretaker to administer it
• Ability to tolerate oral intake of food and fluids
• For children who had a chest tube, the tube must have
been discontinued 12-24 hours before discharge with
no clinical signs of deterioration
• Availability of a follow-up plan before discharge
• Other opportunistic pathogens include Fusarium spe-
cies and Pneumocystis jirovecii (formerly known as
Pneumocystis carinii).
• Viral pathogens to be considered include rubeola, cy-
tomegalovirus, varicella zoster virus, and Epstein-Barr
virus.
• Atypical mycobacteria are a significant pathogen in
children infected with human immunodeficiency virus
(HIV).
• HIV-positive patients or patients receiving immuno-
suppressive or chronic steroid therapy must be treated
for latent tuberculosis. (21)
The treatment of HIV-infected children depends
on their CD4 cell count. Most children in the United
States benefit now from antiretrovirals and have nor-
mal immune status so their treatment parallels those
without HIV infection. Those children whose CD4
cell count is low are at risk of unusual pathogens, such
as Pneumocystis jirovecii or cryptococcus; consulting
with an infectious disease specialist is recommended.
(28)
Cystic Fibrosis
Pneumonia in patients with cystic fibrosis is caused by in-
fection by S aureus, P aeruginosa, and H influenzae
(mostly nontypable strains) early in their disease. Older
children with cystic fibrosis have multiple drug-resistant
gram-negative organisms, such as Burkholderia cepacia,
Stenotrophomonas maltophilia, and Achromobacter xylo-
soxidans. Aspergillus species and nontuberculous myco-
bacteria also may also cause disease in this population.
These patients rarely get rid of their bacteria, so reviewing
previous cultures is very important.
infectious diseases pneumonia
Sickle Cell
In patients with sickle cell anemia who present with fever,
hypoxia, and respiratory distress due to acute chest syn-
drome, atypical bacterial pathogens are primarily the cul-
prits. Other causes include S pneumoniae, S aureus, and
H influenzae.
Other special considerations for therapy include the
following:
• Residence or travel to certain geographic areas that are
endemic for specific pathogens, such as tuberculosis
(Asia, Africa, Latin America, and Eastern Europe),
or exposure to individuals at high risk for tuberculosis,
including homeless, incarcerated individuals, and
HIV-infected patients.
• Exposure to certain animals such as the deer mouse
(hantavirus), bird droppings (Histoplasmosis), birds
(Chlamydophila psittaci), sheep, goats, or cattle (Coxiella
burnetii – Q fever)
Prevention and/or Control
The most effective prevention method based on strong
evidence is active immunization of children against
H influenzae type b, S pneumoniae, influenza, and per-
tussis. Influenza virus vaccine should be administered an-
nually to all infants 6 months or older and to adult
caretakers of infants younger than 6 months. The latter
should also receive the pertussis vaccine. High-risk infants
should receive the RSV-specific monoclonal antibody–
based on the American Academy of Pediatrics recom-
mendation. (4)(16) Several measures can be adopted
to prevent or decrease transmission. Because transmission
occurs by droplet or contact, good hand washing and
good personal hygiene are the most important measures.
Standard isolation precaution is required in hospitalized
patients with pneumococcal pneumonia and negative iso-
lation in patients with TB. Other measures include limit-
ing exposure to infected individuals and to cigarette
smoke. Additional infection control measures based on
cause include the following:
• Respiratory syncytial and parainfluenza viruses – gown
and gloves (ie, contact precautions).
• Influenza virus, group A Streptococcus (for the first 24
hours of treatment), MSSA, Bordetella pertussis (until pa-
tient has received 5 days of effective therapy), and M
pneumoniae – mask within 3 ft (ie, droplet precautions).
• Adenovirus – contact and droplet precautions.
• Methicillin-resistant S aureus – special organism pre-
cautions; contact and droplet precautions and dedi-
cated patient equipment.
Pediatrics in Review Vol.34 No.10 October 2013 453
infectious diseases pneumonia
Summary Points and Practice
Changes
• On the basis of strong evidence, chest radiographs are
not routinely needed to make the diagnosis of
pneumonia, particularly in suspected CAP in a child
with mild lower respiratory symptoms who is
a candidate for outpatient management. (16)
• On the basis of strong evidence, infants younger than
3 months with suspected bacterial pneumonia will
likely benefit from hospitalization.
• Moderate evidence indicates that blood cultures
should not be routinely performed in a child older than
3 to 6 months with suspected CAP who is fully
immunized, who has nontoxic effects, and who is
a candidate for outpatient management.
• On the basis of moderate evidence, blood cultures may
recover the causative organism in children
hospitalized with severe pneumonia, in those who do
not demonstrate clinical response despite adequate
antibiotic coverage, or in children with complicated
pneumonia.
• On the basis of moderate evidence, fever and
tachypnea are the most sensitive clinical signs of
pneumonia, particularly after the first 3 days of illness
• On the basis of strong evidence, oral antibiotics are as
effective as intravenous antibiotics in the treatment
of mild-moderate CAP. (5)
(The evidence-based practice guidelines for the manage-
ment of CAP in children older than 3 months (16) serves as
a resource for the clinician desiring more details related to
decisions surrounding diagnosis and management.)
References
1. Ebell MH. Clinical diagnosis of pneumonia in children. Am Fam
Physician. 2010;82(2):192–193
2. Puligandla PS, Laberge JM. Respiratory infections: pneumonia,
lung abscess, and empyema. Semin Pediatr Surg. 2008;17(1):
42–52
3. Browne LR, Gorelick MH. Asthma and pneumonia. Pediatr
Clin North Am. 2010;57(6):1347–1356
4. Schlaudecker EP, Frenck RW Jr. Adolescent pneumonia. Adolesc
Med State Art Rev. 2010;21(2):202–219, vii–viii
5. Wilder RA. Question 1: are oral antibiotics as efficacious as
intravenous antibiotics for the treatment of community acquired
pneumonia? Arch Dis Child. 2011;96(1):103–104
6. World Health Organization. Pneumonia. Fact sheet No. 331. April
2013. http://www.who.int/mediacentre/factsheets/fs331/en/
7. Shah S, Sharieff GQ. Pediatric respiratory infections. Emerg Med
Clin North Am. 2007;25(4):961–979, vi
8. Esposito S, Principi N. Unsolved problems in the approach to
pediatric community-acquired pneumonia. Curr Opin Infect Dis.
2012;25(3):286–291
9. Scott JA, Wonodi C, Moisi JC, et al; Pneumonia Methods
Working Group. The Definition of pneumonia, the assessment of
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severity, and clinical standardization in the Pneumonia Etiology
Research for Child Health study. Clin Infect Dis. 2012;54(Suppl
2):S109–S116.
10. Lynch JP III, Zhanel GG. Streptococcus pneumoniae: epide-
miology and risk factors, evolution of antimicrobial resistance, and
impact of vaccines. Curr Opin Pulm Med. 2010;16(3):217–225
11. Virkki R, Juven T, Rikalainen H, Svedström E, Mertsola J,
Ruuskanen O. Differentiation of bacterial and viral pneumonia in
children. Thorax. 2002;57(5):438–441
12. Nohynek H, Madhi S, Grijalva CG. Childhood bacterial
respiratory diseases: past, present, and future. Pediatr Infect Dis J.
2009;28(10 Suppl):S127–S132
13. Prayle A, Atkinson M, Smyth A. Pneumonia in the developed
world. Paediatr Respir Rev. 2011;12(1):60–69
14. Don M, Canciani M, Korppi M. Community-acquired pneu-
monia in children: what’s old? What’s new? Acta Paediatr. 2010;99
(11):1602–1608
15. Mulholland S, Gavranich JB, Gillies MB, Chang AB. Anti-
biotics for community-acquired lower respiratory tract infections
secondary to Mycoplasma pneumoniae in children. Cochrane Data-
base Syst Rev. 2012;9(Issue 9):CD004875 10.1002/14651858.
CD00487.pub4
16. Bradley JS, Byington CL, Shah SS, et al; Pediatric Infectious
Diseases Society and the Infectious Diseases Society of America.
Executive summary: the management of community-acquired
pneumonia in infants and children older than 3 months of age:
clinical practice guidelines by the Pediatric Infectious Diseases
Society and the Infectious Diseases Society of America. Clin Infect
Dis. 2011;53(7):617–630
17. Shah VP, Tunik MG, Tsung JW. Prospective evaluation of
point-of-care ultrasonography for the diagnosis of pneumonia
in children and young adults. JAMA Pediatr. 2013;167(2):
119–125
18. Mularoni A, Furfaro E, Faraci M, et al. High Levels of b-D-
glucan in immunocompromised children with proven invasive
fungal disease. Clin Vaccine Immunol. 2010;17(5):882–883
19. Hage CA, Knox KS, Davis TE, Wheat LJ. Antigen detection in
bronchoalveolar lavage fluid for diagnosis of fungal pneumonia.
Curr Opin Pulm Med. 2011;17(3):167–171
20. Boonsarngsuk V, Niyompattama A, Teosirimongkol C, Sriwanichrak
K. False-positive serum and bronchoalveolar lavage Aspergillus
galactomannan assays caused by different antibiotics. Scand J Infect
Dis. 2010;42(6-7):461–468
21. Ranganathan SC, Sonnappa S. Pneumonia and other respira-
tory infections. Pediatr Clin North Am. 2009;56(1):135–156, xi
22. Chang CC, Cheng AC, Chang AB. Over-the-counter (OTC)
medications to reduce cough as an adjunct to antibiotics for acute
pneumonia in children and adults. Cochrane Database Syst Rev. 2012;
2(Issue 2):CD006088 10.1002/14651858.CD006088.pub3
23. Lassi ZS, Haider BA, Bhutta ZA. Zinc supplementation for the
prevention of pneumonia in children aged 2 months to 59 months.
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10.1002/14651858.CD005978.pub2
24. Yakoob MY, Theodoratou E, Jabeen A, et al. Preventive zinc
supplementation in developing countries: impact on mortality and
morbidity due to diarrhea, pneumonia and malaria. BMC Public
Health. 2011;11(Suppl 3):S23 http://www.biomedcentral.com/
1471-2458/11/S3/S23
25. Clifford V, Tebruegge M, Vandeleur M, Curtis N. Question 3:
can pneumonia caused by penicillin-resistant Streptococcus pneumo-
niae be treated with penicillin? Arch Dis Child. 2010;95(1):73–77
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26. Sutijono D, Hom J, Zehtabchi S. Efficacy of 3-day versus 5-day
antibiotic therapy for clinically diagnosed nonsevere pneumonia in
children from developing countries. Eur J Emerg Med. 2011;18(5):
244–250
27. Gilchrist FJ. Is the use of chest physiotherapy beneficial in
children with community acquired pneumonia? Arch Dis Child.
2008;93(2):176–178
28. Punpanich W, Groome M, Muhe L, Qazi SA, Madhi SA.
Systematic review on the etiology and antibiotic treatment of
pneumonia in human immunodeficiency virus-infected children.
Pediatr Infect Dis J. 2011;30(10):e192–e202
29. Wonodi CB, Deloria-Knoll M, Feikin DR, et al; Pneumonia
Methods Working Group and PERCH Site Investigators. Evalua-
tion of risk factors for severe pneumonia in children: the Pneumonia
Etiology Research for Child Health study. Clin Infect Dis. 2012;54
(Suppl 2):S124–S131
30. Chang AB, Chang CC, O’Grady K, Torzillo PJ. Lower
respiratory tract infections. Pediatr Clin North Am. 2009;56(6):
1303–1321
31. Esposito S, Cohen R, Domingo JD, et al. Do we know when,
what, and for how long to treat? antibiotic therapy for community-
acquired pneumonia. Pediatr Infect Dis J. 2012;31(6):e78–e85

PIR Quiz
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answer form will be printed in the journal.

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1. Anticipatory guidance to parents of children recovered from pneumonia includes discussion about the length
of time that cough may persist. What is the length of time that cough may normally persist after a community-
acquired pneumonia?
A. 2 weeks.
B. 4 weeks.
C. 2 months.
D. 3 months.
E. 4 months.

2. Prevention of pneumonia in children includes active immunization of adult caretakers of infants younger than
6 months against which of the following pathogens?
A. Bordetella pertussis.
B. Haemophilus influenzae type b.
C. Neisseria meningitidis.
D. Respiratory syncytial virus.
E. Tuberculosis.

3. A 10-year-old boy presents with a history of fever, headache, malaise, mild sore throat, and worsening
nonproductive cough. Lung examination reveals diffuse crackles. Chest radiographs reveal bilateral diffuse
patchy infiltrates. The next step in management is to prescribe:
A. Amoxicillin.
B. Amoxicillin-clavulanate.
C. Azithromycin.
D. Cephalexin.
E. Penicillin.

Pediatrics in Review Vol.34 No.10 October 2013 455

infectious diseases pneumonia

4. A previously healthy, fully immunized 3-year-old girl presents with a 4-day history of gradual onset of runny
nose, cough, fatigue, and slightly fast breathing. She continues to drink liquids but refuses solid foods.
Temperature is 38.3˚C. Physical examination reveals a tired-appearing child with mild tachypnea and subtle
intercostal retractions. Lung examination reveals adequate aeration and crackles over all lung fields bilaterally.
The next step in management is:
A. Amoxicillin (50 mg/kg daily).
B. Blood culture.
C. Chest radiographs.
D. Close observation and follow-up.
E. Complete blood cell count.

5. One week ago, a previously healthy 6-year-old boy was seen in the outpatient clinic with a 5-day history of
fever, chills, fatigue, muscle aches, and cough. Laboratory testing revealed a diagnosis of influenza A for which
he was not treated because of delay in diagnosis. Today he returned to the clinic looking significantly worse,
with tachypnea, dyspnea, and retractions. Chest radiography suggests a small empyema in the right lower lobe.
The next step in management is to prescribe:
A. Ampicillin.
B. Amoxicillin-clavulanate.
C. Azithromycin.
D. Ceftriaxone and clindamycin.
E. Penicillin.

Parent Resources from the AAP at HealthyChildren.org

• English only: http://www.healthychildren.org/English/health-issues/conditions/chest-lungs/Pages/Pneumonia.aspx

Corrections
In the April 2013 article “Pelvic Inflammatory Disease” (Trent M. Pediatr Rev. 2013;34(4):163–172), the video link at the
end of the second-to-the-last paragraph in the section titled “Does Outpatient Treatment Work for Adolescents?” should
read as follows: http://www.youtube.com/watch?v=lGuXF8vpujQ.
Readers can also search PID and Johns Hopkins on the general YouTube web page to locate the video.
Also, the beginning of the second sentence in the following paragraph should read, “One Brazilian trial has demonstrated
that ceftriaxone 250 mg intramuscularly (IM) plus 1 g of azithromycin given orally at baseline each week for 2 weeks…”.
The journal regrets these errors.

456 Pediatrics in Review Vol.34 No.10 October 2013

 Article genital system disorders

Hernias and Hydroceles

Lane S. Palmer, MD*
Practice Gap
Medical management of hernias and hydroceles has changed; pediatricians need to
Author Disclosure be aware that the urgency to surgically correct these entities depends on the nature
Dr Palmer has of the hernia or hydrocele and the likelihood of incarceration or spontaneous
disclosed no financial resolution.
relationships relevant
to this article. This
Objectives After completing this article, readers should be able to:
commentary does not
contain discussion of 1. Derive the differential diagnosis of a mass in the inguinal area in an infant: hydrocele,
unapproved/ inguinal hernia, trauma, or tumor.
investigative use of 2. Understand the history and physical examination differences between an inguinal
a commercial product/ hernia and a hydrocele.
device. 3. Plan the evaluation of a patient with a mass in the inguinal area.
4. Appreciate the principles in the surgical management of the hernia and hydrocele in
infants and children.
Hernias and hydroceles present within embryologic and clinical continuums that are com-
monly encountered by pediatricians. These conditions are typically discovered by pediatricians
on routine physical examination or after a bulge in the groin and/or scrotum is noted by the
child’s caretaker. The common nature of the inguinal hernia-hydrocele is documented by au-
topsy studies reporting an incidence of a patent processus vaginalis in 80% to 94% in newborn
infants. The importance of identifying these conditions based on the history and physical ex-
amination findings lies in averting their complications and ensuring proper referral for further
management.

Embryology of the Inguinal Canal

Inguinoscrotal abnormalities in children are best understood by reviewing the under-
lying embryology of testicular descent and the inguinal region development. At approx-
imately 6 weeks of gestation, the primitive germ cells migrate from the yolk sac to the
genital ridge located high on the posterior wall of the abdomen where they differentiate
into a testis or an ovary during the next 2 weeks. During the next few weeks of fetal
elongation, the gonad becomes located near the internal inguinal ring at 3 months
of gestation. During the third month and before testicular descent, the peritoneum
bulges into the inguinal canal as the processus vaginalis. The gubernaculum forms from
the caudal end of the mesonephros and is attached to the lower pole of the testis, where
it serves to guide its descent into the scrotum. Starting in the seventh month of gesta-
tion, the testes descend through each inguinal canal, pushing the vaginalis ahead of it
toward the scrotum during a few days, and then migrate from the external ring to the
lower scrotum during the next 4 weeks.
The process vaginalis obliterates after testicular descent is complete. The portion of the
processus vaginalis that is adjacent to the testes becomes the tunica vaginalis. Failure of the
processus vaginalis to obliterate leads to the clinical entities described below.
In girls, the canal of Nuck, corresponding to the processus vaginalis in girls, usually ob-
literates earlier and enters into the labium majora. The gubernacular remnant in girls becomes
the ovarian and uterine ligaments.

*Departments of Urology and Pediatrics, Hofstra North Shore-LIJ School of Medicine, and Department of Pediatric Urology, Cohen
Children’s Medical Center of New York, Long Island, NY.

Pediatrics in Review Vol.34 No.10 October 2013 457

genital system disorders hernias and hydroceles

is highest in neonates and infants and

Figure 1. Hernia and hydroceles. From Palmer LS. Scrotal swelling and pain. In: McInerny
TK, Adam HM, Campbell D, Kamat DK, Kelleher KJ, eds. American Academy of Pediatrics is likely related to later descent of
Textbook of Pediatric Care. Elk Grove Village, IL: American Academy of Pediatrics; the right testis and obliteration of
2009:1717–1724.
Definitions
Indirect Inguinal Hernia
Complete failure of the processus vaginalis to obliterate leads
to a large communication between the abdomen at the level
of the internal ring and the testis (Figure 1). The protrusion
of intra-abdominal contents into the peritoneal sac defines
the hernia. These contents include omentum/bowel or
ovary/fallopian tube, and they may extend distally from
the inguinal region to the scrotum or labia. Therefore, most
indirect inguinal hernias are congenital.
Communicating Hydrocele
Communicating hydrocele is the presence of peritoneal
fluid in a patent processus vaginalis that protrudes across
the internal inguinal ring and extends distally ending
along the inguinal canal or reaching the scrotum.
decreases with age. Hernias are re-
ported in up to 30% of premature
hernias. Among full-term infants,
the incidence of hernias is highest in
the first year of life, peaking with ap-
proximately one-third presenting in
the first 6 months, predominantly
in the first few months. Several stud-
ies report a male predilection (6:1).
The predilection for a right-sided
(56.2%) patent processus vaginalis
the processus vaginalis. Left-sided
(27.5%) hernias are more likely to
be associated with an occult right-
sided hernia. Hernias are present bilaterally in 16.2%;
the incidence rate of bilateral congenital inguinal hernia
based on a range from several retrospective and a few pro-
spective studies is approximately 15% to 25%. A family
history of inguinal hernias is reported in approximately
20% of probands, and similarly there is a higher incidence
among twins. Although an inguinal hernia is usually an
isolated finding, there are several associated conditions
of which the pediatrician should be aware (Table 1).
Signs and Symptoms
An inguinal hernia and a communicating hydrocele typ-
ically present as a painless bulge localized to the groin or
extending along the cord structures to the hemiscrotum
or into the vulva in girls (Figure 2). The bulge is usually

Hydrocele of the Spermatic Cord Conditions Associated

Table 1.
Hydrocele of the spermatic cord is a fluid collection present
along the spermatic cord between the obliterated portion With an Inguinal Hernia
of the processus vaginalis proximally from the internal ring Prematurity
and distally to the tunica vaginalis surrounding the testicle. Positive family history
Presence of a ventricoperitoneal shunt
Cystic fibrosis
Scrotal Hydrocele Ascites
Scrotal hydrocele is the presence of fluid surrounding the Congenital dislocation of the hip
testicle that is contained by the tunica vaginalis while the Undescended testis
processus vaginalis is obliterated from the internal ring to Hypospadias
the upper extent of the tunica vaginalis. Disorders of sexual differentiation
Exstrophy-epispadias complex
Prune belly (triad or Eagle-Barrett) syndrome
Ehlers-Danlos syndrome
Epidemiology Hunter-Hurler syndrome
The incidence rate of inguinal hernias is roughly 1% to 4% or Marfan syndrome
approximately 10 to 20 per 1000 live births. The incidence

458 Pediatrics in Review Vol.34 No.10 October 2013


Figure 2. Inguinal bulge present in the upper right hemiscrotum in a male (left) and into may facilitate protrusion of the
the right in a girl (right).
painless and may be present at all times or only during
periods of increased intra-abdominal pressure, such as
during crying or bowel movements. The bulge may
not be detectable when the child is supine and the peri-
toneal fluid or intra-abdominal contents spontaneously
pass back into the abdomen. It is helpful to determine
whether the bulge is smallest during sleep and larger
when the child is standing. This intermittent presence
of the bulge distinguishes the reducible inguinal hernia
and communicating hydrocele from a scrotal hydrocele
or hydrocele of the spermatic cord. The child with an in-
carcerated inguinal hernia will have a bulge that does not
reduce spontaneously. With incarceration, the child may
be irritable or inconsolable, have decreased appetite, and
present with signs of bowel obstruction (abdominal dis-
tention, vomiting, and lack of flatus or stool).
The scrotal hydrocele may be present from birth or ap-
pear after an inflammatory or infectious process or after
scrotal trauma. The size of the hydrocele may vary and
even extend proximally though the inguinal canal to
the internal ring, making it difficult to distinguish from
a hernia or communicating hydrocele. The hydrocele of
the spermatic cord is also generally painless and variable
in size. It may be confused for the testis because of its
round-oval shape.
Physical Examination
Although the history is important, the physical examina-
tion is vital in determining the nature of the inguinoscro-
tal abnormality. Because most of these children are not
yet walking, most examinations start with the child in
the supine position. The older child should first be
genital system disorders hernias and hydroceles
examined in the standing position.
Inspection should start at the lower
abdomen in the area of the lower
skin creases and then proceed along
the inguinal canal into the scrotum.
The presence of a bulge or asymme-
try between the 2 sides should be
sought. If the child is crying, the ex-
aminer should try to assess whether
a bulge becomes present or in-
creases during that time and im-
proves or disappears when the child
is consoled. Having the older child
jump up and down several times
bulge.
Palpation moving systematically
in a craniocaudal direction should
start on the asymptomatic side followed by the reported
symptomatic side. Gentle palpation to determine pres-
ence of swelling begins by using 1 to 2 fingers first in
the area superior and lateral to the pubic tubercle, pro-
ceeding along the cord structures of the inguinal ring
and ending in the scrotum. The proximal and distal ex-
tent of the swelling needs to be determined, if possible,
to help make the diagnosis. Hernias and communicating
hydroceles start at the level of the internal ring and can
end at variable locations. Applying gentle pressure up-
ward and slightly laterally can frequently reduce the con-
tents of the hernia sac. The palpation of a silk-stocking
sign implies thicker cord structures (ie, the presence of
a hernia) and is sought by rubbing the cord structures
side to side near the pubic tubercle. The sensation is that
of rubbing silk together. A hydrocele of the spermatic
cord may feel like a testis because of its shape. The exam-
iner should be able to palpate cord structures both above
and below the round-oblong hydrocele and a separate tes-
tis distally. Scrotal hydroceles vary in size and may be diffi-
cult to distinguish from a hernia when a scrotal hydrocele
extends up to the internal ring. In general, the examiner
should be able to palpate the cord structures above the
superior aspect of the hydrocele. The fluid surrounding
the testicle contained by the tunica vaginalis should trans-
illuminate using a bright light; however, neonatal bowel
may also transilluminate, leading to uncertainty as to the
diagnosis. The examiner should assess the presence and
nature of the 2 testes. The palpation of a normal testis
and the bulge above it indicates the entity to be a hernia
or hydrocele of the cord. In a hydrocele, the testis may be
palpable within the surrounding fluid unless the hydrocele
is tense, in which case the testis may not be discerned.
Pediatrics in Review Vol.34 No.10 October 2013 459
genital system disorders hernias and hydroceles
Laboratory and Radiologic Imaging
The accurate diagnosis of a hernia and/or hydrocele is
most commonly made based on the history and physical
examination, thus making the use of adjuvant studies rel-
atively unnecessary. Serum studies should be ordered
when there is concern for bowel obstruction of an incar-
cerated hernia. Imaging is often of limited utility. Her-
niorrhaphy is of historical interest in which water soluble
contrast was injected infraumbilically into the abdomen
and delayed pelvic radiographs were taken to see contrast
in a hernia sac. Ultrasonography can be helpful in identify-
ing an elongated echolucent area from the groin that ex-
tends anteromedially in the spermatic cord. However,
this is not commonly found when the hernia sac is small.
Other times omentum or bowel with its attendant peristalsis
can be identified in a large hernia sac. In the presence of
a presumed hydrocele, a sonogram can be helpful to identify
the presence of an unpalpable testicle surrounded by hydro-
cele fluid. Ultrasonography is useful in identifying the pres-
ence of blood surrounding the testis in a child with a history
of scrotal trauma or the presence of a solid testicular mass.
Incarceration
Incarceration of the hernia, or the inability of the hernia to
spontaneously reduce, occurs in 6% to 18% of patients and
in 30% of infants younger than 2 months. This high inci-
dence emphasizes the need to repair a hernia fairly promptly
in young children. Structures that may become incarcerated
include small bowel, appendix, omentum, colon, Meckel di-
verticulum, ovary, or fallopian tube. The signs and symp-
toms of incarceration include a hard bulge present in the
groin with or without pain, irritability, and redness. An at-
tempt at reducing the incarcerated hernia by applying gentle
pressure from the bottom of the hernia toward the internal
ring should be undertaken but may require conscious seda-
tion to facilitate muscle relaxation and to provide analgesia
to achieve successful reduction. Sedation or narcotic analge-
sia must be used judiciously and with appropriate monitor-
ing in neonates and ill-appearing children. The only
exception to attempting to perform reduction is in the case
of a long-standing incarceration with signs and symptoms
of peritonitis and strangulation of the hernia.
Differential Diagnosis
Although the primary components of the differential di-
agnosis are those defined above (hernia, communicating
hydrocele, hydrocele of the spermatic cord, and hydro-
cele), additional diagnoses should be kept in mind and
ruled out (Table 2). Lipoma of the spermatic cord may
460 Pediatrics in Review Vol.34 No.10 October 2013
be difficult to differentiate from a hernia filled with omen-
tum on both physical examination and ultrasonography,
thereby requiring surgical exploration to differentiate.
The incidence of torsion of the testis is highest during
the neonatal period and adolescence. In neonatal torsion,
the hard testis is painless and the cord is normal on pal-
pation. Torsion of the testis or a testicular appendage
presents as an acute process that in adolescents is painful
and may be confused with acute pain from an incarcer-
ated hernia. The scrotal examination should allow the ex-
aminer to distinguish torsion from an incarcerated hernia;
in the latter the proximal cord cannot be discerned but
the testis can, whereas in the former fullness of the distal
cord may be palpable, indicating the point of torsion.
Prolonged torsion may be associated with the develop-
ment of a hydrocele, making the testis difficult to palpate.
The diagnosis may be very difficult in the undescended
testis that undergoes torsion. The blue-dot sign may
be seen, indicating the presence of a necrotic testicular
appendage seen through a hydrocele and the scrotal skin.
Trauma to the testis may result in painful swelling of the
scrotum, often with associated ecchymosis. The history
should lead to the performance of ultrasonography to assess
the presence of hematocele around the testis and the integ-
rity of the testis. Testes tumors often present as painless tes-
ticular masses without any palpable abnormalities of the
cord or inguinal canal that should be determined on phys-
ical examination, ultrasonography, and ultimately surgical
exploration.
Indications for Surgery
Inguinal Hernia
Surgical repair of an inguinal hernia is generally advised
shortly after its diagnosis is made given the significant rate
Differential Diagnosis of
Table 2.
an Inguinoscrotal Swelling
Inguinal hernia
Communicating hydrocele
Noncommunicating hydrocele
Hydrocele of the spermatic cord
Torsion of the testis or a testicular appendage
Lipoma of the spermatic cord
Hematocele
Epididymitis
Varicocele
Testicular tumors
Suppurative inguinal lymphadenitis

and risk of associated complications. In the absence of in-
carceration or for an easily reducible hernia, outpatient
surgery can be performed within a few weeks. Surgery
should be performed more urgently if there is moderate
difficultly in successfully reducing the hernia. In either
case, the parents should be advised to return if signs
and symptoms of incarceration occur. For hernias that
are difficult to reduce or require sedation, surgery should
be performed with even greater urgency; an irreducible
hernia requires immediate exploration. Hernias in prema-
ture infants can be repaired before hospital discharge.
However, surgery may need to be delayed in extremely
low-birth-weight (<1500 g) or premature infants and
in children with congenital heart disease, pulmonary dis-
ease, sepsis, or metabolic disease because of the increased
risk of anesthesia. The timing of operation for premature
infants with reducible inguinal hernias is controversial
and is the basis for a current multicenter clinical trial.
Hydroceles
Communicating and noncommunicating hydroceles
(Figure 3) have the potential to resolve spontaneously in
infants and can therefore be observed until age 1 year
and then corrected if it is still present or if the hydrocele en-
larges. Hydroceles of the spermatic cord do not tend to re-
solve spontaneously but seldom pose urgency for repair;
therefore, these should be repaired after age 1 year as well.
Surgical Considerations
Surgical Technique
Pediatricians should be familiar with the salient surgical
steps of hernia repair, leading to the ligation of the hernia
sac at the level of the internal ring. A small transverse
Figure 3. Intraoperative photograph of a left hydrocele
exposed through a scrotal incision. The large volume of fluid
can be seen through the thin wall of the tunica vaginalis.
genital system disorders hernias and hydroceles
incision is made in the lowest inguinal skin crease, and dis-
section proceeds to the external oblique aponeurosis, which
is incised, if needed, to reach the internal ring. The ilioin-
guinal nerve is avoided, and the cremaster muscle fibers
are gently teased apart, exposing the hernia sac on the ante-
romedial surface of the spermatic cord. The sac is gently
separated free from the spermatic vessels and vas deferens
and then divided. Proximally, the sac is gently dissected free
to the level of the internal ring, where it is ligated after
checking for the absence of intra-abdominal contents
(Figure 4). The distal sac may be left in place or excised.
A hydrocele should be drained if present. The wound is
closed in layers and local anesthetic placed in the area of
the ilioinguinal nerve and in the subcutaneous tissue.
Laparoscopic Herniorrhaphy
Despite the popularity of laparoscopic hernia repair in
adults, the various available techniques have not been
widely adopted for herniorrhaphy in children given the
small incision, rapidity of the procedure, and high success
rate of the standard open technique. A multicenter series
of 933 laparoscopic repairs reported recurrent hernias in
3.4% (follow-up, 2 months to 7 years), a rate higher than
after open repair. (1) However, there appears to be an
advantage in identification of contralateral inguinal hernia,
cosmesis, and less postoperative analgesia with laparos-
copic approaches. (2)(3)
Incarcerated Inguinal Hernia
An irreducible hernia should be explored immediately. If
the hernia reduces spontaneously on the induction of
anesthesia, standard herniorrhaphy can be performed
Figure 4. Intraoperative photograph of the hernia sac
dissected from the spermatic cord up to the internal inguinal
ring before ligation.
Pediatrics in Review Vol.34 No.10 October 2013 461
genital system disorders hernias and hydroceles
because nonviable bowel is unlikely to reduce spontane-
ously. However, if there is cloudy or bloody fluid or a foul
odor after opening the sac, the reduced bowel should be
identified and inspected for viability. If viable bowel re-
mains entrapped, it can be reduced. If the bowel is ische-
mic or discolored, it is covered with warm, saline-soaked
sponges and then examined after several minutes for
signs of viability. If the viability of the bowel is uncertain
or if there is necrosis present, the segment of bowel
should be resected. Bowel resections are reported in
1.4% to 1.8% of incarcerated hernias and in 4% to 7%
of irreducible cases.
Exploration of the Contralateral Side
In the child with a unilateral hernia, the need to explore
the contralateral side remains controversial. Infants with
unilateral inguinal hernias have a patent contralateral
processus vaginalis in 60% during the first few months
of life. By age 2 years, 20% of these hernias are obliter-
ated, and half of the remaining 40% became clinical her-
nias. The goal of contralateral exploration is to avoid
asynchronous hernia development and its attendant risks
and costs. However, surgical exploration can result in in-
jury to the vas deferens, testes, and ilioinguinal nerve and
may be unnecessary. Historically, routine bilateral explo-
ration was undertaken because of the reported 60% to
70% incidence of a contralateral patent processus vaginalis.
In a recent survey (4) 51% of surgeons perform routine con-
tralateral exploration in premature infants, 40% perform
Figure 5. Intraoperative image through a 70 lens placed though the hernia sac dem-
˚
onstrating a closed (A) and open (B) contralateral internal inguinal ring. The ring is
located at the junction of the vas deferens coming in medially and the descending
internal spermatic ring.
462 Pediatrics in Review Vol.34 No.10 October 2013
exploration in boys younger than 2 years, and 13% perform
exploration in boys ages 2 to 5 years. In female patients,
routine contralateral exploration was performed by 39%
of surgeons in those younger than 5 years.
Several methods attempt to avoid contralateral explo-
rations with negative results, such as probing, herniorrha-
phy, and inducing a pneumoperitoneum to delineate
structures. However, these attempts have insufficient ac-
curacy. In contrast, transperitoneal diagnostic laparos-
copy offers a rapid, direct, and accurate inspection of
the contralateral internal inguinal ring by passing a 30°
or 70° oblique scope through the open hernia sac
(Figure 5). A meta-analysis of 964 laparoscopic evaluations
identified a sensitivity of 99.4% and specificity of 99.5%. (5)
One-third to half of children have a patent contralateral
processus vaginalis, with higher rates in infants younger
than 1 year. However, a patent processus does not neces-
sarily infer a clinically significant hernia; the reported risk of
developing a metachronous contralateral inguinal hernia af-
ter open unilateral hernia repair in children is 7.2%. (6) The
question of exploring the contralateral side, however, re-
mains unanswered because no study has followed up chil-
dren with a known open contralateral internal inguinal ring
and determined the rate of progression to a clinical hernia.
Complications
Complications after inguinal hernia repair are unusual and may
be related to technical factors (recurrence, iatrogenic cryptor-
chidism) or to the underlying process
of incarceration (bowel ischemia, go-
nadal infarction, and testicular atro-
phy). Wound infection, although less
than 1% of all reported series, is much
more common in irreducible cases.
Recurrent Hernia
The recurrence of an inguinal hernia
after an uncomplicated open her-
niorrhaphy occurs in 0.5% to 1% of
cases, up to 2% when performed in
premature infants and in 3% to 6% af-
ter repair of an incarcerated hernia.
Recurrences generally occur within
1 year (50%) or 2 years (75%) after
the original surgery. (7) Recurrent
hernias may result from failure to
identify or to securely ligate the her-
nia sac at the original surgery, liga-
tion of the sac distal to the internal
ring, a tear in the sac in which

a peritoneal strip remains along the cord structures, or the
presence of increased intra-abdominal pressure, such as
from a ventriculoperitoneal shunt. Recurrent hernias re-
quire additional surgery for repair.
Iatrogenic Cryptorchidism
Iatrogenic cryptorchidism can occasionally result after
hernia repair. It is important for the surgeon to ascertain
the proper position of the testis before concluding sur-
gery. If an undescended testis is observed preoperatively,
a concurrent orchiopexy should be performed.
Testis Infarction
Testicular infarction and its subsequent atrophy occurs in
4% to 12% of cases of an incarcerated hernia and in even
an higher percentage when the hernia is not reducible.
The mechanism is presumably due to compression of
the gonadal vessels by the irreducible hernia, although
some atrophic testes develop as a result of damage in-
curred during repair of a difficult incarcerated hernia.
During surgery, if viability is unclear, the testis could
be left in place and its viability assessed later.
Summary
• Inguinoscrotal abnormalities in children are best
understood by understanding the embryology of
testicular descent and the failure of the processus
vaginalis to properly obliterate.
• The inguinal hernia, communicating hydrocele,
hydrocele of the spermatic cord, and scrotal hydrocele
should be differentiated based on a history and
physical examination in most cases, with selective use
of ultrasonography.
• The urgency to surgically correct these entities
depends on the nature of the hernia or hydrocele and
the likelihood of incarceration or spontaneous
resolution.
Parent Resources From the AAP at HealthyChildren.org
• English: http://www.healthychildren.org/English/health-issues/conditions/abdominal/Pages/Inguinal-Hernia.aspx
• Spanish: http://www.healthychildren.org/spanish/health-issues/conditions/abdominal/paginas/inguinal-hernia.aspx
genital system disorders hernias and hydroceles
• Open standard herniorrhaphy remains the most
common surgical approach, and concurrent
transinguinal laparoscopy allows quick and accurate
inspection of the contralateral internal inguinal ring
and the need for bilateral repair of an inguinal hernia.
References
1. Schier F, Montupet P, Esposito C. Laparoscopic inguinal
herniorrhaphy in children: a three-center experience with 933
repairs. J Pediatr Surg. 2002;37(3):395–397
2. Wang KS, Committee on Fetus and Newborn, and Section on
Surgery. Assessment and management of inguinal hernias in infants.
Pediatrics. 2012;130(4):768–773
3. Alzahem A. Laparoscopic versus open inguinal herniotomy in infants
and children: a meta-analysis. Pediatr Surg Int. 2011;27(6):605–612
4. Levitt MA, Ferraraccio D, Arbesman MC, Brisseau GF, Caty
MG, Glick PL. Variability of inguinal hernia surgical technique:
a survey of North American pediatric surgeons. J Pediatr Surg.
2002;37(5):745–751
5. Miltenburg DM, Nuchtern JG, Jaksic T, et al. Laparoscopic
evaluation of the pediatric inguinal hernia—a meta-analysis.
J Pediatr Surg. 1998;33(6):874–879
6. Ron O, Eaton S, Pierro A. Systematic review of the risk of
developing a metachronous contralateral inguinal hernia in chil-
dren. Br J Surg. 2007;94(7):804–811
7. Wright JE. Recurrent inguinal hernia in infancy and childhood.
Pediatr Surg Int. 1994;9:164
Suggested Readings
Holcomb GW III, Brock JW III, Morgan WM III. Laparoscopic
evaluation for a contralateral patent processus vaginalis.
J Pediatr Surg. 1994;29(8):970–974
Krieger NR, Shochat SJ, McGowan V, Hartman GE. Early hernia
repair in the premature infant: long-term follow-up. J Pediatr
Surg. 1994;29(8):978–982
Misra D, Hewitt G, Potts SR, Brown S, Boston VE. Inguinal
herniotomy in young infants, with emphasis on premature
neonates. J Pediatr Surg. 1994;29(11):1496–1498
Rowe MI, Copelson LW, Clatworthy HW. The patent processus
vaginalis and the inguinal hernia. J Pediatr Surg. 1969;4(1):
102–107
Pediatrics in Review Vol.34 No.10 October 2013 463
genital system disorders hernias and hydroceles

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1. You have just examined a 3-month-old boy for the first time. You notice the right hemiscrotum is larger than
the left. There is a firm mass in the right hemiscrotum that is nontender and nonreducible, but you can palpate
a testicle within the mass. A normal spermatic cord is palpable above the mass. The parents tell you the mass
has been present since birth, does not vary in size throughout the day, but has become somewhat smaller since
birth. Which of the following is the most likely diagnosis?
A. Hydrocele of the spermatic cord.
B. Inguinal hernia.
C. Scrotal hydrocele.
D. Testicular tumor.
E. Testicular torsion.
2. Which diagnostic modality is the most useful in diagnosing an inguinal hernia in a child?
A. Computed tomography.
B. Physical examination.
C. Radiographic herniogram.
D. Scrotal ultrasonography.
E. Transillumination.
3. A 13-year-old boy presents with a 2-hour history of right scrotal pain that began acutely. There is no history of
trauma and no similar past episodes. Physical examination reveals tenderness to direct palpation of the upper
portion of the testicle and epididymis, although the spermatic cord above the testicle is normal and nontender.
The testicle is in a normal position in the scrotum. A blue dot is noticed in the upper scrotum overlying the
point of maximum tenderness. The most likely diagnosis is:
A. Acute hydrocele.
B. Epididymitis.
C. Incarcerated inguinal hernia.
D. Testicular torsion.
E. Torsion of an appendix testis.
4. The scenario in which you would most likely find identical pathologic findings on the contralateral side is:
A. Communicating hydrocele.
B. Hydrocele of the cord.
C. Male left-sided inguinal hernia.
D. Male right-sided inguinal hernia.
E. Noncommunicating hydrocele.
5. Which of the following is most likely to resolve spontaneously?
A. Female inguinal hernia.
B. Hydrocele.
C. Hydrocele of the spermatic cord.
D. Male inguinal hernia.
E. Testicular torsion.

464 Pediatrics in Review Vol.34 No.10 October 2013


The reader is encouraged to write
possible diagnoses for each case before
turning to the discussion.
Author Disclosure
Drs Speakman, Buryk, Goretzke,
Srinivasan, Growdon, Taggart,
Rothwell, Washko, and Stevens have
disclosed no financial relationships
relevant to this article. This
commentary does not contain
discussion of unapproved/
investigative use of a commercial
product/device.
We invite readers to contribute case
presentations and discussions. Please
inquire first by contacting Dr Deepak
Kamat at DKamat@med.wayne.edu.
Case 1: Acute Onset of Confusion, Slurred Speech, and
Ataxia in a 15-Year-Old Boy
Case 2: Polyuria, Weight Loss, and Hyperglycemia in
a Teenage Girl
Case 3: Orthopnea and Fever in a 2½-Year-Old Boy
Case 1 Presentation
A 15-year-old boy presents with a 12-
hour history of progressive confusion,
slurred speech, and ataxia. He was
seen earlier in the week for rhinorrhea,
cough, and fever and was diagnosed as
having a viral illness. His symptoms
improved until 12 hours before pre-
sentation when he became moody,
confused, and ataxic. He denies any
weakness, headache, diarrhea, consti-
pation, visual changes, neck stiffness,
photophobia, or phonophobia. He
also denies any toxic ingestions and
drug or alcohol use. He has not had
any immunizations recently.
He weighs 126.3 kg, and his vital
signs are as follows: heart rate, 96 beats
per minute; blood pressure, 121/80
mm Hg; respiratory rate, 16 breaths
per minutes; oxygen saturation, 99%
on room air; and temperature, 37°C.
He is awake although somnolent, re-
quiring frequent prompting to answer
questions. His sensations are normal,
and strength is 5/5 in all extremities.
Deep tendon reflexes are absent in
the lower extremities, with down-
going plantar responses. He is un-
able to support himself in a sitting
or standing position. Rapid alterna-
tive movements are slow and delib-
erate without obvious dysmetria.
Findings on the remainder of the
neurologic and the cardiac, respira-
tory, abdominal, genitourinary, and
rectal examinations are normal.
The result of a noncontrast head
computed tomography (CT) is nor-
mal. Cerebrospinal fluid (CSF) anal-
ysis reveals 5 red blood cells, 600
white blood cells (WBCs) (87% lym-
phocytes), and normal levels of
index of suspicion
protein and glucose. The results of
polymerase chain reaction tests on
CSF for herpes simplex virus, varicella
zoster virus (VZV), Epstein-Barr vi-
rus (EBV), cytomegalovirus, human
herpes virus 6, and adenovirus are
negative. The result of nasopharyn-
geal washing is negative for influenza
A and B. A further study elucidates
the diagnosis.
Case 2 Presentation
A 14-year-old girl with attention-
deficit/hyperactivity disorder (ADHD),
not currently taking any medications,
is referred to the emergency depart-
ment (ED) to rule out type 1 diabetes
mellitus. Symptoms began 5 weeks
earlier with low-grade fevers, fatigue,
and myalgias. She was diagnosed as
having a viral illness by her pediatri-
cian. The following week, she devel-
ops sinus congestion and headaches
and is prescribed azithromycin for
presumed sinusitis. Her sinus conges-
tion improves, but the headaches and
fatigue persist.
During the following 3 weeks, she
develops polydipsia (drinking more
than 20 cups of liquid per day), poly-
uria, nocturia (awakening 3 times per
night to urinate), and night sweats
and loses a total of 10 lb. She also
has significant polyphagia and begins
eating 7 to 8 full meals per day. In ad-
dition, she experiences episodes of
“shakiness,” palpitations, and dia-
phoresis. She makes another visit to
her pediatrician during which a non-
fasting chemistry panel is notable for
a chloride level of 96 mEq/L, a bicar-
bonate level of 28 mEq/L, and
Pediatrics in Review Vol.34 No.10 October 2013 465
index of suspicion
a glucose level of 131 mg/dL. Her
urinalysis result is normal. She is sent
home with a home glucometer to
rule out hypoglycemia as a cause of
her “shakiness” and diaphoresis.
On the day of presentation, the girl’s
blood glucose level is 280 mg/dL at
home, so she calls her pediatrician,
who refers her to the ED. Her initial
vital signs in the ED are as follows:
temperature, 36.9°C; heart rate, 120
beats per minute; respiratory rate, 24
breaths per minute; and blood pres-
sure, 90/54 mm Hg. She is alert
and awake but appears fatigued. Phys-
ical examination demonstrates a palpa-
ble spleen tip 1 cm below the left
costal margin but is otherwise within
normal limits.
Her initial blood glucose level is
89 mg/dL, and her urinalysis result
is negative for glucose and ketones.
Her hemoglobin A1C level returns at
5.9%. While in the ED, she becomes
acutely tachycardic, diaphoretic, and
hypertensive, with a blood pressure
of 192/144 mm Hg. She is admitted
to the intensive care unit, where an
imaging study confirms the diagnosis.
Case 3 Presentation
A 2½-year-old boy presents to the
ED with a history of difficulty breathing
that has worsened during the last 4 days
and now is even present at rest. He has
had fevers to 39.4°C, rhinorrhea,
cough, nausea, and lack of appetite.
There is no previous history of asthma,
difficulty breathing, or environmental
allergies. His prenatal, perinatal, and
postnatal courses were uneventful and
immunizations are up to date.
Vital signs are as follows: temper-
ature, 38.8°C; heart rate, 190 beats
per minute; respiratory rate, 50 to
60 breaths per minute; and blood
pressure, 94/68 mm Hg during expi-
ration and 78/64 mm Hg during in-
spiration. Room air oxygen saturation
is 79%. He prefers to sit yet is quite
466 Pediatrics in Review Vol.34 No.10 October 2013
uncomfortable. He is grunting with
nasal flaring and supraclavicular, inter-
costal, and subcostal retractions. He
has a clear nasal discharge. The jugular
veins are distended. Heart sounds are
distant, and no murmur is heard. He
has bibasilar crackles but no wheezing.
There is no evidence of hepatomegaly.
His right great toe has a paronychia
with surrounding erythema.
Laboratory evaluation reveals an el-
evated WBC count of 29
103/mL,
with 87% segmented neutrophils, 6%
bands, 8% lymphocytes, and 7% mono-
cytes. His PaO2 is 78 mm Hg (40%
fraction of inspired oxygen). Further
evaluation confirms the diagnosis.
Case 1 Discussion
On the second day of hospitalization,
magnetic resonance imaging (MRI)
of the brain revealed 2 focal areas
of diffusion restriction: both in the
midline of the corpus callosum, one
involving the genu and another the
splenium (Fig 1). Both lesions had
increased T2 signal, and neither had
an increased uptake of contrast.
The patient improved significantly
by the fourth day of admission with-
out any therapy; he was able to walk
independently, and his cognitive
functioning was back to baseline.
His gait improved to normal level 4
weeks later. Subsequent MRI of the
brain 8 weeks later revealed complete
resolution of lesions described above
without any atrophy. Thus, a diagno-
sis of mild encephalitis/encephalopa-
thy with reversible splenial lesion
(MERS) was made.
Differential Diagnosis
Lesions of the corpus callosum have
been described in several other clin-
ical conditions, most notably with
epilepsy, multiple sclerosis (MS), and
acute disseminated encephalomy-
elitis (ADEM), as well as in patients
receiving antiseizure medications. It
is important to distinguish MERS, a
self-resolving entity, from other con-
ditions, specifically ADEM. Typi-
cally, ADEM present weeks after an
acute illness, and although the CSF
can reveal a mild pleocytosis, the cell
count is often normal. MRI of the
brain in ADEM classically reveals
multiple extracallosal lesions. How-
ever, the corpus callosum can also
be involved. Diffusion restriction is
also unusual. Often treatment with
corticosteroids and/or intravenous
immunoglobulin is required to assist
with recovery. Recurrences can rarely
occur, and it can result in permanent
neurologic sequelae. Lesions of the
corpus callosum are common in MS.
MS is characterized by dissemination
of lesions through the central nervous
system and presenting with varying
clinical manifestations that involve dif-
ferent areas of the brain during
months to years. Encephalopathy
and marked CSF pleocytosis would
argue strongly against the first attack
of MS in this case. Other rare condi-
tions, such as CNS lymphoma, dif-
fuse axonal injury, and extrapontine
myelinolysis, can also cause callosal
lesions. However, the clinical mani-
festations are quiet different in these
conditions.
The Condition
Encephalitis is defined as inflammation
of the brain secondary to infection, re-
sulting in neurologic dysfunction.
MERS is a clinicoradiologic diagnosis
in which a lesion of the splenium of
the corpus callosum is detected on
MRI in association with viral enceph-
alitis. The most commonly reported
viruses include EBV, adenovirus, in-
fluenza A virus, VZV, and rotavirus.
The most common presenting
symptom of MERS is altered level
of consciousness or occasionally sei-
zures. Other less common symptoms
include ataxia, motor dysfunction,

Figure 1. Diffusion weighted imaging of
the brain in the axial plane demonstrat-
ing lesions in the genu and splenium of
the corpus callosum.
vertigo, and hallucinations. The diag-
nosis is usually not considered until
characteristic lesions are seen on neu-
roimaging studies. The hallmark of
MERS is a transient, isolated lesion
Figure 2. Nuclear medicine MIBG scan revealing intense radiotracer uptake within the left adrenal gland (red arrow).
in the splenium. Follow-up neuro-
imaging studies performed several
weeks after initial presentation reveal
resolution of the lesions. No specific
treatment is required for MERS be-
cause it is a self-resolving condition
without permanent neurologic se-
quelae. It is important to distinguish
MERS from other similar entities that
require more in-depth investigation
and prolonged treatment courses.
The clinical presentation in our pa-
tient represents a variant of MERS
in which lesions occur in both the
splenium and genu of the corpus
callosum.
Lessons for the Clinician
• MERS is a rare clinical condition;
however, should be considered in
the appropriate setting.
index of suspicion
• MERS is a self-resolving condition
without any permanent sequelae.
• MERS is a clinicoradiologic diag-
nosis, and brain MRI is an essential
study to help diagnose and differ-
entiate it from other similar but se-
vere neurologic conditions.
(Capt Julie Speakman, USAF, MC,
Lt Melissa Buryk, MC, USN Depart-
ment of Pediatrics, Naval Medical
Center Portsmouth, Portsmouth, VA,
and Sean Goretzke, MD, Pediatric
Neurology, Cardinal Glennon Child-
ren’s Medical Center, St. Louis, MO )
The views expressed in this article are
those of the authors and do not neces-
sarily reflect the official policy or po-
sition of the Department of the Navy,
Department of Defense or the United
States Government. I am a military
Pediatrics in Review Vol.34 No.10 October 2013 467
index of suspicion

service member. This work was pre-

pared as part of my official duties.
Title 17 U.S.C. 105 provides that
“Copyright protection under this ti-
tle is not available for any work of
the United States Government.” Ti-
tle 17 U.S.C. 101 defines a US gov-
ernment work as a work prepared
by a military service member or em-
ployee of the US government as part
of that person’s official duties.

Case 2 Discussion Figure 3. Abdominal MRI revealing a 3.9-cm left adrenal pheochromocytoma (red
In the intensive care unit, the girl’s
arrows).
blood pressure is controlled with ni-
fedipine and hydralazine. Ophthalmo-
logic examination demonstrates grade had no further recurrence of her tumor time of diagnosis and are also at in-
IV severe acute hypertensive retino- 3 years out. creased risk of malignant disease. Pre-
pathy with edematous, hyperemic op- vious studies have demonstrated
tic discs, macular exudates and edema, The Condition that up to 50% of children with pheo-
dilated venules, cotton-wool spots, Pheochromocytomas are catecholamine- chromocytomas have malignant dis-
and flame hemorrhages. The results secreting tumors that arise from the ease compared with only 10% of
of urine toxicology screening are neg- chromaffin cells of the adrenal me- adults.
ative, but levels of 24-hour urine dulla. They are a rare cause of hyper- The clinical manifestations of pheo-
metanephrines and normetanephrines tension in children, occurring in chromocytomas are caused by cate-
are found to be elevated with levels of approximately 1% of all children with cholamine excess, which occurs when
347 mg/24 h (reference range, 33- hypertension. When compared with the tumors secrete epinephrine, nor-
185 mg/24 h) and 11,297 mg/24 h adults with pheochromocytomas, chil- epinephrine, and dopamine. Al-
(reference range, 57-286 mg/24 h), dren with the disease are far more though approximately 50% of adults
respectively. Serum dopamine and likely to have bilateral disease, extrare- with pheochromocytomas present
norepinephrine levels are also found nal disease, or multiple tumors at the with the classic triad of intermittent
to be elevated at 160 pg/mL (refer-
ence range, 0-20 pg/mL) and
19,111 pg/mL (reference range,
85-1250 pg/mL), respectively. Serum
epinephrine is 109 pg/mL (reference
range, 18-460 pg/mL). A nuclear
medicine meta-iodo-benzyl-guanidine
(MIBG) scan reveals intense radio-
tracer uptake within the left adrenal
gland (Fig 2), and abdominal MRI
reveals a 3.9-cm left adrenal mass,
consistent with a pheochromocy-
toma without malignant features
(Fig 3). The girl undergoes a-
and b-blockade with doxazosin
and atenolol before surgical resec-
tion, which confirms the diagnosis
of pheochromocytoma. She has Figures 4. Chest radiograph reveals cardiomegaly and a left-sided pleural effusion.

468 Pediatrics in Review Vol.34 No.10 October 2013


diaphoresis, tachycardia, and head-
aches, children rarely present with
these symptoms. Instead, they often
present with vague symptoms, such
as back pain, abdominal pain, or ab-
dominal distension secondary to
mass effect. Sustained or malignant
hypertension caused by catecholamine
release is another common presenting
symptom in children, occurring in
approximately 60% of pediatric pa-
tients with pheochromocytomas.
Other less common clinical mani-
festations in children include psychiatric
disturbances, dilated cardiomyopathy,
and constipation.
Rarely, as was the case with this
patient, the clinical presentation of
Figure 5. Electrocardiogram reveals low voltages and diffuse ST-segment elevation (a)
and increased voltages after the pericardial fluid was drained (b).
pheochromocytoma can mimic that
of type 1 diabetes mellitus. Symptoms
such as weight loss, polyuria, and
polydipsia can be seen along with hy-
perglycemia. The polydipsia is second-
ary to increased serum osmolality
from hyperglycemia and dehydration,
whereas the polyuria is secondary to
an osmotic diuresis. Hyperglycemia
was reported in association with pheo-
chromocytoma as early as 1912. The
hyperglycemia is thought to be sec-
ondary to both decreased insulin
secretion and increased insulin resis-
tance due to the release of excessive
catecholamines. Elevated levels of epi-
nephrine are known to induce hepatic
gluconeogenesis and inhibit peripheral
index of suspicion
glucose use, whereas elevated levels
of norepinephrine result in increased
glycogenolysis in both muscle and
the liver, suppressed plasma insulin
concentrations, and elevated plasma
glucagon levels. Hyperglycemia and
impaired glucose tolerance have been
estimated to occur in up to 75% of
patients with pheochromocytomas,
but true diabetes is present in only
one-third of patients. As a result,
it has been suggested that the pres-
ence of diabetes in children with hy-
pertension may be a useful marker
for pheochromocytoma.
Although hyperglycemia is often
seen in pheochromocytoma, dia-
betic ketoacidosis is rare, and only
several cases have been reported. Al-
though our patient had hyperglyce-
mia related to excess catecholamine
secretion, she did not have true dia-
betes. Her hemoglobin A1C level
was only mildly elevated at 5.9%,
and her ophthalmologic examina-
tion findings were consistent with
acute hypertensive retinopathy, indi-
cating that both her hyperglycemia
and hypertension were likely epi-
sodic in nature.
Differential Diagnosis
Although this patient’s initial pre-
sentation was concerning for type
1 diabetes mellitus, her blood glu-
cose level was normal in the ED
and her hemoglobin A1C level was
only mildly elevated, which made
type 1 diabetes mellitus less likely.
Although polyuria, polydipsia, and
weight loss are most commonly
seen in diabetes mellitus, a broader
differential diagnosis should be
considered in patients presenting
with atypical symptoms. This pa-
tient’s tachycardia, diaphoresis, “shak-
iness,” hypertension, and intermittent
hyperglycemia were all concerning
for sympathetic overload or excessive
catecholamine release. The differential
diagnosis for increased sympathetic
Pediatrics in Review Vol.34 No.10 October 2013 469
index of suspicion
Figure 6. An echocardiogram reveals the presence of a large pericardial effusion.
activity includes several primary diag-
noses aside from pheochromocytoma
such as sympathomimetic ingestions,
catecholamine-secreting tumors such
as neuroblastomas, and panic at-
tacks. Sympathomimetics include
illicit drugs, such as cocaine, phency-
clidine, methamphetamines, and both
Figure 7. CT scan of the chest reveals a loculated pericardial effusion and left lower
lobe pneumonia.
470 Pediatrics in Review Vol.34 No.10 October 2013
screen result was negative, making
this diagnosis less likely. Catechol-
amine-secreting tumors can result
in transient hypertension; however,
they are less common in adolescents
and tend to occur in younger chil-
dren. Panic disorders may also mimic
sympathetic overactivity and typically
present with the sudden onset of fear,
anxiety, tachycardia, headaches, and
chest pain. Although patients with
underlying hypertension have a higher
prevalence of panic attacks, panic at-
tacks typically do not cause hyperten-
sion, hyperglycemia, or weight loss
and should be considered only after
other diagnoses have been effectively
ruled out.
Treatment and Prognosis
Treatment of pheochromocytoma
is primarily surgical, although medi-
cal preparation with both a- and
b-blockade is required before sur-
prescription and over-the-counter med-
gical resection. The goal of a- and
ications, such as pseudoephedrine,
b-blockade is to reduce the risk of
methylphenidate, and monoamine
perioperative complications from sud-
oxidase inhibitors. Although this
den catecholamine release. It has been
patient was previously taking meth-
found that normalization of blood
ylphenidate for treatment of her
pressure and resolution of symptoms
ADHD, she had not taken the medica-
before surgical resection are both
tion in weeks, and her urine toxicology
associated with improved perioperative
outcomes and fewer complications.
The prognosis of pheochromocy-
toma depends on whether the dis-
ease is isolated or metastatic and
whether it is associated with a famil-
ial syndrome. Although surgical re-
section is frequently curative in
isolated tumors, children with fa-
milial disease are at high risk for
recurrence.
Lessons for the Clinician
• Pheochromocytoma classically pre-
sents with episodic headaches, tachy-
cardia, and diaphoresis in adults but
may present with sustained hyper-
tension and nonspecific symptoms
in children.
 index of suspicion

Isonicotinylhydrazine • Given that several of the less com-

mon clinical manifestations of pheo-
chromocytoma overlap with those

EBV¼Epstein-Barr virus; CMV¼cytomegalovirus; HBV¼hepatitis B virus; HCV¼hepatitis C virus; HIV¼human immunodeficiency virus; HHV6¼human herpes virus 6; SLE¼systemic lupus
of type 1 diabetes mellitus, clinicians
Procainamide

Daunorubicin
Doxorubicin
Hydralazine

Penicillins should consider a broad differential

Phenytoin

diagnosis in patients with atypical

Drugs

presentations of hyperglycemia.
(Saranya Srinivasan, MD, Children’s
Hospital Los Angeles, Los Angeles, CA
Chylopericardium

Amanda Growdon, MD, Boston Child-

Hypothyroid

ren’s Hospital, Boston, MA)

Metabolic
Noninfectious

Uremia

Case 3 Discussion
Chest radiography revealed cardiome-
Lymphoma
Neoplastic

galy and a left-sided pleural effusion

(Fig 4, a and b) Electrocardiography
revealed low voltages and diffuse
ST-segment elevation (Fig 5a). Echo-
Ankylosing spondylitis

cardiography performed in the ED

confirmed the presence of a large
Giant cell arteritis
Sjögren syndrome

Systemic sclerosis

granulomatosis
Behçet syndrome

Rheumatic fever

pericardial effusion with tamponade

Churg-Strauss
Autoimmune

Polymyositis

Scleroderma
syndrome

physiology (Fig 6). Immediate man-

Sarcoidosis

Wegener

agement included percutaneous peri-

cardiocentesis and placement of a
SLE

TTP
RA

pigtail catheter into the pericardial

sac. A large amount (180 mL) of pu-
rulent fluid was drained from the peri-
Echinococcus

erythematosus; RA¼rheumatoid arthritis; TTP¼thrombotic thrombocytopenic purpura.

Toxoplasma

cardial space. The fluid was sent for

Parasitic

smear and culture.

The patient was then admitted to
the critical care unit and was treated
with intravenous ceftazidime, vanco-
Blastomycosis
Aspergillosis

Histoplasma

mycin, and ibuprofen. His respiratory

status improved immediately, and
Candida
Fungal

electrocardiography voltages increased

Causes of Pericarditis

on subsequent testing (Fig 5b).

Infectious

(pneumonia and

Hospital Course
Coxiella burnetii
Meningococcus
Staphylococcus

tuberculosis)
Streptococcus

The patient had immediate improve-

Haemophilus
influenzae
Mycoplasma

Gonococcus
Salmonella

ment after pericardiocentesis, but he

Chlamydia

Leptospira
Legionella
Bacterial

Listeria

became symptomatic with grunting

the following day, and his WBC
count continued to increase. A CT
scan of the chest (Fig 7) revealed a lo-
Coxsackievirus

culated pericardial effusion beyond

Adenovirus
Parvovirus

Echovirus

the tip of the catheter and left lower

Influenza

Varicella

lobe pneumonia. He was treated

HHV6
CMV
Viral

HBV

HCV
EBV
Table.

HIV

surgically with a pericardial window

procedure and bacitracin washout.

Pediatrics in Review Vol.34 No.10 October 2013 471

index of suspicion
Pericardial drains were placed that
were slowly withdrawn during several
days after drainage had ceased. Peri-
cardial fluid cultures, blood cultures,
and paronychia debridement all yielded
methicillin-sensitive Staphylococcus au-
reus, and the antimicrobial regimen
was changed to oxacillin for the re-
mainder of his antibiotic course.
He fully recovered without compli-
cations or need for additional surgi-
cal intervention.
The Condition
Pericarditis is inflammation of the
pericardium caused by infiltration of
granulocytes and lymphocytes into
the pericardial space. Vascular perme-
ability is also increased, causing protein
and fluid to leak into the pericardial
space, which, if severe, can compro-
mise hemodynamics. (1) The causes
for pericarditis can be divided into
infectious or noninfectious (Table).
Bacterial pericarditis (purulent peri-
carditis) accounts for 5% of cases
and may result from spread of con-
tiguous pneumonia or by hematoge-
nous seeding. Staphylococcus aureus
is the most common cause of bacte-
rial pericarditis.
The classic clinical presentation of
pericarditis is substernal chest pain that
is relieved with sitting or leaning for-
ward. Supine positioning can signifi-
cantly worsen their symptoms. In
children, nonspecific symptoms, in-
cluding fever, shortness of breath,
cough, or abdominal pain, are often
the presenting conditions. A thorough
physical examination is paramount in
making the diagnosis. Tachycardia,
neck vein distension, and narrow pulse
pressure may be present. A pericardial
friction rub is pathognomonic for peri-
carditis but may be absent in the set-
ting of a large pericardial effusion
because the surfaces of the pericardium
and heart are no longer adjacent.
Pulsus paradoxus is an important
maneuver to assess for tamponade if
472 Pediatrics in Review Vol.34 No.10 October 2013
signs and symptoms of effusion are
present. It is performed by slowly de-
flating a manual blood pressure cuff,
noting when Korotkoff sounds are
heard only during the expiratory
phase of respiration. The cuff deflation
is then continued, again slowly, until
Korotkoff sounds are heard during
inspiration and expiration. A de-
crease of more than 10 mm Hg in
systolic blood pressure between
these points increases the likeli-
hood of tamponade by 3.3-fold
(noncardiac causes of pulsus para-
doxus affect both systolic and dia-
stolic blood pressure).
Diagnosis
Diagnostic evaluation includes per-
forming chest radiography, electro-
cardiography, and echocardiography
and measuring levels of cardiac en-
zymes (to evaluate for concurrent
myocarditis) and C-reactive protein.
The chest radiograph is often normal
in acute disease. If cardiomegaly is
present, an underlying effusion is
likely. The “water bottle silhouette”
is usually not visualized until approx-
imately 250 mL of fluid has accumu-
lated in the pericardial space. (1)
Electrocardiographic changes are ob-
served in 90% of cases of pericardial
disease and include decreased vol-
tages, diffuse ST-segment elevation
(ST depression in aVR and V1),
and PR segment depression. These
changes evolve to T-wave inversion
in late disease. Low QRS complex
voltages and electrical alternans
(cyclic, variable height in the QRS
complex) may be observed in the
presence of a pericardial effusion. (2)
Although the echocardiography
results can be normal in patients with
acute pericarditis, echocardiography
is useful for evaluating pericardial ef-
fusion and should be performed
whenever an effusion is suspected.
It should be an integral part of the
evaluation for all high-risk patients.
Management
Determining the risk factors helps
decide whether hospitalization is
necessary or whether the patient
can be treated as an outpatient. Poor
prognostic factors for pericardial
effusion include temperature higher
than 38°C, subacute onset, large
pericardial effusion, cardiac tampo-
nade, or a poor response to 1 week
of nonsteroidal anti-inflammatory
drugs (NSAIDs). Hospitalization and
pericardial fluid analysis to determine
the cause of the effusion are needed
if any of these poor prognostic factors
are present. (3)
Ibuprofen is the first-line treatment
to suppress inflammation in all causes
of pericarditis. Most cases of pericardi-
tis are due to viral infection or idio-
pathic (which are presumed to also
be viral infections) in nature and have
a self-limiting course. Low-risk pa-
tients can be treated without hospital-
ization with NSAIDs, and 60% of
patients will recover within a week.
Lack of improvement should prompt
further careful evaluation.
Bacterial pericarditis is treated ini-
tially with broad-spectrum antibiotics
and must include coverage for staph-
ylococci until culture results are avail-
able. (1) Purulent pericarditis may
require performing a surgical pericar-
dial window for adequate drainage.
In the recovery stage of purulent peri-
carditis, the pericardium may constrict
the heart, requiring surgical pericardial
stripping. The patient must be evalu-
ated serially for findings of constriction.
Lessons for the Clinician
• In young children, pericarditis can
present with nonspecific symptoms,
resulting in delayed diagnosis.
• If a patient demands a sitting posi-
tion, do not force them to lie flat.
• Examine the patient carefully for
diminished heart sounds and pul-
sus paradoxus.
 index of suspicion

• An immediate echocardiographic
evaluation is absolutely necessary.
• Electrocardiographic abnormalities
are present in 90% of pericarditis cases.
• Viral infections are most common
cause of pericarditis and can be
managed conservatively.
• NSAIDs are the mainstay of treat-
ment, with additional therapies di-
rected to the specific cause of the
effusion, once determined.
(Luke Taggart, DO, Ben Rothwell,
MD, Todd Washko, MD, Alicia
Stevens, MD, Tulane University, New
Orleans, LA)
To view Suggested Reading lists
for these cases, visit http://pedsinreview.
aappublications.org and click on the
“Index of Suspicion” Link.

Parent Resources from the AAP at HealthyChildren.org

Case 1
• English: http://www.healthychildren.org/English/safety-prevention/immunizations/Pages/Japanese-Encephalitis-Vac-
cine-What-You-Need-to-Know.aspx
• Spanish: http://www.healthychildren.org/spanish/safety-prevention/immunizations/paginas/japanese-encephalitis-vac-
cine-what-you-need-to-know.aspx
Case 2:
• English only: http://www.healthychildren.org/English/health-issues/conditions/chronic/Pages/Causes-of-High-Blood-
Glucose-and-Low-Blood-Glucose.aspx
Case 3:
• English only: http://www.healthychildren.org/English/health-issues/conditions/fever/Pages/When-to-Call-the-Pediatri-
cian.aspx

Thank You!

The journal extends a special thank you to the following reviewers and CME
question writers (other than our editorial board members) of 2013 articles:

Derek Bell, MD OJ Sahler, MD

Athos Bousvaros, MD, MPH Michael A. Scharf, MD
Chin-To Fong, MD George B. Segel, MD
Howard B. Ginsburg, MD Nancy Spector, MD
Melissa Held, MD Gina Sucato, MD, MPH
Eduardo Lara-Torre, MD Martin Ulshen, MD
Elizabeth McAnarney, MD Wyn Wheeler, PharmD
Gary Neidich, MD H. Stephen Williams, MD
Sydney Rice, MD, MS

Pediatrics in Review Vol.34 No.10 October 2013 473

visual diagnosis

10-Year-Old Girl With Fever and

Altered Mental Status
Cynthia Ho, MD,* Manisha Israni, MD,† and Jeffrey Johnson, MD*

Figure 1. Rapidly spreading area of ecchymosis with the
development of a bullous lesion.
Author Disclosure
Drs Ho, Israni, and Johnson have disclosed no financial
relationships relevant to this article. This commentary does
not contain discussion of unapproved/investigative use of
a commercial product/device.
Presentation
A 10-year-old obese girl presents with fever and combat-
ive behavior during the past 2 hours. According to the
patient’s mother, the girl had experienced fatigue the
night before admission and developed fever the following
morning. By that afternoon, her parents became increas-
ingly concerned about her agitated mental status and
called emergency medical services.
In the emergency department, she is disoriented and
uncooperative. Her vital signs are notable for a rectal
temperature of 41°C, pulse of 187 beats per minute,
blood pressure of 108/79 mm Hg, respiratory rate
of 25 breaths per minute, and oxygen saturation of
78% on room air. On physical examination, her skin
is cold and clammy and capillary refill is 10 seconds.
A tender 1
1-cm area of ecchymosis is noted over
her left lateral breast, which the parents had not noted
previously.
She is aggressively resuscitated with isotonic fluids,
and blood cultures are drawn. Broad-spectrum antimi-
crobial coverage with vancomycin, clindamycin, and pi-
peracillin-tazobactam is initiated. She is intubated for
hypoxemic respiratory failure and shock. A urinary cath-
eter is placed, and minimal urine output is noted.
Within 6 hours of initial presentation, she requires in-
travenous dopamine and epinephrine for hemodynamic
support.
Laboratory tests reveal the following abnormali-
ties: pH 7.03; PCO 2, 40 mm Hg; bicarbonate, 10
mmol/L; creatinine, 2.01 mg/dL; lactate, 7.8 mmol/L;
aspartate aminotransferase, 81 U/L; alanine aminotrans-
ferase, 43 U/L; white blood cells, 6900/cumm, with
81.5% neutrophils (20% bands), 10.7% lymphocytes,
7.2% monocytes, and 0.6% eosinophils. The ecchymotic
area rapidly expands, and a bullous lesion appears within
the area (Fig 1). A clinical diagnosis is made.

*Department of Pediatrics, Los Angeles County þ University of Southern California Medical Center, Los Angeles, CA.
†
Departments of Internal Medicine and Pediatrics, University of California, San Francisco, San Francisco, CA.

474 Pediatrics in Review Vol.34 No.10 October 2013

 visual diagnosis

Diagnosis: Necrotizing Fasciitis recognized as superantigens by macrophages and other

A surgeon was consulted, and a bedside needle aspirate antigen-presenting cells. This activates macrophages
returned “dishwater” fluid. On the basis of this clinical and T cells to produce cytokines (tumor necrosis factor
picture, she was presumed to have necrotizing fasciitis a and interleukins 1 and 6), which are partly responsible
and was immediately taken to the operating room for de- for the profound systemic inflammatory response seen
bridement of the affected area. with necrotizing fasciitis. A cascade of events is triggered
that results in endothelial damage, tissue edema, and im-
paired capillary blood flow, the final common pathway of
Discussion
multiorgan failure.
Necrotizing fasciitis is a rare and rapidly progressive soft
Rapidly establishing the diagnosis has been recog-
tissue infection characterized by necrosis of subcutaneous
nized as the greatest challenge in caring for patients with
fat and muscle fascia. Given the fulminant and destructive
necrotizing soft tissue infections. Classic symptoms asso-
nature of this toxin-mediated disease, bacteria that cause
ciated with necrotizing fasciitis are severe pain, erythema,
necrotizing fasciitis are frequently referred to in the pop-
fever, swelling, and tachycardia. Localized pain out of
ular press as “flesh-eating bacteria.”
proportion to the physical examination in a child who
There are 2 types of necrotizing fasciitis (Table 1).
is systemically ill should raise a concern of necrotizing soft
Type 1 infection is a polymicrobial infection caused by
tissue infection. Because necrotizing fasciitis affects
anaerobes and gram-negative bacteria. Risk factors in-
deeper tissue layers, patients who present early in their
clude diabetes mellitus and other immune-compromising
course may have localized pain and hemodynamic abnor-
conditions. In contrast, type 2 infections are monomicro-
malities without overlying skin change.
bial infections that occur in previously healthy individuals.
The initial cutaneous manifestations of necrotizing
Streptococcus pyogenes or Staphylococcus aureus are the most
fasciitis can vary from no skin involvement to an ill-
common causative pathogens. Community-associated
defined erythematous lesion. Because the underlying soft
methicillin-resistant S aureus (CA-MRSA) has been in-
tissue is affected more extensively than the dermal or epi-
creasingly described as a causative organism in certain parts
dermal layer, edema extends beyond the erythematous
of the United States. Risk factors for type 2 necrotizing
border. Similarly, crepitus may be palpated before the de-
fasciitis include localized tissue injury from disruption of
velopment of overt skin findings, although this is uncom-
skin integrity (lacerations, burns, puncture wounds), mus-
mon with type 2 infections. The progression of skin
cle strain, blunt trauma, varicella infection, and obesity.
findings is fulminant and occurs over hours (rarely days).
Commonly, no precipitating event or risk factor is found
Erythema progresses to violaceous necrotic lesions,
when S pyogenes is identified as the infecting agent.
vesicles, and bullae. Once the lesion becomes necrotic,
Microbial invasion of subcutaneous tissues occurs
the skin and underlying area can become insensate.
from external trauma or direct extension from another in-
Laboratory findings are nonspecific. Leukocytosis and
fected organ (eg, urogenital organs in the setting of Four-
elevations in serum creatine kinase and lactate levels can
nier gangrene). Bacterial endotoxins and exotoxins cause
be expected. Evidence of multiorgan system failure devel-
tissue ischemia, necrosis, and the hallmarks of necrotizing
ops within 24 hours of infection. Blood cultures are pos-
soft tissue infections—microvascular thrombosis of capil-
itive in less than 20% of patients with type 1 necrotizing
laries and thrombosis of perforating vessels to the skin.
fasciitis and 60% of patients with type 2 infection.
Rapidly progressive cases of type 2 necrotizing infec-
Radiographic studies should not delay surgical inter-
tions are caused by virulent strains of S aureus and group
vention; however, if obtained, a noncontrast computed
A b-hemolytic streptococci that express multiple proteins
tomography (CT) scan is preferred because it is more ex-
(eg, M-1; M-3; pyrogenic exotoxins A, B, and C; and
pedient and can detect the presence of gas in the fascial
streptolysin O in the case of streptococci) that are
planes more effectively than magnetic resonance imaging
(MRI). Findings on CT include inflammatory changes,
fascial edema and thickening, abscesses, and gas forma-
Abbreviations tion. Plain radiographs may reveal subcutaneous gas;
CA-MRSA: community-associated methicillin-resistant however, lack of subcutaneous emphysema does not rule
Staphylococcus aureus out the possibility of a necrotizing soft tissue infection.
CT: computed tomography The utility of ultrasonography for the diagnosis of necro-
MRI: magnetic resonance imaging tizing fasciitis is limited at this time and requires further
study.

Pediatrics in Review Vol.34 No.10 October 2013 475

visual diagnosis

Table 1. Characteristics of Type 1 and Type 2 Necrotizing Fasciitis

Type Characteristics Microbiology Risk factors Treatmenta
1 More common type Polymicrobial Diabetes mellitus Piperacillin-tazobactam,
(w75%) Anaerobes (Clostridium, Immunocompromised carbapenem, or
perfringens, Bacteroides, cefepime plus
Peptostreptococcus) metronidazole
PLUS gram-negative organisms
(Escherichia coli, Klebsiella,
Enterobacter, Proteus,
Pseudomonas aeruginosa)
2 More common in Monomicrobial Healthy individuals Vancomycin, daptomycin,
young patients or linezolid
Associated with toxic Streptococcus pyogenes (group A) Varicella infection PLUS clindamycin
shock syndrome Staphylococcus aureus for antitoxin activity
(including CA-MRSA)
CA-MRSA¼community-associated methicillin-resistant Staphylococcus aureus.
a
Empiric broad-spectrum antibiotic coverage should be initiated to cover causes of both type 1 and type 2 necrotizing fasciitis. Type 3 necrotizing fasciitis due
to Vibrio vulnificus is not universally recognized.

Differential Diagnosis treatment against CA-MRSA, such as vancomycin, should

Differential diagnosis for pain localized to soft tissues and be initiated as well. After surgical source control is accom-
rapidly progressive septic shock includes necrotizing soft plished, an antibiotic course of 10 to 14 days is usually
tissue infections (myositis, fasciitis, cellulitis), purpura ful- sufficient.
minans, pyomyositis, and gas gangrene.

Management
Emergency surgery with aggressive debridement and an-
tibiotic therapy are the mainstays of treatment. Surgical
source control is crucial; antibiotic therapy without appro-
priate surgical intervention is uniformly fatal. A high level
of suspicion is critical, and the diagnosis should be made at
the bedside because significant clinical deterioration and
unnecessary delay of definitive surgical treatment can oc-
cur while attempting to pursue radiologic studies.
After the initial debridement, further debridement is
usually required on a scheduled basis until clinical stabi-
lization and borders of viable tissue are identified. Re-
sected tissue should be sent for Gram stain and culture
in addition to blood cultures. After all necrotic tissue has
been resected, wound closure may require split-thickness
skin grafting or myocutaneous tissue reconstruction.
Empiric antibiotic therapy should be broad and in-
clude coverage for gram-positive, gram-negative, and
anaerobic organisms. Acceptable regimens include a car-
bapenem, piperacillin-tazobactam, or the combination of
cefepime and metronidazole for coverage of gram-negative Figure 2. Extensive surgical debridement of the left axilla,
enteric organisms and anaerobes. Clindamycin should also breast, flank, and abdomen down to the level of the anterior
be included for its antitoxin activity. Finally, targeted superior iliac spine.

476 Pediatrics in Review Vol.34 No.10 October 2013


There are no standards for postoperative wound care,
although many centers are using vacuum-assisted wound
closure systems before definitive surgical skin closure pro-
cedures. Use of intravenous immunoglobulin (particu-
larly for cases with proven S pyogenes) and hyperbaric
oxygen for necrotizing fasciitis has been described, but
the efficacy of these therapies is uncertain at this time.
Prognosis
The mortality rate is high and estimated to be 24% to
58%. Timing to surgical debridement is the only variable
reported to be predictive of survival.
Patient Course
The patient underwent emergency and extensive surgical
debridement of her left axilla, breast, flank, and abdomen
down to the level of the anterior superior iliac spine (Fig
2). Intraoperatively, portions of the pectoralis major, pec-
toralis minor, latissimus dorsi, and serratus anterior ap-
peared grossly necrotic and were removed. Blood
culture results were negative. Tissue culture yielded S pyo-
genes (group A) on the second hospital day.
During the first week of hospitalization, she under-
went daily debridement in the operating room until all
necrotic tissue was resected. She was weaned off vasoac-
tive medications by the fourth hospital day and extubated
after 2 weeks. A split-thickness skin graft for wound cov-
Parent Resources from the AAP at HealthyChildren.org
• English only: http://www.healthychildren.org/English/health-issues/conditions/fever/Pages/When-to-Call-the-Pediatrician.aspx
Answer Key for October 2013 Issue:
Sinusitis: 1. A; 2. B; 3. B; 4. B; 5. C.
Pneumonia: 1. E; 2. A; 3. C; 4. D; 5. D.
Hernias and Hydroceles: 1. C; 2. B; 3. E; 4. C; 5. B.
visual diagnosis
erage was performed by the plastic surgeon on hospital
day 28. She was finally discharged after 2 months of hos-
pitalization and returned to school with future plans for
staged reconstructive surgery.
Summary
Necrotizing soft tissue infections are rare but deadly in-
fections. Diagnosis is made clinically with a high index of
suspicion. Definitive treatment includes emergency surgi-
cal debridement, broad-spectrum antibiotics, and support-
ive care in the intensive care unit. The initial antibiotic
regimen should be broad and cover gram-negative, anaer-
obic, and gram-positive organisms. Increased mortality is
associated with delay in operative intervention.
Suggested Reading
1. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection:
diagnosis and management. Clin Infect Dis. 2007;44(5):
705–710
2. Miller LG, Perdreau-Remington F, Rieg G, et al. Necrotizing
fasciitis caused by community-associated methicillin-resistant Staph-
ylococcus aureus in Los Angeles. N Engl J Med. 2005;352(14):
1445–1453
3. Sarani B, Strong M, Pascual J, Schwab CW. Necrotizing fasciitis:
current concepts and review of the literature. J Am Coll Surg. 2009;
208(2):279–288
4. Endorf FW, Garrison MM, Klein MB, Richardson A, Rivara FP.
Characteristics, therapies, and outcome of children with necrotizing
soft tissue infections. Pediatr Infect Dis J. 2012;31(3):221–223
Pediatrics in Review Vol.34 No.10 October 2013 477